2024 AHA/ASA Performance and Quality Measures for Spontaneous Intracerebral Hemorrhage: A Report From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released a revised spontaneous intracerebral hemorrhage guideline in 2022. A working group of stroke experts reviewed this guideline and identified a subset of recommendations that were deemed suitable for creating performance measures. These 15 performance measures encompass a wide spectrum of intracerebral hemorrhage patient care, from prehospital to posthospital settings, highlighting the importance of timely interventions. The measures also include 5 quality measures and address potential challenges in data collection, with the aim of future improvements.

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024.

The Formal Demography of Peak Population.

When will the human population peak? In this article, we build on classical results by Ansley Coale, who showed that when fertility declines steadily, births reach their maximum before fertility reaches replacement level, and the decline in total population size does not occur until several decades after fertility has reached that level. We extend Coale's results by modeling longevity increases, net immigration, and a slowdown in fertility decline that resembles current projections. With these extensions, our models predict a typical lag between replacement-level fertility and population decline of about 35 to 40 years, consistent with projections by the United Nations and about 15 years longer than the lag predicted by Coale. Our analysis helps reveal underlying factors in the timing of peak population.

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. METHODS: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. RESULTS: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. CONCLUSIONS: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis.

BACKGROUND: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood. METHODS: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. RESULTS: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL. CONCLUSIONS: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.

Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage.

Importance: Intracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice. Objective: To evaluate whether DTT time is associated with outcome among patients with anticoagulation-associated ICH treated with reversal interventions. Design, Setting, and Participants: This cohort study used data from the American Heart Association Get With The Guidelines-Stroke quality improvement registry. Patients with ICH who presented within 24 hours of symptom onset across 465 US hospitals from 2015 to 2021 were included. Data were analyzed from January to September 2023. Exposures: Anticoagulation-associated ICH. Main Outcomes and Measures: DTT times and outcomes were analyzed using logistic regression modeling, adjusted for demographic, history, baseline, and hospital characteristics, with hospital-specific random intercepts to account for clustering by site. The primary outcome of interest was the composite inpatient mortality and discharge to hospice. Additional prespecified secondary outcomes, including functional outcome (discharge modified Rankin Scale score, ambulatory status, and discharge venue), were also examined. Results: Of 9492 patients with anticoagulation-associated ICH and documented reversal intervention status, 4232 (44.6%) were female, and the median (IQR) age was 77 (68-84) years. A total of 7469 (78.7%) received reversal therapy, including 4616 of 5429 (85.0%) taking warfarin and 2856 of 4069 (70.2%) taking a non-vitamin K antagonist oral anticoagulant. For the 5224 patients taking a reversal intervention with documented workflow times, the median (IQR) onset-to-treatment time was 232 (142-482) minutes and the median (IQR) DTT time was 82 (58-117) minutes, with a DTT time of 60 minutes or less in 1449 (27.7%). A DTT time of 60 minutes or less was associated with decreased mortality and discharge to hospice (adjusted odds ratio, 0.82; 95% CI, 0.69-0.99) but no difference in functional outcome (ie, a modified Rankin Scale score of 0 to 3; adjusted odds ratio, 0.91; 95% CI, 0.67-1.24). Factors associated with a DTT time of 60 minutes or less included White race, higher systolic blood pressure, and lower stroke severity. Conclusions and Relevance: In US hospitals participating in Get With The Guidelines-Stroke, earlier anticoagulation reversal was associated with improved survival for patients with ICH. These findings support intensive efforts to accelerate evaluation and treatment for patients with this devastating form of stroke.

Hypotension During Vasopressor Infusion Occurs in Predictable Clusters: A Multicenter Analysis.

