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Purpose: The modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs). Methods: This is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses. Results: In total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = − 0.546, while with RAND-36 physical and mental component scores the correlation was r = − 0.439and r = − 0.574 respectively, and with SS-QoL it was r = − 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was − 0.08 (SD 0.915). None of the hypotheses for responsiveness were met. Conclusion: The results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints. Registration: URL: https://trialsearch.who.int; Unique identifier: NL7859, Date of first administration: 08-07-2019 [ABSTRACT FROM AUTHOR]

Four-Dimensional Computed Tomography Angiography (4D CTA) seems a promising technique for capturing vessel motion of cerebral arteries, which may help to assess pathological conditions such as intracranial aneurysms. The goal of our current observational study is to capture the lumen diameter of cerebral arteries during three subsequent cardiac cycles with 4D CTA and to assess vessel motion, anticipating consistent expansion patterns within each cardiac cycle. Eighteen adult patients with unruptured and untreated intracranial aneurysms were recruited at Radboud University Medical Center. Three cardiac cycles were captured, on a wide detector CT system, using ECG-gated 4D CTA. To reduce the impact of small head movements during the acquisition, a rigid-body registration was employed. Three 10 mm segments of cerebral arteries were selected. The total deformation of the vessel lumen was calculated using a deformable registration algorithm and was used as a substitute measure for vessel motion. No pulsations could be registered, which was probably caused by pulsation motion below threshold of detection in combination with insufficient Signal-to-Noise Ratio. Further studies need to investigate if large intracranial structures can be evaluated and if using a novel scanner with a high spatial resolution would result in reproducible measurements of arteries this size., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Frederick J.A. Meijer reports a relationship with Canon Medical Systems Corporation that includes: speaking and lecture fees. Hieronymus D. Boogaarts reports a relationship with Stryker that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Dynamic Computed Tomography Angiography (4D CTA) has the potential of providing insight into the biomechanical properties of the vessel wall, by capturing motion of the vessel wall. For vascular pathologies, like intracranial aneurysms, this could potentially refine diagnosis, prognosis, and treatment decision-making., Purpose: The objective of this research is to determine the feasibility of a 4D CTA scanner for accurately measuring harmonic diameter changes in an in-vitro simulated vessel., Methods: A silicon tube was exposed to a simulated heartbeat. Simulated heart rates between 40 and 100 beats-per-minute (bpm) were tested and the flow amplitude was varied, resulting in various changes of tube diameter. A 320-detector row CT system with ECG-gating captured three consecutive cycles of expansion. Image registration was used to calculate the diameter change. A vascular echography set-up was used as a reference, using a 9 MHz linear array transducer. The reproducibility of 4D CTA was represented by the Pearson correlation (r) between the three consecutive diameter change patterns, captured by 4D CTA. The peak value similarity (pvs) was calculated between the 4D CTA and US measurements for increasing frequencies and was chosen as a measure of temporal resolution. Spatial resolution was represented by the Sum of the Relative Percentual Difference (SRPD) between 4D CTA and US diameter change patterns for increasing amplitudes., Results: The reproducibility of 4D CTA measurements was good (r ≥ 0.9) if the diameter change was larger than 0.3 mm, moderate (0.7 ≤ r < 0.9) if the diameter change was between 0.1 and 0.3 mm, and low (r < 0.7) if the diameter change was smaller than 0.1 mm. Regarding the temporal resolution, the amplitude of 4D CTA was similar to the US measurements (pvs ≥ 90%) for the frequencies of 40 and 50 bpm. Frequencies between 60 and 80 bpm result in a moderate similarity (70% ≤ pvs < 90%). A low similarity (pvs < 70%) is observed for 90 and 100 bpm. Regarding the spatial resolution, diameter changes above 0.30 mm result in SRPDs consistently below 50%., Conclusion: In a phantom setting, 4D CTA can be used to reliably capture reproducible tube diameter changes exceeding 0.30 mm. Low pulsation frequencies (40 or 50 bpm) provide an accurate measurement of the maximum tube diameter change., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6-24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation., Methods: MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6-24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220., Findings: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2-6) in the endovascular treatment group and 6 (2-6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00-1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60-1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group., Interpretation: Our results show that the effectiveness of late-window (after 6-24 h) endovascular treatment in improving clinical outcomes is sustained for up to 2 years in a population preselected based on the presence of collateral flow on CT angiography. This finding might be important for prompting further evaluations of cost-effectiveness, health-care policy development, and clinical decision making., Funding: The Dutch Organization for Health Research and Health Innovation (ZonMW), Collaboration for New Treatments of Acute Stroke Consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Health Holland Top Sector Life Sciences & Health, and the Netherlands Brain Foundation., Competing Interests: Declaration of interests RJvO and WHvZ report financial support for the current manuscript from the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium (which was financed for the current study by the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, the Netherlands Brain Foundation, Stryker, Medtronic, and Cerenovus), all paid to their institution. WHvZ reports speakers fees from Stryker, Cerenovus, Nicolab, Philips, Medtronic, and Microvention, and consulting fees from Philips, all paid to their institution; participated in the advisory boards of WeTrust (Philips) and ANAIS (Anaconda), all paid to their institution; and participated in the advisory board of InExtremis (CHU Montpellier, Montpellier, France), for which no payments were received. YBWEMR reports being a minor shareholder of Nicolab. CBLMM reports grants from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, TWIN Foundation, European Commission, Healthcare Evaluation Netherlands, Stryker, and Boehringer Ingelheim (all paid to their institution); and is a (minority interest) shareholder of Nicolab. AvdL reports financial support for this study by grants from The Netherlands Organization for Health Research and Development, and the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, Brain Foundation Netherlands, Medtronic, and Cerenovus, all paid to their institution; reports grants from Stryker, Thrombolytic Science, Health Holland Top Sector Life Sciences & Health, Penumbra, GE Healthcare, Philips Healthcare, Boehringer Ingelheim, and Siemens Healthineers, all paid to their institution; participates in the advisory board of ESCAPE-MEVO; reports a speakers fee from Siemens Healthineers (paid to their institution); is a research leader of the CONTRAST consortium; and is part of the Research Cie of the European Society of Radiology. DWJD reports funding from the Dutch Heart Foundation, Netherlands Brain Foundation, the Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Penumbra, Stryker, Medtronic, Thrombolytic Science, and Cerenovus (all unrestricted grants for research), paid to their institution; participated in the data safety monitoring board of the ACT Global, TESLA, and LATE-MT trial; and was the research leader for the CONTRAST Consortium until 2023. AAP reports a grant from Siemens Healthineers, paid to their institution. HDB reports an unrestricted grant from Stryker, paid to their institution. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA., Methods: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability., Results: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac., Conclusions: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Objectives: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH., Methods: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade ( p = 0.10)., Results: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56)., Discussion: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care., Trial Registration Information: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013)., Classification of Evidence: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Objective: To describe the incidence, risk factors, and prognostic relevance of intracranial haemorrhage (ICH) immediately after endovascular treatment (EVT) for ischaemic stroke in the anterior circulation., Methods: EVT records from 2010 to 2019 were screened. Included patients underwent DECT within 3h post-EVT. Virtual native reconstructions were evaluated for ICH according to the Heidelberg criteria and grouped into Heidelberg classes (HCs): [HC1] haemorrhagic infarction (HI)1, HI2 and parenchymal haematoma (PH)1; [HC2] PH2; [HC3] i.a. intraventricular and subarachnoid haemorrhage. If ICH corresponding to multiple HCs was observed, we assumed that the (largest) parenchymal ICH would have the greatest prognostic impact. Hence, a single HC was attributed by the following order of severity: HC2, HC1, HC3. The primary outcome was the modified Rankin Scale (mRS) at 90 days. The effect of asymptomatic ICH (aICH) and symptomatic ICH (sICH) of (1) HC1 or HC2 and (2) HC3 on patient outcomes was evaluated with multivariable regression after multiple imputation., Results: Out of 651 records, 498 patients were included. Eighty-one (16%) patients showed ICH on post-EVT DECT, of which 19 were classified as HC1 (21% symptomatic), 6 as HC2 (100% symptomatic), and 56 as HC3 (14% symptomatic). ICH development was mainly associated with unfavourable procedural characteristics. Both aICH and sICH of HC1 or HC2 were associated with the mRS (aICH: adjusted [a]cOR 4.92, 95%CI [1.48-16.35]; sICH: acOR 12.97, 95%CI [2.39-70.26]) and mortality (aICH: aOR 10.08, 95%CI [2.48-40.88]; sICH: aOR 9.92, 95%CI [1.48-66.31]). Likewise, sICH of HC3 was associated with the mRS and mortality (acOR 19.91, 95%CI [4.03-98.35], and aOR 13.23, 95%CI [2.27-77.18], respectively). aICH of HC3 was not significantly associated with the mRS or mortality (acOR 0.87, 95%CI [0.48-1.57], and cOR 0.84, 95%CI [0.32-2.20], respectively)., Conclusions: Immediate post-EVT ICH is a frequent finding. Except for aICH of HC3, any ICH is associated with poor long-term clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial or personal relationships that could be viewed as influencing the work reported in this paper. The authors declare the following financial or personal relationships that could be viewed as influencing the work reported in this paper: H.D. Boogaarts received consultation fees from Stryker Neurovascular (paid to the institution). W.H. van Zwam received consultation fees from Stryker, Nicolab and Cerenovus (paid to the institution), and is a DSMB member of the Philips’ We-Trust study, Anaconda's Solonda study, and In Extremis study (all funding paid to the institution). A.A. Postma received an institutional grant from Siemens Healthineers and Bayer Healthcare., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The MR CLEAN-LATE trial has shown that patient selection for endovascular treatment (EVT) in the late window (6-24 h after onset or last-seen-well) based on the presence of collateral flow on CT-angiography is safe and effective. We aimed to assess the cost-effectiveness of late-window collateral-based EVT-selection compared to best medical management (BMM) over a lifetime horizon (until 95 years of age)., Materials and Methods: A model-based economic evaluation was performed from a societal perspective in The Netherlands. A decision tree was combined with a state-transition (Markov) model. Health states were defined by the modified Rankin Scale (mRS). Initial probabilities at 3-months post-stroke were based on MR CLEAN-LATE data. Transition probabilities were derived from previous literature. Information on short- and long-term resource use and utilities was obtained from a study using MR CLEAN-LATE and cross-sectional data. All costs are expressed in 2022 euros. Costs and quality-adjusted life years (QALYs) were discounted at a rate of 4% and 1.5%, respectively. The effect of parameter uncertainty was assessed using probabilistic sensitivity analysis (PSA)., Results: On average, the EVT strategy cost €159,592 (95% CI: €140,830-€180,154) and generated 3.46 QALYs (95% CI: 3.04-3.90) per patient, whereas the costs and QALYs associated with BMM were €149,935 (95% CI: €130,841-€171,776) and 2.88 (95% CI: 2.48-3.29), respectively. The incremental cost-effectiveness ratio per QALY and the incremental net monetary benefit were €16,442 and €19,710, respectively. At a cost-effectiveness threshold of €50,000/QALY, EVT was cost-effective in 87% of replications., Discussion and Conclusion: Collateral-based selection for late-window EVT is likely cost-effective from a societal perspective in The Netherlands., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: This study was supported by a grant from the Dutch organization for Health research and Health innovation (ZonMw). H.B. received consultation fees from Stryker Neurovascular (paid to the institution). A.P. received an institutional grant from Siemens Healthineers and Bayer Healthcare. W.Z. received consultation fees from Stryker, Nicolab and Cerenovus (paid to the institution), and is a DSMB member of the Philips’ We-Trust study, Anaconda’s Solonda study, and In Extremis study (all funding paid to the institution).

Background: Difficult-to-treat aneurysms of the distal posterior cerebral artery (PCA) can often be treated by parent artery occlusion. A cerebrovascular bypass can complement PCA occlusion to curb the risk of ischemic complications. An in situ bypass may be considered when the occipital artery or superficial temporal artery cannot serve as a bypass donor. This article describes the use of a side-to-side bypass of superior cerebellar artery as a donor to the PCA via an extreme lateral supracerebellar infratentorial approach (ELSCIT). This bypass approach can be a useful surgical strategy for PCA revascularization., Methods: A 40-year-old woman underwent a side-to-side PCA-superior cerebellar artery bypass via the ELSCIT approach for to treat a complex and previously coiled PCA aneurysm. The bypass was followed by endovascular aneurysm and parent artery occlusion., Results: Postoperatively, the patient experienced transient, partial trochlear nerve palsy of the left eye without ischemic lesions on magnetic resonance imaging. The clinical condition was stable, and angiography showed a patent bypass and complete aneurysm occlusion 12 months after surgery., Conclusions: The ELSCIT approach offers access to the medial and distal PCA that is suitable for a side-to-side PCA-superior cerebellar artery bypass. This type of approach and bypass may be of value when revascularization of a P2-P3 portion of the PCA is needed, but a suitable occipital artery or superficial temporal artery is not available., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Model-based health economic evaluations of ischemic stroke are in need of cost- and utility estimates related to relevant outcome measures. This study aims to describe societal cost- and utility estimates per modified Rankin Scale (mRS)-score at different time points within 2 years post stroke., Methods: Included patients had a stroke between 3 months and 2.5 years ago. mRS and EQ-5D-5L were scored during a telephone interview. Based on the interview date, records were categorized into a time point: 3 months (3M; 3-6 months), 1 year (Y1; 6-18 months), or 2 years (Y2; 18-30 months). Patients completed a questionnaire on healthcare utilization and productivity losses in the previous 3 months. Initial stroke hospitalization costs were assessed. Mean costs and utilities per mRS and time point were derived with multiple imputation nested in bootstrapping. Cost at 3 months post stroke were estimated separately for endovascular treatment (EVT)-/non-EVT-patients., Results: 1106 patients were included from 18 Dutch centers. At each time point, higher mRS-scores were associated with increasing average costs and decreasing average utility. Mean societal costs at 3M ranged from €11 943 (mRS 1, no EVT) to €55 957 (mRS 5, no EVT). For Y1, mean costs in the previous 3 months ranged from €885 (mRS 0) to €23 215 (mRS 5), and from €1655 (mRS 0) to €22 904 (mRS 5) for Y2. Mean utilities ranged from 0.07 to 0.96, depending on mRS and time point., Conclusions: The mRS-score is a major determinant of costs and utilities at different post-stroke time points. Our estimates may be used to inform future model-based health economic evaluations., Competing Interests: Author Disclosures Links to the disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

