Code ICH: A Call to Action.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Real-World Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion: Results of the BArONIS Study.

OBJECTIVE: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. RESULTS: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. INTERPRETATION: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60.

Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

BACKGROUND: Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. METHODS: We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3 h of onset], at 24 h, and at 72 h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. RESULTS: A total of 781 patients with supratentorial ICH (mean age 65 years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6 mL, p = 0.053) and PHE volumes (11.1 vs. 10.5 mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24 h (19.0 vs. 14.0 mL, p < 0.001; 22.2 vs. 15.7 mL, p < 0.001) and 72 h (16.0 vs. 11.8 mL, p < 0.001; 28.7 vs. 19.9 mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6 mL at 24 h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5 mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. CONCLUSIONS: Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.

Exploring Hematoma Expansion Shift With Recombinant Factor VIIa: A Pooled Analysis of 4 Randomized Controlled Trials.

BACKGROUND: Hematoma expansion shift (HES) analysis can be used to assess the biological effect of a hemostatic therapy for intracerebral hemorrhage. In this study, we applied HES analysis to individual patient data from 4 randomized controlled trials evaluating rFVIIa (recombinant factor VIIa) 80 µg/kg to placebo. METHODS: We generated polychotomous strata of HES using absolute growth thresholds (≤0/<6/≥6 mL) and quintiles of percent volume change. The relationship between treatment and HES was assessed using proportional odds models. Differences in subgroups based on baseline volume (≥ or <20 mL), and time from symptom onset to treatment (≤ or >2 hours) were explored with testing for interactions. RESULTS: The primary analysis included 721 patients. At 24 hours, 36% (134/369) of rFVIIa-treated patients exhibited no hematoma expansion as compared with 25% of placebo (88/352)-treated patients. Significant expansion (≥6 mL) was reduced by 10% in those treated with rFVIIa-(adjusted common odds ratio [acOR], 0.57 [95% CI, 0.43-0.75]). An examination of percent change similarly showed a shift across the spectrum of expansion (acOR, 0.61 [95% CI, 0.47-0.80]). In both groups, mild-to-moderate expansion was observed in 38% to 47% of patients, depending on the threshold used. Differences in absolute HES between the rFVIIa and placebo groups were more pronounced in patients with baseline hemorrhage volumes ≥20 mL (acOR, 0.48 [95% CI, 0.30-0.76] versus <20 mL: acOR, 0.67 [95% CI, 0.47-0.95]; Pinteraction=0.02). No treatment interaction in patients treated within 2 or after 2 hours from onset was observed (acOR, 0.42 [95% CI, 0.19-0.91 versus >2 hours: acOR, 0.59 [95% CI, 0.44-0.79]; Pinteraction=0.30). CONCLUSIONS: The association between rFVIIa and hematoma growth arrest is most pronounced in patients with larger baseline volumes but is evident across the full spectrum of treated patients.

Association Between Soluble Intercellular Adhesion Molecule-1 and Intracerebral Hemorrhage Outcomes in the FAST Trial.

