Time intervals from subarachnoid hemorrhage to rebleed

The most threatening early complication and predictor of poor outcome after an aneurysmal subarachnoid hemorrhage (aSAH) is a rebleed. To evaluate what proportion of rebleeds might be prevented by early treatment, we assessed the time interval from the initial hemorrhage to rebleed, and the location of the patient at the time of rebleed. Patient characteristics, World Federation of Neurological Surgeons grade on admission and modified Rankin Scale outcome scores, referring hospitals and time intervals from initial hemorrhage to treatment of 293 patients treated between 2008 and 2011 were evaluated. Time intervals to rebleeds and location of the patients at the time of rebleed were retrieved. Rebleeds were confirmed by CT in 12 % of patients, and an additional 4 % of patients was diagnosed as having a possible rebleed. Sixty percent of rebleeds occurred after admission to the treatment center. Almost all rebleeds occurred within 24 h, with a median time interval between initial hemorrhage and rebleed of 180 min. A significantly shorter time to treatment and a higher mortality were seen in the group of patients with a rebleed. Approximately, one in six patients with an aSAH had a rebleed, of which a majority might have been preventable because they occurred after admission to the treatment center. A reduction in the rebleed rate seems feasible by securing the aneurysm as soon as possible by improving in-hospital logistics for early aneurysm treatment. Alternative options, such as immediate administration of antifibrinolytics, are being explored in a multicenter trial.     

Aneurysm Treatment <24 Versus 24–72 h After Subarachnoid Hemorrhage

Introduction

In patients with aneurysmal subarachnoid hemorrhage (aSAH), it is unclear whether aneurysm treatment <24 h after ictus results in better outcomes than treatment 24–72 h after aSAH. We studied whether aneurysm occlusion <24 h is associated with better outcomes than occlusion 24–72 h after aSAH.

Methods

We used two cohorts of patients with aSAH: (1) the UMC Utrecht cohort with patients admitted between 2008 and 2012 and (2) the International Subarachnoid Aneurysm Trial cohort. Aneurysm treatment was categorized into <24 h and 24–72 h after ictus. We calculated adjusted risk ratios (aRRs) with 95 % confidence intervals (CIs) using Poisson regression analyses for poor functional outcome (death or dependency) for both cohorts separately, and performed a pooled analysis based on individual patient data. We also performed a worst-case scenario analysis wherein all patients with rebleeding >3 h after admission were re-categorized into the group with aneurysm treatment 24–72 h after aSAH.

Results

We included 1,238 patients (UMC Utrecht cohort: n = 330; ISAT: n = 908). The aRR for poor outcome after treatment <24 h was in the UMC Utrecht cohort 1.84 (95 % CI: 1.25-2.70), in ISAT 1.14 (95 % CI 0.84–1.55), in the pooled analysis 1.37 (95 % CI 1.11–1.68), and in the worst-case scenario pooled analysis 1.24 (95 % CI 1.01–1.52).

Conclusion

Our results suggest that aneurysm occlusion can be performed in day time within 72 h after ictus, instead of on an emergency basis. However, due to the retrospective, non-randomized design of our study, our results cannot be considered as definitive evidence.     

Circadian fluctuations in onset of perimesencephalic hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) occurs more often during working hours and in the evening, and thus at times of relatively high blood pressure, with an even distribution over the days of the week in most studies. Perimesencephalic hemorrhage (PMH) is a non-aneurysmal subset of subarachnoid hemorrhage (SAH) without known circadian fluctuation. We studied the time and day of onset in a large series of patients with PMH. For all 249 PMH patients included in our SAH-database we analyzed the time (categorized in 2- and 6-h intervals) and day of onset by calculating rate ratios (RRs) with corresponding 95 % confidence intervals (CIs) for time and day, with the afternoon and Saturday as reference. The risk of PMH was lower between 2–4 AM (RR 0.14; 95 % CI 0.03–0.63), 4–6 AM (RR 0.21; 95 % CI 0.06–0.75) and 6–8 AM (RR 0.07; 95 % CI 0.01–0.54). A tendency towards higher risks in the morning and afternoon was observed. Analyzing the time of onset in 6-h intervals also showed a lower risk (RR 0.35; 95 % CI 0.21–0.58) during night hours (12–6 AM). The risk of PMH was evenly distributed over the days of the week. PMH occurs less often during night hours. The pattern of PMH during the day shows similarities to that seen in aSAH, although the differences over the day are not statistically significant, as they are in aSAH. The occurrence of PMH is evenly distributed over the days of the week, as it is in aSAH.     

