Clinical course of patients with conservatively managed cerebral cavernous malformations.

INTRODUCTION: There is uncertainty whether patients with a cerebral cavernous malformation (CCM) should undergo conservative or surgical treatment, resulting in practice variation among hospitals. Our objective was to report clinical outcomes of patients with primarily conservatively managed CCMs. PATIENTS AND METHODS: This single-center cohort study included consecutive adult CCM patients, diagnosed in 2000-2023, who underwent conservative management as primary treatment strategy. Data were extracted from medical records, and we systematically conducted telephone and questionnaire follow-up. Functional status was assessed on the modified Rankin Scale (mRS). RESULTS: Of 345 patients, we included 265 patients with a CCM (median age 46 years; 45% male). At baseline, 131 (49%) patients presented with symptomatic hemorrhage (SH), and 134 (51%) with other symptoms or asymptomatically. During 58 months (IQR 35-94) median follow-up, 51 (19%) patients experienced a SH, 33 (12%) a seizure, and 13 (5%) focal neurological deficits. Fourteen (5%) patients underwent intervention (surgery n = 11, radiosurgery n = 4). Presentation with SH was associated with higher annual bleeding rates (6.0% vs 1.5%, p < 0.001), and higher cumulative 5-/10-year bleeding risks (31%/41% vs 7%, p < 0.001). Brainstem CCM was associated with higher cumulative 5-/10-year bleeding risks (27%/38% vs 17%/21%, p = 0.038). Nineteen (7%) patients died; two (0.8%) directly attributable to CCM. Of 246 surviving patients, 205 (83%) completed the questionnaire. At follow-up, 172/224 (77%) patients were functionally independent (mRS score ⩽2). DISCUSSION AND CONCLUSION: The majority of conservatively managed CCM patients remained free of a SH during follow-up. Few patients required intervention, and death attributable to the CCM was rare. These data may help patient counseling and treatment decisions.

Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH. PATIENTS AND METHODS: A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0-3) at 6 months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0-3, 3-6 and >6 h). RESULTS: Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62-1.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p < 0.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6 h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72-1.27) with no evidence of effect modification on the time to start of TXA (p = 0.53). DISCUSSION AND CONCLUSIONS: This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6 h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.

Reducing the global burden of cerebral venous thrombosis: An international research agenda.

BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.

Transarterial Embolization of Anterior Cranial Fossa Dural AVFs as a First-Line Approach: A Single-Center Study.

BACKGROUND AND PURPOSE: Endovascular treatment has been increasingly used for anterior cranial fossa dural AVFs. Evidence on the safety and efficacy of different endovascular treatment strategies is limited. We report clinical and angiographic outcomes of patients with anterior cranial fossa dural AVFs who underwent treatment using transarterial embolization with n-BCA as a first-line approach. MATERIALS AND METHODS: Consecutive patients undergoing treatment for anterior cranial fossa dural AVFs at the Amsterdam University Medical Centers between 2010 and 2023 were retrospectively included. Transarterial embolization was used as a first-line approach, while transvenous treatment and surgery were used in cases of unsuccessful transarterial embolization. Treatment was evaluated on the basis of the angiographic cure rate, procedural complications, and clinical outcome. RESULTS: Fourteen patients were included with 15 anterior cranial fossa dural AVFs. All patients underwent primary endovascular treatment (12 transarterial, 1 transvenous, and 1 combined). Complete occlusion using only transarterial embolization was reached in 69% of patients (9/13), while the overall complete occlusion by endovascular treatment was reached in 79% of patients (11/14). Navigation and embolization were performed through the ophthalmic artery in 13 patients, with no procedural complications. Visual acuity was preserved in all patients. Three patients underwent an operation after failed endovascular treatment. All patients had complete anterior cranial fossa dural AVF occlusion at follow-up. CONCLUSIONS: Treatment of anterior cranial fossa dural AVFs using transarterial embolization with n-BCA as a first-line approach is a safe and feasible first-line treatment strategy. No visual complications due to embolization through the ophthalmic artery occurred in this study.

