Nonpharmacological interventions to improve the cognitive function among persons with traumatic brain injury: A systematic review.

PURPOSE: The systematic review aimed to evaluate the effectiveness of nonpharmacological interventions (NPIs) for improving cognitive function among persons with traumatic brain injury. DESIGN: A systematic review. METHODS: This systematic review was registered in PROSPERO and followed the PRISMA guideline. PubMed, ScienceDirect, Scopus, SpringerLink, Wiley Online Library, JSTOR, and Taylor & Francis were systematically searched for relevant articles of peer-reviewed studies published between 2008 and 2022. Two independent researchers conducted study selection, data extraction, and data quality assessment. FINDINGS: Twenty-one studies met inclusion criteria, numbering a total of 757 participants. Six groups of NPIs were effective in improving cognitive functioning among persons with traumatic brain injury, including multimodal cognitive training, technology innovation, memory training, executive function training, physical activity, and sensory stimulation programs. Pooled evidence revealed that NPIs had a large effect on memory (d = 0.80, p < 0.05 to d = 2.03, p < 0.000), processing speed (d = 1.58, p < 0.05), and cognitive behavior (d = 1.63, p < 0.001 to d = 8.91, p 0.003). There was a medium effect on executive function (d = 0.5, p < 0.01 to d = 0.62, p < 0.05), attention (d = 0.5, p < 0.01), and intelligence (d = 0.57 to d = 0.59, p = 0.000). For visuospatial function and language, there was a significant increase post-intervention. CONCLUSION: Evidence from this systematic review indicates that NPIs, specifically the use of multimodal cognitive training and sensory stimulation programs, were effective in improving cognitive function outcomes among persons with traumatic brain injury, with medium to large effect sizes. CLINICAL RELEVANCE: Nonpharmacological interventions (NPIs) can enhance cognitive function in individuals with traumatic brain injury. These findings can guide healthcare professionals in clinical settings and support the development of technology applications for cognitive rehabilitation using NPIs.

Subarachnoid Hemorrhage Outcomes in an Endovascular Right of First Refusal Neurosurgical Environment.

BACKGROUND: Randomized controlled trials demonstrate that endovascular techniques yield improved outcomes compared with microsurgical approaches. However, not all patients are suitable candidates for endovascular management. This study aimed to determine if healthy patients managed microsurgically could achieve functional outcomes comparable to patients managed endovascularly. METHODS: Patients treated for ruptured aneurysmal subarachnoid hemorrhage at 2 level 1 stroke centers from January 2012 through December 2020 were retrospectively reviewed. All cases were evaluated in an endovascular right of first refusal neurosurgical environment. We collected relevant clinical and follow-up data and created a generalized linear model to identify differences between patients treated endovascularly versus microsurgically. A propensity score model accounting for these differences was used to predict patient outcomes. Functional outcomes were independently assessed using the modified Rankin Scale (mRS) with good functional outcome defined as modified Rankin Scale score <3. RESULTS: The study included 588 patients (211 microsurgical, 377 endovascular); median age was 58 years (interquartile range: 40-86 years); in-hospital mortality was 13%. Age, aneurysm size, and aneurysm location significantly predicted treatment modality (all P < 0.05). After greedy-type matching (210 microsurgical, 210 endovascular), patients managed microsurgically were less likely to be discharged home (odds ratio = 0.6, 95% confidence interval 0.4-0.9, P = 0.01). Functional differences disappeared over time; patients in the 2 treatment arms had similar functional outcomes at 3 months (odds ratio = 1.1, 95% confidence interval 0.7-1.8, P = 0.66) and 1 year after subarachnoid hemorrhage (odds ratio = 1.3, 95% confidence interval 0.8-2.1, P = 0.38). CONCLUSIONS: In an endovascular right of first refusal neurosurgical environment, practitioners can treat patients who are not good endovascular candidates microsurgically and achieve functional outcomes comparable to patients managed endovascularly.

