The outcomes measured and reported in observational studies of incidental and untreated intracranial meningioma: A systematic review.

Background: The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies. Methods: A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative. Results: Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n = 27 and prospective n = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas. Conclusions: Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies.

The outcomes measured and reported in intracranial meningioma clinical trials: A systematic review.

Background: Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials. Methods: Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative. Results: Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n = 33, phase 3 n = 14. Common interventions included: Surgery n = 13, radiotherapy n = 8, and pharmacotherapy n = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas. Conclusions: Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials.

Risk factor synergism in aneurysmal subarachnoid hemorrhage: a cross-sectional study.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) accounts for 5-10% of strokes but a disproportionately large amount of stroke-related morbidity. Several risk factors have been described, including smoking, hypertension, increasing age, and female sex. METHODS: This cross-sectional study examined all patients with aSAH within a nationally representative catchment from 01/01/2017 to 31/12/2020. Patients with aneurysmal SAH were identified from multiple sources, including a prospective database and death records. The population was estimated from projections from a door-to-door census and risk factors from stratified random sampled surveys conducted on a yearly basis. Poisson regression models were used to estimate the incidence and incidence rate ratios (IRRs) for risk factors with 95% confidence intervals (95% CIs). RESULTS: We identified 875 cases of aSAH in 11,666,807 patient-years of follow-up, which corresponded to a crude incidence of 7.5 per 100,000 patient-years (95% CI 7-8) and a standardized incidence of 6.1/100,000 (95% CI 5.6-6.5). Smoking was the strongest individual risk factor, with a standardized incidence of 24/100,000 (95% CI 20-27) in smokers compared with 2.6/100,000 (2.1-3.2) in non-smokers (age-adjusted IRR 9.2, 95% CI 6.3-13.6). Hypertension (age-adjusted IRR 3.1, 95% CI 2.2-4.3) and female sex (age-adjusted IRR 1.8, 95% CI 1.4-2.3) were also associated with increased incidence. The highest incidence was observed in hypertensive smokers (standardized incidence 63/100,000, 95% CI 41-84), who had a lifetime risk of aSAH of 6.7% (95% CI 5.4-8.1) after age 35. Compared with participants who were non-smokers without hypertension, the age-adjusted IRR in hypertensive smokers was 27.9 (95% CI 15.9-48.8). CONCLUSION: Smoking is the most prominent individual risk factor for aSAH. Smoking and hypertension appear to interact to increase the risk of aSAH synergistically.

Meningioma in the elderly.

Meningiomas are the most common primary intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. The incidence of meningioma increases with age to 50 per 100,000 in patients older than 85. As the population ages, an increasing proportion of meningioma patients are elderly. Much of this increase is accounted for by an increase in incidental, asymptomatic diagnoses, which have a low risk of progression in the elderly. The first-line treatment of symptomatic disease is resection. Fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) can be considered as primary treatment where surgery is not feasible, or as adjuvant therapy in cases of subtotal resection or high grade histopathology. The role of RT/SRS, particularly following gross total resection of atypical meningioma, is unclear and requires further evaluation. There is an increased risk of perioperative and postoperative morbidity in the elderly and therefore management decisions must be tailored to individual circumstances. Good functional outcomes can be achieved in selected patients and age alone is not a contraindication to intervention. The immediate postoperative course is an important determinant of prognosis. Therefore, careful preoperative evaluation and avoidance of complications are necessary to optimize outcomes.

Multi-layered repair of high-flow CSF fistulae following endoscopic skull base surgery without nasal packing or lumbar drains: technical refinements to optimise outcome.

AIMS: Post-operative CSF leak remains a significant problem following endoscopic skull base surgery, particularly when there is a high-flow intra-operative CSF leak. Most skull base repair techniques are accompanied by the insertion of a lumbar drain and/or the use of nasal packing which have significant shortcomings. Our aim was to review the results of a large series of endoscopic skull base cases where a high-flow intra-operative CSF leak rate was encountered and repaired to assess if modifications in technique could reduce the post-operative CSF leak rate. METHODS: A retrospective review of a prospectively maintained database of skull base cases performed by a single surgeon over a 10-year period was performed. Data regarding patient demographics, underlying pathology, skull base repair techniques and post-operative complications were analysed. RESULTS: One hundred forty-two cases with high-flow intra-operative CSF leak were included in the study. The most common pathologies were craniopharyngiomas (55/142, 39%), pituitary adenomas (34/142, 24%) and meningiomas (24/142, 17%). The CSF leak rate was 7/36 (19%) when a non-standardised skull base repair technique was used. However, with the adoption of a standardised, multi-layer repair technique, the post-operative CSF leak rate decreased significantly (4/106, 4% vs. 7/36, 19%, p = 0.006). This improvement in the rate of post-operative CSF leak was achieved without nasal packing or lumbar drains. CONCLUSION: With iterative modifications to a multi-layered closure technique for high-flow intra-operative CSF leaks, it is possible to obtain a very low rate of post-operative CSF leak, without lumbar drains or nasal packing.

The shrinking vestibular schwannoma.

We present a case of spontaneous 79% regression in the size of a vestibular schwannoma (VS). A 41-year-old lady with a large (36 mm) vestibular schwannoma underwent serial follow-up MRI scans which demonstrated the shrinkage over 9 years; the highest relative spontaneous regression recorded in the literature for vestibular schwannoma of this size.

