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Objective: Hematoma expansion (HE) predicts disability and death after acute intracerebral hemorrhage (ICH). Aspirin and anticoagulants have been associated with HE. We tested the hypothesis that P2Y12 inhibitors predict subsequent HE in patients. We explored laboratory measures of P2Y12 inhibition and dual antiplatelet therapy with aspirin (DAPT)., Methods: We prospectively identified patients with ICH. Platelet activity was measured with the VerifyNow-P2Y12 assay. Hematoma volumes for initial and follow-up CTs were calculated using a validated semi-automated technique. HE was defined as the difference between hematoma volumes on the initial and follow-up CT scans. Nonparametric statistics were performed with Kruskal-Wallis H, and correction for multiple comparisons performed with Dunn's test., Results: In 194 patients, 15 (7.7%) were known to take a P2Y12 inhibitor (clopidogrel in all but one). Patients taking a P2Y12 inhibitor had more HE compared to patients not taking a P2Y12 inhibitor (3.5 [1.2-11.9] vs. 0.1 [-0.8-1.4] mL, p = 0.004). Patients taking DAPT experienced the most HE (7.2 [2.6-13.8] vs. 0.0 [-1.0-1.1] mL, p = 0.04). The use of P2Y12 inhibitors was associated with less P2Y12 activity (178 [149-203] vs. 288 [246-319] P2Y12 reaction units, p = 0.005)., Interpretation: Patients taking a P2Y12 inhibitor had more HE and less P2Y12 activity. The effect was most pronounced in patients on DAPT, suggesting a synergistic effect of P2Y12 inhibitors and aspirin with respect to HE. Acute reversal of P2Y12 inhibitors in acute ICH requires further study., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Seizures are a harmful complication of acute intracerebral hemorrhage (ICH). "Early" seizures in the first week after ICH are a risk factor for deterioration, later seizures, and herniation. Ideally, seizure medications after ICH would only be administered to patients with a high likelihood to have seizures. We developed and validated machine learning (ML) models to predict early seizures after ICH., Methods: We used two large datasets to train and then validate our models in an entirely independent test set. The first model ("CAV") predicted early seizures from a subset of variables of the CAVE score (a prediction rule for later seizures)-cortical hematoma location, age less than 65 years, and hematoma volume greater than 10 mL-whereas early seizure was the dependent variable. We attempted to improve on the "CAV" model by adding anticoagulant use, antiplatelet use, Glasgow Coma Scale, international normalized ratio, and systolic blood pressure ("CAV + "). For each model we used logistic regression, lasso regression, support vector machines, boosted trees (Xgboost), and random forest models. Final model performance was reported as the area under the receiver operating characteristic curve (AUC) using receiver operating characteristic models for the test data. The setting of the study was two large academic institutions: institution 1, 634 patients; institution 2, 230 patients. There were no interventions., Results: Early seizures were predicted across the ML models by the CAV score in test data, (AUC 0.72, 95% confidence interval 0.62-0.82). The ML model that predicted early seizure better in the test data was Xgboost (AUC 0.79, 95% confidence interval 0.71-0.87, p = 0.04) compared with the CAV model AUC., Conclusions: Early seizures after ICH are predictable. Models using cortical hematoma location, age less than 65 years, and hematoma volume greater than 10 mL had a good accuracy rate, and performance improved with more independent variables. Additional methods to predict seizures could improve patient selection for monitoring and prophylactic seizure medications., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: To test the hypothesis that appearances of intracranial hematomas on diagnostic computed tomography (CT) are not idiosyncratic and reflect a biologically plausible mechanism, we evaluated the association between hematoma appearance on CT, biomarkers of platelet activity, and antiplatelet or anticoagulant medication use prior to admission., Methods: We studied 330 consecutively identified patients from 2006 to 2019. Biomarkers of platelet activity (platelet aspirin assay) and medication history (aspirin, clopidogrel) were prospectively recorded on admission. A blinded interpreter recorded the presence of hematoma appearances from the diagnostic scan. Associations were tested with parametric or nonparametric statistics, as appropriate., Results: The black hole sign (101, 30%) was most prevalent, followed by the island sign (57, 17%) and blend sign (32, 10%). There was reduced platelet activity in patients with a black hole sign (511 [430-610] vs. 562 [472-628] aspirin reaction units, P = 0.01) or island sign (505 [434-574] vs. 559 [462-629] aspirin reaction units, P = 0.004). Clopidogrel use prior to admission was associated with the black hole sign (odds ratio 2.25, 95% confidence interval 1.02-4.98, P = 0.04)., Conclusions: In patients with acute intracerebral hemorrhage, hematoma appearances on CT are associated with biomarkers of platelet activity and clopidogrel use prior to admission. Appearances of intracranial hematomas on CT may reflect reduced hemostasis from antiplatelet medication use., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objectives: Early seizures are a common complication of intracerebral hemorrhage, occurring in ~10% of patients. However, the independent effect of early seizures on patient outcomes, particularly health-related quality of life, is unclear. Without a potential benefit to patient outcomes, the widespread use (~40%) of prophylactic seizure medications has no reasonable chance of improving patient outcomes. We tested the hypothesis that health-related quality of life at follow-up is different between patients with and without early seizures (and secondarily, with nonconvulsive status epilepticus) after intracerebral hemorrhage., Design: Patients with intracerebral hemorrhage were enrolled in an observational cohort study that prospectively collected clinical data and health-related quality of life at follow-up., Setting: Academic medical center., Patients: One-hundred thirty-three patients whose health-related quality of life was assessed 3 months after intracerebral hemorrhage onset., Measurements and Main Results: Health-related quality of life was obtained at 3 months after intracerebral hemorrhage onset. T Scores of health-related quality of life were modeled with multivariable linear models accounting for severity with the intracerebral hemorrhage Score and hematoma location. Health-related quality of life was measured with National Institutes of Health Patient Reported Outcomes Measurement Information System/Neuroquality of life, expressed in T Scores (U.S. normal 50 ± 10). The modified Rankin Scale (a global measure) was a secondary outcome. There were 12 patients (9%) with early seizures. T Scores of health-related quality of life at follow-up were lower (worse) in patients with early seizure compared with patients without an early seizure (44 [32.75-51.85] vs 30.25 [18.9-39.15]; p = 0.04); results for other domains of health-related quality of life were similar. The association persisted in multivariable models. There was no association between early seizures and prophylactic seizure medications (p = 0.4). Results for patients with nonconvulsive status epilepticus were similar. There was no association between early seizures and the modified Rankin Scale at 3 months., Conclusions: Early seizures and nonconvulsive status epilepticus were associated with lower health-related quality of life at follow-up in survivors of intracerebral hemorrhage., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes.

Background/objective: Demonstrating a benefit of acute treatment to patients with intracerebral hemorrhage (ICH) requires identifying which patients have a potentially modifiable outcome, where treatment could favorably shift a patient's expected outcome. A decision rule for which patients have a modifiable outcome could improve the targeting of treatments. We sought to determine which patients with ICH have a modifiable outcome., Methods: Patients with ICH were prospectively identified at two institutions. Data on hematoma volumes, medication histories, and other variables of interest were collected. ICH outcomes were evaluated using the modified Rankin Scale (mRS), assessed at 14 days and 3 months after ICH, with "good outcome" defined as 0-3 (independence or better) and "poor outcome" defined as 4-6 (dependence or worse). Supervised machine learning models identified the best predictors of good versus poor outcomes at Institution 1. Models were validated using repeated fivefold cross-validation as well as testing on the entirely independent sample at Institution 2. Model fit was assessed with area under the ROC curve (AUC)., Results: Model performance at Institution 1 was strong for both 14-day (AUC of 0.79 [0.77, 0.81] for decision tree, 0.85 [0.84, 0.87] for random forest) and 3 month (AUC of 0.75 [0.73, 0.77] for decision tree, 0.82 [0.80, 0.84] for random forest) outcomes. Independent predictors of functional outcome selected by the algorithms as important included hematoma volume at hospital admission, hematoma expansion, intraventricular hemorrhage, overall ICH Score, and Glasgow Coma Scale. Hematoma expansion was the only potentially modifiable independent predictor of outcome and was compatible with "good" or "poor" outcome in a subset of patients with low hematoma volumes, good Glasgow Coma scale and premorbid modified Rankin Scale scores. Models trained on harmonized data also predicted patient outcomes well at Institution 2 using decision tree (AUC 0.69 [0.63, 0.75]) and random forests (AUC 0.78 [0.72, 0.84])., Conclusions: Patient outcomes are predictable to a high level in patients with ICH, and hematoma expansion is the sole-modifiable predictor of these outcomes across two outcome types and modeling approaches. According to decision tree analyses predicting outcome at 3 months, patients with a high Glasgow Coma Scale score, less than 44.5 mL hematoma volume at admission, and relatively low premorbid modified Rankin Score in particular have a modifiable outcome and appear to be candidates for future interventions to improve outcomes after ICH.

