Clinical Neuroanatomy, 28 ed.

The Brain Stem and Cerebellum

The brain stem includes the medulla and pons, located ventral to the cerebellum. In addition to housing essential ascending and descending tracts, the brain stem contains nuclei that are essential for maintenance of life. As a result of the relatively tight packaging of numerous ascending and descending tracts, as well as nuclei, within the brain stem, even small lesions within it can injure multiple tracts and nuclei within it and thus can produce very significant neurologic deficits. The cerebellum, located just dorsal to the brain stem, plays a major role in motor coordination. Because of its proximity to the brain stem, injuries which cause swelling of the cerebellum can compress the brain stem, and thus can rapidly become life-threatening.


The lower part of the cranial portion of the neural tube (neuraxis) gives rise to the brain stem. The brain stem is divided into the mesencephalon and rhombencephalon (Fig 7–1).


FIGURE 7–1  Four stages in early development of brain and cranial nerves (times are approximate). A: 3½ weeks. B: 4½ weeks. C: 7 weeks. D: 11 weeks.

The primitive central canal widens into a four-sided pyramid shape with a rhomboid floor (Fig 7–2). This becomes the fourth ventricle, which extends over the future pons and the medulla.


FIGURE 7–2  Schematic illustration of the widening of the central cavity in the lower brain stem during development.

The neural tube undergoes local enlargement and shows two permanent flexures: the cephalic flexure at the upper end and the cervical flexure at the lower end. The cephalic flexure in an adult brain is the angle between the brain stem and the horizontal plane of the brain (see Fig 1–6).

The central canal in the rostral brain stem becomes the cerebral aqueduct. The roof of the rostral fourth ventricle undergoes intense cellular proliferation, and this lip produces the neurons and glia that will populate both the cerebellum and the inferior olivary nucleus.

The quadrigeminal plate, the midbrain tegmentum, and the cerebral peduncles develop from the mesencephalon (midbrain; see Fig 7–1), and the cerebral aqueduct courses through it. The rhombencephalon (see Fig 7–1A) gives rise to the metencephalon and the myelencephalon. The metencephalon forms the cerebellum and pons; it contains part of the fourth ventricle. The myelencephalon forms the medulla oblongata; the lower part of the fourth ventricle lies within this portion of the brain stem.

As in the spinal cord, the embryonic brain stem has a central gray core with an alar plate (consisting mostly of sensory components) and a basal plate (composed primarily of motor components). The gray columns are not continuous in the brain stem, however, and the development of the fourth ventricle causes wide lateral displacement of the alar plate in the lower brain stem. The basal plate takes the shape of a hinge (see Fig 7–2). The process is reversed at the other end, resulting in the rhomboid shape of the floor of the fourth ventricle. In addition, long tracts, short neuronal connections, and nuclei become apposed to the brain stem. The cranial nerves, like the spinal nerves, take their origin from the basal plate cells (motor nerves) or from the alar plate cell groups (sensory nerves). Unlike spinal nerves, most cranial nerves emerge as one or more bundles of fibers from the basal or basilateral aspect of the brain stem (Figs 7–1 and 7–3).


FIGURE 7–3  Ventral view of the brain stem, in relation to cerebral hemispheres and cerebellum, showing the cranial nerves.


Main Divisions and External Landmarks

Three major external divisions of the brain stem are recognizable: the medulla (medulla oblongata), the pons together with the cerebellum, and the midbrain (mesencephalon) (Figs 7–3 and 7–4). The three internal longitudinal divisions of the brain stem are the tectum (mainly in the midbrain), tegmentum, and basis (see Fig 7–4). Thus, the pons, for example, can be considered to consist of a dorsal pontine tegmentum and a ventral basis pontis. The main external structures, seen from the dorsal aspect, are shown in Figure 7–5. The superior portion of the rhomboid fossa (which forms the floor of the fourth ventricle) extends over the pons, whereas the inferior portion covers the open portion of the medulla. The closed medulla forms the transition to the spinal cord.


FIGURE 7–4  Drawing of the divisions of the brain stem in a midsagittal plane. The major internal longitudinal divisions are the tectum, tegmentum, and basis. The major external divisions are the midbrain, pons, and medulla.


FIGURE 7–5  Dorsolateral aspect of the brain stem (most of cerebellum removed).

Three pairs of cerebellar peduncles (inferior, middle, and superior) form connections with the cerebellum. The dorsal aspect of the midbrain shows four hillocks: the two superior and the two inferior colliculi, collectively called the corpora quadrigemina or quadrigeminal plate.

Internal Structural Components

A. Descending and Ascending Tracts

All descending tracts that terminate in the spinal cord (eg, the corticospinal tract; see Chapter 5) pass through the brain stem. In addition, several descending fiber systems terminate or originate in the brain stem. Similarly, all ascending tracts (eg, the spinothalamic tracts) that reach the brain stem or the cerebral cortex pass through part or all of this region; other ascending tracts originate in the brain stem. The brain stem is, therefore, an important conduit or relay station for many longitudinal pathways, both descending and ascending (Table 7–1).

TABLE 7–1  Major Ascending and Descending Pathways in the Brain Stem.


B. Cranial Nerve Nuclei

Almost all the cranial nerve nuclei are located in the brain stem. (The exceptions are the first two cranial nerve nuclei, which are evaginations of the brain itself.) Portions of the cranial nerves also pass through the brain stem.

C. Cerebellar Peduncles

The pathways to and from the cerebellum pass through three pairs of cerebellar peduncles, as described later in the Cerebellum section.

D. Descending Autonomic System Pathways

These paths to the spinal cord pass through the brain stem (see Chapter 20).

E. Reticular Formation

Several of these areas in the tegmentum of the brain stem are vitally involved in the control of respiration; cardiovascular system functions; and states of consciousness, sleep, and alertness (see Chapter 18).

