The use of thalamotomy in the treatment of levodopa-induced dyskinesia.
Peak dose dyskinesia is a major problem in the treatment of parkinsonian patients with levodopa and yet this remains the best pharmacological agent for treating the condition. The hypothesis which this research set out to test was that thalamotomy in the area of the thalamus which receives the input from the medial segment of the globus pallidus would decrease or prevent the dyskinesia. A well established primate model of parkinsonism was used. Eight monkeys (Macaca fascicularis) were rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Regular dosing with levodopa or apomorphine reliably resulted in peak dose dyskinesia. Thalamotomy was carried out using a radiofrequency electrode. To ensure that the appropriate area of the thalamus was targeted, that is the area receiving the pallidal input, an anatomical tracing study was carried out. The anterograde anatomical tracer horseradish peroxidase, covalently bound to wheatgerm agglutinin, was injected into the medial segment of the globus pallidus bilaterally in three monkeys. The target site for thalamotomy was accurately worked out from the tracings obtained. Chorea was usually abolished and always reduced by a thalamotomy in the pallidal terminal territory. This result was obtained after 10 thalamotomies: 4 animals receiving bilateral lesions, with an interval between operations, and 2 animals undergoing unilateral surgery. Lesions in three control sites were carried out and had no permanent effect on chorea. The effect of lesions in other areas was also assessed. Dystonia was not relieved by any thalamic lesion. Thalamotomy is a long established procedure used to help parkinsonian tremor. Appropriately placed thalamotomy should be considered for the relief of disabling peak dose dyskinesia, which is predominantly choreic, in parkinsonian patients on otherwise successful levodopa therapy.
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Department of Neurosurgery, Walton Hospital, U.K.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001931:Brain Mapping; D004409:Dyskinesia, Drug-Induced / Q000601:surgery*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008252:Macaca fascicularis; D008297:Male; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000188:drug therapy*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000601:surgery; D013238:Stereotaxic Techniques; D013788:Thalamus / Q000601:surgery*
D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine