Microcirculation and Plasticity After Stroke

Study Overview
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Brief Summary
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Reperfusion is the main goal of early medical interventions after stroke, such as thrombolysis and thrombectomy. Recanalization works only if applied early - the earlier the better, but with a statistical cutoff of 4.5 hours where risk of hemorrhage outweighs the benefit. Recently, this cutoff has been put into perspective using standardized perfusion measurements by magnetic resonance imaging (MRI) or computed tomography (CT). Two trials have shown that revascularization is beneficial up to 24 hours after stroke onset if patient selection is based on perfusion imaging. This suggests interindividual differences in the temporal evolution of an infarction. One explanation for interindividual differences is the variability of the collateral blood supply to the brain, which in turn can maintain different perfusion pressures around the infarct core, also called the penumbra region. Insufficient recruitment of these collateral pathways is an independent negative predictor of poor outcome; the insufficiency may in part be explained by insufficient dilatation of arterioles (low dilator reserve). So far, interventions to improve collateral perfusion, e.g., induced hypertension, have not demonstrated effectiveness, likely because our understanding of collateral perfusion, demand-dependent dilatation of arteries (cerebrovascular reserve, CVR) and their effect on microcirculation is insufficient. Functional recovery after a brain lesion is based on plasticity. Plasticity involves the creation of new synapses, fibers (axons and dendrites) and lasting modification to synaptic strength as well as the formation and migration of new neurons. In the cortex surrounding an infarct, plasticity is facilitated by ischemia via modification of gene expression, i.e. a certain time window after stroke, and is stimulated by activity and training. Tissue microcirculatory status and perfusion surrounding the stroke lesion may play a role in the formation of this plasticity. The investigators will analyze the contributions of pre-existing vascular networks, the impact of stroke-affected vessels, timing and degree of recanalization success, brain excitability, and short-term intra-cortical inhibition to better understand how these factors relate to functional recovery after stroke.

Official Title
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The Interplay of Microcirculation and Plasticity After Ischemic Stroke

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Other: Observation of microcirculation and plasticity of the brain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≤72h First-ever clinical ischemic stroke at hospital admission Occlusion of M1-segment of the middle cerebral artery, and/ or intracranial internal carotid artery, and perfusion deficits with cortical involvement 18 years or above Living independent before stroke (mRS ≤3) Written informed consent of the patient or the when the patient is not able to participate in the consenting procedure, the written authorization of an independent doctor who is not involved in the research project to safeguard the interests of the patient; in that case, post-hoc written informed consent of the patient is needed, or when the patient remains unable to participate in the informed consent procedure, written informed consent of a next of kind Exclusion Criteria: Major cardiac, psychiatric and/ or neurological diseases Early seizures Known or suspected non-compliance, drug and/ or alcohol abuse Contra-indications for Magnetic Resonance Imaging and Transcranial Magnetic Stimulation, such as a history of seizure, prior electroconvulsive therapy, deep brain stimulators or other metal in the head, skull defect, pacemaker; neuroleptic medication; known allergic reaction to contrast material Documented evidence that the patient does not want to participate in any scientific study or, in case of lack of documented evidence, no behavior and/or expression(s) that indicate(s) refusal of the patient to participate in research

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Single-group study<br>Assessment of microcirculation, brain plasticity and clinical function | Other: Observation of microcirculation and plasticity of the brain<br>* Assessment of microcirculation, brain plasticity and clinical function<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain microcirculation | Change in microcirculation of the brain as measured by magnetic resonance imaging (MRI) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Change in brain plasticity | Change in plasticity of the brain as measured by transcranial magnetic stimulation (TMS) | 7, 45 and 90 days after stroke onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale | Neurological impairments (scale range 0-42, higher values represent a worse outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Fugl-Meyer Motor Assessment - Upper Extremity Subscale | Upper limb motor function (scale range 0-66, higher values represent a better outcome) | 7, 45 and 90 days after stroke onset | 
| Fugl-Meyer Motor Assessment - Lower Extremity Subscale | Lower limb motor function (scale range 0-34, higher values represent a better outcome) | 7, 45 and 90 days after stroke onset | 
| Finger extension 1 | Ability to extend the fingers (scale range 0-2, higher values represent a better outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Finger extension 2 | Ability to extend the fingers (scale range 0-10, higher values represent a better outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Finger extension 3 | Ability to extend the fingers (scale range 0-3, higher values represent a worse outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Trunk Control Test | Trunk ability (scale range 0-100, higher values represent a better outcome) | 7 and 90 days after stroke onset | 
| Functional Ambulation Categories | Walking ability (independence) (scale range 0-5, higher values represent a better outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Ten-Meter Walk Test | Gait speed and cadence (scale range is time in seconds, higher values represent a worse outcome) | 7, 45 and 90 days after stroke onset | 
| Modified Rankin Scale | Global disability (scale range 0-5, higher values represent a worse outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Mobilization | Amount of mobilization (scale range is time in minutes, higher values represent a better outcome) | <72 hours; 7 days | 
| Concomitant movement therapy | Intensity of therapy based on charts (scale range is time in minutes, higher values represent a better outcome) | <72 hours; 7, 45 and 90 days after stroke onset | 
| Related Serious Events | Serious Events (1. death; 2. life-threatening illness or injury; 3. in-patient or prolonged hospitalization; 4. medical or surgical intervention to prevent life threatening illness; 5. led to fetal distress, death or a congenital abnormality or birth defect) | <72 hours; 7, 45 and 90 days after stroke onset | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microcirculation, Plasticity, Cohort studies