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Objective To describe trajectories of functioning up to 5 years after traumatic brain injury (TBI) that required inpatient rehabilitation in the United States using individual growth curve models conditioned on factors associated with variability in functioning and independence over time. Design Secondary analysis of population-weighted data from a multicenter longitudinal cohort study. Setting Acute inpatient rehabilitation facilities. Participants A total of 4624 individuals 16 years and older with a primary diagnosis of TBI. Main outcome measures Ratings of global disability and supervision needs as reported by participants or proxy during follow-up telephone interviews at 1, 2, and 5 years postinjury. Results Many TBI survivors experience functional improvement through 1 and 2 years postinjury, followed by a decline in functioning and decreased independence by 5 years. However, there was considerable heterogeneity in outcomes across individuals. Factors such as older age, non-White race, lower preinjury productivity, public payer source, longer length of inpatient rehabilitation stay, and lower discharge functional status were found to negatively impact trajectories of change over time. Conclusions These findings can inform the content, timing, and target recipients of interventions designed to maximize functional independence after TBI.

Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.

Rhythmic auditory stimulation (RAS) has been well researched with stroke survivors and individuals who have Parkinson’s disease, but little research exists on RAS with people who have experienced traumatic brain injury (TBI). This pilot study aimed to (1) assess the feasibility of the study design and (2) explore potential benefits. This single-arm clinical trial included 10 participants who had a 2-week control period between baseline and pretreatment. Participants had RAS daily for a 2-week treatment period and immediately completed post-treatment assessments. Participants then had a 1-week control period and completed follow-up assessment. The starting cadence was evaluated each day of the intervention period due to the variation in daily functioning in this population. All 10 participants were 1–20 years post-TBI with notable deviations in spatial-temporal aspects of gait including decreased velocity, step symmetry, and cadence. All participants had a high risk of falling as defined by achieving less than 22 on the Functional Gait Assessment (FGA). The outcome measures included the 10-m walk test, spatial and temporal gait parameters, FGA, and Physical Activity Enjoyment Scale. There were no adverse events during the study and gait parameters improved. After the intervention, half of the participants achieved a score of more than 22 on the FGA, indicating that they were no longer at high risk of experiencing falls.

Background and Purpose: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. Methods: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of Results: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase ( P =0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase ( P =0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery ( P =0.01). Conclusions: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

Objectives To identify risk factors and develop a prediction score for in-hospital symptomatic venous thromboembolism in critically ill patients. Design Retrospective cohort study. Setting Henry Ford Health System, a five-hospital system including 18 ICUs. Patients We obtained data from the electronic medical record of all adult patients admitted to any ICU (total 264 beds) between January 2015 and March 2018. Interventions None. Measurements and main results Symptomatic venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both, diagnosed greater than 24 hours after ICU admission and confirmed by ultrasound, CT, or nuclear medicine imaging. A prediction score (the ICU-Venous Thromboembolism score) was derived from independent risk factors identified using multivariable logistic regression. Of 37,050 patients who met the eligibility criteria, 529 patients (1.4%) developed symptomatic venous thromboembolism. The ICU-Venous Thromboembolism score consists of six independent predictors: central venous catheterization (5 points), immobilization greater than or equal to 4 days (4 points), prior history of venous thromboembolism (4 points), mechanical ventilation (2 points), lowest hemoglobin during hospitalization greater than or equal to 9 g/dL (2 points), and platelet count at admission greater than 250,000/μL (1 point). Patients with a score of 0-8 (76% of the sample) had a low (0.3%) risk of venous thromboembolism; those with a score of 9-14 (22%) had an intermediate (3.6%) risk of venous thromboembolism (hazard ratio, 6.7; 95% CI, 5.3-8.4); and those with a score of 15-18 (2%) had a high (17.7%) risk of venous thromboembolism (hazard ratio, 28.1; 95% CI, 21.7-36.5). The overall C-statistic of the model was 0.87 (95% CI, 0.85-0.88). Conclusions Clinically diagnosed symptomatic venous thromboembolism occurred in 1.4% of this large population of ICU patients with high adherence to chemoprophylaxis. Central venous catheterization and immobilization are potentially modifiable risk factors for venous thromboembolism. The ICU-Venous Thromboembolism score can identify patients at increased risk for venous thromboembolism.

