Neuro-Ophthalmology and Neuro - Otology: A Case-Based Guide For Clinicians and Scientists Daniel Gold

Neuro-
Ophthalmology
and Neuro-
Otology
A Case-Based Guide for Clinicians
and Scientists
Daniel Gold
123
Neuro-Ophthalmology and
Neuro-Otology
Daniel Gold
Neuro-
Ophthalmology and
Neuro-Otology
A Case-Based Guide
for Clinicians and Scientists
Daniel Gold
Division of Neuro-Visual & Vestibular Disorders
The Johns Hopkins University School of Medicine
Baltimore, MD
USA
ISBN 978-3-030-76874-4 ISBN 978-3-030-76875-1 (eBook)

https://doi.org/10.1007/978-3-030-76875-1
© Springer Nature Switzerland AG 2021

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Preface
As a first-year neurology resident, I saw my first patient with

spontaneous nystagmus and a skew deviation due to the acute ves-
tibular syndrome with Dr. Stephen Reich (a fellow eye movement
enthusiast), and I immediately fell in love with the bedside ocular
motor and vestibular exam. I wanted to learn more about eye
movements and read about the “HINTS” exam to diagnose stroke
in the acute vestibular syndrome (Drs. Jorge Kattah and David
Newman-Toker). I was then introduced to Walsh & Hoyt’s Clini-
cal Neuro-Ophthalmology (edited by Drs. Neil Miller, Nancy
Newman, Valerie Biousse, and John Kerrison), and The Neurol-
ogy of Eye Movements (by Drs. John Leigh and David Zee),
Neuro-Ophthalmology Illustrated (by Drs. Valérie Biousse and
Nancy Newman), and Liu, Volpe, and Galetta’s Neuro-
Ophthalmology: Diagnosis & Management became my prized
possessions (little did I know that these authors would become my
future mentors and colleagues). While I came across excellent
neuro-ophthalmology and neuro-otology textbooks and review
guides, I couldn’t locate a single clinically based resource that
married these two subspecialties. While it was apparent to me that
there was considerable overlap between visual and vestibular dis-
orders, there appeared to be a significant knowledge gap at the
interface of neuro-ophthalmology and neuro-otology. Addition-
ally, while visual and vestibular symptoms are so common,
remarkably few clinicians seemed comfortable evaluating patients
with these complaints.
v
vi Preface
Throughout my training, I had the great fortune of being sur-

rounded by master clinicians, and I was inspired not only by their
clinical acumen and bedside manner, but also their penchant for
recording eye movements. When I became an attending myself,
the lines between “neuro-ophthalmology” and “neuro-otology”
blurred within my practice, and I began to record videos of every-
thing I felt had educational value. My burgeoning database of vid-
eos turned into my own collection through the North American
Neuro-Ophthalmology Society’s (NANOS) Neuro-Ophthalmol-
ogy Virtual Education Library (NOVEL), with substantial assis-
tance and encouragement from Nancy Lombardo and Dr. Kathleen
Digre. My passion for clinical care, the bedside exam, and the
desire to formalize my NOVEL Collection became the impetus
for this book – a one-stop shop for clinical neuro-ophthalmology
and neuro-otology using a case (and video)-based approach.
While all of the basics are included here, there are enough clinical
pearls, figures, and video examples throughout to keep even the
most advanced and experienced readers satiated.
In addition to going through this book chapter by chapter, it
can also be used when the reader is in a pinch – e.g., my patient
has acute onset prolonged vertigo … what do I ask or examine
first? For these real-time situations, start with the symptom-based
tables. Not sure what neuro-ophthalmic or audiovestibular testing
is necessary for your patient? There are tables and electronic sup-
plemental materials for that. Not sure how to examine saccades or
use your new Maddox rod? It’s all here for you in the form of
videos and other interactive resources. I hope this practical
resource can be used to enthuse and educate current and future
neurologists, ophthalmologists, otolaryngologists, neurosur-
geons, audiologists, physical therapists, internists, emergency
medicine providers, as well as scientists looking for a clinical per-
spective, and I hope to inspire others as my mentors and col-
leagues have inspired me. I would also like to dedicate this book
to my family for their support and patience, and to my patients for
their generosity in sharing their stories (as well as their eyes).
Baltimore, MD, USA Daniel Gold

Acknowledgments
I would like to acknowledge and thank the following mentors,

colleagues, and trainees for their advice, guidance, and feedback
throughout this process. Their willingness to contribute their valu-
able time and expertise has been essential to the creation of this
book: Dr. Stephen Reich (for inspiring and encouraging me to
write a book in the first place, also content review and contribu-
tion of figures); Dr. David Zee (for inspiration, content review,
and contribution of ideas); Dr. Neil Miller (for content review,
contribution of figures and ideas); Dr. Collin McClelland (for
content review, contribution of figures and ideas); Dr. Victoria
Pelak (for content review and contribution of ideas); Dr. Vivek
Patel (for content review); Dr. Veeral Shah (for content review and
contribution of figures); Dr. Marc Levin (for content review); Dr.
Ari Shemesh (for content review); Dr. Tony Brune (for content
review, and for helping create many videos); Dr. Olwen Murphy
(for helping create several figures and for content review); Dr.
David Hale (for content review); Dr. Elizabeth Fracica (for con-
tent review); Dr. Paul Chang (for content review); Dr. Nicholas
Hac (for content review); Justin Bosley (our ophthalmic/vestibu-
lar technician, for being excellent at what he does)
vii
Contents
1 Preparing for the Exam�� 1

1.1 Equipment for the Afferent Neuro-Ophthalmology
Bedside Exam �� 1
1.1.1 Vision�� 1
1.1.2 Pupils, Eyelids, Orbits�� 2
1.2 Equipment for the Efferent Neuro-Ophthalmic/
Vestibular Bedside Exam�� 2
Reference �� 3
2 Disorders of the Pupils, Eyelids, and Orbits�� 5
2.1 Pupil�� 5
2.1.1 Anisocoria—The History�� 5
2.1.2 Anisocoria—The Exam�� 15
2.1.3 Pharmacologic Testing�� 16
2.1.4 Horner’s Syndrome �� 17
2.1.5 Aneursymal Third Nerve Palsy�� 22
2.1.6 Tonic Pupil�� 25
2.2 Eyelid (Ptosis and Spasm)�� 28
2.2.1 Ptosis—The History�� 28
2.2.2 Ptosis—The Exam�� 28
2.2.3 Levator Dehiscence�� 29
2.2.4 Myasthenia Gravis�� 34
2.2.5 Eyelid Spasms�� 38
2.3 Orbit/Globe �� 41
2.3.1 Orbital Disorders—The History �� 42
2.3.2 Orbital Disorders—The Exam�� 42
ix
x Contents
2.3.3 Thyroid Eye Disease �� 44

2.3.4 Eye Pain (Acute Angle Closure
Glaucoma)�� 46
2.3.5 Red Eye (Carotid Cavernous Fistula) �� 49
References�� 52
3 Loss of Vision and Other Visual Symptoms�� 55
3.1 Vision Loss—The History�� 55
3.2 Vision Loss—The Examination�� 55
3.3 Interpretation of Monocular or Binocular
Visual Fields—Dr. Neil Miller’s 10 Visual
Field Rules to Live by�� 68
3.4 Ancillary Testing in Neuro-Ophthalmology �� 74
3.5 Prechiasmal (Monocular Vision Loss) �� 74
3.5.1 Retina�� 76
3.5.2 Optic Nerve�� 85
3.6 Chiasmal Visual Disorders��102
3.6.1 Pituitary Tumor ��102
3.7 Retrochiasmal Visual Disorders��105
3.7.1 The History ��105
3.7.2 The Exam��105
3.7.3 Treatment Options��105
3.7.4 Optic Tract��105
3.7.5 Lateral Geniculate Nucleus (LGN)��106
3.7.6 Optic Radiations��108
3.7.7 Occipital Lobe/Striate Cortex ��110
3.8 Higher Cortical Visual Disorders��111
3.8.1 Posterior Cortical Atrophy��111
3.8.2 Hallucinations ��117
3.8.3 Visual Snow��119
References��121
4 Motility and Ocular Motor Disorders��125
4.1 The History ��125
4.2 The Exam��126
Contents xi
4.3 Subarachnoid Space, Cavernous Sinus,

Orbital Apex��135
4.3.1 Subarachnoid Space��135
4.3.2 Cavernous Sinus��137
4.3.3 Orbital Apex��141
4.4 Medulla ��142
4.4.1 Lateral Medullary (Wallenberg)
Syndrome (Including Skew Deviation
and Saccadic Dysmetria)��142
4.5 Pons��151
4.5.1 Medial Longitudinal Fasciculus
Syndrome��151
4.5.2 Horizontal Gaze Palsies��156
4.5.3 Sixth Nerve ��160
4.6 Midbrain��164
4.6.1 Third Nerve��164
4.6.2 Fourth Nerve ��167
4.6.3 Vertical Gaze Palsies��174
4.6.4 Progressive Supranuclear Palsy��179
4.7 Cerebellum��182
4.7.1 Syndrome of the Flocculus and
Paraflocculus (Tonsil) ��184
4.7.2 Syndrome of the Nodulus and Ventral
Uvula��187
4.7.3 Syndrome of the Dorsal Vermis
and Posterior Fastigial Nucleus��188
References��189
5 Oscillopsia, Nystagmus, and Other Abnormal
Movements��191
5.1 The History—How to Approach Oscillopsia
and Nystagmus��191
5.2 The Exam—Does My Patient Have Nystagmus
or Something Else? ��192
xii Contents
5.3 Nystagmus��194
5.3.1 Horizontal Nystagmus (Bruns
Nystagmus) ��194
5.3.2 Periodic Alternating Nystagmus ��205
5.3.3 Downbeat Nystagmus ��206
5.3.4 Upbeat Nystagmus��210
5.3.5 Torsional Nystagmus��214
5.3.6 Oculopalatal Tremor ��216
5.3.7 Multiple Sclerosis Acquired Pendular
Nystagmus��219
5.4 Saccadic Intrusions, Oscillations, and Other
Nystagmoid Movements ��222
5.4.1 Square Wave Jerks (SWJ)
and Related Saccadic Intrusions ��222
5.4.2 Opsoclonus/Ocular Flutter��223
5.4.3 Superior Oblique Myokymia��226
References��228
6 Vestibular Disorders��231
6.1 The Vestibular History��231
6.1.1 TRIAGE��231
6.1.2 TiTrATE��231
6.1.3 Test��233
6.2 The Vestibular Examination��233
6.3 Bedside Auditory Testing��239
6.4 Laboratory Testing of Audiovestibular
Disorders ��240
6.5 Vestibular Syndromes ��240
6.5.1 Acute Vestibular Syndrome��240
6.5.2 Episodic Vestibular Syndrome��252
6.5.3 Chronic Vestibular Syndrome ��285
References��298
7 Pediatric Clinical Pearls��305
7.1 Neuroblastoma��305
7.2 Neurofibromatosis Type 1 (NF-1)��306
Contents xiii
7.3 Abnormal Development of the Visual

Pathways (Optic Nerve Hypoplasia)��307
7.4 Infantile Nystagmus (IN)��307
7.5 Abnormal (but Characteristic) Eye
Movements��308
7.6 Esotropia—Infantile or Acquired?��310
7.7 Idiopathic Intracranial Hypertension��310
7.8 Optic Neuritis��312
7.9 Myasthenia Gravis��312
7.10 Ocular Motor Palsies (Third, Fourth,
Sixth Nerve Palsies)��313
7.11 Retinal Disorders Mimicking Neurologic
Disease��314
7.12 Vertigo and Dizziness ��315
References��315
Index��317
List of Figures
Fig. 2.1 Oculosympathetic pathway for pupillary dilation:

The oculosympathetic tract is an uncrossed pathway
that begins in the hypothalamus, with fibers descend-
ing in the brainstem (first order, commonly affected
in a lateral medullary syndrome), synapsing in the
lower cervical/upper thoracic spinal cord (interome-
diolateral cell columns of C8–T2, also referred to as
the ciliospinal center of budge) and continuing on as
the second order fibers (in proximity to the lung
apex). The tract ascends and then synapses in the
superior cervical ganglion. The third order neuron
leaves the ganglion, with sudomotor fibers following
the external carotid artery (explanation for absence
of anhidrosis with an internal carotid artery dissec-
tion), while the remaining fibers ascend with the
internal carotid artery (explanation for dissection
causing a painful Horner’s syndrome). The third
order fibers innervate the eyelid (superior [Muller
muscle] and inferior tarsal muscles) and pupillary
dilator muscles to open the eyelids and dilate the
pupils, respectively. A lesion along the oculosympa-
thetic tract causes a Horner’s syndrome with ptosis
and miosis, and sometimes clinically apparent
anhidrosis (with first or second order but not third
order)�� 13
Fig. 2.2 Parasympathetic pathway for pupillary constric-
tion: When a bright light is shone in one eye, light
xv
xvi List of Figures
enters the pupil and hyperpolarizes retinal

photoreceptors that activate retinal ganglion cells.
These signals propagate along the optic nerves,
chiasm, optic tracts, and fibers responsible for the
light reflex then synapse in the dorsal midbrain (prior
to reaching the lateral geniculate nucleus) at the
pretectal nuclei, then to the Edinger–Westphal
nucleus (EWN) of the oculomotor nucleus. From
here, efferent fibers travel with the oculomotor nerve
to the ciliary ganglion and, finally, innervate the
constrictor ( sphincter) muscles for bilateral
pupillary constriction�� 14
Fig. 2.3 Structures of the eye and ocular adnexa: Seen here
is a normal right eye, with clinically relevant
structures and landmarks labeled. Also note that the
position of the corneal light reflex can assist in ocular
alignment evaluation in a patient with poor vision
(i.e., Hirschberg and Krimsky tests)�� 15
Fig. 2.4 Dilute (0.1%) pilocarpine testing to diagnose a
tonic pupil: This is a patient with a slightly mydri-
atic left pupil that constricted to a near stimulus but
not to light. There was also segmental constriction of
the iris appreciated with slit lamp exam. Dilute
pilocarpine was instilled OU, and 45 minutes later,
there was no effect on the normal (right) pupil but
clear constriction of the mydriatic (left) pupil,
supporting the diagnosis of a left tonic pupil. (Photos
courtesy of Dr. Collin McClelland)�� 17
Fig. 2.5 Apraclonidine testing to diagnose a Horner’s
syndrome: Apraclonidine (0.5%) testing was
performed within 1 week of onset of Horner’s
syndrome. Testing was positive in that anisocoria
reversed (as well as ptosis)—i.e., the previously
miotic right (Horner’s syndrome) pupil was now
slightly mydriatic�� 18
Fig. 2.6 Right Horner’s syndrome due to right internal
carotid artery (ICA) dissection: More prominent
anisocoria in dark versus light is apparent in this
List of Figures xvii
case, which is highly suggestive of a Horner’s pupil

(related to poor sympathetic activation causing a
“dilation lag” in the miotic [right] pupil). There is
also mild upper lid ptosis but no anhidrosis (which is
typical of a third order lesion). MR images include
axial fluid attenuated inversion recovery (FLAIR)
and time of flight (TOF) MR angiogram demonstrat-
ing a crescent sign in the right ICA�� 19
Fig. 2.7 The eyelid exam—marginal reflex distance
(MRD) 1 and 2: For documentation and comparative
purposes, the MRD1 (upper eyelid margin to corneal
light reflex, normal is ~4–5 mm) and MRD2 (corneal
light reflex to lower eyelid margin, normal is ~5 mm)
should be recorded, especially when ptosis is
suspected. The palpebral fissure is simply the
MRD1 + MRD2 and will be widened with a seventh
NP and narrowed with ptosis (from any etiology).
A light source and measuring device are all that
are needed�� 20
Fig. 2.8 Right third NP due to right posterior communicat-
ing (PCOM) artery aneurysm: The combination of
severe ptosis, mydriasis, and a “down and out” appear-
ance OD are all typical of a right third NP, which in
this case was due to right PCOM aneurysm seen on
the axial CT angiogram (left) and CTA 3D reconstruc-
tion (right). Because the pupillary fibers travel in the
outer portion of the third nerve, the pupil is almost
always involved with aneurysmal (or other) compres-
sion and is typically spared with a microvascular
insult. (CT images courtesy of Dr. Judy Huang)�� 22
Fig. 2.9 Clinical features of a left tonic pupil: Seen here
is a patient with anisocoria with a mydriatic pupil
OS that constricted poorly to light but much better to
a near target. Additionally, when asked to look from
a near to a distant target, slow (tonic) dilation was
observed. Dilute (0.1% pilocarpine) constricted the
mydriatic (left) pupil but not the normal (right)
pupil�� 26
xviii List of Figures
Fig. 2.10 The eyelid exam—levator function (LF) and lid

crease: For documentation and comparative pur-
poses, the lid crease (upper eyelid margin to the
insertion of the levator palpebrae muscle, normal
~6–10 mm) and LF (the white dotted line represents
the LF, or the distance between the upper lid in
downgaze [yellow arrowhead] compared to upgaze,
while ensuring that the frontalis muscle does not
contribute to the eyelid movement, normal ~14–16
mm) should be recorded in millimeters. A high lid
crease is typical of disinsertion (dehiscence) of the
levator muscle, while diminished LF is suggestive of
extraocular muscle weakness (e.g., third NP, myas-
thenia gravis, or myopathy)�� 30
Fig. 2.11 Levator dehiscence—a common cause of
mechanical ptosis: Look for the combination of
upper lid ptosis and a high lid crease, with lack of
fatigability and normal levator function. It is typi-
cally bilateral and may be associated with other signs
(e.g., prominent superior sulcus, “sagging eye
syndrome” [esotropia greater at distance]) in the
aging population, and when unilateral, also consider
trauma, ocular surgery, or contact lens wear/eye
rubbing�� 30
Fig. 2.12 Structures relevant to eyelid opening and closing:
The seventh cranial nerve is responsible for eyelid
closure and innervates the orbicularis oculi (OO)
muscles, while eyelid opening depends mainly on the
third cranial nerve (levator palpebrae, i.e., severe
ptosis with a third NP) as well as the oculosympa-
thetic tract (superior and inferior tarsal muscles, i.e.,
mild upper lid [and sometimes lower lid or upside
down] ptosis with a Horner’s syndrome)�� 31
Fig. 2.13 Chronic right facial nerve palsy with aberrant
regeneration (synkinesia): The top left photo shows
the patient at rest with a slightly flattened right
nasolabial fold (suggestive of weakness) and
narrowed right palpebral fissure (typical of synkine-
List of Figures xix
sia months later, whereas there’s widening of the

ipsilateral palpebral fissure with an acute facial
palsy). The top right photo demonstrates poor right
eyelid closure (orbicularis oculi weakness) with
abnormal activation (synkinesia) of the lower face
(orbicularis oris) on the right. The bottom left photo
demonstrates inability to elevate the right brow (fron-
talis weakness), again with abnormal right o. oris
activation (synkinesia). The bottom right photo
demonstrates an asymmetric smile (due to right o.
oris weakness) with abnormal activation
(synkinesia) of the right o. oculi�� 32
Fig. 2.14 Bilateral ptosis and ophthalmoplegia in myasthe-
nia gravis: In this montage, the top photo represents
primary gaze where right ptosis (yellow asterisk) and
an outward deviation of the eyes (exotropia) can be
seen. The ptosis was variable, fatigable, and there
was mild orbicularis oculi weakness bilaterally. In
the bottom photos, bilateral adduction pareses (white
asterisks) are apparent in lateral gaze. In the bottom
right photo there is more ptosis OD in right gaze,
with resultant left eyelid retraction (black asterisk,
note that the superior sclera is visible) due to
Hering’s law�� 35
Fig. 2.15 Left hemifacial spasm: Between spasms, the face
was symmetric and facial muscle strength (inner-
vated by the seventh nerve) was normal. During
spasms, there was contraction mainly of the left
orbicularis oculi (eyelid closure) as well as the left
orbicularis oris and risorius (causing an upward and
leftward deviation of the mouth). Despite the
contraction of the o. oculi, the left eyebrow does not
depress (instead, there is slight elevation due to
simultaneous frontalis contraction), a finding known
as the “other Babinski sign.” (Photo courtesy
of Dr. Stephen Reich)�� 39
Fig. 2.16 Bony structures relevant to the orbit: The frontal,
sphenoid, maxillary, ethmoid, and lacrimal bones
xx List of Figures
make up the orbit. Structures passing through the

optic canal include the optic nerve, oculosympathetic
tract, and ophthalmic artery. Structures passing
through the superior orbital fissure include the
superior ophthalmic vein and cranial nerves 3, 4, 6,
and V1 (ophthalmic branch of the trigeminal nerve).
Structures passing through the foramen rotundum
include V2 (maxillary branch of the trigeminal
nerve)�� 42
Fig. 2.17 Typical orbital and neuroimaging signs in thyroid
eye disease (TED): Seen in the top left photo are
typical orbital signs of TED. Additionally, she had
proptosis as demonstrated by abnormal Hertel
exophthalmometer measurements (27 mm OU) as
well as anterior globe displacement on axial CT
relative to the interzygomatic (yellow) line. Orbital
CT and MRI are both effective modalities to visual-
ize enlarged extraocular muscles in TED. Typically,
the muscles tend to be involved in the following
order: inferior rectus (IR), medial rectus (MR),
superior rectus (SR), lateral rectus, followed by occa-
sional involvement of the oblique muscles. In the
images above, bilateral medial rectus (white asterisk)
enlargement is most prominent, but there is also mild
enlargement of bilateral inferior rectus (yellow
asterisk) and superior rectus muscles (black asterisk),
a slightly larger lateral rectus on the right (black
arrowhead) compared to the left and normal appear-
ing bilateral superior oblique muscles (yellow
arrowhead). (Photo and images courtesy of Dr.
Amanda Henderson) Seen in the bottom left photo is
an example of severe proptosis in another patient
with TED. Viewing the globes from above or from
below (as in this case) allows for a qualitative
assessment of globe position when an exophthal-
mometer is unavailable. (Photo courtesy of
Dr. Ryan Walsh)�� 43
List of Figures xxi
Fig. 2.18 How can I tell if it’s safe to dilate my patient?

Evaluation of the angle is best performed with a slit
lamp (using the Van Herick’s technique, where the
depth of the peripheral anterior chamber is compared
to the corneal thickness) or during gonioscopy.
However, a rapid (albeit less accurate) way to assess
the anterior chamber depth is to shine a (temporal)
light source parallel to the plane of the iris and to
look for a shadow on the nasal iris. If a shadow
appears nasal to the pupil, the patient should not be
dilated without first seeing an ophthalmologist. The
patient above had a normal anterior chamber depth
(i.e., no shadow was seen), and was safely
dilated�� 47
Fig. 2.19 Red eye due to carotid-cavernous fistula (CCF):
Note the appearance of small, tortuous conjunctival
vessels with extension to the limbus (arrowheads).
These “corkscrew” vessels (yellow arrow points to
one example) result from arterialization of the veins.
The time of flight (TOF) MR angiogram images
demonstrate abnormal filling of the cavernous sinus
(white arrow) and arterialization of the superior
ophthalmic vein (yellow arrowhead), while the T1
contrast-enhancement image shows an enlarged
medial rectus muscle (due to congestion, white
dashed arrow) in the affected, proptotic
left eye. (Photos and images courtesy of
Dr. Collin McClelland)�� 50
Fig. 3.1 The fundus exam—structures to identify and
evaluate: During routine ophthalmoscopy, the
following structures are of particular interest: the
optic disc and cup (and record the cup:disc ratio
when able), neuroretinal rim (e.g., is it pale due to
optic neuropathy? is there a thin rim due to a large
cup from glaucoma?), and follow the course of the
retinal arteries and veins (e.g., A-V nicking due to
hypertension? arterial plaque due to retinal occlu-
sion?). The fovea/macula and peripheral retina are
xxii List of Figures
more difficult to visualize on undilated examination,

but evaluation is important when maculopathy or
retinopathy is suspected. The papillomacular bundle
may be preferentially affected by certain conditions
including Leber’s hereditary optic neuropathy or
nutritional disorders (e.g., B12 deficiency), resulting
in temporal optic nerve pallor and central or
centrocecal scotomas. A cilioretinal artery is a
normal variant, and if present in a patient with a
central retinal artery occlusion, it can be responsible
for relatively preserved central visual function as a
portion of the macula continues to be perfused
by the unaffected choroidal circulation�� 67
Fig. 3.2 Layers of the retina as seen with optical
coherence tomography (OCT): In order from inner
to outer retina: RNFL, retinal nerve fiber layer; GCL,
ganglion cell layer; IPL, inner plexiform layer; INL,
inner nuclear layer; OPL, outer plexiform layer;
ONL, outer nuclear layer; ELM, external limiting
membrane; EZ, ellipsoid zone; RPE, retinal pigment
epithelium. Note that the GCL gives rise to the
RNFL, which then makes up the optic nerve (ON)
(Images courtesy of Dr. Kara Della Torre)�� 71
Fig. 3.3 Abnormal monocular visual fields with auto-
mated static perimetry—is it retina or optic
nerve? A monocular visual field defect is almost
always pre-chiasmal, but the appearance of the visual
field cannot distinguish optic neuropathy from
retinal/macular disease without additional informa-
tion (e.g., optic nerve is normal, swollen, or pale;
dyschromatopsia and relative afferent pupillary
defect are present with optic neuropathy; e.g.,
metamorphopsia with macular disease, abnormal
fundus exam with retinopathy/maculopathy). Each
abnormal visual field above could be due to optic
nerve or retinal disease, and an example of each has
been given (IIH, idiopathic intracranial hypertension;
LHON, Leber’s hereditary optic neuropathy; BRVO,
List of Figures xxiii
branch retinal vein occlusion; NAION, nonarteritic

anterior ischemic optic neuropathy; BRAO, branch
retinal artery occlusion; RP, retinitis pigmentosa;
ON, optic neuropathy; CRAO, central retinal artery
occlusion)�� 71
Fig. 3.4 Typical visual field defects associated with
discrete lesions along the visual pathways: Specific
monocular or binocular visual field defects can be
highly localizing when the neuroanatomy of the
visual pathways is understood. The temporal visual
field corresponds to the nasal retina, while the nasal
visual field corresponds to the temporal retina. (1)
Left optic nerve lesion—while an optic neuropathy
can cause a variety of monocular visual field defects
(see Fig. 3.3), a complete lesion will cause no light
perception vision loss in the affected eye (the violet
color = a combination of damage to both nasal and
temporal fibers). (2) Lesion at the junction of
proximal left optic nerve and chiasm—a junctional
lesion, when complete, can cause complete monocu-
lar vision loss OS due to optic neuropathy, but
because some fibers originating in the right inferona-
sal retina decussate in the chiasm and then bulge
forward into the left anterior chiasm/proximal nerve
(anatomically known as “Wilbrand’s knee,” a
somewhat controversial concept), a small superotem-
poral (“junctional”) scotoma can be seen in the right
eye. (3) Chiasmal lesion—due to involvement of the
crossing fibers (responsible for temporal visual fields)
coming from right and left eyes, bitemporal hemiano-
pia is the result. (4) Left optic tract lesion—since this
is a retrochiasmal lesion, a right homonymous
hemianopia (HH, and usually a mild right relative
afferent pupillary defect) is the result. When incom-
plete, these tend to be incongruous (asymmetric).
When complete, the HH is nonlocalizing (e.g., it
could be tract or could be occipital). (5) Left lateral
geniculate nucleus lesion—there are two characteris-
xxiv List of Figures
tic visual field patterns: (a) right homonymous

quadruple sectoranopia and (b) right homonymous
horizontal sectoranopia. (6) Left temporal lobe
(Meyer’s loop)—right superior quadrantic defect
(“pie in the sky”), which when incomplete, may be
incongruous. (7) Left parietal lobe—right HH that is
more dense inferiorly (“pie on the floor”) and often
incomplete. (8) Left occipital lobe, superior to
calcarine fissure—right inferior quadrantic defect,
congruous (symmetric) when incomplete, often with
macular sparing (i.e., sparing of the occipital pole/tip
due to dual vascular circulation). (9) Left occipital
lobe, inferior to calcarine fissure—right superior
quadrantic defect, congruous, often with macular
sparing. (10) Right complete occipital lesion with
sparing of the pole can be a complete left HH, or
congruous when incomplete, macular sparing. (11)
Right occipital pole lesion—left homonymous
central scotoma�� 72
Fig. 3.5 Relative afferent pupillary defect (rAPD)
and other findings of a unilateral optic neuropa-
thy: Patients with unilateral optic nerve disease
typically have loss of visual acuity, dyschromatopsia,
visual field loss, the optic nerve itself may appear
normal (e.g., acute retrobulbar optic neuritis) or
abnormal (e.g., optic nerve pallor months after an
optic neuritis attack), and a relative afferent pupillary
defect (rAPD) is a prominent feature of an optic
neuropathy (unless there is bilateral optic nerve
involvement). This patient has a compressive left
optic neuropathy due to a meningioma, and aside
from hand motions visual acuity and inability to see
any color plates during testing, there was diffuse
visual field loss OS, optic nerve pallor, and a clear
left rAPD as seen with the swinging flashlight test.
It’s as if the patient is in a bright room OD (i.e., the
pupil constricts), but then when moving the light
List of Figures xxv
from the right to the left eye, it’s as if the patient is

moving into a darker room
(i.e., the pupil dilates). The light should be held for
the same duration on each eye; if the light is held on
one eye longer than the fellow eye, this may cause a
false positive in a normal patient. The examiner must
be careful when looking for a rAPD in a patient with
anisocoria because less light is entering the smaller
pupil; occasionally, this can create the false appear-
ance of a rAPD on the side of the miosis�� 75
Fig. 3.6 Hollenhorst plaque in a patient with retinal TIA:
While the patient had normal vision by the time he
was evaluated, an asymptomatic cholesterol
embolus (Hollenhorst plaque) was seen in the
affected eye�� 76
Fig. 3.7 Vascular supply of the optic nerve head,
choroid, and retina: The ophthalmic artery is a
branch of the internal carotid artery, which in turn,
supplies the posterior ciliary (to choroid and outer
retina) and central retinal (to inner retina) arteries.
The central retinal artery (CRA) enters the optic
nerve about 1 cm posterior to the globe, and an
embolus may become lodged as the CRA pierces the
dural sheath of the nerve, or posterior to the lamina
cribosa, resulting in a CRA occlusion (CRAO,
involvement of inner retinal layers, sparing of optic
nerve head, outer retina, and choroid). The arterial
circle of Zinn–Haller supplies the optic nerve head,
which is made up of anastomoses from branches of
short posterior ciliary arteries (from posterior ciliary
artery, PCA), the adjacent pial network, and choroi-
dal vessels. Hypoperfusion of the PCA is the likely
cause for nonarteritic anterior ischemic optic
neuropathy. Ophthalmic artery pathology (e.g.,
thromboembolic and giant cell arteritis) results in
ischemia of the retina, choroid, and optic nerve.
(Redrawn and modified with permission from: Digre
xxvi List of Figures
KB, Corbett JJ Practical Viewing of the optic Disc.

Boston: Butterworth-Heineman 2003)�� 78
Fig. 3.8 The fundus appearance of nonarteritic anterior
ischemic optic neuropathy (NAION): Seen here is
a patient with typical neuro-ophthalmic signs of
NAION including (1) ipsilateral (OS) optic nerve
swelling, slightly more superiorly with associated
splinter hemorrhage (arrow), no discernible cup OS;
(2) ipsilateral (OS) inferior arcuate defect (correlat-
ing with the superior optic nerve head being most
affected); and (3) contralateral (OD) “disc at risk,”
crowded with small cup:disc ratio (about 0.2).
Several months later, optic nerve atrophy had
developed OS, which was visible as superior
segmental pallor (arrowhead)�� 86
Fig. 3.9 The fundus appearance of giant cell arteritis
(GCA): Several typical features of GCA are seen in
this patient with bilateral involvement. Right eye:
pallid/chalky-white severe optic nerve head edema
with multiple splinter hemorrhages (arrows); Left
eye: mild segmental (superior) swelling and inferior
hemorrhage. The bilaterality and pallid swelling OD
are very concerning for GCA and would be highly
atypical for nonarteritic anterior ischemic optic
neuropathy (NAION). Additionally, if there is optic
nerve (unilateral or bilateral) and retinal involve-
ment (branch or central retinal artery occlusion;
cotton wool spots), GCA should be assumed until
proven otherwise. Vision did not recover despite
high dose steroids, and severe bilateral optic nerve
pallor and retinal vessel attenuation was apparent
months later�� 89
Fig. 3.10 Clinical and radiologic features of typical optic
neuritis: Despite vision loss in the right eye (severe
field loss in the right eye, with an artifactual rim
defect seen inferiorly in the left eye, i.e., disappeared
when the patient was repositioned and retested)
associated with pain, the right optic nerve appeared
List of Figures xxvii
normal due to the retrobulbar location of the optic

neuritis (“the patient sees nothing and you see
nothing”). T2 hyperintensity of the right optic nerve
was apparent (top MRI), which can be seen acutely
or chronically in a variety of optic neuropathies.
However, contrast enhancement of the right optic
nerve was also demonstrated, a finding that is
common with an acute inflammatory/autoimmune
optic neuropathy�� 91
Fig. 3.11 Atypical fundus features in optic neuritis:
Consider an atypical cause (e.g., neuromyelitis
optica, anti-myelin oligodendrocyte glycoprotein
[MOG], neurosarcoidosis) when any of the following
features are present in an adult with optic neuritis:
(1) bilateral involvement, (2) severe swelling, (3)
hemorrhage (arrow), (4) light perception or no light
perception vision, (5) retinal exudates, and/or (6)
steroid dependence�� 92
Fig. 3.12 Radiologic features of atypical optic neuritis:
A 50-year-old woman with neuromyelitis optica
(previous attack of myelitis and + aquaporin antibod-
ies) presented with severe bilateral eye pain and
vision loss (diffuse depression OD and mainly
temporal loss OS). MRI demonstrated asymmetri-
cally enlarged and T2 hypertense optic chiasm (right
> left, white arrow) with contrast enhancement of the
chiasm (yellow arrow), prechiasmatic right optic
nerve, infundibulum, and bilateral optic nerve
sheaths (orange arrows, a finding that is generally
more typical of anti-MOG)�� 93
Fig. 3.13 Clinical features of papilledema: Visual acuity and
color vision are almost always normal early in the
course of idiopathic intracranial hypertension (IIH),
and automated static visual field perimetry should be
followed closely. Enlarged blind spots (due to
distortion of the peripapillary retina by the swollen
optic nerve) are commonly seen, as well as nasal and
peripheral inferior and superior defects as the disease
xxviii List of Figures
progresses. The fundus photos above the visual fields

come from the same patient, with the white arrows
pointing to several examples of vessels on the disc
being partially obscured by edema (Frisen grade 4).
The arrowheads point to temporal concentric
peripapillary wrinkles (the fundus photo to the left
comes from another patient, with chronic [Frisen
grade 2] papilledema who had developed optic
atrophy—note the optic nerve pallor), another
potential manifestation of elevated intracranial
pressure (along with retinal and choroidal folds).
Hemorrhages are also commonly seen in patients
with active papilledema. Fundus photography is an
excellent way to document the fundus examination
when available, and the Frisen papilledema grading
scale should be used when possible: Grade 0—no
halo of obscuration of the peripapillary nerve fiber
layer; Grade 1—obscuration of the peripapillary
retina with a C-shaped halo (sparing temporal
margin) of retinal nerve fiber layer edema; Grade
2—circumferential halo without obscuration of
blood vessels; Grade 3—major vessel(s) are
obscured by edema as they exit the
disc; Grade 4—major vessel(s) are obscured by
edema on the disc; Grade 5—partial or complete
obscuration of all vessels�� 96
Fig. 3.14 Clinical features of advanced papilledema: While
visual acuity and color vision are spared in early
idiopathic intracranial hypertension (IIH), in more
advanced disease, they are often involved. This
patient has 20/50 acuity OU and mild dyschromatop-
sia. Additionally, there was severe peripheral visual
field loss/constriction. While there were no active
features of papilledema (e.g., hemorrhage, obscura-
tion of blood vessels, edema), this was because they
were severely atrophic and unable to swell. The
arrows point to gliotic changes that give the disc
margins a greyish appearance, and the arrowhead
List of Figures xxix
points to a retinochoroidal collateral vessel. These

collateral vessels may develop in certain conditions,
typically due to retinal venous outflow impairment—
i.e., blood will drain via the choroidal venous system
instead. In addition to chronic papilledema, collater-
als may also be seen with optic nerve meningiomas,
gliomas, sarcoidosis, central retinal venous occlu-
sion, and glaucoma�� 98
Fig. 3.15 Optic nerve head drusen—a common cause of
pseudo-papilledema: This patient was referred out
of concern for papilledema, after being found to have
an abnormal optic nerve appearance on routine
ophthalmoscopy. Visual acuity and color vision were
normal, there was no relative afferent pupillary
defect, and static automated perimetry demonstrated
bilateral nasal step defects (more inferior OS and
more superior OD, black arrows), compatible with
retinal nerve fiber layer (RNFL) injury. The white
arrows point out the typical “lumpy bumpy” (i.e.,
yellow elevations) appearance of optic nerve head
drusen, which can damage the RNFL, leading to
(generally, mild and asymptomatic) visual field loss.
Because the optic nerve can be elevated by the
drusen (visible or buried drusen), and because the
disc margins can be obscured, patients may be
misdiagnosed with papilledema, when in fact this is
a common cause of “pseudo-papilledema.” While the
drusen are clearly visible in this patient, oftentimes
this is not the case and the examiner should look for
other features of an anomalous optic disc (e.g., small
and crowded, anomalous vascular branching patterns
[early branching and trifurcations], lack of venous
engorgement, irregular elevation of the optic disc,
lack of vessel or RNFL obscuration, and intact
spontaneous venous pulsations). Orbital ultrasound
and enhanced depth optical coherence tomography
are often used to aid in the diagnosis (especially for
the more challenging to diagnose buried drusen), and
xxx List of Figures
occasionally drusen can also be seen on a CT scan

(yellow arrow, note that CT should not be ordered
specifically for this purpose)�� 99
Fig. 3.16 Radiologic features of elevated intracranial
pressure: The following neuroimaging signs support
the diagnosis of elevated intracranial pressure: (1)
distention of the optic nerve sheaths (white arrow-
head); (2) flattening of the posterior sclera (white
dashed arrows); (3) empty sella (white arrow); and
(4) transverse venous sinus stenosis (black arrow,
bilateral in this case). Protrusion of the swollen optic
nerve head into the vitreous (black arrowhead) is a
finding that may be seen with optic nerve edema/
elevation due to a variety of etiologies. Tortuosity of
the optic nerve is another common finding with
elevated intracranial pressure�� 101
Fig. 3.17 Clinical and radiologic features of chiasmal
compression: This patient was found to have a
bitemporal hemianopia and bilateral optic nerve
pallor on clinical exam. The grayscale maps (top)
demonstrate left > right and superior > inferior visual
field loss, suggestive of greater compression of the
left and inferior aspect (respectively) of the optic
chiasm, and MRI demonstrated a pituitary macroad-
enoma (white arrows). The grayscale maps demon-
strate lower visual sensitivity as darker regions,
although these are not compared to any normative
database. The total deviation maps (bottom) are
generated by comparing the measured thresholds to
an age-corrected normal. In this example, the total
deviation maps more clearly demonstrate the
bitemporal nature of the defect than the grayscale
maps. Analysis of the entire report allows for more
accurate interpretation and localization�� 103
Fig. 3.18 Typical visual field and optical coherence
tomography (OCT) features of an optic tract
syndrome: While visual acuity and color vision were
normal, this patient had a very incongruous (asymmet-
List of Figures xxxi
ric) right homonymous hemianopia (only able to

demonstrate right temporal field loss OD to confronta-
tion and only a mild nasal defect was seen OS with
automated static perimetry), in addition to a mild right
relative afferent pupillary defect (rAPD). The combina-
tion of an incongruous right homonymous hemianopia
and right rAPD was highly localizing to the right left
optic tract, which was felt to be due to a chronic infarct
seen on MRI. A characteristic OCT pattern of ganglion
cell layer-inner plexiform layer homonymous hemiat-
rophy was also demonstrated (black arrows demon-
strate the focal sectoral thinning—nasal OD and
temporal OS—outside the 99% limit of normal). This
pattern may be seen with any chronic retrochiasmal
lesion as retrograde transsynaptic degeneration occurs
but is more common (and faster to develop)
with optic tract lesions�� 107
Fig. 3.19 Lateral geniculate nucleus (LGN) lesions cause
distinct homonymous visual field defects: The top
visual field is an example of a homonymous horizon-
tal sectoranopia, which can be a manifestation of
lateral choroidal artery territory ischemia (posterior
circulation). The bottom visual field is an example of
a homonymous quadruple sectoranopia, which can
be a manifestation of anterior choroidal artery
territory ischemia (anterior circulation). (Visual
fields courtesy of Dr. Neil Miller)�� 108
Fig. 3.20 A “pie in the sky” defect due to temporal lobe
(Meyer’s loop) injury: This is a patient with remote
history of traumatic brain injury with associated
right temporal lobe encephalomalacia (white
arrows). Since the inferior optic radiations travel
through the (right) temporal lobe (Meyer’s loop),
injury can cause a (left) incongruous (asymmetric)
homonymous superior quadrantic visual field
defect, as seen here�� 109
Fig. 3.21 Congruous visual field defects due to occipital
injury: (A) This patient was found to have a (mainly
xxxii List of Figures
left) parieto-occipital parasagittal meningioma with

associated right homonymous visual field defect,
which worsened slightly following partial resection.
Postoperative automated static perimetry demon-
strated a very congruous (symmetric, white asterisk
indicates the physiologic blind spot OD; otherwise,
the two visual fields are identical) right incomplete
inferior quadrantic visual field defect, correlating
with the left occipital hyperintensity (black dashed
line, superior to the calcarine fissure) seen on the
postoperative MRI (black solid arrow points to
residual meningioma). (B) This patient had a severe
cardiomyopathy and experienced several cardioem-
bolic strokes, two of which involved the left occipital
lobe causing two distinct congruous visual field
defects: (1) an incomplete right homonymous
hemianopia (black dashed line) and (2) a right
homonymous central scotoma (from left
occipital tip ischemia)�� 112
Fig. 3.22 Bilateral homonymous visual field defects and
parieto-occipital atrophy in a patient with
posterior cortical atrophy (PCA): At the top, the
black arrows point to a left homonymous hemiano-
pia, that is slightly more dense inferiorly and
suggestive of right parietal and/or right occipital lobe
(superior to the calcarine fissure) involvement. The
black dashed arrows point to a right homonymous
inferior quadrantic visual field defect, due to left
parieto-occipital involvement. On the bottom left are
two fluorodeoxyglucose (FDG)-positron emission
tomography (PET) images, with the white arrows
pointing to bilateral parieto-occipital hypometabo-
lism, while the dashed arrows point to bilateral
parieto-occipital atrophy seen on MRI�� 113
Fig. 3.23 How the brain makes sense of what it sees—the
dorsal and ventral visual pathways, and a
three-tiered approach to vision: (1) Ventral
(“what”) stream—this begins with the ‘P’ retinal
List of Figures xxxiii
ganglion cells ➔ parvocellular layers of the lateral

geniculate nucleus (LGN, 3–6) ➔ V1/striate cortex
(in blue) ➔ V4/V4a (fusiform and lingual gyri) ➔
occipitotemporal regions. (2) Dorsal (“where”)
stream—this begins with the ‘M’ retinal ganglion
cells ➔ magnocellular layers of the LGN (1, 2) ➔
V1/striate cortex ➔ V5/V5a ➔ occipitoparietal
regions. *For objective identification (general visual
agnosia)—in the left hemisphere, think “words”
(pure alexia) and in the right hemisphere, think
“faces and places” (prosopagnosia, topographagno-
sia). (The classification of cerebral visual dysfunc-
tion using a three-tiered approach is courtesy of Dr.
Jason Barton. The figure was developed with the
input of Dr. Victoria Pelak)�� 114
Fig. 4.1 Evaluating ocular alignment using Hirschberg
and Krimsky tests: This patient suffered severe
vision loss in the right eye due to optic neuritis
which led to an exotropia (XT) over several years.
When a penlight is shone in both eyes, the left eye
(white arrow) is the fixating eye because the light
reflex is centered in the pupil, while the light reflex
in the right eye is more medial than it should be
(white dashed line), owing to the fact that the right
eye is deviated outward. This is the Hirschberg test,
and is a quick and easy method to evaluate for
strabismus, especially effective in kids, uncoopera-
tive patients, or patients with poor monocular or
binocular vision. The Krimsky test was then per-
formed where base-in prism was placed on the
fixating (left) eye until the light reflex was centered
in the (previously exotropic) right eye (yellow
arrow). Because this was achieved once 35 prism
diopters (PD) of base in prism were placed, she had
a ~ 35 PD exotropia (approximate because this is not
as accurate a test as alternate cover or cover–uncover
using prism)�� 128
xxxiv List of Figures
Fig. 4.2 Multiple contralateral ocular motor palsies

due to neoplastic seeding of the subarachnoid
space: This patient had (1) an abduction paresis OD
(white asterisk) due to right lateral rectus (sixth
nerve) palsy, and (2) poor depression OS (black
asterisk) in down/right gaze, suggestive of a left
superior oblique (fourth nerve) palsy. There was a
slight rightward head tilt which cannot be appreci-
ated in this montage. Ocular alignment examination
demonstrated an esotropia that was worse in right
gaze (due to right sixth NP), and a left hypertropia
that was worse in right and downgaze, as well as
with left head tilt (due to left fourth NP)�� 136
Fig. 4.3 The course of the sixth (VI) nerve: The sixth
nucleus is located dorsally, adjacent to the fourth
ventricle, in the lower pons. The genu of the facial
(seventh) nerve wraps around the sixth nucleus,
creating the facial colliculus, which bulges into the
fourth ventricle. After the sixth nerve leaves the
pons, it follows a vertical course along the clivus and
then to the petrous apex where it penetrates the dura,
passing under the petroclinoid (Gruber’s) ligament in
Dorello’s canal, where it is tethered and particularly
susceptible to low or elevated intracranial pressure
states. It then enters the cavernous sinus (adjacent to
the sympathetic plexus which surrounds the internal
carotid artery), travels through the superior orbital
fissure to enter the orbit, and then passes through the
annulus of Zinn to finally innervate the ipsilateral
lateral rectus muscle�� 137
Fig. 4.4 Ocular motility and alignment findings in a
left third NP: This patient (with hypertension
and diabetes) suffered a microvascular left third NP.
In primary gaze, there is complete ptosis OS (levator
palpebrae, black asterisk), and with the left eyelid
manually elevated, there was also adduction paresis
OS and exotropia in right gaze (medial rectus, MR,
List of Figures xxxv
yellow asterisk), supraduction paresis OS and right

hypertropia in upgaze (superior rectus, SR, white
asterisk), infraduction paresis OS, and left hypertro-
pia in downgaze (inferior rectus, IR, red asterisk).
There was additional poor pupillary reactivity OS
(with mild left mydriasis) due to mild involvement of
the pupillary sphincter muscle (PCOM aneurysm and
structural lesions had been ruled out, and her third
NP resolved over 2–3 months as expected; however,
patients with a microvascular third can occasionally
have minimal pupil involvement, typically with
<1 mm of anisocoria). The third nerve also inner-
vates the inferior oblique muscle, which can be
challenging to diagnose when affected in combina-
tion with other muscles. The black arrow in the top
right photo (a different patient also with an isolated
left third NP) points to a nasal conjunctival blood
vessel during upgaze, and the yellow arrow points to
the same conjunctival blood vessel in downgaze.
Although the eye depresses poorly (due to IR
paresis), the movement of the blood vessel is a
result of incycloduction OS due to the intact left
superior oblique muscle (the same finding can be
seen in the montage as well)�� 138
Fig. 4.5 Multiple ipsilateral ocular motor palsies due to
cavernous sinus meningioma: This patient had
(1) left medial rectus, superior and inferior rectus
(white asterisks, left eyelid is manually elevated in
downgaze) paresis, mild ptosis (levator palpebrae,
yellow asterisk), and a poorly reactive pupil OS (due
to parasympathetic involvement but without anisoco-
ria, probably due to additional oculosympathetic
involvement), all due to a left partial third NP;
(2) mild left lateral rectus (sixth nerve, black
asterisk) paresis; and (3) evidence of left superior
oblique (fourth nerve) paresis given no observable
incycloduction of the left eye in downgaze (not
apparent in this montage). There was also diminished
xxxvi List of Figures
facial sensation in the distributions of left V1 and V2.

Although there was mild ptosis OS, in right gaze,
there was a slight elevation of the left eyelid, a
consequence of aberrant regeneration of the left third
nerve. In this situation, some of the fibers innervating
the left medial rectus had been injured by chronic
third nerve compression, which led to a “miswiring”
phenomenon where those regenerating fibers wound
up innervating the left levator palpebrae instead.
Aberrant regeneration of the third nerve is suggestive
of chronic compression or injury and can be seen
following traumatic brain injury, mass lesion (e.g.,
meningioma), and aneurysmal (e.g., posterior
communicating artery) compression, among others.
The white arrows point to her meningioma, and the
top center figure (coronal view) of the cavernous
sinus demonstrates the proximity of these cranial
nerves to one another. The sympathetic plexus
surrounds the internal carotid artery (ICA), and given
its proximity to the sixth nerve, the combination of a
Horner’s syndrome and an ipsilateral sixth nerve
palsy is highly localizing to the cavernous sinus.
Mild oculosympathetic pathway injury could have
contributed to her mild ptosis, and perhaps the
fact that her poorly reactive left pupil was not
mydriatic, but more in-depth pharmacologic
drop (e.g., apraclonidine) testing was not
performed�� 140
Fig. 4.6 Orbital apex syndrome due to aspergillus:
An immunocompromised man presented with
1 day of right eye pain, redness, swelling, and
binocular diplopia. There was peri-ocular edema
and proptosis, as well as infraduction and adduc-
tion deficits OD. CT orbits (coronal view, left
image more anterior, right image more posterior)
demonstrating a lesion in the medial orbit (yellow
asterisk) with extension into the right ethmoid and
maxillary sinuses (white asterisks). Note also
List of Figures xxxvii
thickening of the left nasal mucosa and opacifica-

tion of both supraorbital ethmoid sinuses seen in
the image on the left. Biopsy of this lesion led to
the diagnosis of aspergillus (septate hyphae with a
45-degree branching pattern). (Images courtesy of
Dr. Neil Miller)�� 141
Fig. 4.7 Anatomy and physiology of the saccadic path-
ways: When a saccade is desired (or reflexively
triggered), signals project from the saccade-related
cortical eye fields to the superior colliculus, which
serves to integrate and relay commands to the
saccade generating brainstem circuitry. The inferior
cerebellar peduncle (ICP) carries climbing fibers to
the dorsal vermis, which has an inhibitory influence
over the Purkinje cells. These Purkinje cells normally
inhibit the ipsilateral fastigial nucleus, and the
fastigial nucleus sends excitatory fibers to the
contralateral excitatory burst neuron (EBN)/inhibi-
tory burst neuron (IBN) pair within the paramedian
pontine reticular formation (PPRF). The IBN project
contralaterally to inhibit the sixth nucleus to prevent
unwanted saccades in this direction, while the EBN
project ipsilaterally to excite the sixth nucleus to
facilitate saccades in this direction (an example of
reciprocal innervation)�� 143
Fig. 4.8 Lateral medullary lesion causing saccadic
dysmetria: A lesion of the left lateral medulla and
inferior cerebellar peduncle (ICP) will cause
decreased climbing fiber inhibition of the left dorsal
vermis causing simple-spike (inhibitory) discharge of
Purkinje cells to increase. Increased Purkinje cell
firing leads to increased inhibition of the ipsilateral
(left) fastigial nucleus, with a resultant decrease in
excitation of the right excitatory burst neuron/
inhibitory burst neuron (EBN/IBN) pair. This will
lead to less excitation of the ipsilateral (right) sixth
nucleus and less inhibition of the contralateral (left)
sixth nucleus, with an end result of right hypometria
xxxviii List of Figures
and left hypermetria (and ipsipulsion or leftward

ocular lateropulsion)�� 144
Fig. 4.9 Brainstem semicircular canal pathways:
(1) Horizontal canal pathway—afferents originating
in the horizontal canals (HC) of the (right) labyrinth
first synapse in the (right) ipsilateral vestibular
nucleus (VN). Two pathways exist: (a) medial
longitudinal fasciculus (MLF, allows for conjugate
horizontal eye movements)—projections from (right)
ipsilateral VN to (left) contralateral sixth nucleus,
which innervates left lateral rectus (LR) and right
medial rectus (MR, via the right MLF), resulting in
conjugate leftward eye movements; (b) ascending
tract of Dieters (ATD)—the (right) ipsilateral VN
also projects directly to the (right) ipsilateral MR,
thus bypassing the interneurons traveling from left
sixth nucleus to right MR subnucleus via the MLF
(this accessory tract explains how a patient with an
adduction paresis/lag due to internuclear ophthal-
moplegia can have a normal/near normal adduction
movement with head impulse test). (2) Anterior canal
pathway—afferents originating in the anterior canals
(AC) of the labyrinth first synapse in the ipsilateral
vestibular nucleus. Three pathways exist: (a) medial
longitudinal fasciculus (MLF)—right AC afferents to
right medial vestibular nucleus (MVN), decussate
and ascend via the left MLF to the elevator muscles
(right superior rectus [SR] and left inferior oblique
[IO]); (b) ventral tegmental tract (VTT)—right AC
afferents to right caudal superior vestibular nucleus
(SVN), decussate and ascend via the left VTT to the
elevator muscles; (c) brachium conjunctivum
(BC)—right AC afferents to right rostral SVN,
ascend (more laterally) and decussate via the BC to
the elevator muscles). (3) Posterior canal pathway—
afferents originating in the posterior canals (PC) of
the labyrinth first synapse in the ipsilateral vestibular
nucleus. One pathway exists: (a) MLF—right PC
List of Figures xxxix
afferents to right MVN, decussate and ascend via the

left MLF to the depressor muscles (right superior
oblique [SO] and left inferior rectus [IR]). LVN =
lateral vestibular nucleus�� 145
Fig. 4.10 Vascular distribution and anatomy relevant
to the lateral medullary (Wallenberg) syndrome:
This axial section of the medulla highlights those
structures that, when damaged, are responsible for
the vestibular and ocular motor features of the
Wallenberg syndrome. Fibers coming from the (left)
peripheral utricle synapse in the (left) vestibular
nucleus, explaining why a skew deviation is common
in a Wallenberg syndrome. With a left Wallenberg
skew, the left hypotropic eye is predictably ipsilateral
to the injury because the lesion is caudal to the
pontomedullary decussation of the utriculo-ocular
motor fibers (and the ocular tilt reaction [OTR] will
be ipsiversive, e.g., head tilt and ocular counter roll
are toward the left). Although various pathways exist
from the utricle and semicircular canals to their
respective ocular motor nuclei, many of these
pathways travel through the medial longitudinal
fasciculus (MLF, which, in the medulla, is not yet
carrying interneurons from the sixth nucleus).
Involvement of the (left) inferior cerebellar peduncle
(ICP) may result in asymmetry of the saccade
facilitation/inhibition pathways, resulting in ipsilat-
eral (left) ocular lateropulsion, ipsilateral (leftward)
saccadic hypermetria, and contralateral (rightward)
saccadic hypometria in a (left) Wallenberg syndrome.
If the medial medulla is also involved, there can be
other manifestations that are not typically seen with
a pure Wallenberg syndrome. The nucleus prepositus
hypoglossi (NPH) and medial vestibular nucleus
(MVN) complex is important for horizontal gaze-
holding (neural integration). Fibers from the horizon-
tal semicircular canals project to the MVN, thus
providing an explanation for an abnormal ipsilateral
xl List of Figures
horizontal head impulse test (HIT), which is occa-

sionally seen with a lesion involving the medial
vestibular nucleus. Gaze-evoked nystagmus and loss
of the horizontal vestibulo–ocular reflex in Wer-
nicke’s encephalopathy can also be explained
by NPH–MVN dysfunction�� 146
Fig. 4.11 The utriculo-ocular motor pathway and
physiologic ocular tilt reaction (OTR): The OTR
consists of the triad of skew deviation, head tilt, and
ocular counter roll. Beginning caudally with the
right utriculo-ocular motor pathway: the right
labyrinth contains the linear acceleration detectors
(otoliths), including the saccule and utricle. The
utricles also respond to head tilt, so that if the head
is tilted to the right (solid curved arrow above), the
right utricle will fire and initiate the physiologic
OTR. These utricular afferents will synapse in the
right vestibular nucleus in the medulla.
The utriculo-ocular motor fibers which began on the
right side then decussate at the level of the ponto-
medullary junction and ascend as part of the left
medial longitudinal fasciculus (MLF). Afferents
travel via the MLF to their respective cyclovertical-
acting ocular motor nuclei (III and IV) in the left
midbrain, resulting in elevation and incycloduction
OD (due to superior rectus [SR] and superior
oblique [SO] muscles, respectively, seen as the
curved, dashed arrow OD) and depression and
excycloduction (due to inferior rectus [IR] and
inferior oblique [IO] muscles, respectively, seen as
the curved, dashed arrow OS). Finally, some of the
utricle afferents ascending to the left MLF will
synapse in the left interstitial nucleus of Cajal
(INC), which is responsible for vertical and
torsional gaze-holding. This ensures that the eyes
will stay in their new orbital position while the head
tilt is maintained. However, the vertical “skewing”
of the eyes and ocular counter roll are negligible in
List of Figures xli
the physiologic OTR. Instead, the major component

of the physiologic OTR will be a large head tilt to
reorient the head back to gravitational vertical
(consider the example of a motorcyclist going
around a tight curve to the right causing a rightward
body/head tilt, the head will reflexively tilt to the
left, back to gravitational vertical)�� 146
Fig. 4.12 Skew deviation and the pathologic ocular tilt
reaction (OTR): A skew deviation is a non-paralytic
vertical ocular misalignment that is due to imbal-
ance in the utriculo-ocular motor pathways. While
vestibular jerk nystagmus is a consequence of static
semicircular canal pathway imbalance (e.g., left-
beating nystagmus due to acute right vestibular
hypofunction from vestibular neuritis), an ocular tilt
reaction, which includes skew deviation, head tilt,
and ocular counter roll, is a consequence of static
utricle pathway imbalance. In the example of a left
medullary lesion, the utriculo-ocular motor pathway
is affected just as the afferents enter the brainstem,
thus creating a central utricle asymmetry. Because
utricle afferents on the right are intact/relatively
hyperactive compared to the lesioned afferents on
the left, the brain falsely perceives a rightward head
tilt (e.g., tilting the head to the right normally
excites the right utricle) even though no rightward
head tilt has occurred. There is an attempt to
reorient the head to gravitational vertical (with the
false assumption that the head is initially too far to
the right), but this results in a pathologic (leftward)
ipsilesional head tilt instead. A skew deviation (left
hypotropia causing vertical diplopia) and ocular
counter roll (top poles of both eyes rotate toward the
left ear) make up the other components of the
pathologic OTR, resulting from the damaged left
utriculo-ocular motor pathway and intact right
pathway. The OTR will be ipsiversive when the
lesion is caudal to the utriculo-ocular motor pathway
xlii List of Figures
decussation at the pontomedullary junction (i.e., the

‘low-low’ rule – the LOWer eye will be ipsilateral to
the lesion when it occurs LOWer than the decussa-
tion, as in this case) and will be contraversive when
the lesion is caudal to the decussation (i.e., the
‘high-high’ rule – the HIGHer eye will be ipsilateral
to the lesion when it occurs HIGHer than the
decussation, due to a medial longitudinal fasciculus
or interstitial nucleus of Cajal lesion)�� 148
Fig. 4.13 Vertebral artery dissection causing a lateral
medullary (Wallenberg) syndrome: This patient
suffered a left vertebral artery dissection (black
arrows demonstrate the missing segment of left
vertebral artery on MR angiography, compared to the
normal right vertebral artery, yellow arrow), which
caused left posterior inferior cerebellar artery (PICA)
territory ischemia that presented clinically as a left
lateral medullary stroke (white arrow, hyperintensity
seen on diffusion-weighted imaging, DWI); ICP,
inferior cerebellar artery; IVN, inferior vestibular
nucleus; MVN, medial vestibular nucleus; NPH,
nucleus prepositus hypoglossi; MLF, medial
longitudinal fasciculus�� 149
Fig. 4.14 Left medial longitudinal fasciculus (MLF)
stroke causing a left internuclear ophthalmople-
gia (INO): This patient with vascular risk factors
suffered acute binocular diagonal diplopia with mild
vertigo. Examination demonstrated an adduction
paresis OS (black asterisk) with associated abducting
nystagmus OD in right gaze, suggestive of INO and
explaining the horizontal component of her diplopia.
Ocular alignment examination also demonstrated a
comitant left hypertropia due to skew deviation, with
associated rightward head tilt, and ocular counter roll
(top poles of both eyes rotated toward the right ear),
making up the triad of the ocular tilt reaction (OTR).
There was also subtle spontaneous torsional nystag-
List of Figures xliii
mus (top poles toward the left ear). MR diffusion-

weighted imaging (DWI) demonstrated a
well-circumscribed infarct involving the left MLF. It
was thought that her stroke was due to small vessel
ischemia in the distribution of the paramedian basilar
artery perforators. The MLF carries fibers respon-
sible for (1) conjugate horizontal eye movements
(i.e., left INO was explained by involvement of the
interneurons connecting right sixth nucleus to left
medial rectus subnucleus), (2) utriculo-ocular motor
reflex (i.e., responsible for her left hypertropia/skew
deviation and OTR), and (3) vertical semicircular
canal pathways (i.e., anterior/posterior canal involve-
ment responsible for her mild vertigo and spontane-
ous torsional nystagmus)�� 153
Fig. 4.15 Anatomy of an internuclear ophthalmoplegia
(INO) and horizontal gaze palsy: The patient to the
left suffered a right medial longitudinal fasciculus
(MLF) stroke that caused a right INO. The right
MLF normally contains interneurons that travel from
the left sixth nucleus to the right medial rectus (MR)
subnucleus of III. This allows the left sixth nucleus
to innervate not only the left lateral rectus (LR), but
also the right MR via the MLF to ensure horizontal
conjugate movements to the left. However, when
there’s a right MLF lesion, the left LR is normally
innervated by the intact sixth nucleus, while the right
MR is not. This can lead to a complete adduction
(MR) paresis as in this case, or sometimes there’s no
obvious motility deficit but rather a slower adducting
saccade (adduction lag) in the affected eye, most
noticeable when assessing horizontal saccades. With
a right MLF lesion, there is usually an abducting
nystagmus in the left eye, likely reflecting an
adaptive response in an attempt to adduct the eye.
Because the right MR and left LR are a yoked pair
that receive the same innervation, the normal left LR
xliv List of Figures
may be overactivated with a resultant abducting

nystagmus. Because the descending convergence
pathways that lead to bilateral MR contraction are
unaffected by a (more caudal) MLF lesion, conver-
gence may overcome the adduction paresis of the
INO, which would not occur with a MR palsy due to
a third nerve palsy. Note that the right MLF also
contains utriculo-ocular motor and vertical (anterior
and posterior) semicircular canal pathways that
originate in the left labyrinth (these pathways
decussate at the pontomedullary junction). For
comparison, a patient with a left horizontal gaze
palsy (due to multiple sclerosis) is included on the
right. Note that the interneurons from the left sixth
nucleus to the right MR subnucleus are still affected
(but in the left sixth nucleus itself, not the right
MLF), causing an adduction deficit in the right eye
(just like the patient with right INO, which can also
be overcome by adduction). However, because the
fibers that would normally activate the left LR are
also affected, the patient cannot abduct the left eye.
This constellation of findings is known as a (left)
horizontal gaze palsy�� 155
Fig. 4.16 Horizontal gaze palsy due to multiple sclerosis
(MS): This patient had a known history of MS with a
previous attack of optic neuritis OD (central scotoma
seen in the Humphrey visual field top right) and
demyelinating periventricular white matter lesions
(top left images) seen on MRI. She woke up with
horizontal diplopia and the inability to move the eyes
to the left. On exam, she had a left horizontal gaze
palsy: (1) left horizontal gaze palsy (severe abduc-
tion paresis OS, yellow asterisk, and adduction
paresis OD, white asterisk) due to left sixth nucleus
injury (which would normally activate left lateral
rectus directly as well as right medial rectus via
interneurons travelling through the right medial
longitudinal fasciculus, MLF); (2) normal right
List of Figures xlv
horizontal gaze; and (3) normal adduction OD with

convergence (bottom photo). Because the conver-
gence signals descend from supratentorial regions to
synapse on the medial rectus subnuclei in the
midbrain, adduction deficits due to lesions involving
the MLF and/or sixth nucleus may be overcome by
having the patient converge�� 157
Fig. 4.17 Eight-and-a-half syndrome due to dorsal pontine
tuberculoma: This patient had a mild right lower
motor neuron facial palsy (demonstrated in the
photos as a slightly widened right palpebral fissure,
black double-sided arrow) due to right seventh
fascicle injury. She also had a right one-and-a-half
syndrome: (1) right horizontal gaze palsy (severe
abduction paresis OD unable to cross the midline,
gray asterisk, and milder adduction paresis OS, white
asterisk) due to right sixth nucleus injury, (2) right
internuclear ophthalmoplegia (INO, adduction
paresis OD, yellow asterisk) due to right medial
longitudinal fasciculus (MLF) injury. There was
improved adduction OU with convergence. The
combination of right seventh NP + right one-and-a-
half syndrome is sometimes referred to as the
eight-and-a-half syndrome, and is highly localizing
to the region of the right facial colliculus/dorsal pons
(region within red dashed circle). In fact, the patient
was found to have a dorsal pontine ring-enhancing
lesion with surrounding vasogenic edema, which was
diagnosed as a tuberculoma. This patient was seen
acutely, but given the proximity of the descending
central tegmental tract (CTT, a part of Mollaret’s
triangle), patients with dorsal pontine pathology may
develop oculopalatal tremor weeks or months
following the initial injury. MCP middle cerebellar
peduncle, VI cranial nerve 6, VII cranial nerve 7, VIII
cranial nerve 8�� 158
Fig. 4.18 Vascular distribution and anatomy (including
sixth, seventh, eighth nerves, MLF) of the pons: In
xlvi List of Figures
this axial section of the pons, the proximity of the

seventh and eighth fascicles can be appreciated. A
lateral inferior pontine syndrome (anterior inferior
cerebellar artery, AICA territory), which could
involve both of these fascicles, can cause acute
prolonged vertigo accompanied by an abnormal
ipsilateral horizontal head impulse test (HIT, fascicle
of CN8) and ipsilateral lower motor neuron facial
palsy (fascicle of CN7). Although a “central” acute
vestibular syndrome typically has a normal HIT,
exceptions exist where an abnormal HIT can be due
to a stroke. Commonly, an abnormal HIT can be seen
with lesions affecting the root entry zone of CN8, or
those involving the vestibular nucleus or with
labyrinthine ischemia (AICA territory). A lesion
involving the middle cerebellar peduncle (MCP)
itself can also result in acute prolonged vertigo, but if
the fascicle of CN8 is spared, HIT will be normal. A
dorsal midline lesion can cause unilateral or bilateral
internuclear ophthalmoplegia (INO) due to medial
longitudinal fasciculus injury (MLF, usually stroke
or multiple sclerosis). Dorsal pontine injury can also
cause a horizontal gaze palsy (sixth nucleus) or a
gaze palsy + INO, causing a one-and-a-half syn-
drome (+/− seventh NP). Finally, the central tegmen-
tal tract (CTT) is in this vicinity as well, making
oculopalatal tremor a finding to look for months after
suffering a pontine lesion (e.g., hemorrhagic caver-
noma). VI cranial nerve 6, VII cranial nerve 7, VIII
cranial nerve 8�� 159
Fig. 4.19 Ocular motility and alignment findings in a left
sixth nerve palsy: This patient (with hyperten-
sion and diabetes) suffered a microvascular left
sixth NP causing a complete abduction paresis OS
(lateral rectus, LR, white asterisk) with an
esotropia greater in left gaze�� 160
Fig. 4.20 Central anatomy of the oculomotor nerve and
characteristic features of a nuclear third NP: This
List of Figures xlvii
patient has a complete left third NP (severe left

ptosis, mydriatic unreactive pupil OS, left medial,
superior, and inferior rectus palsies), which could
either result from a central or peripheral left third
NP. However, she also had a right superior rectus
(SR) palsy as well as mild ptosis OD. Bilateral
upgaze paresis can be explained by a left nuclear
third NP due to the fact that the (1) left SR subnu-
cleus is injured (left midbrain hemorrhage in the
setting of a familial multiple cavernous malformation
syndrome in this case) causing a right SR palsy due
to the decussation of these fibers, and (2) fibers that
originated in the right SR subnucleus and then
decussated to join the left third nerve are also
damaged, causing a left SR palsy. Finally, the central
caudal nucleus (CCN), a midline structure that
innervates bilateral levator palpebrae muscles, can
also be partially injured by with a unilateral third
nucleus lesion, causing ipsilateral greater than
contralateral ptosis, as seen in this case. Given the
orientation of the various fibers that make up the
fascicle of the third nerve (seen in the figure above
from medial to lateral), certain patterns of muscle
and/or pupil involvement can have additional
localizing value, although involvement or sparing
can be variable, making this anatomy less clinically
useful. P pupil, IR inferior rectus, LP levator
palpebrae, MR medial rectus, SR superior rectus,
IO inferior oblique�� 165
Fig. 4.21 The course of the third nerve: The third nucleus
lies at the ventral border of the periaqueductal gray
matter, at the level of the superior colliculus. In
between the two nuclei is the midline central caudal
nucleus (CCN), which innervates bilateral levator
palpebrae muscles (explaining how a unilateral
nuclear third can cause bilateral ptosis). The third
nerve fascicle (which contains fibers responsible the
pupillary sphincter [P], inferior rectus [IR], levator
xlviii List of Figures
palpebrae [LP], medial rectus [MR], superior rectus

[SR], and inferior oblique [IO] are located medial to
lateral) travels anteriorly through the tegmentum, the
red nucleus, the substantia nigra, and finally exits the
midbrain medially from the cerebral peduncles. The
peripheral portion of the third nerve courses between
the superior cerebellar and posterior cerebral arteries
and then passes the posterior communicating artery
(PCOM aneurysm causes compression here) and the
temporal lobe uncus (uncal herniation can cause
compression here), then above the petroclinoid
(Gruber’s) ligament (while the sixth nerve travels
under) and into the cavernous sinus where it is
located laterally. The separation into superior (SR,
LP) and inferior (P and ciliary body, MR, IR, IO)
divisions occurs in the anterior sinus, and these
branches then travel through the superior orbital
fissure to enter the orbit, passing through the annulus
of Zinn before innervating their respective muscles.
(Castro O, Johnson LN, Mamourian AC. Isolated
inferior oblique paresis from brain-stem infarction.
Perspective on oculomotor fascicular organization in
the ventral midbrain tegmentum. Arch
Neurol. 1990;47(2):235–7)�� 166
third nerve) of the rostral midbrain: In this axial
section of the midbrain at the level of the superior
colliculus, the paired third nuclei are located
ventral to the periaqueductal grey, and the midline
central caudal nucleus (CCN) is located in
between. PCA posterior cerebral artery, SCA
superior cerebellar artery�� 167
Fig. 4.23 Ocular motility and exam findings in a left
fourth NP: The top left photos are from a patient with
left hypertropia who had a Parks–Bielschowsky
three-step test consistent with a left fourth NP: (1) left
hypertropia (LHT), (2) LHT increased in contralateral
(right) gaze, and (3) LHT increased in ipsilateral (left)
List of Figures xlix
head tilt. He had additional features of a congenital

fourth NP including, (1) significant ipsilateral (left)
inferior oblique overaction in right gaze (white arrow
showing the upward deviation of the left eye in
adduction), (2) large vertical fusional amplitude (e.g.,
able to fuse a large LHT of at least 15 prism diopters,
which is why his fourth nerve palsy was asymptom-
atic), and (3) longstanding contralateral (right)
compensatory head tilt (not seen in these images, but
apparent in old photos dating back to childhood). The
patient in the bottom photo also has a left fourth NP,
with an apparent depression deficit in adduction OS
(asterisks) due to left superior oblique (SO) paresis
(secondary action of the SO is depression). Evaluation
of fundus torsion can be very helpful in differentiating
a left fourth NP from a skew deviation (either could
cause a LHT) in that the hypertropic eye will be
excycloducted in a fourth nerve palsy (owing to the
primary action of the SO which is incycloduction).
Compare this to the incycloducted hypertropic eye in a
skew deviation, which will be accompanied by
excycloduction of the hypotropic eye (both eyes rotate
in the same direction, which is known as an ocular
counterroll)�� 168
Fig. 4.24 Central anatomy of the trochlear nerve and
characteristic features of a nuclear fourth NP:
This patient suffered a hemorrhage of the left caudal
midbrain causing a right fourth NP. This is due to the
fact that the left fourth nerve originates in the left
dorsal midbrain, exits dorsally and decussates to the
right side where it then wraps around the brainstem
to eventually innervate the right superior oblique
muscle. A (right) “central” fourth NP will often have
associated neuro-ophthalmic features including, (1)
(left) internuclear ophthalmoplegia from (left) medial
longitudinal fasciculus (MLF) injury, (2) (left)
Horner’s syndrome from (left) oculosympathetic
l List of Figures
tract injury, (3) ipsi- or contralateral relative afferent

pupillary defect (without involvement of acuity, color
or field) due to injury to the brachium of the superior
colliculus, or neurologic signs including (4) (left)
hemi-ataxia from (left) superior cerebellar
peduncle/brachium conjunctivum injury�� 169
Fig. 4.25 The course of the fourth nerve: The fourth
nucleus lies at the ventral border of the
periaqueductal gray matter, at the level of the
inferior colliculus. The fascicles exit the nucleus
dorsally and decussate at the anterior medullary
velum (anterior floor of the fourth ventricle), and
then exit the brainstem dorsally. The peripheral
portion of the fourth nerve (left fourth nerve origi-
nated in the right fourth nucleus and vice versa) runs
laterally around the upper pons and then passes
between the superior cerebellar and posterior
cerebral arteries before reaching the prepontine
cistern and then the cavernous sinus where it is
located laterally. The fourth nerve travels through the
superior orbital fissure and continues above the annu-
lus of Zinn to then innervate the superior oblique
muscle�� 170
fourth nerve) of the caudal midbrain: In this axial
section of the midbrain at the level of the inferior
colliculus, the fourth nuclei are located ventral to the
periaqueductal grey, dorsal to the medial longitudinal
fasciculus (MLF) and medial to the oculosympa-
thetic tract. Fascicles exit the nucleus dorsally and
decussate at the anterior medullary velum before
exiting the midbrain dorsally on the contralateral
side. PCA posterior cerebral artery, SCA superior
cerebellar artery�� 171
Fig. 4.27 Brainstem structures involved in normal ocular
motor function: This is a sagittal representation of
the brainstem demonstrating the relative locations of
the ocular motor nuclei (III [including the midline
List of Figures li
central caudal nucleus or CCN], IV, VI), neural

integrators (INC for vertical/torsional gaze holding,
nucleus prepositus hypoglossi [NPH] for horizontal
gaze holding), and saccadic burst neurons (riMLF for
vertical/torsional, paramedian pontine reticular
formation [PPRF] for horizontal). The posterior com-
missure (PC) plays a role in upward gaze as well,
explaining the characteristic upgaze palsy in a
dorsal midbrain (Parinaud’s) syndrome�� 175
Fig. 4.28 Common lesions and localizations for
characteristic midbrain ocular motor syndromes
as seen on MRI: (a) Dorsal midbrain (Parinaud’s)
syndrome—complete upgaze palsy (among other
findings) typically associated with extrinsic compres-
sion of the dorsal midbrain (dashed line), in this case
due to a glioblastoma multiforme of the pineal gland
seen on noncontrast sagittal T1 (arrow). (b) Rostral
interstitial medial longitudinal fasciculus (riMLF)
syndrome—complete downward saccadic palsy (and
very slow upward saccades) typically associated with
an intrinsic lesion, in this case bilateral riMLF
infarcts (arrows) from artery of Percheron ischemia
seen on axial MR-diffusion-weighted imaging
(DWI). (c) (Left) interstitial nucleus of Cajal (INC)
syndrome—complete contraversive (rightward)
ocular tilt reaction (i.e., right head tilt, left hypertro-
pia due to skew deviation, ocular counter roll with
top poles of both eyes rotated toward the right ear)
and spontaneous torsional nystagmus (top poles
beating toward the left ear), in this case due to a left
INC infarct (arrow) seen on axial MR-DWI. (d)
Patients with progressive supranuclear palsy (PSP)
often have significant midbrain atrophy, a feature that
is not surprising based on the vertical saccadic and
vertical gaze palsies that are so typical of this
disorder. With axial (T1 in this patient) MRI views,
the tegmentum atrophy (arrow) can create the
“Mickey Mouse” sign. With sagittal MRI views, the
lii List of Figures
midbrain atrophy may give the appearance of a

hummingbird (where the pons is the body, midbrain
is the head)�� 176
Fig. 4.29 Dorsal midbrain (Parinaud’s) syndrome due to
mesodiencephalic hemorrhage: This patient
demonstrated the main clinical features of Parinaud’s
syndrome including, (1) eyelid retraction (Collier’s
sign, note how much superior sclera is visible in the
photo), (2) pupillary light-near dissociation (no
constriction to light, brisk constriction to a near
stimulus), (3) upgaze palsy, (4) convergence-retrac-
tion nystagmus during attempted upgaze. The CT on
the right demonstrates the rostral midbrain location
of the hemorrhage. (Video and image created with
the assistance of Drs. Amir Kheradmand and
Jiaying Zhang)�� 177
Fig. 4.30 Cerebellar structures involved in normal vestibu-
lar and ocular motor function: Seen here is in
inferior view of the flocculus, paraflocculus (tonsil),
nodulus, and uvula, which together make up the
vestibulocerebellum. The fastigial nucleus (FN) and
ocular motor vermis play important roles in saccadic
accuracy. MCP middle cerebellar peduncle, SCP
superior cerebellar peduncle, ICP inferior cerebellar
peduncle. (Modified and redrawn with permission
from: Shemesh and Zee [12])�� 183
Fig. 4.31 Structure and function of the vestibulocerebel-
lum: Think of these four structures as two func-
tional units: (1) flocculus/paraflocculus (tonsil),
e.g., optimization of gaze-holding, smooth pursuit,
modulate the high frequency vestibulo-ocular
reflex, inhibit anterior semicircular canal pathways,
and (2) nodulus/uvula, e.g., important role in
velocity storage. The posterior inferior cerebellar
artery (PICA) supplies the paraflocculus, nodulus,
and uvula (labeled on T2 axial images), while the
anterior inferior cerebellar artery (AICA)
List of Figures liii
supplies the flocculus (labeled on a T1 axial

image)�� 185
Fig. 5.1 Is it nystagmus or a saccadic intrusion/oscilla-
tion? Nystagmus can be classified into pendular and
jerk waveforms (which are typically generated with
video-oculography, video-nystagmography, or
electro-nystagmography), where both are generated
by a slow, pathologic phase. In pendular nystagmus,
the characteristic appearance is the result of back-to-
back slow phases. Jerk nystagmus can have constant,
increasing or decreasing slow phase velocity:
vestibular nystagmus has a linear slow phase velocity
due to vestibulo-ocular reflex imbalance; gaze-
evoked nystagmus has a decreasing slow phase
velocity due to a leaky neural integrator (i.e., a
problem with the gaze-holding machinery); congeni-
tal nystagmus and certain posterior fossa disorders
can cause an increasing slow phase velocity due to
an unstable neural integrator. In jerk nystagmus, the
slow (pathologic) phase is followed by the fast
(named) phase. Nystagmus should be distinguished
from oscillations and intrusions, particularly given
disparate localizations and etiologies. These include
saccadic intrusions (e.g., square wave jerks) and
saccadic oscillations (e.g., ocular flutter and opsoclo-
nus). Saccadic intrusions consist of saccades with an
intersaccadic interval (i.e., a brief pause between
movements), while saccadic oscillations lack this
interval. Square wave jerks are small saccades that
move the line of sight away from the target and then
return to fixation 200 ms later, and the name derives
from the fact that the waveforms have a square-like
appearance. Macrosaccadic oscillations are saccades
that take the eye off target and oscillate the line of
sight about the object of regard—these movements
straddle fixation, and are often seen in association
with hypermetric saccades. Ocular flutter is confined
to the horizontal vector whereas opsoclonus has
liv List of Figures
horizontal, vertical and torsional components, and

occurs in bursts; however, the differential diagnosis,
implications, and treatment of flutter and opsoclonus
are essentially the same�� 193
Fig. 5.2 Common lesions and localizations for nystagmus
as seen on MRI: (a) Upbeat nystagmus (UBN)—
typically associated with midline brainstem lesions,
especially involving the dorsal medulla (nucleus of
Roller, nucleus intercalatus). Seen here are bilateral
dorsal medullary (axial) FLAIR hyperintensities
(arrow) in a patient with pure UBN due to multiple
sclerosis. (b) Torsional nystagmus—this is usually
the result of a brainstem lesion affecting the central
utriculo-ocular motor or vertical semicircular canal
pathways (pure torsional nystagmus with symmetric
injury to the anterior and posterior pathways, and
vertical-torsional nystagmus typically results from
asymmetric injury). This patient suffered a right
interstitial nucleus of Cajal stroke seen on axial MR
diffusion-weighted imaging (DWI, arrow) causing
torsional nystagmus with the top poles of both eyes
beating toward the right ear (accompanied by a
contraversive ocular tilt reaction, which is another
common feature). (c) Downbeat (DBN) and gaze-
evoked nystagmus (GEN)—while a discrete floccu-
lus/paraflocculus lesion may be seen, diffuse
cerebellar atrophy (on sagittal T1) is commonly seen
as in this patient with a cerebellar degeneration
causing DBN, GEN, saccadic pursuit and limb/gait
ataxia. (d) Oculopalatal tremor (OPT)—a dorsal
pontine hemorrhage involving the descending
inhibitory central tegmental tract is a common cause
of OPT, seen here as a hypointensity in the dorsal
pons (arrow) on axial gradient echo sequence (note
that inferior olivary hypertrophy/hyperintensity is
commonly seen on FLAIR/T2, but this represents
physiologic changes that have occurred within
Mollaret’s triangle rather than representing the insult
List of Figures lv
itself - see Fig. 5.7). (e) Bruns nystagmus—seeing

vestibular nystagmus in left gaze and gaze-evoked
nystagmus in right gaze should alert the clinician to a
large right cerebellopontine angle tumor, such as a
vestibular schwannoma (axial T1 contrast, arrow,
image courtesy of Dr. Jeffrey Sharon). (f) Periodic
alternating nystagmus (PAN)—this localizes well to
the nodulus (arrow) and ventral uvula, as seen on this
axial diffusion-weighted image in a patient with PAN
due to an acute stroke. Central paroxysmal positional
nystagmus (CPPN)—commonly downbeat in straight
head hanging or prone and apogeotropic in Dix-
Hallpike and supine roll—is commonly
seen with nodulus lesions as well�� 202
Fig. 5.3 Disorders and localizations to consider in
patients presenting with chronic imbalance and
downbeat nystagmus (DBN): All patients with
evidence of cerebellar dysfunction require an MRI of
the brain, preferably with contrast and susceptibility
weighted imaging (SWI). (a) In this patient with
superficial siderosis (SS), SWI demonstrates
hypointense signal (arrows) involving the brainstem,
cerebellum, as well as the vestibulocochlear nerves
(this patient also had bilateral vestibular and hearing
loss), that is indicative of hemosiderin deposition
lining these structures. The source of the hemosid-
erin could not be elucidated in his case. (b) In this
patient with multiple system atrophy (MSA), there
was mild DBN (in addition to gaze-evoked nystag-
mus) when upright and a significant increase in DBN
when supine. On exam, there were parkinsonian
symptoms including bradykinesia and rigidity, and
axial T2 demonstrated pontine atrophy with a
cross-shaped (arrows) hyperintensity within the pons
(an early “hot cross bun sign”). The bottom image
demonstrates a more prominent “hot cross bun sign”
(hyperintense on FLAIR) in advanced MSA (Image
courtesy of Dr. David Zee). (c) A young woman
lvi List of Figures
presented with occipital headaches (worse with

coughing), DBN and imbalance, and MRI demon-
strated a Chiari malformation causing tonsillar
(paraflocculus) herniation, with a peg-like appear-
ance of the tonsils (arrow). Her severe imbalance was
due to both cerebellopathy and a myelopathy
(hyperreflexia, ankle clonus, + Babinski)
from an associated syrinx�� 207
Fig. 5.4 MRI in Wernicke’s encephalopathy: These two
images demonstrate FLAIR hyperintensities
involving the periventricular region anterior to the
fourth ventricle (white arrow), and periaqueductal
area (dashed arrow), which are common MRI
findings in Wernicke’s. Also look for lesions
affecting the mammillary bodies and bilateral
thalami�� 211
Fig. 5.5 Vascular distribution and anatomy relevant
to the medial medullary syndrome: This axial
section of the medulla highlights those structures
that, when damaged, are often responsible for
spontaneous upbeat nystagmus (UBN). The nucleus
of Roller and nucleus intercalatus normally have an
inhibitory influence over the cerebellar flocculus, and
when there is a lesion of Roller/intercalatus, there is
less inhibition of the flocculus. The Purkinje cells of
the flocculus normally inhibit the antigravity or
upward anterior semicircular canal (SCC) pathways.
With a lesion of Roller/intercalatus, the flocculus
will over-inhibit the anterior SCC pathways, causing
relative over-activation of the posterior SCC path-
ways which will generate a downward slow phase.
The fast/position-reset phase will be upward, and
these alternating slow (downward) and fast (upward)
phases are responsible for UBN�� 212
Fig. 5.6 The cyclovertical extraocular muscles and their
semicircular canal innervation: When stimulated,
each of the 6 angular acceleration detecting semicir-
cular canals (3 on the right and 3 on the left)
List of Figures lvii
responds with a conjugate eye movement, with the

vector(s) indicated above. PC, posterior canal; HC,
horizontal (also known as lateral) canal; AC=anterior
(also known as superior) canal. (1) When the right
AC (red) is stimulated as in exposure to a loud noise
in superior (or anterior) canal dehiscence syndrome,
excitatory slow phases that are upward and torsional
(towards left ear) are generated. This is due to
contraction of the right superior rectus (up and
incycloduction OD) and left inferior oblique (up and
excycloduction OS) muscles (both also in red). Fast
phases are in the opposite direction—downbeat and
torsional toward the right (ipsilateral) ear—are then
seen clinically. (2) When the right HC (green) is
stimulated as in a rapid rightward head turn, the
vestibulo-ocular reflex (VOR) results in a conjugate
eye movement to the left via contraction of the right
medial rectus and left lateral rectus muscles (also in
green). (3) When the right PC (blue) is stimulated as
in right PC benign paroxysmal positional vertigo
(BPPV), excitatory slow phases that are downward
and torsional (towards left ear) are generated. This is
due to contraction of the right superior oblique
(down and incycloduction OD) and left inferior
rectus (down and excycloduction OS) muscles (both
also in blue). Fast phases are in the opposite direc-
tion - upbeat and torsional towards the right (ipsilat-
eral) ear—are then seen clinically�� 215
Fig. 5.7 The Guillain-Mollaret triangle, and its role in
oculopalatal tremor (OPT): Also referred to as the
dentato-olivary pathway, reflecting the three points
of this imaginary triangle: (1) dentate nucleus, (2)
red nucleus, and (3) inferior olivary nucleus. The
olive sends decussating climbing fibers through the
contralateral inferior cerebellar peduncle that travel
from the Purkinje cells of the cerebellar cortex to the
dentate nucleus; the dentate sends decussating fibers
(via the superior cerebellar peduncle) that wrap
lviii List of Figures
around the contralateral red nucleus; these fibers

descend from red nucleus to the ipsilateral inferior
olive via the central tegmental tract (CTT). Injury to
any of these structures may result in oculopalatal
tremor (OPT). Since the CTT normally inhibits the
ipsilateral inferior olive, damage to the CTT results
in decreased inhibition of the ipsilateral olive
resulting from transsynaptic degeneration. Hypertro-
phic inferior olivary degeneration occurs as swollen
and vacuolated neurons come into contact with each
other and corresponds to MRI T2/FLAIR hyperinten-
sity (on the right)�� 218
Fig. 6.1 Audiometry: what does it look like and how
do I interpret it? An audiogram measures a patient’s
auditory threshold responses with pure-tone stimuli
across a range of sound frequencies that are impor-
tant for human communication, typically 250 Hz –
8000 Hz. The threshold is the sound intensity level at
which an individual detects the tone 50% of the time.
Hearing loss severity is referenced to a healthy
population (a). An audiologist generally assesses
both air-conducted (circles) and bone-conducted
sound (brackets). Both results are graphed with
frequency on the x-axis, measured in Hertz (Hz), and
the threshold for sound intensity on the y-axis,
measured in decibels hearing level (dB HL). (b)
Sensorineural hearing loss can be differentiated from
(c) conductive hearing loss by the presence of an
air-bone gap in which a d ifference exists between
air-conduction and bone-conduction thresholds.
Some patients with both conductive and sensorineu-
ral components of hearing loss in the same ear are
said to have mixed hearing loss (d). In patients with
age-related hearing loss (b), an audiogram typically
displays symmetric hearing loss primarily at higher
frequencies between 2000 and 8000 Hz. Only right
ear data are graphed for simplicity. (Courtesy of Drs.
Carrie Nieman and Bryan Ward) [17]�� 241
List of Figures lix
Fig. 6.2 What is the cause of my patient’s hearing loss?

This is a flowsheet that can be used to differentiate
multiple causes of hearing loss. The onset and
chronicity of hearing loss is a critical starting point
in understanding whether urgent action is needed,
such as in the setting of suspected stroke or sudden
sensorineural hearing loss. For hearing loss that has
been present for months to years, differentiating
whether the loss is primarily symmetric or asymmet-
ric is another point that should prompt consideration
of referral and further evaluation. Regardless of the
underlying cause of hearing loss, including age-
related hearing loss, assessment and interventions
can and should be offered. (Courtesy of Drs. Carrie
Nieman and Bryan Ward) [17]�� 243
Fig. 6.3 Vascular supply of the labyrinth: In the HINTS
“Plus” examination (Head Impulse, Nystagmus,
Test of Skew, “Plus” is a bedside test of auditory
function using finger rub), loss of hearing is seen as a
red flag or dangerous finding in the acute vestibular
syndrome. As seen above, the basilar artery supplies
the anterior inferior cerebellar artery, which supplies
the internal auditory artery so that an acute vestibu-
lopathy accompanied by partial or complete
sensorineural hearing loss can be not only
“peripheral” but also dangerous (e.g., due to
labyrinthine stroke)�� 244
Fig. 6.4 Innervation of the labyrinth: When a patient
experiences a bout of vestibular neuritis, typically the
superior division or the superior and inferior divi-
sions are involved and rarely is the inferior division
involved in isolation. Knowledge of the specific
innervation patterns of the semicircular canals and
otoliths allows for accurate localization and insight
into etiology. The superior division innervates the
anterior and horizontal canals, utricle, as well as
some innervation to the saccule. The inferior division
innervates the posterior canal and provides most of
lx List of Figures
the saccular innervation. Cervical vestibular evoked

myogenic potentials (c-VEMPs) can help to eluci-
date inferior division involvement with damage to
the saccule, while ocular-VEMPs can help to
elucidate superior division involvement with damage
to the utricle. As another example, if the horizontal
(HC) and anterior canals (AC) are the only canals
affected in a patient with the acute vestibular
syndrome, the localization is usually vestibular
neuritis with involvement of the superior division of
the vestibular nerve. However, if the HC and
posterior canals (PC) are the only canals affected,
since these canals only synapse in the medial
vestibular nucleus (MVN, whereas the AC sends
afferents to both MVN and superior vestibular
nucleus), the possibility of a brainstem disorder
should be considered (e.g., ischemia of the vestibular
nucleus). While a HIT performed in the plane of the
HC can easily be interpreted at the bedside, assess-
ment in the planes of the AC and
PC is technically challenging. Therefore, the
function of the AC and PC is best evaluated by
the video head impulse test; U, utricle;
S, saccule; C, cochlea�� 245
Fig. 6.5 Anatomy of the labyrinth: The labyrinth
consists of the (1) semicircular canals (SCC)—angu-
lar acceleration detectors (posterior, horizontal, and
anterior); (2) otoliths—linear acceleration detectors
(utricle and saccule); (3) cochlea—auditory function.
The dense otoconia, which are contained mainly
within the utricle, may spontaneously slough off with
aging or due to head trauma, and if they enter one of
the SCCs (most to least commonly affected—
posterior, horizontal, and anterior), benign
paroxysmal positional vertigo (BPPV) will result.
(Figure reproduced with permission from
Gold et al. [10])�� 257
List of Figures lxi
Fig. 6.6 Anatomy of the semicircular canal (SCC)

and directions of excitation: Left: Each SCC
contains an area of outpouching called the ampulla,
which is where the cupula is located. When the
cupula is deflected by the flow of endolymph (due to
a head rotation or otoconia moving with gravity) in
an excitatory direction, the vestibular nerve firing
rate will increase. If the cupula is deflected in the
opposite (inhibitory) direction, the vestibular nerve
firing rate will decrease. Right: For example, when
the head is turned quickly to the right, there will be
right horizontal canal (HC) excitation due to
ampullopetal (toward the ampulla) endolymph flow
with simultaneous left HC inhibition due to
ampullofugal (away from the ampulla) endolymph
flow. The combination of right HC excitation and left
HC inhibition optimizes the horizontal vestibulo-
ocular reflex (VOR), by causing contraction of the
right medial rectus and left lateral rectus (i.e.,
efferent portion of the VOR causing a conjugate
leftward movement) and simultaneous relaxation of
right lateral rectus and left medial rectus. While the
ampullopetal direction is excitatory for the HC, the
ampullofugal direction is excitatory for the anterior
(AC) and posterior canals (PC). For example,
otoconia in PC-benign paroxysmal positional vertigo
(BPPV) almost always flow in an (excitatory)
ampullofugal direction, causing a characteristic
robust upbeat-torsional (toward the lowermost,
affected ear) nystagmus. However, when the patient
is brought from the Dix-Hallpike back to a seated
position, the otoconia will flow in the opposite
(inhibitory or ampullopetal) direction, causing a
weaker downbeat-torsional (toward the unaffected
ear) nystagmus. (Figure on the left reproduced with
permission from Gold et al. [10])�� 258
Fig. 6.7 Canalith repositioning (Epley) maneuver for
right PC BPPV: (a) First the patient is placed in the
lxii List of Figures
long-sitting position. (b) The head is rotated 45

degrees to the right. (c) Then the patient is lowered
quickly into the supine position with the head in
20-30 degrees of cervical extension. (d) Then the
patient’s head is 90 degrees to the left. (e) The
patient is rolled into a left-side lying position with
the head maintained in 45 degrees of rotation to the
left so that the head is facing the floor. (f) Then the
patient sits up slowly with the head still facing down
toward the floor and rotated 45 degrees to the left. (g)
Slowly, the head is moved back to a neutral position.
Note that each position should be maintained for at
least 30-60 seconds or until nystagmus and/or vertigo
cease (Figure reproduced with permission from Gold
DR, Morris L, Kheradmand A, Schubert MC.
Repositioning maneuvers for benign paroxysmal
positional vertigo. Curr Treat Options Neurol.
2014;16(8):307.)�� 261
Fig. 6.8 Semont maneuver for right PC-BPPV:
(a) First the patient sits at the edge of the table.
(b) The head is turned 45 degrees to the left. (c) The
patient is rapidly brought into a right side-lying
position, which is maintained for 1 minute. (d)
Without stopping in the center, the patient is quickly
moved from right to left side-lying positions within
1.5 seconds, with initial 45 degrees of leftward
rotation maintained throughout. This position is
maintained for 1 minute. (e) The patient is slowly
brought back to a seated position with the leftward
head position maintained. (f) The head is slowly
moved back to neutral. (Figure reproduced with
permission from Gold DR, Morris L, Kheradmand A,
Schubert MC. Repositioning maneuvers for benign
paroxysmal positional vertigo. Curr Treat
Options Neurol. 2014;16(8):307.)�� 262
Fig. 6.9 BBQ roll for right geotropic HC-BPPV:
(a) The patient begins in the long-sitting position.
List of Figures lxiii
(b) The patient is brought into a supine position with

the head elevated 30 degrees. (c) The patient’s head
(or whole body if there’s a poor cervical range of
motion) should be rotated 90 degrees to the right side
and maintained for 30 seconds or until the nystagmus
and vertigo resolve completely. (d) The head is
rotated back to neutral. (e) The head is moved 90
degrees to the left side. (f) The patient is brought into
a prone position. (g) The head (body) continues to
rotate 90 degrees so that the right ear is down toward
the floor. (h) The head is rotated another 90 degrees
back to neutral and the patient is brought back into
the long-sitting position. Each position is maintained
for 30 seconds or until the nystagmus and vertigo
completely resolve. (Figure reproduced with
permission from Gold DR, Morris L, Kheradmand A,
Schubert MC. Repositioning maneuvers for
benign paroxysmal positional vertigo. Curr
Treat Options Neurol. 2014;16(8):307.)�� 265
Fig. 6.10 Gufoni maneuver for right apogeotropic
HC-BPPV or left geotropic HC-BPPV: (a) The
patient starts in a seated position. (b) The patient is
moved quickly to the unaffected side (side of weaker
nystagmus – e.g., to the right in right apogeotropic or
in left geotropic HC-BPPV). The head remains in a
neutral spine orientation, and this position is held for
about 1 minute. (c) Then, the head is moved 45
degrees towards the ceiling (for apogeotropic) or 45
degrees toward the floor (for geotropic) and is held
for 2 minutes. (d) The patient is guided back to a
seated position. (Figure reproduced with permission
from Gold DR, Morris L, Kheradmand A, Schubert
MC. Repositioning maneuvers for benign paroxys-
mal positional vertigo. Curr Treat Options Neurol.
2014;16(8):307.)�� 266
Fig. 6.11 Differential diagnosis of the episodic vestibular
syndrome: (a) Superior canal dehiscence syndrome
lxiv List of Figures
(SCDS), in addition to the typical clinical features, a

dehiscent superior (anterior) semicircular canal
should also be visualized on CT (yellow arrows) as
seen in this Dyna CT (flat panel CT with reconstruc-
tion in the plane of the left superior canal—note that
this can be an incidental finding [image courtesy of
Dr. John Carey]); (b) Vestibular paroxysmia (VP), in
addition to the typical clinical features, neurovascu-
lar compression involving the eighth cranial nerve is
usually identified, especially on heavily T2-weighted,
high-resolution imaging (arrow points to a
dolichoectatic basilar artery that was in contact with
the left eighth nerve—note that this can be incidental
finding); (c) Transient ischemic attack (TIA)—urgent
evaluation is indicated when a vestibular TIA is
suspected to exclude high-grade posterior
circulation stenosis (e.g., due to dissection
or atherosclerosis)�� 271
Fig. 6.12 Video head impulse test demonstrating
bilateral vestibular loss: Bilateral vestibular loss is
a common cause of head movement-dependent
oscillopsia, and in these patients, evaluating the
vestibulo-ocular reflex (VOR) is essential. While the
bedside HIT is usually enough to make the diagnosis
of unilateral or bilateral vestibular loss, the video
HIT has advantages: 1) overt corrective saccades can
be identified (occurring after the head movement,
visible to the examiner at the bedside, black arrow),
2) covert corrective saccades can be identified
(occurring during the head movement, and can be
invisible at the bedside, black arrowhead), 3) a gain
can be calculated to quantify the VOR (gain = ratio
of eye movement velocity to head movement
velocity, where typically a value below 0.6-0.7 is
considered abnormal). In this case, the gains in the
planes of the left and right horizontal (lateral) canals
were 0.18 and 0.38, respectively, and consistent with
bilateral vestibular loss�� 296
List of Tables
Table 2.1 Help me now with anisocoria�� 6

Table 2.2 Help me now with ptosis�� 8
Table 2.3 Help me now with diplopia�� 10
Table 3.1 Help me now with acute onset persistent
vision loss�� 56
Table 3.2 Help me now with subacute to chronic
vision loss��60
Table 3.3 Common neuro-ophthalmic ancillary tests�� 69
Table 3.4 Help me now with transient vision loss�� 79
Table 4.1 My patient has ocular misalignment—where do
I start?�� 130
Table 5.1 Help me now with nystagmus & intrusions/
oscillations�� 195
Table 6.1 Common audiovestibular lab tests�� 234
Table 6.2 Help me now with acute onset prolonged
dizziness & vertigo�� 246
Table 6.3 Help me now with episodic
Table 6.4 Help me now with positional
Table 6.5 Help me now with chronic
lxv
List of Videos\Electronic
Supplemental Materials (ESM)
ESM 1.1 Maddox and red glass testing

ESM 2.1 Localization of ophthalmoplegia
Video 2.1 The complete triad of Horner’s syndrome: This
patient has the triad of Horner’s syndrome – ipsi-
lateral ptosis, miosis, and anhidrosis. She noticed
ptosis OD years prior, with clear evidence of a
Horner’s syndrome. Imaging of the oculosympa-
thetic tract was unrevealing. The patient also
mentioned that with exercise, the left side of her
face will sweat and turn red while the right side
won’t. She took a picture of herself following
vigorous exercise which demonstrates her right
facial anhidrosis and paleness, compared with
marked left facial flushing. https://collections.lib.
utah.edu/ark:/87278/s69k7kwh
Video 2.2 Aberrant regeneration of the 3rd nerve follow-
ing trauma: This is a 20-year-old woman who
suffered a traumatic brain injury and experienced
diplopia upon awakening from a coma several
weeks after the injury. She had a partial left 3rd
nerve palsy (adduction spared), and when she
looked to the right and down, her mildly ptotic lid
elevated. Aberrant regeneration of CN 3 occurs
mainly with trauma or with compressive lesions
(e.g., posterior communicating aneurysm, menin-
gioma). The elevation in right gaze is explained by
the fact that fibers that originally innervated the
lxvii
lxviii List of Videos\Electronic Supplemental Materials (ESM)
medial rectus get misrouted to the left levator

palpebrae, while the elevation in down gaze is
explained by the fact that fibers that originally
innervated the left inferior rectus get misrouted to
the left levator causing levator activation and lid
elevation. https://collections.lib.utah.edu/
ark:/87278/s6cc48cg
Video 2.3 Clinical features of a tonic pupil: This video
depicts the common features of a tonic pupil,
including poor pupil reactivity to light and better
constriction to a near stimulus, as well as a tonic
(slow) dilation of the affected pupil when looking
from near to distance. https://collections.lib.utah.
edu/ark:/87278/s61p390k
Video 2.4 Two causes of divergence insufficiency – ‘sag-
ging eye’ syndrome and cerebellar dysfunction:
This is a 70-year-old patient who was orthophoric
at near with a comitant esotropia at distance
without abduction paresis, consistent with diver-
gence insufficiency (DI). With age, patients may
develop an esodeviation greater at distance due to
‘sagging eye syndrome‘, thought to be due to
age-related orbital involutional changes that can
cause divergence issues due to lateral rectus-supe-
rior rectus band rupture or distention causing the
lateral rectus muscles to be at a mechanical
disadvantage. This patient has other features of this
syndrome including a prominent superior sulcus
and levator disinsertion with high lid creases. How-
ever, DI can also be seen with cerebellar disease
(ocular motor vermis and/or flocculus), and this
patient also had gaze-evoked with rebound
nystagmus, and saccadic smooth pursuit. Symp-
tomatically, she did well with base-out prisms
placed in her distance glasses. https://collections.
lib.utah.edu/ark:/87278/s6xh3pxk
Video 2.5 Cogan’s lid twitch, lid hopping, and enhanced
ptosis in myasthenia gravis: This is a 60-year-old
List of Videos\Electronic Supplemental Materials (ESM) lxix
woman with MG who displays typical eyelid signs

including Cogan’s lid twitch, lid hopping (appreci-
ated during horizontal smooth pursuit in this
patient), and enhanced ptosis (in accordance with
Hering’s law of equal innervation to the two
levator muscles). https://collections.lib.utah.edu/
ark:/87278/s64t9t1t
Video 2.6 Eyelid signs in Miller Fisher syndrome (MFS)
mimicking myasthenia gravis: This is a 50-year-
old woman who presented with imbalance and
diplopia that developed over three days following
two weeks of upper respiratory infection. Exami-
nation was remarkable for limb and gait ataxia,
absent deep tendon reflexes, ptosis OS, lid retrac-
tion OD (but with intermittent ptosis OD as well),
a Cogan’s lid twitch and enhanced ptosis, in
addition to sluggish pupils OU. There were
abduction > adduction and milder vertical motility
deficits OU, and given the constellation of sluggish
pupils, ataxia, areflexia and ptosis with ophthalmo-
paresis in the setting of the preceding respiratory
illness, MFS was suspected and anti-Gq1b
antibodies returned very elevated several days later.
Although there was ophthalmoparesis with a
Cogan’s lid twitch, fatigable and enhanced ptosis
(based on Herring’s law of equal innervation of
bilateral levator palpebrae muscles – these are
features that are highly suspicious for myasthenia
gravis), from an ocular standpoint, the sluggish
pupils should make the clinician think of MFS or
even botulism. This case also highlights the fact
that the Cogan’s lid twitch is not exclusively seen
with MG. In her case, there was also intermittent
lid retraction OD. Since she had ptosis mainly OS,
more levator tone was required to elevate the left
eyelid. However, given Herring’s law of equal
levator innervation, there was corresponding
increased levator tone on the right which resulted
lxx List of Videos\Electronic Supplemental Materials (ESM)
in an eyelid retraction. However, as she became

more fatigued throughout the exam, ptosis became
apparent OU. (Video and legend created with the
assistance of Drs. Roksolyana Tourkevich, William
Tsao, Jiaying Zhang, William Motley)
Video 2.7 The triad of Miller Fisher syndrome: This is a
young man who presented with ptosis, ophthal-
moplegia and gait imbalance several weeks after a
GI illness. MFS was diagnosed, IVIG therapy was
initiated, and anti-Gq1b antibodies came back
extremely elevated. The typical triad of MFS
includes ophthalmoplegia, ataxia, and hyporeflexia
which were all present in this case. https://
collections.lib.utah.edu/ark:/87278/s66m6w3z
ESM 3.1 Expanded acute onset persistent vision loss
differential
Video 3.1 Clinical features of a unilateral optic neuropa-
thy: This video depicts the common features of an
optic neuropathy, including relative afferent
pupillary defect (rAPD), with ipsilateral pallor and
loss of visual field due to a compressive menin-
gioma. https://collections.lib.utah.edu/ark:/87278/
s6m95jb6
Video 3.2 Parieto-occipital tumor causing loss of ipsile-
sional optokinetic nystagmus and contralesional
homonymous hemianopia: A normal optokinetic
nystagmus (OKN) response is seen with an
optokinetic drum that was directed contralesionally
(to the left), but OKN was poor when the drum was
directed ipsilesionally (to the right). The patient
had a right parieto-occipital anaplastic astrocy-
toma, which also caused a complete left homony-
mous hemianopia. (Video and legend created with
the assistance of Dr. Tony Brune). https://collec-
tions.lib.utah.edu/ark:/87278/s6h45w40
ESM 4.1 Midbrain structures relevant to normal eyelid
function
List of Videos\Electronic Supplemental Materials (ESM) lxxi
Video 4.1 Evaluating the range of eye movements: Assess

versions (both eyes viewing) and ductions (each
eye individually viewing), especially in patients
with diplopia or when a motility deficit is sus-
pected. Look for spontaneous nystagmus or
saccadic intrusions/oscillations in primary gaze
and gaze-evoked nystagmus in eccentric gaze.
https://collections.lib.utah.edu/ark:/87278/s6vt51rq
Video 4.2 Evaluating ocular alignment: Alternate cover test
allows for detection of the total deviation (eso, exo
or hyper) – i.e., phoria (misalignment with one eye
viewing) + tropia (misalignment with both eyes
viewing). Use the cover-uncover test to see what
component of the total deviation is due to a tropia.
Neurologic causes of diplopia including ocular
motor palsies and skew deviation will typically
cause a tropia, although the presence of a tropia
does not necessarily mean that the patient’s
strabismus is neurologic (e.g., an infantile esotro-
pia syndrome). https://collections.lib.utah.edu/
ark:/87278/s67400kp
Video 4.3 Evaluating convergence: The assessment of
convergence includes measuring alignment at near
versus distance, near point of convergence and con-
vergence amplitude. Near point of convergence is
assessed by bringing a fixation target toward the
bridge of the patient’s nose. The distance at which
binocular fixation is lost or diplopia is experienced
is recorded. Convergence amplitude is determined
by placing base out prisms of increasing power
over one eye while the patient views a near target.
The highest prism power before binocular fixation
is lost or diplopia is experienced is the convergence
amplitude. Although the specific diagnostic criteria
for convergence insufficiency may differ, typically
the diagnosis is made when: 1) the near point of
convergence is greater than 10 centimeters, 2) the
convergence amplitude is less than 15 prism
lxxii List of Videos\Electronic Supplemental Materials (ESM)
diopters, and 3) there is an exodeviation greater

than 10 PD at near, or the exodeviation at near is at
least four prism diopters greater than what is
recorded at distance. (Video and legend created
with the assistance of Dr. Tony Brune and Justin
Bosley) https://collections.lib.utah.edu/ark:/87278/
s6zd22m0
Video 4.4 Convergence insufficiency in progressive
supranuclear palsy: This is a 70-year-old woman
with progressive supranuclear palsy with com-
plaints of difficulty reading. Her husband noticed
that she would frequently close one eye when
attempting to read while she noticed that words
were not clear on the page, although this improved
by covering one eye. On her exam, she was
orthophoric at distance and had a symptomatic
(experienced diplopia) exotropia at near (>10
prism diopters). Additionally, her near point of
convergence was about 20 cm (normal is <10 cm),
and her convergence amplitude was 4 PD (base out
prism – normal is >15 PD). Convergence insuffi-
ciency is common following concussion/TBI or
with parkinsonism. Square wave jerks are common
in PSP, and hers are shown here as well. https://
collections.lib.utah.edu/ark:/87278/s6m07z61
Video 4.5 Evaluating saccades: The examiner should note:
conjugacy (a lag of the adducting eye may be seen
with an internuclear ophthalmoplegia); accuracy
(posterior fossa lesions commonly produce
saccadic dysmetria [overshooting or undershoot-
ing]); velocity (if slow, may suggest a lesion of the
burst neurons in the pons [paramedian pontine
reticular formation, PPRF – horizontally] or
midbrain [rostral interstitial medial longitudinal
fasciculus, riMLF – vertically]). https://collections.
lib.utah.edu/ark:/87278/s6md27q9
Video 4.6 Saccadic dysmetria and ipsipulsion in lateral
medullary (Wallenberg) syndrome: This patient
List of Videos\Electronic Supplemental Materials (ESM) lxxiii
suffered a right lateral medullary stroke, and

examination demonstrated saccadic hypermetria to
the right (ipsilesional), hypometria to the left
(contralesional) and rightward ocular lateropulsion
(ipsilesional, also known as ipsipulsion). The
pattern of saccadic dysmetria can be highly
localizing to the lateral medulla due to inferior
cerebellar peduncle involvement. https://collec-
tions.lib.utah.edu/ark:/87278/s65176w6
Video 4.7 Slow ipsiversive horizontal saccades in a
brainstem syndrome due to paramedian pontine
reticular formation (PPRF) involvement: This is
a patient with a complicated brainstem syndrome
that developed following head and neck cancer
diagnosis (status post surgery and radiation), that
included left (lower motor neuron) 7th and 8th
nerve palsies, in addition to slow saccades to the
left with normal saccades in other directions. With
an optokinetic stimulus moved to the right, there
were no leftward fast phases. Leftward eye
movements with pursuit and the head impulse test
to the right (the vestibulo-ocular reflex is respon-
sible for conjugate eye movements to the left)
appeared to be of normal speed. This constellation
of findings (i.e., normal pursuit and VOR, abnor-
mal saccades) argued for a left PPRF lesion and
against a left 6th nuclear lesion, although MRI did
not demonstrate a discrete pontine lesion. (Video
and legend created with the assistance of Dr. Tony
Brune) https://collections.lib.utah.edu/ark:/87278/
s6n058z5
Video 4.8 Three cases of internuclear ophthalmoplegia
(INO) in multiple sclerosis, brought out by
testing horizontal saccades: This video includes 3
patients each with a known history of MS found to
have unilateral or bilateral INOs on their exam. In
the first 2 patients, the INOs are relatively subtle,
without an adduction paresis. However, with rapid
lxxiv List of Videos\Electronic Supplemental Materials (ESM)
horizontal saccades, an adduction lag is apparent

which is suggestive of an INO. In the 3rd patient,
there were bilateral INOs with bilateral adduction
paresis. https://collections.lib.utah.edu/ark:/87278/
s6tj1wb3
Video 4.9 Evaluating smooth pursuit: Use a small fixation
target and move it slowly in horizontal and vertical
planes. https://collections.lib.utah.edu/ark:/87278/
s6r24925
Video 4.10 Saccadic pursuit and skew deviation due to a
middle cerebellar peduncle stroke: This is a
50-year-old woman who underwent resection of a
left-sided acoustic neuroma, and post-operatively,
she had vertigo, binocular diplopia, left hemi-
ataxia and severe gait ataxia. MR diffusion
weighted imaging demonstrated an acute stroke
involving the left middle cerebellar peduncle
(MCP) and lateral pons, which was responsible for
her left-sided appendicular and gait ataxia, skew
deviation, mild left fascicular 6th nerve palsy,
gaze-evoked nystagmus (right-beating nystagmus
[RBN] in right gaze and left-beating nystagmus
[LBN] in left), and impaired smooth pursuit. There
was mild spontaneous RBN that was accentuated
with the ‘penlight-cover test’, where fixation is
partially removed by occluding one eye while
shining a bright light in the fellow (un-occluded)
eye, in this case using the light of the video
camera. The RBN increased in right gaze in
accordance with Alexander’s Law (nystagmus
increases in the direction of the fast phase – gaze-
evoked nystagmus to the left and vestibular
nystagmus to the right can also be referred to as
Bruns nystagmus), and there was left unilateral
vestibular loss with an abnormal head impulse test
to the left due to left CN 8 injury from the acoustic
neuroma and/or its resection. However, fascicular
involvement of CN 8 in the pons could not be
List of Videos\Electronic Supplemental Materials (ESM) lxxv
excluded. https://collections.lib.utah.edu/
ark:/87278/s6kh4n5k
Video 4.11 Ipsilesional smooth pursuit and vestibulo-ocular
reflex suppression (VORS) impairment due to
hemispheric stroke: This is a 20 year-old man
who suffered a left middle cerebral artery stroke
years prior. Smooth pursuit and VORS were
saccadic/choppy in appearance to the left (ipsile-
sional) and normal to the right. When pursuit and
VORS are asymmetrically impaired, the lesion will
be ipsilateral to the direction of the eye movement
abnormality. https://collections.lib.utah.edu/
ark:/87278/s6j70rkm
Video 4.12 Evaluating vestibulo-ocular reflex suppression
(VORS): Impairment in pursuit and VORS are
almost always both normal or both abnormal,
except when the VOR is absent or markedly
diminished in which case there is no VOR to
suppress, so that VORS appears more normal than
pursuit. When this is the case, consider conditions
that cause both cerebellar impairment (i.e.,
saccadic smooth pursuit) and vestibular loss (i.e.,
the same patient can have normal/near normal-
appearing VORS, also with an abnormal head
impulse test) such as cerebellar ataxia, neuropathy,
vestibular areflexia syndrome (CANVAS). https://
collections.lib.utah.edu/ark:/87278/s6bw0r9q
Video 4.13 Gaze-evoked nystagmus and saccadic vestibulo-
ocular reflex suppression (VORS) in spinocer-
ebellar ataxia type 6: On exam, there was no clear
spontaneous downbeat nystagmus (DBN) in
primary gaze, although DBN could clearly be
provoked by convergence. Other ocular motor
features included saccadic pursuit and VORS
(suggestive of a normal VOR – i.e., there was a
VOR to suppress, but given the pursuit deficit,
VORS was saccadic) horizontally and vertically, in
addition to an alternating skew deviation (right
lxxvi List of Videos\Electronic Supplemental Materials (ESM)
hypertropia in right gaze and left hypertropia in left

gaze), gaze-evoked and rebound nystagmus.
Saccades were normal. Head impulse test was
normal. These are all typical ocular motor features
of a flocculus/paraflocculus syndrome. https://
collections.lib.utah.edu/ark:/87278/s6vx45m7
Video 4.14 Saccadic smooth pursuit with (near) normal
vestibulo-ocular reflex suppression (VORS):
This is a 70 year-old woman with the subacute
onset of severe imbalance and dizziness. On her
initial examination, she had prominent gaze-
evoked nystagmus and bilateral vestibular loss.
Smooth pursuit was saccadic, although VORS
looked much less saccadic (nearly normal).
Usually pursuit and VORS are both normal or both
saccadic, but when pursuit is impaired and there is
bilateral vestibular loss, there is no VOR to
suppress, so VORS can look normal or better than
pursuit. Her visually-enhanced VOR (slowly
rotating the head side to side while the patient
fixates on the examiner’s nose) was also saccadic
given the combination of impaired pursuit and
bilateral vestibular loss. She was diagnosed with an
anti-GAD-related cerebellar syndrome, and there
was marked improvement in ocular motor and
vestibular abnormalities following treatment with
intravenous immunoglobulin. Neoplastic work-up
was unrevealing. https://collections.lib.utah.edu/
ark:/87278/s6wx1bgp
Video 4.15 Evaluating optokinetic nystagmus (OKN):
During the bedside evaluation of optokinetic
nystagmus (OKN), the patient is instructed to look
at each red (or white) square as it moves past.
Because this is not a full-field visual stimuli, using
an optokinetic flag mainly allows the examiner to
quickly evaluate for right/left and up/down symme-
try and for impairment of smooth pursuit (slow
phases) and saccades (fast phases) in horizontal
List of Videos\Electronic Supplemental Materials (ESM) lxxvii
and vertical directions. Or, a patient with poor

vertical saccades may only generate a horizontal
nystagmus when the OK stimulus is oriented
diagonally. The optokinetic flag can be helpful at
the bedside to: 1) bring out a subtle adduction lag
suggestive of internuclear ophthalmoplegia, 2)
better appreciate convergence-retraction nystagmus
in Parinaud’s syndrome, 3) determine whether
downward fast phases are present or absent in
someone with parkinsonism (loss of the downward
fast phases is one of the first ocular motor signs of
progressive supranuclear palsy), among other affer-
ent uses (e.g., abnormal ipsilateral OKN in a
patient with unilateral parietal pathology; in the
assessment of a patient with functional vision loss,
etc). This differs from the ‘true’ OKN caused by
full-field visual stimuli (e.g., looking out of the
window of a moving train), which normally acts to
supplement the vestibular response during pro-
longed rotation. (Video and legend created with the
assistance of Dr. Tony Brune and Justin Bosley).
https://collections.lib.utah.edu/ark:/87278/s6k68htv
Video 4.16 The virtual (telemedicine) ocular motor exami-
nation: This video demonstrates one approach to
performing the ocular motor examination virtually
in a normal subject. (Video created with the
assistance of Dr. Olwen Murphy) https://collec-
tions.lib.utah.edu/ark:/87278/s6x9815p
Video 4.17 Contralateral 4th and 6th nerve palsies due to
leukemic meningitis: This patient experienced
diagonal diplopia (with both horizontal and vertical
components) due to a right 6th NP and left 4th
NP. While the 6th NP is marked, the evaluation of
ocular alignment is essential to make the diagnosis
of a 4th NP Also note the mild depression deficit
OS in down/right gaze due to left superior oblique
paresis. https://collections.lib.utah.edu/ark:/87278/
s63n5tg3
lxxviii List of Videos\Electronic Supplemental Materials (ESM)
Video 4.18 Cavernous sinus mass causing ipsilateral 3rd

and 4th nerve palsies: This patient had a known
right cavernous sinus mass due to Ewing’s sar-
coma, and presented with diplopia. He had a right
3rd NP, right 4th NP, and mild right 6th NP. This
video demonstrates that in addition to the right 3rd
(ptosis, mydriasis, impaired adduction, supra- and
infraduction), in downgaze, there is no clear
incycloduction of the right eye, suggesting that the
right 4th nerve is also involved. This is a subtle
sign, but should be sought since a 3rd NP + an
ipsilateral 4th NP is suggestive of a cavernous
sinus localization. https://collections.lib.utah.edu/
ark:/87278/s6186g5w
Video 4.19 Multiple ipsilateral ocular motor palsies and
aberrant regeneration of the 3rd nerve due to
cavernous sinus meningioma: This is a 50-year-
old woman presenting with a partial 3rd nerve
palsy (mild pupil involvement), partial 6th nerve
palsy, and no clear incycloduction in downgaze,
suggestive of additional 4th nerve palsy, all on the
left. With compressive lesions involving the 3rd
nerve, often aberrant regeneration develops – in
this case, injury to the left 3rd nerve caused
miswiring so that some of the fibers destined for
the left medial rectus instead went to the left
levator palpebrae. When adducting the left eye, the
eyelid elevated slightly. There was no evidence of
aberrant regeneration involving the pupil or ocular
motility. https://collections.lib.utah.edu/ark:/87278/
s6wx16kc
Video 4.20 A central HINTS exam in the acute vestibular
syndrome due to a lateral medullary stroke:
This patient experienced the acute vestibular
syndrome due to left lateral medullary stroke from
left vertebral artery dissection. Two months later
he was examined and the following ocular motor/
vestibular findings were observed: 1) with fixation-
List of Videos\Electronic Supplemental Materials (ESM) lxxix
removed, there was right-beating nystagmus (with

a slight torsional component, top poles beating
towards the right ear), 2) head impulse testing HIT
in the planes of the horizontal canals was normal,
3) there was a skew deviation with a left (ipsile-
sional) hypotropia. Therefore, the HINTS (Head
Impulse, Nystagmus, Test of Skew) exam was
consistent with a central localization based on the
normal HIT and presence of a skew deviation.
Additionally, there was saccadic dysmetria, with
hypermetric saccades to the (ipsilesional) left side
and hypometric saccades to the (contralesional)
right side. Although not shown here, there was also
leftward ocular lateropulsion, a finding which is
usually seen ipsilateral to hypermetric saccades.
(Video courtesy of Dr. Tzu-Pu Chang) https://
collections.lib.utah.edu/ark:/87278/s6546m8r
Video 4.21 Dysmetric saccades and ipsipulsion with eyelid
closure and vertical saccades due to lateral
medullary lesion: This patient experienced
oscillopsia and vertical diplopia, due to spontane-
ous torsional nystagmus and a skew deviation
(right hypotropia), respectively. The pattern of
saccadic dysmetria and ocular lateropulsion
localized to the right lateral medulla including: 1)
hypermetric saccades to the right, 2) a rightward
trajectory with vertical saccades, and 3) rightward
ocular lateropulsion (i.e., eyes drift to the right
with eyelid closure, also apparent on her MRI), as
well as the torsional nystagmus. These are features
that are commonly seen with a (right) lateral
medullary syndrome (in addition to her right
hypotropia), as the climbing fibers connecting
(left) inferior olive to (right) dorsal vermis are
injured in the (right) inferior cerebellar peduncle.
https://collections.lib.utah.edu/ark:/87278/
s64r24wd
lxxx List of Videos\Electronic Supplemental Materials (ESM)
Video 4.22 A complete lateral medullary (Wallenberg)

syndrome: This patient experienced the acute
onset of vertigo, dysarthria, dysphagia and
dysphonia/hoarseness (nucleus ambiguus), ptosis
and imbalance. Her examination localized to a left
lateral medullary (Wallenberg) syndrome – there
was decreased sensation on the left side of the face
(spinal trigeminal nucleus and tract) and the right
arm and leg (spinothalamic tract), a left Horner’s
syndrome (oculosympathetic tract), left hemi-
ataxia (inferior cerebellar peduncle), leftward
ocular lateropulsion (apparent throughout the video
during blinks – during eyelid closure, there is
conjugate deviation to the left, and when the
eyelids open, the eyes move to the right into
primary gaze) which is usually seen with ipsile-
sional (left) hypermetric saccades and contral-
esional (right) hypometric saccades, due to injury
of the climbing fibers traveling through the inferior
cerebellar peduncle on the left side. An ipsiversive
(leftward) ocular tilt reaction is also commonly
seen due to involvement of the utriculo-ocular
motor pathway (e.g., left hypotropia from skew
deviation, left head tilt, leftward ocular counter-
roll). (Video courtesy of Dr. Stephen Reich) https://
collections.lib.utah.edu/ark:/87278/s6963fhm
Video 4.23 Ocular motor and vestibular features of the
medial longitudinal fasciculus (MLF) syndrome:
This patient suffered a left MLF stroke causing 1)
left internuclear ophthalmoplegia (INO) due to
involvement of the interneurons traveling from
right 6th nucleus to left medial rectus subnucleus
via the MLF (responsible for conjugate rightward
gaze) 2) contraversive (rightward) ocular tilt
reaction (OTR – skew deviation causing a left
hypertropia; ocular counterroll with the top poles
rotated toward the right ear; right head tilt) due to
involvement of the utriculo-ocular motor pathways
List of Videos\Electronic Supplemental Materials (ESM) lxxxi
(originating in the right labyrinth), 3) spontaneous

(primarily) torsional nystagmus, with quick phases
of the superior poles directed towards the ipsile-
sional (left) side (due to involvement of the central
anterior and posterior semicircular canal pathways
that originated in the right labyrinth – acute nystag-
mus is usually mixed upbeat-torsional or down-
beat-torsional), 4) vestibulo-ocular reflex (VOR)
loss in the planes of the vertical semicircular canals
(posterior canal [PC] > anterior canal [AC]
pathway involvement because there’s only 1
brainstem pathway for PC compared to 3 pathways
for AC), 5) horizontal VOR – with the horizontal
head impulse test, the velocity of the adducting eye
(ipsilateral to an MLF lesion) movement can be
relatively preserved – i.e., much better than what
would be expected based on bedside testing with a
significant adduction lag due to an INO. This is
presumably due to an extra-MLF pathway, the
ascending tract of Dieters, which goes directly
from the vestibular nucleus to the ipsilateral medial
rectus subnucleus, thus bypassing the MLF
pathways, 6) vertical gaze-evoked nystagmus –
there was upbeat nystagmus (UBN) in upgaze and
downbeat nystagmus (DBN) in downgaze,
although it’s not clear whether this results from
descending fibers going from interstitial nucleus of
Cajal (INC) to the medullary nucleus of Roller
and/or involvement of the nearby paramedian tract
(PMT) cell groups (thought to receive inputs from
the INC that are transmitted to the cerebellar
flocculus). (Video and legend created with the
assistance of Dr. Tony Brune) https://collections.
lib.utah.edu/ark:/87278/s68m15w9
Video 4.24 Acute medial longitudinal fasciculus (MLF)
stroke with prominent spontaneous vertical-
torsional nystagmus: This patient suffered a left
MLF stroke, and had a skew deviation causing a
lxxxii List of Videos\Electronic Supplemental Materials (ESM)
left hypertropia (due to utriculo-ocular motor

pathway involvement in the MLF), in addition to a
left internuclear ophthalmoplegia causing an
exotropia and adduction paresis OS (due to
involvement of the interneurons connecting right
6th nucleus to left medial rectus subnucleus by the
left MLF). There was particularly prominent
spontaneous upbeat-torsional nystagmus in this
case as well (due to involvement of the central
vertical semicircular canal pathways in the MLF).
The torsional component of MLF-related spontane-
ous nystagmus is almost always ipsiversive – e.g.,
with a left MLF stroke, the top poles will beat
towards the left ear, and this is because of damage
to central fibers that originated in the 1) right
posterior semicircular canal (SCC), 2) right
anterior SCC or 3) right posterior and anterior
SCCs. Because of unopposed left anterior and
posterior SCC afferents (when normally stimu-
lated, the left anterior and posterior SCCs cause the
top poles to move towards the right ear), the slow
torsional phase will be towards the right ear, and
the fast phase will cause the top poles to beat
towards the left ear. Additionally, there are often
dissociated vertical components, again mainly due
to central vertical (anterior and posterior) SCC
injury. The most common pattern is upbeat-tor-
sional (ipsiversive) nystagmus, where there is more
upbeat in the contralesional eye than in the
ipsilesional eye. This is the pattern seen in the
video. Because the right anterior SCC, when
normally stimulated, causes excitation of the right
superior rectus and left inferior oblique, a lesion
involving the right anterior SCC pathway (at the
level of the left MLF in this case) will lead to less
excitation of the elevators and relative hyperactiv-
ity of the antagonist depressors. Because the right
inferior rectus is a strong depressor, there is a more
List of Videos\Electronic Supplemental Materials (ESM) lxxxiii
of a downward slow phase OD compared to OS

and therefore, a more marked upbeat component
OD compared to OS. The other patterns of
spontaneous nystagmus are: downbeat-torsional
(ipsiversive) nystagmus, where there is more
downbeat in the ipsilesional eye than in the
contralesional eye (related to posterior SCC
pathway damage, or the opposite of the situation
described above); hemi-see saw or jerky see saw
nystagmus where the torsional component is
ipsiversive, there is upbeat OD and downbeat OS,
related to injury of the posterior and anterior SCC
pathways and/or utricle-ocular motor pathways
(that are also responsible for skew deviation – i.e.,
slow phase up in the hypertropic left eye (fast
phase down, or downbeat OS), and slow phase
down in the hypotropic right eye (fast phase up, or
upbeat OD). (Video and legend created with the
assistance of Dr. Roksolyana Tourkevich) https://
collections.lib.utah.edu/ark:/87278/s6rz39rq
Video 4.25 Three cases of internuclear ophthalmoplegia
(INO) due to stroke: This video shows 3 patients
with vascular risk factors who suffered strokes of
the MLF resulting in unilateral INO in each case.
In the second case, INO was diagnosed status post
cardiac catherization and MRI was found to be
normal. In the third case, the patient had a clear
left medial rectus palsy several days prior, but at
the time of this exam, there was no adduction
paresis and only a subtle adduction lag OD with
horizontal saccades. https://collections.lib.utah.
edu/ark:/87278/s65t6v56
Video 4.26 Two patients with dorsal pontine strokes
causing horizontal gaze palsy and one-and-a-
half syndromes: The first patient presented with
double vision and hemiparesis due to a right
pontine ischemic stroke. His exam was significant
for a right horizontal gaze palsy due to right 6th
lxxxiv List of Videos\Electronic Supplemental Materials (ESM)
nucleus involvement and right internuclear

ophthalmoplegia (INO) (together, a one-and-a-half
syndrome). There was also a right lower motor
neuron (LMN) facial palsy from a fascicular right
7th NP (also known as “eight-and-a-half syn-
drome” given the 7th + one-and-a-half syndrome).
There was also upbeating nystagmus in upgaze due
to involvement of the vertical gaze holding
pathways (possibly from the paramedian tracts).
Convergence only improved adduction deficits
mildly. The second patient presented with facial
weakness, hemiparesis, and vertigo with oscillop-
sia due to a left dorsal pontine hemorrhage. He was
unable to look left (with pursuit, saccades, or with
the vestibular-ocular reflex), which localized to the
left 6th nucleus; there was a left LMN 7th NP
(together with the gaze palsy, an “eight syn-
drome”). There was also upbeat-torsional nystag-
mus towards the right ear, presumably due to
involvement of the vertical semicircular canal
pathways (mainly involving the anterior pathways
given downward slow and upward fast phase). The
anterior canal pathways travel through the superior
conjunctivum, ventral tegmental tract, and medial
longitudinal fasciculus (MLF), whereas the
posterior canal pathways travel through the MLF
only. Convergence only improved his adduction
deficit mildly. https://collections.lib.utah.edu/
ark:/87278/s6g48ckf
Video 4.27 Microvascular 6th nerve palsy: This is a 90
year-man with HTN, HLD, DM who woke up with
horizontal diplopia. Two years prior, he was
diagnosed with a microvascular right 6th nerve
palsy that resolved over several months. There was
little concern for giant cell arteritis, myasthenia
gravis, or a mass lesion in the absence of typical
symptoms or accompanying signs, and a new
microvascular left 6th nerve palsy was diagnosed.
List of Videos\Electronic Supplemental Materials (ESM) lxxxv
With saccades to the left, not only was abduction

severely limited OS, but there was significant
slowing of the leftward abducting saccades even
when looking from the right to center, which is
typical of a paretic process. In contrast, if an
abducting saccade were made from the right to
center with normal/near normal speed and it
stopped abruptly (due to an abduction deficit OS),
this should raise suspicion for a restrictive process
such as thyroid eye disease. https://collections.lib.
utah.edu/ark:/87278/s62v6km4
Video 4.28 Duane’s retraction syndrome, type 1: During an
evaluation for vestibular complaints, this patient
was incidentally found to have impaired abduction
OS. In adduction, there was narrowing of the
palpebral fissure OS, a result of globe retraction
due to co-contraction of the medial and lateral
rectus muscles. This constellation of findings was
consistent with a longstanding history of Duane
syndrome type 1, and argues strongly against an
acquired sixth nerve palsy for instance. There were
no complaints of diplopia, and she was already
aware of this diagnosis. https://collections.lib.utah.
edu/ark:/87278/s6cz6x1g
Video 4.29 Miller Fisher syndrome (MFS) causing ophthal-
moparesis, sluggish pupils and imbalance: This
is a 45 year-old woman who presented with mild
imbalance and diplopia. There had been a preced-
ing viral illness several weeks prior. Examination
demonstrated horizontal gaze paresis (sparing
unilateral adduction), mild gait ataxia (no clear
appendicular ataxia), and hyperreflexia. Pupils
were sluggish OU. Her anti-Gq1b antibodies came
back very high and MFS was diagnosed. IVIG was
given, and there was gradual improvement (of all
symptoms/signs) back to her baseline over 3–6
months. While the typical triad includes ophthal-
moplegia, ataxia, and HYPOreflexia, occasionally,
lxxxvi List of Videos\Electronic Supplemental Materials (ESM)
HYPERreflexia is seen instead as in our patient.

There may also be overlap between MFS and
Bickerstaff’s brainstem encephalitis – however, our
patient had no symptoms or signs (aside from
potentially her hyperreflexia) referable to the brain-
stem. Brain MRI was normal. https://collections.
lib.utah.edu/ark:/87278/s62v64d2
Video 4.30 Midbrain strokes causing bilateral 3rd nerve
and pseudo-6th nerve palsies: This is a man who
suffered right>left midbrain strokes due to endo-
carditis, who complained of the inability to move
his eyes as well as dream-like hallucinations (due
to peduncular hallucinosis). There was a presumed
nuclear 3rd nerve palsy on the right (i.e., respon-
sible for his mydriatic pupil, absent supra- and
infraduction, adduction, complete ptosis OD and
incomplete ptosis OS, and probably responsible for
at least some of his supraduction paresis OS), with
partial 3rd (fascicular) nerve palsy possibly
explaining infra- and supraduction paresis,
unreactive pupil OS and perhaps incomplete ptosis
OS. In addition to adduction and vertical deficits
attributable to midbrain ischemia, he also had
right>left abduction pareses that were attributed to
pseudo-6th or pseudoabducens palsies in the
absence of pontine ischemia on several MRIs
(done weeks apart), and no pontine neurologic/
ocular motor signs on his examination. Interest-
ingly, despite his pseudoabducens pareses being
due to a presumed “supranuclear” etiology, they
could not be overcome by VOR. This has been
reported, and perhaps due to the fact that the VOR/
head impulse test is simply not a strong enough
vestibular stimulus (compared to cold water
calorics for instance) https://collections.lib.utah.
edu/ark:/87278/s6642zc1
Video 4.31 A ‘central’ 4th nerve palsy due to midbrain
hemorrhage: This patient had a right hypertropia
List of Videos\Electronic Supplemental Materials (ESM) lxxxvii
that worsened in left and down gaze in addition to

right head tilt, and improved in left head tilt. There
was subjective excyclotorsion OD with double
Maddox rod testing. This was consistent with a
right 4th nerve palsy. He had experienced a left
midbrain hemorrhage which had bled several years
prior to this evaluation making the localization of
his 4th nerve palsy “central”. Given the proximity
of the left 4th nucleus and its fascicle to the left
medial longitudinal fasciculus (MLF) and oculo-
sympathetic tract, when a left internuclear ophthal-
moplegia (INO) and/or left Horner’s syndrome,
respectively, is seen with a right (CONTRALAT-
ERAL) 4th nerve palsy, a ‘central’ 4th NP is
strongly suggested relating to the decussating
course of the 4th nerve. However, an isolated 4th NP
can also be central and related to nuclear and/or
fascicular injury, and will be contralesional as in
this case. (Video and legend created with the
assistance of Dr. Kemar Green) https://collections.
lib.utah.edu/ark:/87278/s6hf1tbf
Video 4.32 Alternating hypertropias in two patient due to
bilateral 4th nerve palsies and alternating skew
deviation: Seen here are two patients with alternat-
ing hypertropias. The first is a 70-year-old woman
with a diagnosis of cerebellar ataxia, neuropathy,
vestibular areflexia syndrome (CANVAS). In the
video, both spontaneous downbeat nystagmus
(DBN) and gaze-evoked nystagmus (GEN) are
apparent, in addition to a right hypertropia in right
gaze and a left hypertropia in left gaze, also
referred to as an alternating skew deviation or an
abducting hypertropia. The combination of these
three findings (DBN, GEN, alternating skew) is
highly suggestive of cerebellar flocculus/parafloc-
culus disease. The second patient is a 40-year-old
woman who also has an alternating hypertropia,
although in her case this is an adducting hypertro-
pia due to bilateral 4th nerve palsies. In her case,
lxxxviii List of Videos\Electronic Supplemental Materials (ESM)
there is a right hypertropia in left gaze and a left

hypertropia in right gaze. https://collections.lib.
utah.edu/ark:/87278/s6d83n91
Video 4.33 Neuro-ophthalmic features of the dorsal
midbrain (Parinaud’s) syndrome: This patient
presented with diplopia, headaches, and difficulty
looking up, and was found to have a mass
involving the pineal gland – pathology led to the
diagnosis of glioblastoma multiforme. Major
features of a Parinaud’s syndrome were present
including: upgaze palsy, convergence retraction
nystagmus, light-near dissociation, and mild
eyelid retraction. Lesions involving the posterior
commissure (PC) often affect upward eye
movements (PC doesn’t carry fibers responsible
for downward movements). The pupillary light
reflex pathway can be affected as the result of
damage to the pretectal nucleus or the fibers from
pretectal nucleus to Edinger-Westphal (EW)
nucleus. The pathways responsible for pupillary
constriction during the near reflex do not travel
through the pretectal nucleus, and synapse
directly on EW. Because they are spared, light-
near dissociation is the result. https://collections.
lib.utah.edu/ark:/87278/s62263dq
Video 4.34 Bilateral rostral interstitial nucleus of Cajal
(riMLF) strokes causing vertical saccadic palsy:
This is a 65 year-old-man who suffered the abrupt
onset of loss of consciousness followed by
difficulty looking down. MRI demonstrated
bilateral rostral midbrain strokes in the distribution
of the artery of Percheron. He could not initiate
downward saccades and had fair upward saccades.
However, downward vestibulo-ocular reflex and
smooth pursuit was preserved, thus supporting the
supranuclear origin of his downward motility
issues. Although the riMLF is responsible for
initiation of vertical saccades, projections to the
List of Videos\Electronic Supplemental Materials (ESM) lxxxix
depressor muscles are ipsilateral whereas projec-

tions to the elevator muscles are bilateral – there-
fore, unilateral riMLF damage will cause difficulty
with initiation of downward>>upward saccades,
while bilateral damage generally abolishes all
vertical and torsional saccadic movements. In his
case, injury to the riMLFs was felt to be incom-
plete given fair upward saccades. https://collec-
tions.lib.utah.edu/ark:/87278/s6qg2g63
Video 4.35 A rostral midbrain stroke causing unilateral
riMLF and INC syndromes: This is a 65 year-old
man who experienced the sudden onset of diplopia,
dysarthria and imbalance. An MRI performed the
following day showed a left rostral midbrain
stroke. The patient was seen in clinic 10 days later
(when the video was taken), and by that time the
diplopia was purely vertical. The patient had ocular
motor findings due to involvement of two distinct
rostral midbrain structures: 1) Left interstitial
nucleus of Cajal (INC) a. Incomplete ocular tilt
reaction including a left hypertropia from skew
deviation (25 prism diopters) and ocular counter-
roll (top poles rotated toward the right ear on
dilated fundus exam), but without a head tilt – this
was due to involvement of the utriculo-ocular
motor pathway. b. Vertical gaze-evoked nystag-
mus – the INC is responsible for vertical and
torsional gaze holding, while the medullary
nucleus prepositus hypoglossi-medial vestibular
nucleus complex is responsible for horizontal gaze
holding. 2) Left rostral interstitial MLF (riMLF) a.
Torsional nystagmus, top poles beating toward the
RIGHT ear (with torsional nystagmus associated
with a LEFT INC, the top poles should beat
ipsilaterally, or top poles toward the LEFT ear).
With a unilateral riMLF lesion, if torsional
nystagmus is seen, it will beat contralaterally as in
this case. b. Slow vertical saccades, slower
xc List of Videos\Electronic Supplemental Materials (ESM)
downward compared to upward. This is because

the innervation for upward saccades is bilateral
(i.e., unilateral riMLF innervates bilateral superior
rectus and inferior oblique) while the innervation
for downward saccades is unilateral (i.e., unilateral
riMLF innervates ipsilateral inferior rectus and
superior oblique). c. Absent ipsitorsional quick
phases in the roll plane when the patient’s head
was slowly tilted to the left side. When his head is
tilted slowly to the right, the eyes will counterroll
with top poles toward the left ear due to the
physiologic ocular tilt reaction, but as the head
continues to tilt, a quick torsional phase will need
to be generated toward the right ear. Since the
riMLF contains the vertical and torsional burst
neurons, quick torsional phases toward the left
(ipsilesional) ear cannot be generated with a left
head tilt in this patient, although they were normal
with head tilt to the right side due to the intact right
riMLF. Three months after the stroke, there was no
vertical misalignment in straight ahead gaze,
although there was still a small left hypertropia in
downgaze. However, his slow vertical saccades
remained. The patient also happened to have
asteroid hyalosis in the vitreous OD much more
than OS (apparent in the video). https://collections.
lib.utah.edu/ark:/87278/s6mm0pz4
Video 4.36 Paroxysmal ocular tilt reaction: This patient
suffered a left sided hypertensive hemorrhagic
stroke 2 years prior, resulting in right hemiparesis,
dysarthria and vertical diplopia. The initial vertical
diplopia resolved completely and about 6 months
following the hemorrhage the patient began to
experience many episodes of vertical diplopia and
oscillopsia throughout the day, lasting minutes to
hours at a time. MRI demonstrated hemosiderin
deposition in the left corona radiata, globus
pallidus, and rostral left midbrain. She was
List of Videos\Electronic Supplemental Materials (ESM) xci
evaluated in clinic about 1 year following the

hemorrhage, and the video was taken at that time.
Her exam was consistent with a paroxysmal OTR
(pOTR) due to presumed left interstitial nucleus of
Cajal (INC) excitation/irritation (in this case,
presumably related to hemosiderin products), and
her pOTR was ipsiversive and included a large
right hypertropia from skew deviation, ocular
counterroll (top poles toward left ear), and left
head tilt. The pOTR occurred every few seconds,
and then the head and eye position would return to
normal, followed by another combined eye/head
(OTR) movement. At the time of the initial stroke,
it was reported that there was a 25 prism diopter
hypertropia, although the side of the hypertropia
could not be found in the notes. Presumably, there
was initial dysfunction of the left INC, causing a
skew deviation with left hypertropia and a patho-
logical OTR resulting from damage to the utriculo-
ocular motor (or graviceptive-ocular motor – i.e.,
utricle and vertical semicircular canal afferents)
pathway rostral to the decussation of these fibers.
With a left INC lesion (e.g., stroke), a contraver-
sive OTR would be expected, including left
hypertropia from skew deviation, ocular counter-
roll (top poles toward right ear), and right head tilt.
There was no improvement with carbamazepine
and its use was limited by side effects. Gabapentin
resulted in a reduction in the duration and fre-
quency of pOTR episodes (e.g. the pOTR would
cycle on and off for minutes at a time, and then
abrupt stop – when she was asymptomatic and
there was no evidence of pOTR, her alignment was
normal and there was no abnormal head position or
nystagmus). However, the appearance of the pOTR
during episodes was the same while being treated
with gabapentin as it was prior to any medication
xcii List of Videos\Electronic Supplemental Materials (ESM)
therapy. https://collections.lib.utah.edu/ark:/87278/
s6gt9z78
Video 4.37 Complete saccadic palsy following pulmonary
thrombectomy: This patient underwent pulmonary
thrombectomy for a pulmonary embolus. Immedi-
ately following the procedure, she was unable to
move her eyes. This video exam (she is the
passenger in a car during a telemedicine appoint-
ment) was performed 4 months after the onset. She
was unable to make saccades horizontally or
vertically, although horizontal and vertical smooth
pursuit and the vestibulo-ocular reflexes (VOR)
were intact, as was the range of eye movements.
When asked to look out the window at passing
scenery (i.e., an optokinetic stimulus), the slow
phase was clearly present, but because she could
not generate a fast phase (saccades), the eyes were
pinned to the right side. This could happen while
walking and looking to the sides as well. She had a
pure saccadic palsy in both horizontal and vertical
planes; therefore, this did not localize to the
paramedian pontine reticular formation (PPRF) or
rostral interstitial medial longitudinal fasciculus
(riMLF), respectively. Because the excitatory burst
neurons (EBN, responsible for saccades) and the
omnipause cells are both ensheathed by the
perineuronal nets, and because a patient with this
rare disorder at autopsy (typically due to cardiac
surgery) was shown to have normal EBN and
omnipause cells, the prevailing theory for a
post-surgery saccadic palsy is that ischemia of the
perineuronal nets may be the culprit. Fortunately,
she was able to adapt by using head movements
(the VOR) to move the eyes in the intended
direction. https://collections.lib.utah.edu/
ark:/87278/s68h45z9
Video 4.38 Ocular motor signs in early progressive supra-
nuclear palsy (PSP): Exam demonstrated square
List of Videos\Electronic Supplemental Materials (ESM) xciii
wave jerks, supranuclear downward>upward palsy

(i.e., improved with the vertical vestibulo-ocular
reflex [VOR]), slow and hypometric horizontal
saccades with very slow down>up saccades
(especially apparent with optokinetic tape),
convergence insufficiency, and saccadic smooth
pursuit and VOR suppression. Since upgaze can
become impaired to some degree with normal
aging (whether this is related to changes involving
the orbital tissues or whether this is in part
supranuclear is not clear), poor downgaze in a
patient with a gait/balance disorder is more
diagnostically meaningful. (Video and legend
created with the assistance of Dr. Roksolyana
Tourkevich) https://collections.lib.utah.edu/
ark:/87278/s6gr0vxw
Video 4.39 Advanced progressive supranuclear palsy (PSP)
with complete ophthalmoplegia but preserva-
tion of the horizontal vestibulo-ocular reflex
(VOR): This patient had complete vertical and
horizontal ophthalmoplegia, although the VOR
could overcome the horizontal gaze palsy (but not
the vertical gaze palsy). When VOR suppression
was tested by having the patient look at the light of
the camera while rotating (combined eye-head
movement) in a chair, the intact VOR drove the
eyes to the right when the chair was turned to the
left and to the left when the chair was turned to the
right. In this case, she was completely unable to
suppress her VOR. Normally, when VOR suppres-
sion (VORS) is impaired, the appearance is choppy
or saccadic – this is explained by saccades supple-
menting the impaired pursuit/VORS response. In
her case, she was unable to generate saccades, so
the eyes drifted laterally (due to an intact VOR)
without a mechanism (i.e., saccades) to get them
back to the fixation target. MRI demonstrated
‘Mickey mouse sign’, an appearance created by
xciv List of Videos\Electronic Supplemental Materials (ESM)
midbrain tegmentum atrophy on axial images.

https://collections.lib.utah.edu/ark:/87278/s6wx-
2sks
Video 4.40 Vertical gaze palsy, abnormal optokinetic
nystagmus and inability to suppress blinking to
light in progressive supranuclear palsy (PSP):
This patient had a vertical supranuclear gaze palsy
(i.e., it could be overcome by the vertical vestib-
ulo-ocular reflex [VOR]), saccadic smooth pursuit
and VOR suppression (not shown), and hypometric
and slow horizontal saccades, and with an optoki-
netic flag, there were weak fast phases (saccades)
horizontally, and absent fast phases vertically.
Slowing of downward saccades and loss of the
downward fast phase with an optokinetic flag are
commonly early signs in PSP, which tend to
precede the development of the downgaze/vertical
palsy. Additionally, patients with PSP tend to have
difficulty suppressing blinks when a bright light is
shone into the eyes – a finding akin to the glabellar
reflex, which is often present in neurodegenerative
conditions such as Parkinson’s disease. https://
collections.lib.utah.edu/ark:/87278/s6810bdv
Video 4.41 Downbeat and gaze-evoked nystagmus,
impaired smooth pursuit, and saccadic hyper-
metria in spinocerebellar ataxia type 8: This
patient also had a symptomatic esotropia at
distance consistent with divergence insufficiency,
which is a common cause of strabismus (due to
involvement of ocular motor vermis and/or
flocculus) in cerebellar degenerations. https://
collections.lib.utah.edu/ark:/87278/s6dj8q9h
Video 4.42 Gaze-evoked and rebound nystagmus, saccadic
pursuit and vestibulo-ocular reflex suppression
(VORS) in a cerebellar degeneration: This
patient experienced a several year long history of
imbalance due to cerebellar ataxia of unclear
List of Videos\Electronic Supplemental Materials (ESM) xcv
etiology. Seen in this video are common ocular

motor signs in patients with advanced cerebellar
dysfunction including: 1) saccadic smooth pursuit,
2) saccadic VORS (a combined eye-head move-
ment; the fact that pursuit and VORS appear to be
equally saccadic also tells the examiner that the
VOR is present – i.e., if VORS was normal/
near-normal appearing but pursuit was saccadic,
this would imply that there is no VOR to suppress),
3) gaze-evoked and rebound nystagmus. https://
collections.lib.utah.edu/ark:/87278/s6907ch7
Video 4.43 Paraflocculus (tonsillar) ocular motor syndrome
and saccadic dysmetria in a patient with Chiari
malformation: This is a 25-year-old woman
presenting with 6 months or progressive imbalance,
binocular vertical diplopia, and occipital headaches,
which were brought on or aggravated by coughing
or sneezing. Examination demonstrated hyperre-
flexia in the arms and legs with sustained clonus at
the ankles and Babinski reflexes bilaterally in
addition to gait and limb ataxia. There were a
variety of ocular motor abnormalities as well (see
below). Contrast-enhanced MRI demonstrated
peg-like cerebellar tonsils extending 2.9 cm below
the foramen magnum (more tonsillar herniation on
the right), and flattening of the dorsal medulla
(right>left). There was also syringohydromyelia of
the cervical and proximal thoracic spinal cord with
cord parenchymal thinning. Taken together, this was
consistent with a Chiari type I malformation. While
there was bilateral tonsillar herniation, it was worse
on the right. In fact, the following findings were
suggestive of a right paraflocculus (tonsillar) ocular
motor syndrome: 1) weak right-beating (ipsilateral)
spontaneous nystagmus (not seen in the video); 2)
strong and (slightly) asymmetric right more than left
gaze-evoked nystagmus (ipsilateral>contralateral)
– in her case, there was also downbeat and torsion in
xcvi List of Videos\Electronic Supplemental Materials (ESM)
lateral and down/lateral gaze (perhaps due to

bilateral paraflocculus compression); 3) impaired
smooth pursuit and vestibulo-ocular reflex suppres-
sion (VORS) toward the right (ipsilateral); 4) there
was also a fairly comitant right hypertropia (a skew
deviation), ocular counterroll (top poles toward the
left ear), and subjective visual vertical tilt 5 degrees
to the left with the bucket test – taken together, this
was consistent with a contraversive partial ocular tilt
reaction (no clear head tilt). Head impulse test was
normal. There was also saccadic dysmetria with
hypermetria to the right and hypometria to the left
(limb ataxia was worse on the right side as well). It
was felt that this was due to compression of the right
inferior cerebellar peduncle, affecting climbing
fibers from left inferior olive to right dorsal vermis.
She underwent suboccipital craniectomy and C1
laminectomy, and when she was seen 6 months
following surgery, all ocular motor findings had
resolved with the exception of mild residual
gaze-evoked nystagmus. https://collections.lib.utah.
edu/ark:/87278/s64r3f70
Video 4.44 Periodic Alternating Nystagmus and Central
Head-Shaking Nystagmus from Nodulus Injury:
This patient suffered a gunshot wound to the
cerebellum. When he regained consciousness days
later, he experienced oscillopsia due to periodic
alternating nystagmus (PAN). He was started on
baclofen 10 mg bid, and had a dramatic response
and only had moderate spontaneous left-beating
nystagmus (without PAN) along with gaze-evoked
nystagmus. The dose was increased to 20 mg 4
times/day which was tolerated well, and nystagmus
and oscillopsia resolved completely. However,
following 10–15 seconds of 2–3 Hz horizontal
head-shaking, there was robust left-beating
nystagmus. This could be explained by injury to
the nodulus, a localization that explains both PAN
List of Videos\Electronic Supplemental Materials (ESM) xcvii
and certain central patterns of head-shaking

nystagmus (HSN) such as this (i.e., robust HSN in
the absence of unilateral vestibular loss). Neuronal
circuits responsible for velocity storage (which
normally prolong the vestibulo-ocular reflex
response beyond the mechanical limitations of the
semicircular canal cupula) are mainly located in
the vestibular nucleus and nodulus. Disinhibition
of velocity storage due to nodulus injury can
therefore contribute to PAN or central HSN as in
this case. https://collections.lib.utah.edu/
ark:/87278/s64b892v
Video 4.45 Paraneoplastic cerebellar degeneration causing
severe saccadic hypermetria: This is a patient
who was diagnosed with anti-Yo antibody-related
cerebellar syndrome due to ovarian cancer 2 years
prior to this video. She complained of oscillopsia
due to spontaneous upbeat nystagmus (presumably
the result of brainstem involvement), and on
examination, she had intermittent saccadic
intrusions, hypermetric saccades (in all planes),
saccadic smooth pursuit and vestibulo-ocular reflex
suppression. MRI demonstrated severe brainstem
and cerebellar a trophy. https://collections.lib.utah.
edu/ark:/87278/s6bz9v92
ESM 5.1 Expanded nystagmus & saccadic intrusions/
oscillations differential
Video 5.1 Head movement independent (‘sitting’)
oscillopsia – a common symptom of nystagmus
and s accadic intrusions/oscillations: This video
is an example of what a patient with spontaneous
nystagmus or saccadic intrusions/oscillations
experiences visually during the abnormal eye
movements – i.e., oscillopsia (illusion of move-
ment of the stationary environment) is the result.
Compare this to head movement dependent
(‘walking’) oscillopsia, which is typically due
bilateral vestibular loss
xcviii List of Videos\Electronic Supplemental Materials (ESM)
Video 5.2 Jerk nystagmus: This is an example of jerk

nystagmus due to a central vestibular lesion. The
slow phase is the pathologic phase (to the left)
which initiates the movement, and is followed by a
fast position reset mechanism (to the right). Jerk
nystagmus is named after the fast phase. This
patient presented with the acute vestibular syn-
drome due to a demyelinating brainstem lesion,
which led to the diagnosis of neuromyelitis optica.
She has spontaneous right-beating nystagmus
(RBN), that stays unidirectional (RB) in all
directions of gaze, even to the left. To the right,
there is more intense RBN in accordance with
Alexander’s law (i.e., vestibular nystagmus will
increase in the direction of the fast fast)
Video 5.3 Pendular nystagmus: This is an example of
pendular nystagmus, where like jerk nystagmus,
the slow phase initiates the movement. However,
unlike jerk nystagmus, there is no fast phase, but
rather back to back slow phases resembling a
pendulum. Pendular nystagmus is named after the
vector, making this mainly a horizontal (with a
slight elliptical trajectory) pendular nystagmus.
This patient presented with ‘sitting’ oscillopsia
(from her nystagmus) due to a progressive neuro-
degenerative disorder (of unknown etiology) that
led to severe atrophy of the brainstem and cerebel-
lum over years
Video 5.4 Saccadic intrusions (square wave jerks, SWJ):
Seen here are SWJ, which is the most common
example of a saccadic intrusion. Here the patient is
fixating on the camera, and all of the sudden a
saccade takes the eyes off the fixation target,
there’s a brief intersaccadic interval, and then the
eyes return to the target. Therefore, the saccade is
the culprit that initiates the movement, rather than
the slow phase (which is the culprit with jerk or
pendular nystagmus). The intrusions occur quite
List of Videos\Electronic Supplemental Materials (ESM) xcix
frequently (many more than would be expected

given his age alone), and these prominent SWJ
were related to a progressive cerebellar degenera-
tion in his case
Video 5.5 Head movement dependent (‘walking’) oscil-
lopsia – a common symptom of bilateral
vestibular loss: This video is an example of what
a patient with bilateral vestibular loss experiences
while walking. Without a vestibulo-ocular reflex
(VOR), there is no mechanism to ensure retinal
stability of the world with each head movement,
and oscillopsia (illusion of movement of the
stationary environment) is the result. Jumpy
vision during ambulation or when driving on a
bumpy road for example is highly suggestive of
bilateral vestibular loss, and head impulse testing
and evaluation of the VOR are warranted. Head
movement independent (‘sitting’) oscillopsia is
typically due nystagmus or saccadic intrusions/
oscillations. https://collections.lib.utah.edu/
details?id=1213442
Video 5.6 Bruns nystagmus due to a cerebellopontine
angle vestibular schwannoma: This patient
experienced headache and imbalance leading to an
MRI which showed a left sided cerebellopontine
angle (CPA) vestibular schwannoma. Because of
involvement of the left brainstem/cerebellum (e.g.,
dysfunction of the neural integrator/gaze holding
apparatus) by the CPA mass, there was left-beating
ipsilesional “gaze-evoked” nystagmus in left gaze.
Note the larger amplitude and lower frequency
gaze-evoked nystagmus in left gaze. Because of
involvement of the left 8th cranial nerve, there was
right-beating contralesional “vestibular” nystagmus
in right gaze (in accordance with Alexander’s law).
Note the smaller amplitude and higher frequency
vestibular nystagmus in right gaze. https://collec-
c List of Videos\Electronic Supplemental Materials (ESM)
tions.lib.utah.edu/ark:/87278/s60p4p3j (Video
courtesy of Dr. Veeral Shah)
Video 5.7 Latent nystagmus due to infantile esotropia:
This patient had a history of amblyopia and
intermittent eye crossing. On exam, he had a large
angle esotropia, and other features of an infantile
esotropia syndrome including: latent nystagmus
(right-beating nystagmus when fixating with the
right eye and left-beating nystagmus when fixating
with the left eye), inferior oblique overaction OU,
and monocular nasotemporal optokinetic asymme-
try (not included in the video). https://collections.
lib.utah.edu/ark:/87278/s6k393bz
Video 5.8 Periodic alternating nystagmus (PAN) and
cross-coupled head-shaking nystagmus in
cerebellar degeneration: This patient presented
with progressive imbalance and oscillopsia over
years, and examination demonstrated alternating
right-beating and left-beating nystagmus every
90–120 seconds (with a null period in between)
consistent with PAN. PAN localizes to the nodulus/
ventral uvula, and is occasionally seen with
cerebellar degenerations (SCA 6 among others).
Baclofen can be helpful for PAN, and therapy was
initiated in this particular patient with mild
improvement. She also had hypermetric saccades,
saccadic smooth pursuit and vestibulo-ocular reflex
suppression, gaze-evoked nystagmus, as well as a
cross-coupled response with head-shaking – i.e.,
with horizontal head-shaking, vertical nystagmus
(downbeating) was apparent). This is another
central vestibular/ocular motor sign, and can also
be seen with nodulus/uvula pathology as well as
with flocculus/paraflocculus involvement – this
finding can be seen at the end of the video. This
patient had a pan-cerebellar syndrome involving
the vestibulocerebellum as well as the fastigial
nucleus (saccadic hypermetria) and other regions.
List of Videos\Electronic Supplemental Materials (ESM) ci
s62k013r
Video 5.9 Periodic alternating nystagmus (PAN) due to
spinocerebellar ataxia type 6: This patient
presented with imbalance for several years and
more recently oscillopsia. On examination, there
was saccadic pursuit in addition to gaze-evoked
nystagmus with rebound, raising suspicion for a
cerebellar flocculus/paraflocculus localization.
Additionally, there was PAN, which localizes to
the nodulus/ventral uvula. Every 90–120 seconds
there was a transition from right-beating to
left-beating, etc. Baclofen lessened his oscillopsia,
and genetic testing for SCA 6 was positive. https://
collections.lib.utah.edu/ark:/87278/s6np5spp
Video 5.10 Paraneoplastic downbeat nystagmus (DBN) and
cerebellar ataxia due to small cell lung carci-
noma: This patient experienced the subacute
progression of imbalance and oscillopsia over
weeks, due to a paraneoplastic cerebellar syndrome
from lung cancer. Examination demonstrated
spontaneous DBN and gaze-evoked nystagmus
(causing a ‘side pocket’ appearance), hypermetric
saccades, saccadic smooth pursuit and vestibulo-
ocular reflex suppression (not shown in this video).
DBN improved significantly following intravenous
immunoglobulin and treatment of the cancer.
(Video and legend created with the assistance of
Drs. Tony Brune and Kelly Sloane) https://collec-
tions.lib.utah.edu/ark:/87278/s6dn80mw
Video 5.11 Downbeat nystagmus causing severe oscillopsia:
This patient experienced progressive ataxia and
oscillopsia over two years of unknown etiology.
Unfortunately, trials of 4-aminopyridine, clonaz-
epam, baclofen, and chlorzoxazone were ineffec-
tive. After 2 years, significant cerebellar atrophy
was apparent on his MRI. https://collections.lib.
utah.edu/ark:/87278/s6wq42f0
cii List of Videos\Electronic Supplemental Materials (ESM)
Video 5.12 Abnormal visually-enhanced vestibulo-ocular

reflex (vVOR) in cerebellar ataxia, neuropathy,
vestibular areflexia syndrome (CANVAS): This
patient complained of chronic (unexplained cough),
progressive numbness in the legs and feet, gait
instability, and oscillopsia when walking or with
head movements. Examination showed excessive
square-wave jerks, bilateral horizontal gaze-evoked
nystagmus, bilaterally abnormal head impulse
testing, saccadic vVOR (seen with slow head
turning to the right and left, abnormal due to
combination of poor pursuit and bilateral vestibular
loss). A clinical diagnosis of cerebellar ataxia,
neuropathy, and vestibular areflexia syndrome
(CANVAS) was made. An impaired or saccadic
vVOR suggests that there is failure of both the
pursuit and (usually bilateral) vestibular systems,
and CANVAS should be considered, especially
when neuropathy and chronic cough are also present
Video 5.13 Positional downbeat nystagmus due to a
cerebellar degeneration: This patient mainly
complained of dizziness and vertical oscillopsia
when assuming a supine position. She was found
to have a significant exacerbation in her (very
mild) baseline downbeat nystagmus with straight
head hanging, and in right and left Dix-Hallpike.
Although positional downbeat nystagmus (pDBN)
can be seen with the uncommon anterior canal
variant of BPPV, usually it is seen with disorders
of the cerebellum or cervicomedullary junction.
When pDBN is seen in a patient with parkinson-
ism, multiple system atrophy should be a consider-
ation. In this patient, the downbeat was in isolation,
there was no cerebellar ataxia, and extensive
evaluation was unrevealing. She did well with
4-aminopyridine and there was no progression over
List of Videos\Electronic Supplemental Materials (ESM) ciii
at least 2 years. https://collections.lib.utah.edu/

ark:/87278/s66t3w9k
Video 5.14 Spontaneous upbeat nystagmus (UBN) in acute
Wernicke’s encephalopathy: Always consider the
possibility of Wernicke’s encephalopathy when a
patient presents acutely with spontaneous UBN, in
addition to a brainstem stroke, demyelinating
lesion, or encephalitis. (Video and legend created
with the assistance of Dr. Julia Carlson) https://
collections.lib.utah.edu/ark:/87278/s6h74j6d
Video 5.15 Reversal of vertical nystagmus over time and
with convergence in anti-DPPX encephalitis – a
similar pathophysiology to Wernicke’s encepha-
lopathy?: This is a man who initially presented with
spontaneous upbeat and torsional nystagmus, which
led to the diagnosis of anti-DPPX encephalitis. Over
6–12 months, his spontaneous (mainly) upbeat
nystagmus (UBN) transitioned to spontaneous
downbeat nystagmus (DBN). In this video, he has
gaze-evoked nystagmus (e.g., right-beating in right
gaze and left-beating nystagmus in left gaze) with a
downbeat component. While spontaneous downbeat
nystagmus was present in primary gaze, with
convergence, this transitioned to upbeat nystagmus.
Vertical nystagmus reversing with convergence is a
finding often seen in patients with Wernicke’s
encephalopathy. While the semicircular canals
(posterior, horizontal, and anterior) are the angular
acceleration detectors in the labyrinth, the otoliths
(utricle and saccule) are the linear acceleration
detectors and are responsible for the translational
vestibulo-ocular reflex (t-VOR). In order for the
t-VOR to generate appropriate eye movements,
orbital position and vergence angle must be taken
into account. Brainstem structures responsible for
processing otolithic inputs include the medial and
inferior vestibular nuclei (MVN and LVN), which
civ List of Videos\Electronic Supplemental Materials (ESM)
have projections to the cerebellar nodulus (which

also has a role in modulating the t-VOR). In patients
with acute Wernicke’s encephalopathy, gaze-evoked
nystagmus can be attributed to damage involving the
MVN-nucleus prepositus hypoglossi (NPH)
complex, while the horizontal (angular) VOR is
commonly impaired since the horizontal semicircu-
lar canal afferents synapse in the MVN. With
Wernicke’s the transition from spontaneous upbeat
nystagmus (attributed to damage involving the
nucleus of Roller and nucleus intercalatus, which
both inhibit the flocculus) to downbeat nystagmus
with convergence can also be explained by damage
to the MVN and LVN given their role in the
t-VOR. In this patient with anti-DPPX encephalitis,
impairment of MVN-LVN and/or nodulus are all
possible explanation for the transition of DBN to
UBN with convergence. It is possible that the initial
spontaneous upbeat-torsional nystagmus resulted
from asymmetric pontomedullary damage involving
the vertical semicircular canal (SCC) pathways
(multiple MRIs showed no clear T2/FLAIR or
T1-enhancing posterior fossa lesions). Several
theories for the transition of spontaneous UBN
(acutely) to spontaneous DBN (chronically) in this
patient include: 1) Given the proximity of the
paramedian tract nuclei (PTN), the chronic down-
beat nystagmus could relate to vertical SCC
pathway recovery with persistent PTN damage –
i.e., a similar (or identical) mechanism to the
prevailing theory for transition of acute UBN to
chronic DBN in Wernicke’s encephalopathy. Since
the PTN normally excites the flocculus, damage to
the PTN can cause relative hypoactivity of the
flocculus and an upward bias (slow phase drift since
anterior canal [upward or anti-gravity] pathways are
overactive) with resultant downbeat nystagmus. 2)
The patient also developed gaze-evoked nystagmus
List of Videos\Electronic Supplemental Materials (ESM) cv
in lateral and up and down gaze after 6–12 months,

likely related to dysfunction of the flocculus/
paraflocculus rather than the MVN-NPH given its
presence in horizontal and vertical gaze. The
spontaneous DBN and saccadic pursuit and VOR
suppression that also developed are also suggestive
of a flocculus/paraflocculus syndrome. It is therefore
possible that the acute asymmetric vertical SCC
pathway injury recovered, but flocculus/parafloccu-
lus impairment developed chronically. https://
collections.lib.utah.edu/ark:/87278/s6bg75c3
Video 5.16 Ocular motor signs in brainstem demyelinating
disease – spontaneous upbeat nystagmus (UBN),
vertical gaze-evoked nystagmus, slow saccades,
bilateral vestibular loss, internuclear ophthal-
moplegia (INO): Salient findings included the
following, which could be correlated with MRI
hyperintensities throughout the brainstem (no
involvement of the cerebellum): 1) Spontaneous
UBN: this caused vertical oscillopsia that was
independent of head movements. UBN often
localizes to the dorsal caudal medulla (nucleus of
Roller and nucleus intercalatus), and in fact,
hyperintense T2/FLAIR signal was present
bilaterally in this region (see arrows in figure).
Visual acuities were impaired in part due to
bilateral optic neuritis, but also given her spontane-
ous nystagmus. 2) Hypoactive VOR: this caused
oscillopsia that depended on head movements
(e.g., walking) and bilateral vestibular loss was
shown on bedside and video head impulse testing
(HIT). Afferents from the horizontal semicircular
canals (SCC) synapse in the medial vestibular
nucleus (hyperintense T2/FLAIR signal was
present in the region of the MVN-nucleus preposi-
tus hypoglossi complex bilaterally; see arrows in
figure), while afferents from the vertical SCC
synapse on other vestibular subnuclei that in turn
cvi List of Videos\Electronic Supplemental Materials (ESM)
project rostrally via the medial longitudinal

fasciculus (MLF) to the trochlear and oculomotor
nuclei. Bilateral dorsal pontine hyperintense T2/
FLAIR signal was present in the region of the
MLFs (see arrows in the figure). 3) Bilateral
adduction paresis: this was responsible for hori-
zontal diplopia from bilateral internuclear ophthal-
moplegia (INO) with adduction deficits and
abducting nystagmus OU from bilateral lesions in
the MLF. Notably, even when unilateral or bilateral
INOs are present, HIT/video HIT in the plane of
the horizontal SCCs is typically normal/near
normal. As an example, a patient with a right INO
can have a right adduction deficit (or lag) with
leftward gaze. However, when a HIT is performed
to the right (requiring activation of the right medial
rectus), the afferents from the horizontal SCC can
bypass the MLF lesion (via the ascending tract of
Deiters), allowing for preservation of the efferent
limb of the horizontal VOR. In this patient’s case,
hypofunction in the planes of the horizontal SCC
could be explained by bilateral MVN lesions. 4)
Vertical gaze-evoked nystagmus: this was due to
vertical gaze holding impairment from either
lesions in the interstitial nucleus of Cajal (INC)
involvement in the rostral midbrain (see arrows in
figure), or from lesions in the medially located
pontomedullary paramedian tracts (receive vertical
gaze holding signals from INC and relay to
cerebellar flocculus). 5) Slow horizontal saccades:
while the slow adducting saccades could be
explained by bilateral INOs, the abducting
saccades were also slow and fast phases were poor
with an optokinetic stimulus. Vertical saccades
appeared to be normal when taking into account
her significant UBN. Given widespread dorsal
pontine disease (see arrows in figure on sagittal
FLAIR), it is likely that paramedian pontine
List of Videos\Electronic Supplemental Materials (ESM) cvii
reticular formation (PPRF) was involved. https://

collections.lib.utah.edu/ark:/87278/s64517rm
Video 5.17 Lateral pontine stroke involving the superior
vestibular nucleus causing spontaneous upbeat-
torsional nystagmus: A 65-year-old man pre-
sented to the emergency department with
spontaneous vertigo and unsteadiness, and was
noted to have spontaneous upbeat nystagmus
(UBN), also with a torsional component (top poles
beating toward the right ear) that was most
noticeable in right and up gaze. General neurologic
exam was non-focal although there was severe
imbalance. Brain MRI demonstrated a small left
dorsolateral pontine stroke (see end of video for
diffusion-weighted imaging on the left and FLAIR
on the right), that involved the left superior
vestibular nucleus. While the posterior semicircu-
lar canal (SCC) afferents synapse in the vestibular
nucleus and then ascend the medial longitudinal
fasciculus (MLF) only, the anterior SCC afferents
synapse in the vestibular nucleus and ascend via
one of three pathways: 1) MLF, 2) ventral tegmen-
tal tract, and 3) brachium conjunctivum (BC, aka,
superior cerebellar peduncle). Anterior SCC
afferents synapse in the rostral SVN on their way
to join the BC, and in this patient’s case, it was
thought that ischemia in this region was respon-
sible for his UB-torsional nystagmus. Anterior
SCC afferents destined for the BC would originate
in the left labyrinth and synapse in the left SVN
prior to their decussation. If left anterior SCC
afferents were injured – normally responsible for
torsional slow phase with top poles rotating toward
the right ear and an upward slow phase (sometimes
referred to as the “anti-gravity” pathway) – there
would be a relative predominance of posterior SCC
tone (causing downward slow phase) and right
sided anterior and posterior SCC tone (causing
cviii List of Videos\Electronic Supplemental Materials (ESM)
torsional slow phase with top poles toward the left

ear). These slow phases in turn generate fast phases
upward (UBN) and torsional toward the right ear,
which is what is seen in this patient. While UBN is
typically thought to localize to the midline medulla
or to paramedian pontomesencephalic regions
(MLF, BC), this patient demonstrates that a lateral
pontine insult can also cause this finding. (Video
courtesy of Dr. Tzu-Pu Chang) https://collections.
lib.utah.edu/ark:/87278/s6kx02v4
Video 5.18 Torsional nystagmus due to medullary tumor:
This patient experienced headaches which led to an
MRI and the diagnosis of a right medullary
pilocytic astrocytoma, confirmed pathologically.
Examination was performed a year after the initial
diagnosis, and several months prior to this exam
oscillopsia was experienced for the first time. MRI
demonstrated that the cystic portion had increased
in size and it was thought that her newly appreci-
ated nystagmus and resultant oscillopsia were
related to this interval change. On exam, she had
spontaneous torsional nystagmus, which was unidi-
rectional in right and left gaze, with the top poles
beating towards the right ear in each position.
Saccades, smooth pursuit and the vestibulo-ocular
reflex were unremarkable. Pure torsional nystag-
mus is almost always central in origin. An acute
destructive lesion (e.g., vestibular neuritis) causing
unilateral vestibular loss will cause contralesional
horizontal-torsional nystagmus related to unop-
posed semicircular canal (SCC) afferents contralat-
erally. For pure torsional nystagmus to result from
a peripheral lesion, certain SCCs must be spared
(e.g., both horizontal SCCs, which will cancel out
so that a horizontal jerk component is not seen;
both vertical SCCs on one side) while others must
be strategically damaged (e.g., both vertical SCCs
on the opposite side). In contrast, damaging the
List of Videos\Electronic Supplemental Materials (ESM) cix
central fibers originating from both vertical SCCs

on one side due to a medullary lesion is a much
more common cause of torsional nystagmus. Pure
torsional nystagmus may also result from unilateral
interstitial nucleus of Cajal (ipsiversive nystagmus)
or rostral interstitial medial longitudinal fasciculus
(contraversive) injury, while vertical-torsional
nystagmus may result from medullary (direction
can be less predictable depending on how caudal or
rostral the injury occurs), medial longitudinal
fasciculus (ipsiversive), or superior cerebellar
peduncle localizations, among others. https://
collections.lib.utah.edu/ark:/87278/s6n62k3m
Video 5.19 Oculopalatal tremor (OPT) and internuclear
ophthalmoplegia (INO) due to a hemorrhagic
pontine cavernoma: This is a 60-year-old woman
who experienced 2 episodes of vertigo, nausea and
vomiting, which was felt to be related to recurrent
hemorrhage of a pontine cavernoma that was
adjacent to the fourth ventricle. The cavernoma
was resected, and diplopia and left facial palsy
were noted after the surgery. About 6 months later,
balance worsened and oscillopsia was experienced
for the first time. At the time that this video was
taken, more than 12 months had passed since the
surgery. Deficits included left lower motor neuron
(LMN) facial palsy (damage to the left fascicle of
CN7), left INO (damage to the left medial longitu-
dinal fasciculus), in addition to vertical-torsional
pendular nystagmus and palatal tremor, consistent
with oculopalatal tremor. Review of a recently
obtained MRI showed bilateral hyperintensity of
the inferior olives (IO) on MRI T2/FLAIR
sequences due to hypertropic olivary degeneration
(HOD). In her case, HOD was related to injury of
the descending central tegmental tract (CTT) as it
passed through the pons, thereby removing normal
inhibition of the IO by the CTT. (Video and legend
cx List of Videos\Electronic Supplemental Materials (ESM)
created with the assistance of Dr. Tony Brune)

s618790z
Video 5.20 Acute vestibular neuritis with unidirectional
nystagmus and abnormal video head impulse
test (vHIT): This patient presented to the emer-
gency department (ED) 2 days prior to the video
recording with acute onset prolonged vertigo,
nausea, head motion intolerance, unsteadiness and
spontaneous nystagmus, consistent with the acute
vestibular syndrome. Video-oculography examina-
tion in the ED demonstrated mixed left-beating and
torsional (top poles beating toward left ear)
nystagmus that was unidirectional (i.e., left-beating
in all directions of gaze) and increased in left gaze
in accordance with Alexander’s law. There was no
loss of hearing, video head impulse test was
abnormal to the right (low gain and corrective
saccades), and test of skew was normal (i.e.,
vertical alignment was normal with alternate cover
test). Per the HINTS exam (Head Impulse,
Nystagmus, Test of Skew) and in the absence of
hearing loss, he was diagnosed with right-sided
vestibular neuritis. He was given steroids and
presented for follow-up 2 days later (the day of this
recording). Nystagmus was much less intense than
it had been in the ED, and symptomatically, he was
much improved. https://collections.lib.utah.edu/
ark:/87278/s6pg73w3
Video 5.21 Spontaneous torsional nystagmus and ocular tilt
reaction (OTR): This patient experienced “a delay
in focusing” with “some twisting movement” that
began about 18 months prior to this video with
mild progression over days or weeks. For the same
period of time, he experienced intermittent vertical
diplopia. MRI done months after the onset was
unremarkable, as was a second contrast-enhanced
MRI done several months prior to this video.
List of Videos\Electronic Supplemental Materials (ESM) cxi
Evaluation for neoplastic/paraneoplastic, infec-

tious, inflammatory, autoimmune disorders was
unrevealing and his symptoms had been subjec-
tively stable for over a year. Oscillopsia – There
was spontaneous torsional nystagmus (top poles
beating toward the right ear) in primary gaze with
a very slight downbeat (DB) component. The
torsional nystagmus is unidirectional in all
directions of gaze, although there was more DB in
right gaze. Gabapentin or baclofen trial was
discussed and deferred given the mild nature of his
oscillopsia (mainly experienced in right gaze).
Diplopia – There was a small-angle right hypertro-
pia of 1 PD in primary gaze that measured 2 PD in
right gaze and was otherwise comitant on 3-step
testing. Ocular counterroll (OCR, top poles toward
the left ear) was present on fundus photos, and
with bucket test, there was a 5 degree leftward tilt
in subjective visual vertical (SVV). Taken together,
he had evidence of a partial ocular tilt reaction
(OTR) including skew deviation, OCR, and SVV
(a perceptual consequence of the OTR), but
without a noticeable static head tilt. The slow
phase of his torsional nystagmus caused the top
poles to rotate toward the left ear, which was also
in the direction of the OCR from his partial
OTR – therefore, imbalance in the utricle-ocular
motor pathways explained his OTR and could be
an explanation for his torsional nystagmus as well
(no clear jerky or hemi-seesaw nystagmus was
seen). Or, in addition to central utricle pathway
damage, fairly symmetric central damage to
posterior and anterior semicircular pathways could
be responsible for his mainly torsional nystagmus.
Otherwise, there were no other neuro-ophthalmic
or neurologic signs to suggest a lesion in the lateral
medulla, medial longitudinal fasciculus or intersti-
tial nucleus of Cajal (any of which could cause
cxii List of Videos\Electronic Supplemental Materials (ESM)
OTR and spontaneous torsional or vertical-tor-

sional nystagmus). https://collections.lib.utah.edu/
ark:/87278/s6vt71tc
Video 5.22 Oculopalatal tremor (OPT) with prominent
pendular nystagmus, bilateral horizontal gaze
palsy, and bilateral facial palsies: Seen here are
classic features of OPT, including vertical pendular
nystagmus, palatal myoclonus, and MRI evidence
of inferior (medullary) olivary hypertrophy. Given
the proximity of the central tegmental tract to the
abducens nuclei and facial nerve fascicles, she also
had horizontal gaze palsy and facial diplegia.
(Video and legend created with the assistance of Dr.
Tony Brune) https://collections.lib.utah.edu/
ark:/87278/s6mh1mnm
Video 5.23 Oculopalatal tremor (OPT) and one-and-a-half
syndrome due to pontine hemorrhage: This
patient suffered a midline pontine hemorrhage
(left>right) shortly after being put on a blood
thinner. Immediately afterwards, right hemiparesis
and hemi-anesthesia, left lower motor neuron
(LMN) facial palsy and ophthalmoparesis were
noted. Months later, he experienced oscillopsia as
well. At the time that this video was taken, he was
about 6 months from the pontine hemorrhage.
There was mainly vertical pendular nystagmus
noted in the left eye, and there were vertical and
horizontal (convergent-divergent) components in
the right eye, along with palatal tremor, which is
known as oculopalatal tremor (OPT). Vertical
movements were normal and horizontal motility
exam demonstrated a left internuclear ophthal-
moplegia
(INO -damage to the left medial longitudinal
fasciculus [MLF]) and left horizontal gaze palsy
(damage to left 6th nucleus affecting fibers
destined for left lateral rectus and interneurons
destined for right medial rectus via right MLF),
List of Videos\Electronic Supplemental Materials (ESM) cxiii
and a partial right 6th nerve palsy, related to injury

of the right 6th fascicle. The combination of left
INO and left horizontal gaze palsy is also referred
to as a one-and-a-half syndrome. Disjunctive
nystagmus is common in OPT, and given the
proximity of the descending central tegmental tract
(CTT) to the fascicle/nucleus of CN6 and MLF,
horizontal motility deficits may cause disjunctive
horizontal components as in this patient who
couldn’t adduct or abduct OS (i.e., nystagmus was
pure vertical OS). Typically, pendular nystagmus in
OPT is vertical, torsional, or vertical-torsional,
although there may be horizontal components as
well, sometimes with a convergent-divergent
pattern. Review of a recently obtained MRI
showed hyperintensity of the left inferior olive (IO)
on MRI T2/FLAIR sequences due to hypertropic
olivary degeneration (HOD). In his case, HOD was
related to injury of the descending central tegmen-
tal tract (CTT) as it passed through the pons,
thereby removing normal inhibition of the IO by
the CTT. (Video and legend created with the
assistance of Dr. Tony Brune) https://collections.
lib.utah.edu/ark:/87278/s6wh6sfc
Video 5.24 Subtle torsional pendular nystagmus in oculo-
palatal tremor (OPT): This patient presented with
imbalance, and MRI demonstrated a right cerebel-
lar cavernous malformation. She underwent
surgery to resect the malformation, and post-opera-
tively experienced right hemiparesis and ataxia.
Six months after the surgery, balance worsened and
vision became “blurry” despite normal afferent
function. Exam demonstrated mild torsional
pendular nystagmus OU and subtle rhythmic
twitching of the right mentalis (not seen in the
video). Palatal tremor was also seen, synchronous
with the facial muscle twitching. When the patient
was asked to gently close her eyes, vertical ocular
cxiv List of Videos\Electronic Supplemental Materials (ESM)
oscillations (again synchronous with the palatal

tremor) were apparent. Even when nystagmus due
to oculopalatal tremor (OPT) is subtle or absent,
eyelid closure will usually bring out (e.g., palatal
tremor without nystagmus is usually seen with
progressive ataxia and palatal tremor [PAPT],
although rhythmic oscillations can still be brought
out with gentle eyelid closure) or accentuate
vertical ocular oscillations, a finding that is
sometimes referred to as ocular synchrony. MRI
T2/FLAIR sequences demonstrated a hyperintense
left inferior olivary nucleus (figure), consistent
with the theory of olivary hypertrophy, which is
thought to generate OPT. When pendular nystag-
mus of unclear origin is appreciated, regardless of
whether it is subtle, monocular, disjunctive,
dissociated or conjugate, the examiner must have a
suspicion for OPT and view the palate at rest.
https://collections.lib.utah.edu/ark:/87278/s6rc1227
Video 5.25 Eyelid closure and oculopalatal tremor (ocular
synchrony): The first patient in this video suffered
a traumatic brain injury with brainstem injury
resulting in damage to Mollaret’s triangle and
palatal tremor. Inferior olivary hypertrophy was
noted on her MRI, although no vertical and/or
torsional pendular nystagmus was present even
when observing closely with the ophthalmoscope.
However, when she was asked to close her eyes,
large amplitude vertical ocular oscillations were
appreciated. When her eyes were observed with
infrared video goggles in the dark, no oscillations
were present; therefore, the oscillations seem to
result from the eyelid closure itself rather than
removal of visual inputs. A second patient with
progressive ataxia and palatal tremor (PAPT)
demonstrated the same finding of palato-ocular or
simply ocular synchrony, and the exact mechanism
is not well understood. It can be seen in patients
List of Videos\Electronic Supplemental Materials (ESM) cxv
who have pendular nystagmus at baseline, or in

patients with palatal tremor and inferior olivary
hypertrophy who have no spontaneous nystagmus,
as in these two patients. https://collections.lib.utah.
edu/ark:/87278/s68665bw
Video 5.26 Acquired pendular nystagmus (APN) multiple
sclerosis (MS): This patient had a 15 year history
of MS, and for the last 12 months, he experienced
horizontal oscillopsia. On examination, there were
central ocular motor abnormalities including
gaze-evoked nystagmus, saccadic smooth pursuit,
and hypermetric saccades which were attributable
to his posterior fossa demyelinating disease.
Additionally, there was horizontal pendular
nystagmus, and this abated briefly with the
termination of saccades and with blinks, both of
which commonly suppress APN (albeit tran-
siently). His vision was 20/100 OU with 0/10 HRR
plates OU with temporal pallor OU. Because
pendular nystagmus is commonly seen in MS
patients, it has been suggested that the nystagmus
might result from a prolonged response time for
visual processing, supported by the fact that
nystagmus is commonly more intense in the eye
with poorer vision. However, pendular nystagmus
doesn’t change with visual feedback removed, and
inducing visual delays by itself is not capable of
causing the oscillations seen in MS. Therefore, it’s
likely that instability in the neural integrator (gaze
holding machinery) plays a significant role in
many cases, and his severe posterior fossa disease
was likely to have contributed to neural integrator
dysfunction. https://collections.lib.utah.edu/
ark:/87278/s6nc9v0z
Video 5.27 Elliptical acquired pendular nystagmus (APN)
in multiple sclerosis (MS): This patient with a
10+ year history of MS and bilateral optic nerve
disease presented oscillopsia for 1 year, due to
cxvi List of Videos\Electronic Supplemental Materials (ESM)
elliptical APN which seen on exam. The appear-

ance of elliptical nystagmus is the result of out of
phase horizontal and vertical (pendular) compo-
nents, and can be especially visually debilitating.
She had a variety of posterior fossa lesions on
MRI, and there was mild improvement with
gabapentin. https://collections.lib.utah.edu/
ark:/87278/s6qn9w2n
Video 5.28 Elliptical acquired pendular nystagmus (APN)
of unknown etiology suppressed by blinks and
saccades: This is a 70-year-old man who experi-
enced the gradual onset of oscillopsia over weeks
about 3 months prior to this video recording.
Examination demonstrated elliptical pendular
nystagmus which was atypical for infantile
nystagmus or oculopalatal tremor (no palatal
tremor on exam, and no inferior olivary hyperin-
tensity on MRI). The remainder of the ocular
motor and neurologic exam was normal. Contrast-
enhanced MRI months prior was normal. Consis-
tent with APN, the movements briefly suppressed
following blinks, and suppressed to a more
significant degree following saccades. One theory
for APN is that it is due to an unstable neural
integrator. In this case, blinking and saccades may
serve to reset this unstable system, albeit tran-
siently. This patient remained stable and work-up
remained unremarkable for at least 6 months.
s6673nxw
Video 5.29 Monocular horizontal acquired pendular
nystagmus in multiple sclerosis (MS): Seen here
are two patients, both with MS and monocular
(OS) horizontal pendular nystagmus causing
monocular oscillopsia. The first patient seen in the
video has normal afferent function and no evidence
of optic nerve disease in either eye, while the
second patient has severe OS>OD optic nerve
List of Videos\Electronic Supplemental Materials (ESM) cxvii
disease related to multiple episodes of optic

neuritis (there was also a slight torsional pendular
nystagmus component). Although rare, when APN
occurs it is typically due to MS (or oculopalatal
tremor), it has been suggested that the nystagmus
might result from a prolonged response time for
visual processing, supported by the fact that
nystagmus is commonly more intense in the eye
with poorer vision. However, APN doesn’t change
with visual feedback removed, and inducing visual
delays by itself is not capable of causing the
oscillations seen in MS. Therefore, it’s likely that
instability in the neural integrator (gaze holding
machinery) also plays a significant role in many
cases. Explanations for monocular pendular
nystagmus in these patients includes 1) ipsilateral
afferent dysfunction or 2) perhaps within the
unstable neural integrator, certain monocular-pro-
jecting cell populations are preferentially damaged.
https://collections.lib.utah.edu/ark:/87278/s6q852cf
Video 5.30 The appearance of infantile nystagmus in adults:
Seen here are two adult patients with infantile
nystagmus demonstrating characteristic features
including: mixed pendular and jerk nystagmus
(usually gaze-evoked) waveforms; nystagmus is
horizontal even in vertical gaze; nystagmus damps
with convergence; strabismus and a latent nystag-
mus component (common but not always present);
association with albinism. Also, there is often a null
point where nystagmus is minimal, and optokinetic
nystagmus may be in the opposite direction of what
would be expected given the direction of an
optokinetic stimulus. https://collections.lib.utah.
edu/ark:/87278/s67693mg
Video 5.31 Common ocular motor and neurologic signs in
progressive supranuclear palsy (PSP): Seen in
this video are convergence insufficiency (frequent
closure of the right eye to minimize diplopia),
cxviii List of Videos\Electronic Supplemental Materials (ESM)
supranuclear gaze palsy (with sparing of the

vertical vestibulo-ocular reflex), saccadic smooth
pursuit and VOR suppression, hypometric horizon-
tal saccades, square wave jerks, astonished facies
with eyelid retraction, procerus sign, and the
applause sign. https://collections.lib.utah.edu/
ark:/87278/s60p4nv0
Video 5.32 Saccadic intrusions and oscillations with an
intersaccadic interval: Seen here are patients with
saccadic intrusions that have intersaccadic intervals.
When square wave jerks are prominent or when
they interfere with visual fixation, neurodegenera-
tive conditions should be considered, mainly those
involving the posterior fossa (e.g., cerebellar
degeneration, tumors) and the basal ganglia (e.g.,
progressive supranuclear palsy, Parkinson’s
disease). Macrosaccadic oscillations are often
associated with significant saccadic hypermetria
due to cerebellar pathology, which was true of the
last patient in this video. https://collections.lib.utah.
edu/ark:/87278/s6gr0mmz
Video 5.33 Ocular bobbing: This patient with hepatic enceph-
alopathy developed abnormal eye movements
consistent with ocular bobbing. Head CT did not
show any acute changes. Ocular bobbing almost
always localizes to the pons, although cerebellar
pathology has also (rarely) been identified as a
cause. Typical bobbing consists of rhythmic, down-
ward jerks followed by a slower return to primary
position. Horizontal eye movements are usually
absent. Other patterns may be seen include:
atypical bobbing, which is similar to typical
bobbing, but with some residual horizontal gaze;
pretectal V-pattern pseudo-bobbing, which consists
of downward and convergent jerks with a slow
return to primary gaze (usually related to obstruc-
tive hydrocephalus; reverse bobbing, which
consists of a rapid upward jerks with a slow return
List of Videos\Electronic Supplemental Materials (ESM) cxix
to primary position; ocular dipping or inverse

bobbing, which consists of slow downward
movements over 2 seconds, remaining in down-
gaze for 2–10 seconds followed by a rapid move-
ment upward to primary gaze; converse bobbing,
which consists of an initial slow upward movement
over 1–5 seconds, remaining in upgaze for 1–10
seconds followed by a rapid movement downward
to primary gaze. (Video courtesy of Dr. Stephen
Reich) https://collections.lib.utah.edu/ark:/87278/
s6vx45c3
Video 5.34 Post-infectious ocular flutter and myoclonus
syndrome: This patient presented with oscillopsia
following a viral illness. She described being easily
startled, with “shakiness” of the head/neck and
body. She had myoclonus and ocular flutter (no
intersaccadic interval), with the latter especially
evident following saccades. Convergence and
gentle eyelid closure are other ways to provoke
flutter or opsoclonus. https://collections.lib.utah.
edu/ark:/87278/s6fr3jwj
Video 5.35 Opsoclonus provoked by convergence: This
patient experienced a parainfectious opsoclonus-
myoclonus syndrome. Opsoclonus was intermit-
tently evident in primary position, but was
consistently provoked by convergence. Occasion-
ally, opsoclonus (back-to-back saccades in
horizontal, vertical, torsional planes without an
intersaccadic interval) or ocular flutter (in the
horizontal plane only) can be subtle or even
difficult to distinguish from high frequency jerk
nystagmus. However, these saccadic oscillations
can be provoked with certain maneuvers such as
eyelid closure (i.e., observing the corneal bulge
under eyelids), following voluntary saccades, or
with convergence. The underlying pathophysiology
of opsoclonus/flutter is thought to relate to one or
more of the following: heightened membrane
cxx List of Videos\Electronic Supplemental Materials (ESM)
excitability of the glutaminergic excitatory burst

neurons (EBN); increasing firing when EBNs are
released from inhibitory release from omnipause
cells (which inhibit burst neurons during fixation),
referred to as post-inhibitory rebound; decreased
glycinergic (omnipause cell) inhibition. https://
collections.lib.utah.edu/ark:/87278/s6b02t5j
Video 5.36 Voluntary ocular flutter: This patient experienced
intermittent complaints of horizontal oscillopsia
for 1 year. On examination, all classes of eye
movements were normal, and neurologic examina-
tion was normal. MRI of the brain had been
performed previously and was normal. When
viewing any visual target at near, rapid horizontal
back-to-back saccades without a clear intersac-
cadic interval were seen. The flutter-like move-
ments only occurred with a convergence effort, and
miosis was noted as well. They could only be
sustained for several seconds at a time and
voluntary flutter was diagnosed. https://collections.
lib.utah.edu/ark:/87278/s6t18rxj
Video 5.37 Superior oblique myokymia (SOM): This patient
presented with episodes of monocular oscillopsia
and vertical diplopia due to right SOM. The primary
action of the superior oblique (SO) is incycloduc-
tion, which generated the quick phase of these
movements resulting in oscillopsia OD. The
secondary action of the SO is depression, which was
responsible for a right hypotropia resulting in
binocular vertical diplopia. https://collections.lib.
utah.edu/ark:/87278/s69w3q5b
Video 5.38 Prominent monocular elliptical pendular
nystagmus in multiple sclerosis (MS): This is a
patient who experienced bilateral attacks of optic
neuritis (OS>OD) decades prior, was subsequently
diagnosed with MS, and more recently experienced
monocular oscillopsia due to elliptical pendular
nystagmus in the left eye only. Even with ophthal-
List of Videos\Electronic Supplemental Materials (ESM) cxxi
moscopy OD, there was no trace of nystagmus.