F. Monoaminergic Pathways

These paths include three important systems: the serotonergic pathways from the raphe nuclei (see Chapter 3); the noradrenergic pathways in the lateral reticular formation and the extensive efferents from the locus ceruleus; and the dopaminergic pathway from the basal midbrain to the basal ganglia and others.


The functional composition of the lower 10 cranial nerves can be analyzed by referring to the development of their nuclei (Fig 7–6). The nerves are usually referred to by name or by Roman numeral (Table 7–2).


FIGURE 7–6  Cranial nerve nuclei. Left: Dorsal view of the human brain stem with the positions of the cranial nerve nuclei projected on the surface. Motor nuclei are on the left; sensory nuclei are on the right. Right:Transverse sections at the levels indicated by the arrows.

Motor (Efferent) Components

Three types of basal plate derivatives (motor nuclei) are located within the brain stem (see Table 7–2).

TABLE 7–2  Cranial Nerves and Nuclei in the Brain Stem.


General somatic efferent (SE or GSE) components innervate striated muscles that are derived from somites and are involved with movements of the tongue and eye, such as the hypoglossal nucleus of XII, oculomotor nucleus of III, trochlear nucleus of IV, and abducens nucleus of VI.

Branchial efferent (BE) components, sometimes referred to as special visceral efferents (SVE), innervate muscles that are derived from the branchial arches and are involved in chewing, making facial expressions, swallowing, producing vocal sounds, and turning the head. Examples include the masticatory nucleus of V; facial nucleus of VII; ambiguus nucleus of IX, X, and XI; and spinal accessory nucleus of XI located in the cord.

General visceral efferent (VE or GVE) components are parasympathetic preganglionic components that provide autonomic innervation of smooth muscles and the glands in the head, neck, and torso. Examples include the Edinger–Westphal nucleus of III, superior salivatory nucleus of VII, inferior salivatory nucleus of IX, and dorsal motor nucleus of X.

Sensory (Afferent) Components

Two types of alar-plate derivatives can be distinguished in the brain stem and are comparable to similar cell groups in the spinal cord (see Table 7–2).

General somatic afferent (SA or GSA) components receive and relay sensory stimuli from the skin and mucosa of most of the head: main sensory, descending, and mesencephalic nuclei of V.

General visceral afferent (VA or GVA) components relay sensory stimuli from the viscera and more specialized taste stimuli from the tongue and epiglottis: solitary nucleus for visceral input from IX and X and gustatory nucleus for special visceral taste fibers from VII, IX, and X.

Six special sensory (SS) nuclei can also be distinguished: the four vestibular and two cochlear nuclei that receive stimuli via vestibulocochlear nerve VIII. These nuclei are derived from the primitive auditory placode in the rhombencephalon (Fig 7–7A).



FIGURE 7–7  A: Key to levels of sections. B–G: Schematic transverse sections through the brain stem. The corticospinal tracts and the dorsal column nuclei/medial lemnisci are shown in color so that they can be followed as they course through the brain stem.

Differences Between Typical Spinal and Cranial Nerves

The simple and regular pattern of organization of spinal nerves is not found in cranial nerves. There is no single blueprint and the cranial nerves must thus be learned one-by-one. A single cranial nerve may contain one or more functional components; conversely, a single nucleus may contribute to the formation of one or more cranial nerves. Although some cranial nerves are solely efferent, most are mixed, and some contain many visceral components. The cranial nerves are described in detail in Chapter 8.


The medulla (medulla oblongata) can be divided into a caudal (closed; Fig 7–7B) portion and a rostral (open; Fig 7–7C) portion. The division is based on the absence or presence of the lower fourth ventricle.

Ascending Tracts

In the caudal, closed part of the medulla, the relay nuclei of the dorsal column pathway (nucleus gracilis and nucleus cuneatus) give rise to a crossed fiber bundle, the medial lemniscus. The lower part of the body is represented in the ventral portion of the lemniscus and the upper part of the body in the dorsal. The spinothalamic tract (which crossed at spinal cord levels) continues upward throughout the medulla, as do the spinoreticular tract and the ventral spinocerebellar pathway. The dorsal spinocerebellar tract and the cuneocerebellar tract continue into the inferior cerebellar peduncle.

Descending Tracts

The corticospinal tract in the pyramid begins to cross at the transition between medulla and spinal cord; this decussation takes place over several millimeters. Most of the axons in this tract arise in the motor cortex. Some fibers from the corticospinal tract, which originate in the sensory cerebral cortex, end in the dorsal column nuclei and may modify their function, thus acting to filter incoming sensory messages.

The descending spinal tract of V has its cell bodies, representing all three divisions of this tract, in the trigeminal ganglion. The fibers of the tract convey pain, temperature, and crude touch sensations from the face to the first relay station, the spinal nucleus of V, or pars caudalis. The mandibular division is represented dorsally in the nucleus, and the ophthalmic division is represented ventrally. A second-order pathway arises from the cells in the spinal nucleus and then crosses and ascends to end in the thalamus.

The medial longitudinal fasciculus is an important pathway involved with control of gaze and head movements. It descends into the cervical cord. The medial longitudinal fasciculus arises in the vestibular nuclei and carries vestibular influences downward (see Fig 17–2). More rostrally in the pons, the medial longitudinal fasciculus carries projections rostrally from the vestibular nuclei to the abducens, trochlear, and oculomotor nuclei and from the lateral gaze center in the pons to the oculomotor nuclei (see Fig 8–7).

The tectospinal tract carries descending axons from the superior colliculus in the midbrain to the cervical spinal cord. It relays impulses controlling neck and trunk movements in response to visual stimuli.

Cranial Nerve Nuclei

The hypoglossal nucleus, the dorsal motor nucleus of the vagus, and the solitary tract and nucleus are found in the medulla, grouped around the central canal; in the open medulla, these nuclei lie below the fourth ventricle (Fig 7–7C). The hypoglossal nucleus, which is homologous to the anterior horn nucleus in the cord, sends its fibers ventrally between the pyramid and inferior olivary nucleus to exit as nerve XII. This nerve innervates all the tongue muscles.

