Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Biospecimens and Biomarkers.

BACKGROUND: In patients with disorders of consciousness (DoC), laboratory and molecular biomarkers may help define endotypes, identify therapeutic targets, prognosticate outcomes, and guide patient selection in clinical trials. We performed a systematic review to identify common data elements (CDEs) and key design elements (KDEs) for future coma and DoC research. METHODS: The Curing Coma Campaign Biospecimens and Biomarkers work group, composed of seven invited members, reviewed existing biomarker and biospecimens CDEs and conducted a systematic literature review for laboratory and molecular biomarkers using predetermined search words and standardized methodology. Identified CDEs and KDEs were adjudicated into core, basic, supplemental, or experimental CDEs per National Institutes of Health classification based on level of evidence, reproducibility, and generalizability across different diseases through a consensus process. RESULTS: Among existing National Institutes of Health CDEs, those developed for ischemic stroke, traumatic brain injury, and subarachnoid hemorrhage were most relevant to DoC and included. KDEs were common to all disease states and included biospecimen collection time points, baseline indicator, biological source, anatomical location of collection, collection method, and processing and storage methodology. Additionally, two disease core, nine basic, 24 supplemental, and 59 exploratory biomarker CDEs were identified. Results were summarized and generated into a Laboratory Data and Biospecimens Case Report Form (CRF) and underwent public review. A final CRF version 1.0 is reported here. CONCLUSIONS: Exponential growth in biomarkers development has generated a growing number of potential experimental biomarkers associated with DoC, but few meet the quality, reproducibility, and generalizability criteria to be classified as core and basic biomarker and biospecimen CDEs. Identification and adaptation of KDEs, however, contribute to standardizing methodology to promote harmonization of future biomarker and biospecimens studies in DoC. Development of this CRF serves as a basic building block for future DoC studies.

Thematic Analysis of Psychosocial Stressors and Adaptive Coping Strategies Among Informal Caregivers of Patients Surviving ICU Admission for Coma.

BACKGROUND: Family caregivers of patients with severe acute brain injury (SABI) admitted to intensive care units (ICUs) with coma experience heightened emotional distress stemming from simultaneous stressors. Stress and coping frameworks can inform psychosocial intervention development by elucidating common challenges and ways of navigating such experiences but have yet to be employed with this population. The present study therefore sought to use a stress and coping framework to characterize the stressors and coping behaviors of family caregivers of patients with SABI hospitalized in ICUs and recovering after coma. METHODS: Our qualitative study recruited a convenience sample from 14 US neuroscience ICUs. Participants were family caregivers of patients who were admitted with ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, or hypoxic-ischemic encephalopathy; had experienced a comatose state for > 24 h; and completed or were scheduled for tracheostomy and/or gastrostomy tube placement. Participants were recruited < 7 days after transfer out of the neuroscience ICU. We conducted live online video interviews from May 2021 to January 2022. One semistructured interview per participant was recorded and subsequently transcribed. Recruitment was stopped when thematic saturation was reached. We deductively derived two domains using a stress and coping framework to guide thematic analysis. Within each domain, we inductively derived themes to comprehensively characterize caregivers' experiences. RESULTS: We interviewed 30 caregivers. We identified 18 themes within the two theory-driven domains, including ten themes describing practical, social, and emotional stressors experienced by caregivers and eight themes describing the psychological and behavioral coping strategies that caregivers attempted to enact. Nearly all caregivers described using avoidance or distraction as an initial coping strategy to manage overwhelming emotions. Caregivers also expressed awareness of more adaptive strategies (e.g., cultivation of positive emotions, acceptance, self-education, and soliciting social and medical support) but had challenges employing them because of their heightened emotional distress. CONCLUSIONS: In response to substantial stressors, family caregivers of patients with SABI attempted to enact various psychological and behavioral coping strategies. They described avoidance and distraction as less helpful than other coping strategies but had difficulty engaging in alternative strategies because of their emotional distress. These findings can directly inform the development of additional resources to mitigate the long-term impact of acute psychological distress among this caregiver population.

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

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

A reassessment of hemoglobin and hematoma expansion in intracerebral hemorrhage.