Background: Reliably capturing sub-millimeter vessel wall motion over time, using dynamic Computed Tomography Angiography (4D CTA), might provide insight in biomechanical properties of these vessels. This may improve diagnosis, prognosis, and treatment decision making in vascular pathologies., Purpose: The aim of this study is to determine the most suitable image reconstruction method for 4D CTA to accurately assess harmonic diameter changes of vessels., Methods: An elastic tube (inner diameter 6 mm, wall thickness 2 mm) was exposed to sinusoidal pressure waves with a frequency of 70 beats-per-minute. Five flow amplitudes were set, resulting in increasing sinusoidal diameter changes of the elastic tube, measured during three simulated pulsation cycles, using ECG-gated 4D CTA on a 320-detector row CT system. Tomographic images were reconstructed using one of the following three reconstruction methods: hybrid iterative (Hybrid-IR), model-based iterative (MBIR) and deep-learning based (DLR) reconstruction. The three reconstruction methods where based on 180 degrees (half reconstruction mode) and 360 degrees (full reconstruction mode) raw data. The diameter change, captured by 4D CTA, was computed based on image registration. As a reference metric for diameter change measurement, a 9 MHz linear ultrasound transducer was used. The sum of relative absolute differences (SRAD) between the ultrasound and 4D CTA measurements was calculated for each reconstruction method. The standard deviation was computed across the three pulsation cycles., Results: MBIR and DLR resulted in a decreased SRAD and standard deviation compared to Hybrid-IR. Full reconstruction mode resulted in a decreased SRAD and standard deviations, compared to half reconstruction mode., Conclusions: 4D CTA can capture a diameter change pattern comparable to the pattern captured by US. DLR and MBIR algorithms show more accurate results than Hybrid-IR. Reconstruction with DLR is >3 times faster, compared to reconstruction with MBIR. Full reconstruction mode is more accurate than half reconstruction mode., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

General microvascular perfusion and its heterogeneity are pathophysiological features of delayed cerebral ischemia (DCI) that are gaining increasing attention. Recently, CT perfusion (CTP) imaging has made it possible to evaluate them radiologically using mean transit time (MTT) and its heterogeneity (measured by cvMTT). This study evaluates the effect of multimodal rescue therapy (intra-arterial nimodipine administration and elevation of blood pressure) on MTT and cvMTT during DCI in aneurysmal subarachnoid haemorrhage (aSAH) patients. A total of seventy-nine aSAH patients who underwent multimodal rescue therapy between May 2012 and December 2019 were retrospectively included in this study. CTP-based perfusion impairment (MTT and cvMTT) on the day of DCI diagnosis was compared with follow-up CTP after initiation of combined multimodal therapy. The mean MTT was significantly reduced in the follow-up CTP compared to the first CTP (3.7 ± 0.7 s vs. 3.3 ± 0.6 s; p < 0.0001). However, no significant reduction of cvMTT was observed (0.16 ± 0.06 vs. 0.15 ± 0.06; p = 0.44). Mean arterial pressure was significantly increased between follow-up and first CTP (98 ± 17 mmHg vs. 104 ± 15 mmHg; p < 0.0001). The combined multimodal rescue therapy was effective in addressing the general microvascular perfusion impairment but did not affect the mechanisms underlying microvascular perfusion heterogeneity. This highlights the need for research into new therapeutic approaches that also target these pathophysiological mechanisms of DCI.

Purpose: To determine the incidence and predictors of cerebral arterial air emboli (CAAE) on immediate post-endovascular treatment (EVT) dual-energy CT (DECT) in acute ischaemic stroke (AIS) patients, and describe their association with clinical outcomes., Methods: EVT records from 2010 to 2019 were screened. Exclusion criteria included intracerebral haemorrhage on post-EVT DECT. In the affected middle cerebral artery (MCA)-territory, circular and linear (length ≥ 1.5*width) CAAE were counted. Clinical data were collected from prospective records. The modified Rankin Scale (mRS) at 90 days was the primary outcome. Multivariable linear, logistic, and ordinal regression were used to analyse the effect of (1) linear CAAE and (2) isolated circular CAAE., Results: Out of 651 EVT-records, 402 patients were included. In 65 patients (16%), at least one linear CAAE was found in the affected MCA-territory. 17 patients (4%) showed isolated circular CAAE. Multivariable regression showed an association between both the presence and the number of linear CAAE and the mRS at 90 days (presence: adjusted (a)cOR 3.10, 95%CI 1.75-5.50; number: acOR 1.28, 95%CI 1.13-1.44), NIHSS at 24-48 h (presence: aβ 4.15, 95%CI 1.87-6.43; number: aβ 0.88, 95%CI 0.42-1.34), mortality at 90 days (presence: aOR 3.34, 95%CI 1.51-7.40; number: aOR 1.24, 95%CI 1.08-1.43) and stroke progression (presence: aOR 4.01, 95%CI 1.96-8.18; number: aOR 1.31, 95%CI 1.15-1.50). Isolated circular CAAE were not significantly associated with any outcome measure., Conclusion: CAAE were found frequently on post-EVT CT imaging. The presence and the number of linear CAAE, but not circular CAAE, are associated with unfavourable short- and long-term clinical outcomes., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The temporalis muscle area (TMA) has been proclaimed as a surrogate parameter for estimating skeletal muscle mass. Pilot studies in Asian populations suggested temporal muscle thickness (TMT) and TMA as prognostic factors for neurological outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. This study aimed to validate these findings in a larger European patient cohort. We retrospectively analyzed age, sex, aneurysm location, treatment, World Federation of Neurosurgical Societies (WFNS) grade, Fisher score, and modified Rankin Score (mRS) at six months in patients with aSAH. TMT and TMA measurements were obtained from initial native CT scans. Logistic regression with the dichotomized six-month mRS as the outcome incorporating TMT, weighted average of TMT, or TMA as predictors was performed. Of the included 478 patients, 66% were female, the mean age was 56, and 48% of patients had an mRS of three to six after six months. The mean TMT at the level of the Sylvian fissure was 5.9 (±1.7) mm in males and 4.8 (±1.8) mm in females. The mean TMA was 234.5 (±107.9) mm 2 in females and 380 (±134.1) mm 2 in males. WFNS grade ( p < 0.001), Fisher score ( p < 0.001), and age ( p < 0.05) correlated significantly with the mRS after six months. No correlation was found between mRS after six months and the TMT at the Sylvian fissure ( p = 0.3), the weighted average of TMT ( p = 0.1), or the TMA ( p = 0.1). In this central European patient cohort of 478 individuals, no significant associations were found between TMT/TMA and neurological outcomes following aSAH. Further prospective studies in diverse patient populations are necessary to determine the prognostic value of TMA and TMT in aSAH patients.

Background: The Woven Endobridge (WEB) is designed to treat intracranial wide-neck bifurcation aneurysms, preventing subarachnoid hemorrhage. The translational value of animal models used for WEB device testing is unknown. With this systematic review, we aim to identify the existing animal models used in testing the WEB device and compare the efficacy and safety outcomes to those of prospective clinical studies., Methods: This study was funded by ZonMw: project number 114024133. A comprehensive search was performed in PubMed and in EMBASE via the Ovid interface. The following exclusion criteria were used: 1) not an original full-length research paper, 2) not an in vivo animal study or a human study, 3) no WEB implantation, 4) if in humans: not a prospective study. The SYRCLE risk of bias tool (animal studies) and the Newcastle-Ottawa quality assessment scale for cohort studies (clinical studies) were used to assess risks of bias. A narrative synthesis was performed., Results: Six animal studies and 17 clinical studies met the inclusion criteria. The rabbit elastase aneurysm model was the only animal model used to assess WEB device performance. Safety outcomes were never reported in animal studies. Efficacy outcomes were more heterogeneous in animal studies than in clinical studies, which could be due to limited external validity of the animal models in terms of aneurysm induction and dimensions. Both animal and clinical studies were predominantly single-arm studies, and were at unclear risk of several types of bias., Conclusions: The rabbit elastase aneurysm model was the only pre-clinical animal model used to assess WEB device performance. Safety outcomes were not evaluated in animal studies and could therefore not be compared to clinical outcomes. Efficacy outcomes were more heterogeneous in animal studies than in clinical studies. Future research should focus on improving methodology and reporting in order to draw accurate conclusions on the performance of the WEB device., (© 2023. The Author(s).)

