Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial.

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections. METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts. CONCLUSION: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

Reoperation-requiring postoperative intracranial haemorrhage after posterior fossa craniotomy: Retrospective case-series.

Introduction: Studies report rates of treatment-requiring postoperative intracranial haemorrhage after craniotomy around 1-2%, but do not distinguish between supratentorial and posterior fossa operations. Reports about intracranial haemorrhages' temporal occurrence show conflicting results. Recommendations for duration of postoperative monitoring vary. Research question: To determine the rate, temporal pattern and clinical presentation of reoperation-requiring postoperative intracranial posterior fossa haemorrhage. Material and methods: This retrospective case-series identified cases operated with posterior fossa craniotomy or craniectomy between January 1, 2007 and December 31, 2021 by an electronic search in the patient administrative database, and collected data about patient- and treatment-characteristics, postoperative monitoring, and the occurrence of haemorrhagic and other serious postoperative complications. Results: We included 62 (n = 34, 55% women) cases with mean age 48 (interquartile range 50) years operated for tumours (n = 34, 55%), Chiari malformations (n = 18, 29%), ischemic stroke (n = 6, 10%) and other lesions (n = 3, 5%). One (2%) 66-year-old woman who was a daily smoker operated with decompressive craniectomy and infarct resection, developed a reoperation-requiring postoperative intracranial haemorrhage after 25.5 h. In four (6%) cases, other serious complications requiring reoperation or transfer from the post anaesthesia care unit or regular bed wards to the intensive care unit occurred after 0.5, 6, 9 and 54 h, respectively. Discussion and conclusion: Treatment-requiring postoperative intracranial haemorrhage and other serious complications after posterior fossa craniotomies occur over a wide timespan and are difficult to capture with a standardized postoperative monitoring time. This indicates that the duration of monitoring should be individualized based on assessment of risk factors.

Prevalence of intracranial artery stenosis in a general population using 3D-time of flight magnetic resonance angiography.

BACKGROUND: Data on prevalence of intracranial artery stenosis (ICAS) in Western populations is sparse. The aim of the study was to assess the prevalence and risk factors for ICAS in a mainly Caucasian general population. METHODS: We assessed the prevalence of ICAS in 1847 men and women aged 40 to 84 years who participated in a cross-sectional population-based study, using 3-dimensional time-of-flight 3 Tesla magnetic resonance angiography. ICAS was defined as a focal luminal flow diameter reduction of ≥50 %. The association between cardiovascular risk factor levels and ICAS was assessed by multivariable regression analysis. RESULTS: The overall prevalence of ICAS was 6.0 % (95 % confidence interval (CI) 5.0-7.2), 4.3 % (95 % CI 3.1-5.7) in women and 8.0 % (95 % CI 6.3-10.0) in men. The prevalence increased by age from 0.8 % in 40-54 years age group to 15.2 % in the 75-84 years age group. The majority of stenoses was located to the internal carotid artery (52.2 %), followed by the posterior circulation (33.1 %), the middle cerebral artery (10.8 %) and the anterior cerebral artery (3.8 %). The risk of ICAS was independently associated with higher age, male sex, hypertension, hyperlipidemia, diabetes mellitus, current smoking and higher BMI. CONCLUSIONS: The prevalence of ICAS in a general population of Caucasians was relatively high and similar to the prevalence of extracranial internal carotid artery stenosis in previous population-based studies.

Anatomical variations in the circle of Willis are associated with increased odds of intracranial aneurysms: The Tromsø study.

PURPOSE: Studies on patients suggest an association between anatomical variations in the Circle of Willis (CoW) and intracranial aneurysms (IA), but it is unclear whether this association is present in the general population. In this cross-sectional population study, we investigated the associations between CoW anatomical variations and IA. METHODS: We included 1667 participants from a population sample with 3 T MRI time-of-flight angiography (40-84 years, 46.5% men). Saccular IAs were defined as protrusions in the intracranial arteries ≥2 mm, while variants of the CoW were classified according to whether segments were missing or hypoplastic (< 1 mm). We used logistic regression, adjusting for age and IA risk factors, to assess whether participants with incomplete CoW variants had a greater prevalence of IA and whether participants with specific incomplete variants had a greater prevalence of IA. RESULTS: Participants with an incomplete CoW had an increased prevalence of IA (OR, 2.3 [95% CI 1.05-5.04]). This was mainly driven by the variant missing all three communicating arteries (OR, 4.2 [95% CI 1.7-1 0.3]) and the variant missing the P1 segment of the posterior cerebral artery (OR, 3.6 [95% CI 1.2-10.1]). The combined prevalence of the two variants was 15.4% but accounted for 28% of the IAs. CONCLUSION: The findings suggest that an incomplete CoW is associated with an increased risk of IA for adults in the general population.

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. METHODS: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256.

Prevalence of unruptured intracranial aneurysms: impact of different definitions - the Tromsø Study.

