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Background: Minorities constitute groups with higher risk of stroke and stroke severity. Disparities in stroke care may result from greater prevalence of risk factors, barriers to medical care, and lower utilization of preventive therapies. Insurance status may be one limiting factor in access to care and preventive measures. Purpose: We hypothesize that vascular risk factors differ between racial groups and that insurance status may affect stroke treatment, secondary prevention measures, stroke severity, and outcomes. Methods: We included 1061 consecutive patients with ischemic stroke (2005-2008) in our local Get-With-The-Guidelines (GWTG) database. Multivariate logistic regression analysis was used to evaluate the relation of race and insurance status to risk factors, intravenous thrombolytic therapy (IV-tPA) use, stroke severity (National Institute of Health Stroke Scale [NIHSS]), hospital complications, and ambulatory status at discharge. Results: Whites were older than Non-Whites (mean age 65 vs 62 years, p

A 55-year-old woman presented with recurrent episodes of headache, vision changes, and language disturbances. Brain MRI showed multifocal white matter lesions, microhemorrhages, and enlarged perivascular spaces. After an extensive and unrevealing workup, she underwent a biopsy of brain and meninges that revealed thick and hyalinized leptomeningeal and cortical vessel walls that were strongly positive for β-amyloid by immunohistochemical staining, suggestive of cerebral amyloid angiopathy (CAA). CAA can present as a spectrum of inflammatory responses to the deposition of amyloid-β in the vessel walls. Her clinical presentation, radiologic, and histopathologic findings supported a diagnosis of probable CAA-related inflammation (CAA-ri). Although an uncommon entity, it is important to recognize it because most patients respond to immunosuppressive therapy.

Intracerebral hemorrhage is a stroke subtype with high mortality and poor functional outcome in survivors. Its main causes are hypertension, cerebral amyloid angiopathy, and anticoagulant treatment. Hematomas have a high frequency of expansion in the first hours after symptom onset, a process associated with neurologic deterioration and poor outcome. Control of severe hypertension, reversal of anticoagulant effect, and management of increased intracranial pressure are the mainstays of management of intracerebral hemorrhage in the acute phase. Surgical evacuation of the hematoma by conventional craniotomy does not improve outcomes, but minimally invasive techniques may be a valuable approach that deserves further evaluation.

Background and Purpose: Fewer women than men tend to be enrolled in clinical trials of intracerebral hemorrhage. It is unclear whether this reflects lower prevalence of intracerebral hemorrhage in women, selection bias, or poor recruitment efforts. We undertook this study to examine differences between men and women in the reasons for exclusion from the iDEF trial (Intracerebral Hemorrhage Deferoxamine). Methods: The screen failure log included 29 different reasons for exclusion. Chi-square statistics were used to evaluate the differences in reasons for exclusion between men and women. Results: A total of 38.2% of participants in iDEF were women. Three thousand nine hundred eighty-two women (45.7%) and 4736 men (54.3%) were screen failures ( P P =0.1). Patients or families declined participation in 1.26% of women versus 1.31% of men ( P =0.9). More women than men failed screening because of age>80 (22.40% versus 12.61%; adjusted P =0.0007) and preexisting do-not-resuscitate/do-not-intubate (3.69% versus 2.83%; adjusted P =0.067). Conclusions: Lower rates of women enrollment in the iDEF trial may be attributed to older age. Inability to obtain consent or declining participation was similar between women and men, arguing against selection bias. Our findings should be confirmed in other intracerebral hemorrhage trials to determine best strategies to improve women’s representation in future trials.