Background: An association between spontaneous hyperventilation, delayed cerebral ischemia, and poor clinical outcomes has been reported in subarachnoid hemorrhage. We evaluated the relationship between early pCO 2 changes, ischemic lesions and outcomes in patients with intracerebral hemorrhage (ICH)., Methods: Consecutive patients with spontaneous ICH were enrolled in an observational cohort study conducted between 2006 and 2019. Patient characteristics and discharge outcome were prospectively recorded. Arterial blood gas (ABG) measurements and mechanical ventilation settings in the first 72 h of admission were retrospectively collected. MRI images were adjudicated for diffusion-restricted lesions consistent with ischemia and distant from the hematoma. We examined the associations between pCO 2 changes, ischemic lesions, and discharge outcomes by univariate and adjusted analyses., Results: ABG data were available for 220 patients. Hyperventilation occurred in 52 (28%) cases and was not associated with clinical severity. Lower initial pCO 2 was associated with greater risk of in-hospital death (OR 0.94 per mmHg, 95%CI [0.89, 0.996], p = 0.042) after adjustment for ICH Score, pneumonia and mechanical ventilation requirements. MRI data were available for 33 patients. Lower pCO 2 was associated with a higher risk of ischemic lesions, except in patients with low initial systolic blood pressure (p < 0.05 for main and blood pressure interaction effects), after adjustment for other predictors., Conclusions: In ICH patients with spontaneous ventilation, lower pCO 2 was independently associated with greater risk of in-hospital death. In patients with elevated initial blood pressure, who undergo blood pressure reduction per guideline recommendations, lower pCO 2 was associated with increased risk to develop ischemic lesions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Hemorrhages are a serious complication of brain surgery, and magnesium has shown hemostatic properties in hemorrhagic stroke and non-neurological surgeries. External ventricular drain (EVD) insertion is an advantageous model of emergency neurosurgical hemorrhage risk because it is common, standardized, and the operator is blinded to the outcome during the procedure. We tested the hypothesis that low magnesium is associated with risk of hemorrhagic complications from EVD insertion., Methods: Patients with spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage were enrolled in a prospective, observational study. Demographic and clinical variables were prospectively recorded, including serum magnesium measurements. Catheter tract hemorrhage (CTH) was measured on postoperative head computed tomography within 48 hours of EVD insertion., Results: We observed 50 CTH among 327 EVD procedures (15.3%) distributed similarly among intracerebral hemorrhage (21/116 [18.1%]) and subarachnoid hemorrhage (29/211 [13.7%]). Magnesium was lower in patients with CTH compared with those without (median 1.8 versus 2.0 mg/dL, P <0.0001). Higher magnesium was associated with lower odds of CTH (odds ratio 0.67 per 0.1 mg/dL magnesium [95% CI, 0.56-0.78], P <0.0001) after adjustment for other risk factors, with similar effect in the intracerebral hemorrhage and subarachnoid hemorrhage subgroups. Preprocedural increase in magnesium (odds ratio 0.68 [0.52-0.85]) and dose of preprocedural magnesium sulfate (odds ratio 0.67 [0.40-0.97]) were associated with reduced CTH risk after adjustment for initial magnesium and other risk factors., Conclusions: Lower magnesium at the time of EVD insertion was an independent predictor of hemorrhagic complications. Baseline risk was attenuated by preprocedural increases in magnesium, suggesting a therapeutic opportunity.

Objectives: The circadian system modulates many important physiologic processes, synchronizing tissue-specific functions throughout the body. We sought to characterize acute alterations of circadian rhythms in critically ill patients and to evaluate associations between brain dysfunction, systemic multiple organ dysfunction, environmental stimuli that entrain the circadian rhythm (zeitgebers), rest-activity rhythms, and the central circadian rhythm-controlled melatonin secretion profile., Design: Prospective study observing a cohort for 24-48 hours beginning within the first day of ICU admission., Setting: Multiple specialized ICUs within an academic medical center., Patients: Patients presenting from the community with acute onset of either intracerebral hemorrhage as a representative neurologic critical illness or sepsis as a representative systemic critical illness. Healthy control patients were studied in using modified constant routine in a clinical research unit., Interventions: None., Measurements and Main Results: Light, feeding, activity, medications, and other treatment exposures were evaluated along with validated measures of encephalopathy (Glasgow Coma Scale), multiple organ system function (Sequential Organ Failure Assessment score), and circadian rhythms (profiles of serum melatonin and its urinary metabolite 6-sulphatoxymelatonin). We studied 112 critically ill patients, including 53 with sepsis and 59 with intracerebral hemorrhage. Environmental exposures were abnormal, including light (dim), nutritional intake (reduced or absent and mistimed), and arousal stimuli (increased and mistimed). Melatonin amplitude and acrophase timing were generally preserved in awake patients but dampened and delayed with increasing encephalopathy severity. Melatonin hypersecretion was observed in patients exposed to catecholamine vasopressor infusions, but unaffected by sedatives. Change in vasopressor exposure was the only factor associated with changes in melatonin rhythms between days 1 and 2., Conclusions: Encephalopathy severity and adrenergic agonist medication exposure were the primary factors contributing to abnormal melatonin rhythms. Improvements in encephalopathy and medical stabilization did not rapidly normalize rhythms. Urinary 6-sulphatoxymelatonin is not a reliable measure of the central circadian rhythm in critically ill patients.

