Thalamotomy for the alleviation of levodopa-induced dyskinesia: experimental studies in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated parkinsonian monkey.
This work set out to test the hypothesis that thalamotomy in the area of the thalamus which receives the input from the medial segment of the globus pallidus would decrease or prevent levodopa-induced dyskinesia. Peak dose dyskinesia is a major problem in the treatment of parkinsonian patients with levodopa therapy but this remains the best pharmacological agent for treating the condition. The hypothesis was derived from previous work which has suggested that reduced pallidal inhibition of the thalamus results in dyskinesia [Crossman (1990) Movement Dis. 5, 100-108]. A neuroanatomical tracing study was carried out prior to the thalamotomy work, using the anterograde tracer wheatgerm-agglutinin conjugated to horseradish peroxidase. This delineated the anterior part of the ventrolateral thalamus in the primate in terms of its afferent inputs. Wheatgerm agglutinin-horseradish peroxidase was injected into the medial segment of the globus pallidus bilaterally in three Macaca fascicularis and traced to terminals in the ventral thalamus and other brain areas. The appropriate thalamic area involved was plotted on atlas sections in preparation for stereotactic thalamotomy. Previous studies of neuronal input to the ventral thalamus are confusing due to the different nomenclatures used by different workers. Early workers used cytoarchitectonic boundaries which do not correspond with function. There are also differences in nomenclature between man, monkey and other animals. The current study maps the pallidal terminal territory within the thalamus in terms of stereotactic co-ordinates related to a published macaque atlas [Shantha et al. (1968) A Stereotaxic Atlas of the Java Monkey Brain. S. Karger, Basel] and can thus be used by other workers in the field. A well-established primate model of Parkinsonism was used for the thalamotomy study. Eight monkeys (Macaca fascicularis) were rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Regular dosing with levodopa or apomorphine reliably resulted in peak-dose dyskinesia which was scored in terms of its choreic and dystonic components. A radiofrequency electrode was used to create the ablative lesions. Chorea was always reduced and frequently abolished by a thalamotomy located in the pallidal terminal territory. This result was obtained after 10 thalamotomies in a total of six animals. Four animals received bilateral lesions, with an interval between operations and two animals underwent unilateral surgery.(ABSTRACT TRUNCATED AT 400 WORDS)
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Department of Cell and Structural Biology, University of Manchester, U.K.
Sambrook
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Crossman
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D000344:Afferent Pathways / Q000601:surgery; D000818:Animals; D001058:Apomorphine / Q000627:therapeutic use / Q000633:toxicity; D001370:Axonal Transport; D001931:Brain Mapping; D002819:Chorea / Q000139:chemically induced / Q000601:surgery; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000601:surgery*; D004421:Dystonia / Q000139:chemically induced / Q000601:surgery; D005917:Globus Pallidus / Q000473:pathology; D006735:Horseradish Peroxidase; D007980:Levodopa / Q000627:therapeutic use / Q000633:toxicity*; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000188:drug therapy; D013238:Stereotaxic Techniques; D013788:Thalamus / Q000473:pathology / Q000601:surgery*; D014909:Wheat Germ Agglutinins
D014909:Wheat Germ Agglutinins; D007980:Levodopa; D006735:Horseradish Peroxidase; D001058:Apomorphine