Minimum Clinically Important Difference of Montreal Cognitive Assessment in aneurysmal subarachnoid hemorrhage patients

Cognitive impairment is a major factor contributing to poor functional outcome after subarachnoid hemorrhage caused by a ruptured cerebral aneurysm (aSAH). Montreal Cognitive Assessment (MoCA) has been shown to be superior to the Mini-Mental State Examination in screening for cognitive domain deficit and correlating to functional outcome in aSAH patients. The aim of the current study was to determine the Montreal Cognitive Assessment (MoCA) score change that was associated with change of health in general in an aSAH patient cohort. We recruited aSAH patients from a regional neurosurgical center over a 3-year period. Patient assessments including MoCA and global rating of change (GRoC) were carried out at at 3 and 12 months after aSAH. Anchor-based and distribution-based approaches were adopted to calculate the Minimum Clinically Important Difference (MID). One hundred and seventy-five aSAH patients completed both 3-month and 1-year assessments and consented for participation. Employing the distribution-based approach for the 3-month and 1-year MoCA scores, the MID estimates equated to a change of 2.0 and 1.1 respectively. Employing the anchor-based approach (with GRoC), the MID estimate of MoCA (median, IQR) was 2, 1–4. In conclusion, we found that the MID of MoCA score associated with change of health in general in aSAH patients was 2. The MID provides guidance for future clinical trial design targeting on cognitive dysfunction after aSAH.     

Continuous EEG Monitoring for Early Detection of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage: A Pilot Study

Introduction

Early identification of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is a major challenge. The aim of this study was to investigate whether quantitative EEG (qEEG) features can detect DCI prior to clinical or radiographic findings.

Methods

A prospective cohort study was performed in aSAH patients in whom continuous EEG (cEEG) was recorded. We studied 12 qEEG features. We compared the time point at which qEEG changed with the time point that clinical deterioration occurred or new ischemia was noted on CT scan.

Results

Twenty aSAH patients were included of whom 11 developed DCI. The alpha/delta ratio (ADR) was the most promising feature that showed a significant difference in change over time in the DCI group (median ?62 % with IQR ?87 to ?39 %) compared to the control group (median +27 % with IQR ?32 to +104 %, p = 0.013). Based on the ROC curve, a threshold was chosen for a combined measure of ADR and alpha variability (AUC: 91.7, 95 % CI 74.2–100). The median time that elapsed between change of qEEG and clinical DCI diagnosis was seven hours (IQR ?11–25). Delay between qEEG and CT scan changes was 44 h (median, IQR 14–117).

Conclusion

In this study, ADR and alpha variability could detect DCI development before ischemic changes on CT scan was apparent and before clinical deterioration was noted. Implementation of cEEG in aSAH patients can probably improve early detection of DCI.

     

Impact of aneurysm morphology on aneurysmal subarachnoid hemorrhage severity,cerebral infarction and functional outcome

ObjectiveAneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity. The objective was to evaluate, whether specific morphological aneurysm characteristics could serve as predictive values for aSAH severity, disease-related complications and clinical outcome.MethodsA total of 453 aSAH patients (mean age: 54.9 ± 13.8 years, mean aneurysm size: 7.5 ± 3.6 mm) treated at a single center were retrospectively included. A morphometric analysis was performed based on angiographic image sets, determining aneurysm location, aneurysm size, neck width, aneurysm size ratios, aneurysm morphology and vessel size. The following outcome measures were defined: World Federation of Neurosurgical Societies (WFNS) grade 4 and 5, Fisher grade 4, vasospasm, cerebral infarction and unfavorable functional outcome.ResultsRegarding morphology parameters, aneurysm neck width was an independent predictor for Fisher 4 hemorrhage (OR: 1.1, 95%CI: 1.0–1.3, p = 0.048), while dome width (OR: 0.92, 95%CI: 0.86–0.97, p = 0.005) and internal carotid artery location (OR: 2.1, 95%CI: 1.1–4.2, p = 0.028) predicted vasospasm. None of the analyzed morphological characteristics prognosticated functional outcome. Patient age (OR: 0.95, 95%CI: 0.93–0.96, p < 0.001), WFNS score (OR: 4.8, 95%CI: 2.9–8.0, p < 0.001), Fisher score (OR: 2.3, 95%CI: 1.4–3.7, p < 0.001) and cerebral infarction (OR: 4.5, 95%CI: 2.7–7.8, p < 0.001) were independently associated with unfavorable outcome.ConclusionsThe findings indicate a correlation between aneurysm morphology, Fisher grade and vasospasm. Further studies will be required to reveal an independent association of aneurysm morphology with cerebral infarction and functional outcome.     

Long-term outcome after aneurysmal subarachnoid hemorrhage—risks of vascular events,death from cancer and all-cause death

Smoking and hypertension are risk factors for aneurysmal subarachnoid hemorrhage (aSAH), but also for other cardiovascular diseases and cancer. Few prospective data are available on the very long term risks of vascular diseases and vascular, cancer-related and overall death after aSAH. We determined vascular events and survival status in 1,765 patients with aSAH admitted to our center from 1985 to 2010. Cumulative risks were estimated with survival analysis. We compared risks of vascular, cancer-related and all-cause death with the general population with standardized mortality ratios (SMRs). Incidences of vascular events and death were compared with those after TIA/minor stroke. Conditional on surviving 3 months after aSAH, the risk of death was 8.7 % (95 % CI 7.3–10.1) within 5 years, 17.9 % (16.1–19.9) within 10 years, 29.5 % (27.3–31.8) within 15 years, and 43.6 % (41.2–46.1) within 20 years after SAH. The SMR for all-cause death was 1.8 (1.6–2.1), for vascular death 2.0 (95 % CI 1.6–2.5) and for cancer-related death 1.2 (0.9–1.5; sensitivity analysis 1.4; 95 % CI 1.1–1.8). The increased SMR for all-cause death persevered up to 20 years after aSAH. Compared with TIA/minor stroke patients, the age- and sex-adjusted cumulative incidence on vascular events was lower for aSAH patients [hazard ratio (HR) 0.48; 95 % CI 0.40–0.57); the HR for all-cause death was 0.96 (95 % CI 0.84–1.10). After aSAH, risks of vascular events and death, and probably also that of cancer-related death, are higher than in the general population. Although the long-term risk of vascular events was lower in aSAH patients than in TIA/minor stroke patients, the risk of death was similar.     

SSRI/SNRI Use is Not Associated with Increased Risk of Delayed Cerebral Ischemia After aSAH

Background

To determine the effect of selective serotonin reuptake inhibitor (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) use on the risk of symptomatic vasospasm and delayed cerebral ischemia (DCI) in patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH).

Methods

Retrospective review of consecutive patients with aSAH at Mayo Clinic, Rochester from January 2001 to December 2013. The variables collected and analyzed included age, sex, SSRI/SNRI use, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3–6) within 1 year.

Results

579 [females 363 (62.7 %)] patients with a median age of 55 (IQR 47–65) years were admitted with aSAH during the study period. WFNS at nadir was IV–V in 240 (41.5 %), and modified Fisher score was 3–4 in 434 (75.0 %). 81 (13.9 %) patients had been prescribed an SSRI or SNRI prior to admission and all continued to receive these medications during hospitalization. Symptomatic vasospasm was present in 154 (26.4 %), radiological infarction in 172 (29.5 %), and DCI in 250 (42.9 %) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p = 0.458), symptomatic vasospasm (p = 0.097), radiological infarction (p = 0.972), or poor functional outcome at 3 months (p = 0.376).

Conclusions

The use of SSRI/SNRI prior to and during hospitalization is not associated with DCI or functional outcome in patients with aSAH.

