Cerebral vasospasm following tumor resection: Illustrative cases and review of the literature.

BACKGROUND: Cerebral vasospasm (CV) after tumor resection is a rare event, although it is associated with poorer postoperative outcomes and increased morbidity and mortality. Given the potential for neurologic injury secondary to CV, there is a need for further understanding of this phenomenon. Therefore, the purpose of this study is to investigate the risk factors of CV following intracranial tumor resection. METHODS: A literature review was conducted identifying 61 studies (40 individual case reports, 14 case series, and 7 cohort studies) reporting 179 individual cases. Additionally, two illustrative cases were presented. RESULTS: Post-tumor resection CV was reported more often in males (58.0 %) than females (42.0 %), with an average age of onset of 47.3 years in males compared to 40.4 years in females. Of those specified, CV most commonly occurred in posterior fossa tumors (51.8 %), followed by the sellar/suprasellar region (36.6 %). The most common pathologies were schwannoma (31.8 %), pituitary adenoma (27.8 %), meningioma (15.2 %), and craniopharyngioma (9.9 %). Vasospasm most commonly occurred diffusely in the anterior circulation (60.2 %), with MCA and ACA involvement indicated in 72.7 % and 64.8 % of all cases, respectively. Symptomatically, CV most commonly presented with altered mental status (73.9 %) or weakness (60.9 %), specifically hemiparesis (37.0 %) or altered consciousness (22.8 %). Most cases of vasospasm presented within the first week (58.4 %), with 97.7 % occurring within the first 2 weeks. A higher mortality rate was associated with onset before 3 days (n=6/13; 46.2 %). Mortality was reported in 17.3 % (n=18) of all cases and residual deficits were reported in 53.5 % (n=46) of those patients who survived. CONCLUSION: Most reports on CV involved posterior fossa tumors, the anterior circulation (most frequently the MCA), and tumors of varying histologies. Tumor location and vascular involvement may be related to distribution of spasm and symptomatology. Early onset of vasospasm may furthermore be related to poorer outcomes.

[Postoperative Management of Aneurysmal Subarachnoid Hemorrhage].

Delayed cerebral ischemia(DCI) is one of the most significant complications of subarachnoid hemorrhage. Despite significant evolution in understanding DCI pathophysiology, vasospasm affecting cerebral vessels of large and moderate diameters remain the only clinically measurable component of DCI and is therefore the primary target for intervention in the postoperative management of subarachnoid hemorrhage. In Japan, fasudil hydrochloride and ozagrel sodium are widely used to prevent vasospasms; however, their effects are sometimes insufficient. Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage. This was demonstrated in a recent randomized phase 3 trial, leading to the approval of clazosentan by the Pharmaceuticals and Medical Devices Agency in Japan. Recent advances in our understanding of subarachnoid hemorrhage will facilitate improved management to reduce the incidence of DCI.

Drugs associated with reversible cerebral vasoconstriction syndrome: A pharmacovigilance study in vigiBase®.

BACKGROUND: Data on drug-induced reversible cerebral vasoconstriction syndrome (RCVS) are scarce. We aimed to describe RCVS characteristics with drugs previously identified as associated with RCVS and investigate potential signals related to other drugs. METHODS: VigiBase® was queried for all reports of RCVS until 31 May 2023. A descriptive study was performed on reports concerning drug classes known to precipitate RCVS. To identify new drugs, a disproportionality analysis was conducted. RESULTS: In total, 560 reports were included. RCVS occurred in patients aged between 45-64 years (40%) and 18-44 years (35%), mainly in females (72.5%). Drugs were antidepressants (38.4%), triptans (6.4%), nasal decongestants (3.7%) and immunosupressants (8.7%). In 50 cases, antidepressants were in association with drugs known to precipitate RCVS. The median time to onset was 195 days for antidepressants and much shorter (1-10 days) for triptans, nasal decongestants and immunosuppressants. The outcome was favorable in 87% of cases, and fatal in 4.4%. We found a disproportionality signal with 14 drugs: glucocorticoids, bupropion, varenicline, mycophenolic acid, aripiprazole, trazodone, monoclonal antibodies (erenumab, ustekinumab and tocilizumab), leuprorelin and anastrozole. CONCLUSIONS: The present study confirms the role of vasoconstrictors in the onset of RCVS, particularly when used in combination and found potential signals, which may help clinicians envisage an iatrogenic etiology of RCVS.