Likelihood of spontaneous closure of cavernous sinus dural arteriovenous fistulas based on clinical and radiological findings.

BACKGROUND: Cavernous sinus dural arteriovenous fistula (CSDAVF) is a rare condition that radiologists would encounter in their careers. We aim to describe the clinical and radiological characteristics of this condition, and to provide a management workflow. METHODS: In our retrospective study, we studied 27 patients with CSDAVF from January 2007 to August 2020. Patients with direct cavernous sinus AVFs and patients with incomplete date were excluded. Clinical and radiological data were collected and analyzed. RESULTS: Fourteen patients were conservatively treated with spontaneous resolution while 13 patients had endovascular intervention performed. In the intervention group, seven patients had intra-cranial reflux seen on radiological imaging and six patients had clinical deterioration, hence requiring intervention. Clinically, among our patients, 21 had proptosis, 20 had conjunctiva hyperaemia, 18 had extraocular movement limitation, 13 had raised intraocular pressure, 11 had chemosis, ten had ocular pain, nine had ocular bruit, eight had headache and six had worsening visual acuity. Radiologically, a concurrence was seen between superior ophthalmic vein thrombosis and spontaneous resolution of the CSDAVF, as compared to those who underwent intervention. A paradoxical increase of ocular symptoms was seen despite a decrease of flow or stagnation of contrast in radiological imaging of CSDAVF. CONCLUSIONS: In our study, 52% of CSDAVF closed spontaneously. As deterioration of ocular symptoms in patients with CSDAVF might also reflect spontaneous progressive occlusion, it warrants dynamic vascular imaging to check the status of venous outflow. Patients with CSDAVF with corticovenous reflux or deterioration of visual acuity need more urgent (endovascular) treatment.

Development of the SAFETEA Scores for Predicting Risks of Complications of Preventive Endovascular or Microneurosurgical Intracranial Aneurysm Occlusion.

OBJECTIVE: Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics. METHODS: For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics. RESULTS: Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved <30 days, 140 (10.9%) had persisting neurological symptoms, and 6 died (0.5%)). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were: size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment; branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n=752), the c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points). CONCLUSIONS: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial.

BACKGROUND AND OBJECTIVES: The ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at six months. METHODS: The ULTRA-trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013 and January 20, 2020. After confirmation of subarachnoid hemorrhage on non-contrast computer tomography, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care, or usual care only. In this post-hoc analysis, we included all ULTRA-participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome. RESULTS: Of the 813 ULTRA-trial patients who had an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio (aOR) 0·92; 95% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52). DISCUSSION: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment.

OBJECTIVES: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. MATERIALS AND METHODS: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. RESULTS: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. CONCLUSIONS: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke. METHODS: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621. FINDINGS: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores. INTERPRETATION: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

Improvements in Endovascular Treatment for Acute Ischemic Stroke: A Longitudinal Study in the MR CLEAN Registry.

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.

Large practice variations in diagnosis and treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) contributes to poor outcomes after subarachnoid hemorrhage (SAH). The pathophysiology of DCI is not fully understood, which has hindered the adoption of a uniform definition. Furthermore, a reliable diagnostic test and an effective evidence-based treatment are lacking. This could lead to variations in care. METHODS: A web-based survey on the variations in the definition, diagnosis, and treatment of DCI was designed and sent to 314 intensivists, neurologists, and neurosurgeons of all 9 hospitals in the Netherlands who care for patients with SAH. The responders were categorized into physicians responsible for the coordination of SAH care and those who were not. For questions on the definition and diagnosis, only the responses from the coordinating physicians were evaluated. For the treatment questions, all the responses were evaluated. RESULTS: The response rate was 34% (106 of 314). All 9 hospitals were represented. Of the responses, 27 did not provide answers for the definition, diagnosis, or treatment questions; 79 responses were used for analysis. Signs of vasospasm were required by 21 of the 47 coordinating physicians (44%) when considering DCI. Of the 47 coordinating physicians, 24 (51%) did not use a diagnostic test results for a positive diagnosis of DCI. When patients were discharged within 21 days, 33 of the 73 responders (45%) did not provide a prescription for nimodipine continuation. Finally, all but one hospital had treated DCI with hypertension induction. CONCLUSIONS: We found large variations in the definition, diagnosis, and treatment of DCI in the Netherlands. In the absence of evidence-based treatment, standardization of management seems warranted in an effort to optimize DCI care.

Hemodynamic changes after intracranial aneurysm growth.

OBJECTIVE: For accurate risk assessment of unruptured intracranial aneurysms, it is important to understand the underlying mechanisms that lead to rupture. It is known that hemodynamic anomalies contribute to aneurysm growth and rupture, and that growing aneurysms carry higher rupture risks. However, it is unknown how growth affects hemodynamic characteristics. In this study, the authors assessed how hemodynamic characteristics change over the course of aneurysm growth. METHODS: The authors included patients with observed aneurysm growth on longitudinal MRA in the period between 2012 and 2016. Patient-specific vascular models were created from baseline and follow-up images. Subsequently, intraaneurysmal hemodynamic characteristics were computed using computational fluid dynamics. The authors computed the normalized wall shear stress, oscillatory shear index, and low shear area to quantify hemodynamic characteristics. Differences between baseline and follow-up measurements were analyzed using paired t-tests. RESULTS: Twenty-five patients with a total of 31 aneurysms were included. The aneurysm volume increased by a median (IQR) of 26 (9-39) mm3 after a mean follow-up period of 4 (range 0.4-10.9) years. The median wall shear stress decreased significantly after growth. Other hemodynamic parameters did not change significantly, although large individual changes with large variability were observed. CONCLUSIONS: Hemodynamic characteristics change considerably after aneurysm growth. On average, wall shear stress values decrease after growth, but there is a large variability in hemodynamic changes between aneurysms.

The added value of cerebrospinal fluid analysis in patients with subarachnoid hemorrhage after negative noncontrast CT.

OBJECTIVE: In patients presenting within 6 hours after signs and symptoms of suspected subarachnoid hemorrhage (SAH), CSF examination is judged to be no longer necessary if a noncontrast CT (NCCT) scan rules out SAH. In this study, the authors evaluated the performance of NCCT to rule out SAH in patients with positive CSF findings. METHODS: Between January 2006 and April 2018, 1657 patients were admitted with a nontraumatic SAH. Of these patients, 1546 had positive SAH findings on the initial NCCT and 111 patients had an NCCT scan that was reported as negative in the acute setting, but with positive CSF examination for subarachnoid blood. Demographic data, World Federation of Neurosurgical Societies grade, and SAH time points (ictus, time of NCCT, and time of lumbar puncture) were collected. All 111 NCCT scans were reevaluated by an experienced neuroradiologist. RESULTS: Of the 111 patients with positive CSF findings, SAH was initially missed on NCCT in 25 patients (23%). Reevaluation of 21 patients presenting within 6 hours of symptom onset confirmed NCCT negative findings in 12 (5 aneurysms), an aneurysmal SAH (aSAH) pattern in 8 (7 aneurysms), and a perimesencephalic pattern in 1 patient. Reevaluation of 90 patients presenting after 6 hours confirmed negative NCCT findings in 74 patients (37 aneurysms), aSAH pattern in 10 (4 aneurysms), and a perimesencephalic pattern in 6 (2 aneurysms). CONCLUSIONS: CSF examination is still mandatory to rule out SAH as NCCT can fail to show blood, even within 6 hours after symptom onset. In addition, the diagnosis SAH was frequently missed during initial reporting.