     

Preventive Antibiotics and Delayed Cerebral Ischaemia in Patients with Aneurysmal Subarachnoid Haemorrhage Admitted to the Intensive Care Unit

Introduction

Delayed cerebral ischemia (DCI) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Development of DCI is multifactorial, and inflammation, with or without infection, is one of the factors independently associated with development of DCI and poor outcome. We thus postulated that preventive antibiotics might be associated with a reduced risk of DCI and subsequent poor outcome in aSAH patients.

Methods

We performed a retrospective cohort-study in intensive care units (ICU) of three university hospitals in The Netherlands. We included consecutive aSAH patients with minimal ICU stay of 72 h who received either preventive antibiotics (SDD: selective digestive tract decontamination including systemic cefotaxime or SOD: selective oropharyngeal decontamination) or no preventive antibiotics. DCI was defined as a new hypodensity on CT with no other explanation than DCI. Hazard ratio’s (HR) for DCI and risk ratio’s (RR) for 28-day case-fatality and poor outcome at 3 months were calculated, with adjustment (aHR/aRR) for clinical condition on admission, recurrent bleeding, aneurysm treatment modality and treatment site.

Results

Of 459 included patients, 274 received preventive antibiotics (SOD or SDD) and 185 did not. With preventive antibiotics, the aHR for DCI was 1.0 (95 % CI 0.6–1.8), the aRR for 28-day case-fatality was 1.1 (95 % CI 0.7–1.9) and the aRR for poor functional outcome 1.2 (95 % CI 1.0–1.4).

Conclusions

Preventive antibiotics were not associated with reduced risk of DCI or poor outcome in aSAH patients in the ICU.

     

Delay in Diagnosis of Basilar Artery Stroke

Background

Basilar artery stroke causes substantial morbidity and mortality. Although its unusual clinical presentation potentially contributes to a delay in diagnosis, this problem has not been systematically studied. We compared intervals between symptom onset, initial presentation, and diagnosis in stroke due to basilar artery (BA) versus left middle cerebral artery (LMCA) occlusion to determine the presence of and potential reasons for diagnostic delay in BA stroke.

Methods

We retrospectively identified 21 consecutive adult patients diagnosed with BA stroke between 2009 and 2011 from our hospital’s prospective stroke registry. Patients were age-, sex-, and race-matched with 21 LMCA stroke patients from the same period. All subjects had confirmed clinical and radiographic diagnosis of stroke due to occlusion or stenosis of the BA, LMCA, or left internal carotid artery. Time to diagnosis was determined independently by two investigators through medical record review. The pre-specified primary outcome was latency from emergency department (ED) arrival to stroke diagnosis.

Results

Median time from ED arrival to diagnosis was 8 h 24 min (IQR: 2:43–26:32) for BA and 1 h 23 min (IQR: 0:41–1:45; p < 0.001) for LMCA. Median time from symptom onset to ED arrival was 7 h 44 min (IQR 1:23–21:30) for BA and 1 h 2 min (IQR 0:36–9:41; p = 0.06) for LMCA. Four of 21 (19 %) BA patients were diagnosed within a 4-h time frame to make intravenous thrombolysis possible compared to 13 of 21 (62 %) LMCA patients (p = 0.01).

Conclusions

Our results suggest that both pre-hospital and in-hospital processes cause substantial, clinically significant delays in the diagnosis of BA stroke.

     

Relationship Between Cardiac Dysfunction and Cerebral Perfusion in Patients with Aneurysmal Subarachnoid Hemorrhage

Introduction

Cardiac dysfunction may occur after aneurysmal subarachnoid hemorrhage (aSAH). Although it is associated with poor outcome, the pathophysiological mechanism of this association remains unclear. We investigated the relationship between cardiac function and cerebral perfusion in patients with aSAH.

Methods

We studied 72 aSAH patients admitted within 72 h after ictus with echocardiography and cerebral CT perfusion within 24 h after admission. Cardiac dysfunction was defined as myocardial wall motion abnormalities or positive troponin. In patients with and without cardiac dysfunction, we calculated the mean perfusion [cerebral blood flow (CBF) and time-to-peak (TTP)] in standard regions of interest and calculated differences with 95 % confidence intervals (95 % CI).

