Temporal Profile of Blood-Brain Barrier Breakdown in Reversible Cerebral Vasoconstriction Syndrome

Abstract

Background and Purpose— Reversible cerebral vasoconstriction syndrome (RCVS) has a unique temporal course of vasoconstriction. Blood-brain barrier (BBB) breakdown is part of the pathophysiology of RCVS, but its temporal course is unknown. We aimed to investigate the temporal profile of BBB breakdown and relevant clinical profiles in a large sample size. Methods— In this prospective observatory bicenter study, patients who underwent contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging within 2 months from onset were included. The presence and extent of BBB breakdown were evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. Contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging data were analyzed using a semiautomated segmentation technique to quantitatively measure the area of Gadolinium leakage into cerebrospinal fluid space. The univariable and multivariable linear regressions were performed to investigate the independent effect of time from onset with adjustment for other covariates. Results— In the 186 patients with angiogram-proven RCVS included in this analysis, BBB breakdown was observed in 52.6%, 56.8%, 30.3%, 40.0%, and 23.8% in the first, second, third, fourth, and ≥fifth week after onset. The extent of BBB breakdown peaked at first and second week, whereas the peak of vasoconstriction was observed at the third week after onset. Multivariable analysis showed the second week from onset (β, 3.35 [95% CI, 0.07–6.64]; P =0.046) and blood pressure surge (β, 3.84 [95% CI, 1.75–5.92]; P <0.001) were independently associated with a greater extent of BBB breakdown. A synergistic effect of time from onset and blood pressure surge was found ( P for interaction=0.006). Conclusions— Frequency and extent of BBB breakdown are more prominent during the early stage in patients with RCVS, with an earlier peak than that of vasoconstriction. The temporal course of BBB breakdown may provide a pathophysiologic background of the temporal course of neurological complications of RCVS.

Early Fluid Attenuation Inversion Recovery Sulcal Contrast Enhancement Correlates with Severity of Reversible Cerebral Vasoconstriction Syndrome

“…In all cases of available follow-up MRI, CE FLAIR signal subsided to undetectable along with the resolution of vasospasm. A multivariate analysis exploring the association of demographic factors and neurological score components with the severity of CE FLAIR signal revealed only positive correlation with PRES like edema (effect estimate, 3.922; 95% confidence interval, 0.29 to 0.753; P =0.037) suggesting an overall more benign clinical course in our cohort in comparison to previous reports [ 5 , 6 ].…”

“…A multivariate analysis exploring the association of demographic factors and neurological score components with the severity of CE FLAIR signal revealed only positive correlation with PRES like edema (effect estimate, 3.922; 95% confidence interval, 0.29 to 0.753; P=0.037) suggesting an overall more benign clinical course in our cohort in comparison to previous reports. 5,6 We suggest that contrasted enhancement on FLAIR imaging may reflect an early vasogenic process 7,8 of either delayed blood flow or local BBB disruption with a capillary leak as proposed recently in an earlier mentioned cohort 5 and in a later very compelling study, also of Asian population. 6 The earlier studies showed a correlation between leptomeningeal gadolinium enhancement on FLAIR imaging and neurological outcome, leading to diagnostic changes in unclear cases.…”

“…We suggest that contrasted enhancement on FLAIR imaging may reflect an early vasogenic process [ 7 , 8 ] of either delayed blood flow or local BBB disruption with a capillary leak as proposed recently in an earlier mentioned cohort [ 5 ] and in a later very compelling study, also of Asian population [ 6 ]. The earlier studies showed a correlation between leptomeningeal gadolinium enhancement on FLAIR imaging and neurological outcome, leading to diagnostic changes in unclear cases.…”

“…The score was devised according to previously described markers of RCVS severity. 6 The grading of contrast enhanced fluid attenuation inversion recovery (CE FLAIR) included the composite of intensity of sulci enhancement by contrast (0, no signal; 1, for mild signal; 2, for substantial signal) with its distribution throughout the brain (1 point for each involved lobe-including cerebellar hemispheres; 0-10).…”

“…Multivariate logistic regression analysis was used to assure that the score components were not affected by demographic or clinical variables. The score was devised according to previously described markers of RCVS severity [ 6 ]. The grading of CE FLAIR included the composite of intensity of sulci enhancement by contrast (0, no signal; 1, for mild signal; 2, for substantial signal) with its distribution throughout the brain (1 point for each involved lobe—including cerebellar hemispheres; 0–10).…”