The Effect of Age on Cerebral Vasospasm and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The association between patient age and cerebral arterial vasospasm (CVS) and delayed cerebral ischemia (DCI) risk following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. This study aims to assess the role of age on aSAH-related complications. METHODS: Single-center retrospective study comprising aSAH patients treated between January 2009 and March 2023. Age was analyzed as continuous and categorical variables (<60 yrs vs. ≥60 yrs and by decade). Outcomes of interest included radiographic CVS, DCI, cerebral infarction, in-hospital mortality, length-of-stay (LOS), ventriculoperitoneal shunt placement, and modified Rankin Scale (mRS) scores at discharge and 3-month follow-up. RESULTS: Nine hundred and twenty-five aSAH patients were included. Most (n = 598; 64.6%) were <60 yrs old (46 ± 9.1 yrs). CVS likelihood was lower in the older cohort (aOR = 0.56 [0.38-0.82]). Patients ≥60 yrs had higher mortality rates (aOR = 2.24 [1.12-4.47]) and worse mRS scores at discharge (aOR = 2.66 [1.91-3.72]) and 3-month follow-up (aOR = 2.19 [1.44-3.32]). Advanced age did not have a significant effect on DCI or cerebral infarction risk. Higher in-hospital mortality was documented with increasing age (P < 0.001). A significant interaction between CVS and age for the outcome of DCI was documented, with a stronger positive effect on poor outcomes (i.e., higher odds of DCI) among patients aged <60 years compared to those aged ≥60. CONCLUSIONS: There is an inverse relationship between patient age and CVS incidence following aSAH. Nonetheless, patients ≥60 yrs had comparable DCI rates, higher in-hospital mortality, and worse functional outcomes than their younger counterparts. Routine screening and reliance on radiographic CVS as primary marker for aSAH-related complications should be reconsidered, particularly in older patients.

Cerebral vasospasm in patients with traumatic subarachnoid hemorrhage, a possible point of intervention?

OBJECTIVE: To determine the incidence of vasospasm in traumatic brain injury patients with traumatic subarachnoid hemorrhage. METHODS: IRB approval was obtained for this retrospective chart review. An institutional trauma database was queried for adult patients with traumatic brain injury (TBI) and traumatic subarachnoid hemorrhage (tSAH) seen on CT head obtained within 20 days. The presence of vasospasm on CTA was determined by radiology report. Association between categorical background characteristics and intracranial vasospasm was assessed by the chi-square test and association between a continuous variables and intracranial vasospasm was assessed by a paired t-test. RESULTS: 1142 patients with traumatic SAH were identified from the trauma database. 792 patients were excluded: 142 for age <18, 632 did not have CT angiography, and 18 had non-traumatic SAH. 350 patients were analyzed, of which 28 (8 %) had vasospasm. Traumatic vasospasm was associated with higher-grade TBI based on Cochran-Armitage trend test (p < 0.05). Vasospasm patients had longer length of stay in the ICU (mean days 13.64 vs 7.24, P < 0.001), and had a higher incidence of death (39.29 % vs 20.81 %), although this did not reach statistical significance. CONCLUSION: Intracranial vasospasm, specifically in patients with tSAH, is associated with more severe TBI and longer stays in the ICU. Our incidence is smaller compared to other studies likely due to the retrospective nature and the infrequency of obtaining CT angiography after initial presentation. Prospective studies are warranted as the incidence is significant and may represent a point of intervention for TBI.

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.

Incidence and Outcomes of Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Registry-based Descriptive Trial in Kobe City.

The current study aims to evaluate the incidence and results of aneurysmal subarachnoid hemorrhage (aSAH) throughout Kobe City. Based on a multicenter retrospective registry-based descriptive trial involving all 13 primary stroke centers in Kobe City, patients with aSAH treated between October 2017 and September 2019 were studied. A total of 334 patients were included, with an estimated age-adjusted incidence of 11.12 per 100,000 person-years. Curative treatment was given to 94% of patients, with endovascular treatment (51%) preferred over surgical treatment (43%). Of the patients, 12% were treated by shunt surgery for sequential hydrocephalus with a worse outcome at 30 days or discharge (14% vs. 46%, odds ratio (OR): 0.19, 95% confidence interval (CI): 0.088-0.39, p-value <0.001). As for vasospasm and delayed cerebral ischemia, most patients were given intravenous fasudil infusion (73%), with endovascular treatment for vasospasm in 24 cases (7.2%). The fasudil group had more good outcomes (42% vs. 30%, OR: 1.64, 95% CI: 0.95-2.87, p-value = 0.075) and significantly less death (3.3% vs. 35%, OR: 0.064, 95% CI: 0.024-0.15, p-value <0.001) at 30 days or discharge. Mortality rose from 12% at 30 days or discharge to 17% at 1 year, but neurological function distribution improved over time (modified Rankin Scale 0-2 was 39% at 30 days or discharge, 53% at 60 days, and 63% at 1 year). Our retrospective registered trial presented various statistics on aSAH, summarizing the current treatment status and prognosis.