Hunt-Hess Score at 48 Hours Improves Prognostication in Grade 5 Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Patients with Hunt-Hess (HH)5 aneurysmal subarachnoid hemorrhage (SAH) have high mortality rates. Despite an initial moribund exam, a subset of patients progress to favorable outcomes. OBJECTIVE: To evaluate the utility of delayed HH grading to improve prognostication. METHODS: We retrospectively reviewed patients undergoing treatment of ruptured aneurysms at two level 1 stroke centers from January 2012 through December 2020. We collected relevant clinical information and developed a multivariate cox regression model to identify independent predictors of mortality. To evaluate the utility of delayed examinations in predicting outcomes, we re-assessed the HH grade at 48 hours post admission and constructed a logistic regression model with potential confounders to predict mortality. RESULTS: From 2012 to 2020, 621 patients underwent treatment for aneurysmal SAH. We identified 63 HH5 patients (10%) with a mean age of 58 years. Among these patients, the median length of stay was 14 days, with 3 patients passing away within 48 hours. The overall mortality rate was 63% at 24 months. To predict mortality, our cox regression model found only age to be significant (P = 0.002). Delayed HH grading improved prognostication at 48 hours and remained significant on multivariate analysis as a predictor of mortality (P = 0.0001). We observed a significant difference in mortality between patients HH5 and patients HH4 or lower at 48 hours (P = 0.0003). CONCLUSIONS: Delayed reassessment of HH grade 48 hours postadmission is a predictor of mortality, suggesting reassessment at 48 hours in high grade SAH leads to better prognostication.

What a Rat Race: A Case Study of Rat Bite Fever in an Emergency Department.

Rat bite fever is an acute illness caused by bacteria from rodents. In the United States, rat bite fever is considered rare; however, actual incidence is unknown because of lack of mandatory disease reporting requirements. Risk of development of rat bite fever after being bitten by a rat is approximately 10%. Early treatment is imperative as death is a potential complication. The following case study demonstrates the gravity of the syndrome.

Iron homeostasis pathway DNA methylation trajectories reveal a role for STEAP3 metalloreductase in patient outcomes after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Following aneurysmal subarachnoid hemorrhage (aSAH), the brain is susceptible to ferroptosis, a type of iron-dependent cell death. Therapeutic intervention targeting the iron homeostasis pathway shows promise for mitigating ferroptosis and improving recovery in animal models, but little work has been conducted in humans. DNA methylation (DNAm) plays a key role in gene expression and brain function, plasticity, and injury recovery, making it a potentially useful biomarker of outcomes or therapeutic target for intervention. Therefore, in this longitudinal, observational study, we examined the relationships between trajectories of DNAm in candidate genes related to iron homeostasis and acute (cerebral vasospasm and delayed cerebral ischemia) and long-term (Glasgow Outcome Scale [GOS, unfavorable = 1-3] and death) patient outcomes after aSAH. RESULTS: Longitudinal, genome-wide DNAm data were generated from DNA extracted from post-aSAH cerebrospinal fluid (n = 260 participants). DNAm trajectories of 637 CpG sites in 36 candidate genes related to iron homeostasis were characterized over 13 days post-aSAH using group-based trajectory analysis, an unsupervised clustering method. Significant associations were identified between inferred DNAm trajectory groups at several CpG sites and acute and long-term outcomes. Among our results, cg25713625 in the STEAP3 metalloreductase gene (STEAP3) stood out. Specifically, in comparing the highest cg25713625 DNAm trajectory group with the lowest, we observed significant associations (i.e., based on p-values less than an empirical significance threshold) with unfavorable GOS at 3 and 12 months (OR = 11.7, p = 0.0006 and OR = 15.6, p = 0.0018, respectively) and death at 3 and 12 months (OR = 19.1, p = 0.0093 and OR = 12.8, p = 0.0041, respectively). These results were replicated in an independent sample (n = 100 participants) observing significant associations with GOS at 3 and 12 months (OR = 8.2, p = 0.001 and OR = 6.3, p = 0.0.0047, respectively) and death at 3 months (OR = 2.3, p = 0.008) and a suggestive association (i.e., p-value < 0.05 not meeting an empirical significance threshold) with death at 12 months (OR = 2.0, p = 0.0272). In both samples, an additive effect of the DNAm trajectory group was observed as the percentage of participants with unfavorable long-term outcomes increased substantially with higher DNAm trajectory groups. CONCLUSION: Our results support a role for DNAm of cg25713625/STEAP3 in recovery following aSAH. Additional research is needed to further explore the role of DNAm of cg25713625/STEAP3 as a biomarker of unfavorable outcomes, or therapeutic target to improve outcomes, to translate these findings clinically.

