Introduction Cerebral venous thrombosis (CVT) is associated with a risk of late seizures, particularly in patients with severe disease requiring decompressive surgery. The DIAS3 score was developed to predict late seizures after CVT, but its performance in surgically treated patients is unknown. We aimed to validate the DIAS3 score in a high-risk cohort of CVT patients treated by decompressive surgery. Methods This was a substudy of the DECOMPRESS2 - a prospective, multicentre cohort, including patients with CVT treated with decompressive surgery. Patients with available data on the occurrence and timing of seizures following CVT were included. Late seizures were defined as those occurring more than 7 days after CVT diagnosis, up to 1 year follow-up. We calculated DIAS3 score for all included patients. Predictive performance was assessed only for the 1-year risk of late seizures. Discrimination was evaluated using receiver operating characteristic analysis, and calibration by comparing predicted and observed seizure risks. Diagnostic performance was assessed across multiple probability thresholds. Results Eighty-nine patients were included (median age 38 years; 69.7% female). Late seizures occurred in 22 patients (24.7%). The mean predicted 1-year seizure risk according to the DIAS3 score was 28.4%. The DIAS3 score showed poor discrimination (area under the curve 0.44, 95% confidence interval 0.30-0.59) and poor calibration. Across all tested thresholds, sensitivity and specificity showed an expected trade-off, but overall predictive accuracy was limited. Conclusion The DIAS3 score demonstrated poor discrimination and calibration in CVT patients treated by decompressive surgery. These findings suggest that the DIAS3 score should not be used to predict late seizures in this high-risk surgical subgroup.

The ULTRA trial evaluated the impact of ultra-early and short-term tranexamic acid (TXA) treatment in patients with subarachnoid hemorrhage (SAH) and found no clinical benefit at six months. This post-hoc analysis examines whether TXA improves quality of life (QoL) at three and six months. The ULTRA trial was a randomized, controlled, multicenter study conducted from July 2013 to July 2019. Patients received either TXA or standard care. This analysis included patients who completed at least one QoL questionnaire. The primary endpoint was QoL, assessed using the EQ-5D-3L questionnaire at three and six months. Linear mixed models adjusted for confounders were used to analyze the association between TXA and QoL. Of the 955 ULTRA patients, approximately 25

The ULTRA trial demonstrated no improvement in clinical outcome at 6 months in patients with subarachnoid hemorrhage (SAH) when treated with ultra-early and short-term tranexamic acid (TXA). In this post hoc analysis, we evaluated the effect of TXA in females and males on clinical outcome after aneurysmal SAH (aSAH). The ULTRA trial was a prospective, randomized, controlled, open-label trial, conducted between 2013 and 2020. Patients with spontaneous SAH were assigned to ultra-early, short-term TXA in addition to usual care, or usual care only. In this study, we only included ULTRA participants with radiologically proven aSAH. We analyzed the potential effect of sex on the association between treatment group and clinical outcome by assessing effect modification, and evaluated the effect of TXA separately in females and males. The primary endpoint was clinical outcome at 6 months, assessed by the distribution of the modified Rankin Scale (mRS). Odds ratios (OR) and adjusted OR (aOR) with 95

INTRODUCTION:Non-aneurysmal, non-traumatic subarachnoid hemorrhage (nSAH) refers to cases where a causative aneurysm cannot be identified. We studied 6-months' outcomes in nSAH patients. PATIENTS AND METHODS:From a prospective SAH registry of all nSAH patients admitted between 2012 and 2023, relevant complications and outcomes were collected. Functional outcome and return-to-work at 6 months were assessed using the modified Rankin Scale (mRS), quality of life with the EuroQol-5Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS), and an institutional 14-item questionnaire for assessment of residual symptoms. RESULTS:325 consecutive nSAH patients were included (192 non-perimesencephalic, non-aneurysmal subarachnoid hemorrhage (NPSAH); 133 perimesencephalic subarachnoid hemorrhage (PMSAH)). 303 (93%; 180 NPSAH and 123 PMSAH) were available at follow-up (7 patients died). Favorable functional outcome (mRS-score 0-2) was reported in 271 (89%) patients and did not differ between NPSAH- and PMSAH. One hundred forty-one (77%) patients returned to work, whereas only 71 (39%) patients reached their previous level of work. PMSAH patients were more likely to return to work (68/96 (71%) NPSAH and 73/87 (84%) PMSAH, respectively, p = 0.036). Furthermore, PMSAH patients were more likely to fully return to work (p = 0.028). The mean (SD) EQ-5D and EQ-VAS scores were 0.827 (0.184) and 74 (16), respectively. The HADS-A and -D scores were deviant (score > 7 points) in 53 (23%) and 48 (21%) patients, respectively. Only 39 patients (16%) denied experiencing residual symptoms. Increased fatigue (n = 164; 68%), increased concentration difficulties (n = 130; 54%), and increased forgetfulness (n = 121; 50%) were the most frequently reported residual symptoms. DISCUSSION AND CONCLUSION:This study reveals that the majority of nSAH patients reports residual symptoms and did not return to their previous level of work at 6 months follow-up, despite a favorable functional outcome. These findings nuance the perception of a good outcome, as suggested in previous studies, warranting further research on possible rehabilitative interventions and counseling in these patients.

