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Background and ObjectivesLarge hemispheric infarctions (LHIs) are associated with significant morbidity and mortality, with limited data on therapeutic anticoagulation (AC) management. We provide a descriptive analysis of the type of therapeutic AC used, the timing of introduction, rate of of radiographic vs symptomatic hemorrhagic transformation (HT), and patient outcomes.MethodsThis was a retrospective review of patients with acute ischemic stroke admitted to the Neurosciences intensive care unit at a tertiary care center from January 2012 to December 2018. Inclusion criteria included admission imaging with stroke size ≥ two-thirds of the middle cerebral artery territory, ± other vascular territory, and need for therapeutic AC. HT categories included hemorrhagic infarction types 1 and 2 and parenchymal hematoma types 1 and 2. The primary outcome included HT with and without an associated clinical change. Secondary outcomes included disposition at discharge and modified Rankin Scale (mRS) score at discharge and at follow-up when available.ResultsA total of 2,317 patients were screened, 380 met the inclusion criteria for LHI, and 105 received AC. The mean age was 64 years (SD 16.8), and 50% (n = 53) were female. The mean admission NIH Stroke Scale score was 20 (SD 5.9). The mean poststroke timing to initiation of AC was 17 days (SD 10.1) (median 14 [interquartile range 10–19 days]). Indications for AC included atrial fibrillation (51%), cardiac thrombus (19%), venous thromboembolism (19%), and other (10%). Heparin was most commonly used in the very early (≤7 days) group (n = 11, 79%), whereas vitamin K antagonists without a bridge were the most commonly used among the entire cohort (n = 54, 51%). Radiographic HT was seen in 68 patients (65%) before AC initiation. After initiation of AC, 70 patients had repeat imaging, with 6 cases (6%) of worsening radiographic HT and 4 cases (4%) of symptomatic deterioration, of which 3 required reversal of AC. At discharge, 7 patients (7%) had a good outcome (mRS score 0–2).DiscussionAlthough radiographic HT is common among patients with LHI, it does not always portend symptomatic clinical deterioration. Further research regarding AC timing and safety is necessary.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed post-hospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18–1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11–0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Background Intracerebral hemorrhage has been associated with changes in various weather conditions. The primary aim of this study was to examine the collective influence of temperature, barometric pressure, and dew point temperature on the incidence of primary spontaneous intracerebral hemorrhage (sICH). Methods Between January 2013 and December 2016, patients with sICH due to hypertension or amyloid angiopathy with a known time of onset were identified prospectively. Meteorological variables 6 hours prior to time of onset were obtained from the National Oceanic Atmospheric Administration via two weather stations. Using a Monte-Carlo simulation, random populations of meteorological conditions in a 6-hour time window during the same years were generated. The actual meteorological conditions 6-hours prior to sICH were compared to those from the randomly generated populations. The false discovery rate method was used to identify significant meteorological variables. Results Time of onset was identified in 455 of 603 (75.5%) patients. Distribution curves for change in temperature, mean barometric pressure, and change in barometric pressure 6-hours prior to hemorrhage ictus were found to be significantly different from the random populations. (FDR approach P Conclusions We concluded that barometric pressure primarily influences the incidence of intracerebral hemorrhage. The association described in the literature between temperature and intracerebral hemorrhage is likely confounded by variations in barometric pressure.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. We describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease, and investigate the role of sex on outcome. Methods: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers from Chicago metropolitan area. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. Results: The study included 83 patients. Median age was 64 years and the majority were Blacks (47%) followed by Hispanics (28%) and whites (16%). Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Higher proportions of male experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p=0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared to female, males had higher mortality (38% vs. 13%; p=0.02) and were less likely to be discharged home (12% vs. 33%; p=0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR=1.47, 95% CI=1.03-2.09) Conclusion: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Highlights • COVID-19 disease is associated with stroke • All strokes subtypes are seen in association with COVID-19, with ischemic stroke being most prevalent • The most common etiology for ischemic stroke in SARS-CoV2 infection is cryptogenic • Sex plays an important role in stroke outcomes in patients with COVID-19 disease • Males have higher rates of ICU admission, in-hospital complications and more likely to have worse outcome at hospital discharge compare with females, Background and Purpose Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. Methods This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. Results The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03–2.09). Conclusion In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Background: COVID-19 has been associated with increased risk of venous and arterial thromboembolism including ischemic stroke. We report on patients with acute ischemic stroke and concomitant COVID-19 in a diverse patient population. Methods: This is a retrospective analysis of patients hospitalized with acute ischemic stroke (AIS) and COVID-19 to our comprehensive stroke center in Chicago, IL, between March 1, 2020, and April 30, 2020. We reviewed stroke characteristics, etiologies, and composite outcomes. We then compared our cohort with historic patients with AIS without COVID-19 admitted in the same time frame in 2019 and 2020. Results: Out of 13 patients with AIS and COVID-19, Latinos and African-Americans compromised the majority of our cohort (76.8%), with age ranging from 31-80 years. Most strokes were cortical (84.6%) and more than 50% of patients had no identifiable source, and were categorized as embolic stroke of unknown source (ESUS). A trend toward less alteplase administration was noted in the COVID-19 stroke patients compared to the non-COVID group from 2020 and 2019 (7.1 vs. 20.7% p 0.435 and 7.1 vs. 27.2% p 0.178). Endovascular thrombectomy was performed in 3 (23%) patients. Systemic thrombotic complications occurred in 3 (23%) COVID-19 AIS patients. Median National Institutes of Health Stroke Scale and modified Rankin Scale at discharge were 11 (IQR 4-23) and 4 (IQR 3-4), respectively. In the logistic regression model corrected for age and sex, COVID-19 was associated with discharge to mRS > 2 (p 0.046, OR 3.82, CI 1.02-14.3). Eight patients (63.8%) were discharged home or to acute rehabilitation, and two deceased from COVID-19 complications. Conclusion: AIS in the setting of COVID-19 is associated with worse outcomes, especially among African-American and Latino populations. Large vessel disease with ESUS was common suggesting an increased risk of coagulopathy and endothelial dysfunction as a potential etiology.

