Emerging Noninvasive Approaches for the Suppression of Pathological Tremor

Abstract

Pathological tremor affects over 40 million people worldwide, significantly impairing daily activities and quality of life. Pharmacological treatments show limited efficacy, with up to 30% discontinuation rates, while surgical interventions like deep brain stimulation achieve significant tremor reduction but are often unsuitable due to age, comorbidities, or personal preference. Recently, the need for safe and effective alternatives has led to the development of innovative, noninvasive, and patient-friendly technologies for tremor management. This clinical application review analyzed 134 studies (1969-2025), categorizing them into three major modalities, focusing on their underlying neurophysiological mechanisms, with a special emphasis on the clinical perspective. The three considered modalities were force-controlling (orthoses and functional electrical stimulation), central neuromodulation (transcranial magnetic stimulation, transcranial electrical stimulation, low-intensity focused ultrasound, and transcutaneous spinal cord stimulation), and peripheral neuromodulation (afferent stimulation and vibration). Force-controlling strategies showed promising acute effects, though clinical translation remains limited by poor wearability and the development of muscle fatigue. Central neuromodulation produced moderate effects, while peripheral neuromodulation has gained clinical traction, with several devices now being commercially available. However, heterogeneity in study design, patient populations, and technology maturity remain the main obstacles for the direct comparison of techniques. Future research should prioritize larger multicenter trials, standardized outcome measures, and accessibility considerations to enable personalized, evidence-based treatment selection for diverse tremor populations.