Background: In patients with mild disabilities after aneurysmal subarachnoid hemorrhage (aSAH), invisible symptoms might be easily overlooked during consultations in the outpatient clinic. We hypothesize that the Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage (SOS-SAH), a disease-specific patient-reported outcome measure, might aid in screening for symptoms after aSAH. The objective of this explorative study is to evaluate the perceived impact of using the SOS-SAH in daily clinical practice for patients after aSAH, as well as to explore potential barriers to further implementation., Methods: This multi-method study consists of a quantitative and a qualitative component. To evaluate differences in quality of care, a patient experience survey was sent to patients receiving usual care and to patients who received the SOS-SAH. A multiple linear regression model was applied, with the intervention group and case mix adjusters as independent variables. We described differences in the number of symptoms discussed between patients receiving usual care and those receiving care post-implementation. Following implementation, 16 patients and 6 healthcare professionals were interviewed about their perceptions concerning the impact of and barriers to using the SOS-SAH. A thematic analysis was performed to identify the main themes., Results: The survey did not reveal any differences between the usual-care group and the post-implementation group on the scales of the patient experience survey. After implementation of the SOS-SAH, the number of symptoms discussed during consultation did not increase. The interviews suggest that the SOS-SAH may improve the preparation of patients by providing them with greater insight into their complaints and by raising issues for the consultation. It could also enhance the structure and efficiency of consultation, in addition to improving communication about issues that matter to patients. All patients and healthcare professionals recommended continuing the use of the SOS-SAH in daily practice., Conclusions: Although no quantitative improvements were found in patient experience and symptoms discussed during consultation, implementation of the SOS-SAH could aid in screening for symptoms in patients after aSAH, and it might have a positive influence on patient preparation, while helping to structure consultations between patients and healthcare professionals., (© 2023. The Author(s).)

Background: Previous randomised controlled trials could not demonstrate that surgical evacuation of intracerebral haemorrhage (ICH) improves functional outcome. Increasing evidence suggests that minimally invasive surgery may be beneficial, in particular when performed early after symptom onset. The aim of this study was to investigate safety and technical efficacy of early minimally invasive endoscopy-guided surgery in patients with spontaneous supratentorial ICH., Methods: The Dutch Intracerebral Haemorrhage Surgery Trial pilot study was a prospective intervention study with blinded outcome assessment in three neurosurgical centres in the Netherlands. We included adult patients with spontaneous supratentorial ICH ≥10mL and National Institute of Health Stroke Scale (NIHSS) score ≥2 for minimally invasive endoscopy-guided surgery within 8 h after symptom onset in addition to medical management. Primary safety outcome was death or increase in NIHSS ≥4 points at 24 h. Secondary safety outcomes were procedure-related serious adverse events (SAEs) within 7 days and death within 30 days. Primary technical efficacy outcome was ICH volume reduction (%) at 24 h., Results: We included 40 patients (median age 61 years; IQR 51-67; 28 men). Median baseline NIHSS was 19.5 (IQR 13.3-22.0) and median ICH volume 47.7mL (IQR 29.4-72.0). Six patients had a primary safety outcome, of whom two already deteriorated before surgery and one died within 24 h. Sixteen other SAEs were reported within 7 days in 11 patients (of whom two patients that already had a primary safety outcome), none device related. In total, four (10%) patients died within 30 days. Median ICH volume reduction at 24 h was 78% (IQR 50-89) and median postoperative ICH volume 10.5mL (IQR 5.1-23.8)., Conclusions: Minimally invasive endoscopy-guided surgery within 8 h after symptom onset for supratentorial ICH appears to be safe and can effectively reduce ICH volume. Randomised controlled trials are needed to determine whether this intervention also improves functional outcome., Trial Registration: Clinicaltrials.gov : NCT03608423, August 1st, 2018., (© 2023. The Author(s).)

Objective: To determine the association between early post-endovascular treatment (EVT) contrast extravasation (CE) on dual-energy CT (DECT) and stroke outcomes., Methods: EVT records in 2010-2019 were screened. Exclusion criteria included the occurrence of immediate post-procedural intracranial haemorrhage (ICH). Hyperdense areas on iodine overlay maps were scored according to the Alberta Stroke Programme Early CT Score (ASPECTS), thus forming a CE-ASPECTS. Maximum parenchymal iodine concentration and maximum iodine concentration relative to the torcula were recorded. Follow-up imaging was reviewed for ICH. The primary outcome measure was the modified Rankin Scale (mRS) at 90 days., Results: Out of 651 records, 402 patients were included. CE was found in 318 patients (79%). Thirty-five patients developed ICH on follow-up imaging. Fourteen ICHs were symptomatic. Stroke progression occurred in 59 patients. Multivariable regression showed a significant association between decreasing CE-ASPECTS and the mRS at 90 days (adjusted (a)cOR: 1.10, 95% CI: 1.03-1.18), NIHSS at 24-48 h (aβ: 0.57, 95% CI: 0.29-0.84), stroke progression (aOR: 1.14, 95% CI: 1.03-1.26) and ICH (aOR: 1.21, 95% CI: 1.06-1.39), but not symptomatic ICH (aOR 1.19, 95% CI: 0.95-1.38). Iodine concentration was significantly associated with the mRS (acOR: 1.18, 95% CI: 1.06-1.32), NIHSS (aβ: 0.68, 95% CI: 0.30-1.06), ICH (aOR: 1.37, 95% CI: 1.04-1.81) and symptomatic ICH (aOR: 1.19, 95% CI: 1.02-1.38), but not stroke progression (aOR: 0.99, 95% CI: 0.86-1.15). Results of the analyses with relative iodine concentration were similar and did not improve prediction., Conclusions: CE-ASPECTS and iodine concentration are both associated with short- and long-term stroke outcomes. CE-ASPECTS is likely a better predictor for stroke progression.

