Linearity and Non-linearity of Cerebral Autoregulation

Study Overview
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Brief Summary
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Injured brain tissue supplied by a disturbed state of cerebral autoregulation (CA) is at risk of secondary ischemia, e.g. in patients with stroke, subarachnoid hemorrhage, intracerebral hemorrhage or bacterial Meningitis. Up to now, there is lack of a simple and easy to perform bed side test that would allow for to intervene when CA failure is indicated. For this purpose, we explore the dynamics of the interplay between blood pressure and cerebral blood flow velocity using transcranial Doppler ultrasound (or near infrared spectroscopy derived haemoglobin concentration changes) as a measure of CA. To describe these dynamics different mathematical models are used, but they all still need validation and proof of concept because these dynamics are poorly understood with respect to the factors which influence the composition of the mathematical models. Objectives: To what amount is CA disturbed in the different stroke subgroups ? Is a disturbed CA a risk factor of poorer outcome ?

Detailed Description
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We investigate which factors determine the dynamics of CA under the assumption that disturbed dynamics of the relation blood pressure (BP) - cerebral blood flow velocity CBFv) indicate a disturbed CA. Factors to be considered relevant are BP, blood carbon dioxide (CO2) concentration (measured as endtidal CO2 concentration), autonomic nervous system function such as heart rate, pulse pressure amplitude and baroreflex sensitivity, movement or psychological tasks, and in the patients the kind and the severity of the underlying disease. Via different mathematical models the effects of these variables on CBFv as the Output function is evaluated. The most frequently used approach is the use of Transfer functions. In the registry will include the patients with acute strokes hospitalized at our stroke center. We will include every stroke patient with any Kind and severity of stroke syndromes who gives informed consent and who has a so called temporal ultrasound window to insonate the middle cerebral artery. BP will be measure noninvasively by a Finapres device. Items registered are Age, gender, cerebrovascular risk factors, temperature, mean BP and ist variability on days 1-3, stroke classification using TOAST, Perfusion Computed Tomography and MRI, and at the time of the simultaneous recordings of CBFv and BP the endtidal CO2, mean BP, mean pulsatility index, and after Transfer function analysis coherence, gain and Phase in different frequency ranges

Official Title
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Linearity and Non-linearity of Cerebral Autoregulation

Conditions
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Stroke, Acute

Intervention / Treatment
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* Diagnostic Test: Assessment of CA
* Diagnostic Test: Assesment of CA only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: every typ of ischemic stroke of any severity presence of a temporal bone window Exclusion Criteria: Age < 18 years, pregnancy no informed consent. absence of a temporal bone window

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with stroke<br>Patients with stroke of all subtypes, with and without different Kind of Lysis therapy | Diagnostic Test: Assessment of CA<br>* As part of our routine stroke work up, each patient receives an initial CT scan with CT perfusion to indicate thrombolysis therapy (intravenous, mechanical, or both, depending on the time since first stroke symptoms and perfusion-mismatch), an MRI within 2 days, extracranial and transcranial Duplex ultrasound, echocardiography, continuous Monitoring of BP, O2, body temperature, NIHSS and Glagow Coma Scale (GCS) every 6 hours. Assessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates<br>|
| Controls<br>Healthy controls of all Ages above 18 years | Diagnostic Test: Assesment of CA only<br>* Assessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of modified Rankin Scale (mRs) : 0, no symptoms. 1, no significant disability. 2, slight disability. 3, moderate disability. 4, moderate severe disability. 5, severe disability. 6, dead | Clinical outcome | 3 months | 
| State of cerebral autoregulation (CA) | Transfer function estimates (gain, phase) between low frequency oscillations in BP and CBFv. A low gain and a high phase indicate good CA, a high gain and a low phase a poor CA state. Typically, a phase of 1 radian indicates a good CA, a phase of 0.2 a very poor one. | Assessment on days 1-3 after stroke onset | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Cerebral autoregulation, Doppler, Carotid disease