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.

Treatment outcomes and the role of the DES scheme in the appropriate treatment selection for high-grade dural arteriovenous fistulas.

OBJECTIVE: Endovascular and microsurgical treatment are viable options for the majority of Borden type III dural arteriovenous fistulas (dAVFs). The aim of this study was to examine treatment outcomes in a comparative analysis of endovascular and surgical treatment modalities for Borden type III fistulas and explore clinical implications of the DES scheme in selecting ideal candidates for surgical therapy. METHODS: Patients diagnosed with dAVFs with leptomeningeal venous drainage admitted to the Departments of Neurosurgery or Neuroradiology of the University Hospital Zurich between January 2014 and October 2021 were included in this study. Comprehensive patient data including demographics, clinical presentation, and dAVF characteristics, including established classifications, were collected. Treatment outcomes were assessed based on postinterventional angiography findings. In addition, treatment-related complications were assessed based on the Clavien-Dindo classification. RESULTS: Among all Borden type III dAVFs, 15 were initially treated endovascularly (60% complete occlusion rate) and 10 with microsurgical disconnection (90% complete occlusion rate) (p = 0.18). Subgroup analysis of dAVFs meeting the criteria for directness and exclusivity based on the DES scheme showed a 100% complete occlusion rate after microsurgical disconnection, whereas embolization achieved a complete occlusion rate of 60% (p = 0.06). There was no significant difference in the rate or severity of treatment-related complications between treatment modalities. CONCLUSIONS: This study suggests that microsurgical disconnection is a viable primary treatment modality for Borden type III dAVFs, particularly for dAVFs that meet the criteria of directness and exclusivity according to the DES scheme. The DES scheme demonstrates its relevance in selecting the most appropriate treatment strategy for affected patients.

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events. METHODS: We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO2) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. RESULTS: Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke. CONCLUSIONS: Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

Safety and Effectiveness of an Enhanced Recovery Protocol in Patients Undergoing Burr Hole Evacuation for Chronic Subdural Hematoma.

BACKGROUND AND OBJECTIVES: Enhanced recovery programs may be especially useful in patients with chronic subdural hematoma or hygroma (cSDH), who frequently exhibit frailty and multimorbidity. We aim to evaluate the real-world safety and effectiveness of an enhanced recovery protocol in this population. METHODS: From a prospective registry, burr hole evacuations for cSDH carried out under the protocol (including early thromboprophylaxis, no flat bed rest, early mobilization without drain clamping, and early resumption of antithrombotic medication) were extracted, along with those procedures carried out within the past year before protocol change. Propensity score-based matching was carried out. A range of clinical and imaging outcomes were analyzed, including modified Rankin Scale as effectiveness and Clavien-Dindo adverse event grading as safety primary end points. RESULTS: Per group, 91 procedures were analyzed. At discharge, there was no significant difference in the modified Rankin Scale among the standard and enhanced recovery groups (1 [1; 2] vs 1 [1; 3], P = .552), or in Clavien-Dindo adverse event grading classifications of adverse events (P = .282) or occurrence of any adverse events (15.4% vs 20.9%, P = .442). There were no significant differences in time to drain removal (2.00 [2.00; 2.00] vs 2.00 [1.25; 2.00] days, P = .058), time from procedure to discharge (4.0 [3.0; 6.0] vs 4.0 [3.0; 6.0] days, P = .201), or total hospital length of stay (6.0 [5.0; 9.0] vs 5.0 [4.0; 8.0] days, P = .113). All-cause mortality was similar in both groups (8.8% vs 4.4%, P = .289), as was discharge disposition (P = .192). Other clinical and imaging outcomes were similar too (all P > .05). CONCLUSION: In a matched cohort study comparing perioperative standard of care with a novel enhanced recovery protocol focusing on evidence-based drainage, mobilization, and thromboprophylaxis regimens as well as changes to the standardized reuptake of oral anticoagulants and antiaggregants, no differences in safety or effectiveness were observed after burr hole evacuation of cSDH.

