Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders. RESULTS: We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16; P<0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01-1.29; P=0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; P=0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04-1.61; P=0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03-1.47; P=0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93-1.52; P=0.16). CONCLUSIONS: Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines.

Cerebral Microbleeds and Risk of Intracerebral Hemorrhage Post Intravenous Thrombolysis.

BACKGROUND: Stroke patients who have cerebral micro bleeds (CMBs) could be potentially at a greater risk for symptomatic intracerebral hemorrhage (sICH) than those patients without CMBs. The aim of our study was to investigate whether the presence and burden of CMBs are associated with post IVT sICH. METHODS: In this multicenter study, consecutive patients treated with intravenous tissue plasminogen activator were prospectively identified and analyzed. Patients without magnetic resonance imaging (MRI) within 24 hours of treatment were excluded. CMBs were defined as round or oval, hypointense lesions with associated blooming on T2*-weighted MRI up to 10 mm in diameter. Outcome measures included the occurrence of sICH or death. RESULTS: Of 672 patients with IVT (mean age 62 ± 14 years, 52% men, median admission NIHSS: 7 points), 103 patients had CMBs on T2*-MRI. Ten patients had more than 10, whereas the remaining 93 patients had 1-10 CMBs on T2*-MRI. The rates of sICH did not differ between patients with and patients without 1-10 CMBs (5.8% versus 3.5%; P = .27). However, sICH occurred more frequently (P = .0009) in patients with > 10 CMBs (30%, 95% confidence interval [CI] by the adjusted Wald method: 10%-61%). After adjusting for potential confounders, the presence of >10 CMBs on T2*-MRI was independently (P = .0004) associated with a higher likelihood for sICH (odds ratio [OR]:13.4, 95%CI:3.2-55.9). CONCLUSIONS: Our findings indicate an increased risk of sICH after IVT when more than 10 CMBs are present.

Study of Ebola Virus Disease Survivors in Guinea.

BACKGROUND: There is a paucity of data regarding health consequences of Ebola virus disease among survivors. METHODS: We surveyed 105 Ebola virus disease survivors postdischarge from an Ebola treatment unit in Guinea using a standard data collection form. Patients rated recovery as the percentage of improvement in functional status, where 0% represents "unable to perform" and 100% represents "able to perform at prior level." RESULTS: The mean ± standard deviation time interval between hospital discharge and administration of questionnaire was 103.5 ± 47.9 days in 105 survivors. Anorexia was reported by 103 patients, with varying severity levels: mild (n = 33), moderate (n = 65), or severe (n = 5). Reported pain according to site was chest (30.7%), joint (86.7%), muscle (26.7%), and back (45.7%), among others. Recovery in functional status was graded as mild (10%-30%) (n = 2 [1.9%]), moderate (40%-70%) (n = 52 [50.0%]), and excellent (80%-100%) (n = 50 [48.1%]). Severity of arthralgia (R(2) = 0.09; P = .008) was directly associated with lower recovery in functional status in multivariate analysis. CONCLUSIONS: Ebola virus disease survivors frequently reported anorexia and arthralgia. Severity of arthralgia was related to lower functional recovery. There may be a role for focused screening and intervention for symptoms identified in this study of survivors.

Neuroanatomical Localization of the Vestibular Cortex: A Case Report.

Vertigo, a symptom of illusory movement, is caused by asymmetry of the vestibular system. The vestibular system consists of the vestibular labyrinth, cranial nerve VIII, brainstem vestibular nuclei, cerebellum, ocular motor nuclei, spinal cord, and less well-defined cerebral projections. In this day and age of artificial intelligence, machine learning, advanced imaging, and cutting-edge research in the field of neurology, the exact cortical control of vestibular function is still uncharted. A 45-year-old woman with a past medical history of labyrinthitis about 4.5 years ago (resolved) presented to hospital due to severe dizziness, emesis, and mild vertical diplopia for the past few days. Her symptom of dizziness i.e. room spinning was continuous without any postural component. MRI of the brain revealed a small stroke in the left hippocampal area, more specifically alveus of hippocampus. The patient was started on dual antiplatelet therapy and atorvastatin for secondary stroke prevention. Follow-up visit as an outpatient at one-month post hospital discharge was unremarkable without any recurrence of vertigo symptoms. We believe this may indicate that the limbic lobe has a much larger role in vestibular functioning than previously thought, and may control more vestibular operations than any other central nervous system area.

