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Background: Hemophagocytic lymphohistiocytosis (HLH) is an inherited syndrome characterized by immune dysregulation. Central nervous system (CNS)-isolated disease is a rare presentation of familial HLH. We present a case of pediatric CNS-isolated HLH with a presentation complicated by unusual hemorrhagic intraparenchymal lesions., Case Presentation: A 15-year-old male presented with ataxia and MRI findings of multiple hemorrhagic lesions in his cerebral white matter, brainstem, and cerebellum, suggestive of vasculitis. After failing to improve with steroids and plasmapheresis, and progression to acute neurologic decompensation, new brainstem hemorrhages were noted. Further workup revealed 2 PRF1 mutations, confirming a diagnosis of familial CNS-HLH. He was later found to have a platelet granule defect, explaining his atypical neuroradiologic findings. The patient received treatment per the HLH-1994 protocol and underwent stem cell transplantation. Two years post-transplant, his perforin expression is nearly normal and his neurologic deficits have significantly improved., Conclusions: This case illustrates the variability in presentation of isolated CNS-HLH. Although rare, it is important to include this diagnosis on the differential in patients with CNS hemorrhagic lesions. If initial diagnostic studies remain inconclusive or response to early treatments is poor, CNS-HLH should be considered, as delay in diagnosis and treatment significantly affects morbidity and mortality., (© 2024. The Author(s).)

Backgroung: Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines suggest that patients with mTBI can be safely discharged from the emergency department. Although half of patients with mTBI with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients' ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up., Study Design: A single-center prospective cohort study including adult trauma patients with ICH or skull fracture and a Glasgow Coma Scale of 13 to 15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as an RLA less than 8. We compared ECI and non-ECI groups for demographics, injury profile, CT imaging (eg Rotterdam CT score) and outcomes with bivariate analysis. Thirty-day follow-up telephone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms., Results: From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% vs 46.3%, p = 0.003) and higher Rotterdam CT score (p = 0.004) compared with those without ECI. On 30-day follow-up, 6 of 21 (26.6%) patients had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms., Conclusions: More than one-third of mTBI patients with ICH had ECI. At 30-day postdischarge follow-up, more than one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI before discharge as a significant portion may have ongoing difficulties reintegrating into work and society., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Cerebellar mutism syndrome (CMS) is a frequent complication of surgical intervention on posterior fossa in children. It has been only occasionally reported in adults and its features have not been fully characterized. In children and in young adults, medulloblastoma is the main reason for neurosurgery. A single case of postsurgical CMS is presented in an adult patient with a cerebellar hemorrhage and a systematic review of the published individual cases of CMS in adults was done. Literature review of individual cases found 30 patients, 18/30 (60%) males, from 20 to 71 years at diagnosis. All but one case was post-surgical, but in one of the post-surgical cases iatrogenic basilar artery occlusion was proposed as cause for CMS. The causes were: primary tumors of the posterior fossa in 16/22 (72.7%) metastasis in 3/30 (10%), ischemia in 3/30 (10%) cerebellar hemorrhage in 3/30 (10%), and benign lesions in 2/30 (6.7%) patients. 8/30 patients (26.7%) were reported as having persistent or incomplete resolution of CMS within 12 months. CMS is a rare occurrence in adults and spontaneous cerebellar hemorrhage has been reported in 3/30 (10%) adult patients. The generally accepted hypothesis is that CMS results from bilateral damage to the dentate nucleus or the dentate-rubro-thalamic tract, leading to cerebro-cerebellar diaschisis. Several causes might contribute in adults. The prognosis of CMS is slightly worse in adults than in children, but two thirds of cases show a complete resolution within 6 months., (© 2024. Fondazione Società Italiana di Neurologia.)

An 80-year-old woman with a history of rheumatoid arthritis, hypertension, and hyperlipidemia, and no family history of hyperkinesis developed suddenly involuntary movement and visited our hospital two-day after onset. Neuro-examination revealed hemichorea-hemiballismus in the right side of the body, including the face (Suppl. video). Blood tests revealed neither hyperglycemia nor acanthocyte. Brain MRI showed acute microbleeding in the left subthalamic nucleus (Figure 1A-C). Although she was treated with haloperidol (max. 4.5 mg/day), hemichorea-hemiballismus did not subside. Repetitive transcranial magnetic stimulation (rTMS) with a low-frequency protocol (LFP) (1 Hz, 1200 pulses, with a stimulus intensity of 90% of the resting motor threshold, 3 days/week for 2-week) was applied to the left precentral knob (Figure 1D). Its effect was drastic, as the symptoms disappeared for half-hour after rTMS. Hemichorea-hemiballism then reappeared but was attenuated by repeated rTMS. The symptoms disappeared after one-month. Subthalamic nucleus lesions can develop hemichorea-hemiballism (1). According to a study on Huntington's disease and diabetic hemichorea-hemiballism, increased thalamocortical drive may increase the excitability of excitatory and inhibitory circuits of the frontal cortex as the etiologies of hyperkinesia (2-3). However, the target points of rTMS in treating hemichorea-hemiballism have not been consistent in literature. Moreover, rTMS with a LFP on the bilateral supplementary motor areas is effective in treating chorea in Huntington's disease (2). Additionally, rTMS on the ipsilateral precentral knob (primary motor cortex) with continuous θ burst stimulation (cTBS), which decreases the excitability and inhibitory cortical circuits, was effective in treating contralateral hemichorea caused by midbrain hemorrhage (3). Similar to cTBS, LFP can suppress cortical excitation (4); therefore, we applied rTMS with LFP on the primary motor cortex to treat hemichorea-hemiballism. Our results were drastic for both short- and long-term efficiency. This is the first report of the efficacy of rTMS with LFP in treating hemichorea-hemiballism caused by encephalorrhagia.

An 80-year-old woman with a history of rheumatoid arthritis, hypertension, and hyperlipidemia, and no family history of hyperkinesis developed suddenly involuntary movement and visited our hospital two-day after onset. Neuro-examination revealed hemichorea-hemiballismus in the right side of the body, including the face (Suppl. video). Blood tests revealed neither hyperglycemia nor acanthocyte. Brain MRI showed acute microbleeding in the left subthalamic nucleus (Figure 1A-C). Although she was treated with haloperidol (max. 4.5 mg/day), hemichorea-hemiballismus did not subside. Repetitive transcranial magnetic stimulation (rTMS) with a low-frequency protocol (LFP) (1 Hz, 1200 pulses, with a stimulus intensity of 90% of the resting motor threshold, 3 days/week for 2-week) was applied to the left precentral knob (Figure 1D). Its effect was drastic, as the symptoms disappeared for half-hour after rTMS. Hemichorea-hemiballism then reappeared but was attenuated by repeated rTMS. The symptoms disappeared after one-month. Subthalamic nucleus lesions can develop hemichorea-hemiballism (1). According to a study on Huntington's disease and diabetic hemichorea-hemiballism, increased thalamocortical drive may increase the excitability of excitatory and inhibitory circuits of the frontal cortex as the etiologies of hyperkinesia (2-3). However, the target points of rTMS in treating hemichorea-hemiballism have not been consistent in literature. Moreover, rTMS with a LFP on the bilateral supplementary motor areas is effective in treating chorea in Huntington's disease (2). Additionally, rTMS on the ipsilateral precentral knob (primary motor cortex) with continuous θ burst stimulation (cTBS), which decreases the excitability and inhibitory cortical circuits, was effective in treating contralateral hemichorea caused by midbrain hemorrhage (3). Similar to cTBS, LFP can suppress cortical excitation (4); therefore, we applied rTMS with LFP on the primary motor cortex to treat hemichorea-hemiballism. Our results were drastic for both short- and long-term efficiency. This is the first report of the efficacy of rTMS with LFP in treating hemichorea-hemiballism caused by encephalorrhagia.