The sudden transition to virtual therapeutic services during the COVID-19 pandemic provided a unique opportunity to explore telehealth as a platform for delivering early intervention (EI) services. Through retrospective chart review of 93 children, we collected the following data: demographics, diagnosed conditions, therapy type, service format, and provider-reported participant goal achievement (1=no progress, 2=little progress, 3=moderate progress, 4=great deal of progress, 5=outcome achieved) over a six-month period before and after transitioning to telehealth. Pre- and post-transition progress scores were compared using the Wilcoxon signed-rank test. Results demonstrated maintained progress among children who transitioned from in-person to virtual services for similar therapy types. Children receiving speech therapy in-person and virtually demonstrated increased achievement (3.00 vs 3.33; p=0.032). Participants receiving a particular therapy post-transition but not in-person attained similar achievement as those who received the same therapy only in-person. Our research suggests that teletherapy may be a viable option for delivering EI services.

A 62-year-old man presented with a syncopal episode followed by left hemiparesis. Symptoms started right after landing from a 2-hour flight. The week prior to presentation he had general malaise, nausea, vomiting, and poor appetite. He was diagnosed with pneumonia and completed a course of cefdinir. His medical history was relevant for paroxysmal atrial fibrillation (AF), for which he underwent catheter ablation 1 month prior to presentation, when he was on apixaban, started 2 weeks prior to the procedure, and continued until the presentation to our hospital.

Infants with high-grade (III-IV) intraventricular hemorrhage have been reported to have worse neurodevelopmental outcomes than those without, but outcomes of infants with low-grade (I-II) intraventricular hemorrhage are mixed. We sought to compare neurodevelopmental outcomes of infants with low-grade intraventricular hemorrhage to those with no intraventricular hemorrhage. This is a retrospective cohort study of very preterm (≤32 weeks’ gestation) infants evaluated between 24 and 42 months chronologic age using the Bayley Scales of Infant Development, 3rd edition, to determine neurodevelopmental outcomes. Linear regression was used to control for potential confounders. There was no difference in outcome scores between groups when controlling for confounding variables. Infants with low-grade intraventricular hemorrhage, however, had higher rates of enrollment in early intervention services (64% vs 49%, P = .023). Low-grade intraventricular hemorrhage itself may not significantly increase the risk of neurodevelopmental impairment through the first 3 years of life considering other conditions of prematurity.

Background and Purpose— Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods— Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4–6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results— Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8–54.7) and 82.9% (95% CI, 75.3–88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8–72.1) and specificity of 75.2% (95% CI, 66.8–82.4). Overall accuracy was significantly improved with the revised definition ( P =0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31–4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6–65.5]; specificity, 78.3% [95% CI, 40.2–85.1]; aOR, 2.40 [95% CI, 1.23–4.69]). Conclusions— In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Background and Purpose— Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods— We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results— The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76–0.87) compared with 0.78 at baseline (95% CI, 0.72–0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79–0.89) compared with 0.76 at baseline (95% CI, 0.70–0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76–0.88) compared with 0.74 at baseline (95% CI, 0.67–0.81) for modified ICH Score. Conclusions— Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

Hyperglycemia is reported to predict worse outcome in patients with stroke, including intracerebral hemorrhage (ICH). In 83 consecutive cases of ICH at a tertiary stroke center, hyperglycemia (serum glucose >7 mmol/L) compared to normoglycemia at presentation was associated with higher rates of in-hospital mortality (51.2% vs. 26.2%, OR 2.3, CI 1.2–7.6, p = 0.02). The association with in-hospital mortality withstood adjustment for age, ICH volume, intraventricular hemorrhage, and infratentorial ICH location, but not baseline Glasgow Coma Scale. Acute hyperglycemia is associated with in-hospital mortality in spontaneous ICH patients, though this may be an indirect, rather than a causal relationship.

Objectives To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age. Study design The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models. Results One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age. Conclusions Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

Conventional understanding of acute onset language deficits indicates that fluent aphasias are due to perisylvian lesions in the dominant hemisphere, most often in the setting of acute stroke. Case studies and retrospective analyses, however, suggest the need to keep ictal phenomena as an alternative diagnostic possibility. The following case illustrates an epileptic mechanism of sudden onset fluent aphasia mimicking an acute stroke presentation. We utilize the case to illustrate means by which to differentiate stroke versus ictal etiology by way of electroencephalography/response to antiseizure drugs as well as perfusion/diffusion imaging. We review the literature case reports to demonstrate that isolated fluent aphasia typically localizes to left-hemispheric, temporal foci. Finally, we provide a brief synthesis of potential neurologic mechanisms by which left temporal lesions may cause fluent aphasia.