Background: Seizures are a morbid complication of intracerebral hemorrhage (ICH) and increase the risk for herniation, status epilepticus, and worse patient outcomes. Prophylactic levetiracetam is administered to approximately 40% of patients with ICH. It is unclear which patients are consciously selected for treatment by physicians. We sought to determine how patients are selected for treatment with prophylactic levetiracetam after ICH., Methods: We administered an adaptive conjoint analysis using decision making software to an NIH Stroke Trials Network Working Group. The adaptive conjoint analysis determines the most influential attributes for making a decision in an iterative, algorithm-driven process. We asked respondents which would most influence a decision to administer prophylactic levetiracetam. The attributes and their levels were taken from published phenotypes associated with prophylactic seizure medications and the likelihood of seizures after ICH: hematoma location (lobar or basal ganglia), hematoma volume (<=10 mL or >10 mL), level of consciousness (Glasgow Coma Scale 5-12 or Glasgow Coma Scale 13-15), age (<65 or ≥65 years), and race (White or Caucasian or Black/African American). The algorithm terminated when the attributes were ranked from most to least influential., Results: The study sample included 27 respondents who completed the adaptive conjoint analysis out of 42 who responded to the survey with a mean age of 43.4 ± 9.4 years. The attribute with the greatest weight was hematoma location (30%), followed by reduced level of consciousness (24%), hematoma volume (19%), race (14%), and age (13%). Ranks of attributes were different (P < .001)., Conclusions: The decision to administer prophylactic levetiracetam to patients with ICH is driven by lobar hematoma location and depressed level of consciousness. Future research on prophylactic seizure medication could focus on patients most likely to receive it., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Spontaneous intracerebral hemorrhage is a disabling form of stroke, and some patients will require nutritional interventions for dysphagia. We sought to determine if socioeconomic status indicators mediate whether minorities undergo gastrostomy tube placement., Materials and Methods: Patients with spontaneous intracerebral hemorrhage were enrolled in a single center, observational cohort study from 2010 to 2017. A socioeconomic index score was imputed using neighborhood characteristics by patients' ZIP code, according to an established method utilizing 6 indicators of wealth/income, education, and occupation. Multivariable logistic regression models were generated and stratified by racial/ethnic groups to determine the association of socioeconomic status with gastrostomy tube placement., Results: Among 512 patients, 93 (18.2%) underwent gastrostomy tube placement. There were 245 Whites, 220 Blacks, and 47 Hispanic. Blacks underwent the highest percentage of gastrostomy placement (22.7%), and Whites had the lowest percentage (13.5%). Among patients with gastrostomy, Blacks and Hispanics had lowest median socioeconomic index (-2.1 [IQR: -3.0, .7]; .7 [IQR: -1.6, 2.9], respectively, P < .001). Increasing intracerebral hemorrhage score was correlated with higher odds of gastrostomy across all groups (P values ≤ .01) but only Hispanics had reduced adjusted odds of gastrostomy with increasing socioeconomic index (OR .56; 95% .33-.84; P = .01)., Discussion: Racial/ethnic minorities had lower socioeconomic index and underwent more gastrostomy placement. Socioeconomic index was independently associated with gastrostomy only in Hispanics, in whom the odds of gastrostomy decreased with increasing socioeconomic index. Summary & Conclusion: Differences in utilization of gastrostomy were evident among minorities, and socioeconomic status may mediate this relationship among Hispanics., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aim: Performance measures have been extensively studied for acute ischemic stroke, leading to guideline-established benchmarks. Factors influencing care efficiency for intracerebral hemorrhage (ICH) are not well delineated. We sought to identify factors associated with early recognition of ICH and to assess the association between early recognition and completion of emergency care tasks., Methods: Consecutive patients with spontaneous ICH were enrolled in an observational cohort study conducted from 2009 to 2017 at an urban comprehensive stroke center, excluding patient transferred from other hospitals. We used stroke team activation as the indicator of early recognition and measured completion times for multiple ICH-relevant performance metrics including door to computed tomography (CT) acquisition and door to hemostatic medication initiation., Results: We studied 204 cases. All stroke-related performance times were faster in patients managed with stroke team activation compared to no activation, including quicker door to CT acquisition (median 24 versus 48 minutes, P < .001) and door to hemostatic medication initiation (63 versus 99 minutes, P = .005). These associations were confirmed in adjusted models. Stroke codes were activated in 43% of cases and were more likely in patients with shorter onset-to-arrival times, higher National Institutes of Health Stroke Scale scores, and higher Glasgow Coma Scale scores., Conclusions: Stroke team activation was associated with more rapid diagnostic and therapeutic interventions for patients with ICH, but activation did not occur in the majority of cases, implying absence of early recognition. A stroke team activation process improves care performance, but leveraging the advantages of existing systems will require improved triage tools to identify ICH in the acute setting., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To compare the clinical characteristics and outcomes of primary intracerebral hemorrhage (ICH) with and without methamphetamine exposure., Methods: We performed a retrospective analysis of patients diagnosed with spontaneous, nontraumatic ICH over a 3-year period between January 2013 and December 2016. Demographics, clinical measures, and outcomes were compared between ICH patients with positive methamphetamine toxicology tests vs those with negative methamphetamine toxicology tests., Results: Methamphetamine-positive ICH patients were younger than methamphetamine-negative ICH patients (52 vs 67 years, p < 0.001). Patients with methamphetamine-positive ICH had higher diastolic blood pressure (115 vs 101, p = 0.003), higher mean arterial pressure (144 vs 129, p = 0.01), longer lengths of hospital (18 vs 8 days, p < 0.001) and intensive care unit (ICU) stay (10 vs 5 days, p < 0.001), required more days of IV antihypertensive medications (5 vs 3 days, p = 0.02), and had more subcortical hemorrhages (63% vs 46%, p = 0.05). The methamphetamine-positive group had better premorbid modified Rankin Scale (mRS) scores ( p < 0.001) and a greater change in functional ability as measured by mRS at the time of hospital discharge ( p = 0.001). In multivariate analyses, methamphetamine use predicted both hospital length of stay (risk ratio [RR] 1.54, confidence interval [CI] 1.39-1.70, p < 0.001) and ICU length of stay (RR 1.36, CI 1.18-1.56, p < 0.001), but did not predict poor outcome (mRS 4-6)., Conclusions: Methamphetamine use is associated with earlier age at onset of ICH, longer hospital stays, and greater change in functional ability, but did not predict outcome., (© 2019 American Academy of Neurology.)

Background: Fever is associated with worse outcome after intracerebral hemorrhage (ICH). Autonomic dysfunction, commonly seen after brain injury, results in reduced heart rate variability (HRV). We sought to investigate whether HRV was associated with the development of fever in patients with ICH., Methods: We prospectively enrolled consecutive patients with spontaneous ICH in a single-center observational study. We included patients who presented directly to our emergency department after symptom onset, had a 10-second electrocardiogram (EKG) performed within 24 h of admission, and were in sinus rhythm. Patient temperature was recorded every 1-4 h. We defined being febrile as having a temperature of ≥ 38 °C within the first 14 days, and fever burden as the number of febrile days. HRV was defined by the standard deviation of the R-R interval (SDNN) measured on the admission EKG. Univariate associations were determined by Fisher's exact, Mann-Whitney U, or Spearman's rho correlation tests. Variables associated with fever at p ≤ 0.2 were entered in a logistic regression model of being febrile within 14 days., Results: There were 248 patients (median age 63 [54-74] years, 125 [50.4%] female, median ICH Score 1 [0-2]) who met the inclusion criteria. Febrile patients had lower HRV (median SDNN: 1.72 [1.08-3.60] vs. 2.55 [1.58-5.72] msec, p = 0.001). Lower HRV was associated with more febrile days (R = - 0.22, p < 0.001). After adjustment, lower HRV was independently associated with greater odds of fever occurrence (OR 0.92 [95% CI 0.87-0.97] with each msec increase in SDNN, p = 0.002)., Conclusions: HRV measured on 10-second EKGs is a potential early marker of parasympathetic nervous system dysfunction and is associated with subsequent fever occurrence after ICH. Detecting early parasympathetic dysfunction may afford opportunities to improve ICH outcome by targeting therapies at fever prevention.

Background: Gastrostomy placement after intracerebral hemorrhage indicates the need for continued medical care and predicts patient dependence. Our objective was to determine the optimal machine learning technique to predict gastrostomy., Methods: We included 531 patients in a derivation cohort and 189 patients from another institution for testing. We derived and tested predictions of the likelihood of gastrostomy placement with logistic regression using the GRAVo score (composed of Glasgow Coma Scale ≤12, age >50 years, black race, and hematoma volume >30 mL), compared to other machine learning techniques (kth nearest neighbor, support vector machines, random forests, extreme gradient boosting, gradient boosting machine, stacking). Receiver Operating Curves (Area Under the Curve, [AUC]) between logistic regression (the technique used in GRAVo score development) and other machine learning techniques were compared. Another institution provided an external test data set., Results: In the external test data set, logistic regression using the GRAVo score components predicted gastrostomy (P < 0.001), however, with a lower AUC (0.66) than kth nearest neighbors (AUC 0.73), random forests (AUC 0.74), Gradient boosting machine (AUC 0.77), extreme gradient boosting (AUC 0.77), (P < 0.01 for all compared to logistic regression). Results from the internal test set were similar., Conclusions: Machine learning techniques other than logistic regression (eg, random forests, extreme gradient boost, and kth nearest neighbors) were significantly more accurate for predicting gastrostomy using the same independent variables. Machine learning techniques may assist clinicians in identifying patients likely to need interventions., (Copyright © 2018. Published by Elsevier Inc.)