The dorsal motor nucleus of X is a preganglionic parasympathetic nucleus that sends its fibers laterally into nerves IX and X. It controls parasympathetic tone in the heart, lungs, and abdominal viscera. The superior salivatory nucleus, located just rostral to the dorsal motor nucleus, gives rise to parasympathetic axons that project in nerve VII, via the submandibular and pterygopalatine ganglia, to the submandibular and sublingual glands and the lacrimal apparatus. This nucleus controls salivary secretion and lacrimation.

The ill-defined ambiguus nucleus gives rise to the branchial efferent axons in nerves IX and X. It controls swallowing and vocalization.

The solitary nucleus (also called the nucleus solitarius) is an elongated sensory nucleus in the medulla that receives axons from nerves VII, IX, and X. The adjacent solitary tract contains the terminating axons of these nerves. The rostral part of the solitary nucleus is sometimes referred to as the gustatory nucleus. The solitary nucleus conveys information about taste and visceral sensations. Secondary fibers ascend from the solitary nucleus to the ventroposteromedial (VPM) nucleus in the thalamus, which projects, in turn, to the cortical area for taste (area 43, located near the operculum).

The four vestibular nuclei—superior, inferior (or spinal), medial, and lateral—are found under the floor of the fourth ventricle, partly in the open medulla and partly in the pons. The ventral and dorsal cochlear nuclei are relay nuclei for fibers that arise in the spiral ganglion of the cochlea. The pathways of the vestibular and cochlear nuclei are discussed in Chapters 16 and 17.

Inferior Cerebellar Peduncle

peduncle is a stalk-like bundle of nerve fibers containing one or more axon tracts. The inferior cerebellar peduncle is formed in the open medulla from several components: the cuneocerebellar and the dorsal spinocerebellar tracts, fibers from the lateral reticular nucleus, olivocerebellar fibers from the contralateral inferior olivary nucleus, fibers from the vestibular division of nerve VIII, and fibers that arise in the vestibular nuclei. All fibers are afferent to the cerebellum.


Many pathways to and from the medulla and several spinal cord tracts are identifiable in cross sections of the pons (Fig 7–7D and E).

Basis Pontis

The base of the pons (basis pontis) contains three components: fiber bundles of the corticospinal tracts, pontine nuclei that have received input from the cerebral cortex by way of the corticopontine pathway, and pontocerebellar fibers from the pontine nuclei, which cross and project to most of the neocerebellum by way of the large middle cerebellar peduncle. Along the midline of the pons and part of the medulla lie the raphe nuclei. Serotonin-containing neurons in these nuclei project widely to the cortex and hippocampus, basal ganglia, thalamus, cerebellum, and spinal cord. These cells are important in controlling the level of arousal and modulate the sleep–wake cycle. They also modulate sensory input, particularly for pain.

Pontine Tegmentum

The tegmentum of the pons is more complex than the base. The lower pons contains the nucleus of nerve VI (abducens nucleus) and the nuclei of nerve VII (the facial, superior salivatory, and gustatory nuclei). The branchial motor component of the facial nerve loops medially around the nucleus of nerve VI. The upper half of the pons harbors the main sensory nuclei of nerve V (Figs 7–7E and 7–8). The medial lemniscus assumes a different position (lower body, medial; upper body, lateral), and the spinothalamic tract courses even more laterally as it travels through the pons.


FIGURE 7–8  Schematic drawing of the trigeminal system.

The central tegmental tract contains descending fibers from the midbrain to the inferior olivary nucleus and ascending fibers that run from the brain stem reticular formation to the thalamus, and runs dorsolateral to the medial lemniscus. The tectospinal tract (from midbrain to cervical cord) and the medial longitudinal fasciculus are additional components of the pontine tegmentum.

Middle Cerebellar Peduncle

The middle cerebellar peduncle is the largest of the three cerebellar peduncles. It contains fibers that arise from the contralateral basis pontis and end in the cerebellar hemisphere.

Auditory Pathways

The auditory system from the cochlear nuclei in the pontomedullary junction includes fibers that ascend ipsilaterally in the lateral lemniscus (see Chapter 16). It also includes crossing fibers (the trapezoid body) that ascend in the opposite lateral lemniscus. A small superior olivary nucleus sends fibers into the cochlear division of nerve VIII as the olivocochlear bundle (see Fig 7–7D); this pathway modifies the sensory input from the organ of Corti in the cochlea.

Trigeminal System

The three divisions of the trigeminal nerve (nerve V; see Figs 7–7D and E and 7–8) all project to the brain stem. Fine touch function is relayed by the main sensory nucleus; pain and temperature are relayed into the descending spinal tract of V; and proprioceptive fibers form a mesencephalic tract and nucleus in the midbrain. The second-order neurons from the main sensory nucleus cross and ascend to the thalamus. The descending spinal tract of V sends fibers to the pars caudalis (the spinal nucleus in the medulla), the pars interpolaris (a link between trigeminal afferent components and the cerebellum), and the pars oralis. The masticatory nucleus, which is medial to the main sensory nucleus, sends branchial efferent fibers into the mandibular division of nerve V to innervate most of the muscles of mastication and the tensor tympani of the middle ear.


The midbrain forms a transition (and fiber conduit) to the cerebrum (see Figs 1–2 and 7–9). It also contains a number of important cell groups, including several cranial nerve nuclei.


FIGURE 7–9  Corticobulbar pathways to the nuclei of cranial nerves VII and XII. Notice that the facial nucleus for muscles of the upper face receives descending input from the motor cortex on both sides, whereas the facial nucleus for lower facial muscles receives input from only the contralateral cortex.

Basis of the Midbrain

The base of the midbrain contains the crus cerebri, a massive fiber bundle that includes corticospinal, corticobulbar, and corticopontine pathways (see Figs 7–7G and 7–9). The base also contains the substantia nigra. The substantia nigra (whose cells contain neuromelanin) receives afferent fibers from the cerebral cortex and the striatum; it sends dopaminergic efferent fibers to the striatum. The substantia nigra plays a key role in motor control. Degeneration of the substantia nigra occurs in Parkinson’s disease (see Chapter 13). The external aspect of the basis of the midbrain is called the cerebral peduncle.