The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01–1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57–0.71). Youden’s method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09–3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61–5.42) were similar to HEP scores ≥ 4. The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Rationale and hypothesisSurgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials.Methods and designMISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study.Study outcomesThe primary outcome measure is dichotomized modified Rankin Scale 0–3 vs. 4–6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Intracerebral hemorrhage is a stroke subtype with high mortality and poor functional outcome in survivors. Its main causes are hypertension, cerebral amyloid angiopathy, and anticoagulant treatment. Hematomas have a high frequency of expansion in the first hours after symptom onset, a process associated with neurologic deterioration and poor outcome. Control of severe hypertension, reversal of anticoagulant effect, and management of increased intracranial pressure are the mainstays of management of intracerebral hemorrhage in the acute phase. Surgical evacuation of the hematoma by conventional craniotomy does not improve outcomes, but minimally invasive techniques may be a valuable approach that deserves further evaluation.

To report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities.We conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS.PRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS.PRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.

Background: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. Summary: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22–26 months corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs. placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22–26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95(th) percentile for age, and 40% had a diastolic blood pressure (DBP) >95(th) percentile for age. SBP >90(th) percentile occurred less often among recipients of erythropoietin (p95(th) percentile or DBP >90(th) or >95(th) percentiles. CONCLUSIONS: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22–26 months cGA. Recombinant erythropoietin (rhEpo) may protect ELGANs against long-term elevated SBP, but does not appear to protect from AKI, low eGFR, albuminuria or elevated DBP at 22–26 months cGA.

Background: An exclusive human milk (EHM) diet in extremely low birth weight (ELBW) infants (birth weight ≤1,000 g) is linked to an increased likelihood of extrauterine growth restriction (EUGR, we...

Background and Purpose— The role of dietary fat on cardiovascular health and mortality remains under debate. Because the APOE is central to the transport and metabolism of lipids, we examined associations between plasma fatty acids and the risk of stroke, coronary heart disease, and mortality by APOE-ε4 genotype. Methods— We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic fatty acids were measured at baseline by gas chromatography. All-cause stroke, ischemic stroke, coronary heart disease, and all-cause mortality events were identified prospectively using standardized protocols. Each cohort used Cox models to separately relate fatty acid levels to the risk of developing each event during ≤10 years of follow-up adjusting for potential confounders and stratifying by APOE genotype (ε4 carriers versus noncarriers). We then meta-analyzed summary statistics using random-effects models. Results— On average, participants had a mean age of 74 years, 61% were women, and 21% (n=483) were APOE-ε4 carriers. Meta-analysis results showed that, only among APOE-ε4 carriers, every SD unit increase in linoleic acid was associated with a reduced risk of all-cause stroke (hazard ratio [HR], 0.54 [95% CI, 0.38–0.78]), ischemic stroke (HR, 0.48 [95% CI, 0.33–0.71]), and all-cause mortality (HR, 0.70 [95% CI, 0.57–0.85]). In contrast, every SD unit increase in palmitic acid was related to an increased risk of all-cause stroke (HR, 1.58 [95% CI, 1.16–2.17]), ischemic stroke (HR, 1.76 [95% CI, 1.26–2.45]), and coronary heart disease (HR, 1.48 [95% CI, 1.09–2.01]), also in APOE-ε4 carriers only. Results for docosahexaenoic acid and arachidonic acid were heterogeneous between cohorts. Conclusions— These exploratory results suggest that APOE-ε4 carriers may be more susceptible to the beneficial or adverse impact of fatty acids on cardiovascular disease and mortality. In this subgroup, higher linoleic acid was protective for stroke and mortality, whereas palmitic acid was a risk factor for stroke and coronary heart disease. The mechanisms underlying these novel findings warrant further investigation.