Objective To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. Methods We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the “Neuro first” group had neurological manifestations upon initial assessment, and the “COVID first” group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. Results A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The “COVID-19 first” group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). Conclusion Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

BACKGROUND/OBJECTIVE: Diffusion weighted imaging (DWI) lesions have been well described in patients with acute spontaneous intracerebral hemorrhage (sICH). However, there are limited data on the influence of these lesions on sICH functional outcomes. We conducted a prospective observational cohort study with blinded imaging and outcomes assessment to determine the influence of DWI lesions on long-term outcomes in patients with acute sICH. We hypothesized that DWI lesions are associated with worse modified Rankin Scale (mRS) at 3 months after hospital discharge. METHODS: Consecutive sICH patients meeting study criteria were consented for an magnetic resonance imaging (MRI) scan of the brain and evaluated for remote DWI lesions by neuroradiologists blinded to the patients’ hospital course. Blinded mRS outcomes were obtained at 3 months. Logistic regression was used to determine significant factors (p < 0.05) associated with worse functional outcomes defined as an mRS of 4–6. The generalized estimating equation (GEE) approach was used to investigate the effect of DWI lesions on dichotomized mRS (0–3 vs 4–6) longitudinally. RESULTS: DWI lesions were found in 60 of 121 patients (49.6%). The presence of a DWI lesion was associated with increased odds for an mRS of 4–6 at 3 months (OR 5.987, 95% CI 1.409–25.435, p = 0.015) in logistic regression. Using the GEE model, patients with a DWI lesion were less likely to recover over time between 14 days/discharge and 3 months (p = 0.005). CONCLUSIONS: DWI lesions are common in primary sICH, occurring in almost half of our cohort. Our data suggest that DWI lesions are associated with worse mRS at 3 months in good grade sICH and are predictive of impaired recovery after hospital discharge. Further research into the pathophysiologic mechanisms underlying DWI lesions may lead to novel treatment options that may improve outcomes associated with this devastating disease.

PURPOSE OF REVIEW: The optimal management of external ventricular drains (EVD) in the setting of acute brain injury remains controversial. Therefore, we sought to determine whether there are optimal management approaches based on the current evidence. RECENT FINDINGS: We identified 2 recent retrospective studies on the management of EVDs after subarachnoid hemorrhage (SAH) which showed conflicting results. A multicenter survey revealed discordance between existing evidence from randomized trials and actual practice. A prospective study in a post-traumatic brain injury (TBI) population demonstrated the benefit of EVDs but did not determine the optimal management of the EVD itself. The recent CLEAR trials have suggested that specific positioning of the EVD in the setting of intracerebral hemorrhage with intraventricular hemorrhage may be a promising approach to improve blood clearance. SUMMARY: Evidence on the optimal management of EVDs remains limited. Additional multicenter prospective studies are critically needed to guide approaches to the management of the EVD.

Nontraumatic convexity subarachnoid hemorrhage (cSAH) is a nonaneurysmal variant that is associated with diverse etiologies.With IRB approval, we retrospectively reviewed consecutive nontraumatic cSAH from July 1, 2006 to July 1, 2016. Data were abstracted on demographics, medical history, neuroimaging, etiology, and clinical presentation.We identified 94 cases of cSAH. The cases were classified according to the following etiologies: reversible cerebral vasoconstriction syndrome (RCVS) 17 (18%), cerebral amyloid angiopathy (CAA) 15 (16%), posterior reversible encephalopathy syndrome 16 (17%), cerebral venous thrombosis 10 (11%), large artery occlusion 7 (7%), endocarditis 6 (6%), and cryptogenic 25 (27%). Early rebleeding occurred in 9 (10%) patients. Time from initial imaging to CT rebleeding was 40 hours (range, 5-74). CAA was associated with the highest mean age at 75.8 and RCVS the lowest at 47.6 years (P.0001). Among patients with RCVS, initial vascular imaging was negative in 6 (35%), and repeat imaging documented vasoconstriction at a mean delay of 5 days (range, 3-16).There were significant differences among the subgroups in cSAH, with CAA presenting as older men with transient neurological deficits, and RCVS presenting as younger women with thunderclap headache. Rebleeding was seen in 10% of cSAH patients. One-third of RCVS patients with cSAH required repeat vascular imaging to diagnose vasoconstriction.

