Clinical prediction models for aneurysmal subarachnoid hemorrhage: a systematic review update.

BACKGROUND: A systematic review of clinical prediction models for aneurysmal subarachnoid hemorrhage (aSAH) reported in 2011 noted that clinical prediction models for aSAH were developed using poor methods and were not externally validated. This study aimed to update the above review to guide the future development of predictive models in aSAH. METHODS: We systematically searched Embase and MEDLINE databases (January 2010 to February 2022) for articles that reported the development of a clinical prediction model to predict functional outcomes in aSAH. Our reviews are based on the items included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) checklist, and on data abstracted from each study in accord with the Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) 2014 checklist. Bias and applicability were assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST). RESULTS: We reviewed data on 30 466 patients contributing to 29 prediction models abstracted from 22 studies identified from an initial search of 7858 studies. Most models were developed using logistic regression (n=20) or machine learning (n=9) with prognostic variables selected through a range of methods. Age (n=13), World Federation of Neurological Surgeons (WFNS) grade (n=11), hypertension (n=6), aneurysm size (n=5), Fisher grade (n=12), Hunt and Hess score (n=5), and Glasgow Coma Scale (n=8) were the variables most frequently included in the reported models. External validation was performed in only four studies. All but one model had a high or unclear risk of bias due to poor performance or lack of validation. CONCLUSION: Externally validated models for the prediction of functional outcome in aSAH patients have now become available. However, most of them still have a high risk of bias.

What are the predictors of delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage? An up-to-date systematic review.

PURPOSE: Delayed Cerebral Ischaemia (DCI) remains an important preventable driver of poor outcome in aneurysmal subarachnoid haemorrhage (aSAH). Our ability to predict DCI is based on historical patient cohorts, which use inconsistent definitions for DCI. In 2010, a definition of DCI was agreed upon and published by a group of aSAH experts. The aim of this study was to identify predictors using this agreed definition of DCI. METHODS: We conducted a literature search of Medline (PubMed) to identify articles published since the publication of the 2010 consensus definition. Risk factors and prediction models for DCI were included if they: (1) adjusted for confounding factors or were derived from randomised trials, (2) were derived from prospectively collected data and (3) included adults with aSAH. The strength of studies was assessed based on quality, risk of bias and applicability of studies using PROBAST. RESULTS: Eight studies totalling 4,542 patients were included from 105 relevant articles from 4,982 records. The most common reason for not including studies was failure to use the consensus definition of DCI (75%). No prediction models were identified in the eligible studies. Significant risk factors for DCI included the presence of onsite neuro-interventional services, high Neuropeptide Y, admission leucocytosis, neutrophil:lymphocyte >5.9 and Fisher Grade > 2. All studies had a high or unclear risk of bias. CONCLUSIONS: Only a few studies with high risk of bias have investigated the predictors using consensus-defined DCI. Further studies are warranted to clarify risk factors of DCI in the modern era.

Aneurysm management in patients over 80 years old with good grade subarachnoid haemorrhage.

BACKGROUND: An increasing proportion of aneurysmal subarachnoid haemorrhage (aSAH) occurs in older patients, in whom there is widespread variability in treatment rates due to a different balance of risks. Our aim was to compare outcomes of patients over 80 years old with good grade aSAH who underwent treatment of their aneurysm with those who did not. METHODS: Adult patients with good grade aSAH admitted to tertiary regional neurosciences centres contributing to the UK and Ireland Subarachnoid Haemorrhage Database (UKISAH) and a cohort of consecutive patients admitted from three regional cohorts were included for analysis. Outcomes were functional outcome at discharge, three months and survival at discharge. RESULTS: In the UKISAH, patients whose aneurysm was treated were more likely to have a favourable outcome at discharge (OR 2.34, CI 1.12-4.91, p = .02), at three months (OR 2.29, CI 1.11-4.76, p = .04), and lower mortality (10% vs. 29%, OR 0.83, CI 0.72-0.94, p < .01). In the regional cohort, a similar pattern was seen, but after correction for frailty and comorbidity there was no difference in survival (HR 0.45, CI 0.12-1.68, p = .24) or favourable outcome at discharge (OR 0.83, CI 0.23-2.94, p = .77) and at three months (OR 1.03, CI 0.25-4.29, p = .99). CONCLUSIONS: Better early functional outcomes in those undergoing aneurysm treatment appear to be explained by differences in frailty and comorbidity. Therefore, treatment decisions in this patient group are finely balanced with no clear evidence overall of either benefit or harm in this cohort.