Objective To describe incidence, clinical characteristics, complications, and outcomes in posttraumatic hydrocephalus (PTH) after traumatic brain injury (TBI) for patients treated in an inpatient rehabilitation program. Design Cohort study with retrospective comparative analysis. Setting Inpatient rehabilitation hospital. Participants All patients admitted for TBI from 2009 to 2013 diagnosed with PTH (N=59), defined as ventriculomegaly, delayed clinical recovery discordant with injury severity, hydrocephalus symptoms, or positive lumbar puncture results. Interventions None. Main Outcome Measures Primary measures were incidence of PTH and patient and injury characteristics. Secondary measures included frequency and timing of ventriculoperitoneal (VP) shunt, related complications, emergence from and duration of posttraumatic amnesia (PTA), Rancho Los Amigos Scale (RLAS) score, and FIM score at rehabilitation admission and discharge. Results Of 701 patients with TBI admitted, 59 (8%) were diagnosed with PTH. Of these, the median age was 25 years, with 73% being men. At initial presentation, 52 (88%) did not follow commands. Fifty-two (90%) patients with PTH had a VP shunt placed. Median time from injury to shunt placement was 69 (range, 9–366) days. Seven (12%) patients with PTH experienced postsurgical seizure, 3 (6%) had shunt infection, and 7 (12%) had shunt malfunction. Thirty-six (61%) patients with PTH emerged from PTA during rehabilitation. Median total FIM score at rehabilitation admission was 20 (range, 18–76), and at discharge it was 43 (range, 18–118). Injury severity predicted outcome at rehabilitation admission, whereas shunt timing predicted outcome at rehabilitation discharge. Conclusions Incidence of PTH was observed in 8% of patients with TBI in inpatient rehabilitation. Earlier shunting predicted improved outcome during rehabilitation. Future studies should prospectively examine clinical decision rules, type, and timing of intervention and the coeffectiveness of rehabilitation treatment on outcomes.

Importance Traumatic brain injury (TBI) leads to 2.9 million visits to US emergency departments annually and frequently involves a disorder of consciousness (DOC). Early treatment, including withdrawal of life-sustaining therapies and rehabilitation, is often predicated on the assumed worse outcome of disrupted consciousness. Objective To quantify the loss of consciousness, factors associated with recovery, and return to functional independence in a 31-year sample of patients with moderate or severe brain trauma. Design, Setting, and Participants This cohort study analyzed patients with TBI who were enrolled in the Traumatic Brain Injury Model Systems National Database, a prospective, multiyear, longitudinal database. Patients were survivors of moderate or severe TBI who were discharged from acute hospitalization and admitted to inpatient rehabilitation from January 4, 1989, to June 19, 2019, at 1 of 23 inpatient rehabilitation centers that participated in the Traumatic Brain Injury Model Systems program. Follow-up for the study was through completion of inpatient rehabilitation. Exposures Traumatic brain injury. Main Outcomes and Measures Outcome measures were Glasgow Coma Scale in the emergency department, Disability Rating Scale, posttraumatic amnesia, and Functional Independence Measure. Patient-related data included demographic characteristics, injury cause, and brain computed tomography findings. Results The 17 470 patients with TBI analyzed in this study had a median (interquartile range [IQR]) age at injury of 39 (25-56) years and included 12 854 male individuals (74%). Of these patients, 7547 (57%) experienced initial loss of consciousness, which persisted to rehabilitation in 2058 patients (12%). Those with persisting DOC were younger; had more high-velocity injuries; had intracranial mass effect, intraventricular hemorrhage, and subcortical contusion; and had longer acute care than patients without DOC. Eighty-two percent (n = 1674) of comatose patients recovered consciousness during inpatient rehabilitation. In a multivariable analysis, the factors associated with consciousness recovery were absence of intraventricular hemorrhage (adjusted odds ratio [OR], 0.678; 95% CI, 0.532-0.863;P = .002) and intracranial mass effect (adjusted OR, 0.759; 95% CI, 0.595-0.968;P = .03). Functional improvement (change in total functional independence score from admission to discharge) was +43 for patients with DOC and +37 for those without DOC (P = .002), and 803 of 2013 patients with DOC (40%) became partially or fully independent. Younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion were associated with better functional outcome. Findings were consistent across the 3 decades of the database. Conclusions and Relevance This study found that DOC occurred initially in most patients with TBI and persisted in some patients after rehabilitation, but most patients with persisting DOC recovered consciousness during rehabilitation. This recovery trajectory may inform acute and rehabilitation treatment decisions and suggests caution is warranted in consideration of withdrawing or withholding care in patients with TBI and DOC.