Large hemispheric infarctions (LHI) are associated with significant morbidity and mortality. Leukocytosis has been observed to directly correlate with stroke severity but has not been specifically described in the LHI population. We hypothesized that patients with LHI and leukocytosis on admission have worse clinical outcomes.Retrospective study of patients admitted to the neurosciences intensive care unit at a tertiary care center with the diagnosis of acute ischemic stroke from Jan 2012 to Dec 2018. Inclusion criteria included admission imaging with stroke size greater than two-thirds of the middle cerebral artery territory, with or without other vascular territory involvement. Patients were excluded if antibiotics were started on admission for presumed infection. White blood cell count was recorded at admission, along with Modified Rankin Scale on admission and discharge, need for mechanical ventilation, tracheostomy, and discharge disposition. Logistic regression was used for association measures.Of the 2,318 patients that were screened, 360 met inclusion criteria. Mean age was 64, median was 63; 51.7% were female. Mean and median NIHSS were 21. Leukocytosis on admission was seen in 139 patients (38.6%), and it was associated with need for mechanical ventilation (p0.0001, OR 2.54, [1.64-3.95]) and mortality during hospitalization (p0.0003, OR 2.66, [1.56-4.55]). Results persisted after correction for age and sex in a logistic regression model.Leukocytosis on admission in patients with LHI significantly correlated with mortality and need for mechanical ventilation. There was a trend towards association with poor outcome at discharge, although not statistically significant. Further research may identify how leukocytosis and other SIRS markers may be used to prognosticate outcomes in this challenging patient population.

Objectives Higher glycemia on admission has been associated with diffusion weighted imaging (DWI) lesions in patients with spontaneous intracerebral hemorrhage (sICH). However, the influence of longitudinal glycemia after admission and during a patient's hospitalization on DWI lesions in sICH has not been studied. Our aim was to compare longitudinal glycemia in sICH patients with and without DWI lesions. Material and Methods Glycemia measurements were abstracted on participants enrolled in a prospective observational study examining predictors for DWI lesions in sICH. Univariate analysis was used to compare mean longitudinal glycemia in sICH patients with and without DWI lesions. Logistical regression was used to determine whether mean longitudinal glycemia was predictive of DWI lesions. Results DWI lesions were found in 60 of the 121 (49.6%) participants. Mean time-to-MRI was 99.6 h (SD ± 89). During this time interval, 2,101 glucose measurements were analyzed with a median number of 7 (IQR 12, 1-261) measurements per patient. Mean longitudinal glycemia was higher in the DWI positive group compared to the DWI negative group until time-to-MRI (132 mg/dL vs 122 mg/dL, p = 0.03). Mean longitudinal glycemia was found to be predictive of DWI lesions (OR 1.02, 95% CI 1.005 to 1.035, p = 0.011). Conclusions Mean longitudinal glycemia was higher in sICH patients with DWI lesions compared to those without DWI lesions. Future research into the association between higher glycemia and DWI lesions in sICH may provide insight into a pathophysiologic mechanism.

Introduction Apnea testing remains essential for the clinical evaluation of brain death determination. In patients who test positive for SARS-CoV-2, disconnecting the patient from the ventilator and introducing high flow oxygen into the endotracheal tube increases the risk for aerosolization of airway secretions and exposure of the examiner. Methods Case report of a patient with an intracerebral hemorrhage that evolved to significant cerebral edema and herniation, who underwent apnea test using a method involving a t-piece and an HME filter. Results Patient successfully pronounced brain dead using a safe method to minimize exposure to SARS-CoV-2. Conclusion At a time where healthcare workers are at high risk of exposure to COVID-19, the above described method is a safe process for apnea testing in declaration of brain death.

There is a paucity of outcomes data in patients over 80 years presenting with intracerebral hemorrhage (ICH). The primary aim of our study is to describe outcomes in this patient population.Retrospective study of patients admitted with primary ICH from January 2012 to July 2018. Data were obtained from the Rush University Get With The Guidelines database; only patients 80 or above were included.A total of 1713 patients were screened and 220 patients met inclusion criteria. About 68.2% were female and mean age was 85.6 years old. Median ICH score on admission was 2 (IQR 1-3). Location of ICH included: deep (48.2%), lobar (40%), and cerebellum (9.5%). ICH etiologies included hypertensive (51.8%), cerebral amyloid angiopathy (26.8%), coagulopathy (5.9%), and the remaining were undetermined. CT angiograms were performed in 34.5% (n = 76) of patients; of these patients one arteriovenous malformation was identified. Patients underwent the following procedures: external ventricular drains (8.6%), decompression (3.6%), and ventriculoperitoneal shunts (1.8%). Tracheostomy and percutaneous gastrostomy placement were performed in 8.2%. About 4.5% had seizures and 1.5% were treated for status epilepticus. Disposition at hospital discharge included: subacute nursing facility ([SNF] 24.1%), acute rehabilitation (23.2%), hospice (18.2%), death (18.2%), home (11.8%), long-term acute care facility ([LTAC] 3.6%), and unknown (1%). Patients with an ICH score ≥2 on admission had a roughly 6 times higher chance of experiencing an unfavorable outcome (LTAC, SNF, or death), when compared to patients with lower ICH score.This study shows that a significant proportion (35%) of ICH patients ≥80 years old have a good outcome, with discharge to home or to rehabilitation. Our data suggest that older patients with ICH presenting with supratentorial hemorrhages (volume30 cc) without intraventricular extension can have good outcomes despite their age.

