THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES QUEBEC COOPERATIVE STUDY OF FRIEDREICH'S ATAXIA Familial Periodic Ataxia Responsive to Acetazolamide

Twocases,afather and son, of recurrent cerebellarataxiain the same family are reported, suggestingafamilial trait for the dysfunction. In the older male the onset of each episode (30-90 min.) was signalled by dysarthria which then progressed towards gait ataxia; the son presented closely similar clinical symptoms. Physical examination and blood chemistry revealed no obvious neurological deficit or biochemical abnormalities, with the exception of I-III and III-IV evoked auditory wave interpeak latencies, which were found markedly abnormal on the left side in the father but not in the son; the EEG of both individuals showed some diffuse, slow wave abnormalities. A low dose of acetazolamide, 250 mg daily, has successfully repressed recurrence of the attacks over the past six months. Temporary withdrawal for 14 days of the carbonic anhydrase inhibitor in the father coincided with two observed ataxic episodes. RESUME: Nous rapportons deux cas dans la meme famille (pere et fils) d'ataxie cerebelleuse recurrente. Chez le pere, le debut de chaque episode (30-90 min.) se manifestait par une dysarthrie qui progressait ensuite jusqu'a une ataxie de la marche. Le fils presentait des symptomes semblables. L'examen physique et biochmique ne revela aucun deficit neurologique evident et aucune anomalie biochimique, mais les latences interpics des ondes du potentiel auditif evoque I-III et III-IV furent trouv6es nettement anormales a gauche chez le pere, mais non chez le fils. L'EEG des deux individus a montre quelques anomalies diffuses des ondes lentes. Une faible dose d'acetazolamide, 250 mg par jour, a reussi a supprimer les episodes ataxiques pour plus de 6 mois. Une periode de retrait de cet inhibiteur de I'anhydrase carbonique, d'une duree de 14 jours chez le pere,a coincide avec deux episodes observes. Can. J. Neurol. Sci. 1984; 11:550-553 Episodic manifestations of central nervous system dysfunctions are common in clinical neurology (epilepsy, transient ischemic attacks, classical migraine); they often demonstrate a familial preponderance. In these conditions, it is believed that a principal and consistent combination of events triggers a metabolic cascade which not only is responsible for the appearance of the neurological syndrome, but which also limits the process and permits full recovery. Since repeated episodes may eventually lead to permanent CNS damage,and since they also are always socially debilitating in that they restrict job opportunities, it is imperative that treatment should aim at total suppression of the episodes. A number of rare conditions, most clearly hereditary, temporarily disturb motor functions. The best known are those marked by periodic paralyses (Engel, 1981): periodic ataxia (Parker, 1946) and familial paroxysmal choreoathetosis (Horner and Jackson, 1969). While these conditions have unknown etiologies, other conditions with a similar clinical pattern such as potassium disturbances (paralysis), alcohol or drug intoxications (ataxia), streptococcal infection or pregnancy (chorea) are better known. This paper describes a new family where both the father and son exhibit periodic ataxia. It also confirms the efficacy of acetazolamide in suppressing the clinical incidents; the drug has previously been reported to be beneficial in four other families (Griggs et al., 1978; Donat and Auger, 1979; Zasorin et al., 1983; Aimard et al., 1983). Finally, we discuss the possible mechanisms by which the carbonic anhydrase (CA) inhibitor, acetazolamide, acts to reduce or prevent the appearance of ataxic episodes.