Background: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes., Methods: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used., Results: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH., Conclusions: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs., Methods: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs., Results: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs., Discussion: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH., Classification of Evidence: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Background and Objectives: Acute stent thrombosis (AST) is not uncommon and even catastrophic during intracranial stenting angioplasty in patients with symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). The purpose of this study was to investigate whether adjuvant intravenous tirofiban before stenting could reduce the risk of AST and periprocedural ischemic stroke in patients receiving stent angioplasty for symptomatic ICAS., Methods: A prospective, multicenter, open-label, randomized clinical trial was conducted from September 9, 2020, to February 18, 2022, at 10 medical centers in China. Patients intended to receive stent angioplasty for symptomatic high-grade ICAS were enrolled and randomly assigned to receive intravenous tirofiban or not before stenting in a 1:1 ratio. The primary outcomes included the incidence of AST within 30 minutes after stenting, periprocedural new-onset ischemic stroke, and symptomatic intracranial hemorrhage. The outcomes were analyzed using logistic regression analysis to obtain an odds ratio and 95% confidence interval., Results: A total of 200 participants (122 men [61.0%]; median [interquartile ranges] age, 57 [52-66] years) were included in the analysis, with 100 participants randomly assigned to the tirofiban group and 100 participants to the control (no tirofiban) group. The AST incidence was lower in the tirofiban group than that in the control group (4.0% vs 14.0%; adjusted odds ratio, 0.25; 95% CI 0.08-0.82; p = 0.02). No significant difference was observed in the incidence of periprocedural ischemic stroke (7.0% vs 8.0%; p = 0.98) or symptomatic intracranial hemorrhage between the 2 groups., Discussion: This study suggests that adjuvant intravenous tirofiban before stenting could lower the risk of AST during stent angioplasty in patients with symptomatic high-grade ICAS., Trial Registration Information: URL: chictr.org.cn; Unique identifier: ChiCTR2000031935., Classification of Evidence: This study provides Class II evidence that for patients with symptomatic high-grade ICAS, pretreatment with tirofiban decreases the incidence of acute stent thrombosis. This study is Class II due to the unequal distribution of involved arteries between the 2 groups.

Pulmonary embolism is a common complication after intracranial hemorrhage. As thrombolysis is contraindicated in this situation, surgical pulmonary embolectomy may be indicated in case of high-risk pulmonary embolism but requires transient anticoagulation with heparin during cardiopulmonary bypass. We report the case of a patient with a history of heparin-induced thrombocytopenia who presented with a high-risk pulmonary embolism 10 days after the spontaneous onset of a voluminous intracerebral hematoma. Despite high doses of heparin required to run the cardiopulmonary bypass and subsequent anticoagulation by danaparoid sodium, the brain hematoma remained stable and the patient was discharged without complications 30 days after surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Prehospital triage and treatment of patients with acute coma is challenging for rescue services, as the underlying pathological conditions are highly heterogenous. Recently, glial fibrillary acidic protein (GFAP) has been identified as a biomarker of intracranial hemorrhage. The aim of this prospective study was to test whether prehospital GFAP measurements on a point-of-care device have the potential to rapidly differentiate intracranial hemorrhage from other causes of acute coma., Methods: This study was conducted at the RKH Klinikum Ludwigsburg, a tertiary care hospital in the northern vicinity of Stuttgart, Germany. Patients who were admitted to the emergency department with the prehospital diagnosis of acute coma (Glasgow Coma Scale scores between 3 and 8) were enrolled prospectively. Blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min) shortly after hospital admission., Results: 143 patients were enrolled (mean age 65 ± 20 years, 42.7% female). GFAP plasma concentrations were strongly elevated in patients with intracranial hemorrhage (n = 51) compared to all other coma etiologies (3352 pg/mL [IQR 613-10001] vs. 43 pg/mL [IQR 29-91.25], p < 0.001). When using an optimal cut-off value of 101 pg/mL, sensitivity for identifying intracranial hemorrhage was 94.1% (specificity 78.9%, positive predictive value 71.6%, negative predictive value 95.9%). In-hospital mortality risk was associated with prehospital GFAP values., Conclusion: Increased GFAP plasma concentrations in patients with acute coma identify intracranial hemorrhage with high diagnostic accuracy. Prehospital GFAP measurements on a point-of-care platform allow rapid stratification according to the underlying cause of coma by rescue services. This could have major impact on triage and management of these critically ill patients., (© 2024. The Author(s).)

A 63-year-old male patient with a history of hypertension presented to the emergency department with a one-day history of dizziness, nausea, and vomiting.

Purpose: Acute ischemic stroke is currently among the main causes of mortality in Western countries. The current guidelines suggest different flowcharts of diagnostic work-up and treatment modalities, including endovascular thrombectomy. Immediately after intra-arterial recanalization, a brain CT scan is usually performed to assess for the presence of peri-procedural complications; in this setting, it is very hard, if possible, to differentiate blood from iodinated contrast material, which is normally present in ischemic tissue because of BBB disruption. Dual-energy CT may be used for this purpose, exploiting its ability to discriminate different materials., Materials and Methods: We retrospectively studied 44 patients with acute ischemic stroke who were treated with endovascular recanalization at San Giovanni Bosco Hospital in Turin and were then scanned with DECT technology. Subsequent scan was used as standard, since iodine from contrast staining is usually reabsorbed in 24 h and blood persists longer. A χ 2 test of independence was performed to examine the relationship between blood detected by DECT scan after the endovascular procedure and the presence of blood in the same areas on the following scans, with a significant result: χ 2 (1, N = 37) = 10.7086, p = 0.0010., Results: Patients with blood detected on DECT scans had a double chance of having hemorrhagic infarction in follow-up scans, (RR 2.02). The sensitivity and specificity of DECT were respectively 70% and 90%, with an overall diagnostic accuracy of 76% and a positive and negative predictive value, respectively, of 95% and 53%., Conclusion: Dual-energy CT scan after endovascular recanalization in ischemic stroke identifies early hemorrhagic infarction with excellent specificity and good overall diagnostic accuracy, representing a reliable diagnostic tool in everyday clinical practice., (© 2024. Italian Society of Medical Radiology.)