The corticobulbar fibers from the motor cortex to interneurons of the efferent nuclei of cranial nerves are homologous with the corticospinal fibers. The corticobulbar fibers to the lower portion of the facial nucleus and the hypoglossal nucleus are crossed (from the opposite cerebral cortex). All other corticobulbar projections are bilaterally crossed (from both cortices).

The fibers of the oculomotor (III) nerve exit between the cerebral peduncles (see Fig 7–6) in the interpeduncular fossa. The fibers of the trochlear (IV) nerve exit on the other side of the midbrain, the tegmentum (see Fig 7–5).

Midbrain Tegmentum

The tegmentum of the midbrain contains all the ascending tracts from the spinal cord or lower brain stem and many of the descending systems. A large red nucleus receives crossed efferent fibers from the cerebellum and sends fibers to the thalamus and the contralateral spinal cord via the rubrospinal tract. The red nucleus is an important component of motor coordination.

Two contiguous somatic efferent nuclear groups lie in the upper tegmentum: the trochlear nucleus (which forms contralateral nerve IV) and the oculomotor nuclei (which have efferent fibers in nerve III). Each eye muscle innervated by the oculomotor nerve has its own subgroup of innervating cells; the subgroup for the superior rectus muscle is contralateral, whereas the others are ipsilateral to the innervated muscle. The preganglionic parasympathetic system destined for the eye (a synapse in the ciliary ganglion) has its origin in or near the Edinger–Westphal nucleus.

Close to the periventricular gray matter lie the bilateral locus ceruleus nuclei. Neurons in these nuclei contain norepinephrine and project widely to the cortex, hippocampus, thalamus, midbrain, cerebellum, pons, medulla, and spinal cord. These neurons regulate the sleep–wake cycle and control arousal; they may also modulate the sensitivity of sensory nuclei.


The tectum, or roof, of the midbrain is formed by two pairs of colliculi and the corpora quadrigemina. The superior colliculi contain neurons that receive visual as well as other input and serve ocular reflexes; the inferior colliculiare involved in auditory reflexes and in determining the side on which a sound originates. The inferior colliculi receive input from both ears, and they project to the medial geniculate nucleus of the thalamus by way of the inferior quadrigeminal brachium. The superior quadrigeminal brachium links the lateral geniculate nucleus and the superior colliculus. The colliculi contribute to the formation of the crossed tectospinal tracts, which are involved in blinking and head-turning reflexes after sudden sounds or visual images.

Periaqueductal Gray Matter

The periaqueductal gray matter contains descending autonomic tracts as well as endorphin-producing cells that suppress pain. This region has been used as the target for brain-stimulating implants in patients with chronic pain.

Superior Cerebellar Peduncle

The superior cerebellar peduncle contains efferent fibers from the dentate nucleus of the cerebellum to the opposite red nucleus (the dentatorubrothalamic system) and the ventral spinocerebellar tracts. The cerebellar fibers decussate just below the red nuclei.


The vessels that supply the brain stem are branches of the vertebrobasilar system (Fig 7–10; see also Chapter 12). Circumferential vessels are the posterior inferior cerebellar artery, the anterior inferior cerebellar artery, the superior cerebellar artery, the posterior cerebral artery, and the pontine artery. Each of these vessels sends small branches into the underlying brain stem structures along its course. Other vessels are classified as median (paramedian) perforators because they penetrate the brain stem from the basilar artery. Small medullary and spinal branches of the vertebral artery make up a third group of vessels.


FIGURE 7–10  Principal arteries of the brain stem (ventral view).

Lesions of the Brain Stem

The brain stem is anatomically compact, functionally diverse, and clinically important. Even a single, relatively small lesion nearly always damages several nuclei, reflex centers, tracts, or pathways. Such lesions are often vascular in nature (eg, infarct or hemorrhage), but tumors, trauma, and degenerative or demyelinating processes can also injure the brain stem. The following are typical syndromes caused by intrinsic (intra-axial) lesions of the brain stem.

Medial (basal) medullary syndrome usually involves the pyramid, part or all of the medial lemniscus, and nerve XII. If it is unilateral, it is also known as alternating hypoglossal hemiplegia (Fig 7–11); the term refers to the finding that the cranial nerve weakness is on the same side as the lesion, but the body paralysis is on the opposite side. Larger lesions can result in bilateral defects. The area involved is supplied by the anterior spinal artery or by medial branches of the vertebral artery.


FIGURE 7–11  Clinical syndromes associated with medullary lesions (compare with Fig 7–7C).

Lateral medullary, or Wallenberg’ssyndrome involves some (or all) of the following structures in the open medulla on the dorsolateral side (see Fig 7–11): inferior cerebellar peduncle, vestibular nuclei, fibers or nuclei of nerve IX or X, spinal nucleus and tract of V, spinothalamic tract, and sympathetic pathways. (Involvement of the sympathetic pathways may lead to Horner’s syndrome.) The affected area is supplied by branches of the vertebral artery or, most commonly, the posterior inferior cerebellar artery. An example is provided in Clinical Illustration 7–1.

Lesions Near the Brain Stem

Space-occupying processes (eg, tumors, aneurysms, brain herniation) in the area surrounding the brain stem can affect the brain stem indirectly. Several disorders, discussed next, are typically caused by extrinsic (extra-axial) lesions.

Cerebellopontine angle syndrome may involve nerve VIII or VII or deeper structures. It is most often caused by a tumor that begins by affecting the Schwann cells of a cranial nerve in that region (eg, a tumor at nerve VIII; see Fig 7–3).

A tumor in the pineal region may compress the upper quadrigeminal plate and cause vertical gaze palsy, loss of pupillary reflexes, and other ocular manifestations. There may be accompanying obstructive hydrocephalus.

