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Intracerebral haemorrhage (ICH) and small vessel ischaemic stroke (SVS) are the most severe manifestations of cerebral small vessel disease. In a cross-phenotype genome-wide association analysis, Chung et al. identify two novel associations at 2q33 and 13q34 plus a previously identified locus at 1q22 for non-lobar ICH and SVS risk.

Background and Purpose— Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods— Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results— Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215–242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163–185) in 2015 ( P <0.05), compared with 282 (95% CI, 263–301) in 1993/1994 to 211 (95% CI, 198–225) in 2015 ( P <0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions— Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Background and Purpose In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke–Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. Methods CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. Results Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01–1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70–4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51–3.76; P=0.52). Conclusions The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen.

Basilar artery occlusions (BAOs) are a subset of posterior circulation strokes. Particular issues relevant to BAOs include variable and stuttering symptoms at onset resulting in delays in diagnosis, high morbidity and mortality, and uncertain best management. Despite better imaging techniques, diagnosis, and therefore treatment, is often delayed. We will present the most common signs and symptoms of posterior circulation strokes. Data on optimal treatment strategies are gathered from multiple case series, registries, and one randomized trial, which was stopped early. Possible etiologies of BAOs, acute, and subacute treatment strategies and special topics in neuroimaging of the posterior fossa are discussed. This review may be helpful to neurohospitalists who are managing patients with acute stroke as well as emergency room physicians and neurologists.

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Background and Purpose The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose recombinant tissue plasminogen activator (rt-PA) plus the glycoprotein 2b/3a inhibitor, eptifibatide, in acute ischemic stroke (AIS) compared to rt-PA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full dose rt-PA plus eptifibatide. Methods CLEAR-FDR was a single-arm, prospective, open-label, multi-site study. Patients aged 18-85 years treated with 0.9 mg/kg IV rt-PA within three hours of symptom onset were enrolled. After obtaining consent, eptifibatide (135 mcg/kg bolus and 2 hour infusion at 0.75 mcg/kg/min) was administered. The primary endpoint was the proportion of patients who experienced sICH within 36 hours. An independent clinical monitor adjudicated if a sICH had occurred and an independent neuroradiologist reviewed all images. The stopping rule was three sICHs within the first 19 patients or four sICHs within 29 patients. Results From October 2013 to December 2014, 27 AIS patients were enrolled. Median age was 73 years (Range 34-85, IQR 65-80) and median NIHSS was 12 (Range 6-26, IQR 9-16). One sICH (3.7%, 95% CI 0.7%-18%) was observed. Conclusion These results demonstrate comparable safety of full dose rt-PA plus eptifibatide with historical rates of sICH with rt-PA alone and support proceeding with a phase 3 trial evaluating full dose rt-PA combined with eptifibatide to improve outcomes after AIS.

Background and Purpose: Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality. Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this. We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities. Methods: Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke. We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year. Results: Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%–46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana. Results compared with the prior year and time trend analyses were consistent. Reperfusion treatments also appeared to decline by 31% (95% CI, 3%–51%), and specifically thrombolysis by 33% (95% CI, 4%–55%), but this finding had less precision. Conclusions: Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly. Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study. Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.