Background: Fever is associated with worse functional outcomes after intracerebral hemorrhage (ICH); however, there are few prospective data to quantify the relationship with health-related quality of life (HRQoL). We tested the hypothesis that increased burden of fever is independently associated with decreased HRQoL at follow-up., Methods: In this prospective observational cohort study of 106 ICH patients admitted to a tertiary care hospital between 2011 and 2015, we recorded the highest core temperature each calendar day for 14 days after ICH onset. Fever burden was defined as the number of days with a fever ≥ 100.4 °F (38 °C). HRQoL outcomes were measured with Neuro-QoL domains of Cognitive Function and Mobility at 28 days, 3 months, and 1 year. Results were analyzed using mixed effects regression analysis., Results: Each additional day with a fever was independently associated with lower Mobility HRQoL (T-score - 0.9, [- 1.6 to - 0.2]; p = 0.01) and Cognitive Function HRQoL (T-score - 1.3 [- 2.0 to - 0.6]; p = 0.001) after correction for National Institutes of Health Stroke Scale score on admission, age, and time to follow-up., Conclusions: Each additional day with a fever was predictive of worse HRQoL domains of Cognitive Function and Mobility after ICH up to 1 year. These data extend previous evidence on the negative association of fever and functional outcomes to the domains of Cognitive Function and Mobility HRQoL. HRQoL outcomes may be a sensitive and powerful way to measure the efficacy of fever control in future research.

Objective: We tested the hypothesis that the maximally treated intracerebral hemorrhage (max-ICH) score is superior to the ICH score for characterizing mortality and functional outcome prognosis in patients with ICH, particularly those who receive maximal treatment., Methods: Patients presenting with spontaneous ICH were enrolled in a prospective observational study that collected demographic and clinical data. Mortality and functional outcomes were measured by using the modified Rankin Scale at 3 months. The ICH score and max-ICH score incorporate measures of symptom severity, age, hematoma volume, hematoma location, and intraventricular hemorrhage, with the max-ICH score also including a term for oral anticoagulation and having 16 score categories vs 11 for the ICH score. We compared the area under the receiver operating characteristic curve (AUC) for the ICH score and max-ICH score for both mortality and poor functional outcome, defined as modified Rankin Scale scores 4-6., Results: We analyzed outcomes for 372 patients, including 71 patients (19%) in whom care limitation/withdrawal of life support was instituted. Both the ICH score and max-ICH score showed good prognostic performance for 3-month mortality and poor functional outcomes in the full group as well as the subgroup with maximal treatment (i.e., no care limitations; AUC range 0.80-0.86), with no significant difference in AUC between the scores for either endpoint in either group., Conclusions: External validation with direct comparison of the ICH score and max-ICH score shows that their prognostic performance is not meaningfully different. Alternatives to simple scores are likely needed to improve prognostic estimates for patient care decisions., (© 2018 American Academy of Neurology.)

Objectives: Prophylactic levetiracetam is currently used in ~40% of patients with intracerebral hemorrhage, and the potential impact of levetircetam on health-related quality of life is unknown. We tested the hypothesis that prophylactic levetiracetam is independently associated with differences in cognitive function health-related quality of life., Design: Patients with intracerebral hemorrhage were enrolled in a prospective cohort study. We performed mixed models for T-scores of health-related quality of life, referenced to the U.S. population at 50 ± 10, accounting for severity of injury and time to follow-up., Setting: Academic medical center., Patients: One-hundred forty-two survivors of intracerebral hemorrhage., Interventions: None., Measurements and Main Results: T-scores of Neuro-Quality of Life Cognitive Function v2.0 was the primary outcome, whereas Neuro-Quality of Life Mobility v1.0 and modified Rankin Scale (a global functional scale) were secondary measures. We prospectively documented if prophylactic levetiracetam was administered and retrieved administration data from the electronic health record. Patients who received prophylactic levetiracetam had worse cognitive function health-related quality of life (T-score 5.1 points lower; p = 0.01) after adjustment for age (p = 0.3), National Institutes of Health Stroke Scale (p < 0.000001), lobar hematoma (p = 0.9), and time of assessment; statistical models controlling for prophylactic levetiracetam and the Intracerebral Hemorrhage Score, a global measure of intracerebral hemorrhage severity, yielded similar results. Lower T-scores of cognitive function health-related quality of life at 3 months were correlated with more total levetiracetam dosage (p = 0.01) and more administered doses of levetiracetam in the hospital (p = 0.03). Patients who received prophylactic levetiracetam were more likely to have a lobar hematoma (27/38 vs 19/104; p < 0.001), undergo electroencephalography monitoring (15/38 vs 21/104; p = 0.02), but not more likely to have clinical seizures (4/38 vs 7/104; p = 0.5). Levetiracetam was not independently associated with the modified Rankin Scale scores or mobility health-related quality of life (p > 0.1)., Conclusions: Prophylactic levetiracetam was independently associated with lower cognitive function health-related quality of life at follow-up after intracerebral hemorrhage.

Objective: We evaluated whether reduced platelet activity detected by point-of-care (POC) testing is a better predictor of hematoma expansion and poor functional outcomes in patients with intracerebral hemorrhage (ICH) than a history of antiplatelet medication exposure., Methods: Patients presenting with spontaneous ICH were enrolled in a prospective observational cohort study that collected demographic, clinical, laboratory, and radiographic data. We measured platelet activity using the PFA-100 (Siemens AG, Germany) and VerifyNow-ASA (Accumetrics, CA) systems on admission. We performed univariate and adjusted multivariate analyses to assess the strength of association between those measures and (1) hematoma growth at 24 hours and (2) functional outcomes measured by the modified Rankin Scale (mRS) at 3 months., Results: We identified 278 patients for analysis (mean age 65 ± 15, median ICH score 1 [interquartile range 0-2]), among whom 164 underwent initial neuroimaging within 6 hours of symptom onset. Univariate association with hematoma growth was stronger for antiplatelet medication history than POC measures, which was confirmed in multivariable models (β 3.64 [95% confidence interval [CI] 1.02-6.26], P = .007), with a larger effect size measured in the under 6-hour subgroup (β 7.20 [95% CI 3.35-11.1], P < .001). Moreover, antiplatelet medication history, but not POC measures of platelet activity, was independently associated with poor outcome at 3 months (mRS 4-6) in the under 6-hour subgroup (adjusted OR 3.6 [95% CI 1.2-11], P = .023)., Conclusion: A history of antiplatelet medication use better identifies patients at risk for hematoma growth and poor functional outcomes than POC measures of platelet activity after spontaneous ICH., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH)., Methods: Patients presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months., Results: We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate ( p = 0.02), parsimoniously adjusted ( p = 0.002), and fully adjusted models ( p = 0.006), as well as greater hematoma growth ( p = 0.004, p = 0.005, and p = 0.008, respectively) and larger final hematoma volumes ( p = 0.02, p = 0.001, and p = 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64, p = 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth., Conclusions: These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH., (© 2017 American Academy of Neurology.)

Background and Purpose: We investigated potential disparities in the use of prophylactic seizure medications in patients with intracerebral hemorrhage., Methods: Review of multicenter electronic health record (EHR) data with simultaneous prospective data recording. EHR data were retrieved from HealthLNK, a multicenter EHR repository in Chicago, Illinois, from 2006 to 2012 (multicenter cohort). Additional data were prospectively coded (single-center cohort) from 2007 through 2015., Results: The multicenter cohort comprised 3422 patients from 4 HealthLNK centers. Use of levetiracetam varied by race/ethnicity ( P =0.0000008), with whites nearly twice as likely as blacks to be administered levetiracetam (odds ratio: 1.71; 95% confidence interval, 1.43-2.05; P <0.0001). In the single-center cohort (n=450), hematoma location, older age, depressed consciousness, larger hematoma volume, no alcohol abuse, and race/ethnicity were associated with levetiracetam administration ( P ≤0.04). Whites were nearly twice as likely as blacks to receive levetiracetam (odds ratio: 1.9; 95% confidence interval, 1.25-2.89; P =0.002); however, the association was confounded by history of hypertension, higher blood pressure on admission, and deep hematoma location. Only hematoma location was independently associated with levetiracetam administration ( P <0.00001), rendering other variables, including race/ethnicity, nonsignificant., Conclusions: Although multicenter EHR data showed apparent racial/ethnic disparities in the use of prophylactic seizure medications, a more complete single-center cohort found the apparent disparity to be confounded by the clinical factors of hypertension and hematoma location. Disparities in care after intracerebral hemorrhage are common; however, administrative data may lead to the discovery of disparities that are confounded by detailed clinical data not readily available in EHRs., (© 2017 American Heart Association, Inc.)