ANGPT1 methylation and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients.

Background: Delayed cerebral ischemia (DCI) is a common secondary complication and an important cause of disability and mortality among patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Knowledge on DCI pathogenesis, risk factors, and biomarkers are essential for early detection and improved prognosis. To investigate the role of DNA methylation in DCI risk, we conducted an epigenome-wide association study (EWAS) in 68 patients followed up to 1 year after the initial aneurysm rupture. Blood samples were collected within 48 h post hemorrhage and used for DNA methylation profiling at ~ 450k CpG sites. A separate cohort of 175 patients was sequenced for the top CpG sites from the discovery analysis for a replication of the EWAS findings. Results: EWAS did not identify any epigenome-wide significant CpGs. The top signal, cg18031596, was annotated to ANGPT1, a gene with critical functions in angiogenesis after vascular injury. Post hoc power calculations indicated a well-powered discovery analysis for cg18031596. Analysis of the replication cohort showed that four out of the five CpG sites sequenced at the ANGPT1 locus passed a Bonferroni-adjusted significance threshold. In a pooled analysis of the entire sample, three out of five yielded a significant p-value, and the top association signal (p-value = 0.004) was seen for a CpG that was not originally measured in the discovery EWAS. However, four ANGPT1 CpG sites had an opposite effect direction in the replication analysis compared to the discovery EWAS, marking a failure of replication. We carefully examined this observed flip in directions and propose several possible explanations in addition to that it was a random chance that ANGPT1 ranked at the top in the discovery EWAS. Conclusions: We failed to demonstrate a significant and consistent effect of ANGPT1 methylation in DCI risk in two cohorts. Though the replication attempt to weaken the overall support of this gene, given its relevant function and top rank of significance in the EWAS, our results call for future studies of larger aSAH cohorts to determine its relevance for the occurrence of DCI.

Methylation Data Processing Protocol and Comparison of Blood and Cerebral Spinal Fluid Following Aneurysmal Subarachnoid Hemorrhage.

One challenge in conducting DNA methylation-based epigenome-wide association study (EWAS) is the appropriate cleaning and quality-checking of data to minimize biases and experimental artifacts, while simultaneously retaining potential biological signals. These issues are compounded in studies that include multiple tissue types, and/or tissues for which reference data are unavailable to assist in adjusting for cell-type mixture, for example cerebral spinal fluid (CSF). For our study that evaluated blood and CSF taken from aneurysmal subarachnoid hemorrhage (aSAH) patients, we developed a protocol to clean and quality-check genome-wide methylation levels and compared the methylomic profiles of the two tissues to determine whether blood is a suitable surrogate for CSF. CSF samples were collected from 279 aSAH patients longitudinally during the first 14 days of hospitalization, and a subset of 88 of these patients also provided blood samples within the first 2 days. Quality control (QC) procedures included identification and exclusion of poor performing samples and low-quality probes, functional normalization, and correction for cell-type heterogeneity via surrogate variable analysis (SVA). Significant differences in rates of poor sample performance was observed between blood (1.1% failing QC) and CSF (9.12% failing QC; p = 0.003). Functional normalization increased the concordance of methylation values among technical replicates in both CSF and blood. SVA improved the asymptotic behavior of the test of association in a simulated EWAS under the null hypothesis. To determine the suitability of blood as a surrogate for CSF, we calculated the correlations of adjusted methylation values at each CpG between blood and CSF globally and by genomic regions. Overall, mean within-CpG correlation was low (r < 0.26), suggesting that blood is not a suitable surrogate for global methylation in CSF. However, differences in the magnitude of the correlation were observed by genomic region (CpG island, shore, shelf, open sea; p < 0.001 for all) and orientation with respect to nearby genes (3' UTR, transcription start site, exon, body, 5' UTR; p < 0.01 for all). In conclusion, the correlation analysis and QC pipelines indicated that DNA extracted from blood was not, overall, a suitable surrogate for DNA from CSF in aSAH methylomic studies.

