OBJECTIVES:Intracerebral hemorrhage is a devastating disorder with no current treatment. Whether perihematomal edema is an independent predictor of neurologic outcome is controversial. We sought to ...determine whether perihematomal edema expansion rate predicts outcome after intracerebral hemorrhage.
DESIGN:Retrospective cohort study.
SETTING:Tertiary medical center.
PATIENTS:One hundred thirty-nine consecutive supratentorial spontaneous intracerebral hemorrhage patients 18 years or older admitted between 2000 and 2013.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema volumes were measured from CT scans obtained at presentation, 24-hours, and 72-hours postintracerebral hemorrhage. Perihematomal edema expansion rate was the difference between initial and follow-up perihematomal edema volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) perihematomal edema expansion rate at 24 hours and 90-day mortality and 2) perihematomal edema expansion rate at 24 hours and 90-day modified Rankin Scale score. Perihematomal edema expansion rate between admission and 24-hours postintracerebral hemorrhage was a significant predictor of 90-day mortality (odds ratio, 2.97; 95% CI, 1.48–5.99; p = 0.002). This association persisted after adjusting for all components of the intracerebral hemorrhage score (odds ratio, 2.21; 95% CI, 1.05–4.64; p = 0.04). Similarly, higher 24-hour perihematomal edema expansion rate was associated with poorer modified Rankin Scale score in an ordinal shift analysis (odds ratio, 2.40; 95% CI, 1.37–4.21; p = 0.002). The association persisted after adjustment for all intracerebral hemorrhage score components (odds ratio, 2.07; 95% CI, 1.12–3.83; p = 0.02).
CONCLUSIONS:Faster perihematomal edema expansion rate 24-hours postintracerebral hemorrhage is associated with worse outcome. Perihematomal edema may represent an attractive translational target for secondary injury after intracerebral hemorrhage.
The use and effectiveness of current stroke reperfusion therapies are limited by the complications of reperfusion injury, which include increased cerebrovascular permeability and haemorrhagic ...transformation. Sphingosine-1-phosphate (S1P) is emerging as a potent modulator of vascular integrity via its receptors (S1PR). By using genetic approaches and a S1PR2 antagonist (JTE013), here we show that S1PR2 plays a critical role in the induction of cerebrovascular permeability, development of intracerebral haemorrhage and neurovascular injury in experimental stroke. In addition, inhibition of S1PR2 results in decreased matrix metalloproteinase (MMP)-9 activity in vivo and lower gelatinase activity in cerebral microvessels. S1PR2 immunopositivity is detected only in the ischemic microvessels of wild-type mice and in the cerebrovascular endothelium of human brain autopsy samples. In vitro, S1PR2 potently regulates the responses of the brain endothelium to ischaemic and inflammatory injury. Therapeutic targeting of this novel pathway could have important translational relevance to stroke patients.
Although statins have been associated with increased risk of spontaneous intracerebral hemorrhage, their relationship with cerebral microbleeds (CMBs) formation is poorly understood. We ...systematically reviewed previously published studies reporting on the association between CMBs presence and current statin use.
We performed a systematic search in MEDLINE and SCOPUS databases on October 24, 2019 to identify all cohorts from randomized-controlled clinical trials or observational studies reporting on CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Random effects model was used to calculate the pooled estimates. We included 7 studies (n = 3734 participants): unselected general population n = 1965, ischemic stroke n = 849, hemorrhagic stroke n = 252 and patients with hypertension over the age of 60 n = 668. Statin use was not associated with CMBs presence in either unadjusted (OR = 1.15, 95%CI: 0.76–1.74) or adjusted analyses (OR = 1.09, 95%CI: 0.64–1.86). Statin use was more strongly related to lobar CMB presence (OR = 2.01, 95%CI: 1.48–2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR = 2.26, 95%CI: 0.86–5.91). Except for the analysis on the unadjusted probability of lobar CMBs presence, considerable heterogeneity was present in all other analyses (I2 > 60%). Our findings suggest that statin treatment seems not to be associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.
•The relationship of statins with cerebral microbleeds (CMBs) formation is unknown.•This meta-analysis evaluates the association between CMBs presence and statin use.•Unadjusted and adjusted analyses uncovered no association of statins with CMBs presence.•Statin use was related to a two-fold higher chance for lobar CMB presence.•This association was consistent, but no statistically significant, in adjusted analysis.
Perihematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH). PHE measurement on computed tomography (CT) is challenging, and the principles used to detect PHE have not ...been described fully. We developed a systematic approach for CT-based measurement of PHE.
Two independent raters measured PHE volumes on baseline and 24-hour post-ICH CT scans of 20 primary supratentorial ICH subjects. Boundaries were outlined with an edge-detection tool and adjusted after inspection of the 3 orthogonal planes. PHE was delineated with the additional principle that it should be (a) more hypodense than the corresponding area in the contralateral hemisphere and (b) most hypodense immediately surrounding the hemorrhage. We examined intra- and interrater reliability using intraclass correlation coefficients and Bland-Altman plots for interrater consistency. CT-based PHE was also compared using magnetic resonance imaging-based PHE detection for 18 subjects.
Median PHE volumes were 22.7 cc at baseline and 20.4 cc at 24 hours post-ICH. There were no statistically significant differences in PHE measurements between raters. Interrater and intrarater reliability for PHE were excellent. At baseline and 24 hours, interrater intraclass correlation coefficients were 0.98 (0.96-1.00) and 0.98 (0.97-1.00); intrarater intraclass correlation coefficients were 0.99 (0.99-1.00) and 0.99 (0.98-1.00). Bland-Altman analysis showed the bias for PHE measurements at baseline and 24 hours, -0.5 cc (SD, 5.4) and -3.2 cc (SD, 5.0), was acceptably small. PHE volumes determined by CT and magnetic resonance imaging were similar (23.9±16.9 cc versus 23.9±16.0 cc, R(2) = 0.98, P<0.0001).
Our method measures PHE with excellent reliability at baseline and 24 hours post-ICH.
Summary Correct diagnosis of acute stroke is of paramount importance to clinicians to enable selection of correct treatments and to ensure prevention of acute complications, including recurrent ...stroke. Timely diagnosis can be difficult in some cases because patients with acute stroke can present with atypical or uncommon symptoms that suggest another cause altogether. Publications on these patients suggest that the following strategies could help to reduce misdiagnosis. First, clinicians should suspect stroke in any patient with abrupt onset of neurological symptoms. Second, clinicians should be aware that some patients will initially present with various uncommon and atypical stroke symptoms. Third, a complete and systematic neurological examination should be routinely done in patients presenting with acute neurological symptoms because this might shed light on the true nature of the problem. Finally, clinicians should be aware that even with the most sophisticated neuroimaging tests, stroke might be missed in the early hours after the event.
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