A similar but physiologically and genetically unrelated paroxysmal ataxia (EA-1) is characterized by episodes that may be precipitated by exercise and by the presence of muscle myokymia (rippling) between attacks. Vertigo does not occur and acetazolamide is less effective or not effective at all. The disorder is caused by an abnormality of the potassium channel gene on chromosome 12 (see Table 38-5).
Both of these episodic ataxias are therefore “channelopathies” (differing from the muscular and neuromuscular disorders discussed in Chap. 46). Also of interest is spinocerebellar atrophy type 6, a progressive condition in which a mutation has been traced to same gene implicated in the EA-2 acetazolamide-responsive paroxysmal ataxia, but this disorder is not paroxysmal and results in progressive ataxia, dysarthria, and loss of proprioception.
Differential Diagnosis of the Degenerative Ataxias in Adults (See Also Table 5-3)
Sporadic forms of cerebellar ataxia in adults are in some instances traceable to strokes involving cerebellar pathways (Safe et al). These are, of course, of acute onset. Some cases of ataxia are alcoholic-nutritional in origin, and a few are related to excessive use of drugs or therapeutic medications, especially antiepileptic drugs, which may in a few cases cause a slowly progressive and permanent ataxia. The paraneoplastic variety of cerebellar degeneration often enters into the differential diagnosis; it occurs mostly in women with breast or ovarian cancers and evolves much more rapidly than any of the heredodegenerative forms. The more rapid onset of ataxia and the presence of anti-Purkinje cell antibodies (anti-Yo; see “Paraneoplastic Cerebellar Degeneration” in
Chap. 30) are central to identifying the nature of this disease. In adult practice, many instances that are not attributable to a paraneoplastic disorder or to alcohol-nutritional deficiency turn out to be, or at least are attributed to, multiple system atrophy, cerebellar type. Organic mercury induces subacute cerebellar degeneration, and adulterated heroin causes a more abrupt and severe ataxic syndrome. Rare cases of ataxia have been associated with celiac disease and Whipple disease, and metronidazole as noted in Chap. 5. Ataxia may also be an early and prominent manifestation of Creutzfeldt-Jakob disease caused by a prion (see Chap. 32) or of an inherited metabolic disease (see Chap. 36). Of the latter, late-onset GM2 gangliosidosis may simulate cerebellar degeneration in adults. Rare cases of aminoacidopathy manifesting for the first time in adult life have also provoked a cerebellar syndrome (see Chap. 36).