Psychometric Properties of the Patient Assessment of Own Functioning Inventory Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the psychometric properties of the Patient Assessment of Own Functioning Inventory (PAOFI) following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The PAOFI was completed by 182 participants 3 months after verified aSAH. Exploratory factor analysis was used to evaluate the underlying factor structure of the PAOFI and reliability and concurrent validity were evaluated for each subscale. RESULTS: A three-factor structure accounted for 58.9% of the extracted variance. Cronbach's alpha coefficients for extracted factors ranged from .867 to .924. The PAOFI subscales demonstrated concurrent validity with neuropsychological tests measuring similar constructs. CONCLUSION: There is evidence of reliability and validity of the PAOFI following aSAH. Further studies are needed to confirm these results.

Genetic Variability in the Iron Homeostasis Pathway and Patient Outcomes After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND/OBJECTIVE: Iron can be detrimental to most tissues both in excess and in deficiency. The brain in particular is highly susceptible to the consequences of excessive iron, especially during blood brain barrier disruption after injury. Preliminary evidence suggests that iron homeostasis is important during recovery after neurologic injury; therefore, the exploration of genetic variability in genes involved in iron homeostasis is an important area of patient outcomes research. The purpose of this study was to examine the relationship between tagging single nucleotide polymorphisms (SNPs) in candidate genes related to iron homeostasis and acute and long-term patient outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This study was a longitudinal, observational, candidate gene association study of participants with aSAH that used a two-tier design including tier 1 (discovery, n = 197) and tier 2 (replication, n = 277). Participants were followed during the acute outcome phase for development of cerebral vasospasm and delayed cerebral ischemia (DCI) and during the long-term outcome phase for death and gross functional outcome using the Glasgow Outcome Scale (GOS; poor = 1-3). Genetic association analyses were performed using a logistic regression model adjusted for age, sex, and Fisher grade. Approximate Bayes factors (ABF) and Bayesian false discovery probabilities (BFDP) were used to prioritize and interpret results. RESULTS: In tier 1, 235 tagging SNPs in 28 candidate genes were available for analysis and 26 associations (20 unique SNPs in 12 genes) were nominated for replication in tier 2. In tier 2, we observed an increase in evidence of association for three associations in the ceruloplasmin (CP) and cubilin (CUBN) genes. We observed an association of rs17838831 (CP) with GOS at 3 months (tier 2 results, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.14-3.86, p = 0.018, ABF = 0.52, and BFDP = 70.8%) and GOS at 12 months (tier 2 results, OR = 1.86, 95% CI 0.98-3.52, p = 0.058, ABF = 0.72, and BFDP = 77.3%) as well as rs10904850 (CUBN) with DCI (tier 2 results, OR = 0.70, 95% CI 0.48-1.02, p = 0.064, ABF = 0.59, and BFDP = 71.8%). CONCLUSIONS: Among the genes examined, our findings support a role for CP and CUBN in patient outcomes after aSAH. In an effort to translate these findings into clinical utility and improve outcomes after aSAH, additional research is needed to examine the functional roles of these genes after aSAH.

Genetic Variability and Trajectories of DNA Methylation May Support a Role for HAMP in Patient Outcomes After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND/OBJECTIVE: Preclinical evidence suggests that iron homeostasis is an important biological mechanism following aneurysmal subarachnoid hemorrhage (aSAH); however, this concept is underexplored in humans. This study examined the relationship between patient outcomes following aSAH and genetic variants and DNA methylation in the hepcidin gene (HAMP), a key regulator of iron homeostasis. METHODS: In this exploratory, longitudinal observational study, participants with verified aSAH were monitored for acute outcomes including cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) and evaluated post-discharge at 3 and 12 months for long-term outcomes of death and functional status using the Modified Rankin Scale (mRS; poor = 3-6) and Glasgow Outcome Scale (GOS; poor = 1-3). Participants were genotyped for two genetic variants, and DNA methylation data were collected from serial cerebrospinal fluid over 14 days post-aSAH at eight methylation sites within HAMP. Participants were grouped based on their site-specific DNA methylation trajectory, with and without correcting for cell-type heterogeneity (CTH), and the associations between genetic variants and inferred DNA methylation trajectory groups and patient outcomes were tested. To correct for multiple testing, an empirical significance threshold was computed using permutation testing. RESULTS: Genotype data for rs10421768 and rs7251432 were available for 241 and 371 participants, respectively, and serial DNA methylation data were available for 260 participants. Acute outcome prevalence included CV in 45% and DCI in 37.1% of the overall sample. Long-term outcome prevalence at 3 and 12 months included poor GOS in 23% and 21%, poor mRS in 31.6% and 27.3%, and mortality in 15.1% and 18.2%, respectively, in the overall sample. Being homozygous for the rs7251432 variant allele was significantly associated with death at 3 months (p = 0.003) and was the only association identified that passed adjustment for multiple testing mentioned above. Suggestive associations (defined as trending toward significance, p value < 0.05, but not meeting empirical significance thresholds) were identified between the homozygous variant allele for rs7251432 and poor GOS and mRS at 3 months (both p = 0.04) and death at 12 months (p = 0.02). For methylation trajectory groups, no associations remained significant after correction for multiple testing. However, for methylation trajectory groups not adjusted for CTH, suggestive associations were identified between cg18149657 and poor GOS and mRS at 3 months (p = 0.003 and p = 0.04, respectively) and death at 3 months (p = 0.04), and between cg26283059 and DCI (p = 0.01). For methylation trajectory groups adjusted for CTH, suggestive associations were identified between cg02131995 and good mRS at 12 months (p = 0.02), and between cg26283059 and DCI (p = 0.01). CONCLUSIONS: This exploratory pilot study offers preliminary evidence that HAMP may play a role in patient outcomes after aSAH. Replication of this study and mechanistic investigation of the role of HAMP in patient outcomes after aSAH are needed.

