Prognostic Significance of Sentinel Headache Preceding Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Sentinel headache (SH) is often assumed to portend an increased risk of delayed cerebral ischemia (DCI) and aneurysm rebleeding. This study aimed to re-evaluate the associations between SH and aneurysm rebleeding, DCI, and outcome after SAH. METHODS: We retrospectively analyzed 1102 patients with spontaneous SAH and available data regarding history of SH who were enrolled in the Columbia University SAH Outcomes Project between 1996 and 2009. Patients were asked whether they had experienced any episodes of acute, sudden-onset severe headache in the 2 weeks preceding the most recent bleeding event. DCI was defined as neurologic deterioration, infarction, or both due to vasospasm. Rebleeding was defined as the appearance of new hemorrhage on computed tomography. Outcome was assessed at 3 months by telephone interview using the modified Rankin Scale. RESULTS: SH was reported in 152 (14%) of 1102 patients. There were no significant differences between patients with and without SH with regard to admission Hunt-Hess grade or modified Fisher Scale. There was also no difference with regard to the frequency of aneurysm rebleeding (10% vs. 8%, P = 0.42), DCI (18% vs, 20%, P = 0.64), moderate-or-severe angiographic vasospasm on follow-up angiography (51% vs. 56%, P = 0.43), highest recorded mean middle cerebral artery flow velocity on transcranial Doppler (134 versus 128 cm/s, P = 0.30), or the distribution of modified Rankin Scale scores at 3 months. CONCLUSIONS: A history of sentinel headache before the clinical diagnosis of SAH does not imply an increased risk of DCI or further rebleeding, and carries no prognostic significance.

Medical Treatment Failure for Symptomatic Vasospasm After Subarachnoid Hemorrhage Threatens Long-Term Outcome.

Background and Purpose- Symptomatic vasospasm is a common cause of morbidity and mortality after subarachnoid hemorrhage. We sought to identify predictors and the long-term impact of treatment failure with hypertensive therapy for symptomatic vasospasm. Methods- We performed a retrospective analysis of 1520 subarachnoid hemorrhage patients prospectively enrolled in the Columbia University SAH Outcomes Project between August 1996 and August 2012. One hundred ninety-eight symptomatic vasospasm patients were treated with vasopressors to raise arterial blood pressure, with and without volume expansion. Treatment response, defined as complete or near-complete resolution of the initial neurological deficit, was adjudicated in weekly meetings of the study team based on serial clinical examination after hypertensive treatment. Outcome was evaluated at 1 year with the modified Rankin Scale. Results- Twenty-one percent of the 198 patients who received hypertensive therapy did not respond to treatment. Treatment failure was associated with an increased risk of death or severe disability at 1 year (modified Rankin Scale score of 4-6; 62% versus 25%; P<0.001). Failure of medical therapy was also associated with an admission troponin I level >0.3 µg/L (64% versus 28%; P=0.001), aneurysm coiling (43% versus 20%; P=0.004), and involvement of >1 symptomatic vascular territory at onset (39% versus 22%; P=0.02). In multivariable analysis, treatment failure was independently associated only with troponin I elevation (adjusted odds ratio, 4.30; 95% CI, 1.69-11.09; P=0.002). Conclusions- Failure to respond to induced hypertension for symptomatic vasospasm threatens 1-year outcome. Subarachnoid hemorrhage patients with symptomatic vasospasm who have elevated initial troponin I levels, indicative of neurogenic cardiac injury, are at twice the risk of medical treatment failure. Expedited endovascular therapy should be considered in these patients.

