Letter to editor: Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: A retrospective evaluation of a 12-year single-center experience.

This critique examines a 12-year retrospective study on serum magnesium concentration-guided administration of magnesium sulfate in 548 patients with aneurysmal subarachnoid hemorrhage (aSAH). The study reported that maintaining serum magnesium levels between 2 and 2.5 mmol/L reduced rates of delayed cerebral infarction and improved clinical outcomes. However, limitations due to its retrospective nature, single-center design, and unequal treatment group sizes may affect generalizability. Future multicentric randomized controlled trials are recommended to validate these findings and refine magnesium dosing strategies for aSAH treatment.

Cilostazol May Improve Outcomes Even in Patients with Aneurysmal Subarachnoid Hemorrhage Aged 75 Years and Older: Multicenter Cohort Study and Propensity Score-Matched Analyses.

BACKGROUND: The opportunities to treat elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) are increasing globally, but the outcome remains poor. This study seeks to investigate treatment-related factors that can modify functional outcomes in patients with aSAH aged ≥75 years. METHODS: A total of 202 patients with aSAH aged ≥75 years prospectively enrolled in 9 primary stroke centers from 2013 to 2021 were retrospectively analyzed. Clinical variables including treatments for hydrocephalus, angiographic vasospasm, and delayed cerebral ischemia were compared between patients with good (modified Rankin Scale [mRS] score 0-2) and poor (mRS score 3-6) outcomes at 90 days from onset, followed by multivariate analyses to find independent outcome determinants. A modifiable treatment-related variable was evaluated after propensity score matching with adjustments for age, sex, pre-onset mRS score, aSAH severity, and treatment modality. RESULTS: More than half of patients showed World Federation of Neurological Societies grades IV-V on admission. Univariate analyses showed that advanced age, worse pre-onset mRS score, more severe neurologic status on admission, higher modified Fisher grade on admission computed tomography scans, and acute and chronic hydrocephalus were associated with poor outcomes. In contrast, administration of a phosphodiesterase type III inhibitor, cilostazol, was associated with good outcomes in both univariate (P = 0.036) and multivariate analyses (adjusted odds ratio, 0.305; 95% confidence interval, 0.097-0.955; P = 0.042). Propensity score matching analyses showed that patients treated with cilostazol had better outcomes (P = 0.016) with fewer incidences of delayed cerebral infarction (P = 0.008). CONCLUSIONS: Even in patients with aSAH aged ≥75 years, cilostazol administration may lead to better outcomes by suppressing the development of delayed cerebral infarction.

Impact of ventriculo-cisternal irrigation on prevention of delayed cerebral infarction in aneurysmal subarachnoid hemorrhage: a single-center retrospective study and literature review.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and delayed cerebral infarction (DCI) by washing out subarachnoid clots earlier after aneurysm surgery. METHODS: We retrospectively identified 340 subarachnoid hemorrhage (SAH) patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. As VCI therapy, a ventricular drain/cisternal drain was placed during aneurysm surgery, and lactated Ringer's solution was used for irrigation until day 4 of SAH, followed by intracranial pressure control at 5-10 cmH2O until day 14. RESULTS: The median age was 65 years (interquartile range 52-75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: grade I or II, 175 patients (51%); grade III or IV, 84 (25%); and grade V, 81 (24%). With VCI management in all patients, total vasospasm occurred in 162 patients (48%), although the DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventive factor against DCI occurrence (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.07-0.67; P = 0.008), while additional surgery (4.76, 1.62-13.98; P = 0.005) and dyslipidemia (3.27, 1.24-8.63; P = 0.017) were associated with DCI occurrence. CONCLUSION: Managing vasospasms with VCI after SAH is considered a safe and effective method to prevent DCI. Early surgery after SAH may be associated with a decreased risk of DCI with VCI therapy.