BACKGROUND: In patients with spontaneous intracerebral hemorrhage (ICH), prior studies identified an increased risk of hematoma expansion (HE) in those with lower admission hemoglobin (Hgb) levels. We aimed to reproduce these findings in an independent cohort. METHODS: We conducted a cohort study of patients admitted to a Comprehensive Stroke Center for acute ICH within 24 hours of onset. Admission laboratory and CT imaging data on ICH characteristics including HE (defined as >33% or >6 mL), and 3-month outcomes were collected. We compared laboratory data between patients with and without HE and used multivariable logistic regression to determine associations between Hgb, HE, and unfavorable 3-month outcomes (modified Rankin Scale 4-6) while adjusting for confounders including anticoagulant use, and laboratory markers of coagulopathy. RESULTS: Among 345 patients in our cohort (mean [SD] age 72.9 [13.7], 49% male), 71 (21%) had HE. Patients with HE had similar Hgb versus those without HE (mean [SD] 13.1 [1.8] g/dl vs. 13.1 [1.9] g/dl, p=0.92). In fully adjusted multivariable models, Hgb was not associated with HE (OR per 1g/dl 1.01, 95% CI 0.86 -1.17, p = 0.94), however higher admission Hgb levels were associated with lower odds of unfavorable 3-month outcome (OR 0.83 per 1 g/dl Hgb, 95% CI 0.72-0.96, p=0.01). CONCLUSION: We did not confirm a previously reported association between admission Hgb and HE in patients with ICH, although Hgb and HE were both associated with poor outcome. These findings suggest that the association between Hgb and poor outcome is mediated by other factors.

Impact of Delirium on Outcomes After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site. METHODS: We performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4-6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site. RESULTS: Of 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3-16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8-5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17-0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7-5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2-4.3]). CONCLUSIONS: Acute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.

Statewide Emergency Medical Services Protocols for Status Epilepticus Management.

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.

Risk Factors for Opioid Utilization in Patients with Intracerebral Hemorrhage.

BACKGROUND: Headache is a common presenting symptom of intracerebral hemorrhage (ICH) and often necessitates treatment with opioid medications. However, opioid prescribing patterns in patients with ICH are not well described. We aimed to characterize the prevalence and risk factors for short and longer-term opioid use in patients with ICH. METHODS: We conducted a retrospective cohort study using data from a single-center registry of patients with nontraumatic ICH. This registry included data on demographics, ICH-related characteristics, and premorbid, inpatient, and postdischarge medications. After excluding patients who died or received end-of-life care, we used multivariable regression models adjusted for premorbid opioid use to determine demographic and ICH-related risk factors for inpatient and postdischarge opioid use. RESULTS: Of 468 patients with ICH in our cohort, 15% (n = 70) had premorbid opioid use, 53% (n = 248) received opioids during hospitalization, and 12% (n = 53) were prescribed opioids at discharge. The most commonly used opioids during hospitalization were fentanyl (38%), oxycodone (30%), morphine (26%), and hydromorphone (7%). Patients who received opioids during hospitalization were younger (univariate: median [interquartile range] 64 [53.5-74] vs. 76 [67-83] years, p < 0.001; multivariable: odds ratio [OR] 0.96 per year, 95% confidence interval [CI] 0.94-0.98) and had larger ICH volumes (univariate: median [interquartile range] 10.1 [2.1-28.6] vs. 2.7 [0.8-9.9] cm3, p < 0.001; multivariable: OR 1.05 per cm3, 95% CI 1.03-1.08) than those who did not receive opioids. All patients who had external ventricular drain placement and craniotomy/craniectomy received inpatient opioids. Additional risk factors for increased inpatient opioid use included infratentorial ICH location (OR 4.8, 95% CI 2.3-10.0), presence of intraventricular hemorrhage (OR 3.9, 95% CI 2.2-7.0), underlying vascular lesions (OR 3.0, 95% CI 1.1-8.1), and other secondary ICH etiologies (OR 7.5, 95% CI 1.7-32.8). Vascular lesions (OR 4.0, 95% CI 1.3-12.5), malignancy (OR 5.0, 95% CI 1.5-16.4), vasculopathy (OR 10.0, 95% CI 1.8-54.2), and other secondary etiologies (OR 7.2, 95% CI 1.8-29.9) were also risk factors for increased opioid prescriptions at discharge. Among patients who received opioid prescriptions at discharge, 43% (23 of 53) continued to refill their prescriptions at 3 months post discharge. CONCLUSIONS: Inpatient opioid use in patients with ICH is common, with some risk factors that may be mechanistically connected to primary headache pathophysiology. However, the lower frequency of opioid prescriptions at discharge suggests that inpatient opioid use does not necessarily lead to a high rate of long-term opioid dependence in patients with ICH.

