Category: Surgical Therapy: Parkinson's Disease
Objective: This study investigated the effect of long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN) on motor behavior in a parkinsonian monkey treated with L-Dopa and pramipexole.
Background: The dopamine precursor (L-Dopa) is the most effective pharmacotherapy for Parkinson’s disease (PD), but adverse effects hamper its chronic use; most patients experience motor complications including L-Dopa-induced dyskinesias (LID). At this stage, DBS, a surgery consisting in the permanent implantation of intracerebral leads usually in the STN, the main driving force of the basal ganglia, can be offered.
Method: We used the best translational animal model for PD, i.e. macaque monkey lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin causing permanent symptoms of PD by destroying midbrain dopamine neurons. This MPTP monkey was treated with L-Dopa for one month to develop dyskinesias as in PD patients. Then, DBS 4-contact leads (tailored for monkeys) were implanted bilaterally in the STN, connected to an implantable pulse generator (Boston Scientific Vercise PC device). Motor behavior was measured before STN surgery, 1 month and 5 months after continuous STN DBS, and under pharmacological treatments (L-Dopa optimal and sub-optimal dose, and pramipexole).
Results: A significant improvement in the antiparkinsonian response to L-Dopa (optimal dose) was measured after STN DBS as compared to before surgery. Duration of the response to a suboptimal dose of L-Dopa increased following 1 and 5 months of STN DBS but remained unchanged with an optimal dose or pramipexole. A prehension task showed that DBS with L-Dopa and pramipexole decreased the time to reach a cranberry as compared to before DBS surgery. Under basal condition, the more important effect of DBS was a significant reduction of tremor.
Conclusion: This is the first report of a long-term DBS stimulation in a MPTP monkey with LID. We showed under basal condition a reduction of tremor. DBS extended the duration of the antiparkinsonian effect of L-Dopa, LID remaining modest. DBS improved prehension under L-Dopa and pramipexole treatment. Behavior of additional DBS monkeys will be investigated as well as their brain molecular correlates.
To cite this abstract in AMA style:M. Bourque, S. Carrondo-Cottin, M. Parent, L. Cantin, B. Gosselin, M.E Tremblay, T. Di Paolo. Long-term effect of deep brain stimulation in a monkey model of Parkinson’s disease with L-Dopa–induced dyskinesias [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/long-term-effect-of-deep-brain-stimulation-in-a-monkey-model-of-parkinsons-disease-with-l-dopa-induced-dyskinesias/. Accessed December 7, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-effect-of-deep-brain-stimulation-in-a-monkey-model-of-parkinsons-disease-with-l-dopa-induced-dyskinesias/