OBJECT Seizures are relatively common after aneurysmal subarachnoid hemorrhage (aSAH). Seizure prophylaxis is controversial and is often based on risk stratification; middle cerebral artery (MCA) aneurysms, associated intracerebral hemorrhage (ICH), poor neurological grade, increased clot thickness, and cerebral infarction are considered highest risk for seizures. The purpose of this study was to evaluate the impact of recent cocaine use on seizure incidence following aSAH. METHODS Prospectively collected data from aSAH patients admitted to 2 institutional neuroscience critical care units between 1991 and 2009 were reviewed. The authors analyzed factors that potentially affected the incidence of seizures, including patient demographic characteristics, poor clinical grade (Hunt and Hess Grade IV or V), medical comorbidities, associated ICH, intraventricular hemorrhage (IVH), hydrocephalus, aneurysm location, surgical clipping and cocaine use. They further studied the impact of these factors on “early” and “late” seizures (defined, respectively, as occurring before and after clipping/coiling). RESULTS Of 1134 aSAH patients studied, 182 (16%) had seizures; 81 patients (7.1%) had early and 127 (11.2%) late seizures, with 26 having both. The seizure rate was significantly higher in cocaine users (37 [26%] of 142 patients) than in non-cocaine users (151 [15.2%] of 992 patients, p = 0.001). Eighteen cocaine-positive patients (12.7%) had early seizures compared with 6.6% of cocaine-negative patients (p = 0.003); 27 cocaine users (19%) had late seizures compared with 10.5% non-cocaine users (p = 0.001). Factors that showed a significant association with increased risk for seizure (early or late) on univariate analysis included younger age (< 40 years) (p = 0.009), poor clinical grade (p = 0.029), associated ICH (p = 0.007), and MCA aneurysm location (p < 0.001); surgical clipping was associated with late seizures (p = 0.004). Following multivariate analysis, age < 40 years (OR 2.04, 95% CI 1.355–3.058, p = 0.001), poor clinical grade (OR 1.62, 95% CI 1.124–2.336, p = 0.01), ICH (OR 1.95, 95% CI 1.164–3.273, p = 0.011), MCA aneurysm location (OR 3.3, 95% CI 2.237–4.854, p < 0.001), and cocaine use (OR 2.06, 95% CI 1.330–3.175, p = 0.001) independently predicted seizures. CONCLUSIONS Cocaine use confers a higher seizure risk following aSAH and should be considered during risk stratification for seizure prophylaxis and close neuromonitoring.

To study the predictive relationship among persons with traumatic brain injury (TBI) between an objective indicator of injury severity (the adapted Marshall computed tomography [CT] classification scheme) and clinical indicators of injury severity in the acute phase, functional outcomes at inpatient rehabilitation discharge, and functional and participation outcomes at 1 year after injury, including death.The sample involved 4895 individuals who received inpatient rehabilitation following acute hospitalization for TBI and were enrolled in the Traumatic Brain Injury Model Systems National Database between 1989 and 2014.Head CT variables for each person were fit into adapted Marshall CT classification categories I through IV.Prediction models were developed to determine the amount of variability explained by the CT classification categories compared with commonly used predictors, including a clinical indicator of injury severity.The adapted Marshall classification categories aided only in the prediction of craniotomy or craniectomy during acute hospitalization, otherwise making no meaningful contribution to variance in the multivariable models predicting outcomes at any time point after injury.Results suggest that head CT findings classified in this manner do not inform clinical discussions related to functional prognosis or rehabilitation planning after TBI.CT: computed tomography; DRS: disability rating scale; EGOS: extended Glasgow outcome scale; FIM: functional independence measure; NDB: National Data Base; PTA: posttraumatic amnesia; RLOS: rehabilitation length of stay; SPOS: semipartial omega squared statistic; TBI: traumatic brain injury; TBIMS: Traumatic Brain Injury Model Systems.

Purpose To compare aneurysmal subarachnoid hemorrhage (aSAH) outcomes between high- and low-volume referral centers with dedicated neurosciences critical care units (NCCUs) and shared neurosurgical, endovascular, and neurocritical care practitioners. Materials and Methods Prospectively collected data of aSAH patients admitted to 2 institutional NCCUs were reviewed. NCCU A is a 22-bed unit staffed 24/7 with overnight in-house NCCU fellow and resident coverage. NCCU B is a 14-bed unit with home call by NCCU attending/fellow and in-house residents. Results A total of 161 aSAH patients (27%) were admitted to NCCU B compared with 447 at NCCU A (73%). Among factors that independently impacted hospital mortality, there were no differences in baseline characteristics: mean age (A: 53.5 ± 14.1 years, B: 53.1 ± 13.6 years), poor grade Hunt and Hess (A: 28.2%, B: 26.7%), presence of multiple medical comorbidities (A: 28%, B: 31.1%), and associated cocaine use (A: 11.6%, B: 14.3%). There was no significant difference in hospital mortality (A: 17.9%, B: 18%), poor functional outcome (A: 30%, B: 25.4%), aneurysm rerupture (A: 2.8%, B: 2.4%), or delayed cerebral ischemia (A: 14.1%, B: 16.1%). Conclusions The noninferior outcomes at the lower SAH volume center suggests that provider expertise, not patient volume, is critical to providing high-quality specialized care.

Background and Purpose— Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods— A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results— Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P P P Conclusions— Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events.

