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Clinical Neurology and Neuroanatomy: A Localization-Based Approach

Chapter 9: The Brainstem and Cranial Nerves

OVERVIEW OF BRAINSTEM ANATOMY

The three levels of the brainstem from superior to inferior are the midbrain, pons, and medulla. The midbrain is just inferior to the bilateral thalami, and the
medulla transitions inferiorly into the cervical spinal cord. Most simply, the brainstem can be thought of as a “spinal cord for the head and neck”: Just as the
spinal cord has sensory information coming in and motor information going out for the extremities and torso, the brainstem has sensory information
coming in and motor information going out for the head and neck. In addition to somatic sensory information, however, the brainstem also receives
vestibular, auditory, taste, and visceral sensory information. Motor functions of the brainstem include control of ocular, pupillary, facial, laryngeal,
pharyngeal, and visceral musculature.

Understanding the brainstem requires a general framework for what is there and where it is. As far as what is in the brainstem, there are five general
categories of structures:

1. The descending motor pathways for the extremities and torso (corticospinal tracts; see Ch. 4)

2. The ascending somatosensory pathways from the extremities and torso (dorsal columns and spinothalamic tracts; see Ch. 4)

3. The cranial nerve nuclei and associated structures

4. Connections with the cerebellum (the cerebellar peduncles; see Ch. 8)

5. The reticular activating system and ascending neurotransmitter-specific projection pathways: substantia nigra (dopamine), locus coeruleus
(norepinephrine), median raphe nuclei (serotonin), pedunculopontine nuclei (acetylcholine)

As points of orientation for where structures are in the brainstem, the following principles apply at all three levels of the brainstem (Fig. 9–1):

The corticospinal tracts run in the anterior (ventral) aspect of the brainstem.

The somatosensory pathways for the extremities and torso move a bit over the course of their ascent, but are most often posterior (dorsal) within the
brainstem (with the exception of the mid-medulla, where the medial lemnisci are medial and extend anteriorly; see Ch. 4).

The cranial nerve nuclei are all posterior (dorsal).

In general, the motor cranial nerve nuclei are closest to the midline, and their cranial nerves emerge medially/anteriorly (CN 4 is an exception in
that it exits posteriorly).

The motor cranial nerve nuclei innervating skeletal muscle are at the midline: CNs 3, 4, and 6 (innervating extraocular muscles) and CN 12
(innervating tongue muscles).

The motor cranial nerve nuclei innervating branchial muscles are more lateral: CN 7 (facial muscles), CN 5 (jaw muscles), and CNs 9 and 10
(muscles of the larynx/pharynx)

The sensory and special sensory cranial nerve nuclei are all more lateral than the motor cranial nerve nuclei: sensory nuclei of CN 5, vestibular and
cochlear nuclei (CN 8), and nucleus solitarius (for taste and visceral sensation)

The cerebellar peduncles all arise from the posterior/dorsal brainstem (logically, since the cerebellum is posterior to the brainstem)

The ascending neurotransmitter-specific projection pathways are found throughout the brainstem, but the reticular-activating system involved in
maintaining arousal and consciousness reside in the upper pons and midbrain.

FIGURE 9–1
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Chapter 9: The Brainstem and Cranial Nerves,
Schematic
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of brainstem anatomy. A: Posterior view of the brainstem with cerebellum removed revealing the locations of the cranial nerve nuclei. B–E:
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Axial sections demonstrating locations of cranial nerve nuclei and exiting cranial nerves in the midbrain (B), upper pons (C), midpons (D), and medulla (E).
Reproduced with permission from Waxman S: Clinical Neuroanatomy, 27th ed. New York: McGraw-Hill Education; 2013.
 The cerebellar peduncles all arise from the posterior/dorsal brainstem (logically, since the cerebellum is posterior to LYCEUM OF THE PHILIPPINES
the brainstem)

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The ascending neurotransmitter-specific projection pathways are found throughout the brainstem, but the reticular-activating system involved in
maintaining arousal and consciousness reside in the upper pons and midbrain.

FIGURE 9–1

Schematic of brainstem anatomy. A: Posterior view of the brainstem with cerebellum removed revealing the locations of the cranial nerve nuclei. B–E:
Axial sections demonstrating locations of cranial nerve nuclei and exiting cranial nerves in the midbrain (B), upper pons (C), midpons (D), and medulla (E).
Reproduced with permission from Waxman S: Clinical Neuroanatomy, 27th ed. New York: McGraw-Hill Education; 2013.