Association of asymptomatic cerebral vasospasm with outcomes in survivors of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm (cVSP) is a common complication in aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP is poorly understood. We sought to determine the association of asymptomatic cVSP with functional outcome and hospital length of stay (LOS). METHODS: We performed a retrospective study of a prospectively collected cohort of patients with aSAH who survived hospitalization at an academic center between 2016 and 2021. We defined cVSP based on transcranial Doppler criteria. Multivariate logistic and multiple linear regression analyses were used to determine the association of asymptomatic cVSP with poor functional outcome (defined as modified Rankin scale 3-6 at 3 months after discharge) and hospital length of stay (LOS). RESULTS: The cohort consisted of 201 aSAH patients with a mean age 54.9 years (SD 13.6) and 60% were female. One hundred nine patients (54%) experienced cVSP, of whom 43 patients (39%) were asymptomatic. Patients with asymptomatic cVSP were younger (mean 50.5 years [SD 10.6] vs 61 years [SD12.5]; p < 0.001) and had longer ICU LOS (median 13 days [IQR12-20] vs median 12 days [IQR9-15], p = 0.018) compared to those without cVSP. However, after adjusting with other variables asymptomatic cVSP was not associated with longer ICU or hospital LOS. Asymptomatic cVSP was not associated with poor outcome either (p = 0.14). CONCLUSION: Asymptomatic cVSP, which was more common in younger patients, was neither associated with poor functional outcome nor hospital LOS.  Larger prospective studies are needed to assess the significance of asymptomatic cVSP on long-term outcomes.

Volumetric White Matter Hyperintensity Ranges Correspond to Fazekas Scores on Brain MRI.

INTRODUCTION: White matter hyperintensity (WMH) is an abnormal T2 signal in the deep and subcortical white matter visualized on MRI associated with hypertension, cerebrovascular disease, and aging. The Fazekas (Fz) scoring system is a commonly used qualitative tool to assess the severity of WMH. While studies have compared Fazekas scores to other scoring methods, the comparison of Fazekas scores and volume of WMH using current semiautomated volumetric techniques has not been studied. METHODS: We reviewed MRI studies acquired at our institution between 2015 and 2017. Relative WMH was scored by one author trained in Fazekas scoring. A board certified neuroradiologist scored them independently for confirmation. Manual segmentations of WMH were completed using 3D Slicer 4.9. A 3D model was formed to quantify WMH in milliliters (mL). ANOVA tests were performed to determine the association of Fazekas scores with corresponding WMH volumes. RESULTS: Among the 198 patients in our study, WMH were visualized in 163 (Fz1: n=66; Fz2: n=49; Fz3: n=48). WMH volumes significantly differed according to Fazekas score (F = 141.1, p<0.001), with increasing WMHV associated with higher Fazekas scores: Fz1, range 0.1-8.3 mL (mean 3.7, SD 2.3); Fz2, range 6.0-17.7 mL (mean 10.8, SD 3.1); Fz3, range 14.2-77.2 mL (mean 35.2, SD 17.9); and Fz3 (excluding 11 outliers above 50 mL), 14.2-47.0 mL (mean 27.1, SD 8.9). CONCLUSION: Fazekas scores correspond with distinct ranges of WMH volume with relatively little overlap, but scores based on volumes are more efficacious. A modified Fazekas from 0-4 should be considered.

Detection of Atrial Fibrillation After Central Retinal Artery Occlusion.