Simple endovascular coiling: An effective long-term solution for wide-necked ruptured middle cerebral artery aneurysms? A 10-years retrospective study.

BACKGROUND: Endovascular coiling is usually the first line treatment modality for most ruptured intracranial aneurysms. However, there is still some debate as to whether microsurgical clipping or coiling is the treatment of choice for complex wide-necked ruptured middle cerebral artery (MCA) aneurysms. Our aim was to assess the efficacy, safety and longevity of simple endovascular coiling for ruptured MCA aneurysms. METHODS: This was a single-centre 10 years retrospective study (2008-2019) of all endovascularly treated patients with ruptured MCA aneurysms (n = 148). Patients were treated with simple coiling (n = 111), balloon-assisted coiling (n = 13), dual micro-catheter coiling (n = 19), balloon-assisted and dual micro-catheter coiling (n = 4) and woven endobridge (WEB) device (n = 1). The standard follow-up protocol consisted of Magnetic Resonance angiography at 6, 12 and 24 months. Our primary endpoints were mortality at 2, 12 and 24 months and dependency at discharge. Secondary endpoints included aneurysm occlusion, complications, re-canalisation, rebleeding and retreatment rates. RESULTS: All-cause mortality at 2, 12 and 24 months was 4.7% (n = 7), 8.1% (n = 12) and 10.8% (n = 16), respectively. 81.3% of patients remained independent in activities of daily livings (ADLs) at the point of discharge. Over a mean follow-up period of 19.7 months, we demonstrated re-bleeding and re-treatment rates of 2.7% (n = 4) and 4.1% (n = 6) respectively. Complete occlusion was achieved in 54% (n = 79) of aneurysms, with recanalisation observed in 18.2% (n = 27) of the patients. CONCLUSIONS: Our results demonstrate that simple endovascular coiling techniques offer a safe and effective solution in the management of ruptured MCA aneurysms without the requirement for re-treatment either surgically or endovascularly using endoluminal stents or other devices.

Radiologically defined acute hydrocephalus in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Ventriculomegaly is common in aneurysmal subarachnoid haemorrhage (aSAH). An imaging measure to predict the need for cerebrospinal fluid (CSF) diversion may be useful. The bicaudate index (BCI) has been previously applied to aSAH. Our aim was to derive and test a threshold BCI above which CSF diversion may be required. METHODS: Review of prospective registry. The derivation group (2009-2015) included WFNS grade 1-2 aSAH patients who deteriorated clinically, had a repeat CT brain and underwent CSF diversion. BCI was measured on post-deterioration CTs and the lower limit of the 95% confidence interval (95%CI) was the hydrocephalus threshold. In a separate test group (2016), in WFNS ≥ 2 patients, we compared BCI on diagnostic CTs with CSF diversion within 24 hours. RESULTS: The derivation group (n = 62) received an external ventricular (n = 57, 92%) or lumbar drain (n = 5, 8%). Mean post-deterioration BCI was 0.19 (95%CI 0.17-0.22) for age ≤49 years, 0.22 (95%CI 0.20-0.23) for age 50-64 years and 0.24 (95%CI 0.22-0.27) for age ≥65 years. Hydrocephalus thresholds were therefore 0.17, 0.20 and 0.22, respectively. In the test group (n = 105), there was no significant difference in BCI on the diagnostic CT between good and poor grade patients aged ≤49 years (p = 0.31) and ≥65 years (p = 0.96). 30/66 WFNS ≥ 2 patients underwent CSF diversion, although only 15/30 (50%) exceeded BCI thresholds for hydrocephalus. CONCLUSION: A significant proportion of aSAH patients may undergo CSF diversion without objective evidence of hydrocephalus. Our threshold values require further testing but may provide an objective measure to aid clinical decision making in aSAH.

