Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review.

BACKGROUND: Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models. METHODS AND RESULTS: We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016-2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri-interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used. CONCLUSIONS: Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.

Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage: A systematic review of published prediction models with risk of bias and clinical applicability assessment.

BACKGROUND: Pre-treatment rebleeding following aneurysmal subarachnoid hemorrhage (aSAH) increases the risk of death and a poor neurological outcome. Current guidelines recommend aneurysm treatment "as early as feasible after presentation, preferably within 24 h of onset" to mitigate this risk, a practice termed ultra-early treatment. However, ongoing debate regarding whether ultra-early treatment is independently associated with reduced re-bleeding risk, together with the recognition that re-bleeding occurs even in centres practicing ultra-early treatment due to the presence of other risk-factors has resulted in a renewed need for patient-specific re-bleed risk prediction. Here, we systematically review models which seek to provide patient specific predictions of pre-treatment rebleeding risk. METHODS: Following registration on the International prospective register of systematic reviews (PROSPERO) CRD 42023421235; Ovid Medline (Pubmed), Embase and Googlescholar were searched for English language studies between 1st May 2002 and 1st June 2023 describing pre-treatment rebleed prediction models following aSAH in adults ≥18 years. Of 763 unique records, 17 full texts were scrutinised with 5 publications describing 4 models reviewed. We used the semi-automated template of Fernandez-Felix et al. incorporating the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for data extraction, risk of bias and clinical applicability assessment. To further standardize risk of bias and clinical applicability assessment, we also used the published explanatory notes for the PROBAST tool and compared the aneurysm treatment practices each prediction model's formulation cohort experienced to a prespecified benchmark representative of contemporary aneurysm treatment practices as outlined in recent evidence-based guidelines and published practice pattern reports from four developed countries. RESULTS: Reported model discriminative performance varied between 0.77 and 0.939, however, no single model demonstrated a consistently low risk of bias and low concern for clinical applicability in all domains. Only the score of Darkwah Oppong et al. was formulated using a patient cohort in which the majority of patients were managed in accordance with contemporary, evidence-based aneurysm treatment practices defined by ultra-early and predominantly endovascular treatment. However, this model did not undergo calibration or clinical utility analysis and when applied to an external cohort, its discriminative performance was substantially lower that reported at formulation. CONCLUSIONS: No existing prediction model can be recommended for clinical use in centers practicing contemporary, evidence-based aneurysm treatment. There is a pressing need for improved prediction models to estimate and minimize pre-treatment re-bleeding risk.

Predicting the formation of mixed pattern hemorrhages in ruptured middle cerebral artery aneurysms based on a decision tree model: A multicenter study.

OBJECTIVE: Mixed-pattern hemorrhages (MPH) commonly occur in ruptured middle cerebral artery (MCA) aneurysms and are associated with poor clinical outcomes. This study aimed to predict the formation of MPH in a multicenter database of MCA aneurysms using a decision tree model. METHODS: We retrospectively reviewed patients with ruptured MCA aneurysms between January 2009 and June 2020. The MPH was defined as subarachnoid hemorrhages with intracranial hematomas and/or intraventricular hemorrhages and/or subdural hematomas. Univariate and multivariate logistic regression analyses were used to explore the prediction factors of the formation of MPH. Based on these prediction factors, a decision tree model was developed to predict the formation of MPH. Additional independent datasets were used for external validation. RESULTS: We enrolled 436 patients with ruptured MCA aneurysms detected by computed tomography angiography; 285 patients had MPH (65.4%). A multivariate logistic regression analysis showed that age, aneurysm size, multiple aneurysms, and the presence of a daughter dome were the independent prediction factors of the formation of MPH. The areas under receiver operating characteristic curves of the decision tree model in the training, internal, and external validation cohorts were 0.951, 0.927, and 0.901, respectively. CONCLUSION: Age, aneurysm size, the presence of a daughter dome, and multiple aneurysms were the independent prediction factors of the formation of MPH. The decision tree model is a useful visual triage tool to predict the formation of MPH that could facilitate the management of unruptured aneurysms in routine clinical work.

Daily patterns of fatigue after subarachnoid haemorrhage: an ecological momentary assessment study.