Complications of reversible cerebral vasoconstriction syndrome in relation to age.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) has a heterogenous clinical and radiological presentation. We investigated whether RCVS complications vary according to age. PATIENTS AND METHODS: In a pooled French cohort of 345 patients with RCVS, we assessed (1) rates of clinical and radiological complications, and (2) the functional outcome at 3 months according to age as a continuous variable, and in young patients aged ≤ 49 years versus those aged ≥ 50 years. The Commission Nationale Informatique et Liberté and the local ethics committee approved this study (registration number: 202100733). RESULTS: The risk for any focal deficit and for any brain lesion were independently associated with increasing age (OR 1.4, 95% CI 1.1-1.8; p = 0.014, and OR 1.6, 95% CI 1.2-2.1; p < 0.001, respectively). Subtypes of brain lesions independently associated with increasing age were subarachnoid haemorrhage (OR 1.7, 95% CI 1.3-2.3; p < 0.001) and intracerebral haemorrhage (OR 1.5, 95% CI 1.1-2.2; p = 0.023). Frequency of cervical artery dissections peaked at age 30-39, and young age was independently associated with cervical artery dissections (OR 13.6, 95% CI 2.4-76.6; p = 0.003). Age had no impact on the functional outcome, with a modified Rankin scale score of 0-1 in > 96% of patients. CONCLUSION: Age seems to influence rates and types of complications of RCVS, with young age being associated with cervical artery dissections, and increasing age with haemorrhagic complications. If confirmed in larger prospective studies, recognition of age-specific patterns might help to guide clinical management and to identify complications in cases of RCVS and vice versa.

Early stellate ganglion block for improvement of postoperative cerebral blood flow velocity after aneurysmal subarachnoid hemorrhage: results of a pilot randomized controlled trial.

OBJECTIVE: Stellate ganglion block (SGB) is a commonly used sympathetic nerve block technique that may have benefits for patients with aneurysmal subarachnoid hemorrhage (aSAH) in the early stage. Cerebral vasospasm (CVS), one of the most common complications of aSAH, is accompanied by an abnormal increase in cerebral blood flow velocity (CBFV) and neurological dysfunction. In this pilot study the authors sought to determine the feasibility of early SGB for CVS in aSAH patients by observing the incidence of symptomatic CVS. METHODS: Prior to receiving surgical treatment, patients with aSAH were randomly assigned to the SGB group or the non-SGB group. The primary outcome was the incidence of symptomatic CVS within 14 ± 2 days after the onset of aSAH. As a higher CBFV is often associated with CVS and a poor prognosis, the mean CBFV of the middle cerebral artery was observed immediately after surgery and on postoperative days 1, 2, 3, 5, and 7. Other secondary outcomes included transcranial Doppler (TCD)/CTA-type CVS, delayed cerebral ischemia during hospitalization, new cerebral infarction within 3 months, adverse events (AEs), and clinical prognosis. RESULTS: Symptomatic CVS occurred in 40% of patients in the non-SGB group and in 20% in the SGB group (RR 0.50, 95% CI 0.22-1.16). Continuous TCD sonography revealed that the postoperative mean CBFV was lower in the SGB group than in the non-SGB group (F = 3.608, p = 0.02). In addition, the percentages of patients with CVS evaluated by TCD (TCD-CVS) and total new infarctions within 3 months were also significantly lower than those in patients with CVS (TCD-CVS 36.7% vs 70%, RR 0.52, 95% CI 0.31-0.89, and total new infarctions 26.7% vs 53.3%, RR 0.50, 95% CI 0.25-0.99). In terms of AEs and mortality, there were no significant differences between the two groups. CONCLUSIONS: This pilot study demonstrated for the first time, to the authors' knowledge, that early SGB is feasible and has the potential to reduce the risk of CVS and improve the prognosis of aSAH. This method may be a new treatment for patients with aSAH that may have more advantages than traditional therapeutic drugs and is worth further study. Clinical trial registration no.: NCT04691271 (ClinicalTrials.gov).