Objectives: Our goal was to quantify the independent association of brain microbleeds with future intracranial hemorrhage (ICrH). Microbleed findings on brain magnetic resonance imaging (MRI) may identify distinctive risk factors for ICrH which could inform the anticoagulant therapy decision for atrial fibrillation (AF) patients. Our study design includes patients with MRIs for numerous reasons, not limited to evaluation of stroke., Materials and Methods: The source population was all patients with AF from a nationwide Swedish health care register. Case patients had an ICrH between 2006 and 2013 and ≥1 brain MRI for an unrelated condition before the ICrH. Each case was matched to four controls who had a brain MRI without a subsequent ICrH. The MRIs were re-reviewed by neuroradiologists. Associations between MRI findings and subsequent ICrH were assessed using logistic regression, adjusting for comorbidities and antithrombotic medications., Results: A total of 78 cases and 312 matched controls were identified; 29 cases and 79 controls had MRI sequences suitable for analysis of microbleeds. Patients with ≥10 microbleeds had a markedly increased risk of ICrH (adjusted odds ratio 14.56; 95 % confidence interval: 2.86-74.16, p < 0.001). All patients with ≥10 microbleeds had microbleeds in the lobar region and ≥10 lobar microbleeds was associated with intracerebral hemorrhages, univariable OR 8.54 (2.01-36.33), p = 0.004., Conclusions: Leveraging a nationwide database with brain imaging obtained prior to ICrH, we identified a strong association between ≥10 microbleeds on brain MRI and subsequent ICrH among AF patients. Lobar brain regions were involved whenever there were ≥10 microbleeds. Brain MRIs may help optimize the anticoagulation decision in selected AF patients., Competing Interests: Declaration of competing interest Daniel E. Singer: Research support from: Bristol Myers Squibb; Consultant: Bristol Myers Squibb, Fitbit (Google), Medtronic, Pfizer. David Cheng, Sara Aspberg, Anders von Heijne, and Bruna Gigante have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: The presence of urinary incontinence (UI) in acute stroke patients indicates poor outcomes in men and women. However, there is a paucity and inconsistency of data on UI risk factors in this group and hence we conducted a sex-specific analysis to identify risk factors., Methods: Data were collected prospectively (2014-2016) from the Sentinel Stroke National Audit Program for patients admitted to four UK hyperacute stroke units. Relevant risk factors for UI were determined by stepwise multivariable logistic regression, presented as odds ratios (OR) and 95% confidence intervals (CI)., Results: The mean (±SD) age of UI onset in men (73.9 year ± 13.1; n = 1593) was significantly earlier than for women (79.8 year ± 12.9; n = 1591: p < 0.001). Older age between 70 and 79 year in men (OR = 1.61: CI = 1.24-2.10) and women (OR = 1.55: CI = 1.12-2.15), or ≥80 year in men (OR = 2.19: CI = 1.71-2.81), and women (OR = 2.07: CI = 1.57-2.74)-reference: <70 year-both predicted UI. In addition, intracranial hemorrhage (reference: acute ischemic stroke) in men (OR = 1.64: CI = 1.22-2.20) and women (OR = 1.75: CI = 1.30-2.34); and prestroke disability (mRS scores ≥ 4) in men (OR = 1.90: CI = 1.02-3.5) and women (OR = 1.62: CI = 1.05-2.49) (reference: mRS scores < 4); and stroke severity at admission: NIHSS scores = 5-15 in men (OR = 1.50: CI = 1.20-1.88) and women (OR = 1.72: CI = 1.37-2.16), and NIHSS scores = 16-42 in men (OR = 4.68: CI = 3.20-6.85) and women (OR = 3.89: CI = 2.82-5.37) (reference: NIHSS scores = 0-4) were also significant. Factors not selected were: a history of congestive heart failure, hypertension, atrial fibrillation, diabetes and previous stroke., Conclusions: We have identified similar risk factors for UI after stroke in men and women including age >70 year, intracranial hemorrhage, prestroke disability and stroke severity., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies., Methods: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone., Results: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB., Conclusions: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy., (© 2024. The Author(s).)

Rationale: Cerebral venous thrombosis (CVT) is a relatively uncommon but fatal disease. It can be caused by a variety of hereditary or acquired thrombotic diseases. Initial presentation with intracranial hemorrhage (ICH) in CVT is rare but can further complicate the therapeutic measures and prognosis. Cases of CVT presented with ICH in patients with alcoholic liver disease (ALD) have not been described in the literature, and it might be related with hemostatic abnormalities in ALD patients., Patient Concerns: We report 2 cases of men admitted to our hospital who were diagnosed with CVT but initially presented with symmetrical crescent-shaped ICH; both of them were ALD patients., Diagnoses: Cerebral imaging revealed extended CVT in both cases. The first case was a 64-year-old man with ALD deteriorated with unconsciousness and convulsions; computed tomography showed symmetrical crescent-shaped ICH in the right temporal lobe, and magnetic resonance venography revealed CVT. Another 50-year-old man with ALD complained about dizziness and weakness of his right limbs; computed tomography revealed symmetrical crescent-shaped ICH in bilateral parietal and occipital lobes, and magnetic resonance venography revealed CVT., Interventions: The first patient was referred to the endovascular thrombectomy. Both of them were treated with anticoagulation treatment., Outcomes: Favorable outcomes were observed in both patients., Lessons: Symmetrical or multiple crescent-shaped ICH requires a high suspicion in the diagnosis of CVT; even with hemorrhage, it is still important to initiate anticoagulation therapy promptly. The crescent-shaped ICH might be a new sign for CVT, and further studies are needed in the underlying mechanisms of ALD and potential thrombophilia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for clinicians, complicated by the expanding range of anticoagulant agents available in modern clinical practice, including direct OACs and, more recently, factor XI and XII inhibitors. A review of the current literature found support for resuming OAC in the majority of patients after ICH based on pooled retrospective data showing that resumption is associated with a lower risk of mortality and thromboembolism without a significantly increased risk of recurrent hemorrhage. The optimal time to resume OAC is less clear; however, the available evidence suggests that the composite risk of both recurrent hemorrhage and thromboembolism is likely minimized, somewhere between 4 and 6 weeks, after ICH in most patients. Specific considerations to guide the optimal resumption time in the individual patient include ICH location, mechanism, and anticoagulant class. Patients with mechanical heart valves and intracerebral malignancy represent high-risk groups who require more nuanced decision making. Here, we appraise the literature with the aim of providing a practical guide for clinicians while also discussing priorities for future investigation., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Mild traumatic brain injury (mTBI) is a common cause of admission to the Emergency Department (ED). Many patients are elderly on oral anticoagulant therapy (OAT) at increased risk of immediate and delayed intracranial hemorrhage (ICH). To investigate the frequency of delayed ICH (DICH) in old patients with mTBI in OAT and the occurrence of complications related to the ED stay. In this single-center retrospective study, we recruited all patients in OAT aged 65 and over, admitted for mTBI to the ED of our Hospital in Florence from March 2019 to February 2021. Clinical variables were collected and cranial computed tomography (CT) scans reviewed. The primary outcome was the frequency of DICH occurring within 30 days since the trauma after a first negative CT. Secondary outcomes included need of neurosurgical intervention and death for DICH, and hospital-related complications. Statistical analyses were conducted using IBM SPSS Statistics (version 22). Among 363 enrolled patients, there were 31 acute ICH (8.5%) at the first CT scan, while in the 316 negative included patients, 10 DICH (3.2%) were identified. Among the latter, no neurosurgical treatment, or death due to ICH occurred. Overall, 25 cases (6.9%) had iatrogenic complications during the 24-h observation period, often serious, such as respiratory failure after sedation due to restlessness, or COVID-19 infection. The low frequency of DICH and the occurrence of several iatrogenic complications suggest that the risk-benefit ratio of a 24-h ED observation is not advantageous in elderly with mTBI., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Whether asymptomatic intracranial hemorrhage (ICH) affects the clinical outcomes in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains unclear. This study aimed to address this uncertainty., Methods: We retrospectively analyzed patients with acute ischemic stroke and internal carotid or middle cerebral (M1 segment) artery occlusion treated with MT between April 2011 and March 2021 at a single center. All patients had a premorbid modified Rankin scale (mRS) score ≤ 2 and an anterior circulation occlusion and underwent magnetic resonance imaging at admission. Asymptomatic ICH was defined as ICH without symptomatic ICH defined by the SITS-MOST criteria. A favorable outcome was defined as an mRS score ≤ 2 at 90 days after stroke onset., Results: Our study included 349 patients; 62% were men, the median age was 76 [67-83] years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 15 [8-21]. As determined via computed tomography, 103 (30%) patients had ICH (20 symptomatic and 83 asymptomatic). The favorable outcome rate was significantly lower for asymptomatic vs. no ICH (30% vs. 67%, p < 0.01). In a multivariate regression analysis, a high NIHSS score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p < 0.01) and low Alberta Stroke Program Early CT Score (OR, 0.78; 95% CI, 0.65-0.92; p < 0.01) were independent risk factors for ICH., Conclusions: Asymptomatic ICH is associated with poor clinical outcome at 90 days after stroke onset., Competing Interests: Declaration of competing interest Kazumi Kimura received lecture fees from Bristol-Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Bayer Healthcare Co. Ltd., and Daiichi Sankyo Co.; research funding from Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co., Pfizer Japan Inc., Medtronic Co. Ltd., and Teijin Pharma Ltd., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal antithrombotic strategies for patients with atrial fibrillation who experience ischemic stroke (IS) despite direct oral anticoagulant (DOAC) therapy remain inconclusive. This study compared outcomes for patients with DOAC treatment failure who changed or retained their prestroke DOAC., Methods and Results: This retrospective cohort study analyzed data from the National Health Insurance Research Database from 2012 to 2020. Patients with atrial fibrillation who experienced IS during DOAC therapy were assigned to either (1) the DOAC-change group: changing prestroke DOAC or (2) the DOAC-retain group: retaining prestroke DOAC. The primary outcome was a composite of recurrent IS and transient ischemic attack. The secondary outcomes included intracranial hemorrhage, major bleeding, systemic thromboembolism, and all-cause death. Propensity score-based inverse probability of treatment weighting was applied to balance the baseline characteristics between the DOAC-change and DOAC-retain groups. The Cox proportional hazards model compared the risk of outcomes between the 2 groups. In total, 1979 patients were enrolled (609 DOAC-change patients and 1370 DOAC-retain patients). The incidence rates of recurrent IS or transient ischemic attack were 7.20 and 6.56 per 100 person-years in the DOAC-change and DOAC-retain groups, respectively (hazard ratio [HR], 1.07 [95% CI, 0.87-1.30]). A nonsignificantly higher incidence rate of intracranial hemorrhage was observed in the DOAC-change group compared with the DOAC-retain group (0.75 versus 0.53 per 100-person-years; HR, 1.49 [95% CI, 0.78-2.83]). The systemic thromboembolism, major bleeding, and death rates were comparable between the DOAC-change and DOAC-retain groups., Conclusions: Changing prestroke DOAC does not reduce the risk of recurrent cerebral ischemia in patients with atrial fibrillation who develop IS during DOAC therapy. However, future studies should continue to observe the potential trends of increased intracranial hemorrhage risk.