Antiplatelet therapy and outcomes after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: The efficacy of antiplatelet therapy (APT) after aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We performed a systematic review and meta-analysis to summarize the associations of APT use after aSAH with outcomes. METHODS: We searched published medical literature to identify cohort studies involving adults with aSAH. The exposure was APT use after aSAH. Outcome measures were good functional outcome (modified Rankin Score 0-2 or Glasgow Outcome Scale 4-5), delayed cerebral ischemia (infarcts on neuroimaging), and intracranial hemorrhage. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between APT and SAH outcomes. RESULTS: A total of 14 studies with 4228 aSAH patients were included. APT after aSAH was associated with good functional outcome (pooled relative risk, 1.08; 95% confidence interval, [CI], 1.02-1.15; I2 = 45%, p for heterogeneity = 0.04), but there was no relationship with delayed cerebral ischemia (pooled relative risk, 0.80; 95% confidence interval, [CI], 0.63-1.02; I2 = 61%, p for heterogeneity <0.01) or intracranial hemorrhage (pooled relative risk, 1.50; 95% confidence interval, [CI], 0.98-2.31; I2 = 0, p for heterogeneity =0.71). In additional analyses, APT resulted in good functional outcomes in endovascularly-treated patients. When stratified by type of medication, aspirin, clopidogrel, and ticlopidine were associated with good functional outcomes. CONCLUSIONS: APT after aSAH was associated with a modest improvement in functional outcome, but there was no relationship with delayed cerebral ischemia or intracranial hemorrhage.

Japanese nationwide questionnaire survey on delayed cerebral infarction due to vasospasm after subarachnoid hemorrhage.

Background and purpose: Various prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021. Methods: In 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan. Of them, 162 hospitals (29% response rate) responded to the questionnaire. Of these, 158 were included in this study, while four hospitals that responded insufficiently were excluded. The efficacy of treatments for reducing DCI were examined through a logistic regression analysis. Results: Among 3,093 patients treated with aneurysmal SAH, 281 patients (9.1%) were diagnosed with DCI related to cerebral vasospasm. Coil embolization had significantly lower DCI frequency (6.9%), compared to microsurgical clipping (11.8%, odds ratio, 0.90; 95% confidential intervals, 0.84-0.96; P, 0.007). In addition, cilostazol administration was associated with significantly lower DCI frequency (0.48; 0.27-0.82; 0.026). The efficacy of cilostazol in reducing DCI remained unchanged after adjustment for covariates. The most effective combination of multiple prophylactic drugs in reducing DCI related to cerebral vasospasm was cilostazol, fasudil, and statin (0.38; 0.22-0.67; 0.005). Conclusions: This study elucidated the trends in prophylactic drugs to prevent cerebral vasospasm and frequency of DCI after aneurysmal SAH in Japan. Coil embolization and cilostazol administration showed effectiveness in reducing DCI related to cerebral vasospasm in 2021.

Early recanalization and vasospasm after endovascular treatment in a case of ruptured vertebral artery dissecting aneurysm associated with COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant structural changes in acute care hospitals. COVID-19-associated stroke has gained attention, with abnormal coagulation and vascular endothelial damage being recognized. While ischemic cases are commonly reported, hemorrhagic cases have also been reported. This report presents a case of ruptured vertebral artery dissection aneurysm associated with COVID-19, resulting in subarachnoid hemorrhage (SAH). The treatment course, challenges in managing cerebral vasospasm, and early recanalization achieved through endovascular therapy are described. Case Description: A 67-year-old male patient was brought to our hospital for emergency treatment of impaired consciousness that occurred while recovering from COVID-19. He underwent endovascular internal trapping using coils, and although the rupture did not recur, he required long-term tracheal management, which resulted in a cerebral infarction caused by cerebral vasospasm. In addition, early recanalization was seen, which required retreatment. Conclusion: This case highlights the challenges in managing COVID-19-associated SAH and emphasizes the need for infection control measures and proper postoperative care. Establishing protocols for detecting and managing cerebral vasospasm is essential.

Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: a retrospective evaluation of a 12-year single-center experience.