OBJECTIVE To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment. METHODS SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs

Purpose We examined the incidence of seizures following ischemic stroke in a community-based sample. Methods All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. Results An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24h from stroke onset and half of all seizures occurred within the first 30days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Conclusions Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures.

Transcatheter closure of patent foramen ovale (PFO) has been demonstrated in clinical trials and meta-analyses to reduce the risk of subsequent stroke in patients who present with cryptogenic strokes [(1)][1]. In the REDUCE trial, PFO closure with the septal occluders (W.L. Gore, Newark, Delaware)

ObjectiveTo determine whether the receipt of therapeutic services of very-low-birth-weight (VLBW; ≤1500 g) neonates inadvertently delivered at community Level 2 and 3 neonatal intensive care units (NICUs) compared with those born at a well-baby nursery (WBN; Level 1) differed.MethodsThis is a retrospective study of neonates who were born at Level 1 (WBN), 2, 3, and 4 NICUs and discharged from a Level 4 hospital (n = 529). All infants were evaluated at the Regional Neonatal Follow-up Program at 12 ± 1 months corrected gestational age (CA) and assessed for use of therapeutic services including: early intervention (EI), occupational therapy (OT), physical therapy (PT), speech therapy (ST), and special education (SE).ResultsCompared to infants born at community Level 2 and 3 NICU hospitals, those outborn at a community Level 1 WBN had significantly higher utilization of EI (90% vs. 62%) and PT (83% vs. 61%) at 12 months CA. This association persisted when controlling for covariates. Infants who required EI had significantly lower Bayley-III cognitive scores at 3 years of age.ConclusionVLBW infants outborn at WBN (Level 1) hospitals required more outpatient therapeutic services than those born at hospitals with NICU facilities. These results suggest that delivering at the appropriate community hospital level of care might be advantageous for long-term outcomes.

Background and Purpose— Stroke at midlife has a disproportionately large impact on disability-adjusted life-years lost. Ischemic stroke incidence may be increasing at this age. We investigated long-term trends in ischemic stroke incidence and changes in stroke risk factors in a community sample stratified by stroke onset at middle and older age. Methods— In the Framingham Study, surveillance for incident stroke is ongoing since 1948. We examined age-adjusted and sex-adjusted 10-year incidence of ischemic stroke using Cox models in persons aged 35 to 54 and ≥55 years at start of follow-up. Tests for linear trend were performed over 4 epochs, controlling for the distance in time between intervals. Further, we calculated the mean 10-year risk of stroke at each epoch and for both age groups, based on vascular risk factors from the Framingham Stroke Risk Profile. Results— There were 153, 197, 176, and 165 incident ischemic strokes within each epoch beginning in 1962 (n=3966), 1971 (n=5779), 1987 (n=5133), and 1998 (n=6964). Most ischemic strokes at midlife (n=71) were because of atherosclerotic brain infarction (n=50) or cardioembolism (n=19). Using the risk in the 1962 epoch as the reference, the risk of ischemic stroke at midlife did not significantly decline (hazard ratio, 0.87; 95% CI, 0.74–1.02; P trend =0.09). Incidence of ischemic stroke declined in the older group (hazard ratio, 0.82; 95% CI, 0.77–0.88; P trend Conclusions— Long-term rates of ischemic stroke declined in our community sample; the decline was greater in older as compared with younger adults. Early prevention, focused on modification of cardiovascular risk factors, is important to see sustained declines in stroke incidence and mortality at midlife.

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.]

Summary Background Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18–80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770. Findings Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7–22.6] vs eight [14·8%, 6·6–27·1], p=0·542), 7 day mortality (zero [0%, 0–8·4] vs one [1·9%, 0·1–9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1–12·6] vs five [9·3%, 3·1–20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1–12·6] vs zero [0%, 0–6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0–35·6] vs three [7·1%; 1·5–19·5]; p=0·051). Interpretation MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. Funding National Institute of Neurological Disorders and Stroke, Genentech, and Codman.