Results

In 35 patients with cardiac dysfunction minimal CBF was 15.83 mL/100 g/min compared to 18.59 in 37 without (difference of means ?2.76; 95 % CI ?5.43 to ?0.09). Maximal TTP was 26.94 s for patients with and 23.10 s for patients without cardiac dysfunction (difference of means 3.84; 95 % CI 1.63–6.05). Mean global CBF was 21.71 mL/100 g/min for patients with cardiac dysfunction and 24.67 mL/100 g/min for patients without cardiac dysfunction (?2.96; 95 % CI ?6.19 to 0.27). Mean global TTP was 25.27 s for patients with cardiac dysfunction and 21.26 for patients without cardiac dysfunction (4.01; 95 % CI 1.95–6.07).

Conclusion

aSAH patients with cardiac dysfunction have decreased focal and global cerebral perfusion. Further studies should evaluate whether this relation is explained by a direct effect of cardiac dysfunction on cerebral circulation or by an external determinant, such as a hypercatecholaminergic or hypometabolic state, influencing both cardiac function and cerebral perfusion.

     

Early Predictors of Prolonged Stay in a Critical Care Unit Following Aneurysmal Subarachnoid Hemorrhage

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurologic emergency that typically warrants initial monitoring in a critical care setting. The aim of this study is to identify clinical and radiologic features on admission that predict a protracted critical care admission following aSAH.

Methods

Exploratory posthoc analysis was performed on the 413 patients enrolled in Clazosentan to Overcome Neurological iSChemia and Infarction OccUrring after Subarachnoid hemorrhage (CONSCIOUS-1), a prospective randomized control trial of clazosentan for the prevention of vasospasm after aSAH. The association between potential clinical and radiographic covariates, and the length of stay (LOS) in a critical care unit after aSAH was determined using a Cox proportional hazards model. Covariates with a significance level of p < 0.20, on univariate analysis, were entered into a multivariate forward conditional analysis to identify independent predictors of prolonged LOS.

Results

The mean LOS was 12.6 ± 10.6 days. On multivariate analysis, age (hazard ratio [HR] 1.01, 95 % confidence interval [CI] 1.00–1.02; p = 0.032), a history of hypertension (HR 1.30, CI 1.01–1.67; p = 0.045), and a World Federation of Neurosurgical Societies Score of IV–V on admission (HR 1.38, CI 1.05–1.81; p = 0.02) were the clinical features associated with a greater critical care LOS following aSAH. Intracerebral hemorrhage (HR 1.50, CI 1.03–2.21; p = 0.004) and increasing intraventricular clot burden (HR 1.08, CI 1.03–1.14; p = 0.037) on admission computed tomography were the radiologic features associated with prolonged LOS.

Conclusions

We have identified several early risk factors associated with a prolonged critical care stay following aSAH.     

The association between hyponatraemia and long-term functional outcome in patients with aneurysmal subarachnoid haemorrhage: A single centre prospective cohort study

To assess the association between hyponatraemia and long-term functional outcome and other relevant outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) we conducted a prospective cohort study in a Neurosciences Intensive Care Unit (ICU) in Sydney, Australia. The primary exposure variable was hyponatraemia (Na⁺ <135 mmol/L). The primary outcome was favourable outcome, a score of 5–8 on the extended Glasgow Outcome Score (GOSe) at 12 months. We also measured mortality, the incidence of delayed cerebral ischaemia (DCI) and cerebral arterial vasospasm and duration of ICU and hospital admission. There were 200 participants, 111 (56%) developed hyponatraemia. Hyponatraemia was not associated with favourable outcome at 12 months (unadjusted odds ratio [OR] OR 1.31, 95% confidence interval [CI] 0.65–2.65, p = 0.56). The result was similar after adjustment for baseline covariates (adjusted OR 0.60, 95% CI 0.16–1.99, p = 0.43). There was no association between hyponatraemia and the incidence of DCI (OR 0.95, 95% CI 0.46 to 2.0, p > 0.99) nor cerebral arterial vasospasm (OR 1.4, 95% CI 0.8 to 2.5, p = 0.27). Those who developed hyponatraemia had a longer median duration of ICU admission (17 days, interquartile range [IQR] 12 to 20, compared to 13 days, IQR 8–21, p = 0.02) and longer median duration of hospital admission (24 days, IQR 21–30, compared to 22 days IQR 14–31, p = 0.05). While hyponatraemia is common following aSAH, it is not associated with worse long-term functional outcome, increased rate of DCI, nor cerebral arterial vasospasm. Hyponatraemia in patients with aSAH was associated with longer duration of ICU and hospital admission.     