Background: Intracranial hemorrhage is a severe cranial disease in the perinatal period. We aimed to explore the feasibility and accuracy of three-dimensional (3D) ultrasonography for the quantitative evaluation of neonatal intracranial hemorrhage., Methods: A total of 374 neonates with suspected intracranial hemorrhage from January 2017 to December 2019 were selected to be primarily screened by cranial ultrasonography and then diagnosed by cranial CT scan. The examination results were compared to analyze the feasibility and accuracy of 3D ultrasonography in quantifying blood loss., Results: CT scan showed that there were 102 cases of Papile grade I, 106 cases of grade II, 124 cases of grade III and 42 cases of grade IV. 3D ultrasonography showed that there were 108 cases of Papile grade I, 98 cases of grade II, 130 cases of grade III and 38 cases of grade IV. The diagnostic results of these two methods were not significantly different (P>0.05). The accuracies of CT scan for subventricular, intraventricular, subdural, subarachnoid and intraparenchymal hemorrhages were 47.33%, 31.24%, 94.62%, 91.73% and 91.35% respectively, and those of 3D ultrasonography were 98.74%, 96.37%, 91.51%, 90.41% and 97.64% respectively. The accuracies of 3D ultrasonography were significantly superior to those of CT scan for subependymal, intraventricular and intraparenchymal hemorrhages (P<0.05)., Conclusions: Neonatal intracranial hemorrhage can be well diagnosed by cranial ultrasonography which timely provides evidence for clinicians, thereby elevating the cure rate and reducing the mortality rate and incidence rate of sequelae. 3D ultrasonography is feasible and accurate for the quantitative evaluation of neonatal intracranial hemorrhage, thus being of great significance to prognostic determination in clinical practice.

Background: We aim to elucidate the contribution of early dynamic changes in the neutrophil-to-lymphocyte ratio (NLR) to poor clinical outcomes in acute ischemic stroke patients after endovascular treatment (EVT)., Methods: Acute ischemic stroke patients who underwent EVT were consecutively recruited from January 2019 to July 2022. Blood cell counts were sampled at admission and at following 24 hours after EVT. Clinical outcome measures included 3-month functional dependence (modified Rankin scale of 3-6), symptomatic intracranial hemorrhage, and mortality at 7 days and 30 days. Multinomial logistic regressions were used to evaluate the association of changes in the NLR with unfavorable outcomes., Results: A total of 590 patients were included in the final analysis. The multinomial logistic model indicated that the increasing changes in the NLR after EVT was an independent factor for poor outcomes; the adjusted odds ratio was 1.06 (95% confidence interval [CI] 1.03-1.10; P < 0.001) at poor 3-month functional outcomes, 1.07 (95% CI 1.04-1.10; P < 0.001) at symptomatic intracranial hemorrhage, 1.08 (95% CI 1.05-1.12; P < 0.001) at mortality at 7 days, and 1.04 (95% CI 1.02-1.07; P = 0.001) at mortality at 30 days. Areas under the curve of changes in NLR to discriminate adverse outcomes were 0.725, 0.687, 0.664, and 0.659, respectively. The optimal cutoff values were 5.77 (56.6% sensitivity, 81.0% specificity), 6.92 (60.0% sensitivity, 77.0% specificity), 8.64 (51.0% sensitivity, 82.0% specificity), and 8.64 (48.7% sensitivity, 83.0% specificity), respectively., Conclusions: The NLR in acute ischemic stroke patients increased remarkably independent of successful reperfusion. Elevated changes in the NLR might predict malignant hemorrhagic transformation, adverse functional outcomes, and short-term mortality., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT's specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes., Methods: In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT)., Results: Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0-2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0-2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy., Conclusions: Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique., Competing Interests: Competing interests: DFK received research support from Microvention, Medtronic, Neurogami, Cerenovus, Insera Therapeutics, Brainomix, MIVI Biosciences, and Stryker; received royalties from Medtronic; has ownership interest in Superior Medical Experts and Nested Knowledge, Marblehead Medical, Conway Medical, Monarch Biosciences, and Piraeus Medical; and serves on the advisory boards of Vesalio and NoNo Inc. RK received research support from Cerenovus, Medtronic, Endovascular Engineering, Frontier Bio, Sensome, Endomimetics, Ancure LLC, Neurogami Medical, MIVI Biosciences, Monarch Biosciences, Stryker, Conway Medical, Piraeus Medical, and Bionaut Labs., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks., Design: Population-based retrospective cohort study., Participants: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching., Exposure: Warfarin use within 14 days of IE diagnosis., Main Outcomes and Measures: Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up., Results: The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression., Conclusions and Relevance: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis., Key Points: Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe?, Findings: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The association of COVID-19 with higher bleeding risk and worse outcomes in acute ischemic stroke (AIS) undergoing revascularization may be related to the presence of infection symptoms. We aimed to assess the safety and outcomes of revascularization treatments in patients with AIS with asymptomatic COVID-19 (AS-COVID) or symptomatic COVID-19 (S-COVID)., Methods: We conducted an international multicenter retrospective cohort study of consecutive AIS tested for SARS-CoV-2, receiving intravenous thrombolysis and endovascular treatment between 2020 and 2021. We compared COVID-negative controls, AS-COVID, and S-COVID using multivariable regression. We assessed symptomatic intracranial hemorrhage (symptomatic intracerebral hemorrhage), mortality, and 3-month disability (modified Rankin Scale score)., Results: Among 15 124 patients from 105 centers (median age, 71 years; 49% men; 39% treated with intravenous thrombolysis only; and 61% with endovascular treatment±intravenous thrombolysis), 849 (5.6%) had COVID-19, of whom 395 (46%) were asymptomatic and 454 (54%) symptomatic. Compared with controls, both patients with AS-COVID and S-COVID had higher symptomatic intracerebral hemorrhage rates (COVID-controls, 5%; AS-COVID, 7.6%; S-COVID, 9.4%; adjusted odds ratio [aOR], 1.43 [95% CI, 1.03-1.99]; aOR, 1.63 [95% CI, 1.14-2.32], respectively). Only in patients with symptomatic infections, we observed a significant increase in mortality at 24 hours (COVID-controls, 1.3%; S-COVID, 4.8%; aOR, 2.97 [95% CI, 1.76-5.03]) and 3 months (COVID-controls, 19.5%; S-COVID, 40%; aOR, 2.64 [95% CI, 2.06-3.37]). Patients with COVID-19 had worse 3-month disability regardless of disease symptoms although disability was affected to a greater extent in symptomatic patients (aOR for worse modified Rankin Scale score shift: AS-COVID, 1.25 [95% CI, 1.03-1.51]; S-COVID, 2.10 [95% CI, 1.75-2.53]). S-COVID had lower successful recanalization (74.9% versus 85.6%; P <0.001), first pass recanalization (20.3% versus 28.3%; P =0.005), and a higher number of passes., Conclusions: In AIS undergoing revascularization treatments, both AS-COVID and S-COVID influence the risk of intracranial bleeding and worse clinical outcomes. The magnitude of this effect is more pronounced in symptomatic infections, which also present less favorable recanalization outcomes. These findings emphasize the impact of SARS-CoV-2 infection on the prognosis of revascularized AIS independent of symptom status., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895462., Competing Interests: Disclosures Dr Nguyen is on the Advisory Board of Idorsia. Dr Michel received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the University of Lausanne. The other authors report no conflicts. Global COVID-19 Stroke Registry: R. Herzig received research grants from the Ministry of Health of the Czech Republic (Grant number DRO – UHHK 00179906) and Charles University, Czech Republic (Cooperatio Program). C. Nolte received research grants from the German Ministry of Research and Education, the German Center for Neurodegenerative Diseases, and the German Center for Cardiovascular Research and is a speaker and advisory for Abbott, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer Pharma. S. Tjoumakaris is on Advisory Medtronic and MicroVention. J. Min is on Advisory Medtronic and Abbott. M.-A. Khan received research grants from National Institutes of Health, Spectrum Health-Michigan State University Research Alliance, and Genentech. A. Zini received consultation and travel expenses from Alexion-AstraZeneca, CSL Behring, and Boehringer Ingelheim and is on the steering committee of the OCEANIC-STROKE trial (A Study to Test Asundexian to Prevent a Clot-Related Stroke in Participants After an Acute Ischemic Stroke or High-Risk TIA/Mini-Stroke). A. Slowik and P. Wrona received research grant from European Research Area Network (ERA-NET) - Network of European Funding for Neuroscience Research (NEURON)/21/2020 Identification and clinical validation of biomarkers for long-term outcome after cerebral ischaemia (iBioStroke).

Background: Prognosis following cerebral venous thrombosis (CVT) is more favorable than other stroke types, but longer-term literature is limited, and trends over time are under-explored., Objective: Using administrative data, we examined factors associated with mortality in the inpatient setting, at 30 days and at one year following hospital discharge among a large consecutive cohort of Canadian patients with CVT., Design/methods: CVT patients from British Columbia (BC), Canada from 2000 to 2017 were identified using ICD diagnosis codes from the BC subset of the Canadian Institute for Health Information's Discharge Abstract Database. Logistic regression was used to investigate factors associated with inpatient mortality and survival analysis with Cox regression was used to explore factors associated with mortality at 30 days and one year., Results: Of 554 incident CVT patients identified, 508 (92 %) survived their index admission. Older age (OR 1.04, 95 % CI 1.03-1.06, p < 0.01) and the presence of seizures (OR 2.31, 95 % CI 1.08-4.94, p = 0.03) or intracranial bleeding (OR 2.28, 95 % CI 1.08-4.85, p = 0.03) were associated with increased odds of inpatient mortality. Mortality after hospital discharge was 3.0 % at 30 days and 9.4 % at one year. Older age (HR 1.05, 95 % CI 1.02-1.08, p < 0.01 at 30 days; HR 1.05, 95 % CI 1.04-1.07, p < 0.01 at 1 year) and having recent or active malignancy (HR 4.17, 95 % CI 1.51-11.52, p < 0.01 at 30 days; HR 4.60, 95 % CI 2.60-8.11, p < 0.01 at 1 year) were significantly associated with higher risks of mortality at 30 days and one year after discharge. There were decreases in inpatient mortality over the study period, but this was offset by higher mortality within 30 days after discharge in the later study epochs., Conclusions: Among patients discharged with a diagnosis of CVT, one-year mortality was high at 9.4 %. Older age and a history of cancer were associated with higher mortality after discharge., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TSF has received in-kind study medication from Bayer Canada (ClinicalTrials.gov: NCT03178864) and has received honoraria from Servier for speaker's bureau work. Other authors have no interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: One of the most important complications of stroke after intracranial haemorrhage surgery is impaired quality of life. This study was conducted to determine the impact of spiritual care on the quality of life of stroke patients., Methods: This single-blind clinical trial with a pre-test and post-test design was conducted on 100 stroke patients. Participants were recruited and randomly assigned to a control group and an intervention group. The stroke-specific quality of life (SS -QoL) scale was used to assess the quality of life of stroke patients. The intervention group received four sessions of spiritual care., Results: The independent t -test showed no significant difference between the two groups in the mean quality of life score ( t =-0.120, P =0.281) and its dimensions before the intervention. However, after the intervention, the results showed a significant difference between the two groups in terms of the mean quality of life score ( t =1.984, P <0.001) and its dimensions. In addition, the results of the paired t -test showed that in the intervention group, the mean score of quality of life ( t =5.161, P <0.001) and its dimensions were significantly different before and after the intervention. Furthermore, the results showed that before and after the intervention in the control group, the mean score of quality of life ( t =1.109, P =0.614) and its dimensions were not significantly different., Conclusions: Based on this results, the authors strongly recommend the use of spiritual care as a holistic care and complementary method to improve the symptoms and quality of life of stroke patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Clinical translation of the extracorporeal artificial placenta (AP) is impeded by the high risk for intracranial hemorrhage in extremely premature newborns. The Nitric Oxide Surface Anticoagulation (NOSA) system is a novel non-thrombogenic extracorporeal circuit. This study aims to test the NOSA system in the AP without systemic anticoagulation., Methods: Ten extremely premature lambs were delivered and connected to the AP. For the NOSA group, the circuit was coated with DBHD-N 2 O 2 /argatroban, 100 ppm nitric oxide was blended into the sweep gas, and no systemic anticoagulation was given. For the Heparin control group, a non-coated circuit was used and systemic anticoagulation was administered., Results: Animals survived 6.8 ± 0.6 days with normal hemodynamics and gas exchange. Neither group had any hemorrhagic or thrombotic complications. ACT (194 ± 53 vs. 261 ± 86 s; p < 0.001) and aPTT (39 ± 7 vs. 69 ± 23 s; p < 0.001) were significantly lower in the NOSA group than the Heparin group. Platelet and leukocyte activation did not differ significantly from baseline in the NOSA group. Methemoglobin was 3.2 ± 1.1% in the NOSA group compared to 1.6 ± 0.6% in the Heparin group (p < 0.001)., Conclusions: The AP with the NOSA system successfully supported extremely premature lambs for 7 days without significant bleeding or thrombosis., Impact: The Nitric Oxide Surface Anticoagulation (NOSA) system provides effective circuit-based anticoagulation in a fetal sheep model of the extracorporeal artificial placenta (AP) for 7 days. The NOSA system is the first non-thrombogenic circuit to consistently obviate the need for systemic anticoagulation in an extracorporeal circuit for up to 7 days. The NOSA system may allow the AP to be implemented clinically without systemic anticoagulation, thus greatly reducing the intracranial hemorrhage risk for extremely low gestational age newborns. The NOSA system could potentially be applied to any form of extracorporeal life support to reduce or avoid systemic anticoagulation., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Importance: Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs)., Objective: To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs., Design, Setting, and Participants: This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO., Exposures: NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment., Main Outcomes and Measures: The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model., Results: Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis., Conclusions and Relevance: In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.

