Chapter 8: The Cerebellum and Approach to Ataxia

The output of the motor cortex (and the adjacent premotor and supplementary cortices) is shaped by input from the basal ganglia and cerebellum. The basal ganglia and cerebellum participate in corticocortical loops that begin and end in motor regions. The basal ganglia are involved in the initiation and patterning of movements (see Ch. 7), and the cerebellum is involved in the coordination of movements. Both structures are also involved in cognition and eye movements. Lesions of the cerebellum can lead to incoordination of movements (ataxia), imprecision of movements (dysmetria), difficulty with rapid alternating movements (dysdiadochokinesia), truncal and gait instability, and difficulty with articulation of speech (dysarthria). Due to cerebellar involvement in oculomotor and vestibular function, cerebellar lesions can also cause nystagmus, vertigo, nausea, and vomiting.

Overall Structure of the Cerebellum

Like the brain, the cerebellum has two hemispheres consisting of a cortex, deep white matter, and deep gray matter (the bilateral dentate, emboliform, globose, and fastigial nuclei) (Fig. 8–1). At the midline, a cerebellar structure called the vermis lies between the hemispheres. The midline vermis controls coordination of the middle of the body, so pathology of the vermis leads to truncal and gait instability. The laterally placed cerebellar hemispheres control the lateral parts of the body: the limbs. Therefore, lesions of the cerebellar hemisphere can cause limb ataxia. Lesions in the cerebellar hemispheres cause deficits in the arm and/or leg ipsilateral to the affected hemisphere (in contrast to lesions of the cerebral hemispheres which cause deficits in the arm and/or leg contralateral to the affected hemisphere).

The left and right flocculi and the midline nodulus (together referred to as the flocculonodular lobe) are anterior cerebellar structures involved in vestibular function and eye movements.

The Cerebellar Peduncles

In order to coordinate movements, the cerebellum must have access to two types of information (Figs. 8–2, 8–3, and 8–4):

• What the brain wants the body to do

• Where the body is in space

After determining what needs to be done to get the body from where it is to where the brain wants it to go, the cerebellum computes a plan and sends it back to the motor regions to carry out the appropriate adjustments to coordinate ongoing movements.

To accomplish these goals, the cerebellum needs two inputs (one with information about what the brain wants the body to do, one with information about where the body is in space) and one output (to tell the brain how to guide further movements). This information travels in the three paired cerebellar peduncles (superior, middle, and inferior cerebellar peduncles on each side), which are the conduits of information into and out of the cerebellum. The cerebellar peduncles should not be confused with the cerebral peduncles (the name given to the corticospinal tracts at the level of the midbrain).

Inferior Cerebellar Peduncles: Input From Below

The inferior cerebellar peduncles mostly carry input in from inferiorly: The vestibulocerebellar tracts (vestibular information about where the head is in space), spinocerebellar tracts (proprioceptive information about where the body is in space), and olivocerebellar tracts (involved in motor learning) all travel through the inferior cerebellar peduncles to the cerebellum. The inferior cerebellar peduncles enter the cerebellum at the most inferior level of the brainstem: the medulla. All pathways traveling through the inferior cerebellar peduncles project to the ipsilateral cerebellar hemisphere except the olivocerebellar tracts, which cross. There is one minor exception to the inferior cerebellar peduncles being input pathways: The cerebellum sends output back to the vestibular system and this passes through the inferior cerebellar peduncles.

Middle Cerebellar Peduncles: Input From The Cerebral Hemispheres

The middle cerebellar peduncles carry input from the cerebral hemispheres to the cerebellum about what the brain wants the body to do. The corticopontocebellar fibers arise from motor regions, descend with the corticospinal tracts, and cross in the anterior pons to enter the contralateral cerebellum via the middle cerebellar peduncles. The majority of fibers in the “bulge” of the anterior pons are these crossing corticopontocerebellar fibers en route to the middle cerebellar peduncles.

Superior Cerebellar Peduncles: Output Back to the Brain

The superior cerebellar peduncles predominantly send information superiorly, communicating the cerebellum’s plan back to the brain. The superior cerebellar peduncles exit the cerebellum by way of the upper pons, and cross at the junction of the upper pons/lower midbrain. Some crossed fibers synapse with the red nucleus (contralateral to the cerebellar hemisphere of origin), while others continue to the ventral lateral (VL) nucleus of the thalamus (contralateral to the cerebellar hemisphere of origin), which projects to cortical motor regions. There is one minor exception to the superior cerebellar peduncles being output pathways: One component of the spinocerebellar tracts (the ventral spinocerebellar tracts) enters the cerebellum through the superior cerebellar peduncles.

