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ABSTRACT BACKGROUND Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series. OBJECTIVE To analyze the benefit/risk profile of antiplatelet use in SAH patients. METHODS This retrospective case–control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale < 3) were compared in both groups. RESULTS Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P < .001, adjusted odds ratio = 0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P = .02, adjusted odds ratio = 1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P = .02 vs P = .51 for major bleeding events). CONCLUSION Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.

•Decompressive craniectomy (DC) is a standard neurosurgical procedure against intractable intracranial hypertension.•The clinical utility of DC after subarachnoid hemorrhage (SAH) remains unclear.•We systematically searched 4 databases for articles on DC in aSAH.•The mean DC rate was 10.9 % (range 3.3%–25.6%).•Good initial clinical condition and younger patients’ age increased the chance of good outcome after DC.•Younger age, presence of ICH, poor initial clinical condition and treatment modality were associated with the indication to DC. Decompressive craniectomy (DC) is a standard neurosurgical procedure against intractable intracranial hypertension. Patients with severe aneurysmal subarachnoid hemorrhage (aSAH) are prone to intracranial hypertension, necessitating DC in certain cases. However, the clinical utility of DC after aSAH remains unclear. Hereby we present a systematic review and meta-analysis summarizing the published studies on DC in aSAH patients. We systematically searched PubMed, Scopus, Web of Science and Cochrane Library for articles published before Jul 10, 2019 reporting on rates, outcome, indications, timing and complications of SAH patients undergoing DC. Of 1085 identified unique records, 28 observational studies published between 1993 and 2018 were included. In total, data of 2788 aSAH patients was extracted including 2014 patients with DC. The mean DC rate was 10.9 % (range 3.3%–25.6%). Good initial clinical condition (p = 0.01; odds ratio (OR) = 2.93; confidence interval (95 % CI) 1.30–6.61) and younger patients’ age (p = 0.02; mean difference (MD) = −4.50; 95 % CI -8.36 – −0.64) increased the chance of good outcome after DC. Overall, patients with primary DC showed a tendency towards better outcome than those that underwent secondary DC (p = 0.08; OR = 1.50; 95 % CI 0.96–2.35). Younger age (p < 0.00001; MD = −3.63; 95 % CI −5.20 to −2.06), presence of intracerebral hemorrhage (ICH; p < 0.00001; OR = 6.63; 95 % CI 3.98–11.03), poor initial clinical condition (p < 0.00001; OR = 4.81; 95 % CI 2.88–8.03) and treatment modality (coiling, p < 0.00001; OR = 0.19; 95 % CI 0.10−0.35) were associated with the indication to DC. Around 10 % of aSAH individuals undergo DC. Younger individuals, with poor initial clinical condition, additional ICH and aneurysm clipping are more likely to be selected for DC. Due to expected outcome benefit, younger individuals with good-grade aSAH should be considered for early decompression in case of increased intracranial pressure.

Despite recent advances in neuro-intensive care, there is still considerable mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). In this long-term monocentric observational cohort study, we aimed to analyze the rates, timing, and predictors of mortality after SAH. All consecutive SAH cases treated between January 2003 and June 2016 were included. Patients’ demographic characteristics, previous medical history, SAH-related parameters, and available post-treatment follow-up data were collected and evaluated as potential mortality predictors in univariate and multivariate analyses. Of 992 patients, 179 died during the initial treatment and 33 during the follow-up time reaching an overall mortality rate of 21.4 %. Of over 119 tested variables, we identified the following independent predictors in the final multivariate Cox regression analysis: age >55 years (p<0.0001); World Federation of Neurosurgical Societies (WFNS) admission grade IV or V (p=0.025); Hijdra sum score ≥15 points (p=0.003); intracranial pressure (ICP) increase (p<0.0001); and delayed cerebral ischemia (DCI) (p<0.0001). Being exposed to all five risk factors resulted in the case fatality rate of 75 % within a median survival of 14 days, compared to 2.5 % within a median of 1525 days when none of these features were present. The initial impact of aneurysmal bleeding is amongst the major mortality causes after SAH. Of potentially preventable adverse events, ICP increase and DCI occurring during initial treatment also present eminent clinical relevance for patients’ survival in the long-term follow-up. Further ICP and DCI management optimization might help to decrease the mortality rate after SAH. •Age, WFNS, Hijdra sum, ICP elevation and DCI predict long-term mortality after aSAH.•Being exposed to all predictors is associated with 75 %, to none with 2.5 % mortality.•Higher count of predictor exposure leads to higher mortality and shorter survival.