Neurocardiac Injury Assessed by Strain Imaging Is Associated With In-Hospital Mortality in Patients With Subarachnoid Hemorrhage.

OBJECTIVES: This study sought to test the hypothesis that speckle tracking strain echocardiography can quantify neurocardiac injuries in patients with aneurysmal subarachnoid hemorrhage (SAH), which is associated with worse clinical outcome. BACKGROUND: SAH may be a life-threatening disease associated with variable degrees of neurocardiac injury. Strain imaging has the potential to detect subtle myocardial dysfunction which is additive to conventional measurements. METHODS: A total of 255 consecutive patients were prospectively enrolled with acute SAH, who were admitted to the intensive care unit with echocardiography studies within 72 h. Left ventricular (LV) and right ventricular (RV) strains were acquired from standard apical views. Abnormal LV global longitudinal strain (GLS) and RV free-wall strain were pre-defined as <17% and <23% (absolute values), respectively. RESULTS: Performing LV GLS was feasible in 221 patients (89%) 53 ± 10 years of age, 71% female, after excluding those with previous cardiac disease. Abnormal LV GLS findings were observed in 53 patients (24%) and were associated with worse clinical severity, including a Hunt-Hess grade >3 (34% vs. 15%; p = 0.005) and biomarker evidence of neurocardiac injury and higher troponin values (1.50 [interquartile range (IQR): 0.01 to 3.87] vs. 0.01 [IQR: 0.01 to 0.22] ng/ml; p < 0.001). A reverse Takotsubo pattern of segmental strain was observed in 49% of patients (apical sparing and reduced basal strain). Importantly, LV GLS was more strongly associated with in-hospital mortality than left ventricular ejection fraction (LVEF), even after adjusting for clinical severity (odds ratio [OR]: 3.11; 95% confidence interval [CI]: 1.12 to 8.63; p = 0.029). RV strain was measured in 159 subjects (72%); abnormal RV strain was added to LV GLS for predicting in-hospital mortality (p = 0.007). CONCLUSIONS: Neurocardiac injury can be detected by LV GLS and RV strain in patients with acute SAH. LV GLS was significantly associated with in-hospital mortality. RV strain, when available, added prognostic value to LV GLS. Abnormal myocardial strain is a marker for increased risk of in-hospital mortality in SAH and has clinical prognostic utility.

Psychosocial Comorbidities Related to Return to Work Rates Following Aneurysmal Subarachnoid Hemorrhage.

