An Acute Randomized Controlled Trial of Noninvasive Peripheral Nerve Stimulation in Essential Tremor

Abstract

Objective To evaluate the safety and effectiveness of a wrist‐worn peripheral nerve stimulation device in patients with essential tremor (ET) in a single in‐office session. Methods This was a randomized controlled study of 77 ET patients who received either treatment stimulation (N = 40) or sham stimulation (N = 37) on the wrist of the hand with more severe tremor. Tremor was evaluated before and immediately after the end of a single 40‐minute stimulation session. The primary endpoint compared spiral drawing in the stimulated hand using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Archimedes spiral scores in treatment and sham groups. Additional endpoints included TETRAS upper limb tremor scores, subject‐rated tasks from the Bain and Findley activities of daily living (ADL) scale before and after stimulation as well as clinical global impression‐improvement (CGI‐I) rating after stimulation. Results Subjects who received peripheral nerve stimulation did not show significantly larger improvement in the Archimedes spiral task compared to sham but did show significantly greater improvement in upper limb TETRAS tremor scores (p = 0.017) compared to sham. Subject‐rated improvements in ADLs were significantly greater with treatment (49% reduction) than with sham (27% reduction; p = 0.001). A greater percentage of ET patients (88%) reported improvement in the stimulation group as compared to the sham group (62%) according to CGI‐I ratings (p = 0.019). No significant adverse events were reported; 3% of subjects experienced mild adverse events. Conclusions Peripheral nerve stimulation in ET may provide a safe, well‐tolerated, and effective treatment for transient relief of hand tremor symptoms.

Intramuscular Stimulation of Muscle Afferents Attains Prolonged Tremor Reduction in Essential Tremor Patients

“…In fact, Tass et al [29] showed in Parkinsonian monkeys that coordinated reset neuromodulation of the subthalamic nucleus had more pronounced after-effects than classical neuromodulation with DBS-like (high) intensity. Pahwa et al [11] have also suggested that modulation of afferent pathways may produce an effect in supraspinal centers such as the Ventral Intermediate Nucleus (VIM), which is a brain target for DBS or HIFU for tremor.…”

“…Recent studies have shown that stimulation of afferent nerve fibers below motor threshold (below MT) may also modulate tremor without the main drawbacks of stimulation above MT [7], [9]. For instance, a wrist-worn peripheral nerve stimulator showed its potential to reduce tremor right after stimulation compared to sham [10], [11]. Another study tested stimulation below MT of several upper limb muscles and reported reduction of wrist tremor during stimulation and also 5 minutes following the end of stimulation [12].…”

Treatment of essential tremor: current status

“…Another non-invasive form of treatment is the handheld assistive device using active cancellation of tremor technology, which has shown some promise in reducing tremor amplitude and severity while performing tasks in a limited pilot trial 121. Efficacy of non-invasive peripheral nerve stimulation was assessed in a randomised controlled study by Pahwa et al 122. Subjects receiving a single in-office session of peripheral nerve stimulation showed transient relief in hand tremor symptoms.…”

Local Vibrational Therapy for Essential Tremor Reduction: A Clinical Study

“…This research (with the same device) was followed with a pivotal study, where it was shown that subjects who received peripheral nerve stimulation did not show a significantly larger improvement in the Archimedes spiral task compared to sham but did show a significantly greater improvement in upper limb TETRAS tremor scores ( p = 0.017) compared to sham. No significant adverse events were reported; 3% of subjects experienced mild adverse events [ 24 ]. Vibrating Gaussian noise emitting manipulandum has been shown to improve motor performance.…”

“…We did not identify major safety risks during the clinical study; however, the local hand arm vibration is associated with the development of certain conditions: Raynaud’s phenomenon, carpal tunnel syndrome [ 28 ], vibration-induced white finger disease [ 29 ], finger pain, back pain, muscular pain or fatigue [ 30 ], chronic subdural hematoma (local application to the head) [ 31 ], skin irritation (including redness, itchiness, and/or swelling) [ 24 ], finger blood flow reduction [ 30 , 31 , 32 , 33 ], and neck and upper limb musculoskeletal disorders. Vibration can increase the postural and rest tremor [ 34 ], exacerbate Dupuytren’s contracture, and have various osteoarticular effects (hand and carpal bone vacuoles and cysts, Kienbock’s disease, navicular pseudoarthrosis, olecranon spurs, and osteoarthrosis of the wrist and elbow joints).…”