OBJECTIVE: To examine the daily course of, and factors associated with, momentary fatigue after subarachnoid haemorrhage, and to explore subgroups of patients with distinct diurnal patterns of fatigue. DESIGN: Observational study using ecological momentary assessment. SUBJECTS: A total of 41 participants with subarachnoid haemorrhage. METHODS: Patients with fatigue were included within one year post-onset. Momentary fatigue (scale 1-7) was assessed with repeated measurements (10-11 times/day) during 7 consecutive days. Multilevel-mixed-model analyses and latent-class trajectory modelling were conducted. RESULTS: Mean (standard deviation; SD) age of the group was 53.9 (13.0) years, 56% female, and mean (SD) time post-subarachnoid haemorrhage onset was 9.3 (3.2) months. Mean (SD) momentary fatigue over all days was 3.22 (1.47). Fatigue increased significantly (p < 0.001) over the day, and experiencing more burden of fatigue and day type (working day vs weekend day) were significantly (p < 0.05) associated with higher momentary fatigue. Three subgroups could be distinguished based on diurnal patterns of fatigue. The largest group (n = 17, 41.5%) showed an increasing daily pattern of fatigue. CONCLUSION: Momentary fatigue in patients with subarachnoid haemorrhage increases over the day, and diurnal patterns of fatigue differ between  participants. In addition to conventional measures, momentary measures of fatigue might provide valuable information for physicians to optimize personalized management of fatigue after subarachnoid haemorrhage.

Unraveling the interplay between daily life fatigue and physical activity after subarachnoid hemorrhage: an ecological momentary assessment and accelerometry study.

BACKGROUND: Fatigue is one of the most commonly reported symptoms after subarachnoid hemorrhage (SAH) and is indirectly associated with physical activity (PA). Associations between fatigue and PA are primarily examined based on conventional measures (i.e. a single fatigue score or average PA levels), thereby assuming that fatigue and PA do not fluctuate over time. However, levels of fatigue and PA may not be stable and may interrelate dynamically in daily life. Insight in direct relationships between fatigue and PA in daily life, could add to the development of personalized rehabilitation strategies. Therefore we aimed to examine bidirectional relationships between momentary fatigue and PA in people with SAH. METHODS: People (n = 38) with SAH who suffer from chronic fatigue were included in an observational study using Ecological Momentary Assessment (EMA) and accelerometry. Momentary fatigue was assessed on a scale from 1 to 7 (no to extreme fatigue), assessed with 10-11 prompts per day for 7 consecutive days using EMA with a mobile phone. PA was continuously measured during this 7-day period with a thigh-worn Activ8 accelerometer and expressed as total minutes of standing, walking, running and cycling in a period of 45 min before and after a momentary fatigue prompt. Multilevel mixed model analyses including random effects were conducted. RESULTS: Mean age was 53.2 years (SD = 13.4), 58% female, and mean time post SAH onset was 9.5 months (SD = 2.1). Multilevel analyses with only time effects to predict fatigue and PA revealed that fatigue significantly (p < 0.001) increased over the day and PA significantly (p < 0.001) decreased. In addition, more PA was significantly associated with higher subsequent fatigue (ß = 0.004, p < 0.05) and higher fatigue was significantly associated with less subsequent PA (ß=-0.736, p < 0.05). Moreover, these associations significantly differed between participants (p < 0.001). CONCLUSIONS: By combining EMA measures of fatigue with accelerometer-based PA we found that fatigue and PA are bidirectionally associated. In addition, these associations differ among participants. Given these different bidirectional associations, rehabilitation aimed at reducing fatigue should comprise personalized strategies to improve both fatigue and PA simultaneously, for example by combining exercise therapy with cognitive behavioral and/or energy management therapy.

Assessment of rehabilitation following subarachnoid haemorrhage in China: findings from the Chinese Stroke Center Alliance.

BACKGROUND: Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. METHODS: To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. RESULTS: Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.04 to 1.05) and care such as dysphagia screening (OR, 1.88; 95% CI, 1.73 to 2.04), DVT prophylaxis (OR, 1.56; 95% CI, 1.41 to 1.72) and vessel evaluation (OR, 1.80; 95% CI, 1.63 to 1.98). For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay (OR, 1.96; 95% CI, 1.81 to 2.12), a higher modified Rankin Scale (mRS) score at discharge (OR, 1.49; 95% CI, 1.36 to 1.64), and higher rates of discharge to a rehabilitation center (OR, 3.23; 95% CI, 1.81-5.75). CONCLUSION: More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients.