Background: Central retinal artery occlusion (CRAO) causes sudden, irreversible blindness and is a form of acute ischemic stroke. In this study, we sought to determine the proportion of patients in whom atrial fibrillation (AF) is detected by extended cardiac monitoring after CRAO. Methods: We performed a retrospective, observational cohort study using data from the Optum deidentified electronic health record of 30.8 million people cross-referenced with the Medtronic CareLink database of 2.7 million people with cardiac monitoring devices in situ. We enrolled patients in 3 groups: (1) CRAO, (2) cerebral ischemic stroke, and (3) age-, sex-, and comorbidity-matched controls. The primary end point was the detection of new AF (defined as ≥2 minutes of AF detected on a cardiac monitoring device). Results: We reviewed 884 431 patient records in common between the two databases to identify 100 patients with CRAO, 6559 with ischemic stroke, and 1000 matched controls. After CRAO, the cumulative incidence of new AF at 2 years was 49.6% (95% CI, 37.4%­61.7%). Patients with CRAO had a higher rate of AF than controls (hazard ratio, 1.64 [95% CI, 1.17­2.31]) and a comparable rate to patients with stroke (hazard ratio, 1.01 [95% CI, 0.75­1.36]). CRAO was associated with a higher incidence of new stroke compared with matched controls (hazard ratio, 2.85 [95% CI, 1.29­6.29]). Conclusions: The rate of AF detection after CRAO is higher than that seen in age-, sex-, and comorbidity-matched controls and comparable to that seen after ischemic cerebral stroke. Paroxysmal AF should be considered as part of the differential etiology of CRAO, and those patients may benefit from long-term cardiac monitoring.

Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

[Figure: see text].

Early Neurological Changes and Interpretation of Clinical Grades in Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Hunt and Hess (HH) and World Federation of Neurological Surgeons (WFNS) grades are commonly used to report clinical severity of aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine the impact of early neurological changes and the timing of clinical grade assignment on the prognostication accuracy. METHODS: We retrospectively reviewed a cohort of consecutive patients with aSAH who were admitted to an academic center. Patients with confirmed aneurysmal cause were included. Relevant clinical data including daily clinical grades, imaging data and functional outcome were analyzed. Favorable outcome was defined as mRS 0 to 3. Early neurological improvement (ENI) and early neurological deterioration (END) were respectively defined as any improvement or deterioration of HH grades from hospital day 1 to the earliest time from hospital day 2 to 5. RESULTS: Of 310 patients, 24% experienced early neurological changes from hospital day 1 to 3. For each point increase in HH grades from day 1 to day 3, the odds ratio for worse outcome was 2.57 (95% CI [1.74-3.79]) and for each point decrease in HH grades from day 1 to day 3, the odds ratio for worse outcome was 0.28 (95% CI [0.17-0.47]). Receiver Operating Characteristic curve analysis revealed that clinical grades on day 3 had higher accuracy in predicting worse outcome than clinical grades on day 1. CONCLUSION: Early changes in neurological status can alter trajectory of hospital course and functional outcome. The prognostic accuracy of the clinical grades from hospital day 3 is significantly greater than those on admission.

Gender Disparities in Stroke Code Activation in Patients with Intracerebral Hemorrhage.

OBJECTIVES: Routine implementation of protocol-driven stroke "codes" results in timelier and more effective acute stroke management. However, it is unclear if patient demographics contribute to disparities in stroke code activation. We aimed to explore these demographic factors in a retrospective cohort study of patients with intracerebral hemorrhage (ICH). MATERIALS AND METHODS: We identified consecutive patients with non-traumatic ICH who presented directly to our Comprehensive Stroke Center over 2 years and collected data on demographics, clinical features, and stroke code activation. We used multivariable logistic regression to examine differences in stroke code activation based on patient demographics while adjusting for initial clinical features (NIH Stroke Scale, FAST [facial drooping, arm weakness, speech difficulties] vs. non-FAST symptoms, time from last-known-well [LKW], and systolic blood pressure [SBP]). RESULTS: Among 265 patients, 68% (n=179) had a stroke code activation. Stroke codes occurred less frequently in women (62%) than men (72%) and in non-white (57%) vs. white patients (70%). Non-stroke code patients were less likely to have FAST symptoms (37% vs. 87%) and had lower initial SBP (mean±SD 159.3±34.2 vs. 176.0±31.9 mmHg) than stroke code patients. In our primary multivariable models, neither age nor race were associated with stroke code activation. However, women were significantly less likely to have stroke codes than men (OR 0.49 [95% CI 0.24-0.98]), as were non-FAST symptoms (OR 0.11 [95% CI 0.05-0.22]). CONCLUSIONS: Our data suggest gender disparities in emergency stroke care that should prompt further investigations into potential systemic biases. Increased awareness of atypical stroke symptoms is also warranted.