Background: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA)., Methods: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220., Findings: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10])., Interpretation: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow., Funding: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation., Competing Interests: Declaration of interests RJvO and WHvZ report financial support for the current manuscript from the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium (which was financed for the current study by the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, the Netherlands Brain Foundation, Stryker, Medtronic, and Cerenovus), all paid to their institution. WHvZ reports speaker fees from Stryker, Cerenovus, and Nicolab, and consulting fees from Philips, all paid to institution; participated in the advisory boards of WeTrust (Philips) and ANAIS (Anaconda), all paid to institution; and participated in the advisory boards of InEcxtremis (CHU Montpellier, Montpellier, France) and DISTAL (University Hospital Basel, Basel, Switzerland), studies for which no payments were received. AvdL reports financial support for this study by grants from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, the Netherlands Brain Foundation, Medtronic, and Cerenovus, all paid to institution; reports grants from Stryker, Thrombolytic Science, Penumbra, GE Healthcare, Philips Healthcare, and Siemens Healthineers, all paid to institution; reports payments from Siemens Healthineers, all paid to institution; participates in the advisory board of ESCAPE-MEVO; and is a research leader of the CONTRAST consortium. CBLMM reports grants from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, TWIN Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker (all paid to institution); and is a (minority interest) shareholder of Nicolab. MU reports research grants from the Dutch Heart Foundation, the Netherlands Organisation for Health Research and Development, and Belgian Health Care Knowledge Centre, all paid to institution; and support to attend the Stroke Symposium Johnson & Johnson 2022. BR reports being the chair of the Writing Committee of the Dutch Stroke Guideline. DWJD reports funding from the Dutch Heart Foundation, Netherlands Brain Foundation, the Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Penumbra, Stryker, Medtronic, Thrombolytic Science, and Cerenovus (all unrestricted grants for research), paid to institution. JMC reports receiving research support from Bayer, AstraZeneca, and Medtronic for research, all paid to institution; and is a co-founder and shareholder of TrianecT. HDB reports consulting fees from Stryker Neurovascular, all paid to institution. AAP reports institutional grants from Siemens Healthcare and Bayer Healthcare, paid to institution. BJE reports funding from the Netherlands Organisation for Health Research and Development and Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Nicolab, all paid to institution. HBvdW reports research grants from the Dutch Heart Foundation, European Commission, and Stryker; consultancy fees from Bayer and TargED, all paid to institution; and stocks in Philips. RPHB reports research grants from the Netherlands Organisation for Health Research and Developmen and the Dutch Ministry of Economic Affairs and Climate Policy, an unrestricted grant from Siemens Healthineers, and consulting fees from Guerbet, all paid to institution. P-JvD reports consulting fees from Stryker and Philips, all paid to institution. YBWEMR reports being a minor shareholder of Nicolab. IRvdW reports consulting fees from Philips (paid to IRvdW) and is a stockholder and inventor of a patent owned by Neurophyxia. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The eCLIPs bifurcation remodelling system is a non-circumferential implant that bridges the neck from outside of a bifurcation aneurysm. The goal of the multicenter, post-marketing European eCLIPs Safety, FeasIbility, and Efficacy Study (EESIS), was to present the efficacy and safety results of the eCLIPs device after 365 days of follow-up., Methods: All patients were to receive an eCLIPs in conjunction with coils. The study was conducted according to good clinical practices and included independent adjudication of safety and efficacy outcomes., Results: Twenty patients were enrolled at four European centers. Mean age was 60 years (range 41-74) and aneurysms were located at the basilar tip (n=19) and carotid tip (n=1). Average aneurysm dome height was 6.0 mm (range 2.0-15.0). Mean neck length was 5.1 mm (range 2.6-8.5). The technical success rate was 90% (18 of 20). No major territorial strokes or deaths occurred between the index procedure and after 365 days of follow-up. Complete occlusion was achieved in 60% of patients (12 of 20 patients) and 67% of patients with an eCLIPs device (12 of 18) after 365 days of follow-up. Adequate occlusion (complete occlusion and neck remnant) was achieved in 80% of patients (16 of 20 patients) and 89% of patients with an eCLIPs device (16 of 18 patients) after 365 days of follow-up., Conclusion: In this small series, treatment with eCLIPs was feasible, safe, and efficacious, considering the challenging nature of the aneurysms., Trial Registration Number: ClinicalTrials.gov NCT02607501., Competing Interests: Competing interests: JDV: consultant for Stryker Neurovascular and Evasc. LS: consultant for Evasc. HDB: consultant for Stryker Neurovascular and Evasc. WHvZ: speaker fees from Stryker, Cerenovus, and NicoLab; consultancy fees from Philips. TRM: co-inventor of eCLIPs and equity position at Evasc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Entrustable professional activities (EPAs) represent an assessment framework with an increased focus on competency-based assessment. Originally developed and adopted for undergraduate medical education, concerns over resident ability to practice effectively after graduation have led to its implementation in residency training but yet not in vascular neurosurgery. Subjective assessment of resident or fellow performance can be problematic, and thus, we aim to define core EPAs for neurosurgical vascular training., Methods: We used a nominal group technique in a multistep interaction between a team of experienced neurovascular specialists and a medical educator to identify relevant EPAs. Panel members provided feedback on the EPAs until they reached consent., Results: The process produced seven core procedural EPAs for vascular residency and fellowship training, non-complex aneurysm surgery, complex aneurysm surgery, bypass surgery, arteriovenous malformation resection, spinal dural fistula surgery, perioperative management, and clinical decision-making., Conclusion: These seven EPAs for vascular neurosurgical training may support and guide the neurosurgical society in the development and implementation of EPAs as an evaluation tool and incorporate entrustment decisions in their training programs., (© 2022. The Author(s).)

Purpose: Hydrocephalus requiring permanent CSF shunting after aneurysmal subarachnoid hemorrhage (aSAH) is frequent. It is unknown which type of valve is optimal. This study evaluates if the revision rate of gravitational differential pressure valves (G-DPVs, GAV® system (B Braun)) (G-DPV) is comparable to adjustable pressure valves (Codman Medos Hakim) (APV) in the treatment of post-aSAH hydrocephalus., Methods: The use of a gravitational differential pressure valve is placed in direct comparison with an adjustable pressure valve system. A retrospective chart review is performed to compare the revision rates for the two valve systems., Results: Within the registry from Radboud University Medical Center, 641 patients with a SAH could be identified from 1 January 2013 until 1 January 2019, whereas at the Heinrich Heine University, 617 patients were identified, totaling 1258 patients who suffered from aSAH. At Radboud University Medical Center, a gravitational differential pressure valve is used, whereas at the Heinrich Heine University, an adjustable pressure valve system is used. One hundred sixty-six (13%) patients required permanent ventricular peritoneal or atrial shunting. Shunt dysfunction occurred in 36 patients: 13 patients of the 53 (25%) of the gravitational shunt cohort, and in 23 of the 113 (20%) patients with an adjustable shunt (p = 0.54). Revision was performed at a mean time of 3.2 months after implantation with the gravitational system and 8.2 months with the adjustable shunt system. Combined rates of over- and underdrainage leading to revision were 7.5% (4/53) for the gravitational and 3.5% (4/113) for the adjustable valve system (p = 0 .27)., Conclusion: The current study does not show a benefit of a gravitational pressure valve (GAV® system) over an adjustable pressure valve (CODMAN ® HAKIM®) in the treatment of post-aSAH hydrocephalus. The overall need for revision is high and warrants further improvements in care., (© 2022. The Author(s).)

Background: Aneurysmal rerupture is one of the most important determents for outcome after aneurysmal subarachnoid hemorrhage and still occurs frequently because individual risk assessment is challenging given the heterogeneity in patient characteristics and aneurysm morphology., Objective: To develop and internally validate a practical prediction model to estimate the risk of aneurysmal rerupture before aneurysm closure., Methods: We designed a multinational cohort study of 2 prospective hospital registries and 3 retrospective observational studies to predict the risk of computed tomography confirmed rebleeding within 24 and 72 hours after ictus. We assessed predictors with Cox proportional hazard regression analysis., Results: Rerupture occurred in 269 of 2075 patients. The cumulative incidence equaled 7% and 11% at 24 and 72 hours, respectively. Our base model included hypertension, World Federation of Neurosurgical Societies scale, Fisher grade, aneurysm size, and cerebrospinal fluid drainage before aneurysm closure and showed good discrimination with an optimism corrected c-statistic of 0.77. When we extend the base model with aneurysm irregularity, the optimism-corrected c-statistic increased to 0.79., Conclusion: Our prediction models reliably estimate the risk of aneurysm rerupture after aneurysmal subarachnoid hemorrhage using predictor variables available upon hospital admission. An online prognostic calculator is accessible at https://www.evidencio.com/models/show/2626 ., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: The aim of this study was to investigate the diagnostic accuracy of the pulsatility curve to predict shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH)., Methods: Lumbar cerebrospinal fluid dynamics were derived from an automatic lumbar infusion test (LIT) protocol. All patients were treated with ventriculoperitoneal shunting and re-examined 6 months after shunting. Patient demographics and outcomes were gathered in a prospective, electronic database that spanned from January 2012 to January 2020. A validated iNPH scale was used to assess patients preoperatively and 6 months postoperatively. The relationship of the relative pulse pressure coefficient (RPPC), delta amplitude, successful lowering of amplitude, and the pressure-value at a hypothetical amplitude of zero (P 0 ), resistance to outflow (R out ), and outcome, were assessed using receiver operating characteristic (ROC) curves., Results: We included 38 patients. The RPPC, delta amplitude, successful lowering of amplitude, and P 0 parameters did not predict shunt response. Mean P 0 was 0.5 (IQR 0.4-0.9) in improved patients and 0.4 (IQR 0-1.2) in non-improved patients. The delta amplitude was 0.16 kPa (IQR 0.10-0.23) in improved patients and 0.18 kPa (IQR 0.11-0.24) in non-improved patients. Furthermore, we found a technical failure rate of pulsatility curve measurements of 32%., Conclusion: Pulsatility curve results were not suitable in predicting shunt response in our cohort. The diagnostic value of LIT in case of normal pressure hydrocephalus should be subject to more rigorous research., (© 2022. The Author(s).)