Purpose Ability to return to work (RTW) after stroke has been shown to have positive psychosocial benefits on survivors. Although one-fifth of aneurysmal subarachnoid hemorrhage (aSAH) survivors suffer from poor psychosocial outcomes, the relationship between such outcomes and RTW post-stroke is not clear. This project explores the relationship between age, gender, race, marital status, anxiety and depression and RTW 3 and 12 months post-aSAH. Methods Demographic and clinical variables were collected from the electronic medical record at the time of aSAH admission. Anxiety and depression were assessed at 3 and 12 months post-aSAH using the State Trait Anxiety Inventory (STAI) and Beck's Depression Inventory-II (BDI-II) in 121 subjects. RTW for previously employed patients was dichotomized into yes/no at their 3 or 12 month follow-up appointment. Results Older age was significantly associated with failure to RTW at 3 and 12 months post-aSAH (p = 0.003 and 0.011, respectively). Female gender showed a trending but nonsignificant relationship with RTW at 12 months (p = 0.081). High scores of depression, State anxiety, and Trait anxiety all had significant associations with failure to RTW 12 months post-aSAH (0.007 ≤ p ≤ 0.048). At 3 months, there was a significant interaction between older age and high State or Trait anxiety with failure to RTW 12 months post-aSAH (p = 0.025, 0.042 respectively). Conclusions Patients who are older and suffer from poor psychological outcomes are at an increased risk of failing to RTW 1-year post-aSAH. Our interactive results give us information about which patients should be streamlined for therapy to target their psychosocial needs.

Vasopressor Infusion After Subarachnoid Hemorrhage Does Not Increase Regional Cerebral Tissue Oxygenation.

INTRODUCTION: Vasopressors are commonly used after aneurysmal subarachnoid hemorrhage (aSAH) to sustain cerebral pressure gradients. Yet, the relationship between vasopressors and the degree of cerebral microcirculatory support achieved remains unclear. This study aimed to explore the changes in cerebral and peripheral regional tissue oxygen saturation (rSO2) as well as blood pressure (BP) before and after vasopressor infusion in patients with aSAH. METHODS: Continuous noninvasive cerebral and peripheral rSO2 was obtained using near-infrared spectroscopy for up to 14 days after aSAH. Within-subject differences in rSO2 before and after the commencement of vasopressor infusion were analyzed controlling for Hunt and Hess grade and vasospasm. RESULTS: Of 45 patients with continuous rSO2 monitoring, 19 (42%) received vasopressor infusion (all 19 on norepinephrine, plus epinephrine in 2 patients, phenylephrine in 4 patients, and vasopressin in 2 patients). In these 19 patients, their vasopressor infusion times were associated with higher BP (systolic [b = 15.1], diastolic [b = 7.3], and mean [b = 10.1]; P = .001) but lower cerebral rSO2 (left cerebral rSO2 decreased by 4.4% [b = -4.4, P < .0001]; right cerebral rSO2 decreased by 5.5% [b = -5.5, P = .0002]). CONCLUSIONS: Despite elevation in systemic BP during vasopressor infusion times, cerebral rSO2 was concurrently diminished. These findings warrant further investigation for the effect of induced hypertension on cerebral microcirculation.

Evaluation of APOE Genotype and Ability to Perform Activities of Daily Living Following Aneurysmal Subarachnoid Hemorrhage.

Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often experience unfavorable functional outcomes that result in a reduced ability to independently perform activities of daily living. The apolipoprotein E gene ( APOE) encodes for a protein known to facilitate lipid transport and aid in neuronal repair within the central nervous system and to moderate the inflammatory response, making functional variations in this gene likely candidate biomarkers to predict outcomes following aSAH. In the present work, we examined the relationship between APOE genotype and the ability to perform activities of daily living as measured by the Barthel Index (BI) score at 3 months ( n = 298) and 12 months ( n = 288) following aSAH. APOE genotypes were determined using polymerase chain reaction followed by restriction digestion and gel electrophoresis and treated as binary variables depending on the presence or absence of alleles E4 and E2. Multiple logistic regression was used to determine whether APOE genotype accounted for variability in BI score after controlling for age, sex, and severity of clinical condition as measured by the Hunt and Hess classification. No significant association was found between the presence of allele E4 and BI score at 3 ( p = .20) or 12 months ( p = .29) or between the presence of allele E2 and BI score at 3 ( p = .23) or 12 months ( p = .86) after controlling for covariates. The results of this study do not support a relationship between APOE genotype and the ability to perform activities of daily living after aSAH.

