Aseptic meningitis and Fabry disease.

OBJECTIVE: Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features. METHODS: We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases. RESULTS: Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis. INTERPRETATION: Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.

Multifocal and Microvascular Involvement in Ischemic Stroke During COVID-19: A Cohort Study With Comparison With Non-COVID-19 Stroke.

Introduction: Thromboembolic events, including ischemic stroke, are major complications of coronavirus disease 2019 (COVID-19). The clinical characteristics of COVID-19-related stroke are not clearly defined, and few controlled studies assessed the underlying mechanisms of cerebrovascular complications of COVID-19. This single-center retrospective observational study compared stroke characteristics between patients with and without COVID-19. Methods: This study included all patients hospitalized between March 1, 2020, and April 30, 2020, in Colmar Hospital for ischemic stroke as confirmed by imaging. The characteristics of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by real-time reverse transcriptase polymerase chain reaction or serology were compared with those without SARS-CoV-2 infection. Result: Among 772 patients, nine COVID-19 patients were compared with 50 patients without COVID-19. The following inflammatory and procoagulant marker levels were significantly higher in the COVID-19 group than those in the control group: C-reactive protein, 57.3 ± 43.4 vs. 15.0 ± 30.6 mg/L, p < 0.001; fibrinogen, 5.89 ± 1.75 vs. 4.03 ± 1.26 g/L, p < 0.001; and D-dimer, 4,833.9 ± 6,549.4 vs. 1,028.6 ± 942.6 ng/ml, p < 0.001. The rates of multifocal cerebral territory involvement (4 vs. 7, p = 0.05), microvascular involvement (4 vs. 6, p = 0.04), and thrombophilia (4 vs. 4, p = 0.014) were significantly higher in the COVID-19 group than in the control group, whereas no significant intergroup differences were found in the stroke mechanisms, i.e., cardio-embolic, atherosclerotic, small vessel disease, and cryptogenic. Conclusion: COVID-19-related stroke is characterized by hypercoagulability and hyperinflammation that may favor strokes via microvascular circulation abnormalities, microthrombus formation, and multifocal lesions.

SOFIA catheter for direct aspiration of large vessel occlusion stroke: A single-center cohort and meta-analysis.

BACKGROUND AND PURPOSE: Direct aspiration (DA) using large-bore distal aspiration catheters is an established strategy for the endovascular thrombectomy (EVT) of large-vessel occlusion stroke (LVOS). However, the performance of individual catheters like SOFIA has yet to be examined. METHODS: We present a cohort of 144 consecutive patients treated with first-line DA and SOFIA 6 F Plus catheter for LVOS. We also conducted a systematic review of the literature searching multiple databases for reports on thrombectomy with DA and SOFIA catheters and performed a meta-analysis of recanalization, safety, and clinical outcomes. RESULTS: In the study cohort a successful recanalization (mTICI 2b-3) rate of 75.7% was achieved with DA alone, the global rate for functional independence (90-day mRS 0-2) was 40.3%. For the metanalysis we selected nine articles that included a total of 758 patients treated with first-line thrombectomy with the SOFIA catheters. The mTICI 2b-3 rate was 71.6% (95%CI, 66.3-76.5%) while a rescue stent-retriever was used in 24.1% (95%CI, 17.7-31.9%) of cases. The overall mTICI2b-3 rate after DA and rescue therapy was 88.9% (95%CI, 82.6-93.1%). We found a pooled estimate of 45.6% (95%CI, 38.6-52.8%) for functional independence, a mortality within 90 days of 19% (95%CI, 14.1-25.0%) and a rate of 5.8% (95%CI, 4.2-8.0%) of symptomatic intracranial hemorrhage. CONCLUSION: The DA approach for LVOS with the SOFIA catheters is highly effective with an efficacy and safety profile comparable to those found in contemporary thrombectomy trials and observational studies that use other devices or approaches.

Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol.

INTRODUCTION: Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT. METHODS AND ANALYSIS: DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0-2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0-2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment. ETHICS AND DISSEMINATION: The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT03969511.