Objective: Prophylactic medications can be a source of preventable harm, potentially affecting large numbers of patients. Few data exist about how clinicians change prescribing practices in response to new data and revisions to guidelines about preventable harm from a prophylactic medication. We sought to determine the changes in prescribing practice of seizure medications for patients with intracerebral hemorrhage (ICH) across a metropolitan area before and after new outcomes data and revised prescribing guidelines were published., Methods: We conducted an observational study using electronic medical record data from 4 academic medical centers in a large US metropolitan area., Results: A total of 3,422 patients with ICH, diagnosed between 2007 and 2012, were included. In 2009, after a publication found an association of phenytoin with higher odds of dependence or death, the use of phenytoin declined from 9.6% in 2009 to 2.2% in 2012 (p < 0.00001). Conversely, the use of levetiracetam more than doubled, from 15.1% in 2007 to 35% in 2012 (p < 0.00001). Use of levetiracetam varied among the 4 institutions from 6.7% to 29.8% (p < 0.00001)., Conclusions: New data that led to revised prescribing guidelines for prophylactic seizure medications for patients with ICH were temporally associated with a significant decrease in use of the medication, potentially reducing adverse outcomes. However, a corresponding increase in the use of an alternative medication, levetiracetam, occurred despite limited knowledge about its potential effects on outcomes. Future guideline changes should anticipate and address alternatives., (© 2016 American Academy of Neurology.)

Background: Delirium predicts higher long-term cognitive morbidity. We previously identified a cohort of patients with spontaneous intracerebral hemorrhage and delirium and found worse outcomes in health-related quality of life (HRQoL) in the domain of cognitive function., Objective: We tested the hypothesis that agitation would have additional prognostic significance on later cognitive function HRQoL., Methods: Prospective identification of 174 patients with acute intracerebral hemorrhage, measuring stroke severity, agitation, and delirium, with a standardized protocol and measures. HRQoL was assessed using the Neuro-QOL at 28 days, 3 months, and 1 year. Functional outcomes were measured with the modified Rankin Scale., Results: Among the 81 patients with HRQoL follow-up data available, patients who had agitation and delirium had worse cognitive function HRQoL scores at 28 days (T scores for delirium with agitation 20.9 ± 7.3, delirium without agitation 30.4 ± 16.5, agitation without delirium 36.6 ± 17.5, and neither agitated nor delirious 40.3 ± 15.9; p = 0.03) and at 1 year (p = 0.006). The effect persisted in mixed models after correction for severity of neurologic injury, age, and time of assessment (p = 0.0006) and was not associated with medication use, seizures, or infection., Conclusions: The presence of agitation with delirium in patients with intracerebral hemorrhage may predict higher risk of unfavorable cognitive outcomes up to 1 year later., (Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Delirium symptoms are associated with later worse functional outcomes and long-term cognitive impairments, but the neuroanatomical basis for delirium symptoms in patients with acute brain injury is currently uncertain. We tested the hypothesis that hematoma location is predictive of delirium symptoms in patients with intracerebral hemorrhage, a model disease where patients are typically not sedated or bacteremic., Methods: We prospectively identified 90 patients with intracerebral hemorrhage who underwent routine twice-daily screening for delirium symptoms with a validated examination. Voxel-based lesion-symptom mapping with acute computed tomography was used to identify hematoma locations associated with delirium symptoms (N = 89)., Results: Acute delirium symptoms were predicted by hematoma of right-hemisphere subcortical white matter (superior longitudinal fasciculus) and parahippocampal gyrus. Hematoma including these locations had an odds ratio for delirium of 13 (95 % CI 3.9-43.3, P < 0.001). Disruption of large-scale brain networks that normally support attention and conscious awareness was thus associated with acute delirium symptoms., Conclusions: Higher odds ratio for delirium was increased due to hematoma location. The location of neurological injury could be of high prognostic value for predicting delirium symptoms.

Purpose of Review: This article updates neurologists on recent insights and management strategies of intracerebral hemorrhage (ICH)., Recent Findings: Blood pressure reduction likely improves outcomes in patients with intracerebral hemorrhage, although not by the expected mechanism of reducing hematoma growth. One formulation of prothrombin complex concentrate for reversing severe bleeding associated with warfarin is now approved by the US Food and Drug Administration (FDA), and specific reversal therapies for the novel oral anticoagulants are in development. Neurologic monitoring frequently detects ICH worsening that requires an intervention. Platelet transfusion and pharmacologic platelet activation are promising and often used as part of patient management but have not yet been shown to improve patient outcomes., Summary: Measurable progress continues toward establishing effective therapies to improve outcomes in patients with ICH. Blood pressure reduction and reversal of medications that exacerbate bleeding are likely to improve outcomes. Recommendations for neuromonitoring will help clinicians at the bedside attend to the most important abnormalities and optimize later quality of life. This article reviews standards for diagnosis and severity of ICH, monitoring and treatment of complications in the hospital, available interventions, and the measurement of outcomes.

Background: We sought to determine whether a quantitative neurocheck biomarker could characterize the temporal pattern of early neurologic changes after intracerebral hemorrhage (ICH), and the impact of those changes on long-term functional outcomes., Methods: We enrolled cases of spontaneous ICH in a prospective observational study. Patients underwent a baseline Glasgow Coma Scale (GCS) assessment, then hourly neurochecks using the GCS in a neuroscience intensive care unit. We identified a period of heightened neurologic instability by analyzing the average hourly rate of GCS change over 5 days from symptom onset. We used a multivariate regression model to test whether those early GCS score changes were independently associated with 3-month outcome measured by the modified Rankin Scale (mRS)., Results: We studied 13,025 hours of monitoring from 132 cases. The average rate of neurologic change declined from 1.0 GCS points per hour initially to a stable baseline of .1 GCS points per hour beyond 12 hours from symptom onset (P < .05 for intervals before 12 hours). Change in GCS score within the initial 12 hours was an independent predictor of mRS at 3 months (odds ratio, .81 [95% confidence interval, .66-.99], P = .043) after adjustment for age, hematoma volume, hematoma location, initial GCS, and intraventricular hemorrhage., Conclusions: Neurochecks are effective at detecting clinically important neurologic changes in the intensive care unit setting that are relevant to patients' long-term outcomes. The initial 12 hours is a period of frequent and prognostically important neurologic changes in patients with ICH., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Worthwhile interventions for intracerebral hemorrhage or subarachnoid hemorrhage generally hinge on whether they improve the odds of good outcome. Although good outcome is correlated with mobility, correlations with other domains of health-related quality of life, such as cognitive function and social functioning, are not well described. We tested the hypothesis that good outcome is more closely associated with mobility than other domains., Design: We defined "good outcome" as 0 through 3 (independent ambulation or better) versus 4 through 5 (dependent) on the modified Rankin Scale at 1, 3, and 12 months. We simultaneously assessed the modified Rankin Scale and health-related quality of life using web-based computer adaptive testing in the domains of mobility, cognitive function (executive function and general concerns), and satisfaction with social roles and activities. We compared the area under the curve between different health-related quality of life domains., Setting: Neurologic ICU with web-based follow-up., Patients: One hundred fourteen patients with subarachnoid hemorrhage or intracerebral hemorrhage., Interventions: None., Measurement and Main Results: We longitudinally followed 114 survivors with data at 1 month, 62 patients at 3 months, and 58 patients at 12 months. At 1 month, area under the curve was highest for mobility (0.957; 95% CI, 0.904-0.98), higher than cognitive function-general concerns (0.819; 95% CI, 0.715-0.888; p = 0.003 compared with mobility), satisfaction with social roles and activities (0.85; 95% CI, 0.753-0.911; p = 0.01 compared with mobility), and cognitive function-executive function (0.879; 95% CI, 0.782-0.935; p = 0.058 compared with mobility). Optimal specificity and sensitivity for receiver operating characteristic analysis were approximately 1.5 SD below the U.S. population mean., Conclusions: Health-related quality of life assessments reliably distinguished between good and poor outcomes as determined by the modified Rankin Scale. Good outcome indicated health-related quality of life about 1.5 SD below the U.S. population mean. Associations were weaker for cognitive function and social function than mobility.