Vasospasm risk following aneurysmal subarachnoid hemorrhage in older adults.

OBJECTIVE: Cerebral arterial vasospasm is a dreaded sequela of aneurysm rupture and can result in significant narrowing of the surrounding vasculature and subsequent cerebral ischemia. Treatment interventions are associated with distinct side effect profiles, including the risk of thrombosis and worsened ischemia, which may be associated with increased mortality-especially in older adults. An improved understanding of the likelihood of vasospasm in elderly patients would enable clinicians and patients to better consider the risks and benefits of vasospasm prophylaxis in this vulnerable population. This retrospective chart review aimed to assess the relationship between age at onset and the incidence of cerebral vasospasm among patients treated at the University of North Carolina Medical Center with spontaneous aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Electronic health record data from the Epic Systems Corp. database, compiled by the Carolina Data Warehouse for Health, were analyzed for patients older than 18 years who were previously treated for an SAH secondary to aneurysm at the University of North Carolina Medical Center within the past 10 years, ranging from June 2011 through June 2021. Logistic regression was used to calculate odds ratios and to determine the association of age with the occurrence of vasospasm following aSAH. RESULTS: Of the 386 cases analyzed, 149 patients (38.6%) were older than 65 years at the time of aSAH. A total of 192 of the 386 patients (49.7%) developed vasospasm within the first 3-21 days following aSAH. Among the patients who developed vasospasm, only 31 of 192 patients (16.1%) were older than 65 years at the time of aneurysm rupture. Odds ratio calculations revealed that older adults (> 65 years) were 8 times less likely to develop vasospasm compared to their younger counterparts (p < 0.0001; 95% CI 5.0-13.0). CONCLUSIONS: This study found that older patients are less likely to develop cerebral vasospasm following aSAH than are younger individuals. Age-associated changes in arteriosclerosis, inflammatory responses, and CSF dynamics may mitigate vascular narrowing in response to aSAH. This finding suggests that the aSAH treatment and vasospasm prevention paradigms should be revised to minimize potentially unnecessary interventions and avoid adverse outcomes for older adults.

Impact of Early Out-of-Bed Mobilization on Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cohort Study.

BACKGROUND: Effects of early mobilization are not well documented in patients with aneurysmal subarachnoid hemorrhage (aSAH). Only a few studies have investigated it through progressive mobilization protocols and suggested that it is safe and feasible. This study aimed to determine the impact of early out-of-bed mobilization (EOM) on 3-month functional outcome and cerebral vasospasm (CVS) occurrence in patients with aSAH. METHODS: A retrospective review of consecutive patients admitted to the intensive care unit with a diagnosis of aSAH was performed. EOM was defined as out-of-bed (OOB) mobilization performed before or on day 4 after aSAH onset. The primary outcome was 3-month functional independence (i.e., a modified Rankin Scale below 3) and the occurrence of CVS. RESULTS: A total of 179 patients with aSAH met the inclusion criteria. Thirty-one patients constituted the EOM group, and 148 patients were in the delayed out-of-bed mobilization group. Functional independence was more frequent in the EOM group than in the delayed out-of-bed mobilization group (n = 26 [84%] vs. n = 83 [56%], P = 0.004). In a multivariable analysis, EOM was an independent predictor of functional independence (adjusted odds ratio = 3.11; 95% confidence interval, 1.11-10.36; P < 0.05). The delay between bleeding and first OOB mobilization was also identified as an independent risk factor for the occurrence of CVS (adjusted odds ratio = 1.12; 95% confidence interval = 1.06-1.18, P < 0.001). CONCLUSIONS: EOM was independently associated with favorable functional outcome after aSAH. The delay between bleeding and OOB mobilization was an independent risk factor for reduced functional independence and CVS occurrence. Prospective randomized trials are necessary to confirm these results and improve clinical practice.

Incidence and Prediction of Chronic Depression Following Aneurysmal Subarachnoid Hemorrhage: A Single-Center 17-Year Experience.