The Cranial Nerve Nuclei

The 12 cranial nerves can be divided into three groups of four that mostly correspond to the three brainstem levels with a few exceptions denoted by
asterisks:

Midbrain: 1*-2-3-4

Pons: 5*-6-7-8*

Medulla: 9-10-11*-12

The exceptions are as follows:

CN 1 and CN 11 do not connect with the brainstem.

CN 5 has nuclei at all three levels of the brainstem (although its fibers enter at the level of the pons as would be expected from the pons = 5*-6-7-8*
schema; see Ch. 13).

For CN 8, the vestibular nuclei are in the medulla and the cochlear nuclei are at the pontomedullary junction.

CN 2 can be considered a partial exception: Although CN 2’s main projections are the visual pathways, which do not project to the brainstem (see Ch. 6),
the afferent limb of the pupillary light reflex is communicated by CN 2 to the midbrain as would be expected by the midbrain = 1*-2-3-4 schema.

The Cerebellar Peduncles

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The three cerebellar peduncles nearly correspond to the three levels of the brainstem, with one exception (point 3 below; see also Fig. 8–3).

1. The inferior cerebellar peduncles connect the medulla to the cerebellum.

 For CN 8, the vestibular nuclei are in the medulla and the cochlear nuclei are at the pontomedullary junction. LYCEUM OF THE PHILIPPINES
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CN 2 can be considered a partial exception: Although CN 2’s main projections are the visual pathways, which do not project to the brainstem (see Ch. 6),
the afferent limb of the pupillary light reflex is communicated by CN 2 to the midbrain as would be expected by the midbrain = 1*-2-3-4 schema.

The Cerebellar Peduncles

The three cerebellar peduncles nearly correspond to the three levels of the brainstem, with one exception (point 3 below; see also Fig. 8–3).

1. The inferior cerebellar peduncles connect the medulla to the cerebellum.

2. The middle cerebellar peduncles connect the pons to the cerebellum.

3. Although things would have been simpler if the superior cerebellar peduncles connected to the midbrain to give one pair of cerebellar peduncles per
brainstem level, the superior cerebellar peduncles connect the cerebellum to the upper pons (en route to connections with the midbrain and thalamus).

The Arterial Supply of the Brainstem

The vascular supply of the brainstem corresponds to its three levels, with one pair of circumferential arteries per level of the brainstem (Fig. 9–2):

1. Superior cerebellar arteries (SCAs) for the midbrain (though the superior midbrain is supplied by the PCAs)

2. Anterior inferior cerebellar arteries (AICAs) for the pons

3. Posterior inferior cerebellar arteries (PICAs) for the medulla

FIGURE 9–2

Schematic of the arterial supply of the brainstem. A: Anterior view of the brainstem demonstrating the vertebrobasilar system and circumferential
vessels (SCA, AICA, PICA). B–E: Axial sections demonstrating blood supply of brainstem at the level of the midbrain (B), pons (C), upper medulla (D), and
lower medulla (E). Reproduced with permission from Martin J: Neuroanatomy Text and Atlas, 4th ed. New York: McGraw-Hill Education; 2012.

These arteries all have “cerebellar” in their names since they not only supply the brainstem, but also the cerebellum posterior to it. Most commonly, the
SCAs and AICAs arise from the basilar artery and the PICAs from the vertebral arteries. The anterior spinal artery arises from the vertebral arteries and
supplies the medial medulla and anterior spinal cord. At the level of the pons and midbrain, the midline basilar artery supplies the medial brainstem through
penetrating branches.

Tables 9-1, 9-2, 9-3, and 9-4 summarize the structures of the brainstem (Table 9-1), the afferent and efferent limbs of the brainstem reflexes (Table 9-2), the
cranial nerve functions, associated nuclei, and skull foramina of entry and exit (Table 9-3), and the cranial nerve nuclei (Table 9-4). Individual cranial nerves
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and their associated pathways are discussed in more detail in Chapters 10-14.
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TABLE 9–1
Brainstem Structures.
These arteries all have “cerebellar” in their names since they not only supply the brainstem, but also the cerebellum posterior to it. Most commonly, the
SCAs and AICAs arise from the basilar artery and the PICAs from the vertebral arteries. The anterior spinal artery arises from the vertebral arteries and
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supplies the medial medulla and anterior spinal cord. At the level of the pons and midbrain, the midline basilar artery supplies the medial brainstem through
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penetrating branches.