https://collections.lib.utah.edu/ark:/87278/s6352s3s
Video 5.39 Superior oblique myokymia (SOM) as seen with
videooculography and Frenzel goggles: Patients
with superior oblique myokymia (SOM) com-
monly present with complaints of monocular
oscillopsia and/or vertical diplopia, which are
related to the primary and secondary actions of the
SO (incycloduction and depression, respectively).
In many cases, SOM represents a neurovascular
compression syndrome involving the 4th cranial
nerve, although irritation by a compressive mass
lesion is also possible. Additionally, the clinician
should consider SOM in any patient complaining
of transient visual symptoms or blurriness that last
for <5 seconds and occur many times throughout
the day. Monocular blurriness can result from
alternating contraction and relaxation of the
affected SO. Binocular blurriness can result from
subtle vertical-torsional ocular misalignment
during attacks. In each case, the SOM was subtle
and could only be appreciated with the slit lamp,
ophthalmoscope, video-oculography (VOG), or
with the magnification of Frenzel goggles. Each of
the three patients here responded well to gabapen-
tin, although a variety of other anti-seizure
medications may be beneficial. Unfortunately,
there is no robust evidence for one particular
therapy over another, and randomized controlled
trials are lacking for SOM. https://collections.lib.
utah.edu/ark:/87278/s6993k7q
ESM 6.1 An introduction to audiometry
ESM 6.2 An introduction to video head impulse testing
ESM 6.3 An introduction to electronystagmography (ENG),
and videonystagmography (VNG) or videooculog-
raphy (VOG)
ESM 6.4 An introduction to rotary chair testing
ESM 6.5 An introduction to caloric testing
cxxii List of Videos\Electronic Supplemental Materials (ESM)
ESM 6.6 An introduction to vestibular evoked myogenic

potentials
ESM 6.7 A flowsheet approach to the patient with acute
onset prolonged vertigo
ESM 6.8 A flowsheet approach to the patient with (recent
onset) spontaneous episodic vestibular syndrome
ESM 6.9 An optokinetic stimulation home exercise program
Video 6.1 Evaluating dynamic visual acuity: After assess-
ing static binocular visual acuity, dynamic visual
acuity (DVA) is determined by repeating the test
during horizontal and vertical head shaking at 2–3
Hz. Dynamic visual acuity is most important to test
when bilateral vestibular loss is suspected. A loss
of at least 4 lines is typical of bilateral vestibular
loss (generally horizontally and vertically), and
normal patients without vestibular loss should not
lose more than 1 line or so on the acuity chart.
Patients with unilateral vestibular loss may loss
2–3 lines on the acuity chart (usually horizontal
DVA is more impaired than vertical DVA), and this
can vary with the chronicity and degree of vestibu-
lar loss https://collections.lib.utah.edu/
details?id=1307318. (Video and legend created
Bosley)
Video 6.2 Evaluating the vestibulo-ocular reflex (VOR)
with visually enhanced VOR (vVOR) and head
impulse test (HIT): (1) vVOR—since smooth
pursuit and VOR systems are both active during
slow head movements, if eye movements are
choppy/saccadic with this maneuver, this means that
there is impairment of both pursuit (often cerebellar)
and vestibular systems (usually bilateral vestibular
loss) as in cerebellar ataxia, neuropathy, vestibular
areflexia syndrome (CANVAS). (2) HIT—since
smooth pursuit cannot supplement the VOR at high
frequencies, an HIT allows the examiner to isolate
List of Videos\Electronic Supplemental Materials (ESM) cxxiii
and evaluate only the VOR. During a normal HIT,

the patient’s eyes stay fixated on the visual target
(usually the examiner’s nose) during high velocity
low amplitude head impulses, as in this case. When
the head is moved horizontally, the horizontal canals
are mainly being evaluated (with minimal contribu-
tion from vertical semicircular canals), although
the HIT can be performed to evaluate anterior and
posterior canals as well https://collections.lib.utah.
edu/details?id=187678
Video 6.3 Ramsay-Hunt syndrome causing unilateral
deafness, and abnormal head impulse test
involving all three semicircular canals: This
patient experienced the onset of right facial
weakness, vertigo and right hearing loss over
several hours, and was found to have a right lower
motor neuron facial nerve palsy, deafness in the
right ear, spontaneous left-beating nystagmus, and
vesicles were noted in and around the right
external acoustic meatus on otoscopy, leading to
the diagnosis of herpes zoster infection (Ramsay-
Hunt syndrome). Steroids and anti-virals were
given acutely. This examination was performed
several weeks later, and there were abnormal head
impulses in the planes of right horizontal, anterior,
and posterior semicircular canals. Severe unilateral
vestibular loss was responsible for his significant
head movement dependent oscillopsia, which
improves with time and physical therapy. https://
collections.lib.utah.edu/ark:/87278/s68s7zm7
Video 6.4 Video head impulse test (HIT) demonstrating
bilateral vestibular loss: Bilateral vestibular loss
is a common cause of head movement-dependent
oscillopsia, and in these patients, evaluating the
vestibulo-ocular reflex (VOR) is essential. While
the bedside HIT is usually enough to make the
diagnosis of unilateral or bilateral vestibular loss,
the video HIT has advantages: 1) overt corrective
cxxiv List of Videos\Electronic Supplemental Materials (ESM)
saccades can be identified (occurring after the head

movement, visible to the examiner at the bedside,
black arrow), 2) covert corrective saccades can be
identified (occurring during the head movement,
and can be invisible at the bedside, black arrow-
head), 3) a gain can be calculated to quantify the
VOR (gain = ratio of eye movement velocity to
head movement velocity, where typically a value
below 0.6–0.7 is considered abnormal). In this
case, the gains in the planes of the left and right
horizontal (lateral) canals were 0.18 and 0.38,
respectively, and consistent with bilateral vestibu-
lar loss https://collections.lib.utah.edu/ark:/87278/
s6t20cf1. (Video and legend created with the
assistance of Justin Bosley)
Video 6.5 Provocative maneuvers to accentuate or
provoke peripheral vestibular nystagmus—
removal of fixation, vibration, head-shaking:
With an acute destructive process like vestibular
neuritis that causes significant unilateral vestibular
loss, spontaneous nystagmus is always present.
However, over days to months, spontaneous
nystagmus should resolve completely. In a patient
with vestibular neuritis involving the right side,
left-beating mixed horizontal-torsional spontane-
ous nystagmus will be seen acutely. Over weeks,
compensatory processes will take place (centrally
and peripherally) and the patient may only have
mild left-beating nystagmus with removal of
fixation—e.g., while wearing the infrared video
goggles (such as used in this video). Certain
provocative maneuvers will transiently increase
vestibular imbalance, causing an increase in
left-beating nystagmus in a patient post right
vestibular nystagmus. These maneuvers are ideally
performed with fixation removed since peripheral
vestibular nystagmus is maximal under this
condition. Vibration-induced nystagmus is usually
List of Videos\Electronic Supplemental Materials (ESM) cxxv
a sign of vestibular asymmetry. Vibration is applied

to each mastoid and to the vertex of the cranium.
Bony transmission of vibration (when the vibrator
is placed on one mastoid or over the vertex)
simultaneously stimulates the right and left
vestibular apparatus. In a patient with right
unilateral vestibular loss, vibration will cause (or
accentuate) a rightward (ipsilateral) slow phase,
and this is followed by a leftward (contralateral)
fast phase. Head-shaking nystagmus is assessed
after 10–15 cycles of 2 Hz head-shaking in the
horizontal and vertical planes. Nystagmus can be
induced with either central or peripheral vestibular
disease. In a patient with right unilateral vestibular
loss, horizontal head-shaking will cause (or
accentuate) a rightward (ipsilateral) slow phase,
and this is followed by a leftward (contralateral)
fast phase. In central disorders, a spontaneous
horizontal nystagmus may reverse directions
(usually lateral medullary syndrome) or a vertical
(usually downbeat with lesions involving the
flocculus) nystagmus may be seen after horizontal
head shaking. NOTE: This video is intended to
demonstrate the techniques for examination using
provocative maneuvers. The subject depicted does
not have nystagmus in this demonstration https://
collections.lib.utah.edu/details?id=1307321.
(Video and legend created with the assistance of
Dr. Tony Brune and Justin Bosley)
Video 6.6 Vibration-induced nystagmus in a patient with
acute vestibular neuritis: This is a 60-year-old
man who experienced the sudden onset of vertigo,
oscillopsia, imbalance, nausea and vomiting. He
was seen in the emergency department within
hours and had spontaneous right-beating (RBN)
and torsional (top poles toward right ear) nystag-
mus that was unidirectional in all directions of
gaze; an abnormal head impulse test to the left side
cxxvi List of Videos\Electronic Supplemental Materials (ESM)
(a corrective saccade with head impulses to the

left); and a negative test of skew (no vertical
refixation movement with alternate cover testing);
and there was no unilateral hearing loss. Taken
together, his exam suggested a peripheral (benign)
pattern of the HINTS “Plus” exam (Head Impulse,
Nystagmus, Test of Skew, where “Plus” refers to
whether hearing loss is present), and a diagnosis of
left vestibular neuritis was made. One week later,
the patient was seen as an outpatient. The sponta-
neous RBN was much less prominent and the
patient was much less symptomatic. A video head
impulse test (vHIT) was performed, which
demonstrated the corrective saccades seen at the
bedside, as well as a gain asymmetry between the
impaired (left) and normal (right) sides. It was felt
that the gain was >1 to the right mainly due to
goggle slippage during the vHIT. This may have
increased the gain on the impaired side as well.
With horizontal head-shaking and vibration, the
baseline RBN increased substantially. Seen in the
video is the vibration-induced RBN. Skull vibra-
tion induces nystagmus with unilateral vestibular
loss (slow phase toward the paretic ear) that is
time-locked to the vibratory stimulation. It also
beats in the same direction regardless of whether
the right or left mastoid is stimulated, or whether
the vibrator is placed over the vertex. This is
because the stimulus is effectively transmitted to
both labyrinths. Since vibration is a stimulus that
excites semicircular neurons, when vestibular
asymmetry exists (e.g., left peripheral vestibulopa-
thy due to vestibular neuritis), the unaffected
(right) side will be activated normally while the
affected (left) side will not. This will create a slow
phase drift toward the paretic ear as in this patient
with a contralesional nystagmus https://collections.
lib.utah.edu/ark:/87278/s66t541n
List of Videos\Electronic Supplemental Materials (ESM) cxxvii
Video 6.7 Head-shaking-induced nystagmus in a patient

with previous vestibular neuritis: This patient
experienced the abrupt onset of imbalance,
dizziness and left-sided hearing loss 4 months prior
to this examination. He was found to have herpetic
vesicles in the left external auditory canal and
diagnosed with Ramsay Hunt syndrome. On exam
(4 months after the onset), there was an abnormal
head impulse test (HIT) to the left side, and with
fixation-removed, there was very mild right-beat-
ing nystagmus. However, following 15 seconds of
2–3 Hz horizontal head-shaking, there was robust
right-beating nystagmus. Video HIT showed
left-sided vestibular loss with low gains (<0.7—
gain is calculated with this system as the area
under the eye movement velocity curve/area under
the head movement velocity curve) and corrective
saccades in the planes of the horizontal, anterior
and posterior canals, which is commonly seen with
Ramsay Hunt syndrome. Ewald’s second law states
that ampullopetal endolymph flow will cause
greater stimulation than ampullofugal flow within
the horizontal canals. Head-shaking, therefore,
leads to transiently asymmetric vestibular afferents
when unilateral vestibular loss is present, leading
to a contralesional post-head-shake nystagmus as
in this patient. Head-shaking is one of several
provocative maneuvers that can bring out a
patient’s underlying vestibular asymmetry months
or even years after the insult occurs (vibration and
hyperventilation are others) https://collections.lib.
utah.edu/ark:/87278/s6f80x5q
Video 6.8 Intense head-shaking-induced nystagmus
without unilateral vestibular loss – a ‘central’
sign and its relationship to velocity storage:
Evaluating for nystagmus provoked by head-shak-
ing, so-called head-shaking nystagmus (HSN),
should be performed in all patients with complaints
of dizziness or vertigo, regardless of the chronicity.
cxxviii List of Videos\Electronic Supplemental Materials (ESM)
The maneuver is performed by passively moving

the head horizontally (can also be performed
vertically) at 2 Hz for about 15 cycles, and can
help in differentiation of peripheral versus central
etiologies. Peripheral vestibular loss – e.g., in a
patient with right sided vestibular neuritis, sponta-
neous left-beating nystagmus (LBN) is seen
acutely, and over time only mild fixation removed
LBN will be appreciated. Because of Ewald’s
second law which states that ampullopetal endo-
lymph flow will cause greater stimulation than
ampullofugal flow within the horizontal canals,
head-shaking will lead to transient, but clinically
meaningful, asymmetric vestibular afferents even
after central compensation has occurred. With a
subacute or chronic right unilateral vestibulopathy,
fixation-removed LBN is seen and will increase
following horizontal head-shaking. A velocity
storage mechanism exists to assist in the prolonga-
tion of labyrinthine semicircular canal inputs,
beyond the mechanical constraints of the labyrin-
thine structures. Without such a mechanism,
vestibular afferents would cease firing after just a
few seconds of sustained rotational stimuli given
the mechanical properties of the cupula and
endolymph. Therefore, a central mechanism must
be in place to prolong these signals, especially
during sustained rotations. It is mainly thought that
central patterns of HSN relate to dysfunction of the
central velocity storage mechanisms. Lesions
causing central HSN usually involve the GABA-
ergic inhibitory projections from nodulouvular
regions to vestibular nucleus, which can result in
the disinhibition of velocity storage. Central
patterns include 1) unusually robust HSN elicited
by weak head-shaking, 2) strongly biphasic HSN,
3) nystagmus that reverses direction after head-
shaking (e.g., LBN becomes RBN), 4) strong HSN
in patients without clear unilateral vestibular loss
List of Videos\Electronic Supplemental Materials (ESM) cxxix
(this patient), or 5) cross-coupled HSN (e.g.,

vertical nystagmus after horizontal head-shaking,
usually downbeat and associated with vestibulocer-
ebellar lesions). (Video and legend created with the
assistance of Dr. Kemar Green) https://collections.
lib.utah.edu/details?id=
1295175. (Video and legend created with the
assistance of Dr. Kemar Green)
Video 6.9 Cross-coupled head-shaking-induced nystag-
mus—a “central” sign: This patient had spontane-
ous torsional nystagmus with the top poles of the
eyes beating toward the right ear in all directions of
gaze, and following horizontal head-shaking (HS),
there was downbeat nystagmus (so-called “cross-
couping” nystagmus given vertical nystagmus after
horizontal HS), which is a well-described central
pattern. This cross-coupled response is usually due
to a vestibulocerebellar lesion (likely flocculus or
nodulus), and in cases with flocculus impairment,
it may be related to disinhibition of the (upward or
anti-gravity) anterior canal (AC) pathways.
Horizontal HS can therefore cause an upward bias
due to uninhibited AC pathways (while horizontal
canals are mainly stimulating with horizontal HS,
so too are the vertical canals), with a resultant
downward fast phase causing downbeat nystagmus
s6m08nrv
Video 6.10 Evaluating for pressure-induced nystagmus:
Superior canal dehiscence syndrome (SCDS) is
caused by a third mobile window in the inner ear.
This allows for transmission of sound or pressure
to the superior canal. Tragal compression and/or
glottic and pinched nose Valsalva may provoke
vertigo and vertical-torsional nystagmus in the
plane of the superior (anterior) canal. As an
example, a patient with right SCDS may have
downbeat-torsional (toward right ear) nystagmus
provoked by pinched nose Valsalva, which is an
cxxx List of Videos\Electronic Supplemental Materials (ESM)
excitatory pattern of nystagmus. Nystagmus and

vertigo are also commonly triggered by loud
environmental noises, or provoked by loud tones in
the clinic https://collections.lib.utah.edu/
Bosley)
Video 6.11 Nystagmus in superior canal dehiscence
syndrome (SCDS) provoked by pinched-nose
Valsalva: This patient complained of autophony
(e.g., hearing his own heartbeat, noting that his
own voice sounded too loud) and dizziness
triggered with loud noises and straining at times.
With pinched-nose Valsalva maneuver, there was
downbeat-torsional (toward the right ear) nystag-
mus, suggestive of excitation of the right anterior
canal (slow phase down and torsion toward left ear,
with position reset/fast phase in the opposite
directions). There was more downbeat nystagmus
in right gaze, and more torsional (toward right ear)
nystagmus in left gaze. Superior canal dehiscence
(SCD) was demonstrated on the right side on CT
temporal bones and SCD syndrome was diagnosed.
Valsalva and pinched-nose/nasal Valsalva maneu-
vers should be performed when there is a suspicion
for SCDS (noise/pressure triggers, autophony +
vertigo attacks, etc.) https://collections.lib.utah.
edu/details?id=1213443, https://collections.lib.
utah.edu/ark:/87278/s6md2nwh. (Video courtesy
of Dr. John Carey)
Video 6.12 Evaluating for hyperventilation-induced
nystagmus: Hyperventilation induced nystagmus
is tested by asking the patient to take quick deep
breaths (~1/s) for 40–60 seconds. This decreases
ICP and increases CSF pH. This can be helpful in
diagnosing irritative conditions of the vestibular
nerve, including a vestibular schwannoma or
neurovascular compression (vestibular paroxys-
List of Videos\Electronic Supplemental Materials (ESM) cxxxi
mia). With these irritative disorders, nystagmus is

usually in an excitatory pattern with contralateral
slow phases and fast phases directed toward the
side of the lesion (in contrast to a paretic or
inhibitory pattern where the slow phase is ipsile-
sional). Hyperventilation can also accentuate the
nystagmus of unilateral vestibular loss due to
transient central decompensation. In cerebellar
disease (e.g., spinocerebellar ataxia), a downbeat
nystagmus may be provoked or accentuated due to
pH-induced exacerbation of cerebellar Purkinje
fiber calcium channel dysfunction https://collec-
tions.lib.utah.edu/details?id=1307319. (Video and
legend created with the assistance of Dr. Tony
Brune and Justin Bosley)
Video 6.13 Vibration and hyperventilation-induced
nystagmus due to vestibular schwannoma: This
patient presented with imbalance, and with fixation
removed on her examination (with Frenzel
goggles), there was no spontaneous nystagmus.
Using a handheld vibrator to vibrate the mastoids
and vertex, there was a rightward slow phase and
corrective leftward fast phase (left-beating nystag-
mus). Vibration is an excitatory vestibular stimu-
lus, and when vestibular asymmetry is present,
vibration can transiently exacerbate this asymme-
try and generate a slow phase that is ipsilateral to
the pathology/vestibular hypofunction (toward the
right in this case). After hyperventilating the
patient for 40 seconds, there was robust right-beat-
ing and torsional (toward right ear) nystagmus.
Hyperventilation transiently alters neuronal
conductivity across a demyelinated segment of the
eighth cranial nerve (e.g., acoustic neuroma or neu-
rovascular compression), and can generate
excitatory> inhibitory pattern of nystagmus
(excitatory in this case with contralesional,
leftward slow phase, and ipsilesional, rightward
cxxxii List of Videos\Electronic Supplemental Materials (ESM)
fast phases). MRI demonstrated a right-sided

vestibular schwannoma which explained both the
right hypofunction (LBN with vibration), and the
excitatory pattern (RBN) of her hyperventilation-
induced nystagmus https://collections.lib.utah.edu/
details?id=1213447
Video 6.14 Hyperventilation-induced downbeat nystagmus
in a cerebellar disorder: This patient presented
with a chronic progressive cerebellar degeneration
of unclear etiology (worsening over at least 10
years) characterized by gait and limb ataxia,
gaze-evoked nystagmus, saccadic pursuit and
vestibulo-ocular reflex suppression, an esotropia
greater at distance, along with very mild downbeat
nystagmus (DBN), mainly seen with the ophthal-
moscope. This constellation of ocular motor signs
localizes well to the flocculus/paraflocculus.
Following 40 seconds of hyperventilation, which
induces alkalosis and alters intra- and extracellular
calcium concentrations, she demonstrated promi-
nent DBN. This finding has been described in
patients with cerebellar pathology, and has been
theorized to relate to sensitivity of cerebellar
voltage-gated calcium channels (e.g., P/Q-type or
other abnormal ion channels) to the alkalosis
induced by hyperventilation https://collections.lib.
utah.edu/ark:/87278/s6g77x3f
Video 6.15 The virtual (telemedicine) vestibular examina-
tion: This video demonstrates one approach to
performing the vestibular examination virtually in
a normal subject https://collections.lib.utah.edu/
ark:/87278/s6sj78fz. (Video created with the
assistance of Dr. Olwen Murphy)
Video 6.16 Evaluating auditory function with Rinne and
Weber tests: The Rinne test is an assessment of
auditory thresholds to air and bone conduction of
sound. The Weber test is a comparison of bone
conducted sound of either ear. Conductive hearing
List of Videos\Electronic Supplemental Materials (ESM) cxxxiii
loss results in a loss of air conducted greater than

bone conducted sound, whereas sensorineural
hearing loss results in the loss of both air and bone
conducted sound. Peripheral vestibular disease
affecting the labyrinth or the eighth cranial nerve
can be associated with sensorineural hearing loss.
In these cases, the sensitivity to air conduction will
remain greater than to bone conduction. Weber will
lateralize away from the side of sensorineural
hearing loss. As an example, destruction of the
right labyrinth (e.g., bacterial labyrinthitis) will
cause decreased hearing in the right ear, and air
conduction will be greater than bone conduction in
the right (affected) and left (unaffected) ears.
Weber will lateralize to the left (unaffected) ear. In
the case of superior semicircular canal dehiscence
(SCDS), there may be increased sensitivity to bony
transmission of sound through a (third mobile
window) as well as conductive hearing loss, with
bone conduction greater than air conduction and
Weber lateralizing to the side of the dehiscence. A
bedside test used for SCDS that highlights this
increased sensitivity to bony transmission of sound
involves placing a tuning fork on the malleolus,
and in patients with SCDS, it may be heard in the
affected ear https://collections.lib.utah.edu/
Bosley)
Video 6.17 A “peripheral” HINTS exam in acute vestibular
neuritis: This patient presented with the acute
vestibular syndrome, and on examination, had
left-beating nystagmus and an abnormal head
impulse test to the right (a catch-up saccade can be
seen as her head is moved quickly to the right—her
eyes move with the head to the right for a split
second given loss of the vestibulo-ocular reflex,
and there is a catch-up saccade back to the left so
cxxxiv List of Videos\Electronic Supplemental Materials (ESM)
she can refixate on the target) are both explained

by acute loss of vestibular function on the right
side (right-sided vestibular neuritis). There was no
skew deviation and no hearing loss. As the
vestibular neuritis decreases the baseline tonic
activity of the affected (right) eighth cranial nerve,
there is relative hyperactivity involving the left
eighth cranial nerve, which leads to the false
perception of leftward head turning. In response,
rightward slow phases are generated, which
represents the slow (pathologic) phase of her
nystagmus. The rightward fast phase is the position
reset mechanism and creates the rhythmic slow and
fast phases. Her left-beating nystagmus (LBN) is
unidirectional—i.e., it remains LB in all directions
of gaze—and follows Alexander’s law where the
nystagmus increases in intensity in the direction of
the fast phase (to the left in this case). If unidirec-
tional nystagmus is seen beating to the left, an
abnormal head impulse to the right must be seen to
reassure the clinician that this is a peripheral
etiology. Additionally, a skew deviation must be
absent, and unilateral hearing loss (ipsilateral to
the side of the unilateral vestibular loss) should be
absent. When acute unilateral hearing loss is
present, labyrinthine ischemia should be consid-
ered, which is the rationale for the 4-step HINTS+
exam (Head Impulse, Nystagmus, Test of Skew, +
evaluation of auditory function). This patient had a
“peripheral” HINTS pattern, and MRI (while not
necessary, was already completed) was unrevealing
s6546h55s
Video 6.18 A “central” HINTS exam in an acute lateral
pontine/middle cerebellar peduncle (MCP)
demyelinating lesion: This patient presented with
vertigo, diplopia and mild left facial weakness (not
seen in the video). On exam, there was right-beat-
List of Videos\Electronic Supplemental Materials (ESM) cxxxv
ing nystagmus (RBN) in primary gaze that

increased in right gaze (in accordance with
Alexander’s law), and the RBN stayed unidirec-
tional, but lessened, in left gaze. This is a pattern
of nystagmus that is usually peripheral, especially
when nystagmus increases when fixation is
removed. However, this can also be central,
especially when there is no change in nystagmus
with removal of fixation. There was a positive or
abnormal head impulse test (HIT) with leftward
impulses of the head, which is also usually a sign
of peripheral pathology. With alternate cover
testing, there was a right hyperdeviation, which
was comitant and associated with a left head tilt
and leftward ocular counterroll (top poles of the
eyes toward the left ear). Taken together, this was
thought to be related to utricle pathway pathology
causing an ocular tilt reaction, with the skew
deviation responsible for his diplopia. Using
HINTS (Head Impulse, Nystagmus, Test of Skew),
the presence of a skew deviation should lead the
examiner to assume a “central” etiology until
proven otherwise, despite the “peripheral” appear-
ance of the nystagmus and HIT. It is important to
note that while unidirectional nystagmus and an
abnormal HIT can suggest a peripheral etiology,
either one can be seen with a central etiology. A
skew deviation may result from peripheral utricle
pathology (at the level of labyrinth or eighth
cranial nerve—e.g., post acoustic neuroma
resection), although generally these “peripheral”
skews tend to be small in magnitude and short-
lived. Regardless, since peripheral skews are rare,
when present, a central etiology must first be ruled
out. This patient was found to have a demyelinat-
ing lesion (leading to the diagnosis of MS) in the
region of the MCP/root entry zone of cranial
nerves 7 and 8. MCP lesions are common in MS,
cxxxvi List of Videos\Electronic Supplemental Materials (ESM)
and patients typically present with vertigo and

nystagmus. The ocular tilt reactions seen in
demyelinating and ischemic lesions involving the
MCP are almost always ipsiversive as it was in this
case. Finally, there was a mild left lower motor
neuron facial palsy, which along with the abnormal
HIT is suggestive of a root entry zone localization
if due to a central etiology. Or, an inflammatory,
neoplastic or infectious process (e.g., herpes
zoster/Ramsay Hunt syndrome) causing multiple
cranial neuropathies should be considered when
peripheral. Our patient’s RBN and abnormal HIT
to the left could have been explained by a left
eighth cranial neuropathy, although the prominent
skew deviation would have been atypical. In this
patient’s case, possible localizations for the
abnormal HIT to the left include (in order of most
to least likely): root entry zone of CN 7/8; intra-
axial eighth nerve fascicle; vestibular nucleus
complex. Had this patient suffered a stroke, left
labyrinthine ischemia (due to AICA-territory
ischemia) would be another explanation for
abnormal HIT on the left and unidirectional RBN,
although ipsilesional hearing loss is generally
present due to cochlear ischemia https://collec-
tions.lib.utah.edu/details?id=1291717. (Video
courtesy of Dr. Tzu-Pu Chang)
Video 6.19 A “peripheral” skew deviation causing vertical
diplopia in acute vestibular neuritis—a rare
occurrence: This hypertensive man developed
acute onset continuous vertigo and presented to the
Emergency Department (ED) after several hours of
symptoms. He was noted to have spontaneous
nystagmus and had a normal brain MRI within the
first 24 hours. The first portion of the video was
recorded during his hospitalization, and if his head
was in any position other than left ear down, he
experienced severe vertigo and nausea. Nystagmus
List of Videos\Electronic Supplemental Materials (ESM) cxxxvii
was left-beating (LB) with a torsional component

(top poles beating toward left ear), the LB lessened
in right gaze, remained LB in vertical gaze, and
increased in left gaze (in accordance with Alexan-
der’s law). Nystagmus also increased in intensity
with fixation removed, which combined with his
unidirectional and mixed horizontal-torsional
nystagmus, were features suggestive of a periph-
eral vestibular localization (but could still be seen
with a central disorder). The patient was extremely
symptomatic but allowed the examiner to perform
one single head impulse test (HIT), which was
abnormal to the right side (i.e., when the head was
moved quickly to the right, the eyes initially
moved with the head to the right due to a deficient
vestibulo-ocular reflex involving the right horizon-
tal canal, and this was followed by a catch-up
saccade back to the left to the examiner’s nose).
The patient also experienced binocular vertical
diplopia, and a right hypotropia was apparent in
primary gaze with cover-uncover testing, which
was consistent with a skew deviation. Finally,
while there was no clear ocular lateropulsion to the
right while upright, rightward horizontal gaze
deviation was noted on the MRI. However, this
finding does not predict a central localization.
Examination at 1 week showed much improved LB
nystagmus, although the right hypotropia persisted.
This was measured as 4 prism diopters, and was
constant in right, left, up, down gaze and with right
and left head tilt. Fundus photos showed a mild
ocular counterroll with top poles toward the right
ear, which paired with his skew deviation (right
hypotropia) suggested a partial ocular tilt reaction
(in the absence of a clear head tilt) from utriculo-
ocular pathway (or graviceptive-ocular motor
pathway [mediating inputs from vertical semicircu-
lar canals and the utricle]) involvement. His HIT to
cxxxvii List of Videos\Electronic Supplemental Materials (ESM)
the right remained abnormal and video HIT

demonstrated low gains and overt saccades in the
planes of the right horizontal and anterior canals,
both of which are innervated by the superior
division of the vestibular nerve. The utricle is also
innervated by the superior division of the vestibu-
lar nerve, and while a skew is possible in a
peripheral vestibular disorder, this is rare, and a
peripheral skew deviation tends to be small and
transient. Although right-sided vestibular neuritis
with a “peripheral” skew deviation was suspected
as the cause, given the possibility of a false-nega-
tive MRI as an inpatient (MRI was done within 24
hours of symptom onset), a second MRI with and
without contrast was ordered. This was normal,
and the diagnosis of right vestibular neuritis was
confirmed. The patient improved significantly over
the following months. Of note, patients with
vestibular neuritis tend to have more intense
nystagmus and vertigo with the bad (affected) ear
down, which is why the patient maintained a left
ear down position throughout most of his hospital-
ization https://collections.lib.utah.edu/ark:/87278/
s6ht70fx
Video 6.20 A “central” HINTS exam in a lateral medullary
syndrome: This patient presented with the acute
vestibular syndrome in addition to vertical diplo-
pia. Examination demonstrated several aspects of
the left lateral medullary (Wallenberg) syndrome to
an acute demyelinating lesion: ipsilesional (left)
ocular lateropulsion (ipsipulsion, as well as
hypermetric saccades to the left, hypo to the right,
not seen in the video), ipsilesional (left) hypotropia
from skew deviation, and subtle right-beating
nystagmus (not seen in the video). There was also
an abnormal head impulse test, which although
typically seen as a “peripheral” sign, can be central
in origin as in this case (due to left vestibular
List of Videos\Electronic Supplemental Materials (ESM) cxxxix
nucleus involvement) https://collections.lib.utah.

edu/details?id=187730
Video 6.21 Gaze-evoked and rebound nystagmus in a
cerebellar syndrome: This patient presented with
a cerebellar degeneration of unknown etiology, and
had a variety of cerebellar ocular motor findings,
including gaze-evoked nystagmus with rebound
(e.g., left-beating nystagmus in left gaze, transi-
tioning to right-beating when he looks back to
primary), saccadic smooth pursuit and failure of
VOR suppression, and saccadic dysmetria. In some
cases, the distinction between physiologic end
point nystagmus (EPN) and pathologic gaze-
evoked nystagmus (GEN) can be difficult. Findings
suggestive of EPN include relatively small
amplitude, fatigues, abates in ¾ eccentric position
(far enough in that both eyes can view the target),
and the absence of rebound nystagmus (occasion-
ally, normal people may have a beat or two), often
with a horizontal-slight torsional (toward the
ipsilateral ear) component. Findings suggestive of
GEN include larger amplitude, doesn’t fatigue, still
present in ¾ eccentric position (far enough in that
both eyes can view the target), and presence of
rebound or centripetal nystagmus. Centripetal
nystagmus is a nystagmus in eccentric gaze, in
which the fast phase beats “centripetally” toward
primary gaze https://collections.lib.utah.edu/
ark:/87278/s6089dz6
Video 6.22 Posterior canal BPPV—nystagmus provoked by
the Dix—Hallpike maneuver: When the patient
was moved into the right Dix–Hallpike maneuver,
after a brief latency, upbeat-torsional (toward the
lowermost or affected [right] ear) nystagmus was
seen. The patient was then treated with an Epley
maneuver, and was later rechecked with the right
Dix–Hallpike maneuver. At that point, the maneu-
ver did not provoke nystagmus and vertigo,
cxl List of Videos\Electronic Supplemental Materials (ESM)
demonstrating that the Epley maneuver had been

successful in moving the otoconia out of the right
posterior canal. Examination features in this case
that reassure the examiner that they are dealing
with BPPV (as opposed to a central positional
nystagmus variant) include the following: fatigabil-
ity (not shown here, but with repetitive Dix–Hall-
pike maneuvers, the vertigo and nystagmus
become less and less prominent); a brief latency
between Dix–Hallpike and the onset of vertigo/
nystagmus (as the otoconia moves to the most
dependent part of the canal during Dix–Hallpike, it
drags the endolymph with it, and this endolymph
flow deflects the cupula causing vestibular excita-
tion—because deflection of the cupula does not
occur instantaneously during the Dix–Hallpike, a
brief latency is the consequence); a crescendo-
decrescendo nystagmus; the expected pattern of
nystagmus is observed given the laterality of the
specific Dix–Hallpike maneuver performed (e.g.,
right Dix–Hallpike produces nystagmus with an
upbeat component and with a torsional component,
with the top poles beating toward the lowermost/
affected [right] ear); vertigo and nystagmus
respond to properly performed repositioning
(Epley or other) maneuvers https://collections.lib.
utah.edu/ark:/87278/s6s79d1w. (Video courtesy of
Dr. Marco Mandala)
Video 6.23 Posterior canal BPPV—reversal of nystagmus
when going from Dix–Hallpike to seated: This is
a patient with typical posterior canal (PC) benign
paroxysmal positional vertigo (BPPV), which was
provoked by the Dix–Hallpike maneuver. When the
patient is moved into the right Dix–Hallpike
maneuver, after a brief latency, upbeat-torsional
(toward the lowermost or affected [right] ear)
nystagmus is seen. There is a crescendo-decre-
scendo pattern and nystagmus and vertigo resolve.
List of Videos\Electronic Supplemental Materials (ESM) cxli
With the right Dix–Hallpike maneuver, the right

PC is stimulated by movement of the otoconial
particles and an excitatory pattern of nystagmus
results. In this case, the right superior oblique and
left inferior rectus muscles are stimulated which
initiates the downward and torsional (toward left
ear) slow phase. An upbeat-torsional (toward right
ear) fast phase is then generated until the otoconia
fall to the most dependent portion of the PC and
there is no longer flow of endolymph or deflection
of the cupula. However, when the patient is
brought from right Dix–Hallpike back to a seated
position, the otoconia move in the opposite
(inhibitory) direction, and a downbeat-torsional
nystagmus is then seen https://collections.lib.utah.
edu/details?id=1281864. (Video courtesy of Dr.
Marco Mandala)
Video 6.24 Posterior canal BPPV—treatment with Epley
and Semont maneuvers: (1) Epley/canalith
repositioning maneuver (CRP)—to treat right
posterior canal (PC)-BPPV (each position main-
tained for at least 30 seconds or until nystagmus
and/or vertigo cease): (a) First the patient is placed
in the long-sitting position, (b) The head is rotated
45 degrees to the right, (c) Then the patient is
lowered quickly into the supine position with the
head in 30 degrees of cervical extension, (d) Then
the patient’s head is 90 degrees to the left, (e) The
patient is rolled into a left-side lying position with
the head maintained in 45 degrees of rotation to the
left so that the head is facing the floor, (f) Then the
patient sits up slowly with the head still facing
down toward the floor and rotated 45 degrees to the
left, (g) Slowly, the head is moved back to neutral.
(2) Semont maneuver—to treat right posterior
canal (PC)-BPPV: (a) The patient is placed in a
seated position on the treatment table, (b) The head
is turned 45 degrees to the left, (c) The patient is
cxlii List of Videos\Electronic Supplemental Materials (ESM)
quickly brought into a right side-lying position

which is maintained for 1 minute, (d) The patient
is then guided quickly from right to left side-lying
positions within 1.5 seconds without stopping in
the center, (e) The head is maintained in 45 degrees
of leftward rotation so that the head is facing the
ground and this is position is held for 1 minute, (f)
The patient is guided into a seated position slowly
with the head maintained in 45 degrees of leftward
rotation, (g) The head is moved slowly back to
neutral https://collections.lib.utah.edu/
details?id=187680. (Video created with the
assistance of Drs. Michael Schubert, Amir Kherad-
mand, and Laura Morris)
Video 6.25 Horizontal canal BPPV (geotropic variant)—
nystagmus provoked by the supine roll test: This
is a patient with the geotropic (nystagmus beating
toward the ground) variant of left horizontal canal
(HC) benign paroxysmal positional vertigo
(BPPV). In a patient with geotropic (nystagmus
beating toward the ground) HC BPPV, by rapidly
moving from a sitting to a supine position with the
head straight, particles will move away from the
ampulla to the most dependent portion of the canal,
resulting in an ampullofugal flow and nystagmus
that beats away from the affected side. If otoconia
are located close to the ampulla as they typically
are with apogeotropic HC BPPV, particles will
move toward the cupula and provoke an ampullop-
etal flow and nystagmus that beats toward the
affected side. The right-beating nystagmus (RBN)
when going from upright to supine position in this
patient with geotropic HC BPPV suggested that the
left HC was involved. With supine roll testing
(where the head is rolled 90 degrees to the right
and to the left), there was weaker right-beating
nystagmus (RBN) with right roll test, and stronger
LBN with left roll test—this also suggests that the
List of Videos\Electronic Supplemental Materials (ESM) cxliii
left HC was involved. Since the otoconia are

typically located in the most dependent part of the
canal in geotropic HC BPPV, when the left side is
affected, rotating the head 90 degrees to the left
allows particles to move toward the ampulla,
producing an ampullopetal flow which is an
excitatory stimulus—i.e., a robust LBN will result.
Rotating the head 90 degrees to the right allows
particles move away from the cupula (ampullofu-
gal), which is an inhibitory stimulus—i.e., a
weaker RBN will result. In contrast, supine roll
testing in apogeotropic HC BPPV results in
nystagmus that is stronger toward the unaffected
side (e.g., stronger LBN with right roll compared
to RBN with left roll suggests left HC involve-
ment). The opposite is true of the geotropic variant,
where nystagmus is stronger with the affected ear
down (e.g., left ear was the affected side, and left
roll test demonstrated stronger nystagmus as
compared to right roll test). Or more simply, when
dealing with geo- or apogeo-HC BPPV, the
nystagmus is more intense when beating toward
the affected ear https://collections.lib.utah.edu/
details?id=1281862. (Video courtesy of Dr. Marco
Mandala)
Video 6.26 Horizontal canal BPPV (apogeotropic vari-
ant)—nystagmus provoked by the supine roll
test: This is a patient with the apogeotropic
(nystagmus beating toward the sky) variant of right
horizontal canal (HC) benign paroxysmal posi-
tional vertigo (BPPV). In a patient with geotropic
(nystagmus beating toward the ground) HC BPPV,
by rapidly moving from a sitting to a supine
position with the head straight, particles will move
away from the ampulla to the most dependent
portion of the canal, resulting in an ampullofugal
flow and nystagmus that beats away from the
affected side. If otoconia are located close to the
cxliv List of Videos\Electronic Supplemental Materials (ESM)
ampulla as they typically are with apogeotropic

HC BPPV, particles will move toward the cupula
and provoke an ampullopetal flow and nystagmus
that beats toward the affected side. The right-beat-
ing nystagmus (RBN) when going from upright to
supine position in this patient with apogeotropic
HC BPPV suggested that the right HC was
involved. With supine roll testing (where the head
is rolled 90 degrees to the right and to the left),
there was weaker left-beating nystagmus (LBN)
with right roll test, and stronger RBN with left roll
test—this also suggests that the right HC was
involved. Since the otoconia are typically located
close to the ampulla with apogeotropic HC BPPV,
when the right side is affected, rotating the head 90
degrees to the left allows particles to move toward
the cupula (ampullopetal), which is an excitatory
stimulus—i.e., a robust RBN will result. Rotating
the head 90 degrees to the right allows particles
move away from the cupula, which is an inhibitory
stimulus (ampullofugal)—i.e., a weaker LBN will
result. In contrast, supine roll testing in geotropic
nystagmus results in nystagmus that is stronger
toward the affected side (e.g., stronger RBN with
right roll compared to LBN with left roll suggests
right HC involvement). The opposite is true of the
apogeotropic variant, where nystagmus is weaker
with the affected ear down (e.g., right ear was the
affected side, and right roll test demonstrated
weaker nystagmus as compared to left roll test). Or
more simply, when dealing with geo- or apogeo-
HC BPPV, the nystagmus is more intense when
beating toward the affected ear https://collections.
lib.utah.edu/details?id=1281861. (Video courtesy
of Dr. Marco Mandala)
Video 6.27 Horizontal canal BPPV (apogeotropic vari-
ant)—pseudo-spontaneous nystagmus and local-
ization with bow and lean: This is a 70-year-old
List of Videos\Electronic Supplemental Materials (ESM) cxlv
woman presenting to the Emergency Department

with positional vertigo that was determined to be
due to the apogeotropic variant of right horizontal
canal (HC) benign paroxysmal positional vertigo
(BPPV). When her head is in a neutral position
with the head in axis with the trunk, there is a
pseudo-spontaneous nystagmus. The term “pseudo-
spontaneous” is used because the nystagmus is
created by otoconia within the HC sliding down to
the most dependent portion of the canal, owing to
its orientation—i.e., the most anterior portion of
the HC is at about 20–30 degree higher than the
posterior portion. Therefore, some patients with
HC-BPPV may have an unprovoked “pseudo-spon-
taneous” nystagmus (unrelated to damage to the
vestibular system) when the head is in a neutral
position. In the case of right apogeotropic HC
BPPV, leaning the head backward (the lean portion
of the bow and lean test) will cause otoconial
particles to slide posteriorly in an ampullopetal
(excitatory) direction, which will generate a
(strong) slow phase to the left and a fast phase to
the right (right-beating nystagmus toward the
affected ear). Because the orientation of the HC is
in a similar (but less vertical) position with the
head in axis with the trunk, for the same reasons,
the pseudo-spontaneous nystagmus will be
right-beating (toward the affected ear). Bowing the
head forward (the bow portion of the bow and lean
test) will cause otoconial particles to slide anteri-
orly in an ampullofugal (inhibitory) direction,
creating a (weak) slow phase to the right and a fast
phase to the left (left-beating nystagmus toward the
healthy ear) https://collections.lib.utah.edu/
ark:/87278/s68h2wk9. (Video created with the
assistance of Dr. Ari Shemesh)
Video 6.28 Horizontal canal BPPV—treatment with the
BBQ roll maneuver: To treat right horizontal
cxlvi List of Videos\Electronic Supplemental Materials (ESM)
canal (HC)-BPPV (each position maintained for at

least 30 seconds or until nystagmus and/or vertigo
cease): (a) First the patient is placed in the long-
sitting position, (b) Then in a supine position with
the head elevated 30 degrees, (c) Then the patient’s
head (or whole body) is rotated 90 degrees to the
right, (d) Then the patient’s head (or whole body)
is rotated back to neutral, (e) Then the patient’s
head (or whole body) is rotated 90 degrees to the
left, (f) Then the patient’s whole body is rotated
into a prone position, (g) To move the patient out
of the BBQ roll maneuver, the patient should be
rolled another 90 degrees so that the patient’s head
(or whole body) is rotated 90 degrees to the right,
(h) Finally, the patient is brought back into the
long-sitting position https://collections.lib.utah.
edu/details?id=187682. (Video created with the
Video 6.29 Horizontal canal BPPV—treatment with the
Gufoni maneuver: (1) To treat right apogeotropic
(beating toward the sky with right ear down and
with left ear down—e.g., left beating nystagmus
with right supine roll test or with right ear down;
right beating nystagmus with left supine roll test or
with left ear down) horizontal canal (HC) BPPV:
(a) The patient is placed in a seated position on the
treatment table, (b) With the head in a neutral spine
orientation, the patient is quickly moved onto the
side ipsilateral to the weaker nystagmus (to the
right side in the right apogeotropic variant) and this
position is held for 2 minutes, (c) The patient’s
head is rotated 45 degrees toward the ceiling and
this position is held for 2 minutes, (d) Finally, the
patient is brought back into a seated position. (2)
To treat right geotropic (beating toward the ground
with right ear down and with left ear down—e.g.,
right beating nystagmus with right supine roll test
List of Videos\Electronic Supplemental Materials (ESM) cxlvii
or with right ear down; left beating nystagmus with

left supine roll test or with left ear down) horizon-
tal canal (HC) BPPV: (a) The patient is placed in a
seated position on the treatment table, (b) With the
head in a neutral spine orientation, the patient is
quickly moved onto the side ipsilateral to the
weaker nystagmus (to the left side in the right
geotropic variant) and this position is held for 2
minutes, (c) The patient’s head is rotated 45
degrees toward the ground and this position is held
for 2 minutes, (d) Finally, the patient is brought
back into a seated position https://collections.lib.
utah.edu/ark:/87278/s6q55z98. (Video created with
the assistance of Drs. Michael Schubert, Amir
Kheradmand, and Laura Morris)
Video 6.30 Central positional nystagmus due to a posterior
fossa tumor—when to worry: This patient
presented with positional dizziness and nystagmus,
and examination with video Frenzel goggles and
removal of fixation demonstrated the following:
when upright, there was no nystagmus; in bow
(head flexed forward), there was down- and
right-beating nystagmus (RBN); in lean (head
extended back) there was upbeat- and left-beating
nystagmus (LBN); when supine, there was initially
RBN, which transitioned slowly to upbeat nystag-
mus and finally LBN; in right supine roll test (head
rotated 90 degrees to the right with head slightly
flexed) there was initially LB apogeotropic nystag-
mus (i.e., beating away from the earth) that slowed
over seconds and transitioned to RBN; and in left
supine roll test (head rotated 90 degrees to the left),
there was initially RB apogeotropic nystagmus that
slowed and gradually transitioned to LBN (the
video cuts off before this can be seen). MRI was
obtained, which demonstrated a tumor originating
in the fourth ventricle, which was eventually
diagnosed as a subependymoma. When positional
cxlviii List of Videos\Electronic Supplemental Materials (ESM)
vertigo and nystagmus are central in origin, apogeo-

tropic positional nystagmus is usually related to
pathology involving the nodulus/uvula, geotropic
positional nystagmus is usually related to pathology
involving the paraflocculus (tonsil), and positional
downbeat nystagmus is often caused by bilateral
flocculus impairment. Central apogeotropic
nystagmus is much more common than central
geotropic nystagmus. Other ocular motor abnor-
malities are usually present and/or there is gait
imbalance, but rarely central positional nystagmus/
vertigo occurs in isolation. In this particular case,
neuroimaging was indicated due to the following
red flags: (1) The nystagmus was not in the plane of
a particular semicircular canal and changed
unpredictably with various head position (e.g., bow
and lean caused down- and upbeat nystagmus,
respectively); (2) The typical crescendo-decre-
scendo pattern of upbeat-torsional nystagmus
triggered by Dix–Hallpike, which would suggest
PC BPPV (the most common type of BPPV,
especially common following head trauma), was
lacking; (3) Repeated, properly performed Epley
maneuvers (treatment for PC BPPV) did not resolve
the symptoms or nystagmus; (4) Vomiting persisted
even as positional vertigo improved; (5) Mild
gaze-evoked nystagmus was present laterally
(regardless of the otherwise normal neurologic
exam), which suggests dysfunction of the neural
integrators—nucleus prepositus hypoglossi-medial
vestibular nucleus complex or its connections with
the cerebellar flocculus/paraflocculus; (6) While
there was apogeotropic nystagmus with supine roll
test, which could suggest HC BPPV, the nystagmus
occurred without a clear latency, and quickly
transitioned to nystagmus in the opposite direction.
The mechanism for central positional apogeotropic
nystagmus may relate to impaired ability of the
List of Videos\Electronic Supplemental Materials (ESM) cxlix
vestibulocerebellum (mainly nodulus/uvula) to

accurately estimate the direction of gravity due to
abnormal otolithic (utricular) inputs. This can result
in a directional error away from true earth vertical,
and this bias is thought to cause erroneous head
rotation signals that lead to pathological nystagmus
s6hj0x9w. (Video courtesy of Dr. Tzu-Pu Chang)
Video 6.31 Anterior canal BPPV—nystagmus provoked in
straight head-hanging position: Although the
anterior canal (AC) variant of benign paroxysmal
positional vertigo (BPPV) is rare, mainly owing to
its orientation relative to gravity (which makes
otoconial debris much less likely to enter it), it can
occur. Because of the relatively para-sagittal
orientation of the AC (more so than the posterior
canal), in a patient with AC BPPV, nystagmus may
be provoked by the right or left Dix–Hallpike
maneuvers, as well as with straight head hanging,
as it was in this particular patient. A right Dix–Hall-
pike maneuver will stimulate the right posterior
canal (PC) as well as the left AC. This patient was
diagnosed with left AC BPPV—left AC excitation
causes stimulation of left superior rectus and right
inferior oblique muscles, initiating an upward and
torsional (toward right ear) slow phase. This
generates downward-torsional (toward left ear) fast
phases, as seen here. She was treated with reposi-
tioning maneuvers, but there was no response in the
office. Her neurologic and ocular motor/vestibular
examinations were otherwise unremarkable, and
when she returned 1 week later, the positional
nystagmus had spontaneously resolved. Alterna-
tively, there are some patients who may have
otoconia in the distal, non-ampullary arm of the
PC. If this is the case, it may be possible to produce
an inhibitory pattern of nystagmus, so that some
cases labeled as AC BPPV may actual be an
cl List of Videos\Electronic Supplemental Materials (ESM)
atypical variant of PC BPPV. This possibility could

not be excluded in her case https://collections.lib.
utah.edu/ark:/87278/s6hq7wmw. (Video courtesy of
Dr. Marco Mandala)
Video 6.32 Anterior Canal BPPV—treatment with the deep
head hanging maneuver: Regardless of whether it
is thought that the patient has right or left anterior
canal (AC) involvement, the deep head hanging
maneuver is performed in the same way. (a) First
the patient is placed in the long-sitting position; (b)
Then the patient is moved into a supine position
with the head in at least 30 degrees of cervical
extension; (c) Allow nystagmus and vertigo to
resolve (at least 30 seconds); (d) Bring the head
into cervical flexion with the chin touching the
chest; (e) After 30 seconds the patient is brought
back to a seated position with cervical flexion
maintained; (f) The head is brought back into a
neutral position https://collections.lib.utah.edu/
ark:/87278/s6fn4fv6. (Video created with the
Video 6.33 Positional downbeat nystagmus due to a
cerebellar degeneration: This patient experienced
vertical oscillopsia for 6+ months, and on examina-
tion, was found to have very mild downbeat
nystagmus (DBN) in primary gaze, with a slight
increase in lateral gaze. She mainly complained of
dizziness and oscillopsia when laying down. She
was found to have significant provocation of her
DBN with straight head hanging and in right and
left Dix–Hallpike. Although positional downbeat
nystagmus (pDBN) can be seen with the uncom-
mon anterior canal variant of BPPV, usually it is
seen with disorders of the cerebellum or cervico-
medullary junction. When pDBN is seen in a
patient with parkinsonism, multiple system atrophy
should be a consideration. In this patient, the
List of Videos\Electronic Supplemental Materials (ESM) cli
downbeat was in isolation, there was no cerebellar

ataxia, and extensive evaluation was unrevealing.
She had a dramatic response to 4-aminopyridine
and remained stable over several years https://
collections.lib.utah.edu/ark:/87278/s66t3w9k
Video 6.34 Positional nystagmus during an attack of
vestibular migraine: A 50-year-old woman
presented to clinic after experiencing multiple
episodes of hours-long vertigo attacks that were
associated with headache, photophobia, and
phonophobia. She had a history of motion sickness
and migraine headaches in her teenage years. She
was diagnosed with vestibular migraine. She
presented to the emergency department during a
typical attack at which time video-oculography
(VOG) recordings were performed. Video head
impulse test was normal, and VOG (with removal
of fixation) showed no spontaneous, gaze-evoked,
or head-shaking-induced nystagmus. However,
there was persistent positional (7 degree/second
peak slow phase velocity) downbeat-torsional (top
poles toward the right ear) nystagmus in right and
left Dix–Hallpike, with milder downbeat-torsional
nystagmus with straight head-hanging and prone
positions. While her vertigo was continuous, head
movements (including positional maneuvers)
aggravated her vestibular symptoms rather than
triggering them. It was felt that her positional
nystagmus was “central”—not due to benign
paroxysmal positional vertigo (BPPV)—for the
following reasons: (1) nystagmus was not in the
plane of a particular semicircular canal (e.g., no
difference in the nystagmus vector with right
versus left Dix–Hallpike), (2) there was no
crescendo-decrescendo pattern to the nystagmus,
(3) the nystagmus persisted for as long as the
patient was kept in each position, (4) while
downbeat-torsional nystagmus may represent
clii List of Videos\Electronic Supplemental Materials (ESM)
anterior canal BPPV or apogeotropic posterior

canal BPPV, her nystagmus did not behave as
would be expected in either of these variants. A
variety of patterns of nystagmus can be seen during
vestibular migraine attacks including spontaneous
horizontal, upbeat, or downbeat nystagmus, with
positional nystagmus being especially common.
Because she was otherwise in the midst of a typical
vestibular migraine attack, it was felt that her
nystagmus was also migrainous https://collections.
lib.utah.edu/ark:/87278/s6f249xk
Video 6.35 Spinocerebellar ataxia type 3 with gaze-evoked
nystagmus and bilateral vestibular loss: This
patient, with a known diagnosis of spinocerebellar
ataxia type 3 (SCA 3), presented with severe
imbalance and head movement-induced oscillop-
sia. On examination, she had (1) bilateral vestibu-
lar loss (BVL) demonstrated by bilaterally
abnormal head impulse test (HIT, with corrective
saccades and low gains seen bilaterally with
bedside and video HIT), as well as (2) cerebellopa-
thy demonstrated by gaze-evoked nystagmus and
saccadic smooth pursuit. Her vestibulo-ocular
reflex suppression (VORS) was nearly normal
appearing because there was no VOR to suppress
(given her BVL). SCA 3 is in the differential
diagnosis of chronic, progressive imbalance due to
BVL and cerebellopathy in addition to other SCAs
(mainly 1, 4, 6, 25), as well as multiple system
atrophy, superficial siderosis (also with bilateral
hearing loss), CANVAS (cerebellar ataxia,
neuropathy, vestibular areflexia syndrome), and
Friedreich’s ataxia among others https://collec-
tions.lib.utah.edu/ark:/87278/s60k7jb4
Video 6.36 Bilateral vestibular loss and head tremor
causing a “pseudonystagmus”: This patient
presented with complaints of imbalance, dizziness,
and horizontal oscillopsia. On exam, she had a
List of Videos\Electronic Supplemental Materials (ESM) cliii
high frequency, low amplitude (mainly horizontal)

head tremor, and with ophthalmoscopy, the optic
nerve was clearly oscillating back and forth at the
same frequency as her head tremor, which was
responsible for her horizontal oscillopsia. In her
case, she also had bilateral vestibular loss demon-
strated by abnormal head impulse testing in the
planes of right and left horizontal canals (also in
anterior and posterior canals, not seen in this
video). If a patient with a head tremor has an
impaired or absent vestibulo-ocular reflex (VOR),
the eyes will move with the head with each head
oscillation, and oscillopsia will result. The term
“pseudonystagmus” has been used to indicate
oscillopsia (not due to nystagmus) that results from
the combination of bilateral vestibular loss and
head tremor https://collections.lib.utah.edu/
ark:/87278/s62z4z8g
Video 7.1 Oculogyric crisis: This is a patient with neuroleptic-
induced oculogyric crisis. (Video courtesy of
Dr. Stephen Reich) https://collections.lib.utah.edu/
ark:/87278/s6r53dvc
Preparing for the Exam 1
1.1 quipment for the Afferent Neuro-

E
Ophthalmology Bedside Exam
1.1.1 Vision
• Near card (near) or Snellen chart or computer monitor (dis-

tance)
• Reading glasses (+2.00 or +3.00)—for best corrected near
acuity in a patient with presbyopia (who does not have their
spectacles)
• Pinhole—for best corrected acuity, to account for refractive
error (can poke a hole in paper with a safety pin)
• A red object can be presented to each eye individually to see if
the red looks less bright or “desaturated” in one eye compared
to the other. Two (identical) red objects can also be presented
simultaneously in different visual hemifields or quadrants for
color comparison when a subtle field defect is suspected
• Striped ribbon, paper, flag/tape, drum for optokinetic nystag-
mus—can be helpful in some cases where functional vision
loss is suspected
Supplementary Information The online version of this chapter (https://doi.

org/10.1007/978-3-030-76875-1_1) contains supplementary material, which
is available to authorized users.
© Springer Nature Switzerland AG 2021 1

D. Gold, Neuro-Ophthalmology and Neuro-Otology,
https://doi.org/10.1007/978-3-030-76875-1_1
2 1 Preparing for the Exam
• Amsler grid—when macular disease is present, metamorphop-

sia (wavy lines on the grid) is common (this can be easily
printed out from the internet). This can also help characterize
central field defects at the bedside
• A transilluminator or penlight—to evaluate pupil reactivity
and to look for a relative afferent pupillary defect (rAPD)
• Direct ophthalmoscope or Panoptic with spare batteries for
fundus exam
• Short lasting dilating drops (typically phenylephrine 2.5% and
tropicamide 1%, usually combined with slit lamp examination
to evaluate the anterior segment, optic nerve, and macula as
well as indirect ophthalmoscope to evaluate the periphery)
1.1.2 Pupils, Eyelids, Orbits
• Measurement tool for pupil diameter, palpebral fissures, and

lid creases (in mm). There is usually a ruler and/or pupil gauge
on a near visual acuity card.
• A transilluminator or penlight—to assess pupillary reactivity
and size in light and dark
• Hertel exophthalmometer (when available) to evaluate for
proptosis
1.2 quipment for the Efferent Neuro-

E
Ophthalmic/Vestibular Bedside Exam
• Ocular motor/motility
–– A small fixation target for saccades, smooth pursuit, conver-
gence
–– Occluder for alternate cover test/cover-uncover ± Maddox
rod (ESM 1.1) to evaluate ocular alignment (it is also help-
ful to quantify strabismus with prism when possible)
–– Striped ribbon, paper, flag/tape, drum for optokinetic nys-
tagmus (can use your fingertips too)—for example, a quick
screen to see if pursuit/saccades are present and symmetric;
to assist in the diagnosis of subtle internuclear ophthalmo-
Reference 3
plegia (adduction lag), convergence-retraction nystagmus,

progressive supranuclear palsy (poor or absent downward
fast phase)
• Vestibular
–– Near card or eye chart—static (monocular) and dynamic
(binocular) visual acuity
–– A transilluminator or penlight—penlight cover test to
remove fixation
–– Direct ophthalmoscope or Panoptic with spare batteries—
occlusive fundoscopy to remove fixation
–– Frenzel goggles (+20/+30 diopter lenses, provides magnifi-
cation and illumination)—removal of fixation for vestibular
(e.g., Dix-Hallpike) exam
–– Foam pad—a patient with bilateral vestibular loss may be
able to maintain balance while standing on the pad with eyes
open, but will experience severe imbalance with eyes closed
–– Bucket test—you can make one of these yourself! The
bucket test is an easy bedside method of evaluating the sub-
jective visual vertical (SVV), which can be thought of as a
perceptual consequence of the ocular tilt reaction (e.g., left
lateral medullary stroke causes an ipsiversive OTR—left
head tilt, ocular counterroll with top poles of both eyes
rotated toward the left ear, left hypotropia, leftward SVV
tilt). The SVV is usually much more tilted with a central
utriculo-ocular motor pathway lesion (lateral medullary
stroke) as compared to a peripheral lesion (vestibular neuri-
tis). The bucket test can also assess each eye individually to
get an idea of subjective torsion—for example, a patient
with an acute left fourth nerve palsy (NP) has normal SVV
OD (right eye), but a slight leftward SVV tilt OS (left eye),
due to the fact that the paretic left superior oblique is held in
relative excycloduction [1].
Reference
1. Zwergal A, Rettinger N, Frenzel C, Dieterich M, Brandt T, Strupp M. A
bucket of static vestibular function. Neurology. 2009;72(19):1689–92.
Disorders of the Pupils,
Eyelids, and Orbits
2
2.1 Pupil (Tables 2.1, 2.2, and 2.3; ESM 2.1)
2.1.1 Anisocoria—The History
A few pearls:
• Pain + ptosis and anisocoria—consider aneurysmal third NP or

Horner’s syndrome due to carotid dissection
• Anisocoria of unclear duration—review old photos to establish
chronicity
• Anisocoria + ptosis and/or other neurologic symptoms/signs—
think about the course of the oculosympathetics (Fig. 2.1) and
the third nerve (Table 2.3; ESM 2.1; Fig. 2.2)
• Do not forget about the possibility of an ocular disorder—ask
about ocular history including prior surgeries, injections, laser
treatments, trauma, inflammation (uveitis)
• Do not forget about the possibility of pharmacologic d ilation—
ask about current medications, recent unintentional exposure
(e.g., a pet’s eye drops), medications with anti-cholinergic


https://doi.org/10.1007/978-3-030-76875-1_2
6
Table 2.1 Help me now with anisocoria: What to examine and urgent diagnostic considerations
Affected Anisocoria Constriction Constriction Pupil
pupil worse in… to light to near dilation Ptosis Motility Pain Other
Horner Miotic Dark Normal Normal Lag, Mild Normal + Lower lid
pupil (SNS) (small slow (dissection) (upside down)
pupil or − ptosis;
dilates anhidrosis;
poorly) reversal of
anisocoria and
ptosis with
apraclonidinea
Third nerve Mydriatic Light Poor or Poor or none Normal Mild IR, SR, + (PCOM Mydriasis due to
(PNS) (large pupil none (except in the to MR aneurysm) 3rd NP without
constricts rare case of severe paresis or − lid or EOM
poorly) aberrant common involvement is
regeneration rare; 1%
of the 3rd N) pilocarpine
constrictsb
Tonic pupil Mydriatic Light Poor or Normal “Tonic”, None None – Dilute (0.1%)
(PNS) (large pupil none (light-near slow pilocarpine
constricts dissociation) constrictsb;
poorly) sectoral
constriction of
the iris
2 Disorders of the Pupils, Eyelids, and Orbits
Pupil
Pharmaco- Mydriatic Light None None None None None – 1% pilocarpine

logicc (marked) does not
constrictb;
consider ocular
causes tood
Physiologic Neither Equal in Normal Normal Normal None None – Normally
(normally light and <1 mm of
unequal dark anisocoria;
pupils) review old
photos to
establish
chronicity
SNS sympathetic nervous system, PNS parasympathetic nervous system, NP nerve palsy, IR inferior rectus, SR superior rectus, MR
medial rectus, PCOM posterior communicating artery, EOM extraocular muscles
a
Apraclonidine 0.5% or 1% drops will dilate the Horner’s pupil (causing a reversal in anisocoria), often with improvement in ptosis as
well. Apraclonidine will not dilate a normal pupil
b
Pilocarpine is a cholinergic agonist, which at 1% concentration, should constrict a normal pupil, or a mydriatic pupil due to a third
nerve palsy or a tonic pupil, but will NOT constrict a pharmacologically dilated pupil. Dilute pilocarpine at 0.1% will only constrict a
tonic pupil (due to denervation hypersensitivity)
c
Consider offending PO anti-cholinergic medications with bilateral mydriasis, consider accidental exposure (e.g., scopolamine patch,
pet’s eye drops, ill-fitting mask with ipratropium inhaler) when mydriasis is unilateral
d
Do not forget about ocular causes of anisocoria including uveitis, tear of the iris, etc. A slit lamp examination is needed when there
is uncertainty. Abnormally-shaped pupils can also be congenital (e.g., aniridia, iris coloboma, and associated with optic nerve hypo-
plasia or optic nerve coloboma, respectively)
7
8
Table 2.2 Help me now with ptosis: What to examine and urgent diagnostic considerations
MRD 2
Ipsilateral Degree of Unilateral MRD 1 (lower Palpebral Levator
pupil ptosis or bilateral (upper lid) lid) fissure Lid crease function Motility Pain
Horner’s Miotic Mild Unilateral Narrow Can be Narrow Normal Normal Normal + (dissection) or
syndrome (dilation (superior narrow −
(SNS) lag in dark) tarsal (inferior
muscle) tarsal
muscle)
Third nerve Mydriatic Mild to Unilateral Narrow Normal Narrow Normal Poor IR, SR, + (PCOM
(PNS) (poor severe (bilateral if (levator MR aneurysm) or −
constriction nuclear palpebrae) paresis
to light) third NP) common
Myasthenia Pupils Mild to Either Narrow Usually Narrow Normal Poor IR, SR, –
gravis isocoric severe, may (levator normal MR, LR
fluctuate palpebrae) paresis
during common
exam
Levator Pupils Mild Bilateral is Narrow Normal Narrow Increased Normal Normal –
dehiscence isocoric common, (disinsertion due to
(mechanical) can be of the levator disinserted
unilateral palpebrae) muscle
Facial palsy Pupils None— Appearance Larger than Larger Wide Normal Normal Normal − (unless pain
Pupil
isocoric widened of normal than (upper and (instead, due to corneal

palpebral unilateral normal lower difficult exposure)
fissure in ptosis facial to close
the affected weakness) the eye)
eye
(pseudo-
ptosis in
the fellow
eye)a
SNS sympathetic nervous system, PNS parasympathetic nervous system, PCOM posterior communicating artery, IR inferior rectus, SR superior rectus,
MR medial rectus, LR lateral rectus
a
Due to orbicularis oculi weakness with a facial palsy, eyelid closure is impaired so that the palpebral fissure is wider than it should be. This can make the
contralateral (normal) eyelid appear ptotic relative to the affected (facial paresis) side. Of note, synkinesia of the facial nerve is a common occurrence
following a facial palsy (develops months later), and commonly leads to a narrowed palpebrae fissure on the affected side. In this situation, mild ipsilateral
upper and lower facial weakness is usually apparent, and aberrant regeneration can be easily demonstrated—e.g., blinking will cause contraction of the
ipsilateral orbicularis oris and chewing, talking, pursing the lips together will cause contraction of the ipsilateral orbicularis oculi.
9
10
Table 2.3 Help me now with diplopia: What to examine and urgent diagnostic considerations
Effect of
Image distance and Ocular
separation direction Head position Pupils Eyelids EOM paresis alignment Other
Monocular Any, in one None Normal Normal Normal None Normal Consider dry eye,
double vision eye (or both cataract, retinal
(this is eyes) pathology, refractive
common!) error
Third NP Any Worse at near Chin up/down Ipsilateral Ipsilateral MR, SR, IR and/or IO Exo- worse Consider PCOM
depending on with MR posture mydriasis ptosis in aneurysm (pupil
which EOMs paresis; worse depending on common common contra-gaze involvement is
are involved up with SR SR/IR (MR); common, but the
paresis; worse involvement hyper- due pupil may also be
down with IR (respectively); to SR, IR, spared with
paresis contra- head IO paresis aneurysmal
turn with MR compression), GCA,
paresis microvascular, head
trauma, mimics*
Fourth NP Vertical and/ Worse with Head tilt Normal Normal SO Hyper-, Consider congenital
or diagonal contralateral contra- to (unless (unless central (can appear normal) worse in fourth NP with a
and down hypertropic central fourth NP contra-, longstanding head
gaze eye fourth NP with down gaze tilt, microvascular,
with contra- and head trauma, mimics*
contra- Horner’s) ipsi- head
Horner’s) tilt
Sixth NP Horizontal Worse with Ipsi- head turn Normal Normal LR Eso- worse Consider intracranial
Pupil
ipsi- gaze at (unless (unless in ipsi- gaze pressure (high or

distance cavernous cavernous (LR) low), microvascular,
sinus with sinus with head trauma, mimics*
ipsi- ipsi- Horner’s)
Horner’s)
INO Horizontal Worse at near Contra- head Normal Normal MR (or may just see Exo- worse Usually from MLF
and turn an adduction lag with in stroke or
contra- gaze saccades) contra- demyelinating lesion,
gaze “pseudo-INO” in MG
Skew Vertical and/ Same in all Head tilt Normal Normal Non-paralytic Hyper- that Think brainstem
deviation or diagonal directions contra- to is usually lesion; commonly an
hypertropic comitant acute MLF lesion will
eye cause skew and INO
Myasthenia Any Any Any Normal Unilateral or Any pattern Any pattern Look for fatiguability,
gravis bilateral ptosis eyelid twitch or
common hopping, proximal
limb and neck
weakness
Thyroid eye Any Any Any Normal Retraction Restriction of IR > Any pattern History of
disease common MR > SR > LR > hyperthyroid is
oblique muscles common, but patient
may be hypo- or
euthyroid
(continued)
11
12
Table 2.3 (continued)

Effect of
Image distance and Ocular
separation direction Head position Pupils Eyelids EOM paresis alignment Other
Convergence Horizontal Near only Normal Normal Normal Non-paralytic Exotropia Common with head
insufficiency at near trauma, Parkinson’s,
PSP
Divergence Horizontal Distance only Normal Normal Normal Non-paralytic Esotropia at Can be due to
insufficiency distance “sagging eye” with
high lid creases; due
to cerebellar disease
with gaze-evoked
nystagmus
NP nerve palsy, MR medial rectus, LR lateral rectus, SR superior rectus, IR inferior rectus, IO inferior oblique, GCA giant cell arteritis,
PCOM posterior communicating artery, MG myasthenia gravis, SO superior oblique, INO internuclear ophthalmoplegia, PSP progressive
supranuclear palsy
* With pupil-sparing, always include thyroid eye disease and myasthenia gravis on the differential.
Pupil 13
Trigeminal nerve (V1)
Hypothalamus
Sympathetics to eyelid
Midbrain
Pons Sympathetics to the pupil
Long ciliary nerve

Medulla
Nasociliary nerve
Sudomotor fibers
Cervical
External carotid artery
spinal cord
Internal carotid artery
Superior cervical ganglion

C8-T2
Inferior cervical ganglion
1st order
2nd order
3rd order
Fig. 2.1 Oculosympathetic pathway for pupillary dilation: The oculosympa-

thetic tract is an uncrossed pathway that begins in the hypothalamus, with
fibers descending in the brainstem (first order, commonly affected in a lateral
medullary syndrome), synapsing in the lower cervical/upper thoracic spinal
cord (interomediolateral cell columns of C8–T2, also referred to as the cilio-
spinal center of budge) and continuing on as the second order fibers (in prox-
imity to the lung apex). The tract ascends and then synapses in the superior
cervical ganglion. The third order neuron leaves the ganglion, with sudomo-
tor fibers following the external carotid artery (explanation for absence of
anhidrosis with an internal carotid artery dissection), while the remaining
fibers ascend with the internal carotid artery (explanation for dissection caus-
ing a painful Horner’s syndrome). The third order fibers innervate the eyelid
(superior [Muller muscle] and inferior tarsal muscles) and pupillary dilator
muscles to open the eyelids and dilate the pupils, respectively. A lesion along
the oculosympathetic tract causes a Horner’s syndrome with ptosis and mio-
sis, and sometimes clinically apparent anhidrosis (with first or second order
but not third order)
14 2 Disorders of the Pupils, Eyelids, and Orbits
Pretectal Posterior
nucleus commissure
Superior
colliculus
EWN
Lateral
Red geniculate
nucleus nucleus
Oculomotor
nerve (III)
Optic tract
Chiasm
Ciliary ganglion
Optic nerve
Fig. 2.2 Parasympathetic pathway for pupillary constriction: When a bright

light is shone in one eye, light enters the pupil and hyperpolarizes retinal
photoreceptors that activate retinal ganglion cells. These signals propagate
along the optic nerves, chiasm, optic tracts, and fibers responsible for the light
reflex then synapse in the dorsal midbrain (prior to reaching the lateral genic-
ulate nucleus) at the pretectal nuclei, then to the Edinger–Westphal nucleus
(EWN) of the oculomotor nucleus. From here, efferent fibers travel with the
oculomotor nerve to the ciliary ganglion and, finally, innervate the constrictor
(sphincter) muscles for bilateral pupillary constriction
Pupil 15
properties (e.g., scopolamine patch, ipratropium inhaler [in a

hospitalized patient])
2.1.2 Anisocoria—The Exam
A few pearls:
• The pupil responses (constriction, dilation—see below) and

cranial nerve exam are most important here, but thorough oph-
thalmic/neuro-ophthalmic (e.g., slit lamp to diagnose iris tear
or visualize segmental constriction) and neurologic (e.g.,
Adie’s syndrome with tonic pupil + absent deep tendon
reflexes) exams can offer additional clues.
• Two muscles that control the size of the pupil (Fig. 2.3): (1)
dilator muscle → mydriasis (dilation via sympathetics,
Fig. 2.1), and (2) sphincter muscle → miosis (constriction via
parasympathetics, Fig. 2.2).
Sclera (covered by conjunctiva)
Iris
Pupil
Lateral Caruncle
canthus
Medial
canthus
Limbus
Conjunctival
vessel Corneal light reflex
Fig. 2.3 Structures of the eye and ocular adnexa: Seen here is a normal right
eye, with clinically relevant structures and landmarks labeled. Also note that
the position of the corneal light reflex can assist in ocular alignment evalua-
tion in a patient with poor vision (i.e., Hirschberg and Krimsky tests)
• Anisocoria with normal constriction OU (both eyes)—con-

sider oculosympathetic lesion or physiologic anisocoria.
• Anisocoria with poor dilation in the miotic pupil—high suspi-
cion for oculosympathetic lesion. Consider apraclonidine topi-
cal drop testing.
• Anisocoria with poor constriction in the mydriatic pupil—con-
sider third NP, tonic pupil, pharmacologic.
• Light-near dissociation: If one or both pupils constricts poorly
to light, evaluate their response to near (i.e., activation of the
near triad of accommodation, miosis, and convergence). If a
near stimulus causes more constriction than light, there is
“light-near dissociation.” Include on the differential of light-
near dissociation (when small and irregular, sometimes referred
to as Argyll Robertson pupils): bilateral—dorsal midbrain
(Parinaud) syndrome, severe bilateral optic neuropathies; uni-
lateral or bilateral— neurosyphilis, diabetes/dysautonomia,
previous retinal laser photocoagulation; unilateral—aberrant
regeneration of the third nerve (e.g., adduction of the affected
eye will constrict the affected pupil due to pupillary sphincter
innervation by some of the fibers originally destined for the
medial rectus).
2.1.3 Pharmacologic Testing
• Pilocarpine—helpful with a mydriatic, poorly reactive pupil…

is it a third NP, tonic pupil, or pharmacologic?
A cholinergic agonist that should constrict a normal pupil at
1% concentration, including a mydriatic pupil due to third
nerve palsy or a tonic pupil. However, 1% will not constrict a
pharmacologically dilated pupil (unless the offending medica-
tion—e.g., nebulized ipratropium—is wearing off). Dilute pilo-
carpine at 0.1% will not constrict a pupil unless denervation
hypersensitivity has occurred, as with a tonic pupil (Fig. 2.4).
• Apraclonidine—helpful to determine whether a miotic pupil is
due to Horner’s syndrome.
0.5% or 1% drops will dilate the Horner’s pupil (causing a
reversal in anisocoria) due to denervation hypersensitivity
(weak alpha-1 agonist action), often with improvement in pto-
Pupil 17
OD OS
Mydriasis OS with light-near dissociation
45 minutes after instillation of dilute pilocarpine OU
Fig. 2.4 Dilute (0.1%) pilocarpine testing to diagnose a tonic pupil: This is
a patient with a slightly mydriatic left pupil that constricted to a near stimulus
but not to light. There was also segmental constriction of the iris appreciated
with slit lamp exam. Dilute pilocarpine was instilled OU, and 45 minutes
later, there was no effect on the normal (right) pupil but clear constriction of
the mydriatic (left) pupil, supporting the diagnosis of a left tonic pupil. (Pho-
tos courtesy of Dr. Collin McClelland)
sis as well. It may take days for this hypersensitivity to develop.

Apraclonidine will not dilate a normal pupil (Fig. 2.5).
2.1.4 Horner’s Syndrome
Case: A 45-year-old man presented to the emergency depart-

ment (ED) with 5 days of right-sided face and neck pain, and
droopiness of the right eyelid. Several days prior to ptosis, he was
in a car accident causing a whiplash injury without loss of con-
sciousness. Examination demonstrated normal afferent function,
motility/ocular alignment, and neurologic examination. Both pto-
sis and miosis were observed on the right, with normal pupillary
Right (upper and lower lid) ptosis and miosis 45 minutes after instillation of apraclonidine OU –
reversal of anisocoria and ptosis
Fig. 2.5 Apraclonidine testing to diagnose a Horner’s syndrome: Apraclonidine

(0.5%) testing was performed within 1 week of onset of Horner’s syndrome.
Testing was positive in that anisocoria reversed (as well as ptosis)—i.e., the pre-
viously miotic right (Horner’s syndrome) pupil was now slightly mydriatic
constriction OU, but poor dilation (in the dark) OD. There was no
subjective or objective indication of diminished sweating on the
right face (i.e., anhidrosis). Concern was very high for a right
Horner’s syndrome, and MR angiogram performed in the ED
demonstrated narrowing of the right internal carotid artery (ICA)
with an intimal flap consistent with a dissection. IV heparin ther-
apy was initiated and MRI of the brain did not demonstrate
diffusion-weighted imaging hyperintensities.
Video: Video 2.1.
Relevant Figures, Tables: Figs. 2.1, 2.5, 2.6, and 2.7; Tables 2.1
and 2.2.
Key questions to ask: Acute and painful Horner’s syndrome is

especially concerning. With a more chronic, painless Horner’s
syndrome, consider the anatomy of the oculosympathetic tract.
• Any symptoms referable to the brainstem (e.g., diplopia,

ataxia, numbness in lateral medullary syndrome—first order)?
• Smoking history (e.g., Pancoast lung tumor—second order)?
• Surgeries/procedures in or around the neck and cervical spine
(first, second, or third order)?
• Head or neck trauma that could be responsible for carotid dis-
section (third order)?
Pupil 19
Axial FLAIR TOF MRA
Light: mild ptosis and miosis OD
Right internal carotid artery dissection

Dark: more anisocoria due to dilation lag OD
Fig. 2.6 Right Horner’s syndrome due to right internal carotid artery (ICA)
dissection: More prominent anisocoria in dark versus light is apparent in this
case, which is highly suggestive of a Horner’s pupil (related to poor sympa-
thetic activation causing a “dilation lag” in the miotic [right] pupil). There is
also mild upper lid ptosis but no anhidrosis (which is typical of a third order
lesion). MR images include axial fluid attenuated inversion recovery (FLAIR)
and time of flight (TOF) MR angiogram demonstrating a crescent sign in the
right ICA
Key findings to elicit: A miotic Horner’s pupil will dilate

slower than the fellow pupil (i.e., a dilation lag). Anisocoria due
to an oculosympathetic tract lesion will be more pronounced in
the dark (owing to the dilation lag). There will be mild upper lid
ptosis (superior tarsal or Mueller’s muscle—milder ptosis than a
third NP), although lower lid ptosis (i.e., inverse or upside-down
ptosis) is commonly seen as well. While the clinician may be
confronted with an isolated Horner’s syndrome, the presence of a
unilateral Horner’s + other findings allow for precise localiza-
tion—for example, contralateral fourth nerve palsy indicates
midbrain; features of the Wallenberg syndrome (ipsilateral hypo-
tropia due to skew deviation; ipsilateral body and ocular latero-
pulsion; limb ataxia; ipsilateral saccadic hypermetria and
contralateral hypometria; decreased sensation of ipsilateral face
and contralateral arm/leg); upper and lower limb hyperreflexia,
ankle clonus, + Babinski indicates cervical spinal cord; ipsilat-
eral V1, V2, third, fourth, sixth nerve palsy indicates cavernous
sinus. Because the sudomotor fibers travel separately with the
external carotid artery, anhidrosis can be seen with first- and sec-
MRD1
Palpebral fissure
MRD2
Fig. 2.7 The eyelid exam—marginal reflex distance (MRD) 1 and 2: For
documentation and comparative purposes, the MRD1 (upper eyelid margin to
corneal light reflex, normal is ~4–5 mm) and MRD2 (corneal light reflex to
lower eyelid margin, normal is ~5 mm) should be recorded, especially when
ptosis is suspected. The palpebral fissure is simply the MRD1 + MRD2 and
will be widened with a seventh NP and narrowed with ptosis (from any etiol-
ogy). A light source and measuring device are all that are needed
ond-order lesions, but not with third-order lesion (e.g., internal

carotid artery dissection).
How do I approach (history and exam) the patient with aniso-

coria or ptosis when Horner’s syndrome is a consider-
ation? See Tables 2.1 and 2.2.
Pitfalls: A patient with mild ptosis (e.g., mechanical ptosis from

disinsertion of the levator palpebrae muscle—so-called levator
Pupil 21
dehiscence, which is common with aging) + physiologic anisoco-

ria (also common, usually <1 mm) may be confused with Horner’s
syndrome. Pharmacologic drop testing (usually apraclonidine in
adult, cocaine in young kids) can be valuable to confirm a Horner’s
pupil. See “Pharmacologic Testing” section above.
Do not miss this! A carotid dissection causing painful Horner’s

syndrome (3rd order). However, in a patient with head/neck pain,
Horner’s syndrome and vertigo, don’t forget about a vertebral
artery dissection causing brainstem ischemia (1st order Horner’s).
What is next? If a patient presents with ptosis or anisocoria

that was noticed by the patient or an observer but the chronicity
is unknown, review of old photos is essential. If the examiner is
confident in the diagnosis of an acute/subacute Horner’s syn-
drome (again, consider pharmacologic confirmation) but there
are no clear symptoms or signs to localize the lesion, neuroim-
aging along the entire oculosympathetic tract is generally rec-
ommended. This can be accomplished by ordering
contrast-enhanced MRI of the head, neck, and upper chest (to
rule out lung apex mass lesion), in addition to MR angiogram of
the neck (carotid dissection). CT of the head may miss a brain-
stem lesion, but contrast-enhanced CT of the neck (to upper
chest) with CT angiogram can adequately visualize the remain-
der of the oculosympathetic tract.
Treatment options: Acutely, either anti-coagulation or anti-

platelet agents are recommended to minimize the risk of stroke
when carotid dissection is the cause (depends on acuity and other
factors). Periodic use of apraclonidine or brimonidine can
temporarily resolve ptosis as needed; surgical correction is

another option.
If you can only remember one thing… A painful Horner’s

syndrome should be considered due to carotid dissection until
proven otherwise! Consider apraclonidine testing when unsure of
the diagnosis and/or chronicity to help guide the imaging workup.
Want to know more? [1, 2]
2.1.5 Aneursymal Third Nerve Palsy
Case: A 45-year-old woman experienced the abrupt onset of a

severe right-sided headache, followed minutes later by near-
complete ptosis involving the right eye. Examination in the emer-
gency department demonstrated severe ptosis OD (preventing
double vision), with impaired supraduction, infraduction, and
adduction OD. Additionally, the right pupil was mydriatic and did
not constrict to light or to near, and there was more anisocoria
noted in bright light. Abduction was spared OD suggesting nor-
mal sixth nerve function. With attempted depression of the right
eye, there was incycloduction suggesting normal fourth nerve
function. CT angiogram of the head demonstrated a right poste-
rior communicating artery aneurysm (PCOM), for which she
underwent urgent clipping.
Severe ptosis OD
Mydriasis OD with more anisocoria in light
Fig. 2.8 Right third NP due to right posterior communicating (PCOM)

artery aneurysm: The combination of severe ptosis, mydriasis, and a “down
and out” appearance OD are all typical of a right third NP, which in this case
was due to right PCOM aneurysm seen on the axial CT angiogram (left) and
CTA 3D reconstruction (right). Because the pupillary fibers travel in the outer
portion of the third nerve, the pupil is almost always involved with aneurys-
mal (or other) compression and is typically spared with a microvascular
insult. (CT images courtesy of Dr. Judy Huang)
Pupil 23
Figure: Fig. 2.8.
Key questions to ask when a third NP is suspected:

• Previous trauma?
• Vascular risk factors (especially diabetes—microvascular eti-
ology)?
• Inquire about headaches (aneurysmal compression or other
mass lesion?) and other neurologic symptoms (e.g., unilateral
weakness due to midbrain stroke?)
• Known history or suspicion for an infectious, inflammatory, or
autoimmune disorder?
• Ask about giant cell arteritis symptoms (ESR/CRP when pres-
ent) in patients >50–55 years old.
• Ask about ptosis, dysphagia, and weakness, which could sug-
gest a neuromuscular junction disorder (myasthenia gravis)
when pupils are spared.
Key findings to elicit:

• Evaluate function of the muscles innervated by the third
nerve—that is, unilateral ptosis (levator palpebrae), adduction
paresis (MR), supraduction paresis (SR), infraduction paresis
(IR), inferior oblique (IO—usually not clinically apparent
unless in isolation, which is a rare occurrence), mydriasis (due
to impaired pupillary constriction).
• Evaluate limb strength and coordination (e.g., midbrain stroke
can cause third NP and contralateral hemi-ataxia, and/or hemi-
paresis), function of other cranial nerves (e.g., meningitis
involving multiple cranial neuropathies in the subarachnoid
space), function of V1/V2, fourth, and sixth NP (e.g., mass or
inflammation of the cavernous sinus), and optic nerve function
(e.g., pituitary apoplexy, orbital mass, or infection).

coria, ptosis, or diplopia when third NP is a consider-
ation? Tables 2.1 and 2.2; ESM 2.1.
Pitfalls: Slight anisocoria (generally 1 mm or less of ipsilateral

mydriasis) can be seen with a vasculopathic third NP, but is a
diagnosis of exclusion. While complete ptosis and motility defi-

cits involving ipsilateral MR, SR, and IR without pupil involve-
ment in an older patient with vascular risk factors is usually
microvascular/vasculopathic, this can still be the initial presenta-
tion of a PCOM aneurysm or mass lesion. A patient with a mydri-
atic unreactive pupil in isolation (i.e., without ptosis, SR, IR, MR
paresis) almost never has a third NP. Instead, consider:
• Pharmacologic causes (e.g., recent atropine or other anti-

cholinergic drops belonging to relatives or pets, contact with a
scopolamine patch, nebulizers/inhalers in an inpatient—

pilocarpine 1% drops will constrict a mydriatic pupil due to a
third NP, but not a pharmacologically dilated pupil)
• Adie’s tonic pupil (check pupillary constriction to a near stim-
ulus)
• Iris tear due to trauma
• Previous ocular surgery
• Infection (uveitis).
Do not miss this! When ptosis, SR, IR, or MR function is partial

or when the pupil is involved, PCOM aneurysm/structural causes
must be excluded urgently. When there is no pupil involvement,
also consider myasthenia gravis. Miller Fisher syndrome is
another cause of ophthalmoparesis and a mydriatic poorly respon-
sive pupil(s), and the mydriasis can rarely occur in isolation. With
bilateral ptosis and superior rectus paresis, consider a unilateral
nuclear third NP. Also look for evidence of aberrant regeneration
of the third nerve (Fig. 4.5), which suggests a chronic compres-
sive lesion (e.g., meningioma, PCOM aneurysm) or previous
trauma (see example Video 2.2). Aberrant regeneration does not
occur due to a microvascular third NP.
What is next? Urgent CT or MR angiogram in most cases, in

addition to (or followed by) contrast-enhanced MRI when
diagnostic uncertainty remains. When the clinician indicates the
correct side of the suspected third NP and in the hands of an expe-
rienced radiologist, CTA or MRA is almost always sufficient to
diagnose a PCOM aneurysm. Rarely is catheter angiography nec-
essary.
Pupil 25
Treatment options: A microvascular (diabetic) third NP is most

common in the older population, and this should resolve com-
pletely within 3 months (sometimes up to 6 months). Other etiolo-
gies may result in more permanent deficits in which case ptosis
and/or strabismus surgery or prism therapy should be considered.
When the ptosis is severe, diplopia is not experienced by the
patient.
If you can only remember one thing… While a third NP due to

a PCOM aneurysm usually involves the pupil, any pattern of
internal (pupil) or external (extraocular muscle) ophthalmoplegia
can be aneurysmal. Always exclude an aneurysm first and fore-
most!
Want to know more? [3]
2.1.6 Tonic Pupil
Case: A 65-year-old woman was referred for anisocoria. She

noticed that for at least the last 6 months, there was increased sen-
sitivity to light and there had been a noticeable change in the
appearance of her pupils. On examination, she had a 5 mm myd-
riatic pupil OS that constricted minimally to light, but constricted
much better to a near stimulus. However, after constricting to a
near target, the pupil was slow to re-dilate to its original size when
looking at distance. The right pupil was 3 mm in diameter and
constricted briskly to light and near stimuli. Examination of
motility and eyelid function was unremarkable with normal align-
ment and no ptosis. Upon review of old photos, it seemed that the
right pupil had been slightly mydriatic for at least 12 months.
With a slit lamp, it was apparent that there was sectoral constric-
tion of the right pupil, with the inferior iris constricting slightly,
while the superior segment did not constrict.
Figure: Fig. 2.9 (Video 2.3).

Mydriasis OS No constriction to light OS
Constriction OU to a near target Slow (tonic) dilation, near to distance
Fig. 2.9 Clinical features of a left tonic pupil: Seen here is a patient with
anisocoria with a mydriatic pupil OS that constricted poorly to light but much
better to a near target. Additionally, when asked to look from a near to a dis-
tant target, slow (tonic) dilation was observed. Dilute (0.1% pilocarpine) con-
stricted the mydriatic (left) pupil but not the normal (right) pupil
Key questions to ask: Trying to establish the chronicity is

important and review of old photos is usually the best way.
• Have you experienced double vision or droopy eyelid (con-

sider third NP)?
• Any sweating/flushing asymmetry (consider Ross and related
dysautonomia syndromes)?
• Any recent exposure to eye drops (belonging to a family mem-
ber or pet)?
• Preceding trauma (may damage the ciliary ganglion also think
about a traumatic third NP or traumatic iris tear)?
• Past infection/inflammation/surgeries (consider previous uve-
itis causing synechia [iris may adhere to cornea or lens], or a
surgical pupil can be caused by a variety of ocular procedures)?