BACKGROUND: Neutrophil-mediated inflammation in the acute phase of intracerebral hemorrhage (ICH) worsens outcome in preclinical studies. sICAM-1 (soluble intercellular adhesion molecule-1), an inducible ligand for integrins and cell-cell adhesion molecules, is critical for neutrophil extravasation. We aimed to determine whether serum levels of sICAM-1 are associated with worse outcomes after ICH. METHODS: We conducted a post hoc secondary analysis of an observational cohort using data from the FAST trial (Factor-VII for Acute Hemorrhagic Stroke Treatment). The study exposure was the admission serum level of sICAM-1. The coprimary outcomes were mortality and poor outcome (modified Rankin Scale score 4-6) at 90 days. Secondary radiological outcomes were hematoma expansion at 24 hours and perihematomal edema expansion at 72 hours. We used multiple linear and logistic regression analyses to test for associations between sICAM-1 and outcomes, after adjustment for demographics, ICH severity characteristics, change in the systolic blood pressure in the first 24 hours, treatment randomization arm, and the time from symptom onset to study drug administration. RESULTS: Of 841 patients, we included 507 (60%) with complete data. Hematoma expansion occurred in 169 (33%), while 242 (48%) had a poor outcome. In multivariable analyses, sICAM-1 was associated with mortality (odds ratio, 1.53 per SD increase [95% CI, 1.15-2.03]) and poor outcome (odds ratio, 1.34 per SD increase [CI, 1.06-1.69]). In multivariable analyses of secondary outcomes, sICAM-1 was associated with hematoma expansion (odds ratio, 1.35 per SD increase [CI, 1.11-1.66]), but was not associated with log-transformed perihematomal edema expansion at 72 hours. In additional analyses stratified by treatment assignment, similar results were noted in the recombinant activated factor-VII arm, but not in the placebo arm. CONCLUSIONS: Admission serum levels of sICAM-1 were associated with mortality, poor outcome, and hematoma expansion. Given the possibility of a biological interaction between recombinant activated factor-VII and sICAM-1, these findings highlight the need to further explore the role of sICAM-1 as a potential marker of poor ICH outcomes.

A Pilot Study of the Fluctuating Mental Status Evaluation: A Novel Delirium Screening Tool for Neurocritical Care Patients.

BACKGROUND: Delirium occurs frequently in patients with stroke and neurocritical illness but is often underrecognized. We developed a novel delirium screening tool designed specifically for neurocritical care patients called the fluctuating mental status evaluation (FMSE) and aimed to test its usability and accuracy in a representative cohort of patients with intracerebral hemorrhage (ICH). METHODS: We performed a single-center prospective study in a pilot cohort of patients with ICH who had daily delirium assessments throughout their admission. Reference-standard expert ratings were performed each afternoon using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and were derived from bedside assessments and clinical data from the preceding 24 h. Paired FMSE assessments were performed by patients' clinical nurses after receiving brief one-on-one training from research staff. Nursing assessments were aggregated over 24-h periods (including day and night shifts), and accuracy of the FMSE was analyzed in patients who were not comatose to determine optimal scoring thresholds. RESULTS: We enrolled 40 patients with ICH (mean age 71.1 ± 12.2, 55% male, median National Institutes of Health Stroke Scale score 16.5 [interquartile range 12-20]), of whom 85% (n = 34) experienced delirium during their hospitalization. Of 308 total coma-free days with paired assessments, 208 (68%) were rated by experts as days with delirium. Compared with expert ratings, FMSE scores ≥ 1 had 86% sensitivity and 73% specificity on a per-day basis, whereas FMSE scores ≥ 2 had 68% sensitivity and 82% specificity. Accuracy remained high in patients with aphasia (FMSE scores ≥ 1: 83% sensitivity, 77% specificity; FMSE scores ≥ 2: 68% sensitivity, 85% specificity) and decreased arousal (FMSE scores ≥ 1: 80% sensitivity, 100% specificity; FMSE scores ≥ 2: 73% sensitivity, 100% specificity). CONCLUSIONS: In this pilot study, the FMSE achieved a high sensitivity and specificity in detecting delirium. Follow-up validation studies in a larger more diverse cohort of neurocritical care patients will use score cutoffs of ≥ 1 as "possible" delirium and ≥ 2 as "probable" delirium.

Frailty and outcomes in lacunar stroke.

BACKGROUND: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described. OBJECTIVE: To analyze the association between frailty and outcomes in LS. METHODS: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10th edition (ICD-10) diagnosis codes. The 11-point modified frailty scale (mFI-11) was used to group patients into severely frail and non-severely frail cohorts. Demographics, clinical characteristics, and complications were defined. Health care resource utilization (HRU) was evaluated by comparing total hospital charges and length of stay (LOS). Other outcomes studied were discharge disposition and inpatient death. RESULTS: Of 48,980 patients with LS, 10,830 (22.1%) were severely frail. Severely frail patients were more likely to be older, have comorbidities, and pertain to lower socioeconomic status categories. Severely frail patients with LS had worse clinical stroke severity and increased rates of complications such as urinary tract infection (UTI) and pneumonia (PNA). Additionally, severe frailty was associated with unfavorable outcomes and increased HRU. CONCLUSION: Severe frailty in LS patients is associated with higher rates of complications and increased HRU. Risk stratification based on frailty may allow for individualized treatments to help mitigate adverse outcomes in the setting of LS.

Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. METHODS: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). RESULTS: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P=0.001) and early neurological deterioration (31 versus 17%, P=0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P<0.001) and 24 hours (14 versus 38mL, P<0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P=0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P=0.01). CONCLUSIONS: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke.

BACKGROUND: Evidence regarding the utilization and outcomes of endovascular thrombectomy (EVT) for pediatric ischemic stroke is limited, and justification for its use is largely based on extrapolation from clinical benefits observed in adults. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify pediatric patients with ischemic stroke (<18 years old) during the period of 2010 to 2019. Complex samples statistical methods were used to characterize the profiles and clinical outcomes of EVT-treated patients. Propensity adjustment was performed to address confounding by indication for EVT based on disparities in baseline characteristics between EVT-treated patients and those medically managed. RESULTS: Among 7365 pediatric patients with ischemic stroke identified, 190 (2.6%) were treated with EVT. Utilization significantly increased in the post-EVT clinical trial era (2016-2019; 1.7% versus 4.0%; P<0.001), while the use of decompressive hemicraniectomy decreased (2.8% versus 0.7%; P<0.001). On unadjusted analysis, 105 (55.3%) EVT-treated patients achieved favorable functional outcomes at discharge (home or to acute rehabilitation), while no periprocedural iatrogenic complications or instances of contrast-induced kidney injury were reported. Following propensity adjustment, EVT-treated patients demonstrated higher absolute but nonsignificant rates of favorable functional outcomes in comparison with medically managed patients (55.3% versus 52.8%; P=0.830; adjusted hazard ratio, 1.01 [95% CI, 0.51-2.03]; P=0.972 for unfavorable outcome). Among patients with baseline National Institutes of Health Stroke Scale score >11 (75th percentile of scores in cohort), EVT-treated patients trended toward higher rates of favorable functional outcomes compared with those treated medically only (71.4% versus 55.6%; P=0.146). In a subcohort assessment of EVT-treated patients, those administered preceding thrombolytic therapy (n=79, 41.6%) trended toward higher rates of favorable functional outcomes (63.3% versus 49.5%; P=0.060). CONCLUSIONS: This cross-sectional evaluation of the clinical course and short-term outcomes of pediatric patients with ischemic stroke treated with EVT demonstrates that EVT is likely a safe modality which confers high rates of favorable functional outcomes.

Association of Elevated Body Mass Index with Functional Outcome and Mortality following Acute Ischemic Stroke: The Obesity Paradox Revisited.

