DOPA-RESPONSIVE DYSTONIA - PATHOLOGICAL AND BIOCHEMICAL OBSERVATIONS IN A CASE

We report the first neuropathological and neurochemical study of a pat ient with dopa-responsive dystonia. She had onset of foot dystonia at age 5 years and by age 8 years it was generalized with prominent right leg and arm involvement. On levodopa 750 mg daily she had complete sy mptomatic improvement that was sustained for 11 years until death. Pat hological studies revealed normal numbers of hypopigmented substantia nigra neurons, normal tyrosine hydroxylase (TH) immunoreactivity and T H protein in the SN, no inclusion bodies or gliosis, and no evidence o f a degenerative process in the striatum. Biochemical studies revealed reduced dopamine in the substantia nigra and striatum (8% in the puta men and 18% of control in the caudate) with a similar but not identica l subregional distribution as in idiopathic Parkinson's disease. In th e striatum, TH protein and TH activity was reduced, with the loss more pronounced in the putamen than the caudate. The GBR 12935 binding to DA transporter was normal in the caudate and at the lower end of the r ange of control values in the putamen. We conclude that disturbed dopa mine synthetic capacity or a reduced arborization of striatal dopamine terminals may be the major disturbance in dopa-responsive dystonia.