• Light-near dissociation (poor or no constriction to light with
much better response to a near stimulus [use the patient’s fin-
ger as the target]);
• Slow (tonic) dilation of the affected eye following constriction
to a near stimulus;
Pupil 27
• Look for sectoral constriction with a slit lamp or with magnifi-

cation (ophthalmoscope) when possible;
• Evaluate deep tendon reflexes (Adie’s, Ross, and related dys-
autonomia syndromes).

coria when tonic pupil is a consideration? Table 2.1.
Pitfalls: A third NP almost never presents with an isolated uni-

lateral mydriatic pupil in the complete absence of motility or lid
deficits. However, if the onset seems to be acute, there is no sec-
toral constriction or light-near dissociation, no clear ocular cause
(e.g., iris tear, uveitis), and no exposure to eye drops, it is reason-
able to treat this as a possible acute third NP and rule out PCOM
aneurysm and lesion involving the third nerve.
Do not miss this! Other causes of mydriasis: Pharmacologically

dilated pupil, third NP. Other causes of light-near dissociation:
Neurosyphilis (usually bilateral and pupils can be small), dorsal
midbrain localization (Parinaud’s syndrome, bilateral), following
retinal photocoagulation in diabetic retinopathy (unilateral or
bilateral).
What is next? If light-near dissociation is appreciated in addi-

tion to tonic dilation of the involved mydriatic pupil, no further
testing is required when lid and extraocular function is normal. If
the onset is acute and third NP cannot be excluded, CTA or MRA
to rule out PCOM aneurysm is warranted in addition to contrast-
enhanced MRI if angiogram is unrevealing.
Treatment options: A higher power + diopter lens may be

required for reading. Over time, the mydriatic pupil will usually
decrease in size.
If you can only remember one thing… It is extremely rare to

have a third NP present with a mydriatic pupil that is unreactive to
light in complete isolation. Evaluate for light-near dissociation
and consider the possibility of a pharmacologic pupil prior to
MRI and MRA/CTA.
2.2 yelid (Ptosis and Spasm) (Tables 2.1, 2.2,

E
and 2.3; ESM 2.1)
2.2.1 Ptosis—The History
A few pearls:
• When the exact onset is unknown, review old photos

• Ptosis + pain—consider third NP (e.g., aneurysmal) or Horner’s
syndrome due to carotid artery dissection
• Ptosis + diplopia—consider third NP, myasthenia gravis (MG),
Miller Fisher syndrome
• Ptosis with variability or diurnal variation—consider MG
• Isolated ptosis in the elderly, or in a patient who wears contact
lenses, rubs the eyes, or is status post ocular surgery—consider
levator dehiscence syndrome
2.2.2 Ptosis—The Exam
A few pearls:
• Evaluate ocular motility and alignment—abnormal in third NP,

normal in isolated Horner’s syndrome
• Measure marginal reflex distance 1 and 2 (distance from cor-
neal light reflex to upper lid [MRD1, normal ~4–5 mm] and to
lower lid [MRD2, normal ~5 mm])
–– Can have upper and lower lid ptosis (and reduced MRD 1 and
2) in Horner’s syndrome; severe ptosis (and greater MRD1
reduction) is typical in third NP as compared to Horner’s;
–– Reduced MRD1 (often bilateral) in levator dehiscence;
–– Variable MRD1 and 2 measurements in myasthenia gravis
(MG) (Fig. 2.7).
Eyelid 29
• Measure palpebral fissure (distance from upper to lower lid or

MRD1 + MRD2)
–– Widened in facial nerve (orbicularis oculi) palsy.
• Measure levator function (upper lid position when looking
down compared to when looking up when minimizing frontalis
contraction, normal ~14–16 mm)
–– Reduced with neuropathic (third NP) and neuromuscular
(MG) ptosis;
–– Intact with levator dehiscence/mechanical ptosis.
• Measure lid crease height (normal ~6–10 mm)
–– Increased with levator dehiscence/mechanical ptosis
(Figs. 2.10 and 2.11).
• Evaluate facial nerve function—CN7 is responsible for eyelid
closure (orbicularis), while CN3 is responsible for eyelid open-
ing (levator palpebrae). If a patient has facial/orbicularis weak-
ness and ptosis, consider myasthenia gravis or multiple cranial
neuropathies (Fig. 2.12). A facial palsy will cause ipsilateral
widening of the palpebral fissure due to weakness of eyelid
closure (i.e., orbicularis oculi muscles), which can make the
normal eye look relatively ptotic (so-called pseudo-ptosis).
Aberrant regeneration (facial synkinesia) is a common occur-
rence, and this can lead to ipsilateral narrowing of the palpe-
bral fissure, giving the appearance of ipsilateral relative ptosis
(Fig. 2.13).
2.2.3 Levator Dehiscence
Case: A 70-year-old woman presented with bilateral ptosis and

intermittent diplopia. The ptosis was first noted about 5 years ago
and had been stable over time. The diplopia began 6 months ago,
and was binocular, horizontal, and only experienced at distance.
There was no diurnal variation to the ptosis or diplopia. Cranial
nerve exam was unremarkable, ductions were normal and ocular
alignment demonstrated normal alignment at near with a comitant
(i.e., the same in all directions of gaze) symptomatic esotropia at
distance, leading to the diagnosis of divergence insufficiency (DI).
Eyelid examination demonstrated high lid creases OU with mar-
Lid crease
White dotted line represents levator function - distance between upper eyelid
margin in downgaze (yellow arrowhead) and then in upgaze
Fig. 2.10 The eyelid exam—levator function (LF) and lid crease: For docu-
mentation and comparative purposes, the lid crease (upper eyelid margin to the
insertion of the levator palpebrae muscle, normal ~6–10 mm) and LF (the
white dotted line represents the LF, or the distance between the upper lid in
downgaze [yellow arrowhead] compared to upgaze, while ensuring that the
frontalis muscle does not contribute to the eyelid movement, normal ~14–16
mm) should be recorded in millimeters. A high lid crease is typical of disinser-
tion (dehiscence) of the levator muscle, while diminished LF is suggestive of
extraocular muscle weakness (e.g., third NP, myasthenia gravis, or myopathy)
Prominent
superior sulcus
Small MRD1
Normal MRD2
High lid crease
Fig. 2.11 Levator dehiscence—a common cause of mechanical ptosis: Look

for the combination of upper lid ptosis and a high lid crease, with lack of
fatigability and normal levator function. It is typically bilateral and may be
associated with other signs (e.g., prominent superior sulcus, “sagging eye
syndrome” [esotropia greater at distance]) in the aging population, and when
unilateral, also consider trauma, ocular surgery, or contact lens wear/eye rub-
bing
Eyelid 31
OO Orbital m.
Orbital septum Levator

palpebrae m.
OO Preseptal m.
Conjunctiva
Levator
aponeurosis
Superior tarsal
OO Pretarsal m. (Muller) m.
Tarsus
OO Preseptal m.
OO Pretarsal m.
OO Orbital m.
Fig. 2.12 Structures relevant to eyelid opening and closing: The seventh cra-
nial nerve is responsible for eyelid closure and innervates the orbicularis oculi
(OO) muscles, while eyelid opening depends mainly on the third cranial
nerve (levator palpebrae, i.e., severe ptosis with a third NP) as well as the
oculosympathetic tract (superior and inferior tarsal muscles, i.e., mild upper
lid [and sometimes lower lid or upside down] ptosis with a Horner’s syn-
drome)
ginal reflex distance 1 (MRD1) measurements of 1–2 mm

(decreased from normal) and MRD2 measurements of 4–5 mm
(normal). Orbicularis strength was normal and there was no fatiga-
bility with prolonged upgaze, no enhanced ptosis or Cogan’s lid
twitch, and normal levator function OU. There was a prominent
superior sulcus bilaterally. Taken together, she was diagnosed with
mechanical ptosis due to levator dehiscence. The combination of
levator dehiscence/disinsertion, DI (also referred to as “sagging eye
syndrome” in this context), and prominent superior sulci were com-
patible with age-related orbital involutional changes.
Figure: Fig. 2.11.
Fig. 2.13 Chronic right facial nerve palsy with aberrant regeneration (synki-
nesia): The top left photo shows the patient at rest with a slightly flattened
right nasolabial fold (suggestive of weakness) and narrowed right palpebral
fissure (typical of synkinesia months later, whereas there’s widening of the
ipsilateral palpebral fissure with an acute facial palsy). The top right photo
demonstrates poor right eyelid closure (orbicularis oculi weakness) with
abnormal activation (synkinesia) of the lower face (orbicularis oris) on the
right. The bottom left photo demonstrates inability to elevate the right brow
(frontalis weakness), again with abnormal right o. oris activation (synkine-
sia). The bottom right photo demonstrates an asymmetric smile (due to right
o. oris weakness) with abnormal activation (synkinesia) of the right o. oculi
Eyelid 33
Key questions to ask:

• Ask about diurnal variation, diplopia, and other symptoms
suggestive of myasthenia gravis (MG, see case below).
• When abrupt, unilateral and associated with diplopia, consider
third NP.
• When abrupt, isolated, and unilateral, consider Horner’s syn-
drome.
• Try to establish chronicity—oftentimes reviewing old photos
can be helpful.
• Also ask about contact lens use, frequent eye rubbing, ocular
surgery or trauma, any of which can damage the levator muscle
causing disinsertion.

• In this case, other signs were present to suggest orbital changes
due to aging (e.g., prominent superior sulcus, “sagging eye
syndrome” causing esotropia greater at distance).
• Look closely for anisocoria, especially when levator dehis-
cence is unilateral or asymmetric, considering Horner’s (ptosis
+ miosis), third NP (ptosis + mydriasis), as well as physiologic
anisocoria.
• With levator dehiscence, look for normal levator function,
reduced MRD1 and normal MRD2, normal orbicularis func-
tion, and high lid creases.
• If aging-related eyelid/orbital signs are absent in a patient with
DI, look closely for gaze-evoked nystagmus and other “cere-
bellar” signs—DI is common in patients with cerebellar ataxia
(Video 2.4).
How do I approach (history and exam) the patient with pto-

sis? See Tables 2.1 and 2.2.
Pitfalls: Not every patient with ptosis needs an MRI! Almost

always, a focused history and exam will lead to the correct diag-
nosis. If ptosis is isolated (i.e., no motility/alignment, pupillary
abnormalities) and unilateral, and there is suspicion for MG, try
the ice test and other bedside maneuvers (see “Myasthenia Gravis”
below).
Do not miss this! When acute, Horner’s syndrome and third NP

are the most dangerous etiologies, but pupils and/or motility are
almost always abnormal. MG should be considered in any patient
with ptosis and/or diplopia without pupil involvement. Consider
chronic progressive external ophthalmoplegia (CPEO) with
progressive bilateral ptosis and ophthalmoparesis. These patients
will not have diplopia if ophthalmoparesis is symmetric.
What is next? The diagnosis of levator dehiscence can easily be

made with a focused history and examination, and in such cases,
the patient can be reassured and no further testing is needed.
When there is suspicion for third NP or Horner’s syndrome, neu-
roimaging is often indicated (see Tables 2.1 and 2.2 regarding
clinical differentiation). If there are eyelid signs (or ice test) sug-
gestive of MG, acetylcholine receptor antibodies should be
checked first.
Treatment options: If the ptosis impacts visual function (i.e.,

affects the superior visual field), eyelid surgery is often an option.
If you can only remember one thing… Remember that not all
ptosis is neurologic! Levator dehiscence is a common mechanical
cause of ptosis.
2.2.4 Myasthenia Gravis
Case: A 50-year-old woman presented to clinic with several

months of fluctuating ptosis and diplopia. The horizontal binocu-
lar diplopia was initially intermittent, but became more constant
in the last few weeks, seeming to be worse by the end of the day.
The ptosis was minimal in the morning and also increased
throughout the day. She denied proximal weakness, dysphagia, or
dysarthria. Visual function was normal, general neurologic exam
was normal, but there was a large angle exotropia due to severe
Eyelid 35
bilateral adduction deficits, which could not be overcome by con-

vergence. There was no abducting nystagmus in right or left gaze.
The ptosis OD was variable, fatigable, and there was right > left
frontalis contraction to assist with keeping her eyes open.
Orbicularis oculi strength was also impaired OD > OS. Vertical
ductions appeared normal, although there were also intermittent
complaints of a vertical component to her diplopia. When looking
from down to straight ahead, there was a subtle overshoot of the
eyelid consistent with a Cogan’s lid twitch. After sitting with her
eyes closed and with an ice pack (ice test) over the right (ptotic)
eye for several minutes, there was a brief improvement in her pto-
sis, but not her strabismus. Suspicion was very high for myasthe-
nia gravis, and acetylcholine receptor antibodies (binding)
returned positive, confirming the diagnosis. CT of the chest did
not demonstrate a thymoma. Pyridostigmine was tried with partial
improvement in the ptosis (not the strabismus), and she was then
put on prednisone with significant improvement over weeks.
Figure: Fig. 2.14.
R L
*
*
* *
Fig. 2.14 Bilateral ptosis and ophthalmoplegia in myasthenia gravis: In this

montage, the top photo represents primary gaze where right ptosis (yellow
asterisk) and an outward deviation of the eyes (exotropia) can be seen. The
ptosis was variable, fatigable, and there was mild orbicularis oculi weakness
bilaterally. In the bottom photos, bilateral adduction pareses (white asterisks)
are apparent in lateral gaze. In the bottom right photo there is more ptosis OD
in right gaze, with resultant left eyelid retraction (black asterisk, note that the
superior sclera is visible) due to Hering’s law
Key questions to ask: Diplopia and/or ptosis are very common

in the initial presentation of MG, and can be seen in isolation
about 50% of the time. Diurnal variation is typical for ocular and
generalized MG (weakness, dysphagia, dysarthria). Ask about a
history of other autoimmune disease, or recent use of immune
checkpoint inhibitor medications for cancer. When a partial
(pupil-sparing) third NP or internuclear ophthalmoplegia is pos-
sible, inquire about risk factors and associated symptoms for these
respective disorders.

• Fatigue in proximal muscles (deltoids, hip and neck flexors).
• Ptosis and/or diplopia induced by prolonged upgaze.
• Other eyelid signs (e.g., curtaining and enhanced ptosis) are
based on Hering’s law of equal innervation where bilateral
levator palpebrae muscles receive equal innervation. By manu-
ally elevating the ptotic (right) lid, innervation will be reduced
bilaterally, which can result in drooping (curtaining) of the
non-ptotic (left) lid. By manually elevating the non-ptotic (left)
lid, innervation will be reduced bilaterally, which can result in
more drooping of the ptotic lid (enhanced ptosis). Hering’s law
may also result in eyelid retraction that is contralateral to the
ptotic eyelid (Fig. 2.14).
• Look for Cogan’s lid twitch—have the patient look down and
then back to primary gaze, and the lid may overshoot the target
or appear to twitch.
• Similarly, the examiner may see an eyelid twitch with pursuit
or saccades, which is known as lid hopping (Video 2.5). How-
ever, these lid signs can be seen in other disorders causing pto-
sis (Video 2.6).
• Rest test and/or ice test can transiently improve ptosis and/or
diplopia as well.
How do I approach (history and exam) the patient with ptosis

or diplopia when MG is a consideration? See Tables 2.2 and
2.3; ESM 2.1.
Eyelid 37
Pitfalls: Keep in mind that (when the pupils are uninvolved) MG

can mimic any ocular motor disorder including: third, fourth,
sixth, internuclear ophthalmoplegia (note that in this case specifi-
cally, the adduction paresis could not be overcome by conver-
gence and there was no abducting nystagmus), horizontal gaze
palsy, one-and-a-half syndrome. All of the eyelid signs above
(twitch, enhanced ptosis, etc.) can be seen in other disorders caus-
ing ptosis.
Do not miss this! Always consider mechanical causes of ptosis

(levator dehiscence in the aging population, contact lens wearers,
history of surgery or eyelid trauma, frequent eye rubbing, etc.)
and evaluate old photos to establish chronicity;
• Consider Lambert Eaton syndrome (often paraneoplastic and
associated with voltage- gated calcium channel antibodies)
with autonomic features, pupil involvement, hyperreflexia;
• Miller Fisher syndrome with preceding viral illness, ophthal-
moparesis, ataxia, hyporeflexia, poor pupillary constriction
(Video 2.7);
• Botulism with pupil involvement and risk factors (e.g., black
tar heroin).
What is next?
• Acetylcholine receptor antibodies (ACHR, always order bind-
ing, rarely modulating and/or blocking antibodies are positive
when binding is negative) should be ordered when there is any
suspicion for MG.
• If ACHR antibodies are negative, consider anti-MUSK (espe-
cially with prominent bulbar symptoms) and anti-LRP4 anti-
bodies.
• Consider single-fiber EMG (frontalis muscles) or edropho-
nium/neostigmine tests (measuring ptosis and/or ocular align-
ment and motility pre and post) when antibodies are negative.
• CT chest to evaluate for thymoma.
Treatment options: Pyridostigmine can help with symptoms

(ptosis, weakness, etc.), but it tends not to be as effective for dip-
lopia. Usually, immunosuppression is required in the form of
prednisone or steroid-sparing agents. IVIG or plasma exchange
are often indicated during severe exacerbations or crises.
Thymectomy is always indicated when thymoma is present, but it
has been shown to be beneficial in cases where thymoma is absent
as well (mainly younger ACHR+ patients with generalized dis-
ease early in the course, although the ocular MG population has
been less well studied).
If you can only remember one thing… MG can cause any

(pupil-sparing) combination of ptosis and strabismus! Always
consider this diagnosis.
2.2.5 Eyelid Spasms
Case: A 55-year-old man presented with episodes of involuntary

left eyelid closure, worsening in frequency and intensity over the
past 6 months. Episodes occurred many times throughout the day
and were provoked by stress, smiling, or other voluntary facial
movements. Neurologic and neuro-ophthalmic examinations
were normal. During the exam, there was intermittent spasm of
the left eyelid (orbicularis oculi), as well as simultaneous involve-
ment of muscles of the left lower face (especially orbicularis oris
and risorius). This was typical of left hemifacial spasm (HFS),
which in his case was due to left facial nerve (neurovascular)
compression by the left anterior inferior cerebellar artery in the
internal auditory canal. Therapy with onabotulinumtoxinA injec-
tions was initiated, with very good results.
Figure: Fig. 2.15.

Eyelid 39
Frontalis
O. Oculi
O. Oris and
risorius
Fig. 2.15 Left hemifacial spasm: Between spasms, the face was symmetric
and facial muscle strength (innervated by the seventh nerve) was normal.
During spasms, there was contraction mainly of the left orbicularis oculi
(eyelid closure) as well as the left orbicularis oris and risorius (causing an
upward and leftward deviation of the mouth). Despite the contraction of the
o. oculi, the left eyebrow does not depress (instead, there is slight elevation
due to simultaneous frontalis contraction), a finding known as the “other
Babinski sign.” (Photo courtesy of Dr. Stephen Reich)

HFS
• Any other symptoms referable to the brainstem, specifically
the pons (e.g., horizontal double vision due to an ipsilateral
sixth NP;
• Sensory loss due to trigeminal involvement)?
• If the eyelid spasms are unilateral, is the lower face spared
(think about eyelid myokymia, which is extremely common)?
Blepharospasm
• Are both eyes involved?

• History of other forms of dystonia, parkinsonism (or medica-
tions such as anti-psychotics cause parkinsonism or other iat-
rogenic movement disorders)?
• Is photophobia present?
Key findings to elicit: HFS—typical spasms will almost always

be seen in the office, and can usually be triggered by having the
patient forcefully close the eyes and then open them (eyelid
spasms) or following a smile (lower face). Evaluate the function
of adjacent cranial nerves. The “other Babinski sign” may also be
seen in HFS, where orbicularis oculi spasm causes eyelid closure,
but because of simultaneous frontalis contraction (probably a con-
sequence of peripheral co-activation and not seen in blepharo-
spasm), the eyebrow may rise or at least fail to depress (as in this
case). Blepharospasm—spasms are bilateral and forceful eyelid
closure can often trigger spasms in the clinic. Blepharospasm can
be associated with photophobia, and can be reactive in response to
dry eye or ocular surface disease—ophthalmic exam should be
performed. Patients often have a sensory trick (e.g., pushing on a
certain part of the face or head) to diminish spasms. Evaluate for
signs of parkinsonism, other areas of dystonia involvement.
Evaluate for bilateral lower facial involvement that could suggest
Meige syndrome.
Pitfalls: Very early HFS may only affect the orbicularis oculi
and can mimic eyelid myokymia (i.e., subtle upper and/or eyelid
contractions that are benign and usually occur in the setting of
sleep deprivation, stress, or caffeine). If typical spasms are not
observed in the clinic, have the patient take videos of their spasms
at home. Synkinesia of the seventh CN (suggestive of prior dam-
age to the seventh CN with aberrant regeneration) can sometimes
be mistaken for HFS—for example, with o oculi contraction
(blinking), there can be involuntary o oris contraction, and with o
oris contraction (smiling), there can be involuntary o oculi con-
traction (Fig. 2.15). Blepharospasm is almost never due to a struc-
tural lesion, but can rarely be associated with neurodegenerative
Orbit/Globe 41
diseases (more common with progressive supranuclear palsy than

Parkinson’s disease).
Do not miss this! While HFS is usually due to neurovascular

contact involving the seventh CN, it can be due to a pontine/cer-
ebellopontine angle mass or lesion. Consider synkinesia/aberrant
regeneration of CN7 (Fig. 2.13) and eyelid myokymia in the dif-
ferential of unilateral lid spasms, and consider ocular surface dis-
ease (reactive) and functional etiologies in the differential of
blepharospasm.
What is next? MRI in HFS with thin cuts through the internal
auditory canal, which is not usually necessary in typical cases of
blepharospasm.
Treatment options: Botulinum toxin is usually first line for both

and various toxins are effective for HFS/blepharospasm, and pre-
tarsal may be more efficacious than preseptal injections (Fig. 2.12).
The side effects of medications (e.g., carbamazepine, benzodiaz-
epines) may outweigh the benefits of such medications, but can
occasionally be beneficial. Surgical options can also be consid-
ered in refractory cases—neurovascular decompression for HFS;
deep brain stimulation for blepharospasm (rarely performed), or
eyelid myomectomy for both. Consider FL-41 tinted lenses when
photophobia is present in blepharospasm.
If you can only remember one thing… The diagnoses of HFS

and blepharospasm can be made with a high degree of certainty at
the bedside, and botulinum toxin injections are usually highly
efficacious.
Want to know more? [8–10]
2.3 Orbit/Globe
Table 2.3, Fig. 2.16 and ESM 2.1.

Frontal bone
Sphenoid bone Optic canal
lesser wing
Optic strut
Superior orbital Lacrimal bone

fissure
Sphenoid bone, Ethmoid bone

greater wing
Foramen rotundum Maxillary bone
Fig. 2.16 Bony structures relevant to the orbit: The frontal, sphenoid, maxil-
lary, ethmoid, and lacrimal bones make up the orbit. Structures passing
through the optic canal include the optic nerve, oculosympathetic tract, and
ophthalmic artery. Structures passing through the superior orbital fissure
include the superior ophthalmic vein and cranial nerves 3, 4, 6, and V1 (oph-
thalmic branch of the trigeminal nerve). Structures passing through the fora-
men rotundum include V2 (maxillary branch of the trigeminal nerve)
2.3.1 Orbital Disorders—The History
A few pearls:
• Typical symptoms of orbital disease include protrusion of one

or both globes (proptosis), peri-ocular swelling, blurriness or
loss of vision, diplopia (due to mass effect on the globe,
extraocular muscles and/or ocular motor nerves), pain, injec-
tion and “red eye,” and/or ptosis.
• Consider an orbital lesion with gaze-evoked amaurosis, where
eye movement in a particular direction results in transient
vision loss—this can be due to direct mass effect of the optic
nerve or vascular compromise. This phenomenon may also
occur with papilledema—that is, a less common type of tran-
sient visual obscuration.
2.3.2 Orbital Disorders—The Exam
A few pearls:
Orbit/Globe 43
• A comprehensive ophthalmic/neuro-ophthalmic examination

is essential. Knowledge of the bony anatomy and neurovascu-
lar structures traveling through the orbit (e.g., superior orbital
fissure) allow for accurate localization, even when obvious
orbital signs such as proptosis are absent (Fig. 2.17).
• Evaluate retropulsion by having the patient close the eyes, and
with your thumbs, push gently backward on the upper eyelids.
Normally, this should feel soft, without resistance. In patients
Superior scleral show

Temporal flare *
Injected vessels Axial CT

Inferior scleral show
*
*
*
Coronal CT
Fig. 2.17 Typical orbital and neuroimaging signs in thyroid eye disease
(TED): Seen in the top left photo are typical orbital signs of TED. Addition-
ally, she had proptosis as demonstrated by abnormal Hertel exophthalmome-
ter measurements (27 mm OU) as well as anterior globe displacement on
axial CT relative to the interzygomatic (yellow) line. Orbital CT and MRI are
both effective modalities to visualize enlarged extraocular muscles in
TED. Typically, the muscles tend to be involved in the following order: infe-
rior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus, fol-
lowed by occasional involvement of the oblique muscles. In the images
above, bilateral medial rectus (white asterisk) enlargement is most prominent,
but there is also mild enlargement of bilateral inferior rectus (yellow asterisk)
and superior rectus muscles (black asterisk), a slightly larger lateral rectus on
the right (black arrowhead) compared to the left and normal appearing bilat-
eral superior oblique muscles (yellow arrowhead). (Photo and images cour-
tesy of Dr. Amanda Henderson) Seen in the bottom left photo is an example
of severe proptosis in another patient with TED. Viewing the globes from
above or from below (as in this case) allows for a qualitative assessment of
globe position when an exophthalmometer is unavailable. (Photo courtesy of
Dr. Ryan Walsh)
with thyroid eye disease or other orbital pathology, resistance

is often appreciated in one or both eyes.
• Relative globe position can be evaluated by simply comparing
the position of the two eyes by looking from above (e.g., patient
is 45° reclined, while the examiner is at the head of the patient
looking down) or looking from below (e.g., have the patient
assume a chin-up head position with the examiner looking up
from the chin toward the eyes). This will allow for asymmetric
exophthalmos (e.g., proptosis due to orbital inflammation or thy-
roid eye disease) or enophthalmos (e.g., retraction of the globe
due to metastatic breast cancer) to be appreciated. However, the
globe position should be quantified (and compared over time)
using a Hertel exophthalmometer, whenever possible.
2.3.3 Thyroid Eye Disease
Case: A 45-year-old woman presented with a complaint of

“bulging” eyes for the past 3 months. She also complained of a
sandy/gritty sensation OU and double vision when looking far to
the right and to the left. She had experienced recent unintentional
weight loss, palpitations, and heat intolerance. Exam demon-
strated mild abduction deficits OU with a corresponding esotropia
worse in right and left gaze, while abducting saccades appeared
normal in velocity, but terminated abruptly due to the motility
deficits. There was eyelid retraction OU with scleral show inferi-
orly and superiorly, elevated position of the lateral upper lid (tem-
poral flare), and when having the patient look down, the upper
eyelid was slower to depress than the globe itself (lid lag). Slit
lamp exam demonstrated punctate epithelial erosions (due to dry
eye/ocular surface irritation from corneal exposure), and mea-
surements using a Hertel exophthalmometer were 27 mm OU
(normal is typically <20 mm). Thyroid function tests demon-
strated low TSH and high free T4, and CT orbits demonstrated
enlarged inferior, medial (responsible for bilateral abduction defi-
cits due to restriction), and superior rectus muscles, without evi-
dence of tendon involvement. The diagnoses of hyperthyroidism
and thyroid eye disease (TED) were made.
Orbit/Globe 45
Figure: Fig. 2.17.
Key questions to ask: TED should always be on the differential

in a patient presenting with proptosis, lid retraction, and/or diplo-
pia. Ask about a history of autoimmune diseases, especially thy-
roid disease (hyperthyroidism is more common than a euthyroid
or hypothyroid state). When rapid and painful, consider other
orbital disorders (see “Eye Pain” below). When motility deficits
are symmetric, there may be little to no diplopia.
Key findings to elicit: The eyelid signs that are seen in this
patient are common (e.g., temporal flare, lid retraction, scleral
show, lid lag). Medial and inferior rectus tend to be involved first
(causing restrictive abduction and supraduction deficits, respec-
tively), followed by superior and then lateral rectus muscle
involvement. Because this patient’s abduction deficits were
restrictive and not paretic, abducting saccade velocities appeared
normal. The oblique muscles are rarely involved to a significant
degree. Exposure keratopathy (due to lid retraction) can be
responsible for pain and blurry vision, and optic nerve compres-
sion is possible in severe cases due to extraocular muscle enlarge-
ment, or tethering due to significant proptosis.
How do I approach (history and exam) the patient with diplo-

pia when TED is a consideration? Table 2.3; ESM 2.1.
Pitfalls: TED is a subacute/chronic condition that is not associ-

ated with severe pain. When the onset of orbital signs is acute and/
or painful, infiltrative/compressive (metastases), infectious (bac-
terial, fungal), vascular (carotid cavernous fistula), and inflamma-
tory (nonspecific orbital inflammation [aka, orbital inflammatory
syndrome, orbital pseudotumor], IgG4 disease, granulomatous)
disorders must be considered.
Do not miss this! While rare, metastases (e.g., carcinoid tumor)

to the eye muscles may occur and can mimic TED and cause vari-
ably symmetric enlargement of the extraocular muscles (in addi-
tion to the etiologies in “Pitfalls” above), also consider lymphoma,
amyloidosis, sarcoidosis, polymyositis, among others in atypical

cases.
What is next? If there are no red flags, a CT, MRI, or orbital

ultrasound (also can evaluate for high reflectivity, typical of TED)
can demonstrate enlargement of the typical extraocular muscles
with sparing of the tendons (inflammatory disease often involves
the tendons), and tends to be symmetric.
Treatment options: When mild, conservative measures such as

artificial tears +/− supplementing with selenium (but not in
patients with prostate cancer) may suffice, and TED typically
becomes inactive in 2–3 years. Thyroid disease should be treated
when present. Steroids or even radiation can be used in more
severe cases, as well as decompressive orbital surgery when optic
neuropathy is present. Newer immunologic agents include tepro-
tumumab and tocilizumab.
If you can only remember one thing… Like MG, TED should
always be on the differential diagnosis of diplopia, and orbital
signs can be minimal or absent at presentation.
2.3.4 Eye Pain (Acute Angle Closure Glaucoma)
Case: A 60-year-old man presented with complaints of inter-

mittent severe throbbing right head and eye pain, mainly trig-
gered by walking into a dark room, associated with nausea,
blurry vision, and seeing haloes. He experiences several migraine
headaches each year, although this pain was unlike his typical
migraine pain. He mentioned that at his last vision appointment a
year prior, his eyes were not dilated because of something that
his ophthalmologist saw. Neuro-ophthalmic afferent and efferent
Orbit/Globe 47
Light source
No shadow
1) Shine a beam of light parallel to the plane of the iris

2) If there’s a shadow on the nasal iris, the angle is narrow and the patient
should not be dilated (note that this patient has a normal angle)
Fig. 2.18 How can I tell if it’s safe to dilate my patient? Evaluation of the
angle is best performed with a slit lamp (using the Van Herick’s technique,
where the depth of the peripheral anterior chamber is compared to the corneal
thickness) or during gonioscopy. However, a rapid (albeit less accurate) way
to assess the anterior chamber depth is to shine a (temporal) light source par-
allel to the plane of the iris and to look for a shadow on the nasal iris. If a
shadow appears nasal to the pupil, the patient should not be dilated without
first seeing an ophthalmologist. The patient above had a normal anterior
chamber depth (i.e., no shadow was seen), and was safely dilated
examination including cranial nerve evaluation was unremark-

able. Corneal reflexes were normal and there was no loss of sen-
sation in the distribution of the trigeminal nerve. Eye pain was
not brought on by eye movements, or palpation of the globe or
periocular regions (e.g., around the trochlea). When the beam
from a penlight was shown parallel to the plane of the iris (i.e.,
temporally to nasally), a shadow could be seen on the nasal iris,
an indication that the iris was displaced too far forward and that
the anterior chamber angle was narrow (Fig. 2.18). This finding
was confirmed by ophthalmology during slit lamp examination
and gonioscopy. His painful attacks were attributed to bouts of
acute angle closure glaucoma.

• Associated with eye movements (e.g., optic neuritis/perineuri-
tis or myositis)?
• Symptoms of dry eye/ocular surface irritation (e.g., gritty/sandy

or foreign body sensation, tearing, crusting on eyelashes)?
• Diplopia/vision loss or red eye (e.g., sphenocavernous local-
ization or carotid-cavernous fistula)?
• Symptoms of giant cell arteritis (GCA, can cause head and eye
pain with or without vision loss and/or diplopia)?
• Certain medications (such as topiramate) may precipitate angle
closure, especially when bilateral.

• Does palpation around the trochlea or lacrimal gland repro-
duce pain (think of trochleitis or dacryoadenitis, respec-
tively)?
• Evidence of optic neuropathy (e.g., optic neuritis/perineuritis)
and/or CN 3, 4, 6, V1/2 that could suggest sphenocavernous
localization (e.g., Tolosa Hunt)?
• If orbital signs (e.g., proptosis) are seen, consider thyroid eye
disease (pain is usually mild and due to corneal irritation),
infection (bacterial, fungal), malignancy, nonspecific orbital
inflammation, posterior scleritis.
• Evaluate the angle of the anterior chamber indirectly by using
a penlight (when nasal shadow is seen, the angle is narrow and
pharmacologic dilation could precipitate an attack of acute
angle closure).
• Ophthalmologic examination is essential to measure intraocu-
lar pressures, and to evaluate the angles more thoroughly with
slit lamp and gonioscopy.
• At the time of an acute angle closure attack, the following may
be seen: cloudy/edematous cornea, red eye, vision loss, fixed
and dilated pupil, elevated IOP.
Pitfalls: Some head pain can be referred from the eye. Patients
with angle closure glaucoma can have throbbing pain and nausea
and/or vomiting, which can easily be mistaken for migraine.
Do not miss this! Giant cell arteritis can cause unilateral or bilat-
eral eye and/or head pain, and if not diagnosed expeditiously, can
Orbit/Globe 49
lead to irreversible vision loss. With unilateral pain, consider vas-

cular abnormalities such as aneurysm or dissection, and rule out
pituitary apoplexy with abrupt onset severe headache accompa-
nied by vision loss and/or ocular motor palsy/palsies.
What is next? Expeditious evaluation by ophthalmology. When

pain is associated with acute vision loss or cranial neuropathy,
referral to the emergency department is usually warranted.
Treatment options: Once acute angle closure glaucoma is diag-

nosed by an ophthalmologist, oral carbonic anhydrase inhibitors,
or topical beta blockers or alpha-2 agonists are typically used to
lower IOP. Laser peripheral iridotomy is often performed once the
acute attack has subsided.
If you can only remember one thing… Not all head pain is
neurologic!
2.3.5 Red Eye (Carotid Cavernous Fistula)
Case: A 70-year-old woman presented to clinic with 2 weeks of

progressive binocular diplopia with injection and proptosis
OS. She had no complaints of vision loss, eye pain, or constitu-
tional symptoms, although she did have headaches. On examina-
tion, she had normal acuity and color vision, intraocular pressures
(IOP) were 20 OD and 21 OS, Hertel exophthalmometer mea-
surements were 17 OD and 20 OS. Abduction OS was about 75%
of normal, and there was a corresponding esotropia that increased
in left gaze. She also had corkscrew conjunctival and episcleral
vessels OS, with extension to the limbus. Contrast-enhanced MRI
Close-up OS Zoomed-in OS
TOF MRA
T1 Axial (contrast)
TOF MRA
Fig. 2.19 Red eye due to carotid-cavernous fistula (CCF): Note the appear-
ance of small, tortuous conjunctival vessels with extension to the limbus
(arrowheads). These “corkscrew” vessels (yellow arrow points to one exam-
ple) result from arterialization of the veins. The time of flight (TOF) MR
angiogram images demonstrate abnormal filling of the cavernous sinus (white
arrow) and arterialization of the superior ophthalmic vein (yellow arrow-
head), while the T1 contrast-enhancement image shows an enlarged medial
rectus muscle (due to congestion, white dashed arrow) in the affected, pro-
ptotic left eye. (Photos and images courtesy of Dr. Collin McClelland)
demonstrated proptosis OS and congestion of the left medial rec-

tus (responsible for her diplopia), while MR angiography showed
abnormal filling of the left cavernous and arterialization of the left
superior ophthalmic vein, findings consistent with the suspected
clinical diagnosis of left carotid-cavernous fistula (CCF). The fis-
tula was coiled with resolution of signs and symptoms over the
subsequent weeks.
Figure: Fig. 2.19.

• Was there preceding head trauma? (direct, high-flow CCFs
may be traumatic, and lead to fistulous connection between
intracavernous ICA and the sinus)
• If spontaneous and without preceding trauma, is there a history
of connective tissue disease? (e.g., fibromuscular dysplasia,
Ehlers–Danlos syndrome)
Orbit/Globe 51
• Pulsatile tinnitus?
• Vision loss?
• Diplopia?
• Facial sensory loss?
• Head or eye pain (significant pain is typical of orbital inflam-
mation)?
• Constitutional symptoms (consider infection, malignancy)?
• History of thyroid disease or thyroid eye disease (TED)?

• Audible bruit (usually heard best over the closed eyelid);
• Motility deficits and ocular misalignment due to ocular motor
cranial nerve palsy (most commonly sixth nerve) or extraocu-
lar muscle congestion;
• Venous stasis retinopathy or optic neuropathy;
• Corkscrew conjunctival and episcleral vessels (due to arteriali-
zation);
• Pulsatile exophthalmos;
• Proptosis;
• Elevated IOP.
Pitfalls: Low-flow CCFs may drain posteriorly and not cause

orbital signs such as red eye, although may still cause ocular
motor palsies. These are often spontaneous.
Do not miss this! Main differential diagnoses consist of TED,

orbital cellulitis, nonspecific orbital inflammation (aka, orbital
inflammatory syndrome), primary malignancy or metastases,
lymphoproliferative disease (e.g., lymphoma, IgG4-related dis-
ease).
What is next? While MRI and CT are diagnostically insensitive

and may appear normal, usually there is at least subtle evidence of
a CCF (e.g., proptosis, congestion in the orbit/extraocular mus-
cles, enlarged or arterialized superior ophthalmic vein, abnormal
filling or contrast leakage in the cavernous sinus among others).
However, conventional angiography should be performed when
suspicion is high even in the absence of typical MRI/CT signs,
both to confirm the diagnosis and identify the specific vessels

involved, especially for therapeutic planning.
Treatment options: Direct, high-flow, traumatic CCFs require

closure. Spontaneous, indirect low-flow fistulas may resolve with-
out intervention, although when vision is involved, closure is usu-
ally pursued.
If you can only remember one thing… A red eye is not always
ophthalmic (e.g., infectious)—it can be vascular and potentially
dangerous! These are often misdiagnosed and subtle neuroimag-
ing signs are overlooked.
Read These Books! [15–17]
References
1. Rehmani A, Mehta I, Smith E. Treatment of ptosis using brimonidine
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the MRI era. J Neuroophthalmol. 2017;37(3):268–72.
3. Elmalem VI, Hudgins PA, Bruce BB, Newman NJ, Biousse
V. Underdiagnosis of posterior communicating artery aneurysm in nonin-
vasive brain vascular studies. J Neuroophthalmol. 2011;31(2):103–9.
4. Gross JR, McClelland CM, Lee MS. An approach to anisocoria. Curr
Opin Ophthalmol. 2016;27(6):486–92.
5. Ahmad K, Wright M, Lueck CJ. Ptosis. Pract Neurol. 2011;11(6):332–
40.
6. O’Hare M, Doughty C. Update on ocular myasthenia gravis. Semin
Neurol. 2019;39(6):749–60.
7. Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A,
et al. International consensus guidance for management of myasthenia
gravis: 2020 update. Neurology. 2021;96(3):114–22.
8. Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A. Blepharospasm
40 years later. Mov Disord. 2017;32(4):498–509.
9. Simpson DM, Hallett M, Ashman EJ, Comella CL, Green MW, Gronseth
GS, et al. Practice guideline update summary: botulinum neurotoxin for
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the treatment of blepharospasm, cervical dystonia, adult spasticity, and

headache: report of the guideline development subcommittee of the
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10. Stamey W, Jankovic J. The other Babinski sign in hemifacial spasm.
Neurology. 2007;69(4):402–4.
11. Patel A, Yang H, Douglas RS. A new era in the treatment of thyroid eye
disease. Am J Ophthalmol. 2019;208:281–8.
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of thyroid eye disease. Curr Opin Ophthalmol. 2019;30(5):401–6.
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the neurologist. Neurol Clin. 2014;32(2):489–505.
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aetiology, investigation, and management. Eye (Lond). 2018;32(2):
164–72.
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New York: Thieme; 2020.
16. Liu GT, Volpe NJ, Galetta SL. Neuro-ophthalmology: diagnosis and
management. 3rd ed. Philadelphia: Elsevier; 2019.
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ophthalmology: the essentials. 4th ed. Philadelphia: Wolters Kluwer;
2021.
Loss of Vision and Other
Visual Symptoms
3
3.1 Vision Loss—The History (Tables 3.1

and 3.2; ESM 3.1)
• If it is monocular, think prechiasmal—optic nerve or retina or

other ocular cause (see (1) Prechiasmal section below)
• If it is binocular, think bilateral prechiasmal (simultaneous or
sequential), chiasmal or retrochiasmal (see (2) Chiasmal and
(3) Retrochiasmal below)
3.2 ision Loss—The Examination (see

V
Chapter 1 for equipment, testing should be
performed in each eye individually)
• Best corrected visual acuity (distance and/or near)

• Color vision (dyschromatopsia?)
• Amsler grid with central vision complaints (metamorphopsia
[lines wavy] or central field loss [lines missing]?)


https://doi.org/10.1007/978-3-030-76875-1_3
Table 3.1 Help me now with acute onset persistent vision loss
56
Optic nerve
Age exam Pain Laterality Retinal exam Distinguishing feature
Typical <40–50, Normal in 2/3 Prominent Unilateral (bilateral Normal Evolving over hours to days;
(adult) women > men (mild- is rare) prominent rAPD and
optic moderate dyschromatopsia; MR ON
neuritis swelling in enhancement common, OCB
1/3) present in majority
Typical <18 Swelling in Usually Bilateral > unilateral Normal Evolving over hours to days;
(peds) 2/3 present no rAPD if bilateral and
optic symmetric; MR ON
neuritis enhancement common
Atypical Usually <50 Normal or Usually Bilateral or Normal Mainly anti-MOG (optic
optic swollen present unilateral nerve sheath enhancement)
neuritis and NMO (chiasmal
involvement), consider
sarcoidosis, syphilis and
othersa
GCA >50–55 Swollen in Eye pain Unilateral> bilateral ± CWS, Rapid onset over seconds,
AAION> and/or BRAO minutes or hours; headaches,
normal in headache temporal/scalp tenderness,
PION common jaw claudication,
constitutional symptoms,
symptoms of polymyalgia
rheumatica, diplopia
3 Loss of Vision and Other Visual Symptoms
NAION >50–55 Swollen If present, Unilateral (bilateral Normal (rare Rapid onset over seconds,
mild is rare) macular star) minutes or hours; the
fellow eye should be
crowded and have a small
cup:disc ratio (“disc at
risk”); vascular risk factors
present; if vision loss is
mild, swelling is bilateral
and diabetes retinopathy is
present, consider diabetic
Vision loss—the examination…
papillopathy
BRAO/ Older patient Normal “Absent Unilateral Retinal pallor/ Rapid onset over seconds,
CRAOb with vascular (swollen if (unless due whitening, minutes or hours; central
risk factors ophthalmic to GCA)” cherry red vision may be relatively
artery spot, box car spared in CRAO if a
involvement) appearance in cilioretinal artery is present;
vessels, retinal if there is only mild vision
emboli loss due to a BRAO, rAPD
may be absent; retinal vein
occlusion can have nerve
swelling, tortuous vessels,
hemorrhage, CWS
(continued)
57
58
Optic nerve
Age exam Pain Laterality Retinal exam Distinguishing feature
Functional Any age, may or Normal Absent Unilateral or Normal A diagnosis of exclusion
vision lossc may not have bilateral (i.e., rule out visual pathway
psychiatric disease) and inclusion (i.e.,
co-morbidities there are a variety of bedside
techniques that can
demonstrate the non-
physiologic nature of the
vision loss)
rAPD relative afferent pupillary defect, ON optic nerve, anti-MOG myelin oligodendrocyte glycoprotein, NMO neuromyelitis optica,
GCA giant cell arteritis, AAION arteritic anterior ischemic optic neuropathy, PION posterior ischemic optic neuropathy, CWS cotton
wool spots, BRAO branch retinal artery occlusion, NAION non-arteritic anterior ischemic optic neuropathy, CRAO central retinal
artery occlusion
a
Infectious etiologies to consider in the differential of optic neuropathy: Lyme, syphilis, tuberculosis, HIV, Epstein-Barr virus, cyto-
megalovirus, coronavirus
b
Other retinal disorders to consider: Central serous retinopathy—central loss and photopsia, abnormal exam and macular OCT; retinal
detachment—flashes, floaters, then vision loss (usually peripheral to central); macular edema or macular hole—central vision loss,
metamorphopsia; acute zonal occult outer retinopathy (AZOOR)—enlarged blind spot(s), photopsias, can have optic nerve swelling
c
If the patient complains of peripheral visual field loss, be sure to exclude conditions that affect the optic nerves such as glaucoma or
papilledema (both should be apparent with ophthalmoscopy), retinal disorders such as retinitis pigmentosa, and rarely bilateral hom-
onymous hemianopias with bilateral macular sparing can be responsible (rare, and a vertical step should be seen). With organic
peripheral vision loss (e.g., glaucoma), when the stimulus size is doubled and the target distance is doubled (e.g., test each eye indi-
vidually, and move 1 finger from peripheral to central in each quadrant at 3 feet taking note of when the patient can see the target, then
do the same with 2 fingers at 6 feet), the visual fields should double in size (a cone shape). With functional peripheral field loss, the
fields will often stay the same despite doubling the stimulus and distance (a tunnel shape). If the patient claims complete blindness in
one or both eyes if an optokinetic stimulus generates nystagmus in the affected eye(s), then this tells you that the vision is probably
20/400 or better but doesn’t prove that the vision is normal
59
Table 3.2 Help me now with subacute to chronic vision loss
60
History Optic nerve exam Retinal exam Laterality MRI Other

Optic nerve Progressive Pallor (but can Normal Unilateral > Compressive If optic nerve atrophy in one
compression unilateral vision have unilateral bilateral meningioma or eye and swelling in the other
loss ON swelling if other mass, optic (Foster-Kennedy syndrome),
the compression nerve sheath think frontal mass lesion
is anterior) meningioma (CT compressing one nerve and
can be helpful here, causing elevated ICP
look for linear (papilledema in the fellow
calcification along eye)
the optic nerve, aka
“tram-tracking”)
Chiasmal Progressive Bilateral ON Normal Bilateral Sellar/para-sellar With slow chiasmal
bilateral vision pallor is common (bitemporal) > mass lesion compression, temporal
loss (temporal unilateral (meningioma, defects are often not
thinning with (monocular macro-adenoma, recognized by the patient.
OCT RNFL and temporal) cranio- These patients commonly
nasal thinning pharyngioma); have failed refraction,
with OCT GCL enhancement cataract surgery, etc.—visual
OU) (lymphocytic fields are the key!
hypophysitis,
sarcoidosis,
Erdheim-Chester
disease)
Retro-chiasmal Usually more Normal Normal Bilateral Mass or While the vision loss is
acute/subacute, (commonly see (homonymous— inflammatory lesion homonymous, the patient
but can be homonymous more congruous involving optic tract, often perceives vision loss to
chronic OCT GCL with posterior thalamus, optic be on the side of the temporal
thinning with lesions [occipital], radiations (through loss—visual fields are the key
chronic optic tract incongruous with temporal, parietal for localization
lesions—can have anterior lesions lobes), occipital
mild pallor with [optic tract]) lobe—e.g.,
tract pathology meningioma and
too) other tumors, PML,
posterior cortical
atrophy (see below)
Posterior Progressive Normal Normal Bilateral May see parietal or Usually due to Alzheimer’s
cortical vague visual (unilateral or parieto-occipital dementia, often precedes
atrophy complaints, bilateral atrophy on MRI or significant cognitive
difficulty homonymous hypometabolism on symptoms. Consider other
reading and defects, inferior PET scan neurodegenerative disorders
navigating; predominance (Lewy body dementia) in the
simultanagnosia given parietal differential and prion disease
is commona involvement) when rapidly progressive
(continued)
61
62

Elevated ICP/ Headaches, Bilateral Rare macular Bilateral ≫ In IIH: transverse IIH is the most common
papilledema transient visual swelling, star or unilateral sinus stenosis, cause, especially in an
obscurations, obscuration of macular flattening of overweight female, but a mass
pulsatile blood vessels, edema posterior sclera, lesion must be excluded
tinnitus, weight papillary or distension of optic expeditiously. Less commonly
gain, peripheral peripapillary nerve sheath, empty due to acute (e.g., viral or
vision loss when hemorrhage sella bacterial) or chronic (e.g.,
moderate-severe, sarcoidosis) meningitis. Rarely
central vision due to elevated protein from a
loss when very schwannoma or spinal tumor
advanced (ependymoma)b
Nutritional or Progressive Temporal pallor Usually Bilateral ≫ Can see optic nerve Consider B12 (check level
metabolic central vision with thinning of normal unilateral central T2 hyperintensity, and methylmalonic acid);
optic loss, may also the or cecocentral although this can folate (RBC folate level);
neuropathy have neuropathy, papillomacular scotomas occur with any optic thiamine; copper deficiency
myelopathy bundle nerve disorder (copper and zinc levels); ask
about bowel surgery,
malnutrition, alcohol,
smoking history, and
medicationsd; dominant optic
atrophy, Leber hereditary
optic neuropathy
Other Comprehensive Varies depending Varies Unilateral or Depends on Consider Lyme, syphilis,
infectious, medical and on etiology— depending on bilateral etiology—e.g., optic sarcoidosis, fungal infections,
inflammatory, neurologic normal, pale, etiology (e.g., nerve sheath tuberculosis, progressive
autoimmune history and swollen; macular star involvement and/or optic neuropathies in MS
optic examination is associated uveitis, in syphilis, optic nerve
neuropathy especially vitritis, retinitis, sarcoidosis) enhancement with
important etc. syphilis or
sarcoidosis
Functional There may or Normal Normal Bilateral or Normal If the peripheral visual fields
vision lossc may not have unilateral are affected, look for a
been a specific “cloverleaf” pattern on

inciting event automated perimetry,
non-physiologic tunneling of
fields (e.g., by doubling the
target size and distance, the
fields should double in size
regardless of the degree of
vision loss).
(continued)
63
64

Retinopathye Ask about Normal or Abnormal in Bilateral > Normal When it is not clear whether
photophobia, atrophy with advanced unilateral the etiology is optic
photopsias, advanced disease cases (bony (consider a neuropathy or retinopathy,
nyctalopia (night spicules and condition like RP VEP (abnormal in the
blindness) hyper- with peripheral former) and ERG (abnormal
pigmentation loss) in the latter) can be helpful. If
in the diffuse constriction, check
peripheral vitamin A level, and if
retina in normal appearance of optic
retinitis nerves and retinae (especially
pigmentosa) with normal VEP/ERG and
OCT), consider functional
Glaucoma Isolated Large cup:disc Normal Bilateral> Normal Consider glaucoma with
progressive ratio and elevated unilateral cupped nerves with
vision loss IOP in most normal-appearing
neuroretinal rims (i.e., no
pallor), and absence of
dyschromatopsia and
rAPD. Don’t forget about
normal tension glaucoma
with normal IOP
ON optic nerve, ICP intracranial pressure, OCT optical coherence tomography, RNFL retinal nerve fiber layer, GCL ganglion cell layer,
OU both eyes, IIH idiopathic intracranial hypertension, PML progressive multifocal leukoencephalopathy, PET positron emission tomogra-
phy, RP retinitis pigmentosa, VEP visual evoked potentials, ERG electroretinogram, IOP intraocular pressure
a
Aside from being essential to evaluate for optic nerve disease, Ishihara or HRR (Hardy Rand and Rittler) color plates serve as a rapid
screening test for simultanagnosia in posterior cortical atrophy—e.g., the patient will be able to identify the individual colors that
make up the circles, but will not be able to put the pieces (circles) together to form the whole (numbers or shapes). If an older patient
with normal ocular and anterior visual pathway examination and vague visual complaints performs poorly on color vision testing (that
is not due to congenital color blindness), consider PCA
b
Rarely, the vision loss due to “fulminant” idiopathic intracranial hypertension is acute in onset; rule out mass lesion urgently when-
ever papilledema is present; typically vision loss consists of mild field loss (enlarged blind spots) with normal acuity and color vision
and no rAPD. If central (acuity) and color vision are abnormal, damage to the optic nerves is quite advanced (be concerned!), or there
is optic nerve injury due to another process (e.g., optic neuritis)
c
If the patient complains of peripheral visual field loss, be sure to exclude conditions that affect the optic nerves such as glaucoma or
papilledema (both should be apparent with ophthalmoscopy), retinal disorders such as retinitis pigmentosa, and rarely bilateral hom-
onymous hemianopias with bilateral macular sparing can be responsible (rare, and a vertical step is common in this situation). see
Table 3.1 Help me now with acute onset persistent vision loss above for a description of some useful examination techniques when
functional vision loss is suspected
d
Consider toxicity in the differential as well including ethambutol, methanol, amiodarone, lead, arsenic, tacrolimus, vigabatrin, among
others
e
Other retinal disorders to consider: Central serous retinopathy—central loss and photopsia, abnormal exam and macular OCT; macu-
lar edema or macular hole—central vision loss, metamorphopsia; acute zonal occult outer retinopathy (AZOOR)—enlarged blind
spot(s), photopsias, can have optic nerve swelling
65
66 3 Loss of Vision and Other Visual Symptoms
• Visual fields to confrontation—line up eye to eye with the

patient and have them look at your nose, evaluate one eye at a
time by having them count your fingers (usually displaying 1,
2, or 5 fingers) on one hand at a time or both hands simultane-
ously while assessing all 4 quadrants within the central 20–30
degrees. Example: show 1 finger on your left hand in the supe-
rior temporal quadrant while simultaneously showing 2 fingers
on your right hand in the inferior nasal quadrant of their right
eye, and ask the patient, “how many fingers do you see?” If the
patient sees 3 fingers, assess the other quadrants next, and if
the patient says something other than 3, evaluate these 2 quad-
rants individually and more thoroughly. Use finger counting as
an initial rapid screen although more detailed testing is often
needed when a field defect is suspected, including finger/hand
comparison or red color comparison, for example, if a mon-
ocular inferior altitudinal defect is suspected OD, have the
patient cover OS while the examiner holds one finger/hand/red
object above the horizontal meridian and the other (identical
target) the same distance below the horizontal meridian while
the patient looks at the examiner’s nose, and ask the patient if
one target is seen less clearly than the other. This allows for
comparison to the right and left of the vertical meridian (e.g.,
homonymous hemianopia and bitemporal hemianopia), above
and below the horizontal meridian (e.g., arcuate or altitudinal
defect), or for comparison of one quadrant to another. How-
ever, none of these is a substitute for automated static visual
field perimetry (e.g., Humphrey or Octopus) or dynamic
perimetry (e.g., Goldmann)!
• Swinging flashlight test to evaluate for a rAPD—in a dark
room with the patient fixating on a distant target (a near tar-
get will induce miosis), first evaluate the reactivity of each
pupil. Then, shine the light in the right eye for several sec-
onds (e.g., 2), then the left eye for the same period of time
(e.g., 2 s—if the light is held on one eye longer than the
other, this can create the false appearance of a rAPD in a
normal patient), then the right eye, left eye, etc. Constriction
of each pupil should be symmetric, and if dilation is seen in
one pupil during the swinging flashlight test, this represents
Vision loss—the examination… 67
a rAPD in that eye and is typically attributed to optic nerve

disease.
• Perform a fundus examination with particular attention to the
optic nerve head (e.g., swelling, pallor?), arteries (e.g., Hol-
lenhorst or other plaques) and veins (e.g., arteriovenous nick-
ing, tortuosity due to retinal vein occlusion, papilledema), as
well as the macula (e.g., loss of foveal reflex, exudates, and
pigmentary changes) (Fig. 3.1) (dilated slit lamp and indirect
evaluation is often needed to evaluate for anterior segment
Optic disc Papillomacular bundle
Cup
Fovea
Neuro-retinal rim Macula
Cilioretinal artery
Artery
Vein
Fig. 3.1 The fundus exam—structures to identify and evaluate: During rou-
tine ophthalmoscopy, the following structures are of particular interest: the
optic disc and cup (and record the cup:disc ratio when able), neuroretinal rim
(e.g., is it pale due to optic neuropathy? is there a thin rim due to a large cup
from glaucoma?), and follow the course of the retinal arteries and veins (e.g.,
A-V nicking due to hypertension? arterial plaque due to retinal occlusion?).
The fovea/macula and peripheral retina are more difficult to visualize on
undilated examination, but evaluation is important when maculopathy or reti-
nopathy is suspected. The papillomacular bundle may be preferentially
affected by certain conditions including Leber’s hereditary optic neuropathy
or nutritional disorders (e.g., B12 deficiency), resulting in temporal optic
nerve pallor and central or centrocecal scotomas. A cilioretinal artery is a
normal variant, and if present in a patient with a central retinal artery occlu-
sion, it can be responsible for relatively preserved central visual function as a
portion of the macula continues to be perfused by the unaffected choroidal
circulation
d isease [as well as stereoscopic evaluation of the optic nerve

and macula] and peripheral retinal pathology, respectively)
• Evaluate for orbital signs (injection, chemosis, and proptosis)
• Evaluate for anisocoria and eyelid function
• Evaluate the function of all cranial nerves (especially the third,
fourth, sixth nerves, V1 and V2 given the possibility of a sphe-
nocavernous or orbital localization)
• Neuro-ophthalmic evaluation commonly includes formal
visual field testing and optical coherence tomography (Fig. 3.2)
of the retinal nerve fiber layer (RNFL), macula and inner plexi-
form layer-ganglion cell layer (IPL-GCL), and fundus photog-
raphy, although certain situations call for additional ophthalmic
testing with fluorescein angiography, fundus autofluorescence
imaging, orbital ultrasound, electroretinogram and visually
evoked potentials (Table 3.3)
3.3 I nterpretation of Monocular or Binocular

Visual Fields—Dr. Neil Miller’s 10 Visual
Field Rules to Live by
1. Monocular visual field defects are almost always prechias-

mal—think ophthalmic (anywhere from cornea to retina) or
neuro-ophthalmic (optic nerve). Visual field defects due to
retinal and optic nerve disease may respect the horizontal
meridian and are indistinguishable; however, fundus exam is
usually abnormal in retinal disease (see “Retina” and “Optic
nerve”) (Figs. 3.3 and 3.4)
2. Bitemporal defects that respect the vertical meridian localize
to the optic chiasm (see “Chiasm” below) (Fig. 3.4)
3. Homonymous (and bilateral) defects are due to retro-chiasmal
pathology (see “Retrochiasmal” below) (Fig. 3.4)
4. Complete homonymous defects are nonlocalizing, for example,
this can be due to a retrochiasmal lesion anywhere from optic
tract to occipital lobe (see “Retrochiasmal” below) (Fig. 3.4)
5. Visual acuity is unaffected by a homonymous visual field
defect (the patient has use of half a macula; see
“Retrochiasmal” below) (Fig. 3.4)
Table 3.3 Common neuro-ophthalmic ancillary tests
Optic Optic Chronic
nerve nerve Optic Optic retinal /
disorder swelling nerve nerve BRAO Unexplained Unexplained macular Retro-
(no (not swelling head or central peripheral disorder Chiasmal chiasmal
Test swelling) AION) (AION) drusen CRAO vision loss vision loss suspected disorder disorder
Fundus photos + ++ ++ ++ + + + + + −
OCT RNFL/GCLa ++ ++ ++ + + + + ++ + +b
FA − + + ++ ++ + − ++ − −
FAF − − − + − + + ++ − −
Perimetry (static ++ ++ ++ + ++ ++ ++ ++ ++ ++
or dynamic)c
Orbital ultrasound − ++ − ++ − − − − − −
Visual-evoked + + − − − ++ − − − +
potentialsd
Electroretinogramd − − − − − ++ (mf/p) ++ (ff) ++ (p) − −
BRAO branch retinal artery occlusion, CRAO central retinal artery occlusion, OCT optical coherence tomography, RNFL retinal nerve
Interpretation of Monocular or Binocular Visual Fields…
fiber layer, GCL ganglion cell layer, FA fluorescein angiography, FAF fundus autofluorescence imaging, mf multifocal electroretino-
gram, p pattern electroretinogram, ff full field electroretinogram, AION anterior ischemic optic neuropathy (vasculitic or non-vascu-
litic)
− Not usually helpful
+ May be helpful
++ Very helpful
69
(continued)
70
a
OCT of the retinal nerve fiber layer (RNFL) is most beneficial when interpreted in conjunction with OCT of the macula and ganglion
cell layer (GCL). When clear optic nerve swelling is present, OCT of the RNFL is less helpful and OCT of the GCL is most helpful
since these measurements reflect the integrity/structure of the neurons without the confounding presence of optic nerve edema. OCT
angiography is relatively new technology that is expensive, not widely available, and its benefits and pitfalls/artifacts are not as well
understood as more established testing such as FA
b
OCT may be helpful in some cases of chronic retrochiasmal lesions following retrograde trans-synaptic degeneration. In these cases,
a homonymous pattern of hemi-macular thinning may be demonstrated on the GCL analysis
c
Perimetric testing mainly consists of static (e.g., Humphrey, Octopus) or dynamic (e.g., Goldmann) testing. Static perimetry is more
widely available, and tends to be less technician dependent and more reproducible. Typically, 10-2 field testing is for disorders affect-
ing central vision (maculopathies) while 24-2 and 30-2 are excellent for optic nerve disorders (including glaucoma). Patients who are
uncooperative, inattentive, cognitively impaired, or who perform poorly with static perimetry are usually better served by dynamic
(Goldmann) testing. Dynamic testing can also evaluate the entire field of vision (e.g., 30-2 will only evaluate the central 30 degrees of
vision because the vast majority of the neurons making up the optic nerve subserve this area), which can be helpful when complaints
are mainly of peripheral vision loss (e.g., retinitis pigmentosa)
d
When the clinician is unsure as to whether vision loss is due to retinopathy/maculopathy or optic neuropathy, ordering an electroret-
inogram (ERG) along with visual-evoked potentials (VEP) is often beneficial. If the VEP is abnormal while ERG is normal, the
localization is usually optic nerve. If the ERG is abnormal while the VEP is normal, the localization is usually retina/macula. More
specifically, when central vision loss is present (but unclear if nerve or retina), multifocal and pattern ERG are the preferred tests while
when peripheral vision loss is present (but unclear if nerve or retina), full field ERG is the preferred test
Interpretation of Monocular or Binocular Visual Fields… 71
RNFL GCL
IPL
ON
INL
ONL ELM
EZ
OPL RPE
Fig. 3.2 Layers of the retina as seen with optical coherence tomography
(OCT): In order from inner to outer retina: RNFL, retinal nerve fiber layer;
GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear
layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ELM, external
limiting membrane; EZ, ellipsoid zone; RPE, retinal pigment epithelium.
Note that the GCL gives rise to the RNFL, which then makes up the optic
nerve (ON) (Images courtesy of Dr. Kara Della Torre)
Normal left visual field Enlarged blind spot Centrocecal Central

(Mild IIH or white dot syndrome?) (LHON or cilioretinal A occlusion?) (Optic neuritis or maculopathy?)
Arcuate Altitudinal Peripheral constriction Diffuse depression

(Glaucoma or BRVO?) (NAION or BRAO?) (Advanced IIH or RP?) (Compressive ON or CRAO?)
Fig. 3.3 Abnormal monocular visual fields with automated static perime-
try—is it retina or optic nerve? A monocular visual field defect is almost
always pre-chiasmal, but the appearance of the visual field cannot distinguish
optic neuropathy from retinal/macular disease without additional information
(e.g., optic nerve is normal, swollen, or pale; dyschromatopsia and relative
afferent pupillary defect are present with optic neuropathy; e.g., metamor-
phopsia with macular disease, abnormal fundus exam with retinopathy/macu-
lopathy). Each abnormal visual field above could be due to optic nerve or
retinal disease, and an example of each has been given (IIH, idiopathic intra-
cranial hypertension; LHON, Leber’s hereditary optic neuropathy; BRVO,
branch retinal vein occlusion; NAION, nonarteritic anterior ischemic optic
neuropathy; BRAO, branch retinal artery occlusion; RP, retinitis pigmentosa;
ON, optic neuropathy; CRAO, central retinal artery occlusion)
Right Left
Visual field defects

Left Right
Optic nerve Optic
nerve 1
Chiasmal 1 lesion
lesion 2
2 Optic
Meyer’s loop 3
3 tract
6 lesion
4
Temporal 4
lobe
5a
5
5b
7 Lateral
geniculate
6
body
10 7
8
Optic
radiation 8
Occipital 9 9
lobe lesion
11
10
11
Fig. 3.4 Typical visual field defects associated with discrete lesions along
the visual pathways: Specific monocular or binocular visual field defects can
be highly localizing when the neuroanatomy of the visual pathways is under-
stood. The temporal visual field corresponds to the nasal retina, while the
nasal visual field corresponds to the temporal retina. (1) Left optic nerve
lesion—while an optic neuropathy can cause a variety of monocular visual
field defects (see Fig. 3.3), a complete lesion will cause no light perception
vision loss in the affected eye (the violet color = a combination of damage to
both nasal and temporal fibers). (2) Lesion at the junction of proximal left
optic nerve and chiasm—a junctional lesion, when complete, can cause com-
plete monocular vision loss OS due to optic neuropathy, but because some
fibers originating in the right inferonasal retina decussate in the chiasm and
then bulge forward into the left anterior chiasm/proximal nerve (anatomically
known as “Wilbrand’s knee,” a somewhat controversial concept), a small
superotemporal (“junctional”) scotoma can be seen in the right eye. (3)
Chiasmal lesion—due to involvement of the crossing fibers (responsible for
temporal visual fields) coming from right and left eyes, bitemporal hemiano-
pia is the result. (4) Left optic tract lesion—since this is a retrochiasmal
lesion, a right homonymous hemianopia (HH, and usually a mild right rela-
tive afferent pupillary defect) is the result. When incomplete, these tend to be
(continued)
Interpretation of Monocular or Binocular Visual Fields… 73
incongruous (asymmetric). When complete, the HH is nonlocalizing (e.g., it

could be tract or could be occipital). (5) Left lateral geniculate nucleus
lesion—there are two characteristic visual field patterns: (a) right homony-
mous quadruple sectoranopia and (b) right homonymous horizontal sec-
toranopia. (6) Left temporal lobe (Meyer’s loop)—right superior quadrantic
defect (“pie in the sky”), which when incomplete, may be incongruous. (7)
Left parietal lobe—right HH that is more dense inferiorly (“pie on the floor”)
and often incomplete. (8) Left occipital lobe, superior to calcarine fissure—
right inferior quadrantic defect, congruous (symmetric) when incomplete,
often with macular sparing (i.e., sparing of the occipital pole/tip due to dual
vascular circulation). (9) Left occipital lobe, inferior to calcarine fissure—
right superior quadrantic defect, congruous, often with macular sparing. (10)
Right complete occipital lesion with sparing of the pole can be a complete left
HH, or congruous when incomplete, macular sparing. (11) Right occipital
pole lesion—left homonymous central scotoma
Fig. 3.4 (continued)
6. Optic tract lesions cause incongruous (asymmetric) homony-

mous visual field defects. However, a complete homonymous
hemianopia can also be seen with a tract lesion (see Rule #4
and “Retrochiasmal—Optic tract” below) (Fig. 3.4)
7. Lateral geniculate nucleus lesions cause incomplete homony-
mous visual field defects that are distinct from all other retro-
chiasmal defects (i.e., horizontal sectoranopia and quadruple
sectoranopia; see “Retrochiasmal—LGN” below) (Fig. 3.4)
8. Temporal lobe lesions, when incomplete, produce incongru-
ous superior quadrantic homonymous defects (so-called “pie
in the sky”; see “Retrochiasmal—Optic radiations” below)
(Fig. 3.4)
9. Parietal lobe lesions can produce incomplete homonymous
visual field defects, more dense inferiorly (so-called “pie on
the floor”). Other neurologic symptoms are typically present
including neglect, (visual and tactile) extinction and other
visuospatial abnormalities (consider posterior cortical atro-
phy, if progressive; see “Retrochiasmal—Optic radiations”
below) (Fig. 3.4)
10. Occipital lobe lesions produce congruous (symmetric) hom-
onymous visual field defects. However, a complete
homonymous hemianopia can also be seen with an occipital
lesion (see Rule #4). Macular sparing may be seen when the
occipital pole is unaffected (probably due to dual circulation),

and conversely, a homonymous central scotoma is highly sus-
picious for an occipital pole lesion. Bilateral congruous hom-
onymous hemianopias are almost always due to bilateral
occipital lesions and can affect visual acuity (see
“Retrochiasmal—Occipital lobe” below) (Fig. 3.4)
3.4 Ancillary Testing in Neuro-

Ophthalmology
Table 3.3
3.5 rechiasmal (Monocular Vision Loss)

P
Tables 3.1 and 3.2; ESM 3.1
1 . It is monocular, what do I need to know first?

(a) Acute, subacute, or chronic?—e.g. is this dangerous and
urgent (e.g., giant cell arteritis causing ischemic optic neu-
ropathy and central retinal artery occlusion)?
(b) Painful or painless?—e.g. optic neuritis is usually painful.
(c) Age of the patient?—e.g., optic neuritis is common in the
young, nonarteritic ischemic optic neuropathy in the older
population
2. It is monocular, but is there a rAPD?
(a) Vision loss with moderate to severe rAPD (Fig. 3.5; Video
3.1)
• Usually due to an optic neuropathy (see “Optic nerve”
section below), less commonly due to significant retinal
damage (e.g., central retinal artery occlusion)—with the
latter, the retinal pathology is almost always visible on
fundus exam.
(b) Vision loss with mild or no rAPD
• Consider bilateral optic nerve disease (either bilateral
symmetric acute optic neuropathies or pre-existing field
loss in one eye due to glaucoma, now with new optic
neuropathy in the fellow eye); pupils are often sluggishly
reactive to light bilaterally.
Prechiasmal (Monocular Vision Loss) 75
Swinging flashlight test
R L
Left Optic Nerve Pallor

OD constricts briskly
L R
Left Optic Nerve
Compression by
Meningioma
OS dilates ( rAPD )
Fig. 3.5 Relative afferent pupillary defect (rAPD) and other findings of a uni-
lateral optic neuropathy: Patients with unilateral optic nerve disease typically
have loss of visual acuity, dyschromatopsia, visual field loss, the optic nerve
itself may appear normal (e.g., acute retrobulbar optic neuritis) or abnormal
(e.g., optic nerve pallor months after an optic neuritis attack), and a relative
afferent pupillary defect (rAPD) is a prominent feature of an optic neuropathy
(unless there is bilateral optic nerve involvement). This patient has a compres-
sive left optic neuropathy due to a meningioma, and aside from hand motions
visual acuity and inability to see any color plates during testing, there was dif-
fuse visual field loss OS, optic nerve pallor, and a clear left rAPD as seen with
the swinging flashlight test. It’s as if the patient is in a bright room OD (i.e., the
pupil constricts), but then when moving the light from the right to the left eye,
it’s as if the patient is moving into a darker room (i.e., the pupil dilates). The
light should be held for the same duration on each eye; if the light is held on one
eye longer than the fellow eye, this may cause a false positive in a normal
patient. The examiner must be careful when looking for a rAPD in a patient
with anisocoria because less light is entering the smaller pupil; occasionally,
this can create the false appearance of a rAPD on the side of the miosis
• Consider neuroretinitis or other retinal/macular disease

where dyschromatopsia and rAPD can be mild and pro-
portional to field and acuity loss (while dyschromatopsia
and rAPD are often quite prominent and can be out of
proportion to acuity and field loss with optic neuropa-
thy). A macular star may not be present at presentation
but develop over weeks.
• Consider functional with severe unilateral vision loss,
normal nerve and retina/macula, and no rAPD.
• Consider functional or bilateral occipital lesions (strokes
causing bilateral homonymous hemianopias) with severe
bilateral vision loss and brisk pupillary light reflexes.
3.5.1 Retina
3.5.1.1 Retinal TIA (Amaurosis Fugax)

Case A 65-year-old man with a history of hypertension and
hyperlipidemia experienced the abrupt onset of monocular vision
loss OD, with onset “like a curtain coming down.” There was no
headache, no positive visual phenomena, and vision returned
completely 15 minutes later. Two weeks prior, he experienced
mild unexplained left arm weakness for about 1 hour, which
resolved spontaneously. Following his transient vision loss, he
presented to the emergency department, at which time afferent
examination was normal. There was no rAPD, and optic nerves
and retinae appeared normal with the exception of a Hollenhorst
plaque (i.e., a refractile cholesterol embolus) that was lodged in
the inferior retinal artery. The diagnosis of a retinal transient isch-
emia attack (TIA) was made, and MRI of the brain with diffusion-
weighted imaging was normal without evidence of infarction,
although MR angiography demonstrated severe (>90%) carotid
stenosis on the right, which was thought to be causative. There
were no symptoms or signs suggestive of giant cell arteritis
(GCA), and CBC, ESR, and CRP were normal. He underwent
urgent carotid endarterectomy (CEA) and experienced no further
transient visual or neurologic symptoms.
R R L
Fig. 3.6 Hollenhorst plaque in a patient with retinal TIA: While the patient
had normal vision by the time he was evaluated, an asymptomatic cholesterol
embolus (Hollenhorst plaque) was seen in the affected eye
Video/Photo Fig. 3.6
Key questions to ask When amaurosis fugax is suspected, ask

about symptoms related to GCA (headaches, jaw claudication,
scalp tenderness, etc., see GCA section below) as well as about
smoking and vascular risk factors. Sudden onset monocular vision
loss, especially when ascending or descending (e.g., like a cur-
tain), lasting minutes, and without headache or positive visual
phenomena is highly suggestive of a vascular event.
Key findings to elicit If the vision loss is persistent at the time of

the examination, look for a cherry red spot (due to a pale, isch-
emia retina surrounding the normally perfused maculae, which is
supplied by the choroidal circulation), segmentation of blood (due
to sluggish flow) in arterial columns (also referred to as boxcar-
ring), and/or arterial attenuation suggestive of retinal artery occlu-
sion (central or branch retinal artery occlusion, CRAO, or BRAO,
respectively). If there is evidence of optic nerve (e.g., swelling)
and retinal ischemia (CRAO, branch retinal artery occlusion, cot-
ton wool spots), consider GCA. If the retina is pale (due to isch-
emia), but there is no cherry red spot and optic nerve swelling is
also present, this is suggestive of ophthalmic artery occlusion,
which affects both retinal and choroidal circulation (can also be
GCA-related). If symptoms have resolved, look closely at the vas-
culature and for arterial plaques (Figs. 3.7 and 3.2)
How do I approach (history and exam) the patient with acute

and transient vision loss?
Tables 3.1 and 3.4; ESM 3.1
Pitfalls While migrainous visual aura can produce negative phe-

nomena (e.g., loss of vision), monocular vision loss in a patient
with vascular risk factors is highly concerning for retinal isch-
emia. Sudden onset of new visual phenomena in a patient without
a long and strong migraine history deserves urgent workup. It is
more important to distinguish vascular from non-vascular causes
Arterial circle Branch of

Retina Choroid of Zinn-Haller retinal artery
Sclera
Optic
nerve
Posterior Central
ciliary artery retinal
artery
Fig. 3.7 Vascular supply of the optic nerve head, choroid, and retina: The
ophthalmic artery is a branch of the internal carotid artery, which in turn, sup-
plies the posterior ciliary (to choroid and outer retina) and central retinal (to
inner retina) arteries. The central retinal artery (CRA) enters the optic nerve
about 1 cm posterior to the globe, and an embolus may become lodged as the
CRA pierces the dural sheath of the nerve, or posterior to the lamina cribosa,
resulting in a CRA occlusion (CRAO, involvement of inner retinal layers,
sparing of optic nerve head, outer retina, and choroid). The arterial circle of
Zinn–Haller supplies the optic nerve head, which is made up of anastomoses
from branches of short posterior ciliary arteries (from posterior ciliary artery,
PCA), the adjacent pial network, and choroidal vessels. Hypoperfusion of the
PCA is the likely cause for nonarteritic anterior ischemic optic neuropathy.
Ophthalmic artery pathology (e.g., thromboembolic and giant cell arteritis)
results in ischemia of the retina, choroid, and optic nerve. (Redrawn and mod-
ified with permission from: Digre KB, Corbett JJ Practical Viewing of the
optic Disc. Boston: Butterworth-Heineman 2003)
than it is to distinguish monocular from binocular transient vision

loss.
Do not miss this! Occasionally, retinal ischemia can be due to

vasospasm (migrainous or other). This is a diagnosis of exclu-
sion as thromboembolic causes must first be evaluated for.
Patients with acute onset vision loss need urgent ophthalmic/
neuro-ophthalmic evaluation to rule out an ocular cause, for
Table 3.4 Help me now with transient vision loss: Historical and examination features to narrow the differential diagnosis
Age Timing Pain Laterality Examination Other
Amaurosis >50 years Abrupt onset, Absent Unilateral Normal in Anterior circulation:
fugax (retinal ascending or between, may Ipsilateral carotid disease
TIA) descending, see (atherosclerosis, dissection)
lasting minutes Hollenhorst is most common; consider
plaque cardioembolic and other
stroke mechanisms including
hypercoagulability; consider
GCA or high-grade carotid
stenosis with bright light
amaurosis (i.e., patient
Prechiasmal (Monocular Vision Loss)
cannot see after exposure to

a bright light)
Giant cell >50 years Abrupt onset, Eye pain or Unilateral or bilateral May be Inflammation of the
arteritis (GCA) spontaneous or headache normal, look temporal artery; usually with
can be bright common for evidence associated headache, jaw
light-induced of optic nerve claudication, constitutional
and/or retinal symptoms, diplopia
ischemia
(continued)
79
80
Age Timing Pain Laterality Examination Other

Hypoperfusion Any age Closely Absent Bilateral Normal (check Associated orthostatic
associated with vital signs and lightheadedness/dizziness,
postural evaluate for can have “tunnel” vision or
changes (e.g., orthostatic diffuse vision loss
sitting to hypotension) bilaterally; associated with
standing) inadequate hydration,
medications, or autonomic
dysfunction; consider
vertebrobasilar insufficiency
in older patients with
vascular risk factors and
bilateral transient vision loss
Migrainous Any age Progression A headache Bilateral > unilateral Normal Positive visual phenomena
visual aura (but be over minutes may or may (scintillating scotoma) are
concerned and lasting not follow more common than negative
if new minutes to an visual aura (vision loss), although either
onset in hour or so, may is possible
someone be a typical
>50 years (e.g.,
old) light-induced)
migraine trigger
Age Timing Pain Laterality Examination
Other
Seizure (ictal or Usually Abrupt onset, Absent Bilateral Normal
Positive visual phenomena
postictal) <50 years seconds in (ictal) are more common
duration than negative (ictal or
postictal)
Uhthoff’s Usually Associated Absent Unilateral > bilateral Evidence of There is typically a known
phenomena <50 years with strenuous optic atrophy history of optic neuritis (or
activity, hot in the affected less commonly other optic
shower/bath, eye neuropathy) in the affected
fever eye; may be due to
subclinical optic neuropathy
in multiple sclerosis patient
Transient visual Usually Associated Headache is Bilateral or unilateral Papilledema TVO’s are common in IIH in
Prechiasmal (Monocular Vision Loss)
obscurations <50 years with changes common when papilledema is addition to pulsatile tinnitus
(TVO’s due to in posture or with asymmetric and headaches
papilledema) head position elevated
intracranial
pressure
A few transient vision loss caveats: consider ocular causes such as tear film abnormalities and corneal epithelial disease (e.g., dry eye),
other corneal disease (e.g., erosion), anterior chamber abnormalities (e.g., uveitis, hyphema), vitreous floaters, acute angle closure
glaucoma (topiramate can be a trigger for this). Patients may not be sure whether transient vision loss was unilateral or bilateral (e.g.,
etiologies causing homonymous involvement such as ischemia, migraine, seizure); however, the distinction between vascular or non-
vascular is more important
81
example, a patient with a retinal detachment may experience

descending vision loss like a curtain coming down. Although
Susac syndrome is rare, consider this diagnosis with BRAOs,
headaches, cognitive symptoms, audiovestibular loss, and/or
corpus callosal MRI lesions (“snowball” or “cannonball” seen
on sagittal MRI).
What is next? Patients presenting with persistent vision loss due

to BRAO/CRAO or transient vision loss due to amaurosis fugax
must undergo an expeditious TIA/stroke workup. This should
include MRI brain (looking for diffusion-weighted imaging
lesions—this provides further evidence not only for ischemia, but
also for stroke mechanism—for example, bihemispheric DWI
hyperintensities in multiple vascular territories are highly suspi-
cious for a cardioembolic source), MR or CT angiography, and/or
carotid ultrasound to evaluate the ipsilateral carotid artery, echo-
cardiogram, and cardiac monitor (e.g., atrial fibrillation). Consider
GCA and check ESR and CRP urgently when there is any suspi-
cion. If vascular workup is unremarkable, consider hypercoagula-
bility workup, especially in patients with personal or family
history of clotting disorders or cancer.
Treatment options Unfortunately, there is no clear evidence-

based treatment for BRAO/CRAO, and management varies
widely from institution to institution (e.g., ocular massage, ante-
rior chamber paracentesis, intra-ocular pressure-lowering agents,
hyperbaric treatment, intra-arterial, or intra-venous tPA). For sec-
ondary stroke prevention following amaurosis or BRAO/CRAO,
the stroke workup should guide you (e.g., CEA with severe ipsi-
lateral carotid disease or anticoagulation with atrial fibrillation).
If you can only remember one thing… Like a cerebral TIA, a

retinal TIA requires urgent stroke workup!

3.5.1.2 Photopsias
Case A 45-year-old woman presented to the clinic with com-
plaints of transient visual disturbances. She had a history of
migraine headaches going back to her teenage years and expe-
rienced three episodes in the last 3 years of the following: first,
a spot would appear with shimmering edges, which was bilat-
eral and homonymous—this spot would expand and move
across the visual field over minutes. Sometimes, this was also
associated with zig-zag or “broken” lines. Each of these epi-
sodes (which would last from 10–30 min) was followed by a
typical migraine headache. This last happened 2 weeks ago, at
which time she was seen by an optometrist who referred her to
neurology. In the last week, she experienced several episodes
of looking to the right or to the left and seeing a silver “flash”
temporally OD, especially notable in dim lighting. There was
the occasional appearance of a “floater” OD as well, but she
denied vision loss. Dilated fundus examination did not demon-
strate retinal tears or detachment, but a Weiss ring was seen
OD, suggestive of vitreous detachment from the optic nerve.
She was diagnosed with episodes of visual aura related to
migraine as well as acute posterior vitreous detachment (PVD)
causing the flashes.
Key questions to ask
• New floaters, flashes, vision loss? (e.g., retinal tear/detach-

ment)
• Positive visual phenomena such as bilateral and homonymous
scintillating scotoma lasting minutes? (e.g., migraine)
• Pulsating silver dots, synchronous with heartbeat, more notice-
able on a light background? (e.g., entopic phenomena)
• Color-tinged vision? (e.g., yellow—digitalis; blue/green—
erectile dysfunction medications)
• Bilateral and simultaneous? (e.g., vertebrobasilar insufficiency,
migraine, entopic, drug-induced, hypo-/hyperglycemia)
• Are there central sparkles/twinkling? (e.g., retinopathy—reti-
nitis pigmentosa; maculopathy—neovascular macular degen-
eration; optic nerve— papilledema)
• Did the symptoms begin after cataract surgery? (pseudophakic

dysphotopsia can cause positive [light streaks, arcs, flashes,
and starbursts] or negative [peripheral temporal arc-shaped
dark line or shadow] disturbances)
Key findings to elicit Rule out retinal tear/detachment when sus-

pected. A Weiss ring can be visualized with a direct ophthalmo-
scope or Panoptic although the focus must be anterior to the optic
nerve. Otherwise, evaluation of the maculae, retinae, and optic
nerves should be normal when migraine is suspected.
Pitfalls Be concerned when a patient with vascular risk factors

has a first attack of transient visual symptoms (positive or nega-
tive phenomena) or when migraine history is remote, weak, or
absent.
Do not miss this! In a patient with vascular risk factors, con-

sider carotid disease when symptoms are monocular or vertebro-
basilar insufficiency when visual symptoms are bilateral and
simultaneous. Typically, transient visual symptoms that are vas-
cular cause a negative (e.g., vision loss) disturbance, although
positive symptoms can also be experienced. Consider seizures
when a positive visual symptom is homonymous and experi-
enced for seconds at a time, especially in a patient with known
epilepsy.
What is next? When a vascular etiology is suspected, urgent

imaging of the carotid arteries (when symptoms are monocular)
or the posterior circulation (when symptoms are bilateral) in addi-
tion to MRI to look for diffusion-weighted imaging h yperintensities
is required. If a vascular etiology is suspected and vessels are pat-
ent, cardioembolic etiologies must be explored as well.
Treatment options Visual aura related to migraine can be man-

aged just as migraine headaches would be, for example, migraine
diet, lifestyle modifications (stress reduction and sleep hygiene),
vitamins (riboflavin or magnesium), or a variety of preventive
prescription medications.
If you can only remember one thing… Do not blame all tran-
sient positive (and negative) visual phenomena on migraine!
3.5.2 Optic Nerve
3.5.2.1 N AION (nonarteritic anterior ischemic optic

neuropathy)
Case A 65-year-old man with a history of hypertension and dia-
betes woke up with inferior vision loss OS. He denied new head-
aches, jaw claudication, constitutional symptoms, or temporal
tenderness, and was otherwise asymptomatic. Examination dem-
onstrated normal acuities OU, mild dyschromatopsia OS, moder-
ate relative APD OS, in addition to optic nerve swelling OS with
hemorrhage superiorly. The right optic nerve was normal but
crowded and with a cup:disc ratio of 0.2. Static (Humphrey)
visual field perimetry demonstrated an inferior (arcuate) visual
field defect OS. CRP and ESR were normal, and nonarteritic ante-
rior ischemic optic neuropathy (NAION) was diagnosed. There
was no change in his vision over the next 6 months of follow-up,
although superior pallor was noted OS months later, a conse-
quence of the mainly superior optic nerve head injury.
Figure Fig. 3.8
Key questions to ask Most importantly, the distinction between

NAION and giant cell arteritis (GCA) must be made. In patients
without obvious vascular risk factors, occasionally the distinction
between ION and optic neuritis can be difficult—mild ocular dis-
comfort is sometimes endorsed in the former, but significant pain is
common in the latter. Hypercoagulability can be considered with
bilateral NAION or with a family history or other personal history
of clotting disorders, although the etiology is not thought to be pri-
marily embolic (especially, given the extremely small caliber of the
anastomotic branches making up the arterial circle of Zinn–Haller).
R L acute
L chronic
L R
Fig. 3.8 The fundus appearance of nonarteritic anterior ischemic optic neu-
ropathy (NAION): Seen here is a patient with typical neuro-ophthalmic signs
of NAION including (1) ipsilateral (OS) optic nerve swelling, slightly more
superiorly with associated splinter hemorrhage (arrow), no discernible cup
OS; (2) ipsilateral (OS) inferior arcuate defect (correlating with the superior
optic nerve head being most affected); and (3) contralateral (OD) “disc at
risk,” crowded with small cup:disc ratio (about 0.2). Several months later,
optic nerve atrophy had developed OS, which was visible as superior segmen-
tal pallor (arrowhead)
Key findings to elicit Features of an optic neuropathy including

rAPD; swelling and hemorrhage (can be segmental) of the affected
optic nerve head with a “disc at risk” (typically <0.3 cup:disc) in
the fellow eye; altitudinal or arcuate defects are common (Fig. 3.3)

vision loss?
Table 3.1; ESM 3.1
Pitfalls If the following are present, think GCA: light percep-

tion only or no light perception vision, chalky white/pale edema,
retinal cotton wool spots; if significant pain is present, consider
optic neuritis in a young patient and GCA in an older patient.
Also consider atypical causes of optic neuritis in patients >50
years old, including neuromyelitis optica, syphilis, sarcoidosis
among others.
Do not miss this! GCA!
What is next? ESR, CRP, CBC (looking for anemia and high
platelets), if there is ANY suspicion for GCA in a patient who is
>50–55 years old. Contrast-enhanced MRI brain and orbits in a
patient when there is diagnostic uncertainty (e.g., optic nerve
enhancement in optic neuritis; optic nerve sheath enhancement in
GCA or anti-myelin oligodendrocyte glycoprotein (MOG)). If
phosphodiesterase-5 inhibitors are used for erectile dysfunction,
sleep apnea is present, or blood pressure agents are taken immedi-
ately prior to sleep, counsel the patient about a possible associa-
tion. There is a ~20% risk of developing NAION in the fellow eye
in the next 5 years.
Treatment options Unfortunately, there is currently no evidence-

based medicine (e.g., steroids) or surgery (e.g., decompression)
for NAION.
If you can only remember one thing… If you do not see a “disc
at risk” in the fellow (unaffected) eye, consider other etiologies!
3.5.2.2 Giant Cell Arteritis (GCA)

Case A 70-year-old woman presented to the ED with new onset
headaches and vision loss. The headaches began 1 week prior and
were right sided. She was not previously a headache person. She
also noticed tenderness over the scalp while combing her hair, in
addition to jaw discomfort when chewing. She abruptly lost vision
in the right eye on the morning of presentation to the emergency
department (ED). On exam, she had normal cranial nerve and eye
movement exams. She had no light perception vision OD, and in
the left eye, acuity was 20/30 with normal color vision and fields to
confrontation. There was a significant rAPD OD. Funduscopy dem-
onstrated swelling of the right optic nerve with a pale appearance as
well as splinter hemorrhages in both eyes (including the left eye).
Both ESR and CRP returned significantly elevated, and intravenous
(IV) steroids were started in the ED. Unfortunately, there was no

improvement OD, and she experienced new abrupt onset vision loss
OS to light perception (LP) only in the next 24 hours. Temporal
artery biopsy done 1 day later showed granulomatous inflammation
with giant cells, destruction of elastic fibers, and fragmentation of
the internal elastic lamina, confirming the diagnosis of giant cell
arteritis (GCA). Headaches, scalp tenderness, and jaw claudication
resolved rapidly with steroids, and she was discharged on predni-
sone by mouth. Inflammatory markers trended down significantly
over the weeks, but vision did not improve from LP OU.
Figure Fig. 3.9
Key questions to ask in a patient >50–55 years old with acute

vision loss (especially with associated pain)
GCA symptoms:
• Constitutional symptoms (fever, night sweats, chills)?
• History (or symptoms) of polymyalgia rheumatica?
• Headaches or eye pain?
• Scalp tenderness?
• Jaw claudication?
• Amaurosis fugax (sometimes bright light induced) or persis-
tent vision loss?
• Also ask about vascular risk factors that might contribute to
nonarteritic anterior ischemic optic neuropathy or retinal artery
occlusion.
• Transient or persistent diplopia?
Key findings to elicit GCA can cause (transient or permanent)

diplopia due to ischemia of the ocular motor nerves and/or extra-
ocular muscles. Palpate the temporal arteries to evaluate the pulse
and assess for ropiness/hardness. On the fundus exam, evaluate for
optic nerve head swelling or hemorrhage and features of retinal
ischemia (e.g., cotton wool spots, which are retinal nerve fiber
layer infarcts). Posterior ischemic optic neuropathy (PION) is rare,
but optic nerves will appear normal due to the retrobulbar location
and is often due to GCA or seen in the setting of cardiac or spine
surgery (especially with associated anemia or hypotension).
Acute R L
3 months
R L
later
Fig. 3.9 The fundus appearance of giant cell arteritis (GCA): Several typical
features of GCA are seen in this patient with bilateral involvement. Right eye:
pallid/chalky-white severe optic nerve head edema with multiple splinter
hemorrhages (arrows); Left eye: mild segmental (superior) swelling and infe-
rior hemorrhage. The bilaterality and pallid swelling OD are very concerning
for GCA and would be highly atypical for nonarteritic anterior ischemic optic
neuropathy (NAION). Additionally, if there is optic nerve (unilateral or bilat-
eral) and retinal involvement (branch or central retinal artery occlusion; cot-
ton wool spots), GCA should be assumed until proven otherwise. Vision did
not recover despite high dose steroids, and severe bilateral optic nerve pallor
and retinal vessel attenuation was apparent months later

vision loss?
Table 3.1; ESM 3.1
Pitfalls Typical symptoms of GCA may be lacking about 20% of

the time in a GCA patient presenting with vision loss. This makes
it especially important to always keep GCA on the differential
diagnosis in an older patient, and ESR and CRP should be checked
if there is any suspicion.
Do not miss this! When GCA is considered, steroid therapy

should be initiated immediately and temporal artery biopsy (TAB)
arranged. While other diagnostic modalities (e.g., cranial ultra-
sound, contrast-enhanced MRI) may offer additional clues, a TAB
is almost always still necessary.
What is next? Intravenous steroids may be favored over oral ste-

roids when there is profound vision loss, when the patient experi-
ences attacks of amaurosis due to GCA, or when there is early
evidence of involvement in the fellow eye (as in this case).
Treatment options Steroids are the treatment of choice acutely,

either PO or IV. Steroids are generally the mainstay for chronic
therapy as well, although side effects can be significant and vari-
ous steroid-sparing agents are sometimes used for maintenance.
Tocilizumab is a new medication that has been approved by the
FDA, and while expensive, it can be used in place of or in addition
to (allowing for smaller prednisone dosing) steroids.
If you can only remember one thing… GCA should be on the

differential diagnosis of transient or persistent vision loss or dip-
lopia in any patient >50–55 years old, even when typical symp-
toms are lacking (e.g., headaches).
3.5.2.3 Optic Neuritis

Case A 20-year-old woman complained of eye pain OD that was
aggravated by palpation and eye movements, followed by vision
loss in the same eye hours later. The vision loss progressively
worsened over the next 24 h until she presented to the emergency
department. Examination demonstrated counting fingers vision
centrally at 2 feet OD with normal vision OS. There was a promi-
nent rAPD OD, and the optic nerves and retinae appeared normal
OU. Clinically, the diagnosis of optic neuritis was made. MRI of
the brain was performed which did not show any demyelinating
lesions, although there was a T2 hyperintensity and T1 contrast
T2 Coronal
R L
T1 Coronal with contrast
L R
Fig. 3.10 Clinical and radiologic features of typical optic neuritis: Despite
vision loss in the right eye (severe field loss in the right eye, with an artifac-
tual rim defect seen inferiorly in the left eye, i.e., disappeared when the
patient was repositioned and retested) associated with pain, the right optic
nerve appeared normal due to the retrobulbar location of the optic neuritis
(“the patient sees nothing and you see nothing”). T2 hyperintensity of the
right optic nerve was apparent (top MRI), which can be seen acutely or chron-
ically in a variety of optic neuropathies. However, contrast enhancement of
the right optic nerve was also demonstrated, a finding that is common with an
acute inflammatory/autoimmune optic neuropathy
enhancement of the right optic nerve. Intravenous steroids were

given for 3 days with improvement to 20/400 centrally OD. By
3 months, her vision was back to 20/25 OD with persistent dys-
chromatopsia and rAPD, and temporal pallor. Follow-up MRI at
1 year was also normal without evidence of lesions suggestive of
multiple sclerosis (MS).
Figure Fig. 3.10

• History of other vision loss/episodes? (previous optic neuritis)
• History of neurologic symptoms? (symptomatic demyelinat-
ing lesions of brain or spinal cord)
• Personal or family history of autoimmune disease? (MS or
related)
Key findings to elicit Typical: Due to the retrobulbar location of

the inflammation, the fundus exam will often appear normal.
Mild-moderate unilateral optic nerve swelling can occur in about
1/3 of cases in adults (swelling and bilateral involvement more
common in kids—see Chapter 7: Pediatric Clinical Pearls).
Significant dyschromatopsia and rAPD are prominent features
(compared to a maculopathy or neuroretinitis for instance).
Atypical: Retinal/macular exudates, bilateral involvement, or
severe swelling with hemorrhages in an adult, consider other eti-
ologies (Fig. 3.11).

vision loss?
Table 3.1; ESM 3.1
Pitfalls While central vision is often involved with optic neuritis

(involvement of the papillomacular bundle, Fig. 3.1), any pattern
Fig. 3.11 Atypical fundus features in optic neuritis: Consider an atypical

cause (e.g., neuromyelitis optica, anti-myelin oligodendrocyte glycoprotein
[MOG], neurosarcoidosis) when any of the following features are present in
an adult with optic neuritis: (1) bilateral involvement, (2) severe swelling, (3)
hemorrhage (arrow), (4) light perception or no light perception vision, (5)
retinal exudates, and/or (6) steroid dependence
of monocular vision loss can be seen (Fig. 3.3). Remember that a

maculopathy can be responsible for central vision loss as well, so
dilated examination is warranted in these patients. If a macular
star (may be absent acutely or missed with undilated direct oph-
thalmoscopic exam) is seen or there is optic nerve edema with a
mild or no rAPD, ask about recent exposure to kittens or cat
scratches (neuroretinitis due to Bartonella henselae)
Do not miss this! Along with atypical findings on the fundus exam
(see above), no light perception vision, steroid dependency (e.g.,
recurrence or worsening symptoms when coming off prednisone),
and bilateral simultaneous or chiasmal involvement should lead the
clinician to consider neuromyelitis optica (NMO), anti–myelin oli-
godendrocyte glycoprotein (anti-MOG), neurosarcoidosis, syphilis,
neuroretinitis especially when a macular star is present among oth-
ers (Fig. 3.12). If there is no pain and vision loss is unilateral, bilat-
eral simultaneous, or sequential, consider Leber’s hereditary optic
neuropathy.
T2 Coronal T1 Coronal with contrast T1 Coronal with contrast
Fig. 3.12 Radiologic features of atypical optic neuritis: A 50-year-old

woman with neuromyelitis optica (previous attack of myelitis and + aquapo-
rin antibodies) presented with severe bilateral eye pain and vision loss (dif-
fuse depression OD and mainly temporal loss OS). MRI demonstrated
asymmetrically enlarged and T2 hypertense optic chiasm (right > left, white
arrow) with contrast enhancement of the chiasm (yellow arrow), prechias-
matic right optic nerve, infundibulum, and bilateral optic nerve sheaths
(orange arrows, a finding that is generally more typical of anti-MOG)
What is next? Brain MRI to assess risk for multiple sclerosis—

if no brain lesions, risk of developing MS is about 20% at 15 years.
If 3 or more brain lesions, risk is about 90% at 15 years, or
depending on other signs/symptoms, the patient may meet
McDonald 2017 criteria for a diagnosis of MS at presentation.
MRI of the cervical and thoracic cord may be helpful to search for
asymptomatic lesions, and should always be performed when
symptoms/signs indicative of a myelopathy are present. Lumbar
puncture is often needed in atypical cases to exclude other etiolo-
gies and to look for oligoclonal bands (common in MS). When
atypical features are present, other inflammatory, autoimmune,
paraneoplastic, and infectious etiologies should be explored.
Consider testing for NMO, a nti-MOG, and other atypical etiolo-
gies when appropriate. Contrast-enhancement involving the optic
nerve(s) ± chiasm is typically seen with demyelinating diseases
(MS, NMO, anti-MOG, and acute disseminated encephalomyeli-
tis [ADEM]), but also consider neoplasm (lymphoma, leukemia,
and glioma) and infection (viral, syphilis, and Lyme), as well as
radiation-induced, sarcoidosis, and vasculitis in the differential.
Treatment options IV steroids for 3–5 days followed by an oral

steroid taper can help to hasten visual recovery/mitigate pain,
although the final visual outcome is likely to be the same with or
without steroids in typical optic neuritis. Fortunately, visual prog-
nosis for these patients is favorable, with >90% achieving 20/40
acuity or better. For NMO and MOG, more aggressive therapies
are often needed acutely if there is no steroid response (e.g.,
plasma exchange).
If you can only remember one thing… Not all central vision
loss in a young patient (especially female) is optic neuritis! A
dilated fundus exam may provide important clues (e.g., macular
star in neuroretinitis) or may lead to a non-neurologic diagnosis
(central serous chorioretinopathy).

