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Background and Aim: To assess associations between clinical severity and possible dysfunction of autonomic cardiovascular modulation within the acute phase after spontaneous subarachnoid hemorrhage (SAH)., Methods: In this prospective observational study, in 51 patients with spontaneous SAH, Hunt-and-Hess scores (H&H) were assessed and cardiovascular autonomic modulation was monitored within 24 h after SAH-onset. From 5 min time-series of R-R-intervals (RRI) and blood-pressure (BP) recordings, we calculated autonomic parameters including time-domain [RRI-coefficient-of-variation (RRI-CV) and square-root-of-the-mean-squared-differences-of-successive-RRIs (RMSSD)] and frequency-domain parameters [low- and high-frequency-powers of RRI- and BP-modulation (RRI-LF-, RRI-HF-, SBP-LF-powers) and RRI-total-powers]. Data were compared to those of 20 healthy volunteers., Results: RRI- and BP-values did not differ between groups. Yet, parameters of sympathetic (RRI-LF-powers 141.0 (18.9-402.4) ms 2 vs 442.3 (246.8-921.2) ms 2 , p = 0.001) and total autonomic modulation (RRI-CV 2.4 (1.2-3.7) ms 2 vs 3.7 (3.1-5.3) ms 2 , p = 0.001) were significantly lower in patients than in controls. Subgroup analyses (patients with H&H < 3 vs H&H ≥ 3) and Spearman-rank-correlations revealed increasing loss of sympathetic (RRI-LF-powers 338.6 (179.7-710.4) ms 2 vs 72.1 (10.1-175.9) ms 2 , p = 0.001, rho = - 0.524) and total autonomic modulation (RRI-CV 3.5 (2.3-5.4) ms 2 vs 1.6 (1.0-2.8) ms 2 , p < 0.001, rho = - 0.519) with higher H&H-scores. Multiple-logistic-regression underlined the significant influence of H&H-scores on sympathetic (RRI-LF-powers, p = 0.033) and total autonomic modulation (RRI-CV, p = 0.040) compared to possible confounders (e.g., age, intubation)., Conclusion: Within the acute phase, spontaneous SAH induces a decrease in sympathetic and total autonomic cardiovascular modulation. Higher H&H-scores were associated with increasing autonomic dysfunction and may therefore augment the risk of cardiovascular complications and poor clinical outcome., (© 2022. The Author(s).)

Background and Objectives: In patients with lobar intracerebral hemorrhage (ICH), etiologic characterization represents a tradeoff between feasibility, resource allocation, and diagnostic certainty. This study investigated the accuracy and clinical utility of the simplified Edinburgh CT criteria to identify underlying cerebral amyloid angiopathy (CAA)., Methods: This external validation analyzed 210 consecutive patients with lobar ICH and available CT and MRI studies from a prospective single-center observational cohort study (2006-2015, Longitudinal Cohort Study on ICH Care [UKER-ICH,] NCT03183167). We investigated the interrater variability and diagnostic accuracy of the simplified Edinburgh CT-based criteria for identification of ICH associated with probable CAA according to MRI-based modified Boston criteria as a reference standard. We evaluated the utility of the simplified Edinburgh criteria by decision curve analysis, comparing the theoretical clinical net benefit (weighted benefit-harm at varying threshold probabilities) of the high-risk category (finger-like projections and subarachnoid hemorrhage) for ruling in and the low-risk category (neither finger-like projections nor subarachnoid hemorrhage) for ruling out with the assumptions of no or all patients having CAA (default strategies)., Results: Of 210 patients, 70 (33.3%) had high risk, 67 (31.9%) had medium risk, and 73 (34.8%) had low risk for CAA-associated ICH according to simplified Edinburgh CT criteria, showing moderate interrater variability. Discrimination was good (area under the receiver operating characteristics curve 0.74, 95% CI 0.67-0.81) without evidence of poor calibration (Hosmer-Lemeshow, p = 0.54) for validation of MRI-based diagnosis of probable CAA (n = 94 of 210, 44.8%). The rule-in criteria (high risk), had 87.1% (79.3%-92.3%) specificity, and the rule-out criteria (low risk), had 80.9% (71.1%-88.0%) sensitivity. Decision curve analysis suggested a theoretical clinical net benefit for ruling in but not for ruling out probable CAA compared to default strategies., Discussion: Applying the simplified Edinburgh CT criteria during diagnostic workup seems clinically useful and may accurately identify CAA in patients with lobar ICH., Trial Registration Information: ClinicalTrials.gov Identifier: NCT03183167., Classification of Evidence: This study provides Class II evidence that in patients with lobar hemorrhages, the simplified Edinburgh criteria accurately identify those at high risk of CAA., (© 2022 American Academy of Neurology.)