COveRs to impRove EsthetiC ouTcome after Surgery for Chronic subdural hemAtoma by buRr hole trepanation-Results of a Swiss Single-Blinded, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Burr hole trepanation to evacuate chronic subdural hematoma (cSDH) results in bony skull defects that can lead to skin depressions. We intend to study the effect of burr hole covers to prevent skin depressions and improve the esthetic result. METHODS: In a randomized trial, we enrolled adult patients with symptomatic cSDH. Patients received burr hole trepanation with (intervention) vs without burr hole covers (control) in a 1:1 ratio. Patients requiring evacuation of bilateral cSDHs served as their internal control. Primary outcome was satisfaction with the esthetic result of the scar, measured from 0 (dissatisfied) to 10 (very satisfied) on the Esthetic Numeric Analog (ANA) scale at 90 days. Secondary outcomes included ANA scale, rates of skin depression, complications, as well as neurological, disability, and health-related quality of life outcomes until 12 months. RESULTS: We included 78 patients (55 with unilateral and 23 with bilateral cSDH; median age 78 years, 83% male) between 03/2019 and 05/2021, 50 trepanations for the intervention and 51 for the control group. In an intention-to-treat analysis, the ANA scale scores were 9.0 (intervention) and 8.5 (control arm) at 90 days (P = .498). At 12 months, the ANA scale scores were 9.0 and 8.0 for the intervention and control groups, respectively (P = .183). Skin depressions over the frontal burr hole were noted by 35% (intervention) and 63% (control) of patients at 90 days (P = .009) and by 35% and 79% (P < .001) at 12 months, respectively. There were no differences in complications, neurological, disability, and health-related quality of life outcomes. CONCLUSION: Satisfaction with the esthetic result of the scar was inherently high. This study does not show evidence for improvement on the ANA scale by applying a burr hole cover. The application of burr hole covers resulted in less skin depressions and did not negatively affect complication rates or outcomes.

Mixed Reality for Cranial Neurosurgical Planning: A Single-Center Applicability Study With the First 107 Subsequent Holograms.

BACKGROUND AND OBJECTIVES: Mixed reality (MxR) benefits neurosurgery by improving anatomic visualization, surgical planning and training. We aim to validate the usability of a dedicated certified system for this purpose. METHODS: All cases prepared with MxR in our center in 2022 were prospectively collected. Holographic rendering was achieved using an incorporated fully automatic algorithm in the MxR application, combined with contrast-based semiautomatic rendering and/or manual segmentation where necessary. Hologram segmentation times were documented. Visualization during surgical preparation (defined as the interval between finalized anesthesiological induction and sterile draping) was performed using MxR glasses and direct streaming to a side screen. Surgical preparation times were compared with a matched historical cohort of 2021. Modifications of the surgical approach after 3-dimensional (3D) visualization were noted. Usability was assessed by evaluating 7 neurosurgeons with more than 3 months of experience with the system using a Usefulness, Satisfaction and Ease of use (USE) questionnaire. RESULTS: One hundred-seven neurosurgical cases prepared with a 3D hologram were collected. Surgical indications were oncologic (63/107, 59%), cerebrovascular (27/107, 25%), and carotid endarterectomy (17/107, 16%). Mean hologram segmentation time was 39.4 ± 20.4 minutes. Average surgical preparation time was 48.0 ± 17.3 minutes for MxR cases vs 52 ± 17 minutes in the matched 2021 cohort without MxR (mean difference 4, 95% CI 1.7527-9.7527). Based on the 3D hologram, the surgical approach was modified in 3 cases. Good usability was found by 57% of the users. CONCLUSION: The perioperative use of 3D holograms improved direct anatomic visualization while not significantly increasing intraoperative surgical preparation time. Usability of the system was adequate. Further technological development is necessary to improve the automatic algorithms and reduce the preparation time by circumventing manual and semiautomatic segmentation. Future studies should focus on quantifying the potential benefits in teaching, training, and the impact on surgical and functional outcomes.

Challenges in Coagulation Management in Neurosurgical Diseases: A Scoping Review, Development, and Implementation of Coagulation Management Strategies.