Background: Clinical outcomes are typically assessed by trained staff. We tested the hypothesis that outcomes reported by the patient or a caregiver on the web would be correlated with a validated interview., Methods: We assessed surviving patients with intracerebral and subarachnoid hemorrhage at 1- , 3- , and 12-month follow-up with a validated interview for the modified Rankin Scale (mRS, a validated ordinal scale from 0, no symptoms to 5, severe disability). Health-related quality of life (HRQoL) was assessed on the web with NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and Neuro-QOL using computer adaptive testing by the patient, proxy reporting by a caregiver, or proxy entry by study staff., Results: A coincident mRS and HRQoL assessment was available for 149 (71 %) of 209 patients at one, three, or 12 months. There were 89 assessments with proxy entry by study staff, 89 by the patient on the web, and 58 with proxy report by a caregiver on the web. PROMIS physical function assessments were completed in median of 4 questions, and T scores were associated with the mRS (P < 0.001), regardless of respondent. Mean T scores in every category of the mRS were different from every other category (P ≤ 0.003 for all). Results were similar for Neuro-QOL mobility., Conclusions: Web-based HRQoL assessment with NIH PROMIS and Neuro-QOL is feasible and correlated with a validated interview for the mRS. T scores distinguished between individual categories of the mRS, detecting modest differences in physical function and mobility HRQoL that are difficult to detect with the mRS. PROMIS and Neuro-QOL provide powerful and sensitive outcomes for potentially large cohorts.

Background: Seizures are common in patients with subarachnoid hemorrhage, potentially by inciting cortical irritability. Seizures are also commonly seen after intracerebral hemorrhage (ICH), although the mechanisms and risk factors within that population are not well understood. The objective of this study is to evaluate whether subarachnoid hemorrhage extension (SAHE) is associated with early seizures in patients with primary ICH., Methods: Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. Patients were managed per a structured protocol. SAHE was identified on imaging by expert reviewers blinded to outcomes. Electroencephalograms were routinely obtained in patients with unexplained, poor level of arousal. Seizure was determined by clinically observed convulsions or traditional electroencephalographic criteria. Early seizures were defined as occurring within 3 days of hemorrhage. A binary logistic regression model was developed to test whether the occurrence of SAHE was independently associated with seizures., Results: A total of 234 patients were studied. Of these, 93 (40%) had SAHE and 9 (4%) had early seizures. SAHE was associated with early seizures (P = .03). No additional variables were identified by regression modeling to mediate the association between SAHE and early seizures (odds ratio 5.62 [95% confidence interval 1.14-27.7], P = .034)., Conclusions: SAHE is associated with early seizures in patients with primary ICH. Further study is needed to confirm these findings and determine whether modifications to routine care based on the presence of SAHE would be of benefit., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Intraventricular hemorrhage (IVH) may be difficult to detect especially when in small amounts and may affect outcomes. The objective of this study was to compare the sensitivity of magnetic resonance imaging (MRI) vs computed tomography (CT) for the identification and quantification of IVH., Methods: Patients with primary intracerebral hemorrhage were enrolled into a prospective registry between December 2006 and June 2013. Diagnostic and surveillance neuroimaging studies were analyzed for the presence of IVH and quantified by Graeb score. In subjects who developed IVH and underwent both MRI and CT, each MRI was paired with the CT scan done at the closest time point, and Graeb scores were compared with the Wilcoxon signed rank test for related samples., Results: There were 289 subjects in the cohort with IVH found in 171. Sixty-eight pairs of MRI and CT were available for comparison. CT failed to detect IVH in 3% of cases, whereas MRI was 100% sensitive. MRI and CT yielded equal Graeb scores in 72% of the pairs, and MRI Graeb score was higher in 24% (P = .007)., Conclusions: MRI identifies small volumes of IVH in cases not detected by CT and yields higher estimates of intraventricular blood volume. These data indicate that consideration of technical differences is needed when comparing images from the 2 modalities in the evaluation for IVH., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Minimizing hematoma growth in high-risk patients is an attractive strategy to improve outcomes after intracerebral hemorrhage. We tested the hypothesis that desmopressin (DDAVP), which improves hemostasis through the release of von Willebrand factor, improves platelet activity after intracerebral hemorrhage., Methods: Patients with reduced platelet activity on point-of-care testing alone (5), known aspirin use alone (1), or both (8) received desmopressin 0.4 μg/kg IV. We measured Platelet Function Analyzer-epinephrine (Siemens AG, Germany) and von Willebrand factor antigen from baseline to 1 hour after infusion start and hematoma volume from the diagnostic to a follow-up computed tomographic scan., Results: We enrolled 14 patients with of mean age 66.8±14.6 years, 11 (85%) of whom were white and 8 (57%) were men. Mean Platelet Function Analyzer-epinephrine results shortened from 192±18 seconds pretreatment to 124±15 seconds (P=0.01) 1 hour later, indicating improved plate activity. von Willebrand factor antigen increased from 242±96% to 289±103% activity (P=0.004), indicating the expected increase in von Willebrand factor. Of 7 (50%) patients who received desmopressin within 12 hours of intracerebral hemorrhage symptom onset, changes in hematoma volume were modest, -0.5 (-1.4 to 8.4) mL and only 2 had hematoma growth. One patient had low blood pressure and another had a new fever within 6 hours of desmopressin administration., Conclusions: Intravenous desmopressin was well tolerated and improved platelet activity after acute intracerebral hemorrhage. Larger studies are needed to determine its potential effects on reducing hematoma growth versus platelet transfusion or placebo., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00961532., (© 2014 American Heart Association, Inc.)

Background: Extension of hemorrhage into the subarachnoid space in primary intracerebral hemorrhage (ICH) has recently been associated with poor outcomes, although the mechanisms underlying that association are uncertain. The objectives of this study are to confirm the association between fever and poor outcomes after ICH, and to determine whether subarachnoid hemorrhage extension (SAHE) is associated with fevers., Methods: Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. SAHE was identified on imaging by blinded expert reviewers. Patient temperature was recorded hourly, and we defined febrile as any recorded temperature >38 °C within the first 14 days. Regression models were developed to test whether fever was associated with poor outcome and whether the occurrence of SAHE was a predictor of fever., Results: Of the 235 patients studied, 39.7 % had SAHE and 58 % had fever. Fever was associated with higher modified Rankin scores at 3 months (odds ratio, OR 1.8 [1.04-3.12], p = 0.04) after adjustment for ICH score. SAHE was a predictor of fevers (OR 1.82 [95 % confidence interval 1.02-3.24], p = 0.04) after adjustment for ICH score, and remained significant after adjustment for other confounders like pneumonia identified in the univariate analysis., Conclusions: Our data confirm the deleterious effect of fever on the outcome of patients with ICH and show that SAHE is an independent predictor of fever after ICH. SAHE may provoke dysfunctional thermoregulation similar to what is observed after aneurysmal subarachnoid hemorrhage, creating mechanistic pathway between SAHE and poor functional outcomes.