Vertical gaze palsy, also called Parinaud’s syndrome, is an inability to move the eyes up or down. It is caused by compression of the tectum and adjacent areas (eg, by a tumor of the pineal gland; see Figs 7–13 and 7–14).


FIGURE 7–12  Clinical syndromes associated with pontine lesions (compare with Fig 7–7D).


FIGURE 7–13  Clinical syndromes associated with midbrain lesions (compare with Fig 7–7G).


FIGURE 7–14  Magnetic resonance image showing, in the sagittal plane, a mass lesion (arrow heads) in the patient described in Case Illustration 7–3. The mass lesion, which was shown on biopsy to be a germinoma, compressed the quadrigeminal plate and obstructed the cerebral aqueduct [arrow]. (Case illustration and image used with permission from Joachim Baehring, MD, Yale University School of Medicine.)

Other tumors near the brain stem include medulloblastoma, ependymoma of the fourth ventricle, glioma, meningioma, and congenital cysts. Medulloblastoma, a cerebellar tumor (usually of the vermis) that occurs in childhood, may fill the fourth ventricle and block the CSF pathway. Although compression of the brain stem is rare, the tumor has a tendency to seed to the subarachnoid space of the spinal cord and the brain.


A 49-year-old landscape artist, who had visited many countries in Europe, Asia, and Africa, was admitted to the hospital because of a sudden onset of facial numbness, ataxia, vertigo, nausea, and vomiting. Examination revealed impaired sensation over the left half of the face. The arm and leg on the left side were clumsy, and there was an intention tremor on the left. A left-sided Horner’s syndrome—myosis (a constricted pupil), ptosis (a weak, droopy eyelid), and decreased sweating over the forehead—was apparent. There was subjective numbness of the right arm, although no abnormalities could be detected on examination. Over the ensuing 12 hours, the patient had difficulty swallowing and complained of intractable hiccups. Vibratory and position senses were now impaired in the left arm, the vocal cord was paralyzed, and the gag reflex was diminished. On the right side, there was impaired pain and temperature sensibility. Magnetic resonance imaging demonstrated an abnormality, presumably infarction, in the lateral medulla on the left side, and a presumptive diagnosis of Wallenberg’s syndrome (lateral medullary syndrome) on the basis of occlusion of the posterior inferior cerebellar artery was made.

Arteriography revealed occlusion of the posterior inferior cerebellar artery. Lumbar puncture revealed 40 white blood cells (mostly lymphocytes) per milliliter of cerebrospinal fluid (CSF). Serologic testing was positive for syphilis. The patient was treated with penicillin. Over the ensuing 6 months, many of his deficits resolved, and he resumed his activities, including painting.

This case illustrates the development of the lateral medullary syndrome (Wallenberg’s syndrome) as a result of occlusion of the posterior inferior cerebellar artery. Because so many structures are packed closely together in the relatively small brain stem, occlusion of even relatively small arteries, such as the posterior inferior cerebellar arteries, can have profound effects.

In this case, vascular occlusion was due to syphilitic arteritis, a form of tertiary neurosyphilis. Although neurosyphilis is now rare, meningovascular syphilis was a common cause of brain stem strokes in the preantibiotic era. In evaluating strokes, it is essential to consider all of the disorders that can lead to cerebrovascular compromise. In this case, treatment with penicillin arrested the patient’s neurosyphilis and may have prevented further cerebrovascular events.

Basal pontine syndromes can involve both the corticospinal tract and a cranial nerve (VI, VII, or V) in the affected region, depending on the extent and level of the lesion (Fig 7–12). The syndrome is called alternating abducens (VI), facial (V), or trigeminal hemiplegia (V). If the lesion is large, it may include the medial lemniscus. The vascular supply comes from the perforators, or pontine branches, of the anterior inferior cerebellar artery.

The locked-in syndrome results from large lesions of the basal pons that interrupt the corticobulbar and corticospinal pathways bilaterally, thus interfering with speech, facial expression, and the capacity to activate most muscles. These pontine lesions are usually due to infarcts or hemorrhages. Somatosensory pathways and the reticular system are usually spared so that patients remain awake and aware of their surroundings. Eye movements are often spared. Patients can sometimes, therefore, communicate via a crude code in this tragic syndrome and can survive in this state for years. An example is provided in Clinical Illustration 7–2.


Gross Structure

The cerebellum is located behind the dorsal aspect of the pons and the medulla. It is separated from the occipital lobe by the tentorium and fills most of the posterior fossa. A thinner midline portion, the vermis, separates two lateral lobes, or cerebellar hemispheres (Fig 7–15). The external surface of the cerebellum displays narrow, ridge-like folds termed folia, most of which are oriented transversely.


FIGURE 7–15  Midsagittal section through the cerebellum.

The cerebellum consists of the cerebellar cortex and the underlying cerebellar white matter (see Cerebellar Cortex section). Four paired deep cerebellar nuclei are located within the white matter of the cerebellum, above the fourth ventricle. (Because they lie in the roof of the ventricle, they are sometimes referred to as roof nuclei.) These nuclei are termed, from medial to lateral, the fastigial, globose, emboliform, and dentate.

Because of the location of the fourth ventricle, ventral to the cerebellum, mass lesions or swelling of the cerebellum (eg, because of edema after an infarct) can cause obstructive hydrocephalus.


The cerebellum is divided into two symmetric hemispheres; they are connected by the vermis, which can be further subdivided (see Fig 7–15). The phylogenetically old archicerebellum consists of the flocculus, the nodulus (nodule of the vermis), and interconnections (flocculonodular system); it is concerned with equilibrium and connects with the vestibular system. The paleocerebellum consists of the anterior portions of the hemispheres and the anterior and posterior vermis and is involved with propulsive, stereotyped movements, such as walking. The remainder of the cerebellum is considered the neocerebellum and is concerned with the coordination of fine movement.