Objective: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. Results: uHG was higher in spot sign patients ( p p 4.7 mL/h ( p = 0.002) and the CTA spot sign ( p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03–1.10) and clinical outcomes. Conclusions: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients.

Background and Purpose— The computed tomographic angiography spot sign as a predictor of hematoma expansion is limited by its modest sensitivity and positive predictive value. It is possible that hematoma expansion in spot-positive patients is missed because of decompression of intracerebral hemorrhage (ICH) into the ventricular space. We hypothesized that revising hematoma expansion definitions to include intraventricular hemorrhage (IVH) expansion will improve the predictive performance of the spot sign. Our objectives were to determine the proportion of ICH nonexpanders who actually have IVH expansion, determine the proportion of false-positive spot signs that have IVH expansion, and compare the known predictive performance of the spot sign to a revised definition incorporating IVH expansion. Methods— We analyzed patients from the multicenter PREDICT ICH spot sign study. We defined hematoma expansion as ≥6 mL or ≥33% ICH expansion or >2 mL IVH expansion and compared spot sign performance using this revised definition with the conventional 6 mL/33% definition using receiver operating curve analysis. Results— Of 311 patients, 213 did not meet the 6-mL/33% expansion definition (nonexpanders). Only 13 of 213 (6.1%) nonexpanders had ≥2 mL IVH expansion. Of the false-positive spot signs, 4 of 40 (10%) had >2 mL ventricular expansion. The area under the curve for spot sign to predict significant ICH expansion was 0.65 (95% confidence interval, 0.58–0.72), which was no different than when IVH expansion was added to the definition (area under the curve, 0.66; 95% confidence interval, 0.58–0.71). Conclusions— Although IVH expansion does indeed occur in a minority of ICH nonexpanders, its inclusion into a revised hematoma expansion definition does not alter the predictive performance of the spot sign.

Background and Purpose— Cerebral microbleeds (CMB) represent a common magnetic resonance imaging marker of cerebral small vessel disease, increasingly recognized as a subclinical marker of stroke and dementia risk. CMB detection may reflect the cumulative effect of vascular risk burden and be a marker of higher mortality. We investigated the relation of CMB to risk of death in community dwelling participants free of stroke and dementia. Methods— We evaluated 1963 Framingham Original and Offspring Cohort participants (mean age 67 years; 54% women) with available brain magnetic resonance imaging and mortality data. Using Cox proportional hazards models, we related CMB to all-cause, cardiovascular, and stroke-related mortality. Results— Participants with CMB (8.9%) had higher prevalence of cardiovascular risk factors and use of preventive medications. During a mean follow-up of 7.2±2.6 years, we observed 296 deaths. In age- and sex-adjusted analysis, CMB were associated with increased all-cause mortality (hazards ratio, 1.39; 95% confidence interval 1.03–1.88), a relation that was no longer significant after adjustment for cardiovascular risk and preventive medication use (hazards ratio, 1.15; 95% confidence interval, 0.82–1.63). Conclusions— CMBs may represent the deleterious effect of cardiovascular risk factors in the cerebral vasculature. Although their presence was associated with increased all-cause mortality, the effect was no longer present after accounting for vascular risk factors and preventive treatment use. Further studies are required to clarify the role of cardiovascular preventive therapies for prevention of mortality in persons with incidental detection of CMB.

Background and Purpose— To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. Methods— We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. Results— We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. Conclusions— We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF.

