Microcirculation and Plasticity After Stroke

University of Zurich49 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in brain microcirculation

Change in microcirculation of the brain as measured by magnetic resonance imaging (MRI)

Time frame: <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)

Time frame: 7, 45 and 90 days after stroke onset

Secondary Outcomes

National Institutes of Health Stroke Scale

Neurological impairments (scale range 0-42, higher values represent a worse outcome)

Time frame: <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)

Time frame: 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)

Time frame: 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)

Time frame: <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)

Time frame: <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)

Time frame: <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)

Time frame: 7 and 90 days after stroke onset

Functional Ambulation Categories

Walking ability (independence) (scale range 0-5, higher values represent a better outcome)

Time frame: <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)

Time frame: 7, 45 and 90 days after stroke onset

Modified Rankin Scale

Global disability (scale range 0-5, higher values represent a worse outcome)

Time frame: <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)

Time frame: <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)

Time frame: <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)

Time frame: <72 hours; 7, 45 and 90 days after stroke onset

Microcirculation and Plasticity After Stroke

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts