Background: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its... Show moreBackground: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI.Methods: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4-6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses.Results: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17-2.27) and at day 5 after DCI 1.04 (95% CI 0.84-1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results.Conclusions: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3-/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI. Show less
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 6 months. An expected... Show moreBackground and Objectives The ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal 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 6 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 noncontrast CT, 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 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes.Results Of the 813 ULTRA trial patients who experienced 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% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52).Discussion Ultra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.Classification of Evidence This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage. Show less
Algra, A.M.; Greving, J.P.; Wermer, M.J.H.; Walderveen, M.A.A. van; Schaaf, I.C. van der; Zwan, A. van der; ... ; Vergouwen, M.D.I. 2022
Background and Objectives In counseling patients with an unruptured intracranial aneurysm (UIA), quality of life (QoL) outcomes are important for informed decision making. We evaluated QoL outcomes... Show moreBackground and Objectives In counseling patients with an unruptured intracranial aneurysm (UIA), quality of life (QoL) outcomes are important for informed decision making. We evaluated QoL outcomes in patients with and without preventive aneurysm occlusion at multiple time points during the first year after UIA diagnosis and studied predictors of QoL outcomes. Methods We performed a prospective cohort study in patients aged >= 18 years with a newly diagnosed UIA in 2 tertiary referral centers in the Netherlands between 2017 and 2019. Patients were sent QoL questionnaires at 7 (aneurysm occlusion) or 5 (no occlusion) moments during the first year after diagnosis. We collected baseline data on patient and aneurysm characteristics, passive coping style (Utrecht Coping List), occlusion modality, and neurologic complications. We assessed health-related QoL (HRQoL) with the EuroQol 5 dimensions (EQ-5D), emotional functioning with the Hospital Anxiety and Depression Scale (HADS), and restrictions in daily activities with the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). We used a linear mixed-effects model to assess the course of QoL over time and to explore predictors of QoL outcomes. Results Of 153 eligible patients, 99 (65%) participated, of whom 30/99 (30%) underwent preventive occlusion. Patients undergoing occlusion reported higher baseline levels of passive coping, anxiety and depression, and restrictions than patients without occlusion. During recovery after occlusion, patients reported more restrictions compared with baseline (adjusted USER-P decrease 1 month post occlusion: -12.8 [95% CI -23.8 to -1.9]). HRQoL and emotional functioning gradually improved after occlusion (EQ-5D increase at 1 year: 8.6 [95% CI 0.1-17.0] and HADS decrease at 1 year: -5.4 [95% CI -9.4 to -1.5]). In patients without occlusion, the largest HRQoL improvement occurred directly after visiting the outpatient aneurysm clinic (EQ-5D increase: 9.2 [95% CI 5.5-12.8]). At 1 year, QoL outcomes were comparable in patients with and without occlusion. Factors associated with worse QoL outcomes were a passive coping style in all patients, complications in patients with occlusion, and higher rupture risks in patients without occlusion. Discussion After UIA diagnosis, QoL improves gradually after preventive occlusion and directly after counseling at the outpatient clinic in patients without occlusion, resulting in comparable 1-year QoL outcomes. A passive coping style is an important predictor of poor QoL outcomes in all patients with UIA. Show less
Background: Young patients with aneurysmal subarachnoid hemorrhage (aSAH) and a history of migraine may have an increased risk of delayed cerebral ischemia. We investigated this potential... Show moreBackground: Young patients with aneurysmal subarachnoid hemorrhage (aSAH) and a history of migraine may have an increased risk of delayed cerebral ischemia. We investigated this potential association in a prospective cohort of aSAH patients under 50 years of age. Methods: In our prospective cohort study, we included patients with aSAH under 50 years of age from 3 hospitals in the Netherlands. We assessed lifetime migraine history with a short screener. Delayed cerebral ischemia was defined as neurological deterioration lasting >1 hour not attributable to other causes by diagnostic workup. Adjustments were made for possible confounders in multivariable Cox regression analyses, and adjusted hazard ratios were calculated. Results: We included 236 young aSAH patients (mean age, 41 years; 64% women) of whom 44 (19%) had a history of migraine (16 with aura). Patients with aSAH and a history of migraine were not at increased risk of developing delayed cerebral ischemia compared with patients without migraine (25% versus 20%; adjusted hazard ratio, 1.16 [95% CI, 0.57-2.35]). Additionally, no increased risk was found in migraine patients with aura (adjusted hazard ratio, 0.85 [95% CI, 0.30-2.44]) or in women (adjusted hazard ratio, 1.24 [95% CI, 0.58-2.68]). Conclusions: Patients with aSAH under the age of 50 years with a history of migraine are not at increased risk of delayed cerebral ischemia. Show less
Kamp, L.T. van der; Rinkel, G.J.E.; Verbaan, D.; Berg, R. van den; Vandertop, W.P.; Murayama, Y.; ... ; Vergouwen, M.D.I. 2021
IMPORTANCE Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with... Show moreIMPORTANCE 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 datawere 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 1mmor greater increase in 1 direction at follow-up imaging.MAIN OUTCOMES AND MEASURES The primary outcomewas 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 (7mmor 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. Show less
Background: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year... Show moreBackground: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year risks of rupture based on six easily retrievable patient and aneurysm characteristics. We assessed whether management decisions on UIAs changed after implementation of the PHASES score. Patient and methods: We included all patients with UIAs who were referred to two Dutch tertiary referral centers for aneurysm care in the Netherlands (University Medical Center Utrecht (UMCU) and Leiden University Medical Center (LUMC)) between 2011 and 2017. Analyses were done on an aneurysm level. We calculated the overall proportion of UIAs with a decision to treat before and after PHASES implementation and studied the influence of age and center on post-implementation management changes. Results: We included 623 patients with 803 UIAs. The proportion of UIAs with a decision to treat was 123/360 (34.2%) before and 117/443 (26.4%) after PHASES implementation (absolute risk difference:-7.8%; 95% CI: -14.1 to-1.4). The decision to treat was made at a higher median PHASES score after implementation (7 points (IQR 5;10) pre-versus 8 points (IQR 5;10) post-implementation; p = 0.14). The reduced proportion with a treatment decision after implementation was most pronounced in patients <50 years (-22.3%; 95% CI:-39.2 to -3.4) and was restricted to treatment decisions made at the UMCU (-10.6%; 95% CI:-18.5 to-2.5). Discussion and conclusions: Management of UIAs changed following implementation of the PHASES score, but the impact of PHASES implementation on treatment decisions differed across age subgroups and centers. Show less
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... Show moreBackground 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. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Show less
Background and Purpose: Delayed cerebral ischemia (DCI) is a major contributor to the high morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Spreading depolarizations may play a... Show moreBackground and Purpose: Delayed cerebral ischemia (DCI) is a major contributor to the high morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Spreading depolarizations may play a role in DCI pathophysiology. Because patients with migraine are probably more susceptible to spreading depolarizations, we investigated whether patients with aneurysmal subarachnoid hemorrhage with migraine are at increased risk for DCI. Methods: We included patients with aneurysmal subarachnoid hemorrhage from 3 hospitals in the Netherlands. We assessed lifetime migraine history with a short screener. DCI was defined as neurological deterioration lasting >1 hour not attributable to other causes by diagnostic work-up. Adjustments were made for possible confounders in multivariable Cox regression analyses and adjusted hazard ratios (aHR) were calculated. We assessed the interaction effects of age and sex. Results: We included 582 patients (mean age 57 years, 71% women) mostly with mild to moderate aneurysmal subarachnoid hemorrhage of whom 108 (19%) had a history of migraine (57 with aura). Patients with migraine were not at increased risk of developing DCI compared with patients without migraine (22% versus 24%, aHR, 0.89 [95% CI, 0.56-1.43]). Additionally, no increased risk was found in patients with migraine with possible aura (aHR, 0.74 [95% CI, 0.39-1.43]), in women (aHR, 0.88 [95% CI, 0.53-1.45],P-interaction=0.859), or in young patients aged <50 years (aHR, 1.59 [95% CI, 0.72-3.49]), although numbers in these subgroups were limited. We found an interaction between migraine and age with an increased risk of DCI among young patients with migraine (P-interaction=0.075). Conclusions: Patients with migraine are in general not at increased risk of DCI. Future studies should focus in particular on young SAH patients, in whom there might be an association between migraine history and development of DCI. Show less
Dijkland, S.A.; Jaja, B.N.R.; Jagt, M. van der; Roozenbeek, B.; Vergouwen, M.D.I.; Suarez, J.I.; ... ; SAHIT Collaboration 2020
OBJECTIVE Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of... Show moreOBJECTIVE Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH).METHODS The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country differences were quantified with the median odds ratio (MOR), which can be interpreted as the ratio of odds of unfavorable outcome between a typical high-risk and a typical low-risk center or country.RESULTS The proportion of patients with unfavorable outcome was 27% (n = 1599). The authors found substantial between-center differences (MOR 1.26, 95% CI 1.16-1.52), which could not be explained by patient characteristics and timing of aneurysm treatment (adjusted MOR 1.21, 95% CI 1.11-1.44). They observed no between-country differences (adjusted MOR 1.13, 95% CI 1.00-1.40).CONCLUSIONS Clinical outcomes after aSAH differ between centers. These differences could not be explained by patient characteristics or timing of aneurysm treatment. Further research is needed to confirm the presence of differences in outcome after aSAH between hospitals in more recent data and to investigate potential causes. Show less