Predictors of In-Hospital Mortality and Home Discharge in Patients with Aneurysmal Subarachnoid Hemorrhage: A 4-Year Retrospective Analysis.

BACKGROUND: Factors associated with discharge disposition and mortality following aneurysmal subarachnoid hemorrhage (aSAH) are not well-characterized. We used a national all-payer database to identify factors associated with home discharge and in-hospital mortality. METHODS: The National Inpatient Sample was queried for patients with aSAH within a 4-year range. Weighted multivariable logistic regression models were constructed and adjusted for age, sex, race, household income, insurance status, comorbidity burden, National Inpatient Sample SAH Severity Score, disease severity, treatment modality, in-hospital complications, and hospital characteristics (size, teaching status, and region). RESULTS: Our sample included 37,965 patients: 33,605 were discharged alive and 14,350 were discharged home. Black patients had lower odds of in-hospital mortality compared with White patients (adjusted odds ratio [aOR] = 0.67, 95% confidence interval [CI] 0.52-0.86, p = 0.002). Compared with patients with private insurance, those with Medicare were less likely to have a home discharge (aOR = 0.58, 95% CI 0.46-0.74, p < 0.001), whereas those with self-pay (aOR = 2.97, 95% CI 2.29-3.86, p < 0.001) and no charge (aOR = 3.21, 95% CI 1.57-6.55, p = 0.001) were more likely to have a home discharge. Household income percentile was not associated with discharge disposition or in-hospital mortality. Paradoxically, increased number of Elixhauser comorbidities was associated with significantly lower odds of in-hospital mortality. CONCLUSIONS: We demonstrate independent associations with hospital characteristics, patient characteristics, and treatment characteristics as related to discharge disposition and in-hospital mortality following aSAH, adjusted for disease severity.

Antibiotic-impregnated versus standard silicone catheter for external ventricular drainage in acute hydrocephalus associated to aneurysmal subarachnoid hemorrhage: a budget impact analysis from a single center Italian cohort.

BACKGROUND: Acute hydrocephalus is a frequent complication of aneurysmal subarachnoid hemorrhage, and it is generally treated by external ventricular drainage. In the last decades, antibiotic-impregnated ventricular catheters have been introduced in the neurosurgical practice in order to reduce secondary cerebrospinal fluid infections which increase morbidity, mortality, and health care costs. METHODS: Data of 100 patients treated at Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2012 and December 2019 were retrospectively reviewed in order to determine the cost-effectiveness and budget impact of antibiotic impregnated versus non-impregnated catheters in the management of patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. A budget impact model was built depending on the use of antibiotic impregnated versus non-impregnated catheters. The model was populated with data extrapolated from existing literature concerning the Italian healthcare setting and national tariffs. RESULTS: A 25% reduction in the number of cerebrospinal fluid infections was achieved by using antibiotic impregnated catheters, resulting in an overall saving equal to €5730.52/patient. Expanding results to a 100-patient sample, the possible savings would amount to €573,052.40 for the National Health Service. CONCLUSIONS: Antibiotic impregnated catheters use was associated to a reduction in cerebrospinal fluid infections rate as well as in costs related to hospital care when compared to nonimpregnated catheters. Thus these catheters represent, besides lifesaving, cost-saving devices that reduce the economic burden and ensure a safe clinical outcome in patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. The present study provides concrete evidence of the benefit of Antibiotic impregnated catheters to decision-makers responsible of defining health policies.

A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial.

Health Care Expenditures Associated with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage: A Propensity-Adjusted Analysis.

OBJECTIVE: The additional hospital costs associated with delayed cerebral ischemia (DCI) have not been well investigated in prior literature. In this study, the total hospital cost of DCI in aneurysmal subarachnoid hemmorhage (aSAH) patients treated at a single quaternary center was analyzed. METHODS: All patients in the Post-Barrow Ruptured Aneurysm Trial treated for an aSAH between January 1, 2014, and July 31, 2019, were retrospectively analyzed. DCI was defined as cerebral infarction identified on computed tomography, magnetic resonance imaging, or autopsy after exclusion of procedure-related infarctions. The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis. Propensity score covariate-adjusted linear regression analysis included age, sex, open versus endovascular treatment, Hunt and Hess score, and Charlson Comorbidity Index score. RESULTS: Of the 391 patients included, 144 (37%) had DCI. Patients with DCI had a significantly greater cost compared to patients without DCI (mean standard deviation $112,081 [$54,022] vs. $86,159 [$38,817]; P < 0.001) and a significantly greater length of stay (21 days [11] vs. 18 days [8], P = 0.003, respectively). In propensity-adjusted linear regression analysis, both DCI (odds ratio, $13,871; 95% confidence interval, $7558-$20,185; P < 0.001) and length of stay (odds ratio, $3815 per day; 95% confidence interval, $3480-$4149 per day; P < 0.001) were found to significantly increase the cost. CONCLUSIONS: The significantly higher costs associated with DCI further support the evidence that adverse effects associated with DCI in aSAH pose a significant burden to the health care system.