BACKGROUND: Previous literature has identified a survival advantage in acute ischemic stroke (AIS) patients with elevated body mass indices (BMIs), a phenomenon termed the "obesity paradox." OBJECTIVE: The aim of this study was to evaluate the independent association between obesity and clinical outcomes following AIS. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify AIS patients from 2015 to 2018. Multivariable logistic regression and Cox proportional hazards modeling were performed to evaluate associations between obesity (BMI ≥ 30) and clinical endpoints following adjustment for acute stroke severity and comorbidity burden. RESULTS: Among 1,687,805 AIS patients, 216,775 (12.8%) were obese. Compared to nonobese individuals, these patients were younger (64 vs. 72 mean years), had lower baseline NIHSS scores (6.9 vs. 7.9 mean score), and a higher comorbidity burden. Multivariable analysis demonstrated independent associations between obesity and lower likelihood of mortality (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI]: 0.71, 0.82, p < 0.001; hazard ratio 0.84, 95% CI: 0.73, 0.97, p = 0.015), intracranial hemorrhage (aOR 0.87, 95% CI: 0.82, 0.93, p < 0.001), and routine discharge to home (aOR 0.97, 95% CI: 0.95, 0.99; p = 0.015). Mortality rates between obese and nonobese patients were significantly lower across stroke severity thresholds, but this difference was attenuated among high severity (NIHSS > 20) strokes (21.6% vs. 23.2%, p = 0.358). Further stratification of the cohort into BMI categories demonstrated a "U-shaped" association with mortality (underweight aOR 1.58, 95% CI: 1.39, 1.79; p < 0.001, overweight aOR 0.64, 95% CI: 0.42, 0.99; p = 0.046, obese aOR 0.77, 95% CI: 0.71, 0.83; p < 0.001, severely obese aOR 1.18, 95% CI: 0.74, 1.87; p = 0.485). Sub-cohort assessment of thrombectomy-treated patients demonstrated an independent association of obesity (BMI 30-40) with lower mortality (aOR 0.79, 95% CI: 0.65, 0.96; p = 0.015), but not with routine discharge. CONCLUSION: This cross-sectional analysis demonstrates a lower likelihood of discharge to home as well as in-hospital mortality in obese patients following AIS, suggestive of a protective effect of obesity against mortality but not against all poststroke neurological deficits in the short term which would necessitate placement in acute rehabilitation and long-term care facilities.

The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. METHODS: REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. DISCUSSION: In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. TRIAL REGISTRATION (ADDITIONAL FILE 1): ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018-000241-39).

Cardiac arrest in spontaneous subarachnoid hemorrhage and associated outcomes.

OBJECTIVE: The authors sought to analyze a large, publicly available, nationwide hospital database to further elucidate the impact of cardiopulmonary arrest (CA) in association with subarachnoid hemorrhage (SAH) on short-term outcomes of mortality and discharge disposition. METHODS: This retrospective cohort study was conducted by analyzing de-identified data from the National (Nationwide) Inpatient Sample (NIS). The publicly available NIS database represents a 20% stratified sample of all discharges and is powered to estimate 95% of all inpatient care delivered across hospitals in the US. A total of 170,869 patients were identified as having been hospitalized due to nontraumatic SAH from 2008 to 2014. RESULTS: A total of 5415 patients (3.2%) were hospitalized with an admission diagnosis of CA in association with SAH. Independent risk factors for CA included a higher Charlson Comorbidity Index score, hospitalization in a small or nonteaching hospital, and a Medicaid or self-pay payor status. Compared with patients with SAH and not CA, patients with CA-SAH had a higher mean NIS Subarachnoid Severity Score (SSS) ± SD (1.67 ± 0.03 vs 1.13 ± 0.01, p < 0.0001) and a vastly higher mortality rate (82.1% vs 18.4%, p < 0.0001). In a multivariable model, age, NIS-SSS, and CA all remained significant independent predictors of mortality. Approximately 18% of patients with CA-SAH survived and were discharged to a rehabilitation facility or home with health services, outcomes that were most predicted by chronic disease processes and large teaching hospital status. CONCLUSIONS: In the largest study of its kind, CA at onset was found to complicate roughly 3% of spontaneous SAH cases and was associated with extremely high mortality. Despite this, survival can still be expected in approximately 18% of patients.

Cerebral vasospasm following arteriovenous malformation rupture: a population-based cross-sectional study.

