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Deep cerebellar stimulation reduces ataxic motor symptoms in the shaker rat.

Annals of Neurology 2019 March 11
OBJECTIVE: Degenerative cerebellar ataxias (DCAs) affect up to 1 in 5,000 people worldwide, leading to incoordination, tremor, and falls. Loss of Purkinje cells, nearly universal across DCAs, dysregulates the dentatothalamocortical network. To address the paucity of treatment strategies, we developed an electrical stimulation-based therapy for DCAs targeting the dorsal dentate nucleus.

METHODS: We tested this therapeutic strategy in the Wistar Furth shaker rat model of Purkinje cell loss resulting in tremor and ataxia. We implanted shaker rats with stimulating electrodes targeted to the dorsal dentate nucleus and tested a spectrum of frequencies ranging from 4 to 180 Hz.

RESULTS: Stimulation at 30 Hz most effectively reduced motor symptoms. Stimulation frequencies over 100 Hz, commonly used for Parkinsonism and essential tremor, worsened incoordination, while frequencies within the tremor physiologic range may worsen tremor.

INTERPRETATIONS: Low-frequency deep cerebellar stimulation may provide a novel strategy for treating motor symptoms of degenerative cerebellar ataxias. This article is protected by copyright. All rights reserved.

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