The self-reported needs of patients following subarachnoid hemorrhage (SAH).

Background: Despite advances in the acute care of subarachnoid haemorrhage, longer-term services remain under-developed. Clinical measures are commonly used to assess outcome and quality of life, but patient-reported needs and the extent to which they are met have not been measured. This information is essential to plan and develop evidence-based, patient-centred services. The aim of this study was to describe the frequency and type of self-reported met and unmet needs of subarachnoid haemorrhage survivors, explore whether these differ early and late in recovery and the factors associated with whether needs were met.Methods: A census cross-sectional postal survey of 400 subarachnoid haemorrhage survivors discharged from a large neurosurgical unit. The Self-Reported Needs after Stroke Questionnaire was modified and used to measure the self-reported needs of subarachnoid haemorrhage survivors and the extent to which they were met 1-2 years and 3-5 years post haemorrhage.Results: 203 (51%) participants responded: 122/260 (47%) from the early and 81/143 (57%) from the late cohort. 63% were female; mean age was 55 years. 86% of survivors reported one or more need, and 78% reported at least one unmet need (median 6, range 1-19). The most commonly reported need related to fatigue (66%). This and several other health needs were reported as unmet in over 80% of identified cases. We found no consistent factors that were associated with needs remaining unmet.Conclusion: Most subarachnoid haemorrhage survivors in both cohorts had unmet needs. Future research should aim to inform the development of post-discharge services to address the persistent long-term needs identified.Implications for rehabilitationSubarachnoid haemorrhage survivors report a number of needs 1-2 years and 3-5 years post haemorrhage.Needs relating to fatigue, memory, concentration, headache and anxiety were the most commonly reported.A large proportion of needs were described as unmet.The design of rehabilitation services for subarachnoid haemorrhage survivors should consider the self-reported needs described in this study.

CT angiogram negative perimesencephalic subarachnoid hemorrhage: is a subsequent DSA necessary? A systematic review.

BACKGROUND: Perimesencephalic subarachnoid hemorrhage (PMSAH) is a benign subtype with distinct clinical-radiologic features. Digital subtraction angiography (DSA) remains the gold standard investigation for exclusion of a macrovascular cause, although increasingly more clinicians rely solely on CT angiography (CTA). The primary aim of this systematic review was to evaluate the current literature regarding the negative predictive value of CTA. METHODS: A systematic search in concordance with the PRISMA checklist was performed for studies published between 2000 and 2018. Studies with ≥10 adult patients diagnosed on a non-contrast brain CT with a PMSAH, who underwent a negative CTA and were subsequently subject to a DSA, were included. Simple pooled analysis was performed to inform the negative predictive value (95% CI) of CTA and the risk of DSA- and CTA-related complications. RESULTS: Eighteen studies (669 patients) were included. All patients were subject to at least one DSA, the first one mostly performed within 24 hours of CTA (68.6%). 144 patients (21.5%) underwent a second DSA and a third repeat DSA was performed in one patient. The overall negative predictive value of CTA was 99.0% (95% CI 97.8% to 99.5%). The risk of complications following DSA and CTA were 1.35% (3/222) and 0% (0/41), respectively. CONCLUSIONS: Undertaking a DSA after a negative CTA may not add any further diagnostic value in patients with PMSAH and may lead to net harm. This observation needs to be validated in a large-scale prospective multicenter study with complete case ascertainment and robust data on CTA and DSA complications.

Predictors of Outcome in Aneurysmal Subarachnoid Hemorrhage Patients: Observations From a Multicenter Data Set.

