The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determine the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We found that DRPLA mutation in only one Japanese patient, who was previously diagnosed with this disease. We identified the MJD mutation in 41% of the overall patient group, which included 38 autosomal dominant kindreds of Portuguese origin; the frequency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to date, the MJD mutation seems to be the most common cause of dominantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repeat expansions.

Thirty-three outpatient epileptics with normal CT scans (group 1) and 31 patients with cerebellar and brain stem (CBS) atrophy (group 2) were randomly included in this study. There were no significant statistical differences between the groups with regard to age, education, and number of grand mal and other seizures. Statistical analyses showed that group 2 had a longer history of epilepsy with a consequently longer duration of phenytoin (PHT) consumption. Neuropsychological assessment revealed lower performance by this group on the following measures: full I.Q. scale, verbal I.Q. scale, performance I.Q. scale, information, arithmetic, block design, object assembly, digit symbol, Stroop test forms I and II, the B-M dexterity test, and the simple visual and auditory reaction time. No significant differences were observed between the two groups for the remaining 5 subtests from the WAIS scale, for the immediate recall and the delayed recall subtests belonging to Wechsler memory scale as well as for visual and auditory movement time. Analysis of the composite scores of neuropsychological performance showed that the cerebellum interferes with the following complex behavioral functions: (i) visuo-spatial organization for a concrete task, a function related to the cerebello-parietal loops' (ii) planning and programming of daily activities, a function related to the cerebello-frontal loops; and (iii) the speed of information processing, a mainly subcortical function.

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