Delayed cerebral infarction (DCI) is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). The benefits of magnesium sulfate as an alternative treatment are controversial, and most previous studies examined its benefits only as adjunctive treatment to traditional nimodipine. We retrospectively analyzed aSAH patients records with magnesium sulfate between 2010 and 2021. We aimed for a serum magnesium concentration of 2-2.5 mmol/l between post-hemorrhage days 3 and 12. The patients were separated in three groups based on average serum magnesium concentration (magnesium >2 mmol/l, reduced magnesium 1.1-1.9 mmol/l, and no magnesium). Additionally, we assessed delayed cerebral infarction (DCI) and clinical outcome at follow-up, using the modified Rankin Scale (mRS), categorized in favorable (0-3) and unfavorable outcome (4-5). In this analysis, 548 patients were included. Hereof, radiological evidence of DCI could be found in 23.0% (n = 126) of patients. DCI rates were lower if patients' average serum magnesium was higher than 2 mmol/l (magnesium 18.8%, n = 85; reduced magnesium 38.3%, n = 23; no magnesium 51.4%, n = 18; p < 0.001). Also, at the last follow-up, patients in the group with a higher serum magnesium concentration had better outcome (favorable outcome: magnesium 64.7%, n = 293; reduced magnesium 50.0%, n = 30; no magnesium 34.3%, n = 12; p < 0.001). This 12-year study reveals the value of serum concentration-guided magnesium administration in aSAH patients. Our findings demonstrate the safety and efficacy when titrated to a serum concentration of 2-2.5 mmol/l. We observed higher rates of delayed cerebral infarction and unfavorable outcomes in patients with serum concentrations below 2 mmol/l.

Effect of Cilostazol on Delayed Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage Using Explainable Predictive Modeling.

The studies interpreting DCI, a complication of SAH, and identifying correlations are very limited. This study aimed to investigate the effect of cilostazol on ACV and DCI after coil embolization for ruptured aneurysms (n = 432). A multivariate analysis was performed and explainable artificial intelligence approaches were used to analyze the contribution of cilostazol as a risk factor on the development of ACV and DCI with respect to global and local interpretation. The cilonimo group was significantly lower than the nimo group in ACV (13.5% vs. 29.3; p = 0.003) and DCI (7.9% vs. 20.7%; p = 0.006), respectively. In a multivariate logistic regression, the odds ratio for DCI for the cilonimo group, female sex, and aneurysm size was 0.556 (95% confidence interval (CI), 0.351-0.879; p = 0.012), 3.713 (95% CI, 1.683-8.191; p = 0.001), and 1.106 (95% CI, 1.008-1.214; p = 0.034). The risk of a DCI occurrence was significantly increased with an aneurysm size greater than 10 mm (max 80%). The mean AUC of the XGBoost and logistic regression models was 0.94 ± 0.03 and 0.95 ± 0.04, respectively. Cilostazol treatment combined with nimodipine could decrease the prevalence of ACV (13.5%) and DCI (7.9%) in patients with aSAH.

Acute hydrocephalus and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral infarction (DCIn) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of morbi-mortality; yet, the causes for DCIn remain incompletely understood. OBJECTIVE: We tested the hypothesis that acute hydrocephalus could be related to the occurrence of DCIn, independently of the occurrence and severity of vasospasm. METHODS: Radiological and clinical data of patients treated at a single large volume academic center for aSAH between 2017 and 2019 were retrospectively analyzed. DCIn was defined as imaging stigma of cerebral infarction visible on 6-week imaging follow-up after aSAH. Hydrocephalus was defined on baseline imaging as a relative bicaudate index above 1. Cerebral vasospasm was defined by reduction of artery diameter in comparison with initial diameter. We used uni- and multivariable models to test the associations between these variables, hydrocephalus and DCIn. RESULTS: Of 164 included patients, vasospasm occurred in 58 patients (35.4%), and DCIn in 47 (28.7%). Acute hydrocephalus was present in 85 patients (51.8%) on baseline CT. No relation was found between acute hydrocephalus and delayed cerebral infarction in our multivariate analysis (adjusted OR: 1.20 95% CI [0.43-3.37]; p = 0.732). Only vasospasm occurrence was independently associated with DCIn (adjusted OR: 10.97 95% CI [4.60-26.01]). CONCLUSION: Our study did not show an association between acute hydrocephalus and DCIn after aSAH, after adjustment for the presence and severity of cerebral vasospasm.

Clinical Predictive Models for Delayed Cerebral Infarction After Ruptured Intracranial Aneurysm Clipping for Patients: A Retrospective Study.

