Cerebral Reorganization in Cervical Myelopathy Measured by Navigated Transcranial Magnetic Stimulation

Study Overview
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Brief Summary
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In degenerative cervical myelopathy (DCM) the dynamics of disease progression and the outcome after surgical decompression vary inter individually and do not necessarily correlate with radiological findings. By better characterization of the underlying pathophysiology this study aims to improve diagnostic power in DCM using Navigated transcranial magnetic stimulation (nTMS).

Detailed Description
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120 patients with DCM due to cervical spinal canal stenosis will be examined preoperatively and postoperatively with nTMS. On the basis of the initial Japanese Orthopedic Association (JOA) Score two patient groups will be established (JOA≤12/>12). The resting motor threshold, recruitment curve, cortical silent period and motor area will be determined. Accordingly, 40 healthy subjects will be examined. To the investigators knowledge, this study is the first to analyze changes of corticospinal excitability and reorganization in patients with cervical spondylotic myelopathy with navigated TMS. In the present study, there was a significant difference in parameters of excitability and motor area activation between the severely symptomatic and clinically stable patient group. The investigators analysis showed that chronic CSM induces a recruitment of the non-primary motor area and corticospinal disinhibition, so that axonal damage can be compensated through recruitment of new cortical and supplementary motor connections, to a certain degree. Upon exhaustion of these mechanisms further axonal damage translates directly into new neurological deficits. These results lay the ground for a novel concept in CSM, the corticospinal reserve capacity. This study lays the foundation for future research to examine the pathomechanisms in CSM. Functional reorganization occurs on a spinal as well as on a cortical level. The concept of the corticospinal reseve capacity describes a compensatory, increased recruitment of non primary motor areas and corticospinal disinhibition in order to preserve motor function. By detecting the degree of reorganization, a stratification for an unfavourable as well as stable clinical course could be made. This innovative approach to describe the pathomechanisms in CSM might revise current concepts of clinical diagnostics and might have an impact on future treatment strategies.

Official Title
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Cerebral Reorganization in Cervical Myelopathy

Conditions
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Degenerative Myelopathy

Intervention / Treatment
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* Diagnostic Test: Navigated transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with symptomatic/asymptomatic cervical spondylotic myelopathy scheduled for surgery (anterior and/ or posterior decompression) or conservative treatment. The radiological inclusion criteria are cervical spinal stenosis (C3-C7) associated with or without intramedullary high signal intensity lesion on T2-weighted MRI due to disc protrusion or spondylosis. healthy subjects without any neurological disease Exclusion Criteria: Exclusion criteria are other pathologies in the vicinity of the corticospinal tract above the lesion site (i.e. tumor, infarction), neuroinflammatory disease, high grade paresis of the upper extremity (BMRC<3), the existence of a cardiac pacemaker, deep brain stimulation electrodes or pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mild myelopathy (JOA>12)<br>40 patients (JOA>12) suffering from symptomatic or asymptomatic degenerative cervical myelopathy scheduled for surgery or conservative treatment. The radiological inclusion criteria are cervical spinal stenosis associated with or without intramedullary high signal intensity lesion on T2-weighted MRI. Exclusion criteria are other pathologies in the vicinity of the corticospinal tract above the lesion site (i.e. tumor, infarction), neuroinflammatory disease, high grade paresis of the upper extremity (BMRC<3), the existence of a cardiac pacemaker, deep brain stimulation electrodes or pregnancy. By means of navigated transcranial magnetic stimulation the resting motor threshold, recruitment curve, cortical silent period and motor area will be determined. | Diagnostic Test: Navigated transcranial magnetic stimulation<br> <br> |
| moderate myelopathy<br>40 patients (JOA≤12) suffering from symptomatic degenerative cervical myelopathy scheduled for surgery (anterior and/ or posterior decompression) or conservative treatment. The radiological inclusion criteria are cervical spinal stenosis associated with or without intramedullary high signal intensity lesion on T2-weighted MRI. Exclusion criteria are other pathologies in the vicinity of the corticospinal tract above the lesion site (i.e. tumor, infarction), neuroinflammatory disease, high grade paresis of the upper extremity (BMRC<3), the existence of a cardiac pacemaker, deep brain stimulation electrodes or pregnancy. By means of navigated transcranial magnetic stimulation the resting motor threshold, recruitment curve, cortical silent period and motor area will be determined. | Diagnostic Test: Navigated transcranial magnetic stimulation<br> <br> |
| healthy control<br>As a control group, 40 subjects will be included into the study. Exclusion criteria and examination protocol are identical with the patient group. By means of navigated transcranial magnetic stimulation the resting motor threshold, recruitment curve, cortical silent period and motor area will be determined. | Diagnostic Test: Navigated transcranial magnetic stimulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corticospinal reserve capacity | Comparison of corticospinal reserve capacity (defined by recruitment curve, cortical silent period, motor area) compared to healthy control group | preoperative | 
| Change in corticospinal reserve capacity | Postoperative change in corticospinal reserve capacity compared to clinical symptoms | 9 months, 24 months postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebral reorganization, TMS