OBJECTIVE: The incidence and risk factors for chronic depression after aneurysmal subarachnoid hemorrhage (aSAH) are described. METHODS: Patients with aSAH treated at a single institution (January 1, 2003-December 31, 2019) and a modified Rankin Scale score ≤3 at follow-up who were evaluated for chronic depression were analyzed. Chronic depression was defined using a depression screening questionnaire as ≥5 positive answers for symptoms lasting >2 weeks. A predictive model was designed for the primary outcome of depression. RESULTS: Among 1419 patients with aSAH, 460 patients were analyzed; 130 (28%) had major depressive disorder. Mean follow-up was >6 years. Higher depression rates were associated with tobacco smoking (odds ratio [OR] = 2.64, P < 0.001), illicit drug use (OR = 2.35, P = 0.007), alcohol use disorder (1.92, P = 0.04), chronic obstructive pulmonary disease (COPD) (OR=2.68, P = 0.03), and vasospasm requiring angioplasty (OR=2.09, P = 0.048). The predictive model included tobacco smoking, illicit drug use, liver disease, COPD, diabetes, nonsaccular aneurysm type, anterior communicating artery or anterior cerebral artery aneurysm location, refractory spasm requiring angioplasty, and a modified Rankin Scale score at discharge of >1 (P ≤ 0.03). The model performed with appropriate goodness of fit and an area under the receiver operator curve of 0.70 for depression. Individual independent predictors of depression were tobacco smoking, COPD, diabetes, and nonsaccular aneurysm. CONCLUSIONS: A substantial percentage of patients had symptoms of depression on follow-up. The proposed predictive model for depression may be a useful clinical tool to identify patients at high risk for developing depression who warrant early screening and evaluation.

Risk factors associated with vasospasm after non-traumatic subarachnoid hemorrhage: a retrospective analysis of 456 patients.

BACKGROUND: The pathophysiology of vasospasm (VS) after non-traumatic subarachnoid hemorrhage is not completely understood. Several risk factors associated with VS were previously reported, partially with conflicting results. The aim of this study was to identify patients at increased risk for VS. METHODS: Retrospective analysis of data from all patients treated in our institutional intensive care unit (ICU) between 2010 and 2016 after non-traumatic subarachnoid hemorrhage. Possible contributing factors for VS studied were: age, sex, aneurysm-localization, treatment option, ICU-stay, ICU mortality, pre-existing condition, medication history, World Federation of Neurosurgical Societies (WFNS) grading system, modified Fisher scale. RESULTS: We obtained data from 456 patients. 184 were male and 272 female patients, respectively. Mean age was 57.7±13.9 and was not different between sexes. In 119 patients, VS was diagnosed after subarachnoid hemorrhage. Incidence of VS was not different between sexes (male: 22.3%, female: 28.7%, P=0.127). Patients with VS were significantly younger (mean age 52.2 vs. 59.7, P<0.001), meanwhile patients aged 36-40 yrs. had the highest incidence of VS. Most VS were found after rupture of middle cerebral artery-aneurysms. Higher incidence of VS was found after aneurysm clipping compared to coiling. VS developed more often in patients with more severe WFNS grade and Fisher scale. In multivariate analysis, age, previous drug abuse and history of anticoagulants were associated with the incidence of VS. CONCLUSIONS: Younger age, middle cerebral artery-aneurysms, aneurysm clipping, previous drug abuse and history of anticoagulants were associated with a higher incidence of VS after non-traumatic subarachnoid hemorrhage. No gender difference was found.

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.

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.

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.

Treatment during cerebral vasospasm phase-complication association and outcome in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Aneurysm treatment during cerebral vasospasm (CVS) phase is frequently considered as particularly dangerous, mainly because of the risk of cerebral infarct. OBJECTIVE: We aimed to evaluate the risk of aneurysmal subarachnoid haemorrhage (aSAH)-specific complications and functional outcome in patients treated during CVS phase. METHODS: We retrospectively analysed a large, retro- and prospectively collected database of aSAH patients admitted to our department between March 2006 and March 2020. We conducted a uni- and multivariable logistic regression analysis to evaluate influencing factors on rebleeding, cerebral infarct, Glasgow Outcome Score (GOS) at discharge and mortality and assessed the rate of angiographic vasospasm on admission. RESULTS: We included 853 patients. The majority of patients were female (66.6%), mean age was 57.3 years. Out of 853 included patients, 92 (10.8%) were treated during CVS phase, 312 (36.6%) underwent clipping and 541 (63.4%) endovascular treatment. Treatment during CVS phase was significantly associated with cerebral infarct in the multivariable logistic regression analysis, unrelated to the nature of intervention (OR 2.42, 1.29-4.54 95% CI p-value = 0.006). However, patients treated during CVS phase did not have increased risk of unfavourable outcome by GOS on discharge. In addition, they did not have a higher rate of rebleeding or mortality. CONCLUSIONS: Treatment during CVS phase was significantly associated with a higher rate of cerebral infarct as confirmed by imaging. This did not reflect on GOS on discharge, rebleeding, or mortality. Aneurysm treatment during CVS phase is relatively safe and should not be postponed due to the risk of rebleeding and subsequent devastating deterioration.