Background: The Hunt and Hess grade and World Federation of Neurological Surgeons (WFNS) scale are commonly used to predict mortality after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to improve the accuracy of mortality prediction compared with the aforementioned scales by creating the ‘‘SAH score.’’ Methods: The aSAH database at our institution was analyzed for factors affectingin-hospital mortality using multiple logistic regressionanalysis. Scores were weighted based on relative risk of mortality after stratification of each of these variables. Glasgow Coma Scale (GCS) was subdivided into groups of 3-4 (score51), 5-8 (score 5 2), 9-13 (score 5 3), and 14-15 (score 5 4). Age was categorized into 4 subgroups: 18-49 (score 5 1), 50-69 (score 5 2), 70-79 (score 5 3), and 80 years or more (score 5 4). Medical comorbidities were subdivided into none (score 5 1), 1 (score 5 2), or 2 or more (score 5 3). Results: In total, 1134 patients were included; all-cause SAH hospital mortality was 18.3%. Admission GCS, age, and medical comorbidities significantly affected mortality after multivariate analysis (P , .05). Summated scores ranged from 0 to 8 with escalating mortality at higher scores (0 5 2%, 1 5 6%, 2 5 8%, 3 5 15%, 4 5 30%, 5 5 58%, 6 5 79%, 7 5 87%, and 8 5 100%). Positive predictive value (PPV) for scores in the range 7-8 was 88.5%, whereas 6-8 was 83%. Negative predictive value (NPV) was 94% for range 0-2 and 92% for 0-3. The area under the curve (AUC) for the SAH score was .821 (good accuracy), compared with the WFNS scale (AUC .777, fair accuracy) and the Hunt and Hess grade (AUC .771, fair accuracy). Conclusions: The SAH score was found to be more accurate in predicting aSAH mortality compared with the Hunt

Background and Purpose— Acute cocaine use has been temporally associated with aneurysmal subarachnoid hemorrhage (aSAH). This study analyzes the impact of cocaine use on patient presentation, complications, and outcomes. Methods— Data of patients admitted with aSAH between 1991 and 2009 were reviewed to determine impact of acute cocaine use (C). These patients were compared with aSAH patients without recent cocaine exposure (NC) in relation to their presentation, complications such as aneurysmal rerupture and delayed cerebral ischemia, and outcomes including hospital mortality and functional outcome. Results— Data of 1134 aSAH patients were reviewed; 142 patients (12.5%) had associated cocaine use. Cocaine users were more likely to be younger (mean age: C, 49±11; NC, 53±14; P P >0.05), associated intraventricular hemorrhage (C, 56%; NC, 51%; P >0.05), or hydrocephalus on admission Head CT (C, 49%; NC, 52%; P >0.05). Aneurysm rerupture incidence was higher among cocaine users (C, 7.7%; NC, 2.7%; P P P P Conclusions— Acute cocaine use was associated with a higher risk of aneurysm rerupture and hospital mortality after aSAH.

Management of aneurysmal subarachnoid hemorrhage (aSAH) has evolved over the past 2 decades, including refinement of neurosurgical techniques, availability of endovascular options, and evolution of neurocritical care; their impact on SAH outcomes is unclear.Prospectively collected data of patients with aSAH admitted to Johns Hopkins Medical Institutions between 1991 and 2009 were analyzed. We compared survival to discharge and functional outcomes at initial clinic appointment postdischarge (30-120 days) in patients admitted between 1991 and 2000 (phase 1 [P1]) and 2000 and 2009 (phase 2 [P2]), respectively, using dichotomized Glasgow Outcome Scale (good outcome: Glasgow Outcome Scale 4-5).A total of 1134 consecutive patients with aSAH were included in the analysis (P1 46.4%, P2 53.6%). There were higher rates of poor grade Hunt and Hess (P1 23%, P2 28%; P.05), admission Glasgow Coma Scale score lower than 8 (P1 14%, P2 21%; P.005), known medical comorbidites (P1 54%, P2 64%; P = .005), associated intraventricular hemorrhage (P1 47%, P2 55%; P.05), and older population (P1 51.5%, P2 53.5%; P.05) in P2. Good outcomes were more common in P2 (71.5%) compared with P1 (65.2%), with 2-fold adjusted odds of good outcomes after correction for various confounding factors (P.001).Our institutional experience over 2 decades confirms that patients with aSAH have shown significant outcome improvements over time.