Background: Data regarding the influence of concomitant parenchymatous hematoma (PH) on long-term outcomes in patients with atraumatic subarachnoid hemorrhage (SAH) are scarce. Further, it is not established if these patients benefit from surgical intervention., Aim: The aim of this study was to determine the influence of concomitant PH in SAH patients on functional long-term outcome, and whether these patients may benefit from surgical hematoma evacuation., Methods: Over a 5-year period, all consecutive patients with SAH treated at the Departments of Neurology, Neuroradiology, and Neurosurgery, at the University Hospital Erlangen (Germany) were recorded. In addition to the clinical and imaging characteristics of SAH, we documented the presence, location, and volume of PH as well as treatment parameters. Outcome assessment at 12 months included functional outcome (modified Rankin scale (mRS), favorable = 0-2), health-related quality of life, and long-term complications. For outcome analysis, a propensity score matching (ratio 1:1, caliper 0.1) was performed to compare SAH patients with and without PH. Sub-analyses were performed regarding PH treatment (surgical evacuation vs. conservative)., Results: A total of 494 patients with atraumatic SAH were available. Eighty-five (17.2%) had PH on initial imaging. SAH patients with PH had a worse clinical condition on admission and had a greater extent of subarachnoid/intraventricular hemorrhage. Median PH volume was 11.0 ml (5.4-31.8) with largest volumes observed in patients with ruptured middle cerebral artery (MCA)-aneurysm (31.7 ml (16.3-43.2)). After propensity-score matching (PSM), patients with PH had worse functional outcomes at 12 months (modified Rankin scale (mRS) 0-2: PH 31.8% vs. ØPH57.7% p < 0.001), and a lower rate of self-reported health compared to patients without PH (EQ-5D VAS: PH 50(30-70) vs. ØPH 80(65-95); p < 0.001). In PH patients, surgical evacuation was associated with a higher rate of favorable outcome at 12 months compared to those treated conservatively (surgery 14/28 (50.0%) vs. conservative 14/57 (24.6%); adjusted odds-ratio (OR; 95%CI): 1.34 (1.08-1.66); p = 0.001), irrespective of aneurysm location. Subgroup-analysis revealed positive associations of surgical hematoma evacuation with outcome in subgroups with larger PH volumes (>10 ml; OR (95%CI): 1.39 (1.09-1.79)), frontal PH location (OR 1.59 (1.14-2.23)), and early surgery (within 600 min after onset; OR 1.42 (1.03-1.94))., Conclusions: Concomitant PH occurs frequently in patients with SAH and is associated with functional impairment after 1 year. Surgical evacuation of PH may improve outcomes in these patients, irrespective of aneurysm-location.