Objective: A nomogram was developed in this work to predict the probability of delayed cerebral infarction (DCI) after ruptured intracranial aneurysms (RIA) clipping. Methods: Clinical data of patients with intracranial aneurysm were obtained from the neurosurgery department of the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2020. A total of 419 patients receiving surgery of ruptured intracranial aneurysm clipping were included and a total of 37 patients with DCI were set as the observation group. The control group consisted of 382 patients without DCI. Risk factors of DCI were screened by univariate and multivariate logistic regression analysis and included in the nomogram. Results: Univariate analysis showed that female (P = 0.009), small aneurysm (P = 0.031), intraoperative aneurysm rupture (P = 0.007) and cerebral vasospasm (P < 0.001) were risk factors for postoperative DCI while smoking history (P = 0.044) were protective factors for postoperative DCI. Multivariate Logistic regression analysis showed that small aneurysm (P = 0.002, OR = 3.332, 95%-7.104), intraoperative aneurysm rupture (P = 0.004, OR = 0.122, 95%-CI, 0.029-0.504)and cerebral vasospasm (P < 0.001, OR = 0.153, 95%-CI, 0.070-0.333) were independent risk factors of postoperative DCI. The calibration curve of the probability of occurrence showed that the nomogram was in good correspondence with the observed results with a C-index of 0.766 (95% CI, 0.684-0.848). Meanwhile, the Decision curve analysis (DCA) showed that the established predictive model had a good clinical net benefit. Conclusion: The well-established nomogram is expected to be an effective tool to predict the occurrence of DCI after intracranial ruptured aneurysm and can be used to assist clinicians to develop more effective treatment strategies and improve the prognosis of patients.

The Role of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in the Context of Aneurysmal Subarachnoid Hemorrhage (aSAH)-A Prospective Observational Study.

Objective: Outcome after aneurysmal subarachnoid hemorrhage (aSAH) is highly variable and largely determined by early brain injury and delayed cerebral ischemia (DCI). Soluble urokinase plasminogen activator receptor (suPAR) represents a promising inflammatory marker which has previously been associated with outcome in traumatic brain injury and stroke patients. However, its relevance in the context of inflammatory changes after aSAH is unclear. Here, we aimed to characterize the role of circulating suPAR in both serum and cerebrospinal fluid (CSF) as a novel biomarker for aSAH patients. Methods: A total of 36 aSAH patients, 10 control patients with unruptured abdominal aneurysm and 32 healthy volunteers were included for analysis. suPAR was analyzed on the day of admission in all patients. In aSAH patients, suPAR was also determined on the day of DCI and the respective time frame in asymptomatic patients. One- and two-sample t-tests were used for simple difference comparisons within and between groups. Regression analysis was used to assess the influence of suPAR levels on outcome in terms of modified Rankin score. Results: Significantly elevated suPAR serum levels (suPAR-SL) on admission were found for aSAH patients compared to healthy controls, but not compared to vascular control patients. Disease severity as documented according to Hunt and Hess grade and modified Fisher grade was associated with higher suPAR CSF levels (suPAR-CSFL). In aSAH patients, suPAR-SL increased daily by 4%, while suPAR-CSFL showed a significantly faster daily increase by an average of 22.5% per day. Each increase of the suPAR-SL by 1 ng/ml more than tripled the odds of developing DCI (OR = 3.06). While admission suPAR-CSFL was not predictive of DCI, we observed a significant correlation with modified Rankin's degree of disability at discharge. Conclusion: Elevated suPAR serum level on admission as a biomarker for early inflammation after aSAH is associated with an increased risk of DCI. Elevated suPAR-CSFL levels correlate with a higher degree of disability at discharge. These distinct relations and the observation of a continuous increase over time affirm the role of inflammation in aSAH and require further study.

Basic Surveillance Parameters Improve the Prediction of Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Background: To establish a practical risk chart for prediction of delayed cerebral infarction (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) by using information that is available until day 5 after ictus. Methods: We assessed all consecutive patients with aSAH admitted to our service between September 2008 and September 2015 (n = 417). The data set was randomly split into thirds. Two-thirds were used for model development and one-third was used for validation. Characteristics that were present between the bleeding event and day 5 (i.e., prior to >95% of DCI diagnoses) were assessed to predict DCI by using logistic regression models. A simple risk chart was established and validated. Results: The amount of cisternal and ventricular blood on admission CT (Hijdra sum score), early sonographic vasospasm (i.e., mean flow velocity of either intracranial artery >160 cm/s until day 5), and a simplified binary level of consciousness score until day 5 were the strongest predictors of DCI. A model combining these predictors delivered a high predictive accuracy [the area under the receiver operating characteristic (AUC) curve of 0.82, Nagelkerke's R 2 0.34 in the development cohort]. Validation of the model demonstrated a high discriminative capacity with the AUC of 0.82, Nagelkerke's R 2 0.30 in the validation cohort. Conclusion: Adding level of consciousness and sonographic vasospasm between admission and postbleed day 5 to the initial blood amount allows for simple and precise prediction of DCI. The suggested risk chart may prove useful for selection of appropriate candidates for interventions to prevent DCI.

Incremental Versus Immediate Induction of Hypertension in the Treatment of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a common complication of aneurysmal subarachnoid hemorrhage and contributes to unfavorable outcome. In patients with deterioration despite prophylactic nimodipine treatment, induced hypertension (iHTN) can be considered, although the safety and efficacy of induction are still a matter of debate. In this study, two iHTN treatment algorithms were compared with different approaches toward setting pressure targets. METHODS: In a cohort of 325 consecutive patients with subarachnoid hemorrhage, 139 patients were treated by induced hypertension as a first tier treatment. On diagnosing DCI, blood pressure was raised via norepinephrine infusion in 20-mm Hg increments in 37 patients (iHTNincr), whereas 102 patients were treated by immediate elevation to systolic pressure above 180 mm Hg (iHTNimm). Treatment choice was based on personal preference of the treating physician but with a gradual shift away from incremental elevation. Both groups were evaluated for DCI-caused infarction, the need of additional endovascular rescue treatment, the occurrence of pressor-treatment-related complications, and clinical outcome assessed by the extended Glasgow outcome scale after 12 months. RESULTS: The rate of refractory DCI requiring additional rescue therapy was comparable in both groups (48.9% in iHTNincr, 40.0% in iHTNimm; p = 0.332). The type of induced hypertension was not independently associated with the occurrence of DCI-related infarction in a logistic regression model (odds ratio 1.004; 95% confidence interval 0.329-3.443; p = 0.942). Similar rates of pressor-treatment-related complications were observed in both treatment groups. Favorable outcome was reached in 44 (43.1%) patients in the immediate vs. 10 (27.0%) patients in the incremental treatment group (p = 0.076). However, only Hunt and Hess grading was identified as an independent predictor variable of clinical outcome (odds ratio 0.422; 95% confidence interval 0.216-0.824; p = 0.012). CONCLUSIONS: Immediate induction of hypertension with higher pressure targets did not result in a lower rate of DCI-related infarctions but was not associated with a higher complication rate compared with an incremental approach. Future tailored blood pressure management based on patient- and time-point-specific needs will hopefully better balance the neurological advantages versus the systemic complications of induced hypertension.

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

Levels of bioactive adrenomedullin in plasma and cerebrospinal fluid in relation to delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhage: A prospective observational study.

OBJECTIVES: Adrenomedullin (ADM) has been identified as a promising biomarker of mortality and outcome in sepsis, heart failure and after major surgery. A recently developed assay specific for bioactive adrenomedullin (bio-ADM) has not yet been assessed in aneurysmal subarachnoid hemorrhage (aSAH). The objective of this prospective trial was to assess the time course of bio-ADM after aSAH in relation to the development of delayed cerebral ischemia (DCI) and its association with clinical outcome. METHODS: Bio-ADM levels in plasma and cerebrospinal fluid (CSF) were measured during five predefined epochs, for up to 21 days in 30 aSAH patients: early, (day 0 to day 3); acute, (day 4 to day 8); early critical, (day 9 to day 12); late critical, (day 13 to day 15), and late (day 16 to day 21). DCI was diagnosed clinically or based on multimodal monitoring and imaging, and the occurrence of DCI-related cerebral infarction, and outcome after 12 months (extended Glasgow outcome scale), was noted. RESULTS: Higher median bio-ADM levels in plasma during the acute phase were predictive of long-term unfavorable outcome (AUC = 0.97; 95% CI 0.91 to 1.00; p < 0.001). Early critical bio-ADM levels during DCI were lower in CSF and confirmed DCI occurrence (AUC = 0.80; 95% CI 0.59 to 1.00; p = 0.044). CONCLUSION: The dynamics of bio-ADM levels in CSF present a fairly different course compared to plasma with observed higher bio-ADM concentrations in patients spared from DCI and/or developing favorable outcome.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial.