To characterize associations between antiepileptic drugs with sedating or anesthetic effects (third-line antiepileptic drugs) vs. other antiepileptic agents, and short-term outcomes, in status epilepticus. Furthermore, to evaluate the role of adverse hemodynamic and respiratory effects of these agents in status epilepticus treatment.Retrospective comparative analysis.Tertiary academic medical center with two emergency departments and two neurologic intensive care units.Adults admitted with a diagnosis of status epilepticus defined as seizures lasting continuously5 mins, or for discrete periods in succession.None.Of 126 patients with 144 separate status epilepticus admissions, 57 were female (45%) with mean age 54.7 ± 15.7 yrs. Status epilepticus was convulsive in 132 cases (92%). Status epilepticus etiologies included subtherapeutic antiepileptic drugs (43%), alcohol or other nonantiepileptic drug (13%), and acute central nervous system disease (12%). Third-line antiepileptic drugs were administered in 47 cases (33%). Seventy-eight status epilepticus episodes (54%) had good outcomes (Glasgow Outcome Score = 1, 2) at the time of hospital discharge. On univariate analysis, poor outcome (Glasgow Outcome Score2) was associated with older age (mean 59.8 ± 15.5 vs. 50.5 ± 13.8 yrs, p.001), acute central nervous system disease (21% vs. 4%, p = .001), mechanical ventilation (76% vs. 53%, p = .004), longer duration of ventilation (median 10 days [range 1-56] vs. 2 days [range 1-10], p.001), treatment with vasopressors (35% vs. 5%, p.001), and treatment with third-line antiepileptic drugs (51% vs. 17%, p.001). Death was associated with acute central nervous system disease, prolonged ventilation, treatment with vasopressors, and treatment with third-line antiepileptic drugs. Predictors of poor outcome among all status epilepticus episodes were older age (odds ratio 1.06; 95% confidence interval 1.03-1.09; p.001), treatment with third-line antiepileptic therapy (odds ratio 5.64; 95% confidence interval 2.31-13.75; p.001), and first episode of status epilepticus (odds ratio 3.73; 95% confidence interval 1.38-10.10; p = .010). Among status epilepticus episodes treated by third-line antiepileptic drugs, predictors of poor outcome were older age (odds ratio, 1.09; 95% confidence interval 1.01-1.18; p = .038) and longer ventilation (odds ratio, 1.47; 95% confidence interval 1.08-2.00; p = .015). Predictors of mortality among all status epilepticus episodes were treatment with third-line antiepileptic drugs (odds ratio, 12.08; 95% confidence interval 2.30-63.39; p = .003) and older age (odds ratio, 1.06; 95% confidence interval 1.00-1.12; p = .045).Third-line antiepileptic drug therapies with sedating or anesthetic effects predicted poor outcome and death in status epilepticus. Hypotension requiring vasopressor therapy and duration of mechanical ventilation induced by these agents may be contributing factors, especially when pentobarbital is used. These findings may inform decision making on drug therapy in status epilepticus and help develop safer and more effective treatment strategies to improve outcome.

Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN.Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels136 mmol/L and hypomagnesaemia as levels1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores.About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P0.001), respiratory rate (P0.001), and kcal/h (P0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers.Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.

Cerebral infarction is a common complication of aneurysmal subarachnoid hemorrhage (SAH), but usually occurs several days after onset as a complication of vasospasm or aneurysm repair. The frequency, causes, and clinical impact of acute infarction associated with the primary hemorrhage are poorly understood.We evaluated the presence of cerebral infarction on admission CT in 487 patients admitted within 3 days of SAH onset to our center between July 1996 and September 2002. Infarctions due to angiography or treatment complications were rigorously excluded. Outcome at 3 months was assessed with the modified Rankin Scale.A total of 17 patients (3%) had acute infarction on admission CT; eight had solitary and nine had multiple infarcts. Solitary infarcts usually appeared in the vascular territory distal to the ruptured aneurysm, whereas multiple infarcts tended to be territorial and symmetric. Global cerebral edema (P0.001), coma on presentation (P = 0.001), intraventricular hemorrhage (P = 0.002), elevated APACHE-II physiological subscores (P = 0.026) and loss of consciousness at onset (P = 0.029) were associated with early cerebral infarction. Mortality (P = 0.003) and death or moderate-to-severe disability (mRS 4-6, P = 0.01) occurred more frequently in the early cerebral infarction group.Early cerebral infarction on CT is a rare but devastating complication of acute SAH. The observed associations with coma, global cerebral edema, intraventricular hemorrhage, and loss of consciousness at onset suggest that intracranial circulatory arrest may play a role in the pathogenesis of this disorder.