A 53-year-old architect led a productive life until, over several hours, weakness in his arms and legs developed, together with double vision and difficulty swallowing. Examination revealed weakness and hyperreflexia of the arms and legs, bilateral Babinski’s responses, facial weakness on both sides, and dysphagia. Lateral gaze was limited and nystagmus was present. A provisional diagnosis of basilar artery thrombosis was made. Arteriography confirmed this diagnosis.

Over the next 2 days, despite aggressive treatment, the patient’s deficits progressed. Total paralysis of all extremities and marked weakness of the face developed. As a result of weakness of the bulbar musculature, swallowing was impaired, and the patient could not protrude his tongue. Lateral eye movements were impaired, but vertical eye movements were maintained. The patient remained awake, with apparently preserved mentation. He was able to communicate using eye blinks and vertical eye movements. Sensation, tested via simple yes–no questions answered with eye blinks, appeared to be intact. Magnetic resonance imaging demonstrated a large infarct involving the base of the pons. The patient remained in this state, communicating with friends and family via eye blinks, for the next 5 months. He died after a cardiopulmonary arrest.

This case illustrates the locked-in syndrome. The infarction, in the base of the pons, destroyed the corticospinal and corticobulbar tracts and thus produced paralysis of the limbs and bulbar musculature. Preservation of the oculomotor and trochlear nuclei and of their nerves permitted some limited eye movement that was used for communication. Sensation was preserved, probably because the infarction did not involve the medial lemniscus and spinothalamic tracts, which are located dorsally within the pons.

This case also illustrates that consciousness can be maintained even when there is significant damage in the brain stem if the reticular system is spared.

Dorsal pons syndrome affects nerve VI or VII or their respective nuclei, with or without involvement of the medial lemniscus, spinothalamic tract, or lateral lemniscus. The “lateral gaze center” is often involved (see Fig 8–7). At a more rostral level, nerve V and its nuclei may no longer be functioning. The affected area is supplied by various perforators (pontine branches) of the circumferential arteries.

Peduncular syndrome, also called alternating oculomotor hemiplegia and Weber’s syndrome in the basal midbrain, involves nerve III and portions of the cerebral peduncle (Fig 7–13). There is a nerve III palsy on the side of the lesion and a contralateral hemiparesis (because the lesion is above the pyramidal decussation). The arterial supply is by the posterior perforators and branches of the posterior cerebral artery.

Benedikt’s syndrome, situated in the tegmentum of the midbrain, may damage the medial lemniscus, the red nucleus, and nerve III and its nucleus and associated tracts (see Fig 7–13). This area is supplied by perforators and branches of circumferential arteries.


An 18-year-old college student experienced postprandial nausea for three months. He vomited a few times and lost 6 pounds. When he started noticing vertical diplopia, a medical work-up was initiated. On neurologic examination, his pupils were 5 mm in diameter. There was light-near dissociation of pupillary response (constriction upon attempt to converge but not to light exposure). Convergence resulted in retractory nystagmus. An asymmetric upgaze palsy was observed. Funduscopic examination revealed papilledema. The deep tendon reflexes were brisk. General physical examination was unremarkable. Magnetic resonance imaging of the brain demonstrated a mass lesion [arrow heads, Fig 7-14] within the pituitary region, which compressed the quadrigeminal plate and obstructed the cerebral aqueduct [arrow]. An endoscopic biopsy revealed germinoma. The patient was successfully treated with radiation therapy.


The cerebellum has several main functions: coordinating skilled voluntary movements by influencing muscle activity, and controlling equilibrium and muscle tone through connections with the vestibular system and the spinal cord and its gamma motor neurons. There is a somatotopic organization of body parts within the cerebellar cortex (Fig 7–16). In addition, the cerebellum receives collateral input from the sensory and special sensory systems.


FIGURE 7–16  Cerebellar homunculi. Proprioceptive and tactile stimuli are projected as shown in the upper (inverted) homunculus and the lower (split) homunculus. The striped area represents the region from which evoked responses to auditory and visual stimuli are observed. (Redrawn and reproduced, with permission, from Snider R: The cerebellum. Sci Am 1958;199:84.)

As might be predicted from the cerebellar homunculi, the vermis tends to control coordination and muscle tone of the trunk, whereas each cerebellar hemisphere controls motor coordination and muscle tone on the same side of the body.


Three pairs of peduncles, located above and around the fourth ventricle, attach the cerebellum to the brain stem and contain pathways to and from the brain stem (see Fig 7–5 and Table 7–3). The inferior cerebellar pedunclecontains many fiber systems from the spinal cord (including fibers from the dorsal spinocerebellar tracts and cuneocerebellar tract; see Fig 5–17) and lower brain stem (including the olivocerebellar fibers from the inferior olivary nuclei, which give rise to the climbing fibers within the cerebellar cortex). The inferior cerebellar peduncle also contains inputs from the vestibular nuclei and nerve and efferents to the vestibular nuclei.

TABLE 7–3  Functions and Major Terminations of the Principal Afferent Systems to the Cerebellum.*


The middle cerebellar peduncle consists of fibers from the contralateral pontine nuclei. These nuclei receive input from many areas of the cerebral cortex.

The superior cerebellar peduncle, composed mostly of efferent fibers, contains axons that send impulses to both the thalamus and spinal cord, with relays in the red nuclei (see Chapter 13). Afferent fibers from the ventral spinocerebellar tract also enter the cerebellum via this peduncle.

Afferents to the Cerebellum

Afferents to the cerebellum are carried primarily via the inferior and middle cerebellar peduncles, although some afferent fibers are also present in the superior cerebellar peduncles (see prior section). These afferents end in either climbing fibers or mossy fibers in the cerebellar cortex, both of which are excitatory (Table 7–4). Climbing fibers originate in the inferior olivary nucleus and synapse on Purkinje cell dendrites. Mossy fibers are formed by afferent axons from the pontine nuclei, spinal cord, vestibular nuclei, and reticular formation: They end in specialized glomeruli, where they synapse with granule cell dendrites.

TABLE 7–4  Excitatory and Inhibitory Effects.


