Neuromodulation-Induced-Cortical-Prehabilitation In High Grade Glioma Close To The Motor Pathway: Analysis Of The Cortical Brain Plasticity Through Navigated Transacranial Magnetic Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 63
- 主要终点
- Measurement of neuroplasticity with nTMS
研究概览
简要总结
The goal of this clinical trial is to learn whether Neuromodulation-Induced-Cortical-Prehabilitation (NICP)-using physical therapy (constraint-induced movement training, CIM) alone or combined with repetitive transcranial magnetic stimulation (rTMS)-can promote motor-cortex neuroplasticity before surgery in adults with high-grade gliomas near the motor pathway. It will also learn about the feasibility and safety of these prehabilitation strategies around the time of surgery. The main questions it aims to answer are:
- Does CIM (with or without rTMS) produce measurable motor-cortex plasticity from baseline to pre-surgery as assessed by neuronavigated TMS (nTMS)?
- Does adding rTMS to CIM lead to greater neuroplastic changes than CIM alone?
- What clinical, radiological, and neurophysiological outcomes are observed after surgery in participants who receive prehabilitation compared with controls?
Researchers will compare standard care (control) vs CIM-based physical therapy vs CIM plus rTMS to see if these approaches induce preoperative neuroplastic changes that may support better surgical outcomes. Participants will:
- Be randomized to one of three groups: control, CIM physical therapy, or CIM + rTMS• Undergo nTMS motor mapping and excitability testing at baseline (T0) and the day before surgery (T1)
- Undergo planned tumor surgery (according to standard methods of care) and complete postoperative clinical, imaging, and neurophysiological follow-up assessments.
详细描述
Background. The Neuromodulation-Induced-Cortical-Prehabilitation (NICP) is a groundbreaking idea to promote plastic brain changes and, theoretically, to increase the Extent of Resection in brain gliomas improving the surgical outcomes. Moreover, given the infiltrative nature of brain gliomas, NICP could be consistently worthwhile for the patient's clinical outcome, reducing the likelihood of premeditated neurologic sequelae and/or the time-to-recovery during the post-surgical rehabilitation.
Hypothesis, Research Need. Up to date only small case series have analysed NICP-induced neuroplasticity, complicating data interpretation. Our study aims to thoroughly measure through neuronavigated Transcranial-Magnetic-Stimulation (nTMS) the plastic brain changes of Physical Therapy (in particular Constraint-Induced-Movements - CIM), repetitive-TMS (rTMS) and the combination of these two techniques in high-grade gliomas (HGGs) close to the motor pathway before surgery to improve surgical outcomes for the benefit of the patient.
Methodology. This is a multi-center, prospective, randomized pilot trial. The patients are randomized in 3 groups (A. Control Group, B. Physical Therapy Group, C. Physical Therapy+rTMS Group; randomization 1:2:2). The participants undergo motor cortex analysis through nTMS at the baseline - T0 - and the day before surgery - T1. Postoperative clinical, radiological and neurophyisiological outcomes are also gathered.
Patient Enrolment:
- Department of Neurosurgery, Hospital of Bolzano (SABES-ASDAA), Bolzano, Italy
- Department of Neurosurgery, Azienda Ospedaliera Universitaria Integrata (AOUI) di Verona, Italy
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Suspect of High Grade Glioma in MRI
- •Any case of cortical/subcortical HGG radiologically close to Motor Pathway and, thus, where intraoperative monitoring assistance is usually required
- •Preservation of motor function (at least ≥ 3 according to Medical Research Council classification)
- •Signed informed Consent
排除标准
- •Refusal to Study participation
- •Multifocal/Bilateral Disease
研究组 & 干预措施
Control (no NICP)
Physical Therapy Group
Physical Therapy Group: patients who undergo only physical therapy
Physical Therapy protocol for the 10 days preceding surgery: 6h/day Constraint Induced Movement - CIM (immobilization of the ipsilesional hand - unaffected side) + 1h twice a day of fine motor skills focused exercises (e.g. 9-hole peg test) on the controlateral hand (affected side)
干预措施: Physical Therapy (Procedure)
Combined Therapy Group: patients who undergo physical therapy + rTMS
Repetitive Transcranial Magnetic Stimulation protocol for the 10 days preceding surgery: This will be done following standard protocols mediated from the protocols for motor and language function in stroke, i.e, daily sessions of 1Hz rTMS for 20 minutes applied to the contralesional hemisphere. • Physical Therapy protocol for the 10 days preceding surgery: 6h/day Constraint Induced Movement - CIM (immobilization of the ipsilesional hand - unaffected side) + 1h twice a day of fine motor skills focused exercises (e.g. 9-hole peg test) on the controlateral hand (affected side)
干预措施: Combined Therapy Group (Procedure)
结局指标
主要结局
Measurement of neuroplasticity with nTMS
时间窗: From the date of randomization until the date of surgery, assessed up to 15 days
Cortical changes in motor representations will be addressed with Neuronavigated TMS mapping of the motor representations (MEP amplitude and waveforms) of the cortical surface of the peri-Rolandic region on individual anatomical images (Nextim NBS System 5 in Bolzano/EbNeruo STM9000 in Verona). We will consider as primary outcome variable the extension of the cortical surface from which MEPs can be obtained by neuronavigated TMS on the affected hemisphere during the procedure of neuronavigation. This index will be calculated quantitatively as surface area, on the flattened cortical surface, and on the "density" of MEP amplitude on such surface. In addition, we will carry out a quantitative analysis of how many excitable points are present in different cortical regions, by applying the cortical atlas by Glasser et al. (2016) to the patient's brain. In this way we will also be able to quantify the extension of excitable points to the premotor or even non-motor cortical regions.
Measurement of neuroplasticity with TMS
时间窗: From the date of randomization until the date of surgery, assessed up to 15 days
1. Single-pulse indexes of motor cortical excitability (unit of measure milli Volt - mV): * Cortical Silent Period (CSP) * Recruitment (input-output) Curve (RC) * Resting Motor Threshold (rMT) and intehemispheric rMT ratio (rMT ratio) 2. Dual-pulse measures of cortical excitability (Adimensional; they are MEP-derived ratios . MEP amplitudes are measured in mV).): * Short-latency intracortical inhibition/facilitation (SICI and SICF) * Short-latency afferent inhibition (SAI)
次要结局
- Measurement of neuroplasticity with TMS (after surgery)(At 1 month and 3 months after surgery)
- Measurement of neuroplasticity with TMS(At 1 month and 3 months after surgery)
研究者
Pier Paolo Berti
MD
Azienda Sanitaria dell'Alto Adige