White Blood Cell Count Improves Prediction of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Immune dysregulation has long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To determine the relationship of inflammatory cell biomarkers with DCI. METHODS: We evaluated 849 aSAH patients who were enrolled into a prospective observational cohort study and had a white blood cell (WBC) differential obtained within 72 h of bleed onset. RESULTS: WBC count > 12.1 × 109/L (odds ratio 4.6; 95% confidence interval [CI]: 1.9-11, P < 0.001) was the strongest Complete Blood Count (CBC) predictor of DCI after controlling for clinical grade (P < .001), thickness of SAH blood on admission computed tomography (P = .002), and clipping aneurysm repair (P < .001). A significant interaction between clinical grade and WBC count (odds ratio 0.8, 95% CI: 0.6-1.0, P = .02) revealed that good-grade patients with elevated WBC counts (49%: 273/558) had increased odds for DCI indistinguishable from poor-grade patients. Multivariable Cox regression also showed that elevated WBC counts in good-grade patients increased the hazard for DCI to that of poor-grade patients (hazard ratio 2.1, 95% CI 1.3-3.2, P < .001). Receiver operating characteristic curve analysis of good-grade patients revealed that WBC count (area under the curve [AUC]: 0.63) is a stronger DCI predictor than the modified Fisher score (AUC: 0.57) and significantly improves multivariable DCI prediction models (Z = 2.0, P = .02, AUC: 0.73; PPV: 34%; NPV: 92%). CONCLUSION: Good-grade patients with early elevations in WBC count have a similar risk and hazard for DCI as poor-grade patients. Good-grade patients without elevated WBC may be candidates to be safely downgraded from the intensive care unit, leading to cost savings for both patient families and hospitals.

Predicting delayed cerebral ischemia after subarachnoid hemorrhage using physiological time series data.

To develop and validate a prediction model for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) using a temporal unsupervised feature engineering approach, demonstrating improved precision over standard features. 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Baseline information and standard grading scales were evaluated: age, sex, Hunt Hess grade, modified Fisher Scale (mFS), and Glasgow Coma Scale (GCS). An unsupervised approach applying random kernels was used to extract features from physiological time series (systolic and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (Partial Least Squares, linear and kernel Support Vector Machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.58. Combined demographics and grading scales: AUC 0.60. Random kernel derived physiologic features: AUC 0.74. Combined baseline and physiologic features with redundant feature reduction: AUC 0.77. Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that our models achieve higher classification accuracy.

Primary Intracerebral Hemorrhage: A Closer Look at Hypertension and Cerebral Amyloid Angiopathy.

BACKGROUND/PURPOSE: Primary intracerebral hemorrhage (ICH) studies often use hematoma location rather than ICH etiologies when assessing outcome. Characterizing ICH using hematoma location is effective/reproducible, but may miss heterogeneity among these ICH locations, particularly lobar ICH where competing primary ICH etiologies are possible. We subsequently investigated baseline characteristics/outcome differences of spontaneous, primary ICH by their etiologies: cerebral amyloid angiopathy (CAA) and hypertension. METHODS: Primary ICH clinical/outcomes data were prospectively collected between 2009 and 2015. Modified Boston criteria were used to identify "probable/definite" and "possible" CAA-ICH, which were evaluated separately. SMASH-U criteria were used to identify hypertension ICH. Medication and systemic disease coagulopathy ICH were excluded. Baseline characteristics/outcomes among "probable/definite" CAA-ICH, "possible" CAA-ICH, and hypertension ICH were compared using logistic regression. Mortality models using ICH etiologies compared to hematoma location as predictor variables were assessed. RESULTS: Two hundred and four hypertension ICHs, 55 "probable/definite" CAA-ICHs, and 46 "possible" CAA-ICHs were identified. Despite older age and larger ICH volumes, lower hospital mortality was seen in "probable/definite" CAA-ICH versus hypertension ICH (OR 0.2; 95% CI 0.05-0.8; p = 0.02) after adjusting for female gender, components of ICH score, and EVD placement. There were no mortality differences between "possible" CAA-ICH and hypertension ICH. However, lower hospital mortality was seen in "probable/definite" versus "possible" CAA-ICH (OR 0.2; 95% CI 0.04-0.7; p = 0.02). When using ICH etiology rather than hematoma location, hospital mortality models significantly improved (χ2: [df = 2, N = 305] = 6.2; p = 0.01). CONCLUSIONS: Further investigation is required to confirm the mortality heterogeneity seen within our primary ICH cohort. Hematoma location may play a role for these findings, but the mortality differences seen among lobar ICH using CAA-ICH subtypes and a failure to identify mortality differences between "possible" CAA-ICH and hypertension ICH suggest the limitations of accounting for hematoma location alone.

