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

Context: Machado-Joseph disease (MJD), an autosomal dominant spinocerebella r degeneration caused by an expanded CAG repeat on chromosome 14q32.1, is a heterogeneous disorder for clinical manifestations. The reasons for the wi de 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 s everity of gait and limb ataxia, dysarthria, dysphagia, fasciculations, pyr amidal syndrome, and ophthalmoplegia (P < .02). The most severe forms of nu clear ophthalmoplegia were associated with type 1 MJD, whereas those of sup ranuclear ophthalmoplegia were associated with type 3 MJD (P < .001). It wa s also found that higher mean (CAG)(n) lengths were associated with worse d egrees of the pyramidal syndrome and dystonia (P < .001). The presence and severity of nystagmus, eye lid retraction, rigidity and/or bradykinesia, an d optic atrophy were nor clearly associated with any of the predictive vari ables under study. Conclusions: Disease duration can explain part of the heterogeneity of atax ia, dysarthria, dysphagia, fasciculations, pyramidal syndrome, and ophthalm oplegia, in MJD. Type 1 MJD was positively associated with nuclear ophthalm oplegia; type 3 MJD was positively associated with supranuclear ophthalmopl egia. Higher mean CAG lengths were found to correlate with the pyramidal sy ndrome and dystonia. Nystagmus, eyelid retraction, rigidity and/or bradykin esia, and optic atrophy were hardly attributable to any known reason or var iable.