Peripheral nerve stimulation for essential tremor: a GRADE-assessed systematic review and meta-analysis

Essential tremor (ET) is a common movement disorder; its management remains challenging despite the availability of multiple treatment options. Pharmacological therapies are often limited in efficacy and tolerability, while surgical options, although effective, are invasive and expensive. Peripheral nerve stimulation (PNS) has emerged as a non-invasive neuromodulation approach. However, different stimulation protocols, small samples, and inconsistent outcome reporting preclude firm conclusions. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of PNS for ET. A literature search was conducted through PubMed, Scopus, Web of Science, and Cochrane CENTRAL databases till January 2026. The primary outcome was the change in tremor intensity, as measured by the TETRAS Performance Scale (TETRAS-PS). Secondary outcomes included functional disability, assessed by the Bain and Findley Activities of Daily Living (BF-ADL) scale, clinical improvement assessed using the clinical global impression - improvement (CGI-I) scale, as well as safety outcomes. Quality assessment was performed using the Risk of Bias-2 (RoB-2) and the NIH single-arm tools. Certainty of evidence was assessed using GRADE approach. A meta-analysis was performed, calculating the mean difference (MD) with 95% confidence intervals (CIs) using Review Manager 5.4.1. Twelve studies, involving 914 participants, met the inclusion criteria, including four RCTs. Our analysis of RCTs demonstrated that active PNS produced a statistically significant reduction in tremor intensity (TETRAS-PS; MD=-0.92, 95%CI [-1.63 to -0.21], P = 0.01, I2 = 0) and an improvement in functional outcomes (BF-ADL; MD=-1.90, 95%CI [-2.97 to -0.83], p = 0.0005, I2 = 0). Benefits were observed immediately and persisted for up to three months in longitudinal studies. Adverse events were generally mild and limited mainly to transient skin irritation; no device-related serious adverse events were reported. PNS was associated with short-term reduction in tremor severity and functional impairment in patients with ET, with an overall acceptable safety profile, suggesting that it may serve as a middle ground option between pharmacotherapy and invasive neurosurgical approaches. However, further larger and longer randomized trials with refined sham controls are needed to confirm its efficacy, durability, and optimize stimulation strategies. CRD420261282826.