Review of studies on dynamic cerebral autoregulation in the acute phase of stroke and the relationship with clinical outcome

Abstract

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.

Keywords: INFOMATAS; Ischemic stroke; cerebral perfusion; clinical outcome; dynamic cerebral autoregulation.

Figure 1.

(a & b) a: Flow diagram of studies identification for ischemic and intracerebral haemorrhage stroke. b: flow diagram of studies identification for subarachnoid haemorrhage stroke.

Figure 2.

Schematic representation of the main findings concerning dynamic cerebral autoregulation (CA) status at the acute stage of stroke and clinical outcome. From the upper to bottom rows of figures are represented ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. From left to right, we depicted, sequentially, head computed topographies representative of each stroke type, dynamic CA impairment pattern measured by three methods (just for exemplification), and proposed lesion mechanisms linking CA impairment to the clinical outcome, which is in the last position. In ischemic stroke, a patient with large vessel occlusion presents with reduced phase (impaired CA) in the affected hemisphere but not in the contralateral one. These patients developed hemorrhagic transformation and cerebral edema causing midline shift, hampering the clinical recovery with severe neurological deficits as measured by the National Institutes of Health Stroke Scale (NIHSS). In the intracerebral hemorrhage patient, dynamic CA was assessed invasively with an intracranial pressure probe to measure the pressure-reactivity index (PRx). As compared to patients with better clinical course, these patients showed a PRx plateau pattern mostly near the threshold of 0.3 (darker line), which is believed to be the limit of a competent CA. This occurs in patients with large hematoma volumes and it is not known if CA is a reflex of stroke severity. This has also not been proved to be an independent prognostic factor in the long term. Finally, in subarachnoid hemorrhage, a patient is represented in whom there is a steeper response of cerebral flow velocity to pressure oscillations (darker line); this predicted the development of vasospasm and delayed cerebral ischemia..

Figure 3.

(a & b). a: main findings from the articles; dark blue, common findings for all three clinical conditions (IS, ICH and SAH); intermediate blue, common finding for IS/ICH and ICH/SAH; light blue, findings for each clinical condition. b (left): main limitations from the articles; dark blue, common limitations for all three clinical conditions (IS, ICH and SAH); intermediate blue, common limitations for IS/ICH and ICH/SAH; light blue, limitations for each clinical condition. b (right): perspectives for future studies based on the limitations.