Post-stroke Immunological Changes in Young Stroke Patients

Study Overview
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Brief Summary
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In the present study, the investigators aim to elucidate the role of T-cells on cognitive decline in younger stroke patients, using repeated cognitive testing, brain imaging, and immunological analyses in the first 6 month after stroke. The examiners will investigate (i) the extent and duration of stroke-induced changes in T cell function within the peripheral blood of patients; and (ii) post-stroke cognitive functions.

Detailed Description
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Demands from society on stroke patients of younger age are in most cases higher than for elderly stroke patients, because of occupational obligations and often their role as a caregiver for a young family. For example, return to their former workplace may be impossible even if cognitive deficits, e.g., in the memory domain, are only minor according to standardized tests. Thus, cognitive function after stroke is of utmost importance for activities of daily life and quality of life in young stroke patients. In order to prevent or at least reduce post-stroke cognitive decline, the mechanisms underlying the decline need to be further elucidated, to eventually develop new preventive and therapeutic approaches. T-cell activation is associated with destruction of brain tissue. In neurodegenerative diseases that primarily impair cognitive functions, e. g., Alzheimers Disease, T-cells were identified as important mediators of disease pathology. Activation of cells of the adaptive immune system, most importantly T-cells, has been also investigated in experimental stroke. Here, these cells significantly contribute to secondary brain tissue damage. Stroke is associated with massive changes of the central and peripheral immune response. The investigators and other groups demonstrated that despite an overall lymphopenia, T-cells are functionally intact and pro-inflammatorily polarized, for at least two weeks post-stroke. Depletion of T cells has been shown to reduce infarct volume and to improve outcome in mice post-experimental stroke.

Official Title
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Role of Th1-lymphocytes in the Development of Vascular Cognitive Impairment in Young Stroke Patients

Conditions
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Stroke, Ischemic, Cognitive Decline

Intervention / Treatment
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* Other: Analysis of T-lymphocytes


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Acute stroke that occurred within the last 72 hours as defined by acute neurological deficit in combination with an acute ischaemic infarct as documented by either a Diffusion weighted imaging (DWI)-positive lesion on MR imaging or a new lesion on a CT scan; only cortical/subcortical infarcts will be included Age > 18; ≤ 55 Provision of written informed consent or through a surrogate as appropriate Willingness to participate in follow-up National Institute of Health Stroke Scale Score (NIHSS) ≥ 4 German as first language (neuropsychological tests and cut-offs developed for native speakers) Exclusion criteria Patients are excluded if they are not able to give informed consent due to severe cognitive deficits Signs of infection on admission (C-reactive protein ≥ 50 mg/L) Patients receiving immunosuppressive drugs or diagnosed with a malignancy or severe neurological diseases other than stroke (e.g., neurodegenerative movement disorders, motoneuron diseases)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Group A (young stroke)<br>Young stroke patients (≤ 55); Analysis of T-lymphocytes regarding: post-stroke t-cell priming (activation marker, polarization), cognitive tests; structural MRI | Other: Analysis of T-lymphocytes<br>* Analysis of T-lymphocytes regarding the development of cognitive function after stroke<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune alterations, as determined via T-cell subtypes and function in comparison to cognitive outcome after stroke | The pro-inflammatorily primed T-cell response after stroke is associated with post-stroke cognitive decline, cognitive decline over time in young stroke patients | 3 years |