Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients

Abstract

Background and Purpose— The high prevalence of hyperintense acute reperfusion marker (HARM) seen after endovascular therapy is suggestive of blood-brain barrier disruption and hemorrhage risk and may be attributable to multiple thrombectomy passes needed to achieve recanalization. Methods— Patients with acute stroke were included if they were screened from January 2015 through February 2019, received an acute ischemic stroke diagnosis involving the anterior circulation, treated with or without IV tPA (intravenous tissue-type plasminogen activator), consented to the NINDS Natural History Study, and imaged with a baseline magnetic resonance imaging before receiving endovascular therapy. Consensus image reads for HARM and hemorrhagic transformation were performed. Good clinical outcome was defined as 0–2 using the latest available modified Rankin Scale score. Results— Eighty patients met all study criteria and were included in the analyses. Median age was 65 years, 64% female, 51% black/African American, median admit National Institutes of Health Stroke Scale=19, 56% treated with IV tPA, and 84% achieved Thrombolysis in Cerebral Infarction score of 2b/3. Multiple-pass patients had significantly higher rates of severe HARM at 24 hours (67% versus 29%; P =0.001), any hemorrhagic transformation (60% versus 36%; P =0.04) and poor clinical outcome (67% versus 36%; P =0.008). Only age (odds ratio, 1.1; 95% CI, 1.01–1.12; P =0.022) and severe HARM at 24 hours post-endovascular therapy were significantly associated with multiple passes (odds ratio, 7.2; 95% CI, 1.93–26.92; P =0.003). Conclusions— In this exploratory study, multiple thrombectomy passes are independently associated with a significant increase in blood-brain barrier disruption detected at 24 hours. Patients with HARM post-endovascular therapy had a >7-fold increase in the odds of having multiple- versus single-pass thrombectomy. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00009243.

CSF enhancement on post-contrast fluid-attenuated inversion recovery images; a systematic review

“…2 ). Most studies were performed in cases with ischemic stroke, transient ischemic attack (TIA), and/or intracerebral hemorrhage (ICH) (n = 20) ( Villringer, 2017 , Ostwaldt, 2015 , Ostwaldt, 2014 , Warach and Latour, 2004 , Latour et al, 2004 , Choi, 2017 , Dechambre, 2000 , Forster et al, 2016 , Gupta, 2017 , Henning et al, 2008 , Hjort, 2008 , Kim, 2005 , Luby, 2019 , Nadareishvili, 2018 , Lee, 2015 , Lee, 2016 , Lee, 2018 , Rozanski, 2010 , Kidwell et al, 2011 , Jolink, et al, 2019 , Barr, 2010 ). Six studies described patients who underwent cardiovascular or intracranial vascular surgery ( Cho, 2014 , Ogami et al, 2011 , Wilkinson, 2000 , Li, 2018 , Suthiphosuwan et al, 2018 , Merino, 2013 ), nine studies patients with multiple sclerosis (MS) (one of these included stroke cases as a positive control ( Eisele, 2015 ) ( Eisele, 2015 , Absinta, 2015 , Bergsland, 2019 , Harrison, 2017 , Jonas et al, 2018 , Zivadinov, 2017 , Zivadinov, 2018 , Zurawski, 2020 , Ighani, 2020 ), four studies patients with meningitis ( Ahmad et al, 2015 , Alonso, 2015 , Fukuoka, 2010 , Splendiani, 2005 ), two studies reported on memory clinic patients and normal aging ( Freeze, 2017 , Freeze et al, 2019 ), one study on Susac syndrome and MS ( Coulette, 2019 ), one study on familial amyloid polyneuropathy ( Hirai, 2005 ), and one study included a mix of diseases, which were presented as follows: inflammatory and immune-mediated neurologic diseases (neuromyelitis optica spectrum disorder, immune-mediated encephalitis, immune-mediated cerebellar ataxia, systemic inflammatory diseases with white matter MRI abnormalities not suggestive for MS and Susac syndrome), noninflammatory neurologic diseases (small vessel disease, migraine, neurodegenerative diseases, compressive myelopathy), human T-lymphotropic virus (HTLV) infection,...…”

“…Twenty-one studies assessed CSF enhancement in cases with stroke ( supplemental table e-2 ). Fourteen studies examined acute ischemic stroke, including nine studies with non-selective and non-overlapping study samples with a total of 1148 cases and a pooled mean age of 70 years ( Ostwaldt, 2015 , Warach and Latour, 2004 , Latour et al, 2004 , Choi, 2017 , Forster et al, 2016 , Gupta, 2017 , Hjort, 2008 , Kim, 2005 , Luby, 2019 , Nadareishvili, 2018 ). The reported prevalence of CSF enhancement in these studies ranged from 12% to 65%, with a pooled prevalence estimate of 27% (95% CI 25–30).…”

“…The term HARM was introduced in 2004 by Warach and Latour because they hypothesized that enhancement of the CSF space in acute ischemic stroke was related to reperfusion injury ( Warach and Latour, 2004 ). Since then, many studies in acute ischemic stroke ( Villringer, 2017 , Ostwaldt, 2015 , Ostwaldt, 2014 , Choi, 2017 , Forster et al, 2016 , Gupta, 2017 , Henning et al, 2008 , Hjort, 2008 , Luby, 2019 , Nadareishvili, 2018 , Lee, 2015 , Lee, 2016 , Lee, 2018 , Rozanski, 2010 ), but also studies in hemorrhagic stroke ( Kidwell et al, 2011 , Jolink, et al, 2019 ), treatment for carotid artery disease ( Cho, 2014 ), and cardiac surgery ( Merino, 2013 ), have adopted the term. By comparison, the term ‘LME’ refers to the abnormal accumulation of contrast media in the pia mater, arachnoid mater, and/or the subarachnoid space, and has also been used by studies in a variety of diseases, including ischemic stroke ( Wilkinson, 2000 ), MS ( Absinta, 2015 , Harrison, 2017 , Coulette, 2019 , Coulette, 2019 , Zurawski, 2020 , Ighani, 2020 , Ahmad et al, 2015 , Alonso, 2015 , Fukuoka, 2010 , Splendiani, 2005 , Freeze et al, 2019 ), and meningitis ( Ahmad et al, 2015 , Alonso, 2015 , Fukuoka, 2010 ).…”

“…Locations of CSF enhancement included sulci, subarachnoid space, ventricles, and cisterns. From studies in acute ischemic stroke it could be inferred that the enhancement was frequently observed in, but not necessarily restricted to, the same vascular territory and hemisphere as the infarction ( Ostwaldt, 2015 , Warach and Latour, 2004 , Latour et al, 2004 , Henning et al, 2008 , Kim, 2005 , Luby, 2019 , Lee, 2016 , Choi, 2017 , Dechambre, 2000 , Forster et al, 2016 ). In contrast, two studies in ICH reported that CSF enhancement was noncontiguous with the hemorrhage ( Kidwell et al, 2011 , Jolink, et al, 2019 ).…”

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

“…One study ( 123 ) found BBB disruption evaluated by non-contrast CT scan within 3 h of the procedure and defined as parenchymal hyperdensity on CT scan (including both blood and contrast medium), occurring in 61% of patients. Multiple thrombectomy passes have also been independently associated with a significant increase in BBB disruption as evaluated by hyperintense acute reperfusion marker (HARM) which is a hyperintensity on T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI following an injection of gadolinium-based contrast agent ( 149 ). An interesting question raised by Renú et al ( 150 ) regarding such an imagological finding is whether this is attributable to MT-induced damage to BBB at a microcirculatory level or by direct damage to the proximal vessel wall where the MT device is deployed.…”