Bleeding and thromboembolic (TE) complications in neurosurgical diseases have a detrimental impact on clinical outcomes. The aim of this study is to provide a scoping review of the available literature and address challenges and knowledge gaps in the management of coagulation disorders in neurosurgical diseases. Additionally, we introduce a novel research project that seeks to reduce coagulation disorder-associated complications in neurosurgical patients. The risk of bleeding after elective craniotomy is about 3%, and higher (14-33%) in other indications, such as trauma and intracranial hemorrhage. In spinal surgery, the incidence of postoperative clinically relevant bleeding is approximately 0.5-1.4%. The risk for TE complications in intracranial pathologies ranges from 3 to 20%, whereas in spinal surgery it is around 7%. These findings highlight a relevant problem in neurosurgical diseases and current guidelines do not adequately address individual circumstances. The multidisciplinary COagulation MAnagement in Neurosurgical Diseases (COMAND) project has been developed to tackle this challenge by devising an individualized coagulation management strategy for patients with neurosurgical diseases. Importantly, this project is designed to ensure that these management strategies can be readily implemented into healthcare practices of different types and with sustainable integration.

Aneurysm treatment within 6 h versus 6-24 h after rupture in patients with subarachnoid hemorrhage.

BACKGROUND: The risk of rebleeding after aneurysmal subarachnoid hemorrhage (aSAH) is the highest during the initial hours after rupture. Emergency aneurysm treatment may decrease this risk, but is a logistic challenge and economic burden. We aimed to investigate whether aneurysm treatment <6 h after rupture is associated with a decreased risk of poor functional outcome compared to aneurysm treatment 6-24 h after rupture. METHODS: We used data of patients included in the ULTRA trial (NCT02684812). All patients in ULTRA were admitted within 24 h after aneurysm rupture. For the current study, we excluded patients in whom the aneurysm was not treated <24 h after rupture. We calculated crude and adjusted risk ratios (aRR) with 95% confidence intervals using Poisson regression analyses for poor functional outcome (death or dependency, assessed by the modified Rankin Scale) after aneurysm treatment <6 h versus 6-24 h after rupture. Adjustments were made for age, sex, clinical condition on admission (WFNS scale), amount of extravasated blood (Fisher score), aneurysm location, tranexamic acid treatment, and aneurysm treatment modality. RESULTS: We included 497 patients. Poor outcome occurred in 63/110 (57%) patients treated within 6 h compared to 145/387 (37%) patients treated 6-24 h after rupture (crude RR: 1.53, 95% CI: 1.24-1.88; adjusted RR: 1.36, 95% CI: 1.11-1.66). CONCLUSION: Aneurysm treatment <6 h is not associated with better functional outcome than aneurysm treatment 6-24 h after rupture. Our results do not support a strategy aiming to treat every patient with a ruptured aneurysm <6 h after rupture.

Successful weaning versus permanent cerebrospinal fluid diversion after aneurysmal subarachnoid hemorrhage: post hoc analysis of a Swiss multicenter study.

OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

Incisional CSF leakage after intradural cranial surgery in children: incidence, risk factors, and complications.

OBJECTIVE: The risk of cerebrospinal fluid (CSF) leakage after cranial surgery and its associated complications in children are unclear because of variable definitions and the lack of multicenter studies. In this study, the authors aimed to establish the incidence of CSF leakage after intradural cranial surgery in the pediatric population. In addition, they evaluated potential risk factors and complications related to CSF leakage in the pediatric population. METHODS: The authors performed an international multicenter retrospective cohort study in three tertiary neurosurgical referral centers. Included were all patients aged 18 years or younger who had undergone cranial surgery to reach the subdural space during the period between 2015 and 2021. Patients who died or were lost to follow-up within 6 weeks after surgery were excluded. The primary outcome measure was the incidence of CSF leakage, defined as leakage through the skin, within 6 weeks after surgery. Univariable and multivariable logistic regression analyses were performed to identify risk factors for and complications related to CSF leakage. RESULTS: In total, 759 procedures were identified, performed in 687 individual patients. The incidence of CSF leakage was 7.5% (95% CI 5.7%-9.6%). In the multivariate model, independent risk factors for CSF leakage were hydrocephalus (OR 4.5, 95% CI 2.2-8.9) and craniectomy (OR 7.6, 95% CI 3.0-19.5). Patients with CSF leakage had higher odds of pseudomeningocele (5.7, 95% CI 3.0-10.8), meningitis (21.1, 95% CI 9.5-46.8), and surgical site infection (7.4, 95% CI 2.6-20.8) than patients without leakage. CONCLUSIONS: CSF leakage risk in children after cranial surgery, which is comparable to the risk reported in adults, is an event of major concern and has a serious clinical impact.