3.5.2.4 Papilledema
Case A 30-year-old woman complained of headaches for the last
3 months with episodes of “graying out vision” OU for the last
2 weeks. Her BMI was 32, and she gained 15 pounds in the last
6 months. She also admitted to “whooshing” in both ears that was
synchronous with her heartbeat. On examination, there was no
rAPD, and normal acuity and color vision. Static visual field
perimetry demonstrated enlarged blind spots OU. She had bilat-
eral optic nerve swelling with obscuration (by edema) of several
of the blood vessels on the optic nerve head, as well as those exit-
ing the nerve. Contrast-enhanced MRI demonstrated distended
optic nerve sheaths and flattening of the posterior sclera OU along
with an empty sella. MR venogram demonstrated bilateral trans-
verse sinus stenosis (TSS), without evidence of venous thrombo-
sis. Opening pressure on lumbar puncture (measured in a lateral
recumbent position with legs extended) was 42 cm of water.
Idiopathic intracranial hypertension (IIH) was diagnosed, and the
patient was started on acetazolamide and counseled on weight
loss.
Figure Fig. 3.13

• Persistent vision loss or transient visual obscurations (TVOs,
postural change induces hypoperfusion of the swollen nerves
as in this case)?
• Headaches?
• Double vision (sixth nerve palsy, unilateral or bilateral, is most
common)?
• Pulsatile tinnitus?
• Recent weight gain?
• Neck or arm pain (radicular irritation due to elevated ICP)?
• Arm, leg or back pain, sensorimotor symptoms? (rarely a spi-
nal tumor can cause elevated ICP)?
• Obstructive sleep apnea?
R L
L R
Fig. 3.13 Clinical features of papilledema: Visual acuity and color vision are
almost always normal early in the course of idiopathic intracranial hyperten-
sion (IIH), and automated static visual field perimetry should be followed
closely. Enlarged blind spots (due to distortion of the peripapillary retina by
the swollen optic nerve) are commonly seen, as well as nasal and peripheral
inferior and superior defects as the disease progresses. The fundus photos
above the visual fields come from the same patient, with the white arrows
pointing to several examples of vessels on the disc being partially obscured
by edema (Frisen grade 4). The arrowheads point to temporal concentric peri-
papillary wrinkles (the fundus photo to the left comes from another patient,
with chronic [Frisen grade 2] papilledema who had developed optic atro-
phy—note the optic nerve pallor), another potential manifestation of elevated
intracranial pressure (along with retinal and choroidal folds). Hemorrhages
are also commonly seen in patients with active papilledema. Fundus photog-
raphy is an excellent way to document the fundus examination when avail-
able, and the Frisen papilledema grading scale should be used when possible:
Grade 0—no halo of obscuration of the peripapillary nerve fiber layer; Grade
1—obscuration of the peripapillary retina with a C-shaped halo (sparing tem-
poral margin) of retinal nerve fiber layer edema; Grade 2—circumferential
halo without obscuration of blood vessels; Grade 3—major vessel(s) are
obscured by edema as they exit the disc; Grade 4—major vessel(s) are
obscured by edema on the disc; Grade 5—partial or complete obscuration of
all vessels
• Anemia or hypertension?
• Hypercoagulable state or use of oral contraceptive/hormonal
drugs? (consider cerebral venous thrombosis)?
• Use of tetra-, mino-, or doxycycline, nitrofurantoin, vitamin A

(or retinoids), growth hormone, Addison’s disease, or other
endocrine disorders?
Key findings to elicit Acuity and color vision are spared until late
in the disease, and rAPD is uncommon unless there is severe and
asymmetric field loss. Formal visual field testing is essential (most
commonly Humphrey automated static perimetry), and the most
common defects include enlarged blind spot, nasal defects, and/or
peripheral loss. Papilledema is almost always present and should be
photographed and graded using the Frisen grading scale (0–5, based
mainly on obscuration of blood vessels, see Fig. 3.13) when possi-
ble. Splinter hemorrhages, located on or around the nerve, are often
seen in acute cases, as well as obscuration of the blood vessels and
retinal nerve fiber layer, in addition to peripapillary wrinkles and
retinal/choroidal folds. Criteria exist for IIH without papilledema as
well, although this rarely leads to vision loss (e.g., ICP may not be
transmitted as well via a narrow optic canal or across the lamina
cribrosa in certain patients due to anatomic variations). Macular
exudate (or a star) may be seen when the papilledema is severe.
Patients with chronic papilledema often develop gliotic changes on
and around the optic nerve head, and retinochoroidal collateral ves-
sels as well as atrophy/pallor can also develop (Fig. 3.14). Notably,
a patient who has developed significant optic atrophy will be unable
to swell if IIH recurs (headache and other ICP symptoms and visual
exam must be relied upon in these cases).
How do I approach (history and exam) the patient with acute,

subacute, or chronic vision loss? Tables 3.1 and 3.2
Pitfalls Remember that not all bilateral optic nerve swelling is

due to elevated ICP. If there is loss of vision, color, or atypical
visual fields defects (e.g., central or centrocecal scotoma), con-
sider other causes of optic neuropathy (e.g., optic neuritis
including NMO and anti-MOG; bilateral anterior ischemic
optic neuropathy in an older patient). Also, remember that optic
nerve head drusen (a “lumpy bumpy” appearance, Fig. 3.15),
can give the appearance of papilledema, so-called pseudopap-
R L
L R
Fig. 3.14 Clinical features of advanced papilledema: While visual acuity and
color vision are spared in early idiopathic intracranial hypertension (IIH), in
more advanced disease, they are often involved. This patient has 20/50 acuity
OU and mild dyschromatopsia. Additionally, there was severe peripheral visual
field loss/constriction. While there were no active features of papilledema (e.g.,
hemorrhage, obscuration of blood vessels, edema), this was because they were
severely atrophic and unable to swell. The arrows point to gliotic changes that
give the disc margins a greyish appearance, and the arrowhead points to a reti-
nochoroidal collateral vessel. These collateral vessels may develop in certain
conditions, typically due to retinal venous outflow impairment—i.e., blood will
drain via the choroidal venous system instead. In addition to chronic papill-
edema, collaterals may also be seen with optic nerve meningiomas, gliomas,
sarcoidosis, central retinal venous occlusion, and glaucoma
illedema. Drusen can be superficial and visible on fundus exam

(Fig. 3.15), or buried and more challenging to diagnosis (see
Table 3.3).
R L
L R
Fig. 3.15 Optic nerve head drusen—a common cause of pseudo-papilledema:

This patient was referred out of concern for papilledema, after being found to
have an abnormal optic nerve appearance on routine ophthalmoscopy. Visual
acuity and color vision were normal, there was no relative afferent pupillary
defect, and static automated perimetry demonstrated bilateral nasal step
defects (more inferior OS and more superior OD, black arrows), compatible
with retinal nerve fiber layer (RNFL) injury. The white arrows point out the
typical “lumpy bumpy” (i.e., yellow elevations) appearance of optic nerve
head drusen, which can damage the RNFL, leading to (generally, mild and
asymptomatic) visual field loss. Because the optic nerve can be elevated by
the drusen (visible or buried drusen), and because the disc margins can be
obscured, patients may be misdiagnosed with papilledema, when in fact this
is a common cause of “pseudo-papilledema.” While the drusen are clearly
visible in this patient, oftentimes this is not the case and the examiner should
look for other features of an anomalous optic disc (e.g., small and crowded,
anomalous vascular branching patterns [early branching and trifurcations],
lack of venous engorgement, irregular elevation of the optic disc, lack of ves-
sel or RNFL obscuration, and intact spontaneous venous pulsations). Orbital
ultrasound and enhanced depth optical coherence tomography are often used
to aid in the diagnosis (especially for the more challenging to diagnose buried
drusen), and occasionally drusen can also be seen on a CT scan (yellow
arrow, note that CT should not be ordered specifically for this purpose)
Do not miss this! Especially when risk factors are present,

venous thrombosis must be ruled out urgently. Be especially con-
cerned with thin patients, papilledema in men, and look for sec-
ondary causes of elevated ICP (see below). The diagnosis of IIH
cannot be made without excluding a mass lesion (with imaging)

or vascular lesion (with contrast-enhanced MRI and MR veno-
gram for cerebral venous thrombosis), meningitis (need imaging
and lumbar puncture), or conditions that may cause abnormal
CSF constituents (elevated CSF protein with a spinal ependy-
moma or Guillain–Barre syndrome). For this reason, papilledema
is a finding that deserves urgent workup. Consider Vogt–
Koyanagi–Harada disease when there is papilledema in addition
to audiovestibular involvement, uveitis, vitiligo, and/or poliosis.
What is next? MRI w/wo and MR venogram to rule out mass

lesion and thrombosis, respectively. Typical features of elevated
ICP (distended optic nerve sheaths, flattening of the posterior
sclera OU, empty sella, and TSS; Fig. 3.16) are commonly seen
on MRI/MRV and support the diagnosis. Lumbar puncture should
be performed to (1) measure the opening pressure and (2) ensure
that the CSF analysis is normal without evidence of i nflammation/
infection (Lyme) or neoplasm (lymphoma). Patients must be fol-
lowed serially for visual testing (especially with automated perim-
etry) and fundus exams. OCT can be helpful to monitor for
damage to the ganglion cell layer and to evaluate the overall thick-
ness of the RNFL, although the RNFL values tend to be less accu-
rate when edema is significant.
Treatment options Acetazolamide is the most commonly used

drug, and it is best to titrate up slowly when possible due to side
effects. Other options include furosemide, methazolamide,
zonisamide, and topiramate (the latter two may offer better head-
ache protection but have less carbonic anhydrase effect).
Counseling for weight management is essential. When acuity and
color vision are affected and field loss is significant, invasive pro-
cedures may be indicated. Surgical options in those patients
refractory to medical therapy or with significant vision loss
include CSF shunting procedures (lumboperitoneal and ventricu-
loperitoneal), optic nerve sheath fenestration, venous sinus stent-
ing, and bariatric surgery. These options depend on many factors
T2 Axial
T1 Sagittal MR Venography
Fig. 3.16 Radiologic features of elevated intracranial pressure: The follow-

ing neuroimaging signs support the diagnosis of elevated intracranial pres-
sure: (1) distention of the optic nerve sheaths (white arrowhead); (2) flattening
of the posterior sclera (white dashed arrows); (3) empty sella (white arrow);
and (4) transverse venous sinus stenosis (black arrow, bilateral in this case).
Protrusion of the swollen optic nerve head into the vitreous (black arrowhead)
is a finding that may be seen with optic nerve edema/elevation due to a variety
of etiologies. Tortuosity of the optic nerve is another common finding with
elevated intracranial pressure
(especially, the institution and available resources) and have not

been compared in a large randomized controlled trial to date.
If you can only remember one thing… Patients with IIH must
be followed closely for symptoms of ICP as well as for fundus
exams and automated perimetry—checking visual acuity and
color vision alone is inadequate!

3.6 Chiasmal Visual Disorders
3.6.1 Pituitary Tumor
Case A 70-year-old man presented with 6 months of visual changes.

He initially noticed that vision in each eye just was not as good as it
had been previously, although the exact onset of visual symptoms
was unclear. He was prescribed new glasses, which did not help. He
was referred for cataract evaluation, and it was felt that cataracts did
not explain his visual symptoms. When looking at words, letters
could go missing. Visual symptoms worsened, and he was referred
to neuro-ophthalmology. Visual acuities were 20/25 OU with mild
dyschromatopsia OU and no rAPD. Pupillary constriction in each
eye was mildly sluggish. With fields to confrontation and static
perimetry, there was a bitemporal hemianopia. He had not experi-
enced neurologic symptoms (including headaches) to suggest a
mass lesion, and he denied known endocrine disease or symptoms.
MRI demonstrated a pituitary macroadenoma with compression of
the chiasm, and he underwent transsphenoidal resection of his ade-
noma with immediate improvement in his bitemporal hemianopia.
Endocrine evaluation was unrevealing, specifically with regard to
growth hormone, prolactin, and ACTH levels. He was followed for
years without further change in visual fields or MRI.
Figure Fig. 3.17

• Are there headaches or focal neurologic symptoms/signs
(hemiparesis and/or hemianesthesia) to suggest a mass lesion?
• Are there endocrine symptoms to suggest pituitary compres-
sion or infiltration? (ask about excessive fatigue, weight
change, mood changes, skin or hair changes, constipation, heat
or cold insensitivity, excessive thirst, excessive urination,
galactorrhea, impotence, change in ring, hat, or shoe size or
coarsening of facial features)
Key findings to elicit Bitemporal defects that respect the vertical

meridian localize to the optic chiasm. Furthermore, the specific
pattern can have localizing value with a compressive lesion, for
Chiasmal Visual Disorders 103
R L
L R
T1 Coronal (contrast)
T1 Axial (contrast)
Fig. 3.17 Clinical and radiologic features of chiasmal compression: This

patient was found to have a bitemporal hemianopia and bilateral optic nerve
pallor on clinical exam. The grayscale maps (top) demonstrate left > right and
superior > inferior visual field loss, suggestive of greater compression of the
left and inferior aspect (respectively) of the optic chiasm, and MRI demon-
strated a pituitary macroadenoma (white arrows). The grayscale maps dem-
onstrate lower visual sensitivity as darker regions, although these are not
compared to any normative database. The total deviation maps (bottom) are
generated by comparing the measured thresholds to an age-corrected normal.
In this example, the total deviation maps more clearly demonstrate the bitem-
poral nature of the defect than the grayscale maps. Analysis of the entire
report allows for more accurate interpretation and localization
example, if the bitemporal hemianopia is most dense superiorly,

the chiasm is being compressed inferiorly by a pituitary macroad-
enoma, as in this case. If the bitemporal loss is most dense inferi-
orly, think about compression superiorly (e.g., craniopharyngioma
or third ventriculomegaly due to hydrocephalus). If the vision loss
is bitemporal but only involves central vision (a central bitempo-
ral hemianopic scotoma), the chiasmal compression must be pos-
terior. Depending on the chronicity and severity of compression,
there may be a loss of acuity, color vision, and optic nerve pallor
can develop, each of which was demonstrated in this case.
Pitfalls If MRI of the brain with attention to the chiasm is nor-

mal, think about uncommon conditions that can also cause or
mimic a bitemporal hemianopia including retinopathies (e.g.,
retinitis pigmentosa), ethambutol toxicity, or even significantly
enlarged blind spots (e.g., papilledema).
Do not miss this! Usually, structural causes of a bitemporal hemi-

anopia include pituitary macroadenoma, suprasellar meningioma,
Rathke cyst, and craniopharyngioma. Occasionally, vascular contact/
compression of the chiasm can cause vision loss. In a child, consider
an optic pathway glioma and neurofibromatosis type 1 (Lisch nod-
ules are usually present on the irises). In the setting of severe head-
ache and bitemporal vision loss (± third, fourth, and/or sixth nerve
palsy), think about pituitary apoplexy. If a patient has bitemporal loss
and diabetes insipidus, consider germinoma, sarcoidosis, lympho-
cytic hypophysitis, and Langerhans cell histiocytosis. Neuromyelitis
optica, anti-MOG, and neurosarcoidosis are other causes of a chias-
mopathy (see “optic neuritis” section above). Rarely, pendular see-
saw nystagmus is also seen with a chiasmal lesion.
What is next? Any patient with a bitemporal hemianopia

requires contrast-enhanced MRI with attention to the chiasm and
pituitary region. Most etiologies will be identified with MRI. When
MRI is normal, consider other etiologies above. With a suprasel-
lar mass lesion, the most common etiologies can be remembered
with the mnemonic SATCHMO—Sarcoid, pituitary Adenoma or
Aneurysm, Teratoma (germ cell/germinoma), Craniopharyngioma,
Histiocytosis (Langerhans), Metastasis, Optic glioma
(hypothalamic-chiasmal).
Treatment options Surgical when vision loss is due to a com-

pressive lesion.
If you can only remember one thing… Always evaluate

visual fields (preferably with static or dynamic perimetry), in
each eye individually, in every patient with unexplained visual
symptoms!

Retrochiasmal Visual Disorders 105
3.7 Retrochiasmal Visual Disorders
3.7.1 The History
Patients with a homonymous hemianopia (HH) often feel that

vision is impaired in the eye with the temporal defect, for exam-
ple, a right HH may be perceived as a right eye problem. The key
is whether this is a bilateral symptom, that is, on the right side of
both eyes or the left side of both eyes.
3.7.2 The Exam
While finger counting is a good visual field screen at the bedside,

formal visual field testing using automated static (Humphrey or
Octopus) or dynamic (Goldmann) perimetry is far more sensitive
in detecting a subtle field defect. Comparison of hands/fingers or
red targets presented in different visual hemifields and quadrants
can help to identify relative visual field impairment for more
accurate bedside localization.
3.7.3 Treatment Options
Various yoked prism solutions have been proposed, but many

patients do not tolerate these solutions well. There is currently no
strong evidence for neuroplasticity-based vision therapy pro-
grams.
3.7.4 Optic Tract
What makes this localization unique?
• While optic tract lesions are fairly uncommon, consider etiologies

including stroke, neoplasm/compression, and trauma (lesions
affecting the tract can be easily overlooked on noncontrast MRI).
• A homonymous hemianopia (HH) due to an optic tract lesion
can be complete, which is nonlocalizing. When incomplete,
homonymous defects due to tract lesions are incongruous

(asymmetric).
• A rAPD is often seen in the eye with temporal loss, for exam-
ple, a patient with a left optic tract lesion causing incongruous
right HH will also have a (usually mild) right rAPD. The right
rAPD is thought to be due to the fact that ~53% of the fibers
cross in the chiasm (i.e., right optic nerve to left optic tract),
whereas ~47% of fibers from the right optic nerve remain
uncrossed in the chiasm and travel through the right optic tract.
• Bilateral optic nerve pallor can be seen due to the involvement
of presynaptic (i.e., proximal to lateral geniculate nucleus)
ganglion cell axons in the optic tract. For example, a left optic
tract lesion may cause mild temporal pallor OS and mild tem-
poral and nasal pallor OD (“bow tie” atrophy).
• Chronically, a characteristic OCT pattern of ganglion cell
layer–inner plexiform layer homonymous hemiatrophy is often
seen, due to retrograde transsynaptic degeneration.
• Fibers responsible for the pupillary light reflex leave the optic
tract just prior to synapsing in the lateral geniculate nucleus,
traveling to the midbrain pretectal nuclei and then to the
Edinger–Westphal nucleus. Therefore, a lesion of the brachium
of the superior colliculus can cause a rAPD without loss of
acuity, color vision or field, and may be associated with other
midbrain signs (e.g., a central fourth nerve palsy).
Figure Figs. 3.18 and 3.4
3.7.5 Lateral Geniculate Nucleus (LGN)
• While a pure LGN lesion is uncommon, the associated visual

field defects are unique and can be highly localizing.
• Look for one of the following: (1) horizontal sectoranopia
[lateral choroidal artery—posterior circulation] or (2) qua-
Incongruous right
L R
homonymous hemianopia
R L
Homonymous
hemiatrophy of GCL-IPL
on OCT
Fig. 3.18 Typical visual field and optical coherence tomography (OCT) fea-
tures of an optic tract syndrome: While visual acuity and color vision were
normal, this patient had a very incongruous (asymmetric) right homonymous
hemianopia (only able to demonstrate right temporal field loss OD to confron-
tation and only a mild nasal defect was seen OS with automated static perime-
try), in addition to a mild right relative afferent pupillary defect (rAPD). The
combination of an incongruous right homonymous hemianopia and right rAPD
was highly localizing to the right left optic tract, which was felt to be due to a
chronic infarct seen on MRI. A characteristic OCT pattern of ganglion cell
layer-inner plexiform layer homonymous hemiatrophy was also demonstrated
(black arrows demonstrate the focal sectoral thinning—nasal OD and temporal
OS—outside the 99% limit of normal). This pattern may be seen with any
chronic retrochiasmal lesion as retrograde transsynaptic degeneration occurs
but is more common (and faster to develop) with optic tract lesions
druple sectoranopia [anterior choroidal artery—anterior cir-

culation]). If due to a stroke, identification of one of these
homonymous patterns may provide a better understanding of
stroke mechanism, for example, if there is a right horizontal
sectoranopia due to left lateral choroidal artery (posterior
circulation) ischemia and left hemiparesis due to right mid-
dle cerebral artery (anterior circulation) ischemia, the fact
that there are bilateral strokes in two different vascular dis-
tributions is suggestive of a cardioembolic (e.g., atrial fibril-
lation) etiology.
Homonymous horizontal
sectoranopia (lateral
choroidal artery)
Homonymous quadruple
sectoranopia (anterior
choroidal artery)
Fig. 3.19 Lateral geniculate nucleus (LGN) lesions cause distinct homony-
mous visual field defects: The top visual field is an example of a homony-
mous horizontal sectoranopia, which can be a manifestation of lateral
choroidal artery territory ischemia (posterior circulation). The bottom visual
field is an example of a homonymous quadruple sectoranopia, which can be a
manifestation of anterior choroidal artery territory ischemia (anterior circula-
tion). (Visual fields courtesy of Dr. Neil Miller)
• Similar to an optic tract lesion, OCT GCL-IPL homonymous

hemiatrophy is often seen, as well as bilateral optic nerve pal-
lor when the presynaptic ganglion cell axons are affected.
3.7.6 Optic Radiations
Temporal radiations (Meyer’s loop)

• Meyer’s loop extends forward to within several centimeters of

the tip of the temporal lobe, and an anterior temporal lesion
can cause a superior quadrantic (“pie in the sky”) visual field
defect. When incomplete, the defect is often incongruous
(Figs. 3.20 and 3.4)
• A temporal lobe lesion may be responsible for epilepsy as well
as a HH, or a HH due to Meyer’s loop injury may result from
epilepsy surgery.
Parietal radiations
• Lesions can cause incomplete homonymous visual field

defects, more dense inferiorly (so-called “pie on the floor”)
L R
T1 Axial images
Fig. 3.20 A “pie in the sky” defect due to temporal lobe (Meyer’s loop)
injury: This is a patient with remote history of traumatic brain injury with
associated right temporal lobe encephalomalacia (white arrows). Since the
inferior optic radiations travel through the (right) temporal lobe (Meyer’s
loop), injury can cause a (left) incongruous (asymmetric) homonymous supe-
rior quadrantic visual field defect, as seen here
and often congruous (but not as congruous as occipital

lesions).
• Often associated with neurologic or visuospatial symptoms/
signs (e.g., tactile or visual extinction when presented with
bilateral simultaneous stimuli; visual neglect with a nondomi-
nant hemispheric lesion).
• There may also be absent optokinetic nystagmus when the
optokinetic flag/drum is directed ipsilesionally (Video 3.2).
Poor ipsilesional smooth pursuit is also commonly seen.
• With bilateral parietal injury, there may be bilateral (mainly)
inferior defects with features of Balint’s syndrome (oculomo-
tor apraxia, optic ataxia, and/or simultanagnosia).
• Strokes and compressive mass lesions are common etiologies
for optic radiation injury (temporal and parietal).
Figure Fig. 3.4
3.7.7 Occipital Lobe/Striate Cortex
• Occipital strokes usually cause very congruous (symmetric)

homonymous hemianopias, with or without macular sparing
(when present, presumably related to dual blood supply of the
pole). Conversely, a homonymous central scotoma is almost
always related to injury of the occipital pole/tip.
• A lesion involving the occipital lobe inferior to the calcarine
fissure can cause a defect resembling a “pie in the sky”/tem-
poral defect, while a lesion involving the occipital lobe supe-
rior to the calcarine fissure can cause a defect resembling a
“pie on the floor”/parietal defect. When homonymous defects
are incomplete and very congruous, they are probably occipi-
tal in origin. Macular sparing is characteristic of an occipital
lobe lesion.
Higher Cortical Visual Disorders 111
• Stroke is a common etiology, and bilateral homonymous hemi-

anopias (a right HH and a left HH in the same patient) are often
occipital in origin—bilateral defects affect visual acuity unless
macular sparing is present. Pupillary light reflexes should be
normal as these axons synapse in the dorsal midbrain prior to
reaching the lateral geniculate nucleus. Bilateral HH due to
occipital pathology can cause cortical blindness, sometimes
associated with confabulation (e.g., patient will claim that they
have vision even if they are effectively blind), the combination
of which is known as Anton’s syndrome.
• Higher cortical visual syndromes may be seen in association
with temporo-occipital and parieto-occipital lesions (see
“Higher cortical visual disorders” below).
• The posterior occipital lobe subserves central vision, while the
most anterior portion of the occipital lobe is responsible for the
monocular temporal crescent from the contralateral eye (e.g.,
right anterior occipital lobe lesion can cause a small monocular
crescent-shaped peripheral temporal defect in the left eye
only). While this is a rare occurrence, it is an exception to the
rule that any retrochiasmal visual field defect will be homony-
mous.
3.8 Higher Cortical Visual Disorders
3.8.1 Posterior Cortical Atrophy
Case A 65-year-old man presented to clinic with complaints of

worsening vision and difficulty reading for the past 2 years. He also
complained of “bumping into things” on a regular basis as large as
a telephone pole but not necessarily on the right or on the left side.
Frequently, he would have difficulty finding an object on the dinner
table such as a spoon. He was told by one ophthalmologist that
color vision was impaired, while another said that color vision was
a b
L R
*
L R
FLAIR Axial
Fig. 3.21 Congruous visual field defects due to occipital injury: (A) This
patient was found to have a (mainly left) parieto-occipital parasagittal menin-
gioma with associated right homonymous visual field defect, which worsened
slightly following partial resection. Postoperative automated static perimetry
demonstrated a very congruous (symmetric, white asterisk indicates the phys-
iologic blind spot OD; otherwise, the two visual fields are identical) right
incomplete inferior quadrantic visual field defect, correlating with the left
occipital hyperintensity (black dashed line, superior to the calcarine fissure)
seen on the postoperative MRI (black solid arrow points to residual menin-
gioma). (B) This patient had a severe cardiomyopathy and experienced sev-
eral cardioembolic strokes, two of which involved the left occipital lobe
causing two distinct congruous visual field defects: (1) an incomplete right
homonymous hemianopia (black dashed line) and (2) a right homonymous
central scotoma (from left occipital tip ischemia)
normal. Cataract surgery OU improved visual acuity but not his

visual difficulties which worsened over time. Examination demon-
strated 20/25 visual acuities at distance OU (he had difficulty when
a single or multiple lines were presented on the acuity chart but
could see and name letters when presented individually, an example
of “visual crowding”), 0/11 Ishihara color plates (although he was
able to name and distinguish the individual colors on each plate, he
could not see the numbers), there was no rAPD and dilated fundus
exam was normal. Confrontation testing demonstrated impaired
visual fields, especially inferiorly, which was confirmed with auto-
mated perimetry. Interpretation of a Navon figure was abnormal,
for example, when presented with a large F made up of small S’s—

he only saw the S’s. He was able to identify portions of the NIH
Stroke Scale cookie theft drawing but could not provide a cogent
interpretation of the scene. There was no optic ataxia (i.e., he could
point to a target with visual guidance) and no oculomotor apraxia
(i.e., saccades and pursuit were normal). A line cancellation task
was performed normally, and there was no visual neglect. A previ-
ously performed MRI was reviewed, and bilateral parietal and
occipital atrophy were prominent. He was diagnosed with posterior
cortical atrophy (PCA).
L R
FDG PET scan FLAIR Axial
Fig. 3.22 Bilateral homonymous visual field defects and parieto-occipital

atrophy in a patient with posterior cortical atrophy (PCA): At the top, the
black arrows point to a left homonymous hemianopia, that is slightly more
dense inferiorly and suggestive of right parietal and/or right occipital lobe
(superior to the calcarine fissure) involvement. The black dashed arrows point
to a right homonymous inferior quadrantic visual field defect, due to left
parieto-occipital involvement. On the bottom left are two fluorodeoxyglu-
cose (FDG)-positron emission tomography (PET) images, with the white
arrows pointing to bilateral parieto-occipital hypometabolism, while the
dashed arrows point to bilateral parieto-occipital atrophy seen on MRI
Low-level vision Intermediate-vision High-level vision

Dorsal Localization V1/Striate V5/V5a Occipitoparietal
Deficit Inferior hemifield defects Motion (akinetopsia) Space and time/Visuospatial action (Balint
syndrome)
Ventral Localization V1/Striate V4/V4a Occipitotemporal
Deficit Superior hemifield defects Color Object identification (general visual agnosia:
(achromatopsia) left – “words”; right–“faces and places”)*
Dorsal pathway
Posterior
(visuospatial action)
Parietal Cortex
Dors
al
V5/V5a
Striate
Cortex
(V1)
Ventral V4/V4a
Extrastriate
Inferior Cortex (V2/3)
Temporal Cortex
Ventral pathway
(object identification)
Fig. 3.23 How the brain makes sense of what it sees—the dorsal and ventral
visual pathways, and a three-tiered approach to vision: (1) Ventral (“what”)
stream—this begins with the ‘P’ retinal ganglion cells ➔ parvocellular layers
of the lateral geniculate nucleus (LGN, 3–6) ➔ V1/striate cortex (in blue) ➔
V4/V4a (fusiform and lingual gyri) ➔ occipitotemporal regions. (2) Dorsal
(“where”) stream—this begins with the ‘M’ retinal ganglion cells ➔ magno-
cellular layers of the LGN (1, 2) ➔ V1/striate cortex ➔ V5/V5a ➔ occipito-
parietal regions. *For objective identification (general visual agnosia)—in the
left hemisphere, think “words” (pure alexia) and in the right hemisphere,
think “faces and places” (prosopagnosia, topographagnosia). (The classifica-
tion of cerebral visual dysfunction using a three-tiered approach is courtesy
of Dr. Jason Barton. The figure was developed with the input of Dr.
Victoria Pelak)
Key questions to ask Commonly these patients have seen mul-

tiple optometrists and/or ophthalmologists over a period of
months or years, have failed new spectacle prescriptions, and
underwent cataract surgeries or other interventions without suc-
cess. Therefore, a higher cortical visual disorder such as PCA
should be considered in any older patient presenting with vague
progressive visual symptoms, especially after clinically signifi-
cant ophthalmic disease has been excluded. Ask about difficulties

with cognitive function and memory. If the onset is acute, ask
about vascular risk factors (e.g., watershed infarcts affecting
biparieto-occipital lobes).
Key findings to elicit One of the simplest screening tools for

patients with suspected PCA is to use color plates. Assuming that
the patient is not colorblind and having excluded significant bilat-
eral anterior visual pathway disease, the inability to see the num-
bers (Ishihara plates) or shapes (HRR plates) despite being able to
distinguish and identify the individual colors that make up the
numbers/shapes may be due to simultanagnosia. Another quick
screen is the Poppelreuter-Ghent overlapping figures test. If a
higher cortical visual disorder is suspected, consider the follow-
ing:
• Look for simultanagnosia with Navon figure, cookie theft pic-
ture;
• Evaluate hemi-attention with clock drawing, visual extinction,
and line bisection;
• Look for constructional apraxia with intersecting pentagons;
• Evaluate the ability to read and write;
• Evaluate fields to confrontation (and formal perimetry when pos-
sible—although often limited by attention/cognition).
Patients with PCA can have “low-level” visual deficits including

unilateral homonymous hemianopia (visual acuity should be spared)
or bilateral homonymous hemianopias (acuity is often involved), in
addition to visual crowding. Consider “intermediate level” deficits
referable to dorsal and ventral streams including impaired motion
discrimination (akinetopsia) and impaired color (hue) perception
(achromatopsia), respectively. Consider “high-level” deficits includ-
ing ventral stream—visual agnosia, topographagnosia, prosopagno-
sia, alexia, and dorsal stream—Balint syndrome, constructional
apraxia (this organization and approach is courtesy of Drs. Victoria
Pelak and Jason Barton).
What are some common higher cortical visual disorder syn-

dromes based on location?
1. alexia without agraphia (patient can write but cannot read)—

lesion of the left occipital lesion and splenium of the corpus
callosum (visual field defect - right HH);
2. hemiachromatopsia (inability to recognize colors in one
hemifield)—contralateral inferior occipitotemporal lobe
(visual field defect - ipsilateral [to the affected hemifield]
superior quadrantanopia);
3. prosopagnosia (inability to recognize faces)—bilateral
occipitotemporal lobes (visual field defect - bilateral superior
altitudinal defects);
4. optic aphasia (inability to name visual objects)—left occipi-
tal lobe (visual field defect - right HH);
5. topographagnosia (inability to identify familiar landmarks/
buildings)—right inferior occipitotemporal lobes;
6. akinetopsia (inability to perceive motion)—bilateral occipi-
totemporal cortex;
7. Balint syndrome (simultanagnosia, optic ataxia, and oculo-
motor apraxia)—bilateral parietooccipital lobes (visual field
defect - bilateral inferior altitudinal defects);
8. Gerstmann’s syndrome (acalculia, agraphia, finger agnosia,
and right-left confusion)—probably left angular gyrus with
adjacent subcortical involvement.
Pitfalls When there is suspicion for a higher visual cortical dis-

order, a few basic visual and cognitive functions must also be
evaluated [17]. If these functions are impaired, interpretation of
the testing battery above can be particularly challenging and
potentially misleading: 1) poor visual acuity (e.g., macular dis-
ease) may cause difficulty with reading and facial recognition; 2)
abnormal visual fields (e.g., scattered bilateral hemifield defects
due to strokes) can mimic simultanagnosia; 3) patients with apha-
sia or other language disturbances can have difficulty reading; 4)
a patient with poor memory can have difficulty recognizing faces
or places; 5) inattention can negatively impact any/all testing
(these “general starting points” come from Dr. Jason Barton).
Do not miss this! If progressive over years, typically PCA is due

to Alzheimer’s, Lewy body dementia (dementia with Lewy bodies
and Parkinson’s disease dementia), or corticobasal degeneration,

and memory disturbances and cognitive dysfunction may or may
not have already developed. When acute/subacute in onset, con-
sider a structural lesion (bihemispheric strokes or mass lesion) in
the differential, as well as prion disease (Creutzfeldt–Jakob dis-
ease, look closely for cortical ribboning and hyperintensity of the
deep cerebral nuclei on DWI or FLAIR).
If you can only remember one thing… Always think about

PCA in an older patient with progressive, bilateral, unexplained
vision loss in a person who has had normal ophthalmologic
evaluations. Screening with color plates or Poppelreuter-Ghent
overlapping figures is rapid and effective.
3.8.2 Hallucinations
Case An 80-year-old woman with moderate open angle glau-

coma and visually symptomatic cataracts OU presented with
3 weeks of seeing “imaginary animals” such as monkeys that
would appear and move across her vision bilaterally. There was
no loss of time or awareness with these episodes, and they
occurred for seconds to several minutes at a time. She denied
auditory hallucinations or history of psychiatric disorders. Neuro-
ophthalmic examination was unremarkable aside from 20/30 acu-
ities OU (attributed mainly to cataracts) as well as moderate
peripheral visual field loss and optic nerve cupping (attributed to
glaucoma). There was no homonymous visual field defect with
fields to confrontation or with automated perimetry. Ocular motor
and motility exam was normal as well as assessment of cognitive
and general neurologic function. Contrast-enhanced MRI was
unremarkable, notably with normal-appearing occipital lobes.
She was diagnosed with visual hallucinations due to Charles
Bonnet syndrome (CBS).
Key questions to ask The onset and pattern is important since

CBS may be due to a chronic benign ocular condition(s) such as
cataracts or glaucoma, or hallucinations may occur within a hom-
onymous hemianopia in the setting of acute/subacute stroke. If the
latter, urgent neuroimaging is required. If the former, recognition
of the inciting (ocular) event or disorder is important, for example,
if cataracts are the culprit, surgery may resolve the hallucinations.
Hallucinations can be unformed (e.g., a patient with bitemporal
hemianopia due to pituitary macroadenoma with dots and flashes
that are only bitemporal) or formed (e.g., the patient above who
sees animals). Ask about medical and neurologic history as well
as medications (e.g., a patient with Parkinson’s disease may expe-
rience hallucinations, which could be caused or aggravated by a
dopamine agonist).
Key findings to elicit Detailed ophthalmic/neuro-ophthalmic

evaluations are needed to rule out visual pathway disease. Vision
loss can be mild (or absent), and cognitive function is often normal.
Pitfalls A detailed history and examination can almost always

establish the diagnosis of CBS, and those with neuro-ophthalmic
abnormalities (e.g., homonymous hemianopia) must be imaged.
However, recognition of CBS due to cataracts or glaucoma or
another ocular condition can prevent unnecessary workup.
Do not miss this! Prior to diagnosing unformed hallucinations,

consider the possibility of photopsias caused by retinal disorders
such as tear/detachment or posterior vitreous detachment, espe-
cially when unilateral; migraine or epilepsy with positive visual
phenomena, especially when bilateral (and homonymous).
Consider neurodegenerative disease when formed hallucinations
are diagnosed. (Parkinson’s disease—related to or unrelated to
dopaminergic medications—or Lewy body dementia). Consider
peduncular hallucinosis (dream-like hallucinations) when associ-
ated with neurologic or ocular motor findings localizing to the
midbrain (e.g., third nerve palsy). Consider Anton’s syndrome
with bilateral occipital lesions, where the patient is functionally
blind due to bilateral homonymous hemianopias (sparing of the

anterior visual pathways, so pupillary responses are normal), but
will deny being blind and instead confabulate visual scenes and
objects (these are not hallucinations, nor does this represent a psy-
chogenic disorder).
What is next? Patients with symptoms of neurologic (e.g., cogni-

tive deficits, loss of time, or awareness) or neuro-ophthalmic (e.g.,
homonymous hemianopia) disease require contrast-enhanced MRI
and further workup. Patients with CBS due to an obvious ocular
condition and typical history may not require further workup.
Treatment options Commonly, patients recognize that their hal-

lucinations are not real, and the diagnosis of CBS and reassurance
are enough. However, if the hallucinations are disturbing or both-
ersome enough the following are options, although evidence for
their use is limited to case reports and series: antipsychotics,
selective serotonin inhibitors, anticonvulsants, and cholinesterase-
inhibitors.
If you can only remember one thing… This diagnosis can be

made with a high degree of confidence based on a thorough his-
tory and comprehensive ophthalmic/neuro-ophthalmic examina-
tion alone.
3.8.3 Visual Snow
Case A 20-year-old woman presented with a complaint of her

vision looking like “a broken tv.” This was first noticed at least
6 months ago, is diffuse and bilateral but not associated with
vision loss. The tv “static” is most noticeable when looking at a
solid background (e.g., blue sky or white wall), and while she
does have a history of migraine, the visual symptoms do not
seem to correlate with her headaches. She denies typical min-
utes-long positive visual phenomena that might suggest visual

aura, and her symptoms are constant. There was no exposure to
illicit drugs recently or remotely (e.g., drugs with hallucino-
genic properties). In the past 3 months, she has also noticed
seeing afterimages at times, for example, after looking at a
neon sign, the image can persist for seconds even after looking
away. A diagnosis of visual snow (VS) was made with associ-
ated palinopsia.
Key questions to ask Patients with visual snow may see innu-
merable dots, static, or snow throughout their vision. While this
does not disrupt their vision, the experience can be quite symp-
tomatic. The VS syndrome (VSS) is characterized by dots, static,
or snow symptoms and at least two of the following: (1) exagger-
ated entopic phenomena (the patient sees visual effects from
within their own eye), (2) after-images (palinopsia), (3) photo-
phobia, and (4) poor vision in low-light conditions (nyctalopia).
Tinnitus and migraine headaches are other common associated
symptoms.
Key findings to elicit Ophthalmic/neuro-ophthalmic exam

should be normal without evidence of retinal or optic nerve
disease.
Pitfalls Nyctalopia, photophobia, and photopsias are all symp-

toms that can be seen with the VS syndrome or with retinal dis-
ease. Therefore, dilated ophthalmologic exam is essential in these
patients.
Do not miss this! Palinopsia can be a manifestation of an occip-

ital lesion, certain medications (e.g., topiramate), or even epilep-
tic seizures.
What is next? Typically electroretinogram, electroencephalo-

gram, and MRI are low yield in patients with typical VS/VSS
symptoms and normal ophthalmic/neuro-ophthalmic exam.
References 121
Treatment options Case series have suggested that lamotrigine,

acetazolamide, and verapamil may help in certain cases, although
no evidence-based guidelines exist. While a migraine history is
common in these patients, typical migraine management (lifestyle/
dietary modifications, medications, etc.) is usually ineffective.
If you can only remember one thing… Although treatment of

the visual symptoms is often unsatisfactory, making the correct
diagnosis (and reassuring the patient that they will not lose their
vision) can prevent potentially costly and unnecessary testing.
Read these Books! [26–29]
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Motility and Ocular Motor
Disorders
4
4.1 The History
• Non-Neurologic Diplopia
Do not forget (1) monocular double vision (refractive, dry eye,
cataract, retinal, etc.) which is common, and (2) binocular
double vision due to decompensated (childhood) strabismus in
patients with intermittent or constant double vision and a full
range of eye movements (i.e., normal versions and ductions).
In these cases, there is usually a history of a longstanding
abnormal head position (e.g., look for old photographs demon-
strating head tilt in congenital fourth NP), known childhood
strabismus, eye muscle surgery, or amblyopia (sometimes
referred to as “lazy eye”). Decompensated strabismus is often
horizontal and comitant (esotropia (eyes crossed) or exotropia
(eyes deviated outward)), and a congenital fourth nerve palsy
is often the cause of strabismus that is vertical and incomitant.
While longstanding (childhood) strabismus may decompen-
sate and cause diplopia (as a result of normal aging, medica-
tions, medical or neurologic illness, a new or worsening
ophthalmic disorder), many patients will have no symptoms
referable to their longstanding strabismus.


https://doi.org/10.1007/978-3-030-76875-1_4
126 4 Motility and Ocular Motor Disorders
• Neurologic Binocular Diplopia

Certain characteristics (vertical or horizontal; worse in near or
far; right or left; abnormal head position, etc.—see Table 2.3
for further details) can often help to distinguish third vs. fourth
vs. sixth NP when a single ocular motor palsy exists.
• Acute/Subacute Ophthalmoplegia
Myasthenia gravis can mimic any individual (or combination
of) ocular motor palsies or gaze palsies; ptosis is common and
pupils should be normal. Consider Miller Fisher syndrome,
especially with preceding gastrointestinal illness followed by
relatively acute onset of ataxia, hyporeflexia, poorly reactive
pupils, and/or ptosis. Keep botulism toxicity on the differential
diagnosis of ophthalmoplegia and sluggish pupils as well.
Consider Wernicke’s encephalopathy in patients with ophthal-
moparesis with confusion, ataxia, spontaneous upbeat, and/or
gaze-evoked nystagmus. Also consider pituitary apoplexy with
acute onset ocular motor palsy/palsies, vision loss (unilateral
and/or bitemporal hemianopia) and headache.
• Chronic Ophthalmoplegia
Often due to mitochondrial disease such as chronic progressive
external ophthalmoplegia (CPEO), which presents with gradu-
ally progressive ophthalmoplegia (if symmetric, diplopia is
often absent) and ptosis.
4.2 The Exam
(a) Strabismus and motility basics

• Range of Movements
Video 4.1: in nine cardinal positions of gaze with both eyes
viewing (versions). Always check the range of each indi-
vidual eye (ductions) if there is diplopia or if a motility
deficit is suspected. For example, a patient with an esotro-
pia due to a (right) 6th NP will have a (right) abduction
paresis, the extent of which can be best appreciated by
assessing ductions. In contrast, a patient with infantile eso-
tropia should not have an abduction deficit. Sometimes a
patient with a large angle childhood strabismus (i.e., a big
The Exam 127
esotropia or exotropia) can appear to have a motility deficit

with versions, but ductions will prove that the range of
movements in each eye is in fact normal.
• Alignment
Video 4.2: in patients with normal appearing versions
and ductions who do not have complaints of diplopia, at
least assess ocular alignment in primary gaze at mid-
distance/distance (if the visual target is too close, the
examiner will always see a bit of an exodeviation). Start
with alternate cover testing where one eye is occluded,
and then the occluder (or examiner’s hand) is moved to
the fellow eye, and then back and forth as the patient
continues viewing the same visual target. If there is no
movement as each eye is uncovered, ocular alignment
can be said to be orthophoric in primary gaze at that par-
ticular distance. If the diplopia (or binocular symptoms)
depends on target distance, evaluate alignment at near
(symptomatic exotropia due to convergence insuffi-
ciency?) and at distance “(symptomatic esotropia due to
divergency insufficiency?)”. The Maddox rod can be
especially helpful (in a cooperative patient with normal
binocular visual function) in identifying a small hyper-
deviation, especially in patients with saccadic intrusions
or spontaneous nystagmus—for example, appreciating
an alternating skew deviation in lateral gaze in a patient
with downbeat nystagmus (ESM 1.1). In children, unco-
operative patients, or when poor monocular or binocular
vision loss is present, the Hirschberg (corneal light reflex)
test can be used as a quick screen, and the Krimsky test
can then be used to quantify a deviation (Fig. 4.1). If a
horizontal or vertical movement is seen with alternate
cover test, proceed with further evaluation below:
–– First determine whether the refixation movement seen
with alternate cover test is horizontal (an eso or exo) or
vertical (a hyper or hypo— technically, the misalign-
ment should be named for the nonfixating eye [e.g.,
right eye is fixating on the target and the left eye is
deviated downward would be a left hypotropia]), but it
Hirschberg test – corneal

light reflex demonstrates
right exotropia
Krimsky test – base-in

prism placed in front of
the fixating eye until light
reflex is centered in the
non-fixating eye
Fig. 4.1 Evaluating ocular alignment using Hirschberg and Krimsky tests:
This patient suffered severe vision loss in the right eye due to optic neuritis
which led to an exotropia (XT) over several years. When a penlight is shone
in both eyes, the left eye (white arrow) is the fixating eye because the light
reflex is centered in the pupil, while the light reflex in the right eye is more
medial than it should be (white dashed line), owing to the fact that the right
eye is deviated outward. This is the Hirschberg test, and is a quick and easy
method to evaluate for strabismus, especially effective in kids, uncoopera-
tive patients, or patients with poor monocular or binocular vision. The
Krimsky test was then performed where base-in prism was placed on the
fixating (left) eye until the light reflex was centered in the (previously exo-
tropic) right eye (yellow arrow). Because this was achieved once 35 prism
diopters (PD) of base in prism were placed, she had a ~ 35 PD exotropia
(approximate because this is not as accurate a test as alternate cover or
cover–uncover using prism)
is okay to just be consistent and always name the devia-

tion for the hyper-phoric or tropic (higher) eye.
Eso—eyes crossed, small phorias NORMAL
Exo—eyes outward, small phorias NORMAL
Hyper—one eye is higher, ABNORMAL
–– Tropia or Phoria?
Alternate cover test will allow you to see the total
deviation, the tropia (if present) plus the phoria
Cover–uncover test will allow you to determine what
component of the deviation is due to a tropia (e.g.,
acquired/neurologic causes of paralytic strabismus
will almost always cause a tropia)
The Exam 129
Tropia—misalignment with both eyes viewing—

ABNORMAL
Phoria—misalignment with one eye viewing—
USUALLY NORMAL
–– Comitant or Incomitant?
Comitant—misalignment is independent of gaze
direction—often NON-PARALYTIC (e.g., a hyper-
tropia due to a skew deviation will appear the same
in all directions of gaze, primary, right, left, up,
down, right, and left head tilt)
Incomitant—misalignment depends on gaze direc-
tion—often PARALYTIC (e.g., a right sixth NP will
cause a larger esotropia in right gaze than in primary
or left gaze)
–– If ocular alignment testing is abnormal, see
Table 4.1, and using the Maddox rod can also be
helpful in certain situations - (refer to ESM 1.1)
–– Look for associated signs—abnormalities on the neuro-
logic exam (especially referable to the brainstem and
other cranial neuropathies); anisocoria, ptosis
–– When possible, measure the ocular misalignment in prism
diopters using prism bars—quantifying the eso-, exo-, or
hyperin all directions of gaze assists in localization (e.g.,
right hyper increasing in left gaze and right head tilt is
likely to be a right fourth NP); allows one to compare
measurements at different points in time to monitor for
improvement, worsening or stability; quantification also
allows for accurate prescription of therapeutic prism
(press-on or ground-in), when appropriate.
–– Treatment of strabismus/diplopia—occlusion acutely
(anything from semi-opaque tape placed over one spec-
tacle lens to an eye patch), prism therapy, strabismus
surgery when stable and recovery is incomplete.
Regarding treatment for the underlying condition, this
depends upon etiology.
(b) The ocular motor exam
Table 4.1 My patient has ocular misalignment—where do I start?
130
Localization/ Extraocular
etiology paresis Alignment Comitance Other
Horizontal phoria None Esophoria or exophoria Comitant Small comitant horizontal phorias are common
(especially exo- when the visual target is at near)
and usually normal; these can sometimes
decompensate (e.g., with normal aging) causing
an intermittent or constant tropia with diplopia
Vertical phoria None Hyperphoria Usually comitant A small vertical phoria may be normal; however,
can represent a small skew (e.g., in vestibular
neuritis with Maddox rod) if comitant and even if
diplopia is absent; if incomitant, consider mild
fourth NP
Internuclear MR Exotropia worse in Incomitant An acute MLF lesion commonly causes
ophthalmoparesis contralateral gaze ipsilateral INO + ipsilateral hypertropia (due to
(INO)* skew deviation)
3rd NP* MR, SR, IR, Exotropia worse in Incomitant Can be complete or partial (either can represent a
IO contralateral gaze, dangerous etiology such as PCOM aneurysm);
(ipsilateral hypertropia worse in MG may mimic a third NP when there is no
ptosis and vertical gaze pupil involvement
mydriasis are
common)
Congenital None Esotropia or exotropia Comitant Congenital esotropia is often associated with:
horizontal (non- latent nystagmus, IO overaction, DVD
4 Motility and Ocular Motor Disorders
strabismus paralytic)
6th NP* LR Esotropia worse in Incomitant Can be falsely localizing due to low or high
ipsilateral gaze ICP—rule out papilledema
4th NP, congenital SO (usually Hypertropia usually Incomitant (but Look at old photos to see if a longstanding head
The Exam
too subtle to worse in contralateral can have “spread tilt is present; these patients usually have
see) gaze and ipsilateral head of comitance” significant IO overaction in the affected eye in
tilt; may increase in over time) contralateral gaze; may see SO atrophy on MRI
upgaze
4th NP, acquired* SO (may be Hypertropia worse in Incomitant Hypertropia also increases in downgaze; look for
too subtle to contralateral and down excycloduction of the affected hypertropic eye
see) gaze and ipsilateral head (double Maddox rod, fundus photos, dilated eye
tilt exam)
Skew deviation Non- Hypertropia Usually comitant Occasionally, the hypertropia is incomitant and
paralytic can mimic a fourth NP; look for incycloduction
of the hypertropic eye (and excycloduction in the
hypotropic eye) as part of the ocular tilt reaction
INO internuclear ophthalmoplegia, MR medial rectus, MLF medial longitudinal fasciculus, NP nerve palsy, SR superior rectus, IR
inferior rectus, IO inferior oblique, PCOM posterior communication artery, MG myasthenia gravis, DVD dissociated vertical devia-
tion, ICP intracranial pressure, SO superior oblique
*
Always consider the ocular motor palsy mimics in patients with diplopia due to a motility defect, especially myasthenia gravis (often
with ptosis, can mimic third, fourth, sixth NP, INO and other neurologic patterns of strabismus) and thyroid eye disease (often with
lid retraction and lid lag in downgaze)
131
• Convergence
Video 4.3: may bring out or cause reversal of vertical nys-
tagmus (e.g., bring out downbeat nystagmus (DBN) in a
cerebellopathy, transition from upbeat nystagmus (UBN)
to DBN in Wernicke’s encephalopathy), or may accentuate
some acquired forms of nystagmus or damp infantile nys-
tagmus. If the patient complains of binocular blurriness or
double vision while reading and near viewing and the
patient has a near point of convergence >10 cm, conver-
gence insufficiency (CI) is likely, and assessment of align-
ment at distance vs near (exotropia at near but not at
distance) and convergence amplitude can further support
the diagnosis (CI is especially common with parkinsonism
[Video 4.4: or TBI/concussion).
• Saccades
Video 4.5: have the patient rapidly look back and forth
between 2 visual targets, noting the speed, conjugacy,
latency, and accuracy. First have the patient look between an
eccentric target and the examiner’s nose horizontally and
vertically, making assessment of accuracy easier—for
example, overshooting the nose (hypermetria) or under-
shooting the nose (hypometria). Then have the patient make
larger amplitude saccades horizontally and vertically, which
makes assessment of speed and conjugacy easier (e.g.,
adduction lag suggests an internuclear ophthalmoplegia
[INO]). Saccadic dysmetria is seen in cerebellar disease (or
brainstem connections with cerebellum). Ipsilateral hyper-
metria and contralateral hypometria occur in Wallenberg
syndrome (Video 4.6). Slow saccades of normal amplitude
occur in brainstem disease, typically involving burst neu-
rons in the PPRF for horizontal saccades (e.g., SCA 1, 2, 3,
7 among others, Video 4.7) or riMILF for vertical saccades
(e.g., progressive supranuclear palsy, PSP). Slow saccades
The Exam 133
of reduced amplitude occur in ocular motor nerve paresis or

muscle weakness. With thyroid eye disease, saccade speed
is normal but the movements may terminate abruptly due to
motility deficits from extraocular muscle restriction. With
myasthenia gravis, saccades tend to be of normal speed ini-
tially (sometimes faster than normal), but can fatigue with
repeated testing. Slow adducting saccades are seen with an
INO (lesion involving the MLF), which is typically accom-
panied by abducting nystagmus. INO may be due to MS,
stroke, or structural and metabolic injuries (Video 4.8).
• Smooth Pursuit
Video 4.9: have the patient slowly track a target and note
saccadic or “choppy” pursuit (saccades substitute for sub-
normal smooth pursuit gain to catch-up to the target, Video
4.10). Impaired pursuit horizontally and vertically is typi-
cally seen in cerebellar disease (or its connections). If
impairment of pursuit is asymmetric, think about an ipsile-
sional process—for example, saccadic or choppy pursuit to
the left due to a left hemispheric lesion (Video 4.11).
• Vestibulo-Ocular Reflex Suppression (VORS)
Video 4.12: the VOR will need to be suppressed or can-
celled in many normal situations to allow for combined
eye-head movements—for example, turning the eyes and
head together to see in the rear view mirror while driving
prior to a lane change. The VOR is stimulated by the turn-
ing the head toward the mirror, but the VOR will be sup-
pressed so that the eyes can move in the same direction as
the head to allow the foveae to reach the mirror as well.
VORS will generally be saccadic when pursuit is saccadic
and vice versa (Video 4.13), unless there is no VOR to sup-
press as in bilateral vestibular loss. In a condition such as
CANVAS (cerebellar ataxia, neuropathy, vestibular
areflexia syndrome), the cerebellopathy will result in

impaired (saccadic) pursuit while the vestibulopathy will
result in normal/near normal-appearing VOR suppression,
because there is no VOR to suppress (Video 4.14).
• Optokinetic Nystagmus
Video 4.15: at the bedside, using an optokinetic stimulus
can assist in the evaluation of smooth pursuit and saccades.
The slow phases represent smooth pursuit while the fast
phases represent saccades. Since the bedside optokinetic
stimulus used (optokinetic tape/flag, examiner’s fingertips,
or any alternating patterns/lines, optokinetic drum) does
not involve full visual field stimulation (e.g., watching
passing scenery from the window of a moving train), the
optokinetic system is not truly being isolated. Situations in
which bedside OKN can be helpful: (1) rapid assessment
of symmetry and presence/absence of pursuit/saccades in
an uncooperative or difficult to examine patient; (2) subtle
adduction lag in INO; (3) one of the first ocular motor
signs of PSP is loss of the downward fast phase to an opto-
kinetic stimulus directed upward (goes along with down-
ward saccades being slightly slower than upward saccades
initially, and downgaze being more affected than upgaze);
(4) if OKN is seen in a patient with functional monocular
(when the good eye is occluded) or binocular blindness,
this suggests that the patient has at least some vision; (5)
since upward saccades are often affected in dorsal mid-
brain (Parinaud’s syndrome), vertical OKN can demon-
strate poor upward saccades and convergence retraction
nystagmus (when stimulus is directed downward and the
examiner views the patient’s eyes from the side)
• How to perform the telemedicine (virtual) ocular motor
examination: Video 4.16.
Subarachnoid Space, Cavernous Sinus, Orbital Apex 135
4.3 ubarachnoid Space, Cavernous Sinus,

S
Orbital Apex
4.3.1 Subarachnoid Space
What makes this localization unique? Patients can have a sin-

gle cranial neuropathy or multiple (any combination of) ipsilateral
or contralateral cranial neuropathies. Sixth nerve palsy can be a
false localizing sign due to low or high intracranial pressure
within the subarachnoid space. Consider intracranial pressure
abnormalities, skull base tumors, infectious, inflammatory or car-
cinomatosis meningitis, among others. Enhancement of cranial
nerves and enhancing brain lesions (i.e., multi-compartment
enhancement) should raise suspicion for neoplastic diseases
including leukemia, lymphoma, glioma, metastasis; inflamma-
tory/autoimmune disease including neurosarcoidosis; or infec-
tious etiologies including fungal infection, tuberculosis, Lyme
disease. If the cranial nerves, brain parenchyma, and leptomenin-
ges all demonstrate enhancement, lymphoma, leukemia, and
sarcoidosis remain possibilities, and metastatic disease including
glioblastoma multiforme should also be considered.
Figure: Example of a patient with leukemic meningitis causing

right sixth NP and left fourth NP. Figure 4.2 and Video 4.17

pia or ophthalmoplegia? Table 2.3 and ESM 2.1
Pitfalls: Bilateral (or unilateral) sixth NP in low or high ICP rep-

resents a false localizing sign—for example, in idiopathic intra-
cranial hypertension, even though the elevated ICP is diffuse, the
sixth nerves are particularly susceptible to changes in pressure as
they ascend the clivus and then acutely bend forward to penetrate
R L
*
Fig. 4.2 Multiple contralateral ocular motor palsies due to neoplastic seed-
ing of the subarachnoid space: This patient had (1) an abduction paresis OD
(white asterisk) due to right lateral rectus (sixth nerve) palsy, and (2) poor
depression OS (black asterisk) in down/right gaze, suggestive of a left supe-
rior oblique (fourth nerve) palsy. There was a slight rightward head tilt which
cannot be appreciated in this montage. Ocular alignment examination demon-
strated an esotropia that was worse in right gaze (due to right sixth NP), and
a left hypertropia that was worse in right and downgaze, as well as with left
head tilt (due to left fourth NP)
the dura under Gruber’s ligament (in Dorello’s canal). Figure 4.3

Lack of contrast and/or high-resolution thin cuts on MRI can
result in missing subtle cranial nerve abnormalities.
Do not miss this! In the differential diagnosis of unilateral or

contralateral ocular motor palsies should be myasthenia gravis
(pupils spared), thyroid eye disease, and Miller Fisher syndrome
(pupils involved or spared).
What is next? Patients with multiple cranial neuropathies

require an urgent workup including contrast-enhanced brain MRI
(preferably with thin, high resolution cuts through the posterior
fossa), and usually lumbar puncture as well.
Petroclinoid
(Gruber’s)
ligament CN V CN VI
V1
Superior
orbital
fissure
CN VII
Foramen
rotundum V2
Petrous
temporal
V3 bone
Foramen
ovale Internal
Subarachnoid space
Cavernous sinus
Petrous apex
carotid
artery
Orbit
Fig. 4.3 The course of the sixth (VI) nerve: The sixth nucleus is located dor-
sally, adjacent to the fourth ventricle, in the lower pons. The genu of the facial
(seventh) nerve wraps around the sixth nucleus, creating the facial colliculus,
which bulges into the fourth ventricle. After the sixth nerve leaves the pons, it
follows a vertical course along the clivus and then to the petrous apex where it
penetrates the dura, passing under the petroclinoid (Gruber’s) ligament in
Dorello’s canal, where it is tethered and particularly susceptible to low or ele-
vated intracranial pressure states. It then enters the cavernous sinus (adjacent
to the sympathetic plexus which surrounds the internal carotid artery), travels
through the superior orbital fissure to enter the orbit, and then passes through
the annulus of Zinn to finally innervate the ipsilateral lateral rectus muscle
4.3.2 Cavernous Sinus
What makes this localization unique? Ipsilateral involvement

of CN 3, 4, 6, V1, V2, or a combination of these, pain may or may
not be a prominent feature. When a Horner’s syndrome is seen
with an ipsilateral sixth NP, think cavernous sinus. The function
of each cranial nerve must be evaluated. In a patient with a third

NP, the function of the fourth nerve should be assessed by having
the patient attempt downgaze and looking for incycloduction in
the paretic eye. If clearly present, the function of the fourth nerve
is spared (Fig. 4.4). If not present, this implies that there is a third
RIGHT LEFT
SO SO
SR
SR
LR MR MR LR
IO
IR
IR
IO
* *
*
Fig. 4.4 Ocular motility and alignment findings in a left third NP: This
patient (with hypertension and diabetes) suffered a microvascular left third
NP. In primary gaze, there is complete ptosis OS (levator palpebrae, black
asterisk), and with the left eyelid manually elevated, there was also adduction
paresis OS and exotropia in right gaze (medial rectus, MR, yellow asterisk),
supraduction paresis OS and right hypertropia in upgaze (superior rectus, SR,
white asterisk), infraduction paresis OS, and left hypertropia in downgaze
(inferior rectus, IR, red asterisk). There was additional poor pupillary reactiv-
ity OS (with mild left mydriasis) due to mild involvement of the pupillary
sphincter muscle (PCOM aneurysm and structural lesions had been ruled out,
and her third NP resolved over 2–3 months as expected; however, patients
with a microvascular third can occasionally have minimal pupil involvement,
typically with <1 mm of anisocoria). The third nerve also innervates the infe-
rior oblique muscle, which can be challenging to diagnose when affected in
combination with other muscles. The black arrow in the top right photo (a
different patient also with an isolated left third NP) points to a nasal conjunc-
tival blood vessel during upgaze, and the yellow arrow points to the same
conjunctival blood vessel in downgaze. Although the eye depresses poorly
(due to IR paresis), the movement of the blood vessel is a result of incyclo-
duction OS due to the intact left superior oblique muscle (the same finding
can be seen in the montage as well)
NP and ipsilateral fourth NP, which is highly suggestive of a cav-

ernous sinus localization (Video 4.18).
Video: Video 4.19: showing multiple ipsilateral ocular motor

palsies due to cavernous sinus meningioma
Figure: Figure 4.5 showing multiple ipsilateral ocular motor

palsies due to cavernous sinus meningioma

Pitfalls: Do not immediately assume that a painful cavernous

sinus syndrome is due to an inflammatory “Tolosa Hunt” syn-
drome. Other dangerous etiologies must be excluded first (with
contrast-enhanced brain MRI and usually lumbar puncture).
Tolosa Hunt syndrome will characteristically respond to steroids,
but so will many other infectious (e.g., fungal) or neoplastic (e.g.,
lymphoma) conditions.
Do not miss this! In a patient with painful ophthalmoparesis, the

following conditions should also be considered: ophthalmoplegic
migraine (in children), diabetic/vasculopathic ocular motor
palsies, aneurysm, cavernous sinus thrombosis, dural arteriove-
nous fistula, meningioma, nasopharyngeal carcinoma, pituitary
tumors and apoplexy, metastatic tumor, neoplastic (e.g., lym-
phoma), or fungal infection.
What is next? Patients with acute/subacute ophthalmoparesis

require urgent contrast-enhanced brain MRI, occasionally with
CT or MR angiography to evaluate for aneurysm or other vascular
malformations. Many patients will require lumbar puncture as
well.
T1 Coronal
(contrast)
T1 Axial
* (contrast)
R L
* *
* *
*
Fig. 4.5 Multiple ipsilateral ocular motor palsies due to cavernous sinus
meningioma: This patient had (1) left medial rectus, superior and inferior
rectus (white asterisks, left eyelid is manually elevated in downgaze) paresis,
mild ptosis (levator palpebrae, yellow asterisk), and a poorly reactive pupil
OS (due to parasympathetic involvement but without anisocoria, probably
due to additional oculosympathetic involvement), all due to a left partial third
NP; (2) mild left lateral rectus (sixth nerve, black asterisk) paresis; and (3)
evidence of left superior oblique (fourth nerve) paresis given no observable
incycloduction of the left eye in downgaze (not apparent in this montage).
There was also diminished facial sensation in the distributions of left V1 and
V2. Although there was mild ptosis OS, in right gaze, there was a slight eleva-
tion of the left eyelid, a consequence of aberrant regeneration of the left third
nerve. In this situation, some of the fibers innervating the left medial rectus
had been injured by chronic third nerve compression, which led to a “miswir-
ing” phenomenon where those regenerating fibers wound up innervating the
left levator palpebrae instead. Aberrant regeneration of the third nerve is sug-
gestive of chronic compression or injury and can be seen following traumatic
brain injury, mass lesion (e.g., meningioma), and aneurysmal (e.g., posterior
communicating artery) compression, among others. The white arrows point
to her meningioma, and the top center figure (coronal view) of the cavernous
sinus demonstrates the proximity of these cranial nerves to one another. The
sympathetic plexus surrounds the internal carotid artery (ICA), and given its
proximity to the sixth nerve, the combination of a Horner’s syndrome and an
ipsilateral sixth nerve palsy is highly localizing to the cavernous sinus. Mild
oculosympathetic pathway injury could have contributed to her mild ptosis,
and perhaps the fact that her poorly reactive left pupil was not mydriatic, but
more in-depth pharmacologic drop (e.g., apraclonidine) testing was not per-
formed
* *
* *
*
*
Fig. 4.6 Orbital apex syndrome due to aspergillus: An immunocompromised

man presented with 1 day of right eye pain, redness, swelling, and binocular
diplopia. There was peri-ocular edema and proptosis, as well as infraduction
and adduction deficits OD. CT orbits (coronal view, left image more anterior,
right image more posterior) demonstrating a lesion in the medial orbit (yellow
asterisk) with extension into the right ethmoid and maxillary sinuses (white
asterisks). Note also thickening of the left nasal mucosa and opacification of
both supraorbital ethmoid sinuses seen in the image on the left. Biopsy of this
lesion led to the diagnosis of aspergillus (septate hyphae with a 45-degree
branching pattern). (Images courtesy of Dr. Neil Miller)
4.3.3 Orbital Apex
What makes this localization unique? Look for involvement of

CN 3, 4, 6, V1, ipsilateral optic nerve, often with orbital signs
(peri-ocular edema, injection, proptosis, eye pain).
Figure: Figure 4.6

Pitfalls: If a patient with an orbital apex syndrome has a third

NP with mydriasis and an ipsilateral optic neuropathy, an rAPD
can be appreciated in the normal eye by comparing the direct
and consensual light responses. For example, with a left-sided

orbital apex syndrome with an unresponsive and mydriatic left
pupil due to third NP, the examiner should look at the right
pupil (requires another dim light to see the right pupil in the
dark) while performing the swinging flashlight test. If there is
an optic neuropathy OS, when the light is shone in the left eye,
the right pupil will dilate, and when the light is brought to the
right eye, the right pupil will constrict. This is known as a (left)
reverse rAPD.
Do not miss this! Consider the following categories and condi-

tions: (1) infectious including fungal (typically in immunocom-
promised patients, e.g., aspergillus, mucormycosis [in diabetics]),
and bacterial (e.g., orbital and preseptal cellulitis), (2) inflamma-
tory (e.g., sarcoidosis, granulomatosis with polyangiitis
[Wegener’s]), (3) neoplastic (e.g., lymphoma, leukemia, metasta-
sis), (4) vascular (e.g., cerebral venous thrombosis, carotid-
cavernous fistula).
What is next? Patients with an optic neuropathy, orbital signs,

and/or ocular motor palsy/palsies suggestive of the orbital apex
syndrome require an urgent workup, with a contrast-enhanced
orbital CT or MRI to start.
4.4 Medulla
4.4.1 L
ateral Medullary (Wallenberg) Syndrome
(Including Skew Deviation and Saccadic
Dysmetria)
What makes this localization unique from a neuro-ophthalmic

and ocular motor/vestibular standpoint? Look for the follow-
ing: (1) Horner’s syndrome, (2) saccadic dysmetria (inferior cer-
ebellar peduncle affecting saccadic circuitry) (Figs. 4.7 and 4.8),
(3) vertigo and spontaneous nystagmus (central semicircular
Medulla 143
Uncinate fasciculus
(Hook bundle) of the
SCP
llum
ebe
Cer
Pon
Fastigial
s
N.
.
eN
tat
n
Dorsal
De
vermis
PPRF
EBN EBN
VI
Medulla
IBN
ICP (climbing
fibers)
Inferior
olive Inhibitory projection
Excitatory projection
Fig. 4.7 Anatomy and physiology of the saccadic pathways: When a saccade
is desired (or reflexively triggered), signals project from the saccade-related
cortical eye fields to the superior colliculus, which serves to integrate and
relay commands to the saccade generating brainstem circuitry. The inferior
cerebellar peduncle (ICP) carries climbing fibers to the dorsal vermis, which
has an inhibitory influence over the Purkinje cells. These Purkinje cells nor-
mally inhibit the ipsilateral fastigial nucleus, and the fastigial nucleus sends
excitatory fibers to the contralateral excitatory burst neuron (EBN)/inhibitory
burst neuron (IBN) pair within the paramedian pontine reticular formation
(PPRF). The IBN project contralaterally to inhibit the sixth nucleus to prevent
unwanted saccades in this direction, while the EBN project ipsilaterally to
excite the sixth nucleus to facilitate saccades in this direction (an example of
reciprocal innervation)
canal pathways) (Fig. 4.9), (4) gaze-evoked nystagmus (neural

integrators including medial vestibular nucleus [MVN] and
nucleus prepositus hypoglossi [NPH]; however, these structures
will be spared with strictly lateral lesions) (Fig. 4.10), (5) vertical
diplopia due to skew deviation (central utriculo-ocular motor
pathway). Figures 4.11 and 4.12
Case: A healthy 50-year-old man underwent chiropractic ther-

apy, and several days later experienced the abrupt onset of pro-
longed vertigo and spontaneous nystagmus, consistent with the
Right Left
Uncinate fasciculus
(Hook bundle) of the
SCP
llum
ebe
Cer
Pon
Fastigial
s
N. N.
te
nta
Dorsal
De
vermis
PPRF
EBN EBN
VI
Medulla
IBN
ICP (climbing
fibers)
Inferior
olive Inhibitory projection
Excitatory projection
Fig. 4.8 Lateral medullary lesion causing saccadic dysmetria: A lesion of

the left lateral medulla and inferior cerebellar peduncle (ICP) will cause
decreased climbing fiber inhibition of the left dorsal vermis causing simple-
spike (inhibitory) discharge of Purkinje cells to increase. Increased Purkinje
cell firing leads to increased inhibition of the ipsilateral (left) fastigial nucleus,
with a resultant decrease in excitation of the right excitatory burst neuron/
inhibitory burst neuron (EBN/IBN) pair. This will lead to less excitation of
the ipsilateral (right) sixth nucleus and less inhibition of the contralateral
(left) sixth nucleus, with an end result of right hypometria and left hyperme-
tria (and ipsipulsion or leftward ocular lateropulsion)
acute vestibular syndrome. He presented to the emergency depart-

ment where the HINTS (Head Impulse, Nystagmus, Test of Skew)
exam demonstrated the following: (1) head impulse normal (cen-
tral pattern), (2) nystagmus was right-beating and unidirectional
(peripheral or central pattern), and (3) test of skew was positive
(central pattern—i.e., vertical refixation movements with alter-
nate cover testing demonstrating a right hypertropia). Otoscopy
was normal and there was no hearing loss to suggest labyrinthine
ischemia. MRI brain and MRA neck showed acute left lateral
medullary stroke and left vertebral artery occlusion, respectively.
The occlusion was thought to be secondary to an arterial dissec-
Medulla 145
Fig. 4.9 Brainstem semicircular canal pathways: (1) Horizontal canal path-
way—afferents originating in the horizontal canals (HC) of the (right) laby-
rinth first synapse in the (right) ipsilateral vestibular nucleus (VN). Two
pathways exist: (a) medial longitudinal fasciculus (MLF, allows for conjugate
horizontal eye movements)—projections from (right) ipsilateral VN to (left)
contralateral sixth nucleus, which innervates left lateral rectus (LR) and right
medial rectus (MR, via the right MLF), resulting in conjugate leftward eye
movements; (b) ascending tract of Dieters (ATD)—the (right) ipsilateral VN
also projects directly to the (right) ipsilateral MR, thus bypassing the inter-
neurons traveling from left sixth nucleus to right MR subnucleus via the MLF
(this accessory tract explains how a patient with an adduction paresis/lag due
to internuclear ophthalmoplegia can have a normal/near normal adduction
movement with head impulse test). (2) Anterior canal pathway—afferents
originating in the anterior canals (AC) of the labyrinth first synapse in the
ipsilateral vestibular nucleus. Three pathways exist: (a) medial longitudinal
fasciculus (MLF)—right AC afferents to right medial vestibular nucleus
(MVN), decussate and ascend via the left MLF to the elevator muscles (right
superior rectus [SR] and left inferior oblique [IO]); (b) ventral tegmental tract
(VTT)—right AC afferents to right caudal superior vestibular nucleus (SVN),
decussate and ascend via the left VTT to the elevator muscles; (c) brachium
conjunctivum (BC)—right AC afferents to right rostral SVN, ascend (more
laterally) and decussate via the BC to the elevator muscles). (3) Posterior
canal pathway—afferents originating in the posterior canals (PC) of the laby-
rinth first synapse in the ipsilateral vestibular nucleus. One pathway exists: (a)
MLF—right PC afferents to right MVN, decussate and ascend via the left
MLF to the depressor muscles (right superior oblique [SO] and left inferior
rectus [IR]). LVN = lateral vestibular nucleus
tion with resultant posterior inferior cerebellar artery territory

ischemia. There was also saccadic hypermetria to the left and
hypometria to the right, as well as ocular lateropulsion to the left
(i.e., under closed lids, the eyes would drift to the left, and when
he opened his eyelids, the eyes would come back to center).
Ventral
Branches of
Inferior Inferior
olive Basilar & olive
Vertebral A
PICA
ICP IVN
ICP IVN
MVN MVN
NPH MLF Dorsal NPH MLF
Fig. 4.10 Vascular distribution and anatomy relevant to the lateral medullary
(Wallenberg) syndrome: This axial section of the medulla highlights those
structures that, when damaged, are responsible for the vestibular and ocular
motor features of the Wallenberg syndrome. Fibers coming from the (left)
peripheral utricle synapse in the (left) vestibular nucleus, explaining why a
skew deviation is common in a Wallenberg syndrome. With a left Wallenberg
skew, the left hypotropic eye is predictably ipsilateral to the injury because
the lesion is caudal to the pontomedullary decussation of the utriculo-ocular
motor fibers (and the ocular tilt reaction [OTR] will be ipsiversive, e.g., head
tilt and ocular counter roll are toward the left). Although various pathways
exist from the utricle and semicircular canals to their respective ocular motor
nuclei, many of these pathways travel through the medial longitudinal fas-
ciculus (MLF, which, in the medulla, is not yet carrying interneurons from the
sixth nucleus). Involvement of the (left) inferior cerebellar peduncle (ICP)
may result in asymmetry of the saccade facilitation/inhibition pathways,
resulting in ipsilateral (left) ocular lateropulsion, ipsilateral (leftward) sac-
cadic hypermetria, and contralateral (rightward) saccadic hypometria in a
(left) Wallenberg syndrome . If the medial medulla is also involved, there can
be other manifestations that are not typically seen with a pure Wallenberg
syndrome. The nucleus prepositus hypoglossi (NPH) and medial vestibular
nucleus (MVN) complex is important for horizontal gaze-holding (neural
integration). Fibers from the horizontal semicircular canals project to the
MVN, thus providing an explanation for an abnormal ipsilateral horizontal
head impulse test (HIT), which is occasionally seen with a lesion involving
the medial vestibular nucleus. Gaze-evoked nystagmus and loss of the hori-
zontal vestibulo–ocular reflex in Wernicke’s encephalopathy can also be
explained by NPH–MVN dysfunction
Fig. 4.11 The utriculo-ocular motor pathway and physiologic ocular tilt reac-
tion (OTR): The OTR consists of the triad of skew deviation, head tilt, and
ocular counter roll. Beginning caudally with the right utriculo-ocular motor
pathway: the right labyrinth contains the linear acceleration detectors (oto-
liths), including the saccule and utricle. The utricles also respond to head tilt,
so that if the head is tilted to the right (solid curved arrow above), the right
Medulla 147
HEAD TILT
SR
SO
IO INC
IR
IR
IO
MIDBRAIN
III
IV
MLF
PONS
VI
FROM
VN
UTRICLE
MEDULLA
utricle will fire and initiate the physiologic OTR. These utricular afferents will
synapse in the right vestibular nucleus in the medulla. The utriculo-ocular
motor fibers which began on the right side then decussate at the level of the
pontomedullary junction and ascend as part of the left medial longitudinal
fasciculus (MLF). Afferents travel via the MLF to their respective cycloverti-
cal-acting ocular motor nuclei (III and IV) in the left midbrain, resulting in
elevation and incycloduction OD (due to superior rectus [SR] and superior
oblique [SO] muscles, respectively, seen as the curved, dashed arrow OD) and
depression and excycloduction (due to inferior rectus [IR] and inferior oblique
[IO] muscles, respectively, seen as the curved, dashed arrow OS). Finally,
some of the utricle afferents ascending to the left MLF will synapse in the left
interstitial nucleus of Cajal (INC), which is responsible for vertical and tor-
sional gaze-holding. This ensures that the eyes will stay in their new orbital
position while the head tilt is maintained. However, the vertical “skewing” of
the eyes and ocular counter roll are negligible in the physiologic OTR. Instead,
the major component of the physiologic OTR will be a large head tilt to reori-
ent the head back to gravitational vertical (consider the example of a motorcy-
clist going around a tight curve to the right causing a rightward body/head tilt,
the head will reflexively tilt to the left, back to gravitational vertical)
Head Tilt
NORMAL Incyclo (SO) Excyclo (IO)
SR
SO
Depression (IR)
Elevation (SR)
SR
SO
R L
IO INC
IR
IO INC
IR
MIDBRAIN
MIDBRAIN
III
III
IV
IV
MLF
MLF
PONS
PONS
VI
VI
FROM FROM Left Vestibular

VN
UTRICLE
VN
UTRICLE Nucleus Lesion
MEDULLA
MEDULLA
Fig. 4.12 Skew deviation and the pathologic ocular tilt reaction (OTR): A skew
deviation is a non-paralytic vertical ocular misalignment that is due to imbal-
ance in the utriculo-ocular motor pathways. While vestibular jerk nystagmus is
a consequence of static semicircular canal pathway imbalance (e.g., left-beat-
ing nystagmus due to acute right vestibular hypofunction from vestibular neuri-
tis), an ocular tilt reaction, which includes skew deviation, head tilt, and ocular
counter roll, is a consequence of static utricle pathway imbalance. In the exam-
ple of a left medullary lesion, the utriculo-ocular motor pathway is affected just
as the afferents enter the brainstem, thus creating a central utricle asymmetry.
Because utricle afferents on the right are intact/relatively hyperactive compared
to the lesioned afferents on the left, the brain falsely perceives a rightward head
tilt (e.g., tilting the head to the right normally excites the right utricle) even
though no rightward head tilt has occurred. There is an attempt to reorient the
head to gravitational vertical (with the false assumption that the head is initially
too far to the right), but this results in a pathologic (leftward) ipsilesional head
tilt instead. A skew deviation (left hypotropia causing vertical diplopia) and
ocular counter roll (top poles of both eyes rotate toward the left ear) make up
the other components of the pathologic OTR, resulting from the damaged left
utriculo-ocular motor pathway and intact right pathway. The OTR will be
ipsiversive when the lesion is caudal to the utriculo-ocular motor pathway
decussation at the pontomedullary junction (i.e., the ‘low-low’ rule – the
LOWer eye will be ipsilateral to the lesion when it occurs LOWer than the
decussation, as in this case) and will be contraversive when the lesion is caudal
to the decussation (i.e., the ‘high-high’ rule – the HIGHer eye will be ipsilateral
to the lesion when it occurs HIGHer than the decussation, due to a medial lon-
gitudinal fasciculus or interstitial nucleus of Cajal lesion)
Medulla 149
Inferior Branches of
olive Basilar &
Vertebral A
PICA
ICP
IVN
MVN
NPH MLF
MRA - Right vertebral artery Dissected left vertebral artery DWI Axial
Fig. 4.13 Vertebral artery dissection causing a lateral medullary (Wallen-

berg) syndrome: This patient suffered a left vertebral artery dissection (black
arrows demonstrate the missing segment of left vertebral artery on MR angi-
ography, compared to the normal right vertebral artery, yellow arrow), which
caused left posterior inferior cerebellar artery (PICA) territory ischemia that
presented clinically as a left lateral medullary stroke (white arrow, hyperin-
tensity seen on diffusion-weighted imaging, DWI); ICP, inferior cerebellar
artery; IVN, inferior vestibular nucleus; MVN, medial vestibular nucleus;
NPH, nucleus prepositus hypoglossi; MLF, medial longitudinal fasciculus
Videos: Video 4.20: another example of saccadic dysmetria, lat-

eropulsion, and pulsion with vertical saccades: Video 4.21
Figure: Figure 4.13

pia when skew deviation is a consideration, and how can I
localize it? Table 2.3 and ESM 2.1
Key questions to ask: Slurred, speech, difficulty swallowing,

change in voice, hiccups, altered sensation on face, arm/leg, dip-
lopia, vertigo, oscillopsia, vascular risk factors, recent head/neck
trauma, or manipulation

• Non-ocular motor (Video 4.22): a unilateral (left) lateral
medullary (Wallenberg) syndrome could include any of the
following:
–– Dysarthria, dysphagia, and dysphonia/hoarseness (nucleus
ambiguus);
–– Decreased sensation on the ipsilateral (left) side of the face
(spinal trigeminal nucleus and tract) and the contralateral
(right) arm and leg (spinothalamic tract);
–– An ipsilateral (left) Horner’s syndrome (oculosympathetic
tract—miosis, ptosis, anhidrosis);
–– Ipsilateral (left) hemi-ataxia and body pulsion (inferior cer-
ebellar peduncle).
• Ocular motor/vestibular:
–– Ipsilateral (leftward) hypermetric saccades and ocular lat-
eropulsion (ipsipulsion); contralateral (rightward) hypo-
metric saccades (climbing fibers within ipsilateral inferior
cerebellar peduncle);
–– Skew d eviation (utriculo-ocular motor pathway caudal to its
decussation—ipsilesional (left) hypotropia, or lower eye is
on the side of the lesion);
–– Horizontal, horizontal-torsional, torsional nystagmus pat-
terns are most common (central semicircular canal path-
ways—horizontal, posterior, and/or anterior);
–– Ipsilateral (left) vestibulo-ocular reflex (abnormal horizon-
tal head impulse test to the left) may be involved if the hor-
izontal semicircular canal pathway (centrally) is damaged.
Pitfalls: An infarct involving the vestibular nuclei can mimic a

peripheral vestibulopathy—for example, nystagmus can be unidi-
rectional; and/or test of skew can be normal; and/or head impulse
test can be abnormal
Do not miss this! A Wallenberg syndrome is usually related to

ischemia (vertebral artery, PICA), and less likely due to demye-
lination for instance (which tends to affect white matter tracts as
opposed to nuclei). However, infectious, inflammatory, neoplas-
tic, and demyelinating conditions are all possible causes.
Pons 151
What is next? Urgent brain MRI (including DWI) is needed to

evaluate for ischemia, in addition to MR or CT angiogram of the
head and neck (e.g., evaluate for vertebral artery dissection or ath-
erosclerosis).
Treatment options A skew deviation can be treated with prism

or strabismus surgery when recovery is incomplete.
4.5 Pons
4.5.1 Medial Longitudinal Fasciculus Syndrome

and ocular motor/vestibular standpoint? Look for following:
(1) horizontal diplopia due to internuclear ophthalmoplegia
(INO, interneurons connecting sixth nucleus to contralateral
medial rectus subnucleus for conjugate horizontal movements),
(2) vertical diplopia due to skew deviation (central utriculo-ocu-
lar motor pathway) (Figs. 4.11 and 4.12), (3) spontaneous
vertical-
torsional nystagmus (central semicircular canal path-
ways, usually only seen acutely) (Fig. 4.9), (4) oscillopsia and
imbalance due to vertical vestibulo-ocular reflex (VOR) hypo-
function (anterior and posterior canals travel through the MLF)
(Fig. 4.9).
Case: A 60-year-old woman with hypertension and diabetes pre-

sented for evaluation of acute onset diagonal diplopia. There was
an adduction deficit in the left eye, which could be overcome by
convergence. In right gaze, there was abducting nystagmus in the
right eye only, and with rightward saccades, the left eye moved
slowly to the right (i.e., an adduction lag). Leftward saccades
were normal. A very subtle spontaneous torsional nystagmus (top
poles beating toward the left ear) was observed. Although vertical
ductions OU were normal, in addition to an exotropia (from the
left INO), there was also a left hypertropia due to a skew devia-
tion. The combination of her horizontal (exotropia) and vertical
(hypertropia) strabismus resulted in the diagonal description of
her diplopia. MRI confirmed a stroke involving the left MLF, pre-
sumably due to small vessel disease of the basilar artery perfora-
tors given normal MR angiography of the head and neck.
Video: Video 4.23: a similar patient who has prominent sponta-

neous nystagmus: Video 4.24: strokes causing INO Video 4.25
Figure: Figure 4.14

pia when INO or skew deviation is a consideration, and how
can I localize it? Table 2.3 and ESM 2.1
Key questions to ask: The main considerations include (1)

stroke (older)—ask about vascular risk factors, known cerebro-
vascular, or cardiovascular disease; (2) multiple sclerosis (MS,
younger)—ask about optic neuritis and previous neurologic
attacks; (3) partial third NP—ask about headaches or other symp-
toms that might suggest giant cell arteritis or a compressive lesion;
(4) myasthenia gravis (MG)—ask about diurnal variation, ptosis,
proximal weakness.