Deconstructing Poststroke Delirium in a Prospective Cohort of Patients With Intracerebral Hemorrhage.

OBJECTIVES: Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage. DESIGN: Prospective observational cohort study. SETTING: Neurocritical Care and Stroke Units at a university hospital. PATIENTS: Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64). CONCLUSIONS: Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Emphysema: A Potential Risk Factor for Subarachnoid Hemorrhage and Ruptured Aortic Aneurysm

Background and Purpose- Protease/antiprotease imbalance is implicated in the pathogenesis of emphysema and may also lead to vessel wall weakening, aneurysm development, and rupture. However, it is unclear whether emphysema is associated with cerebral and aortic aneurysm rupture. Methods- We performed a retrospective cohort study using outpatient and inpatient claims data from 2008 to 2014 from a nationally representative sample of Medicare beneficiaries ≥66 years of age. Our predictor variable was emphysema, and our outcome was hospitalization for either aneurysmal subarachnoid hemorrhage or a ruptured aortic aneurysm. All predictors and outcomes were defined using previously reported International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithms. Survival statistics and Cox regression were used to compare risk between patients with and without emphysema. Results- We identified 1 670 915 patients, of whom 133 972 had a diagnosis of emphysema. During a mean follow-up period of 4.3 (±1.9) years, we identified 4835 cases of aneurysm rupture, 433 of which occurred in patients with emphysema. The annual incidence of aneurysm rupture was 6.5 (95% CI, 6.4-6.8) per 10 000 in patients without emphysema and 14.6 (95% CI, 13.3-16.0) per 10 000 in patients with emphysema. After adjustment for demographics and known risk factors for aneurysmal disease, emphysema was independently associated with aneurysm rupture (hazard ratio, 1.7; 95% CI, 1.5-1.9). Emphysema was associated with both aneurysmal subarachnoid hemorrhage (hazard ratio, 1.5; 95% CI, 1.3-1.7) and ruptured aortic aneurysm (hazard ratio, 2.3; 95% CI, 1.9-2.8). Conclusions- Patients with emphysema face an increased risk of developing subarachnoid hemorrhage and aortic aneurysm rupture, potentially consistent with shared pathways in pathogenesis.

Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke.

BACKGROUND AND PURPOSE: We sought to determine the long-term risk of seizures after stroke according to age, sex, race, and stroke subtype. METHODS: We performed a retrospective cohort study using administrative claims from 2 complementary patient data sets. First, we analyzed data from all emergency department visits and hospitalizations in California, Florida, and New York from 2005 to 2013. Second, we evaluated inpatient and outpatient claims from a nationally representative 5% random sample of Medicare beneficiaries. Our cohort consisted of all adults at the time of acute stroke hospitalization without a prior history of seizures. Our outcome was seizure occurring after hospital discharge for stroke. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). RESULTS: Among 777 276 patients in the multistate cohort, the annual incidence of seizures was 1.68% (95% confidence interval [CI], 1.67%-1.70%) after stroke versus 0.15% (95% CI, 0.15%-0.15%) among the general population (IRR, 7.3; 95% CI, 7.3-7.4). By 8 years, the cumulative rate of any emergency department visit or hospitalization for seizure was 9.27% (95% CI, 9.16%-9.38%) after stroke versus 1.21% (95% CI, 1.21%-1.22%) in the general population. Stroke was more strongly associated with a subsequent seizure among patients <65 years of age (IRR, 12.0; 95% CI, 11.9-12.2) than in patients ≥65 years of age (IRR, 5.5; 95% CI, 5.4-5.5) and in the multistate analysis, the association between stroke and seizure was stronger among nonwhite patients (IRR, 11.0; 95% CI, 10.8-11.2) than among white patients (IRR, 7.3; 95% CI, 7.2-7.4). Risks were especially elevated after intracerebral hemorrhage (IRR, 13.3; 95% CI, 13.0-13.6) and subarachnoid hemorrhage (IRR, 13.2; 95% CI, 12.8-13.7). Our study of Medicare beneficiaries confirmed these findings. CONCLUSIONS: Almost 10% of patients with stroke will develop seizures within a decade. Hemorrhagic stroke, nonwhite race, and younger age seem to confer the greatest risk of developing seizures.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