Clinical Presentation to the Emergency Department Predicts Subarachnoid Hemorrhage-Associated Myocardial Injury.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently seen in emergency departments. Secondary injury, such as subarachnoid hemorrhage-associated myocardial injury (SAHMI), affects one third of survivors and contributes to poor outcomes. SAHMI is not attributed to ischemia from myocardial disease but can result in hypotension and arrhythmias. It is important that emergency nurses recognize which clinical presentation characteristics are predictive of SAHMI to initiate proper interventions. The aim of this study was to determine whether patients who present to the emergency department with clinical aSAH are likely to develop SAHMI, as defined by troponin I ≥0.3 ng/mL. METHODS: This was a prospective descriptive study. SAHMI was defined as troponin I ≥0.3 ng/mL. Predictors included demographics and clinical characteristics, severity of injury, admission 12-lead electrogardiogram (ECG), initial emergency department vital signs, and pre-hospital symptoms at time of aneurysm rupture. RESULTS: Of 449 patients, 126 (28%) had SAHMI. Patients with SAHMI were more likely to report seizures and unresponsiveness with significantly lower Glasgow coma score and higher proportion of Hunt and Hess grades 3 to 5 and Fisher grades III and IV (all P < .05). Patients with SAHMI had higher atrial and ventricular rates and longer QTc intervals on initial ECG (P < .05). On multivariable logistic regression, poor Hunt and Hess grade, report of prehospital unresponsiveness, lower admission Glasgow coma score, and longer QTc interval were significantly and independently predictive of SAHMI (P < .05). DISCUSSION: Components of the clinical presentation of subarachnoid hemorrhage to the emergency department predict SAHMI. Identifying patients with SAHMI in the emergency department can be helpful in determining surveillance and care needs and informing transfer unit care. Contribution to Emergency Nursing Practice.

A pilot study on the impact of dopamine, serotonin, and brain-derived neurotrophic factor genotype on long-term functional outcomes after subarachnoid hemorrhage.

OBJECTIVES: Many that survive an aneurysmal subarachnoid hemorrhage experience lasting physical disability, which might be improved by medications with effects on the dopaminergic, serotonergic, and brain-derived neurotrophic factor neurotransmitter systems. But it is not clear which patients are most likely to benefit from these therapies. The purpose of this pilot study was to explore the relationship of genetic polymorphisms in these pathways with 12-month functional outcomes after aneurysmal subarachnoid hemorrhage. METHODS: Subjects were recruited at the time of admission as a part of a larger parent study. Genotypes were generated using the Affymetrix genome-wide human single-nucleotide polymorphism array 6.0. Those within dopaminergic, serotonergic, and brain-derived neurotrophic factor pathways were analyzed for associations with functional outcomes at 12 months post aneurysmal subarachnoid hemorrhage using the Glasgow Outcome Scale and the Modified Rankin Scale. RESULTS: The 154 subjects were 55.8 ± 11.3 years old and 74% female; they had Fisher scores of 2.95 ± 0.67, Hunt/Hess scores of 2.66 ± 1.13, and admission Glasgow Coma Scale scores of 12.52 ± 3.79. Single-nucleotide polymorphisms in the serotonin receptor genes 1B and 1E and dopamine receptor D2 were associated with greater disability (odds ratio: 3.88-3.25, confidence interval: 1.01-14.77), while single-nucleotide polymorphisms in the serotonin receptor genes 2A and 2C and dopamine receptor D5 conferred a risk of poor recovery (odds ratio: 3.31-2.32, confidence interval: 1.00-10.80). Single-nucleotide polymorphisms within the same serotonin genes, and within the dopamine receptor gene D2, were associated with greater recovery after aneurysmal subarachnoid hemorrhage (odds ratio: 0.17-0.34, confidence interval: 0.05-0.89). CONCLUSIONS: These data demonstrate that there may be an association between genetic factors and functional outcomes post stroke.

