MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia.
The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D2-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson's disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.
Perlmutter
J S
JS
Department of Neurology and Neurological Surgery (Neurology), Washington University School of Medicine, St. Louis, MO, USA.
Tempel
L W
LW
Black
K J
KJ
Parkinson
D
D
Todd
R D
RD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002339:Carotid Arteries; D015259:Dopamine Agents; D004421:Dystonia / Q000139:chemically induced* / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008297:Male; D009068:Movement; D010215:Papio; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D014743:Videotape Recording
D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine