Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.

Type of headache at onset and risk for complications in reversible cerebral vasoconstriction syndrome.

BACKGROUND: In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without thunderclap headache (TCH), and tended to present more severe forms of RCVS than patients with TCH. We aimed to analyze the risk for complications of RCVS in patients with and without TCH at onset. METHODS: In a pooled cohort of 345 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of neurological complications, and the functional outcome at 3 months. RESULTS: As compared to the 281 patients with TCH at onset, the 64 patients without TCH had a higher risk for any neurological complication (61% vs. 24%, OR 4.9, 95% CI 2.8-8.7, p < 0.001). The association was strongest for cervical artery dissections (28% vs. 5%, OR 8.1, 95% CI 3.7-17.6, p < 0.001), followed by posterior reversible encephalopathy syndrome (17% vs. 3%, OR 7.1, 95% CI 2.7-18.4, p < 0.001), seizures (9% vs. 2.5%, OR 4.1, 95% CI 1.3-12.5, p = 0.019), and subarachnoid hemorrhage (41% vs. 16%, OR 3.5, 95% CI 1.9-6.3, p < 0.001). In multivariable analysis, the risk for any neurological complication remained significantly elevated in the absence of TCH (OR 3.5, 95% CI 1.8-6.8, p < 0.001). The functional outcome was equal in both groups, with a modified Rankin scale score of 0-1 in ≥90% of patients. CONCLUSIONS: Absence of TCH at onset might predict a higher risk of complications in RCVS. Our results warrant further multicentric studies to prove this finding.

The incidence of cerebral arterial vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis.

PURPOSE: To describe a pooled estimated incidence of cerebral arterial vasospasm (aVSP) following aneurysmal subarachnoid haemorrhage (aSAH) and to describe sources of variation in the reported incidence. METHODS: We performed a systematic review and meta-analysis of randomised clinical trials (RCTs) and cohort studies. The primary outcome was the proportion of study participants diagnosed with aVSP. We assessed for heterogeneity based on mode of imaging, indication for imaging, study design and clinical characteristics at a study level. RESULTS: We identified 120 studies, including 19,171 participants. More than 40 different criteria were used to diagnose aVSP. The pooled estimate of the proportion of patients diagnosed with aVSP was 0.42 (95% CI 0.39 to 0.46, I2 = 96.5%). There was no evidence that the incidence aVSP was different, nor that heterogeneity was reduced, when the estimate was assessed by study type, imaging modalities, the proportion of participants with high grade CT scores or poor grade clinical scores. The pooled estimate of the proportion of study participants diagnosed with aVSP was higher in studies with routine imaging (0.47, 95% CI 0.43 to 0.52, I2 = 96.5%) compared to those when imaging was performed when indicated (0.30, 95% CI 0.25 to 0.36, I2 = 94.0%, p for between-group difference < 0.0005). CONCLUSION: The incidence of cerebral arterial vasospasm following aSAH varies widely from 9 to 93% of study participants. Heterogeneity in the reported incidence may be due to variation in the criteria used to diagnose aVSP. A standard set of diagnostic criteria is necessary to resolve the role that aVSP plays in delayed neurological deterioration following aSAH. PROSPERO REGISTRATION: CRD42020191895.

Development of cerebral vasospasm following traumatic intracranial hemorrhage: incidence, risk factors, and clinical outcomes.

OBJECTIVE: Limited evidence exists characterizing the incidence, risk factors, and clinical associations of cerebral vasospasm following traumatic intracranial hemorrhage (tICH) on a large scale. Therefore, the authors sought to use data from a national inpatient registry to investigate these aspects of posttraumatic vasospasm (PTV) to further elucidate potential causes of neurological morbidity and mortality subsequent to the initial insult. METHODS: Weighted discharge data from the National (Nationwide) Inpatient Sample from 2015 to 2018 were queried to identify patients with tICH who underwent diagnostic angiography in the same admission and, subsequently, those who developed angiographically confirmed cerebral vasospasm. Multivariable logistic regression analysis was performed to identify significant associations between clinical covariates and the development of vasospasm, and a tICH vasospasm predictive model (tICH-VPM) was generated based on the effect sizes of these parameters. RESULTS: Among 5880 identified patients with tICH, 375 developed PTV corresponding to an incidence of 6.4%. Multivariable adjusted modeling determined that the following clinical covariates were independently associated with the development of PTV, among others: age (adjusted odds ratio [aOR] 0.98, 95% CI 0.97-0.99; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.80, 95% CI 1.12-2.90; p = 0.015), intraventricular hemorrhage (aOR 6.27, 95% CI 3.49-11.26; p < 0.001), tobacco smoking (aOR 1.36, 95% CI 1.02-1.80; p = 0.035), cocaine use (aOR 3.62, 95% CI 1.97-6.63; p < 0.001), fever (aOR 2.09, 95% CI 1.34-3.27; p = 0.001), and hypokalemia (aOR 1.62, 95% CI 1.26-2.08; p < 0.001). The tICH-VPM achieved moderately high discrimination, with an area under the curve of 0.75 (sensitivity = 0.61 and specificity = 0.81). Development of vasospasm was independently associated with a lower likelihood of routine discharge (aOR 0.60, 95% CI 0.45-0.78; p < 0.001) and an extended hospital length of stay (aOR 3.53, 95% CI 2.78-4.48; p < 0.001), but not with mortality. CONCLUSIONS: This population-based analysis of vasospasm in tICH has identified common clinical risk factors for its development, and has established an independent association between the development of vasospasm and poorer neurological outcomes.

Sex-related differences of invasive therapy in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Sex-related differences in patients with aneurysmal subarachnoid hemorrhage (aSAH) exist. More females than males are affected. Aneurysm location is associated to sex. The relationship between sex and outcome, however, is unclear. Possible differences in management might influence the occurrence of primary and secondary brain injury and thus outcome. The study compares demographics, intensity of treatment, complications, and outcome among females and males with aSAH. METHODS: All consecutive patients with aSAH admitted to the neurocritical care unit, University Hospital Zurich over a 5-year period were eligible in this retrospective study. Patients' characteristics, comorbidities, aSAH severity, frequency of vasospasm/delayed cerebral ischemia, frequency of invasive interventions, and 3-month outcome were compared by sex. Univariate analysis was performed with the data dichotomized by sex, and outcome. Multivariate analysis for prediction of outcomes was performed. RESULTS: Three hundred forty-eight patients were enrolled (64% females). Women were older than men. Comorbidities, scores at admission, and treatment modality were comparable among males and females. Vasospasm and DCI occurred similarly among females and males. Interventions and frequency of intraarterial spasmolysis were comparable between sexes. In the multivariate analysis, increasing age, female sex, increasing comorbidities, WFNS and Fisher grade, and presence of delayed cerebral ischemia were predictors of unfavorable outcome when considering all patients. However, after excluding death as a possible outcome, sex did not remain a predictor of unfavorable outcome. CONCLUSIONS: In the study population, women with aSAH might have present a worse outcome at 3 months. However, no differences by sex that might explain this difference were found in intensity of treatment and management.

Severe headache trajectory following aneurysmal subarachnoid hemorrhage: the association with lower sodium levels.

BACKGROUND: A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. METHODS: This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. RESULTS: Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. CONCLUSION: We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted.

Revisiting the Timeline of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Toward a Temporal Risk Profile.

BACKGROUND: Delayed cerebral ischemia (DCI) is one of the main determinants of clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). The classical description of risk for DCI over time is currently based on the outdated concept of angiographic vasospasm. The goal of this study was to assess the temporal risk profile of DCI, defined by extended clinical and radiological criteria, as well as the impact the time point of DCI onset has on clinical outcome. METHODS: All patients with aneurysmal SAH referred to a single tertiary care center between 2010 and 2018 were considered for inclusion. This study was designed as a retrospective cohort analysis and data were extracted from existing patient files. In conscious patients, DCI was diagnosed clinically, and in unconscious patients, diagnosis was based on perfusion computed tomography imaging and multimodal neuromonitoring. Extended Glasgow Outcome Scale scores were assessed after 12 months and compared between patients with early (< day 7) and late (≥ day 7) DCI onset. RESULTS: The median delay from day of the hemorrhage (day 0) until detection of the first DCI event was 7.0 days, with an interquartile range of 5 days. The probability of DCI development over time demonstrated a bimodal distribution with a peak risk on day 5 (0.084; confidence interval 0.05.5-0.122) and a second peak on day 9 (0.077; confidence interval 0.045-0.120). A total of 27 patients (15.6%) suffered dominant hemispheric or severe bilateral DCI-related infarctions, resulting in the withdrawal of technical life support. Of those, the majority (20 patients, 22.2%) presented with early DCI onset (vs. late onset: 7 patients, 8.4%; p = 0.013). CONCLUSIONS: The risk profile of DCI over time mirrors the description of angiographic vasospasm; however, it comes with an added timely delay of 1 to 2 days. Early occurrence of DCI (before day 7) is associated with a higher infarct load and DCI-related mortality. Although the exact causal relationship remains to be determined, the time point of DCI onset may serve as an independent prognostic criterion in decision-making.

Sodium Variability and Probability of Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Vasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4-14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm. MATERIALS AND METHODS: A single-center retrospective analysis from 2007-2016 was conducted of aSAH patients. Daily serum sodium levels were recorded up to day 14 post-admission. Hyponatremia was defined as a serum sodium value of < 135 mEq/L. We evaluated the relationship to radiologic vasospasm, neurologic deterioration, functional status at discharge, and mortality. A repeated measures analysis using a mixed-effect regression model was performed to assess the interindividual relationship between serum sodium trends and outcomes. RESULTS: A total of 271 aSAH patients were included. There were no significant differences in interindividual serum sodium values over time and occurrence of radiographic vasospasm, neurologic deterioration, functional, or mortality outcomes (p = .59, p = .42, p = .94, p = .99, respectively) using the mixed-effect regression model. However, overall mean serum sodium levels were significantly higher in patients who had neurologic deterioration, poor functional outcome (mRS 3-6), and mortality. CONCLUSIONS: Serum sodium level variations are not associated with subsequent development of cerebral vasospasm in aSAH patients. These findings indicate that serum sodium may not have an impact on vasospasm, and avoiding hypernatremia may provide a neurologic, functional and survival benefit.

The management of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a rare event affecting relatively young patients therefore leading to a high social impact. The management of SAH follows a biphasic course with early brain injuries in the first 72 hours followed by a phase at risk of secondary deterioration due to delayed cerebral ischemia (DCI) in 20 to 30% patients. Cerebral infarction from DCI is the most preventable cause of mortality and morbidity after SAH. DCI prevention, early detection and treatment is therefore advocated. Formerly limited to the occurrence of vasospasm, DCI is now associated with multiple pathophysiological processes involving for instance the macrocirculation, the microcirculation, neurovascular units, and inflammation. Therefore, the therapeutic targets and management strategies are also evolving and are not only focused on proximal vasospasm. In this review, we describe the current knowledge of DCI pathophysiology. We then discuss the diagnosis strategies that may guide physicians at the bedside with a multimodal approach in the unconscious patient. We will present the prevention strategies that have proven efficient as well as future targets and present the therapeutic approach that is currently being developed when a DCI occurs.

Transcranial Doppler findings in a population with clinical probable reversible cerebral vasoconstriction syndrome.

OBJECTIVE: To describe transcranial Doppler (TCD) findings in a population with clinical probable RCVS. Exploratory objectives included the study of clinical characteristics of probable RCVS patients with and without spasm detected by TCD. METHODS: Cross-sectional cohort study of patients with thunderclap headache (TCH) without subarachnoid hemorrhage (SAH) of our neurology and headache center between 2010 and 2019, selecting patients with clinical diagnosis of probable RCVS (negative angiography study) by ICHD-3 criteria and with at least two TCD studies. RESULTS: From 114 TCH patients, 36/114 had probable RCVS by ICHD-3 criteria and had at least two TCD studies available. The mean age at RCVS onset was 42.9years (21-72years); 29/36 (80.6%) were female, 7/28 (25%) had cardiovascular risk factors and 20/36 (55.6%) had history of migraine. Most common triggers were stressful emotion, drugs, valsalva maneuvers and sexual activity. Five/36 (13.9%) had complications and 3/36 (8.3%) had late recurrence. Initial TCD was performed on average of 16 (6-26) days after headache onset. Twenty-nine had vasospasm on TCD, presenting mean flow velocity of MCA (VMCA) of 135.7±17.0cm/s and mean maximum VMCA of 138.3±17.2. Vasospasm was mild in 21/29 patients (72.4%) and moderate in 8/29 (27.6%). Complete VMCA normalization occurred on average 41 (30-70) days after headache onset and 24 (11-47) days after initial TCD. The group of patients with vasospasm detected by TCD had more female patients (26/29, 89.7% vs. 3/7, 42.8%, P=0.016), and more TCH attacks (mean of 3.6 vs. 2.14, P=0.049). CONCLUSION: TCD may be a useful tool in the identification of vasospasm in patients with probable RCVS, supporting the diagnosis of RCVS in patients presenting with recurrent TCH without SAH.

Hyperoxemia and Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm. METHODS: This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO2 values or died within 96 h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO2 measured within 72 h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale. RESULTS: Three hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13 years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt-Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO2 by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO2 between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage. CONCLUSIONS: Hyperoxemia within 72 h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO2 and may represent a modifiable risk factor for vasospasm.

Nicardipine Prolonged Release Implants for Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVES: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH. MATERIALS AND METHODS: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators. RESULTS: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101). CONCLUSIONS: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner.

Post-reversible cerebral vasoconstriction syndrome headache.

BACKGROUND: Chronic headache may persist after the remission of reversible cerebral vasoconstriction syndrome (RCVS) in some patients. We aimed to investigate the prevalence, characteristics, risk factors, and the impact of post-RCVS headache. METHODS: We prospectively recruited patients with RCVS and collected their baseline demographics, including psychological distress measured by Hospital Anxiety and Depression scale. We evaluated whether the patients developed post-RCVS headache 3 months after RCVS onset. The manifestations of post-RCVS headache and headache-related disability measured by Migraine Disability Assessment (MIDAS) scores were recorded. RESULTS: From 2017 to 2019, 134 patients with RCVS were recruited, of whom, 123 finished follow-up interviews (response rate 91.8%). Sixty (48.8%) patients had post-RCVS headache. Migrainous features were common in post-RCVS headache. Post-RCVS headache caused moderate-to-severe headache-related disability (MIDAS score > 10) in seven (11.7%) patients. Higher anxiety level (odds ratio 1.21, p = 0.009) and a history of migraine (odds ratio 2.59, p = 0.049) are associated with post-RCVS headache. Survival analysis estimated that 50% post-RCVS headache would recover in 389 days (95% confidence interval: 198.5-579) after disease onset. CONCLUSIONS: Post-RCVS headache is common, affecting half of patients and being disabling in one-tenth. Higher anxiety level and migraine history are risk factors. Half of the patients with post-RCVS headache would recover in about a year.

Vasospasm and delayed cerebral ischaemia in patients with spontaneous subarachnoid haemorrhage (aneurysmal and pretruncal non-aneurysmal): a centre's perspective.