Objectives: To evaluate audiologic consequences of gunshot wounds (GSWs) to the temporal bone (TB), and to correlate hearing outcomes with neurologic and vascular injuries adjacent to the temporal bone., Study Design: Retrospective case series., Setting: University-based level-one trauma center., Methods: Retrospective review of 35 patients surviving TB ballistic injury, 2012 to 2021. Main outcomes were audiologic results. Demographics, concomitant injuries, CT, and interventions were reviewed., Results: Mean age was 30.7 years; 80% male. Seventeen patients (48.6%) underwent audiologic testing. Mean pure tone average (PTA) was 75 ± 35 dB, bone line average 41 ± 26 dB, and speech discrimination score (SDS) 60 ± 43%. Nineteen (54.3%) demonstrated facial nerve injury (FNI), who were more likely to show SNHL especially anacusis, though their mean PTA and SDS were not statistically different from those without ( P  = .30 and .47, respectively). Radiographic review of those with sensorineural loss (SNHL, 6/17) revealed otic capsule-disrupting fracture (n = 2), pneumolabyrinth (n = 2), intracranial hemorrhage (n = 3). Those with mixed loss (6/17) showed otic capsule-sparing fracture (n = 6), EAC injury (n = 5), ossicular discontinuity (n = 2), and intracranial hemorrhage (n = 4). Two with mastoid tip fractures alone had normal audiograms. Audiometric outcomes were not predicted by concomitant CSF leak, spinal injuries, vascular injuries, cranial neuropathies, or traumatic brain injury., Conclusions: All patterns of hearing loss-conductive, sensorineural, mixed and normal-may be seen following TB ballistic injuries. Trauma severe enough to disrupt the facial nerve is more likely to cause anacusis. However, all should be formally evaluated, since ballistic injuries complicated by neurologic or vascular damage do not necessarily correlate with worse audiologic outcomes, while patients with minimal fractures may demonstrate losses., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Studies focusing on intracranial hemorrhage (ICH) in patients with cerebral venous thrombosis (CVT) are limited; thus, we aimed to identify factors associated with the occurrence of ICH in Thai patients with CVT., Methods: This retrospective cohort study recruited patients with CVT admitted to a tertiary university-based hospital between 2002 and 2022. The baseline characteristics, clinical presentations, radiographic findings, and etiologies were compared between the ICH and non-ICH groups. The factors with p < 0.2 in the univariate analysis were further analyzed using multivariable logistic regression analysis to identify independent factors associated with ICH in patients with CVT., Results: Of 228 screenings, 202 patients were eligible. The incidence rate of ICH was 36.63%. The ICH group showed a higher prevalence of focal neurological deficits (63.51% vs. 26.56%, p < 0.001), seizures (68.92% vs. 21.88%, p < 0.001), dependency status at admission (60.81% vs. 39.84%, p = 0.004), superior sagittal sinus thrombosis (71.62% vs. 39.07%, p < 0.001), superficial cortical vein thrombosis (36.49% vs. 10.16%, p < 0.001), and hormonal use (17.57% vs. 7.03%, p = 0.021) than the non-ICH group. In contrast, the ICH group showed a lower prevalence of isolated increased intracranial pressure (10.81% vs. 21.88%, p = 0.048) than the non-ICH group. Seizures (adjusted odds ratio [aOR], 4.537; 95% confidence interval [CI], 2.085-9.874; p < 0.001), focal neurological deficits (aOR, 2.431; 95% CI, 1.057-5.593; p = 0.037), and superior sagittal sinus thrombosis (aOR, 1.922; 95% CI, 1.913-4.045; p = 0.045) were independently associated with ICH in the multivariable logistic regression analysis., Conclusions: Seizures, focal neurological deficits, and superior sagittal sinus thrombosis are associated with ICH in patients with CVT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Cases with early diagnosis of neonatal tuberous sclerosis syndrome (TSC) are relatively seldom seen, and misdiagnosis of intracranial hemorrhage is even more rare. We retrospectively analyzed the clinical data of a case of neonatal tuberous sclerosis with atypical early symptoms and misdiagnosed as more common intracranial hemorrhage of the newborn., Patient Concerns: The child was female and had no obvious cause of convulsion 12 days after birth. The local hospital was initially diagnosed as "neonatal intracranial hemorrhage, congenital heart disease," and still had convulsions after 5 days of treatment, so it was transferred to neonatal intensive care unit of our hospital., Diagnosis: After admission, cardiac color ultrasound, magnetic resonance imaging, and electroencephalogram were performed, and TSC was diagnosed in combination with clinical symptoms. However, no known pathogenic mutations such as TSC1 and TSC2 were detected by peripheral blood whole exon sequencing., Intervention: After a clear diagnosis, sirolimus, and vigabatrin were given. But there were still convulsions. Topiramate, valproic acid, and oxcarbazepine were successively added to the outpatient department for antiepileptic treatment, and vigabatrin gradually decreased., Outcome: Up to now, although the seizures have decreased, they have not been completely controlled., Conclusions: The TSC of neonatal tuberous sclerosis is different from that of older children. It is usually characterized by respiratory distress and arrhythmia, and may be accompanied by convulsions, but the activity between attacks is normal. However, neonatal intracranial hemorrhage can be caused by premature delivery, birth injury, hypoxia, etc. Its characteristics are acute onset, severe illness, and rapid progression. Consequently, the diagnosis of these 2 diseases should not only be based on medical imaging, but also be combined with their clinical characteristics. When the imaging features are inconsistent with the clinical diagnosis, a comprehensive evaluation should be made again. The timing and pattern of onset of neonatal convulsions can help in differential diagnosis. If there is cardiac rhabdomyoma, subependymal or cortical nodule, skin low melanoma, etc, the possibility of neonatal TSC should be considered, and the diagnosis should be made according to its diagnostic criteria to avoid or reduce misdiagnosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The aim of the study was to establish a reliable scoring tool to identify the probability of symptomatic intracranial hemorrhage (sICH) in anterior circulation stroke patients with contrast enhancement (CE) on brain non-contrast CT (NCCT) after endovascular thrombectomy (EVT)., Methods: We retrospectively reviewed consecutive patients with acute ischemic stroke (AIS) who had CE on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO). We used the Alberta stroke program early CT score (ASPECTS) scoring system to estimate the extent and location of CE. Multivariable logistic regression was performed to derive an sICH predictive score. The discrimination and calibration of this score were assessed using the area under the receiver operator characteristic curve, calibration curve, and decision curve analysis., Results: In this study, 194 of 322 (60.25%) anterior circulation AIS-LVO patients had CE on NCCT. After excluding 85 patients, 109 patients were enrolled in the final analysis. In multivariate regression analysis, age ≥70 years (adjusted OR (aOR) 9.23, 95% CI 2.43 to 34.97, P＜0.05), atrial fibrillation (AF) (aOR 4.17, 95% CI 1.33 to 13.12, P＜0.05), serum glucose ≥11.1 mmol/L (aOR 9.39, 95% CI 2.74 to 32.14, P＜0.05), CE-ASPECTS ＜5 (aOR 3.95, 95% CI 1.30 to 12.04 P＜0.05), and CE at the internal capsule (aOR 3.45, 95% CI 1.03 to 11.59, P＜0.05) and M1 region (aOR 3.65, 95% CI 1.13 to 11.80, P＜0.05) were associated with sICH. These variables were incorporated as the CE-age-glucose-AF (CAGA) score. The CAGA score demonstrated good discrimination and calibration in this cohort, as well as the fivefold cross validation., Conclusion: The CAGA score reliably predicted sICH in patients with CE on NCCT after EVT treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Symptomatic intracranial hemorrhage (sICH) is a common and severe complication in patients with acute ischemic stroke (AIS) after treatment with thrombectomy., Objective: To explore the ability of admission plasma D-dimer levels to predict sICH after thrombectomy., Methods: Between February 2018 and August 2021, consecutive patients with AIS who underwent thrombectomy at our single comprehensive stroke center were retrospectively enrolled. sICH was defined according to the criterion of the Heidelberg Bleeding Classification. Logistic regression analysis was performed to determine the risk factors of sICH. The overall discriminative ability of D-dimer levels in predicting sICH was evaluated by adopting a receiver operating characteristic (ROC) curve., Results: Of the 395 enrolled patients, 48 (12.2%) had sICH. Patients with sICH were older (72.9 vs 69.3 years, P=0.037), more often female (62.5% vs 45.5%, P=0.027), had higher D-dimer levels (2.70 vs 0.74 mg/L, P<0.001), higher National Institutes of Health Stroke Scale score (20 vs 15, P<0.001), lower Alberta Stroke Program Early CT Score (8 vs 9, P<0.001), a higher proportion of internal carotid artery occlusions (56.2% vs 30.3%, P<0.001), and less commonly had large-artery atherosclerosis stroke etiology (12.5% vs 32.3%, P=0.010) than patients without sICH. After adjustment for potential confounders, D-dimer levels (adjusted OR=2.45, 95% CI 1.75 to 3.43, P<0.001) remained significantly associated with sICH. Based on the ROC, the D-dimer as a predictor for predicting sICH, presented with a specificity of 86.2%, a negative predictive value of 94.6%, and an area under the curve of 0.774., Conclusion: Elevated admission D-dimer levels are an independent predictor of sICH in patients with AIS after thrombectomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors., Methods: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay., Results: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses., Conclusion: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use., Methods and Results: A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration., Conclusions: Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.