Objective: To determine whether patient's demographics or severity of illness predict hospital readmission within 30 days following spontaneous intracerebral hemorrhage, to identify readmission associations that may be modifiable at the single-center level, and to determine the impact of readmission on outcomes., Design: We collected demographic, clinical, and hospital course data for consecutive patients with spontaneous intracerebral hemorrhage enrolled in an observational study. Readmission within 30 days was determined retrospectively by an automated query with manual confirmation. We identified the reason for readmission and tested for associations between readmission and functional outcomes using modified Rankin Scale (a validated functional outcome measure from 0, no symptoms, to 6, death) scores before intracerebral hemorrhage and at 14 days, 28 days, and 3 months after intracerebral hemorrhage., Setting: Neurologic ICU of a tertiary care hospital., Patients: Critically ill patients with spontaneous intracerebral hemorrhage., Interventions: Patients received standard critical care management for intracerebral hemorrhage., Measurements and Main Results: Of 246 patients (mean age, 65 yr; 51% female), 193 patients (78%) survived to discharge. Of these, 22 patients (11%) were readmitted at a median of 9 days (interquartile range, 4-15 d). The most common readmission diagnoses were infections after discharge (n = 10) and vascular events (n = 6). Age, history of stroke and hypertension, severity of neurologic deficit at admission, Acute Physiology and Chronic Health Evaluation score, ICU and hospital length of stay, ventilator-free days, days febrile, and surgical procedures were not predictors of readmission. History of coronary artery disease was associated with readmission (p = 0.03). Readmitted patients had similar modified Rankin Scale and severity of neurologic deficit at 14 days but higher (worse) modified Rankin Scale scores at 3 months (median [interquartile range], 5 [3-6] vs 3 [1-4]; p = 0.01)., Conclusions: Severity of illness and hospital complications were not associated with 30-day readmission. The most common indication for readmission was infection after discharge, and readmission was associated with worse functional outcomes at 3 months. Preventing readmission after intracerebral hemorrhage may depend primarily on optimizing care after discharge and may improve functional outcomes at 3 months.

Rationale: The prognostic significance of delirium symptoms in intensive care unit (ICU) patients with focal neurologic injury is unclear., Objectives: To determine the relationship between delirium symptoms and subsequent functional outcomes and quality of life (QOL) after intracerebral hemorrhage., Methods: We prospectively enrolled 114 patients. Delirium symptoms were routinely assessed twice daily using the Confusion Assessment Method for the ICU by trained nurses. Functional outcomes were recorded with modified Rankin Scale (scored from 0 [no symptoms] to 6 [dead]), and QOL outcomes with Neuro-QOL at 28 days, 3 months, and 12 months., Measurements and Main Results: Thirty-one (27%) patients had delirium symptoms ("ever delirious"), 67 (59%) were never delirious, and the remainder (14%) had persistent coma. Delirium symptoms were nearly always hypoactive, were detected mean 6 days after intracerebral hemorrhage presentation, and were associated with longer ICU length of stay (mean 3.5 d longer in ever vs. never delirious patients; 95% confidence interval, 1.5-8.3; P = 0.004) after correction for age, admit National Institutes of Health (NIH) Stroke Scale, and any benzodiazepine exposure. Delirium symptoms were associated with increased odds of poor outcome at 28 days (odds ratio, 8.7; 95% confidence interval, 1.4-52.5; P = 0.018) after correction for admission NIH Stroke Scale and age, and with worse QOL in the domains of applied cognition-executive function and fatigue after correcting for the NIH Stroke Scale, age, benzodiazepine exposure, and time of follow-up., Conclusions: After focal neurologic injury, delirium symptoms were common despite low rates of infection and sedation exposure, and were predictive of subsequent worse functional outcomes and lower QOL.

Objective: We tested the hypothesis that surveillance neuroimaging and neurologic examinations identified changes requiring emergent surgical interventions in patients with intracerebral hemorrhage (ICH)., Methods: Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. Patients were managed in a neuroscience intensive care unit with a protocol that included serial neuroimaging at 6, 24, and 48 hours, and hourly neurologic examinations using the Glasgow Coma Scale and NIH Stroke Scale. We evaluated all cases of craniotomy and ventriculostomy to determine whether the procedure was part of the initial management plan or occurred subsequently. For those that occurred subsequently, we determined whether worsening on neurologic examination or worsened neuroimaging findings initiated the process leading to intervention., Results: There were 88 surgical interventions in 84 (35%) of the 239 patients studied, including ventriculostomy in 52 (59%), craniotomy in 21 (24%), and both in 11 (13%). Of the 88 interventions, 24 (27%) occurred subsequently and distinctly from initial management, a median of 15.9 hours (8.9-27.0 hours) after symptom onset. Thirteen (54%) were instigated by findings on neurologic examination and 11 (46%) by neuroimaging. Demographics, severity of hemorrhage, and hemorrhage location were not associated with delayed intervention., Conclusions: More than 25% of surgical interventions performed after ICH were prompted by delayed imaging or clinical findings. Serial neurologic examinations and neuroimaging are important and effective surveillance techniques for monitoring patients with ICH.

Objective: To evaluate the incidence, characteristics, and clinical consequences of delayed intraventricular hemorrhage (dIVH)., Methods: Patients with primary intracerebral hemorrhage (ICH) were enrolled into a prospective registry between December 2006 and February 2012. Patients were managed, and serial neuroimaging obtained, per a structured protocol. Initial and delayed IVH were identified on imaging, along with ICH volumes, with outcomes blinded. Multivariate models were developed to test whether the occurrence of dIVH was a predictor of functional outcomes independent of known predictors, including the ICH score elements and ICH growth., Results: A total of 216 patients were studied, and 104 (48%) had IVH on initial imaging. Of the 112 with no IVH, 23 (21%) subsequently developed IVH. Emergent surgical intervention, mostly ventriculostomy placement, was required after discovery of dIVH in 10 (43%) of these 23. In multivariate models adjusting for all elements of the ICH score and hematoma growth, dIVH was an independent predictor of death at 14 days (p = 0.015) and higher modified Rankin Scale scores at 3 months (all p = 0.037). The effect of dIVH remained significant in a secondary analysis that adjusted for all other variables significant in the univariate analysis., Conclusions: Similar to hematoma expansion dIVH is independently associated with death and poor outcomes. Because IVH is easily detected by serial neuroimaging and often requires emergent surgical intervention, monitoring for dIVH is recommended.

Background: Anticoagulation increases the risk of intracerebral hemorrhage (ICH), yet whether different underlying disease processes are equally affected is unknown. We tested the hypothesis that coagulopathy, measured by admission international normalized ratio (INR), disproportionately increases the risk for lobar hemorrhages., Methods: Patients with primary ICH were enrolled into a registry between December 2006 and February 2012 with prospective data acquisition and systematic follow up. Logistic regression was used to test whether lobar versus deep ICH location was independently associated with INR, and then whether INR had an influence on mortality. Spearman's correlation coefficient was used to test for an association between INR and hematoma volume separately in the lobar and deep ICH groups., Results: 221 patients were studied. Patients with lobar ICH were older (71 vs. 62 years old, p < 0.001) and more likely to have prior ICH (10 vs. 0 %, p < 0.001). INR >1.4 was observed on admission more frequently in lobar versus deep ICH (19 vs. 8 %, p = 0.02). Lobar ICH location was independently associated with INR >1.4 (OR: 2.51, 95 % CI: 1.03-6.14, p = 0.043). ICH volume correlated with INR in lobar ICH (p = 0.009), but not deep ICH (p = 0.8). Death at 1 month was independently associated with INR >1.4 (OR: 7.6, 95 % CI: 2.4-24.1, p = 0.001) after correction for the ICH Score., Conclusions: Abnormal coagulation occurs disproportionally in lobar versus deep ICH, and is associated with larger ICH volumes and higher mortality. These findings suggest a unique risk interaction between coagulopathy and underlying brain pathology due to cerebral amyloid angiopathy.

Background and Purpose: Leukoaraiosis (LA) is associated with dementia, ischemic stroke, and intracerebral hemorrhage (ICH), but there are few data on how LA might impact outcomes after acute ICH. We tested the hypothesis that the severity of LA on magnetic resonance imaging is related to worse functional outcomes after spontaneous ICH., Methods: We prospectively identified patients with spontaneous acute ICH. LA was identified on magnetic resonance imaging and its severity was graded using the Fazekas method to include a score for the deep white matter and periventricular regions. Outcomes were obtained at 14 days, 28 days, and 3 months with the modified Rankin Scale (mRS; a validated scale from 0 [no symptoms] to 6 [dead]) and analyzed with multivariate logistic regression., Results: Higher Fazekas total (periventricular plus deep white matter) score correlated with higher mRS score at 14 days (P=0.02) and 3 months (P=0.02). This relationship was driven by the periventricular score, for which higher score (more severe disease) correlated with higher National Institute of Health Stroke Scale at 14 days (P=0.03), and higher mRS score at 14 days (P<0.001), 28 days (P=0.004), and 3 months (P=0.005). A higher (more severe) Fazekas periventricular score was associated with dependence or death at 3 months (odds ratio, 1.8 per point; 95% confidence interval, 1.02-3.1; P=0.04) after correction for the ICH score., Conclusions: Increased LA is an independent predictor of worse functional outcomes in patients after spontaneous ICH. The pathophysiology associating LA with worse outcomes requires further study. These data may improve prognostication and selection for clinical trials.