Anemia is a common, treatable condition in patients with aneurysmal subarachnoid hemorrhage (SAH) and has been associated with poor outcome. As there are still no guidelines for anemia management after aneurysm rupture, we aimed to identify outcome-relevant severity of anemia in SAH. We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library for publications before Oct 23rd, 2022, reporting on anemia in SAH patients. The presence and severity of anemia were assessed according to the reported hemoglobin values and/or institutional thresholds for red blood cells transfusion (RBCT). Out of 1863 original records, 40 full-text articles with a total of 14,701 patients treated between 1996 and 2020 were included in the final analysis (mean 445.48 patients per study). A substantial portion of patients developed anemia during SAH (mean pooled prevalence 40.76%, range 28.3–82.6%). RBCT was administered in a third of the cases (mean 32.07%, range 7.8–88.6%), with institutional threshold varying from 7.00 to 10.00 g/dL (mean 8.5 g/dL). Anemia at the onset of SAH showed no impact on SAH outcome. In contrast, even slight anemia (nadir hemoglobin < 11.0–11.5 g/dL) occurring during SAH was associated with the risk of cerebral infarction and poor outcome at discharge and follow-up. The strongest association with SAH outcome was observed for nadir hemoglobin values ranging between 9.0 and 10.0 g/dL. The effect of anemia on SAH mortality was marginal. The development of anemia during SAH is associated with the risk of cerebral infarction and poor outcome at discharge and follow-up. Outcome-relevant severity of post-SAH anemia begins at hemoglobin levels clearly above the thresholds commonly set for RBCT. Our findings underline the need for further studies to define the optimal management of anemia in SAH patients.

Knowledge of the bleeding risk and the long-term outcome of conservatively treated patients with cavernous malformations (CM) is poor. In this work, we studied the occurrence of CM-associated hemorrhage over a 10-year period and investigated risk factors for bleeding. Our institutional database was screened for patients with cerebral (CCM) or intramedullary spinal cord (ISCM) CM admitted between 2003 and 2021. Patients who underwent surgery and patients without completed follow-up were excluded. Analyses were performed to identify risk factors and to determine the cumulative risk for hemorrhage. A total of 91 CM patients were included. Adjusted multivariate logistic regression analysis identified bleeding at diagnosis ( p  = 0.039) and CM localization to the spine ( p  = 0.010) as predictors for (re)hemorrhage. Both risk factors remained independent predictors through Cox regression analysis ( p  = 0.049; p  = 0.016). The cumulative 10-year risk of bleeding was 30% for the whole cohort, 39% for patients with bleeding at diagnosis and 67% for ISCM. During an untreated 10-year follow-up, the probability of hemorrhage increased over time, especially in cases with bleeding at presentation and spinal cord localization. The intensity of such increase may decline throughout time but remains considerably high. These findings may indicate a rather aggressive course in patients with ISCM and may endorse early surgical treatment.

