Transcranial Magnetic Stimulation in Disorder of Consciousness in Acute Severe Cerebrovascular Disease Patients

Study Overview
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Brief Summary
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This study is aimed at evaluating the potential of transcranial magnetic stimulation in patients with acute severe ischemic stroke with DoC while assessing patients with a hybrid neural network evaluation model. This model may be the basis for initiating individualized closed-loop neuromodulation treatment in patients with DoC.

Detailed Description
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Despite continued advances in life-sustaining intensive care for severe brain injury patients, little can be done to promote behavioral recovery in patients with disorder of consciousness (DoC). Arousal is the primary task in the rehabilitation of patients with impaired consciousness. Evidence suggests that some medications and physical therapies can induce wakefulness by reactivating specific pathways that lead to impaired consciousness. However, due to the complexity of the type, degree, location, and other related influencing factors of brain injury, the current commonly used treatment options are not effective for patients with impaired consciousness, and the theoretical basis for benefit is not sufficient. This study is aimed at evaluating the potential of transcranial magnetic stimulation in patients with acute severe ischemic stroke with DoC while assessing patients with a hybrid neural network evaluation model. This model may be the basis for initiating individualized closed-loop neuromodulation treatment in patients with DoC. Before and after a course of treatment (20 days), activation and connectivity of patients' arousal centers will be assessed through a hybrid neural network evaluation model, which consists of comprehensive cortical connectivity parameters (perturbational complexity index and evoked high-frequency oscillations) and region-specific cortical connectivity parameters (short-latency afferent inhibition and mismatch negativity). Each parameter is clinically used to assess a patient's level of cortex connectivity. This hybrid evaluation model may give a comprehensive evaluation of a patient's degree of awareness, and enhance our understanding of the mechanisms underlying these conditions.

Official Title
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Effect of Individual Biofeedback Transcranial Magnetic Stimulation Assessed by a Hybrid Neural Network Evaluation Model on Disorder of Consciousness in Acute Severe Cerebrovascular Disease Patients

Conditions
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Ischemic Stroke, Consciousness Disorder, Transcranial Magnetic Stimulation

Intervention / Treatment
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* Device: Transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 7-28 days after ischemic stroke behavioral profile consistent with a UWS or MCS as assessed with the Coma Recovery Scale Revise prestroke Modified Ranking Scale(mRS) ≤2 Exclusion Criteria: history of vascular malformation or aneurysmal SAH or untreated aneurysm prior to stroke disorder of consciousness prior to stroke impairment of hearing metal implants, e.g. stenting, pacemaker, etc. contraindications to MRI, such as claustrophobia history of epilepsy or epileptic episodes suffering from serious diseases such as malignant tumors, etc., with expected survival time <1 year patient is currently involved with other trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS treatment<br>20 days of repetitive transcranial magnetic stimulation: stimulation site is the left dorsolateral prefrontal cortex, stimulation intensity at 90% RMT, stimulation frequency is 10Hz. A total of 1000 pulses, 10s 10Hz train stimulation, repeated 10 times, each interval 60s, a total of 11 minutes and 40 seconds, 1 treatment per day, a total of 20 days. | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation given to the left dorsolateral prefrontal cortex<br>|
| Experimental: iTBS treatment<br>20 days of intermittent theta-burst stimulation: stimulation site is the left dorsolateral prefrontal cortex, stimulation intensity at 90% RMT, stimulation frequency is 50Hz. A total of 600 pulses, 3 pulses each time, with an interval of 200 ms, for a total of 2 seconds (10 groups), and then repeat the above process after an interval of 10 seconds, a total of 190 seconds, 1 treatment per day, a total of 20 days. | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation given to the left dorsolateral prefrontal cortex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coma Recovery Scale Revised (CRS-R) | The Coma Recovery Scale Revised (CRS-R) is a standard clinical protocol specifically developed to assess a patient's level of consciousness, and does so by evaluating a patient's level of responsiveness to sensory stimulation, their ability to understand language, and to communicate. This procedure is typically administered at bedside. The protocol is divided into 6 sub-scales, each assessing a different area (e.g., visual function, auditory function, communication, arousal), and the final score is calculating by adding all sub-scales.The total score of this scale goes from its minimum, 0, which implied a state of coma, to 23, which implies emergence from a Minimally Conscious State (i.e., eMCS). Higher values thus map onto better outcomes. | Change in maximum CRS-R score from baseline to 1 month | 
| Number of Participants With (Severe) Adverse Events | Number of AEs and SAEs occurring throughout the paradigm. | day 20 (+/-3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hybrid Neural Network Evaluation | The Hybrid Neural Network Evaluation Model consists of comprehensive cortical connectivity parameters (perturbational complexity index and evoked high-frequency oscillations) and region-specific cortical connectivity parameters (short-latency afferent inhibition and mismatch negativity). Each parameter is clinically used to assess a patient's level of cortex connectivity. This hybrid evaluation model may give a comprehensive evaluation of a patient's degree of awareness, and enhance our understanding of the mechanisms underlying these conditions | Change from baseline to day 20 (+/-3) | 
| Number of voxels in which the Functional Magnetic Resonance Imaging (fMRI) signal is significantly associated to TMS across the whole group | Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the TMS stimulation across the tested population. | Change from baseline to 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic Stroke, Consciousness Disorder, Transcranial Magnetic Stimulation, Hybrid Neural Network Evaluation Model