Nutritional assessment of patients with aneurysmal subarachnoid hemorrhage using the modified "Nutrition Risk in the Critically Ill" score, and its association with outcomes.

Introduction: Introduction: subarachnoid hemorrhage (SAH) is a rare and life-threatening cerebrovascular disease. Mitigating the factors that compromise patient recovery during neurocritical care due to SAH is of clinical benefit. Objectives: to evaluate the nutritional risk of patients with aneurysmal subarachnoid hemorrhage using "The Modified Nutrition Risk in the Critically Ill" (mNUTRIC) score, and examine its association with outcomes such as mortality, time of mechanical ventilation, and functional status among survivors. Methods: we designed a cross-sectional study. Patients with SAH admitted to the neurointensive critical care unit (neuroICU) in a tertiary care public hospital were eligible. The inclusion criteria were a minimum stay in the intensive care unit (ICU) of 24 hrs for subarachnoid hemorrhage from a nontraumatic, spontaneously ruptured cerebral aneurysm, and hospital admission within 24 hrs after the onset of symptoms. Results: high nutritional risk as stratified by the mNUTRIC score was associated with discharge type (OR = 0.346; 95 % CI = 0.182-0.650; p = 0.001), acute hypertensive hydrocephalus (OR = 4.371; 95 % CI = 2.283-8.549; p < 0.001), and functional outcome (OR = 0.106; 95 % CI = 0.025-0.0388; p < 0.001). The mNUTRIC score was significantly different among median age (p < 0.001), length of stay in the neuroICU (p = 0.005), SOFA score (p < 0.001), and APACHE II score (p < 0.001) categories. Conclusions: this study demonstrated an association between nutritional risk assessment and outcomes such as length of stay in the neuroICU, type of discharge, functional status, and mortality prediction accuracy.

Introducción: Introducción: la hemorragia subaracnoidea es una forma rara de enfermedad cerebrovascular que pone en peligro la vida del paciente. Reducir los factores que comprometen la recuperación de los pacientes durante los cuidados neurocríticos tiene benefício clínico. Objetivo: evaluar el riesgo nutricional de los pacientes con hemorragia subaracnoidea por aneurisma utilizando la puntuación "The Modified Nutrition Risk in the Critically Ill" (mNUTRIC) y su asociación con resultados como la mortalidad, el tiempo de ventilación mecánica y el estado funcional entre los supervivientes. Método: diseñamos un estudio transversal. Fueron elegibles los pacientes con hemorragia subaracnoidea ingresados en la unidad de cuidados críticos neurointensivos (neuroUCI) de un hospital público de atención terciaria. Los criterios de inclusión fueron una permanencia mínima de 24 horas en la UCI, hemorragia subaracnoidea por rotura espontánea no traumática de aneurisma cerebral, e ingreso hospitalario en las 24 horas siguientes al inicio de los síntomas. Resultados: el alto riesgo nutricional estratificado por la puntuación mNUTRIC se asoció con el tipo de alta (OR = 0,346; IC 95 % = 0,182-0,650; p = 0,001), la hidrocefalia hipertensiva aguda (OR = 4,371; IC 95 % = 2,283-8,549; p < 0,001) y el resultado funcional (OR = 0,106; IC 95 % = 0,025-0,0388; p < 0,001). La puntuación mNUTRIC presentó diferencias estadísticamente significativas entre las medianas de edad (p < 0,001), duración de la permanencia en la neuroUCI (p = 0,005), puntuación SOFA (p < 0,001) y puntuación APACHE II (p < 0,001). Conclusión: este estudio demuestra una asociación de la evaluación del riesgo nutricional con resultados como la necesidad de ventilación mecánica, la duración de la permanencia en la neuroUCI, el tipo de alta, el estado funcional y la precisión en la predicción de la mortalidad.