Background: Published evidence indicates that mean arterial pressure (MAP) below a goal range (hypotension) is associated with worse outcomes, though MAP management failures are common. We sought to characterize hypotension occurrences in ICUs and consider the implications for MAP management. Methods: Retrospective analysis of 3 hospitals' cohorts of adult ICU patients during continuous vasopressor infusion. Two cohorts were general, mixed ICU patients and one was exclusively acute spinal cord injury patients. "Hypotension-clusters" were defined where there were ≥10 min of cumulative hypotension over a 60-min period and "constant hypotension" was ≥10 continuous minutes. Trend analysis was performed (predicting future MAP using 14 min of preceding MAP data) to understand which hypotension-clusters could likely have been predicted by clinician awareness of MAP trends. Results: In cohorts of 155, 66, and 16 ICU stays, respectively, the majority of hypotension occurred within the hypotension-clusters. Failures to keep MAP above the hypotension threshold were notable in the bottom quartiles of each cohort, with hypotension durations of 436, 167, and 468 min, respectively, occurring within hypotension-clusters per day. Mean arterial pressure trend analysis identified most hypotension-clusters before any constant hypotension occurred (81.2%-93.6% sensitivity, range). The positive predictive value of hypotension predictions ranged from 51.4% to 72.9%. Conclusions: Across 3 cohorts, most hypotension occurred in temporal clusters of hypotension that were usually predictable from extrapolation of MAP trends.

Entropy removal of medical diagnostics.

Shannon entropy is a core concept in machine learning and information theory, particularly in decision tree modeling. To date, no studies have extensively and quantitatively applied Shannon entropy in a systematic way to quantify the entropy of clinical situations using diagnostic variables (true and false positives and negatives, respectively). Decision tree representations of medical decision-making tools can be generated using diagnostic variables found in literature and entropy removal can be calculated for these tools. This concept of clinical entropy removal has significant potential for further use to bring forth healthcare innovation, such as quantifying the impact of clinical guidelines and value of care and applications to Emergency Medicine scenarios where diagnostic accuracy in a limited time window is paramount. This analysis was done for 623 diagnostic tools and provided unique insights into their utility. For studies that provided detailed data on medical decision-making algorithms, bootstrapped datasets were generated from source data to perform comprehensive machine learning analysis on these algorithms and their constituent steps, which revealed a novel and thorough evaluation of medical diagnostic algorithms.

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.

Acute care bundles should be used for patients with intracerebral haemorrhage: An expert consensus statement.

PURPOSE: Intracerebral haemorrhage (ICH) is the most devastating form of stroke and a major cause of disability. Clinical trials of individual therapies have failed to definitively establish a specific beneficial treatment. However, clinical trials of introducing care bundles, with multiple therapies provided in parallel, appear to clearly reduce morbidity and mortality. Currently, not enough patients receive these interventions in the acute phase. METHODS: We convened an expert group to discuss best practices in ICH and to develop recommendations for bundled care that can be delivered in all settings that treat acute ICH, with a focus on European healthcare systems. FINDINGS: In this consensus paper, we argue for widespread implementation of formalised care bundles in ICH, including specific metrics for time to treatment and criteria for the consideration of neurosurgical therapy. DISCUSSION: There is an extraordinary opportunity to improve clinical care and clinical outcomes in this devastating disease. Substantial evidence already exists for a range of therapies that can and should be implemented now.

CenSoc: Public Linked Administrative Mortality Records for Individual-level Research.

In the United States, much has been learned about the determinants of longevity from survey data and aggregated tabulations. However, the lack of large-scale, individual-level administrative mortality records has proven to be a barrier to further progress. We introduce the CenSoc datasets, which link the complete-count 1940 U.S. Census to Social Security mortality records. These datasets-CenSoc-DMF (N = 4.7 million) and CenSoc-Numident (N = 7.0 million)-primarily cover deaths among individuals aged 65 and older. The size and richness of CenSoc allows investigators to make new discoveries into geographic, racial, and class-based disparities in old-age mortality in the United States. This article gives an overview of the technical steps taken to construct these datasets, validates them using external aggregate mortality data, and discusses best practices for working with these datasets. The CenSoc datasets are publicly available, enabling new avenues of research into the determinants of mortality disparities in the United States.