Cerebrospinal fluid leakage after intradural spinal surgery in children.

PURPOSE: This study aimed to establish the incidence of CSF leakage in children and associated complications after intradural spinal surgery in three tertiary neurosurgical referral centers and to describe the treatment strategies applied. METHODS: Patients of 18 years or younger who underwent intradural spinal surgery between 2015 and 2021 in three tertiary neurosurgical referral centers were included. Patients who died or were lost to follow-up within six weeks after surgery were excluded. The primary outcome measure was CSF leakage within six weeks after surgery, defined as leakage of CSF through the skin. Secondary outcome measures included the presence of pseudomeningocele (PMC), meningitis, and surgical site infection (SSI). RESULTS: We included a total of 75 procedures, representing 66 individual patients. The median age in this cohort was 5 (IQR = 0-13 years. CSF leakage occurred in 2.7% (2/75) of procedures. It occurred on days 3 and 21 after the index procedure, respectively. One patient was treated with a pressure bandage and an external lumbar drain on day 4 after diagnosis of the leak, and the other was treated with wound revision surgery on day 1 after the leak occurred. In total, 1 patient developed a PMC without a CSF leak which was treated with wound revision surgery. SSI occurred in 10.7%, which included both cases of CSF leak. CONCLUSIONS: CSF leakage after intradural spinal surgery in the pediatric population is relatively rare (2.7%). Nevertheless, the clinical consequences with respect to secondary complications such as infection and the necessity for invasive treatment are serious.

Risk Factors and Management of Incisional Cerebrospinal Fluid Leakage After Craniotomy: A Retrospective International Multicenter Study.

BACKGROUND: Incisional cerebrospinal fluid (iCSF) leakage is a serious complication after intradural cranial surgery. OBJECTIVE: To determine the incidence and risk factors of iCSF leakage after craniotomy. Secondarily, the complications after iCSF leakage and the success rate of iCSF leakage treatment was studied. METHODS: All patients who underwent an intradural cranial surgery from 2017 to 2018 at 5 neurosurgical centers were retrospectively included. Data were retrieved from medical records with 2 months of follow-up. First, univariate regression analyses were performed. Subsequently, identified risk factors were evaluated in a multivariate regression analysis. RESULTS: In total 2310 consecutive patients were included. Total iCSF leakage rate was 7.1% (n = 165). Younger age, male, higher body mass index, smoking, infratentorial surgery, and use of a dural substitute were associated with increased iCSF leakage risk, and use of a sealant reduced that risk. The odds for developing a wound infection and/or meningitis were 15 times higher in patients with iCSF leakage compared with patients without leakage. Initial conservative iCSF leakage treatment failed in 48% of patients. In 80% of cases, external cerebrospinal fluid drainage ceased the iCSF leakage. A total of 32% of patients with iCSF leakage required wound revision surgery. CONCLUSION: iCSF leakage risk increases by younger age, higher body mass index, smoking, infratentorial craniotomy, and dural substitute use, whereas sealant use reduced the risk for iCSF leakage. The leak increases the risk of postoperative infections. When iCSF leakage occurs, immediate external cerebrospinal fluid drainage or wound revision should be considered.

Follow-up neuroimaging after non-perimesencephalic, angiogram-negative subarachnoid hemorrhage.