Objective: In subarachnoid hemorrhage (SAH), transcranial Doppler/color-coded-duplex sonography (TCD/TCCS) is used to detect delayed cerebral ischemia (DCI). In previous studies, quantitative electroencephalography (qEEG) also predicted imminent DCI. This study aimed to compare and analyse the ability of qEEG and TCD/TCCS to early identify patients who will develop later manifest cerebral infarction., Methods: We analysed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artefact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as significant EEG event. Median reduction and duration of alpha power decrease in each channel was determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory., Results: 34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I-V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters., Conclusions: There was a moderate correlation of TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction., Significance: qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction., Competing Interests: Declaration of Competing Interest Tamara M. Müller, Rüdiger Hopfengärtner, Stephan Rampp, Johannes Lang, Jenny Stritzelberger, Caroline Reindl, Maximilian I. Sprügel, Müjgan Dogan Onugoren, Iris Muehlen, Joji B. Kuramatsu, Stefan Schwab: report no disclosures. Stephanie Gollwitzer reports personal fees from Desitin, Eisai, UCB, outside the submitted work. Dominik Madžar reports grants from UCB Pharma and BayerVitalGmbH, outside submitted work. Hagen B. Huttner reports grants from Novartis, grants and personal fees from Bayer AG, grants and personal fees from Daiichi Sankyo, grants and personal fees from Medtronic, grants and personal fees from Portola Pharmaceuticals, outside the submitted work. Hajo M. Hamer: reports personal fees from UCB, Desitin, Eisai, GW, Novartis, IQWiG, Hexal, facetoface, grants from Amgen, Ad-Tech, Bracco, Pfizer, Micromed, Nihon Kohden, personal fees from Arvelle, outside the submitted work., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: For outcome assessment in patients surviving subarachnoid hemorrhage (SAH), the modified Rankin scale (mRS) represents the mostly established outcome tool, whereas other dimensions of outcome such as mood disorders and impairments in social life remain unattended so far., Objective: The aim of our study was to correlate 12-month functional and subjective health outcomes in SAH survivors., Methods: All SAH patients treated over a 5-year period received outcome assessment at 12 months, including functional scores (mRS and Barthel Index [BI]), subjective health measurement (EQ-5D), and whether they returned to work. Analyses - including utility-weighted mRS - were conducted to detect associations and correlations among different outcome measures, especially in patients achieving good functional outcome (i.e., mRS 0-2) at 12 months., Results: Of 351 SAH survivors, 287 (81.2%) achieved favorable functional outcome at 12 months. Contrary to the BI, the EQ-5D visual analog scale (VAS) showed a strong association with different mRS grades, accentuated in patients with favorable functional outcome. Despite favorable functional outcome, patients reported a high rate of impairments in activities (24.0%), pain (33.4%), and anxiety/depression (42.5%). Further, multivariable analysis revealed (i) impairments in activities (odds ratio [OR] [95% confidence interval {CI}]: 0.872 [0.817-0.930]), (ii) presence of depression or anxiety (OR [95% CI]: 0.836 [0.760-0.920]), and (iii) return to work (OR [95% CI]: 1.102 [0.1.013-1.198]) to be independently associated with self-reported subjective health., Conclusion: Established stroke scores mainly focusing on functional outcomes do poorly reflect the high rate of subjective impairments reported in SAH survivors, specifically in those achieving good functional outcome. Further studies are needed to investigate whether psychoeducational approaches aiming at improving coping mechanisms and perceived self-efficacy may result in higher subjective health in these patients., (© 2021 S. Karger AG, Basel.)

Objective: Stroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH)., Methods: This observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008-2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Patients' radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures., Results: Overall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median [IQR] NLR 5.8 [3.0-10.0] for mRS score 0-2 vs NLR 8.3 [4.5-12.6] for mRS score 3-6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR [95% CI] 1.014 [1.001-1.027]; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden's index = 0.211; mRS score 3-6: 94/153 [61.4%] for NLR ≥ 7.05 vs 67/166 [40.4%] for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score-matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3-6 at 3 months: NLR ≥ 7.05 82/133 [61.7%] vs NLR < 7.05 62/133 [46.6%]; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 [27.8%] vs NLR < 7.05 27/133 [20.3%]; p = 0.131)., Conclusions: Among aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.

Background: Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated., Methods: This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome., Results: Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06)., Conclusion: Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact., (© 2015 S. Karger AG, Basel.)

Background: Intraventricular fibrinolysis (IVF) in subarachnoid hemorrhage (SAH) is an emerging strategy aiming to hasten clot lysis, treat hydrocephalus, and reduce permanent shunt rates. Because of clinical heterogeneity of investigated patient effects of IVF on permanent shunt incidence and functional outcome are widely debated. The present study is the first to investigate solely endovascular-treated SAH patients., Methods: Overall, 88 consecutive patients with aneurysmal SAH requiring external ventricular drain placement and endovascular aneurysm closure were included. Functional outcome and shunt dependency were assessed 90 days after event. A matched controlled sub-analysis was carried out to investigate the effects of IVF treatment (n = 14; matching criteria: age, neuro-status and imaging). Multivariate modeling was performed to identify independent predictors for permanent shunt dependency., Results: In IVF-patients neurological status was significantly poorer [Hunt&Hess: IVF = 4(3-5) vs. non-IVF = 3(1-5); p = 0.035] and the extent of ventricular hemorrhage was increased [Graeb Score: IVF = 7(6-8) vs. non-IVF = 3(1-4); p ≤ 0.001]. Consecutive matched controlled sub-analysis revealed no significant therapeutic effect of IVF with respect to shunt dependency rate and functional outcome. Multivariate analysis revealed Graeb score [OR = 1.34(1.02-1.76); p = 0.035] and sepsis [OR = 11.23(2.28-55.27); p = 0.003] as independent predictors for shunt dependency, whereas IVF did not exert significant effects (p = 0.820)., Conclusions: In endovascular-treated SAH patients IVF neither reduced permanent shunt dependency nor influenced functional outcome. Despite established effects on intraventricular clot resolution IVF appears less powerful in SAH as compared to ICH. Given the reported positive effects of lumbar drainage (LD) in SAH, a prospective analysis of a combined treatment approach of IVF and subsequent lumbar drain sOeems warranted aiming to reduce permanent shunting and improve functional outcome.