Dilated optic nerve sheath by ultrasound predicts mortality among patients with acute intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a deadly disease and increased intracranial pressure (ICP) is associated with worse outcomes in this context. OBJECTIVE: We evaluated whether dilated optic nerve sheath diameter (ONSD) depicted by optic nerve ultrasound (ONUS) at hospital admission has prognostic value as a predictor of mortality at 90 days. METHODS: Prospective multicenter study of acute supratentorial primary ICH patients consecutively recruited from two tertiary stroke centers. Optic nerve ultrasound and cranial computed tomography (CT) scans were performed at hospital admission and blindly reviewed. The primary outcome was mortality at 90-days. Multivariate logistic regression, ROC curve, and C-statistics were used to identify independent predictors of mortality. RESULTS: Between July 2014 and July 2016, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3 ± 13.1 years and 12 (27.3%) were female. On univariate analysis, ICH volume on cranial CT scan, ICH ipsilateral ONSD, Glasgow coma scale, National Institute of Health Stroke Scale (NIHSS) and glucose on admission, and also diabetes mellitus and current nonsmoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (odds ratio [OR]: 6.24; 95% confidence interval [CI]: 1.18-33.01; p = 0.03) was an independent predictor of mortality, even after adjustment for other relevant prognostic factors. The best ipsilateral ONSD cutoff was 5.6mm (sensitivity 72% and specificity 83%) with an AUC of 0.71 (p = 0.02) for predicting mortality at 90 days. CONCLUSION: Optic nerve ultrasound is a noninvasive, bedside, low-cost technique that can be used to identify increased ICP in acute supratentorial primary ICH patients. Among these patients, dilated ONSD is an independent predictor of mortality at 90 days.

ANTECEDENTES: A hemorragia intraparenquimatosa (HIP) aguda apresenta elevada morbimortalidade e a presença de hipertensão intracraniana (HIC) confere um pior prognóstico. OBJETIVO: Avaliamos se a dilatação do diâmetro da bainha do nervo óptico (DBNO) através do ultrassom do nervo óptico (USNO) na admissão hospitalar seria preditora de mortalidade. MéTODOS: Estudo multicêntrico e prospectivo de pacientes consecutivos com HIP supratentorial primária aguda admitidos em dois centros terciários. Ultrassom do nervo óptico e tomografia computadorizada (TC) de crânio foram realizados na admissão e revisados de forma cega. O desfecho primário do estudo foi a mortalidade em 3 meses. Análises de regressão logística, curva de característica de operação do receptor (ROC, na sigla em inglês) e estatística-C foram utilizadas para identificação dos preditores independentes de mortalidade. RESULTADOS: Entre julho de 2014 e julho de 2016, 44 pacientes foram incluídos. A idade média foi 62,3 (±13,1) anos e 12 (27,3%) eram mulheres. Na análise univariada, o volume da HIP na TC de crânio, DBNO ipsilateral à HIP, glicemia, escala de coma de Glasgow (ECG) e NIHSS na admissão hospitalar, e também diabetes mellitus e não-tabagista foram preditores de mortalidade. Após análise multivariada, o DBNO ipsilateral à HIP permaneceu como preditor independente de mortalidade (odds ratio [OR]: 6,24; intervalo de confiança [IC] de 95%: 1,18­33,01; p = 0,03). O melhor ponto de corte do DBNO ipsilateral como preditor de mortalidade em 3 meses foi 5,6mm (sensibilidade 72% e especificidade 83%) e área sob a curva (AUC, na sigla em inglês) 0,71 (p = 0,02). CONCLUSãO: O USNO é um método não-invasivo, beira-leito, de baixo custo, que pode ser empregado para estimar a presença de HIC em pacientes com HIP supratentorial primária aguda. A presença de DBNO dilatada é um preditor independente de mortalidade em 3 meses nesses pacientes.

Cerebral small vessel disease modifies outcomes after minimally invasive surgery for intracerebral haemorrhage.