MRI with inclusion of T2-weighted fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted imaging sequences may be helpful in identifying delayed posthypoxic leukoencephalopathy and critical illness microbleeds in patients at risk.

To investigate magnetic resonance imaging (MRI) detection of cerebral infarction (CI) in patients presenting with subarachnoid hemorrhage (SAH). CI is a well-known complication of SAH that is typically detected on computed tomography (CT). MRI has improved sensitivity for acute CI over CT, particularly with multiple, small, or asymptomatic lesions. With IRB approval, 400 consecutive SAH patients admitted to our institution from August 2006 to March 2011 were retrospectively reviewed. Traumatic SAH and secondary SAH were excluded. Data were collected on demographics, cause of SAH, Hunt Hess and World Federation of Neurosurgical Societies grades, and neuroimaging results. MRIs were categorized by CI pattern as single cortical (SC), single deep (SD), multiple cortical (MC), multiple deep (MD), and multiple cortical and deep (MCD). Among 123 (30.8 %) SAH patients who underwent MRIs during their hospitalization, 64 (52 %) demonstrated acute CI. The mean time from hospital admission to MRI was 5.7 days (range 0–29 days). Among the 64 patients with MRI infarcts, MRI CI pattern was as follows: MC in 20 (31 %), MCD in 18 (28 %), SC in 16 (25 %), SD in 3 (5 %), MD in 2 (3 %), and 5 (8 %) did not have images available for review. Most infarcts detected on MRI (39/64 or 61 %) were not visible on CT. The use of MRI increases the detection of CI in SAH. Unlike CT studies, MRI-detected CI in SAH tends to involve multiple vascular territories. Studies that rely on CT may underestimate the burden of CI after SAH.

Objective:To investigate the temporal pattern and relevant associations of CSF inflammatory measures after intraventricular hemorrhage (IVH).Methods:We analyzed prospectively collected CSF cell counts and protein and glucose levels from participants in the Clot Lysis Evaluation of Accelerated Resolution of IVH phase III (CLEAR III) trial. Corrected leukocyte count and cell index were calculated to adjust for CSF leukocytes attributable to circulating blood. Data were chronologically plotted. CSF inflammatory measures (daily, mean, median, maximum, and cases with highest quartile response) were correlated with initial IVH volume, IVH clearance rate, thrombolytic treatment, bacterial infection, and adjudicated clinical outcome at 30 and 180 days.Results:A total of 11,376 data points of CSF results from 464 trial participants were analyzed. Measures of CSF inflammatory response evolved during the resolution of IVH. This was significantly more pronounced with initial IVH volume exceeding 20 mL. Intraventricular alteplase was associated with a significantly augmented inflammatory response compared to saline, even after correcting for initial IVH volume. There was an association but nonpredictive correlation of CSF inflammation measures with culture-positive CSF bacterial infection. None of the CSF inflammatory measures, including cases with upper quartile inflammatory response, was associated with a significant detrimental effect on 30 or 180 days functional outcome or mortality after multivariate adjustment for measures of disease severity.Conclusions:Aseptic CSF inflammation after IVH is primarily dependent on the volume of initial bleed. Thrombolysis intensifies the inflammatory response, with no apparent detrimental effect on clinical outcome.Clinicaltrials.gov identifier:NCT00784134.

Introduction: Re-bleeding can have significant adverse consequences, but has not been well described in isolated nontraumatic convexity subarachnoid hemorrhage (cSAH), and therefore we sought to report the clinical spectrum of re-bleed in this population. Methods: With IRB approval, we retrospectively reviewed consecutive nontraumatic cSAH admitted to our institution from August 1, 2006 to June 1, 2016. cSAH was defined as radiographic hemorrhage isolated to the convexities, without cisternal component. Trauma was excluded. Data was abstracted on demographics, medical history, neuroimaging, etiology, and clinical presentation. Good clinical outcome was defined as modified rankin score of 0-2 at 3 months. Results: Among 93 cSAH patients, re-bleed occurred in 9 (10%) patients. The mean age of patients with re-bleed was 55.6 years (range, 24-68) and 8 (89%) were women. The majority 6 (67%) were Hispanic. Most patients 8 (89%) presented with severe headache. The etiology of cSAH was reversible cerebral vasoconstriction syndrome (RCVS) in 6 (67%), amyloid angiopathy in 1 (11%), cerebral venous thrombosis (CVT) in 1 (11%), and post-procedural related in 1 (11%). Initial re-bleeding was new remote subarachnoid hemorrhage in 1 (11%) and new intracerebral hemorrhage in 8 (89%). Clinical symptoms of initial re-bleeding included isolated worsening headache in 2 (22%), focal neurological deficits in 4 (44%), and no clinical change in 3 (33%). Time from initial neuroimaging documenting cSAH to CT documenting re-bleed was 40 hours (range, 5 - 74), and re-bleed occurred within 60 hrs in most patients (89%). Two patients had subsequent re-bleeding (due to CVT and RCVS) documented at 1.9 and 11.8 hours after the initial re-bleed CT. Good clinical outcome was seen in 7 (78%) . Conclusion: Re-bleeding was seen in 10% of cSAH patients and in the majority of patients occurred early, within 2.5 days. Clinicians should be aware of this potential complication of cSAH.

