Ataxia

4.1 Ataxia I. BACKGROUND. Ataxia is the type of clumsiness that is produced by dysfunction of the cerebellum and its pathways (1). II. PATHOPHYSIOLOGY. The usual syndrome includes hand clumsiness, abnormal or unstable gait, and dysarthria. Many movement abnormalities are seen in cerebellar dysfunction (1). A. Limb Ataxia. 1. Asynergia: decomposition of movements. Instead of the normal smooth performance, there is breakdown of the movement, rendering it irregular. 2. Dysdiadochokinesia: a manifestation of asynergia, this is the breakup and irregularity seen while performing rapid alternating movements. 3. Dysmetria: the misjudging of distance. Dysmetria includes hypermetria (overshooting), hypometria (undershooting), and loss of check (inability to stop a ballistic movement right on target). 4. Intention tremor (see Chapter 9.9, Tremor): Tremor that is characteristically worse during target-directed movements (in comparison with that of posture holding or other actions). 5. Hypotonia: decreased tone is common in cerebellar syndromes. 6. Rebound: sudden displacement of a limb that is holding a posture produces excessive overcorrection. B. Gait/Truncal Ataxia. Characterized by irregular stepping (worse with tiptoe or heel ambulation), increased lateral sway (not a straight line of ambulation), unstable turns, and inability to walk in tandem. Wide-based ambulation, spontaneous retropulsion, and true postural instability are more advanced signs of ataxia. C. Ocular Ataxia. Characterized mostly by dysmetric ocular saccades and tends to be associated with nystagmus. Patients might experience diplopia. D. Ataxic Dysarthria. Global dysarthria but with a very strong component of lingual dysarthria, frequent volume changes (usually with overall hypophonia), and scanning speech. III. EVALUATION A. Initial Workup 1. Diagnoses not to miss: medication induced, Wilson disease, thyroid abnormalities, metabolic abnormalities (liver, kidney, or electrolyte/glucose), vitamin B12, D, and E deficiencies, stroke, multiple sclerosis, hydrocephalus, and tumors (medulloblastoma, astrocytoma, ependymoma, metastasis, and others). 2. Paraneoplastic ataxias often precede structural symptoms from the primary tumor and other usual cancer clues; therefore, diagnosis has important implications. 3. Structural myelopathy is one of the most common causes of truncal ataxia, and early diagnosis avoids progression. Upper motor neuron signs can be present on both structural myelopathy and neurodegenerative ataxias. 4. In children, important etiologies for acute ataxia include intoxication, acephalgic migraine, and cerebellitis (usually varicella-zoster virus). Chronic ataxias would point to congenital defects of metabolism and leukodystrophies. 5. Environmental exposure and use of over-the-counter, herbal, or illegal drugs should be ascertained. Consider heavy metal testing. 6. Basic initial workup to consider: peripheral smear (looking for acanthocytes), pregnancy test, ceruloplasmin, thyroid function, complete metabolic panel (CMP), rapid plasma regain (RPR), vitamin B12 level, methyl malonic acid (MMA), homocysteine, folate, 25-OH vitamin D3, vitamin E, antigliadin antibody, urine drug screen, and paraneoplastic panel. B. Other Tests to Consider in Sporadic Ataxia. Lipoprotein electrophoresis (abetalipoproteinemia), Anti neutrophil cytoplasmic antibody (ANCA), alpha-fetoprotein, HIV, zinc, tissue transglutaminase/endomysial antibody, fragile X-associated tremor and ataxia syndrome (FXTAS) testing, anti-GAD antibody (Stiff person syndrome), quantitative immunoglobulins, human T lymphotrophic virus (HTLV) 1 and 2. Cerebrospinal fluid (CSF) studies should be considered in all acute/subacute cases if not contraindicated. C. Tests to Consider in Familial Ataxias. FXTAS, Friedreich's ataxia (FA) test, autosomal dominant spino-cerebellar ataxia (SCA) panel. D. Brain Imaging (MRI Better Than CT). Imaging is needed in most patients to rule out structural abnormalities (like Chiari or Dandy-Walker malformation), especially in those with rapid or unusual progression or with associated abnormal neurologic examination. E. Cervical and Thoracic Spine Imaging (Usually through MRI). Needed to rule out structural myelopathy as the cause of truncal ataxia. IV. DIAGNOSIS A. Sporadic Ataxia. If initial workup is negative (see above), other etiologies include multiple systems atrophy, celiac disease, Creutzfeldt-Jacob disease, genetic ataxias (like Friedrich ataxia, SCA 2, 3 and 6), and paraneoplastic syndromes (false-negative panel tests are expected). One of the most common causes of ataxia is alcohol abuse. Cerebellar degeneration due to alcohol can be global, but a particular alcohol syndrome, dorsal vermial atrophy, is associated with severe truncal ataxia. B. Genetic Ataxia. A good source of genetic ataxia information includes the Online Mendelian inheritance in Man (OMIM) and the Washington University in St. Louis Neuromuscular web sites (2). Special mention is needed for a relatively new, highly prevalent, commonly undiagnosed disease called FXTAS (3). This syndrome is seen in those carriers of the fragile X premutation who might also have parkinsonism and dementia. MRI of the brain tends to be revealing, including the MCP sign (bilateral T2-hyperintense middle cerebellar peduncle). 1. Dominant ataxias: These include the SCAs, dentatorubral pallidoluysian atrophy (DRPLA), and the episodic ataxias. There are more than 25 SCAs and their differentiation is difficult, rendering the SCA panel genetic testing an option (proper patient genetic counseling is needed). 2. Recessive ataxias: These include FA, abetalipoproteinemia, ataxia telangiectasia syndrome, and the treatable, isolated vitamin E deficiency (TTP1 gene mutation). FA is the most common one and presents with upper motor neuron signs, neuropathy, and cardiomyopathy. It is caused by an expanded GAA repeat on the Frataxin gene.