Desmopressin administration and rebleeding in subarachnoid hemorrhage: analysis of an observational prospective database.

OBJECTIVERebleeding remains a frequent and catastrophic event leading to poor outcome after subarachnoid hemorrhage (SAH). Reduced platelet function after the initial bleed is associated with higher risk of early rebleeding. Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplatelet drugs. The authors hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of rebleeding.METHODSThe authors performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. The authors compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.RESULTSAmong 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.CONCLUSIONSTreatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH.

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

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

Functional Outcomes and Delayed Cerebral Ischemia Following Nonperimesencephalic Angiogram-Negative Subarachnoid Hemorrhage Similar to Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The angiogram-negative subarachnoid hemorrhage (SAH) literature includes patients with perimesencephalic hemorrhage, which is recognized to have a much better outcome than aneurysmal SAH. OBJECTIVE: To evaluate the clinical outcomes of Nonperimesencephalic Angiogram-Negative SAH (NPAN-SAH). METHODS: A prospective, spontaneous SAH database of 1311 patients that accrued between April 2006 and December 2014 was screened. All patients with NPAN-SAH and 2 consecutive negative cerebral angiograms were included. RESULTS: We identified 191 (11%) from a total of 1311 patients with spontaneous SAH. Amongst angiogram-negative patients, 83 (4.9%) were adjudicated to have NPAN-SAH. Patient characteristics were similar across the groups, except NPAN-SAH patients were more likely to be men and had higher rates of diabetes. In a multivariable logistic regression model, NPAN-SAH patients were less likely to develop vasospasm, after adjusting for Fisher grade, sex, and diabetes (odds ratio [OR]: 0.197, 95% confidence interval [CI; 0.07-0.55], P = .002). In another adjusted model accounting for Hunt and Hess clinical grade, NPAN-SAH patients were also less likely to develop vasospasm (OR: 0.2, 95% CI [0.07-0.57], P = .002). We found no statistical significance between 2 groups for rebleed, developing hydrocephalus, seizures, or delayed cerebral ischemia. NPAN-SAH patients were equally associated with poor functional outcome (modified Rankin scale ≥3; OR: 1.16, 95% CI [0.615-2.20], P = .6420), and death (OR: 1.22, 95% CI [0.362-4.132], P = .7455) compared to aneurysmal SAH. CONCLUSION: Although the risk of vasospasm may be lower, patients with NPAN-SAH are equally associated with delayed cerebral ischemia, poor outcome, and death as compared to patients with aneurysmal SAH. Furthers studies may be necessary to further clarify these findings.

Hunt-Hess 5 subarachnoid haemorrhage presenting with cardiac arrest is associated with larger volume bleeds.

AIMS: The mechanism, effects, and outcomes of cardiac arrest (CA) caused by subarachnoid haemorrhage (SAH) remain unclear. We compared SAH patients presenting with CA to other high-grade SAH patients presenting without CA in order to better understand (1) the cause of CA, (2) cerebral pathophysiology following CA, and (3) outcomes of CA in patients with SAH. METHODS: We performed a retrospective analysis of a prospectively collected observational cohort. 31 Hunt-Hess 5 patients that presented with CA were compared to 146 Hunt-Hess 5 patients that presented without CA. Clinical and imaging findings were predefined and adjudicated. Cerebral physiology measures were available for a subset of patients, matched 1:1 by age. RESULTS: Twenty-two (71%) CA patients had pulseless electrical activity/asystole compared to 2 (6%) with a shockable rhythm. The CA patients were younger (OR 0.96, 95% CI 0.93-0.99, p=0.009), had more SAH on CT (OR 1.07, 95% CI 1.01-1.13, p=0.02), and had higher in-hospital mortality (87% vs. 58%, OR 6.2 (2.1-26.6), p=0.004). There were no differences in aneurysm location, cerebral herniation, or ictal seizures. Despite similar cerebral perfusion pressure, CA patients had pathologically lower brain tissue oxygenation, lower glucose, and higher lactate to pyruvate ratios. CONCLUSIONS: CA in SAH is associated with larger volume bleeds. Despite normal cerebral perfusion pressures, CA patients show compromised cerebral physiology.