Tables 9-1, 9-2, 9-3, and 9-4 summarize the structures of the brainstem (Table 9-1), the afferent and efferent limbs of the brainstem reflexes (Table 9-2), the
cranial nerve functions, associated nuclei, and skull foramina of entry and exit (Table 9-3), and the cranial nerve nuclei (Table 9-4). Individual cranial nerves
and their associated pathways are discussed in more detail in Chapters 10-14.

TABLE 9–1
Brainstem Structures.

Cerebellar
Blood Supply Cranial Nerve Nuclei Ascending Projections
Peduncles

Midbrain PCA/SCA/Basilar Pretectal nuclei (CN 2) Reticular activating system

Edinger-Westphal nuclei (CN 3) Substantia nigra (dopamine)
Oculomotor nuclei (CN 3) Median raphe nuclei (serotonin)
Trochlear nuclei (CN 4)
Mesencephalic nuclei of CN 5

Pons AICA/Basilar Superior Motor and principal sensory nuclei of CN 5 Reticular activating system
Middle Abducens nuclei (CN 6) Locus coeruleus (norepinephrine)
Facial nuclei (CN 7) Pedunculopontine nuclei
Superior salivatory nuclei (CN 7) (acetylcholine)
Cochlear nuclei at pontomedullary junction Median raphe nuclei (serotonin)
(CN 8)

Medulla PICA/Vertebral Inferior Spinal tract/nuclei of CN 5 Median raphe nuclei (serotonin)

arteries Vestibular nuclei (CN 8)
Nucleus solitarius (CNs 7, 9, and 10)
Inferior salivatory nuclei (CN 9)
Nucleus ambiguus (CNs 9 and 10)
Hypoglossal nuclei (CN 12)

AICA, anterior inferior cerebellar artery; CN, cranial nerve; PICA, posterior inferior cerebellar artery; SCA, superior cerebellar artery.

TABLE 9–2
Brainstem Reflexes.

Cranial Nerves

Afferent Efferent

Pupillary CN 2 CN 3

Jaw jerk CN 5 CN 5

Corneal CN 5 CN 7

Oculocephalic CN 8 CNs 3, 4, and 6

Gag CN 9 CN 10

CN, cranial nerve

TABLE 9–3
Cranial Nerve Functions, Brainstem Nuclei, and Associated Skull Foramina.
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Cranial Somatic Foramen
Somatic Motor Special Sensory Visceral Motor Visceral Sensory Brainstem Nuclei
Nerve Sensory of Exit
 Gag CN 9 CN 10
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CN, cranial nerve

TABLE 9–3
Cranial Nerve Functions, Brainstem Nuclei, and Associated Skull Foramina.

Cranial Somatic Foramen

Somatic Motor Special Sensory Visceral Motor Visceral Sensory Brainstem Nuclei
Nerve Sensory of Exit

CN 1 Olfaction Cribriform
plate

CN 2 Vision Pretectal nuclei Optic canal

(midbrain)

CN 3 Superior rectus Oculomotor Cavernous

Inferior rectus nucleus sinus→
Medial rectus Edinger- superior
Inferior oblique Westphal orbital
Levator palpebrae nucleus fissure
Pupilloconstrictors (midbrain)

CN 4 Superior oblique Trochlear nucleus Cavernous

(midbrain) sinus→
superior
orbital
fissure

CN 5 Muscles of Face Mesencephalic Ophthalmic

mastication Anterior nucleus of CN 5 (V1):
(temporalis, 2/3 of (midbrain) Cavernous
masseter, tongue Main sensory sinus→
pteryogoids) Dura nucleus of CN 5 superior
Anterior belly of mater (pons) orbital
digastric (shared Motor nucleus fissure
Tensor veli palitini with CN of CN 5 (pons) Maxillary
Tensor tympani 10) Spinal nucleus (V2):
Mylohoid of CN 5
Cavernous
(medulla)
sinus→
foramen
rotundum
Mandibular
(V3):
foramen
ovale