Cost Comparison of Microsurgery vs Endovascular Treatment for Ruptured Intracranial Aneurysms: A Propensity-Adjusted Analysis.

BACKGROUND: In specialized neurosurgical centers, open microsurgery is routinely performed for aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To compare the cost of endovascular vs microsurgical treatment for aSAH at a single quaternary center. METHODS: All patients undergoing aSAH treatment from July 1, 2014, to July 31, 2019, were retrospectively reviewed. Patients were grouped based on primary treatment (microsurgery vs endovascular treatment). The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis. RESULTS: Of 384 patients treated for an aSAH, 234 (61%) were microsurgically treated and 150 (39%) were endovascularly treated. The mean cost of index hospitalization for these patients was marginally higher ($9504) for endovascularly treated patients ($103 980) than for microsurgically treated patients ($94 476) ( P = .047). For the subset of patients with follow-up data available, the mean total cost was $45 040 higher for endovascularly treated patients ($159 406, n = 59) than that for microsurgically treated patients ($114 366, n = 105) ( P < .001). After propensity scoring (adjusted for age, sex, comorbidities, Glasgow Coma Scale score, Hunt and Hess grade, Fisher grade, aneurysms, and type/size/location), linear regression analysis of patients with follow-up data available revealed that microsurgery was independently associated with healthcare costs that were $37 244 less than endovascular treatment costs ( P < .001). An itemized cost analysis suggested that this discrepancy was due to differences in the rates of aneurysm retreatment and long-term surveillance. CONCLUSION: Microsurgical treatment for aSAH is associated with lower total healthcare costs than endovascular therapy. Aneurysm surveillance after endovascular treatments, retreatment, and device costs warrants attention in future studies.

Risk Factor-Guided Early Discharge and Potential Resource Allocation Benefits in Patients with Traumatic Subarachnoid Hemorrhage.

OBJECTIVE: We sought to develop screening criteria predicting the lack of poor neurologic outcomes in patients presenting with traumatic subarachnoid hemorrhage (tSAH) and to evaluate their potential to improve resource allocation in these cases. METHODS: We retrospectively reviewed patients presenting with tSAH to the emergency department (ED) of a tertiary-care institution from 2016 to 2018. We defined good neurologic outcomes as patients with stable/improving neurologic status, who did not require neurosurgical intervention, had no expanding bleed, and needed no hospital readmission. Univariate and multivariate models were generated to predict risk factors inversely associated with good neurologic outcome. RESULTS: A total of 167 patients presented with tSAH from 2016 to 2018. The presence of depressed skull fracture, concomitant spinal fracture, low Glasgow Coma Scale (GCS) score, cranial nerve palsies, disorientation, concomitant hemorrhages, midline shift, increased international normalized ratio (INR), and emergent medical intervention were inversely correlated with likelihood of good neurologic outcome on univariate analysis. Multivariate regression showed that midline shift (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.89; P = 0.04), GCS score <13 (OR, 0.22; 95% CI, 0.05-0.99; P = 0.05), increased INR (OR, 0.18; 95% CI, 0.03-0.85; P = 0.04), and emergent medical intervention (OR, 0.18; 95% CI, 0.04-0.63; P = 0.01) were independently associated with lower likelihood of good neurologic outcome. Forty-six patients without any factors had good outcomes but were held in the ED or admitted to the hospital. These patients (if instead discharged directly) meant a potential cost savings of $179,172. CONCLUSIONS: In our study, we found multiple risk factors inversely associated with good neurologic outcome, namely low GCS score, midline shift, emergent medical intervention, and INR ≥1.4. Our findings may aid clinicians in determining which tSAH patients are candidates for safe early discharge.

Methodological assessment of guidelines for the diagnosis and management of cerebral vasospasm using the AGREE-II tool.