BACKGROUND AND PURPOSE: The mortality and morbidity after aneurysmal subarachnoid hemorrhage has improved because of better diagnosis, early treatment to secure the aneurysm, and better management of disease-specific complications. With these improvements in care, it is not clear if the previously identified independent predictors of a negative outcome have changed. The aim of this study was to identify the independent predictors of an unfavorable outcome (Glasgow Outcome Score 1, 2, and 3) in aneurysmal subarachnoid hemorrhage patients. METHODS: Univariate and multivariate analysis of prospectively collected data on patients presenting with an aneurysmal subarachnoid hemorrhage was performed. Outcome was assessed at discharge. Data were collected from 14 centers in the United Kingdom over a period of 4 years (September 2011-2015). RESULTS: The median age (interquartile range) at presentation of 3341 patients with aneurysmal subarachnoid hemorrhage was 55 (18) years. Most patients were female (n=2288 [68.5%]), presented in good grade (2397 [70%]; World Federation of Neurological Surgeons grade 1 and 2), and were treated by endovascular coiling (n=2600; 75%). The independent predictors of an unfavorable outcome (95% confidence interval [CI]) were increasing age (odds ratio [OR], 1.04; 95% CI, 1.03-1.05; P<0.001), World Federation of Neurological Surgeons grade (OR, 2.06; 95% CI, 1.91-2.22; P<0.001), preoperative rebleeding (OR, 7.41; 95% CI, 4.48-12.30; P<0.001), need for cerebrospinal fluid diversion (OR, 3.25; 95% CI, 2.58-4.09; P<0.001), and delayed cerebral ischemia (OR, 2.21; 95% CI, 1.72-2.83; P<0.001). CONCLUSIONS: These data suggest that potentially modifiable risk factors of preoperative rebleeding and delayed cerebral ischemia are associated with unfavorable outcomes. Understanding the reasons why patients requiring cerebrospinal fluid diversion have 3.25-fold higher adjusted odds of a poor outcome at discharge needs to be studied.

Effect of weekend admission on in-hospital mortality and functional outcomes for patients with acute subarachnoid haemorrhage (SAH).

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is an acute cerebrovascular event with high socioeconomic impact as it tends to affect younger patients. The recent NCEPOD study looking into management of aSAH has recommended that neurovascular units in the United Kingdom should aim to secure cerebral aneurysms within 48 h and that delays because of weekend admissions can increase the mortality and morbidity attributed to aSAH. METHOD: We used data from a prospective audit of aSAH patients admitted between January 2009 and December 2011. The baseline demographic and clinical features of the weekend and weekday groups were compared using the chi-squared test and T-test. Cox proportional hazards models (Proc Phreg in SAS) were used to calculate the adjusted overall hazard of in-hospital death associated with admission on weekend, adjusting for age, sex, baseline WFNS grade, type of treatment received and time from scan to treatment. Sliding dichotomy analysis was used to estimate the difference in outcomes after SAH at 3 months in weekend and weekday admissions. RESULTS: Those admitted on weekends had a significantly higher scan to treatment time (83.05 ± 83.4 h vs 40.4 ± 53.4 h, P < 0.0001) and admission to treatment (71.59 ± 79.8 h vs 27.5 ± 44.3 h, P < 0.0001) time. After adjustments for adjusted for relevant covariates weekend admission was statistically significantly associated with excess in-hospital mortality (HR = 2.1, CL [1.13-4.0], P = 0.01). After adjustments for all the baseline covariates, the sliding dichotomy analysis did not show effects of weekend admission on long-term outcomes on the good, intermediate and worst prognostic bands. CONCLUSIONS: This study provides important data showing excess in-hospital mortality of patients with SAH on weekend admissions served by the United Kingdom's National Health Service.; However, there were no effects of weekend admission on long-term outcomes.

Pre-protection re-haemorrhage following aneurysmal subarachnoid haemorrhage: Where are we now?