Quantitative data on the impact of smoking on genesis of intracranial aneurysms (IA) is sparse. We aimed to analyze the association between lifetime and current smoking exposure and IA characteristics. In this prospective observational cohort study (07/2016–01/2023, n = 918), all patients or next of kin filled out the questionnaire for assessment of smoking habits including the status (no/former/current) and consumption level (heavy vs light current smoker [≥/<10 cigarettes/day], and lifetime exposure in pack-years). The study endpoints were the ruptured status, size, and presence of multiple IA. The distribution of non-, former, light, and heavy smokers was 23.2 %, 25.6 %, 11.2 % and 40 % respectively. The median lifetime smoking exposure was 20 pack-years. Current smokers were at higher risk of presenting with ruptured (adjusted odds ratio [aOR]=1.71, 95 % confidence interval [CI]=1.29–2.26, p < 0.0001), large (≥7 mm, aOR=1.41, 95 % CI=1.05–1.89, p = 0.022) and multiple IA (aOR=1.34, 95 % CI=1.01–1.77, p = 0.045). In the subgroup analysis among ever smokers, heavy smoking additionally increased the risk of IA rupture (aOR=1.83, 95 % CI=1.33–2.50, p < 0.0001) and larger size (aOR=1.65, 95 % CI=1.19–2.30, p = 0.003). Finally, longer history of smoking (>20 pack-years) was related to higher probability of multiple (aOR=1.61, 95 % CI=1.21–2.13, p = 0.001) and large IA (aOR=1.40, 95 % CI=1.04–1.87, p = 0.025). Our data underline the role of smoking in IA genesis, and the importance of smoking cessation for rupture prevention. Current and particularly heavy smoking increases the risk of IA rupture, whereas the chronic exposure over years more likely results in the development of multiple and large IA. •Our manuscript analyses the impact of smoking exposure on the rupture status, size, and number of intracranial aneurysms.•Current smokers were at higher risk of presenting with ruptured, large and multiple IA.•In the subgroup analysis among ever smokers, heavy smoking additionally increased the risk of IA rupture and larger size.•Longer history of smoking (>20 pack-years) was related to higher probability of multiple and large IA.•Our data underline the role of smoking in IA genesis, and the importance of smoking cessation for rupture prevention.

The purpose of this study was to analyze brain natriuretic peptide (BNP) serum levels of patients with chronic subdural hematoma (cSDH) and their clinical implication. Patients with cSDH who underwent surgery in our department between November 2016 and October 2019 were eligible for enrollment in the study. Patients with recurrent bleedings, traumatic brain injury, cSDH associated with other intracranial pathologies, and those with a history of congestive heart failure, renal or endocrine disease were excluded. We measured BNP serum levels pre- and post-operatively and at discharge. The BNP values were analyzed with respect to patient medical history and neurological condition. The Glasgow Coma Scale score and the modified Rankin Scale score classified the clinical and neurological condition at the time of admission and discharge, respectively. The data of 100 surgically treated patients with cSDH (mean age 73.2, range 42 − 94 years, male/female 3.5:1) were analyzed. Pre-operative BNP serum levels (BNP-1) were elevated in 67% of the patients (n = 67; median = 101.6 pg/mL; p < 0.001). These serum levels increased after surgery (p < 0.001) and decreased thereafter (p < 0.001), reaching a level at discharge (day 7) that was not statistically different from BNP-1 (p > 0.05). In addition, elevated BNP-1 showed a significant statistical association with the presence of atrial fibrillation (p < 0.01) and antiplatelet and/or anticoagulant therapy (p < 0.01). This study provides new evidence regarding BNP serum levels and their secretion pattern in patients with cSDH. Whether BNP-1 can predict the long-term functional outcome of patients with cSDH is being investigated in this ongoing prospective study.

The purpose of this study was to investigate the functional outcome following surgical resection of cerebral cavernous malformations (CCM) in pediatric patients. We screened our institutional database of CCM patients treated between 2003 and 2021. Inclusion regarded individuals younger or equal than 18 years of age with complete clinical baseline characteristics, magnetic resonance imaging dataset, and postoperative follow-up time of at least three months. Functional outcome was quantified using the modified Rankin Scale (mRS) score and assessed at admission, discharge, and last follow-up examination. The primary endpoint was the postoperative functional outcome. As a secondary endpoint, predictors of postoperative functional deterioration were assessed. A total of 49 pediatric patients with a mean age of 11.3 ± 5.7 years were included for subsequent analyses. Twenty individuals (40.8%) were female. Complete resection of the lesion was achieved in 44 patients (89.8%), and two patients with incomplete resection were referred for successive remnant removal. The mean follow-up time after surgery was 44 months (IQR: 13 – 131). The mean mRS score was 1.6 on admission, 1.7 at discharge, and 0.9 at the latest follow-up. Logistic regression analysis adjusted to age and sex identified brainstem localization (aOR = 53.45 [95%CI = 2.26 − 1261.81], p  = .014) as a predictor of postoperative deterioration. This study indicates that CCM removal in children can be regarded as safe and favorable for the majority of patients, depending on lesion localization. Brainstem localization implies a high risk of postoperative morbidity and indication for surgery should be balanced carefully. Minor evidence indicates that second-look surgery for CCM remnants might be safe and favorable.