Introduction: Although alterations in fibrinogen and fibrinogen degradation products are well-established after intravenous tissue plasminogen activator (IVtPA) in acute stroke, IVtPA is not recognized to cause markedly abnormal international normalized ratio (INR). Methods: With IRB approval, we prospectively screened 99 consecutive acute stroke patients who received IVtPA admitted from November 1, 2015 to July 1, 2016. Laboratory tests including INR, activated partial thromboplastin time (aPTT), fibrinogen, and d-Dimer were drawn at intervals of 6, 12, 24, and 48 hours. Data was collected on patient demographics, last known normal (LKN), IVtpA dose and timing, and National Institutes of Health Stroke Scale (NIHSS). Post-IVtPA coagulopathy was defined as INR ≥ 1.5. Reference range for fibrinogen was 190 - 395 mg/dL. Results: Among 44 patients prospectively enrolled, the mean age was 66.5 years (range, 32 to 91). Mean time from LKN to IVtPA administration was 2.6 hours (range 0.07 to 10.8). Initial pre-IVTPA mean NIHSS was 14 (range, 3 to 26) and 24 hour mean NIHSS was 7.4, (range 0 to 30). Mean pre-IVtPA INR was 1.05 (range, 0.9 to 1.4). Mean peak post-IVtPA INR was 1.28 (range 1.01 to 3.08). Mean deviation of actual to ideal IVtPA dose was 1.02 mg (range, 22.9 to 14.4). Post IVtPA coagulopathy occurred in 6 patients (14%), with peak INR noted at a mean of 13 hours after IVtPA administration (range, 5.6 to 18.6). Five patients of the six (83%) with post IVtPA coagulopathy had low fibrinogen, and mean fibrinogen nadir was 97 mg/dL (range, 37 to 242). Post-IVtPA coagulopathy was not significantly associated with initial NIHSS, 24 hour NIHSS, LKN to IVtPA time, or deviation of actual IVtPA dose from ideal dose. Conclusion: Post-IVtpA coagulopathy occurs in 14% of patients when studied prospectively and is associated with hypofibrinogenemia, but does not appear to correlate with severity of stroke or IVtPA dosing/timing.

Fever is common in patients with intracerebral hemorrhage (ICH). We sought to identify predictors of fever in patients hospitalized with ICH, and compare infectious fever with noninfectious fever.A retrospective review on consecutive spontaneous ICH patients from April 2009 to March 2010 was performed. Fever was defined as temperature 100.9°F or higher and attributed to infectious versus noninfectious etiology, based upon the National Healthcare Safety Network criteria. Univariate analysis and multivariable logistic regression model were used to determine factors associated with fever and with infection.Among the 351 ICH patients, 136 (39%) developed fever. Factors associated with fever included mean ICH volume, intraventricular hemorrhage (IVH), external ventricular drain (EVD) placement or surgical evacuation, positive microbial cultures, longer length of stay (LOS), and higher in-hospital mortality. Among patients with fever, 96 (71%) were noninfectious and 40 (29%) were infectious. Infectious fever was associated with higher LOS. Noninfectious fever was associated with higher in-hospital mortality. In multivariable analysis, ICH volume (OR = 1.01, P = .04), IVH (OR = 2.0, P = .03), EVD (OR = 3.7, P .0001), and surgical evacuation (OR = 6.78, P .0001) were significant predictors of fever. Infectious fever (OR = 5.26, P = .004), EVD (OR = 4.86, P = .01), and surgical evacuation (OR = 4.77, P = .04) correlated with prolonged LOS when dichotomized using a median of 15 days.Fever is common in ICH patients and is not associated with a clear infectious etiology in the majority of patients. Patients with noninfectious fever have higher in-hospital mortality, but survivors have shorter LOS. Further studies are warranted to better understand fevers in ICH.

Introduction: Cerebrospinal fluid (CSF) pleocytosis has been consistently observed with intraventricular hemorrhage (IVH) in small case series. Its extent, time course, and relation to IVH volume and infection have never been studied in a large cohort with systematic data collection. Hypothesis: Inflammatory response in CSF follows a predictable pattern after IVH, and is more enhanced in cases with higher IVH volume and infection Method: We analyzed prospectively collected samples from 500 patients enrolled in the Clot Lysis Evaluation of Accelerated Resolution (CLEAR) phase III trial. Patients with obstructive IVH requiring external ventricular drainage (EVD) were randomized to receive thrombolytic or placebo injections via EVD. We analyzed 12,291 data points including daily peripheral WBC and RBC counts, CSF RBC, WBC and neutrophil count, protein and glucose. Corrected WBCs (coWBC) reflecting true inflammatory response in the CSF was calculated by controlling for RBC/WBC ratio in a contemporaneous blood sample of the patient. Consecutive values were adjusted to the date of ictus (day 0) and analyzed on days 1-9. Median daily values were chronologically plotted to define the temporal pattern for each parameter. Similar analyses were repeated after stratification based on IVH volume, time to EVD insertion, and presence of culture positive ventriculitis (14 cases, 3%) Result: CSF protein gradually declined with later clearance of RBCs after IVH. There was a surge in coWBC at days 3-5. All parameters of inflammatory response, and most notably the coWBC peak, were greater with larger volume of IVH. Subgroup analyses defined a threshold for significant inflammatory response with initial IVH volume 27mls (P=0.006). Bacterial ventriculitis resulted in significantly higher coWBCs (P Conclusion: Inflammation is an integral response to IVH and is more pronounced with large IVH volume. Bacterial ventriculitis is associated with CSF leukocytosis exceeding the aseptic inflammatory response, notably in lower volume bleeds. These results form a basis for future correlation with treatment rendered, rate of IVH clearance and clinical outcome, with upcoming unblinding of the trial.