Risk of Rupture After Intracranial Aneurysm Growth.

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.

Tranexamic acid for chronic subdural hematoma.

BACKGROUND: There is no consensus on optimal treatment for a chronic subdural hematoma (cSDH). In patients with only moderate symptoms treatment with tranexamic acid (TXA) has been suggested. We report off-label use of TXA in seven patients. METHODS: Between August 2016 and May 2018 we identified seven patients for primary conservative treatment with TXA until satisfactory clinical and radiological status was achieved. Primary outcome was surgery for cSDH evacuation. Radiological follow-up was performed at regular intervals for hematoma volume measurements. RESULTS: Five patients experienced complete resolution of symptoms, one patient had a burr-hole craniostomy five days after initiation of TXA treatment due to an increase of left-sided weakness and dysarthria and in one patient symptoms did not improve. Median follow-up was 15 weeks (range 6-25, without the operated patient). The median total volume before start of treatment was 83 mL (range 11-137) for all patients. At the last follow-up, the median total volume in the non-operated patients decreased by 73% to 33 mL (range 0-77). CONCLUSIONS: TXA could be considered as primary medical treatment in patients with a cSDH and mild symptoms. The results of current randomized clinical trials must be awaited.

Cerebral circulation time on DSA during endovascular treatment in WFNS grade I aneurysmal SAH patients-a predictor of DCI?

PURPOSE: Delayed cerebral ischemia (DCI) remains a contributor to poor outcome following aneurysmal subarachnoid hemorrhage (aSAH). We evaluated cerebral circulation time (CCT) on digital subtraction angiography (DSA) during endovascular treatment (EVT) in WFNS grade I aSAH patients as a predictor of DCI. METHODS: Of 135 consecutive WNFS grade I aSAH patients, 90 were included. Age, gender, time of DSA from ictus (< 72 h or > 72 h), Fisher scale, severe vasospasm, development of DCI, EVD-dependent hydrocephalus, re-bleeding, and procedural complications were recorded. CCT was calculated retrospectively from multiphase DSA. Association with DCI was established through univariate and, subsequently, multivariable logistic regression. An optimal threshold value was identified using ROC curve analysis. Patient groups defined by threshold CCT value, DCI, and, subsequently, time of DSA from ictus were analyzed using χ2 and Fisher's exact test. RESULTS: CCT was the only significant factor in the multivariable logistic regression for the outcome development of DCI (OR/second increase in CCT = 1.46 [95% CI 1.14-1.86, p = .003]). When CCT was dichotomized at 8.5 s, the odds ratio for developing DCI was 7.12 (95% CI 1.93-26.34, p = .003) for CCT > 8.5 s compared with < 8.5 s. There was a significant difference for DCI in all patient groups dichotomized by CCT < 8.5 s and > 8.5 s (all patients, p = .001; patients imaged before and after 72 h of ictus, p = .024 and p = .034, respectively). CONCLUSION: A CCT > 8.5 s on DSA during EVT in WFNS grade I aSAH patients is associated with an increased risk of developing DCI and may aid in the management of high-risk patients.

Thrombectomy for acute ischemic stroke patients with isolated distal internal carotid artery occlusion: a retrospective observational study.