BACKGROUND: Management of incidental unruptured intracranial aneurysms (UIAs) remains challenging and depends on their risk of rupture, estimated from the assumed prevalence of aneurysms and the incidence of aneurysmal subarachnoid haemorrhage. Reported prevalence varies, and consistent criteria for definition of UIAs are lacking. We aimed to study the prevalence of UIAs in a general population according to different definitions of aneurysm. METHODS: Cross-sectional population-based study using 3-dimensional time-of-flight 3 Tesla MR angiography to identify size, type and location of UIAs in 1862 adults aged 40-84 years. Size was measured as the maximal distance between any two points in the aneurysm sac. Prevalence was estimated for different diameter cutoffs (≥1, 2 and 3 mm) with and without inclusion of extradural aneurysms. RESULTS: The overall prevalence of intradural saccular aneurysms ≥2 mm was 6.6% (95% CI 5.4% to 7.6%), 7.5% (95% CI 5.9% to 9.2%) in women and 5.5% (95% CI 4.1% to 7.2%) in men. Depending on the definition of an aneurysm, the overall prevalence ranged from 3.8% (95% CI 3.0% to 4.8%) for intradural aneurysms ≥3 mm to 8.3% (95% CI 7.1% to 9.7%) when both intradural and extradural aneurysms ≥1 mm were included. CONCLUSION: Prevalence in this study was higher than previously observed in other Western populations and was substantially influenced by definitions according to size and extradural or intradural location. The high prevalence of UIAs sized <5 mm may suggest lower rupture risk than previously estimated. Consensus on more robust and consistent radiological definitions of UIAs is warranted.

Survey of European neurosurgeons' management of unruptured intracranial aneurysms: inconsistent practice and organization.

BACKGROUND: The discovery of an unruptured intracranial aneurysm creates a dilemma between observation and treatment. Neurosurgeons' routines for risk assessment and treatment decision-making are unknown. The position of evidence-based medicine in European neurosurgery is considered to be weak, high-grade guidelines do not exist and variations between institutions are probable. We aimed to explore European neurosurgeons' management routines for newly discovered unruptured intracranial aneurysms. METHODS: In cooperation with the European Association of Neurosurgical Societies (EANS), we conducted an online, cross-sectional survey of 420 European neurosurgeons during Spring/Summer 2016 (1533 non-Norwegians invited through the EANS, and 16 Norwegians invited through heads of departments because of the need for additional information for a separate study). We asked about demographic variables, routines for management and risk assessment of newly discovered unruptured intracranial aneurysms and presented a case. We collected information about gross domestic product (GDP) per capita from the International Monetary Fund. RESULTS: The response rate to the invite from the EANS was 26%, with respondents from 47 countries. More than half of the respondents (n = 226 [54%]) reported that their department treated less than 25 unruptured aneurysms yearly. Forty percent said their department used aneurysm size cut-off to guide treatment decisions, with a mean size of 6 mm. Presented with a case, respondents from countries with a lower GDP per capita recommended intervention more often than respondents from higher-income countries. Vascular neurosurgeons more commonly recommended observation. CONCLUSION: The answers to this self-reported survey indicate that many centers have a treatment volume lower than recommended by international guidelines, and that there are socioeconomic differences in care. Better documentation of treatment and outcome, for example with clinical quality registries, is needed to drive improvements of care.

Prerupture Intracranial Aneurysm Morphology in Predicting Risk of Rupture: A Matched Case-Control Study.

BACKGROUND: Maximal size and other morphological parameters of intracranial aneurysms (IAs) are used when deciding if an IA should be treated prophylactically. These parameters are derived from postrupture morphology. As time and rupture may alter the aneurysm geometry, possible morphological predictors of a rupture should be established in prerupture aneurysms. OBJECTIVE: To identify morphological parameters of unruptured IAs associated with later rupture. METHODS: Nationwide matched case-control study. Twelve IAs that later ruptured were matched 1:2 with 24 control IAs that remained unruptured during a median follow-up time of 4.5 (interquartile range, 3.7-8.2) yr. Morphological parameters were automatically measured on 3-dimensional models constructed from angiograms obtained at time of diagnosis. Cases and controls were matched by aneurysm location and size, patient age and sex, and the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, and site of aneurysm) score did not differ between the 2 groups. RESULTS: Only inflow angle was significantly different in cases vs controls in univariate analysis (P = .045), and remained significant in multivariable analysis. Maximal size correlated with size ratio in both cases and controls (P = .015 and <.001, respectively). However, maximal size and inflow angle were correlated in cases but not in controls (P = .004. and .87, respectively). CONCLUSION: A straighter inflow angle may predispose an aneurysm to changes that further increase risk of rupture. Traditional parameters of aneurysm morphology may be of limited value in predicting IA rupture.

Rupture prediction of intracranial aneurysms: a nationwide matched case-control study of hemodynamics at the time of diagnosis.

The authors used computer simulation to investigate the hemodynamics in 36 unruptured aneurysms on the first day the lesions were discovered; 12 of them later ruptured. Knowledge about any differences in hemodynamics at this early stage improves predictions about which patients will get a subarachnoid hemorrhage-a dangerous bleeding in the brain-and helps decide which patients should be treated in advance to avoid the bleeding.

Cerebral Aneurysm Morphology Before and After Rupture: Nationwide Case Series of 29 Aneurysms.

