Hereditary parkinsonism with multiple system degeneration: beneficial effect of anticholinergics, but not of levodopa.

Two siblings who exhibited hereditary parkinsonism with pyramidal signs and cerebellar ataxia are reported. Anticholinergics had a dramatic beneficial effect in both cases, but levodopa did not. This responsiveness, which is similar to that reported in patients with Joseph's disease, suggests dysfunction of an "indirect pathway" involving the globus pallidus and the subthalamic nucleus, in addition to that of the nigrostriatal system. We propose a new hereditary variant of early onset Parkinson's disease distinct from the levodopa sensitive forms of juvenile Parkinson's disease.