Introduction: Fever in intracerebral hemorrhage (ICH) patients can be due to infectious or noninfectious etiology, including central mechanisms. We sought to compare patients with ICH and infectious fever to those with noninfectious fever. Methods: Among 351 consecutive primary ICH patients admitted to our institution from April 2009 to March 2010, 136 (39%) developed fever. Fever was defined as temperature > 100.9°F during hospitalization. Cases were reviewed to determine if the patient had fever due to infectious versus noninfectious etiology. The diagnosis of infection was based on results of microbial cultures and National Healthcare Safety Network criteria. Other data collected included age, sex, maximum temperature (Tmax), medical history, ICH location, intraventricular hemorrhage (IVH), ICH volume as measured by standard ABC/2 bedside calculation, external ventricular drain (EVD) placement, surgical evacuation, length of stay (LOS), and inpatient mortality. Univariate analysis and multivariable logistic regression model were used to determine characteristics associated with infection status. Results: Among the 136 ICH patients with fever, 96 (71%) had noninfectious fever and 40 (29%) had infectious fever. In the univariate analysis, patients with infectious fever did not differ from patients with noninfectious fever with respect to age (61.3 vs 60.1 years, p 0.6), female sex (40% vs 48%, p 0.8), Tmax (102.2 vs 102.2°F, p 0.96), IVH (60% vs 71%, p 0.23), ICH volume (42 vs 40 cc, p 0.8), EVD placement (48% vs 51%, p 0.85), or surgical evacuation (30% vs 29%, p 1.0). Infectious fever was significantly associated with higher LOS (18.2 vs 11.1 days, p Conclusions: Patients with ICH who develop fever associated with an infectious etiology have longer LOS but lower in-hospital mortality. Further studies are warranted to understand fever in ICH patients.

Spectacular shrinking deficit (SSD) is characterized by abrupt onset of a major hemispheric stroke syndrome, followed by dramatic and rapid improvement. We retrospectively identified patients with SSD diagnosed at our institution between December 1, 2007, and June 30, 2009. We reviewed computed tomography perfusion (CTP) imaging to determine perfusion defect as a measure of initial ischemic penumbra, and magnetic resonance imaging diffusion-weighted imaging (DWI) to determine the final infarct core. Among the 472 consecutive ischemic stroke patients, 126 (27%) presented with major hemispheric ischemic stroke syndrome, defined as National Institutes of Health Stroke Scale score (NIHSS) ≥8 in the territory of the middle cerebral artery (MCA) or internal carotid artery (ICA). Out of these patients, we identified 8 SSD patients with available CTP data. In these 8 patients, the mean time to dramatic recovery was 3.4 hours (range, 0.75-7 hours), and the mean time from onset to CTP was 12.7 hours (range, 3-30 hours). All 8 patients had perfusion abnormalities in portions of the MCA territory (partial MCA territory in 5 patients and complete MCA territory in 3 patients). The mean time from onset to MRI DWI was 15.5 hours (range, 7.9-34 hours). Restricted diffusion was present in all patients in the corresponding MCA distribution. Vascular imaging revealed MCA occlusion in 2 patients. Cervical vascular imaging revealed carotid occlusion in 2 patients and high-grade carotid stenosis in 2 patients. The stroke mechanisms were cardioembolism in 2 patients, large artery in 4 patients, and unknown in 2 patients. Four patients had repeat CTP imaging available that demonstrated eventual resolution of the perfusion defect. SSD is associated with a "shrinking" clinical syndrome and a "shrinking" perfusion pattern on CTP that lags behind clinical recovery. CTP imaging corroborates that a larger territory is at risk in SSD and contributes to better understanding of SSD.

Background Temporal patterns in aneurysmal subarachnoid hemorrhage (aSAH) may provide insight into modulation, and therefore, prevention of hemorrhage. We investigated the time of hemorrhage and its relationship to traditional risk factors among patients admitted with aSAH. Methods Admitted patients with aSAH were prospectively followed through outcomes and baseline demographics were abstracted through chart review. The group temporal distribution by hour of onset was summarized with cosinor nonlinear least squares. aSAH onset was gathered into night (2300-0500), morning (0500-1100), afternoon (1100-1700), and evening (0500-2300) daily phases. The odds ratio (OR) with 95% CI was calculated for having an aSAH during the morning, afternoon, and evening hours using night as a reference. Multinomial logit models were fitted using aSAH cases across time blocks to determine their associations with different risk factors. Results 202 patients had the hour of hemorrhage available, and 49 had phase identifiable [total 251: 38 (15%) night, 98 (39%) morning, 58 (23%) afternoon, 57 (23%) evening]. The peak hours of aSAH were between 0700 and 0800 representing 13% of the sample, with a significant cosinor-fitted phase of 7.33(95% CI 5.30, 9.36). For all aSAH cases, morning onset was significantly more common than night onset (OR = 2.58, 95% CI = 1.77-3.75). Nonsmokers were more likely to have aSAH in the morning than smokers (P = 0.043, OR = 3.10, 95% CI = 1.33-7.23). Conclusions aSAH occur in a diurnal, morning prevalent pattern regardless of traditional aSAH risk factors. The association of these risk factors with existing onset patterns should be investigated in future studies.