OBJECTIVE: Studies examining the risk factors and clinical outcomes of arterial vasospasm secondary to cerebral arteriovenous malformation (cAVM) rupture are scarce in the literature. The authors used a population-based national registry to investigate this largely unexamined clinical entity. METHODS: Admissions for adult patients with cAVM ruptures were identified in the National Inpatient Sample during the period from 2015 to 2019. Complex samples multivariable logistic regression and chi-square automatic interaction detection (CHAID) decision tree analyses were performed to identify significant associations between clinical covariates and the development of vasospasm, and a cAVM-vasospasm predictive model (cAVM-VPM) was generated based on the effect sizes of these parameters. RESULTS: Among 7215 cAVM patients identified, 935 developed vasospasm, corresponding to an incidence rate of 13.0%; 110 of these patients (11.8%) subsequently progressed to delayed cerebral ischemia (DCI). Multivariable adjusted modeling identified the following baseline clinical covariates: decreasing age by decade (adjusted odds ratio [aOR] 0.87, 95% CI 0.83-0.92; p < 0.001), female sex (aOR 1.68, 95% CI 1.45-1.95; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.34, 95% CI 1.01-1.79; p = 0.045), intraventricular hemorrhage (aOR 1.87, 95% CI 1.17-2.98; p = 0.009), hypertension (aOR 1.77, 95% CI 1.50-2.08; p < 0.001), obesity (aOR 0.68, 95% CI 0.55-0.84; p < 0.001), congestive heart failure (aOR 1.34, 95% CI 1.01-1.78; p = 0.043), tobacco smoking (aOR 1.48, 95% CI 1.23-1.78; p < 0.019), and hospitalization events (leukocytosis [aOR 1.64, 95% CI 1.32-2.04; p < 0.001], hyponatremia [aOR 1.66, 95% CI 1.39-1.98; p < 0.001], and acute hypotension [aOR 1.67, 95% CI 1.31-2.11; p < 0.001]) independently associated with the development of vasospasm. Intraparenchymal and subarachnoid hemorrhage were not associated with the development of vasospasm following multivariable adjustment. Among significant associations, a CHAID decision tree algorithm identified age 50-59 years (parent node), hyponatremia, and leukocytosis as important determinants of vasospasm development. The cAVM-VPM achieved an area under the curve of 0.65 (sensitivity 0.70, specificity 0.53). Progression to DCI, but not vasospasm alone, was independently associated with in-hospital mortality (aOR 2.35, 95% CI 1.29-4.31; p = 0.016) and lower likelihood of routine discharge (aOR 0.62, 95% CI 0.41-0.96; p = 0.031). CONCLUSIONS: This large-scale assessment of vasospasm in cAVM identifies common clinical risk factors and establishes progression to DCI as a predictor of poor neurological outcomes.

The Curing Coma Campaign International Survey on Coma Epidemiology, Evaluation, and Therapy (COME TOGETHER).

BACKGROUND: Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis. METHODS: As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents. RESULTS: The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians (n = 213, 83%), were from the United States (n = 141, 55%), and represented academic centers (n = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ = 0.552); and inability to follow commands (58%, κ = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%). CONCLUSIONS: There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally.

Transcarotid Access for Mechanical Thrombectomy in Acute Ischemic Stroke: A Meta-Analysis and Systematic Review.

OBJECTIVES: Despite the success of mechanical thrombectomy in large vessel acute ischemic stroke, recanalization may fail due to difficult anatomic access or peripheral arterial occlusive disease. In these cases, transcarotid access may be used as an alternative, but it has not gained prominence due to safety concerns. Our objective was to assess the efficacy and safety of transcarotid access for mechanical thrombectomy. MATERIALS AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to perform a systematic review with articles published from 2010 to 2020 summarizing pre-intervention characteristics, techniques utilized, and outcomes of patients undergoing mechanical thrombectomy via trans-carotid puncture. We performed a meta-analysis of clinical outcomes, reperfusion times and overall complications rates of trans-carotid approach. RESULTS: Six studies describing 80 total attempts at carotid access, 72 of which were successful (90% success rate), were included. Direct carotid puncture was most often used as a rescue technique (87% of patients) secondary to failed femoral access. Successful recanalization was achieved in 76% of patients. 90 day modified Rankin Scale ≤ 2 was achieved in 28% of patients. Carotid puncture-reperfusion time was 32 min (CI = 24-40, p < 0.001). Cervical complications occurred at a rate of 26.5% (95% CI = 17%-38%). Only 1.3% (1/80 patients) had a fatal outcome and 96% of complications required no intervention. CONCLUSIONS: Our results on the safety and efficacy of transcarotid access suggests that this approach is a viable alternative to failed thrombectomy when transfemoral or trans-radial access may be impractical.

Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH). METHODS: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes. RESULTS: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (ß, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (ß 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (ß 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome. CONCLUSIONS: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.

