NeuroImage. Clinical · 2025
Acute effects of a single session of multitarget continuous Theta-Burst stimulation for essential Tremor: A Randomized, Sham-Controlled trial.
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Luo Anling, Huang Hongyan, Feng Jiaming, Zhou Muke, Liu Ling, Xu Yanming
Аннотация
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.
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.