BACKGROUND: Re-haemorrhage is a negative, prognostic predictor of outcome in aneurysmal subarachnoid haemorrhage (aSAH). The process of aSAH care has changed however, and most reports on re-haemorrhage are from a time when aneurysms were treated predominantly by open microneurosurgery. The current frequency and impact of re-haemorrhage on outcome in the 'post-ISAT' era is therefore unknown. The aim of this study was to review current outcome, risk factors and causes for inpatient re-haemorrhage in aSAH patients. METHOD: The departmental aSAH database was reviewed between Jan 2008 and March 2014 (N = 1008) to identify cases of re-haemorrhage. Re-haemorrhage was defined as inhospital deterioration in neurological status with CT confirmation of rebleeding. Binary logistic regression was used to (a) determine the impact of re-haemorrhage on outcome adjusted for age and injury severity and (b) to identify any independent predictors of its occurrence. RESULTS: Re-haemorrhage occurred in 55 (5.4%) of patients and most cases had occurred within 24h of ictus (32, 58.1%). Re-haemorrhage was an independent predictor of death (AOR 10.0, p < 0.0005, 95%CI 4.9, 20.2) and unfavourable outcome (AOR 5.8 p < 0.0005, 95%CI 2.4, 14.0). Only WFNS grade on admission was an independent predictor (AOR 1.7, p < 0.0005, 95%CI 1.4, 1.9) of re-haemorrhage. Of the patients who re-bled, in 20 there was no intention to treat due to severe brain injury and in the remainder, the majority occurred early (<24h) (19/35, 54%), or had complicated aneurysm morphology (10/35, 31%) which necessitated a delayed treatment strategy. CONCLUSIONS: Re-haemorrhage remains a poor prognostic predictor in aSAH and the grade of SAH is an independent risk factor. Earlier treatment of complex aneurysms could offer the most immediate improvements in its incidence.

Impact of specialist neurovascular care in subarachnoid haemorrhage.

BACKGROUND: The management of neurosurgical disorders has become increasingly specialised. The care of patients with subarachnoid haemorrhage (SAH) has generally been part of core neurosurgical practice, provided by general neurosurgeons whatever their specialist interest. The aim of this present study therefore is to ascertain if, and to what extent care provided by a dedicated neurovascular team (compared to care provided by a general neurosurgical team) change patient disposition in SAH. METHODS: This is a retrospective analysis of SAH patients, identified from a departmental database of a single neurosurgical centre. In 2008, the service was reorganised such that a neurovascular team cared for all SAH patients. We compared clinical outcome in people admitted prior to this service reorganisation (Period A, 2004-2007) with patients admitted afterwards (Period B, 2009-2011). Survival and recovery were assessed according to the Glasgow Outcome Scale (GOS). Multi-factorial logistic regression analysis was performed to determine the injury and age adjusted incidence of complications, odds of survival at discharge, discharge home, mortality, good recovery (GOS 5) and favourable outcome, by dichotomising GOS (GOS 4-5 vs. GOS 1-3) at 3 months. RESULTS: 1114 patients were included in the study. The mean age of patients presenting in Period A (n = 543) was younger [50 years (SD 13.5)] than those in Period B (n = 571) [53 years (SD 13)]. Patients admitted in Period B were more likely to present as poor grade (World Federation of Neurological surgeons (WFNS) grades 4 and 5) compared to Period A (26.5% vs. 21.3%). No statistical differences between the groups in the incidence of pre-operative re-bleeding (3% vs. 5%) or rates of delayed cerebral ischaemia (16.1% vs. 16.1%) were observed. After adjustment for age, sex and injury severity, the odds of patient time to discharge, discharge home and good recovery (GOS 5) were 27% (p < 0.001), 45% (p = 0.001) and 93% (p < 0.001) higher respectively in Period B than Period A. CONCLUSIONS: The data presented here demonstrates that management of SAH by a dedicated neurovascular team improves the potential for patient recovery.