The middle cerebellar peduncles and superior cerebellar peduncles both cross, creating a loop between each cerebral hemisphere and the contralateral cerebellar hemisphere. For example, motor regions in the left cerebral hemisphere project to the right cerebellar hemisphere via the crossing middle cerebellar peduncle, and the right cerebellar hemisphere projects back to the motor regions of the left hemisphere by way of the crossing superior cerebellar peduncle. This double crossing means that the relationship between cerebellar deficits and the body is ipsilateral: lesions of the left cerebellar hemisphere (connected with the right cerebral hemisphere) cause left-sided deficits and lesions of the right cerebellar hemisphere (connected with the left cerebral hemisphere) cause right-sided deficits.

All three cerebellar peduncles pass through the brainstem. It would have been simple if each peduncle corresponded to one level of the brain stem, but it does not quite work out this way: the inferior cerebellar peduncles connect the cerebellum and the brainstem at the level of the medulla, and the middle and superior cerebellar peduncles both connect the cerebellum and the brainstem at the level of the pons (mid-pons for the middle cerebellar peduncle, and upper pons for the superior cerebellar peduncle).

The vascular supply of the cerebellum comes from three pairs of circumferential arteries that arise from the vertebrobasilar system: the superior cerebellar arteries (SCAs), the anterior inferior cerebellar arteries (AICAs), and the posterior inferior cerebellar arteries (PICAs). The SCAs and AICAs arise from the basilar artery, and the PICAs usually arise from the vertebral arteries. Since these blood vessels also supply the brainstem, they are discussed in more detail with the vascular supply of the brainstem in Chapter 9.

Ataxia may be present in the limbs if there is pathology of the cerebellar hemispheres. This can be demonstrated on finger–nose and heel–shin testing, and by testing the patient’s ability to rapidly mirror the examiner’s movements (see “Examination of coordination” in Ch. 1). Gait instability/ataxia may be present if there is midline cerebellar (vermis) pathology.

When a patient presents with clumsiness, incoordination, and/or difficulty walking, the history and evaluation must determine whether such symptoms are due to sensory disturbances, weakness, or ataxia. If the problem is indeed ataxia, it is important to note that the lesion is not necessarily cerebellar. The cerebellum is only as good as its inputs and outputs. For example, a lesion affecting any of the cerebellar peduncles can lead to cerebellar ataxia by depriving the cerebellum of the inputs and outputs necessary to perform its functions. Ataxia can also be seen with disruption of the corticopontocerebellar fibers in their descent in the internal capsule or anterior pons, as demonstrated by the ataxia-hemiparesis and dysarthria-clumsy hand lacunar syndromes (see Ch. 7). If the cerebellum does not receive adequate proprioceptive information (from the inferior cerebellar peduncles), it cannot adequately coordinate movements. Therefore, problems anywhere along the dorsal column pathways (large fiber neuropathy, sensory ganglionopathy, pathology of the dorsal columns in the spinal cord) can lead to a type of ataxia known as sensory ataxia.

Distinguishing Cerebellar Ataxia From Sensory Ataxia

Ataxia due to cerebellar causes may be accompanied by additional cerebellar signs such as nystagmus (see Ch. 12), titubation (oscillation of the head and/or trunk at rest), and/or dysarthria (Table 8–1). Such findings should not be present if ataxia is caused by sensory dysfunction due to neuropathy, ganglionopathy, or dorsal column dysfunction (unless there is also concurrent cerebellar pathology). If there is a sensory etiology of ataxia, other sensory signs may be present such as diminished proprioception and vibration sense and Romberg’s sign. If sensory dysfunction is due to peripheral nervous system pathology (i.e., nerves, dorsal root ganglia, or dorsal roots), diminished or absent reflexes may be present.

Romberg’s sign is commonly mistakenly attributed to cerebellar pathology, but it is actually a sign of impaired proprioception. Patients with severe cerebellar dysfunction are often unable to stand with their feet together even with their eyes open, let alone closed. Patients with a deficit in proprioception can stand with their feet together when using vision to compensate, but closing the eyes removes this cue and requires the patient to rely exclusively on proprioception, so the patient may lose her/his balance (Romberg sign).

On finger–nose testing, cerebellar and sensory ataxia have different appearances. Cerebellar ataxia appears as an oscillatory movement perpendicular to the plane of movement (i.e., side-to-side when the patient approaches the target in the finger-nose task) and worsens as the patient approaches the target. Sensory ataxia causes what resembles a “searching” movement in which the affected limb looks as if it is approaching the target with meandering, circular movements. With slow movements under visual guidance, a patient with sensory ataxia may be able to gain reasonable accuracy with finger–nose testing. However, if the examiner leaves the target finger in the same place and asks the patient to continue going back and forth from nose to finger with the eyes closed, the patient will become increasingly inaccurate. This is because removing the patient’s visual compensation requires complete reliance on proprioception, which is impaired in sensory ataxia.