• Specific to (left) MLF
–– Left INO due to damage to interneurons connecting right
sixth nucleus to left medial rectus (adduction paresis or lag
OS and abducting nystagmus OD), which may or may not
be overcome by convergence,
–– Left hypertropia from skew deviation (and other features
of the ocular tilt reaction including right head tilt and ocu-
lar counterroll) due to utriculo- ocular motor pathway
damage,
Pons 153
DWI Axial
Fig. 4.14 Left medial longitudinal fasciculus (MLF) stroke causing a left
internuclear ophthalmoplegia (INO): This patient with vascular risk factors
suffered acute binocular diagonal diplopia with mild vertigo. Examination
demonstrated an adduction paresis OS (black asterisk) with associated
abducting nystagmus OD in right gaze, suggestive of INO and explaining the
horizontal component of her diplopia. Ocular alignment examination also
demonstrated a comitant left hypertropia due to skew deviation, with associ-
ated rightward head tilt, and ocular counter roll (top poles of both eyes rotated
toward the right ear), making up the triad of the ocular tilt reaction (OTR).
There was also subtle spontaneous torsional nystagmus (top poles toward the
left ear). MR diffusion-weighted imaging (DWI) demonstrated a well-
circumscribed infarct involving the left MLF. It was thought that her stroke
was due to small vessel ischemia in the distribution of the paramedian basilar
artery perforators. The MLF carries fibers responsible for (1) conjugate hori-
zontal eye movements (i.e., left INO was explained by involvement of the
interneurons connecting right sixth nucleus to left medial rectus subnucleus),
(2) utriculo-ocular motor reflex (i.e., responsible for her left hypertropia/skew
deviation and OTR), and (3) vertical semicircular canal pathways (i.e., ante-
rior/posterior canal involvement responsible for her mild vertigo and sponta-
neous torsional nystagmus)
–– Acute spontaneous vertical- torsional nystagmus due to

static posterior or anterior semicircular canal (and/or utri-
cle) imbalance and head movement induced oscillopsia
caused by posterior>anterior vestibulo-ocular reflex hypo-
function;
• Neurologic exam
–– Evaluate for other neurologic deficits (especially brainstem)
that might be due to stroke or MS;
• Neuro-ophthalmic exam
–– Evaluate for optic nerve disease/optic neuritis (MS);
–– Evaluate for ptosis (third NP, MG),
–– Poor pupil reactivity and mydriasis (third NP, rarely Miller
Fisher syndrome)
–– Test to see if motility/misalignment is fatigable or variable
(MG).
Pitfalls: It’s rare to have a partial third NP present as medial rec-

tus paresis in complete isolation…INO is much more likely!
Do not miss this! If there is also (even subtle) ipsilateral involve-

ment of the lid, pupil (mydriasis and poor reactivity), superior or
inferior rectus, rule out a posterior communicating artery aneu-
rysm causing a partial third NP urgently.
What is next? Diagnosis of an INO (+/− a skew deviation)

requires urgent neuroimaging, especially given the possibility of
stroke. Contrast-enhanced MRI is preferable when MS or a related
autoimmune/inflammatory disorder is on the differential.
Treatment options Usually, an INO will improve to a significant

degree, and may resolve entirely (e.g., stroke). The skew devia-
tion tends to recover even faster, and likewise, spontaneous
vertical-torsional nystagmus is typically only seen in the acute
setting. If head movement-dependent oscillopsia is present (due
to vertical VOR deficits), vestibular physical therapy can be ben-
eficial. For persistent diplopia due to INO or skew, prism therapy
or strabismus surgery can be considered.
If you can only remember one thing… INO is very common in

MS, and can even be present in patients without diplopia and with
normal motility and ocular alignment. The MLF ensures normal
horizontal conjugate movements (Fig. 4.15). At the bedside, have
the patient make horizontal saccades while looking very closely
Pons 155
Right INO Left horizontal gaze palsy
* * *
*
*
Fig. 4.15 Anatomy of an internuclear ophthalmoplegia (INO) and horizontal

gaze palsy: The patient to the left suffered a right medial longitudinal fasciculus
(MLF) stroke that caused a right INO. The right MLF normally contains inter-
neurons that travel from the left sixth nucleus to the right medial rectus (MR)
subnucleus of III. This allows the left sixth nucleus to innervate not only the left
lateral rectus (LR), but also the right MR via the MLF to ensure horizontal
conjugate movements to the left. However, when there’s a right MLF lesion, the
left LR is normally innervated by the intact sixth nucleus, while the right MR is
not. This can lead to a complete adduction (MR) paresis as in this case, or
sometimes there’s no obvious motility deficit but rather a slower adducting sac-
cade (adduction lag) in the affected eye, most noticeable when assessing hori-
zontal saccades. With a right MLF lesion, there is usually an abducting
nystagmus in the left eye, likely reflecting an adaptive response in an attempt to
adduct the eye. Because the right MR and left LR are a yoked pair that receive
the same innervation, the normal left LR may be overactivated with a resultant
abducting nystagmus. Because the descending convergence pathways that lead
to bilateral MR contraction are unaffected by a (more caudal) MLF lesion, con-
vergence may overcome the adduction paresis of the INO, which would not
occur with a MR palsy due to a third nerve palsy. Note that the right MLF also
contains utriculo-ocular motor and vertical (anterior and posterior) semicircular
canal pathways that originate in the left labyrinth (these pathways decussate at
the pontomedullary junction). For comparison, a patient with a left horizontal
gaze palsy (due to multiple sclerosis) is included on the right. Note that the
interneurons from the left sixth nucleus to the right MR subnucleus are still
affected (but in the left sixth nucleus itself, not the right MLF), causing an
adduction deficit in the right eye (just like the patient with right INO, which can
also be overcome by adduction). However, because the fibers that would nor-
mally activate the left LR are also affected, the patient cannot abduct the left
eye. This constellation of findings is known as a (left) horizontal gaze palsy
for a subtle adduction lag. Using an optokinetic flag/drum/tape

can often make a subtle lag even clearer.
4.5.2 Horizontal Gaze Palsies

and ocular motor/vestibular standpoint? Look for the
following: (1) horizontal gaze palsy (unable to move the eyes
toward the side of the lesion with saccades, pursuit, vestibulo-
ocular reflex due to sixth nucleus involvement, can be unilateral
or bilateral, adduction deficit(s) can often be overcome by conver-
gence), (Fig. 4.16) (2) one-and-a-half syndrome (horizontal gaze
palsy to one side and internuclear ophthalmoplegia to the other
side, adduction deficits can often be overcome by convergence),
(3) eight-and-a-half syndrome (horizontal gaze palsy and lower
motor neuron fascicular seventh NP on one side, internuclear oph-
thalmoplegia on the other side), (Fig. 4.17) (4) horizontal sac-
cadic palsy (cannot make horizontal saccades toward the side of
the lesion, but pursuit and VOR are spared, due to a paramedian
pontine reticular formation, PPRF, lesion), (5) oculopalatal tremor
may develop months later given the adjacent descending central
tegmental tract (Fig. 4.18)
Video: Two stroke patients with horizontal gaze palsy and one-
and-a half syndrome: Video 4.26

Key questions to ask: When a patient suddenly develops a gaze

palsy, stroke is the main consideration, either ischemic or hemor-
rhagic—ask about vascular risk factors. In a younger patient with-
Pons 157
L R
FLAIR Sagittal FLAIR Axial
* *
Fig. 4.16 Horizontal gaze palsy due to multiple sclerosis (MS): This patient
had a known history of MS with a previous attack of optic neuritis OD (cen-
tral scotoma seen in the Humphrey visual field top right) and demyelinating
periventricular white matter lesions (top left images) seen on MRI. She woke
up with horizontal diplopia and the inability to move the eyes to the left. On
exam, she had a left horizontal gaze palsy: (1) left horizontal gaze palsy
(severe abduction paresis OS, yellow asterisk, and adduction paresis OD,
white asterisk) due to left sixth nucleus injury (which would normally acti-
vate left lateral rectus directly as well as right medial rectus via interneurons
travelling through the right medial longitudinal fasciculus, MLF); (2) normal
right horizontal gaze; and (3) normal adduction OD with convergence (bot-
tom photo). Because the convergence signals descend from supratentorial
regions to synapse on the medial rectus subnuclei in the midbrain, adduction
deficits due to lesions involving the MLF and/or sixth nucleus may be over-
come by having the patient converge
out vascular risk factors, ask about previous neurologic attacks

that might suggest demyelination.
Key findings to elicit: Evaluate the range of eye movements,

pursuit, saccades, and the vestibulo-ocular reflex—if all are
affected in one direction, the localization is likely to be the sixth
nucleus. If saccades are the only class of eye movements affected
unilaterally, the localization is paramedian pontine reticular for-
mation (PPRF) Video 4.7. Evaluate facial nerve function as
well—because the fascicles of the seventh CN wrap around the
sixth nucleus, commonly a patient with a unilateral (right) hori-
zontal gaze palsy (with or without an associated right INO) will
T1
T1Axial
Axial(contrast) FLAIR
(contrast) FLAIR Axial
Axial
* * *
Fig. 4.17 Eight-and-a-half syndrome due to dorsal pontine tuberculoma:

This patient had a mild right lower motor neuron facial palsy (demonstrated in
the photos as a slightly widened right palpebral fissure, black double-sided
arrow) due to right seventh fascicle injury. She also had a right one-and-a-half
syndrome: (1) right horizontal gaze palsy (severe abduction paresis OD unable
to cross the midline, gray asterisk, and milder adduction paresis OS, white
asterisk) due to right sixth nucleus injury, (2) right internuclear ophthalmople-
gia (INO, adduction paresis OD, yellow asterisk) due to right medial longitu-
dinal fasciculus (MLF) injury. There was improved adduction OU with
convergence. The combination of right seventh NP + right one-and-a-half syn-
drome is sometimes referred to as the eight-and-a-half syndrome, and is highly
localizing to the region of the right facial colliculus/dorsal pons (region within
red dashed circle). In fact, the patient was found to have a dorsal pontine ring-
enhancing lesion with surrounding vasogenic edema, which was diagnosed as
a tuberculoma. This patient was seen acutely, but given the proximity of the
descending central tegmental tract (CTT, a part of Mollaret’s triangle), patients
with dorsal pontine pathology may develop oculopalatal tremor weeks or
months following the initial injury. MCP middle cerebellar peduncle, VI cra-
nial nerve 6, VII cranial nerve 7, VIII cranial nerve 8
also have a right lower motor neuron facial palsy. Evaluate all
other cranial nerve function as well, especially CN5 and CN8.
Pitfalls Patients with strokes or seizures (especially those

affecting the frontal eye fields) can have a horizontal gaze pref-
erence, which is usually ipsilesional with a stroke (e.g., left
hemispheric stroke causing a left gaze preference due to unop-
posed right frontal eye fields) and contralesional with epileptic
seizures (e.g., a left hemispheric seizure focus causing a tran-
sient right gaze preference due to activation of the left frontal
eye fields). A gaze preference due to stroke may or may not be
overcome by the horizontal vestibulo-ocular reflex acutely. Also
consider myopathic and mitochondrial disorders (chronic pro-
Pons 159
Ventral
Paramedian Basilar A
Circ
umfe
Bas rential
ilar A
VII
CT
AICA
T
MC
VI VI
VIII
P
MLF MLF
Dorsal
Fig. 4.18 Vascular distribution and anatomy (including sixth, seventh, eighth
nerves, MLF) of the pons: In this axial section of the pons, the proximity of the
seventh and eighth fascicles can be appreciated. A lateral inferior pontine syn-
drome (anterior inferior cerebellar artery, AICA territory), which could involve
both of these fascicles, can cause acute prolonged vertigo accompanied by an
abnormal ipsilateral horizontal head impulse test (HIT, fascicle of CN8) and
ipsilateral lower motor neuron facial palsy (fascicle of CN7). Although a “cen-
tral” acute vestibular syndrome typically has a normal HIT, exceptions exist
where an abnormal HIT can be due to a stroke. Commonly, an abnormal HIT
can be seen with lesions affecting the root entry zone of CN8, or those involv-
ing the vestibular nucleus or with labyrinthine ischemia (AICA territory). A
lesion involving the middle cerebellar peduncle (MCP) itself can also result in
acute prolonged vertigo, but if the fascicle of CN8 is spared, HIT will be nor-
mal. A dorsal midline lesion can cause unilateral or bilateral internuclear oph-
thalmoplegia (INO) due to medial longitudinal fasciculus injury (MLF, usually
stroke or multiple sclerosis). Dorsal pontine injury can also cause a horizontal
gaze palsy (sixth nucleus) or a gaze palsy + INO, causing a one-and-a-half
syndrome (+/− seventh NP). Finally, the central tegmental tract (CTT) is in
this vicinity as well, making oculopalatal tremor a finding to look for months
after suffering a pontine lesion (e.g., hemorrhagic cavernoma). VI cranial
nerve 6, VII cranial nerve 7, VIII cranial nerve 8
gressive external ophthalmoplegia), Miller Fisher syndrome,

Wernicke’s encephalopathy in the differential diagnosis of hori-
zontal gaze palsies.
Do not miss this! Remember that myasthenia gravis (MG) can

mimic any ocular motor disorder including horizontal gaze palsy
and one-and-a-half syndrome!
What is next? When associated with severe headache or change

in mental status, consider hemorrhage and order urgent CT scan.
Otherwise, MR with diffusion-weighted imaging is needed when
stroke is suspected and contrast-enhanced MRI when demyelin-

ation is suspected. Consider MG workup with normal imaging.
Given the proximity of the central tegmental tract (part of
Mollaret’s triangle), months after the insult (usually due to hem-
orrhage) patients may develop oculopalatal tremor.
Treatment options: If adduction and abduction deficits are sym-

metric with a unilateral horizontal gaze palsy or if horizontal gaze
palsies are symmetric with bilateral involvement, then diplopia
may not be that bothersome. Fortunately, patients’ ocular motor
deficits tend to improve or resolve, but prism and/or strabismus
surgery can be options for some.
4.5.3 Sixth Nerve
How do I diagnose a sixth NP? Patients typically experience

binocular horizontal diplopia, worse at distance and in the direc-
tion of the paretic lateral rectus. Figure 4.19
What localizations should I be aware of?
(1) (right) sixth nucleus—(right) horizontal gaze palsy (see

“Horizontal gaze palsies” section above);
RIGHT LEFT
SO SO
SR
SR
LR MR MR LR
IO
*
IR
IR
IO
Fig. 4.19 Ocular motility and alignment findings in a left sixth nerve palsy:
This patient (with hypertension and diabetes) suffered a microvascular left
sixth NP causing a complete abduction paresis OS (lateral rectus, LR, white
asterisk) with an esotropia greater in left gaze
Pons 161
(2) (right) fascicle of the sixth nerve— (right) lateral rectus

palsy, can have contralateral (left) hemiparesis (right corti-
cospinal tract) and/or (right) lower motor neuron seventh
NP often due to ischemia;
(3) subarachnoid space— (right) sixth nerve is susceptible to
injury from inflammatory/neoplastic/infectious meningitis,
trauma, high or low intracranial pressure, mass lesion (skull
base tumors);
(4) (right) petrous apex—infection (Gradenigo syndrome)
causing (right) sixth NP and/or (right) facial pain in the tri-
geminal distribution and/or ipsilateral (right) seventh NP
and/or (right) eighth NP;
(5) cavernous sinus/superior orbital fissure—compressive
lesion, carotid-cavernous fistula among others can cause
(right) sixth NP and/or (right) ipsilateral Horner’s syndrome
and/or any combination of (right) third, fourth NP, V1, V2
(an isolated sixth NP due to microvascular ischemia proba-
bly occurs here as well);
(6) orbital—can be an isolated sixth NP or associated with ipsi-
lateral third, fourth NP, V1, orbital signs (proptosis, vision
loss/optic neuropathy).
Video: Video 4.27
Figure: Figures 4.3 and 4.19

pia when a sixth NP is suspected, and how can I localize
it? Table 2.3 and ESM 2.1
Key questions to ask when a sixth NP is suspected:
ology)?
• Inquire about headaches (low or high intracranial pressure
[accompanied by transient visual obscurations, pulsatile tinnitus],
aneurysmal compression or other mass lesion?) and other neuro-

logic symptoms (e.g., unilateral weakness due to pontine stroke?)
• Is there a history of or suspicion for an infectious, inflamma-
tory, or autoimmune disorder?
• Ask about giant cell arteritis symptoms (obtain ESR/CRP
when present) in patients >50–55 years old.
• Ask about ptosis, dysphagia, and weakness that could suggest
a neuromuscular junction disorder (myasthenia gravis [MG],
Lambert Eaton myasthenic syndrome) or Miller Fisher syn-
drome (MFS).
• Ask about thyroid function (thyroid eye disease, TED - in
TED, the lateral rectus is uncommonly involved, although
medial rectus restriction will often cause an abduction deficit).
Key findings to elicit: Thorough neurologic/neuro-ophthalmic

exam as above in “What localizations should I be aware of?”
discussion, also look for fatigable ptosis or proximal weakness
(MG); proptosis, eyelid retraction (TED). If it is asymptomatic
and incidentally seen on examination, look for eye retraction in
adduction and consider Duane’s syndrome (Video 4.28). In
MFS, pupils may be poorly reactive to light, there may be abduc-
tion deficit(s) or more severe ophthalmoparesis, deep tendon
reflexes can be diminished or absent, and ataxia is common as
well (Video 4.29).
Pitfalls: Remember that not everybody who has an abduction def-

icit has a sixth NP! Always consider MG and TED. Occasionally, a
patient will present with an apparent abduction deficit in lateral
gaze to one or both sides which is due to convergence spasm. In this
situation, there is usually a voluntary crossing of the eyes in lateral
gaze—for example, when asked to look to the left, the patient will
cross the eyes (causing miosis OU as part of activation of the near
triad) making adduction OD appear normal but giving the appear-
ance of a left abduction paresis. Testing each eye individually (duc-
tions) will usually prove that abduction is in fact normal and no
Pons 163
workup is needed. Rarely, a patient will experience organic conver-

gence spasm which is usually related to midbrain pathology,
although other abnormal ocular motor signs are almost always pres-
ent.
Do not miss this! Consider the most dangerous causes first, and
always rule out papilledema, which if present, is an emergency!
Pontine strokes causing an isolated sixth NP are rare, but this is
another emergency situation. Most isolated sixth NP are micro-
vascular (when vascular risk factors are present), although iso-
lated sixth nerve palsies are commonly due to a structural or mass
lesion as well. Consider GCA in patients >50–55 years old, which
is a potentially vision-threatening disorder. Rarely, a pseudo-
abducens (or pseudo-sixth) palsy can occur with a thalamic or
midbrain stroke, despite sparing of the pons and course of the
sixth nerve. However, these are almost always accompanied by
other midbrain signs (Video 4.30).
What is next? Urgent neuroimaging when papilledema is pres-

ent or stroke is suspected. Urgent ESR and CRP when GCA is
suspected. Most other situations require contrast-enhanced MRI,
although not as urgently. Acetylcholine receptor antibodies when
MG is suspected, and thyroid function tests and thyroid stimulat-
ing immunoglobulin when TED is suspected.
Treatment options: A microvascular sixth NP should resolve

completely over months (usually within 3, but definitely within 6
months). Depending on the etiology, occlusion (patch over one
eye or semi-opaque tape over one lens), prism therapy, or strabis-
mus surgery may be options.

4.6 Midbrain
4.6.1 Third Nerve
How do I diagnose a third NP? Patients with a complete third

NP won’t experience binocular diplopia due to severe ptosis until
manually elevating the eyelid. Otherwise, a patient with predomi-
nant medial rectus paresis may experience horizontal diplopia
worse at near, while a patient with predominant superior or inferior
rectus paresis may experience vertical diplopia worse in up or
down gaze, respectively. Or, diplopia may be more diagonal due to
the combination of horizontal and vertical components. Figure 4.4

pia when a third NP is suspected, and how can I localize
(1) (right) third nucleus—(right) third NP + left superior rectus

paresis and left mild ptosis (Fig. 4.20);
(2) (right) fascicle of the third nerve—can have a partial or com-
plete right third NP with contralateral (left) hemiparesis (right
corticospinal tract), ipsilateral (right) ataxia (superior cere-
bellar peduncle), and/or contralateral (left) tremor (red
nucleus);
(3) subarachnoid space—susceptible to injury from inflamma-
tory/neoplastic/infectious meningitis, trauma, mass lesion
(skull base tumors);
(4) cavernous sinus/superior orbital fissure—compressive lesion,
carotid-cavernous fistula among others can cause (right) third
NP that can be associated with any combination of (right)
fourth, sixth NP, V1, V2 (an isolated third NP due to micro-
vascular ischemia probably occurs here as well). Because the
superior and inferior divisions of the third NP probably sepa-
rate completely by the anterior cavernous sinus, patients can
have a divisional third NP with this localization—for exam-
ple, a superior division third NP with superior rectus and
Midbrain 165
Red nucleus
Central
caudal nucleus
P IR LP MR SR IO
Medial Lateral
Aemptedupgaze
Attempted upgaze (lids
(lids Severe ptosis
Severe ptosis OS
OS
manually elevated)
manually elevated) Mild ptosis
Mild ptosis OD
OD
Fig. 4.20 Central anatomy of the oculomotor nerve and characteristic fea-
tures of a nuclear third NP: This patient has a complete left third NP (severe
left ptosis, mydriatic unreactive pupil OS, left medial, superior, and inferior
rectus palsies), which could either result from a central or peripheral left third
NP. However, she also had a right superior rectus (SR) palsy as well as mild
ptosis OD. Bilateral upgaze paresis can be explained by a left nuclear third
NP due to the fact that the (1) left SR subnucleus is injured (left midbrain
hemorrhage in the setting of a familial multiple cavernous malformation syn-
drome in this case) causing a right SR palsy due to the decussation of these
fibers, and (2) fibers that originated in the right SR subnucleus and then
decussated to join the left third nerve are also damaged, causing a left SR
palsy. Finally, the central caudal nucleus (CCN), a midline structure that
innervates bilateral levator palpebrae muscles, can also be partially injured by
with a unilateral third nucleus lesion, causing ipsilateral greater than contra-
lateral ptosis, as seen in this case. Given the orientation of the various fibers
that make up the fascicle of the third nerve (seen in the figure above from
medial to lateral), certain patterns of muscle and/or pupil involvement can
have additional localizing value, although involvement or sparing can be vari-
able, making this anatomy less clinically useful. P pupil, IR inferior rectus,
LP levator palpebrae, MR medial rectus, SR superior rectus, IO inferior
oblique
levator palpebrae involvement or an inferior division third NP

with medial, inferior rectus, inferior oblique, and/or pupillary
sphincter muscle involvement;
(5) orbital—can be isolated or associated with ipsilateral fourth,
sixth NP, V1, orbital signs (proptosis, vision loss/optic neu-
ropathy), and this can be a superior or inferior divisional third
NP. Figures 4.21 and 4.22
Anterior
Optic canal
Sphenoid ridge
Superior
Sella turcica orbital fissure
Cavernous sinus
Anterior clinoid
process of Posterior clinoid
sphenoid bone process of
Petrous ridge sphenoid bone
Basilar a
Posterior
cerebral a
Superior
cerebellar a
Red nucleus
Central
caudal nucleus
III
P IR LP MR SR IO
Posterior Medial Lateral
Fig. 4.21 The course of the third nerve: The third nucleus lies at the ventral
border of the periaqueductal gray matter, at the level of the superior colliculus.
In between the two nuclei is the midline central caudal nucleus (CCN), which
innervates bilateral levator palpebrae muscles (explaining how a unilateral
nuclear third can cause bilateral ptosis). The third nerve fascicle (which con-
tains fibers responsible the pupillary sphincter [P], inferior rectus [IR], levator
palpebrae [LP], medial rectus [MR], superior rectus [SR], and inferior oblique
[IO] are located medial to lateral) travels anteriorly through the tegmentum,
the red nucleus, the substantia nigra, and finally exits the midbrain medially
from the cerebral peduncles. The peripheral portion of the third nerve courses
between the superior cerebellar and posterior cerebral arteries and then passes
the posterior communicating artery (PCOM aneurysm causes compression
here) and the temporal lobe uncus (uncal herniation can cause compression
here), then above the petroclinoid (Gruber’s) ligament (while the sixth nerve
travels under) and into the cavernous sinus where it is located laterally. The
separation into superior (SR, LP) and inferior (P and ciliary body, MR, IR, IO)
divisions occurs in the anterior sinus, and these branches then travel through
the superior orbital fissure to enter the orbit, passing through the annulus of
Zinn before innervating their respective muscles. (Castro O, Johnson LN,
Mamourian AC. Isolated inferior oblique paresis from brain-stem infarction.
Perspective on oculomotor fascicular organization in the ventral midbrain teg-
mentum. Arch Neurol. 1990;47(2):235–7)
Midbrain 167
PCA
Basilar A
PCA &
Posterior Red
III Choroidal A III
nucleus
PCA & CCN
SCA
Fig. 4.22 Vascular distribution and anatomy (including third nerve) of the
rostral midbrain: In this axial section of the midbrain at the level of the supe-
rior colliculus, the paired third nuclei are located ventral to the periaqueductal
grey, and the midline central caudal nucleus (CCN) is located in between.
PCA posterior cerebral artery, SCA superior cerebellar artery
4.6.2 Fourth Nerve
How do I diagnose a fourth NP? Patients typically experience

binocular vertical, diagonal, or oblique diplopia, worse in contra-
lateral and down gaze, and ipsilateral head tilt. Figure 4.23

pia when a fourth NP is suspected, and how can I localize
(1) (left) fourth nucleus or

(2) (left) fascicle (both prior to decussation)—(right) fourth NP
+/− contralateral (left) internuclear ophthalmoplegia, (left)
Horner’s syndrome, ipsi- or contralateral relative afferent
pupillary defect, (left) hemi-ataxia (Fig. 4.24 and Video 4.31);
(3) subarachnoid space—susceptible to injury from inflamma-
tory/neoplastic/infectious meningitis, trauma, mass lesion
(skull base tumors);
Left 4th NP
Skew deviation (ocular counterroll)
*
Fig. 4.23 Ocular motility and exam findings in a left fourth NP: The top left
photos are from a patient with left hypertropia who had a Parks–Bielschowsky
three-step test consistent with a left fourth NP: (1) left hypertropia (LHT), (2)
LHT increased in contralateral (right) gaze, and (3) LHT increased in ipsilat-
eral (left) head tilt. He had additional features of a congenital fourth NP
including, (1) significant ipsilateral (left) inferior oblique overaction in right
gaze (white arrow showing the upward deviation of the left eye in adduction),
(2) large vertical fusional amplitude (e.g., able to fuse a large LHT of at least
15 prism diopters, which is why his fourth nerve palsy was asymptomatic),
and (3) longstanding contralateral (right) compensatory head tilt (not seen in
these images, but apparent in old photos dating back to childhood). The patient
in the bottom photo also has a left fourth NP, with an apparent depression
deficit in adduction OS (asterisks) due to left superior oblique (SO) paresis
(secondary action of the SO is depression). Evaluation of fundus torsion can
be very helpful in differentiating a left fourth NP from a skew deviation (either
could cause a LHT) in that the hypertropic eye will be excycloducted in a
fourth nerve palsy (owing to the primary action of the SO which is incycloduc-
tion). Compare this to the incycloducted hypertropic eye in a skew deviation,
which will be accompanied by excycloduction of the hypotropic eye (both
eyes rotate in the same direction, which is known as an ocular counterroll)
(4) cavernous sinus/superior orbital fissure—compressive lesion,

carotid-cavernous fistula among others can cause (right)
fourth NP and/or any combination of (right) third, sixth NP,
V1, V2 (isolated fourth NP due to microvascular ischemia
probably occurs here as well);
(5) orbital—can be isolated or associated with ipsilateral third, sixth
NP, V1, orbital signs (proptosis, vision loss/optic neuropathy).
Midbrain 169
MLF
Oculo-
Sympathetic
Tract
Fig. 4.24 Central anatomy of the trochlear nerve and characteristic features
of a nuclear fourth NP: This patient suffered a hemorrhage of the left caudal
midbrain causing a right fourth NP. This is due to the fact that the left fourth
nerve originates in the left dorsal midbrain, exits dorsally and decussates to
the right side where it then wraps around the brainstem to eventually inner-
vate the right superior oblique muscle. A (right) “central” fourth NP will often
have associated neuro-ophthalmic features including, (1) (left) internuclear
ophthalmoplegia from (left) medial longitudinal fasciculus (MLF) injury, (2)
(left) Horner’s syndrome from (left) oculosympathetic tract injury, (3) ipsi- or
contralateral relative afferent pupillary defect (without involvement of acuity,
color or field) due to injury to the brachium of the superior colliculus, or
neurologic signs including (4) (left) hemi-ataxia from (left) superior cerebel-
lar peduncle/brachium conjunctivum injury
Anterior
Optic canal
Sphenoid ridge Superior
orbital fissure
Sella turcica
Cavernous sinus
Anterior clinoid
process of Posterior clinoid
sphenoid bone process of
sphenoid bone
Petrous ridge
Basilar a
Posterior
cerebral a
Superior
Medial cerebellar a
longitudinal
fasciculus
Oculo-
sympathetic
tract
IV
Posterior
Fig. 4.25 The course of the fourth nerve: The fourth nucleus lies at the ven-
tral border of the periaqueductal gray matter, at the level of the inferior col-
liculus. The fascicles exit the nucleus dorsally and decussate at the anterior
medullary velum (anterior floor of the fourth ventricle), and then exit the
brainstem dorsally. The peripheral portion of the fourth nerve (left fourth
nerve originated in the right fourth nucleus and vice versa) runs laterally
around the upper pons and then passes between the superior cerebellar and
posterior cerebral arteries before reaching the prepontine cistern and then the
cavernous sinus where it is located laterally. The fourth nerve travels through
the superior orbital fissure and continues above the annulus of Zinn to then
innervate the superior oblique muscle
Figure: Figures 4.25 and 4.26
Key questions to ask when a fourth NP is suspected:
ology)?
Midbrain 171
PCA
Basilar
A
PCA &
Posterior
MLF Choroidal A MLF
IV Oculo- IV
PCA & Sympathetic
SCA Tract
Fig. 4.26 Vascular distribution and anatomy (including fourth nerve) of the
caudal midbrain: In this axial section of the midbrain at the level of the infe-
rior colliculus, the fourth nuclei are located ventral to the periaqueductal grey,
dorsal to the medial longitudinal fasciculus (MLF) and medial to the oculo-
sympathetic tract. Fascicles exit the nucleus dorsally and decussate at the
anterior medullary velum before exiting the midbrain dorsally on the contra-
lateral side. PCA posterior cerebral artery, SCA superior cerebellar artery
• Inquire about headaches (aneurysmal compression or other

mass lesion?) and other neurologic symptoms (e.g., unilateral
ataxia due to midbrain stroke?),
• Is there a history of or suspicion for an infectious, inflamma-
tory, or autoimmune disorder?
• Ask about giant cell arteritis symptoms (ESR/CRP when pres-
ent) in patients >50–55 years old.
• Ask about ptosis, dysphagia, and weakness that could suggest
a neuromuscular junction disorder (myasthenia gravis) when
pupils are spared.
• Longstanding head tilt (congenital fourth NP)?
• Orbital signs or known history of thyroid disease (although
isolated superior oblique involvement would be rare for thy-
roid eye disease)?
Key findings to elicit: The Parks–Bielschowsky three-step test:

(1) the higher (hypertropic) eye will be ipsilateral to the fourth
NP; (2) the hypertropia will increase in contralateral gaze, (3) the
hypertropia will increase in ipsilateral head tilt. Patients with a
congenital fourth NP often have a significant inferior oblique
overaction, large vertical fusional amplitude and longstanding
head tilt, and their hypertropia may also increase in up gaze, dis-
tinguishing it from the more typical pattern of increased hypertro-
pia in down gaze that is commonly observed with an acquired
fourth NP. Trauma can also cause bilateral fourth NP with an

alternating hypertropia—that is, right hyper in left gaze and left
hyper in right gaze. Also look for bilateral excycloduction, and a
V-pattern esotropia (i.e., more esotropia in downgaze) (Video
4.32).
Ocular alignment – Is it a fourth NP or a skew deviation? A

skew deviation may rarely be significantly incomitant and mimic a
fourth NP with the three-step test; instead, a skew deviation is typi-
cally comitant. If the vertical misalignment is significantly reduced
in magnitude when rechecking when supine (using alternate cover,
cover-uncover, or a Maddox rod), this is likely to be a skew deviation
(i.e., because utriculo-ocular motor pathway asymmetry is respon-
sible for a skew, reducing the effect of gravity on the utricles by
assuming a supine position can reduce a skew). However, if there is
no improvement in vertical misalignment when going from upright
to supine, the vertical strabismus could still be due to a skew.
Head tilt—Is it a fourth NP or a skew deviation? Patients with

a fourth NP have a compensatory head tilt to the opposite side—for
example, a left fourth nerve palsy will cause a compensatory right-
ward head tilt. The reason is that by tilting the head to the right, the
patient excites the right utricle which initiates the utriculo-ocular
motor reflex, resulting in minute elevation of the right eye and
depression of the left eye and very slight ocular counterroll with top
poles toward the left ear. This will help to minimize retinal image
disparity resulting from the paretic left SO and improves diplopia
(recall that the left eye will be too high and excycloducted, so the
right head tilt will put the eye into a more favorable position). A
patient with a left MLF lesion will have a contraversive OTR with
right head tilt—in this case, the head tilt is pathologic, or an attempt
to correct for an abnormal internal representation of where earth
vertical is located. In other words, with a left MLF lesion (where the
utricle pathways that are injured originated in the right labyrinth,
and the utricle pathways that originated in the left labyrinth are
intact and are relatively hyperactive), the brain thinks that the head/
body is tilting to the left and attempts to compensate. However,
since the head started in a neutral position (rather than a left head
tilt position), the final position will be to the right of earth vertical.
Midbrain 173
Cycloduction—Is it a fourth NP or a skew deviation? Measure

cycloduction/ocular torsion subjectively with double Maddox
rod, bucket test [5] or objectively by measuring the angle between
the fovea and optic nerve—a patient with a left fourth will have
left hypertropia and left excycloduction with no little to no abnor-
mal cycloduction in the right eye acutely. A patient with a left
MLF lesion will have a left hypertropia and left incycloduction in
addition to right excycloduction—this results from the ocular
counterroll portion of the OTR.
Pitfalls: Many patients have a congenital fourth NP as the cause

for their diplopia, which decompensates with normal aging, med-
ical/neurologic disorders, or medications. Ask look at old photos
of the patient to see if a longstanding head tilt was present.
Do not miss this! In a patient presenting with a third NP, look for
incycloduction in downgaze in the paretic eye (focus on a single
conjunctival blood vessel)—if present, the fourth nerve is spared,
and if there is no clear incycloduction, it is likely that there is also
a fourth NP, which suggests a cavernous sinus localization. Also,
a fourth NP + contralateral internuclear ophthalmoplegia and/or
contralateral Horner’s syndrome is highly suggestive of a mid-
brain lesion (“central” fourth NP). Look for an alternating hyper-
tropia (right hyper in left and left hyper in right) + esotropia in
downgaze + bilateral excycloduction in bilateral fourth NP, which
is almost always due to trauma.
What is next? The history and exam should guide the clinician,
but if the patient does not clearly have a congenital fourth NP,
contrast-enhanced MRI should be performed in most cases (unless
a patient is likely to have a microvascular fourth NP and is already
recovering). An atrophic unilateral superior oblique muscle seen
on MRI is also suggest of a longstanding (usually congenital) pro-
cess. ESR and CRP urgently when GCA is suspected.
Treatment options: Patching or occlusion with semi-opaque

tape, prism therapy, and/or strabismus surgery.

4.6.3 Vertical Gaze Palsies
Why can’t my patient look up?

First think about dorsal midbrain (Parinaud’s) syndrome:
• upgaze palsy (posterior commissure carries fibers responsible

for upgaze, not downgaze),
• convergence-retraction nystagmus with attempted upgaze
(asynchronous convergent saccades),
• light-near dissociation (pretectal nuclei are involved while
pathways responsible for the near triad are spared, see Fig. 2.2),
• eyelid retraction (Collier’s sign, likely due to M-group involve-
ment. Refer to ESM 4.1.
Also consider unilateral central (nuclear) third NP (Fig. 4.20)

causing bilateral superior rectus paresis as well as bilateral ptosis;
bilateral third nerve palsies (again, with other features of a third
NP); supranuclear disorders (i.e., usually overcome by a vertical
vestibulo-ocular reflex, VOR, think about progressive supranu-
clear palsy [PSP], although downgaze is usually worse); myasthe-
nia gravis and other conditions. Figures 4.27 and 4.28
Why can’t my patient look down?

If the onset is abrupt, first think about a unilateral or bilateral ros-
tral interstitial medial longitudinal fasciculus (riMLF) lesion
causing a down>upward saccadic palsy (projections from riMLF
to depressor muscles are ipsilateral whereas projections to the
elevator muscles are bilateral—that is, a unilateral riMLF lesion
mainly affects downward saccades, while complete bilateral dam-
age can abolish all vertical saccades) which may be due to an
artery of Percheron stroke. In chronic progressive disorders, think
about supranuclear disorders such as PSP, Niemann–Pick Type C,
among others. Bilateral third NP can cause an inability to look
down, but this will be accompanied by other features of an oculo-
motor palsy. Figures 4.27 and 4.28
Midbrain 175
Fig. 4.27 Brainstem structures involved in normal ocular motor function:

This is a sagittal representation of the brainstem demonstrating the relative
locations of the ocular motor nuclei (III [including the midline central caudal
nucleus or CCN], IV, VI), neural integrators (INC for vertical/torsional gaze
holding, nucleus prepositus hypoglossi [NPH] for horizontal gaze holding),
and saccadic burst neurons (riMLF for vertical/torsional, paramedian pontine
reticular formation [PPRF] for horizontal). The posterior commissure (PC)
plays a role in upward gaze as well, explaining the characteristic upgaze palsy
in a dorsal midbrain (Parinaud’s) syndrome
a b . c. d.
Parinaud’s
riMLF syndrome INC syndrome PSP
syndrome
Fig. 4.28 Common lesions and localizations for characteristic midbrain

ocular motor syndromes as seen on MRI: (a) Dorsal midbrain (Parinaud’s)
syndrome—complete upgaze palsy (among other findings) typically associ-
ated with extrinsic compression of the dorsal midbrain (dashed line), in this
case due to a glioblastoma multiforme of the pineal gland seen on noncontrast
sagittal T1 (arrow). (b) Rostral interstitial medial longitudinal fasciculus
(riMLF) syndrome—complete downward saccadic palsy (and very slow
upward saccades) typically associated with an intrinsic lesion, in this case
bilateral riMLF infarcts (arrows) from artery of Percheron ischemia seen on
axial MR-diffusion-weighted imaging (DWI). (c) (Left) interstitial nucleus of
Cajal (INC) syndrome—complete contraversive (rightward) ocular tilt reac-
tion (i.e., right head tilt, left hypertropia due to skew deviation, ocular counter
roll with top poles of both eyes rotated toward the right ear) and spontaneous
torsional nystagmus (top poles beating toward the left ear), in this case due to
a left INC infarct (arrow) seen on axial MR-DWI. (d) Patients with progres-
sive supranuclear palsy (PSP) often have significant midbrain atrophy, a fea-
ture that is not surprising based on the vertical saccadic and vertical gaze
palsies that are so typical of this disorder. With axial (T1 in this patient) MRI
views, the tegmentum atrophy (arrow) can create the “Mickey Mouse” sign.
With sagittal MRI views, the midbrain atrophy may give the appearance of a
hummingbird (where the pons is the body, midbrain is the head)
Video: Parinaud’s syndrome: Video 4.33: riMLF syndrome:

Video 4.34: a patient with INC and riMLF syndromes from a sin-
gle midbrain stroke: Video 4.35
Figure: Figure 4.29
Key questions to ask: When the onset is acute, Parinaud’s syn-

drome is often due to extrinsic compression of the dorsal mid-
brain (e.g., tumor of the pineal gland, hydrocephalus, shunt
Midbrain 177
Bilateral eyelid retraction and upgaze palsy
Rostral midbrain hemorrhage
Fig. 4.29 Dorsal midbrain (Parinaud’s) syndrome due to mesodiencephalic

hemorrhage: This patient demonstrated the main clinical features of Parin-
aud’s syndrome including, (1) eyelid retraction (Collier’s sign, note how
much superior sclera is visible in the photo), (2) pupillary light-near dissocia-
tion (no constriction to light, brisk constriction to a near stimulus), (3) upgaze
palsy, (4) convergence-retraction nystagmus during attempted upgaze. The
CT on the right demonstrates the rostral midbrain location of the hemorrhage.
(Video and image created with the assistance of Drs. Amir Kheradmand and
Jiaying Zhang)
malfunction), but can be due to intrinsic lesions (e.g., ischemic or

hemorrhagic stroke)—history of surgeries, tumors, and strokes
must be questioned. A riMLF syndrome is often due to an intrin-
sic lesion (e.g., stroke). If chronic and progressive, consider neu-
rodegenerative disease (e.g., PSP).
Key findings to elicit: A detailed evaluation of all classes of

eye movements is essential—for example, despite what appears
to be a vertical gaze palsy, VOR and smooth pursuit may be
spared in PSP or a riMLF syndrome. Other ocular motor find-
ings to localize to the midbrain include pseudo-abducens/sixth
palsy (see sixth nerve section), skew deviation (and other fea-
tures of interstitial nucleus of Cajal, INC, syndrome). Rarely,
irritation of the INC (usually by hemosiderin products) can
cause a paroxysmal ocular tilt reaction (Video 4.36). If there is a
horizontal and vertical saccade palsy, consider neurodegenera-
tive disorders or a lesion involving the perineuronal nets (e.g.,
post-cardiac surgery saccade palsy, Video 4.37).

pia and ophthalmoplegia? Table 2.3 and ESM 2.1
Pitfalls: Remember that myasthenia gravis can mimic any ocular

motor disorder! Also consider myopathic and mitochondrial dis-
orders (chronic progressive external ophthalmoplegia), Miller
Fisher syndrome, Whipple’s disease, Wernicke’s encephalopathy
in the differential diagnosis, although horizontal ophthalmopare-
sis and distinguishing symptoms/signs can usually be appreciated
with each.
Do not miss this! The acute onset of Parinaud’s syndrome or

riMLF syndrome is a consequence of dangerous pathology.
What is next? Urgent neuroimaging with an acute onset, initial

CT to rule out hemorrhage/hydrocephalus, followed by MR with
diffusion-weighted imaging.
Treatment options Prism and/or strabismus surgery in some

depending on the disturbance—for example, not typically helpful
for upgaze or downgaze paresis (although some yoked prism
options exist), may be helpful for a skew deviation or if there is an
associated third NP.
If you can only remember one thing… If the onset is acute and
the patient cannot look up, think dorsal midbrain (Parinaud’s)
syndrome, and if the patient cannot look down, think riMLF. When
chronic, PSP (or another neurodegenerative syndrome) is usually
to blame.

Midbrain 179
4.6.4 Progressive Supranuclear Palsy
Case: A 65-year-old man presented with imbalance and falls

for the last 1–2 years. He experienced difficulty navigating
stairs, had become a messy eater, and developed hypophonia
in the same period of time. Exam demonstrated small horizon-
tal back and forth movements consistent with square wave
jerks, and there was significant difficulty moving the eyes
downward more than upward despite the fact that there was a
normal vertical range of movements when assessing the ves-
tibulo-ocular reflex (VOR). There were slow and hypometric
horizontal saccades with very slow downward more than
upward saccades, with a corresponding absence of a down-
ward fast phase to an optokinetic flag that was moving upward.
Some of the vertical saccades followed a curved arc-like tra-
jectory to get to the target (“round-the-houses” sign). There
were complaints of horizontal diplopia at near with a corre-
sponding exotropia (consistent with convergence insuffi-
ciency (CI)), as well as saccadic smooth pursuit and VOR
suppression (with a normal VOR and head impulse test).
There was severe axial rigidity and postural instability with a
tendency toward falling backward. He could not suppress
blinking when a penlight was repeatedly shone in his eyes.
MR axial images of the midbrain demonstrated significant
atrophy of the tegmentum, consistent with the “Mickey Mouse
sign.” He was diagnosed with PSP.
Video: Video 4.38: patient with ocular motor findings in early

PSP; Video 4.39: patient with advanced PSP and complete oph-
thalmoplegia; Video 4.40: patient with PSP and absent fast phases
with optokinetic flag and inability to suppress blinks to a bright
light; Video 4.4: CI in a patient with progressive supranuclear
palsy (PSP)
Figure: Figure 4.28
Key questions to ask: Visual symptoms are very common in

PSP, are often vague (aside from diplopia due to CI) although
commonly related to reading or tasks requiring focus.
• Ask about symptoms referable to CI (e.g., horizontal binocular

diplopia at near), ask about spectacle correction (e.g., if the
patient wears progressives, bifocals, or trifocals and a down-
ward gaze palsy is present, it will be very difficult for the
patient to see through the reading segment of their glasses),
• Ask about ocular surface irritation/dry eye symptoms (which
commonly causes monocular double vision),
• Consider the possibility of a higher visual cortical disorder
(given the potential for clinical overlap between PSP and
other disorders such as cortical basal degeneration [CBD]—
for example, a patient with CBD may experience simultanag-
nosia).
• Square wave jerks (SWJ, saccadic intrusions that usually do

not affect visual function);
• Supranuclear vertical gaze palsy (down>up at least initially,
complete vertical palsy as the disease progresses);
• Inability to suppress blink to repetitive light stimulus (cannot
habituate);
• Saccades are hypometric horizontally, and are typically much
slower vertically (down>up) than horizontally, and the “round-
the-houses” or the “zig-zag” signs may be seen with vertical
saccades (a single curved arc trajectory or multiple slow oblique
saccades in alternating directions, respectively) [9],
• Saccadic pursuit and VOR suppression;
• The first sign you may see (even before vertical gaze palsy) is
slow (or absent) downward fast phases with an optokinetic
stimulus;
• Also by assessing saccades diagonally (e.g., targets are pre-
sented up-right and down-left) or by using a diagonal optoki-
netic stimulus, you might see pure horizontal saccades with the
former or pure horizontal fast phases with the latter;
Midbrain 181
• Eyelid retraction (M-group in the midbrain ESM 4.1
It is probably the combination of these efferent abnormalities

in addition to ocular pathology (blepharitis, dry eye due to poor
tear production and decreased blink rate) that explains reading/
focusing complaints. Upgaze can become impaired to some
degree with normal aging (whether this is related to changes
involving the orbital tissues or whether this is in part supranuclear
is not clear), poor downgaze in a patient with a gait/balance disor-
der is more diagnostically meaningful.
Pitfalls—when is it Parkinson’s disease (PD)? In patients with

PD, there are often mild-moderate ocular motor abnormalities
(i.e., not nearly as severe or prominent compared to PSP) includ-
ing SWJ, saccadic hypometria, mildly saccadic pursuit/VOR sup-
pression, and convergence insufficiency (tends to be responsible
for most efferent symptoms). However, much like PSP, ocular
surface disease/blepharitis is often present as well, degrading
monocular acuity and causing monocular double vision. PD
patients tend to have tremor, (milder) postural instability, rigidity
and bradykinesia, and other visual symptoms become common as
the disease progresses including illusions (e.g., a pile of clothes
looks like a dog) and hallucinations (e.g., seeing bugs crawling in
the peripheral vision, especially in dimly lit environments), which
can result from PD or dopaminergic drugs.
Do not miss this! If there are also cerebellar ocular motor signs
(gaze-evoked nystagmus, downbeat nystagmus), consider multi-
ple system atrophy or the possibility of the cerebellar variant of
PSP. Clinically, CBD can also have similar features. Significant
(and early) postural instability differentiates PSP from Parkinson’s
disease. If the onset of a supranuclear gaze palsy and PSP-like
features is subacute, consider paraneoplastic disorders (e.g., anti-
Ma and anti-Ta), Whipple’s disease, Creutzfeldt-Jakob disease
among others. Supranuclear vertical gaze disorders can be seen
acutely with ischemia of midbrain structures including rostral
interstitial medial longitudinal fasciculus (riMLF, affects
downward>upward saccades), and the posterior commissure (PC,
affects upward movements).
What is next? PSP is a clinical diagnosis, although MRI can

provide additional clues (e.g., “Mickey Mouse sign” on axial
views, “hummingbird sign” on sagittal views).
Treatment options: Patients with PD will have a favorable

response to dopaminergic drugs, while patients with PSP usually
will not. Artificial tears can help with ocular surface disease.
Avoidance of progressives, bifocals, trifocals by using a stand to
place reading material at eye level with full frame reading glasses.
Convergence exercises and base in prism can be offered for CI.
If you can only remember one thing… A comprehensive ocu-

lar motor examination performed horizontally and vertically
(including optokinetic nystagmus) should be performed in all
patients with significant postural instability.
4.7 Cerebellum
Three syndromes:
(1) flocculus/paraflocculus (tonsil),

(2) nodulus/ventral uvula,
(3) dorsal vermis (ocular motor vermis, OMV) and posterior fas-
tigial nucleus (fastigial ocular motor region, FOR) (Fig. 4.30).
Note that the flocculus/paraflocculus and nodulus/uvula
together make up the vestibulocerebellum.
A case that brings the three syndromes together: A 30-year-

old man with a known diagnosis of spinocerebellar ataxia type
(SCA) 8 presented for visual symptoms. Examination demon-
strated features suggestive of involvement of the following
structures:
Cerebellum 183
= Inhibitory
projection
Ocular
Motor
Vermis
P FN
MCP SC
ICP
Floc
culu
s
lus
cu
loc
raf
Pa Nodulus/
Vental
Uvula
Fig. 4.30 Cerebellar structures involved in normal vestibular and ocular

motor function: Seen here is in inferior view of the flocculus, paraflocculus
(tonsil), nodulus, and uvula, which together make up the vestibulocerebel-
lum. The fastigial nucleus (FN) and ocular motor vermis play important roles
in saccadic accuracy. MCP middle cerebellar peduncle, SCP superior cerebel-
lar peduncle, ICP inferior cerebellar peduncle. (Modified and redrawn with
permission from: Shemesh and Zee [12])
(1) flocculus/paraflocculus—saccadic smooth pursuit, saccadic

vestibulo-ocular reflex (VOR) suppression (which was sig-
nificant enough to cause head movement dependent oscil-
lopsia), downbeat nystagmus (causing head movement
independent oscillopsia), gaze-evoked nystagmus (causing
oscillopsia in lateral gaze) with rebound nystagmus, alternat-
ing skew deviation (causing vertical diplopia in lateral gaze),
(2) nodulus/uvula—apogeotropic positional nystagmus (caus-
ing positional dizziness and oscillopsia),
(3) OMV/FOR
FOR: bilateral saccadic hypermetria (causing difficulty see-
ing clearly after changing gaze);
OMV: divergence insufficiency (esotropia worse at distance caus-
ing horizontal diplopia at distance but not at near, or may localize
to flocculus/paraflocculus—not seen in the video).
There was also severe gait and limb ataxia. Taken together, exam-
ination suggested widespread cerebellar involvement, which was
confirmed on MRI by severe diffuse cerebellar atrophy. Video
4.41
Key questions to ask when you suspect a cerebellar disor-

der: Most important is the onset and duration of disease. If acute
in onset, consider vascular. If subacute in onset, consider infec-
tious/inflammatory/autoimmune disorders in younger patients, in
addition to paraneoplastic disorders in older patients. Typically,
patients will present with years of progressive imbalance and/or
oscillopsia due to a cerebellar degeneration. The presence or
absence of visual symptoms (e.g., retinopathy in SCA7), parkin-
sonism (e.g., multiple system atrophy), gait and limb ataxia +/−
myelopathy/corticospinal tract involvement (e.g., a variety of
SCAs) can provide additional clues. Consider a cervicomedullary
structural lesion (e.g., Chiari malformation, neoplasm) with a ves-
tibulocerebellar disorder and headaches.
4.7.1 Syndrome of the Flocculus

and Paraflocculus (Tonsil) Fig. 4.31
4.7.1.1 G aze-Evoked and Rebound Nystagmus &

Impaired Smooth Pursuit and Vestibulo-
Ocular Reflex Suppression (VORS)
Symmetric involvement of the flocculus/paraflocculus due to
cerebellar degeneration: A 30-year-old woman presented with a
several year long history of imbalance due to cerebellar ataxia of
unclear etiology. Seen in this video are common ocular motor signs
in patients with advanced cerebellar dysfunction including: (1) sac-
cadic smooth pursuit, (2) saccadic vestibulo-ocular reflex suppres-
sion (VORS, a combined eye-head movement; the fact that pursuit
and VORS appear to be equally saccadic also tells the examiner that
the VOR is present—that is, if VORS was normal/near-normal
appearing but pursuit was saccadic, this would suggest that there is
no VOR to suppress due to significant vestibular loss), (3) gaze-
evoked and rebound nystagmus. When right-beating nystagmus
(RBN) is seen in right gaze and left-beating nystagmus (LBN) is
Cerebellum 185
Paraflocculus (tonsil) Flocculus
Nodulus Uvula
Fig. 4.31 Structure and function of the vestibulocerebellum: Think of these

four structures as two functional units: (1) flocculus/paraflocculus (tonsil),
e.g., optimization of gaze-holding, smooth pursuit, modulate the high fre-
quency vestibulo-ocular reflex, inhibit anterior semicircular canal pathways,
and (2) nodulus/uvula, e.g., important role in velocity storage. The posterior
inferior cerebellar artery (PICA) supplies the paraflocculus, nodulus, and
uvula (labeled on T2 axial images), while the anterior inferior cerebellar
artery (AICA) supplies the flocculus (labeled on a T1 axial image)
seen in left gaze, this can be due to physiologic (normal) end-point

nystagmus (EPN) or pathologic gaze-evoked nystagmus (GEN). A
normal patient with EPN will have very symmetric, relatively mild
nystagmus in lateral gaze that fatigues to a degree as the eyes are
kept in eccentric gaze. If the fixation target is brought back to ~75%
of lateral gaze, EPN will resolve. When the eyes are brought back
from lateral to primary gaze in a patient with EPN, rebound nystag-
mus should not be seen (or at least not more than a beat or two).
With GEN, the nystagmus tends to be more intense and sustained in
lateral gaze, and often persists when the eyes are brought back to a
~75% position. Rebound nystagmus is common with GEN - e.g.,

RBN in right gaze is the GEN while a reversal to LBN when the
eyes are brought back to center is the rebound nystag-
mus. Occasionally, mild upbeat nystagmus in upgaze can be seen
with EPN as well, but this should be mild. Otherwise, vertical GEN
is almost always pathologic. If there are other central ocular motor
findings on the exam, nystagmus in lateral gaze is much more likely
to represent GEN than EPN. (this patient—Video 4.42:
Spinocerebellar ataxia type 6 patient with a flocculus/paraflocculus
syndrome Video 4.13)
Asymmetric involvement of the flocculus/paraflocculus due to a

structural lesion (Chiari malformation): A 25-year-old woman
presented with 6 months of progressive imbalance and occipital
headaches, which were brought on or aggravated by coughing or
sneezing. Examination demonstrated hyperreflexia in the arms and
legs with sustained clonus at the ankles and Babinski reflexes bilat-
erally in addition to gait and limb ataxia. On examination, there was
subtle downbeat nystagmus (DBN) in primary gaze that could only
be appreciated with the ophthalmoscope, although DBN was easily
seen in lateral, down, and lateral/down gaze. In lateral gaze, there
was also horizontal gaze-evoked nystagmus. The combination of
DBN and GEN in lateral gaze produces an oblique or diagonal nys-
tagmus that beats down and out, so-called “side-pocket” nystagmus.
Contrast-enhanced MRI demonstrated peg-like cerebellar tonsils
extending 2.9 cm below the foramen magnum (more tonsillar her-
niation on the right), and flattening of the dorsal medulla (right>left).
There was also syringohydromyelia of the cervical and proximal
thoracic spinal cord with parenchymal thinning. Taken together, this
was consistent with a Chiari type I malformation. She underwent
suboccipital craniectomy and C1 laminectomy, and when she was
seen 6 months following surgery, all ocular motor findings had
resolved with the exception of mild residual gaze-evoked nystag-
mus. Her balance remained quite impaired due to persistent myelop-
athy. Fig. 5.4 Video 4.43.
Cerebellum 187
4.7.1.2 Downbeat Nystagmus

Case: See “Downbeat nystagmus” in Chap. 5
4.7.1.3 Alternating Skew Deviation

Case: A 70-year-old woman with a diagnosis of cerebellar
ataxia, neuropathy, vestibular areflexia syndrome (CANVAS)
complained of vertical diplopia in lateral gaze. In the video, both
spontaneous DBN and gaze-evoked nystagmus are apparent, in
addition to a right hypertropia in right gaze and a left hypertropia
in left gaze, also referred to as an alternating skew deviation or an
abducting hypertropia. Compare this to a patient with bilateral
fourth nerve palsies causing right hypertropia in left gaze (due to
right fourth NP) and left hypertropia in right gaze (due to left
fourth NP). Video 4.32.
4.7.2 S
yndrome of the Nodulus and Ventral Uvula
Fig. 4.31
4.7.2.1 C entral Patterns of Head-shaking

and Periodic Alternating Nystagmus (PAN)
Case: A 35-year-old man suffered a gunshot wound to the cere-
bellum. When he regained consciousness days later, he experi-
enced oscillopsia due to periodic alternating nystagmus (PAN).
He was started on baclofen 10 mg bid, and there was a transition
to a persistent, mild spontaneous left-beating nystagmus (without
PAN). The dose was increased to 20 mg 4 times/day, at which
time nystagmus and oscillopsia resolved completely (without side
effects). However, following 10–15 seconds of 2–3 Hz horizontal
head-shaking, there was robust left-beating nystagmus despite the
absence of right unilateral vestibular loss. This could be explained
by injury to the nodulus, a localization that explains both PAN and
certain central patterns of head-shaking nystagmus (HSN) such as
this (i.e., robust horizontal HSN in the absence of unilateral ves-
tibular loss). Neuronal circuits responsible for velocity storage are
mainly located in the vestibular nucleus and nodulus. The main

purpose of velocity storage is to prolong vestibular responses
beyond the mechanical constraints of the semicircular canal,
which improves VOR performance during low-frequency rota-
tions. Disinhibition of velocity storage due to nodulus injury can
therefore contribute to an overactive vestibular response, which
can result in PAN or central HSN. Other “central” HSN patterns
include a reversal from spontaneous nystagmus (e.g., contrale-
sional (right-beating) horizontal nystagmus due to left medullary
stroke and ipsilesional (left-beating) HSN) or vertical HSN fol-
lowing horizontal head-shaking (so-called “cross coupling”).
Video 4.44: Spontaneous downbeat nystagmus may also result
from a nodulus/uvula lesion.
4.7.2.2 Positional Nystagmus

Be concerned about a lesion of the nodulus/uvula in a patient with
apogeotropic positional nystagmus that is associated with neuro-
logic or ocular motor abnormalities, or which persists despite
repeated, properly performed repositioning maneuvers. One the-
ory for apogeotropic central positional nystagmus is that there
may be a mismatch between gravity signals derived from the oto-
lith organs and the velocity storage system.
4.7.3 Syndrome of the Dorsal Vermis

and Posterior Fastigial Nucleus (Figs. 4.7
and 4.8)
4.7.3.1 OMV
• Unilateral lesion—ipsiversive hypometric and contraversive

hypermetric saccades
• Bilateral lesions—bilaterally hypometric saccades
• Bilateral lesions—divergency insufficiency (flocculus may
also contribute). Example of a patient with divergence insuffi-
ciency who has a cerebellopathy and features of sagging eye
syndrome—Video 4.4
References 189
4.7.3.2 FOR
• Unilateral lesion—ipsiversive hypermetric and contraversive

hypometric saccades. However, since each fastigial nucleus
sends fibers through the contralateral fastigial nucleus, a uni-
lateral structural lesion is effectively a bilateral lesion, result-
ing in bilaterally hypermetric saccades. Video 4.45: bilaterally
hypermetric saccades
• Bilateral lesions—bilaterally hypermetric saccades; macrosac-
cadic oscillations and saccadic intrusions (square wave jerks);
exophoria.
Read These Books! [13–15, 16–18]
References
1. Brazis PW. Ocular motor abnormalities in Wallenberg’s lateral medullary
syndrome. Mayo Clin Proc. 1992;67(4):365–8.
2. Brodsky MC, Donahue SP, Vaphiades M, Brandt T. Skew deviation revis-
ited. Surv Ophthalmol. 2006;51(2):105–28.
3. Frohman TC, Galetta S, Fox R, Solomon D, Straumann D, Filippi M,
et al. Pearls & Oy-sters: the medial longitudinal fasciculus in ocular
motor physiology. Neurology. 2008;70(17):e57–67.
4. Tamhankar MA, Biousse V, Ying GS, Prasad S, Subramanian PS, Lee
MS, et al. Isolated third, fourth, and sixth cranial nerve palsies from pre-
sumed microvascular versus other causes: a prospective study.
Ophthalmology. 2013;120(11):2264–9.
5. Zwergal A, Rettinger N, Frenzel C, Dieterich M, Brandt T, Strupp M. A
bucket of static vestibular function. Neurology. 2009;72(19):1689–92.
6. Wong AM, Colpa L, Chandrakumar M. Ability of an upright-supine test
to differentiate skew deviation from other vertical strabismus causes.
Arch Ophthalmol. 2011;129(12):1570–5.
7. Ivanir Y, Trobe JD. Comparing hypertropia in upgaze and downgaze dis-
tinguishes congenital from acquired fourth nerve palsies. J
Neuroophthalmol. 2017;37(4):365–8.
8. Strupp M, Kremmyda O, Adamczyk C, Bottcher N, Muth C, Yip CW,
et al. Central ocular motor disorders, including gaze palsy and nystag-
mus. J Neurol. 2014;261(Suppl 2):S542–58.
9. Fearon C, Field R, Donlon E, Murphy OC, Cronin S, Buckley C, et al.
The “round the houses” sign and “zig-zag” sign in progressive supranu-
clear palsy and other conditions. Parkinsonism & related disorders.

2020;81:94–5.
10. Rivaud-Pechoux S, Vidailhet M, Gallouedec G, Litvan I, Gaymard B,
Pierrot-Deseilligny C. Longitudinal ocular motor study in corticobasal
degeneration and progressive supranuclear palsy. Neurology.
2000;54(5):1029–32.
11. Hoglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang
AE, et al. Clinical diagnosis of progressive supranuclear palsy: the move-
ment disorder society criteria. Mov Disord. 2017;32(6):853–64.
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Clin Neurophysiol. 2019;36(6):405–14.

2021.
16. Brodsky MC. Pediatric neuro-ophthalmology. 3rd ed. New York:

Springer; 2016.
17. Leigh RJ, Zee DS. The neurology of eye movements. 5th ed. New York:
Oxford University Press; 2015.
18. Wong AM. Eye movement disorders. New York: Oxford University

Press; 2008.
Oscillopsia, Nystagmus,
and Other Abnormal
5
Movements
5.1 he History—How to Approach

T
Oscillopsia and Nystagmus
Patients with nystagmus or saccadic intrusions/oscillations often

complain of oscillopsia, or the visual illusion of movement of a
stationary object. When a patient complains of “sitting” oscillopsia
(i.e., oscillopsia that is independent of head movement, Video 5.1),
it is important to understand whether there are associated symp-
toms to indicate a vestibular disorder or a neuro-ophthalmic disor-
der. If the oscillopsia is vestibular in origin, dizziness, vertigo, or
imbalance should also be experienced, and these balance sensa-
tions persist despite eye closure. Ask if the patient is experiencing
simultaneous migrainous symptoms to suggest vestibular migraine;
aural symptoms that might indicate vestibular paroxysmia, supe-
rior canal dehiscence syndrome (SCDS, sound and/or pressure are
triggers in these cases), or Meniere’s attacks; or neurologic symp-
toms that might indicate vascular events. If “sitting” oscillopsia
resolves completely with eye closure, then a vestibular disorder is
unlikely. Instead, consider non-vestibular disorders such as
acquired pendular nystagmus (e.g., due to multiple sclerosis), sac-


https://doi.org/10.1007/978-3-030-76875-1_5
192 5 Oscillopsia, Nystagmus, and Other Abnormal Movements
cadic intrusions (e.g., macrosaccadic oscillations), and superior

oblique myokymia (especially with monocular oscillopsia). Note
that oscillopsia is rarely experienced with infantile nystagmus,
although there are some situations that can cause decompensation
and the experience of occasional oscillopsia, usually later in life
(e.g., change in strabismus or vision [refractive error or new ocular
disease], new neurologic diseases or certain centrally-acting medi-
cations). A patient with pendular nystagmus due to MS with severe
vision loss due to optic nerve disease may experience minimal or
no oscillopsia due to poor visual function.
5.2 he Exam—Does My Patient Have

T
Nystagmus or Something Else? [1]
Not everything that jiggles is nystagmus! Fig. 5.1 Nystagmus

is a rhythmic involuntary movement of the eyes, where the
slow phase is the pathologic phase, and is classified as (1)
jerk—each slow phase is followed by a fast phase (position
reset mechanism) (Video 5.2), or (2) pendular—back to back
slow phases, resembling a pendulum. (Video 5.3). Square wave
jerks are one saccadic intrusion that become more frequent
with aging, but are especially common in neurodegenerative
disorders that affect the cerebellum (progressive ataxia) or
basal ganglia (parkinsonism). These intrusions are initiated by
saccades (not a slow phase), and are therefore distinct from
nystagmus (Video 5.4).
If a patient has continuous “sitting” oscillopsia, nystagmus or
intrusions/oscillations can usually be observed and the diagnosis
can be made (e.g., vertical oscillopsia in downbeat nystagmus). In
contrast, “walking” (head-movement-dependent) oscillopsia is
almost always due to a vestibulo-ocular reflex (VOR) deficit
(Video 5.5) (the concept of “sitting” vs “walking” oscillopsia is
courtesy of Dr. David Newman-Toker).
Oftentimes, the oscillopsia is episodic (especially when ves-
tibular), and so the examiner should try to provoke nystagmus and
typical symptoms (e.g., Dix–Hallpike in benign paroxysmal posi-
tional vertigo, Valsalva and pinched-nose Valsalva in SCDS, hav-
ing the patient look down and contralaterally when superior
The Exam—Does My Patient Have Nystagmus or Something Else? 193
NYSTAGMUS (slow phase is the culprit)

Pendular Jerk (slow phase velocities)
Linear (constant) Decreasing Increasing
INTRUSIONS/OSCILLATIONS (saccade is the culprit)

Square Wave Jerks Macrosaccadic Opsoclonus &
Oscillations Flutter
Fig. 5.1 Is it nystagmus or a saccadic intrusion/oscillation? Nystagmus can

be classified into pendular and jerk waveforms (which are typically generated
with video-oculography, video-nystagmography, or electro-nystagmogra-
phy), where both are generated by a slow, pathologic phase. In pendular nys-
tagmus, the characteristic appearance is the result of back-to-back slow
phases. Jerk nystagmus can have constant, increasing or decreasing slow
phase velocity: vestibular nystagmus has a linear slow phase velocity due to
vestibulo-ocular reflex imbalance; gaze-evoked nystagmus has a decreasing
slow phase velocity due to a leaky neural integrator (i.e., a problem with the
gaze-holding machinery); congenital nystagmus and certain posterior fossa
disorders can cause an increasing slow phase velocity due to an unstable neu-
ral integrator. In jerk nystagmus, the slow (pathologic) phase is followed by
the fast (named) phase. Nystagmus should be distinguished from oscillations
and intrusions, particularly given disparate localizations and etiologies. These
include saccadic intrusions (e.g., square wave jerks) and saccadic oscillations
(e.g., ocular flutter and opsoclonus). Saccadic intrusions consist of saccades
with an intersaccadic interval (i.e., a brief pause between movements), while
saccadic oscillations lack this interval. Square wave jerks are small saccades
that move the line of sight away from the target and then return to fixation 200
ms later, and the name derives from the fact that the waveforms have a square-
like appearance. Macrosaccadic oscillations are saccades that take the eye off
target and oscillate the line of sight about the object of regard—these move-
ments straddle fixation, and are often seen in association with hypermetric
saccades. Ocular flutter is confined to the horizontal vector whereas opsoclo-
nus has horizontal, vertical and torsional components, and occurs in bursts;
however, the differential diagnosis, implications, and treatment of flutter and
opsoclonus are essentially the same
oblique myokymia is suspected). If oscillopsia is only brought on

with convergence and associated with spasm of the near triad, this
is suggestive of voluntary nystagmus/flutter.
While some nystagmus or intrusions (latent/infantile nystag-
mus or square wave jerks, respectively) are benign, others can
suggest a potentially dangerous condition (spontaneous upbeat
nystagmus and/or direction-changing nystagmus in Wernicke’s or
stroke; flutter/opsoclonus in paraneoplastic disorders).
Recognizing the pattern of nystagmus or oscillation/intrusion
assists in diagnosis and localization.
Occasionally, nystagmus is just too subtle to appreciate with-
out using the magnification of the ophthalmoscope or slit lamp
(e.g., observing the conjunctival vessels helps with the evaluation
of torsional nystagmus). Observation of the fundus can assist in
determining the vector (horizontal or elliptical in pendular?
Conjugate or dissociated between the eyes?), and appearance (is
this nystagmus or is this an intrusion, or is there nystagmus AND
intrusions—for example, a patient with downbeat nystagmus
AND square wave jerks?). Ocular microflutter is a benign condi-
tion that is usually chronic and associated with a migraine his-
tory, and does not generally require an extensive workup. In this
disorder, there are short bouts of (horizontal) flutter causing
oscillopsia that are so subtle that they are typically missed with-
out the aid of eye movement recordings or an ophthalmoscope. In
contrast, the acute/subacute onset of ocular flutter (which is
clearly visible at the bedside) can suggest an underlying neoplas-
tic condition.
The approach (history and exam) to the patient with nystag-

mus or oscillations: Table 5.1 and ESM 5.1
5.3 Nystagmus
5.3.1 Horizontal Nystagmus (Bruns Nystagmus)
Case: A 15-year-old girl presented to clinic with headaches, imbal-

ance, left-sided hearing loss, and “jumping” of the vision in lateral
gaze. Her balance difficulties had been progressive over the last
2 years, and she had experienced an increase in headache frequency
Table 5.1 Help me now with nystagmus & intrusions/oscillations: Is it urgent and what should I look for?
Type of
nystagmus A few etiologies
Nystagmus
Appearance or oscillation Localization to consider Medication Distinguishing feature(s)

Peripheral Spontaneous Jerk Semicircular Vestibular neuritis None—usually Unidirectional and contralesional
vestibular horizontal- canal or CN8 (no hearing loss); short-lived (fast phase); follows Alexander’s law;
nystagmus in torsional slow labyrinthitis often mixed horizontal-torsional;
the acute phase (toward (hearing suppression with fixation; associated
vestibular the affected ear) loss—don’t forget with ipsilesional abnormal head
syndrome labyrinthine impulse test (HIT); negative test of
stroke) skew
Central Horizontal, Jerk Brainstem or Stroke, None—usually Can be unidirectional or bidirectional
vestibular torsional, cerebellum demyelination short-lived (gaze-evoked); can follow
nystagmus in horizontal- Alexander’s law; often doesn’t
the acute torsional (each suppress with fixation; HIT is usually
vestibular can be normal, and when a vertical ocular
syndrome ipsilesional or misalignment is seen, skew deviation
contralesional), should be assumed until proven
vertical or otherwise
vertical-torsional
(continued)
195
196
Type of
nystagmus
or A few etiologies
Appearance oscillation Localization to consider Medication Distinguishing feature(s)
Downbeat Upward slow Jerk Usually Neuro- 4-aminopyridine, Increases with convergence and in
nystagmus phase cerebellar degenerative baclofen, lateral gaze; gaze-evoked nystagmus
(DBN) flocculus/ cerebellar ataxia, clonazepam, and impaired pursuit are often
paraflocculus Chiari, chlorzoxazone present; increased with prone,
paraneoplastic, straight head-hanging or other
medication positional maneuvers, in addition to
(lithium) head-shaking, hyperventilation
Upbeat Downward slow Jerk Dorsal medulla Stroke, 4-aminopyridine, Follows Alexander’s law (more UBN
nystagmus phase or ponto- demyelination, memantine, in up gaze); in Wernicke’s, UBN may
(UBN) mesencephalic encephalitis, baclofen transition to DBN with convergence
regions Wernicke’s
Periodic Horizontal slow Jerk Lesion of the Stroke, medication Baclofen, Will be right-beating (RBN) for
alternating phase to the right cerebellar toxicity, memantine 90–120 seconds, will slow and then
nystagmus transitioning to nodulus/ventral neuro- have a null phase (at which time,
the left and back uvula degenerative sometimes downbeat or other
to the right disorder nystagmus or saccadic intrusions can
(every 90–120 be seen), followed by left-beating
seconds) nystagmus (LBN), null phase, RBN,
etc.
5 Oscillopsia, Nystagmus, and Other Abnormal Movements
Gaze-evoked Slow phase Jerk Lesion Stroke, medication None If direction-changing horizontal
nystagmus drifting back to involving the toxicity, nystagmus in far lateral gaze, it is
(GEN) center (due to neural neuro- likely to be physiologic end point
Nystagmus
orbital elastic integrator degenerative nystagmus if low amplitude, it

forces) initiates (nucleus disorder fatigues after several seconds, and if
the movement, prepositus bringing the visual target back to a
fast phase hypoglossi three-quarters gaze position (so that
beating in the horizontally; the target can be seen by the
direction of gaze interstitial adducting eye as well) mitigates the
(e.g., RBN in nucleus of nystagmus; think GEN when the
right; LBN in Cajal amplitude is larger, nystagmus
left) vertically; persists even in three-quarters
flocculus/ position, and if when returning to
paraflocculus primary gaze, the nystagmus changes
horizontally direction—e.g., RBN in right
and vertically followed by LBN when the eyes are
brought back to primary
(continued)
197
198
Type of
nystagmus
or A few etiologies
Oculopalatal Often vertical Pendular Mollaret’s Dorsal pontine Gabapentin, When OPT is due to a pontine lesion
tremor (OPT) and/or torsional triangle hemorrhage memantine, of the central tegmental tract, the
slow phases, can (inferior olive involving central trihexyphenidyl following signs are commonly also
have horizontal [IO] to tegmental tract is seen: lower motor neuron facial palsy,
component as contralateral common; consider fascicular 6th nerve palsy, nuclear 6th
well, can be dentate progressive ataxia causing horizontal gaze palsy,
disjunctive nucleus, and palatal tremor internuclear ophthalmoparesis (INO),
decussates and (PAPT) when one-and-a-half syndrome; when
wraps around structural lesion is pendular nystagmus is seen, always
contra- red absent look at the resting palate; inferior
nucleus and olivary hypertrophy (T2/FLAIR
descends to hyperintensity) on MRI is
ipsi- IO) characteristic; OPT due to a lesion in
Mollaret’s triangle develops weeks to
months after the injury, not acutely
Other Usually Pendular Instability of MS (common); Gabapentin, APN in MS is commonly seen with
acquired horizontal or neural medication/ memantine other ocular motor disorders
pendular elliptical slow integrators (in toxicity localizing to the posterior fossa
Nystagmus
nystagmus phases in MS); (toluene)-induced, including gaze-evoked nystagmus,

(APN) multiple sclerosis associated with stroke, neuro- saccadic pursuit, INO, hypermetric
(MS) (and can be afferent degenerative saccades; APN is usually more
dissociated/ dysfunction disease (rare) prominent in the worse-seeing eye in
disconjugate); (e.g., cataract MS; occasionally, an MS patient may
divergent- causing have APN and normal afferent
convergent slow Heimann- function
phases in Bielschowsky
Whipple disease phenomenon)
Square wave Small horizontal Saccadic Cerebral Parkinson’s Usually visually SWJ can become more frequent with
jerks (SWJ) back-and-forth intrusion cortical, basal disease, asymptomatic, no normal aging especially when
saccades with ganglia, progressive strong evidence for asymptomatic and in isolation; if
intersaccadic cerebellar, supranuclear any medication SWJ are >15/ minute and associated
interval increase with palsy, cerebellar with gaze-evoked nystagmus,
normal aging ataxia saccadic pursuit or other central
ocular motor findings, they are likely
to be pathologic
(continued)
199
200
Type of
nystagmus
or A few etiologies
Ocular flutter Rapid back-to- Saccadic Brainstem Reported in many Acute—steroids, Often associated with myoclonic
/ opsoclonus back saccades intrusion (omnipause infectious (and intravenous jerks involving arms, legs, truncal
horizontally without cells in nucleus postinfectious), immunoglobulin, muscles; exaggerated startle response
(flutter) or intersaccadic raphe paraneoplastic plasma exchange;
horizontally and interval interpositus) or (neuroblastoma in acute or chronic—
vertically cerebellum the very young, rituximab,
(opsoclonus) (fastigial lung and clonazepam,
pathways) gynecological gabapentin,
among others in memantine, others
older), (mainly case
medication-related reports/ series)
conditions
Nystagmus 201
during the same period of time. She did have a history of migraines,
but her recent headaches felt different. Neurologic examination was
normal with the exception of an inability to tandem walk for more
than a few steps, nor could she stand in tandem. Neuro-ophthalmic
examination was normal including afferent function and motility/
ocular alignment. There was very mild spontaneous right-beating
nystagmus (RBN), which was unchanged in up- and downgaze, and
her RBN was more prominent in right gaze where she experienced
mild oscillopsia. In left gaze, there was a larger amplitude left-beat-
ing nystagmus (LBN) and more oscillopsia. Saccades were normal.
Smooth pursuit appeared mildly saccadic in all directions (espe-
cially to the right in the direction of the slow phase), while vestibulo-
ocular reflex suppression (VORS) appeared saccadic in all directions
except to the left, where it appeared normal. Head impulse test (HIT)
was normal to the right and abnormal to the left. With fixation-
removed while wearing Frenzel goggles, RBN was more noticeable,
and RBN increased slightly with mastoid and vertex vibration and
horizontal head-shaking. Following 40 seconds hyperventilation,
there was robust LBN. Otoscopic examination was normal, although
finger rub was diminished on the left side, Rinne demonstrated that
air conduction was greater than bone conduction AU, and Weber
lateralized to the right ear (consistent with a left sensorineural hear-
ing loss). Contrast-enhanced MRI demonstrated a large left cerebel-
lopontine angle tumor thought to be due to vestibular schwannoma,
which was resected and pathology was found to be consistent with
this diagnosis.
Video/figure: Video 5.6 and Fig. 5.2
• Are there episodes of dizziness or vertigo (i.e., less likely to be a

vestibular schwannoma) or just a progressive balance disorder?
• Is there head-movement-dependent (“walking”) oscillopsia to
suggest severe bilateral (or poorly compensated) vestibular loss?.
The combination of progressive headaches, left sided hearing

loss, and imbalance is highly suspicious for a left cerebellopon-
tine angle (CPA) mass lesion causing CN8 dysfunction.
a b c DBN/GEN
UBN Torsional
d e f
OPT Bruns PAN/CPPN
Fig. 5.2 Common lesions and localizations for nystagmus as seen on MRI:
(a) Upbeat nystagmus (UBN)—typically associated with midline brainstem
lesions, especially involving the dorsal medulla (nucleus of Roller, nucleus
intercalatus). Seen here are bilateral dorsal medullary (axial) FLAIR hyperin-
tensities (arrow) in a patient with pure UBN due to multiple sclerosis. (b)
Torsional nystagmus—this is usually the result of a brainstem lesion affecting
the central utriculo-ocular motor or vertical semicircular canal pathways
(pure torsional nystagmus with symmetric injury to the anterior and posterior
pathways, and vertical-torsional nystagmus typically results from asymmetric
injury). This patient suffered a right interstitial nucleus of Cajal stroke seen
on axial MR diffusion-weighted imaging (DWI, arrow) causing torsional nys-
tagmus with the top poles of both eyes beating toward the right ear (accompa-
nied by a contraversive ocular tilt reaction, which is another common feature).
(c) Downbeat (DBN) and gaze-evoked nystagmus (GEN)—while a discrete
flocculus/paraflocculus lesion may be seen, diffuse cerebellar atrophy (on
sagittal T1) is commonly seen as in this patient with a cerebellar degeneration
causing DBN, GEN, saccadic pursuit and limb/gait ataxia. (d) Oculopalatal
tremor (OPT)—a dorsal pontine hemorrhage involving the descending inhibi-
tory central tegmental tract is a common cause of OPT, seen here as a hypoin-
tensity in the dorsal pons (arrow) on axial gradient echo sequence (note that
inferior olivary hypertrophy/hyperintensity is commonly seen on FLAIR/T2,
but this represents physiologic changes that have occurred within Mollaret’s
triangle rather than representing the insult itself - see Fig. 5.7). (e) Bruns
nystagmus—seeing vestibular nystagmus in left gaze and gaze-evoked nys-
tagmus in right gaze should alert the clinician to a large right cerebellopontine
angle tumor, such as a vestibular schwannoma (axial T1 contrast, arrow,
image courtesy of Dr. Jeffrey Sharon). (f) Periodic alternating nystagmus
(PAN)—this localizes well to the nodulus (arrow) and ventral uvula, as seen
on this axial diffusion-weighted image in a patient with PAN due to an acute
stroke. Central paroxysmal positional nystagmus (CPPN)—commonly down-
beat in straight head hanging or prone and apogeotropic in Dix-Hallpike and
supine roll—is commonly seen with nodulus lesions as well
Nystagmus 203
Key findings to elicit: When a CPA angle tumor is suspected:
(1) Evaluate for unilateral hearing loss with finger rub, Rinne/
Weber and perform otoscopy (referrals to audiology and ENT
are also warranted),
(2) Evaluate for unilateral vestibular loss with removal of fixa-
tion and provocative maneuvers such as vibration and head-
shaking (which often increase contralesional vestibular
nystagmus), HIT (HIT can appear normal if compensation
has occurred given the chronicity of the lesion, so video HIT
and calorics are often helpful),
(3) Hyperventilate the patient and look for ipsilesional (excit-
atory) nystagmus,
(4) Evaluate for neurologic (e.g., gait or limb ataxia) or ocular
motor (e.g., saccadic dysmetria, saccadic pursuit/VORS,
gaze-evoked nystagmus) abnormalities to suggest cerebellar
or brainstem compression,
(5) Evaluate for Bruns nystagmus—because of involvement of the
left brainstem/cerebellum (e.g., dysfunction of the neural integra-
tor/gaze holding apparatus, especially compression of the floc-
culus in this case) by the CPA mass, left-beating (ipsilesional)
“gaze-evoked” nystagmus will be seen in left gaze (a larger
amplitude and lower frequency nystagmus). Because of involve-
ment of the left 8th cranial nerve, right-beating (contralesional)
“vestibular” nystagmus will be seen in right gaze (increased RBN
in the direction of the fast phase, in accordance with Alexander’s
law, a smaller amplitude and higher frequency nystagmus).

mus or oscillations: Table 5.1 and ESM 5.1.
Pitfalls: If the schwannoma is small, it can be missed on a non-

contrast MRI that lacks high resolution/thin cuts through the
internal auditory canal (IAC). Because the unilateral vestibular
loss (UVL, due to CN8 compression) occurs over months to years,
the UVL may be very well compensated for and can be missed
with bedside HIT. This is why removal of fixation and utilization
of provocative maneuvers (described above) is particularly impor-
tant. In a patient with horizontal nystagmus, also consider the pos-

sibility of latent nystagmus, which is typically associated with a
known childhood history of strabismus (infantile esotropia).
Latent nystagmus will change direction depending on the viewing
eye—for example, right-beating with the right eye viewing and
left-beating with the left eye viewing (Video 5.7). This nystagmus
will make interpretation of bedside and laboratory vestibular test-
ing particularly challenging even when the vestibular system is
intact. Infantile nystagmus should also be considered, but usually
patients are aware of this history (and their nystagmus) while
patients with latent nystagmus may be unaware.
Do not miss this! Rarely, a vestibular schwannoma can cause, or

present with, vertigo attacks, although progressive hearing loss
and imbalance is a far more typical symptom complex. Consider
neurofibromatosis type 2 when bilateral vestibular schwannomas
are present. In patients with unilateral or bilateral hearing loss,
consider first whether the onset is gradual (symmetric or asym-
metric?) or sudden in onset (with or without vertigo?).
What is next? Contrast-enhanced IAC protocol MRI.
Treatment options: Depending on the symptoms, exact location

and extent of the vestibular schwannoma, surgery may be indicated
with ENT and/or neurosurgery, although gamma knife and similar
therapies may be favored in some, versus watchful waiting in others.
If you can only remember one thing… Bruns nystagmus, char-

acterized by ipsilesional gaze-evoked and contralesional vestibular
nystagmus, is highly localizing to the CP angle. However, another
localization for Bruns nystagmus when hearing loss is absent could
be the (left) medulla—e.g., contralesional (right-beating) vestibular
nystagmus due to involvement of central semicircular canal path-
ways, and ipsilesional (left-beating) gaze-evoked nystagmus due to
involvement of nuclei involved in horizontal gaze-holding (nucleus
prepositus hypoglossi and medial vestibular nucleus).

Nystagmus 205
5.3.2 Periodic Alternating Nystagmus
Case: A 60-year-old woman presented with complaints of sev-

eral years of worsening imbalance and oscillopsia. Examination
demonstrated gait and limb ataxia, hypermetric saccades, sac-
cadic smooth pursuit and vestibulo-ocular reflex suppression
(VORS), and gaze-evoked nystagmus (GEN). She had spontane-
ous horizontal nystagmus that alternated between right-beating
and left-beating every ~100 seconds (with a null or quiet period in
between), consistent with periodic alternating nystagmus (PAN).
Reversible/treatable causes of a cerebellar disorder were unre-
vealing including contrast-enhanced MRI, and a progressive cer-
ebellar ataxia (due to spinocerebellar ataxia type 6 or similar) was
suspected.
Video/Figure: Video 5.8 and Fig. 5.2
Key questions to ask: If the onset is abrupt and/or vascular risk

factors are present, consider stroke and ask about other posterior
circulation symptoms. Ask about headaches (e.g., Chiari, midline
cerebellar tumor), associated neurologic symptoms, and family
history of balance disorders (e.g., spinocerebellar ataxia).
Key findings to elicit: Evaluate for truncal/gait and limb ataxia.

Examine all classes of eye movements for a better understanding
of localization, which can help with the differential diagnosis. In
this case, she had evidence of diffuse cerebellar involvement
which was supported by limb and gait ataxia, saccadic pursuit and
GEN (flocculus/paraflocculus), saccadic hypermetria (fastigial
nucleus), as well as PAN and cross-coupling with head-shaking
(nodulus/uvula).

Pitfalls: In any patient with spontaneous horizontal nystagmus

(that is not obviously related to acute vestibular neuritis/periph-
eral vestibulopathy), observe the nystagmus for at least 120 sec-
onds to specifically evaluate for PAN.
Do not miss this! If the onset of PAN is abrupt, stroke is most

likely. If progressive, consider a degenerative cerebellar condition
(e.g., SCA 6, see example—Video 5.9), or structural lesion (e.g.,
Chiari malformation). In children, consider congenital PAN once
a structural lesion has been excluded.
What is next? Contrast-enhanced MRI, and depending on the

result and chronicity, consideration of cerebellar labs and testing
(inflammatory, infectious, nutritional, paraneoplastic, genetic).
Treatment options: Baclofen has been shown to be beneficial

for patients with PAN. Memantine may help in some cases.
5.3.3 Downbeat Nystagmus
Case: A 60-year-old woman presented with the subacute onset

over several weeks of a gait disorder, dizziness, and oscillopsia.
Examination demonstrated spontaneous DBN with side pocket
nystagmus in lateral gaze (a combination of horizontal gaze-evoked
and downbeat nystagmus, giving an oblique [downward and lateral]
appearance), in addition to hypermetric saccades, saccadic smooth
pursuit and VOR suppression. Contrast-enhanced MRI was normal,
and lumbar puncture demonstrated a mild cerebrospinal fluid pleo-
cytosis with normal protein, glucose, cytology, and flow cytometry.
CT of the chest/abdomen/pelvis revealed a left hilar mass with
extension into the bronchus, and biopsy revealed small cell carci-
noma of the lung. It was thought that a paraneoplastic cerebellopa-
thy was the most likely culprit despite a negative serum
paraneoplastic panel. There was significant subjective improve-
ment in vertical oscillopsia and objective improvement in her
downbeat nystagmus with intravenous immunoglobulin in addition
to treating the malignancy with resection and chemotherapy.
Nystagmus 207
SS MSA (early) Chiari

a b. c.
MSA (advanced)
Fig. 5.3 Disorders and localizations to consider in patients presenting with

chronic imbalance and downbeat nystagmus (DBN): All patients with evi-
dence of cerebellar dysfunction require an MRI of the brain, preferably with
contrast and susceptibility weighted imaging (SWI). (a) In this patient with
superficial siderosis (SS), SWI demonstrates hypointense signal (arrows)
involving the brainstem, cerebellum, as well as the vestibulocochlear nerves
(this patient also had bilateral vestibular and hearing loss), that is indicative
of hemosiderin deposition lining these structures. The source of the hemosid-
erin could not be elucidated in his case. (b) In this patient with multiple sys-
tem atrophy (MSA), there was mild DBN (in addition to gaze-evoked
nystagmus) when upright and a significant increase in DBN when supine. On
exam, there were parkinsonian symptoms including bradykinesia and rigid-
ity, and axial T2 demonstrated pontine atrophy with a cross-shaped (arrows)
hyperintensity within the pons (an early “hot cross bun sign”). The bottom
image demonstrates a more prominent “hot cross bun sign” (hyperintense on
FLAIR) in advanced MSA (Image courtesy of Dr. David Zee). (c) A young
woman presented with occipital headaches (worse with coughing), DBN and
imbalance, and MRI demonstrated a Chiari malformation causing tonsillar
(paraflocculus) herniation, with a peg-like appearance of the tonsils (arrow).
Her severe imbalance was due to both cerebellopathy and a myelopathy
(hyperreflexia, ankle clonus, + Babinski) from an associated syrinx
Video: This patient: Video 5.10; prominent DBN in a cerebellar

degeneration Video 5.11, Figs. 5.2 and 5.3.
Key questions to ask: In patients with DBN, the time course is

most important: (1) if acute, think about a stroke (rare but consider
bilateral vestibulocerebellar ischemia or a lesion of the brainstem
paramedian tracts), infection (cerebellitis), medication (e.g., anti-
convulsants), or other toxicities; (2) if subacute, think about a para-

neoplastic etiology (in an older person) or rarely Creutzfeldt–Jacob
disease; (3) if chronic, think about a structural (e.g., Chiari), heredi-
tary (e.g., spinocerebellar ataxia), neurodegenerative (e.g., multiple
system atrophy), medication-induced (e.g., lithium—may be acute/
subacute as well), or nutritional disorder. If there is associated head-
movement-dependent “walking” oscillopsia (due to bilateral vestib-
ular loss) and/or distal limb numbness/tingling (due to neuropathy),
consider cerebellar ataxia, neuropathy, vestibular areflexia syndrome
(CANVAS—a chronic unexplained dry cough is another common
symptom of this disorder, in addition to a saccadic visually enhanced
vestibulo-ocular reflex [vVOR]—Video 5.12) [5].
Key findings to elicit: If accompanied by gaze-evoked nystag-

mus, impaired pursuit/vestibulo-ocular reflex (VOR) suppression,
normal saccades, think about a flocculus/paraflocculus localization
(consider spinocerebellar ataxia type 6 or similar in chronic con-
ditions). If there is DBN without impaired pursuit/VOR suppres-
sion or gaze-evoked nystagmus, also consider a nodulus/uvula
localization. DBN typically increases in lateral gaze and down-
gaze (another reason why these patients should avoid progressives,
bi- and trifocals), and decreases in up gaze. Evaluate the VOR
(head impulse test, dynamic visual acuity, etc.) given the possibil-
ity of CANVAS, multiple system atrophy, spinocerebellar ataxia
type 3, superficial siderosis, among others that can affect cerebel-
lar and vestibular function. Evaluate for a neuropathy given the
possibility of CANVAS or a nutritional disorder (B12 deficiency).
Evaluate saccades (especially accuracy and velocity) to better
understand the extent of brainstem/cerebellar involvement. A
complete neurologic (including cognitive) and neuro-ophthalmic
(e.g., optic neuropathy in B12 deficiency or maculopathy in SCA
7) examination is essential in these patients.

Pitfalls: A patient may have mild “central” ocular motor exami-

nation findings (such as mild gaze-evoked nystagmus) with little
Nystagmus 209
to no DBN. DBN can be provoked or accentuated by a variety of

maneuvers such as convergence, hyperventilation, horizontal
head-shaking (cross-coupling), prone positioning (or simply lean-
ing forward so the head is between the legs), straight head-hang-
ing or Dix–Hallpike (Video 5.13). Provocation of DBN is a strong
indication of cerebellar dysfunction, especially useful in the eval-
uation of patients with undiagnosed balance disorders.
Do not miss this! Any older patient presenting with the subacute
onset of a DBN/cerebellar syndrome should be worked up expedi-
tiously for a paraneoplastic disorder. The vast majority of the time,
pure DBN does not present acutely and does represent a neurologic
emergency. When it does, think about bilateral strokes (cerebellar
flocculus/paraflocculus or midline brainstem paramedian tracts),
infection (cerebellitis), or medication toxicity. Acute Wernicke’s
encephalopathy can present with vertical nystagmus, although this
is often upbeat nystagmus (UBN). However, UBN can transition to
DBN with convergence, and a gradual evolution to spontaneous
DBN often occurs subacutely/chronically in Wernicke’s.
What is next? All patients require contrast-enhanced MRI to

evaluate for a structural lesion (especially a cervicomedullary
lesion such as Chiari malformation). If normal, focus the workup
based on the onset/timing of symptoms and the presence or
absence of other neurologic signs.
Treatment options: As long as there is no seizure history, trial

of 4-aminopyridine (available as dalfampridine in the United
States, but only indicated to improve gait in multiple sclerosis; a
compounded formulation is another option) is warranted in
patients with oscillopsia due to DBN (some patients can have a
dramatic response). Other medications which may be effective in
select patients include clonazepam, chlorzoxazone, and baclofen.
Unfortunately, large-scale randomized controlled trials are lack-
ing in support of these medications.
Advanced: DBN is usually due to pathology involving the

flocculus/paraflocculus and less commonly the nodulus/uvula
(rarely the paramedian tracts). Theories for its genesis include:

(1) vertical smooth pursuit asymmetry (due to an inherit upward-
downward asymmetry); (2) otolith pathway asymmetry; (3) loss
of inhibition of anterior canal pathways, causing an upward drift
(slow phase) and a downward reset movement (DBN), an ocular
motor finding that is usually associated with flocculus/parafloc-
culus dysfunction, which causes overaction of the anterior canal
(upward or antigravity) pathways relative to posterior canal
(downward or gravity) pathways. This results in a continuous
slow upward phase and subsequent fast downward phase, caus-
ing the DBN.
5.3.4 Upbeat Nystagmus
Case: A 40-year-old woman presented to the hospital with

imbalance, dizziness, confusion, and oscillopsia. In the months
leading up to presentation, she had lost 50 pounds due to poor
oral intake in the setting of a severe depressive episode, in addi-
tion to intractable vomiting in the days leading up to hospital-
ization. Exam demonstrated upbeat nystagmus (UBN) in
primary gaze, and her nystagmus followed Alexander’s law as
UBN typically does—that is, when looking in the direction of
the fast phase (up), her UBN increased in intensity. There was
no gaze-evoked nystagmus, and head impulse test in the planes
of the horizontal canals was normal (although IV thiamine had
already been given). She had severe gait ataxia. Poor nutrition
and vomiting caused thiamine deficiency which led to
Wernicke’s encephalopathy. She was given IV thiamine upon
presentation to the hospital, with gradual improvement in dizzi-
ness, imbalance, and UBN.
Nystagmus 211
Video: Video 5.14, Figs. 5.2, 5.4, and 5.5
Key questions to ask: When UBN is present and acute/subacute

in onset, consider brainstem syndromes caused by ischemia, infec-
tion (encephalitis), paraneoplastic and demyelination and ask
about vascular risk factors and history of previous neurologic and
visual (e.g., optic neuritis) symptoms, respectively. If suspicion is
high for Wernicke’s encephalopathy, inquire about gastric bypass
surgery, malnutrition and/or alcoholism, hyperemesis gravidarum
or other causes of frequent vomiting (e.g., chemotherapy).
Key findings to elicit: Because upbeat nystagmus typically

localizes to the brainstem, evaluate for other posterior circulation
(e.g., homonymous visual field defect) and posterior fossa (e.g.,
skew deviation, ocular lateropulsion, hemi-ataxia) signs. In
Wernicke’s encephalopathy, patients may have an encephalopathy
or confabulate, and oftentimes ataxia and severe gait imbalance
Axial FLAIR
Fig. 5.4 MRI in Wernicke’s encephalopathy: These two images demonstrate

FLAIR hyperintensities involving the periventricular region anterior to the
fourth ventricle (white arrow), and periaqueductal area (dashed arrow), which
are common MRI findings in Wernicke’s. Also look for lesions affecting the
mammillary bodies and bilateral thalami
Ventral
Inferior Anterior Inferior

olive Spinal A olive
Vertebral A
Nucleus of Nucleus of
roller roller
Nucleus Nucleus
intercalatus PICA intercalatus
IC IC
P P
MVN MVN
Dorsal
Fig. 5.5 Vascular distribution and anatomy relevant to the medial medullary
syndrome: This axial section of the medulla highlights those structures that,
when damaged, are often responsible for spontaneous upbeat nystagmus
(UBN). The nucleus of Roller and nucleus intercalatus normally have an
inhibitory influence over the cerebellar flocculus, and when there is a lesion
of Roller/intercalatus, there is less inhibition of the flocculus. The Purkinje
cells of the flocculus normally inhibit the antigravity or upward anterior semi-
circular canal (SCC) pathways. With a lesion of Roller/intercalatus, the floc-
culus will over-inhibit the anterior SCC pathways, causing relative
over-activation of the posterior SCC pathways which will generate a down-
ward slow phase. The fast/position-reset phase will be upward, and these
alternating slow (downward) and fast (upward) phases are responsi-
ble for UBN
with associated dizziness or vertigo is present. In Wernicke’s, the

following ocular motor/vestibular signs should be sought: sponta-
neous UBN (due to dorsal medullary involvement (Fig. 5.5)),
which may transition to downbeat nystagmus (DBN) with conver-
gence (see an example with discussion of mechanism, Video
5.15); horizontal gaze-evoked nystagmus (GEN) is common; oph-
thalmoparesis (especially 6th nerve palsy/palsies) may or may not
be present; UBN may occasionally increase in downgaze (i.e., so-
called anti-Alexander’s law) instead of upgaze in Wernicke’s; loss
of the horizontal vestibulo-ocular reflex (VOR) with relative spar-
ing of the vertical VOR (which can correct within minutes of IV
thiamine administration). Chronically, patients may develop
spontaneous DBN.
Nystagmus 213

Pitfalls: Spontaneous UBN, GEN, and bilateral VOR loss due to

Wernicke’s can occur without ophthalmoparesis. If there is any
suspicion for Wernicke’s encephalopathy, IV thiamine should be
given without delay. The classic triad of confusion, ophthalmople-
gia, and ataxia is often absent.
Do not miss this! The acute onset of UBN is concerning for a

variety of dangerous disorders including brainstem ischemia,
encephalitis, and Wernicke’s encephalopathy. Consider demyelin-
ation as well, including multiple sclerosis (Video 5.16), neuromy-
elitis optica (NMO), as well as anti-myelin oligodendrocyte
glycoprotein (MOG) syndromes. In a young patient with UBN and
new head or neck pain, rule out vertebral artery dissection. If spon-
taneous upbeat-torsional nystagmus is seen, this is often due to
involvement of the anterior semicircular canal pathway, as it trav-
els through the lateral pontine superior vestibular nucleus (Video
5.17), medial longitudinal fasciculus (Video 4.24), ventral tegmen-
tal tract, or brachium conjunctivum/superior cerebellar peduncle.
What is next? Urgent brain MRI to evaluate for ischemia, with

the addition of contrast when there is uncertainty. Vascular imag-
ing of the head and neck when ischemia or vertebral artery dissec-
tion are suspected.
Treatment options: Rapid administration of IV thiamine when

Wernicke’s is suspected. If patients experience oscillopsia from
persistent UBN (relatively rare), consider 4-aminopyridine (avail-
able as dalfampridine in the United States, but only indicated to
improve gait in multiple sclerosis; a compounded formulation is
another option) or memantine.