Spontaneous Elevation of Blood Pressure After SAH: An Epiphenomenon of Disease Severity and Demand,But Not a Surrogate for Outcome?

Background

Spontaneous blood pressure increase is frequently observed after aneurysmal subarachnoid hemorrhage (aSAH). These episodes of spontaneous blood pressure alterations are usually tolerated under the assumption of an endogenous response to maintain cerebral perfusion. The relevance of blood pressure variability and its relationship to disease severity and outcome, however, remain obscure.

Methods

A total of 115 consecutive patients with aSAH were included for this retrospective analysis of a continuously collected data pool. Demographics, initial clinical severity of aSAH (HH°, mFS), treatment modality, clinical course, and outcome (development of DCI, cerebral infarction, and GOS after 3 months) were recorded. Hemodynamic information—recorded automatically with a frequency of 1/15 min—was analyzed for spontaneous blood pressure increase (SBI) and endogenous persistent hypertension (EPH) after exclusion of iatrogenic factors and relevant co-medication. Subgroup analysis included stratification for day 0–3, 4–14, and 14–21.

Results

SBI and EPH incidence varied from 17 to 84% depending on detection threshold (15–35 mmHg) and time period under scrutiny. Incidence of blood pressure increase correlated with disease severity upon admission (p < 0.05), but the anticipated association with outcome was not observed. SBI and EPH were more likely to occur between day 4 and 14 (p < 0.001), but only early occurrence (day 0–3) was associated with higher incidence of DCI (p < 0.05). Persistent blood pressure elevation between day 4 and 21 was associated with fewer DCI. However, no influence of spontaneous upregulation on clinical outcome after three months was observed.

Conclusions

Spontaneous hemodynamic upregulation is a frequent phenomenon after aSAH. Our data support the hypothesis that spontaneous blood pressure alterations reflect an endogenous, demand-driven response correlating with disease severity. Early alterations may indicate an aggravated clinical course, while later upregulation in particular—if permitted—does not translate into a higher risk of unfavorable outcome.

     

Intra-hospital delays in stroke patients treated with rt-PA: impact of preadmission notification

Pre-hospital notification enhances thrombolysis rate and improves intra-hospital delays, but the impact of the notification to the neurologist by the emergency medical system (EMS) call centre remains unknown. Our objective was to compare pre-hospital and in-hospital delays in stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA), with and without pre-hospital notification. We compared baseline characteristics and in-hospital delays in stroke patients treated by rt-PA with a high-level notification (call to EMS and EMS–neurologist discussion), a low-level notification (call to EMS without EMS–neurologist discussion ) and no pre-hospital notification. Of 302 consecutive patients [165 women, 54.6 %; median age 74 years, interquartile range (IQR) 59–83], patients with high-level, low-level and no notification differed for the severity at admission (median National Institutes of Health Stroke Scale scores, respectively, of: 12, IQR 7–17; 9, IQR 6–15, and 8, IQR 6–14, p = 0.029). Patients with high-level notification had shorter (1) admission-to-completion of imaging times (27 min, IQR 14–35) than patients with low-level notification (35 min, IQR 17–54) or no notification (36 min, IQR 30–58) (p < 0.01); (2) door-to-needle times (49 min, IQR 39–62 vs. 57 min, IQR 39–81 vs. 63 min, IQR 51–97; p = 0.003); and (3) onset-to-needle times (140 min, IQR 110–175 vs. 155 min, IQR 106–230 vs. 182 min, IQR 131–234; p < 0.001). They did not differ for onset-to-admission time and imaging-to-needle time. Pre-hospital notification by the EMS reduces intra-hospital delays in patients eligible for rt-PA, but the benefit is higher in the case of discussion between the EMS and the neurologist before admission.     