Does the obesity paradox predict functional outcome in intracerebral hemorrhage?

OBJECTIVEBeing overweight or mildly obese has been associated with a decreased risk of death or hospitalization in patients with cardiovascular disease. Similarly, overweight patients admitted to an intensive care unit (ICU) have improved survival up to 1 year after admission. These counterintuitive observations are examples of the "obesity paradox." Does the obesity paradox exist in patients with intracerebral hemorrhage (ICH)? In this study the authors examined whether there was an association between obesity and functional outcome in patients with ICH.METHODSThe authors analyzed 202 patients admitted to the neurological ICU (NICU) who were prospectively enrolled in the Columbia University ICH Outcomes Project between September 2009 and December 2012. Patients were categorized into 2 groups: overweight (body mass index [BMI] ≥ 25 kg/m2) and not overweight (BMI < 25 kg/m2). The primary outcome was defined as survival with favorable outcome (modified Rankin Scale [mRS] score 0-3) versus death or severe disability (mRS score 4-6) at 3 months.RESULTSThe mean age of the patients in the study was 61 years. The mean BMI was 28 ± 6 kg/m2. The mean Glasgow Coma Scale score was 10 ± 4 and the mean ICH score was 1.9 ± 1.3. The overall 90-day mortality rate was 41%. Among patients with a BMI < 25 kg/m2, 24% (17/70) had a good outcome, compared with 39% (52/132) among those with a BMI ≥ 25 kg/m2 (p = 0.03). After adjusting for ICH score, sex, do-not-resuscitate code status, and history of hypertension, being overweight or obese (BMI ≥ 25 kg/m2) was associated with twice the odds of having a good outcome compared with patients with BMI < 25 kg/m2 (adjusted odds ratio 2.05, 95% confidence interval 1.03-4.06, p = 0.04).CONCLUSIONSIn patients with ICH admitted to the NICU, being overweight or obese (BMI ≥ 25 kg/m2) was associated with favorable outcome after adjustment for established predictors. The reason for this finding requires further study.

Transcranial Doppler Waveforms During Intra-aortic Balloon Pump Counterpulsation for Vasospasm Detection After Subarachnoid Hemorrhage.

BACKGROUND: Transcranial Doppler ultrasound is a standard screening tool for vasospasm after subarachnoid hemorrhage. Prevention of vasospasm-induced delayed cerebral ischemia after subarachnoid hemorrhage depends on optimization of cerebral perfusion pressure, which can be challenged by neurogenic stress cardiomyopathy. Intra-aortic balloon pumps have been utilized to augment cerebral perfusion, but they change the transcranial Doppler waveform, altering its interpretability for vasospasm screening. OBJECTIVE: To assess the features of the transcranial Doppler waveform that correlate with vasospasm. METHODS: We retrospectively reviewed cases of subarachnoid hemorrhage that underwent same-day transcranial Doppler ultrasound and angiography. Transcranial Doppler waveforms were assessed for mean velocity, peak systolic velocity, balloon pump-augmented diastolic velocity, and a novel feature, "delta velocity" (balloon pump-augmented velocity - systolic velocity). Relationship of flow velocity features to vasospasm was estimated by generalized estimating equation models using a Gaussian distribution and an exchangeable correlation structure. RESULTS: There were 31 transcranial Doppler and angiography pairings (12 CT angiography/19 digital subtraction angiography) from 4 patients. Fourteen pairings had proximal vasospasm by angiography. Delta velocity was associated with proximal vasospasm (coefficient -6.8 [95% CI -9.8 to -3.8], P < .001). There was no significant correlation with proximal vasospasm for mean velocity (coefficient -13.0 [95% CI -29.3 to 3.4], P = .12), systolic velocity (coefficient -8.7 [95% CI -24.8 to 7.3], P = .29), or balloon pump-augmented velocity (coefficient -15.3 [95% CI -31.3 to 0.71], P = .06). CONCLUSION: Delta velocity, a novel transcranial Doppler flow velocity feature, may reflect vasospasm in patients with subarachnoid hemorrhage and intra-aortic balloon pumps.

