Contributed by Hubert Fernandez, MD
Head, Movement Disorders
Department of Neurology
Cleveland, Ohio USA
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The diagnosis of ataxic syndromes is becoming increasingly challenging. A complete history, physical examination, and sometimes neuroimaging, as well as extensive laboratory evaluation may be required. In many cases, etiology of ataxia remains uncertain despite a complete workup. Because many chronic cerebellar ataxias are genetically determined, family history should be obtained. Ataxia may also occur sporadically in disorders such as multiple system atrophy, a syndrome that can also present with autonomic instability and parkinsonism.
In younger patients, nutritional abnormalities (some genetically related) such as primary vitamin E deficiency, as well as abnormalities in serum lipoproteins causing fat malabsorption can cause ataxia, as can mitochondrial disease. In older patients, autoimmune syndromes including paraneoplastic syndromes can result in ataxia. Celiac disease, an autoimmune disease with anti-gliadin antibodies, may result in ataxia. Furthermore, ataxia can be associated with multiple sclerosis. The time course of the ataxia is also an important diagnostic feature, as acute ataxic syndromes frequently are related to acute infectious, vascular, structural, or metabolic lesions, while chronic ataxias are more apt to be related to genetic syndromes or slow growing mass lesions.
The diagnosis of ataxia has become more complex with the explosion of genetic causes of ataxia. Identifiable recessive causes of ataxia are more common in children, including a host of metabolic abnormalities such as juvenile forms of GM2 gangliosidoses, sulfatide lipidoses, and other syndromes involving deposition of abnormal metabolic intermediates. Friedreich’s ataxia can occur in children and in young adults, and has occasionally been described in older individuals. Hereditary ataxia with vitamin E deficiency is recessive and can present with symptoms very similar to those found in Friedreich’s ataxia. Abetalipoproteinemia is another recessive cause of vitamin E deficiency, and depending on the severity of the deficit and the related vitamin E deficiency, may occur in children or adults. Case reports in the literature suggest that Vitamin B-12 may also occasionally present with chronic ataxia, often related to loss of proprioception.
There are several identified causes of autosomal dominant ataxia, including 7 syndromes caused by CAG repeats encoding a polyglutamine protein domain (SCA 1, SCA2, SCA3, SCA6, SCA7, SCA17, DRPLA). Genetic testing is available for several of these disorders through a variety of sources. Although most cases of SCA 8 appear to be associated with a CTG expansion, CTG expansions in the same region have been shown to occur in some healthy controls.
Episodic ataxia is a rare and defined dominantly inherited genetic entity. In Episodic ataxia type 1 (EA1), episodes of ataxia, with gait imbalance and slurring of speech, occur spontaneously or can be precipitated by sudden movement, excitement, or exercise. The attacks generally last from seconds to several minutes at a time and may recur many times a day. In Episodic ataxia type 2 (EA2), ataxia lasts hours to days, with interictal eye movement abnormalities.
Exertion and stress commonly precipitate the episodes. EA2 notably is due to a genetic defect in a calcium channel (CACNA1A), and different genetic defects of this channel can cause genetically transmitted familial hemiplegic migraine. A CAG repeat in this gene causes a progressive ataxia (SCA6), and there are overlaps in symptomatology. Patients may have migrainous episodes as well as ataxia, and some patients with the SCA6 mutation may present with episodic ataxia. Acetazolamide may be helpful in the treatment of episodic ataxia.
Evaluation and management of ataxia should focus first on excluding symptomatic causes. Consideration of genetic testing should occur after reversible causes are excluded. Acute onset of ataxia should be considered a neurologic and potentially a neurosurgical emergency until structural, vascular, or toxic causes of acute ataxia are ruled out. In children, reversible causes include a host of metabolic lesions that should be considered, and referral to a pediatric neurologist may be appropriate if initial evaluations are not fruitful. In adults, Vitamin E and occasionally Vitamin B-12 deficiency are rarely a cause of chronic progressive ataxia and should not be overlooked in a diagnostic workup. In patients with an identified genetic cause, testing of unaffected family members should be performed with caution and the involvement of a genetic counselor is often helpful.
After correction of symptomatic causes, management is typically supportive but may include physical, occupational, and speech therapy. Several agents have been inconsistently reported to improve ataxia: amantadine, L-5-hydroxytryptophan, odansetron, physostigmine, branched-chain amino acid therapy, gabapentin, piracetam Surgical ablation or deep brain stimulation surgery of the ventral intermediate nucleus of the thalamus (VIM) may be effective in reducing cerebellar tremor, however, they often do not significantly lessen ataxia, although a few cases have been reported with benefit (e.g. SCA’s).