Neurologic findings in Machado-Joseph disease: relation with disease duration, subtypes, and (CAG)n

Abstract

Context: Machado-Joseph disease (MJD), an autosomal dominant spinocerebellar degeneration caused by an expanded CAG repeat on chromosome 14q32.1, is a heterogeneous disorder for clinical manifestations. The reasons for the wide range of neurologic findings in this disease are poorly understood.

Objective: To explain part of this heterogeneity through the association of the neurologic findings with sex, disease duration, age of onset, clinical type, and size of CAG repeat expansion.

Design: A case-control study.

Setting: Ambulatory care.

Patients: A consecutive sample of 62 patients with MJD.

Main outcome measure: Neurologic signs.

Results: A direct relationship was found between the disease duration and severity of gait and limb ataxia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalmoplegia (P<.02). The most severe forms of nuclear ophthalmoplegia were associated with type 1 MJD, whereas those of supranuclear ophthalmoplegia were associated with type 3 MJD (P<.001). It was also found that higher mean (CAG)(n) lengths were associated with worse degrees of the pyramidal syndrome and dystonia (P<.001). The presence and severity of nystagmus, eyelid retraction, rigidity and/or bradykinesia, and optic atrophy were not clearly associated with any of the predictive variables under study.

Conclusions: Disease duration can explain part of the heterogeneity of ataxia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalmoplegia, in MJD. Type 1 MJD was positively associated with nuclear ophthalmoplegia; type 3 MJD was positively associated with supranuclear ophthalmoplegia. Higher mean CAG lengths were found to correlate with the pyramidal syndrome and dystonia. Nystagmus, eyelid retraction, rigidity and/or bradykinesia, and optic atrophy were hardly attributable to any known reason or variable.