BACKGROUND: Spontaneous subarachnoid haemorrhage (SAH) is a significant cause of stroke and associated with high morbidity and mortality. One substantial complication of SAH is cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). This study aimed to define the clinical profile in patients with SAH, CV and DCI secondary to spontaneous SAH (aneurysmal and pretruncal non-aneurysmal). MATERIALS AND METHODS: We analysed 122 consecutive patients with spontaneous SAH following intracranial aneurysmal and non-aneurysmal information (including patients' pattern characterisation and their possible risk factor association to pre-operative clinical decision and long-term clinical outcome) was documented and analysed. RESULTS: The main clinical presentations for spontaneous SAH following ruptured intracranial aneurysm and nonaneurysm were headache (77%) and nausea/vomiting (62.3%). The most common sites for SAH following ruptured intracranial aneurysm rupture were the anterior and posterior communicating arteries (57.5%). Hypertension was the most common cause for SAH at 64.8%. It was found 26.2% (n=32) out of the 122 patients developed CV and DCI. The mean day of vasospasm was 6.0 ± 2.8 (range: 1-14 days) Age, length of stay, nausea/vomiting and visual field defect were significantly associated (p<0.05) with vasospasm. Mortality rate was also higher in the CV group compared to the group without CV in both at discharge and at 6 months; 281 versus 278 per 1000 and 312 vs 300 per 1000, respectively. CONCLUSION: CV and DCI have a significant incidence among local patients with spontaneous SAH following an intracranial aneurysmal and non-aneurysmal rupture and it is associated with substantial morbidity. Prevention, effective monitoring, and early detection are keys to successful management. Regional investigation using a multicentre cohort to analyse mortality and survival rates may aid in improving national resource management of these patients.

Is Anatomical Variations a Risk Factor for Cerebral Vasospasm in Anterior Communicating Complex Aneurysms Rupture?

Background and Purpose- One-third of ruptured aneurysms are located on the anterior communicating complex with high prevalence of anatomic variations of this arterial segment. In this study, we hypothesized that anatomic variations of the anterior communicating complex increase the risk of angiographic vasospasm. Methods- Retrospective study of prospectively collected data from a monocentric subarachnoid hemorrhage cohort of patients admitted to neurointensive care between 2002 and 2018. Univariate followed by multivariate logistic regression analysis was used to identify factors associated with angiographic vasospasm. Results- One thousand three hundred seventy-four patients with aneurismal subarachnoid hemorrhage were admitted to our institution; 29.8% (n=410) were related to an anterior communicating complex aneurysm rupture; 9.2% (n=38) of them showed an anterior communicating artery variation. Angiographic vasospasm was diagnosed in 55.6% of this subgroup (vs 28.1%, P=0.003). In the multivariate analysis, external ventricular drain (2.2 [1.32-3.65], P=0.003) and anterior communicating artery variation (2.40 [1.2-4.9], P=0.04) were independently and significantly associated with angiographic vasospasm, while age above 60 years (0.3 [0.2-0.7]; P=0.002) was a protective factor. However, anterior communicating artery variation was not statistically associated with ischemic vasospasm or poor neurological outcome after anterior communicating artery aneurysm rupture. Conclusions- Anatomic variation of anterior communicating artery could be a new biomarker to identify patients at risk to develop angiographic vasospasm post-subarachnoid hemorrhage. External validation cohorts are necessary to confirm these results.

