Drug-induced motor complications in dopa-responsive dystonia: Implicationsfor the pathogenesis of dyskinesias and motor fluctuations

Dopa-responsive dystonia (DRD) is characterized by striatal dopamine deplet ion with preserved nigrostriatal terminals. Patients with DRD typically obt ain a marked long-term benefit from low doses of levodopa, with no motor co mplications. By contrast, motor fluctuations and dyskinesias often occur in idiopathic parkinsonism (Parkinson's disease; PD). This suggests that nigr ostriatal denervation may be necessary for the development of these levodop a-related motor complications. Six genetically confirmed DRD cases were stu died. Three of the five patients who were on chronic levodopa therapy devel oped choreic dyskinesias, which disappeared on reduction of medication. Apo morphine also induced dyskinesias. Tn addition, two patients experienced ac ute dystonic reactions after exposure to dopamine receptor-blocking drugs. No patient showed dose-response motor fluctuations during levodopa treatmen t. It is proposed that striatal dopamine deficiency might play a major role in the pathogenesis of drug-induced dyskinesias. Conversely, the loss of n igrostriatal dopamine terminals seems to be a prerequisite for the developm ent of levodopa-related motor fluctuations.