Implications of Post-recanalization Perfusion Deficit After Acute Ischemic Stroke: a Scoping Review of Clinical and Preclinical Imaging Studies

Abstract

The goal of reperfusion therapy for acute ischemic stroke (AIS) is to restore cerebral blood flow through recanalization of the occluded vessel. Unfortunately, successful recanalization does not always result in favorable clinical outcome. Post-recanalization perfusion deficits (PRPDs), constituted by cerebral hypo- or hyperperfusion, may contribute to lagging patient recovery rates, but its clinical significance remains unclear. This scoping review provides an overview of clinical and preclinical findings on post-ischemic reperfusion, aiming to elucidate the pattern and consequences of PRPD from a translational perspective. The MEDLINE database was searched for quantitative clinical and preclinical studies of AIS reporting PRPD based on cerebral circulation parameters acquired by translational tomographic imaging methods. PRPD and stroke outcome were mapped on a charting table, creating an overview of PRPD after AIS. Twenty-two clinical and twenty-two preclinical studies were included. Post-recanalization hypoperfusion is rarely reported in clinical studies (4/22) but unequivocally associated with detrimental outcome. Post-recanalization hyperperfusion is more commonly reported (18/22 clinical studies) and may be associated with positive or negative outcome. PRPD has been replicated in animal studies, offering mechanistic insights into causes and consequences of PRPD and allowing delineation of possible courses of PRPD. Complex relationships exist between PRPD and stroke outcome. Diversity in methods and lack of standardized definitions in reperfusion studies complicate the characterization of reperfusion patterns. Recommendations are made to advance the understanding of PRPD mechanisms and to further disentangle the relation between PRPD and disease outcome.

Dynamics of cerebral blood volume during and after middle cerebral artery occlusion in rats – Comparison between ultrafast ultrasound and dynamic susceptibility contrast-enhanced MRI measurements

“…There is a considerable amount of literature dedicated to elucidating causes and consequences of various (re)perfusion deficits, using different methods of measurement, in clinical and translational settings. 30 Reperfusion dynamics are challenging to study due to their multifaceted nature and often fleeting responses to ischemic events, as demonstrated in the present analyses. Preclinically, a wide array of reperfusion responses have been reported within hours after stroke, ranging from hypoperfusion to hyperperfusion (or hyperemia).…”

“…In the literature, variation in reperfusion status has been attributed to a wide array of factors such as spatial location, mode of recanalization (mechanical or thrombolytic), and vascular comorbidity. 30…”

“…Statistical analyses were performed in R (v4.0.2) 26 using packages tidyverse, 27 lme4, 28 and emmeans. 29…”

Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model

“…Clinical data on post-stroke reperfusion beyond the acute phase (>24 hours post-AIS) have shown normal (normoperfusion), elevated (hyperperfusion) as well as markedly reduced (hypoperfusion) perfusion, which may exist on a continuum. As extensively reviewed recently, 13 several lines of evidence suggest hyperperfusion may be associated with beneficial outcomes in patients, treated 14,15 or untreated, 16,17 while conversely, hyperperfusion has also been associated with hemorrhagic transformation in patients who received reperfusion therapy. 18 Perhaps unsurprisingly, normoperfusion associates with beneficial outcome in patients treated by mechanical thrombectomy.…”

“…15 Lastly, acute post-recanalization hypoperfusion accompanies unfavorable outcomes but appears to be less prevalent than hyperperfusion in patient studies. 13 Although hemodynamic aberrations may already develop within hours after reperfusion therapy, few perfusion studies have been executed in patients as post-recanalization imaging is not standard of care.…”