The Relationships Between BNP and Neurocardiac Injury Severity, Noninvasive Cardiac Output, and Outcomes After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Neurocardiac injury, a type of myocardial dysfunction associated with neurological insult to the brain, occurs in 31-48% of aneurysmal subarachnoid hemorrhage (aSAH) patients. Cardiac troponin I (cTnI) is commonly used to diagnose neurocardiac injury. Brain natriuretic peptide (BNP), another cardiac marker, is more often used to evaluate degree of heart failure. The purpose of this study was to examine the relationships between BNP and (a) neurocardiac injury severity according to cTnI, (b) noninvasive continuous cardiac output (NCCO), and (c) outcomes in aSAH patients. METHOD: This descriptive longitudinal study enrolled 30 adult aSAH patients. Data collected included BNP and cTnI levels and NCCO parameters for 14 days and outcomes (modified Rankin Scale [mRS] and mortality) at discharge and 3 months. Generalized estimating equations were used to evaluate associations between BNP and cTnI, NCCO, and outcomes. RESULTS: BNP was significantly associated with cTnI. For every 1 unit increase in log BNP, cTnI increased by 0.05 ng/ml ( p = .001). Among NCCO parameters, BNP was significantly associated with thoracic fluid content ( p = .0003). On multivariable analyses, significant associations were found between BNP and poor mRS. For every 1 unit increase in log BNP, patients were 3.16 times more likely to have a poor mRS at discharge ( p = .021) and 5.40 times more likely at 3 months ( p < .0001). CONCLUSION: There were significant relationships between BNP and cTnI and poor outcomes after aSAH. BNP may have utility as a marker of neurocardiac injury and outcomes after aSAH.

Impaired Work Productivity After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a sudden debilitating condition affecting individuals during the most productive times of their lives. Treatment advances have reduced mortality rates but increased the number of survivors facing deficits in physical and neuropsychological function. OBJECTIVE: This study examined associations between neuropsychological function and work productivity after aSAH. METHODS: Fifty-two patients with aSAH, employed before hemorrhage, were recruited from an ongoing National Institutes of Health study. Work Limitations Questionnaire (WLQ), neuropsychological tests (executive function, psychomotor speed, attention and mental flexibility, memory), and Patient Assessment of Own Function were completed at 3 and 12 months after aSAH. RESULTS: Subjects in this analysis reported some level of difficulty in work productivity at 3 and 12 months (35% and 30%, respectively) after hemorrhage. Lower WLQ scores in time management and mental/interpersonal subscales were associated with poorer performance in psychomotor function (r = .5, p = .04 and r = .42, p = .09). Poorer mental flexibility and working memory correlated with time management difficulty at 3 months (r = -.4, p = .09 and r = .54, p = .02). Patients performing poorly on story recall tests were more likely to report difficulty with job physical performance (r = -.42, p = .09) and completing work effectively (r = .61, p = .009). Poorer working memory performance was associated with lower scores on mental/interpersonal WLQ subscales (r = .45, p = .05) and overall health-related work productivity loss (r = .47, p = .04). WLQ areas also correlated with participants' perception of their neuropsychological function after aSAH. CONCLUSIONS: These results suggest that neuropsychological deficits impact work quality after hemorrhage and provide strong impetus for future studies so that domain-specific interventions can be implemented to improve outcomes that affect quality of life including work productivity.

Prophylactic Antiepileptics and Seizure Incidence Following Subarachnoid Hemorrhage: A Propensity Score-Matched Analysis.

BACKGROUND AND PURPOSE: The utility of prophylactic antiepileptic drug (AED) administration after spontaneous subarachnoid hemorrhage remains controversial. AEDs have not clearly been associated with a reduction in seizure incidence and have been associated with both neurological worsening and delayed functional recovery in this setting. METHODS: We retrospectively analyzed a prospectively collected database of subarachnoid hemorrhage patients admitted to our institution between 2005 and 2010. Between 2005 and 2007, all patients received prophylactic AEDs upon admission. After 2007, no patients received prophylactic AEDs or had AEDs immediately discontinued if initiated at an outside hospital. A propensity score-matched analysis was then performed to compare the development of clinical and electrographic seizures in these 2 populations. RESULTS: Three hundred and fifty three patients with spontaneous subarachnoid hemorrhage were analyzed, 43% of whom were treated with prophylactic AEDs upon admission. Overall, 10% of patients suffered clinical and electrographic seizures, most frequently occurring within 24 hours of ictus (47%). The incidence of seizures did not vary significantly based on the use of prophylactic AEDs (11 versus 8%; P=0.33). Propensity score-matched analyses suggest that patients receiving prophylactic AEDs had a similar likelihood of suffering seizures as those who did not (P=0.49). CONCLUSIONS: Propensity score-matched analysis suggests that prophylactic AEDs do not significantly reduce the risk of seizure occurrence in patients with spontaneous subarachnoid hemorrhage.