Background Decompressive surgery can be lifesaving in patients with severe cerebral venous thrombosis (CVT) and impending brain herniation. However, data on health-related quality of life (HRQoL) after surgery are limited. Methods DECOMPRESS-2 was a prospective cohort study including adult patients with CVT from 15 centers in 10 countries who underwent decompressive surgery (2011–2019). HRQoL was assessed using EQ5D-3L utility scores, subdomains, and a visual analogue scale (VAS) at 6 and 12 months post-surgery. Complete case analysis, multiple imputation, best- and worst-case analyses were performed. Predictors of EQ5D-score (Tobit regression) and VAS (linear regression) at 12 months were analyzed. Results Of 118 patients, 112 were included (median age 38 years [IQR 27–46], 68% female). At 12-months, EQ5D-3L and VAS were available for 89% and 90% of survivors, respectively. Median EQ5D-3L-score was 0.70 (IQR 0.52–0.85, mean 0.59 [SD 0.38]) and median VAS was 70 (IQR 56–80, mean 69 [SD 18]). Overall, 84% of patients reported problems in ≥1 subdomain of the EQ5D-3L: 68% with usual activities, 59% pain/discomfort, 58% anxiety/depression, 47% with self-care, 43% with mobility. Higher age and residence in a middle-income country (vs. high-income) predicted poorer EQ5D-3L and VAS. Preoperative coma predicted worse EQ5D-3L only. Conclusions Twelve months after decompressive surgery for CVT, over 4 out of 5 survivors reported problems in at least one subdomain of the EQ5D-3L. Higher age, middle-income country status and preoperative coma were negative predictors of quality of life.

BACKGROUND:Endothelial cell activation seems to be an important process in the multifactorial pathophysiology of delayed cerebral ischemia (DCI) and subsequent poor clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). AIM:To assess the association between biomarker levels of endothelial activation and the occurrence of DCI and poor clinical outcome six months after aSAH. METHODS:Between October 2018 and November 2020, 75 aSAH patients were included. Blood samples were taken on admission, days 3-5 and days 9-11 after aSAH. Ten patients with unruptured intracranial aneurysms served as controls. Poor outcome was assessed at six months, defined by a modified Rankin Scale score of 4-6. The cohort was dichotomized into patients with and without DCI and good and poor outcomes. Biomarker levels of von Willebrand factor (vWF), E-selectin, thrombomodulin, syndecan-1 and matrix metalloproteinase (MMP-9) were analyzed and compared between groups by a T-test or Mann-Whitney U test, depending on the normality of the data. RESULTS:Twelve (16.0%) patients developed DCI, and 39 (41.9%) patients had poor outcomes at six months post-aSAH. None of the biomarkers showed significant differences between patients with and without DCI. vWF and syndecan-1 were elevated on admission and on days 9-11 in patients with poor outcomes (p < 0.05 and p = 0.02, respectively). CONCLUSION:Levels of vWF, E-selectin, thrombomodulin, syndecan-1 and MMP-9 were not associated with the occurrence of DCI, although higher levels of vWF and syndecan-1 were associated with poor outcome at six months. Further research is needed to establish the role of these biomarkers in aSAH patients.

INTRODUCTION:The incidence and outcomes of seizures among patients with severe cerebral venous thrombosis treated with decompressive surgery are unknown as are potential predictors of seizures in these patients. PATIENTS AND METHODS:We report data from a multicenter, consecutive cohort including patients with cerebral venous thrombosis treated with decompressive surgery from 15 hospitals in 10 different countries between December 2011 and December 2019. We analyzed the cumulative incidence of seizures within one year after decompressive surgery and performed an exploratory analysis of potential factors associated with the incidence of post-surgery seizures, adjusted for competing mortality risk. RESULTS:Of 116 included patients (median age 38 years [IQR 27-46], 68% female), 26 (22%) had seizures within one year after decompressive surgery. The mortality-adjusted cumulative one-year incidence of a first seizure after surgery was 23% (95% CI 16-31). Only aphasia at presentation predicted post-surgery seizures. Among patients who had a post-surgery seizure, the first seizure occurred despite active treatment with anti-seizure medications in 83% of patients. Recurrent seizures within the first year after surgery were reported in 63% of patients. DISCUSSION AND CONCLUSION:Despite extensive use of anti-seizure medications, in patients with cerebral venous thrombosis treated with decompressive surgery the rate of seizures was 23% (95% CI 16-31) within one year after surgery. Of the patients who had a seizure after surgery, 63% had a recurrent seizure within the first year post-surgery.

BACKGROUND:The prediction of delayed cerebral ischemia (DCI) and poor clinical outcome following aneurysmal subarachnoid hemorrhage (aSAH) is an unmet clinical need to improve on stratification of patients. DCI and poor clinical outcome following aSAH have been associated with hypercoagulability as detected by viscoelastic testing. This study assesses temporal alterations in rotational thromboelastography (ROTEM) coagulation profiles and the discriminative ability of ROTEM parameters for DCI and poor clinical outcome following aSAH. METHODS:ROTEM parameters were measured on admission, days 3-5, and days 9-11 after aSAH and compared between patients with and without DCI, radiological DCI, and poor 6-month clinical outcome as per modified Rankin Scale scores 4-6. Receiver operating characteristic curve analyses were used to calculate areas under the curve (AUCs) and determine cutoff values with a sensitivity > 90% for (radiological) DCI and with a specificity > 90% for poor outcome. RESULTS:Of 160 included patients with aSAH, 31 (19%) had DCI, 16 (10%) had radiological DCI, and 68 (44%) had poor outcome at 6 months. DCI, radiological DCI, and poor clinical outcome were associated with hypercoagulability. The ROTEM parameter with the best discriminative ability for radiological DCI was INTEM clotting time (AUC 0.75) on admission day, with an optimal cutoff value of < 146 s (sensitivity 92%, specificity 47%). For poor outcome, this was increased clot strength by FIBTEM amplitude at 10 minutes (A10, AUC 0.85) on days 3-5, with an optimal cutoff value > 27 mm (specificity 94%, sensitivity 49%). CONCLUSIONS:In this study, ROTEM parameters indicative of increased coagulation had good predictive ability for poor clinical outcome. If independently validated, ROTEM parameters might have the potential to stratify patients with aSAH who may benefit from anticoagulant treatment in future trials with the aim to improve clinical outcome.

Introduction:Decompressive craniectomy (DC) can be lifesaving, but many survivors do not regain independence in daily life. Recovery of consciousness in the first post-operative days is regarded as a prognostic factor, however, literature on the relation between early recovery of consciousness and long-term independence is scarce. Research question:To analyse the relation between recovery of consciousness in the first 14 days post-DC and long-term functional outcome. Material and methods:Glasgow Coma Scale (GCS) motor (M) scores during the first 14 post-DC days of 188 consecutive adult patients undergoing DC for various pathologies were retrospectively extracted from hospital records, together with one-year Glasgow Outcome Scale (GOS) scores. Recovery of consciousness was defined as GCS M6. Outcome was categorised into death (GOS 1), unfavourable survival (GOS 2-3), and favourable survival (GOS 4-5). Results:Overall, 32 % survived favourably, 21 % unfavourably, and 47 % died. One hundred and eight patients (57 %) regained consciousness during the first two post-operative weeks. At one year, 53 % of M6 patients were functionally independent, versus only 4 % of patients who did not regain consciousness during that time-frame (p < 0.001). Chances of functionally independent survival in M6 patients were significantly higher in patients ≤50 years old than in patients >50 years old (71 % versus 27 %, p < 0.001). Discussion and conclusion:Long-term functional outcome of DC patients differed considerably when assorted for early recovery of consciousness, especially when categorised for age. These results may serve to better inform family members and patients during post-DC counselling.

