(See also Overview of Movement and Cerebellar Disorders Overview of Movement and Cerebellar Disorders Voluntary movement requires complex interaction of the corticospinal (pyramidal) tracts, basal ganglia, and cerebellum (the center for motor coordination) to ensure smooth, purposeful movement... read more .)
The cerebellum has 3 parts:
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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.
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Midline vermis (paleocerebellum): It helps coordinate trunk and leg movements. Vermis lesions result in abnormalities of stance and gait.
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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 Cerebellar disorders have numerous causes, including congenital malformations, hereditary ataxias, and acquired conditions. Symptoms vary with the cause but typically include ataxia (impaired... read more ).
Etiology of Cerebellar Disorders
The most common cause of cerebellar disorders is
Congenital malformations
Such malformations are almost always sporadic, often occurring as part of complex malformation syndromes (eg, Dandy-Walker malformation
Hydrocephalus is accumulation of excessive amounts of CSF, causing cerebral ventricular enlargement and/or increased intracranial pressure. Manifestations can include enlarged head, bulging...
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) that affect other parts of the central nervous system (CNS).
Malformations manifest early in life and are nonprogressive. Manifestations vary markedly depending on the structures involved; ataxia is usually present.
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 FXN gene on the long arm of chromosome 9; the FXN gene codes for the mitochondrial protein frataxin. The GAA sequence is repeated 5 to 38 times within the FXN gene in people who do not have Friedreich ataxia; however, in people with Friedreich ataxia, the GAA sequence may be repeated 70 to > 1000 times (1 Etiology reference Cerebellar disorders have numerous causes, including congenital malformations, hereditary ataxias, and acquired conditions. Symptoms vary with the cause but typically include ataxia (impaired... read more ). 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 Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS) Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are characterized by abnormal motions of and, for RLS, usually sensations in the lower or upper extremities, which may... read more , 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 Secondary and Atypical Parkinsonism Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative... read more , and possibly dystonia Dystonias Dystonias are sustained involuntary muscle contractions of antagonistic muscle groups in the same body part, leading to sustained abnormal posturing or jerky, twisting, intermittent spasms that... read more , facial twitching, ophthalmoplegia Internuclear Ophthalmoplegia Internuclear ophthalmoplegia is characterized by paresis of ipsilateral eye adduction in horizontal gaze but not in convergence. It can be unilateral or bilateral. (See also Overview of Neuro-ophthalmologic... read more , and peculiar bulging eyes.
Acquired conditions
Acquired ataxias may result from nonhereditary neurodegenerative disorders (eg, multiple system atrophy
Multiple System Atrophy (MSA)
Multiple system atrophy is a relentlessly progressive neurodegenerative disorder causing pyramidal, cerebellar, and autonomic dysfunction. It includes 3 disorders previously thought to be distinct...
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), systemic disorders, multiple sclerosis
Multiple Sclerosis (MS)
Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness...
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, cerebellar strokes, repeated traumatic brain injury
Traumatic Brain Injury (TBI)
Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function. Diagnosis is suspected clinically and confirmed by imaging (primarily...
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, or toxin exposure, or they may be idiopathic. Systemic disorders include alcoholism
Alcohol Toxicity and Withdrawal
Alcohol (ethanol) is a central nervous system depressant. Large amounts consumed rapidly can cause respiratory depression, coma, and death. Large amounts chronically consumed damage the liver...
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(alcoholic cerebellar degeneration), thiamin deficiency, celiac disease
Celiac Disease
Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption...
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, heatstroke
Heatstroke
Heatstroke is hyperthermia accompanied by a systemic inflammatory response causing multiple organ dysfunction and often death. Symptoms include temperature > 40° C and altered mental status...
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, hypothyroidism
Hypothyroidism
Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as a typical facial appearance, hoarse slow speech, and dry skin and by low levels of thyroid hormones...
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, and vitamin E deficiency
Vitamin E Deficiency
Dietary vitamin E deficiency is common in developing countries; deficiency among adults in developed countries is uncommon and usually due to fat malabsorption. The main symptoms are hemolytic...
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.
Toxins that can cause cerebellar dysfunction include carbon monoxide Carbon Monoxide Poisoning Carbon monoxide (CO) poisoning causes acute symptoms such as headache, nausea, weakness, angina, dyspnea, loss of consciousness, seizures, and coma. Neuropsychiatric symptoms may develop weeks... read more , heavy metals, lithium, phenytoin, and certain solvents. Toxic levels of certain drugs (eg, antiseizure drugs, sedatives in high doses) can cause cerebellar dysfunction and ataxia.
Rarely, subacute cerebellar degeneration
Paraneoplastic syndromes are symptoms that occur at sites distant from a tumor or its metastasis. Although the pathogenesis remains unclear, these symptoms may be secondary to substances secreted...
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occurs as a paraneoplastic syndrome in patients with breast cancer, ovarian cancer, small cell carcinoma of the lung, or other solid tumors. Cerebellar degeneration may precede the discovery of the cancer by weeks to years. Anti-Yo, now called PCA-1 (Purkinje cell cytoplasmic antibody type 1) is a circulating autoantibody that occurs in the serum or cerebrospinal fluid (CSF) of some patients, especially women with breast or ovarian cancer.
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.
Etiology reference
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1. Pandolfo M: Friedreich ataxia. Arch Neurol. 65 (10):1296–1303, 2008. doi:10.1001/archneur.65.10.1296.
Diagnosis of Cerebellar Disorders
Treatment of Cerebellar Disorders
Some systemic disorders (eg, hypothyroidism, celiac disease) and toxin exposure can be treated; occasionally, surgery for structural lesions (tumor, hydrocephalus) is beneficial. However, treatment is usually only supportive (eg, exercises to improve balance, posture, and coordination; devices to help with walking, eating, and other daily activities).
Treatment reference
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1. Zesiewicz TA, Wilmot G, Kuo SH, et al: Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 90 (10):464–471, 2018. doi: 10.1212/WNL.0000000000005055.