BACKGROUND: In approximately 15% of spontaneous subarachnoid hemorrhage (SAH) patients, no bleeding source is found in the initial imaging. These patients can be categorized as either perimesencephalic (PM-SAH) or non-perimesencephalic (NP-SAH) subarachnoid hemorrhage patients. Follow-up imaging is routinely performed after NP-SAH to detect treatable etiologies; however, the optimal follow-up imaging protocol remains unclear. This study examines the optimal time interval to re-imaging and the performance of magnetic resonance imaging and angiography (MRI/A) in this setting. METHODS: In this retrospective study, the records of NP-SAH patients treated at the University Hospital of Zurich (Switzerland) from 2005 to 2018 were analyzed. Clinical and radiological data were collected. Re-imaging data was grouped according to imaging modality and divided into three time-categories after bleeding: short-term (<2 weeks), medium-term (2-8 weeks) and long-term (>8 weeks) re-imaging. RESULTS: Eighty-one NP-SAH patients were included. In 8 patients an aneurysm was diagnosed during re-imaging via digital subtraction angiography (9.9% diagnostic yield). Five aneurysms were detected at short-term in 81 patients (6.2% short-term yield) and three at medium-term re-imaging in 27 patients (11.1% medium-term yield). No aneurysms were found after 8 weeks in 56 patients. Five of these 8 patients also received MRI/A re-imaging, which was able to show the aneurysm in all 5 cases. CONCLUSIONS: Our study emphasizes the importance of re-imaging in NP-SAH patients, which should be done both at short-term and at medium-term follow-up after the hemorrhage. Long-term re-imaging after 8 weeks might not be of diagnostic benefit. MRI/A might be considered as a possible noninvasive re-imaging modality in this setting.

Early versus delayed mobilization after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of efficacy and safety.

OBJECTIVE: A central tenet of Enhanced Recovery After Surgery (ERAS) is evidence-based medicine. Survivors of aneurysmal subarachnoid hemorrhage (aSAH) constitute a fragile patient population prone to prolonged hospitalization within neurointensive care units (NICUs), prolonged immobilization, and a range of nosocomial adverse events. Potentially, well-monitored early mobilization (EM) could constitute a beneficial element of ERAS protocols in this population. Therefore, the objective was to summarize the available evidence on EM strategies in patients with aSAH. METHODS: The authors retrieved prospective and retrospective studies that reported efficacy or safety data on EM (defined as EM in the NICU starting ≤ 7 days after ictus) versus delayed mobilization (DM) (any strategy that comparatively delayed mobilization) after aSAH and were published after January 1, 2000, in PubMed/MEDLINE, Embase, and the Cochrane Library. Random-effects meta-analysis was performed. RESULTS: Ten studies analyzing 1292 patients were included for quantitative synthesis, including 1 randomized, 1 prospective nonrandomized, and 8 retrospective studies. Modified Rankin Scale scores at discharge were not different between the EM and DM groups (mean difference [MD] [95% CI] -0.86 [-2.93 to 1.20] points, p = 0.41). Hospital length of stay in days was markedly reduced in the EM group (MD [95% CI] -6.56 [-10.64 to -2.47] days, p = 0.002). Although there was a statistically significant reduction in radiological vasospasms (OR [95% CI] 0.65 [0.44-0.97], p = 0.03), the reduction in clinically relevant vasospasms was nonsignificant (OR [95% CI] 0.63 [0.31-1.26], p = 0.19). The odds of shunting were significantly lower in the EM group (OR [95% CI] 0.61 [0.39-0.95], p = 0.03). The rates of mortality, pneumonia, and thrombosis were similar among groups (p > 0.05). CONCLUSIONS: Due to a lack of high-quality studies, vastly varying protocols, and resulting statistical clinical and statistical heterogeneity, the level of evidence for recommendations regarding EM in patients with aSAH remains low. The currently available data indicated that mobilization within the first 5 days after aneurysm repair was feasible and safe without significant excessive adverse events, that neurological outcome with EM was almost certainly not worse than with prolonged immobilization, and that there was likely at least some reduction in length of hospital stay. Radiological and clinical vasospasms were not more frequent-with signals even trending toward a decrease-in patients who mobilized early. Higher-quality studies and implementation of full ERAS protocols are necessary to evaluate efficacy and safety with a higher level of evidence and to guide practical implementation through increased standardization. Clinical trial registration no.: CRD42023432828 (www.crd.york.ac.uk/prospero).

