Immunological Biomarkers in Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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Stroke is accompanied by local inflammatory response and systemic immunosuppression. Immunosuppression markers are associated with the occurrence of medical complications (infections), whereas inflammatory markers are associated with worse functional prognosis. This prospective study tries to validate in acute stroke patients the prognostic usefulness of a panel of immune biomarkers that have previously been associated with various clinical outcomes. The identification of beneficial and harmful immune responses in cerebral ischemia will allow the prediction of the clinical course of the patients and will be helpful in designing immunomodulatory therapeutic strategies for acute stroke.

Detailed Description
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Stroke is accompanied by local inflammatory response and systemic immunosuppression. Immunosuppression markers are associated with the occurrence of medical complications (infections), whereas inflammatory markers are associated with worse functional prognosis. This prospective study tries to validate in acute stroke patients the prognostic usefulness of a panel of immune biomarkers that have previously been associated with various clinical outcomes. The immune biomarkers will be assessed at admission, at day 1 after admission and at day 90. The assessed immune biomarker panel includes: Serum cortisol levels. Serum interleukin (IL)-10 levels. Proportion of circulating B lymphocytes (CD3-CD19+ cells). Monocyte surface expression of TLR4, HLA-DR, CD86, and VLA-4. Ex - vivo production of tumor necrosis factor (TNF)-α in monocytes after stimulation with LPS. Proportion of each of the circulating monocyte subpopulations (CD14highCD16-, CD14highCD16+, and CD14dimCD16+). The identification of beneficial and harmful immune responses in cerebral ischemia will allow the prediction of the clinical course of the patients and will be helpful in designing immunomodulatory therapeutic strategies for acute stroke.

Official Title
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Clinical Implications of a Panel of Immunological Biomarkers in Patients With Acute Ischemic Stroke

Conditions
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Ischemic Stroke

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ischemic stroke* stroke onset within 6h* treated with systemic or intraarterial thrombolysis* minimum severity in the NIHSS of 3* age ≥ 18 consent by the patient or the legal representative These items do not apply for healthy subjects. Exclusion Criteria: intracranial hemorrhage signs of infection at admission use of antibiotics, immunosuppressors or corticosteroids in the previous 3 months significant disability (mRS>2) before index stroke

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ischemic stroke<br>Patients with an ischemic stroke admitted within 6 hours of symptom onset, with a minimum severity in the NIHSS of 3 and treated with systemic or intraarterial thrombolysis | |
| Healthy subjects<br>Age-matched individuals free of acute neurological injury | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive immune score for favorable outcome | To establish a predictive immune score for functional outcome. Favorable outcome is defined as a modified Rankin Scale (mRS) score of <3 at day 90+-15 after stroke | 90 +-15 days after onset of symptoms | 
| Predictive immune score for stroke associated infection | To establish a predictive score for stroke associated infection (SAI) based on immune biomarkers. Stroke associated infection is defined as: body temperature > 37.7ºC and symptoms of infection (cough, dyspnea, pleuritic pain, dysuria), or leukocytosis >11000, leukopenia <4000, pulmonary infiltrates in chest X-ray or positive cultures for a pathogen. | 7 days after onset of symptoms | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive immune score for ischemic progression | To establish a predictive score for ischemic progression based in a panel of immune biomarkers. Ischemic progression is defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale(NIHSS) score in the absence of bleeding in the CT scan. | 7 days after onset of symptoms | 
| Predictive immune score for functional outcome over the entire mRS | To establish a predictive score for functional outcome based in a panel of immune biomarkers and using shift analysis of the entire mRS | 90 +-15 days after onset of symptoms | 
| Localization and stroke volume analysis | To investigate the influence of the localization and stroke volume on the occurrence of a stroke associated infection and on neurological outcome | SAI within 7 days and neurological outcome after 3 months after onset of symptoms | 
| Insular cortex involvement and infarct volume | To investigate the influence of insular cortex involvement and infarct volume on the occurrence of a SAI and on the neurological outcome after 3 months | SAI within 7 days and and on the neurological outcome after 3 months | 
| Infection and functional outcome after ischemic stroke | To assess the independent effect of SAI over the functional outcome at 3 months | SAI within 7 days after onset of symptoms and neurological outcome after 3 months | 
| Thrombolysis, immune biomarkers and SAI | To assess the effect of thrombolytic treatment over changes in the immune biomarker panel and over the occurrence of SAI | SAI within 7 days after onset of symptoms | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemic stroke, immune biomarkers, stroke-associated infection, functional outcome, prediction