Resident and Fellow Section Morris Levin, MD, Section Editor

Section of Neurology
Dartmouth Hitchcock Medical Center, Lebanon, NH
TEACHING CASE: MIGRAINE AND PUPIL
DILATION
Jennifer Ault, MD, PhD
Chief Resident in Neurology, Dartmouth Hitch-
cock Medical Center
CASE PRESENTATION
History of Present Illness:The patient is a 32-year-
old physician with seasonal allergies, depression, and
hypothyroidismwho presented to the resident neurol-
ogy clinic for treatment of headaches. At the time of
her visit she hada headache. She states that she hadher
rst headache at approximately 5 to 10 years of age.At
that time she would get a headachewhen the weather
was bad and we went to the mall. These headaches
alsomade her sicktoher stomach. She didne andhad
no headaches during middle school, high school, and
undergraduate college. In her early 20 s, she noticed
her rst migraine. She remembers this day very
clearly and said that the weather was cold and rainy
and she developed a severe headache over the course
of that day. This headache was associated with nausea,
photophobia, and phonophobia. These migraines
came very infrequently in her 20 s, every 1-2 years, and
this included vigorous academic training such as
during her professional training. At the time of a
recent headache she states she was told her right pupil
was enlarged. She has subsequently notedthis ona few
occasions during headache. For the several months
prior to her initial visit, she has had headaches every 2
or 3 weeks. Her headaches are also recently associated
with vertigo, which comes on at the onset of the head-
ache or slightly after the headache begins. She was
using 400 mg of ibuprofen when she has a migraine,
which helped some, and pseudephedrine, which helps
her sleep. Her headaches last greater than 12 hours
and at most 48 hours and seemed to be worsening in
severity, lasting longer and harder to abort. She denied
any other neurologic symptoms such as diplopia, dys-
arthria, dysphagia, syncope, or focal weakness. She had
no visual changes. She had no other aura, which pre-
ceded the headache. A computed tomography (CT)
scan of the head was normal. The patient also has
considerable neck pain, which is bilateral, left greater
than right, and primarily in the upper trapezius and
levator scapulae muscles. Triggers for migraines
appear to be primarily dropping of barometric pres-
sure and possibly stress.
Past Medical History is remarkable for hypothy-
roidism, depression, endometriosis, seasonal allergies,
and asthma, exacerbated by allergies and changes in
elevation.
Family History: There is no known family history
of headache. Her mother is 57 and has bromyalgia
and anxiety. Her father is 63 and has depression. Her
sister has some anxiety and allergies.
Social History: She works here as a physician.
She is single. She denies ethanol (ETOH), smoking, or
drug use.
Medications on initial visit:
1. Cetirizine 10 mg daily.
2. Fluticasone nasal spray daily.
3. Levothyroxine 15 mg daily.
4. Citalopram 10 mg daily.
5. Levonorgestrel and Ethinyl Estradiol 21 one
tablet daily.
6. Albuterol 2 puffs p.r.n.
Physical Exam on initial visit: In general, ill-
appearing, slightly pale female, appears uncomfort-
able. HEENT: Head is normocephalic, atraumatic.
The right pupil was 7 mm and the left pupil 4 mm.
Both pupils are normally reactive to light and
ISSN 0017-8748
doi: 10.1111/j.1526-4610.2010.01837.x
Published by Wiley Periodicals, Inc.
Headache
2011 American Headache Society
324
accommodation. Extraocular movements are intact.
Neck: There is a thyroid enlargement. No thyroid
nodules are palpated. Cervical range of motion is full.
There is tenderness about bilateral trapezius muscles
and left supraspinatus muscle. Both suboccipital
muscles are alsotender topalpation. Lungs are clear to
auscultation bilaterally. Heart: Regular rate and
rhythmwithout murmurs, rubs, or gallops. Extremities
are warm and well perfused. No clubbing, cyanosis, or
edema. Neurologic Examination: Mental status: Crisp.
Cranial nerves II through XII are intact, but notable is
the right pupil which is enlarged to 7 mmbut is briskly
reactive to light. Visual acuity is 20/20 OS and OD.
There is noptosis. Face is symmetric.Tongue protrudes
midline. Palate elevates symmetrically. Hearing is
intact. Visual elds are full. Funduscopic exam reveals
sharp disk margins with no evidence of papilledema.
Motor: 5/5 strength throughout, normal tone, no evi-
dence of atrophy. Reexes: 2+ and symmetrical
throughout with the exception of left brachioradialis
reex which is 1+ and left Achilles reex which is 1+.
There is no clonus. Toes are downgoing. Sensation:
Intact to all 4 modalities throughout. Cerebellar exam:
Normal nger-nose-nger and rapid alternating
movements. There is no dysmetria or tremor. Gait:
Normal. Tandem gait: Normal.
Follow-upOn the day of the initial evaluation,
the patients headache responded well to intramuscu-
lar diclofenac, 60 mg, and within 2 hours, pupils
became equal, remaining normally reactive. Magnetic
resonance imaging (MRI) of the brain, magnetic reso-
nance angiography (MRA) of the Circle of Willis
vessels, and MRA of the carotid and vertebral
systems in the neck were all normal. Topiramate at
50 mg at bedtime seemed to reduce the headache
frequency somewhat. Pupil dilation has occurred
once more with migraine. Rizatriptan helped head-
ache pain acutely and promethazine helped both
nausea and vertigo, which has become rare.