An additional subtle sign of diminished proprioception that may be seen is pseudoathetosis. Athetosis is a movement disorder characterized by writhing movements (see Ch. 23). In a patient with diminished proprioception, when the patient’s arms and hands are stretched out in front of her/him with the eyes closed (as in testing pronator drift), subtle writhing piano playing–like movements of the fingers may be noted. Similar movements of the toes may be noted when testing for Romberg’s sign. These movements may be the digits trying to “find themselves in space” without adequate proprioception to serve that function, and are referred to as pseudoathetosis.

Differential Diagnosis of Cerebellar Ataxia

As with any neurologic problem, once localized, the differential diagnosis arises from an understanding of the time course of symptom onset and evolution.

Hyperacute-onset (over seconds to hours) of cerebellar pathology can be caused by:

• Vascular causes: ischemic stroke, cerebellar hemorrhage (see Ch. 19)

• Acute toxicity: alcohol, cytarabine (see Ch. 24)

Acute- to subacute-onset (over hours to days) of cerebellar pathology can be caused by:

• Inflammatory causes:

  • Postinfectious cerebellitis (most commonly seen in children after a viral illness, most commonly varicella infection)

  • Flare of multiple sclerosis (see Ch. 21)

Subacute to chronic-onset (over weeks to months) of cerebellar pathology can be caused by:

• Infection: progressive multifocal leukoencephalopathy (see Ch. 20)

• Paraneoplastic cerebellar degeneration, which can be associated with anti-Yo (ovarian and breast cancer), anti-Hu (small cell lung cancer), anti-Tr (Hodgkin’s lymphoma), anti-Ma2 (testicular cancer), and anti-GAD (often not associated with a malignancy) antibodies (see Ch. 24)

• Tumor: medulloblastoma (in children), metastatic tumor (in adults)

• Metabolic causes: vitamin E deficiency

Chronic-onset (over months to years) of cerebellar pathology can be caused by:

• Chronic drug/toxin exposure: phenytoin, alcohol

• Degenerative etiologies

  • Acquired: multiple systems atrophy cerebellar type (MSA-C) (see Ch. 22)

  • Inherited:

    • Friedreich’s ataxia (autosomal recessive)

    • Spinocerebellar ataxias (autosomal dominant)

    • Fragile X–associated tremor ataxia syndrome (X-linked)

Vascular, infectious, multiple sclerosis lesion–related, and malignant etiologies of cerebellar disease usually lead to unilateral cerebellar dysfunction, whereas drug-related, metabolic, degenerative, and non-multiple sclerosis inflammatory etiologies (e.g., paraneoplastic or postinfectious) more commonly lead to bilateral cerebellar dysfunction.

Most of these etiologies of cerebellar dysfunction are discussed in Part 2 of this book except the inherited ataxias, which are therefore discussed here.

Inherited Causes of Cerebellar Ataxia

Friedreich’s ataxia—This autosomal recessively inherited ataxia affects the spinocerebellar tracts as well as the dorsal columns, corticospinal tracts, and peripheral nerves. In addition to ataxia and sensory loss developing in young adulthood, most patients develop cardiomyopathy. The causative mutation is in the frataxin gene (caused by GAA repeat).

Spinocerebellar ataxia—This term is applied to a growing number (more than 30) of autosomal dominantly inherited ataxias that are all characterized by adult-onset ataxia, but which can have a variety of additional features such as pyramidal, extrapyramidal, or cognitive dysfunction, and/or neuropathy. The most common spinocerebellar ataxia (SCA) is SCA3 (Machado-Joseph disease), which causes cerebellar dysfunction, cognitive impairment, neuropathy, and, in some cases, extrapyramidal features (e.g., parkinsonism; see Ch. 23). The highest prevalence of SCA3 is in the Azores, and the causative mutation is in the ATXN3 gene (caused by CAG repeat).

Fragile X–associated tremor/ataxia syndrome (FXTAS)—An adult-onset progressive ataxia called fragile X–associated tremor/ataxia syndrome (FXTAS) can be caused by mutations in the same gene (FMR1) that causes fragile X syndrome (a common cause of mental retardation in boys, accompanied by dysmorphic facial features and large testicles). FXTAS occurs in patients with a fewer number of trinucelotide (CGG) repeats than are necessary to produce fragile X syndrome (e.g., in the parent or grandparent of a child with fragile X syndrome), referred to as a premutation. As an X-linked condition, the disorder most commonly occurs in men, but can rarely occur in women in a milder form. Onset of cerebellar ataxia begins most commonly after age 50, and may be accompanied by parkinsonism and/or dementia. A characteristic MRI finding is T2/FLAIR hyperintensities in the bilateral middle cerebellar peduncles (Fig. 8–5).