BACKGROUND AND PURPOSE: Using postrupture morphology to predict rupture risk of an intracranial aneurysm may be inaccurate because of possible morphological changes at or around the time of rupture. The present study aims at comparing morphology from angiograms obtained prior to and just after rupture and to evaluate whether postrupture morphology is an adequate surrogate for rupture risk. METHODS: Case series of 29 aneurysms from a nationwide retrospective data collection. Two neuroradiologists who were blinded to pre- versus postrupture images assessed predefined morphological parameters independently and reached consensus regarding all measurements. Prerupture morphology and respective changes after rupture were quantified and linked to risk factors and to the risk of rupture according to the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm) and unruptured intracranial aneurysm treatment (UIAT) scores. RESULTS: All 1-dimensional parameter medians were significantly larger after rupture, except neck diameter. Number of aneurysms with daughter sacs was 9 (31%) before and 17 (59%) after rupture (P=0.005). Aneurysm growth from the images prior to and just after rupture increased with the time elapsed between images. Aneurysms in patients with hypertension were significantly larger at diagnosis. Prerupture morphology did not differ in relation to smoke status. Clinical risk factors were not significantly associated with morphological change. CONCLUSIONS: The changes in aneurysm morphology observed after rupture reflect the compound effect of time with successive growth and formation of irregularities and the impact of rupture per se. Postrupture morphology should not be considered an adequate surrogate for the prerupture morphology in the evaluation of rupture risk.

Determination of wall tension in cerebral artery aneurysms by numerical simulation.

BACKGROUND AND PURPOSE: Cerebral artery aneurysms rupture when wall tension exceeds the strength of the wall tissue. At present, risk-assessment of unruptured aneurysms does not include evaluation of the lesions shape, yet clinical experience suggests that this is of importance. We aimed to develop a computational model for simulation of fluid-structure interaction in cerebral aneurysms based on patient specific lesion geometry, with special emphasis on wall tension. METHODS: An advanced isogeometric fluid-structure analysis model incorporating flexible aneurysm wall based on patient specific computed tomography angiogram images was developed. Variables used in the simulation model were retrieved from a literature review. RESULTS: The simulation results exposed areas of high wall tension and wall displacement located where aneurysms usually rupture. CONCLUSIONS: We suggest that analyzing wall tension and wall displacement in cerebral aneurysms by numeric simulation could be developed into a novel method for individualized prediction of rupture risk.

Computation of hemodynamics in the circle of Willis.

BACKGROUND AND PURPOSE: Wall shear stress (WSS) and pressure are important factors in the development of cerebral aneurysms. We aimed to develop a computational fluid dynamics simulator for flow in the complete circle of Willis to study the impact of variations in vessel radii and bifurcation angles on WSS and pressure on vessel walls. METHODS: Blood flow was modeled with Navier-Stokes equations as an incompressible newtonian fluid within rigid vessel walls. A model of the circle of Willis geometry was approximated as a network of tubes around cubic curves. Pulsatile inlet flow rates and constant outlet pressure were used as boundary conditions. RESULTS: The simulations confirmed that differences in vessel radii and asymmetric branch angles influence WSS magnitude and spatial distribution. High WSS occurred at locations where aneurysms are frequent and in anatomic variants known to be associated with an increased risk for aneurysm development. CONCLUSIONS: Computational fluid dynamics analysis can be applied to the complete circle of Willis and should be used to study the pathophysiology of this complex vascular structure, including risk factors for aneurysm development. Further development of the method should include simulations with flexible vessel walls.

[Treatment of intracranial aneurysms]. / Behandling av intrakraniale aneurismer.

BACKGROUND: The department of neurosurgery at the University Hospital of North Norway has treated intracranial aneurysms since 1986. This study was conducted in order to evaluate outcomes after the introduction of endovascular therapy in 2000. MATERIAL AND METHODS: We included all patients treated for intracranial aneurysms during the years 1999 through 2002 in a retrospective, cross-sectional study. Data were collected from patient files. RESULTS: We treated 113 aneurysms in 104 patients in 108 procedures. 81 (78 %) patients were treated after a subarachnoid haemorrhage, while 23 (22 %) underwent treatment of an unruptured aneurysm. 75 (66 %) aneurysms were operated with craniotomy and clipping of the aneurysm neck, 38 (34 %) were treated with coiling. The choice of modality was dependent on the location and shape of the lesion. Complications related to the treatment were more common after surgical treatment than after coiling (41 versus 16 %, p=0.009), but the method of treatment did not influence long-term outcome evaluated according to the Glasgow Outcome Scale (GOS). All patients who underwent treatment for an unruptured aneurysm achieved a good outcome (GOS score 4 or 5), while patients treated after subarachnoid haemorrhage experienced significantly (p = 0.003) less favourable outcomes. Regression analysis revealed poor clinical condition (high Hunt & Hess grades) after the haemorrhage as the only independent predictor of outcome. INTERPRETATION: The university hospital has treated an increasing proportion of patients with intracranial aneurysms with endovascular coiling after introduction of this method in 2000. The outcomes presented in this study equal those published from international multicentre trials.