5.3.5 Torsional Nystagmus

A few pearls:
• Usually, spontaneous pure jerk torsional nystagmus localizes

to the medulla/pontomedullary junction (e.g., medullary tumor
Video 5.18) or pontomesencephalic (interstitial nucleus of
Cajal/rostral interstitial nucleus of medial longitudinal fascicu-
lus, Video 4.35) regions and is often due to a brainstem lesion
(e.g., ischemia, demyelination, encephalitis). Pendular tor-
sional nystagmus is often due to oculopalatal tremor (covered
in the next section—Video 5.19).
• Jerk torsional nystagmus is commonly seen in a mixed pattern,
in conjunction with horizontal nystagmus (e.g., mixed
horizontal-torsional nystagmus in vestibular neuritis—Video
5.20), or with vertical nystagmus. Vertical-torsional nystagmus
can be “peripheral,” as in posterior canal benign paroxysmal
positional vertigo (triggered UB-torsional due to stimulation
of a single posterior canal), or “central” as in an acute medial
longitudinal fasciculus stroke (persistent UB-torsional nystag-
mus resulting from involvement of the central anterior semicir-
cular canal pathway).
• Because central (usually brainstem) anterior/posterior semi-
circular canal and/or utriculo-ocular motor pathway injury
is thought to be responsible for pure spontaneous jerk tor-
sional nystagmus, skew deviation or other features of the
ocular tilt reaction (ocular counterroll, head tilt) are com-
monly seen as well—Video 5.21. It is possible to have pure
torsional nystagmus on a peripheral basis, but this would
require strategically damaging a posterior canal along with
the ipsilateral anterior canal, which is an uncommon occur-
rence (Fig. 5.6).
Nystagmus 215
R PC SO
L PC
SR
SR
SO
R HC LR MR MR LR L HC
IR
IR
IO IO
R AC L AC
MUSCLE PRIMARY ACTION SECONDARY ACTION
Superior Rectus (SR) Supraduction Incycloduction
Inferior Rectus (IR) Infraduction Excycloduction
Superior Oblique (SO) Incycloduction Infraduction
Inferior Oblique (IO) Excycloduction Supraduction
Fig. 5.6 The cyclovertical extraocular muscles and their semicircular canal
innervation: When stimulated, each of the 6 angular acceleration detecting
semicircular canals (3 on the right and 3 on the left) responds with a conjugate
eye movement, with the vector(s) indicated above. PC, posterior canal; HC,
horizontal (also known as lateral) canal; AC=anterior (also known as superior)
canal. (1) When the right AC (red) is stimulated as in exposure to a loud noise
in superior (or anterior) canal dehiscence syndrome, excitatory slow phases
that are upward and torsional (towards left ear) are generated. This is due to
contraction of the right superior rectus (up and incycloduction OD) and left
inferior oblique (up and excycloduction OS) muscles (both also in red). Fast
phases are in the opposite direction—downbeat and torsional toward the right
(ipsilateral) ear—are then seen clinically. (2) When the right HC (green) is
stimulated as in a rapid rightward head turn, the vestibulo-ocular reflex (VOR)
results in a conjugate eye movement to the left via contraction of the right
medial rectus and left lateral rectus muscles (also in green). (3) When the right
PC (blue) is stimulated as in right PC benign paroxysmal positional vertigo
(BPPV), excitatory slow phases that are downward and torsional (towards left
ear) are generated. This is due to contraction of the right superior oblique
(down and incycloduction OD) and left inferior rectus (down and excycloduc-
tion OS) muscles (both also in blue). Fast phases are in the opposite direction -
upbeat and torsional towards the right (ipsilateral) ear—are then seen clinically
A few practical points for recognizing and naming torsional nys-

tagmus:
• Sometimes torsional nystagmus can be difficult to appreciate

and to characterize. Viewing a conjunctival blood vessel can
assist in the evaluation of direction, and the nystagmus should
be named by the direction to which the top poles of the eyes
beat—to the right ear or to the left ear. When performing
direct ophthalmoscopy, since the examiner’s line of sight is

parallel to the axis of rotation, the torsional nystagmus will be
in the same direction as the nystagmus viewed without the
ophthalmoscope. Compare this to horizontal or vertical nys-
tagmus, where the axis of rotation is different and the exam-
iner views the optic nerve (which is posterior to the axis of
rotation); therefore, the nystagmus viewed with the direct
ophthalmoscope will be opposite to that viewed without it
(e.g., downbeat nystagmus will appear to be upbeat nystag-
mus with the ophthalmoscope).
Treatment options: There is no strong evidence for any one par-

ticular medication, and torsional nystagmus usually resolves
quickly after a stroke or demyelinating lesion; therefore, medica-
tions are usually not necessary, although gabapentin may help
some patients.
5.3.6 Oculopalatal Tremor
Case: Five years prior to presentation, a 50-year-old woman expe-

rienced the acute onset of right sixth and seventh nerve palsies and
left hemiparesis. Two cavernomas within the right pons (one in the
region of the facial colliculus) were demonstrated by MRI. She then
experienced a second episode of right facial palsy and dysphagia.
Imaging revealed acute pontine hemorrhage and she underwent sur-
gical resection of the cavernoma. Postoperatively, she had facial
diplegia and bilateral horizontal gaze palsies. Several months later,
she experienced vertical oscillopsia. On examination at that time,
she had continuous large amplitude vertical pendular nystagmus
and symmetric palatal tremor. She had bilateral horizontal gaze pal-
sies with intact vertical movements. Convergence increased her
ability to adduct OU slightly. Review of her MRI 2 months postop-
Nystagmus 217
eratively revealed surgical changes to the floor of the fourth ventri-

cle as well as marked hyperintensities of the bilateral inferior
olivary nuclei. This patient presented with classic features of oculo-
palatal tremor (OPT), including vertical pendular nystagmus, pala-
tal tremor, and MRI evidence of inferior (medullary) olivary
hypertrophy. Given the proximity of the central tegmental tract
(CTT) to the abducens nuclei and facial nerve fascicles, she also
had horizontal gaze palsy and facial diplegia. Unfortunately, neither
memantine nor gabapentin resulted in improvement with regard to
(subjective) oscillopsia or (objective) pendular nystagmus.
Video: Video 5.22.
Figure: Figs. 5.2 and 5.7.
Key questions to ask: OPT often develops months (but can be

weeks or years) after a clear inciting event, usually a hemorrhage
(commonly affecting the CTT, but also the dentate nucleus or other
structures that make up Mollaret’s triangle), trauma or less com-
monly, an ischemic stroke or another brainstem syndrome (e.g.,
NMO, sarcoidosis). If there was no inciting event, and symptoms
are progressive over years, consider Alexander disease (a leuko-
dystrophy) or progressive ataxia with palatal tremor (PAPT).
Key findings to elicit: The pendular nystagmus associated with

OPT often has mixed vertical and torsional components (see
example—Video 5.19). However, pure vertical or pure torsional
pendular nystagmus can be seen, as well as a horizontal or
convergent-divergent (also consider Whipple’s disease with this
pattern, usually patients have gastrointestinal symptoms as well)
component. Nystagmus can be disjunctive (different in each eye,
see example—Video 5.23), or very subtle and best seen with oph-
thalmoscopy (see example—Video 5.24). The ocular oscillations
are often accentuated by gentle eyelid closure (referred to as ocu-
lar synchrony), even in a patient where nystagmus is not apparent
with eyes open (see example—Video 5.25). When OPT is sus-
Red N.
IN
MIDBRA
Superior Cerebellar
Peduncle
Central Tegmental Tract

LU
M Purkinje Cell
EL
RE
B (Cortex)
CE
PONS
te
Denta
MEDULLA
Inferior Inferior Cerebellar

Olive Peduncle (Climbing
Fibers)
Fig. 5.7 The Guillain-Mollaret triangle, and its role in oculopalatal tremor
(OPT): Also referred to as the dentato-olivary pathway, reflecting the three
points of this imaginary triangle: (1) dentate nucleus, (2) red nucleus, and (3)
inferior olivary nucleus. The olive sends decussating climbing fibers through
the contralateral inferior cerebellar peduncle that travel from the Purkinje
cells of the cerebellar cortex to the dentate nucleus; the dentate sends decus-
sating fibers (via the superior cerebellar peduncle) that wrap around the con-
tralateral red nucleus; these fibers descend from red nucleus to the ipsilateral
inferior olive via the central tegmental tract (CTT). Injury to any of these
structures may result in oculopalatal tremor (OPT). Since the CTT normally
inhibits the ipsilateral inferior olive, damage to the CTT results in decreased
inhibition of the ipsilateral olive resulting from transsynaptic degeneration.
Hypertrophic inferior olivary degeneration occurs as swollen and vacuolated
neurons come into contact with each other and corresponds to MRI T2/
FLAIR hyperintensity (on the right)
pected, the palate must be viewed at rest, or else the tremor can be
easily overlooked. Subtle facial muscle contraction is often seen,
which is synchronous with palatal tremor. Finally, when OPT is
due to a CTT lesion, lower motor neuron facial palsies, 6th nerve
palsy, internuclear ophthalmoplegia (INO), one-and-a-half syn-
drome, and horizontal gaze palsies are often seen.

Pitfalls: Because OPT begins months following an event (usu-

ally pontine hemorrhage), new oscillopsia (due to pendular nys-
Nystagmus 219
tagmus) and gait imbalance may prompt an expensive and

unnecessary workup. When the suspicion is high, OPT can be
quickly recognized at the bedside and unilateral or bilateral med-
ullary inferior olivary hypertrophy appreciated on MRI. Notably,
the development of OPT does not represent a new hemorrhagic
event or seizure activity.
Do not miss this! OPT may present with palatal tremor and little
to no nystagmus or nystagmus with little to no palatal tremor. The
clinician must have a high suspicion for OPT in these cases.
What is next? If a patient suffered a known hemorrhagic, surgi-

cal or traumatic event and MRI demonstrates hypertrophic olivary
degeneration, no additional workup is needed. Otherwise,
contrast-enhanced brain MRI is necessary, and PAPT and other
degenerative conditions should be considered in the differential.
Treatment options: Like acquired pendular nystagmus in MS,

gabapentin and memantine are the two medications that have the
most evidence for their use.
5.3.7 M
ultiple Sclerosis Acquired Pendular
Nystagmus
Case: A 30-year-old man with a 15-year history of multiple scle-

rosis (MS) presented with “shaking” of vision for the last
12 months. The visual motion of the environment (oscillopsia)
was independent of head movements, and the onset was initially
intermittent, but then gradually became constant over months. He
did not complain of double vision. He did have a history of bilat-
eral attacks of optic neuritis 10+ years ago, and accordingly, his
visual acuity was 20/100 OU with severe dyschromatopsia and
optic nerve pallor OU. On examination, there were ocular motor

abnormalities including gaze-evoked nystagmus, saccadic smooth
pursuit, and hypermetric saccades, signs that were compatible
with demyelinating plaques in the posterior fossa. His oscillopsia
was horizontal and due to horizontal pendular nystagmus, which
suppressed briefly following the termination of saccades and
blinking, which are typical features of acquired pendular nystag-
mus (APN) due to MS.
Video: Video 5.26.
Key questions to ask: Usually, patients with acquired pendular

nystagmus (APN) due to MS have a known history of MS for
years—that is, APN is not a common presenting sign of
MS. Because acute/subacute APN can (rarely) result from a pos-
terior fossa stroke, infection (Whipple’s disease, usually with a
convergent-divergent component—oculomasticatory myorhyth-
mia—often with prominent GI symptoms), toxicities (toluene),
and chronic APN can be due to spinocerebellar ataxia or meta-
bolic disorders (see below), a focused history is essential in the
absence of known MS or a known posterior fossa insult (e.g., pon-
tine hemorrhage causing oculopalatal tremor, OPT).
Key findings to elicit: While APN due to MS is usually horizon-

tal, it can also be vertical or have a convergent-divergent appear-
ance. If horizontal and vertical components are present, the
appearance can be circular or elliptical (see example—Video
5.27). Typically APN due to MS will be suppressed by blinks and
saccades (see example in a patient without MS—Video 5.28). In
MS patients with APN, a variety of other ocular motor abnor-
malities are often seen including gaze-evoked nystagmus, INOs,
saccadic smooth pursuit, and saccadic dysmetria. APN is often
dissociated/disconjugate (more intense in one eye) and may also
be monocular, and when this is the case, it is typically worse or
present in the eye with poorer vision (see examples—Video 5.29).

Nystagmus 221
Pitfalls: When monocular vertical pendular nystagmus in an eye

with poor vision (due to optic nerve disease, but also ophthalmic
conditions such as amblyopia, cataracts, severe refractive error,
etc.) is seen, consider the Heimann–Bielschowsky phenomenon
(HBP), which is benign and of no neurologic consequence. It is
also important to recognize, because correcting the ophthalmic
disorder (e.g., cataract surgery) may lead to resolution.
Recognition of the HBP will also prevent expensive and unneces-
sary neurologic testing. Patients with vision loss due to other eti-
ologies (e.g., retinitis pigmentosa) may develop binocular
conjugate pendular nystagmus, perhaps related to poor calibration
of eye position.
Do not miss this! APN due to MS and OPT are most common.
Although rare, other reported causes of pendular nystagmus
include peroxisomal assembly disorders, toluene abuse, Whipple’s
disease, acute brainstem stroke, spinocerebellar ataxia (SCA),
hereditary spastic paraplegia (SPG7 mutation), celiac disease,
disorders of vitamin E, and coenzyme q10 metabolism. Remember
that infantile nystagmus has mixed waveforms including both
pendular and jerk nystagmus (Video 5.30).
What is next? If APN is diagnosed in a patient with known MS,

aside from obtaining contrast-enhanced MRI to monitor for dis-
ease progression, no additional workup is typically needed. If
there is diagnostic uncertainty, testing should focus on the afore-
mentioned etiologies.
Treatment options: Like OPT, gabapentin and memantine are

the two medications that have the most evidence for their use.

5.4 accadic Intrusions, Oscillations,

S
and Other Nystagmoid Movements
(Fig. 5.1)
5.4.1 S
quare Wave Jerks (SWJ) and Related
Saccadic Intrusions

A few pearls
• SWJ are the most common form of saccadic intrusion, com-

mon with aging, but especially frequent in neurodegenerative
disorders.
• Oftentimes, SWJ are misinterpreted as nystagmus, although
saccades are the culprit (saccades initiate the movements) in
intrusions/oscillations, while a slow phase initiates the move-
ment with jerk or pendular nystagmus.
• When SWJ are particularly frequent (>15/minute), suspicion
should be high for a cerebellar or a parkinsonian syndrome.
The history should focus on symptoms that may occur with
cerebellar ataxia (e.g., oscillopsia, imbalance, dysarthria, inco-
ordination), Parkinson’s disease (PD, e.g., tremor, slowness,
postural instability, stiffness), and progressive supranuclear
palsy (PSP, SWJ are more prominent than in PD, see section
above and see example of SWJ and other typical features of
PSP Video 5.31).
A few practical points
• With SWJ, macro-SWJ (SWJ that are larger in amplitude up

to about 50 degrees), and macrosaccadic oscillations (move-
ments that straddle fixation, usually associated with hyper-
metric saccades and cerebellar disease), there should be an
intersaccadic interval (i.e., there is a short pause between sac-
cades, usually apparent at the bedside, but occasionally eye
Saccadic Intrusions, Oscillations… 223
movement recordings are needed—see examples of these sac-

cadic intrusions/oscillations in Video 5.32). If there is no int-
ersaccadic interval, this is due to ocular flutter or opsoclonus
(see section below).
• Because patients with cerebellar disease can have both intru-
sions (e.g., SWJ) and nystagmus (e.g., downbeat or periodic
alternating nystagmus), eye movement recordings can be help-
ful as well as performing ophthalmoscopy. When viewing the
optic nerve with the magnification of the ophthalmoscope, it
can be easier to identify the upward slow and downward fast
phases associated with DBN and the simultaneous horizontal
back and forth saccadic movements of the SWJ.
• SWJ are usually of no visual consequence and do not require
medication. Occasionally they can cause oscillopsia, and anec-
dotally, benzodiazepines and other medications may be benefi-
cial in a subset of patients.
• There are a variety of spontaneous abnormal eye movements
that can be seen in comatose patients, which can be classified
as “saccadic disorders”, although their exact pathogenesis
remains uncertain (e.g., ocular bobbing—Video 5.33).
5.4.2 Opsoclonus/Ocular Flutter
Case: A 35-year-old woman presented with oscillopsia several

weeks following a flu-like illness. She described being easily star-
tled, with “shakiness” of the head/neck and body. Aside from mild
unsteadiness on her feet, she denied any other neurologic symp-
toms. Examination demonstrated periodic myoclonic jerks involv-
ing the trunk, arms, legs, and neck in addition to frequent
horizontal back-to-back saccadic oscillations with the appearance
of ocular flutter. In fact, with eye movement recordings, there was
no intersaccadic interval seen (in between each saccadic move-
ment), which was compatible with a diagnosis of ocular flutter
(oscillations were only horizontal). Flutter was most prominent
and frequent with convergence or immediately following termina-

tion of saccades in all planes. Workup to evaluate for infectious or
paraneoplastic etiologies was unremarkable (including cerebro-
spinal fluid analysis), she was treated conservatively with gaba-
pentin alone given the fairly mild nature of her symptoms, and her
flutter-myoclonus syndrome resolved over the subsequent weeks.
She recovered completely from this monophasic disorder, which
was thought to be post-infectious in etiology.
Video: Video 5.34.
Key questions to ask: In a young person, ask about preceding

infections. In older patients, the biggest concern is a paraneoplas-
tic disorder (associated with a variety of cancers and antibodies)
so ask about smoking history and other risk factors. However, a
young person can also have a paraneoplastic disorder (e.g., anti-
NMDA antibody-mediated opsoclonus associated with a tera-
toma), while an older person can have opsoclonus due to acute or
resolving infection (see example of opsoclonus—Video 5.35).
Key findings to elicit: In a baby or young child, flutter/opsoclo-

nus can be the initial manifestation of neuroblastoma (see Chap. 7:
Pediatric Clinical Pearls). Episodes of flutter/opsoclonus can be
frequent and striking, or intermittent and/or mild in other cases. In
addition to provoking these oscillations by convergence and with
saccades, the examiner should also observe the corneal bulges
under closed eyelids. Myoclonic jerks (probably related to reticu-
lar formation involvement) may involve the trunk/neck and head,
arms, legs, and truncal, gait and appendicular ataxia may also be
seen.

Pitfalls: Occasionally, a high frequency nystagmus can be mis-

taken for opsoclonus/flutter. In these situations, distinguishing
nystagmus from a saccadic oscillation is essential as the localiza-
tions and etiologies vary widely. Eye movement recordings—
used first to distinguish nystagmus from an intrusion/oscillation
(which is the culprit - slow phase or saccade?), and second to

decide whether the intrusion/oscillation has an inter-saccadic
interval or not (opsoclonus/flutter will have no interval)—can be
very helpful in this setting.
Do not miss this! There are many dangerous etiologies of ops-

oclonus/flutter which should be entertained. In the very young,
neuroblastoma should be considered first, although occasionally
it can be a transient phenomenon in healthy neonates. Ocular
micro-flutter (i.e., only seen with the ophthalmoscope) is a rare
but benign chronic cause of oscillopsia, and is often associated
with migraine. Occasionally, oscillations can be generated voli-
tionally and can mimic pathologic ocular flutter, so-called “vol-
untary flutter.” This can only be sustained for a short time, and is
almost always associated with convergence and other features of
activation of the near triad, including miosis (see example—
Video 5.36). Reported autoimmune causes of opsoclonus/flutter
include multiple sclerosis and neuromyelitis optica; many infec-
tions (especially viral) have been implicated in its pathogenesis
(during or following the infection); structural lesions include
brainstem stroke, hemorrhage, trauma; toxicity (toluene, phe-
nytoin, amitriptyline, diphenhydramine, lithium); neurodegen-
erative disorders (Friedreich’s ataxia) among many others.
What is next? Neuroblastoma should be excluded in the young

(see Chap. 7). If there was a preceding infection, viral (e.g.,
HIV) and bacterial (e.g., Lyme) etiologies should be considered,
and contrast-enhanced brain MRI should be obtained. If there
was no preceding infection, paraneoplastic workup should
include contrast-enhanced brain MRI, body CT (preferably
PET/CT), thorough medical examination, consider mammogra-
phy and pelvis ultrasound in women and testicular ultrasound in
men, paraneoplastic panels in serum and CSF. Autoimmune/
inflammatory disorders should be considered as well depending
on CSF analysis and MRI findings (or lack thereof).
Treatment options: To treat the underlying autoimmune/

immune-mediated or inflammatory etiology, intravenous immu-
noglobulin, plasma exchange, rituximab, or steroids may be
beneficial and diminish the ocular oscillations. Other medica-

tions have been reported to reduce oscillations (and oscillopsia)
including clonazepam, gabapentin, propranolol, memantine,
among others.
5.4.3 Superior Oblique Myokymia
Case: A 40-year-old man presented with complaints of jumping

vision in the right eye, associated with vertical double vision. He
experienced many typical episodes in the office, where simultane-
ous incycloduction and depression could be observed in the right
eye, causing oscillopsia and vertical diplopia, respectively. In
between attacks, vertical ocular alignment was normal. During
attacks, there was a measurable left hypertropia which correlated
with his diplopia. He was diagnosed with right superior oblique
myokymia (SOM). Routine MRI was normal, and unfortunately
high resolution heavily T2-weighted CISS/FIESTA images to
evaluate for neurovascular compression could not be performed.
Symptoms did not respond to timolol ophthalmic drops OD, but
diminished with gabapentin.
Video: Video 5.37.
Key questions to ask: The key with SOM is monocular oscil-

lopsia. The typical causes of spontaneous oscillopsia—nystagmus
and saccadic intrusions—are almost always bilateral and conju-
gate, with some exceptions (e.g., monocular pendular nystagmus
in multiple sclerosis—Video 5.38, or the Heimann–Bielschowsky
phenomenon with unilateral visual deprivation).
Key findings to elicit: To appreciate the sometimes very subtle

incycloduction and/or depression associated with SOM (Video
5.39), the magnification of an ophthalmoscope (focus on a retinal

vessel where torsion can be best appreciated), slit lamp or Frenzel
goggles may be necessary. To trigger an attack, ask the patient to
look in the direction of the action of the superior oblique muscle—
for example, in right SOM, symptoms/signs may be triggered by
looking left, down, left/down, or by tilting the head to the right.
Remember the actions of the SO muscle—the primary action is
incycloduction (which initiates the SOM, and is followed by a
slow drift back to a normal position—this explains monocular
oscillopsia) and the secondary action is depression, which explains
the vertical diplopia that is experienced by many during attacks.

Pitfalls: When symptoms are non-specific (e.g., an episodic

blurriness), the examiner must have a high suspicion for SOM to
understand whether the visual symptom is monocular, whether
oscillopsia is present, and if so, in what plane (patients usually
notice a torsional/rotary component)?
Do not miss this! Aside from other rare causes of monocular oscil-
lopsia (see above), also consider ocular conditions such as iridodo-
nesis (excessive movement of the iris as in a lens subluxation) or
pseudophakodonesis (excessive movement of a lens implant), which
can both be appreciated with slit lamp exam and may be monocular.
Consider ocular neuromyotonia, where patients experience transient
diplopia (usually <60 seconds), typically due to impaired relaxation
of an extraocular muscle following prolonged eccentric gaze—e.g.,
a patient who has been looking down to read for a period of time
moves the eyes back to primary gaze and the left eye is stuck in
downgaze. This can result from persistent left inferior rectus con-
traction due to neurovascular compression of the left third nerve.
This is sometimes also associated with SOM, in addition to thyroid
eye disease, or previous head/neck radiation therapy.
What is next? Because SOM may rarely be caused by a mass

lesion that compresses the peripheral nerve or the midbrain (nucleus/
fascicle) itself, MRI is indicated. Most cases are thought to be due to

neurovascular compression of the fourth or trochlear nerve.
Treatment options: Carbamazepine, oxcarbazepine, gabapen-

tin, and a variety of other anticonvulsant medications can be tried.
Topical drops including timolol may help in some patients as
well.
Read these Books! [23, 24–26, 27]
References
1. Eggers SDZ, Bisdorff A, von Brevern M, Zee DS, Kim JS, Perez-
Fernandez N, et al. Classification of vestibular signs and examination
techniques: nystagmus and nystagmus-like movements. J Vestib Res.
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Vestibular Disorders 6
6.1 The Vestibular History
“TRIAGE—TiTrATE—TEST” [1, 2]—DO NOT TRIAGE

BASED ON SYMPTOM QUALITY ALONE—for example, do not
rely solely on dizzy vs vertigo vs giddiness vs lightheaded as
patients tend to be inconsistent and the symptom quality can be
misleading.
6.1.1 TRIAGE
Screen for common culprits: medication or drug toxicity, meta-

bolic, cardiac, psychiatric.
6.1.2 TiTrATE
1. Timing:
• Onset—acute or gradual.
• Episodic—seconds (benign paroxysmal positional vertigo
(BPPV), vestibular paroxysmia), minutes (migraine,
Menière’s disease, transient ischemic attack (TIA)), hours


https://doi.org/10.1007/978-3-030-76875-1_6
232 6 Vestibular Disorders
(migraine, Menière’s disease, occasionally TIA), days

(migraine).
• Constant—acute vestibular syndrome (AVS) due to
stroke>demyelinating disease (~20% of AVS) or vestibular
neuritis (~80% of AVS).
2. Triggers:
• Positional—triggered by movement.
–– BPPV—lying to seated, seated to lying, rolling over in
bed, looking up or down, brought on by head movement.
–– Orthostatic hypotension—arising from lying or seated
position (should not come on from sitting to lying, which
can differentiate from BPPV).
• Head movement—occurs during or time-locked to move-
ment.
–– Bilateral vestibular loss—most common.
–– Unilateral vestibular loss—acute phase prior to compen-
sation, or chronic and uncompensated.
• Sound—Tullio’s phenomenon.
–– Superior canal dehiscence syndrome—SCDS).
• Valsalva—against closed glottis and/or pinched nose.
–– SCDS.
–– Cervicomedullary junction lesion (Chiari malformation).
• Complex visual stimulation—e.g., grocery store, crowded
environments.
–– Vestibular migraine—also may be triggered by sleep
deprivation, skipping meals, certain foods, menstrual-
related, barometric pressure changes.
–– Persistent postural perceptual dizziness (PPPD).
3. Targeted Exam:
• HINTS “Plus” (Head Impulse, Nystagmus, Test of Skew,
“Plus” = bedside assessment of auditory function using fin-
ger rub) for AVS.
–– Do not forget about associated symptoms common in pos-
terior fossa disease including diplopia, dysarthria, dys-
phagia, dysphonia, loss of sensation, weakness, room tilt
illusion, incoordination, drop attacks, abrupt loss of hear-
ing (remember that the internal auditory artery usually
comes off the anterior inferior cerebellar artery).
• Dix-Hallpike (DH) and supine roll test for BPPV.
The Vestibular Examination 233
• In more chronic balance/vestibular conditions, particular

attention to the general neurologic exam is essential look for
evidence of parkinsonism; cerebellar disease (e.g., gaze-
evoked nystagmus, saccadic smooth pursuit, spontaneous
downbeat nystagmus); myelopathy; neuropathy; vestibular
exam looking for unilateral or bilateral vestibular loss.
6.1.3 Test (Table 6.1)
• A few common examples:

–– Audiogram with hearing loss/changes or any aural symp-
toms (tinnitus, pain, fullness, popping) or when Meniere’s
disease is suspected (ESM 6.1).
–– Vestibular function testing when unilateral or bilateral ves-
tibular loss is suspected and in other special situations (ESM
6.2, 6.3, 6.4, 6.5, and 6.6).
–– MR with diffusion-weighted imaging (DWI) with attention to
the brainstem/cerebellum when stroke is suspected in AVS.
–– Contrast-enhanced MRI with internal auditory canal proto-
col to evaluate for vestibular schwannoma and vestibular
paroxysmia (neurovascular contact with CN8 - should
include heavily T2-weighted CISS or FIESTA images).
–– CT temporal bones when SCDS is suspected.
6.2 The Vestibular Examination
The vestibular examination

The rotational vestibulo-ocular reflex (VOR) allows for retinal
stability during angular movements of the head, both horizontally
(horizontal semicircular canals) and vertically (posterior and
anterior semicircular canals) (Fig. 4.9). For example: a person
with a normal VOR can walk down the street and clearly read a
sign in front of them as the VOR constantly adjusts the eye posi-
tion to keep retinal images stable when the head is in motion. A
person with bilateral vestibular loss will walk down the street and
the sign will appear to jump or bounce—that is, the retinal images
are unstable due to an impaired VOR, so the stationary image will
Table 6.1 Common audiovestibular lab tests
234
TIA/ Cerebellar Vestibular

Test stroke VN VM Menière’s SCDS BPPV VP BVL PPPD syndrome schwannoma
Audiogram + + + ++ ++ − + ++ − − ++
vHIT + ++ − + − − + ++ − + ++
VNG, ENG or
++a ++a + + ++b ++b ++b − − + ++b
VOG
Rotary chair − +c +c − − − − ++ − − +
Calorics +d ++ − ++ − − − ++ − − ++
VEMPs − +e − + ++ − − + − − −
Imagingf ++ − + + ++ − ++ + − ++ ++
VN vestibular neuritis, VM vestibular migraine, VP vestibular paroxysmia, vHIT video head impulse test, VNG video-nystagmography,
ENG electronystagmography, VOG video-oculography, VEMPs vestibular evoked myogenic potentials, SCDS superior canal dehis-
cence syndrome, BPPV benign paroxysmal positional vertigo, BVL bilateral vestibular loss, PPPD persistent postural perceptual
dizziness (no specific test is helpful to make this diagnosis, but patients often develop PPPD as the result of another poorly treated or
anxiety-provoking vestibular disorder—e.g., vestibular migraine, BPPV or vestibular neuritis)
– Not usually helpful
+ May be helpful
++ Very helpful
a
In the acute setting when spontaneous nystagmus is present
b
During provocative maneuvers (including Valsalva, pinched-nose Valsalva, tragal compression, loud sounds, Dix-Hallpike/supine roll
test, hyperventilation)
6 Vestibular Disorders
c
Rotary chair may show slightly low time constants and gains with unilateral vestibular loss, and may show prolonged time constants
in migraine
d
Depending on the posterior fossa localization, there may be caloric weakness with some strokes
e
VEMPs may assist in the localization of inferior versus superior division vestibular neuritis
f
Neuroimaging is needed (MRI internal auditory canal [IAC]) protocol w/wo) in migraine and Menière’s cases where there is diagnos-
tic uncertainty or atypical features. In SCDS, CT temporal bones is the test of choice. For vestibular paroxysmia, heavily T2-weighted
CISS or FIESTA imaging. In BVL, if the cause is clearly ototoxicity from gentamicin for instance, neuroimaging will not be helpful.
Otherwise, neuroimaging is essential
The Vestibular Examination
235
appear to be moving (so-called “walking” oscillopsia Video 5.5).

The following are ways to evaluate VOR function at the bedside.
• Dynamic visual acuity (Video 6.1):

Passive rotation of head (horizontally to evaluate the horizon-
tal SCC and vertically to evaluate the anterior and posterior
SCC function) at 2 Hz while viewing a distance (preferred) or
near eye chart. A decrease in best-corrected vision of two lines
or more from baseline is considered abnormal—patients with
unilateral vestibular may lose two to three lines prior to com-
pensation, while patients with bilateral vestibular loss will lose
four or more lines.
• Visually enhanced VOR (vVOR):
Passive rotation through the entire horizontal or vertical ocular
motor range at 0.5 Hz while fixating on the examiner’s nose.
This combines smooth pursuit and VOR. If pursuit is impaired
and the VOR is hypoactive (e.g., cerebellopathy and bilateral
vestibular loss due to cerebellar ataxia, neuropathy, vestibular
areflexia syndrome, CANVAS), the vVOR will be impaired
and will look choppy or saccadic (Video 5.12). If either system
is functional, this will be smooth.
• Head impulse test (HIT, Video 6.2):
When vVOR is assessed in a patient with unilateral vestibular
loss, the good ear can drive the response; however, when a
rapid HIT is applied, the good ear can no longer compensate
and the VOR deficit will be apparent at the bedside. With the
patient fixating on the examiner’s nose, perform a brief, rapid
head rotation of 15–20° (the novice should start by performing
the HIT from right to center or from left to center - this will
ensure that the head movement doesn’t go too far). In a “nor-
mal” HIT, the eyes will stay on the visual target (usually the
examiner’s nose) with each impulse. In the case of an acute
right peripheral vestibulopathy due to vestibular neuritis, a
rightward HIT will result in the eyes moving to the right with
the head initially, so that a corrective re-fixation saccade will
be needed to move the eyes back to the target, or to the left.
When this corrective saccade is seen, the HIT is “abnormal” or
“positive” which usually suggests a peripheral process (see
The Vestibular Examination 237
example of a patient with Ramsay Hunt syndrome causing

severe unilateral vestibular loss causing abnormal HIT in the
planes of horizontal, anterior and posterior canals—Video
6.3). The HIT will be bilaterally abnormal with bilateral ves-
tibular loss (see example—Video 6.4) [3]. The video HIT
(vHIT, see ESM 6.2) is a rapid, noninvasive test that can quan-
tify the gain of the VOR in addition to demonstrating both
overt corrective saccades (those that are visible to the examiner
at the bedside that occur after the head movements) and covert
corrective saccades (those that are invisible to the examiner at
the bedside that occur with head movements). These can be
particularly helpful weeks, months, or years after a vestibular
injury (e.g., vestibular neuritis), since effective covert saccades
can make the bedside HIT appear normal. Being less predict-
able by varying the velocity and amplitude of the bedside HIT
can help to unmask these covert saccades to assist in the diag-
nosis of peripheral vestibular loss [4, 5].
• Vibration (Video 6.5):
Vibration of the mastoids and vertex will induce an ipsilesional
slow phase with unilateral vestibular loss, more so acutely than
chronically. With peripheral lesions, the slow phase is toward
the affected ear as seen in this patient with vestibular neuri-
tis—Video 6.6 [6].
• Head-shaking (Video 6.5):
Sustained, rapid, back and forth, horizontal head shaking for
~15 secs may produce a spontaneous nystagmus that slowly
abates. With peripheral lesions, the slow phase is toward the
affected ear as in this patient with Ramsay Hunt syndrome—
Video 6.7. With central lesions, the slow phase may be vertical
or the nystagmus may change direction from the baseline
spontaneous nystagmus. If there is strong HSN without clear
unilateral vestibular loss (Video 6.8) or a cross-coupled
response (e.g., horizontal head-shaking causes downbeat nys-
tagmus—Video 6.9), consider a central process [7, 8].
• Pressure-induced (Video 6.10):
Evaluate for nystagmus during Valsalva against a closed glot-
tis, pinched-nose Valsalva, and with tragal compression (pres-
sure in the external auditory canal causing nystagmus,
Hennebert’s sign), which may be seen in SCDS (Video 6.11);

look for Valsalva-induced symptoms and signs with cervico-
medullary lesions such as a Chiari; sound-induced nystagmus
(Tullio’s phenomenon) mainly in SCDS.
• Hyperventilation (Video 6.12):
Alkalosis and changes in ionized calcium from 30–60 seconds
of hyperventilation may improve conduction through an
affected segment of eighth cranial nerve due to vestibular
schwannoma (Video 6.13) or neurovascular compression, usu-
ally causing excitatory nystagmus with a contralesional-
directed slow phase. When a chronic vestibular imbalance has
been compensated for by central mechanisms, hyperventila-
tion can cause a transient decompensation and bring out nys-
tagmus with an ipsilesional slow phase. Hyperventilation can
enhance/produce downbeat nystagmus in cerebellar disease
(perhaps related to a sensitivity of cerebellar calcium channels,
Video 6.14) [9].
• Positional maneuvers:
–– Dix-Hallpike maneuver; Used to test for posterior canal
(PC) BPPV. For example: in a patient with right PC BPPV,
turn the head 45° to the right, and rapidly move en bloc
straight back so that the head is slightly hyperextended
(~20°) and hanging over the edge of the examination table
with the head still turned 45° to the right. This maximally
stimulates the right PC SCC. In right PC-BPPV, the right
Dix-Hallpike will provoke upbeat-torsional nystagmus
towards the right (lowermost) ear, which is due to otoconial
debris falling through the right posterior canal (causing
endolymph movement and cupular deflection in an excit-
atory direction). The nystagmus (a) typically begins with a
short latency (sometimes as long as 30-60 seconds) after
change in head position, (b) lasts less than 1 min, (c) fatigues
with repeated testing, and (d) often reverses direction
(downbeat-torsional towards the left ear with right PC-
BPPV) when the patient sits up again.
–– Supine roll test: Used to test for horizontal canal (HC)
BPPV. For example: in a patient with right geotropic HC
BPPV, have the patient lay down with the head flexed
20–30° (to bring the HC into a position perpendicular to the
Bedside Auditory Testing 239
ground) and then turn the head (or body and head en bloc if
the cervical range of motion is poor) 90° to the right. This
will induce a geotropic (i.e., beating toward the ground)
right-beating nystagmus along with prominent vertigo.
Similar to PC BPPV, a latency and crescendo-decrescendo
appearance will be observed. Then come back to neutral
and roll the head 90° to the left. This will induce a geotropic
left-beating nystagmus, although the nystagmus and vertigo
in this position will be less robust as compared to the right
supine roll position (the opposite will be true for apogeotro-
pic HC BPPV—see BPPV section below) [10].
• The virtual (telemedicine) vestibular examination (Video 6.15).
6.3 Bedside Auditory Testing
• Finger rub:
It has been shown that bedside hearing tests including finger
rub, whispered speech, watch tick, and the Rinne and Weber
tuning fork tests have poor sensitivity to detect hearing loss in
older adults, although their specificity is good. A combination
of bedside tests including Rinne, Weber, and finger rub (espe-
cially the calibrated finger rub auditory screening test or CAL-
FRAST), will achieve the highest sensitivity, although this is
still below acceptable levels and not a substitute for audiome-
try. To perform the CALFRAST test, the patient should close
the eyes and the examiner will stand nose to nose, 6–10 inches
in front of the patient. The examiner will extend both arms
straight outward so that the examiner’s fingers are equidistant
from the examiner’s and subject’s ears, at a distance of approx-
imately 70 cm. First the “CALFRAST-Strong 70” is per-
formed, where the examiner rubs the thumb and distal fingers
together vigorously (but without snapping), one ear at a time
(repeated 3 times in its initial description). If the patient hears
the rubbing, next is the “CALFRAST–Faint 70,” where hear-
ing is assessed using the faintest rub/sounds the examiner can
still hear (at 70 cm). If the patient hears “Faint 70” in both ears,
testing is complete. If “Strong 70” was not heard then the same
strong stimulus is repeated at 35 cm, then 10 cm, then 2 cm—
that is, until the stimulus is heard [11, 12].
• Rinne and Weber (Video 6.16):

The Rinne test is an assessment of auditory thresholds to air
and bone conduction of sound. The Weber test is a comparison
of bone conducted sound of either ear. Conductive hearing loss
results in a loss of air conducted greater than bone conducted
sound, whereas sensorineural hearing loss results in the loss of
both air and bone conducted sound. Peripheral vestibular dis-
ease affecting the labyrinth or the eighth cranial nerve can be
associated with sensorineural hearing loss. In these cases, the
sensitivity to air conduction will remain greater than to bone
conduction. Weber will lateralize away from the side of senso-
rineural hearing loss. As an example, destruction of the right
labyrinth (e.g., bacterial labyrinthitis) will cause decreased
hearing in the right ear, and air conduction will be greater than
bone conduction in the right (affected) and left (unaffected)
ears. Weber will lateralize to the left (unaffected) ear. In the
case of superior semicircular canal dehiscence (SCDS), there
may be increased sensitivity to bony transmission of sound
through a (third mobile window) as well as conductive hearing
loss, with bone conduction greater than air conduction and
Weber lateralizing to the side of the dehiscence.
• Otoscopy:
Evaluate for (herpetic) vesicles, abnormalities of or behind the
eardrum to suggest infection, glomus tumor, or carotid aneurysm.
6.4 aboratory Testing of Audiovestibular

L
Disorders (Fig. 6.1, Table 6.1, ESM 6.1, 6.3,
6.4, 6.5, and 6.6)
6.5 Vestibular Syndromes
6.5.1 Acute Vestibular Syndrome (ESM 6.7)
6.5.1.1 The HINTS History

The acute vestibular syndrome (AVS) is characterized by the
acute onset of continuous vestibular symptoms (usually a sensa-
tion of environmental motion/movement or vertigo which persists
Vestibular Syndromes 241
a Low-pitch High-pitch b Sensorineural Hearing Loss

-10 -10
Quiet Sounds
Normal hearing
0 0
10 10
Slight hearing loss
20 20
Mild hearing loss
30 30
Hearing Level (dB HL)

40 Moderate hearing loss 40
50 50
Moderately severe hearing loss
60 60
Loud Sounds
70 70
Severe hearing loss
80 80
90 90
Profound hearing loss 100
100
110 110
120 120
125 250 500 1k 2k 4k 8k 125 250 500 1k 2k 4k 8k
Frequency (Hz) Frequency (Hz)
c Conductive Hearing Loss

d Mixed Hearing Loss
-10 -10
0 0
10 10
20 20
30 30
40 40
50 50
60 60
70 70
80 80
90 90
100 100
110 110
120 120
125 250 500 1k 2k 4k 8k 125 250 500 1k 2k 4k 8k
Frequency (Hz) Frequency (Hz)
Fig. 6.1 Audiometry: what does it look like and how do I interpret it? An
audiogram measures a patient’s auditory threshold responses with pure-tone
stimuli across a range of sound frequencies that are important for human
communication, typically 250 Hz – 8000 Hz. The threshold is the sound
intensity level at which an individual detects the tone 50% of the time. Hear-
ing loss severity is referenced to a healthy population (a). An audiologist gen-
erally assesses both air-conducted (circles) and bone-conducted sound
(brackets). Both results are graphed with frequency on the x-axis, measured
in Hertz (Hz), and the threshold for sound intensity on the y-axis, measured in
decibels hearing level (dB HL). (b) Sensorineural hearing loss can be differ-
entiated from (c) conductive hearing loss by the presence of an air-bone gap
in which a difference exists between air-conduction and bone-conduction
thresholds. Some patients with both conductive and sensorineural compo-
nents of hearing loss in the same ear are said to have mixed hearing loss (d).
In patients with age-related hearing loss (b), an audiogram typically displays
symmetric hearing loss primarily at higher frequencies between 2000 and
8000 Hz. Only right ear data are graphed for simplicity. (Courtesy of Drs.
Carrie Nieman and Bryan Ward) [17]
with head still and eyes closed), head motion intolerance (symp-
toms are aggravated when moving the head), nausea/vomiting,
imbalance and spontaneous nystagmus (often causing oscillopsia
in addition to vertigo, although the oscillopsia [a visual symptom]
will resolve with eyes closed). About 80% of the time, the AVS is
due to vestibular neuritis, and about 15–20% of the time, it is due
to a central lesion (usually posterior fossa stroke).
6.5.1.2 The HINTS Exam

A three-step bedside ocular motor exam known as HINTS has a
higher sensitivity (96.8%) and specificity (98.5%) to detect a cen-
tral cause of the AVS as compared to MR with diffusion weighted-
imaging (which may miss up to 20% of small posterior fossa strokes
causing isolated vertigo in the first 24–48 hours) in the hands of
subspecialists [13–16]. When evaluating a patient in the ED, some-
times it can be challenging to determine whether a patient’s con-
tinuous dizziness or vertigo is “vestibular” in origin (as opposed to
a cardiac or pharmacologic etiology). If associated symptoms
include internal or external vertigo, nausea, head motion intoler-
ance and imbalance, it is likely that a “vestibular” etiology is to
blame. However, when present, these features do not help differen-
tiate a “central” vestibular from a “peripheral” vestibular etiology.
6.5.1.3 Vestibular Neuritis

Case: A 50-year-old woman with hypertension, dyslipidemia and
pre-diabetes suddenly developed continuous vertigo that gradually
worsened over 60 minutes and she presented to the emergency
department (ED) within hours of onset. Associated symptoms
included nausea and vomiting, head motion intolerance and unsteadi-
ness. There was no diplopia, dysarthria, weakness or sensory symp-
toms. Examination demonstrated horizontal-torsional left-beating
nystagmus (LBN) in primary position and the nystagmus remained
left beating-torsional when she looked laterally or vertically. When
looking to the right, the LBN decreased and when looking to the left,
the LBN increased in intensity, in keeping with Alexander’s law.
With alternate cover testing, there was no vertical ocular misalign-
ment suggestive of skew deviation. With head impulse test (HIT) to
the right, there was a corrective refixation saccade (a positive or
abnormal HIT) and no corrective saccade when her head was turned
quickly to the left. There were no focal findings on neurologic exam,

although she required some assistance to ambulate. Saccades and
smooth pursuit appeared to be normal when taking the spontaneous
nystagmus into account. There was no hearing loss or other aural
symptoms, and otoscopy was n ormal. She was diagnosed with right-
sided vestibular neuritis based on a peripheral pattern of the HINTS
“Plus” (Head Impulse [abnormal—to the right], Nystagmus [unidi-
rectional—LBN], Test of Skew [no vertical refixation saccade],
Plus [no hearing loss]) exam, and was discharged from the ED with
a short course of steroids. At follow-up several days later, there was
significant subjective (vertigo) and objective (nystagmus and bal-
ance) improvement (Figs. 6.2, 6.3 and 6.4).
Video of patient’s exam in the ED: Video 6.17.
Key questions to ask: Is the vertigo or dizziness of sudden

onset, continuous (even with eyes closed and head still) and asso-
ciated with spontaneous nystagmus, nausea/vomiting, head
motion intolerance, imbalance? If so, this is the acute vestibular
syndrome (AVS) and main concerns include stroke (dangerous) or
vestibular neuritis (benign).
Hearing Loss
Gradual Onset Sudden Onset

Hours to Days
Months to Years
Asymmetric Symmetric +/- vertigo + vertigo
Conductive or Sensorineural Age- Noise Sudden Sensorineural Labyrinthitis Stroke

Mixed Hearing Loss Hearing Loss Related Induced Hearning Loss (SSNHL)
Hearing Hearing
Loss Loss Labyrinthine Stroke Brainstem Stroke
Otosclerosis Cholesteatoma Ossicular Superior Vestibular Meniere’s
Chain Canal Schwannoma Disease
Discontinuity Dehiscence Generally symmetric Cerumen impaction Temporal bone fracture
but can be asymmetric
Acute otitis externa Labyrinthine concussion
Less Concerning Pathologies Pathologies in Neurology Practice
Acute otitis media Post-concussion syndrome
Otitis media with effusion Meningitis
Fig. 6.2 What is the cause of my patient’s hearing loss? This is a flowsheet
that can be used to differentiate multiple causes of hearing loss. The onset and
chronicity of hearing loss is a critical starting point in understanding whether
urgent action is needed, such as in the setting of suspected stroke or sudden
sensorineural hearing loss. For hearing loss that has been present for months
to years, differentiating whether the loss is primarily symmetric or asymmet-
ric is another point that should prompt consideration of referral and further
evaluation. Regardless of the underlying cause of hearing loss, including age-
related hearing loss, assessment and interventions can and should be offered.
(Courtesy of Drs. Carrie Nieman and Bryan Ward) [17]
Anterior Inferior
Basilar A.
Cerebellar A.
AC
Internal
Auditory A.
Anterior
Vestibular A.
C
HC
S
PC Main
Posterior Cochlear
Vestibular A. A.
Fig. 6.3 Vascular supply of the labyrinth: In the HINTS “Plus” examination
(Head Impulse, Nystagmus, Test of Skew, “Plus” is a bedside test of auditory
function using finger rub), loss of hearing is seen as a red flag or dangerous
finding in the acute vestibular syndrome. As seen above, the basilar artery sup-
plies the anterior inferior cerebellar artery, which supplies the internal auditory
artery so that an acute vestibulopathy accompanied by partial or complete sen-
sorineural hearing loss can be not only “peripheral” but also dangerous (e.g.,
due to labyrinthine stroke)
Key findings to elicit: In a patient with the AVS, the HINTS Plus
exam should be applied to distinguish if the vertigo is central or
peripheral (to remember this, think of it as the AVS-HINTS
exam—that is, it should not be applied in patients without sponta-
neous nystagmus and ongoing vestibular symptoms). Video-
oculography and video HIT, when performed acutely in the
emergency department, can augment the evaluation by quantifying
the nystagmus and vestibulo-ocular reflex function (see example—
Video 5.20). When possible, also look for central patterns of head-
shaking nystagmus, and evaluate saccades (e.g., saccadic dysmetria
in lateral medullary stroke) and smooth pursuit (e.g., impaired
Fig. 6.4 Innervation of the labyrinth: When a patient experiences a bout of

vestibular neuritis, typically the superior division or the superior and inferior
divisions are involved and rarely is the inferior division involved in isolation.
Knowledge of the specific innervation patterns of the semicircular canals and
otoliths allows for accurate localization and insight into etiology. The superior
division innervates the anterior and horizontal canals, utricle, as well as some
innervation to the saccule. The inferior division innervates the posterior canal
and provides most of the saccular innervation. Cervical vestibular evoked
myogenic potentials (c-VEMPs) can help to elucidate inferior division involve-
ment with damage to the saccule, while ocular-VEMPs can help to elucidate
superior division involvement with damage to the utricle. As another example,
if the horizontal (HC) and anterior canals (AC) are the only canals affected in
a patient with the acute vestibular syndrome, the localization is usually ves-
tibular neuritis with involvement of the superior division of the vestibular
nerve. However, if the HC and posterior canals (PC) are the only canals
affected, since these canals only synapse in the medial vestibular nucleus
(MVN, whereas the AC sends afferents to both MVN and superior vestibular
nucleus), the possibility of a brainstem disorder should be considered (e.g.,
ischemia of the vestibular nucleus). While a HIT performed in the plane of the
HC can easily be interpreted at the bedside, assessment in the planes of the AC
and PC is technically challenging. Therefore, the function of the AC and PC is
best evaluated by the video head impulse test; U, utricle; S, saccule; C, cochlea
with paraflocculus or middle cerebellar peduncle stroke, see exam-

ple—Video 4.10).
The approach to the patient with acute onset prolonged vertigo

or dizziness: Table 6.2.
Table 6.2 Help me now with acute onset prolonged dizziness & vertigo:
What to examine and urgent diagnostic considerations
Bedside AVS from AVS from Other continuous
exam vestibular stroke with dizziness or vertigo
neuritis (VN) spontaneous without spontaneous
with spontaneous nystagmus nystagmusd
nystagmus
Head Abnormal Normal Acute unilateral
Impulse Presence of a Absence of a vestibular loss due to
test (HIT)a catch-up catch-up VN will cause
saccade—e.g., saccade—e.g., in spontaneous
with right a patient with a nystagmus! If no
vestibular neuritis, unilateral spontaneous
if the patient’s cerebellar stroke, nystagmus is present
head is quickly if the patient’s despite acute,
turned to the right, head is quickly ongoing symptoms,
the eyes will move turned to the VN is unlikely.
with the head to right, the eyes Simultaneous
the right which will move to the (symmetric) bilateral
takes the eyes off left keeping vestibular loss is very
the target (usually them on the rare (e.g., Wernicke’s,
the examiner’s visual target ototoxicity due to
nose)—this is (examiner’s gentamicin or
followed by a nose) because bilateral labyrinthine
corrective (overt) the vestibulo- strokes). Instead, the
saccade to the left ocular reflex is history must be relied
to bring the eyes intact; however, upon—e.g.,
back to the visual the HIT is vestibular migraine,
target occasionally effects of medication
abnormal (e.g., anti-seizure,
depending on tricyclic
localization antidepressant,
(e.g., benzodiazepines) or
labyrinthine other toxicity,
ischemia, medical conditions
vestibular (abnormalities in
nucleus) blood pressure,
glucose levels)
(continued)
Nystagmusa Unidirectional Direction- Gaze-evoked
horizontal- changing/ nystagmus is common
torsional gaze-evoked or with medication
nystagmus spontaneous toxicity, typically
Increasing in the vertical without spontaneous
direction of the fast nystagmus nystagmus. Mild
phase in E.g., Right- spontaneous
accordance with beating in right nystagmus (usually
Alexander’s gaze and increased with
law—e.g., with left-beating in removal of fixation)
right VN, there will left gaze or can be seen with
be left-beating vertical vestibular migraine,
nystagmus gaze-evoked as sometimes horizontal,
(acutely, a torsional well; upbeat sometimes vertical.
component will be nystagmus may Ictal positional
apparent as well, be unidirectional nystagmus is also
with top poles of (increasing in common in VM. A
the eyes beating upgaze, patient with an
toward the left ear) following anterior circulation
which will Alexander’s law) stroke (especially in
decrease (but still temporo-parietal
be present) in right regions of the
gaze, increase in “vestibular cortex”)
left gaze, and may also experience
remain left-beating vertigo, oftentimes
in vertical gaze without spontaneous
nystagmus [18].
Test of Normal Abnormal Expect a normal test
Skewa No vertical A vertical of skew unless there
refixation refixation with is an unrelated
movement—note alternate cover strabismus (e.g.,
that many normal test (make sure congenital fourth
people have small the patient can NP).
horizontal phorias see the visual
(eso- or target with both
exophoria), but eyes) should be
this is not a skew assumed to
(which is by represent a skew
definition a deviation until
vertical ocular proven otherwise
misalignment). in the AVS, but
is commonly
absent with a
central etiology.
(continued)
Bedside AVS from AVS from Other continuous
exam vestibular stroke with dizziness or vertigo
neuritis (VN) spontaneous without spontaneous
with spontaneous nystagmus nystagmusd
nystagmus
Auditory Normal Abnormal An isolated cochlear
functionb Spared in If otoscopy is stroke sparing the
vestibular neuritis; normal (no vestibular apparatus
abnormal in vesicles or signs (i.e., no vertigo and
labyrinthitis, of infection) and no spontaneous
although otoscopy the patient has nystagmus) would be
should also be acute unilateral or rare. With symmetric
abnormal bilateral hearing bilateral labyrinthine
loss, consider strokes, there may be
labyrinthine minimal or no
ischemia (due to nystagmus with
redundancy and profound bilateral
decussating fibers vestibular and
of the brainstem auditory loss.
auditory
pathways,
hearing loss due
to a unilateral
[pure] brainstem
lesion is rare)
Head- Contralesional Ipsilesional or When dealing with a
shaking Following vertical non-vestibular cause
nystagmus 15 seconds of E.g., with a right of continuous
(HSN)c 2–3 Hz horizontal vestibular nucleus symptoms, there
head-shaking— spontaneous should be no head
e.g., with right left-beating motion intolerance or
vestibular neuritis, nystagmus may HSN. If there is no
spontaneous reverse direction unilateral vestibular
left-beating to right-beating loss, but strong HSN
nystagmus will HSN; e.g., or with horizontal
intensify with horizontal HS, there’s vertical
horizontal head-shaking in a nystagmus, consider
head-shaking patient with the etiology to be
unilateral central (e.g.,
flocculus or vestibulo-cerebellar
nodulus stroke stroke, vestibular
may provoke migraine)
downbeat HSN
(continued)
Other Peripheral Spontaneous Posterior fossa strokes
vestibular nystagmus may present with
nystagmus should usually will not normal eye
suppress with suppress with movements. In these
fixation and will visual fixation, situations, a thorough
intensify with but it can. Look general neurologic and
removal of for saccadic gait examination is
fixation (e.g., hypermetria in particularly important.
penlight cover one direction Truncal, gait and/or
test, occlusive and hypometria appendicular ataxia
funduscopy) in the other and are common in these
ocular patients. Also consider
lateropulsion thalamic astasia on the
(lateral differential of acute/
medullary subacute onset of
stroke). If significant imbalance
smooth pursuit in the absence of clear
is very saccadic, sensory, motor or
consider cerebellar
paraflocculus or abnormalities. A
middle “pusher syndrome”
cerebellar can manifest from a
peduncle unilateral stroke,
localization where a patient will
use the non-paretic
limbs to “push”
toward the paretic
side, which often
contributes to
imbalance and falls.
(continued)
a
Makes up the HINTS exam, which stands for Head Impulse, Nystagmus,
Test of Skew. If any of the features of the HINTS exam are in a central pat-
tern, the etiology must be assumed to be central until proven otherwise.
Remember that the HINTS exam should only be applied in the acute vestibu-
lar syndrome (e.g., spontaneous nystagmus, continuous vestibular symptoms,
imbalance, head motion intolerance, nausea, and vomiting)
b
Along with HINTS, the addition of evaluating auditory function with finger
rub makes up the HINTS “Plus” exam
c
Central/dangerous etiologies may mimic vestibular neuritis, especially with
vestibular nucleus or labyrinthine ischemia. Because the anterior inferior cer-
ebellar artery supplies the labyrinth and flocculus, floccular ischemia can
result in central HSN (e.g., downbeat nystagmus). Ischemia involving the
vestibular nucleus may cause contralesional spontaneous nystagmus that
reverses direction (becomes ipsilesional) with head-shaking
d
The distinction between vestibular and non-vestibular dizziness can at times
be a challenge. If the patient has internal or external vertigo, nausea and/or
vomiting, imbalance, and head motion intolerance, the etiology is likely to
be vestibular (peripheral or central)
Pitfalls: The Dix-Hallpike maneuver will aggravate symptoms

and spontaneous nystagmus in a patient with the AVS, and as such,
may lead to a misdiagnosis of benign paroxysmal positional ver-
tigo (BPPV). Patients with spontaneous nystagmus do not have
BPPV, with rare exceptions (e.g., pseudonystagmus in horizontal
canal BPPV—see BPPV section). To diagnose vestibular neuritis,
ALL 3 features of the HINTS exam must suggest a peripheral pat-
tern (abnormal HIT when the head is turned in the direction of the
slow phase of the nystagmus; spontaneous unidirectional horizon-
tal-torsional nystagmus; absence of a vertical ocular misalign-
ment). In vestibular neuritis, there should be no hearing loss
although there is hearing loss (by definition) with labyrinthitis.
However, otoscopy is often abnormal with the latter condition.
Therefore, assume stroke until proven otherwise in a patient with
vascular risk factors presenting with the AVS and acute hearing
loss with normal otoscopy.
Do not miss this! Stroke (involving brainstem, cerebellum, or

labyrinth [hearing loss will almost always be present]); Wernicke’s
encephalopathy; demyelinating disease; Ramsay Hunt syndrome
(must perform otoscopy, seventh NP is often present as well).
What is next? The diagnosis of vestibular neuritis can be con-

firmed with a very high degree of confidence when the HINTS Plus
exam conforms to a peripheral/benign pattern. In such cases, no neu-
roimaging is necessary unless there are atypical features (e.g., patient
is immunosuppressed). Audiogram should be obtained in all patients,
especially in those with hearing loss or aural symptoms (ESM 6.1).
VNG, ENG or VOG can be helpful in quantifying and recording
spontaneous or provoked nystagmus (ESM 6.3). Caloric testing can
demonstrate horizontal semicircular canal paresis (ESM 6.5) while
vHIT can demonstrate horizontal and vertical semicircular paresis
(ESM 6.2). Vestibular evoked myogenic potentials (VEMPs) can
assist in the localization by identifying superior division involve-
ment (i.e., abnormal ocular VEMPs from utricle involvement) and/
or inferior division involvement (i.e., abnormal cervical VEMPs
from saccule involvement) (ESM 6.6).
Treatment options: For VN, antiemetics and a vestibular sup-

pressant can help with symptomatic relief, but should not be used
for more than 3 days from symptom onset as doing so delays nor-
mal compensation. Vestibular physical therapy has been shown to
expedite recovery, as well as a short course of corticosteroids in
some patients. Similar to optic neuritis, steroids may hasten recov-
ery, but have not been shown to impact the ultimate clinical out-
come, which in almost all cases is favorable with complete
symptomatic recovery over weeks to months.
Advanced: HINTS caveats: (1) head impulse test—this can be

abnormal in certain stroke syndromes (or other central etiologies)
ipsilaterally due to lesions of the vestibular nucleus, pontine fascicle/
root entry zone of the eighth CN (Video 6.18), labyrinth, or abnormal
contralaterally with lesions of the cerebellar flocculus or medullary
nucleus prepositus hypoglossi; (2) nystagmus—“central” vestibular
nystagmus (e.g., ischemia of the vestibular nucleus) may also be uni-
directional and follow Alexander’s law, and may suppress with visual
fixation; (3) test of skew—because the superior division of the ves-
tibular nerve carries the utricle afferents, a small skew deviation may
be detected with a Maddox rod (not with alternate cover/cover-
uncover tests) and other features of the ocular tilt reaction can be
detected in some (subtle head tilt and ocular counterroll [e.g., appre-
ciated with fundus photos], associated tilt in the subjective visual ver-
tical [same direction as the head tilt])—however, a skew deviation
apparent with “test of skew” that causes vertical diplopia is rare and
should be considered central until proven otherwise (a case of a
“peripheral” skew deviation in vestibular neuritis: Video 6.19) [19,
20]. A “central” skew deviation is much more common and tends to
be larger in amplitude (Video 6.20).
If you can only remember two things… (1) the HINTS exam
can ONLY be applied when spontaneous nystagmus is present
(think of it as the AVS-HINTS exam - concept from Dr. Stephen
Reich). (2) If ANY of the ocular motor findings appear central, you
must assume a central etiology until proven otherwise! For exam-
ple: If a patient with the AVS has an (1) abnormal unilateral HIT,
(2) negative test of skew, and (3) gaze-evoked nystagmus (e.g.,—
Video 6.21), since (3) is in a “central” pattern, assume that the
etiology is central until proven otherwise! This is also why HINTS
is a 3-step test and not a 1-step test!
6.5.2 Episodic Vestibular Syndrome
The approach (history and exam) to the patient with episodic

vertigo or dizziness: Table 6.3
6.5.2.1 Triggered, Episodic Vestibular Syndrome
Positional Vertigo and Nystagmus

The approach (history and exam) to the patient with positional
nystagmus, dizziness or vertigo: Table 6.4
Posterior Canal BPPV

A 65-year-old woman with history of hypertension woke up and
rolled over in bed to the right. Several seconds after changing
position, she experienced an intense sensation of the room spin-
Table 6.3 Help me now with episodic dizziness & vertigo: Typical historical and exam features with common diagnostic consider-
ations
Triggered? Timing Symptomsa/signs Test
Benign Yes—positional <1–2 minutes Vertigo and nystagmus Bedside: Dix-Hallpike (PC)
paroxysmal Supine roll test (HC)
positional
vertigo
Vestibular Syndromes
Superior canal Yes—pressure or Seconds to minutes, Vertigo and nystagmus with Bedside: Valsalva and pinched-
dehiscence sound (Tulio occasional sound/pressure; autophony nose Valsalva, loud sound
syndrome phenomenon) disequilibrium in Lab: Audiogram—supranormal
(hearing internal noises that
between should not normally be bone conduction with air-bone
perceived) gap; lowered VEMP threshold
Vestibular Can be triggered Seconds (also Vertigo and nystagmus, Bedside: hyperventilation
paroxysmia (head position, consider cardiac Imaging: CISS or FIESTA
ipsilateral (usually ictal) aural
hyperventilation) or arrhythmia) symptoms imaging for neurovascular
unprovoked compression of CN8
Vestibular Can be triggered Minutes-hours, can Vertigo, dizziness, imbalance, Bedside: no characteristic findings
migraine (typical migraine be seconds or days motion sickness +/− ictal Lab: no characteristic findings
triggers) or nystagmus, +/− headache, Be concerned by sudden onset,
unprovoked photophobia, phonophobia, sustained or severe head/neck pain
visual aura (think dissection)
(continued)
253
254
Triggered? Timing Symptomsa/signs Test

Menière’s Can be triggered 20 minutes to Vertigo and nystagmus, Bedside: spontaneous horizontal
disease (high sodium meal) 12 hours ipsilateral aural symptoms nystagmus during attacks
or unprovoked Lab: audiometry—low-mid
frequency sensorineural hearing
loss; ipsilateral (to hearing loss)
caloric weakness with normal
head impulse test is common
Transient No Minutes to hours Vertigo and may have Bedside: can apply the HINTS
ischemia attack nystagmus during the episode; exam when spontaneous
+/− hearing loss, symptoms nystagmus is present and
referable to the posterior symptoms are ongoing; usually,
circulationb the history and ABCD2c score
must be relied upon
Imaging: MR with diffusion-
weighted imaging and vascular
imaging of head and neck (MR or
CT angiography)
(continued)
PC posterior canal, HC horizontal canal, CISS constructive interference in steady state, FIESTA fast imaging employing steady-state
acquisition, CN8 cranial nerve 8
a
When approaching the patient with episodic vertigo, remember that spinning vertigo can be due to nonvestibular disorders such as
orthostatic hypotension or cardiac arrhythmia. Assuming a vestibular cause of episodic vertigo, BPPV and vestibular migraine are the
most common. Menière’s is less common and aural symptoms should be prominent. Superior canal dehiscence syndrome and ves-
tibular paroxysmia are uncommon conditions, but since they are amenable to treatment (surgery and antiseizure medications, respec-
tively), they should be included on the differential

b
dysarthria, dysphagia, dysphonia, hemiparesis, facial weakness, sensory loss (one side of face or body), vision loss, incoordination
c
ABCD2 = age (1 if >60 years old), blood pressure (1 if SBP > 140 or DBP > 90), clinical features (2 if unilateral weakness, 1 if speech
disturbance), diabetes (1 if present), duration (0 if <10 minutes, 1 if 10–60 minutes, 2 if >60 minutes)—if the score is 4 or more, high
suspicion for transient ischemic attack (TIA). Even if the score is <4, the patient may still have a TIA
255
Table 6.4 Help me now with positional dizziness & vertigo: What to exam-
ine and urgent diagnostic considerations in a patient with positional dizzi-
ness/vertigo without spontaneous nystagmus
Peripheral Central Other
Positional ++++ − Consider central if there is pure
upbeat-torsional upbeat or pure torsional nystagmus;
nystagmus other common findings with (right)
PC-BPPV: upbeat-torsional (top
poles toward the right ear) in right
DH and milder (in the same
patient) downbeat-torsional (top
poles toward the left ear) in left DH
or when going from right DH back
to upright (otoconia are moving in
an inhibitory direction)
Positional +++ + Rarely, a lesion of the
horizontal paraflocculus can cause geotropic
(geotropic) nystagmus; however, saccadic
nystagmus pursuit, gaze-evoked nystagmus,
ataxia and other signs would be
expected with this localization
Positional ++ ++ Think central especially when there
horizontal is apogeotropic with DH/supine roll
(apogeotropic) test and downbeat with straight
nystagmus head-hanging and/or prone; use
repositioning maneuvers to see if
nystagmus/vertigo resolves or
transitions to geotropic nystagmus;
use bow and lean test to assist in the
diagnosis of HC-BPPV and to
lateralize the involved side
Positional + +++ Although peripheral causes
downbeat include: (1) the apogeotropic
nystagmus variant of PC-BPPV (downbeat-
torsional seen with Dix-Hallpike,
upbeat-torsional and prominent
symptoms when sitting up suggests
otoconia in the short arm of the
PC), and (2) anterior canal BPPV
(downbeat or downbeat-
torsional—this is rare), downbeat
or downbeat-torsional nystagmus
should be considered central until
proven otherwise in most cases
PC posterior canal, BPPV benign paroxysmal positional vertigo, DH Dix-
Hallpike, HC horizontal canal
Otoconia
Otolithic membrane
Sterecilia (short) &
kinocilium (long)
Anterior
Vestibular nerve
(afferents from hair
cells)
Posterior
Utricle
lea
h
Coc
Horizontal Saccule
Fig. 6.5 Anatomy of the labyrinth: The labyrinth consists of the (1) semicir-
cular canals (SCC)—angular acceleration detectors (posterior, horizontal,
and anterior); (2) otoliths—linear acceleration detectors (utricle and saccule);
(3) cochlea—auditory function. The dense otoconia, which are contained
mainly within the utricle, may spontaneously slough off with aging or due to
head trauma, and if they enter one of the SCCs (most to least commonly
affected—posterior, horizontal, and anterior), benign paroxysmal positional
vertigo (BPPV) will result. (Figure reproduced with permission from Gold
et al. [10])
ning around her (i.e., external vertigo). This lasted for about
30 seconds, and then the vertigo subsided. When she repositioned
herself from a lying to a seated position, the vertigo returned for
another 30 seconds. She presented to the Emergency Department
where a left Dix-Hallpike maneuver was normal, but in the right
Dix-Hallpike (DH) position, after a latency of 2–3 seconds there
was vertigo and upbeat nystagmus (UBN) with a torsional com-
ponent (top poles beating toward the right ear). The nystagmus
intensified over the next few seconds (crescendo) and then gradu-
ally abated (decrescendo) and was gone in less than 30 seconds.
An Epley maneuver was performed to treat right posterior canal
(PC) benign paroxysmal positional vertigo (BPPV). After 30 min-
utes, a right DH was repeated, and there was no nystagmus and no
vertigo (Figs. 6.5 and 6.6).
Directions of excitation for each SCC
AC
Endolymph
Ampulla
PC
U
Ampulla
Cupula Ampulla C
HC
Am
To utricle pu
lla S
Vestibular nerve Stereocilia (short)

(afferents from & kinocilium (long)
hair cells)
Ampullopetal (towards ampulla)
Ampullofugal (away from ampulla)
Fig. 6.6 Anatomy of the semicircular canal (SCC) and directions of excitation:
Left: Each SCC contains an area of outpouching called the ampulla, which is
where the cupula is located. When the cupula is deflected by the flow of endo-
lymph (due to a head rotation or otoconia moving with gravity) in an excitatory
direction, the vestibular nerve firing rate will increase. If the cupula is deflected
in the opposite (inhibitory) direction, the vestibular nerve firing rate will
decrease. Right: For example, when the head is turned quickly to the right, there
will be right horizontal canal (HC) excitation due to ampullopetal (toward the
ampulla) endolymph flow with simultaneous left HC inhibition due to ampullof-
ugal (away from the ampulla) endolymph flow. The combination of right HC
excitation and left HC inhibition optimizes the horizontal vestibulo-ocular reflex
(VOR), by causing contraction of the right medial rectus and left lateral rectus
(i.e., efferent portion of the VOR causing a conjugate leftward movement) and
simultaneous relaxation of right lateral rectus and left medial rectus. While the
ampullopetal direction is excitatory for the HC, the ampullofugal direction is
excitatory for the anterior (AC) and posterior canals (PC). For example, otoconia
in PC-benign paroxysmal positional vertigo (BPPV) almost always flow in an
(excitatory) ampullofugal direction, causing a characteristic robust upbeat-tor-
sional (toward the lowermost, affected ear) nystagmus. However, when the
patient is brought from the Dix-Hallpike back to a seated position, the otoconia
will flow in the opposite (inhibitory or ampullopetal) direction, causing a weaker
downbeat-torsional (toward the unaffected ear) nystagmus. (Figure on the left
reproduced with permission from Gold et al. [10])
Video/Figure: Video 6.22.
Key questions to ask: The diagnosis of PC BPPV is usually a

telephone diagnosis—attacks will be triggered by moving the
head up or down, going from lying to supine or supine to lying
(orthostatic hypotension can be symptomatic with this postural
change too) or rolling over in bed (e.g., rolling over in bed to the
right suggests right PC BPPV, unless it is the horizontal canal

variant).
PC-BPPV diagnostic criteria: Canalolithiasis—(1) recurrent

attacks of positional vertigo or positional dizziness provoked by
specific head movements (see above); (2) duration of attacks is
<1 minute; (3) positional nystagmus (UB-torsional, top poles beat-
ing toward the lowermost, affected ear) follows a brief latency of
one or few seconds with the Dix-Hallpike or side-lying (Semont)
maneuver, lasts <1 minute; (4) is not better explained by another
disorder. Cupulolithiasis—typically has the same characteristics,
but with a shorter (or no) latency, longer duration of >1 minute.
Hemodynamic orthostatic dizziness or vertigo: Consider when

dizziness, unsteadiness or vertigo is triggered by postural changes—
lying to sitting/standing or sitting to standing—or when present
when upright and resolved by sitting or lying down, or orthostatic
hypotension, postural tachycardia syndrome or syncope has been
documented on standing or with head-up tilt table test.
Key findings to elicit: When vertigo/dizziness and UB-torsional

nystagmus (top poles beat toward the affected or lowermost ear)
are triggered by DH after a brief latency, the nystagmus is
crescendo-decrescendo and resolves in <30–60 seconds, the diag-
nosis of PC BPPV can be made with near certainty. This can be
localized based on knowledge of semicircular canal (peripheral
and central) anatomy and physiology, and the fact that stimulation
of an individual canal (in this case by otoconia) leads to a predict-
able movement of both eyes (Fig. 5.7). Make sure that the history
is consistent with positional vertigo (e.g., BPPV is so common that
occasionally it is an incidental finding). The UB-torsional nystag-
mus often reverses to downbeat-torsional (with top poles of the
eyes beating toward the opposite ear) on sitting up, which is due to
otoconia flowing in the opposite (inhibitory) direction (see exam-
ple—Video 6.23).
Pitfalls: Horizontal nystagmus due to horizontal canal (HC)

BPPV will commonly be triggered by DH, but will be stronger
with supine roll test. It is important that the PC and HC variants are
distinguished because repositioning maneuvers differ. Especially

following traumatic brain injury, multi-canal (and bilateral) BPPV
can be seen, so that right DH may trigger right PC and right HC
BPPV. Distinguishing between continuous vestibular symptoms
that are aggravated by head movements (e.g., TIA, vestibular neu-
ritis, vestibular migraine) and those that are triggered by head
movements (e.g., BPPV) can sometimes be challenging when tak-
ing the history. Nevertheless, the distinction is important, espe-
cially in the emergency room setting.
Do not miss this! Stroke or cerebellar midline tumor causing

positional vertigo and other patterns of nystagmus (downbeat, pure
upbeat, pure torsional). Fortunately, this is rare.
What is next? If the history and exam fit with PC BPPV, no addi-
tional testing is needed. If the nystagmus vector or pattern is atypical
or unexpected, consider central causes and MRI with attention to the
posterior fossa. CT scan is unnecessary when BPPV is suspected.
Treatment options: Epley or Semont are the most common repo-

sitioning maneuvers (Video 6.24) (Figs. 6.7 and 6.8). Consider
checking vitamin D levels in recurrent BPPV.
Advanced: An “apogeotropic” (downbeat [DB]-torsional nystag-

mus with top poles beating toward unaffected/uppermost ear in
DH) form of PC BPPV is probably due to otoconia located in the
non-ampullary (short) arm, which move in an inhibitory direction.
These patients will have a typical BPPV history, although usually
have more intense symptoms when sitting up (with or without
upbeat-torsional nystagmus). This can mimic the rare anterior
canal variant of BPPV (downbeat-torsional nystagmus with top
poles beating toward affected/lowermost ear in DH). However, if
presumed apogeotropic (short arm) PC BPPV cannot be converted
to typical UB-torsional PC BPPV nystagmus and then treated, a
central etiology should be excluded with MRI (See Table 6.4).

a d
e
b
f g
c
Fig. 6.7 Canalith repositioning (Epley) maneuver for right PC BPPV: (a)
First the patient is placed in the long-sitting position. (b) The head is rotated
45 degrees to the right. (c) Then the patient is lowered quickly into the supine
position with the head in 20-30 degrees of cervical extension. (d) Then the
patient’s head is 90 degrees to the left. (e) The patient is rolled into a left-side
lying position with the head maintained in 45 degrees of rotation to the left so
that the head is facing the floor. (f) Then the patient sits up slowly with the
head still facing down toward the floor and rotated 45 degrees to the left. (g)
Slowly, the head is moved back to a neutral position. Note that each position
should be maintained for at least 30-60 seconds or until nystagmus and/or
vertigo cease (Figure reproduced with permission from Gold DR, Morris L,
Kheradmand A, Schubert MC. Repositioning maneuvers for benign paroxys-
mal positional vertigo. Curr Treat Options Neurol. 2014;16(8):307.)
Horizontal Canal BPPV

A 45-year-old man experienced <60 second-long vertigo attacks
when rolling over in bed to the left more than to the right. In between
positional vertigo attacks, he felt mildly dizzy and off balance, espe-
cially with head movements. A left Dix-Hallpike (DH) maneuver
brought on vertigo symptoms and examination demonstrated mod-
erate left-beating nystagmus (LBN), while a right DH demonstrated
mild right-beating nystagmus (RBN). Supine roll test (head flexed
30° while supine and then turned 90° to the right and to the left) to
the left brought on severe vertigo and there was robust LBN (beating
a d
b e
c f
Fig. 6.8 Semont maneuver for right PC-BPPV: (a) First the patient sits at the
edge of the table. (b) The head is turned 45 degrees to the left. (c) The patient
is rapidly brought into a right side-lying position, which is maintained for 1
minute. (d) Without stopping in the center, the patient is quickly moved from
right to left side-lying positions within 1.5 seconds, with initial 45 degrees of
leftward rotation maintained throughout. This position is maintained for 1
minute. (e) The patient is slowly brought back to a seated position with the
leftward head position maintained. (f) The head is slowly moved back to neu-
tral. (Figure reproduced with permission from Gold DR, Morris L, Kherad-
mand A, Schubert MC. Repositioning maneuvers for benign paroxysmal
positional vertigo. Curr Treat Options Neurol. 2014;16(8):307.)
toward the ground—i.e., geotropic), while roll to the right brought

on milder vertigo and RBN (also geotropic). This was crescendo-
decrescendo, and resolved in <60 seconds. He was treated with a
Gufoni maneuver for left horizontal canal (HC, geotropic variant)
benign paroxysmal positional vertigo (BPPV), and after 30 minutes,
a repeat roll test was performed and was normal.
Video/Figure: An example of geotropic nystagmus: (Video

6.25); an example of apogeotropic nystagmus: (Video 6.26).
Key questions to ask: The diagnosis of HC BPPV is usually a

telephone diagnosis—attacks will be triggered mainly by horizon-
tal head movements (e.g., rolling over in bed), as well as when
lying down. If a patient with left geotropic HC BPPV (i.e., beating
toward the ground with the right and left ears down) rolls to the
left, the otoconia will move in an excitatory direction (ampullope-
tal, or toward the ampulla, which contains the cupula and hair
cells—slow phase contralateral and fast phase ipsilateral) and
result in more intense nystagmus and vertigo. When the same
patient rolls to the right, the otoconia move in an inhibitory direc-
tion (ampullofugal, or away from the ampulla—slow phase ipsilat-
eral and fast phase contralateral), resulting in weaker nystagmus
that is in the opposite direction, as well as less intense vertigo
(Figs. 6.5 and 6.6).
HC-BPPV diagnostic criteria: Canalolithiasis—(1) Recurrent

attacks of positional vertigo/dizziness provoked by lying down
or turning over in the supine position. (2) Duration of <1 min-
ute. (3) Nystagmus with a brief (or no) latency in the supine roll
test, beating horizontally toward the ground (geotropic) in both
right and left ear down positions. (4) Not better explained by
another disorder. Cupulolithiasis—(1) Recurrent attacks of
positional vertigo/dizziness provoked by lying down or turning
over in the supine position. (2) Duration of >1 minute. (3)
Nystagmus with a brief (or no) latency in the supine roll test,
beating horizontally toward the ceiling (apogeotropic) in both
right and left ear down positions. (4) Not better explained by
another disorder.
Key findings to elicit: There are two HC BPPV variants: (1)

geotropic—RBN with right ear down and LBN with left ear
down. Nystagmus and vertigo will be stronger toward the affected
ear. (2) apogeotropic (away from the earth)—LBN with right ear
down and RBN with left ear down. Nystagmus and vertigo will
be stronger toward the unaffected ear. Usually, the diagnosis can
be made, the BPPV can be accurately lateralized and the most
effective treatment can be selected. However, additional maneu-
vers such as sitting to supine and bow and lean should be per-
formed if there is any diagnostic uncertainty (example of bow
and lean in a case of “pseudo-spontaneous” nystagmus due to

apogeotropic HC-BPPV Video 6.27, and see “Advanced” below
and Table 6.4).
Pitfalls: Geotropic positional nystagmus is almost always due to

HC BPPV with few exceptions (e.g., paraflocculus lesion causing
geotropic positional nystagmus and significant impairment of
smooth pursuit). Apogeotropic positional nystagmus can be due to
HC BPPV or a central etiology (e.g., stroke or midline cerebellar
tumor). If apogeotropic positional nystagmus can be transitioned
to geotropic nystagmus (with Gufoni maneuver, or simply hori-
zontal head-shaking) and/or resolved completely, the likelihood
that this is central is very low.
Do not miss this! If apogeotropic positional nystagmus persists

despite appropriate repositioning maneuvers or if ocular motor or
neurologic examination is abnormal (e.g., the patient also has posi-
tional downbeat nystagmus with straight head hanging, gaze-
evoked nystagmus, impaired pursuit), contrast-enhanced MRI is
indicated to exclude stroke or midline cerebellar tumor (a small
nodulus lesion may be missed without contrast).
What is next? If the history and exam fit with HC BPPV, no addi-
tional testing is needed. Consider checking vitamin D levels in
recurrent BPPV.
Treatment options: Gufoni maneuver (Video 6.29) (geotropic or

apogeotropic) or BBQ roll (Video 6.28) (geotropic) are the most
commonly used (Figs. 6.9 and 6.10).
Advanced
• How can I lateralize geotropic HC-BPPV?
The nystagmus and symptoms are most severe when the head
is turned toward the affected ear. Or, simply remember that the
nystagmus will beat toward the affected ear when it is strongest
(this rule also applies to apogeotropic HC-BPPV)—e.g., weak
left-beating (LB) in left roll and strong right-beating (RB) in
right roll = right geotropic HC-BPPV. If the laterality is
a e
b f
c g
d h
Fig. 6.9 BBQ roll for right geotropic HC-BPPV: (a) The patient begins in
the long-sitting position. (b) The patient is brought into a supine position with
the head elevated 30 degrees. (c) The patient’s head (or whole body if there’s
a poor cervical range of motion) should be rotated 90 degrees to the right side
and maintained for 30 seconds or until the nystagmus and vertigo resolve
completely. (d) The head is rotated back to neutral. (e) The head is moved 90
degrees to the left side. (f) The patient is brought into a prone position. (g)
The head (body) continues to rotate 90 degrees so that the right ear is down
toward the floor. (h) The head is rotated another 90 degrees back to neutral
and the patient is brought back into the long-sitting position. Each position is
maintained for 30 seconds or until the nystagmus and vertigo completely
resolve. (Figure reproduced with permission from Gold DR, Morris L, Kher-
admand A, Schubert MC. Repositioning maneuvers for benign paroxysmal
positional vertigo. Curr Treat Options Neurol. 2014;16(8):307.)
a c
b d
Fig. 6.10 Gufoni maneuver for right apogeotropic HC-BPPV or left geotro-
pic HC-BPPV: (a) The patient starts in a seated position. (b) The patient is
moved quickly to the unaffected side (side of weaker nystagmus – e.g., to the
right in right apogeotropic or in left geotropic HC-BPPV). The head remains
in a neutral spine orientation, and this position is held for about 1 minute. (c)
Then, the head is moved 45 degrees towards the ceiling (for apogeotropic) or
45 degrees toward the floor (for geotropic) and is held for 2 minutes. (d) The
patient is guided back to a seated position. (Figure reproduced with permis-
sion from Gold DR, Morris L, Kheradmand A, Schubert MC. Repositioning
maneuvers for benign paroxysmal positional vertigo. Curr Treat Options
Neurol. 2014;16(8):307.)
unclear, perform the bow (head flexed with chin to chest) and
lean (head extended with chin up) test. In bow, the nystagmus
may beat strongly toward the affected side, and in lean, the
nystagmus may beat weakly toward the healthy side—e.g.,
right geotropic HC-BPPV: (strong) RB in bow and (weak) LB
in lean. The sitting to supine positioning test can also be help-
ful, where the patient is quickly brought into a supine position,
which may provoke nystagmus that beats toward the healthy
side—e.g., right geotropic HC-BPPV: LB when the patient is
brought into a supine position.
• How can I lateralize apogeotropic HC-BPPV?
The nystagmus and symptoms are most severe when the head
is turned toward the healthy ear. Or, simply remember that the
nystagmus will beat toward the affected ear when it is strongest
(this rule also applies to geotropic HC-BPPV)—e.g., weak LB
in right roll and strong RB in left roll = right apogeotropic HC-

BPPV. If the laterality (or peripheral versus central localiza-
tion) is unclear, look for pseudo-spontaneous nystagmus where
the nystagmus will be ipsilateral to the affected ear (usually
with fixation-removed) when the patient is seated. Then per-
form the bow (head flexed with chin to chest) and lean (head
extended with chin up) test. In bow, the nystagmus may beat
weakly toward the healthy side, and in lean, the nystagmus
may beat strongly toward the affected side—e.g., right apogeo-
tropic HC-BPPV: (weak) LB in bow and (strong) RB in lean.
The sitting to supine positioning test can also be helpful, where
the patient is quickly brought into a supine position, which
may provoke nystagmus that beats toward the affected side—
e.g., right apogeotropic HC-BPPV: RB when the patient is
brought into a supine position. If the nystagmus does not fol-
low these rules, cannot be lateralized, or does not respond to
properly performed repositioning maneuvers or convert to
geotropic nystagmus, assume central until proven otherwise.
Want to know more? [22–25, 28–30]
Central Positional Nystagmus (CPN)
Case: A 30-year-old woman presented with symptoms of posi-

tional vertigo and was diagnosed with horizontal canal BPPV and
treated with repositioning maneuvers. Positional vertigo improved
mildly, but episodes of positional vomiting occurred without sig-
nificant vertigo/dizziness. Given her persistent symptoms, she was
referred to neurology after several months. General neurologic and
ocular motor examinations were normal with the exception of mild
gaze-evoked nystagmus (e.g., in right gaze, right-beating nystag-
mus: in left gaze, left-beating nystagmus) without rebound nystag-
mus and mild difficulty standing heel to toe (a tandem Romberg).
Examination with video Frenzel goggles (removal of fixation)
showed no spontaneous nystagmus when upright; down and right-
beating nystagmus (RBN) in bow (head flexed forward); upbeat
and left-beating nystagmus (LBN) in lean (head extended back); in
right supine roll test (head rotated 90° to the right with head slightly
flexed) there was LB apogeotropic nystagmus (i.e., beating away
from the earth); and in left supine roll test, there was RB apogeo-
tropic nystagmus. The nystagmus in right and left roll positions

appeared symmetric and symptoms were mild and the same to
each side. While the change in horizontal nystagmus with bow and
lean and the apogeotropic nystagmus with supine roll test made
horizontal canal BPPV a possibility, there were enough atypical
features that MRI was ordered. Contrast-enhanced MRI demon-
strated a tumor originating in the fourth ventricle, which was
resected and pathology was consistent with a subependymoma.
Video of this patient: Video 6.30.
Key questions to ask: Ask about other neurologic symptoms (that

could localize to the brainstem and/or cerebellum), preceding head
or neck trauma (vertebral artery dissection), progressive imbalance
(spinocerebellar ataxia or other degenerative condition).
Key findings to elicit: The most common “central” patterns are

downbeat nystagmus and apogeotropic nystagmus (usually with
Dix-Hallpike/straight head hanging and supine roll, respectively),
although pure upbeat, or pure torsional nystagmus are other pat-
terns that can be seen. Prone positioning will commonly bring out
DBN as well—try simply having the patient bend forward at the
waist and ask them to put their head between their legs—if cere-
bellar dysfunction is present, this will commonly provoke or
aggravate DBN (in fact, in this case there was DBN in the bow/
head-down position that probably would have been more marked
in a prone position). A complete neurologic and ocular motor
examination is particularly important when CPN is suspected.
Pitfalls: In this particular case, neuroimaging was indicated due to

the following red flags: (1) The nystagmus was not in the plane of a
particular semicircular canal and changed unpredictably with vari-
ous head positions (e.g., bow and lean caused down- and upbeat
nystagmus, respectively). (2) The typical crescendo-decrescendo
pattern of PC or HC-BPPV was lacking. (3) Repeated, properly
performed repositioning maneuvers did not resolve the symptoms
or nystagmus. (4) Vomiting persisted even as positional vertigo
improved. (5) Gaze-evoked nystagmus was present (any abnormal
ocular motor signs should raise suspicion for a central process). (6)
Nystagmus was apogeotropic, which is one of the most common

patterns of CPN along with positional DBN.
Do not miss this! Unless positional DBN/DB-torsional nystag-

mus is clearly peripheral (e.g., apogeotropic (short arm) PC
BPPV or anterior canal BPPV [Video 6.31 and one suggested
repositioning maneuver for AC BPPV Video 6.32]) and can be
resolved in the office, assume that it is central until proven oth-
erwise (example of positional DBN due to a cerebellar degen-
eration—Video 6.33). Upbeat-torsional positional nystagmus is
almost always due to PC-BPPV, and geotropic positional nys-
tagmus is almost always due to HC-BPPV, although rarely a
paraflocculus (tonsil) lesion can mimic geotropic HC-BPPV
(see Table 6.4). In these cases, there are typically other ocular
motor or neurologic abnormalities, especially significant smooth
pursuit impairment. However, persistent apogeotropic positional
nystagmus is concerning and is often related to nodulus/ventral
uvula pathology. Do not forget about patients with vestibular
migraine who can have a variety of patterns of spontaneous or
positional nystagmus, usually in the ictal phase (see example of
positional DBN during a vestibular migraine attack—Video
6.34), but also inter-ictally.
What is next? If any red flags are present, contrast-enhanced

MRI, preferably with thin cuts through the posterior fossa (with
attention to the vestibulocerebellum—flocculus/paraflocculus and
uvula/nodulus). If a high-quality MRI does not demonstrate a
structural lesion or abnormal enhancement, if the presentation is
acute—consider stroke (could be falsely negative in the first sev-
eral days after onset); if subacute—consider neoplastic/metastasis,
paraneoplastic, prion disease (Creutzfeldt-Jakob disease), autoim-
mune (antiglutamic acid decarboxylase antibody cerebellar syn-
dromes); if chronic—consider neoplastic, Chiari malformation,
neurodegenerative (spinocerebellar ataxia).
Treatment options: There is no strong evidence for any particu-

lar medication to treat central positional dizziness and nystagmus.
Usually this is not a longstanding disorder that causes significant
symptoms.
Superior Canal Dehiscence Syndrome

Case: A 60-year-old man complained of hearing his heartbeat and
noting that his own voice sounded too loud (examples of autophony)
and dizziness that was triggered by loud noises and straining.
Neurologic exam was normal, and when a 512 Hz tuning fork was
held over the medial malleolus while the patient was standing on the
right and then left foot, vibration was “heard” in the right ear. With
pinched-nose Valsalva maneuver, there was dizziness and downbeat-
torsional (top poles toward the right ear) nystagmus, suggestive of
excitation of the right anterior canal (slow phase down and torsion
towards left ear, with position reset/fast phase in the opposite direc-
tions). Evaluation of the outside audiogram demonstrated an air-bone
gap (see Fig. 6.1) with supra-normal bone conduction thresholds.
Superior canal dehiscence (SCD) of the right ear was suspected, and
this was confirmed with CT of the temporal bones (Fig. 6.11).
Video of this patient: Video 6.11.

• Is autophony present (other examples include hearing joints
creaking and moving, hearing the eyes move, hearing foot-
steps)?
• Are brief episodes of dizziness, vertigo or imbalance brought
on by sound (Tullio’s phenomenon) or pressure (sneezing,
coughing, blowing the nose, straining) triggers?
• Aural symptoms including tinnitus, fullness, popping, pain,
pressure, hearing loss?
Diagnostic criteria: At least one of the following (“third

mobile window”) symptoms: 1) bone conduction hyperacusis;
2) sound-induced vertigo and/or oscillopsia time-locked to the
stimulus; 3) pressure-induced vertigo and/or oscillopsia time-
locked to the stimulus; 4) pulsatile tinnitus. At least one of the
following exam signs/test results: 1) nystagmus consistent with
inhibition or excitation of the superior (anterior) canal triggered

by sound, change in middle ear or intracranial pressure; 2) low-
frequency negative bone conduction thresholds on pure tone
audiometry; 3) enhanced vestibular-evoked myogenic potential
(VEMP) responses (low cervical VEMP thresholds or high ocu-
lar VEMP amplitudes). Must have high resolution temporal
bone CT imaging with multiplanar reconstruction demonstrat-
ing superior canal dehiscence. Must not be better accounted for
by another disorder.
a SCDS b VP c TIA
Vertebral artery
dissection
Dehiscence of the
superior canal
Neurovascular
Compression of CN8
Fig. 6.11 Differential diagnosis of the episodic vestibular syndrome: (a)

Superior canal dehiscence syndrome (SCDS), in addition to the typical clini-
cal features, a dehiscent superior (anterior) semicircular canal should also be
visualized on CT (yellow arrows) as seen in this Dyna CT (flat panel CT with
reconstruction in the plane of the left superior canal—note that this can be an
incidental finding [image courtesy of Dr. John Carey]); (b) Vestibular parox-
ysmia (VP), in addition to the typical clinical features, neurovascular com-
pression involving the eighth cranial nerve is usually identified, especially on
heavily T2-weighted, high-resolution imaging (arrow points to a dolichoec-
tatic basilar artery that was in contact with the left eighth nerve—note that
this can be incidental finding); (c) Transient ischemic attack (TIA)—urgent
evaluation is indicated when a vestibular TIA is suspected to exclude high-
grade posterior circulation stenosis (e.g., due to dissection or atherosclerosis)
• Valsalva (inhibitory nystagmus—upbeat- torsional) and

pinched-nose Valsalva (excitatory nystagmus—downbeat-tor-
sional);
• Tullio’s phenomenon (symptoms/nystagmus triggered by loud
sounds);
• Hennebert’s sign (triggered by pressure in the external auditory
canal—i.e., tragal compression);
• Due to supranormal bone conduction, a tuning fork placed on
the medial malleolus can often be “heard” in the affected ear
(a + malleolus sign).
Pitfalls: SCDS results from the creation of a third mobile window,

allowing for the passage of sound and pressure to cause endolymph
flow and resultant symptoms/signs. While SCDS is primarily epi-
sodic, autophony and disequilibrium can be chronic symptoms.
While patients with clinical features of SCDS are commonly misdi-
agnosed, an incidentally found superior canal dehiscence seen on
CT temporal bones is not uncommon—if symptoms and signs of
SCDS are not seen, these patients should not be referred for sur-
gery. Patients may be referred to ophthalmology or neuro-ophthal-
mology due to their experience of autophony including pulsatile
tinnitus (i.e., concern for elevated intracranial pressure, rule out
papilledema) or eye movements that are audible to the patient.
Do not miss this! A perilymph fistula is another labyrinthine abnor-

mality that may cause similar symptoms. The underlying mechanism
is thought to relate to (1) fracture of the bone of the capsule separating
the inner from middle ear and mastoid, or (2) disruption of the bone or
membranes around the oval or round windows. Sensorineural hearing
loss, vertigo attacks, and chronic disequilibrium can be manifesta-
tions, with etiologies including congenital, following stapedectomy or
trauma. The diagnosis and surgical interventions are somewhat con-
troversial because diagnostic criteria are not well defined. Vestibular
atelectasis is another condition that can cause sound or pressure-
induced symptoms, and is characterized by hearing loss and bilateral
vestibular loss (low frequency vestibulo-ocular reflex [calorics] is
often more affected than at high frequencies [head impulse test]).
Commonly, patients with vestibular migraine are sensitive to loud
sounds (in addition to bright lights); however, this should be distin-

guished from SCDS attacks that are triggered by loud sounds.
What is next? Audiogram—air-bone gap with supra-normal

bone conduction; vestibular-evoked myogenic potentials
(VEMPs)—lowered threshold to elicit cervical and ocular VEMPs;
CT temporal bones looking for the dehiscence.
Relevant audiovestibular testing: ESM 6.1.
Treatment options: Surgery to patch or plug the dehiscence

depends entirely on the severity of the symptoms.
6.5.2.2 Spontaneous, Episodic Vestibular Syndrome

(ESM 6.8, 6.9)
Vestibular Migraine (VM)

Case: A 50-year-old woman presented to clinic after experienc-
ing 10 episodes of hours-long vertigo attacks that were associated
with throbbing headache, photophobia and phonophobia without
aural symptoms. She had a history of motion sickness and migraine
headaches in her teenage years. Video head impulse test (vHIT)
and bedside vestibular and ocular motor examinations were nor-
mal, and she was diagnosed with vestibular migraine. She pre-
sented to the emergency department during a typical hours-long
attack at which time repeat vHIT was normal and VOG showed no
spontaneous, gaze-evoked, or head-shaking-induced nystagmus.
However, there was persistent positional (7°/second peak slow
phase velocity) downbeat-torsional (top poles toward the right ear)
nystagmus in right and left Dix-Hallpike, with milder downbeat-
torsional nystagmus with straight head-hanging and prone posi-
tions. While her vertigo was continuous, head movements
(including positional maneuvers) aggravated her vestibular symp-
toms (rather than triggering them). In her case, vestibular migraine
explained both her ongoing vestibular symptoms and positional
nystagmus. The positional nystagmus had resolved when she was
seen in clinic the following week and a preventive migraine medi-

cation was initiated.