EXPERT COMMENTARY
Morris Levin, MD
Professor of Neurology, Professor of Psychiatry,
Dartmouth Medical School, Co-director, Dartmouth
Headache Center, Lebanon, NH, USA
Director, Dartmouth Neurology Residency
Program, Dartmouth Hitchcock Medical Center,
Lebanon, NH, USA
Director, Dartmouth Headache Medicine Fellow-
ship Program, Dartmouth Hitchcock Medical Center,
Lebanon, NH, USA
Based on the history provided, this patients head-
aches qualify as migraine and migraine with aura. The
aura she experiences recently is vertigo, but on several
occasions she has also had unilateral mydriasis (UM),
sometimes of long duration. Migraine auras can of
course take many formsvisual, tactile, auditory, olfac-
tory, vestibular, and/or cognitive. The mechanism for
some has been postulated to relate to cortical spreading
depression but this is not certain. UM has rarely been
reported to occur in conjunction with migraine. Woods
et al
1
reported a case series of seven patients with typical
migraine and UM. Maggioni et al
2
recently reported a
case with recurrent UM accompanying headaches who
later developed typical migraine aura. Others have
reported cases and case series with recurrent UM
without associated headache, and the term episodic
benign unilateral mydriasis has been suggested.
The mechanism for UM in migraine is unclear and
of course could be due to either sympathetic hyperac-
tivity or parasympathetic hypoactivity. Theories have
included spreading depression in brainstem structures,
sympathetic system hyperactivity induced perhaps by
spreading depression in the hypothalamus, and poste-
rior arterial dilation with compression of cranial nerve
III. Barriga et al
3
in a recent article reported 7 women
and 2 men over an 8-year period of observation with
migraine accompanied by time-linked UM. They pos-
tulated several possible causal factors including: latent
Adies pupil triggered by a migraine attack, ciliary
ganglionic dysfunction produced by the migrainous
process, and ophthalmoplegic migraine (OM) with
selective parasympathycoparesis.
Ophthalmoplegic migraine is dened by the Inter-
national Classication of Headache Disorders 2nd
edition (ICHD II) as follows:
1. At least 2 attacks fullling criterion B.
2. Migraine-like headache accompanied or followed
within 4 days of its onset by paresis of one or more
of the third, fourth, and/or sixth cranial nerves.
Headache 325
3. Parasellar, orbital ssure, and posterior fossa
lesions ruled out by appropriate investigations.
The ICHD comments that This condition is very
rare. It is unlikely that 13.17 Ophthalmoplegic
migraine is a variant of migraine as the headache
often lasts for a week or more and there is a latent
period of up to 4 days from the onset of headache to
the onset of ophthalmoplegia. Furthermore, in some
cases MRI shows gadolinium uptake in the cisternal
part of the affected cranial nerve which suggests that
the condition may be a recurrent demyelinating
neuropathy.
This case is dissimilar to OM in that the episode is
transient, without a latent period, and that there is no
other cranial nerve involvement beyond the cranial
nerve III parasympathetic involvement.
Mydriasis with headache should always alert the
clinician to possibilities of serious neurological or oph-
thalmological illness such as mass lesions affecting the
oculomotor nerve, aneurysm (generally of the poste-
rior communicating artery), and early uncal hernia-
tion. Diagnostic possibilities also include: acute closed
angle glaucoma, Adies tonic pupil, and spasm of the
iris dilator muscle, and these should be ruled out as
well. Neurological exam should include tests for men-
ingismus (suggestive of subarachnoid hemorrhage or
meningeal inammation), ocular tonometry, MRI of
the brain with and without contrast, and vascular
imaging (MR angiography, CT angiography or con-
ventional angiography).
A last topic relevant here is the controversial
Basilar-type Migrainedened in ICHDII as follows:
A At least 2 attacks fullling criteria B-D.
B Aura consisting of at least 2 of the following fully
reversible symptoms, but no motor weakness:
1. Dysarthria.
2. Vertigo.
3. Tinnitus.
4. Hypacusia.
5. Diplopia.
6. Visual symptoms simultaneously in both temporal
and nasal elds of both eyes.
7. Ataxia.
8. Decreased level of consciousness.
9. Simultaneously bilateral paraesthesias.
C At least one of the following:
1. At least one aura symptom develops gradually over
5 minutes and/or different aura symptoms occur
in succession over 5 minutes.
2. Each aura symptom lasts 5 and 60 minutes.
D Headache fullling criteria B-D for 1.1 migraine
without aura begins during the aura or follows aura
within 60 minutes.
E Not attributed to another disorder.
This patient did have vertigo, but no other symptoms
of basilar-type migraine, and certainly no clear progres-
sion of symptomatology or bilaterality of symptoms.
REFERENCE
1. Woods D, OConnor PS, Fleming R. Episodic unilat-
eral mydriasis and migraine. Am J Ophthalmol.
1984;98:229-234.
2. Maggioni F, Mainardi F, Malvindi ML, Zanchin G.
The borderland of migraine with aura: episodic uni-
lateral mydriasis. J Headache Pain. (on-line publica-
tion Sep 23 2010).
3. Barriga FJ, Lopez de Silanes C, Pareja JA. Ciliary
ganglioplegic migraine: Migraine-related prolonged
mydriasis. Cephalalgia. 2010;prepublication.
QUESTIONS FOR DISCUSSION
1. List the various symptoms of migrainous visual
auras.
2. How is ophthalmoplegic migraine diagnosed?
3. With anisocoria, how can mydriasis on one side be
distinguished from miosis on the other?
4. What symptoms generally accompany mydriasis?
This case presentation and discussion meets the
ACGME requirements for residency training in the fol-
lowing core competency areas: Patient Care, Medical
Knowledge, Practice-Based Learning and Improvement,
and Systems-Based Practice.
326 February 2011