Intracortical electrophysiological correlates of blood flow after severe SAH: A multimodality monitoring study.

Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Approximately one in four patients develop progressive neurological deterioration and silent infarction referred to as delayed cerebral ischemia (DCI). DCI is a complex, multifactorial secondary brain injury pattern and its pathogenesis is not fully understood. We aimed to study the relationship between cerebral blood flow (CBF) and neuronal activity at both the cortex and in scalp using electroencephalography (EEG) in poor-grade SAH patients undergoing multimodality intracranial neuromonitoring. Twenty patients were included, of whom half had DCI median 4.7 days (interquartile range (IQR): 4.0-5.6) from SAH bleed. The rate of decline in regional cerebral blood flow (rCBF) was significant in both those with and without DCI and occurred between days 4 and 7 post-SAH. The scalp EEG alpha-delta ratio declined early in those with DCI. In the group without DCI, CBF and cortical EEG alpha-delta ratio were correlated (r = 0.53; p < 0.01) and in the group without DCI, inverse neurovascular coupling was observed at CPP < 80 mmHg. We found preliminary evidence that as patients enter the period of highest risk for the development of DCI, the absence of neurovascular coupling may act as a possible pathomechanism in the development of ischemia following SAH.

Electroencephalographic Periodic Discharges and Frequency-Dependent Brain Tissue Hypoxia in Acute Brain Injury.

Importance: Periodic discharges (PDs) that do not meet seizure criteria, also termed the ictal interictal continuum, are pervasive on electroencephalographic (EEG) recordings after acute brain injury. However, their association with brain homeostasis and the need for clinical intervention remain unknown. Objective: To determine whether distinct PD patterns can be identified that, similar to electrographic seizures, cause brain tissue hypoxia, a measure of ongoing brain injury. Design, Setting, and Participants: This prospective cohort study included 90 comatose patients with high-grade spontaneous subarachnoid hemorrhage who underwent continuous surface (scalp) EEG (sEEG) recording and multimodality monitoring, including invasive measurements of intracortical (depth) EEG (dEEG), partial pressure of oxygen in interstitial brain tissue (Pbto2), and regional cerebral blood flow (CBF). Patient data were collected from June 1, 2006, to September 1, 2014, at a single tertiary care center. The retrospective analysis was performed from September 1, 2014, to May 1, 2016, with a hypothesis that the effect on brain tissue oxygenation was primarily dependent on the discharge frequency. Main Outcomes and Measures: Electroencephalographic recordings were visually classified based on PD frequency and spatial distribution of discharges. Correlations between mean multimodality monitoring data and change-point analyses were performed to characterize electrophysiological changes by applying bootstrapping. Results: Of the 90 patients included in the study (26 men and 64 women; mean [SD] age, 55 [15] years), 32 (36%) had PDs on sEEG and dEEG recordings and 21 (23%) on dEEG recordings only. Frequencies of PDs ranged from 0.5 to 2.5 Hz. Median Pbto2 was 23 mm Hg without PDs compared with 16 mm Hg at 2.0 Hz and 14 mm Hg at 2.5 Hz (differences were significant for 0 vs 2.5 Hz based on bootstrapping). Change-point analysis confirmed a temporal association of high-frequency PD onset (≥2.0 Hz) and Pbto2 reduction (median normalized Pbto2 decreased by 25% 5-10 minutes after onset). Increased regional CBF of 21.0 mL/100 g/min for 0 Hz, 25.9 mL/100 g/min for 1.0 Hz, 27.5 mL/100 g/min for 1.5 Hz, and 34.7 mL/100 g/min for 2.0 Hz and increased global cerebral perfusion pressure of 91 mm Hg for 0 Hz, 100.5 mm Hg for 0.5 Hz, 95.5 mm Hg for 1.0 Hz, 97.0 mm Hg for 2.0 Hz, 98.0 mm Hg for 2.5 Hz, 95.0 mm Hg for 2.5 Hz, and 67.8 mm Hg for 3.0 Hz were seen for higher PD frequencies. Conclusions and Relevance: These data give some support to consider redefining the continuum between seizures and PDs, suggesting that additional damage after acute brain injury may be reflected by frequency changes in electrocerebral recordings. Similar to seizures, cerebral blood flow increases in patients with PDs to compensate for the increased metabolic demand but higher-frequency PDs (>2 per second) may be inadequately compensated without an additional rise in CBF and associated with brain tissue hypoxia, or higher-frequency PDs may reflect inadequacies in brain compensatory mechanisms.