Background and Purpose: Extension of hemorrhage into the subarachnoid space is observed in primary intracerebral hemorrhage (ICH), yet the phenomenon has undergone limited study and is of unknown significance. The objective of this study is to evaluate the incidence, characteristics, and clinical consequences of subarachnoid hemorrhage extension (SAHE) in ICH on functional outcomes., Methods: Patients with primary ICH were enrolled into a prospective registry between December 2006 and June 2012. Patients were managed and serial neuroimaging was obtained per a structured protocol. Presence of any subarachnoid blood on imaging was identified as SAHE by expert reviewers blinded to outcomes. Regression models were developed to test whether the occurrence of SAHE was an independent predictor of functional outcomes as measured with the modified Rankin Scale., Results: Of 234 patients with ICH, 93 (39.7%) had SAHE. Interrater agreement for SAHE was excellent (kappa=0.991). SAHE was associated with lobar hemorrhage location (65% of SAHE vs 19% of non-SAHE cases; P<0.001) and larger hematoma volumes (median 23.8 vs 6.7; P<0.001). Fever (69.9% vs 51.1%; P=0.005) and seizures (8.6% vs 2.8%; P=0.07) were more common in patients with SAHE. SAHE was a predictor of death by day 14 (odds ratio, 4.45; 95% confidence interval, 1.88-10.53; P=0.001) and of higher (worse) modified Rankin Scale scores at 28 days (odds ratio, 1.76 per mRS point; 95% confidence interval, 1.01-3.05; P=0.012) after adjustment for ICH score., Conclusions: SAHE is associated with worse modified Rankin Scale independent of traditional ICH severity measures. Underlying mechanisms and potential treatments of SAHE require further study.

Background: In patients with acute intracerebral hemorrhage (ICH), reduced platelet activity on admission predicts hemorrhage growth and poor outcomes. We tested the hypotheses that platelet transfusion improves measured platelet activity. Further, we hypothesized that earlier treatment in patients at high risk for hemorrhage growth and poor outcome would reduce follow-up hemorrhage size and poor clinical outcomes., Methods: We prospectively identified consecutive patients with ICH who had reduced platelet activity on admission and received a platelet transfusion. We defined high-risk patients as per a previous publication, reduced platelet activity, or known anti-platelet therapy (APT) and the diagnostic CT within 12 h of symptom onset. Platelet activity was measured with the VerifyNow-ASA (Accumetrics, CA), ICH volumes on CT with computerized quantitative techniques, and functional outcomes with the modified Rankin Scale (mRS) at 3 months., Results: Forty-five patients received a platelet transfusion with an increase in platelet activity from 472 ± 50 (consistent with an aspirin effect) to 561 ± 92 aspirin reaction units (consistent with no aspirin effect, P < 0.001). For high-risk patients, platelet transfusion within 12 h of symptom onset, as opposed to >12 h, was associated with smaller follow-up hemorrhage size (8.4 [3-17.4] vs. 13.8 [12.3-62.5] ml, P = 0.04) and increased odds of independence (mRS < 4) at 3 months (11 of 20 vs. 0 of 7, P = 0.01). There were similar results for patients with known APT., Conclusions: In patients at high risk for hemorrhage growth and poor outcome, early platelet transfusion improved platelet activity assay results and was associated with smaller final hemorrhage size and more independence at 3 months.

Background and Purpose: Decreased diffusion (DD) consistent with acute ischemia may be detected on MRI after acute intracerebral hemorrhage (ICH), but its risk factors and impact on functional outcomes are not well-defined. We tested the hypotheses that DD after ICH is related to acute blood pressure (BP) reduction and lower hemoglobin and presages worse functional outcomes., Methods: Patients who underwent MRI were prospectively evaluated for DD by certified neuroradiologists blinded to outcomes. Hemoglobin and BP data were obtained via electronic queries. Outcomes were obtained at 14 days and 3 months with the modified Rankin Scale, a functional scale scored from 0 (no symptoms) to 6 (dead). We used logistic regression for dependence or death (modified Rankin Scale score 4-6)., Results: DD distinct from the hematoma was found on MRI in 39 of 95 patients (41%). DD was associated with greater BP reductions from baseline and a higher risk of dependence or death at 3 months (odds ratio, 4.8; 95% confidence interval, 1.7-13.9; P=0.004) after correction for ICH score (1.8 per point; 95% confidence interval, 1.2-3.1; P=0.01). Lower hemoglobin was associated with worse ICH score, larger hematoma volume, and worse outcomes, but not DD., Conclusions: DD is common after ICH, associated with greater acute BP reductions, and associated with disability and death at 3 months in multivariate analysis. The potential benefits of acute BP reduction to reduce hematoma growth may be limited by DD. The prevention and treatment of cerebral ischemia manifested as DD are potential methods to improve outcomes.

Background: Craniotomy is potentially life-saving in selected patients with intracerebral hemorrhage (ICH). Aside from specific scenarios (cerebellar hemorrhage with hydrocephalus, midline shift from an accessible lesion, etc.) the indications for surgical decompression are controversial. Based on the earlier work that aspirin and reduced platelet activity are associated with larger hemorrhage size and hemorrhage growth, we tested the hypothesis that aspirin or reduced platelet activity would be associated with increased odds of craniotomy, likely through hemorrhage growth., Methods: We prospectively identified patients with spontaneous ICH and routinely measured platelet activity on admission. Patients were prospectively tracked, and outcomes were obtained with the modified Rankin Scale (mRS)., Results: There were 187 patients in the sample. Craniotomy (N = 32, 17%) was associated with a higher initial ICH volume (37.9 [20-63] vs. 12 [5-24] ml, P < 0.001) and location (P = 0.005). In multivariate logistic regression, after controlling for ICH volume and location, any known aspirin use (OR 3.4, 95% CI 1.1-10.4, P = 0.03), platelet activity ≤550 aspirin reaction units (OR 3.1, 95% CI 1.05-9.3, P = 0.04), or an elevated PFA-EPI closure time (OR 3.2, 95% CI 1.02-10.3, P = 0.04) were associated with increased odds of craniotomy. Craniotomy was not associated with mRS at 14 days, 28 days, or 3 months., Conclusions: After correction for ICH volume and location, aspirin use or reduced platelet activity was associated with similar increased odds for craniotomy.

Background: Anti-platelet medication and reduced platelet activity are associated with an increased risk of death after intracerebral hemorrhage (ICH). The optimal assay for assessing platelet activity is not defined. We hypothesized that reduced platelet activity would be common after ICH., Patients and Methods: We prospectively enrolled 72 consecutive patients with ICH and routinely measured platelet activity with both the PFA-100 (Siemens AG, Germany) and the VerifyNow-ASA (Accumetrics, CA, USA) systems on admission. We prospectively recorded anti-platelet medication use prior to ICH., Results: VerifyNow-ASA measurements were associated with aspirin (P = 0.001) and clopidogrel (P = 0.01) use prior to ICH. Combined clopidogrel and aspirin therapy was more potent than either alone. Of 33 patients with reduced platelet activity on the VerifyNow-ASA assay, 14 (42%) were not known to take anti-platelet agents. Of 27 patients with reduced platelet activity on the PFA-100, a related but different 14 (52%) were not known to take anti-platelet agents. There was a poor agreement between the assays (κ = 0.26, P = 0.07) on which patients had reduced platelet activity among the patients not known to take aspirin., Conclusions: A medication history does not reliably identify patients with reduced platelet activity after ICH, and this may explain studies that found no association between known aspirin use and outcomes. Future studies should screen for unknown use of anti-platelet medications after ICH. Neither assay perfectly identified patients who reportedly used anti-platelet medication before ICH.