Predictors of Ventriculoperitoneal shunting following Subarachnoid Hemorrhage treated with External Ventricular Drainage.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is commonly associated with hydrocephalus due to subarachnoid hemorrhage blood products obstructing cerebrospinal fluid outflow. Hydrocephalus after aSAH is routinely managed with temporary external ventricular drainage (EVD) followed by standard EVD weaning protocols, which determine the need for ventriculoperitoneal shunting (VPS). We sought to investigate aSAH patients who initially passed EVD weaning trials and had EVD removal, but later presented with recurrent, delayed, symptomatic hydrocephalus requiring a VPS. METHODS: We conducted a retrospective review of all patients at our tertiary care medical center who presented with aSAH, requiring an EVD. We analyzed variables associated with ultimate VPS dependency during hospitalization. RESULTS: We reviewed 489 patients with aSAH over a 6-year period (2008-2014). One hundred and thirty-eight (28.2%) developed hydrocephalus requiring a temporary EVD. Forty-four (31.9%) of these patients died or had withdrawal of care during admission, and were excluded from final analysis. Of the remaining 94 patients, 29 (30.9%) failed their clamp trial and required VPS. Sixty-five (69.1%) patients passed their clamp trial and were discharged without a VPS. However, 10 (15.4%) of these patients developed delayed hydrocephalus after discharge and ultimately required VPS [mean (range) days after discharge, 97.2 (35-188)]. Compared to early VPS, the delayed VPS group had a higher incidence of symptomatic vasospasm (90.0% vs 51.7%; P = 0.03). When comparing patients discharged from the hospital without VPS, delayed VPS patients also had higher 6- and 12-month mortality (P = 0.02) and longer EVD clamp trials (P < 0.01) than patients who never required VPS but had an EVD during hospitalization. Delayed hydrocephalus occurred in only 7.8% of patients who passed the initial EVD clamp trial, compared to 14.3% who failed the initial trial and 80.0% who failed 2 or more trials. CONCLUSION: Patients who failed their initial or subsequent EVD clamp trials had a small, but increased risk of developing delayed hydrocephalus ultimately requiring VPS. Additionally, the majority of patients who presented with delayed hydrocephalus also suffered symptomatic vasospasm. These associations should be further explored and validated in a larger prospective study.

Vitamin K Antagonist (Phenprocoumon) and Subarachnoid Hemorrhage: A Single-Center, Matched-Pair Analysis.

BACKGROUND: Demographic changes are leading to an aging society with a growing number of patients relying on anticoagulation, and vitamin K antagonists (VKA) are still widely used. As mortality and functional outcomes are worse in case of VKA-associated hemorrhagic stroke, phenprocoumon treatment seems to be a negative prognostic factor in case of subarachnoid hemorrhage (SAH). The purpose of this study was to analyze whether phenprocoumon treatment does worsen the outcome after non-traumatic SAH. METHODS: All patients treated for non-traumatic SAH between January 2007 and December 2016 in our institution were retrospectively analyzed. After exclusion of patients with anticoagulant or antiplatelet treatment other than phenprocoumon, we analyzed 1040 patients. Thirty-three patients (3%) of those were treated with continuous phenprocoumon. In total, 132 out of all 1007 patients without anticoagulant treatment of the remaining patients were matched as control group (ratio = 1:4). RESULTS: Patients with phenprocoumon treatment were significantly older (66.5 years vs. 53.9 years; p < .0001), and admission status was significantly more often poor (66.7% vs. 41.8%, p = .007) compared to all patients without anticoagulant treatment. Further, bleeding pattern and rates of early hydrocephalus did not differ. Matched-pair analysis revealed a significant higher rate of angio-negative SAH in the study group (p = .001). Overall rates of hemorrhagic or thromboembolic complications did not differ (21.4% vs. 18.8%; NS) but were more often fatal, and 30-day mortality rate was significantly higher in the phenprocoumon group than in patients of the matched-pair control group (33% vs. 24%; p < .001). 30% of the phenprocoumon group and 37% of the matched-pair control group reached favorable outcome. However, poor outcome was strong associated with the reason for phenprocoumon treatment. CONCLUSION: Patients with phenprocoumon treatment at the time of SAH are significantly older, admission status is worse, and 30-day mortality rates are significantly higher compared to patients without anticoagulant treatment. However, outcome at 6 months did not differ to the matched-pair control group but seems to be strongly associated with the underlying cardiovascular disease. Treatment of these patients is challenging and should be performed on an interdisciplinary base in each individual case. Careful decision-making regarding discontinuation and bridging of anticoagulation and close observation is mandatory.

Quantitative Modeling of External Ventricular Drain Output to Predict Shunt Dependency in Aneurysmal Subarachnoid Hemorrhage: Cohort Study.