Contrast-induced encephalopathy (CIE) is a rare encephalopathic condition after the administration of a contrast agent. The diagnosis of CIE is challenging because of the heterogeneity and non-specificity of the clinical presentation. The clinical course is usually favorable with full recovery within 48-72 h in most patients, although comorbidity is of relevance and contributes to the clinical outcome. It is expected that the incidence of CIE is currently increasing, due to an increase in endovascular and diagnostic imaging procedures using iodinated contrast. It is important to include CIE in the differential diagnosis when patients deteriorate during, or immediately after, contrast administration, even when only a small amount of non-ionic contrast agent is used. When CIE is considered to be the most likely explanation for the clinical symptoms, it is advised to refrain from unnecessary additional contrast studies such as angiography or perfusion CT., (© 2022. The Author(s).)

Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes., Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days)., Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P <0.001 and 236 versus 270 minutes; P <0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P <0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile., Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Intracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In this study, the results of a personalized aneurysm-on-a-chip model using patient-specific flow parameters and patient-specific cells are presented. CT imaging was used to calculate CFD parameters using an immersed boundary method. A microfluidic device either cultured with human umbilical vein endothelial cells (HUVECs) or human induced pluripotent stem cell-derived endothelial cells (hiPSC-EC) was used. Both types of endothelial cells were exposed for 24 h to either 0.03 Pa or 1.5 Pa shear stress, corresponding to regions of low shear and high shear in the computational aneurysm model, respectively. As a control, both cell types were also cultured under static conditions for 24 h as a control. Both HUVEC and hiPSC-EC cultures presented as confluent monolayers with no particular cell alignment in static or low shear conditions. Under high shear conditions HUVEC elongated and aligned in the direction of the flow. HiPSC-EC exhibited reduced cell numbers, monolayer gap formation and cells with aberrant, spread-out morphology. Future research should focus on hiPSC-EC stabilization to allow personalized intracranial aneurysm models.

Background and Objectives: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS., Methods: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire., Results: The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible., Discussion: The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials., Trial Registration: www.trialregister.nl ; Unique identifier: NL7859., (© 2021. The Author(s).)

Background: patients with a subarachnoid hemorrhage (SAH) might need a flow diverter (FD) placement for complex acutely ruptured intracranial aneurysms (IAs). We conducted a meta-analysis and developed a prediction model to estimate the favorable clinical outcome after the FD treatment in acutely ruptured IAs., Methods: a systematic literature search was performed from 2010 to January 2021 in PubMed and Embase databases. Studies with more than five patients treated with FDs within fifteen days were included. In total, 1157 studies were identified. The primary outcome measure was the favorable clinical outcome (mRS 0-2). Secondary outcome measures were complete occlusion rates, aneurysm rebleeding, permanent neurologic deficit caused by procedure-related complications, and all-cause mortality. A prediction model was constructed using individual patient-level data., Results: 26 retrospective studies with 357 patients and 368 aneurysms were included. The pooled rates of the favorable clinical outcome, mortality, and complete aneurysm occlusion were 73.7% (95% CI 64.7-81.0), 17.1% (95% CI 13.3-21.8), and 85.6% (95% CI 80.4-89.6), respectively. Rebleeding occurred in 3% of aneurysms (11/368). The c-statistic of the final model was 0.83 (95% CI 0.76-0.89). All the studies provided a very low quality of evidence., Conclusions: FD treatment can be considered for complex ruptured IAs. Despite high complication rates, the pooled clinical outcomes seem favorable. The prediction model needs to be validated by larger prospective studies before clinical application.

Objective: Delayed cerebral ischemia (DCI) contributes to morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Continuous improvement in the management of these patients, such as neurocritical care and aneurysm repair, may decrease the prevalence of DCI. In this study, the authors aimed to investigate potential time trends in the prevalence of DCI in clinical studies of DCI within the last 20 years., Methods: PubMed, Embase, and the Cochrane library were searched from 2000 to 2020. Randomized controlled trials that reported clinical (and radiological) DCI in patients with aSAH who were randomized to a control group receiving standard care were included. DCI prevalence was estimated by means of random-effects meta-analysis, and subgroup analyses were performed for the DCI sum score, Fisher grade, clinical grade on admission, and aneurysm treatment method. Time trends were evaluated by meta-regression., Results: The search strategy yielded 5931 records, of which 58 randomized controlled trials were included. A total of 4424 patients in the control arm were included. The overall prevalence of DCI was 0.29 (95% CI 0.26-0.32). The event rate for prevalence of DCI among the high-quality studies was 0.30 (95% CI 0.25-0.34) and did not decrease over time (0.25% decline per year; 95% CI -2.49% to 1.99%, p = 0.819). DCI prevalence was higher in studies that included only higher clinical or Fisher grades, and in studies that included only clipping as the treatment modality., Conclusions: Overall DCI prevalence in patients with aSAH was 0.29 (95% CI 0.26-0.32) and did not decrease over time in the control groups of the included randomized controlled trials.

Background: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population., Methods: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs., Results: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs., Conclusion: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs., Competing Interests: Competing interests: DD and AvdL received funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc., Stryker, Medtronic, Thrombolytic Science, and Cerenovus for research, all paid to institution. Consultation fees were received by DD and AvdL from Stryker and Bracco Imaging. Amsterdam UMC received a grant from Stryker for research led by CM and YR. CM, YR, and HM are shareholders of Nico.lab. Maastricht University MC received funds from Stryker and Cerenovus for consultations by WvZ. MG received consultation fees from Medtronic, Stryker, Microvention, and Mentice. Radboud UMC received funds from Stryker for consultations by Hieronymus Boogaarts., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations., Methods: We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points., Results: The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81)., Conclusions: In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.)., (Copyright © 2021 Massachusetts Medical Society.)

Importance: Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear., Objective: To determine the absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture., Design, Setting, and Participants: Individual patient data were obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth., Exposures: All included aneurysms had growth, defined as 1 mm or greater increase in 1 direction at follow-up imaging., Main Outcomes and Measures: The primary outcome was aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection., Results: A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3% (95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7 mm or larger hazard ratio, 3.1; 95% CI, 1.4-7.2), shape (irregular hazard ratio, 2.9; 95% CI, 1.3-6.5), and site (middle cerebral artery hazard ratio, 3.6; 95% CI, 0.8-16.3; anterior cerebral artery, posterior communicating artery, or posterior circulation hazard ratio, 2.8; 95% CI, 0.6-13.0). In the triple-S (size, site, shape) prediction model, the 1-year risk of rupture ranged from 2.1% to 10.6%., Conclusion and Relevance: Within 1 year after growth detection, rupture occurred in approximately 1 of 25 aneurysms. The triple-S risk prediction model can be used to estimate absolute risk of rupture for the initial period after detection of growth.

