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

• Published in: IEEE transactions on biomedical engineering 2021-06, Vol.68 (6), p.1768-1776
• Main Authors: Pascual-Valdunciel, Alejandro, Gonzalez-Sanchez, Miguel, Muceli, Silvia, Adan-Barrientos, Beatriz, Escobar-Segura, Viviana, Perez-Sanchez, Javier Ricardo, Jung, Moon Ki, Schneider, Andreas, Hoffmann, Klaus-Peter, Moreno, Juan Camilo, Grandas, Francisco, Farina, Dario, Pons, Jose Luis, Barroso, Filipe Oliveira
• Format: Article
• Language: English
• Subjects: Algorithms; Clinical trials; Computational efficiency; Control algorithms; Control theory; Elbow; Elbow (anatomy); Electrical stimuli; Electrodes; Electromyography; Essential tremor; Flexors; Hospitals; Intramuscular; Kinematics; Microsoft Windows; Muscles; Nerves; Neuromodulation; Patients; Reduction; Sensory neurons; Sensory stimulation; Thin films; Tremor; Tremor (Muscular contraction); Tremor reduction; Tremors; Wrist
• ISSN: 0018-9294; 1558-2531; 1558-2531
• DOI: 10.1109/TBME.2020.3015572

This study proposes and clinically tests intramuscular electrical stimulation below motor threshold to achieve prolonged reduction of wrist flexion/extension tremor in Essential Tremor (ET) patients. The developed system consisted of an intramuscular thin-film electrode structure that included both stimulation and electromyography (EMG) recording electrodes, and a control algorithm for the timing of intramuscular stimulation based on EMG (closed-loop stimulation). Data were recorded from nine ET patients with wrist flexion/extension tremor recruited from the Gregorio Marañón Hospital (Madrid, Spain). Patients participated in two experimental sessions comprising: 1) sensory stimulation of wrist flexors/extensors via thin-film multichannel intramuscular electrodes; and 2) surface stimulation of the nerves innervating the same target muscles. For each session, four of these patients underwent random 60-s trials of two stimulation strategies for each target muscle: 1) selective and adaptive timely stimulation (SATS) - based on EMG of the antagonist muscle; and 2) continuous stimulation (CON) of target muscles. Two patients underwent SATS stimulation trials alone while the other three underwent CON stimulation trials alone in each session. Kinematics of wrist, elbow, and shoulder, together with clinical scales, were used to assess tremor before, right after, and 24 h after each session. Intramuscular SATS achieved, on average, 32% acute (during stimulation) tremor reduction on each trial, while continuous stimulation augmented tremorgenic activity. Furthermore, tremor reduction was significantly higher using intramuscular than surface stimulation. Prolonged reduction of tremor amplitude (24 h after the experiment) was observed in four patients. These results showed acute and prolonged (24 h) tremor reduction using a minimally invasive neurostimulation technology based on SATS of primary sensory afferents of wrist muscles. This strategy might open the possibility of an alternative therapeutic approach for ET patients.