BACKGROUND: Minimally invasive surgery (MIS) for spontaneous supratentorial intracerebral haemorrhage (ICH) is controversial but may be beneficial if end-of-treatment (EOT) haematoma volume is reduced to ≤15 mL. We explored whether MRI findings of cerebral small vessel disease (CSVD) modify the effect of MIS on long-term outcomes. METHODS: Prespecified blinded subgroup analysis of 288 subjects with qualified imaging sequences from the phase 3 Minimally Invasive Surgery Plus Alteplase for Intracerebral Haemorrhage Evacuation (MISTIE) trial. We tested for heterogeneity in the effects of MIS and MIS+EOT volume ≤15 mL on the trial's primary outcome of good versus poor function at 1 year by the presence of single CSVD features and CSVD scores using multivariable models. RESULTS: Of 499 patients enrolled in MISTIE III, 288 patients had MRI, 149 (51.7%) randomised to MIS and 139 (48.3%) to standard medical care (SMC). Median (IQR) ICH volume was 42 (30-53) mL. In the full MRI cohort, there was no statistically significant heterogeneity in the effects of MIS versus SMC on 1-year outcomes by any specific CSVD feature or by CSVD scores (all Pinteraction >0.05). In 94 MIS patients with EOT ICH volume ≤15 mL, significant reduction in odds of poor outcome was found with cerebral amyloid angiopathy score <2 (OR, 0.14 (0.05-0.42); Pinteraction=0.006), absence of lacunes (OR, 0.37 (0.18-0.80); Pinteraction=0.02) and absence of severe white matter hyperintensities (WMHs) (OR, 0.22 (0.08-0.58); Pinteraction=0.03). CONCLUSIONS: Following successful haematoma reduction by MIS, we found significantly lower odds of poor functional outcome with lower total burden of CSVD in addition to absence of lacunes and severe WMHs. CSVD features may have utility for prognostication and patient selection in clinical trials of MIS.

Intensive Blood Pressure Reduction is Associated with Reduced Hematoma Growth in Fast Bleeding Intracerebral Hemorrhage.

OBJECTIVE: Patients with spontaneous intracerebral hemorrhage (ICH) at the highest risk of hematoma growth are those with the most potential to benefit from anti-expansion treatment. Large clinical trials have not definitively shown a clear benefit of blood pressure (BP) reduction. We aim to determine whether intensive blood pressure reduction could benefit patients with fast bleeding ICH. METHODS: An exploratory analysis of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) randomized controlled trial was performed. In order to capture not just early bleeding (even if a small amount), but the rate of bleeding (ml/hour), we restricted the study to "Fast bleeding ICH," defined as an ICH volume/onset to computed tomography (CT) time >5 ml/hr. Hematoma growth, as defined as an increase of hematoma volume > 33% between baseline and 24 hours. RESULTS: A total of 940 patients were included (mean age = 62.1 years, 61.5% men), of whom 214 (22.8%) experienced hematoma expansion. Of these, 567 (60.3%) met the definition of "fast bleeding" with baseline ICH volume/time to presentation of at least 5 ml/hr. Intensive BP reduction was associated with a significantly lower rate of hematoma growth in fast bleeding patients (20.6% vs 31.0%, p = 0.005). In a subgroup of 266 (46.9%) fast-bleeding patients who received treatment within 2 hours after symptom onset, intensive BP lowering was associated with improved functional independence (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.06-3.69, p = 0.031). INTERPRETATION: Our results suggest that early use of intensive BP reduction may reduce hematoma growth and improve outcome in fast bleeding patients. ANN NEUROL 2023.

Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study.