Response of Brain Oxygen to Therapy Correlates with Long-Term Outcome After Subarachnoid Hemorrhage

Background

Brain oxygen (P_btO₂) monitoring can help guide care of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients. The relationship between P_btO₂-directed therapy and long-term outcome is unclear. We hypothesized that responsiveness to P_btO₂-directed interventions is associated with outcome.

Methods

Seventy-six aSAH patients who underwent P_btO₂ monitoring were included. Long-term outcome [Glasgow Outcome Score-Extended (GOS-E) and modified Rankin Scale (mRS)] was ascertained using the social security death database and structured telephone interviews. Univariate and multivariate regression were used to identify variables that correlated with outcome.

Results

Data from 64 patients were analyzed (12 were lost to follow-up). There were 530 episodes of compromised P_btO₂ (<20 mmHg) during a total of 7,174 h of monitor time treated with 1,052 interventions. Forty-two patients (66 %) survived to discharge. Median follow-up was 8.5 months (range 0.1–87). At most recent follow-up 35 (55 %) patients were alive, and 28 (44 %) had a favorable outcome (mRS ≤3). In multivariate ordinal regression analysis, only age and response to P_btO₂-directed intervention correlated significantly with outcome. Increased age was associated with worse outcome (coeff. 0.8, 95 % CI 0.3–1.3, p = 0.003), and response to P_btO₂-directed intervention was associated with improved outcome (coeff. ?2.12, 95 % CI ?4.0 to ?0.26, p = 0.03). Patients with favorable outcomes had a 70 % mean rate of response to P_btO₂-directed interventions whereas patients with poor outcomes had a 45 % response rate (p = 0.005).

Conclusions

Response to P_btO₂-directed intervention is associated with improved long-term functional outcome in aSAH patients.     

Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage

Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of cerebral dysfunction that were associated with poor admission clinical grade. Between 1997 and 2008, 850 consecutive SAH patients were enrolled in our prospective database. Demographic data, physiological parameters, and location and volume of blood were recorded. After univariate analysis, significant variables were entered into a logistic regression model to identify significant associations with poor admission clinical grade (Hunt–Hess grade 4–5). Independent predictors of poor admission grade included a SAH sum score >15/30 (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.5–3.6), an intraventricular hemorrhage sum score >1/12 (OR 3.1, 95% CI 2.1–4.8), aneurysm size >10 mm (OR 1.7, 95% CI 1.1–2.6), body temperature ?38.3 °C (OR 2.5, 95% CI 1.1–5.4), and hyperglycemia >200 mg/dL (OR 2.7, 95% CI 1.6–4.5). In a large, consecutive series of prospectively enrolled patients with SAH, the inflammatory response at the time of aneurysm rupture, as reflected by the volume and location of the hemoglobin burden, hyperthermia, and perturbed glucose metabolism, independently predicts poor admission Hunt–Hess grade. Strategies for mitigating the inflammatory response to aneurysmal rupture in the hyper-acute setting may improve the admission clinical grade, which may in turn improve outcomes.     

Aneurysmal subarachnoid hemorrhage in elderly patients: long-term outcome and prognostic factors in an interdisciplinary treatment approach

The number of elderly patients with aneurysmal subarachnoid hemorrhage (SAH) is increasing with the aging of the population. However, management recommendations based on long-term outcome data and analyses of prognostic factors are scarce. Our study focused exclusively on elderly patients aged ≥60 years at the onset of SAH. Patients were selected from an in-house database and compared in cohorts of age 60–69, 70–79, and ≥80, regarding pre-existing medical conditions, treatment, clinical course including complications, and outcome. A multivariate analysis was conducted to identify prognostic factors for death and disability. A total of 256 patients (138 aged 60–69, 93 aged 70–79, 25 aged ≥80) with putative aneurysmal SAH who had been admitted to our hospital between January 1, 1996 and June 30, 2007 were extracted. The median follow-up of our total cohort was 35.5 months (range <1–154 months). Endovascular or conservative aneurysm treatment was applied more often with increasing age (p < 0.006). The 1-year survival rate was 78, 65, and 38 % in the three age groups, respectively (p = 0.0002); most of the patients died from the initial hemorrhage or from medical complications. Patients aged <70 with an initial World Federation of Neurosurgical Societies (WFNS) score of I–III showed the best clinical recovery. WFNS score, age, and clipping/coiling were extracted as prognostic factors from the Cox model. Elderly patients who get admitted with a good WFNS score (I–III) seem to benefit from aggressive treatment whereas caution seems to be warranted particularly in patients ≥70 years of age who get admitted in a WFNS score of IV and V because of their limited short- and long-term prognosis.     