Comparative Safety and Efficacy of Modified TICI 2b and TICI 3 Reperfusion in Acute Ischemic Strokes Treated With Mechanical Thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) is the current standard of care for acute ischemic stroke (AIS) patients with emergent large-vessel occlusions (ELVO). Successful reperfusion of ELVO is traditionally defined by modified Thrombolysis in Cerebral Infarction (mTICI) grades of 2b or 3. OBJECTIVE: To evaluate the comparative safety and efficacy of mTICI 2b and mTICI 3 reperfusion in AIS patients treated with MT. METHODS: Consecutive ELVO patients who underwent MT at 6 high-volume centers were included in this analysis. Standard safety (3-mo mortality, symptomatic intracranial hemorrhage [sICH]) and efficacy (absolute and relative reduction in NIHSS-scores during hospitalization, functional-improvement [shift analysis in mRS-scores], and functional-independence [mRS-scores of 0-2] at 3-mo) were compared between patients who had mTICI 2b and mTICI 3 reperfusion post MT. RESULTS: A total of 416 ELVO patients achieved successful reperfusion with mTICI 2b (n = 216) and mTICI 3 (n = 200) following MT. The mTICI 3 group had significantly (P < .05) greater absolute (11 vs 9 points) and relative (77% vs 63%) reduction in NIHSS-scores during hospitalization, lower sICH (6% vs 12%), and higher 3-mo functional-independence (55% vs 44%) rates. Successful reperfusion with mTICI 3 was independently (P < .05) associated with greater absolute and relative reduction in NIHSS-scores during hospitalization as well as higher odds of 3-mo functional improvement (common odds ratios: 1.67; 95% confidence interval: 1.10-2.56) and functional independence (odds ratio: 2.08; 95% confidence interval: 1.22-3.53) in multivariable regression models adjusting for confounders. CONCLUSION: Successful reperfusion with mTICI 3 was associated with greater neurological improvement during hospitalization and better 3-mo functional outcomes in comparison to mTICI 2b reperfusion.

The association of adult vaccination with the risk of cerebrovascular ischemia: A systematic review and meta-analysis.

There is mounting evidence supporting infection as an independent risk factor for ischemic stroke (IS), while preliminary data indicate that vaccination may prevent IS. We performed a systematic review and meta-analysis of available randomized clinical trials (RCTs) or prospective observational cohorts reporting associations of influenza vaccination (IV) and/or pneumococcal vaccination (PV) with IS. We identified a total of 12 studies (543,311 patients; 47.4% vaccinated). Vaccination was not related to the risk of IS (RR=1.06, 95%CI: 0.74-1.51, p=0.77), with no significant differences (p=0.26) among RCTs (RR=0.66, 95%CI: 0.30-1.47) and observational studies (RR=1.11, 95%CI: 0.76-1.61). Evidence of considerable heterogeneity was identified within observational studies (I2=98%), but not within RCTs (I2=0%). In subgroup analyses according to vaccination type, IV was associated with a significantly lower risk of IS (RR=0.87, 95%CI: 0.79-0.96, p=0.004) with moderate evidence of heterogeneity (I2=53%). No association was seen for PV (RR=1.38, 95%CI: 0.60-3.16, p=0.45), where considerable heterogeneity was identified (I2=97%). In the additional adjusted analyses of observational studies, vaccination tended to be associated with lower risk of IS (HRadjusted=0.87; 95%CI: 0.75-1.01; p=0.07). The findings of this meta-analysis indicate that IV may be associated with a lower risk of IS. This association was not reproduced for PV or the combination of two vaccines. Substantial heterogeneity was detected across observational studies for all outcome events, while moderate to low heterogeneity was identified across included RCTs. These preliminary findings require independent validation in large RCTs.