Management of Chronic Subdural Hematoma: A Systematic Review and Component Network Meta-analysis of 455 Studies With 103 645 Cases.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical condition with a high risk of recurrence after treatment. OBJECTIVE: To assess and compare the risk of recurrence, morbidity, and mortality across various treatments for CSDH. METHODS: A systematic review and meta-analysis was performed. PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched from January 01, 2000, to July 07, 2021. The primary outcome was recurrence, and secondary outcomes were morbidity and mortality. Component network meta-analyses (CNMAs) were performed for surgical and medical treatments, assessing recurrence and morbidity. Incremental risk ratios (iRRs) with 95% CIs were estimated for each component. RESULTS: In total, 12 526 citations were identified, and 455 studies with 103 645 cases were included. Recurrence occurred in 11 491/93 525 (10.8%, 95% CI 10.2-11.5, 418 studies) cases after surgery. The use of a postoperative drain (iRR 0.53, 95% CI 0.44-0.63) and middle meningeal artery embolization (iRR 0.19, 95% CI 0.05-0.83) reduced recurrence in the surgical CNMA. In the pharmacological CNMA, corticosteroids (iRR 0.47, 95% CI 0.36-0.61) and surgical intervention (iRR 0.11, 95% CI 0.07-0.15) were associated with lower risk. Corticosteroids were associated with increased morbidity (iRR 1.34, 95% CI 1.05-1.70). The risk of morbidity was equivalent across surgical treatments. CONCLUSION: Recurrence after evacuation occurs in approximately 10% of cSDHs, and the various surgical interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials.

Prevalence of incidental intracranial findings on magnetic resonance imaging: a systematic review and meta-analysis.

BACKGROUND: As the volume and fidelity of magnetic resonance imaging (MRI) of the brain increase, observation of incidental findings may also increase. We performed a systematic review and meta-analysis to determine the prevalence of various incidental findings. METHODS: PubMed/MEDLINE, EMBASE and SCOPUS were searched from inception to May 24, 2021. We identified 6536 citations and included 35 reports of 34 studies, comprising 40,777 participants. A meta-analysis of proportions was performed, and age-stratified estimates for each finding were derived from age-adjusted non-linear models. RESULTS: Vascular abnormalities were observed in 423/35,706 participants (9.1/1000 scans, 95%CI 5.2-14.2), ranging from 2/1000 scans (95%CI 0-7) in 1-year-olds to 16/1000 scans (95%CI 1-43) in 80-year-olds. Of these, 204/34,306 were aneurysms (3.1/1000 scans, 95%CI 1-6.3), which ranged from 0/1000 scans (95%CI 0-5) at 1 year of age to 6/1000 scans (95%CI 3-9) at 60 years. Neoplastic abnormalities were observed in 456/39,040 participants (11.9/1000 scans, 95%CI 7.5-17.2), ranging from 0.2/1000 scans (95%CI 0-10) in 1-year-olds to 34/1000 scans (95%CI 12-66) in 80-year-olds. Meningiomas were the most common, in 246/38,076 participants (5.3/1000 scans, 95%CI 2.3-9.5), ranging from 0/1000 scans (95%CI 0-2) in 1-year-olds to 17/1000 scans (95%CI 4-37) in 80-year-olds. Chiari malformations were observed in 109/27,408 participants (3.7/1000 scans, 95%CI 1.8-6.3), pineal cysts in 1176/32,170 (9/1000 scans, 95%CI 1.8-21.4) and arachnoid cysts in 414/36,367 (8.5/1000 scans, 95%CI 5.8-11.8). CONCLUSION: Incidental findings are common on brain MRI and may result in substantial resource expenditure and patient anxiety but are often of little clinical significance.

Development of 'Core Outcome Sets' for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings.

INTRODUCTION: Meningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma. METHODS AND ANALYSIS: Two systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups. ETHICS AND DISSEMINATION: Institutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available. TRIAL REGISTRATION NUMBER: COMET study ID 1508.

Preoperative embolisation of brain arteriovenous malformations: a systematic review and meta-analysis.

Preoperative embolisation is a commonly performed adjunct to microsurgical excision of brain arteriovenous malformations (bAVMs), with aims such as lessening the technical difficulty of the microsurgical procedure, reducing operative time, decreasing blood loss, and improving patient functional outcomes. We aim to perform a systematic review of randomised trials and cohort studies evaluating preoperative embolisation of bAVMs published between 01 January 2000 and 31 March 2021 and appraise its role in clinical practice. A MEDLINE search was performed, and articles reporting on outcomes following preoperative embolisation, as an adjunct to microsurgery, were eligible for inclusion. PRISMA reporting and Cochrane Handbook guidelines were followed. The primary outcome measure was the risk of complications associated with preoperative embolisation. The study was registered with PROSPERO (CRD42021244231). Of the 1661 citations, 8 studies with 588 patients met predefined inclusion criteria. No studies specifically compared outcomes of surgical excision of bAVMs between those with and without preoperative embolisation. Spetzler Martin (SM) grading was available in 301 cases. 123 of 298 (41⋅28%) patients presented with haemorrhage. Complications related to embolisation occurred in 175/588 patients (29.4%, 95% CI 19.6-40.2). Permanent neurological deficits occurred in 36/541 (6%, 95% CI 3.9-8.5) and mortality in 6/588 (0.41%, 95% CI 0-1.4). This is the first systematic review evaluating preoperative embolisation of bAVMs. Existing studies assessing this intervention are of poor quality. Associated complication rates are significant. Based on published literature, there is currently insufficient evidence to recommend preoperative embolisation of AVMs. Further studies are required to ascertain if there are benefits of this procedure and if so, in which cases.