Rationale and Evidence for Peripheral Nerve Stimulation for Treating Essential Tremor.

Background: There is growing recognition of peripheral stimulation techniques for controlling arm symptoms in essential tremor (ET). Recently, the FDA gave clearance to the Cala system, a device worn around the wrist to treat arm tremors. The Cala system stimulates the sensory afferents of the peripheral nerves with high-frequency pulses. These pulses are delivered to the median and radial nerves alternately at the tremor frequency of the individual patient. Methods: The PubMed database was searched using the terms ("Essential Tremor"[Mesh] OR "essential tremor" [Title/Abstract] OR "tremor" [Title/Abstract]) AND ("peripheral arm stimulation" [Title/Abstract] OR "Cala device" [Title/Abstract] OR "sensory afferent stimulation" [Title/Abstract] OR "afferent stimulation" [Title/Abstract] OR "arm stimulation" [Title/Abstract] OR "peripheral nerve stimulation" [Title/Abstract]). Results: The search yielded 54 articles. Many studies discussed the rationale and various strategies for peripheral modulation of tremor. While the Cala system was found to be safe and well-tolerated in ET, data on efficacy revealed mixed findings. In a large randomized, blinded trial (n = 77), the primary outcome evaluated with spiral drawing task did not improve but the secondary outcomes reflected by the arm tremor severity and the activities of the daily living score revealed 20-25% improvements. A subsequent trial (n = 323) found that the in-home use of the Cala device led to improvements of similar magnitude lasting for at least three months but the clinical assessments were open-labeled. Discussion: Peripheral stimulation techniques are promising therapeutic modalities for treating ET symptoms. Stimulation of sensory afferent nerve fibers at the wrist can potentially modulate the peripheral and central components of the tremor network. Although the Cala system is user-friendly, safe, and well-tolerated, the current clinical evidence on the efficacy is inconsistent and insufficient. Thus, more data is warranted for implementing peripheral nerve stimulation as a standard of care for ET. Highlights: The current review discusses the rationale, background, and potential mechanisms for using peripheral arm stimulation devices for treating ET. The Cala system is a wrist-worn peripheral nerve stimulation device that received FDA clearance to treat arm tremors. The current review evaluates the evidence for the safety and efficacy of using the Cala system and similar devices in clinical practice.