OBJECTIVE: To describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and β-amyloid burden on PET. METHODS: From the population-based Mayo Clinic Study of Aging, 1,215 participants (53% male) underwent 3-tesla MRI scans with T2* gradient recalled echo sequences from October 2011 to February 2017. A total of 1,123 participants (92%) underwent (11)C-Pittsburgh compound B (PiB)-PET scans. The prevalence of CMBs was derived by adjusting for nonparticipation and standardizing to the Olmsted County, MN, population. The relationship between β-amyloid burden and CMB presence and location was tested using logistic regression models. Ordinal logistic models tested the relationship between CMB frequency and β-amyloid burden. RESULTS: Two hundred seventy-four participants (22.6%) had at least one CMB. CMB frequency increased with age by decade (11% aged 60–69 years, 22% 70–79 years, and 39% 80 years and older). After adjusting for age, sex, and hypertension, PiB standardized uptake value ratio (SUVR) was associated with increased odds of a CMB. The association between PiB SUVR and CMBs was location-specific; PiB SUVR was associated with lobar CMBs but not deep CMBs. Age, hypertension, and PiB SUVR were associated with increasing CMB count. CMB density was greatest in parietal and occipital regions; β-amyloid burden correlated with concentration of CMBs in all lobar regions. Among participants with multiple CMBs, greater PiB uptake occurred in the pre- and postcentral gyri superiorly, the superior parietal lobe and precuneus, the angular gyrus, inferior temporal gyrus, and temporal poles. CONCLUSIONS: The prevalence of CMBs increases with age. In this population-based sample, β-amyloid load was associated with lobar but not with deep CMBs.

ObjectiveTo describe the relationship between intraventricular hemorrhage (IVH) expansion and long-term outcome and to use this relationship to select and validate clinically relevant thresholds of IVH expansion in 2 separate intracerebral hemorrhage (ICH) populations.MethodsWe used fractional polynomial analysis to test linear and nonlinear models of 24-hour IVH volume change and clinical outcome with data from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT)-ICH study. The primary outcome was poor clinical outcome (modified Rankin Scale [mRS] score 4–6) at 90 days. We derived dichotomous thresholds from the selected model and calculated diagnostic accuracy measures. We validated all thresholds in an independent single-center ICH cohort (Massachusetts General Hospital).ResultsOf the 256 patients from PREDICT, 127 (49.6%) had an mRS score of 4 to 6. Twenty-four–hour IVH volume change and poor outcome fit a nonlinear relationship, in which minimal increases in IVH were associated with a high probability of an mRS score of 4 to 6. IVH expansion ≥1 mL (n = 53, sensitivity 33%, specificity 92%, adjusted odds ratio [aOR] 2.68, 95% confidence interval [CI] 1.11–6.46) and development of any new IVH (n = 74, sensitivity 43%, specificity 85%, aOR 2.53, 95% CI 1.22–5.26) strongly predicted poor outcome at 90 days. The dichotomous thresholds reproduced well in a validation cohort of 169 patients.ConclusionIVH expansion as small as 1 mL or any new IVH is strongly predictive of poor outcome. These findings may assist clinicians with bedside prognostication and could be incorporated into definitions of hematoma expansion to inform future ICH treatment trials.

Objective To investigate whether Post-Acute Care Inpatient Rehabilitation (PACIR) admission after NICU stay affects the total length of stay (LOS) of very preterm (VPT: ≤30 weeks of gestation) infants. Methods A retrospective case control study of VPT infants d/c'd from the NICU at Maria Fareri Children's Hospital (MFCH) to either a PACIR (Blythedale Children's Hospital: BH) for convalescent care (cases) or directly home (controls). Results 35 cases and 70 controls. Total LOS (MFCH + BH) was longer for cases [196 vs. 97 days]. At the time of d/c from MFCH, Special Health Care Needs (SHCN) amongst cases were greater than controls, however, became similar at the time of home d/c. The majority of cases achieved habilitation goals at the PACIR. Conclusions Although LOS was longer for patients transferred to a PACIR, habilitation at BH Hospital reduced the SHCN at the time of home d/c amongst cases.