PURPOSE: Acute stroke patients presenting with a distal internal carotid artery occlusion and patent carotid terminus, allowing for collateral flow via the circle of Willis, may have a more favorable natural history. Therefore, benefit of endovascular treatment (EVT) is less evident. We performed an exploratory analysis of EVT results compared to conservative treatment in patients with 'carotid-I' occlusions. METHODS: We report on EVT-treated and non-EVT-treated patients with carotid-I occlusions from the MR CLEAN Registry, MR CLEAN trial, and our comprehensive stroke center. CT-angiography was reviewed on primary collateral patency and choroid plexus enhancement. Perfusion deficits were assessed on CT-perfusion (CTP). Clot migration was assessed by comparing clot location on baseline CTA to its location on periprocedural digital subtraction angiography. Outcomes included 90-day functional independence (mRS 0-2), successful reperfusion and mortality. RESULTS: We included 51 patients. Forty-one patients received EVT, ten patients did not. Intravenous thrombolysis was administered in 32 (78%) EVT-treated patients and 6 (60%) non-EVT-treated patients. CTP, available for 17 patients, showed hypoperfusion on cerebral blood flow maps in 13 (76%) patients. Successful reperfusion after EVT occurred in 23 (56%), and clot migration in 8 patients (20%). Functional independence was achieved in 54% (21/39) of EVT-treated and in 10% (1/10) of non-EVT-treated patients. Mortality was 26% (10/39) and 30% (3/10), respectively. Anterior choroidal artery patency and choroid plexus enhancement were positively associated with functional independence. CONCLUSION: In our population, data suggest improved outcomes after EVT in carotid-I occlusion patients and provide no arguments to withhold EVT in these patients.

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

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.

Arterial Steal to the Penumbra Area in Patients with Acute MCA Occlusion: A Quantitative Angiographic Analysis.

PURPOSE: In acute middle cerebral artery (MCA) occlusion, collateral vessels provide retrograde supply to the occluded territory. We hypothesized that such collateral flow reduces perfusion of the non-occluded donor region (steal effect). MATERIALS AND METHODS: Patients with an MCA occlusion with opacification of both ipsi- and contralateral anterior cerebral arteries (ACA) on angiography prior to endovascular treatment were selected. Arteriovenous transit time (AVTT) for both ACA territories was compared for different grades of collateral supply to the MCA territory. In addition, the influence of diabetes and hypertension was analyzed. After successful revascularization, AVTT was re-assessed to determine reversibility. RESULTS: Forty-one patients were analyzed. An AVTT of 8.6 seconds (standard deviation [SD] 2.4 seconds) was seen in the ACA territory of the affected hemisphere in comparison to 6.6 seconds (SD 2.1 seconds) for the contralateral side (P<0.001). A more prolonged (but not significant) AVTT was seen in cases with a higher collateral grade. No difference in AVTT was seen in patients with diabetes or hypertension. After successful MCA revascularization, AVTT delay was 7.4 seconds (SD 2.1 seconds). CONCLUSION: A cerebral steal effect occurs in patients with an acute MCA occlusion, probably related to augmented flow to the penumbra area.

7T versus 3T MR Angiography to Assess Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Aneurysm size and neck measurements are important for treatment decisions. The introduction of 7T magnetic resonance angiography (MRA) led to new possibilities assessing aneurysm morphology and flow due to the higher signal-to-noise ratio. However, it is unknown if the size measurements on 7T MRA are similar to those on the standard 3T MRA. This study aimed to compare aneurysm size measurements between 7T and 3T MRA. METHODS: We included 18 patients with 22 aneurysms who underwent both 3T and 7T MRA. Three acquisition protocols were compared: 3T time of flight (TOF), 7T TOF, and 7T contrast-enhanced MRA. Each aneurysm on each protocol was measured by at least two experienced neuroradiologists. Subsequently, the differences were evaluated using scatterplots and the intraclass correlation coefficients (ICC) of agreement. RESULTS: There was a good agreement among the neuroradiologists for the height and width measurements (mean ICC: .78-.93); the neck measurements showed a moderate agreement with a mean ICC of .57-.72. Between the MR acquisition protocols, there was a high agreement for all measurements with a mean ICC of .81-.96. Measurement differences between acquisition protocols (0-2.9 mm) were in the range of the differences between the neuroradiologists (0-3.6 mm). CONCLUSION: Our study showed that 7T MRA, both nonenhanced and contrast-enhanced, has a high agreement in aneurysm size measurements compared to 3T. This suggests that 7T is useful for reliable aneurysm size assessment.