Acute effects of a single session of multitarget continuous Theta-Burst stimulation for essential Tremor: A Randomized, Sham-Controlled trial.

BACKGROUND

Current treatments for essential tremor (ET) are suboptimal. This study aims to assess the safety and acute effects of a single session, multitarget continuous theta-burst stimulation (cTBS) applied to the bilateral primary motor cortex (M1) and cerebellum in ET patients, and to explore the underlying mechanisms.

METHODS

ET patients were randomly allocated to either the cTBS group (n = 30, 80 % action motor threshold (AMT)) or the control group (n = 30, sham treatment). The primary outcome was tremor severity, assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS), encompassing part A, B, C and total scores at baseline and 0, 10, and 45 min post-intervention. The secondary outcomes included detailed FTM-TRS subscores (specifically midline tremor [MT] and limb kinetic tremor [LKT]), clinical global impression-improvement (CGI-I) scores, hemodynamic changes, and electrophysiological assessments of cortical excitability and inhibition. Data were analyzed using linear mixed-effects models.

RESULTS

The cTBS group demonstrated immediate improvement in tremor severity. Significant changes in intracortical facilitation (ICF) at 12 ms in the left hemisphere (P = 0.015) and short-interval intracortical inhibition (SICI) at 2 ms in the right hemisphere (P = 0.031) were also observed in the cTBS group. Furthermore, the decrease in left-hemisphere ICF (indicating reduced facilitation) was associated with greater tremor improvement.

CONCLUSION

A single session of multitarget cTBS administered to the bilateral M1 and cerebellum was well-tolerated and effective in reducing tremor severity. These acute anti-tremor effects are potentially mediated through the immediate modulation of corticospinal excitability pathways and cortico-cerebellar connectivity. (No. ChiCTR2200064037).

ABBREVIATIONS: ALKT, all limbs kinetic tremor; AMT, action motor threshold; BMI, body mass index; CGI-I, clinical global impression-improvement; CSP, cortical silent period; cTBS, continuous theta-burst stimulation; CTC, cerebello-thalamo-cortical; DBS, deep brain stimulation; EI, efficacy index; ET, essential tremor; FDR, false discovery rate; fNIRS, functional near-infrared spectroscopy; FTM-TRS, Fahn-Tolosa-Marin tremor rating scales; FTM-TRS-A, part A of FTM-TRS; FTM-TRS-B, part B of FTM-TRS; FTM-TRS-C, part C of FTM-TRS; GI, global improvement; ICF, intracortical facilitation; IQR, interquartile range; LKT, limb kinetic tremor; LLKT, lower limbs kinetic tremor; LTD, long-term depression; M1, primary motor cortex; MEPs, motor-evoked potentials; MT, midline tremor; oxy-Hb, oxy-hemoglobin; PM, premotor cortex; RM-ANOVA, repeated-measures analysis of variance; RMT, rest motor threshold; rTMS, repetitive transcranial magnetic stimulation; SD, standard deviation; SI, severity of illness; SICI, short-interval intracortical inhibition; TMS, transcranial magnetic stimulation; ULKT, upper limbs kinetic tremor.