Background Hematoma expansion is a major predictor of morbidity and mortality after intracerebral hemorrhage (ICH). Both baseline hematoma volume and the CT-angiogram (CTA) spot sign predict hematoma expansion. Because the CTA spot sign may represent foci of active hemorrhage, we hypothesized that patients with smaller baseline hematoma volumes are less likely to be spot sign positive, and therefore less likely to expand. Aim We sought to validate our prior finding that small hematomas are unlikely to expand, and to determine the relationship between baseline hematoma volume, spot sign status, and risk of hematoma expansion. Methods Data were from the prospective PREDICT ICH study. Patients presenting within 6 h of symptom onset with completed baseline CT, CTA, and follow-up CT were included. Baseline hematoma volume was categorized a priori (20 mL). The primary outcome was significant hematoma expansion (≥6 mL, ≥12.5 mL or ≥33%) and secondary outcomes were early neurological worsening, good clinical outcome (modified Rankin Scale 0–3), and mortality at 90 days. Results Among 315 patients meeting the inclusion criteria, baseline hematoma volume category predicted absolute hematoma expansion ( p Conclusion Very small hematomas are unlikely to expand and have a low spot sign prevalence. Hemostatic therapy trials may be best targeted at hemorrhages >3 mL in volume.

To determine the predictive value of (1) maternal, (2) maturational, (3) comorbid and (4) discharge domains associated with preterm infant rehospitalization.Retrospective, cohort study of preterm infants discharged home from a level IV neonatal intensive care unit. Rates of unplanned and planned 6-month readmissions were assessed. The four domains were modeled incrementally and separately to predict relative and combined contributions to the readmission risk.Out of 504 infants, 5% had 30-day readmissions (22 unplanned, three planned). By 6 months, 13% were rehospitalized (52 unplanned, 15 planned). Sixty-seven infants had 96 readmission events with 30% of readmission events elective. The four domains together predicted 78% of total 1-month, all 6-month and unplanned 6-month readmissions. Discharge complexity was as predictive as comorbidity in all models.These four-domain models were more predictive than single domains. Many total readmission events were planned, suggesting parsing planned and unplanned rehospitalizations may benefit quality-improvement efforts.

Background and Purpose— Nine- and 24-point prediction scores have recently been published to predict hematoma expansion (HE) in acute intracerebral hemorrhage. We sought to validate these scores and perform an independent analysis of HE predictors. Methods— We retrospectively studied 301 primary or anticoagulation-associated intracerebral hemorrhage patients presenting Results— The 9- and 24-point HE scores demonstrated acceptable discrimination for HE>6 mL or 33% and >6 mL, respectively (area under the curve of 0.706 and 0.755, respectively). The 24-point score demonstrated appropriate calibration in the PREDICT cohort (χ 2 statistic, 11.5; P =0.175), whereas the 9-point score demonstrated poor calibration (χ 2 statistic, 34.3; P 1.5, Glasgow Coma Scale, and National Institutes of Health Stroke Scale and were included in PREDICT A/B scores. PREDICT A showed improved discrimination compared with both existing scores, whereas performance of PREDICT B varied by definition of expansion. Conclusions— The 9- and 24-point expansion scores demonstrate acceptable discrimination in an independent multicenter cohort; however, calibration was suboptimal for the 9-point score. The PREDICT A score showed improved discrimination for HE prediction but requires independent validation.

Basilar artery stroke causes substantial morbidity and mortality. Although its unusual clinical presentation potentially contributes to a delay in diagnosis, this problem has not been systematically studied. We compared intervals between symptom onset, initial presentation, and diagnosis in stroke due to basilar artery (BA) versus left middle cerebral artery (LMCA) occlusion to determine the presence of and potential reasons for diagnostic delay in BA stroke. We retrospectively identified 21 consecutive adult patients diagnosed with BA stroke between 2009 and 2011 from our hospital’s prospective stroke registry. Patients were age-, sex-, and race-matched with 21 LMCA stroke patients from the same period. All subjects had confirmed clinical and radiographic diagnosis of stroke due to occlusion or stenosis of the BA, LMCA, or left internal carotid artery. Time to diagnosis was determined independently by two investigators through medical record review. The pre-specified primary outcome was latency from emergency department (ED) arrival to stroke diagnosis. Median time from ED arrival to diagnosis was 8 h 24 min (IQR: 2:43–26:32) for BA and 1 h 23 min (IQR: 0:41–1:45; p

