Accelerating Motor Recovery in Glioma Patients Using Postoperative nrTMS

Project Name Clinical Research Protocol on Accelerating Motor Rehabilitation in Postoperative Motor-Deficient Glioma Patients Using nrTMS Research Objectives 1. Investigate the relationship between motor rehabilitation and changes in motor functional networks after nrTMS therapy, and confirm the contralateral hand motor area as an effective rehabilitation target. 2. Validate the efficacy of high-frequency nrTMS stimulation in rehabilitating motor deficits in glioma patients. Study Design \> A randomized, double-blind, sham-controlled clinical trial. Eligible postoperative glioma patients with motor dysfunction will be randomized into nrTMS treatment or sham groups. High-frequency nrTMS or sham stimulation targeting the contralateral hand motor area will be administered for 7 consecutive days. Fugl-Meyer Assessment (FMA) scores and muscle strength of the affected limb will be evaluated to determine the superiority of nrTMS over sham stimulation. Total Cases The study comprises two parts, each enrolling 43 patients. Case Selection Inclusion Criteria: A. Right-handed; B. Age: 25-65 years; C. No prior neurological disease history; D. Awake craniotomy with intraoperative direct cortical stimulation or MEP mapping for motor area localization; E. Postoperative pathology confirms newly diagnosed glioma; F. Willing to undergo nrTMS therapy; G. Persistent motor dysfunction (muscle strength/FMA score not restored to preoperative levels) at postoperative day 7. Exclusion Criteria: A. Tumor crossing midline to the contralateral hemisphere; B. Head motion \>1 mm or rotation \>1° during rs-fMRI acquisition; C. Absence of postoperative motor or speech dysfunction; D. Vulnerable populations (e.g., pregnant women). Treatment Protocol High-frequency nrTMS stimulation targeting the contralateral hand motor area (thumb region). Efficacy Evaluation Primary Outcome: Muscle strength recovery rate of the affected limb. Secondary Outcome: FMA score recovery rate. Safety Evaluation: Pre- and post-treatment MRI to monitor intracranial changes. Statistical Methods (1) Randomization into nrTMS and sham groups. (2) Baseline comparisons using t-tests and chi-square tests. (3) Longitudinal analysis of muscle strength (chi-square) and FMA scores (t-tests) at key timepoints: preoperative, pretreatment, post-treatment, 1/2/3 months postoperatively.

Sex

All

Minimum age

25 Years

Maximum age

65 Years

Inclusion Criteria:

Right-handed.

Age between 25 and 65 years old.

No history of neurological disease treatment before surgery.

Underwent awake surgery with intraoperative direct cortical stimulation or motor evoked potential (MEP) mapping to identify the motor functional area.

Postoperative pathology confirmed as newly diagnosed glioma.

Eligible for navigated repetitive transcranial magnetic stimulation (nrTMS) rehabilitation treatment.

Persistent motor dysfunction (muscle strength or Fugl-Meyer Assessment (FMA) scores not returned to preoperative levels) at 7 days postoperatively.

Signed informed consent.

Exclusion Criteria:

Tumor crossing the midline to the contralateral hemisphere.

Excessive head motion (\>1 mm translation or \>1° rotation) during resting-state functional MRI (rs-fMRI) data acquisition.

Absence of postoperative motor or language motor deficits.

Vulnerable populations (e.g., pregnant women).

• RESULT1. Potgieser AR, de Jong BM, Wagemakers M, Hoving EW, Groen RJ. Insights from the supplementary motor area syndrome in balancing movement initiation and inhibition. Front Hum Neurosci 2014;8:960. 2. Morone G, Capone F, Iosa M, et al. May Dual Transcranial Direct Current Stimulation Enhance the Efficacy of Robot-Assisted Therapy for Promoting Upper Limb Recovery in Chronic Stroke? Neurorehabil Neural Repair 2022;36:800-809. 3. Youssef H, Mohamed NAE, Hamdy M. Comparison of bihemispheric and unihemispheric M1 transcranial direct current stimulations during physical therapy in subacute stroke patients: A randomized controlled trial. Neurophysiol Clin 2023;53:102895. 4. Bikson M, Hanlon CA, Woods AJ, et al. Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic. Brain Stimul 2020;13:1124-1149. 5. Steeves T, McKinlay BD, Gorman D, et al. Canadian guidelines for the evidence-based treatment of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can J Psychiatry 2012;57:144-151. 6. 中国医师协会神经调控专业委员会电休克与神经刺激学组. 重复经颅磁刺激治疗专家共识. 转化医学杂志 2018;7:4-9. 7. Krieg SM, Shiban E, Buchmann N, et al. Utility of presurgical navigated transcranial magnetic brain stimulation for the resection of tumors in eloquent motor areas. J Neurosurg 2012;116:994-1001. 8. 王引言, 方晟宇, 李连旺, et al. 重复经颅磁刺激治疗脑胶质瘤术后运动功能障碍的临床分析(附五例报告). 中华神经外科杂志 2020;36:458-462. 9. Herbet G, Maheu M, Costi E, Lafargue G, Duffau H. Mapping neuroplastic potential in brain-damaged patients. Brain : a journal of neurology 2016;139:829-844. 10. Almairac F, Duffau H, Herbet G. Contralesional macrostructural plasticity of the insular cortex in glioma patients. Neurology 2018:1. 11. Duffau H. Functional Mapping before and after Low-Grade Glioma Surgery: A New Way to Decipher Various Spatiotemporal Patterns of Individual Neuroplastic Potential in Brain Tumor Patients. Cancers (Basel) 2020;12. 12. Duffau H. Hodotopy, neuroplasticity and diffuse gliomas. Neurochirurg