There are also several aminergic inputs to the cerebellum. Noradrenergic inputs, from the locus ceruleus, project widely within the cerebellar cortex. Serotonergic inputs arise in the raphe nuclei and also project to the cerebellar cortex. Most afferent fibers (both mossy and climbing fibers) send collateral branches that provide excitatory inputs to the deep cerebellar nuclei.

Cerebellar Cortex

The cerebellar cortex consists of three layers: the subpial, outer molecular layer; the Purkinje cell layer; and the granular layer, an inner layer composed mainly of small granule cells (Figs 7–17 and 7–18).


FIGURE 7–17  Photomicrograph of a portion of the cerebellum. Each lobule contains a core of white matter and a cortex consisting of three layers—granular, Purkinje, and molecular—of gray matter. H&E stain, 328. (Reproduced, with permission, from Junqueira LC, Carneiro J, Kelley RO: Basic Histology. 8th ed. Appleton & Lange, 1995.)


FIGURE 7–18  Photomicrograph of cerebellar cortex. This staining procedure does not reveal the unusually large dendritic arborization of the Purkinje cell. H&E stain, 3250. (Reproduced, with permission, from Junqueira LC, Carneiro J, Kelley RO: Basic Histology, 8th ed. Appleton & Lange, 1995.)

The cerebellar cortex is arranged as a highly ordered array, consisting of five primary cell types (Figs 7–19 and 7–20):


FIGURE 7–19  Schematic diagram of the cerebellar cortex.


FIGURE 7–20  Diagram of neural connections in the cerebellum. Shaded neurons are inhibitory. “1” and “2” signs indicate whether endings are excitatory or inhibitory. BC, basket cell; GC, Golgi cell; GR, granule cell; NC, cells within deep cerebellar nuclei; PC, Purkinje cell. Connections of the stellate cells are similar to those of the basket cells, except that they end, for the most part, on Purkinje cell dendrites. (Modified with permission from Ganong WF: Review of Medical Physiology. 22nd edition, McGraw-Hill, 2005.)

• Granule cells, with cell bodies located in the granular layer of the cerebellar cortex, are the only excitatory neurons in the cerebellar cortex. The granule cells send their axons upward, into the molecular layer, where they bifurcate in a T-like manner to become the parallel fibers. The nonmyelinated parallel fibers run perpendicular through the Purkinje cell dendrites (like the wires running between telephone poles) and form excitatory synapses on these dendrites. Glutamate appears to be the neurotransmitter at these synapses.

• Purkinje cells provide the primary output from the cerebellar cortex. These unique neurons have their cell bodies in the Purkinje cell layer and have dendrites that fan out in a single plane like the ribs of a Japanese fan or the crossbars on a telephone pole. The axons of Purkinje cells project ipsilaterally to the deep cerebellar nuclei, especially the dentate nucleus, where they form inhibitory synapses.

• Basket cells are located in the molecular layer. These cells receive excitatory inputs from the parallel fibers and project back to Purkinje cells, which they inhibit.

• Golgi cells are also located in the molecular layer and within the granule cell layer. They receive excitatory inputs from parallel fibers and mossy fibers. The Golgi cells send their axons back to the granule cells, which they inhibit.

• Stellate cells are located in the molecular layer and receive excitatory inputs, primarily from the parallel fibers. Like the basket cells, these cells give rise to inhibitory synapses on Purkinje cells.

Deep Cerebellar Nuclei

Four pairs of deep cerebellar nuclei are embedded in the white matter of the cerebellum: fastigial, globose, emboliform, and dentate. Neurons in these deep cerebellar nuclei project out of the cerebellum and thus represent the major efferent pathway from the cerebellum. Cells in the deep cerebellar nuclei receive inhibitory input (gamma-aminobutyric acid [GABA]-ergic) from Purkinje cells. They also receive excitatory inputs from sites outside the cerebellum, including pontine nuclei, inferior olivary nucleus, reticular formation, locus ceruleus, and raphe nuclei. Inputs giving rise to climbing and mossy fibers also project excitatory collaterals to the deep cerebellar nuclei. As a result of this arrangement, cells in the deep cerebellar nuclei receive inhibitory inputs from Purkinje cells and excitatory inputs from other sources. Cells in the deep cerebellar nuclei fire tonically at rates reflecting the balance between the opposing excitatory and inhibitory inputs that converge on them.

Efferents from the Cerebellum

Efferents from the deep cerebellar nuclei project via the superior cerebellar peduncle to the contralateral red nucleus and thalamic nuclei (especially ventrolateral [VL], VPL). From there, projections are sent to the motor cortex. This chain of projections provides the dentatorubrothalamocortical pathway (Fig 7–21). Via this pathway, activity in the dentate nucleus and other deep cerebellar nuclei modulates activity in the contralateral motor cortex. This crossed connection, to the contralateral motor cortex, helps to explain why each cerebellar hemisphere regulates coordination and muscle tone on the ipsilateralside of the body.


FIGURE 7–21  Schematic illustration of some cerebellar afferents and outflow pathways.

In addition, neurons in the fastigial nucleus project via the inferior cerebellar peduncle to the vestibular nuclei bilaterally and to the contralateral reticular formation, pons, and spinal cord. The axons of some Purkinje cells, located in the vermis and flocculonodular lobe, also send projections to the vestibular nuclei.

As outlined in Figure 5–17, much of the input from the spinocerebellar tracts is uncrossed and enters the cerebellar hemisphere ipsilateral to its origin. Moreover, each cerebellar hemisphere projects via the dentatorubrothalamocortical route to the contralateral motor cortex (see Fig 7–21).


The most characteristic signs of a cerebellar disorder are hypotonia (diminished muscle tone) and ataxia (loss of the coordinated muscular contractions required for the production of smooth movements). Unilateral lesions of the cerebellum lead to motor disabilities ipsilateral to the side of the lesion. Alcohol intoxication can mimic cerebellar ataxia, although the effects are bilateral.