BACKGROUND: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer's solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. METHODS: This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0-3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. DISCUSSION: New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer's solution. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645 . Registered on 8 May 2019.

Development of a Delayed Cerebral Infarction Load Scoring System (DCI Score).

Delayed cerebral infarction (DCI) is related to unfavorable outcome after aneurysmal subarachnoid hemorrhage (SAH). There lacks a clear understanding how the DCI load affects cognitive function after SAH. We conducted a literature review on the clinical classification systems on brain hemorrhages and cerebral infarction and devised a Delayed Cerebral Infarction Load Scoring System (DCI Score). DCI Score significantly correlated with Symbol Digit Modalities Test (-0.334, p = 0.032), Color Trail Test (-0.310, p = 0.032), Hong Kong List Learning Test (-0.318, p = 0.036), Verbal Digit Span Forward (-0.382, p = 0.017), and Visual Digit Span Backward (-0.425, p = 0.012). In conclusion, higher DCI load impacted significantly on memory and executive function. DCI Score is a useful system for clinical quantification of DCI load and clinical research.

Effect of Premorbid Antiplatelet Medication Use on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Propensity Score-matched Study.

Introduction Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH) and a major predictor of poor functional outcomes in patients surviving the initial insult. Several theories have postulated that platelet activation, microthrombi formation, and subsequent vasospasm are mechanisms involved. We, therefore, assessed the effect of premorbid antiplatelet medication (APM) use on discharge functional outcomes and cerebral infarction due to DCI in patients presenting with aSAH. Methods Retrospective analysis of patients admitted to a single US center with aSAH from 2007 to 2016 was performed. Patients who were receiving APM prior to admission were then matched to those who did not receive them using nearest-neighbor propensity-score-matching (PSM) controlling for the following variables: age, hypertension, smoking status, Hunt-&-Hess classification, and management type. Results Out of the 267 patients identified, 38 (14.2%) were on APMs when admitted. On univariate analysis, patients on APM were older (p < 0.001) and more likely to be hypertensive (p = 0.005). Modified Rankin Scale (mRS) at discharge was significantly worse for patients on APMs compared to those who were not (mRS 3-6 in 55.3% vs 32.7%; p = 0.007). No significant difference in cerebral infarction due to DCI was found (p = 0.82). PSM resulted in 20 patients in the APMs group and 20 patients in the comparison group. After matching, no significant difference was found in discharge mRS (p = 0.56) and cerebral infarction due to DCI (p = 0.7). Conclusion This study identified no significant effect of admission APMs on discharge functional outcomes and cerebral infarction due to DCI in aSAH patients after matching.

Targeted Temperature Management for Subarachnoid Hemorrhage: Excellent Outcome After Severe Vasospasm-A Case Series.

Targeted temperature management (TTM) might improve outcome of patients with severe subarachnoid hemorrhage (SAH) in which vasospasm, delayed cerebral ischemia (DCI), and increased intracranial pressure (ICP) are frequent and severe complications. A series of patients (n = 3) with severe aneurysmatic SAH were treated by TTM if they developed ICP crisis and/or severe vasospasm diagnosed by angiography. Once these complications were detected, body core temperature (BCT) was rapidly decreased to 35°C or 33°C, if necessary. BCT induced and maintained by surface cooling remained at the desired level for at least 72 hours. Rewarming was performed by 1°C, only if the target parameters ICP and velocities in the serial Doppler sonography indicating macrovascular vasospasm improved to regular levels. In case of increase of ICP or middle cerebral arteries velocities BCT was decreased again to the last effective level. The patients developed vasospasm between days 6 and 12 after SAH. All aneurysms were treated by coiling. BCT was reduced between days 6 and 12 after SAH. Total duration of BCT <36.5°C was between 5.5 and 8 days. It remained <35°C for 4-6 days, and at 33°C for 3 days on average. ICP could be sufficiently controlled in all patients, because no ICP crisis was observed during TTM and after rewarming. Two patients developed minor DCI. Side effects of prolonged ventilation of 7-18 days included pneumonia for two patients that could be treated sufficiently. Other complications were one case of ventriculitis and two temporary deliriums. Outcome of the patients was good because no focal neurological symptoms could be detected after rehabilitation. TTM represents a promising treatment approach for severe SAH in which standard treatment is often limited and experimental. It deserves further clinical investigation in a larger cohort.