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. OBJECTIVES: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review). SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. DATA COLLECTION AND ANALYSIS: Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE. MAIN RESULTS: We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias.  Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence).  Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence). AUTHORS' CONCLUSIONS: The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines.

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.

Surgically treated intradural spinal manifestation of hereditary amyloidogenic transthyretin amyloidosis - A case report and scoping review of the literature.

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant disorder, where a TTR mutations lead to amyloid fibril deposits in tissues and consecutively alter organ function. ATTRv is a multisystemic disorder with a heterogeneous clinical presentation. Spinal leptomeningeal depositions are described only scarcely in the literature. Research question: We present a rare case of surgically treated intradural, extra-medullary amyloidosis with respective clinical, diagnostic and surgical features to raise awareness of this rare entity. Material and methods: Clinical, radiological and operative characteristics were retrieved from the electronical patient management system. Additionally, a scoping literature review on leptomeningeal spinal manifestations of ATTRv was performed. Results: A 45-year-old man with a known ATTRv presented with gait disturbance and paresis of the lower extremities. He had been treated with the siRNA therapeutical Patisiran for 13 months under which his symptoms worsened. An MRI of the spine revealed spinal cord compression with myelopathy at the level of T2 with anterior dislocation of the spinal cord due to an intradural, extramedullary lesion. A laminectomy and opening of the dura with a complete resection of the lesion was performed. The histological examination of the biopsy showed amyloid deposits. At six-month follow-up the patient showed complete normalization of the paresis, gait, sensory and urinary disturbances and resumed his work. Discussion and conclusion: Spinal leptomeningeal deposition of amyloid is a rare occurrence within the framework of ATTRv. Micro-neurosurgical complete resection of the lesion is feasible in patients with preoperative myelopathic symptoms and resulted in complete symptom relief in this case.

Evaluation of patient STress level caused by radiological Investigations in early Postoperative phase After CRANIOtomy (IPAST-CRANIO): protocol of a Swiss prospective cohort study.

INTRODUCTION: Postoperative imaging after neurosurgical interventions is usually performed in the first 72 hours after surgery to provide an accurate assessment of postoperative resection status. Patient frequently report that early postoperative examination after craniotomy for tumour and vascular procedures is associated with distress, exertion, nausea and pain. Delayed postoperative imaging (between 36 and 72 hours postoperatively) may have an advantage regarding psychological and physical stress compared with early imaging. The goal of this study is to evaluate and determine the optimal time frame for postoperative imaging with MRI and CT in terms of medical and neuroradiological implications and patient's subjective stress level. METHODS AND ANALYSIS: Data will be prospectively collected from all patients aged 18-80 years who receive postoperative MRI or CT imaging following a craniotomy for resection of a cerebral tumour (benign and malignant) or vascular surgery. Participants have to complete questionnaires containing visual analogue scores (VAS) for headache and nausea, Body Part Discomfort score and a single question addressing subjective preference of timing of postoperative imaging after craniotomy. The primary endpoint of the study is the difference in subjective stress due to imaging studies after craniotomy, measured just before and after postoperative MRI or CT with the above-mentioned instruments. Subjective stress is defined as a combination of the scores VAS pain, VAS nausea and 0.5* Body Part Discomfort core.This study determines whether proper timing of postoperative imaging can improve patient satisfaction and reduce pain, stress and discomfort caused by postoperative imaging. Factors causing additional postoperative stress are likely responsible for delayed recovery of neurosurgical patients. ETHICS AND DISSEMINATION: The institutional review board (Kantonale Ethikkommission Zürich) approved this study on 4 August 2020 under case number BASEC 2020-01590. The authors are planning to publish the data of this study in a peer-reviewed paper. After database closure, the data will be exported to the local data repository (Zurich Open Repository and Archive) of the University of Zurich. The sponsor (LR) and the project leader (MR.G) will make the final decision on the publication of the results. The data that support the findings of this study are available on request from the corresponding author LT. The data are not publicly available due to privacy/ethical restrictions. TRIAL REGISTRATION NUMBER: NCT05112575; ClinicalTrials.gov.