OBJECTIVE: Functional and morphologic changes in extracranial organs can occur after acute brain injury. The neuroanatomic correlates of such changes are not fully known. Herein, we tested the hypothesis that brain infarcts are associated with cardiac and systemic abnormalities (CSAs) in a regionally specific manner. METHODS: We generated voxelwise p value maps of brain infarcts for poststroke plasma cardiac troponin T (cTnT) elevation, QTc prolongation, in-hospital infection, and acute stress hyperglycemia (ASH) in 1,208 acute ischemic stroke patients prospectively recruited into the Heart-Brain Interactions Study. We examined the relationship between infarct location and CSAs using a permutation-based approach and identified clusters of contiguous voxels associated with p < 0.05. RESULTS: cTnT elevation not attributable to a known cardiac reason was detected in 5.5%, QTc prolongation in the absence of a known provoker in 21.2%, ASH in 33.9%, and poststroke infection in 13.6%. We identified significant, spatially segregated voxel clusters for each CSA. The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were 3 clusters for ASH, the largest of which was in the left hemisphere. We found 2 clusters for poststroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSAs persisted after adjusting for infarct volume. INTERPRETATION: Our results show that there are discrete regions of brain infarcts associated with CSAs. This information could be used to bootstrap toward new markers for better differentiation between neurogenic and non-neurogenic mechanisms of poststroke CSAs. ANN NEUROL 2023;94:1155-1163.

Association Between Hematoma Expansion Severity and Outcome and Its Interaction With Baseline Intracerebral Hemorrhage Volume.

BACKGROUND AND OBJECTIVES: Hematoma expansion (HE) is a major determinant of neurologic deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. We analyzed the prognostic effect of different degrees of HE. METHODS: This was a retrospective analysis of patients with ICH admitted at 8 academic institutions in Italy, Germany, Canada, China, and the United States. All patients underwent baseline and follow-up imaging for HE assessment. Relative HE (rHE) was classified as follows: none (<0%), mild (0%-33%), moderate (33.1%-66%), and severe (>66%). Absolute HE (aHE) was classified as none (<0 mL), mild (0-6.0 mL), moderate (6.1-12.5 mL), and severe (>12.5 mL). Predictors of poor functional outcome (90 days modified Rankin Scale 4-6) were explored with logistic regression. RESULTS: We included 2,163 patients, of whom 1,211 (56.0%) had poor outcome. The occurrence of severe aHE or rHE was more common in patients with unfavorable outcome (13.9% vs 6.5%, p < 0.001 and 18.3% vs 7.2%, p < 0.001 respectively). This association was confirmed in logistic regression (rHE odds ratio [OR] 1.98, 95% CI 1.38-2.82, p < 0.001; aHE OR 1.73, 95% CI 1.23-2.45, p = 0.002) while there was no association between mild or moderate HE and poor outcome. The association between severe HE and poor outcome was significant only in patients with baseline ICH volume below 30 mL. DISCUSSION: The strongest association between HE and outcome was observed in patients with smaller initial volume experiencing severe HE. These findings may inform clinical trial design and guide clinicians in selecting patients for antiexpansion therapies.

Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort).

PURPOSE: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE). METHODS: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS. RESULTS: We included 91 patients with a median (percentile25-percentile75) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001). CONCLUSION: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Mechanistic Implications of Cortical Superficial Siderosis in Patients With Mixed Location Intracerebral Hemorrhage and Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in patients with mixed ICH with cortical superficial siderosis (cSS), a marker strongly associated with CAA. METHODS: Brain MRIs from a prospective database of consecutive patients with nontraumatic ICH admitted to a referral center were reviewed for the presence of CMBs, cSS, and nonhemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces [CSO-EPVS], and multispot white matter hyperintensity [WMH] pattern). The frequencies of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between patients with mixed ICH with cSS (mixed ICH/cSS[+]) and without cSS (mixed ICH/cSS[-]) in univariate and multivariable models. RESULTS: Of 1,791 patients with ICH, 40 had mixed ICH/cSS(+) and 256 had mixed ICH/cSS(-). LVH was less common in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-) (34% vs 59%, p = 0.01). The frequencies of CAA imaging markers, namely multispot pattern (18% vs 4%, p < 0.01) and severe CSO-EPVS (33% vs 11%, p < 0.01), were higher in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-). In a logistic regression model, older age (adjusted odds ratio [aOR] 1.04 per year, 95% CI 1.00-1.07, p = 0.04), lack of LVH (aOR 0.41, 95% CI 0.19-0.89, p = 0.02), multispot WMH pattern (aOR 5.25, 95% CI 1.63-16.94, p = 0.01), and severe CSO-EPVS (aOR 4.24, 95% CI 1.78-10.13, p < 0.01) were independently associated with mixed ICH/cSS(+) after further adjustment for hypertension and coronary artery disease. Among ICH survivors, the adjusted hazard ratio of ICH recurrence in patients with mixed ICH/cSS(+) was 4.65 (95% CI 1.38-11.38, p < 0.01) compared with that in patients with mixed ICH/cSS(-). DISCUSSION: The underlying microangiopathy of mixed ICH/cSS(+) likely includes both HTN-cSVD and CAA, whereas mixed ICH/cSS(-) is likely driven by HTN-cSVD. These imaging-based classifications can be important to stratify ICH risk but warrant confirmation in studies incorporating advanced imaging/pathology.