OBJECTIVE:To evaluate the cost-effectiveness and cost-utility of adding ultra-early and short-term administration of tranexamic acid (TXA) to standard care in patients with subarachnoid hemorrhage (SAH). MATERIALS AND METHODS:An economic evaluation was performed alongside the ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA) trial. The main outcomes were the incremental cost-effectiveness ratio (ICER), expressed as costs per one-point increase in modified Rankin scale (mRS) score, and the incremental cost-utility ratio (ICUR), expressed as costs per quality-adjusted life-year (QALY). Cost-effectiveness acceptability curves (CEACs) were visualized with varying ICER cut-offs. Bootstrapping techniques and sensitivity analyses were performed to account for uncertainty. RESULTS:The ULTRA trial included 955 patients, with 480 assigned to the TXA group and 475 to the control group. The mean mRS score was 3.4 (95% CI: 3.2-3.5) in the TXA group and 3.2 (95% CI: 3.0-3.4) in the control group. The mean QALY was 0.26 (95% CI: 0.24-0.28) in the TXA group and 0.28 (95% CI: 0.26-0.30) in the control group. Mean costs were €62,180 (95% CI: 57,589-66,913) in the TXA group and €58,624 (95% CI: 53,693-63,955) in the control group. The probability of treatment with TXA being cost-effective ranged from 4% to 16% for mRS and from 8% to 16% for QALYs. CONCLUSIONS:Ultra-early and short-term administration of TXA to patients with SAH is not cost-effective. Therefore, we recommend against using TXA for this patient group. TRIAL REGISTRATION:Netherlands Trial Register: NTR3272. CLINICALTRIALS:gov identifier: NCT02684812.

Introduction:Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) contributes significantly to mortality and morbidity. Neuroinflammation and platelet activation are implicated in its pathophysiology. Research question:This study evaluates the association of admission white blood cell count (WBC) and platelet count (PC), and their combination, with DCI and explores their integration into predictive models. Materials and methods:This single-center cohort study utilized data from a prospective SAH registry (December 2011-December 2019). Patients with confirmed aSAH and recorded WBC and PC within 72 h post-ictus were included. Univariate and multivariate regression models with established predictors, consisting of the modified Fisher scale (mFS) and World Federation of Neurological Surgeons grade (WFNS), were performed. Predictive values were assessed using AUCs (95 % CI) and C-statistics. Results:Of 954 reviewed patients, 660 met inclusion criteria, with 178 (27.0 %) developing DCI. Patients who developed DCI had significantly higher admission WBC levels (mean (SD) 14.3 (5.1) × 109/L vs. 12.7 (4.8) × 109/L, p < 0.001), whereas admission PC did not differ significantly (median (IQR) 255 (201-301) × 109/L vs. 241 (205-289) × 109/L, p = 0.196). WBC was predictive of DCI (OR 1.06, 1.03-1.10), but PC was not (OR 1.00, 1.00-1.02). Of established predictors, mFS was significant (OR 6.42, 1.96-21.02), whereas WFNS was not (OR 0.79, 0.54-1.15). Among all variables, WBC demonstrated highest predictive value (AUC: 0.59, 0.54-0.64), surpassing mFS and WFNS, or their combination. A combined model incorporating WBC, PC, mFS, and WFNS yielded the highest predictive value (AUC: 0.63, 0.58-0.68). Discussion and conclusion:Admission WBC and PC offer modest predictive value for DCI, either alone or combined with neurological status and hemorrhage burden. However, WBC demonstrated highest predictive value of all investigated variables and modestly improves prediction models. Future research should evaluate WBC's utility in models with enhanced predictive performance.