Objective: To identify risk factors for refractory fever after subarachnoid hemorrhage (SAH), and to determine the impact of temperature elevation on outcome.Methods: We studied a consecutive cohort of 353 patients with SAH with a maximum daily temperature (Tmax) recorded on at least 7 days between SAH days 0 and 10. Fever (>38.3 °C) was routinely treated with acetaminophen and conventional water-circulating cooling blankets. We calculated daily Tmax above 37.0 °C, and defined extreme Tmax as daily excess above 38.3 °C. Global outcome at 90 days was evaluated with the modified Rankin Scale (mRS), instrumental activities of daily living (IADLs) with the Lawton scale, and cognitive functioning with the Telephone Interview of Cognitive Status. Mixed-effects models were used to identify predictors of Tmax, and logistic regression models to evaluate the impact of Tmax on outcome.Results: Average daily Tmax was 1.15 °C (range 0.04 to 2.74 °C). The strongest predictors of fever were poor Hunt-Hess grade and intraventricular hemorrhage (IVH) (both p < 0.001). After controlling for baseline outcome predictors, daily Tmax was associated with an increased risk of death or severe disability (mRS ≥ 4, adjusted OR 3.0 per °C, 95% CI 1.6 to 5.8), loss of independence in IADLs (OR 2.6, 95% CI 1.2 to 5.6), and cognitive impairment (OR 2.5, 95% CI 1.2 to 5.1, all p ≤ 0.02). These associations were even stronger when extreme Tmax was analyzed.Conclusion: Treatment-refractory fever during the first 10 days after subarachnoid hemorrhage (SAH) is predicted by poor clinical grade and intraventricular hemorrhage, and is associated with increased mortality and more functional disability and cognitive impairment among survivors. Clinical trials are needed to evaluate the impact of prophylactic fever control on outcome after SAH.

Background and Purpose— Cigarette smoking is a risk factor for the formation and rupture of intracranial aneurysms. Few studies have examined predictors of resumption of cigarette smoking after a first episode of subarachnoid hemorrhage (SAH). Methods— Of 620 SAH patients treated between July 1996 and November 2002, we prospectively evaluated continued cigarette use in 152 smokers alive at 3 months. Univariate and multivariate logistic regression analyses were used to identify potential demographic, social, and clinical predictors of continued cigarette use, defined as smoking ≥1 cigarette per week in the month before follow-up. Results— Thirty-seven percent (56 of 152) resumed smoking after their SAH. Patients who continued smoking were younger, were more often black, had begun smoking at an earlier age, and had a higher frequency of prior alcohol or cocaine use and self-reported depression or anxiety than those who quit (all P Conclusions— More than one third of prior smokers continue to use nicotine after SAH. Young age at smoking onset and a history of depression or alcohol use are risk factors for continued cigarette use. Targeted smoking cessation programs are needed to reduce the high rate of smoking resumption after SAH.

Clinical approach to ventilator-associated pneumonia (VAP) in the neurocritical care unit (NCCU) varies widely among physicians despite training and validated criteria. Prospective observational study of all mechanically ventilated patients with suspected VAP over 18 months in an academic NCCU. Patients meeting VAP criteria by a surveillance program (SurvVAP) were compared to treated patients who did not meet surveillance criteria (ClinVAPonly). We identified appropriate/potentially inappropriate antibiotic treatment and factors associated with excessive antibiotic days (EAD). Of 622 ventilated patients, 83 cases were treated as VAP. Of these, 26 (31.3 %) had VAP by CDC criteria (SurvVAP) (VAP rate = 7.3 cases/1,000 ventilator days). Clinical features significantly more prevalent in SurvVAP cases (vs. ClinVAPonly) were change in sputum character, tachypnea, oxygen desaturation, persistent infiltrate on chest X-ray and higher clinical pulmonary infection score, but not positive sputum culture. Treatment with pneumonia-targeted antibiotics for >8 days was significantly more common in ClinVAPonly versus SurvVAP patients (73.7 vs. 30.8 %, p

We have previously reported an increase of 0.6% in the relative risk of aneurysmal subarachnoid hemorrhage (aSAH) in response to every 1°F decrease in the maximum daily temperature (Tmax) in colder seasons from patients presenting to our regional tertiary care center. We hypothesized that this relationship would also be observed in the warmer summer months with ambient temperatures greater than 70°F. From prospectively collected incidence data for aSAH patients, we investigated absolute Tmax, average daily temperatures, intraday temperature ranges, and the variation of daily Tmax relative to 70°F to assess associations with aSAH incidence for patients admitted to our institution between 1991 and 2009 during the hottest months and days on which Tmax > 70°F. For all days treated as a group, the mean Tmax (± standard deviation) was lower when aSAH occurred than when it did not (64.4 ± 18.2°F versus 65.8 ± 18.3°F; p = 0.016). During summer months, the odds ratio (OR) of aSAH incidence increased with lower mean Tmax (OR 1.019; 95% confidence interval 1.001–1.037; p = 0.043). The proportion of days with aSAH admissions was lower on hotter days than the proportion of days with no aSAH (96% versus 98%; p = 0.006). aSAH were more likely to occur during the summer and on days with a temperature fluctuation less than 10°F (8% versus 4%; p = 0.002). During the hottest months of the year in the mid-Atlantic region, colder maximum daily temperatures, a smaller heat burden above 70°F, and smaller intraday temperature fluctuations are associated with increased aSAH admissions in a similar manner to colder months. These findings support the hypothesis that aSAH incidence is more likely with drops in temperature, even in the warmer months.