Background: There has been debate on the use of intravenous thrombolysis (IVT) in patients with ischemic stroke and the recent use of direct oral anticoagulants (DOACs). Studies have compared these patients with non-DOAC groups in terms of outcomes. Herein, we aimed to systematically investigate the association between DOAC use and IVT's efficacy and safety outcomes., Results: A comprehensive systematic search was performed in PubMed, Embase, Scopus, and the Web of Science for the identification of relevant studies. After screening and data extraction, a random-effect meta-analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for comparison of outcomes between patients on DOAC and controls. Six studies were included in the final review. They investigated a total of 254,742 patients, among which 3,499 had recent use of DOACs. The most commonly used DOACs were rivaroxaban and apixaban. The patients on DOAC had significantly higher rates of atrial fibrillation, hypertension, diabetes, and smoking. Good functional outcome defined by modified Rankin Scale (mRS) 0-2 was significantly lower in patients who received DOACs (OR 0.71, 95% CI 0.62 to 0.81, P < 0.01). However, in the subgroup analysis of 90-day mRS 0-2, there was no significant difference between groups (OR 0.71, 95% 0.46 to 1.11, P = 0.14). All-cause mortality was not different between the groups (OR 1.02, 95% CI 0.68 to 1.52, P = 0.93). Similarly, there was no significant difference in either of the in-hospital and 90-day mortality subgroups. Regarding symptomatic intracranial hemorrhage (sICH), the previous DOAC use was not associated with an increased risk of bleeding (OR 0.98, 95% CI 0.69 to 1.39, P = 0.92). A similar finding was observed for the meta-analysis of any ICH (OR 1.15, 95% CI 0.94 to 1.40, P = 0.18)., Conclusions: Based on our findings, IVT could be considered as a treatment option in ischemic stroke patients with recent use of DOACs since it was not associated with an increased risk of sICH, as suggested by earlier studies. Further larger studies are needed to confirm these findings and establish the safety of IVT in patients on DOAC., (© 2023. The Author(s).)

Background: Decreased eosinophil level is associated with poor outcomes after mechanical thrombectomy in patients with acute ischemic stroke (AIS), but the underlying mechanism of this association is elusive. We aimed to assess the mediation effect of symptomatic intracranial hemorrhage (sICH) on the aforementioned association., Methods: A total of 328 consecutive AIS patients undergoing mechanical thrombectomy between May 2017 and March 2021 were analyzed. SICH was defined as any evidence of brain hemorrhage on CT scan with neurological deterioration. Regression analysis was used to assess the effect of eosinophils on sICH, and its effect on poor outcome. Mediation analysis was performed to assess the proportion of total effect by sICH on the association between eosinophils and poor outcome., Results: Multivariate analysis revealed an independent association between eosinophil count and sICH after adjusting for potential confounders (odds ratio, 0.00; 95% CI, 0.00-0.01; P = 0.0141), which is consistent with the result of eosinophil count (dichotomous) as a categorical variable (odds ratio, 0.22; 95% CI, 0.11-0.46; P < 0.0001). Eosinophil count was negatively associated with poor outcome (odds ratio, 0.00; 95% CI, 0.00-0.02; P = 0.0021). Mediation analysis revealed that sICH partially mediated the negative relationship between eosinophil count and poor outcome (indirect effect=-0.1896; 95%CI: -0.3654 - -0.03, P < 0.001)., Conclusion: This study showed an important effect of sICH on the association between eosinophils and poor outcome., (© 2023. The Author(s).)

In the perioperative management of patients with glioblastoma (GBM), physicians face the question of whether and when to administer prophylactic or therapeutic anticoagulation (AC). In this study, we investigate the effects of the timing of postoperative heparinization on thromboembolic events (TE) and postoperative hemorrhage (bleeding, PH) as well as the interactions between the two in the context of an underlying intracerebral malignancy. For this retrospective data analysis, 222 patients who underwent surgery for grade IV glioblastoma, IDH-wildtype (2016 CNS WHO) between 01/01/2014 and 31/12/2019 were included. We followed up for 12 months. We assessed various biographical and clinical data for risk factors and focused on the connection between timepoint of AC and adverse events. Subgroup analyses were performed for pulmonary artery embolism (PE), deep vein thrombosis, and postoperative intracranial hemorrhage (PH) that either required surgical intervention or was controlled radiologically only. Statistical analysis was performed using Mann-Whitney U-Test, Chi-square test, Fisher's exact test and univariate binomial logistic regression. p values below 0.05 were considered statistically significant. There was no significant association between prophylactic AC within 24 h and more frequent major bleeding (p = 0.350). AC in patients who developed major bleeding was regularly postponed by the physician/surgeon upon detection of the re-bleeding; therefore, patients with PH were anticoagulated significantly later (p = 0.034). The timing of anticoagulant administration did not differ significantly between patients who experienced a thromboembolic event and those who did not (p = 0.634). There was considerable overlap between the groups. Three of the six patients (50%) with PE had to be lysed or therapeutically anticoagulated and thereafter developed major bleeding (p < 0.001). Patients who experienced TE were more likely to die during hospitalization than those with major bleeding (p = 0.022 vs. p = 1.00). Prophylactic AC within 24 h after surgery does not result in more frequent bleeding. Our data suggests that postoperative intracranial hemorrhage is not caused by prophylactic AC but rather is a surgical complication or the result of antithrombotic therapy. However, thromboembolic events worsen patient outcomes far more than postoperative bleeding. The fact that bleeding may occur as a complication of life-saving lysis therapy in the setting of a thromboembolic event should be included in this cost-benefit consideration., (© 2023. The Author(s).)