BackgroundOutcome of aneurysmal subarachnoid hemorrhage (SAH) depends strongly on occurrence of symptomatic vasospasm (SV) leading to delayed cerebral ischemia (DCI). Various demographic, radiographic, and clinical predictors of SV have been reported so far, partially with conflicting results. The aim of this study was to analyze the role of patients’ age and sex on SV/DCI risk, especially to identify age and sex-specific risk groups.MethodsAll patients admitted with acute SAH during a 14-year-period ending in 2016 were eligible for this study. The study endpoints were the following: SV requiring spasmolysis, occurrence of DCI in follow-up computed tomography scans and unfavorable outcome at 6 months (modified Rankin scale > 2).ResultsNine hundred ninety-four patients were included in this study. The majority was female (666; 67%). SV, DCI, and unfavorable outcomes were observed in 21.5, 21.8, and 43.6% of the patients, respectively. Younger age (p < 0.001; OR = 1.03 per year decrease) and female sex (p = 0.025; OR = 1.510) were confirmed as independent predictors of SV. Regarding the sex differences, there were three age groups for SV/DCI risk ≤ 54, 55–74, and ≥ 75 years. Male patients showed earlier decrease in SV risk (at ≥ 55 vs. ≥ 75 years in females). Therefore, SAH females aged between 55 and 74 years were at the highest risk for DCI and unfavorable outcome, as compared to younger/older females (p = 0.001, OR = 1.77/p = 0.001, OR = 1.80). In contrast, their male counterparts did not show these risk alterations (p = 0.445/p = 0.822).ConclusionAfter acute SAH, female and male patients seem to show different age patterns for the risk of SV and DCI. Females aged between 55 and 74 years are at particular risk of vasospasm-related SAH complications, possibly due to onset of menopause.Clinical trial registration numberDRKS, Unique identifier: DRKS00008749

Blood pressure management is crucial in the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). Possible association between the blood pressure increase and the risk of delayed cerebral ischemia (DCI) and different systemic complications after aSAH is still a matter of debate. This study aims to elucidate the influence of blood pressure levels on the outcome of aSAH. All consecutive aSAH patients (n = 690) treated between 01/2003 and 06/2016 were included. The mean value of the mean arterial pressure (MAP) during 14 days after ictus was calculated for each individual. According to the institutional standards of vasospasm management, the mean 14 days MAP ≥ 95 mmHg was referred as increased (IMAP) and the patients with and without vasospasm were analyzed separately. Study endpoints were the occurrence of DCI on computed tomography scans, development of cardiac and nephrological complications, and poor outcome 6 months after aSAH (mRS > 2). Associations were tested in univariable/multivariable binary logistic regression analysis. IMAP was documented in 474 (68.7%) cases and was more common in individuals with poor neurological conditions at admission (p < 0.001), severe amount of intracranial blood (p = 0.001) and premorbid hypertension (p < 0.001). IMAP was independently associated with the occurrence of DCI (p = 0.014; aOR = 2.97; 95% CI 1.25–7.09) and poor functional outcome (p = 0.020; aOR = 3.14; 95% CI 1.20–8.22) in patients with vasospasm, but not in counterparts without vasospasm (p = 0.113/p = 0.086). IMAP had no influence on cardiac or nephrological complications. In aSAH individuals with cerebral vasospasm, sustained increase of blood pressure exceeding the therapeutic targets is strongly associated with the risk of DCI and poor outcome. Therefore, such an intrinsic increase of blood pressure might reflect the autoregulatory mechanisms against the impending cerebral ischemia in patients with cerebral vasospasm. Trial registration number: German clinical trial registry (DRKS, Unique identifier: DRKS00008749, 06/09/2015).