OBJECTIVES: Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. METHODS: We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. RESULTS: We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). CONCLUSION: Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.

Duration of Agitation, Fluctuations of Consciousness, and Associations with Outcome in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Agitation is common after subarachnoid hemorrhage (SAH) and may be independently associated with outcomes. We sought to determine whether the duration of agitation and fluctuating consciousness were also associated with outcomes in patients with SAH. METHODS: We identified all patients with positive Richmond Agitation Sedation Scale (RASS) scores from a prospective observational cohort of patients with SAH from 2011 to 2015. Total duration of agitation was extrapolated for each patient using available RASS scores, and 24-h mean and standard deviation (SD) of RASS scores were calculated for each patient. We also calculated each patient's duration of substantial fluctuation of consciousness, defined as the number of days with 24-h RASS SD > 1. Patients were stratified by 3-month outcome using the modified Rankin scale, and associations with outcome were assessed via logistic regression. RESULTS: There were 98 patients with at least one positive RASS score, with median total duration of agitation 8 h (interquartile range [IQR] 4-18), and median duration of substantially fluctuating consciousness 2 days (IQR 1-3). Unfavorable 3-month outcome was significantly associated with a longer duration of fluctuating consciousness (odds ratio [OR] per day, 1.51; 95% confidence interval [CI], 1.04-2.20; p = 0.031), but a briefer duration of agitation (OR per hour, 0.94; 95% CI, 0.89-0.99; p = 0.031). CONCLUSION: Though a longer duration of fluctuating consciousness was associated with worse outcomes in our cohort, total duration of agitation was not, and may have had the opposite effect. Our findings should therefore challenge the intensity with which agitation is often treated in SAH patients.

Agitation After Subarachnoid Hemorrhage: A Frequent Omen of Hospital Complications Associated with Worse Outcomes.

BACKGROUND: Agitated delirium is frequent following acute brain injury, but data are limited in patients with subarachnoid hemorrhage (SAH). We examined incidence, risk factors, and consequences of agitation in these patients in a single-center retrospective study. METHODS: We identified all patients treated with antipsychotics or dexmedetomidine from a prospective observational cohort of patients with spontaneous SAH. Agitation was confirmed by chart review. Outcomes were assessed at 12 months using the modified Rankin Scale (mRS), Telephone Interview for Cognitive Status (TICS), and Lawton IADL (Instrumental Activities of Daily Living) scores. Independent predictors were identified using logistic regression. RESULTS: From 309 SAH patients admitted between January 2011 and December 2015, 52 (17 %) developed agitation, frequently in the first 72 h (50 %) and in patients with Hunt-Hess grades 3-4 (12 % of grades 1-2, 28 % of grades 3-4, 8 % of grade 5). There was also a significant association between agitation and a history of cocaine use or prior psychiatric diagnosis. Agitated patients were more likely to develop multiple hospital complications; and in half of these patients, complications were diagnosed within 24 h of agitation onset. Agitation was associated with IADL impairment at 12 months (Lawton >8; p = 0.03, OR 2.7, 95 % CI, 1.1-6.8) in non-comatose patients (Hunt-Hess 1-4), but not with functional outcome (mRS >3), cognitive impairment (TICS ≤30), or ICU/hospital length of stay after controlling for other predictors. CONCLUSION: Agitation occurs frequently after SAH, especially in non-comatose patients with higher clinical grades. It is associated with the development of multiple hospital complications and may have an independent impact on long-term outcomes.