Background: Detection of multiple intracranial aneurysms (MIAs) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is common and the optimal management of the additional unruptured intracranial aneurysms (UIA) is often a matter of debate. We calculate the incidence and the factors associated with subsequent aSAHs from untreated additional aneurysms in a single-center group of patients with aSAH and MIAs., Methods: Charts of patients with MIAs admitted to our neurosurgery department for aSAH between January 2000 and March 2020 were retrospectively reviewed. Incidence rate and factors associated with subsequent aSAHs were calculated with univariable and multivariable analyses., Results: Of the unruptured aneurysms, 50% were preventively treated. During a median follow-up of 3 years, 20 of 174 patients (11.5%) presented with a second aSAH. Incidence of rupture of an additional untreated aneurysm was 18.05 per 1000 person/years (confidence interval, 10.69-30.47). Rupture incidence of an additional aneurysm located in the anterior circulation was 32.70 per 1000 person/years and 40.73 per 1000 person/years in the posterior circulation. Presence of untreated mirror and de novo aneurysms increased the risk of overall subsequent aSAHs by 16.9-fold and 7.6-fold, respectively. Most untreated additional aneurysms causing a subsequent aSAH were smaller than 7 mm (73.3%), with middle cerebral artery being the most frequent location (40.0%)., Conclusions: Incidence of subsequent aSAHs is high in patients with aSAH-MIA. Untreated mirror and de novo aneurysms are associated with higher rupture risk. Longer follow-up and prophylactic treatment of asymptomatic aneurysms at higher rupture risk are recommended to prevent the significant poor outcome of subsequent aSAHs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective/background: The need for revascularization of the distal posterior cerebral artery (PCA) in the treatment of PCA aneurysms is a contentious issue. Approaches to the PCA, such as the subtemporal route, carry significant perioperative risk. This risk at times outweighs the risk of ischemia associated with endovascular PCA sacrifice. This paper describes the use of an extreme lateral supracerebellar infratentorial (ELSCIT) approach as an alternative technique for distal PCA revascularization., Methods: Between 2016 and 2019, 3 patients underwent a PCA bypass via the ELSCIT approach for the treatment of a PCA aneurysm. In all cases, an end-to-side anastomosis to the P2- or P3-segment of the PCA was made, with the occipital artery as a donor. Bypass procedures were followed by endovascular parent artery occlusion, without ischemic complications., Results: In all 3 cases, the ELSCIT approach offered a broad enough surgical corridor to perform an occipital artery-to-PCA bypass. One patient suffered a cerebrospinal fluid leak that was surgically treated. Patients' clinical conditions were stable on follow-up (mean follow-up of 34 months). All 3 aneurysms remained occluded, and no ischemia was detected on magnetic resonance imaging., Conclusions: The ELSCIT approach offers an alternative route to the distal PCA for extracranial-to-intracranial bypass with seemingly low perioperative morbidity and good surgical access to the PCA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy., Methods: Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SHAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores., Results: The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17)., Conclusions: Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design.

Background: Automated cerebrospinal fluid (CSF) drainage systems allow for the mobilization of patients with an external CSF drain. The aim of this study is to describe the implementation of an automated CSF drainage system in neurosurgical patients with external CSF drains., Methods: A feasibility study was performed using an automated CSF drainage system (LiquoGuard ® 7, Möller Medical GmbH, Fulda, Germany) in adult neurosurgical patients treated with external lumbar or external ventricular drains between December 2017 and June 2020. Limited mobilization was allowed-patients were allowed to adjust their inclined beds, sit in chairs and walk under the supervision of a nurse or physical therapist. The primary outcome was the number of prematurely terminated drainage sessions., Results: Twenty-three patients were included. Drainage was terminated prematurely in eight (35%) patients. In three (13%) of these patients, drainage was terminated due to signs of hydrocephalus. Pressure-controlled drainage in patients with external lumbar drains (ELD) showed inaccurate pressure curves, which was solved by using volume-controlled drainage in ELD patients., Conclusion: The implementation of an automated CSF drainage system (LiquoGuard ® 7) for CSF drainage allows for early mobilization in a subset of patients with external CSF drains. External lumbar drains require volume-based drainage rather than differential pressure-dependent drainage.

Background: Wide necked bifurcation aneurysms (WNBA) are among the most difficult aneurysms to treat. Very low dome-to-neck (DTN) and aspect ratios provide an even greater challenge in the management of WNBAs. We present the safety and efficacy profile for endovascular clip system (eCLIPs) device in the treatment of this subset of WNBAs with very unfavorable morphologies., Methods: In our case series, 24 patients treated at 12 international centers were taken from a larger prospective voluntary post-marketing registry of 65 patients treated with the eCLIPs device and coiling. Those who had WNBAs at either the carotid or basilar terminus with a DTN ratio <1.6 and aspect ratio <1.2 were included. Radiologic and clinical outcomes were assessed immediately after the procedure and at the latest follow-up., Results: The eCLIPs device was successfully deployed in 23 cases (96%). One patient (4.2%) died due to guidewire perforation distal to the implant site. No other complications were documented. After a mean follow-up of 15.8 months (range 3-40 months), good radiologic outcomes (modified Raymond-Roy classification (MRRC) scores of 1 or 2) were documented in 20 of 21 patients (95%) with follow-up data. The lone patient with an MRRC score of 3 showed coiled compaction after incomplete neck coverage with the device., Conclusion: Our series of patients with aneurysms having adverse DTN and aspect ratios demonstrated that the eCLIPs device has a safety and efficacy profile comparable with currently available devices in the treatment of WNBAs., Competing Interests: Competing interests: JDV is a consultant for Evasc; honoraria is paid to his institution. LS is a consultant for, and receives honoraria from, Evasc. TRM is a principal of eVasc Neurovascular, manufacturers of the eCLIPs., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Predicting outcome after aneurysmal subarachnoid hemorrhage (aSAH) is known to be challenging and complex. Machine learning approaches, of which feedforward artificial neural networks (ffANNs) are the most widely used, could contribute to the patient-specific outcome prediction., Objective: To investigate the prediction capacity of an ffANN for the patient-specific clinical outcome and the occurrence of delayed cerebral ischemia (DCI) and compare those results with the predictions of 2 internationally used scoring systems., Methods: A prospective database was used to predict (1) death during hospitalization (ie, mortality) (n = 451), (2) unfavorable modified Rankin Scale (mRS) at 6 mo (n = 413), and (3) the occurrence of DCI (n = 362). Additionally, the predictive capacities of the ffANN were compared to those of Subarachnoid Haemorrhage International Trialists (SAHIT) and VASOGRADE to predict clinical outcome and occurrence of DCI., Results: The area under the curve (AUC) of the ffANN showed to be 88%, 85%, and 72% for predicting mortality, an unfavorable mRS, and the occurrence of DCI, respectively. Sensitivity/specificity rates of the ffANN for mortality, unfavorable mRS, and the occurrence of DCI were 82%/80%, 94%/80%, and 74%/68%. The ffANN and SAHIT calculator showed similar AUCs for predicting personalized outcome. The presented ffANN and VASOGRADE were found to perform equally with regard to personalized prediction of occurrence of DCI., Conclusion: The presented ffANN showed equal performance when compared with VASOGRADE and SAHIT scoring systems while using less individual cases. The web interface launched simultaneously with the publication of this manuscript allows for usage of the ffANN-based prediction tool for individual data (https://nutshell-tool.com/)., (© Congress of Neurological Surgeons 2021.)

Background: The need for external cerebrospinal fluid (CSF) drains in aneurysmal subarachnoid haemorrhage (aSAH) patients is common and might lead to additional complications., Objective: A relation between the presence of an external CSF drain and complication risk is investigated., Methods: A prospective complication registry was analysed retrospectively. We included all adult aSAH patients admitted to our academic hospital between January 2016 and January 2018, treated with an external CSF drain. Demographic data, type of external drain used, the severity of the aSAH and complications, up to 30 days after drain placement, were registered. Complications were divided into (1) complications with a direct relation to the external CSF drain and (2) complications that could not be directly related to the use of an external CSF drain referred to as medical complications RESULTS: One hundred and forty drains were implanted in 100 aSAH patients. In total, 112 complications occurred in 59 patients. Thirty-six complications were drain related and 76 were medical complications. The most common complication was infection (n = 34). Drain dislodgement occurred 16 times, followed by meningitis (n = 11) and occlusion (n = 9). A Poisson model showed that the mean number of complications raised by 2.9% for each additional day of drainage (95% CI: 0.6-5.3% p = 0.01)., Conclusion: Complications are common in patients with aneurysmal subarachnoid haemorrhage of which 32% are drain-related. A correlation is present between drainage period and the number of complications. Therefore, reducing drainage period could be a target for further improvement of care.