INTRODUCTION:Aneurysmal subarachnoid haemorrhage (aSAH) is a severe condition associated with significant morbidity and case fatality rate. Delayed cerebral ischaemia (DCI) is a major factor contributing to poor outcomes. For long, DCI was thought to be caused by vasospasm, induced by blood in the subarachnoid space. Growing experimental and clinical evidence has shown an activation of the coagulation cascade and several other (intravascular) pathophysiological pathways, affecting the cerebral microcirculation. In a retrospective analysis of our aSAH patient registry, we observed lower in-hospital mortality and a significantly higher rate of discharge-to-home in patients treated with high-dose nadroparin, compared with patients treated with low-dose (prophylactic) nadroparin. This observation suggests a potential benefit of higher doses of nadroparin in the acute course after aSAH. We therefore hypothesise that treatment with high-dose nadroparin will improve clinical outcome in endovascularly treated patients with aSAH. METHODS AND ANALYSIS:This is a single-centre, prospective, phase II randomised controlled trial. From January 2022, all eligible patients will be recruited. 100 patients will be randomised to the intervention arm, that is, nadroparin two times per day 5700 AxaIU, or the control arm, that is, nadroparin once daily 2850 AxaIU in patients with body weight ≤100 kg or once daily 5700 AxaIU in patients with body weight >100 kg, both for up to 21 days. The trial includes a 6-month follow-up period. The primary objective is 30-day mortality rate. Secondary outcomes include assessment of DCI, complications during admission, discharge location, clinical outcome (modified Rankin Scale), quality of life and total healthcare costs at 3 and 6 months follow-up. ETHICS AND DISSEMINATION:Approval was obtained from the Medical Research Ethics Committee of the Amsterdam UMC, location Academic Medical Center (AMC) (MREC-number 2020_192), and recruitment has begun. The study results will be submitted for publication in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER:NCT04507178.

BACKGROUND AND OBJECTIVES:Treatment of patients who present with poor clinical condition is often postponed until neurological improvement is observed. Despite previous studies, it is still unclear how survivors perceive their quality of life (QoL). This study aimed to evaluate self-perceived QoL in patients with aneurysmal subarachnoid hemorrhage who present with poor clinical condition, as defined by World Federation of Neurosurgical Societies (WFNS) grades 4 to 5, compared with those who present in more favorable clinical condition (WFNS 1-3). METHODS:Between 2011 and 2021, 1160 patients with aneurysmal subarachnoid hemorrhage were admitted to the Amsterdam UMC. Among the 845 patients who survived, 537 participated in the QoL questionnaires. Patient characteristics, complications, EQ-5D questionnaires, modified Rankin Scale, and Hospital Anxiety and Depression Scale were analyzed using the nonparametric Mann-Whitney U test for continuous variables or the Pearson χ 2 test for categorical variables. RESULTS:Of the 537 responders, 452 (84%) presented with low grade (WFNS 1-3) and 85 (16%) presented with high grade (WFNS 4-5). The high-grade group reported a self-perceived QoL score of 70 (of 100), while the low-grade group reported a score of 75 ( P = .12). The mean EQ-5D index value was 0.74 for the high-grade group and 0.81 for the low-grade group ( P < .01). In the high-grade group, 61 patients (72%) had a favorable outcome (modified Rankin Scale 0-3) compared with 419 (94%) in the low-grade group ( P < .001). CONCLUSION:High-grade WFNS patients rated their QoL as satisfactory, with only a marginal 5-point difference on a 100-point scale compared with low-grade WFNS patients. In addition, almost three-quarters of high-grade WFNS survivors achieved a favorable outcome. Given that a subset of patients, despite presenting with a poor clinical condition, still achieve a favorable outcome, these findings reinforce our perspective advocating for early and comprehensive treatment.

BACKGROUND:Anticoagulation is the mainstay acute therapy for cerebral venous thrombosis (CVT). Decompressive surgery is required in a small minority of patients with large parenchymal lesions and impending herniation, which requires a temporary suspension of anticoagulation. AIM:The objective of this study was to identify the optimal timing for starting or resuming anticoagulation following decompressive surgery. METHODS:Data were collected from the Decompressive Surgery for CVT Study 2 (DECOMPRESS2), a prospective multinational cohort observational study of 118 patients with severe CVT treated by decompressive surgery. We assessed the frequency of new hemorrhagic and venous thrombotic events from admission to discharge in patients who started or resumed anticoagulation <24 h (early) and ⩾24 (late) following surgery, using propensity score matching and logistic regression. Death and disability were evaluated by the modified Rankin scale (mRS > 2) at discharge and at 1 year follow-up and compared between the two groups. RESULTS:Of the 90 patients available for analysis, 35 (39%) started or resumed anticoagulation within the first 24 h after surgery while 55 (61%) did so later than 24 h. Overall frequency of patients with new hemorrhagic or venous thrombotic events from admission to discharge was 26.7% (24 patients), without crude or adjusted for the propensity score statistically significant difference between the early and late anticoagulation groups (<24 h, 11 patients, 31%, vs ⩾24 h, 13 patients, 24%; odds ratio (OR): 0.86; 95% confidence interval (CI): 0.24 to 3.04; χ2 = 0.33, p = 0.57). The distribution of major hemorrhagic events was also comparable: 8 (23%) bleedings in the <24 h, and 9 (16%) in the ⩾24 h (χ2 = 0.24, p = 0.62). No CVT recurred. Two venous thrombotic events occurred in <24 h (6%) and 5 in the ⩾24 h (9%) group. There was no association between anticoagulation timing and death or dependence (mRS 3-6) at discharge (OR: 1.65. 95% CI: 0.30 to 9.01, p = 0.56), or at 1 year follow-up (OR: 2.19, 95% CI: 0.78 to 6.10, p = 0.14). CONCLUSIONS:The results of this cohort study suggest that the timing of anticoagulation therapy following decompressive surgery for CVT does not significantly influence the risk of new bleeding or venous thrombotic events or disability.