OBJECTIVE: Rupture of an intracranial aneurysm is the most common cause of spontaneous subarachnoid hemorrhage. Despite the recent advances in its early detection, diagnosis, and proper treatment, the outcome of patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) remains poor. It is well known that cerebral vasospasm is the most troublesome complication of aSAH, while delayed cerebral ischemia related to cerebral vasospasm constitutes the major cause of unfavorable outcomes in patients with aSAH. The need for evidence-based guidelines is of great importance for the prevention, early detection, and efficient management of aSAH-induced vasospasm. Moreover, guidelines provide young physicians with a valuable tool for practicing defensible medicine. However, the methodology, clinical applicability, reporting clarity, and biases of guidelines must be periodically assessed. In this study, the authors sought to assess the reporting clarity and methodological quality of published guidelines and recommendations. METHODS: A search was performed in the PubMed, Scopus, and Web of Science databases. The search terms used were "clinical practice guidelines," "recommendations," "stroke," "subarachnoid hemorrhage," and "vasospasm" in all possible combinations. The search period extended from 1964 to September 2021 and was limited to literature published in the English language. All published guidelines and recommendations reporting on the diagnosis and management of vasospasm were included. Studies other than those reporting guidelines and recommendations were excluded. The eligible studies were evaluated by three blinded raters, employing the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) analysis tool. RESULTS: A total of 10 sets of guidelines were evaluated in this study. The American Heart Association/American Stroke Association issued guidelines found to have the highest methodological quality and reporting clarity, followed by the European Stroke Organization guidelines and the English edition of the Japanese guidelines issued by the Japanese Society on Surgery for Cerebral Stroke. The interrater agreement was moderate in the current analysis. CONCLUSIONS: These findings support the idea that improvement of currently existing guidelines is feasible in the following domains: the rigor of guidelines and recommendations development, clinical applicability, editorial independence, and stakeholder involvement. Furthermore, periodic updating of published guidelines requires improvement in the future.

Assessment relationship between the femoral artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: an experimental study.

STUDY DESIGN: Animal proof of principle study. OBJECTIVES: To investigate neurodegeneration in rabbit L4-dorsal root ganglion (DRG) cells by creating experimental spinal subarachnoid hemorrhage (SAH), we aimed to show the neuronal pathway between L4-DRG and femoral artery. SETTING: Ataturk University, Medical Faculty, Animal Laboratory, Erzurum, Turkey. METHODS: This study was designed on 20 rabbits, which were randomly divided into three groups: Spinal SAH (n = 8), SHAM (n = 6), and control (n = 6) groups. Animals were followed for 20 days and then killed. Vasospasm index values of the femoral artery and neuron density of L4-DRG were analyzed. RESULTS: The number of degenerated neurons in DRG was higher in the spinal SAH than the control and SHAM groups (p < 0.001). But, the difference between the control group and the SHAM group was not significant. Normal neuron densities were significantly lower in the spine SAH group compared to the SHAM and the control groups. There was a statistically significant increase in vasospasm index values of the spinal SAH group compared to the other two groups (p < 0.001). CONCLUSIONS: Decreased volume of the femoral artery lumen was showed in animals with spinal SAH compared with control and SHAM groups. Increased degeneration of the L4 dorsal root ganglion in animals with spinal SAH was also demonstrated. Our findings might shed light on the planning of future experimental studies and evaluating the clinical relevance of such studies.

Clinical presentation and assessment of older patients presenting with headache to emergency departments: A multicentre observational study.

OBJECTIVE: To describe the characteristics, assessment and management of older emergency department (ED) patients with non-traumatic headache. METHODS: Planned sub-study of a prospective, multicentre, international, observational study, which included adult patients presenting to ED with non-traumatic headache. Patients aged ≥75 years were compared to those aged <75 years. Outcomes of interest were epidemiology, investigations, serious headache diagnosis and outcome. RESULTS: A total of 298 patients (7%) in the parent study were aged ≥75 years. Older patients were less likely to report severe headache pain or subjective fever (both P < 0.001). On examination, older patients were more likely to be confused, have lower Glasgow Coma Scores and to have new neurological deficits (all P < 0.001). Serious secondary headache disorder (composite of headache due to subarachnoid haemorrhage (SAH), intracranial haemorrhage, meningitis, encephalitis, cerebral abscess, neoplasm, hydrocephalus, vascular dissection, stroke, hypertensive crisis, temporal arteritis, idiopathic intracranial hypertension or ventriculoperitoneal shunt complications) was diagnosed in 18% of older patients compared to 6% of younger patients (P < 0.001). Computed tomography brain imaging was performed in 66% of patients ≥75 years compared to 35% of younger patients (P < 0.001). Older patients were less likely to be discharged (43% vs 63%, P < 0.001). CONCLUSIONS: Older patients with headache had different clinical features to the younger cohort and were more likely to have a serious secondary cause of headache than younger adults. There should be a low threshold for investigation in older patients attending ED with non-traumatic headache.