Neuropsychiatric disturbance after aneurysmal subarachnoid hemorrhage

Although aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 3–5% of all strokes, a high degree of morbidity has been reported in this relatively young subset of patients. Neuropsychiatric disturbance has often been neglected in these reports. We aimed to investigate the pattern and pathological factors of chronic neuropsychiatric disturbance in aSAH patients. This cross-sectional observational four-center study was carried out in Hong Kong. Neuropsychiatric outcome (Neuropsychiatric Inventory Chinese Version [CNPI]) assessments were conducted cross-sectionally 1–4 years after ictus. Pathological factors considered were early brain injury as assessed by admission World Federation of Neurosurgical Societies grade, aneurysm treatment (clipping versus coiling), delayed cerebral infarction, and chronic hydrocephalus. One hundred and three aSAH patients’ spouses or caregivers completed the CNPI. Forty-two (41%) patients were reported to have one or more domain(s) of neuropsychiatric disturbance. Common neuropsychiatric disturbance domains included agitation/aggression, depression, apathy/indifference, irritability/lability, and appetite/eating disturbance. Chronic neuropsychiatric disturbance was associated with presence of chronic hydrocephalus. A subscore consisting of the five commonly affected domains seems to be a suitable tool for aSAH patients and should be further validated and replicated in future studies.     

Clinical Value of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratio After Aneurysmal Subarachnoid Hemorrhage

Background

Inflammation and thrombosis are associated with the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are emerging as novel inflammatory markers in stroke. We aimed to identify the association of NLR and PLR with delayed cerebral ischemia (DCI) and 3-month outcome after aSAH.

Methods

Two hundred and forty-seven patients diagnosed with aSAH within 24 h of symptoms onset were enrolled. Clinical, neuroradiological, laboratory, and follow-up data were collected from electronic database. Functional outcome was assessed by modified Rankin Scale. Admission NLR, PLR, and combined NLR-PLR associated with outcomes were evaluated by logistic regression analysis, and we used receiver operating characteristic curves to detect the overall predictive accuracy of these markers.

Results

Fifty-five (22.3 %) patients had unfavorable outcome and 47 (19 %) developed DCI. Both NLR and PLR were correlated with WFNS grade (ρ = 0.35[p < 0.001], ρ = 0.28[p < 0.001]) and modified Fisher grade (ρ = 0.25[p = 0.001], ρ = 0.28[p = 0.003]) and independently related to DCI (OR 2.18, 95 %CI 1.51–3.15, p = 0.016; OR 2.21, 95 %CI 1.61–3.32, p = 0.008) and functional outcome (OR 1.89, 95 %CI 1.52–3.17, p = 0.015; OR 1.77, 95 %CI 1.48–3.21, p = 0.018) at 3 months after aneurysm repair. They had comparable predictive ability in DCI occurrence (area under the curve [AUC] 0.65, 95 %CI 0.55–0.74, p = 0.002; AUC 0.68, 95 %CI 0.60–0.76, p < 0.001) and poor outcome (AUC 0.70, 95 %CI 0.63–0.77, p < 0.001; AUC 0.65, 95 %CI 0.58–0.72, p = 0.001). However, combination of the two indexes showed a better predictive value than each alone (AUC 0.73, 95 %CI 0.66–0.81, p < 0.001 for DCI; AUC 0.76, 95 %CI 0.70–0.83, p < 0.001 for poor outcome).

Conclusions

NLR and PLR as novel inflammatory biomarkers are independent predictors of DCI development and functional outcome after acute aSAH. When combined together, they may help to identify high-risk patients more powerfully.