Background and Purpose— The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography–based planimetry (CTP). Methods— In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. Results— In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC ( r 2 =0.93) than with site-ABC ( r 2 =0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm 3 ; CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P Conclusions— ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.

Background and Purpose— The purpose of this study was to investigate time delays, adherence to guidelines, and their impact on outcomes in patients with warfarin-associated intracerebral hemorrhage transferred from community emergency departments to a comprehensive stroke center. Methods— We collected demographic, clinical, transfer time, treatment, and outcome data for patients transferred to our institution with warfarin-associated intracerebral hemorrhage from community emergency departments. Results— Among 928 patients with intracerebral hemorrhage, 56 (6%) with warfarin-associated intracerebral hemorrhage (median international normalized ratio, 2.55) were transferred to the comprehensive stroke center. Twenty patients received no acute reversal therapy before transfer, only 4 of whom had international normalized ratios ≤1.4 in the community emergency department. Median time of emergency department stay was 3.66 hours and median time to initiation of acute reversal therapy was 4.48 hours. Those who received ≥3 U of fresh–frozen plasma or recombinant activated Factor VIIa (11 patients) before transfer had lower repeat international normalized ratios and better discharge dispositions than those treated less aggressively. Conclusions— Treatment of warfarin-associated intracerebral hemorrhage in community emergency departments is often suboptimal and does not adhere to published guidelines. Treating coagulopathy aggressively before interhospital transfer may improve outcomes and warrants further investigation.

The intracerebral hemorrhage (ICH) score is a simple grading scale that can be used to stratify risk of 30 day mortality in ICH patients. A similar risk stratification scale for subarachnoid hemorrhage (SAH) is lacking. We sought to develop a risk stratification mortality score for SAH. With approval from the Institutional Review Board, we retrospectively reviewed 400 consecutive SAH patients admitted to our institution from August 1, 2006 to March 1, 2011. The SAH score was developed from a multivariable logistic regression model which was validated with bootstrap method. A separate cohort of 302 SAH patients was used for evaluation of the score. Among 400 patients with SAH, the mean age was 56.9 ± 13.9 years (range, 21.5–96.2). Among the 366 patients with known causes of SAH, 292 (79.8 %) of patients had aneurysmal SAH, 65 (17.8 %) were angiogram negative, and 9 (2 %) were other vascular causes. The overall in-hospital mortality rate was 20 %. In multivariable analysis, the variables independently associated with the in-hospital mortality were Hunt and Hess score (HH) (p

Cardiac dysfunction is a well-known complication of subarachnoid hemorrhage (SAH). Our objective was to determine the frequency of troponin abnormalities in SAH and determine its impact on in-hospital mortality. With IRB approval, we retrospectively reviewed 225 consecutive SAH patients admitted to our institution from August 1, 2006 to June 1, 2009. Traumatic SAH patients were excluded. Data were collected on demographics, Hunt and Hess score (HH), in-hospital mortality, and peak troponin values on admission. CT images were independently reviewed and graded by the study neurologist for Fisher grade (FG) and the presence of intraventricular hemorrhage (IVH). Among the 225 SAH patients, the mean age was 57.3 years (range, 21–90). The majority of patients were female (67 %), FG 3 (75 %), and had IVH (62 %). Among the 201 patients with troponin I values, the mean troponin level was 0.93 (range, 0.01–25.8 ng/mL) and 47 (23 %) had elevated troponin I levels. In unadjusted analysis, elevated troponin I level was significantly associated with in-hospital mortality. With multivariable logistic regression adjusting for age, HH, FG, and IVH, elevated troponin I level was no longer associated with in-hospital mortality (p. 0.34). In multivariate analysis, the independent predictors of in-mortality were age and severe grade HH (4–5). Troponin I elevation after SAH is not an independent predictor of in-hospital mortality.

We report a case of global cerebral edema and herniation due to Posterior Reversible Leukoencephalopathy Syndrome (PRES).Case report.A 37-year-old healthy female developed persistent severe occipital headache, and after 1 month of persistent headache, developed an episode of loss of consciousness. CT brain showed diffuse cerebral edema and effacement of the sulci and basal cisterns. Her initial neurological examination was nonfocal but with severe headache. Overnight, she acutely became unresponsive with fixed dilated pupils, tachycardia, and hypertension. She was intubated and treated with hypertonic saline and mannitol with improvement in her clinical status. Intracranial Pressure (ICP) monitor showed elevated ICPs to 37 mmHg which responded to mannitol. MRI brain showed diffuse vasogenic edema predominantly in the white matter without enhancement. Cerebral angiogram was unremarkable. Cerebrospinal fluid including infectious work-up was negative. With supportive care, her mental status improved. On her 3 month follow-up visit, she was asymptomatic and had returned to work. Repeat MRI brain at 3 months showed persistent white matter changes that subsequently resolved at 9 months.Although PRES is typically considered to have a benign clinical course, clinician should be aware that severe cases can present with global cerebral edema and associated complications including intracranial hypertension and herniation.