To evaluate the hypothesis that educational attainment, a marker of cognitive reserve, is a predictor of disability-free recovery (DFR) after moderate to severe traumatic brain injury (TBI).Retrospective study of the TBI Model Systems Database, a prospective multicenter cohort funded by the National Institute on Disability and Rehabilitation Research. Patients were included if they were admitted for rehabilitation after moderate to severe TBI, were aged 23 years or older, and had at least 1 year of follow-up. The main outcome measure was DFR 1 year postinjury, defined as a Disability Rating Scale score of zero.Of 769 patients included, 214 (27.8%) achieved DFR at 1 year. In total, 185 patients (24.1%) had12 years of education, while 390 (50.7%) and 194 patients (25.2%) had 12 to 15 years and ≥16 years of education, respectively. DFR was achieved by 18 patients (9.7%) with12 years, 120 (30.8%) with 12 to 15 years, and 76 (39.2%) with ≥16 years of education (p0.001). In a logistic regression model controlling for age, sex, and injury- and rehabilitation-specific factors, duration of education of ≥12 years was independently associated with DFR (odds ratio 4.74, 95% confidence interval 2.70-8.32 for 12-15 years; odds ratio 7.24, 95% confidence interval 3.96-13.23 for ≥16 years).Educational attainment was a robust independent predictor of 1-year DFR even when adjusting for other prognostic factors. A dose-response relationship was noted, with longer educational exposure associated with increased odds of DFR. This suggests that cognitive reserve could be a factor driving neural adaptation during recovery from TBI.

Lateral brain displacement has been associated with loss of consciousness and poor outcome in a range of acute neurologic disorders. We studied the association between lateral brain displacement and awakening from acute coma.This prospective observational study included all new onset coma patients admitted to the Neurosciences Critical Care Unit (NCCU) over 12 consecutive months. Head computed tomography (CT) scans were analyzed independently at coma onset, after awakening, and at follow-up. Primary outcome measure was awakening, defined as the ability to follow commands before hospital discharge. Secondary outcome measures were discharge Glasgow Coma Scale (GCS), modified Rankin Scale, Glasgow Outcome Scale, and hospital and NCCU lengths of stay.Of the 85 patients studied, the mean age was 58 ± 16 years, 51% were female, and 78% had cerebrovascular etiology of coma. Fifty-one percent of patients had midline shift on head CT at coma onset and 43 (51%) patients awakened. In a multivariate analysis, independent predictors of awakening were younger age (odds ratio [OR] = 1.039, 95% confidence interval [CI] = 1.002-1.079, p = 0.040), higher GCS score at coma onset (OR = 1.455, 95% CI = 1.157-1.831, p = 0.001), nontraumatic coma etiology (OR = 4.464, 95% CI = 1.011-19.608, p = 0.048), lesser pineal shift on follow-up CT (OR = 1.316, 95% CI = 1.073-1.615, p = 0.009), and reduction or no increase in pineal shift on follow-up CT (OR = 11.628, 95% CI = 2.207-62.500, p = 0.004).Reversal and/or limitation of lateral brain displacement are associated with acute awakening in comatose patients. These findings suggest objective parameters to guide prognosis and treatment in patients with acute onset of coma.

Prognostication of mortality or severe disability often prompts withdrawal of technological life support in patients following aneurysmal subarachnoid hemorrhage (aSAH). We assessed admission factors impacting decisions to withdraw treatment after aSAH.Prospectively collected data of aSAH patients admitted to our institution between 1991 and 2009 were reviewed. Patients given comfort care measures were identified, including early withdrawal of treatment (72 h after admission). Independent predictors of treatment withdrawal were assessed with multivariable analysis.The study included 1,134 patients, of whom 72 % were female, 58 % white, and 38 % black or African-American. Mean age was 52.5 ± 14.0 years. In-hospital mortality was 18.3 %. Of the 207 patients who died, treatment was withdrawn in 72 (35 %) and comfort measures instituted early in 31 (15 %). Among patients who died, WOLST was associated with older age (63.6 ± 14.2 years, WOLST vs. 55.6 ± 13.7 years, no WOLST, p0.001); GCS score8 (62 % of WOLST vs. 44 % with no WOLST, p = 0.010); HH3 (72 % of WOLST vs. 53 % with no WOLST, p = 0.008); and hydrocephalus (81 % of WOLST vs. 63 % with no WOLST, p = 0.009). Independent predictors of WOLST were poorer Hunt and Hess grade (AOR 1.520, 95 % CI 1.160-1.992, p = 0.002) and older age (AOR 1.045, 95 % CI 1.022-1.068, p0.001) with the latter also impacting early WOLST decisions.Older age and poor clinical grade on presentation predicted WOLST, and age predicted decisions to withdraw treatment earlier following aSAH. While based on prognosis, and in some cases patient wishes, this may also constitute a self-fulfilling prophecy in others.