CN 6 Lateral rectus Abducens nucleus Cavernous

(pons) sinus→
superior
orbital
fissure

CN 7 Facial muscles External ear Taste anterior 2/3 Lacrimal Facial nucleus Internal
Stapedius of tongue glands (pons) auditory
Stylohoid Nasal glands Superior canal
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Posterior belly of
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digastric glands nucleus (pons)
Sublingual Nucleus
glands solitarius
 orbital
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fissure
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CN 7 Facial muscles External ear Taste anterior 2/3 Lacrimal Facial nucleus Internal
Stapedius of tongue glands (pons) auditory
Stylohoid Nasal glands Superior canal
Posterior belly of Submandibular salivatory
digastric glands nucleus (pons)
Sublingual Nucleus
glands solitarius
(medulla)
(i.e., all glands of
head except
parotid)

CN 8 Hearing Cochlear Internal

Balance (pontomdullary auditory
junction) canal
Vestibular
(medulla)

CN 9 Stylopharyngeus External Taste posterior Parotid glands Carotid body Nucleus Jugular
and 1/3 of tongue ambiguus foramen
middle ear (medulla)
Posterior Inferior
tongue salivatory
nucleus
(medulla)
Nucleus
solitarius
(medulla)

CN 10 All pharyngeal and Pharynx Taste Thoracic and Aortic arch Nucleus Jugular
laryngeal muscles except External epiglottis/pharynx abdominal viscera Thoracic and ambiguus foramen
mylohyoid (CN 5), tensor auditory (except distal 1/3 of abdominal (medulla)
veli palitini (CN 5), meatus colon and viscera Dorsal motor
stylohyoid (CN 7), and Dura of genitourinary (except nucleus of
stylopharyngeus (CN 9) posterior system) distal 1/3 of vagus (medulla)
fossa colon and Nucleus
(except genitourinary solitarius
tentorium) system) (medulla)

CN 11 Sternocleidomastoid Jugular
Trapezius foramen

CN 12 Muscles of the tongue Hypoglossal nucleus Hypoglossal

canal

CN, cranial nerve.

TABLE 9–4
Cranial Nerve Nuclei (Aside From Those Named for Their Associated Cranial Nerves).

Brainstem Level Function(s) Cranial Nerve(s) (CN(s))

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Edinger-Westphal nucleus
Chapter 9: The Brainstem and Cranial Nerves, Midbrain Pupillary constriction CN 3 Page 6 / 8
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Superior salivatory nucleus Pons Submandibular glands CN 7
Sublingual glands
 CN 12 Muscles of the tongue Hypoglossal nucleus Hypoglossal
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canal
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CN, cranial nerve.

TABLE 9–4
Cranial Nerve Nuclei (Aside From Those Named for Their Associated Cranial Nerves).

Brainstem Level Function(s) Cranial Nerve(s) (CN(s))

Edinger-Westphal nucleus Midbrain Pupillary constriction CN 3

Superior salivatory nucleus Pons Submandibular glands CN 7

Sublingual glands
Lacrimal glands
Nasal/palatal glands

Inferior salivatory nucleus Medulla Parotid gland CN 9

Nucleus ambiguus Medulla Laryngeal muscles CNs 9 and 10

Pharyngeal muscles

Nucleus solitarius Medulla Taste CNs 7, 9, and 10

Visceral afferent CNs 9 and 10

CN, cranial nerve.

CLINICAL APPLICATIONS OF BASIC BRAINSTEM ANATOMY

Crossed Signs Due to Brainstem Lesions

Recall that the corticospinal tracts do not cross until the cervicomedullary junction, the dorsal column pathways cross in the medulla, and the spinothalamic
tracts cross in the spinal cord (see Ch. 4). Therefore, throughout most of the brainstem, lesions lead to contralateral weakness and/or sensory symptoms in
the extremities. However, with the exception of CN 4, all cranial nerves project ipsilaterally. Therefore, unilateral lesions of the brainstem cause ipsilateral
sensory and/or motor symptoms in the face, but contralateral symptoms in the body (crossed signs). For example, a lesion affecting the left pons would
cause ipsilateral (left-sided) facial weakness (CN 7) and contralateral (right-sided) arm/leg weakness (not-yet-crossed corticospinal tract).