BACKGROUND AND AIMS:Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disorder characterized by peripheral nerve damage. Although T lymphocytes (T-cells) are implicated in the pathogenesis of CIDP, we previously observed that the frequency of highly expanded T-cell clones (HECs) in peripheral blood of CIDP patients was not different from healthy controls. To investigate if local T-cells might be pathogenic, we employed next-generation sequencing to compare the TCRβ repertoire between peripheral blood and nerve tissue of CIDP patients. METHODS:Adaptive immune receptor repertoire sequencing (AIRR-Seq) of the TCRβ chain was conducted on peripheral blood and nerve tissue obtained from three newly diagnosed CIDP patients. RESULTS:All patients showed high numbers of highly expanded TCRβ clones in nerve tissue that were not detected or detected only in very low frequencies in blood, whereas in blood other HECs were found. Clustering analysis based on CDR3-similarity showed that these nerve tissue-restricted TCRβ clones were distinct from blood clones, as evidenced by the absence of prominent clusters. INTERPRETATION:Unique nerve tissue-restricted TCRβ clones may indicate a highly localized immune response with localized expansion and/or retention of T-cells that could contribute to the pathomechanism of CIDP. Further characterization of the phenotype, antigen target and functionality of these T-cells is essential to determine their pathogenic role.

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.

BACKGROUND:Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort.METHODS:DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression.RESULTS:A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery.CONCLUSIONS:Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

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.

OBJECTIVES:To perform a detailed examination of sodium levels, hyponatremia and sodium fluctuations, and their association with delayed cerebral ischemia (DCI) and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH).DESIGN:An observational cohort study from a prospective SAH Registry.SETTING:Tertiary referral center focused on SAH treatment in the Amsterdam metropolitan area.PATIENTS:A total of 964 adult patients with confirmed aSAH were included between 2011 and 2021.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:A total of 277 (29%) developed DCI. Hyponatremia occurred significantly more often in DCI patients compared with no-DCI patients (77% vs. 48%). Sodium levels, hyponatremia, hypernatremia, and sodium fluctuations did not predict DCI. However, higher sodium levels were significantly associated with poor outcome in DCI patients (DCI onset -7, DCI +0, +1, +2, +4, +5, +8, +9 d), and in no-DCI patients (postbleed day 6-10 and 12-14). Also, hypernatremia and greater sodium fluctuations were significantly associated with poor outcome in both DCI and no-DCI patients.CONCLUSIONS:Sodium levels, hyponatremia, and sodium fluctuations were not associated with the occurrence of DCI. However, higher sodium levels, hypernatremia, and greater sodium fluctuations were associated with poor outcome after aSAH irrespective of the presence of DCI. Therefore, sodium levels, even with mild changes in levels, warrant close attention.

BACKGROUND:Subarachnoid hemorrhage in children is rare. The most common cause is trauma, followed by an arteriovenous malformation, aneurysm or tumor.CASE DESCRIPTION:We describe the case of an 11-year-old girl who developed sudden headache with nausea and vomiting during athletics training. Her neurological exam was normal. With imaging and a lumbar puncture a subarachnoid hemorrhage was diagnosed, based on a ruptured saccular aneurysm of the right middle cerebral artery. Endovascular treatment was unsuccessful, after which the aneurysm was treated surgically. Postoperative recovery was uneventful. Additional tests for underlying conditions were negative.CONCLUSION:Also in a child with acute headache, nausea, and vomiting, the diagnosis of a subarachnoid hemorrhage should be considered, even if neurological examination is normal. Expeditious diagnosis and treatment are important in order to prevent rebleeding.