Background: The International Cooperative Study on the Timing of Aneurysm Surgery suggested that delayed cerebral vasospasm is a significant contributor to mortality (at 6 months) after subarachnoid hemorrhage (SAH). However, the Cincinnati population based study did not find cerebral vasospasm to be a significant contributor to short-term mortality. Methods: We reviewed 350 consecutive non-traumatic SAH patients who were hospitalized at our institution from August 1, 2006 to June 30, 2010. Data were collected on demographics, Hunt and Hess grade, presence of cerebral infarct, symptomatic vasospasm, and in-hospital mortality. Symptomatic vasospasm was defined as cerebral vasospasm that required intra-arterial therapy (pharmacologic vasodilators or angioplasty). Cerebral infarct was defined as any new radiographic infarct seen on CT or MRI (of any cause). Results: Among 350 patients with non-traumatic SAH, the mean age was 56.7 years (range, 21.5 to 89.1) and 68% were aneurysmal. The overall in-hospital mortality rate was 20.2% (71 patients). The causes of in-hospital mortality were withdrawal of support in 53 (75%), brain death in 14 (20%), and cardiopulmonary death in 4 (8%). The mean time to death was 8.1 (range 0 to 31) days, with 36% of deaths occurring within the first 2 days of hospitalization. Among patients with symptomatic cerebral vasospasm or cerebral infarct , 19% (26/139) died. In univariate and multivariate analyses, symptomatic cerebral vasospasm and cerebral infarct were not associated with in-hospital mortality. When the analysis was restricted to patients with aneurysmal SAH, cerebral vasospasm and cerebral infarct were still not predictive of in-hospital mortality. In multivariable analysis, the variables most associated with in-hospital mortality were Hunt and Hess score (HH) (p Conclusions: In-hospital mortality after SAH is associated with initial severity of hemorrhage, rebleeding, and age. Symptomatic cerebral vasospasm and cerebral infarct were not significant contributors of overall in-hospital mortality, and approximately one-third of in-hospital mortality after SAH occurs within the first 2 days of hospitalization. By design, studies that exclude patients with severe SAH tend to over-estimate the contribution of cerebral vasospasm on short-term mortality.

Background and Purpose— The development of comprehensive stroke centers within hub-and-spoke stroke networks offers the opportunity to increase the proportion of acute ischemic stroke patients treated with intra-arterial therapies (IAT). Interhospital transfer delays will be critical in evaluating the success of this strategy. Methods— We collected data on consecutive patients who were transferred to our institution for possible IAT. We defined transfer time as time elapsed from initial transfer call to arrival at our hospital and assessed whether transfer time was a predictor of emergent angiography using multivariable logistic regression. Results— Among 132 patients referred for IAT, 53 (40.2%) were excluded on clinical grounds. The remaining 79 (59.8%) patients (mean age, 61 years; median National Institutes of Health Stroke Scale score, 18; 49.4% male) were analyzed. Sixty-one of 79 (77%) patients underwent emergent angiography for IAT. The median hospital-to-hospital distance was 14.7 (interquartile range, 8.5–21.9) miles and median transfer time was 104 (interquartile range, 80–135) minutes. Transfer time was 33% lower among those who underwent emergent angiography (100.6 versus 149.0 minutes; P P =0.014). The odds of treatment decrease by 2.5% for every minute of transfer time. Conclusions— Delay in hospital-to-hospital transfer is a common reason that acute ischemic stroke patients are excluded from interventional therapy. The likelihood of receiving IAT decreases rapidly by increasing transfer time. Specific goals for transfer time should be considered in future quality standards for hub-and-spoke–organized stroke networks.

Background and Purpose— We aimed to determine the prevalence of acute brain infarcts using diffusion-weighted imaging (DWI) in patients with spontaneous intracerebral hemorrhage (ICH). Methods— We collected data on consecutive patients with spontaneous ICH admitted to our institution between August 1, 2006 and December 31, 2008 and in whom DWI was performed within 28 days of admission. Patients with hemorrhage attributable to trauma, tumor, aneurysm, vascular malformation, and hemorrhagic conversion of arterial or venous infarction were excluded. Restricted diffusion within, contiguous with, or immediately neighboring the hematoma or chronic infarcts was not considered abnormal. Using multivariable logistic regression, we evaluated potential predictors of DWI abnormality including clinical and radiographic characteristics and treatments. A probability value Results— Among 118 spontaneous ICH patients (mean 59.6 years, 47.5% male, and 31.4% white) who also underwent MRI, DWI abnormality was observed in 22.9%. The majority of infarcts were small (median volume 0.25 mL), subcortical (70.4%), and subclinical (88.9%). Factors independently associated with DWI abnormality were prior ischemic stroke ( P =0.002), MAP lowering by ≥40% ( P =0.004), and craniotomy for ICH evacuation ( P =0.001). Conclusion— We found that acute brain infarction is relatively common after acute spontaneous ICH. Several factors, including aggressive blood pressure lowering, may be associated with acute ischemic infarcts after ICH. These preliminary findings require further prospective study.