In patients with cerebellar lesions, there can be the decomposition of movement into its component parts; dysmetria, which is characterized by the inability to place an extremity at a precise point in space (eg, touch the finger to the nose); or intention tremor, a tremor that arises when voluntary movements are attempted. The patient may also exhibit adiadochokinesis (dysdiadochokinesis), an inability to make or difficulty making rapidly alternating or successive movements; ataxia of gait, with a tendency to fall toward the side of the lesion.

A variety of pathologic processes can affect the cerebellum. Tumors (especially astrocytomas) and hypertensive hemorrhage can cause cerebellar dysfunction (Fig 7–22). In some cases cerebellar tumors can compress the underlying fourth ventricle, thereby producing hydrocephalus, a neurosurgical emergency. Cerebellar infarctions can also cause cerebellar dysfunction and, if large, may be accompanied by edema that, again, can compress the fourth ventricle, thus producing hydrocephalus. A number of metabolic disorders (especially those involving abnormal metabolism of amino acids, ammonia, pyruvate, and lactate) and degenerative diseases (including the olivopontocerebellar atrophies) can also cause cerebellar degeneration.


FIGURE 7–22  Magnetic resonance images showing tumor (medulloblastoma), shown by white arrow, originating from midline cerebellar structures, in a 29-year-old man who had experienced headaches upon awakening for a month. On examination, he was unable to tandem walk due to cerebellar dysfunction, and his deep tendon stretch reflexes were brisk, probably due to compression of the corticospinal tracts within the brain stem. As a result of prompt diagnosis, there was complete recovery after craniospinal irradiation and chemotherapy. (Used with permission from Joachim M. Baehring, MD, DSc, Yale University School of Medicine.)

Cerebellum and Brain Stem in Whole-Head Sections

Magnetic resonance imaging shows the cerebellum and its relationship with the brain stem, cranial nerves, skull, and vessels (Fig 7–23). These images are useful in determining the location, nature (solid or cystic), and extent of cerebellar lesions (see later discussion of Chiari malformation).


FIGURE 7–23  Magnetic resonance image of a coronal section through the head at the level of the fourth ventricle.


A 43-year-old woman complained of gradually increasing occipital headaches. She was righthanded and was not sure, but thought that her left hand might have been less facile when knitting. She had fallen a few times, to the left side.

Examination was normal except for signs of cerebellar dysfunction. She displayed an intention tremor on the left side, and coordination of movements of the left upper and lower extremities was poor. The patient did poorly when attempting rapid alternating movements of the left upper extremity (eg, when she was asked to rapidly supinate, then pronate, then supinate the hand) and left lower extremity (when she attempted to tap the floor rapidly with her left foot).

Imaging revealed a glioma involving the left cerebellar hemisphere.

This case illustrates that, in contrast to the cerebral cortex which controls movement on the contralateral side of the body, cerebellar lesions affect movement on the ipsilateral side of the body.


A 60-year-old technician with a history of hypertension had a sudden onset of double vision and dizziness. Three days later (1 day before admission), she noticed a sudden drooping of her right eyelid.

Neurologic examination showed unequal pupils (right smaller than left, both responding to light and accommodation), ptosis of the right eyelid, mild enophthalmos and decreased sweating on the right side of the face, and nystagmus on left lateral gaze. The corneal reflex was diminished on the right but normal on the left. Although pain sensation was decreased on the right side of the face, touch sensation was normal; there was minor right peripheral facial weakness. The uvula deviated to the left, and mild hoarseness was noted. Muscle strength was intact, but the patient could not execute a right finger-to-nose test or make rapid alternating movements. There was an intention tremor of the right arm, and further examination revealed ataxia in the right lower extremity. All reflexes were normal. Pain sensation was decreased on the left side of the body; senses of touch, vibration, and position were intact.

What is the differential diagnosis? What is the most likely diagnosis?


A 27-year-old graduate student was referred with a chief complaint of double vision of 2 weeks’ duration. Earlier he had noticed persistent tingling of all the fingers on his left hand. He also felt as though ants were crawling on the left side of his face and the left half of his tongue and thought that both legs had become weaker recently.

Neurologic examination showed a scotoma in the upper field of the left eye, weakness of the left medial rectus muscle, coarse horizontal nystagmus on left lateral gaze, and mild weakness of the left central facial muscles. All other muscles had normal strength. The deep tendon reflexes were normal on the right and livelier on the left, and there was a left extensor plantar response. The sensory system was unremarkable.

The patient was admitted to the hospital 4 months later because he noticed difficulty in walking and his speech had become thickened. Neurologic examination showed the following additional findings: wide-based ataxic gait, minor slurring of speech, bilateral tremor in the finger-to-nose test, and disorganization of rapid alternating movements. Magnetic resonance imaging revealed numerous lesions. Lumbar puncture showed 56-mg protein with a relatively increased level of gamma globulin, and electrophoresis showed several oligoclonal bands in the CSF. All other CSF findings were normal. Treatment with b-interferon was begun.

What is the differential diagnosis?

Cases are discussed further in Chapter 25.


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Ito M: The Cerebellum and Motor Control. Raven, 1984.

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Raymond JL, Lisberger SG, Mauk MD: The cerebellum: A neuronal learning machine? Science 1996;272:1126.

Riley HA: An Atlas of the Basal Ganglia, Brain Stem and Spinal Cord. Williams & Wilkins, 1943.

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BOX 7–1 Essentials for the Clinical Neuroanatomist

After reading and digesting this chapter, you should know and understand:

•  The main divisions of the brain stem: medulla, pons and cerebellum, midbrain

•  Major tracts within the brain stem

•  Cranial nerve nuclei within the brain stem

•  Vascularization of the brain stem

•  Clinical syndromes associated with medullary (Fig 7–11), pontine (Fig 7–12), and midbrain lesions (Fig 7–13)

•  Anatomy of the cerebellum

•  Functional role of the cerebellum

•  Cerebellar control of motor coordination and muscle tone on the same side of the body

•  Cellular organization of the cerebellar cortex

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