Objectives: We used a prospective clinical trial to examine the risks conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent strokes in the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort. Methods: The SPS3 trial enrolled 3,020 patients with lacunar strokes. Participants were stratified into groups of METS only, DM only, both, or neither using American Heart Association/National Heart, Lung, and Blood Institute and World Health Organization guidelines. Annualized event rates of strokes, myocardial infarction (MI), and all-cause mortality were calculated, and hazard ratios (HRs) referencing the “neither” group were computed, controlling for significantly associated baseline characteristics. Results: Among 2,999 participants, 25% had METS only, 6% had DM only, 32% had both conditions, and 37% had neither. Over a median of 3.8 years of follow-up, there were 274 recurrent strokes (240 ischemic, 34 hemorrhagic) and 74 MIs; among the 240 ischemic strokes, 134 (56%) were lacunar. The rates of any recurrent stroke (HR 1.7, 95% confidence interval [CI] 1.3–2.3) or lacunar stroke (HR 2.4, 95% CI 1.5–3.7) were significantly higher for those with concurrent METS and DM compared with those who had neither. Risk of incident MI was higher in participants with DM (HR 2.8, 95% CI 1.1–7.0) or concurrent DM and METS (HR 2.6, 95% CI 1.4–4.9). Conclusion: METS and DM were significant comorbid conditions in lacunar stroke patients and they were associated with stroke recurrence. In patients with lacunar infarcts, a vigilant approach to prevent development of DM in those with METS may be a potential strategy to reduce recurrent strokes.

Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication.To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature.Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software.Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis.Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to60 trial sites.

Objectives: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. Design: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). Validation: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). Setting: Neurocritical and ICUs. Patients: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. Interventions: None. Measurements and Main Results: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4–6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2–6, 3–6, 5–6, 6). We employed Youden’s J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four–hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden’s method showed an optimum cut point at –0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25–7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08–36.66]). All definitions reproduced well in the validation cohort. Conclusions: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

Objective: We investigated the association between circulating biomarkers of inflammation and MRI markers of small vessel disease. Methods: We performed a cross-sectional study relating a panel of 15 biomarkers, representing systemic inflammation (high-sensitivity C-reactive protein, interleukin-6, monocyte chemotactic protein-1, tumor necrosis factor α, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), vascular inflammation (intercellular adhesion molecule 1, CD40 ligand, P-selectin, lipoprotein-associated phospholipase A 2 mass and activity, total homocysteine, and vascular endothelial growth factor), and oxidative stress (myeloperoxidase) to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease (CSVD) on MRI in 1,763 stroke-free Framingham offspring (mean age 60.2 ± 9.1 years, 53.7% women). Results: We observed higher levels of circulating tumor necrosis factor receptor 2 and myeloperoxidase in the presence of cerebral microbleed (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1–4.1 and OR 1.5, 95% CI 1.1–2.0, respectively), higher levels of osteoprotegerin (OR 1.1, 95% CI 1.0–1.2), intercellular adhesion molecule 1 (OR 1.7, 95% CI 1.1–2.5), and lipoprotein-associated phospholipase A 2 mass (OR 1.5, 95% CI 1.1–2.1), and lower myeloperoxidase (OR 0.8, 95% CI 0.7–1.0) in participants with greater white matter hyperintensity volumes and silent cerebral infarcts. Conclusions: Our study supports a possible role for inflammation in the pathogenesis of CSVD, but suggests that differing inflammatory pathways may underlie ischemic and hemorrhagic subtypes. If validated in other samples, these biomarkers may improve stroke risk prognostication and point to novel therapeutic targets to combat CSVD.