Blood pressure levels post mechanical thrombectomy and outcomes in large vessel occlusion strokes.

OBJECTIVE: There are limited data evaluating the effect of post mechanical thrombectomy (MT) blood pressure (BP) levels on early outcomes of patients with large vessel occlusions (LVO). We sought to investigate the association of BP course following MT with early outcomes in LVO. METHODS: Consecutive patients with LVO treated with MT during a 3-year period were evaluated. Hourly systolic BP (SBP) and diastolic BP (DBP) values were recorded for 24 hours following MT and maximum SBP and DBP levels were identified. LVO patients with complete reperfusion following MT were stratified in 3 groups based on post-MT achieved BP goals: <140/90 mm Hg (intensive), <160/90 mm Hg (moderate), and <220/110 mm Hg or <180/105 mm Hg when pretreated with IV thrombolysis (permissive hypertension). Three-month functional independence was defined as modified Rankin Scale score of 0-2. RESULTS: A total of 217 acute ischemic stroke patients with LVO were prospectively evaluated. A 10 mm Hg increment in maximum SBP documented during the first 24 hours post MT was independently (p = 0.001) associated with a lower likelihood of 3-month functional independence (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.56-0.87) and a higher odds of 3-month mortality (OR 1.49; 95% CI 1.18-1.88) after adjusting for potential confounders. In addition, achieving a BP goal of <160/90 mm Hg during the first 24 hours following MT was independently associated with a lower likelihood of 3-month mortality (OR 0.08; 95% CI 0.01-0.54; p = 0.010) in comparison to permissive hypertension. CONCLUSIONS: High maximum SBP levels following MT are independently associated with increased likelihood of 3-month mortality and functional dependence in LVO patients. Moderate BP control is also related to lower odds of 3-month mortality in comparison to permissive hypertension.

Patterns and Rates of Supplementary Venous Drainage to the Internal Jugular Veins.

BACKGROUND AND PURPOSE: Several studies have found supplemental venous drainage channels in addition to bilateral internal jugular veins for cerebral venous efflux. We performed this study to characterize the supplemental venous outflow patterns in a consecutive series of patients undergoing detailed cerebral angiography with venous phase imaging. METHODS: The venographic phase of the arteriogram was reviewed to identify and classify supplemental cerebral venous drainage into anterior (cavernous venous sinus draining into pterygoid plexus and retromandibular vein) and posterior drainage pattern. The posterior drainage pattern was further divided into plexiform pattern (with sigmoid venous sinus draining into the paravertebral venous plexus), and solitary vein pattern (dominant single draining deep cervical vein) drainage. The posterior plexiform pattern was further divided into 2 groups: posterior plexiform with or without prominent solitary vein. RESULTS: Supplemental venous drainage was seen ipsilateral to internal jugular vein in 76 (43.7%) of 174 venous drainages (87 patients) analyzed. The patterns were anterior (n = 23, 13.2%), posterior plexiform without prominent solitary vein (n = 40, 23%), posterior plexiform with prominent solitary vein (n = 62, 35.6%), and posterior solitary vein alone (n = 3, 1.7%); occipital emissary veins and/or transosseous veins were seen in 1 supplemental venous drainage. Concurrent ipsilateral anterior and posterior supplemental drainage was seen in 6 of 174 venous drainages analyzed. CONCLUSIONS: We provide an assessment of patterns and rates of supplementary venous drainage to internal jugular veins to improve our understanding of anatomical and physiological aspects of cerebral venous drainage.