Medial Versus Lateral Brainstem Syndromes

As discussed above, the descending corticospinal tracts are anterior and medial throughout the three levels of the brainstem, and the motor cranial nerve
nuclei for skeletal muscle (CN 3, CN 4, CN 6, CN 12) are posterior and medial and their associated cranial nerves exit anteriorly and medially (with the
exception of CN 4, the only cranial nerve that exits posteriorly) (Fig. 9-3). The sensory and special sensory cranial nerve nuclei are dorsolateral in the
brainstem. Therefore, lesions of the medial brainstem cause predominantly motor symptoms and signs, whereas lesions of the dorsolateral brainstem
cause predominantly sensory and special sensory symptoms and signs. Since the cerebellar peduncles are positioned on the dorsal/dorsolateral aspects of
the brainstem (and the cerebellum is just posterior to the brainstem and supplied by the same circumferential arteries), dorsolateral brainstem pathology
may cause cerebellar symptoms (e.g., ataxia, nausea/vomiting; see Ch. 8).

FIGURE 9–3

Axial diffusion-weighted MRI of medial and lateral medullary infarction: A: Left medial medullary infarction. B : Left lateral medullary infarction.

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For example, in the medulla, the schema to recall the relevant cranial nerve nuclei is “9-10-11*-12,” but we must remove CN 11 (an exception), and add the
spinal nucleus of CN 5 (pain and temperature sensation in the face; see Ch. 13) and the vestibular nuclei of CN 8. CN 12 innervates skeletal muscle, and so its
may cause cerebellar symptoms (e.g., ataxia, nausea/vomiting; see Ch. 8).
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FIGURE 9–3 Access Provided by:

Axial diffusion-weighted MRI of medial and lateral medullary infarction: A: Left medial medullary infarction. B : Left lateral medullary infarction.

For example, in the medulla, the schema to recall the relevant cranial nerve nuclei is “9-10-11*-12,” but we must remove CN 11 (an exception), and add the
spinal nucleus of CN 5 (pain and temperature sensation in the face; see Ch. 13) and the vestibular nuclei of CN 8. CN 12 innervates skeletal muscle, and so its
nuclei are medial with the bilateral CN 12 exiting anteriorly and medially. The branchial motor nuclei associated with CN 9 and CN 10 are dorsolateral to the
CN 12 nucleus. The spinal nucleus of CN 5 and the special sensory vestibular nuclei (CN 8) are dorsolateral to the nuclei of CN 9 and CN 10. Therefore,
unilateral medial medullary infarction causes ipsilateral tongue weakness (CN 12) and contralateral extremity weakness (due to involvement of the not-yet-
crossed corticospinal tract). In contrast, lateral medullary infarction causes ipsilateral loss of facial pain/temperature sensation (spinal tract and nucleus of
CN 5) and contralateral pain/temperature sensation loss in the extremities (due to involvement of the already-crossed anterolateral tract) as well as vertigo
(vestibular nuclei), nausea/vomiting and ataxia (inferior cerebellar peduncle and cerebellum), dysarthria and dysphagia (nucleus ambiguus), and ipsilateral
Horner’s syndrome (descending oculosympathetic pathway; see. Ch. 10). This constellation of findings in lateral medullary infarction is called Wallenberg’s
syndrome. Medial medullary infarction is caused by occlusion of the anterior spinal artery, and lateral medullary infarction is caused by occlusion of the
vertebral artery or PICA.

When brainstem syndromes are caused by stroke, a lateral syndrome generally suggests occlusion of a circumferential artery (SCA, AICA, PICA), whereas a
medial syndrome generally suggests occlusion of a penetrating branch of the vertebrobasilar system (or the anterior spinal artery at the level of the
medulla). Pathophysiologically, a distal occlusion of a circumferential artery can suggest embolism as the mechanism, whereas a more medial stroke in the
territory of a penetrating branch from one of the vertebral arteries or the basilar artery can suggest atherosclerosis (see Ch. 19).

Locked-in Syndrome

In locked-in syndrome, the patient is awake and conscious, but cannot move or communicate with the exception of blinking and vertical gaze. The portion
of the reticular-activating system responsible for maintaining consciousness and arousal is in the dorsal pons (pontine tegmentum) and midbrain. Ventral
pontine lesions (e.g., basilar artery thrombosis, pontine hemorrhage, central pontine myelinolysis) cause loss of all motor function controlled by the pons
(resulting in quadriplegia, bilateral facial weakness, horizontal gaze palsy), but the patient may still be awake and able to blink and look vertically if the
dorsal pons, midbrain, and structures superior to it (i.e., thalami, cerebral hemispheres) are spared. (In basilar thrombosis, these regions can be perfused
by collateral flow through the posterior communicating arteries to the posterior circulation distal to the occlusion). It is important to distinguish the locked-
in state from coma, since a locked-in patient is conscious (as compared to a comatose patient, who is not).

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