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

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 >100 Hz, commonly used for parkinsonism and essential tremor, worsened incoordination, and frequencies within the tremor physiologic range may worsen tremor.

INTERPRETATION: Low-frequency deep cerebellar stimulation may provide a novel strategy for treating motor symptoms of degenerative cerebellar ataxias. Ann Neurol 2019;85:681-690.