Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.

Background and Purpose: The mechanisms linking systemic inflammation to poor outcome in ischemic stroke are not fully understood. The authors investigated if peripheral inflammation following reperfusion therapy leads to an increase in cerebral edema (CED), thus hindering the clinical recovery. Methods: We designed a single-center study conducted at Centro Hospitalar Universitário São João between 2017 and 2019. Inclusion criteria were being adult, having an anterior circulation acute ischemic stroke, and receiving reperfusion therapy. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and the systemic inflammatory response syndrome criteria were determined. The presence and grade of CED were evaluated on the computed tomography performed 24 hours following event. The clinical outcomes included early neurological deterioration and functional dependence at 90 days. Adjusted odds ratio and 95% CI were obtained by ordinal and logistic regression models. Optimal cutoff values were defined using receiver operating characteristic analysis in the training cohort and validated in an independent data set. Results: Five hundred fifty-three patients were included. Neutrophil-to-lymphocyte increased with higher degrees of CED at 24 hours (adjusted odds ratio, 1.34 [1.09–1.68], P <0.01) and was associated with early neurological deterioration (adjusted odds ratio, 1.30 [1.04–1.63], P <0.05) and poor functional status at 90 days (adjusted odds ratio, 1.79 [1.28–2.48], P <0.01). Platelet-to-lymphocyte was not associated with the outcomes. Systemic inflammatory response syndrome was related to CED due to altered white blood cell counts. Neutrophil-to-lymphocyte was the best predictor with an area under the curve around 0.7. Neutrophil-to-lymphocyte ≥7 had and accuracy, sensitivity, and specificity around 60%. Conclusions: Increased systemic inflammation is linked to the severity of CED early after reperfusion therapy in stroke. Easily obtained inflammatory markers convey early warning alerts for patients at risk of severe neurological complications with an impact on long-term functional outcome. CED quantification should be included as an end point in proof-of-concept trials in immunomodulation in stroke.

Acute stroke is associated with high morbidity and mortality. In the last decades, new therapies have been investigated with the aim of improving clinical outcomes in the acute phase post stroke onset. However, despite such advances, a large number of patients do not demonstrate improvement, furthermore, some unfortunately deteriorate. Thus, there is a need for additional treatments targeted to the individual patient. A potential therapeutic target is interventions to optimize cerebral perfusion guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). This narrative led to the development of the INFOMATAS (Identifying New targets FOr Management And Therapy in Acute Stroke) project, designed to foster interventions directed towards understanding and improving hemodynamic aspects of the cerebral circulation in acute cerebrovascular disease states. This comprehensive review aims to summarize relevant studies on assessing dCA in patients suffering acute ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage. The review will provide to the reader the most consistent findings, the inconsistent findings which still need to be explored further and discuss the main limitations of these studies. This will allow for the creation of a research agenda for the use of bedside dCA information for prognostication and targeted perfusion interventions.

Background and Purpose: Effective cerebral autoregulation (CA) may protect the vulnerable ischemic penumbra from blood pressure fluctuations and minimize neurological injury. We aimed to measure dynamic CA within 6 hours of ischemic stroke (IS) symptoms onset and to evaluate the relationship between CA, stroke volume and neurological outcome. Methods: We enrolled 30 patients with acute middle cerebral artery IS. Within 6 hours of IS we measured for 10 minutes arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler) and end-tidal-CO2. Transfer function analysis (coherence, phase, and gain) assessed dynamic CA, and receiver-operating curves calculated relevant cut-off values. National Institute of Health Stroke Scale was measured at baseline. Computed tomography at 24 hours evaluated infarct volume. Modified Rankin Scale (MRS) at 3 months evaluated the outcome. Results: The odds of being independent at 3 months (MRS 0-2) was 8-fold higher when 6 hours CA was intact (Phase>37 degrees) (OR = 8.0 (IC95% 1.5-42.0), p=0.014). Similarly, infarct volume was significantly smaller with intact CA [median (range) 1.1 (0.2-7.0) vs 13.1 (1.3-110.5) ml, p=0.002]. Conclusions: In this pilot study, early effective CA was associated with better neurological outcome in patients with IS. Dynamic CA may carry significant prognostic implications.