Cerebral Reorganization in Cervical Myelopathy Measured by Navigated Transcranial Magnetic Stimulation (CReMe)

Cerebral Reorganization in Cervical Myelopathy

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).

Study Overview

• Status: Recruiting
• Conditions: Degenerative Myelopathy
• Intervention / Treatment: Diagnostic test: Navigated transcranial magnetic stimulation

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 160

Contacts and Locations

• Study Contact: Name: Anna Zdunczyk, M.D.; Phone Number: 004930450660193; Email: anna.zdunczyk@charite.de

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Department of neurosurgery Charité
    • Contact: Anna Zdunczyk, M.D.; Phone Number: 030/450660193; Email: anna.zdunczyk@charite.de
    • Principal Investigator: Peter Vajkoczy, M.D.
    • Principal Investigator: Thomas Picht, M.D.
    • Sub-Investigator: Sandro Krieg, M.D.
    • Sub-Investigator: Carolin Weiss-Lucas, M.D.
    • Sub-Investigator: Kathleen Seidel, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• patients with symptomatic/asymptomatic cervical spondylotic myelopathy scheduled for surgery or conservative Treatment
• healthy subjects without any neurological disease

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
mild myelopathy (JOA>12); 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
moderate myelopathy; 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
healthy control; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: University Hospital Inselspital, Berne; University Hospital of Cologne; University Hospital Munich; German Spine Society (Deutsche Wirbelsäulenstiftung)
• Investigators: Principal Investigator: Anna Zdunczyk, M.D., Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: October 12, 2017
• First Posted (Actual): October 18, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2017
• Last Update Submitted That Met QC Criteria: October 12, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: cerebral reorganization, TMS
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Spinal Cord Diseases; Bone Marrow Diseases
• Other Study ID Numbers: 89830535

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The study results, study protocol and study report will be shared with other Researchers during international congresses and peer reviewed publications
• IPD Sharing Time Frame: during the time of the study
• IPD Sharing Access Criteria: only as a congress presentation or publication presenting the results of the study
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No