Long-Term Risk of Ischemic Stroke among Elderly Survivors of Non-Traumatic Subarachnoid Hemorrhage.

INTRODUCTION: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. OBJECTIVES: The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH. METHODS: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. RESULTS: Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7-6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4-2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8-3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1-2.3). CONCLUSIONS: In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Assessment of the ECG T-Wave in Patients With Subarachnoid Hemorrhage.

BACKGROUND: Prolongation of the interval from the peak to the end of the T wave (Tp-Te) on a 12-lead electrocardiogram (ECG) is associated with ventricular arrhythmias. The aim of this study was to clarify associations between Tp-Te, Tp-Te/QT, and Tp-Te/rate-corrected QT (QTc) with clinical severity of subarachnoid hemorrhage (SAH) and clinical outcomes. METHODS: This retrospective study included 222 patients with acute SAH (group S) and 306 patients with unruptured cerebral aneurysms (group U). Tp-Te, Tp-Te/QT, and Tp-Te/QTc were manually measured in standard 12-lead ECG recordings on admission and comparisons made between patients in groups S and U. The relationships of these ECG parameters with Hunt and Hess grade and Glasgow outcome scale were analyzed using multiple logistic regression analysis after adjustment for confounding factors. RESULTS: Tp-Te, Tp-Te/QT, and Tp-Te/QTc were significantly greater in group S than in group U (group S: 109±30, 0.26±0.07, and 0.24±0.06 ms; group U: 84±12, 0.22±0.03, and 0.21±0.03 ms, respectively; P < 0.0001). In addition, in the multiple logistic regression analyses these variables were positively correlated with the Hunt and Hess grade (Tp-Te odds ratio [95% confidence interval], 2.414 [1.375-4.238], P=0.002; Tp-Te/QT, 1.886 [1.085-3.277], P = 0.024; Tp-Te/QTc, 1.873 [1.07-3.278], P=0.028, and negatively correlated with Glasgow outcome scale Tp-Te odds ratio [95% confidence interval], 4.168 [2.409-7.209], P<0.001; Tp-Te/QT, 2.434 [1.413-4.192], P=0.001; Tp-Te/QTc 2.953 [1.703-5.123], P<0.001). CONCLUSIONS: Tp-Te, Tp-Te/QT, and Tp-Te/QTc are associated with disease severity and clinical outcome in patients with SAH.

The neuropsychological assessment battery (NAB) is a valuable tool for evaluating neuropsychological outcome after aneurysmatic subarachnoid hemorrhage.

BACKGROUND: Detecting and treating neuropsychological deficits after aneurysmatic subarachnoid hemorrhage (aSAH) play a key role in regaining independence; however, detecting deficits relevant to social and professional reintegration has been difficult and optimal timing of assessments remains unclear. Therefore, we evaluated the feasibility of administering the Neuropsychological Assessment Battery screening module (NAB-S) to patients with aSAH, assessed its value in predicting the ability to return to work and characterized clinical as well as neuropsychological recovery over the period of 24 months. METHODS: A total of 104 consecutive patients treated for aSAH were recruited. After acute treatment, follow up visits were conducted at 3, 12 and 24 months after the hemorrhage. NAB-S, Montreal Cognitive Assessment (MoCA) and physical examination were performed at each follow up visit. RESULTS: The NAB-S could be administered to 64.9, 75.9 and 88.9% of the patients at 3, 12 and 24 months, respectively. Moderate impairment of two or more neuropsychological domains (e.g speech, executive function, etc.) significantly correlated with inability to return to work at 12 and 24 months as well as poor outcome assessed by the extended Glasgow Outcome Scale (GOSE) at 3, 12 and 24 months. The number of patients with favorable outcomes significantly increased from 25.5% at discharge to 56.5 and 57.1% at 3 and 12 months, respectively, and further increased to 74.1% after 24 months. CONCLUSION: The NAB-S can be administered to the majority of patients with aSAH and can effectively detect clinically relevant neuropsychological deficits. Clinical recovery after aSAH continues for at least 24 months after the hemorrhage which should be considered in the design of future clinical trials.

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.