BACKGROUND: Acute hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH); however, attempts to predict shunt-dependent chronic hydrocephalus using clinical parameters have been equivocal. METHODS: Cohort study of aSAH is treated with external ventricular drainage (EVD) placement at our institution, 2001-2016, via logistic regression. EVD-related parameters included mean/total EVD output (days 0-2), EVD days, EVD days ≤ 5 mmHg, and wean/clamp fails. aSAH outcomes assessed included ventriculoperitoneal shunt (VPS) placement, delayed cerebral ischemia (DCI), radiographic infarction (RI), symptomatic vasospasm (SV), age, and aSAH grades. RESULTS: Two hundred and ten aSAH patients underwent EVD treatment for a median 12 days (range 1-54); 85 required VPS (40%). On univariate analysis, EVD output, total EVD days, EVD days ≤ 5 mmHg, and wean/clamp trial failures were significantly associated with VPS placement (p < 0.01 for all parameters). No EVD output parameter demonstrated a significant association with DCI, RI, or SV. On multivariate analysis, EVD output was a significant predictor of VPS placement, after adjusting for age and clinical and radiological grades; the optimal threshold for predicting VPS placement was mean daily output > 204 ml on days 0-2 (OR 2.59, 95% CI 1.31-5.07). Multiple wean failures were associated with unfavorable functional outcome, after adjusting for age, grade, and VPS placement (OR 1.65, 95% CI 1.10-2.47). We developed a score incorporating age, grade and EVD parameters (MAGE) for predicting VPS placement after aSAH. CONCLUSIONS: EVD output parameters and wean/clamp trial failures predicted shunt dependence in an age- and grade-adjusted multivariable model. Early VPS placement may be warranted in patients with MAGE score ≥ 4, particularly following 2 failed wean trials.

Temporal Relationship between Hyponatremia and Development of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage Patients: A Retrospective Observational Study.

BACKGROUND: Hyponatremia is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have reported an association between hyponatremia and vasospasm, however whether hyponatremia directly contributes to the pathogenesis of cerebral vasospasm (CVS), or is a by-product is still unclear. The aim of this study was to explore an association between hyponatremia and CVS after aSAH, and evaluating the temporality of these 2 events. METHODS: A retrospective study of consecutive patients with aSAH admitted to the Baylor St. Luke's Medical center between January 2008 and December 2012 was conducted. Demographics, baseline characteristics, serum sodium levels, and evidence of vasospasm detected by transcranial Doppler, CT Angiogram, MR angiogram, and digital subtracted angiography were collected. Patients were dichotomized into a hyponatremic and a normonatremic group. CVS incidence and clinical outcome was compared between groups. Timing of CVS after initial hyponatremia episodes was recorded Results: One hundred and sixty 4 patients with aSAH were included. Hyponatremia was identified in 66 patients (40.2%) and CVS occurred in 71 subjects (43.2%). The incidence of CVS was higher in the hyponatremic group compared to the normonatremic group, 65.1 % versus 28.5%, respectively (P < .001). Hyponatremia preceded CVS by median 1.5 days suggesting a temporal trend. CONCLUSIONS: Our study shows a significant association between hyponatremia and CVS, with hyponatremia preceding CVS events. This retrospective finding denotes the need for larger prospective studies, aiming to clarify the temporal relationship of serum sodium levels and CVS.

[Reversible cerebral vasoconstriction syndrome - a common cause of thunderclap headache].

Reversible cerebral vasoconstriction is characterized by thunderclap headache and vasoconstriction of cerebral arteries, with or without focal neurologic symptoms. The syndrome is three times more common in women with a mean age around 45 years. In approximately 60% of cases a cause can be identified, commonly after intake of vasoactive substances. The pathophysiology of reversible cerebral vasoconstriction syndrome is unknown, though temporary dysregulation in cerebral vascular tone is thought to be a key underlying mechanism. The syndrome typically follows a benign course; however, complications such as ischemic stroke or intracranial hemorrhage can cause permanent disability or death in a small minority of patients. Vascular imaging reveals alternating cerebral vasoconstriction and vasodilation that normalizes within 12 weeks. Calcium channel antagonists such as nimodipine reduce the frequency of thunderclap headaches but do not decidedly affect the risk of cerebral ischemia or hemorrhage. In this article the epidemiology, risk factors, pathophysiology, symptoms, diagnosis and treatment of RCVS is reviewed.