Factors associated with increased inpatient charges following aneurysmal subarachnoid hemorrhage with vasospasm: A nationwide analysis.

BACKGROUND: Cerebral vasospasm, following aneurysmal subarachnoid hemorrhage (aSAH), can have high-cost implications for inflicted individuals and their families. To our knowledge, factors associated with high inpatient charges have not been explored. We aimed to address this gap. METHODS: The National Inpatient Sample (NIS) was queried between 2016 and 2018 to identify patients with vasospasm following aSAH. Patients in the upper quartile of charges were identified and analyzed using univariate and multivariate analyses for significant contributing variables. RESULTS: We identified 1861 patients with aSAH complicated by vasospasm. Multivariate analysis revealed ten statistically significant variables as independent risk factors in association with higher charges. Patients were more likely to be in the upper quartile of charge when younger (OR 0.99 [0.99-0.98]; p < 0.01), a never smoker (OR 1.38 [1.04-1.83]; p < 0.05), concurrent congestive heart failure (OR 1.63 [1.05-2.54]; p < 0.05), requiring VP shunt placement (OR 2.29 [1.68-3.14]; p < 0.001) or tracheostomy (OR 3.05 [2.22-4.18]; p < 0.001), on mechanical ventilation (OR 1.90 [1.40-2.58]; p < 0.001), paralysis (OR 1.34 [1.04-1.74]; p < 0.05) or neurological deficit (OR 1.59 [1.24-2.03]; p < 0.001) as a complication, and being Hispanic (OR 1.89 [1.36-2.64]; p < 0.001) or "other" (OR 1.76 [1.08-2.88]; p < 0.05) for race. CONCLUSION: Our study elucidates several factors, from certain demographics and requiring adjunctive mechanical support to several procedures, that may contribute to the high-cost implications faced by aSAH patients suffering vasospasm. While many of these factors may not be unexpected, further research is warranted to help elucidate controllable factors and develop trials to identify early interventions to reduce the financial burden on such patients.

Primary angiitis of the central nervous system and reversible cerebral vasoconstriction syndrome: analysis of the National Inpatient Sample.

INTRODUCTION: Primary angiitis of the central nervous system (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS) are two rare syndromes that affect the cerebral vasculature. Both conditions have been shown to cause severe neurologic complications. Distinguishing these two conditions in clinical practice is often challenging. Here, we compare the clinical features and outcomes of RCVS and PACNS hospitalizations against the general adult inpatient population. MATERIALS AND METHODS: We conducted a retrospective review of hospitalizations with a diagnosis of PACNS or RCVS from 2016 to 2018 in the National Inpatient Sample (NIS) database. Multivariate analysis was performed to calculate adjusted odds ratios (ORadj) for hospital outcomes. RESULTS: In the NIS, 3305 hospitalizations had a diagnosis of RCVS and 6035 hospitalizations had a diagnosis of PACNS. RCVS hospitalizations had a significantly greater association with cerebral aneurysms (ORadj 23.80), hemiplegia/hemiparesis following subarachnoid hemorrhage (SAH) (ORadj 324.09), ischemic stroke (ORadj 7.59), and nontraumatic SAH (ORadj 253.61). PACNS hospitalizations had a significantly greater association with hemiplegia/hemiparesis following cerebrovascular accident (CVA) (ORadj 6.16), ischemic stroke (ORadj 11.55), nontraumatic SAH (ORadj 7.29), seizure (ORadj 2.49), and in-hospital mortality (ORadj 2.85). CONCLUSIONS: We performed an analysis of the NIS to better understand RCVS and PACNS hospitalizations. Severe neurologic events including CVA and SAH were elevated in both, but SAH and related hemiplegia/hemiparesis were extremely common among RCVS hospitalizations. In-hospital mortality was elevated in PACNS but not RCVS. This information can be used to help clinicians better understand, distinguish, and diagnose these conditions. Key Points • Despite clear description of RCVS and PACNS in the medical literature, there remains a scarcity of national population-based studies comparing these two entities against the general adult inpatient population. • This study aims to fill knowledge gaps in this area. • Here, we compare the clinical features and outcomes of RCVS and PACNS hospitalizations against the general adult inpatient population.

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.