Cerebellar rTMS stimulation may induce prolonged clinical benefits in essential tremor, and subjacent changes in functional connectivity: An open label trial

Background: Cerebello-thalamo-cortical (CTC) pathways dysfunction is involved in pathological oscillations causing tremor in essential tremor (ET). Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the cerebellum can effectively modulate the cerebellar output. Objective: As one session of rTMS can induce a brief improvement, we hypothesized that repeated sessions might have a cumulative and potentially long-term therapeutic effect on ET. We assessed, in an open label trial, the efficacy of one-week rTMS treatment on tremor and on the motor-CTC dysfunction in ET patients. Methods: Resting-state fMRI functional connectivity was used as an indicator of CTC network integrity in 11 ET patients and 11 healthy subjects. Resting-state fMRI connectivity was quantified at baseline in patients and control subjects between the cerebellum and the motor network, and between the cerebellum and the default brain network (DBN) taken as control. The fMRI study was repeated in patients after 5 days of bilateral 1 Hz rTMS applied to the posterior cerebellar cortex. Tremor was assessed clinically (Fahn-Tolosa-Marin scale) and quantified using electromyographic and accelerometric recordings at baseline (day 1, before the cerebellar stimulation) and after the end of the cerebellar stimulation period at day 5, day 12 and day 29. Results: Repeated rTMS over the cerebellum significantly improved total and specific (tremor, drawing, functional disability) scores, and reduced tremor amplitude (P <0.006). It also re-established the defective information processing in the CTC network (P(Δ|y) > 0.909), but not in the DBN. The effects persisted for 3 weeks after the last session. Conclusion: Cerebellar stimulation could be an effective treatment option for patients with severe essential tremor.