Endovascular Thrombectomy for Treatment of Acute Ischemic Stroke During Pregnancy and the Early Postpartum Period.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) is a rare occurrence during pregnancy and the postpartum period. Existing literature evaluating endovascular mechanical thrombectomy (MT) for this patient population is limited. METHODS: The National Inpatient Sample was queried from 2012 to 2018 to identify and characterize pregnant and postpartum patients (up to 6 weeks following childbirth) with AIS treated with MT. Complications and outcomes were compared with nonpregnant female patients treated with MT and to other pregnant and postpartum patients managed medically. Complex samples regression models and propensity score matching were implemented to assess adjusted associations and to address confounding by indication, respectively. RESULTS: Among 4590 pregnant and postpartum patients with AIS, 180 (3.9%) were treated with MT, and rates of utilization increased following the MT clinical trial era (2015-2018; 1.9% versus 5.3%, P=0.011). Compared with nonpregnant patients with AIS treated with MT, they experienced lower rates of intracranial hemorrhage (11% versus 24%, P=0.069) and poor functional outcome (50% versus 72%, P=0.003) at discharge. Pregnant/postpartum status was independently associated with a lower likelihood of development of intracranial hemorrhage (adjusted odds ratio, 0.26 [95% CI, 0.09-0.70]; P=0.008) following multivariable analysis adjusting for age, illness severity, and stroke severity. Following propensity score matching, pregnant and postpartum patients treated with MT and those medically managed differed in frequency of venous thromboembolism (17% versus 0%, P=0.001) and complications related to pregnancy (44% versus 64%, P=0.034), but not in functional outcome at discharge or hospital length of stay. Pregnant and postpartum women treated with MT did not experience mortality or miscarriage during hospitalization. CONCLUSIONS: This large-scale analysis utilizing national claims data suggests that MT is a safe and efficacious therapy for AIS during pregnancy and the postpartum period. In the absence of prospective clinical trials, population-based cross-sectional analyses such as the present study provide valuable clinical insight.

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN: Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING: Two randomized clinical trials and one multiethnic observational study. PATIENTS: Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.

Differentiation of psychogenic nonepileptic attacks from status epilepticus among patients intubated for convulsive activity.

BACKGROUND AND OBJECTIVE: Patients with psychogenic nonepileptic attacks (PNEA) sometimes receive aggressive treatment leading to intubation. This study aimed to identify patient characteristics that can help differentiate PNEA from status epilepticus (SE). METHODS: We retrospectively identified patients with a final diagnosis of PNEA or SE, who were intubated for emergent convulsive symptoms and underwent continuous electroencephalography (cEEG) between 2012 and 2017. Patients who had acute brain injury or progressive brain disease as the cause of SE were excluded. We compared clinical features and laboratory values between the two groups, and identified risk factors for PNEA-related convulsive activity. RESULTS: Over a six-year period, 24 of 148 consecutive patients (16%) intubated for convulsive activity had a final diagnosis of PNEA rather than SE. Compared to patients intubated for SE, intubated PNEA patients more likely were <50 years of age, female, white, had a history of a psychiatric disorder, had no history of an intracranial abnormality, and had a maximum systolic blood pressure <140 mm Hg (all P < 0.001). Patients with 0-2 of these six risk factors had a 0% (0/88) likelihood of having PNEA, those with 3-4 had a 15% (6/39) chance of having PNEA, and those with 5-6 had an 86% (18/21) chance of having PNEA. Sensitivity for PNEA among those with 5-6 risk factors was 75% (95% CI: 53-89%) and specificity was 98% (95% CI: 93-99%). CONCLUSIONS: In the absence of a clear precipitating brain injury, approximately one in six patients intubated for emergent convulsive symptoms had PNEA rather than SE. Although PNEA cannot be diagnosed only by the presence of these risk factors, these simple characteristics could raise clinical suspicion for PNEA in the appropriate setting. Urgent neurological consultation may prevent unnecessary intubation of this at-risk patient population.