Cerebellar Disorders

By Hector A. Gonzalez-Usigli, MD, Assistant Professor in Neurology, Department of Internal Medicine, Instituto Mexicano del Seguro Social, Guadalajara

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Movement and Cerebellar Disorders
Overview of Movement and Cerebellar Disorders
Chorea, Athetosis, and Hemiballismus
Dystonias
Cervical Dystonia
Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS)
Huntington Disease
Myoclonus
Parkinson Disease
Secondary and Atypical Parkinsonism
Progressive Supranuclear Palsy
Tremor
Cerebellar Disorders

Cerebellar disorders have numerous causes, including congenital malformations, hereditary ataxias, and acquired conditions. Symptoms vary with the cause but typically include ataxia (impaired muscle coordination). Diagnosis is clinical and often by imaging and sometimes genetic testing. Treatment is usually supportive unless the cause is acquired and reversible.

The cerebellum has 3 parts:

Archicerebellum (vestibulocerebellum): It includes the flocculonodular lobe, which is located in the medial zone. The archicerebellum helps maintain equilibrium and coordinate eye, head, and neck movements; it is closely interconnected with the vestibular nuclei.
Midline vermis (paleocerebellum): It helps coordinate trunk and leg movements. Vermis lesions result in abnormalities of stance and gait.
Lateral hemispheres (neocerebellum): They control quick and finely coordinated limb movements, predominantly of the arms.

There is growing consensus that in addition to coordination, the cerebellum controls some aspects of memory, learning, and cognition.

Ataxia is the archetypal sign of cerebellar dysfunction, but many other motor abnormalities may occur (see Table: Signs of Cerebellar Disorders).

Signs of Cerebellar Disorders

Deficit	Manifestation
Ataxia	Reeling, wide-based gait
Decomposition of movement	Inability to correctly sequence fine, coordinated acts
Dysarthria	Inability to articulate words correctly, with slurring and inappropriate phrasing
Dysdiadochokinesia	Inability to perform rapid alternating movements
Dysmetria	Inability to control range of movement
Hypotonia	Decreased muscle tone
Nystagmus	Involuntary, rapid oscillation of the eyeballs in a horizontal, vertical, or rotary direction, with the fast component maximal toward the side of the cerebellar lesion
Scanning speech	Slow enunciation with a tendency to hesitate at the beginning of a word or syllable
Tremor	Rhythmic, alternating, oscillatory movement of a limb as it approaches a target (intention tremor) or of proximal musculature when fixed posture or weight bearing is attempted (postural tremor)

Etiology

Hereditary ataxias

Hereditary ataxias may be autosomal recessive or autosomal dominant. Autosomal recessive ataxias include Friedreich ataxia (the most prevalent), ataxia-telangiectasia, abetalipoproteinemia, ataxia with isolated vitamin E deficiency, and cerebrotendinous xanthomatosis.

Friedreich ataxia results from a gene mutation causing abnormal repetition of the DNA sequence GAA in the gene that codes for the mitochondrial protein frataxin. Inheritance is autosomal recessive. Decreased frataxin levels lead to mitochondrial iron overload and impaired mitochondrial function.

In Friedreich ataxia, gait unsteadiness begins between ages 5 and 15; it is followed by upper-extremity ataxia, dysarthria, and paresis, particularly of the lower extremities. Mental function often declines. Tremor, if present, is slight. Reflexes and vibration and position senses are lost. Talipes equinovarus (clubfoot), scoliosis, and progressive cardiomyopathy are common. By their late 20s, patients may be confined to a wheelchair. Death, often due to arrhythmia or heart failure, usually occurs by middle age.

Spinocerebellar ataxias (SCAs) are the main autosomal dominant ataxias. Classification of these ataxias has been revised many times recently as knowledge about genetics increases. Currently, at least 43 different gene loci are recognized; about 10 involve expanded DNA sequence repeats. Some involve a repetition of the DNA sequence CAG that codes for the amino acid glutamine, similar to that in Huntington disease.

Manifestations of SCAs vary. Some of the most common SCAs affect multiple areas in the central and peripheral nervous systems; neuropathy, pyramidal signs, and restless leg syndrome, as well as ataxia, are common. Some SCAs usually cause only cerebellar ataxia.

SCA type 3, formerly known as Machado-Joseph disease, may be the most common dominantly inherited SCA worldwide. Symptoms include ataxia, parkinsonism, and possibly dystonia, facial twitching, ophthalmoplegia, and peculiar bulging eyes.

Acquired conditions

Acquired ataxias may result from nonhereditary neurodegenerative disorders (eg, multiple system atrophy), systemic disorders, multiple sclerosis, cerebellar strokes, repeated traumatic brain injury, or toxin exposure, or they may be idiopathic. Systemic disorders include alcoholism (alcoholic cerebellar degeneration), celiac disease, heatstroke, hypothyroidism, and vitamin E deficiency. Toxins include carbon monoxide, heavy metals, lithium, phenytoin, and certain solvents. Toxic levels of certain drugs (eg, anticonvulsants) can cause cerebellar dysfunction and ataxia.

In children, primary brain tumors (medulloblastoma, cystic astrocytoma) may be the cause; the midline cerebellum is the most common site of such tumors. Rarely, in children, reversible diffuse cerebellar dysfunction follows viral infections.