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.
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.
CLINICAL ILLUSTRATION 7–3
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.
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 peduncle contains 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 7–3Functions and Major Terminations of the Principal Afferent Systems to the Cerebellum.* ||Download (.pdf) TABLE 7–3 Functions and Major Terminations of the Principal Afferent Systems to the Cerebellum.*
|Afferent Tracts ||Transmits ||Distribution ||Peduncle of Entry Into Cerebellum |
|Dorsal spinocerebellar ||Proprioceptive and exteroceptive impulses from body ||Folia I–VI, pyramis and paramedian lobule ||Inferior |
|Ventral spinocerebellar ||Proprioceptive and exteroceptive impulses from body ||Folia I–VI, pyramis and paramedian lobule ||Superior |
|Cuneocerebellar ||Proprioceptive impulses, especially from head and neck ||Folia I–VI, pyramis and paramedian lobule ||Inferior |
|Tectocerebellar ||Auditory and visual impulses via inferior and superior colliculi ||Folium, tuber, ansiform lobule ||Superior |
|Vestibulocerebellar ||Vestibular impulses from labyrinths, directly and via vestibular nuclei ||Principally flocculonodular lobe ||Inferior |
|Pontocerebellar ||Impulses from motor and other parts of cerebral cortex via pontine nuclei ||All cerebellar cortex except flocculonodular lobe ||Middle |
|Olivocerebellar ||Proprioceptive input from whole body via relay in inferior olive ||All cerebellar cortex and deep nuclei ||Inferior |
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 7–4Excitatory and Inhibitory Effects. ||Download (.pdf) TABLE 7–4 Excitatory and Inhibitory Effects.
|Excitation ||Inhibition |
|Mossy fibers → granule cell ||Basket cell → Purkinje cell body |
|Olive (via climbing fibers) → Purkinje cell ||Stellate cell → Purkinje cell dendrite |
| ||Golgi cell → granule cell |
|Granule cell → Purkinje cell ||Purkinje cell → roof nuclei (including dentate) |
|Granule cell → Golgi cell ||Purkinje cell → lateral vestibular nuclei |
|Granule cell → basket cell ||Purkinje cell → Purkinje cells |
|Granule cell → stellate cell ||Purkinje cell → Golgi cells |
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.
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).
The cerebellar cortex is arranged as a highly ordered array, consisting of five primary cell types (Figs 7–19 and 7–20):
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.
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.)
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.)
Schematic diagram of the cerebellar cortex.
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.)
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 ipsilateral side of the body.
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.
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).
Magnetic resonance image of a coronal section through the head at the level of the fourth ventricle.
CLINICAL ILLUSTRATION 7–4
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.
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