To identify patients most likely to have seizures documented on continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to record the first seizure.Five hundred seventy consecutive patients who underwent cEEG monitoring over a 6.5-year period were reviewed for the detection of subclinical seizures or evaluation of unexplained decrease in level of consciousness. Baseline demographic, clinical, and EEG findings were recorded and a multivariate logistic regression analysis performed to identify factors associated with 1) any EEG seizure activity and 2) first seizure detected after24 hours of monitoring.Seizures were detected in 19% (n = 110) of patients who underwent cEEG monitoring; the seizures were exclusively nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures, 89% (n = 98) were in intensive care units at the time of monitoring. Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI 4.2 to 14.2), age18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% (n = 6), the first seizure was recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after24 hours of monitoring (20% vs 5% of noncomatose patients; OR 4.5, p = 0.018).CEEG monitoring detected seizure activity in 19% of patients, and the seizures were almost always nonconvulsive. Coma, age18 years, a history of epilepsy, and convulsive seizures prior to monitoring were risk factors for electrographic seizures. Comatose patients frequently required24 hours of monitoring to detect the first electrographic seizure.

To determine the effect that acute physiologic derangements have on outcome after subarachnoid hemorrhage (SAH) and to design a composite score summarizing these abnormalities.Prospective observational study.Neuroscience intensive care unit in a tertiary care academic center.Consecutive cohort of 413 patients with SAH admitted within 3 days of SAH onset with 3-month modified Rankin Scale scores.None.Among 20 physiologic variables assessed within 24 hrs of admission, four were independently associated with death or severe disability (modified Rankin Scale score, 4-6) at 3 months in a multivariate analysis: arterio-alveolar gradient of125 mm Hg (odds ratio [OR], 4.5; 95% confidence interval [CI], 2.7-7.6), serum bicarbonate of20 mmol/L (OR, 2.9; 95% CI, 1.6-5.6), serum glucose of180 mg/dL (OR, 2.8; 95% CI, 1.6-4.8), and mean arterial pressure of70 or130 mm Hg (OR, 1.7; 95% CI, 1.0-2.9). Based on their proportional contribution to outcome, we constructed the SAH Physiologic Derangement Score (SAH-PDS; range, 0-8) by assigning the following weights for abnormal findings: arterio-alveolar gradient, 3 points; bicarbonate, 2 points; glucose, 2 points; and mean arterial pressure, 1 point. After controlling for known predictors of death or severe disability (age, admission neurologic status, loss of consciousness, aneurysm size, intraventricular hemorrhage, and rebleeding), the SAH Physiologic Derangement Score was independently associated with poor outcome (OR, 1.3 for each point increase; 95% CI, 1.1-1.6). By contrast, the systemic inflammatory response syndrome score and the Acute Physiology and Chronic Health Evaluation II physiologic subscore did not add predictive value to the model.Acute interventions specifically targeting hypoxemia, metabolic acidosis, hyperglycemia, and cardiovascular instability may improve the outcome of SAH patients. The SAH Physiologic Derangement Score may prove useful for rapidly quantifying the severity of important physiologic derangements in acute SAH.

Objective: Patients with aneurysmal subarachnoid hemorrhage (aSAH) require management in centers with neurosurgical expertise necessitating emergent interhospital transfer (IHT). Our objective was to compare outcomes in aSAH IHTs to our institution with aSAH admissions from our institutional emergency department (ED). Methods: Data for consecutive patients with aSAH admitted to Johns Hopkins Medical Institutions between 1991 and 2009 were analyzed from a prospectively obtained database. We compared inhospital mortality and functional outcomes at first clinical appointment post-aSAH (30-120 days) using dichotomized Glasgow Outcome Scale (good outcome: Glasgow Outcome Scale 4-5) in ED admissions with IHTs. Results: A total of 1134 consecutive patients with aSAH were included in analysis (ED 40.1%, IHT 59.9%). Direct ED admissions had a higher incidence of poor Hunt and Hess grade (4/5) and major medical comorbidities, with no significant differences between the 2 groups in age, intraventricular hemorrhage, and hydrocephalus. In-hospital mortality for ED admissions (14.9%) was significantly lower than that for IHTs (20.5%), with 1.8 times greater adjusted odds of survival after multivariate analysis (P = .001). Emergency department admissions had nearly 2-fold greater odds of good outcomes (odds ratio, 1.89; P b .001) after multivariate analysis. Conclusions: Our institutional ED SAH admissions had significantly better outcomes than did IHTs, suggesting that delays in optimizing care before transfer could deleteriously impact outcomes.