Background: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain., Methods and Results: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks., Conclusions: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban., Registration: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Background: Disruption of the BBB is a harmful event after intracranial hemorrhage (ICH), and this disruption contributes to a series of secondary injuries. We hypothesized that FGF21 may have protective effects after intracranial hemorrhage (ICH) and investigated possible underlying molecular mechanisms., Methods: Blood samples of ICH patients were collected to determine the relationship between the serum level of FGF21 and the [Formula: see text]GCS%. Wild-type mice, SIRT6 flox/flox mice, endothelial-specific SIRT6-homozygous-knockout mice (eSIRT6 -/- mice) and cultured human brain microvascular endothelial cells (HCMECs) were used to determine the protective effects of FGF21 on the BBB., Results: We obtained original clinical evidence from patient data identifying a positive correlation between the serum level of FGF21 and [Formula: see text]GCS%. In mice, we found that FGF21 treatment is capable of alleviating BBB damage, mitigating brain edema, reducing lesion volume and improving neurofunction after ICH. In vitro, after oxyhemoglobin injury, we further explored the protective effects of FGF21 on endothelial cells (ECs), which are a significant component of the BBB. Mitochondria play crucial roles during various types of stress reactions. FGF21 significantly improved mitochondrial biology and function in ECs, as evidenced by alleviated mitochondrial morphology damage, reduced ROS accumulation, and restored ATP production. Moreover, we found that the crucial regulatory mitochondrial factor deacylase sirtuin 6 (SIRT6) played an irreplaceable role in the effects of FGF21. Using endothelial-specific SIRT6-knockout mice, we found that SIRT6 deficiency largely diminished these neuroprotective effects of FGF21. Then, we revealed that FGF21 might promote the expression of SIRT6 via the AMPK-Foxo3a pathway., Conclusions: We provide the first evidence that FGF21 is capable of protecting the BBB after ICH by improving SIRT6-mediated mitochondrial homeostasis., (© 2023. The Author(s).)

Background: The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications., Aims: In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA., Methods: PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early (⩽ 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death., Results: Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10-2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00-13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints., Conclusions: The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H-CD has received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Novo-Nordisk, Pfizer, Portola, and WebMD Global. Boehringer Ingelheim provided financial support for research projects. H-CD received research grants from the German Research Council (DFG) and German Ministry of Education and Research (BMBF). H-CD serves as editor of Neurologie up2date, Info Neurologie & Psychiatrie and Arzneimitteltherapie, as co-editor of Cephalalgia, and on the editorial board of Lancet Neurology and Drugs. GR received speaker’s honoraria and reimbursement for congress traveling and accommodation from Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo and Pfizer. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). KG received support by Alexion Pharma Germany GmbH, Abbott Medical GmbH, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer Pharma GmbH, Springer Medizin Verlag GmbH. CCE is an employee of Boehringer Ingelheim. The other authors declare no conflicts of interest related to the content of the presented work.

Introduction: The observation time in mild traumatic brain injury (mTBI) is controversial. Our aim was to assess the risk of neurological complications in mTBI with and without antithrombotic treatment., Method: We retrospectively evaluated patients with mTBI seen in the emergency room for 3 years. We considered MTBI those with Glasgow ≥13 at admission. A cranial CT was performed in all cases with ≥1 risk factor at admission and at 24 h in those with neurological impairment or initial pathological cranial CT. Complications in the following 3 months were retrospectively reviewed., Results: We evaluated 907 patients with a mean age of 73 ± 19 years. Ninety-one percent presented risk factors, with 60% on antithrombotic treatment. We detected 11% of initial brain hemorrhage, 0.4% at 24 h, and no cases at 3 months. Antithrombotic treatment was not associated with an increased risk of brain hemorrhage (9.9% with vs 11.9% without treatment, p = 0.3). 39% of the hemorrhages presented neurological symptoms (18% post-traumatic amnesia, 12% headache, 8% vomiting, 1% seizures), with 78.4% having mild symptoms. Of the 4 hemorrhages detected at 24 h, 3 were asymptomatic and one case that worsened the initial headache. No asymptomatic patient without lesion on initial clinical cranial CT presented at 24 h., Conclusions: Our study suggests that patients with asymptomatic mTBI, without a lesion on the initial cranial CT, would not require the observation period or CT control regardless of antithrombotic treatment or INR level., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: Neuron-specific enolase (NSE), which is a highly specific marker for neurons, could be a predictor for prognosis in patients with symptomatic intracranial hemorrhage (sICH) with acute ischemic stroke who are receiving endovascular treatment (EVT). This study aimed to investigate the relationship between NSE and sICH in patients with acute anterior circulation stroke undergoing EVT., Methods: A total of 215 consecutive patients with acute stroke treated with EVT were included. Patients with stroke and acute anterior circulation occlusion, receiving EVT treated at our hospital, were enrolled between January 2017 and August 2021. NSE level was measured on arrival at the neurology intensive care unit after EVT. The patients were divided into 2 groups according to whether sICH was present. Univariate and multivariate analyses were performed. NSE level was also incorporated into the TAG score (modified Thrombolysis in Cerebral Infarction score, Alberta Stroke Program Early CT Score, and glucose level), which was developed as a scoring system to predict sICH, and the prediction capability was compared with the TAG score alone. Causal inference was performed using the package DoWhy in Python to evaluate the causal relationship between NSE and sICH., Results: The area under the curve (AUC) value of NSE showed moderate accuracy, with an AUC value of 0.729 (95% confidence interval, 0.655-0.795; P < 0.001). The NSE cutoff value was set at 23.88 ng/mL. When the NSE level ≥23.88 ng/mL, the sensitivity was 58.33% and the specificity was 78.72% (P < 0.001). The AUC for the TAG + NSE score was 0.801 compared with an AUC of 0.632 for the TAG score (Z = 2.034; P = 0.042). A causal inference model using the DoWhy library shows a proportional relationship between NSE and the diagnosis of sICH., Conclusions: This study is the first to show that increased NSE level is an independent predictor of sICH in patients with acute anterior circulation stroke who are undergoing endovascular treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Traumatic middle meningeal artery (MMA)-middle meningeal vein (MMV) fistula (MMA-MMV fistula) and MMA pseudoaneurysm are the 2 main MMA-related vascular diseases occurring after blunt head trauma. These are rare but known causes of delayed intracranial hemorrhage. This study investigated predictors that may aid in the diagnosis of these diseases., Methods: In our department, screening digital subtraction angiography (DSA) is performed for patients with blunt head trauma accompanied by intracranial hemorrhage and skull or facial bone fracture. This study included 87 patients who underwent screening DSA without craniotomy from January 2019 to June 2023. The patients' clinical characteristics were retrospectively collected from the database. Statistical analysis was performed to examine the associations of various evaluation items with MMA-related vascular diseases., Results: The first DSA examination revealed 34 MMA-MMV fistulas and 1 MMA pseudoaneurysm. The second follow-up DSA examination revealed 13 MMA-MMV fistulas and four MMA pseudoaneurysms. Temporal/parietal bone fracture (odds ratio, 5.33; P = 0.0005; 95% confidence interval, 1.95-14.60) was significantly associated with MMA-related vascular diseases. Endovascular treatments were performed in 9 patients. All procedures were successfully completed without complications; no delayed bleeding was observed., Conclusions: Temporal/parietal bone fracture in patients with blunt head trauma is a likely predictor of MMA-related vascular diseases. When initial head computed tomography reveals this pathology, we recommend careful imaging follow-up (e.g., DSA) and treatment as needed, while considering the possibility of MMA-related vascular diseases., (Copyright © 2023 Elsevier Inc. All rights reserved.)