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

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

Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage.

OBJECTIVE The clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome. METHODS The authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up. RESULTS The cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4-3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0-3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4-1.6, p = 0.5). CONCLUSIONS UEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.

Heart Rate Variability for the Early Detection of Delayed Cerebral Ischemia.

Delayed cerebral ischemia is considered the leading cause of death or major disability in subarachnoid hemorrhage after the impact of the initial event and rebleeding. Waiting to treat patients until they exhibit clinical symptoms of ischemia is too late to prevent cerebral infarction for more than 60% of patients, and transcranial Doppler ultrasonography has not proven to be a reliable screening tool to identify high-risk patients. Continuous heart rate variability monitoring may provide an alternative screening strategy to identify patients at high risk for delayed cerebral ischemia. Heart rate variability is a composite reflection of autonomic outflow, neuroendocrine influences, and autonomic responsiveness. Most importantly, heart rate variability is responsive to changes in systemic inflammation, which evidence suggests is important to the causal pathway of delayed cerebral ischemia. The clinical application of continuous heart rate variability monitoring in critical care is relatively recent despite its existence for more than 50 years. Initial studies suggest promise for heart rate variability monitoring as a delayed cerebral ischemia screening tool, but significant research is still required before this approach may achieve clinical applicability and bring benefit to patients.

Prognostication of long-term outcomes after subarachnoid hemorrhage: The FRESH score.

OBJECTIVE: To create a multidimensional tool to prognosticate long-term functional, cognitive, and quality of life outcomes after spontaneous subarachnoid hemorrhage (SAH) using data up to 48 hours after admission. METHODS: Data were prospectively collected for 1,619 consecutive patients enrolled in the SAH outcome project July 1996 to March 2014. Linear models (LMs) were applied to identify factors associated with outcome in 1,526 patients with complete data. Twelve-month functional, cognitive, and quality of life outcomes were measured using the modified Rankin scale (mRS), Telephone Interview for Cognitive Status, and Sickness Impact Profile. Based on the LM residuals, we constructed the FRESH score (Functional Recovery Expected after Subarachnoid Hemorrhage). Score performance, discrimination, and internal validity were tested using the area under the receiver operating characteristic curve (AUC), Nagelkerke and Cox/Snell R(2) , and bootstrapping. For external validation, we used a control population of SAH patients from the CONSCIOUS-1 study (n = 413). RESULTS: The FRESH score was composed of Hunt & Hess and APACHE-II physiologic scores on admission, age, and aneurysmal rebleed within 48 hours. Separate scores to prognosticate 1-year cognition (FRESH-cog) and quality of life (FRESH-quol) were developed controlling for education and premorbid disability. Poor functional outcome (mRS = 4-6) for score levels 1 through 9 respectively was present in 3, 6, 12, 38, 61, 83, 92, 98, and 100% at 1-year follow-up. Performance of FRESH (AUC = 0.90), FRESH-cog (AUC = 0.80), and FRESH-quol (AUC = 0.78) was high. External validation of our cohort using mRS as endpoint showed satisfactory results (AUC = 0.77). To allow for convenient score calculation, we built a smartphone app available for free download. INTERPRETATION: FRESH is the first clinical tool to prognosticate long-term outcome after spontaneous SAH in a multidimensional manner. Ann Neurol 2016;80:46-58.