• Remote or current migraine headaches?
• Even in the absence of headache during an attack, some combi-
nation of photophobia, phonophobia and/or visual aura is often
present.
• Ask about motion (e.g., car sickness) and visual (e.g., 3D mov-
ies, action movies) sensitivities as well.
• Symptoms of vestibular migraine vary widely and may consist
of vertigo, dizziness, lightheadedness, imbalance, rocking,
swaying, feeling of being on a boat or other.
• Aural symptoms including tinnitus, fullness, popping, pain,
pressure, hearing loss (subjective aural symptoms are common
in VM, but patients should not have measurable hearing loss)?
Diagnostic criteria: (1) at least 5 episodes of vestibular symp-

toms (moderate-severe intensity) lasting 5 min-72 hours; (2) cur-
rent or remote migraine history meeting International
Classification of Headache Disorders criteria; (3) one or more
migraine features with >50% of episodes including: a) headache
with at least 2 of the following—unilateral, pulsating, moderate-
severe pain, aggravated by physical activity, b) photophobia and
phonophobia, c) visual aura; (4) not better accounted for by
another diagnosis. For probable VM, (1) >5 episodes of vestibular
symptoms (moderate-severe) lasting 5 min-72 hours; (2) only one
of the criteria (2) and (3) (above) for VM is fulfilled (migraine
history or ictal migraine features); (3) not better accounted for by
another diagnosis.
Key findings to elicit: Inter-ictally, the neurologic, audiologic

and ocular motor exams should be normal. Occasionally, weak
nystagmus will be seen with fixation-removed between attacks,
especially, with head-shaking or positional maneuvers. A variety
of patterns of nystagmus can be seen during vestibular migraine
attacks including spontaneous horizontal, upbeat, or downbeat
nystagmus, with positional nystagmus being especially common.
Similar to patients with persistent postural perceptual dizziness, it

is common that symptoms are aggravated (or provoked) in the
clinic by visual stimulation with an optokinetic flag/drum, although
optokinetic nystagmus is normal.
Pitfalls: If a patient has recurrent vertigo and mild subjective

auditory symptoms (without objective hearing loss), they are much
more likely to have vestibular migraine as compared to Menière’s
disease. However, audiogram is important to evaluate for low to
medium-frequency sensorineural hearing loss (below 2000 Hz),
which is suggestive of Menière’s disease.
Do not miss this! If a patient with vertigo has sudden, severe,

or sustained head or neck pain, be concerned about a vertebral
artery dissection, especially with preceding head/neck trauma.
Patients with posterior fossa transient ischemia attacks or isch-
emic stroke may also experience headaches. Be concerned by a
patient presenting with a first episode of headache and dizziness
(especially older)—the diagnosis of VM cannot be made based
on 1 attack, and other etiologies must be excluded (e.g., mass
lesion, vascular event, and giant cell arteritis). Consider the pos-
sibility of a VM mimic that is responsible for audiovestibular
symptoms and headaches such as Susac syndrome (also with
vision loss from branch retinal artery occlusions, cognitive
changes, cannonball/snowball callosal lesions seen on sagittal
MRI), lupus/antiphospholipid antibody syndrome, Sjogren’s
syndrome, mitochondrial encephalopathy lactic acidosis and
stroke-like episodes (MELAS), cerebral autosomal dominant
arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL), episodic ataxia type 2/hemiplegic migraine/spino-
cerebellar ataxia type 6 (can all be associated with the P/Q-type
calcium channel gene, CACNA1A).
Is there a cervicogenic component? Of note, patients with VM

commonly endorse cervical discomfort. This may be due in part
to the headache syndrome itself, but also as head motion intoler-
ance develops and patients stop moving the head normally, neck
stiffness, spasm and soreness can develop. While the diagnosis of
cervicogenic dizziness/vertigo is controversial, following a

whiplash injury (or related to cervical spine disease), it is possi-
ble that abnormal sensory input from neck proprioceptors could
be responsible for vestibular symptoms triggered by head move-
ments, since it has been shown that sensory information from the
neck is combined with visual and vestibular afferents to deter-
mine head and neck orientation relative to space and gravity.
Physical therapy can be beneficial for cervicogenic symptoms.
What is next? If there is a long and strong history of migraine,

and neurologic, otologic, ocular motor and vestibular exams are
normal without red flags (e.g., a change in headache quality), then
no testing may be needed. If any aural symptoms are endorsed,
audiogram is needed. Remember that the diagnosis of vestibular
migraine also includes that the vestibular symptoms are not better
accounted for by another diagnosis. Therefore, if there is any
uncertainty, the clinician should have a low threshold to order con-
trast-enhanced MRI, with attention to the internal auditory canals.
There is no specific audiovestibular laboratory testing pattern that
is suggestive of VM, although these patients tend to be very sensi-
tive to (and symptoms are often aggravated or provoked by) rotary
chair and caloric testing.
Relevant audiovestibular testing: Audiometry when aural

symptoms are present, rotary chair test can demonstrate prolonged
time constants, and non-localizing nystagmus (especially posi-
tional) can be seen with VOG/VNG, but none of these are diagnos-
tic (ESM 6.1, 6.3, and 6.4):
Treatment options: Essentially the same as for migraine head-

aches—for example, lifestyle and dietary modifications, vitamins/
supplements, a variety of migraine preventive medications
(although large scale randomized controlled trials are lacking).
Abortive medications like triptans may benefit some patients, and
it is reasonable to try these if the patient has prodromal symptoms
prior to their typical attacks. Given the frequency of visual sensi-
tivity/visual vertigo in VM (a feature of other vestibular disorders
as well) occasionally, a visual desensitization (optokinetic stimu-
lation) home program can be beneficial although strong evidence

for its use is lacking. ESM 6.9.
If you can only remember one thing… Although VM is an

extremely common cause of vestibular symptoms (especially in
the young), be careful attributing symptoms to migraine in older
patients or in the acute setting (especially when odd patterns of
nystagmus are seen)—do not overlook a potentially dangerous dis-
order like vertebral artery dissection!
Want to know more? [33, 41–45]
Menière’s Disease (and Hearing Loss)

Case: One year prior to presentation, a 50-year-old man experi-
enced the abrupt onset of symptoms described as “the world
spinning” with associated nausea and vomiting lasting for
30 minutes. There was a preceding fullness and tinnitus in the
right ear, which partially resolved once the vertigo subsided. His
wife noticed “movement of the eyes” during these attacks, and a
home video taken during a typical attack showed robust sponta-
neous left-beating nystagmus. Since that time identical episodes
have occurred about every 2–4 weeks, always associated with
aural symptoms on the right, with a noticeable decline in hearing
in the same ear since the attacks began. He wonders if several
episodes were associated with the consumption of a meal that
was particularly high in sodium. In the last few months, he began
experiencing episodes of “collapse”, where without warning, he
would feel that he was being forced or pushed to the ground
without loss of consciousness. Audiogram demonstrated low-
frequency sensorineural hearing loss in the right ear, and there
was mild caloric weakness in the right ear although bedside and
video head impulse testing (vHIT) was normal bilaterally. He
was diagnosed with Menière’s disease (MD), and the frequency
of attacks diminished with sodium restriction in addition to pre-
scription of a diuretic.
Key questions to ask: Aural symptoms including hearing loss,

tinnitus, fullness, popping, pressure should be present in
Menière’s disease, and are typically associated with recurrent
bouts of vertigo. Remember that patients with vestibular migraine

will often have subjective aural symptoms without objective
hearing loss—always ask about a history of migraine headaches,
and associated migraine features during attacks (headache,
photo/phonophobia). Vestibular migraine and Meniere’s disease
may also co-exist in the same patient. Consider the possibility of
labyrinthine transient ischemia attacks (TIAs) in older patients
with audiovestibular episodes, especially when vascular risk fac-
tors are present. Ask about sudden drop attacks without loss of
consciousness (otolithic crises of Tumarkin), which may occur
with MD, although be aware that drop attacks can rarely be a
symptom of TIA as well.
Diagnostic criteria: Definite MD: (1) Two or more unprovoked

vertigo attacks lasting 20 minutes to 12 hours; (2) Audiogram
documents low- to medium (below 2000 Hz) frequency sensori-
neural hearing loss in one ear on at least one occasion before,
during or after one of the vertigo attacks; (3) Fluctuating hear-
ing, tinnitus or fullness in the affected ear; (4) Symptoms are not
better accounted for by another disorder. Probable MD: (1) Two
or more unprovoked vertigo attacks lasting 20 minutes to
24 hours; (2) Fluctuating aural symptoms (hearing, tinnitus or
fullness) in the affected ear; (3) Symptoms are not better
accounted for by another disorder.
Key findings to elicit: Normal neurologic and ocular motor

examination. Sensorineural hearing loss with Rinne and Weber
with normal otoscopy, and no characteristic vestibular features on
bedside exam (e.g., head impulse test is usually normal unless
intratympanic gentamicin was used), although weak fixation-
removed nystagmus (slow phase may or may not be toward the
side of the caloric weakness and hearing loss) is common along
with mild to moderate head-shaking nystagmus. Commonly, a
reversal of spontaneous nystagmus can be seen during the ictal
phase, as the initial excitatory/irritative (“wrong way”) ipsilesional
nystagmus converts to an inhibitory contralesional nystagmus.
Spontaneous horizontal nystagmus during a MD attack is usually
quite robust as compared to vestibular migraine, which tends to be
milder (also, migraine attacks may be associated with spontaneous

vertical or positional nystagmus). Occasionally, downbeat nystag-
mus during a MD attack can be seen, perhaps due to posterior
semicircular canal and/or saccule involvement.
Pitfalls: Remember that a patient with recurrent vertigo who

endorses subjective aural symptoms but lacks low-medium fre-
quency sensorineural hearing loss is much more likely to have ves-
tibular migraine—always ask about associated features and
migraine history! MD and vestibular migraine can also co-exist.
My patient has hearing loss…where do I start? First, is the

onset gradual (months to years) or abrupt (hours to days)? 1) It is
gradual—first, is it asymmetric or symmetric? a) If asymmetric and
conductive or mixed, consider otosclerosis, cholesteatoma, ossicu-
lar chain discontinuity, superior canal dehiscence syndrome. b) If
asymmetric and sensorineural, consider vestibular schwannoma
and Menière’s disease. c) If gradual and symmetric, consider age or
noise-related hearing loss (which may also be asymmetric). 2) It is
acute—first, is it accompanied by vertigo? a) When associated with
vertigo, consider AICA territory/labyrinthine ischemia with ver-
tigo, acute hearing loss and normal otoscopy. Consider labyrinthitis
(bacterial or viral especially with abnormal otoscopy), and sudden
sensorineural hearing loss with or without vertigo. b) When hearing
loss is in isolation (without vertigo), consider benign conditions
including cerumen impaction, acute otitis externa and media (with
or without effusion). If hearing loss follows trauma, exclude a tem-
poral bone fracture or labyrinthine concussion. If hearing loss
occurs in the setting of fever, nuchal rigidity and other meningitic
symptoms, obtain lumbar puncture to rule out meningitis (Fig. 6.2).
Do not miss these conditions that also cause vertigo and hear-
ing loss! Never assume that a first attack of audiovestibular symp-
toms is due to MD—in fact, in a patient (especially with vascular
risk factors) with acute onset prolonged vertigo and hearing loss
with a normal otoscopic examination, assume labyrinthine (ante-
rior inferior cerebellar artery) ischemia until proven otherwise.
Consider other treatable conditions that can cause hearing loss and
vestibular attacks including otosyphilis, autoimmune inner ear dis-

ease (e.g., Sjogren’s syndrome), Susac and Cogan syndromes
(with associated vision loss from branch retinal artery occlusions
and interstitial keratitis, respectively), granulomatosis with poly-
angiitis, ANCA-positive vasculitis, sarcoidosis, relapsing poly-
chondritis, Vogt-Koyanagi-Harada disease (uveitis, retina and
optic nerve involvement), Lyme disease, meningitis (infectious
and cancer-related), vestibular paroxysmia (although these epi-
sodes are typically <1 minute), third window syndromes (peri-
lymph fistula, canal dehiscence, enlarged vestibular aqueduct).
While a vestibular schwannoma typically presents with gradual
unilateral hearing loss and imbalance, occasionally, vertigo attacks
are the presenting symptom.
What is next? An audiogram should be performed in all vestibu-

lar patients who endorse aural symptoms. Contrast-enhanced MRI
with IAC protocol should be performed in any patient where diag-
nostic uncertainty exists to rule out vestibular schwannoma and
other structural lesions. Cervical vestibular-evoked myogenic
potentials may be delayed or absent, although this is also not diag-
nostic of MD. In MD, while there is typically caloric weakness ipsi-
lateral to the side of the hearing loss, HIT/vHIT is usually normal.
Reasons for (dissociated) normal HIT/vHIT and abnormal calorics
in MD include: (1) they assess two different VOR responses—vHIT
stimulates high frequencies and calorics stimulate low frequencies;
(2) the underlying hydropic pathology in MD causes the horizontal
semicircular canal duct to distend, resulting in a smaller thermally
induced pressure gradient across the cupula with minimal no effect
on responses when rotating the head.
Relevant audiovestibular testing: Audiometry is most impor-

tant, although VEMPs and calorics can also demonstrate abnor-
malities (ESM 6.1, 6.2, 6.3, 6.5, and 6.6):
Treatment options: Reasonable recommendations include

(evidence for each is relatively weak): low sodium diet
(<2000 mg/day, ideally <1500 mg/day), caffeine reduction,
smoking cessation, stress reduction, betahistine (not available in
the United States) and/or diuretic therapy. Intratympanic steroid

injections are an option if conservative measures fail, and intra-
tympanic gentamicin treatment is generally used as a last resort.
Vestibular Paroxysmia
Case: A 90-year-old man presented to clinic complaining of epi-
sodic vertigo for the last 2 months. Attacks occurred multiple
times daily, were stereotyped and consisted of spinning vertigo
for <60 seconds that was associated with nausea, head motion
intolerance, imbalance and tinnitus in the left ear that sounded
like “an engine starting”. There were no associated neurologic or
migrainous symptoms, and no aural symptoms other than tinnitus.
He found that sometimes moving his head by turning to the right
or to the left could mitigate tinnitus during the attacks, while other
times a head movement may be the trigger for vertigo. Given his
sedentary lifestyle, he was unaware of an association between his
attacks and exertion or exercise. However, most of his episodes
were unprovoked. Neurologic and ocular motor examination was
unremarkable, and with hyperventilation, there was mild-moder-
ate left-beating nystagmus. During video-oculography exam, he
began to have a typical attack where he noted that the left ear
“engine” noise began, followed closely by the vertigo. With fixa-
tion-removed, there was prominent spontaneous left-beating nys-
tagmus and vertigo for 45 seconds. An MRI had already been
performed several weeks prior, and a dolichoectatic basilar artery
was clearly in contact with the left seventh and eighth cranial
nerves. He had no symptoms or signs of hemifacial spasm on the
left side, and a clinical diagnosis of vestibular paroxysmia (VP)
(neurovascular compression of the eighth cranial nerve) was
made. Audiogram demonstrated bilateral sloping high-frequency
sensorineural hearing loss, thought to be due to aging and previ-
ous noise exposure. Video head impulse and caloric testing was
within normal limits. Low-dose gabapentin (given his age and
other medications, carbamazepine or oxcarbazepine were
avoided) was prescribed, which led to a decrease in the frequency
and intensity of attacks.
Image: Figure 6.10.
Key questions to ask: Attacks of VP tend to be brief, lasting sec-

onds to several minutes, and may occur many times each day.
Episodes are often spontaneous, but can be provoked by certain head
movements (may cause more compression of the eighth nerve) or
with exercise/exertion (either due to hyperventilation or increased
blood pressure transmitted to the vessel that is in contact with the
nerve). Aural symptoms of fullness, pressure or tinnitus (may have a
“typewriter” quality) tend to occur simultaneously with the vestibular
symptoms given involvement of both vestibular and cochlear fibers.
Diagnostic criteria: Each of the following must be fulfilled: (1)

10 or more attacks or spontaneous spinning or nonspinning ver-
tigo; (2) <1 minute in duration; (3) attacks are stereotyped in a
particular patient; (4) response to treatment (carbamazepine/oxcar-
bazepine); (5) not better accounted for by another diagnosis. For
probable VP: (1) 5 or more episodes; (2) <5 minutes; (3) spontane-
ous occurrence or provoked by certain head movements; (4)
attacks are stereotyped; (5) not accounted for by another diagnosis.
Key findings to elicit: Hyperventilation-induced nystagmus

(tends to be in an excitatory pattern—ipsilesional—as in this
patient), and mild nystagmus can variably be induced by certain
head positions.
Pitfalls: This is a treatable cause of vertigo, but requires a high index

of suspicion. This may overlap with other short-lived causes of ves-
tibular dizziness including benign paroxysmal positional vertigo (both
may be triggered by certain head movements/postures) and superior
semicircular canal dehiscence (where aural symptoms are also com-
mon). Of note, a blood vessel that is in proximity to (or in contact
with) the seventh and eighth cranial nerves on high resolution heavily
T2-weighted FIESTA or CISS images is a common (incidental)
occurrence. In the dizzy patient, the question is whether this finding is
causal or coincidental, and in many cases it is the latter.
Do not miss this! Minutes-long attacks of dizziness and aural

symptoms in a patient with vascular risk factors should also raise
suspicion for labyrinthine transient ischemic attacks. Exertion/

exercise-induced dizziness should raise suspicion for a cardiopul-
monary etiology. Unprovoked brief episodes of dizziness or ver-
tigo may also be due to cardiogenic vertigo—attempt to capture
attacks with a cardiac monitor when symptoms are not clearly ves-
tibular.
What is next? There is no specific pattern of audiovestibular dys-

function. Patients may have evidence of mild unilateral vestibular
loss with vHIT and calorics or unilateral hearing loss seen with
audiometry. If nystagmus (e.g., hyperventilation-induced) is seen,
it may be excitatory (ipsilesional) or inhibitory (contralesional).
Brainstem auditory evoked potentials may demonstrate an ipsile-
sional deficit, but this is not diagnostic.
Relevant audiovestibular testing: Audiometry and some evalu-

ation of the VOR should be performed although abnormal findings
are typically mild or absent. There may be mild unilateral vestibu-
lar loss in some cases. Hyperventilation during VOG/VNG should
be performed (ESM 6.1, 6.2, 6.3, 6.5, and 6.6):
Treatment options: Trial of an antiseizure medication (carbam-

azepine/oxcarbazepine, lamotrigine, gabapentin, others) can be
both diagnostic and therapeutic.
Want to know more? [51, 52, 53]
Vestibular Transient Ischemia Attack (TIA)

Case: A 65-year-old man with a history of hypertension pre-
sented to the emergency department (ED) after experiencing a
20 minute-long attack of vertigo, nausea and vomiting, in addition
to hearing loss in the right ear (which returned to normal by the
time he reached the ED). There was no head or neck pain, light/
sound sensitivity, neurologic or aural symptoms. Blood pressure
was 150/90, and vital signs were otherwise normal. His ABCD2
score (A = age; B = blood pressure; C = clinical features; D = dura-
tion of symptoms; D = diabetes) was calculated as a 3 (1 for
age > 60 years; 1 for blood pressure > 140/90; 0 for clinical fea-
tures [no weakness or speech disturbance]; 1 for duration
10–59 minutes; 0 for diabetes), and suspicion was high for a tran-

sient ischemic attack (TIA). MRI and MR angiography were unre-
markable, although telemetry demonstrated that he was going in
and out of asymptomatic atrial fibrillation (AF). It was felt that his
AF explained a TIA of the right labyrinth.
Image: Figure 6.10.
Key questions to ask: Patients with the acute transient vestibular

syndrome (<24 hours) or episodic vertigo lasting minutes to hours
of unclear etiology should be risk stratified using the ABCD2
score. When equal to or higher than 4, TIA should be strongly
considered. However, patients with a lower (or any) ABCD2 score
can also have a vestibular TIA. Inquire about previous attacks and
hearing loss (consider Menière’s disease) and migraine symptoms/
history.
Key findings to elicit: In a patient presenting with episodes or a

single attack lasting <24 hours (also referred to as the acute transient
vestibular syndrome) who is symptomatic at the time of the evalua-
tion and has spontaneous nystagmus, the HINTS examination can be
applied. In other patients who are asymptomatic at the time of evalu-
ation and/or when spontaneous nystagmus is absent, the HINTS
exam cannot be applied, and typically neurologic and ocular motor/
vestibular evaluation will be unremarkable. The history is most
important in the “spontaneous” episodic vestibular syndrome.
Pitfalls: While posterior circulation symptoms should be sought

(hearing loss, dysarthria, weakness, numbness/tingling, diplopia,
vision loss, etc.), about 10–20% of the time, vestibular symptoms
due to a TIA occur in isolation.
Do not miss this! A patient with preceding head/neck trauma or

new severe head/neck pain with constant or episodic vertigo should
be assumed to have a vertebral artery dissection until proven oth-
erwise. Vestibular migraine and Menière’s disease also last from
minutes to hours and should be considered, but these diagnoses
cannot be made in a patient with a first attack of vertigo. Consider
dangerous conditions first!
What is next? Even if the patient is asymptomatic and/or symp-

toms referable to the posterior circulation are absent, TIA should
be strongly considered, especially in older patients, when vascular
risk factors are present, when the ABCD2 score is 3–4 or higher,
and when a peripheral vestibular disorder cannot be clearly identi-
fied (young people can have strokes and TIAs too!). Evaluation
should include MR with diffusion-weighted imaging to look for
evidence of ischemia, which if present, may also be suggestive of
etiology—for example, if bihemispheric and in multiple vascular
distributions, think cardioembolic. Angiography (MRA or CTA)
of the head and neck is also needed to evaluate for atherosclerosis
and dissection. Cardiac evaluation should include transthoracic
echocardiogram as well as cardiac monitoring.
Treatment options: This depends on the mechanism of TIA

which is why an expeditious workup is so important to prevent
further vascular events.
Advanced: A rare manifestation of TIA/stroke (or vestibular

migraine) is a room tilt illusion (RTI). This usually consists of
flipping or tilting, and is a transient disorder of environmental
visuo-spatial perception consisting of paroxysmal (usually) tilting
of the visual scene off the true vertical, without any alteration in
objects’ color, shape or size. Images may rotate in the coronal roll
plane, or in the sagittal pitch plane. Ischemic or hemorrhagic
(usually posterior fossa), demyelinating, infectious, autoimmune,
epileptic, traumatic, toxic (medications included), neoplastic,
neurodegenerative disorders and migraine have been reported to
cause RTI because of central nervous system or peripheral ves-
tibular system lesions (occasionally attributed to peripheral nerve
pathology as well).
Want to know more? [14–16, 54–58]
6.5.3 Chronic Vestibular Syndrome
The approach (history and exam) to the patient with chronic

dizziness or vertigo: Table 6.5
Table 6.5 Help me now with chronic dizziness & vertigo: Typical historical and exam features with common diagnostic
286
considerations
Aggravating or
alleviating factor(s) Symptoms/signs Exam findings Test
Bilateral vestibular loss Aggravate: Head Imbalance and head Abnormal HIT Video HIT, rotational chair
(BVL, or poorly movements dependent (“walking”) bilaterally, loss of 4 or test and/or calorics (these
compensated unilateral oscillopsia with walking or more lines with tests are complementary,
vestibular loss) movements; vertigo is dynamic visual acuity, not interchangeable);
absent if vestibulopathy is unsteady gait, unable VEMPs may be helpful in
bilateral and simultaneous to stand on foam with certain cases to evaluate the
eyes closed; look for pattern of otolithic
cerebellar signsa involvement; contrast-
enhanced MRI when there
is no clear inciting event
(e.g., gentamicin)
Mal de debarquement Alleviate: passive Feeling of rocking, Unsteadiness is A clinical diagnosis (see
syndrome (MdDS) motion (passenger in swaying, “being on a boat,” common, without Diagnostic Criteria in
a car) following prolonged travel peripheral or central MdDS section)
(e.g., cruise) vestibular findings
Persistent postural Aggravate: upright Non-spinning dizziness, Unsteadiness is A clinical diagnosis (see
perceptual dizziness posture, visual tasks imbalance common, normal exam Diagnostic Criteria in
(PPPD) requiring focus, unless the inciting PPPD section)
visual stimulation even was vestibular
(e.g., vestibular
neuritis)
Cerebellar dizziness Aggravate: motion of Dizziness/vertigo and Look for features of a Contrast-enhanced MRI
head or body imbalance, head vestibulocerebellar with attention to the
independent (“sitting”) syndrome: gaze- posterior fossa; consider
oscillopsia with evoked and rebound audiometry (superficial
spontaneous nystagmus nystagmus, impaired siderosis with CN8
pursuit and VOR involvement); autonomic
suppression, saccadic testing (MSA); vestibular
dysmetria, testing (CANVASa); EMG/

spontaneous DBN, NCS (CANVAS); consider
alternating skew labs for nutritional,
deviation; look for autoimmune, inflammatory,
features of paraneoplastic; differential
oculopalatal tremor: diagnosis will depend on
pendular nystagmus, timing, associated signs,
palatal tremor family history
HIT head impulse test, VEMPs vestibular evoked myogenic potentials, VOR vestibulo-ocular reflex, DBN downbeat nystagmus, CN8
cranial nerve 8, MSA multiple system atrophy, CANVAS cerebellar ataxia, neuropathy, vestibular areflexia syndrome, EMG/NCS elec-
tromyogram/nerve conduction studies
a
If a patient presents with prominent features of BVL, evaluate for cerebellar signs (see “Cerebellar dizziness”). Likewise, if a patient
presents with prominent features of a cerebellar disorder, evaluate the vestibular system. In both situations, a condition that involves
vestibular and cerebellar systems—like cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS)—could be to blame
287
6.5.3.1 Persistent Postural Perceptual Dizziness

Case: A 60-year-old woman presented to clinic with 6 months of
constant daily dizziness. Just prior to her chronic daily symptoms,
she experienced positional vertigo and was diagnosed with benign
paroxysmal positional vertigo (BPPV), which was treated several
times over the months given recurrences. Since the onset of these
attacks, she recalls having experienced a persistent non-spinning
feeling of dizziness “like I’m intoxicated” or “like a brain fog.” She
was prone to anxiety prior to developing BPPV, but now feels espe-
cially anxious and depressed. She has become very bothered by and
sensitive to action movies, movie theaters, and exposure to busy
environments like the mall or grocery store. The dizziness tends to
worsen throughout the day, is maximal when she is upright, and
improves when lying down. Contrast-enhanced MRI of the brain as
well as audiogram and video head impulse test were unremarkable.
Neurologic, ocular motor and vestibular examination was normal,
and she was diagnosed with persistent postural perceptual dizziness
(PPPD) that was thought to be triggered by recurrent BPPV. She
improved over months with the combination of a selective serotonin
reuptake inhibitor (SSRI) medication, vestibular physical therapy
and initiating cognitive behavioral therapy.
Key questions to ask: A variety of chronic non-spinning symp-

toms can be experienced in PPPD, and it is common that another
episodic vestibular syndrome (e.g., BPPV, vestibular migraine)
may co-exist. Triggers include complex visual stimuli, environ-
mental or self-motion, and an upright posture. While there is usu-
ally an inciting event—anything that affects balance or causes
dizziness/vertigo (including a medical or psychiatric event)—there
may not be a clear identifiable trigger in some. A pre-existing his-
tory of anxiety is common, or at least a particularly anxious
response to the inciting event.
Diagnostic criteria: Each of the following must be present: (1)

One or more symptoms of dizziness, unsteadiness, or non-spin-
ning vertigo, present most days for 3 or more months (symptoms
can be hours-long or continuous with waxing/waning intensity).
(2) Persistent symptoms occur without provocation, but are exac-

erbated by upright posture, active or passive motion, visual stim-
uli, or complicated visual patterns. (3) PPPD is precipitated by
conditions that cause dizziness/vertigo or imbalance that may be
vestibular, neurologic, psychological or medical (if the trigger is
acute or episodic, symptoms may be intermittent at first and
become continuous; if the trigger is a chronic disorder, symp-
toms may develop slowly at first and worsen gradually). (4)
Symptoms cause significant distress and/or functional impair-
ment. (5) Symptoms are not better accounted for by another dis-
order.
Key findings to elicit: Because the co-existence of other ves-

tibular conditions (e.g., BPPV) is common, or because a neuro-
vestibular event (e.g., cerebellar stroke) could be the inciting
event, the neurologic, vestibular and ocular motor exams may be
abnormal. However, there are no characteristic bedside exam or
laboratory findings to suggest PPPD per se. Similar to patients
with vestibular migraine, it is common that symptoms are aggra-
vated (or provoked) in the clinic by visual stimulation with an
optokinetic flag/drum, although optokinetic nystagmus is nor-
mal.
Pitfalls: PPPD is a relatively common and often misdiagnosed

condition. Although anxiety and depression are common, this is
not a psychiatric diagnosis, but rather a neuro-otologic diagnosis
with characteristic behavioral features.
Do not miss this! Do not diagnose PPPD in every chronically

dizzy patient—for example, patients with cerebellar pathology
may also experience a chronic dizziness, as well as patients with
medical conditions (postural orthostatic tachycardia syndrome,
orthostatic intolerance/hypotension), or due to the effects of medi-
cations. A patient with PPPD may experience other chronic symp-
toms (pain, headaches, tinnitus, visual snow, etc.); therefore, some
patients may become globally sensitized and develop one or more
chronic syndromes.
What is next? When diagnostic uncertainty exists, excluding a

structural cause (contrast-enhanced MRI IAC protocol) and objec-
tive audiovestibular abnormalities (with audiogram and vestibular
testing) may be indicated.
Treatment options: A combination of reassurance (making the

diagnosis can also prevent unnecessary and potentially costly test-
ing), SSRI/serotonin and norepinephrine reuptake inhibitor
(SNRI), vestibular physical therapy (for head motion intolerance,
visual hypersensitivity, and treatment of co-existing vestibular
pathology such as BPPV or unilateral vestibular loss), in addition
to psychological therapy (cognitive behavioral or health psychol-
ogy) generally leads to improvement over time. Given the fre-
quency of visual sensitivity/visual vertigo (presumably due to
visual dependency, also common in vestibular migraine and may
occur in other vestibular conditions), occasionally, a visual desen-
sitization (optokinetic stimulation) home program can be helpful
to mitigate visual symptoms although strong evidence for its use
is lacking. ESM 6.9.
6.5.3.2 Mal de Debarquement Syndrome

Case: A 40-year-old woman presented to clinic with chronic
daily symptoms of feeling like she is “on a boat” for the last three
months, which developed immediately following a one week
cruise. She also admitted to feelings of rocking, bobbing, and
swaying, which abated when she was the passenger in a car. She
experienced worsening of these symptoms when she was in com-
plicated visual environments (e.g., grocery store or mall). Contrast-
enhanced MRI of the internal auditory canals, audiometry and
vestibular testing were normal, and she was diagnosed with Mal de
Debarquement syndrome (MdDS). There was resolution of symp-
toms with a low dose of long-acting daily benzodiazepines, which
were slowing tapered off several months later without recurrence
of symptoms.
Key questions to ask: MdDS is characterized by chronic feelings

of being on a boat, rocking, bobbing and swaying that abate with
passive motion (i.e., passenger in a car). These sensations are
almost always preceded by a cruise, long car ride or flight. When
an inciting event/travel is lacking, consider other etiologies.
Diagnostic criteria: (1) Non-spinning vertigo with rocking,

swaying, or bobbing that is present continuously or more often
than not. (2) Onset is within 48 hours of exposure to passive motion
(e.g., cruise). (3) Reduction in symptoms with passive motion. (4)
Symptoms persist for >48 hours with three classifications: (a)
symptoms are continuous but the onset was <1 month ago (“in
evolution”), (b) symptoms resolve within a month (“transient”),
(c) symptoms persist for >1 month (“persistent”). (5) Symptoms
are not better accounted for by another disorder.
Key findings to elicit: There are no typical bedside ocular motor

or vestibular findings in MdDS.
Pitfalls: Do not assume that every patient who feels like they are
“on a boat” have MdDS—symptoms of rocking, swaying, bobbing,
etc., may be experienced in patients with vestibular migraine (VM)
or persistent postural perceptual dizziness (PPPD).
Do not miss this! There can be significant overlap between the

symptomatology of MdDS, VM, and PPPD including the quality
of symptoms and visual hypersensitivity.
What is next? There is no characteristic pattern of audiometric or

vestibular laboratory findings in MdDS.
Treatment options: Low-dose long-acting benzodiazepines

(e.g., clonazepam) may be used for treatment and for prophy-
laxis—for example, MdDS symptoms have resolved completely,
but the patient plans on going on another cruise and is fearful of a
recurrence. Newer therapies rely on the concept of vestibulo-
ocular reflex re-adaptation. Simply put, the treatment consists of
moving the visual surroundings while the head is rolled right and
left at the same frequency as the patient’s symptoms.
6.5.3.3 Multifactorial Dizziness and Imbalance

Case: An 80-year-old diabetic man presented with 5 years of pro-
gressive imbalance and a mild non-spinning intermittent dizziness,
that worsens when walking in the dark and on uneven surfaces such
as grass and sand. There was not a strong postural component to the
dizziness, nor did he experience sensitivity to visual stimulation. He
denied severe attacks of dizziness or vertigo. He has experienced
numbness and tingling in his feet for the last several years, thought
to be related to diabetic neuropathy. He was diagnosed with open
angle glaucoma 10 years ago, which has led to mild to moderate
bilateral visual field loss. Ocular motor and vestibular exam were
unremarkable with the exception of mildly saccadic smooth pursuit,
and mild overt corrective saccades that could be appreciated with
bedside HIT as well as with video HIT (vHIT), which demonstrated
low-normal gains in the 0.6 range (where <0.7 is considered abnor-
mal). He lost two lines when dynamic visual acuity was assessed
horizontally and vertically, although head movement dependent
oscillopsia was not a symptom that he experienced. Contrast-
enhanced MRI demonstrated moderate chronic small vessel isch-
emic disease but was otherwise unremarkable. To evaluate for
reversible causes of peripheral neuropathy and mild vestibulopathy,
blood work was ordered to investigate for reversible/treatable causes
including nutritional deficiencies, thyroid disease, syphilis, among
others. It was felt that his unsteadiness was multifactorial, resulting
from a combination of impaired vision (glaucoma), impaired pro-
prioception/joint position sense (diabetic neuropathy), and mild ves-
tibular loss (perhaps related to diabetes and/or aging—that is, a
presbyvestibulopathy). He began vestibular physical therapy, and his
unsteadiness and dizziness improved with therapy and use of cane.
Key questions to ask: In an elderly patient with progressive

unsteadiness and/or dizziness, the following must first be excluded:
neurodegenerative disorders or structural lesions involving the pos-
terior fossa (e.g., ataxia, oculopalatal tremor) or basal ganglia (par-

kinsonism), myelopathy, neuropathy, and vestibulopathy. When
there is nothing specific in the history or on the exam to indicate any
one localization in particular, the etiology is often multifactorial and
due to multisensory impairment, especially in diabetics, which can
cause neuropathy, retinopathy, and (probably) mild vestibulopathy.
Worsening in the dark or in dim lighting is common in patients who
rely heavily on vision for balance and orientation given vestibular or
neuropathic (proprioceptive) deficits. Worsening on uneven surfaces
(which distorts proprioceptive inputs) is common in patients who
have impaired proprioception to begin with (e.g., neuropathy) or in
patients who rely heavily on proprioceptive cues (e.g., bilateral ves-
tibular loss, BVL - this explains why patients with BVL do so poorly
when asked to stand on a foam pad with eyes closed).
Diagnostic criteria for presbyvestibulopathy: All of the follow-

ing should be satisfied: (1) chronic vestibular syndrome for
>3 months, with at least 2 of the following symptoms: imbalance or
unsteadiness, gait disturbance, chronic dizziness, recurrent falls; (2)
mild bilateral peripheral vestibular hypofunction documented by
video head impulse test, calorics or rotary chair testing; (3) age 60
or older; (4) not better accounted for by another disease or disorder.
Key findings to elicit: A thorough general neurologic examina-

tion is essential in patients with progressive imbalance including
sensation, strength, coordination, tendon reflexes, gait assessment.
When the general neurologic exam is unrevealing, the ocular
motor and vestibular examinations often provide important clues
to the etiology (e.g., gaze-evoked nystagmus in cerebellar ataxia;
loss of the downward fast phase of optokinetic nystagmus early in
the course of progressive supranuclear palsy; bilaterally abnormal
head impulse test in bilateral vestibular loss; positional downbeat
nystagmus in multiple system atrophy). Symmetric mild corrective
saccades on the bedside or video head impulse test (with normal
vHIT gains) can be seen in some elderly patients and may simply
be a consequence of aging, although this finding should not be
associated with symptoms and signs of BVL (e.g., “walking”
oscillopsia and abnormal dynamic visual acuity, respectively).
Pitfalls: This is a situation where the patient’s symptoms may be

vague and non-specific, and taking the time to perform a compre-
hensive examination (including evaluation of orthostatic vital
signs) will often lead to the correct diagnosis (or diagnoses).
Assessing visual function (at least acuity and fields) is necessary to
identify any ocular pathology that could be contributing and ame-
nable to treatment (e.g., optic nerve cupping in glaucoma; a hazy
view of the fundus due to a dense cataract; retinal hemorrhages in
a diabetic patient with retinopathy).
Do not miss this! When there is diagnostic uncertainty, these

patients should be followed and re-assessed—for example, the
patient may have been experiencing the initial symptoms of an
evolving neurodegenerative disease with findings that were too sub-
tle to detect on the initial evaluation. Be especially concerned if the
onset is relatively abrupt—consider paraneoplastic and other poten-
tially dangerous disorders. Do not forget about other non-vestibular
factors that could be contributing including medical disease (e.g.,
cardiopulmonary), orthopedic/musculoskeletal (e.g., spinal steno-
sis), autonomic disorders causing significant orthostatic symptoms
and new or recently added medication (consider polypharmacy).
What is next? Contrast-enhanced MRI with attention to the

internal auditory canals is indicated in most if not all patients with
progressive imbalance to rule out a structural etiology such as ves-
tibular schwannoma or normal pressure hydrocephalus for
instance. If there is concern for a neurodegenerative disorder, cer-
tain MRI findings should be sought (e.g., “hot cross bun sign” in
multiple system atrophy). In patients with objective findings such
as neuropathy and vestibulopathy (as in the case above), revers-
ible/treatable etiologies should be excluded. Nutritional deficien-
cies (vitamin B12) should be considered as well.
Relevant audiovestibular testing: Audiometry and some evalu-

ation of the VOR is most helpful (ESM 6.1, 6.2, 6.3, 6.5, and 6.6).
Treatment options: Vestibular physical therapy to minimize the

risk of falls, use of an assistive device may be indicated.
6.5.3.4 Bilateral Vestibular Loss

Case: A 55-year-old man complained of head movement-induced
dizziness and jumping vision for the last 5 years. He noticed that
when walking down the street, the visual scenery bounced and
jumped. When seated with his head still, he was asymptomatic.
Examination demonstrated no spontaneous nystagmus or oscilla-
tions. There was no gaze-evoked nystagmus, and pursuit and sac-
cades were normal. Bedside head impulse test (HIT) demonstrated
visible refixation saccades bilaterally, and video HIT showed overt
correctives saccades in addition to abnormally low gains (0.18 to
the left and 0.38 to the right). His gait was wide-based and unsteady,
although there was no limb ataxia. Strength, tendon reflexes, and
sensation were normal. With both eyes open, he had 20/20 vision.
When the head was moved horizontally and vertically at 2–3 Hz,
the lowest line he could read on the eye chart was 20/60—there-
fore, with dynamic visual acuity (DVA) testing, he lost five lines of
visual acuity in both horizontal and vertical planes. He could stand
on a foam pad with eyes open for at least 10 seconds, and with
eyelid closure, he immediately lost balance. When questioned fur-
ther, he was admitted into the hospital 5 years ago (immediately
prior to symptom onset), at which time he was treated with genta-
micin for endocarditis. He was diagnosed with bilateral vestibular
loss (BVL) due to vestibulotoxicity from gentamicin. He denied
auditory symptoms and audiogram was normal as was a contrast-
enhanced MRI that included the internal auditory canals.
Video: Video 6.4 (Fig. 6.12).
Key questions to ask: Head-movement-induced (“walking”)

oscillopsia is the most characteristic symptom of BVL. Ask about:
• Medications (e.g., aminoglycosides, which could be ototoxic)

• Previous infections (e.g., meningitis)
• Trauma
• Previous diagnosis of unilateral vestibular loss (can rarely have
sequential vestibular neuritis)
Fig. 6.12 Video head impulse test demonstrating bilateral vestibular loss:
Bilateral vestibular loss is a common cause of head movement-dependent
oscillopsia, and in these patients, evaluating the vestibulo-ocular reflex
(VOR) is essential. While the bedside HIT is usually enough to make the
diagnosis of unilateral or bilateral vestibular loss, the video HIT has advan-
tages: 1) overt corrective saccades can be identified (occurring after the head
movement, visible to the examiner at the bedside, black arrow), 2) covert
corrective saccades can be identified (occurring during the head movement,
and can be invisible at the bedside, black arrowhead), 3) a gain can be calcu-
lated to quantify the VOR (gain = ratio of eye movement velocity to head
movement velocity, where typically a value below 0.6-0.7 is considered
abnormal). In this case, the gains in the planes of the left and right horizontal
(lateral) canals were 0.18 and 0.38, respectively, and consistent with bilateral
vestibular loss
• Hearing loss (e.g., bilateral Menière’s disease, Cogan’s syn-

drome, bilateral vestibular schwannomas in neurofibromato-
sis type 2, superficial siderosis [SS] if known cavernomas or
history of hemorrhage, include spinal trauma or hemorrhage).
Diagnostic criteria: (1) unsteadiness when walking or standing

(with head movement-induced blurred vision/oscillopsia and/or
worsening of unsteadiness in darkness and/or on uneven surfaces);
(2) no symptoms while sitting or lying (without head movement);
(3) bilaterally pathological horizontal VOR gain (<0.6) with video
HIT, or demonstrated by calorics or rotary chair testing; (4) not
better accounted for by another disease. Criteria for probable BVL
are the same although instead of bilateral hypofunction confirmed
with vHIT, calorics or rotary chair, the diagnosis relies on the bed-
side HIT being abnormal.
• Bedside HIT is almost always bilaterally abnormal (unless the

patient is using covert saccades to compensate);
• Loss of four or more lines with DVA;

• Inability to stand on a foam pad with eyes closed
• Wide based unsteady gait without limb ataxia.
Neurodegenerative conditions such as multiple system atro-

phy (MSA), spinocerebellar ataxia type 3 (Video 6.35), cerebel-
lar ataxia, neuropathy, and vestibular areflexia syndrome
(CANVAS) can cause BVL (perhaps due to flocculus and/or con-
comitant peripheral cranial nerve 8 involvement), which is why it
is so important to look for central ocular motor abnormalities
(and other neurologic signs) in the evaluation of these patients.
Poorly compensated unilateral vestibular loss will also cause
head movement dependent symptoms (often more horizontal
than vertical), but not to the extent that BVL patients will experi-
ence oscillopsia.
Pitfalls: While an abnormal HIT is usually peripheral, central eti-

ologies can occasionally cause this finding as well. Since the floc-
culus has a role in modulating the high-frequency vestibulo-ocular
reflex, a neurodegenerative disease affecting the flocculus can
cause bilaterally abnormal HITs. A patient with Wernicke’s
encephalopathy can present with BVL (mainly involving the hori-
zontal canals) and horizontal gaze-evoked nystagmus, because the
horizontal canal afferents synapse in the medial vestibular nucleus
(MVN), while the horizontal neural integrator is the nucleus prep-
ositus hypoglossi-MVN complex, respectively.
Do not miss this! If the onset is acute or subacute, consider bilat-

eral anterior inferior cerebellar artery ischemia, oto/vestibulotoxic
medications, thiamine deficiency, meningitis (infectious or lepto-
meningeal), paraneoplastic disorders (e.g., anti-Kelch-11 is a rare
cause of cerebellopathy, vestibulopathy and hearing loss in men
with a testicular seminoma).
What is next? If there was a clear inciting event (e.g., gentamicin),

then extensive workup is usually unnecessary, although baseline ves-
tibular (video HIT, calorics, rotary chair test) testing and audiogram
should be performed. In cases where there is no inciting event, con-
trast-enhanced MRI is needed to evaluate for bilateral tumors, cranial
nerve enhancement, hot cross bun sign (MSA), hemosiderin deposi-

tion within the cerebellum and/or along the eighth cranial nerves in
superficial siderosis, ischemia or features of Wernicke’s encephalop-
athy (when acute/subacute), specific patterns of cerebellar atrophy
suggestive of a particular ataxia (e.g., cerebellar ataxia, neuropathy,
vestibular areflexia syndrome, CANVAS).
Relevant audiovestibular testing: Each of the following tests

may play a role in the evaluation. VEMPs may help with the local-
ization in some cases (e.g., superior and/or inferior division
involvement) (ESM 6.1, 6.2, 6.3, 6.4, 6.5, and 6.6).
Treatment options: Once the treatable and reversible causes are

ruled out (e.g., vitamin B1 or B12 deficiency), vestibular physical
therapy is currently the best option, and some patients can experi-
ence significant adaptation and compensation while others may
not (usually older patients with other co-morbidities that impact
proprioception or vision). Use of vestibular suppressant medica-
tions should be minimized. Implanted vestibular prosthetic devices
may be available outside of clinical trials in the coming years.
Advanced: Rarely, a patient with BVL who also has a head

tremor can experience both “walking” oscillopsia (due to head
movements associated with walking) and “sitting” oscillopsia (a
result of BVL and the head tremor—that is, with each oscillation
of the tremor, the impaired vestibulo-ocular reflexes cannot main-
tain fixation on the object of regard). This is referred to as a pseud-
onystagmus (Video 6.36).
Read These Books! [73, 74]
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55.
72. Boutros PJ, Schoo DP, Rahman M, Valentin NS, Chow MR, Ayiotis AI,
et al. Continuous vestibular implant stimulation partially restores eye-
stabilizing reflexes. JCI Insight. 2019;4(22):e128397.
74. Bronstein A, Lempert T. Dizziness: a practical approach to diagnosis and
management. 2nd ed. Cambridge: Cambridge University Press; 2017.
Pediatric Clinical Pearls 7
7.1 Neuroblastoma
Five things to know:
1. Neuroblastoma is an uncommon cause of isolated pediatric

Horner’s syndrome, but it should always be considered (direct
compression of the oculosympathetic tract). Although
myoclonus- opsoclonus/flutter syndrome is a rare disorder,
neuroblastoma is a common cause in kids (an immune-medi-
ated paraneoplastic phenomenon).
2. While the accompanying myoclonic jerks typically distinguish
opsoclonus/flutter syndromes from other intrusions/oscilla-
tions or nystagmus, triggers for opsoclonus/flutter include eye-
lid closure, convergence, and saccades. Eye movement
recordings can confirm the absence of an intersaccadic
interval.


https://doi.org/10.1007/978-3-030-76875-1_7
306 7 Pediatric Clinical Pearls
3. Opsoclonus/flutter may precede the radiologic identification of

a neuroblastoma, sometimes by months to years.
4. Workup includes urine vanillylmandelic acid (VMA) and

homovanillic acid (HVA) levels; magnetic resonance imaging
(MRI) from the neck down to the pelvis; metaiodobenzylgua-
nidine (MIBG) scintigraphy.
5. Given the extensive nature of this workup, if the presenting
symptom is ptosis and/or miosis, confirmation of a Horner’s
syndrome (versus physiologic anisocoria) is essential, and top-
ical (4% or 10%) cocaine is often used (apraclonidine is typi-
cally avoided in infants and young children given the potential
for excessive lethargy).
7.2 Neurofibromatosis Type 1 (NF-1)
1. NF-1 is a common cause of gliomas, causing anterior visual

pathway (optic nerve, chiasm, or tract) or hypothalamic
involvement.
2. Gliomas involving the optic nerve commonly affect vision (can be
mild or severe), while gliomas involving the chiasm (also vision
loss) or hypothalamus commonly cause endocrine disorders.
3. If vision loss occurs to a significant degree, it tends to occur
early in life (i.e., <7–8 years old).
4. In a child with an optic pathway glioma, presence of any of the
following additional features establishes an NF-1 diagnosis:
café au lait spots, Lisch nodules (iris hamartomas), NF-1 fam-
ily history, neurofibromas on the skin, axillary or inguinal
freckling, sphenoid wing dysplasia (or other bony lesions).
5. A neurofibroma involving the eyelid may be responsible for
ptosis in NF-1, although the mass is usually palpable. An
“S-shaped” eyelid deformity (e.g., more ptosis laterally than
medially) may be seen.

Infantile Nystagmus (IN) 307
7.3 bnormal Development of the Visual

A
Pathways (Optic Nerve Hypoplasia)
1. Common clinical presentations for congenital optic nerve

abnormalities include horizontal strabismus when unilateral
and (infantile) nystagmus when bilateral.
2. Optic nerve hypoplasia, which can be unilateral or bilateral, is
the most common congenital optic nerve abnormality, and can
result in minimal to severe vision impairment.
3. Congenital optic nerve abnormalities are important to recog-
nize because they are commonly associated with central ner-
vous system malformations.
4. Septo-optic dysplasia is a combination of optic nerve hypopla-
sia and absent septum pellucidum, with other associations
including hypopituitarism, corpus callosal and cortical migra-
tional abnormalities.
5. MRI ± endocrine evaluation is indicated in patients with optic
nerve hypoplasia.
7.4 Infantile Nystagmus (IN)
1. IN is typically observed in the first 8–12 weeks of life, with

common associations including bilateral visual pathway dis-
ease such as retinal dystrophy/degeneration (e.g., cone rod
dystrophy, achromatopsia, Leber congenital amaurosis, con-
genital stationary night blindness, related to albinism), foveal
hypoplasia, optic nerve hypoplasia, or structural ocular disease
(e.g., congenital cataracts, aniridia, coloboma, corneal opac-
ity); however, the structure and function of the visual pathways
are often normal. The initial appearance is that of large ampli-
tude, conjugate, slow horizontal back-and-forth pendular
movements, punctuated by foveation periods.
2. Over months to years, the waveform becomes mixed, with

both jerk (velocity-increasing slow phase) and pendular
(smaller amplitude than initially) components of nystagmus.
The jerk nystagmus typically changes direction in lateral gaze
(e.g., right-beating in right gaze and left-beating in left gaze),
and stays horizontal in vertical gaze.
3. In addition to a comprehensive ophthalmic/neuro-ophthalmic
examination (including dilation), electroretinogram and opti-
cal coherence tomography are helpful when retinopathy/macu-
lopathy is suspected, while MRI brain is indicated when a
neurologic etiology is suspected (e.g., evaluate for pituitary
and other abnormalities in optic nerve hypoplasia).
4. While patients rarely experience oscillopsia, vision tends to be
clearer at near, in part due to the fact that convergence damps
the IN.
5. Abnormal head positions may develop to allow the patient
to maximize effectiveness of their null point (i.e., where
nystagmus is minimal and vision is clearest). Eye muscle
surgery may help to correct this by relocating the null point
to a straight-ahead position.
Want to know more? [18, 19, 4, 5, 6]
7.5 bnormal (but Characteristic) Eye

A
Movements
A few things to know:
• Congenital ocular motor apraxia—a few pearls:

–– Usually volitional saccades are involved (e.g., asking the
patient to look at a target), while reflexive/nonvolitional sac-
cades are spared (e.g., fast phases of optokinetic nystagmus);
–– Horizontal saccades affected, vertical spared;
–– Patients learn to use their vestibulo-ocular reflex to compen-
sate by developing large amplitude “head thrusts,” although
these are not apparent until head/neck motor control devel-
ops. Consider ataxia telangiectasia in the differential (espe-
cially with associated severe smooth pursuit impairment).
Abnormal (but Characteristic) Eye Movements 309
• Tonic vertical gaze—a few pearls:

–– Tonic downgaze—can be a benign finding in normal infants
resolving over months, but also consider the “setting sun sign”
from hydrocephalus (appearance is due to eyelid retraction +
downward deviation associated with upgaze paralysis);
–– Tonic upgaze—less common and may be benign and self-
resolving, and may exist on a spectrum with downbeat nystag-
mus (i.e., slow phase upward drift), also consider oculogyric
crisis (Video 7.1), seizures, and ocular tics in the differential.
• Congenital cranial dysinnervation syndromes—a few pearls:
–– Marcus Gunn jaw winking—sucking (motor portion of tri-
geminal nerve) causes elevation of the eyelid (levator
palpebrae);
–– Congenital fibrosis of the extraocular muscles—unilateral or
bilateral, causing downward eye position (from inferior rec-
tus fibrosis and restriction, causes compensatory chin up
position), ptosis, horizontal strabismus;
–– Congenital horizontal gaze palsy with scoliosis—associ-
ated with a ventral flattening of the pons and pontine/med-
ullary hypoplasia;
–– Mobius sequence—horizontal gaze palsy (or impaired
abduction) and facial weakness.
• A few characteristic eye movement findings/patterns:
–– Niemann-Pick disease type C—vertical gaze palsy, mainly
downward;
–– Gaucher’s disease—horizontal gaze palsy;
–– Spasmus nutans—a monocular (or asymmetric) “shimmer-
ing” appearance, associated with head bobbing and head tilt
(consider MRI to rule out chiasmal glioma);
–– Joubert syndrome—tachypnea, ± retinal dystrophy, cere-
bellar vermis hypoplasia (causing “molar tooth sign” on
MRI), various patterns of nystagmus including torsional
pendular or see-saw nystagmus among others;
–– Friedreich’s ataxia—saccadic intrusions (e.g., square wave
jerks) and oscillations (e.g., o cular flutter), hearing and vision
loss (optic atrophy) are common.

7.6 Esotropia—Infantile or Acquired?
1. This is an important distinction because the presentation of

“acute” esotropia may be benign (infantile) or may be danger-
ous (acquired and due to neurologic disease).
2. Abduction should be normal with infantile esotropia, but, nota-
bly, may also appear normal with acquired esotropia due to pos-
terior fossa pathology (e.g., divergence paralysis/insufficiency
[fusional decompensation] due to a cerebellar neoplasm).
3. Look for features of the infantile esotropia syndrome: (1)
latent nystagmus (nystagmus changes direction with monocu-
lar viewing, depending on the eye fixating—for example,
right-beating when fixating with the right eye, left-beating
when fixating with the left eye), (2) inferior oblique overac-
tion, (3) dissociated vertical deviation (one eye drifts upward
under cover), (4) monocular nasotemporal optokinetic asym-
metry (occlude one eye, and when the stimulus is directly
nasally, optokinetic nystagmus will be stronger than when
directly temporally).
4. Look for features of an acquired posterior fossa syndrome: (1)
gaze-evoked nystagmus, (2) spontaneous downbeat nystagmus
(can be subtle but brought out in lateral gaze), (3) saccadic
(impaired) pursuit and vestibulo-ocular reflex suppression.
Rule out papilledema and an abnormal general neurologic
exam can help guide the workup.
5. Brain MRI is indicated when uncertainty exists.
7.7 Idiopathic Intracranial Hypertension

Idiopathic Intracranial Hypertension 311
1. IIH affects (typically non-overweight/obese) pre-pubertal girls

and boys equally, whereas post-pubertal adolescents more
closely resemble the overweight/obese and female adult IIH
population.
2. In a child with papilledema, if contrast-enhanced MRI (rule out
tumor and evaluate for empty sella, flattening of posterior sclera,
distention of optic nerve sheath) and MR venography (rule out
cerebral venous thrombosis and evaluate for transverse venous
stenosis) are normal, lumbar puncture is indicated.
3. If cerebrospinal fluid (CSF) analysis is normal but opening
pressure is high (greater than or equal to 28 cm of water or
greater than or equal to 25 cm of water in a child who is not
sedated or obese), then consider secondary causes of elevated
intracranial pressure that are common in this population—for
example, use of growth hormone and other endocrine distur-
bances, use of tetra-, doxy-, minocycline drugs (often for acne,
in addition to topical tretinoin), oral contraceptives (the latter
being somewhat controversial).
4. If papilledema is present, MRI/MRV and CSF analysis are
normal, and no identifiable secondary causes of elevated intra-
cranial pressure can be identified, IIH can be diagnosed and
treatment typically includes weight loss (in overweight/obese
individuals) + acetazolamide (occasionally furosemide or topi-
ramate among others). Topiramate may assist with weight loss,
and can be used in IIH with little or no visual involvement,
especially in patients who also experience migraine.
5. When there is visual field loss, close monitoring is needed, with
reproducible testing (e.g., automated static perimetry) when
possible. CSF shunting and optic nerve sheath fenestration are
reserved for cases refractory to medical treatment and/or patients
with severe vision loss at presentation (including loss of visual
acuity and color vision that is not due to macular edema).

7.8 Optic Neuritis
1. Bilateral involvement and optic nerve swelling are common

features in children, often with a viral prodrome.
2. The following are true of both adults and children with typical
optic neuritis—(1) the visual prognosis is quite favorable, (2)
optic neuritis is a common presentation of multiple sclerosis.
3. Contrast-enhanced brain MRI is important to look for white
matter lesions typical of multiple sclerosis or acute dissemi-
nated encephalomyelitis (ADEM, other neurologic symp-
toms/signs are usually present in addition to the vision loss).
4. When atypical features are present (e.g., no light perception
vision), test for neuromyelitis optica (NMO) and anti-myelin
oligodendrocyte glycoprotein (anti-MOG, which is also asso-
ciated with ADEM).
5. Contrast-enhanced brain MRI and spine MRI can offer clues as
to the etiology—for example, chiasmal involvement or longitudi-
nally extensive cord lesion in NMO; chiasmal involvement and
neuroendocrine disorders in neurosarcoidosis; characteristic
brain and spine lesions in ADEM; optic nerve sheath enhance-
ment in anti-MOG.
7.9 Myasthenia Gravis
1. Similar to ocular MG in adults, kids with ocular MG tend to be

seropositive less often than those with generalized MG (vari-
able across studies, but ~50% seropositivity in ocular MG).
2. MG workup for adults and children is similar (in addition to bed-
side testing): (1) test for acetylcholine receptor antibodies, and if
negative, consider muscle specific kinase (MuSK) antibodies and
Ocular Motor Palsies (Third, Fourth, Sixth Nerve Palsies) 313
low-density lipoprotein receptor-related protein 4 (LRP-4) anti-

bodies, (2) edrophonium or neostigmine testing can support the
diagnosis when significant improvement in ptosis and/or ocular
motility deficits can be documented, (3) electromyography
(EMG) including repetitive nerve stimulation and single fiber
EMG analysis. (4) Look for bedside MG signs including fatiga-
ble ptosis, variable strabismus, lid twitch, lid curtaining, enhanced
ptosis, ptosis/diplopia improvement with rest and ice tests.
3. MG treatments for adults and children are similar: pyridostig-
mine is typically first-line, and steroids or other immunomodu-
latory agents are often needed; thymectomy when thymoma is
present, but there is evidence for its efficacy in some cases
when thymoma is absent as well (although large scale random-
ized controlled trials are lacking in kids with OMG).
4. Kids with OMG should be followed closely by ophthalmol-
ogy/neuro-ophthalmology to prevent the development of
amblyopia when strabismus or significant ptosis are present.
5. Remember that OMG can mimic any central (e.g., internuclear
ophthalmoplegia) or peripheral (e.g., third [when there is no
pupil involvement], fourth, sixth NP) ocular motor disorder!
7.10 O
cular Motor Palsies (Third, Fourth, Sixth
Nerve Palsies)
What etiologies should I think of?
• Third NP—congenital and traumatic (look for aberrant regen-

eration/synkinesia with these), inflammatory/infectious (men-
ingitis), neoplastic, aneurysmal, ophthalmoplegic migraine; do
not forget about myasthenia gravis when the pupils are spared.
• Fourth NP—congenital (long-standing compensatory head
tilt), traumatic (especially when bilateral); the fourth nerve
decussates dorsally at the level of the inferior colliculus, so a
(right) midbrain syndrome may cause a “central” contrale-
sional (left) fourth NP with an ipsilesional (right) Horner’s

syndrome or (right) internuclear ophthalmoplegia.
• Sixth NP—traumatic, neoplastic, inflammatory/infectious
(meningitis), congenital, high or low intracranial pressure,
benign recurrent sixth NP, ophthalmoplegic migraine; a sixth
NP + an ipsilateral Horner’s syndrome is highly localizing to
the ipsilateral cavernous sinus. Duane’s retraction syndrome
can also mimic a sixth NP.
7.11 R
etinal Disorders Mimicking Neurologic
Disease
A few things to know:
• When peripheral vision loss is the complaint, consider the pos-

sibility of a retinal degeneration involving rods (e.g., retinitis
pigmentosa, RP) with associated night blindness (nyctalopia);
dilated fundus exam with attention to the peripheral retina is
essential (e.g., “bone spicule” hyperpigmentation in RP).
• When central vision loss is the complaint, consider the possi-
bility of a cone dystrophy (e.g., Stargardt disease) with associ-
ated light blindness (hemeralopia), impaired visual acuity,
dyschromatopsia; ophthalmoscopic exam with attention to the
macula (e.g., macular “flecks” in Stargardt disease).
• Family history may or may not be present with cone or rod
dystrophies.
• Electroretinogram (multifocal/pattern for central loss; full-
field for peripheral loss), autofluorescence imaging (e.g.,
allows for visualization of fluorescence related to retinal
disease), and optical coherence tomography can provide diag-
nostic clues.

References 315
7.12 Vertigo and Dizziness
1. Migraine—this is the most common cause of episodic dizzi-

ness/vertigo in childhood, and patients may meet all of the cri-
teria for vestibular migraine, or may instead fit better into
categories of “benign paroxysmal vertigo of childhood” or
“cyclic vomiting” syndromes, both of which probably repre-
sent migraine variants (although the exact pathophysiology
remains elusive).
2. Epileptic vertigo—consider when there is associated loss of
time or awareness, or with a known seizure history. Epileptic
vertigo that is in complete isolation in a patient without other
seizure types is very rare.
3. Episodic ataxia type 2—consider when there are hours-long
attacks of dizziness/vertigo with spontaneous nystagmus and
severe imbalance, binocular double vision or other brainstem
symptoms. Over time, patients typically have inter-ictal ocular
motor abnormalities (e.g., gaze-evoked nystagmus).
Acetazolamide or 4-aminopyridine can be effective for these
syndromes.
Read These Books! [18, 19]
References
1. Musarella MA, Chan HS, DeBoer G, Gallie BL. Ocular involvement in
neuroblastoma: prognostic implications. Ophthalmology.
1984;91(8):936–40.
2. Beres SJ, Avery RA. Optic pathway gliomas secondary to neurofibroma-
tosis type 1. Semin Pediatr Neurol. 2017;24(2):92–9.
3. Capo H, Repka MX, Edmond JC, Drack AV, Blumenfeld L, Siatkowski
RM. Optic nerve abnormalities in children: a practical approach. J
AAPOS. 2011;15(3):281–90.
5. Brodsky MC. Infantile nystagmus-following the trail of evidence. J
AAPOS. 2020;24(2):70–1.
6. Brodsky MC, Dell’Osso LF. A unifying neurologic mechanism for infan-
tile nystagmus. JAMA Ophthalmol. 2014;132(6):761–8.
7. Gilbert AL, Koo EB, Heidary G. Evaluation and management of acute
acquired comitant esotropia in children. Semin Ophthalmol.
2017;32(1):8–13.
8. Brodsky MC. An expanded view of infantile esotropia: bottoms up! Arch
Ophthalmol. 2012;130(9):1199–202.
9. Gaier ED, Heidary G. Pediatric idiopathic intracranial hypertension.
Semin Neurol. 2019;39(6):704–10.
10. Gise RA, Heidary G. Update on pediatric optic neuritis. Curr Neurol
Neurosci Rep. 2020;20(3):4.
11. Mansukhani SA, Bothun ED, Diehl NN, Mohney BG. Incidence and ocu-
lar features of pediatric myasthenias. Am J Ophthalmol. 2019;200:
242–9.
12. Peragallo JH. Pediatric myasthenia gravis. Semin Pediatr Neurol.

2017;24(2):116–21.
13. Holmes JM, Mutyala S, Maus TL, Grill R, Hodge DO, Gray DT. Pediatric
third, fourth, and sixth nerve palsies: a population-based study. Am J
Ophthalmol. 1999;127(4):388–92.
14. Chawla H, Vohra V. Retinal dystrophies. Treasure Island: StatPearls;
2021.
15. Feil K, Bremova T, Muth C, Schniepp R, Teufel J, Strupp M. Update on
the pharmacotherapy of cerebellar ataxia and nystagmus. Cerebellum.
2016;15(1):38–42.
16. van de Berg R, Widdershoven J, Bisdorff A, Evers S, Wiener-Vacher S,
Cushing SL, et al. Vestibular migraine of childhood and recurrent vertigo
of childhood: diagnostic criteria consensus document of the committee
for the classification of vestibular disorders of the Barany society and the
International Headache Society. J Vestib Res. 2020;31(1):1–9.
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DE. Clinical and electrographic findings in epileptic vertigo and dizzi-
ness: a systematic review. Neurology. 2015;84(15):1595–604.

Springer; 2016.
Index
A
ABCD2, 254, 255, 284, 285
Abnormal development of visual pathways, 307
Acetazolamide, 95, 100, 121, 311, 315
Acute angle closure glaucoma, see Eye pain
Acute onset persistent vision loss, 56–59
Acute vestibular syndrome (AVS), 232, 240
vestibular neuritis, 242–252
Akinetopsia, 114–116
Alexia without agraphia, 116
Alternate cover, 2, 127, 128, 144, 172, 242, 247, 251
Alternating skew deviation, 127, 183, 187, 287
Amaurosis fugax, 76–82, 88
Aneursymal third nerve palsy, 22–25
Angle closure glaucoma, 46–49, 81
Anisocoria, 5–16, 18–23, 25–28, 33, 68, 75, 129, 138, 140, 306
tonic (Adie’s) pupil, 6, 7, 15–17, 24–27
Anterior canal, 145, 210, 214, 215, 245, 256, 262, 269–271
Anterior inferior cerebellar artery (AICA) territory, 159
Anti–myelin oligodendrocyte glycoprotein (Anti-MOG), 56, 58, 93, 94, 97,
104, 312
Anton’s syndrome, 111, 118
Apraclonidine, 6, 7, 16–18, 21, 140, 306
Argyll Robertson pupils, 16
Arteritis, see Giant cell arteritis
Audiogram/Audiometry, 233, 234, 239, 241, 251, 253, 254, 270–272,
275–278, 280, 281, 283, 287, 288, 290, 291, 295–297
Audiovestibular lab tests, 234–235, 276, 298
Autophony, 253, 270–272

https://doi.org/10.1007/978-3-030-76875-1
318 Index
B
Baclofen, 187, 196, 206, 209
Balint’s syndrome, 110, 114–116
B12 deficiency, 67, 208, 298
Benign paroxysmal positional vertigo (BPPV), 192, 214, 215, 231–234,
238, 239, 243, 250, 252–269, 282, 288–290
canalith repositioning, 260
Dix–Hallpike maneuver, 3, 192, 202, 209, 233, 234, 238, 250, 253,
256–259, 262, 268, 273
horizontal canals, 259, 262–264
posterior canals, 257, 259, 261, 262
Bilateral ptosis and ophthalmoplegia, 35, 36
Bilateral vestibular loss (BVL), 3, 133, 208, 232–237, 246, 272, 286, 287,
293–298
Bitemporal hemianopia, 66, 68, 72, 102–104, 118, 126
Blepharospasm, 39–41
Botulinum toxin, 41
Botulism, 37, 126
Brachium conjunctivum (BC)/SCP, 183
Brachium of the superior colliculus, 106, 169
Branch retinal artery occlusion (BRAO), 56–58, 69, 71, 77, 82, 275, 280
Bruns nystagmus, 194, 201, 203, 204
Bucket test, 3, 173
C
Calcarine fissure, 73, 110, 112, 113
Calibrated finger rub auditory screening test (CALFRAST), 239
Caloric testing, 251, 276, 281
Carotid-cavernous fistula (CCF), 48, 50, 51, 142, 161, 164, 168
Carotid dissection, 5, 18, 21
Cavernous sinus, 11, 19, 23, 50, 51, 135, 137–141, 161, 164, 166, 168, 170,
173, 314
Celiac disease, 221
Central positional nystagmus (CPN), 188, 267–270
Central retinal artery (CRA), 78
Central retinal artery occlusion (CRAO), 57, 58, 67, 69, 71, 74, 77,
78, 82, 89
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS),
134, 187, 208, 236, 287, 298
Cerebellum, 182, 184
flocculus and paraflocculus (tonsil) syndrome, 184–188
nodulus/uvula, 182, 183, 185, 188, 205, 208, 209, 269
Cerebral venous thrombosis, 96, 100, 142, 311
Cerebrospinal fluid (CSF) shunt, 100, 311
Cervical VEMP, 245, 251, 271, 272, 280
Cervicogenic dizziness, 275
Index 319
Charles Bonnet syndrome (CBS), 117–119

Chiari, 184, 186, 196, 205–209, 232, 238, 269
Chiasm, 14, 68, 72, 93, 94, 102–104, 106, 306
Chlorzoxazone, 196, 209
Chronic progressive external ophthalmoplegia (CPEO), 34, 126, 159, 178
Chronic vestibular, 238, 286, 288–298
Cilioretinal artery, 57, 67
Clonazepam, 196, 200, 209, 226, 292
Coenzyme Q10, 221
Cogan’s lid twitch, 32, 35, 36, 296
Congruous homonymous visual field defect, 61, 73, 74, 110, 112
Convergence-retraction nystagmus, 3, 134, 174, 177
Convergence spasm, 162, 163
Cortical blindness, 111
Cover-uncover, 2, 128, 172
Craniopharyngioma, 103, 104
CT temporal bone, 233, 235, 272
D
Diabetes insipidus, 104
Diagonal diplopia, 151, 153
Diplopia, 10, 18, 23–25, 28, 29, 33–36, 38, 42, 45, 46, 48–51, 56, 79, 88,
90, 125–127, 129–131, 135–137, 139–143, 148–164, 167, 172,
173, 178–180, 183, 187, 226, 227, 232, 242, 252, 284, 313
Disequilibrium of aging, 272
Divergence insufficiency (DI), 12, 29, 127, 183, 188
Dix–Hallpike (DH), 3, 192, 202, 209, 233, 234, 238, 250, 253, 256–259,
262, 268, 273
Dorsal midbrain (Parinaud’s) syndrome, 16, 27, 134, 174–178
Dorsal vermis, 143, 144, 182, 188–189
Double Maddox rod, 131, 173
Downbeat nystagmus (DBN), 127, 132, 181, 183, 186–188, 192, 194, 196,
202, 206–210, 212, 223, 233, 237, 238, 250, 256, 264, 268, 269,
274, 287, 294, 309, 310
Duane’s retraction syndrome, 314
Dural AVM, 139
Dysmetric saccades, 132, 142–151, 203, 220, 244, 287
E
Elevated intracranial pressure, 81, 96, 101, 137, 272, 311
Enlarged blind spot, 58, 65, 95–97, 103
Entopic phenomena, 83, 120
Epilepsy, 84, 109, 118
Episodic vertigo, 252–255, 281, 284, 285
320 Index
Episodic vestibular syndrome, 252–288

Esotropia, 12, 29, 30, 33, 44, 49, 125–127, 129–131, 136, 160, 172, 173,
183, 204, 310
Ethambutol, 65, 103
Exertion-induced dizziness, 283
Exotropia, 12, 34, 35, 125, 127, 128, 130, 132, 138, 151, 152, 179
Extraocular muscles (EOM), 6, 7, 10, 12, 25, 30, 42, 43, 45, 46, 51, 88, 133,
215, 227, 309
Eyelid, 29
levator dehiscence, 8, 28–34, 37
levator function (LF) and lid crease, 30
MRD1 and MRD2, 20
myasthenia gravis, 34–38
myokymia, 39–41
opening and closing, 31
ptosis, 5–11, 13, 16–25, 28–38, 42–45, 48–51, 68, 126, 129–131, 138,
140, 150, 152, 154, 162, 164–166, 171, 174, 304, 306, 309, 313
retraction, 35, 36, 44, 162, 174, 177, 181, 309
spasms, 38–41
Eye pain, 46–49, 51, 56, 79, 88, 90, 93, 141
F
Fastigial nucleus, 143, 144, 182, 183, 188–189, 205
Fistula, 50, 272, 280
FL-41, 41
Flocculus/paraflocculus, 182–188, 196, 197, 202, 203, 205, 207–210, 212,
245, 248–251, 256, 264, 269, 297
Fourth nerve, 22, 138, 140, 167–173, 313
Fourth nerve palsy (NP), 3, 19, 106, 125, 136, 168, 172, 187
nuclear fourth nerve palsy, 169–171
Fungal (orbital) infection, 63, 135, 139
G
Gabapentin, 198–200, 216, 217, 219, 221, 224, 226, 228, 281, 283
Gaze-evoked nystagmus (GEN), 12, 33, 126, 143, 146, 181, 183, 185–187,
193, 196, 197, 199, 202–205, 207, 208, 210, 212, 213, 220, 247,
252, 256, 267, 268, 294, 295, 297, 310, 315
Germinoma, 104
Gerstmann’s syndrome, 116
Giant cell arteritis (GCA), 12, 23, 48, 58, 74, 76, 78, 79, 85, 87–90, 152,
162, 171, 275
Gradenigo syndrome, 161
Gravis, see Myasthenia gravis
Guillain-Mollaret triangle, OPT, 218
Index 321
H
Headache, 21, 22, 46, 76, 77, 79, 83–85, 87, 95, 119, 120, 171, 194, 201,
273–276
Head Impulse, Nystagmus, Test of Skew (HINTS), 232, 240–242
Head impulse test (HIT), 145, 146, 150, 159, 179, 195, 201, 203, 208, 210,
234, 236–237, 242, 244–246, 250–252, 254, 272, 278, 280, 286,
287, 292, 294–297
Head-shaking nystagmus (HSN), 187–188, 196, 201, 205, 209, 237, 248,
250, 264, 273, 274, 278
Hearing loss, 144, 194, 195, 201, 203, 204, 207, 233, 239–241, 243, 244,
248, 250, 251, 254, 271, 272, 274, 275, 277–281, 283, 284,
296, 297
Heimann–Bielschowsky phenomenon, 199, 221, 226
Hemiachromatopsia, 116
Hemifacial spasm (HFS), 38–41, 281
Hemimacular GCL thinning, 69–70
Hemodynamic orthostatic dizziness/vertigo, 259
Hennebert’s sign, 238, 271
Hering’s law, 36
Hertel exophthalmometer, 2, 44, 49
Higher cortical visual disorders, 111–121
hallucinations, 117–119
posterior cortical atrophy, 111, 114–117
visual snow, 119–121
Hirschberg test, 128
Histiocytosis, 104
Hollenhorst plaque, 76, 79
Homonymous visual field defects, 59, 65, 66, 72–75, 105, 107, 110–113,
115, 118, 119
complete homonymous defects, 68
congruous homonymous visual field defects, 68, 73, 112
horizontal sectoranopia, 73, 108
incomplete homonymous visual field defects, 73
incongruous homonymous hemianopia, 73, 106, 107, 109
incongruous superior quadrantic homonymous defects, 73
lateral geniculate nucleus (LGN), 14, 73, 106–108, 111, 114
occipital lobe/striate cortex, 68, 72–74, 110–113, 115, 117
optic radiations, 109, 110
optic tract, 105, 106
optic tract lesions, 73
parietal lobe lesions, 61, 73, 113
parietal radiations, 109, 110
quadruple sectoranopia, 73, 108
temporal radiations, 108
322 Index
Horizontal canals (HC), 145, 210, 238, 245, 250, 255, 256, 258, 259, 262,
267, 268, 297
Horizontal diplopia, 151, 157, 160, 164, 179, 183
Horizontal gaze, 37, 146, 155–160, 175, 198, 204, 206, 216–218, 297, 309
Horizontal nystagmus, 188, 194–205, 214, 254, 259, 267, 278
Horizontal VOR, 296
Horner’s syndrome, 5, 8, 10, 11, 13, 16–21, 28, 31, 33, 34, 137, 140, 142,
150, 161, 167, 169, 173, 305, 306, 314
apraclonidine testing, 18
Horner’s pupil, 7, 16, 19, 21
ICA dissection, 19
Humphrey automated static perimetry, 97
Hydrocephalus, 103, 176, 178, 294, 309
Hypermetric saccades, 150, 188, 189, 193, 199, 205, 206, 220, 222
Hypertropia, 128–131, 136, 138, 144, 152, 153, 168, 171–173, 176, 187, 226
Hyperventilation, 196, 201, 209, 238, 253, 281–283
Hypometric saccades, 150, 188, 189
I
Idiopathic intracranial hypertension, 95, 311
IgG4 disorders, 45, 51
Impaired pursuit, 133, 196, 208, 264, 287, 310
Impaired vestibulo-ocular reflex suppression, 184–186
Incycloduction, 22, 131, 138, 140, 147, 168, 173, 215, 226, 227
Infantile nystagmus, 307
Inflammatory orbital syndrome, 45, 51
Internuclear ophthalmoplegia (INO), 11, 12, 36, 37, 130–134, 145,
151–159, 167, 169, 173, 198, 199, 218, 313, 314
Interstitial nucleus of Cajal (INC), 147, 148, 175–177, 197, 202, 214
Intracranial pressure (ICP), 11, 60, 62, 64, 81, 95–97, 99–101, 131, 135,
137, 143, 144, 146, 149, 161, 183, 271, 272, 311, 314
Intrusions/oscillations, 195–200
opsoclonus/ocular flutter, 193, 194, 200, 223–226, 305, 306
square wave jerks (SWJ), 222, 223
Iridodonesis, 227
K
Krimsky test, 128
L
Labyrinth
anatomy, 257
innervation, 245
vascular supply, 243, 244
Index 323
Lambert Eaton syndrome, 37, 162

Langerhans cell, 104
Latent nystagmus, 204
Lateral medulla, 3, 13, 18, 142–151, 219, 244, 249
Lateral medullary (Wallenberg) syndrome, 142, 143, 145, 149–151
Lateral vestibular nucleus (LVN), 145
Leber’s hereditary optic neuropathy (LHON), 62, 67, 71, 93
Lewy body dementia, 61, 116, 118
Light-near dissociation, 6, 16, 26, 27, 174, 177
Lithium, 196, 208, 225
Loss of vision and other visual symptoms, 68, 75
chiasmal visual disorders, 102–104
higher cortical visual disorders
hallucinations, 117–119
posterior cortical atrophy, 111, 114–117
visual snow, 119–121
optic nerve
GCA, 87–90
NAION, 85–87
optic neuritis, 88–94
papilledema, 95, 97, 100, 101
retina
photopsia, 83–85, 115
retinal TIA, 76, 77, 82
retrochiasmal visual disorders, 105
lateral geniculate nucleus (LGN), 106, 108
occipital lobe/striate cortex, 110, 111
Lumbar puncture, 94, 95, 100, 136, 139, 206, 279, 311
Lymphocytic hypophysitis, 60, 104
Lymphoma, 45, 51, 94, 100, 135, 139, 142
M
Mal de debarquement syndrome, 290–292
Medial longitudinal fasciculus (MLF), 11, 130, 131, 133, 145–149,
151–159, 169, 171–173
Medial vestibular nucleus (MVN), 143, 145, 146, 149, 212, 245, 297
Medulla, 13, 142–150, 186, 196, 202, 204, 212
Meige syndrome, 40
Memantine, 196–200, 206, 213, 217, 219, 221, 226
Meniere’s disease, 232, 233, 254, 275, 277–279, 284, 285, 296
Meningioma, 24, 60, 61, 75, 98, 104, 112, 139, 140
Meyer’s loop, 72, 73, 108, 109
324 Index
Microflutter, 194
Midbrain
fourth nerve, 167, 168, 171–173
progressive supranuclear palsy, 179–182
third nerve, 164
vertical gaze palsies, 174–178
Migraine, 46, 48, 77, 80, 81, 83–85, 118–121, 139, 191, 194, 201, 225, 231,
232, 234, 235, 246–248, 253, 260, 269, 272–279, 284, 285,
288–290, 311, 313–315
Migrainous visual aura, 77, 80
Miller Fisher syndrome, 24, 28, 37, 126, 136, 154, 159, 162, 178
Miotic pupil, 16
Monocular pendular, 226
Monocular visual field defect, 68, 71–73
Motility and ocular motor disorders
cavernous sinus, 137, 139
cerebellum, 182–184, 186–188
medulla, lateral medullary (Wallenberg) syndrome, 142, 143, 145,
149–151
midbrain
fourth nerve, 167, 168, 171–173
PSP, 179–182
third nerve, 164
vertical gaze palsies, 174–178
neurologic binocular diplopia, 126
optokinetic nystagmus, 134
orbital apex, 141, 142
pons
horizontal gaze palsies, 156, 157, 159, 160
medial longitudinal fasciculus syndrome, 151, 152, 154, 156
sixth nerve, 160–163
range of movements, 126
smooth pursuit, 133
subarachnoid space, 135, 136
vestibulo-ocular reflex suppression (VORS), 133
Multifactorial dizziness and imbalance, 292–295
Multiple sclerosis (MS), 81, 91, 94, 152, 155, 157, 159, 191, 199, 202, 209,
213, 219–221, 225, 226, 312
acquired pendular nystagmus, 219–221
Myasthenia gravis (MG), 8, 11, 12, 23, 24, 28–30, 33, 35–38, 126, 131, 133,
136, 152, 154, 159, 162, 171, 174, 178, 312–313
Mydriasis, 6, 7, 10, 15, 17, 22–24, 26, 27, 33, 130, 138, 141, 154
Mydriatic pupil, 7, 16, 24–27
Myelin oligodendrocyte glycoprotein (MOG), 92, 94, 213
Myoclonus, 224, 305
Myositis, 47
Index 325
N
Neglect, 73, 110, 113
Neuroblastoma, 200, 224, 225, 305–306
Neurofibromatosis type 1 (NF-1), 306
Neuromyelitis optica (NMO), 56, 58, 93, 94, 97, 213, 217, 312
Neuro-ophthalmic ancillary tests, 69–70
Neuroretinitis, 75, 92–94
Neurosarcoidosis, 135
Neurovascular compression, 38, 226–228, 238, 253, 270, 281
Nodulus/uvula, 182, 183, 185, 188, 205, 208, 209, 248, 264, 269
Non-arteritic anterior ischemic optic neuropathy (NAION), 57, 58, 71,
85–87, 89
Nucleus of roller/intercalatus, 202, 212
Nucleus prepositus hypoglossi (NPH), 143, 146, 149, 175
Nystagmus, 1–3, 12, 33, 35, 37, 59, 104, 110, 126, 127, 130, 132–134,
142–144, 146, 148, 150–155, 176, 177, 181–188, 191–228,
232–234, 237–239, 242–244, 246–254, 256–271, 273, 274,
276–278, 281–284, 287, 289, 294, 295, 297, 298, 305, 307–310,
315
downbeat nystagmus, 206, 208–210
examination, 192
horizontal nystagmus, 194, 195, 201, 203, 204
multiple sclerosis-related pendular, 219–221
oculopalatal tremor, 216–219
periodic alternating nystagmus, 205, 206
torsional nystagmus, 214, 216
upbeat nystagmus, 194, 210, 211, 213, 214
O
Occipital lobe/striate cortex, 68, 72–74, 110–113, 115, 117
Occipitotemporal lobes, 116
Ocular counterroll, 3, 146–148, 152, 153, 168, 172, 173, 176, 214, 251
Ocular flutter, 193, 194, 200, 223–226, 309
Ocular misalignment, 130–131
Ocular neuromyotonia, 227
Ocular synchrony, 217
Ocular tilt reaction (OTR), 3, 131, 146, 148, 152, 153, 176, 177, 202,
214, 251
Ocular VEMP, 245, 251, 271, 272
Oculopalatal tremor (OPT), 156, 158–160, 198, 202, 214, 216–220,
287, 293
Oculosympathetic pathway for pupillary dilation, 5, 13, 15
One-and-a-half syndrome, 37, 156–160, 198, 218
Open-angle glaucoma, 117, 292
326 Index
Ophthalmoplegia, 12, 25, 34–37, 126, 131, 132, 135, 139, 141, 145, 149,
151–153, 155, 156, 158, 159, 161, 164, 167, 169, 173, 178, 179,
213, 218, 313, 314
Optical coherence tomography (OCT), 64, 68, 69, 71, 99, 107, 308, 317
Optic aphasia, 116
Optic atrophy, 62, 81, 96, 97, 309
Optic nerve
GCA, 87–90
NAION, 85–87
optic neuritis, 88–94
papilledema, 95, 97, 100, 101
Optic nerve hypoplasia, 307
Optic nerve sheath fenestration, 100, 311
Optic nerve swelling, 58, 65, 69, 70, 85, 86, 92, 95, 97, 312
Optic neuritis/perineuritis, 47, 48, 74, 88–94
Optic neuropathy, 16, 46, 48, 51, 58, 62–64, 67, 69–72, 74, 75, 78, 81, 85,
86, 88, 89, 91, 93, 97, 141, 142, 161, 165, 168, 208
Optic radiations, 109, 110
Optokinetic nystagmus, 1, 2, 110, 134, 182, 274, 289, 294, 308, 310
Orbital apex, 135–142
Orbital inflammatory syndrome, 45, 51
Orbit/globe, 42, 44
eye pain, 46–49
red eye, 49–52
thyroid eye disease, 44–46
Oscillopsia, 149, 151, 153, 154, 183, 184, 187, 191–228, 236, 242, 271,
286, 287, 292, 294, 296–298, 308
P
Painful ophthalmoparesis, 139
Palatal tremor, 198, 216–219, 287
Palinopsia, 120
Papilledema, 42, 59, 60, 62, 65, 67, 81, 83, 95–101, 103, 131, 163, 272,
310, 311
Paraflocculus, 182–188, 196, 197, 202, 205, 207–210, 245, 249, 256, 264,
269, 297
Paramedian pontine reticular formation (PPRF), 157
Paramedian tracts, 207, 209, 210
Paraneoplastic, 37, 94, 181, 184, 194, 196, 200, 206, 208, 209, 224, 225,
269, 287, 294, 297, 305
Parasympathetic pathway for pupillary constriction, 5, 14, 15
Parietooccipital lobes, 116
Parinaud (dorsal midbrain) syndrome, 16, 27, 134, 174–178
Parkinsonism, 40, 132, 184, 192, 233, 293
Parkinson’s disease (PD), 181
Index 327
PCOM aneurysm, 6, 8, 10, 22, 24, 25, 27, 130, 138, 166
Pediatric optic neuritis, 312
Peduncular hallucinosis, 118
Pendular nystagmus, 191–193, 198, 199, 216–222, 226, 287
Pendular seesaw nystagmus, 104
Perilymph fistula, 272
Periodic alternating nystagmus (PAN), 187–188, 196, 202, 205–206, 223
Persistent positive visual phenomena of, 77
Persistent postural perceptual dizziness (PPPD), 232, 234, 274, 286, 288, 291
Phoria, 129
Photopsia, 58, 64, 65, 83, 84, 118, 120
Physiologic end-point nystagmus, 197
Physiologic ocular tilt reaction, 146
Pilocarpine, 6, 7, 16, 17, 24, 26
Pituitary apoplexy, 23, 49, 104, 126
Pituitary tumor, 102–104
Pons
horizontal gaze palsies, 156, 157, 159, 160
medial longitudinal fasciculus syndrome, 151, 152, 154, 156
sixth nerve, 160–163
Positional nystagmus, 183, 188, 202, 247, 252, 259, 264, 267, 269, 273,
274, 278
Posterior canal, 145, 151, 153, 210, 214, 215, 237, 238, 245, 252, 255–258
Posterior canal (PC) benign paroxysmal positional vertigo (BPPV), 257,
259, 261, 262
Posterior cortical atrophy, 111, 114–117
Posterior ischemic optic neuropathy (PION), 88
Posterior vitreous detachment (PVD), 83, 118
Postinfectious, 200
Presbyvestibulopathy, 293
Pretectal nuclei, 14, 106, 174
Progressive ataxia with palatal tremor (PAPT), 198, 217, 219
Progressive supranuclear palsy (PSP), 3, 12, 16, 41, 133, 134, 174, 176–182,
199, 222, 294
Propranolol, 226
Proptosis, 2, 42–45, 48–51, 68, 141, 162, 165, 168
Prosopagnosia, 114–116
Pseudo-abducens, 117
Pseudopapilledema, 98
Pseudophakodonesis, 227
Ptosis, 5–11, 13, 16–25, 28–38, 42–45, 48–51, 68, 126, 129–131, 138, 140,
150, 152, 154, 162, 164–166, 171, 174, 304, 306, 309, 313
examination, 28–29
history, 28
Pulsatile tinnitus, 51, 62, 81, 95, 161, 271, 272
328 Index
Pupil
aneursymal third nerve palsy, 22–25
anisocoria, 5, 16
Horner’s syndrome, 5, 17–19, 21
pilocarpine, 16
tonic pupil, 25–28
Pyridostigmine, 35, 38
Q
Quadrantanopia, 116
R
Red eye, 42, 48–52
Relative afferent pupillary defect (rAPD), 75
Retina
photopsia, 83, 84
retinal TIA, 76, 77, 82
Retinal artery, 58, 67, 69, 71, 74, 76–78, 88, 89, 275, 280
Retinal detachment, 58, 82
Retinal disorders mimicking neurologic disease, 314
Retinal ischemia, 77–79, 88
Retinal tear, 83, 84
Retinal transient ischemia attack (TIA), 76, 77, 82
Retinopathy, 27, 51, 57, 58, 64, 65, 67, 70, 71, 83, 184, 293, 294, 308
Retrochiasmal visual disorders, 105
LGN, 106, 108
occipital lobe/striate cortex, 110, 111
Rinne, 201, 203, 239, 240, 278
Room tilt illusion (RTI), 232, 285
Ross syndrome, 26, 27
Rostral interstitial medial longitudinal fasciculus (riMLF), 174–178, 181
S
Saccadic intrusions, 127, 180, 189, 191–193, 196, 199, 200, 222–228, 309
Saccadic pathways, 132, 142–144, 149, 203, 220, 244, 287
Saccadic pursuit, 134, 180, 181, 199, 202, 203, 205, 256
Saccadic VOR suppression, 133, 179–181, 183, 184, 201, 203, 205, 206
Sagging eye syndrome, 32, 33
Sarcoidosis, 46, 56, 60, 62, 63, 86, 94, 98, 104, 135, 142, 217, 280
Scintillating, 80, 83
Index 329
Scleritis, 48
Scotoma, 62, 67, 72–74, 80, 83, 97, 103, 110, 112, 157
Sectoranopia, 73, 106–108
Seizure (occipital), 81, 84, 120, 158, 209, 219, 309, 315
Semicircular canal (SCC), 258
Semicircular canal pathways, 145
Seventh NP (aberrant regeneration), 20, 156, 158, 159, 161, 250
Shunt failure, 176–177
Side pocket nystagmus, 186, 206
Simultanagnosia, 61, 65, 110, 115, 116, 180
Sixth nerve, 19, 22, 51, 68, 95, 104, 135, 136, 140, 160–163, 166, 177,
313–314
Sixth nerve palsy, 11, 23, 29, 126, 129, 131, 135–137, 160–165, 168, 313,
314
Skew deviation, 142, 143, 145, 148–152, 154, 156, 172
Spasms, eyelid, 38–41
Spinocerebellar ataxia (SCA), 132, 167, 171, 182, 184, 186, 205, 206, 208,
220, 221, 268, 269
Square wave jerks (SWJ), 222, 223
Strabismus/diplopia, treatment of, 129
Stroke/TIA, 82, 285
Subarachnoid space, 135, 136
Subjective visual vertical (SVV), 3, 252
Superior canal dehiscence syndrome (SCDS), 232, 270–273
Superior oblique muscle, 138, 169, 170, 173, 227
Superior oblique myokymia (SOM), 192, 226–228
Superior vestibular nucleus (SVN), 145
Susac syndrome, 82
Syphilis, 56, 58, 63, 86, 93, 94, 293
Syringohydromyelia, 186
T
Temporal lobe, 72, 73, 109, 166
Thiamine, 62, 210, 212, 213, 297
Third nerve, 164–167
Third nerve palsy, 5, 8, 10, 16, 19, 22–34, 36, 130, 138, 140, 141, 152, 154,
164, 165, 173, 174, 178, 313
Thyroid eye disease (TED), 11, 12, 43–46, 48, 51, 131, 133, 136, 162,
171, 227
Tolosa Hunt syndrome, 48, 139
Tonic (Adie’s) pupil, 6, 7, 15–17, 24–27
Tonsil (paraflocculus), 182–186, 207, 269
Topiramate, 48, 81, 100, 120, 311
Topographagnosia, 116
330 Index
Torsional nystagmus, 150, 151, 153, 154, 176, 194, 202, 214–216, 238, 247,
256, 259, 262, 268, 269
Torsional pendular nystagmus, 217, 309
Transient ischemia attack (TIA), 76, 79, 232, 255, 270, 283, 284
Transient visual obscurations (TVOs), 42, 62, 81, 95, 161
Transient vision loss, 79–81
Trigeminal nerve, 13, 42, 47, 309
Trigeminal neuralgia, 150
Trochleitis, 48
Tropia, 129
Tullio’s phenomenon, 232, 238, 271
U
Upbeat nystagmus (UBN), 132, 196, 202, 209–213, 257
Upgaze palsy, 174–177
Utriculo-ocular motor pathway, 146–147
Uvula, 182, 183, 185–188, 202, 205, 208, 209, 269
V
Valsalva, 192, 232, 234, 238, 253, 270, 271
Vascular malformation, 139
Velocity storage, 185, 187, 188
Venous thrombosis, 95, 96, 99, 100, 142, 311
Ventral tegmental tract (VTT), 145
Vertebral artery dissection, 21, 149, 151, 213, 268, 270, 275, 277
Vertical diplopia, 143, 148, 151, 164, 183, 187, 226, 227, 252
Vertical gaze palsies, 174, 175, 177, 178
Vertical pendular nystagmus, 216, 217, 221
Vertical-torsional nystagmus, 151, 153, 154, 202, 214
Vertical VOR, 154, 212
Vestibular atelectasis, 272
Vestibular disorders
HINTS (Head Impulse, Nystagmus, Test of Skew), 144
Vestibular migraine (VM), 191, 232, 234, 246–248, 253, 255, 260, 269,
272–276, 278, 279, 285, 288–291, 315
Vestibular neuritis, 242–252
Vestibular paroxysmia, 191, 231, 233–235, 253, 255, 270, 280, 281
Vestibular schwannoma, 201, 202, 204, 233, 234, 238, 243, 279, 280, 294, 296
Vestibular syndrome
chronic vestibular syndrome
bilateral vestibular loss, 295–298
Mal de debarquement syndrome, 290–292
multifactorial dizziness and imbalance, 292–295
persistent postural perceptual dizziness, 288–290
Index 331
episodic vestibular syndrome, 252, 257, 259

Meniere’s disease, 277–281
horizontal canal BPPV, 262–264
posterior canal BPPV, 252, 256–261
superior canal dehiscence syndrome, 270–273
vestibular migraine (VM), 273–277
vestibular paroxysmia, 281–283
vestibular transient ischemia attack (TIA), 283–285, 288
vestibular examination
dynamic visual acuity, 236
head impulse test (HIT), 236
head-shaking, 187–188, 237, 248, 250, 274
hyperventilation, 238
positional maneuvers, 238
pressure-induced, 238
vestibulo-ocular reflex (VOR), 233
vibration, 237
visually enhanced VOR (vVOR), 236
Vestibular transient ischemia attack (TIA), 283–285, 288
Vestibulocerebellum, 182, 183, 185, 269
Vestibulo-ocular reflex (VOR), 151, 179, 183, 192, 208, 212, 215, 233, 236,
237, 258
Vestibulo-ocular reflex suppression (VORS), 133, 184–187
Video head impulse test (vHIT), 234, 237, 251, 273, 277, 280, 283, 294, 296
Video-oculography (VOG), 234, 251, 273, 283
Visual field testing, 68, 97, 105
Visual snow syndrome (VSS), 119–121, 290
Visual vertigo, 276, 290
Visually enhanced vestibulo-ocular reflex (vVOR), 236
Vitamin E, 221
Vogt–Koyanagi–Harada, 100, 280
Voluntary nystagmus/flutter, 194
V-pattern esotropia, 172
W
Wallenberg syndrome, 146, 149, 150
Weber, 201, 203, 239, 240, 278
Wernicke’s encephalopathy, 126, 132, 146, 159, 178, 194, 196, 209–213,
246, 250, 297
Whipple’s, 181, 217, 220, 221
Z
Zonisamide, 100

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ISBN 978-3-030-76874-4 ISBN 978-3-030-76875-1 (eBook)

© Springer Nature Switzerland AG 2021

This Springer imprint is published by the registered company Springer Nature

As a first-year neurology resident, I saw my first patient with

Throughout my training, I had the great fortune of being sur-

Baltimore, MD, USA Daniel Gold

I would like to acknowledge and thank the following mentors,

1 Preparing for the Exam������������������������������������������������ 1

2.3.3 Thyroid Eye Disease ���������������������������������� 44

4.3 Subarachnoid Space, Cavernous Sinus,

7.3 Abnormal Development of the Visual

Fig. 2.1 Oculosympathetic pathway for pupillary dilation:

enters the pupil and hyperpolarizes retinal

case, which is highly suggestive of a Horner’s pupil

Fig. 2.10 The eyelid exam—levator function (LF) and lid

sia months later, whereas there’s widening of the

make up the orbit. Structures passing through the

Fig. 2.18 How can I tell if it’s safe to dilate my patient?

more difficult to visualize on undilated examination,

branch retinal vein occlusion; NAION, nonarteritic

tic visual field patterns: (a) right homonymous

from the right to the left eye, it’s as if the patient is

KB, Corbett JJ Practical Viewing of the optic Disc.

normal due to the retrobulbar location of the optic

progresses. The fundus photos above the visual fields

points to a retinochoroidal collateral vessel. These

occasionally drusen can also be seen on a CT scan

ric) right homonymous hemianopia (only able to

left) parieto-occipital parasagittal meningioma with

ganglion cells ➔ parvocellular layers of the lateral

Fig. 4.2 Multiple contralateral ocular motor palsies

yellow asterisk), supraduction paresis OS and right

facial sensation in the distributions of left V1 and V2.

thickening of the left nasal mucosa and opacifica-

and left hypermetria (and ipsipulsion or leftward

afferents to right MVN, decussate and ascend via the

horizontal head impulse test (HIT), which is occa-

the physiologic OTR. Instead, the major component

decussation at the pontomedullary junction (i.e., the

mus (top poles toward the left ear). MR diffusion-

may be overactivated with a resultant abducting

horizontal gaze; and (3) normal adduction OD with

this axial section of the pons, the proximity of the

patient has a complete left third NP (severe left

palpebrae [LP], medial rectus [MR], superior rectus

head tilt. He had additional features of a congenital

tract injury, (3) ipsi- or contralateral relative afferent

central caudal nucleus or CCN], IV, VI), neural

midbrain atrophy may give the appearance of a

supplies the flocculus (labeled on a T1 axial

horizontal, vertical and torsional components, and

itself - see Fig. 5.7). (e) Bruns nystagmus—seeing

presented with occipital headaches (worse with

responds with a conjugate eye movement, with the

around the contralateral red nucleus; these fibers

Fig. 6.2 What is the cause of my patient’s hearing loss?

the saccular innervation. Cervical vestibular evoked

Baltimore, MD, USA Daniel Gold

1 Preparing for the Exam�� 1

2.3.3 Thyroid Eye Disease �� 44

4.3 Subarachnoid Space, Cavernous Sinus,

7.3 Abnormal Development of the Visual

Table 2.1 Help me now with anisocoria�� 6

ESM 1.1 Maddox and red glass testing

Video 4.1 Evaluating the range of eye movements: Assess

and certain central patterns of head-shaking