Creating conservation strategies with value-focused thinking.

Biodiversity and human well-being strategies are only as good as the set of ideas people think about. We evaluated value-focused thinking (VFT), a framework that emphasizes creating objectives and strategies that are responsive to the objectives. We performed a proof-of-concept study of VFT with 6 conservation planning teams at a global conservation organization. We developed a package of materials related to VFT, including meeting-session agendas, a virtual facilitation template, facilitator's guide, and evaluation questionnaires. We used these materials to test whether VFT applied in a group setting resulted in high-quality conservation strategies and participant satisfaction and whether our materials were scalable, meaning that someone newly trained in VFT could facilitate planning meetings that resulted in high-quality strategies and participant satisfaction, as compared with an experienced VFT facilitator. Net response indicated positive compelling, feasible, creative, and representative ratings for the conservation strategies per team. Participants indicated satisfaction overall, although satisfaction was greater for objectives than for strategies. Among the participants with previous conservation planning experience, all were at least as satisfied with their VFT strategies compared with previously developed strategies, and none were less satisfied (p = 0.001). Changes in participant satisfaction were not related to facilitator type (experienced or inexperienced with VFT) (p > 0.10). Some participants had a preconceived sense of shared understanding of important values and interests before participating in the study, which VFT strengthened. Our results highlight the advantages of structuring the development and evaluation of conservation planning frameworks around VFT.

Creación de estrategias de conservación con el pensamiento orientado a valores Resumen Las estrategias para la biodiversidad y el bienestar humano son tan buenas como el conjunto de ideas en el que piensan las personas. Evaluamos el pensamiento orientado a valores (POV), un marco que promueve la creación de objetivos y estrategias responsivas a los objetivos. Realizamos un estudio de prueba de concepto del POV con seis equipos de planeación de la conservación en una organización mundial de conservación. Desarrollamos un paquete de materiales relacionado con el POV que incluyó orden del día de las reuniones, una plantilla de asesoramiento virtual, una guía para el facilitador y cuestionarios de evaluación. Usamos estos materiales para probar si el POV aplicado en un entorno de grupo da como resultado estrategias de conservación de gran calidad y la satisfacción de los participantes. También probamos si nuestros materiales podían ampliarse, es decir, si alguien con entrenamiento reciente de POV podría facilitar la planeación de reuniones para que resultaran en estrategias de gran calidad y la satisfacción de los participantes en comparación con un facilitador experimentado. Por equipo, la respuesta neta indicó calificaciones positivas, convincentes, factibles, creativas y representativas para las estrategias de conservación. Los participantes indicaron una satisfacción generalizada, aunque ésta fue mayor para los objetivos que para las estrategias. Entre los participantes con experiencia previa en la planeación de la conservación, todos estuvieron satisfechos al menos con sus estrategias de POV en comparación con las estrategias previas y ninguno estuvo menos satisfecho (p= 0.001). Los cambios en la satisfacción de los participantes no estuvieron relacionados con el tipo de facilitador (con o sin experiencia en POV) (p> 0.10). Antes de participar en el estudio, algunos participantes ya tenían un sentido preconcebido del entendimiento compartido de los valores e intereses importantes, lo que el POV fortaleció. Nuestros resultados resaltan las ventajas de la estructuración del desarrollo y la evaluación en torno al POV de los marcos de planeación de la conservación.