Background: Treatment of intracranial aneurysms with flow diverters (FDs) showed promising results. However, a subset of patients treated for posterior communicating artery (PComA) aneurysms has variable occlusion rates. Especially the fetal type-associated PComA aneurysms seemed to respond differently to treatment. We analyze our series of fetal type PComA aneurysms treated with a FD. The literature on this subject is reviewed., Methods: Data from patients treated with FD for all PComA aneurysms at the RadboudUMC Nijmegen were retrospectively analysed. Primary end-point was complete aneurysm occlusion at six months. Secondary end-points were clinical outcome, treatment safety, and results of secondary treatment after non-closure. The results for the fetal PComA aneurysms were compared to the literature., Results: Nineteen consecutive patients harboring 21 PComA aneurysms were treated. Three aneurysms had ipsilateral fetal type PCA (14.3%). Overall, none of the fetal type PcomA aneurysm showed complete occlusion versus 77.8% of the others ( p = 0.03). Mortality and permanent morbidity rates were respectively 5.3% and 0%., Conclusions: FD treatment for PComA aneurysm with fetal type circulation seemed to be less effective compared to other types of PComA aneurysms. Flow characteristics at the PComA bifurcation are thought to be causative Alternative strategies should be considered as first line treatment.

Measurement of intracranial aneurysm wall motion may refine the current rupture risk estimation. A golden standard for measuring aneurysm pulsation is lacking. The aim is to evaluate magnitudes of aneurysm pulsation as published in current literature. Embase and PubMed were searched for publications containing quantitative measures of cardiac-cycle related cerebral aneurysm pulsation (no date or language restrictions). Eleven studies were included, covering 197 unruptured and untreated cerebral aneurysms. Quantitative pulsation measurements were extracted from the studies. Characteristics of the study population and aneurysms were taken into account, as well as the imaging modality, scanning technique and data processing methods used. A meta-analysis was performed of studies with similar methodologies and individual IA measures and locations. The magnitude of the absolute volume pulsations varied between 14 ± 9 mm 3 and 106 ± 123 mm 3 and the mean relative volume change varied between 5 and 36%. The meta-analysis revealed a positive correlation between size and absolute volume change. The relative volume change in Basilar artery aneurysms seems smaller. No authors were contacted for original study data and articles only describing visual pulsations were excluded. The variation in methodologies impedes an accurate estimation of the magnitude of IA pulsations. Validation of aneurysm pulsation measurement is crucial prior to clinical studies evaluating IA pulsatility in relation to IA rupture risk. Prerequisite is a reliable and robust imaging method with high spatial and temporal resolution and standardization of the image analysis methods.

Background: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months., Methods: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812., Findings: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups., Interpretation: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale., Funding: Fonds NutsOhra., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Stroke is the second leading cause of death and a major cause of morbidity worldwide. Retrospective clinical and animal studies have demonstrated neuroprotective effects of iron chelators in people with haemorrhagic or ischaemic stroke. This is the first update of the original Cochrane Review published in 2012., Objectives: To evaluate the effectiveness and safety of iron-chelating drugs in people with acute stroke., Search Methods: We searched the Cochrane Stroke Group Trials Register (2 September 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2019, Issue 9; 2 September 2019), MEDLINE Ovid (2 September 2019), Embase Ovid (2 September 2019), and Science Citation Index (2 September 2019). We also searched ongoing trials registers., Selection Criteria: We included randomised controlled trials (RCTs) of iron chelators versus no iron chelators or placebo for the treatment of acute stroke, including subarachnoid haemorrhage., Data Collection and Analysis: Two review authors independently screened the search results. We obtained the full texts of potentially relevant studies and evaluated them for eligibility. We assessed risk of bias using the Cochrane 'Risk of bias' tool, and the certainty of evidence using the GRADE approach., Main Results: Two RCTs (333 participants) were eligible for inclusion; both compared the iron-chelating agent deferoxamine against placebo. Both studies evaluated participants with spontaneous intracerebral haemorrhage. We assessed one study to have a low risk of bias; the other study had potential sources of bias. The limited and heterogeneous data did not allow for meta-analysis of the outcome parameters. The evidence suggests that administration of deferoxamine may result in little to no difference in deaths (8% in placebo vs 8% in deferoxamine at 180 days; 1 RCT, 291 participants; low-certainty evidence). These RCTs suggest that there may be little to no difference in good functional outcome (modified Rankin Scale score 0 to 2) between groups at 30, 90 and 180 days (placebo vs deferoxamine: 67% vs 57% at 30 days and 36% vs 45% at 180 days; 2 RCTs, 333 participants; low-certainty evidence). One RCT suggests that administration of deferoxamine may not increase the number of serious adverse events or deaths (placebo vs deferoxamine: 33% vs 27% at 180 days; risk ratio 0.81, 95 % confidence interval 0.57 to 1.16; 1 RCT, 291 participants; low-certainty evidence). No data were available on any deaths within the treatment period. Deferoxamine may result in little to no difference in the evolution of National Institute of Health Stroke Scale scores from baseline to 90 days (placebo vs deferoxamine: 13 to 4 vs 13 to 3; P = 0.37; 2 RCTs, 333 participants; low-certainty evidence). Deferoxamine may slightly reduce relative oedema surrounding intracerebral haemorrhage at 15 days (placebo vs deferoxamine: 1.91 vs 10.26; P = 0.042; 2 RCTs, 333 participants; low-certainty evidence). Neither study reported quality of life., Authors' Conclusions: We identified two eligible RCTs for assessment. We could not demonstrate any benefit for the use of iron chelators in spontaneous intracerebral haemorrhage. The added value of iron-chelating therapy in people with ischaemic stroke or subarachnoid haemorrhage remains unknown., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Inflammation-related factors might give further insight into the pathophysiology of vessel wall inflammation and intracranial aneurysm (IA) rupture. One of these factors is the protein complex S100A8/A9, which is released by neutrophils, monocytes, and activated macrophages and is known for its role in cardiovascular disease., Objective: To determine if venous S100A8/A9 levels in patients with a ruptured IA (rIA) or unruptured IA (uIA) are elevated compared with a control group. Second, to assess differences between venous and intra-aneurysmal S100A8/A9 levels of rIA and uIA patients., Methods: A prospective case study was performed between June 2016 and May 2017 in patients harboring a ruptured or unruptured saccular IA. Primary outcome measures were individual S100A8/A9 serum concentrations as measured in venous and intra-aneurysmal blood samples during endovascular treatment. Venous serum S100A8/A9 concentrations from a healthy control group served as a reference., Results: We included 16 patients with either a rIA or uIA and 47 healthy controls. Venous S100A8/A9 concentrations were higher in aneurysm patients (rIA and uIA) than those of healthy controls (P≤0.001). S100A8/A9 concentrations were higher in intra-aneurysmal samples than in venous samples of rIA patients (P=0.011). This difference was not found in uIA patients (P=0.054). Intra-aneurysmal S100A8/A9 levels were higher in rIAs than in uIAs (P=0.04)., Conclusions: Venous S100A8/A9 levels are elevated in patients with both rIAs and uIAs compared with healthy controls and likely represents aneurysm wall inflammation. S100A8/A9 causes macrophage-induced inflammation and degeneration of the vessel wall which might explain higher intra-aneurysmal S100A8/A9 levels found in rIAs than in uIAs., Competing Interests: Competing interests: Joost de Vries and Hieronymus D. Boogaarts are consultants for Stryker Neurovascular., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for "experimental secondary ischemia" (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies.