Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare neurological disorder that may present with headache, seizures, and focal neurological deficits. Brain magnetic resonance imaging (MRI) typically demonstrates T2-FLAIR white matter hyperintensities, often accompanied by cerebral microbleeds. Although corticosteroids are considered effective for CAA-RI, the role of targeted immunotherapy remains unclear. We report a 66-year-old man who developed progressive visual impairment following an episode of headache and fever. Brain MRI demonstrated extensive bilateral parieto-occipital T2-FLAIR white matter hyperintensities accompanied by multiple cerebral microbleeds, with additional periventricular white matter abnormalities. Interleukin-6 (IL-6) levels were elevated in both serum and cerebrospinal fluid (CSF), whereas autoimmune encephalitis antibody panels were negative in both serum and CSF. Genetic testing revealed an apolipoprotein E (APOE) ε3/ε4 genotype. Based on the clinical presentation, neuroimaging findings, and laboratory results, a diagnosis of probable CAA-RI was made. The patient was treated with corticosteroids and tocilizumab, an IL-6 receptor inhibitor. At the 2-month follow-up, his visual field impairment had improved, serum IL-6 levels had decreased, and follow-up brain MRI demonstrated a marked reduction in the extent of the T2-FLAIR white matter hyperintensities. This case describes markedly elevated CSF IL-6 levels in a patient with CAA-RI. Clinical and radiological improvement was observed over the course of treatment, which included corticosteroids and tocilizumab. Elevated IL-6 may reflect active neuroinflammation. However, its causal role in CAA-RI remains uncertain. Further studies are needed to clarify the role of IL-6 signaling in CAA-RI and to evaluate the efficacy and safety of IL-6-targeted therapy.
Background Secondary stroke prevention in patients with atrial fibrillation (AF) who experience an ischemic stroke (IS) despite oral anticoagulation remains challenging, and strategies have focused on antithrombotic optimization or left atrial appendage occlusion. Adjunctive statin therapy might reduce early vascular risk and mortality in this high-risk population. Objectives To evaluate the association between statin therapy at hospital discharge and 90-day all-cause death (primary outcome) in patients with AF experiencing IS despite oral anticoagulation. Design Multicenter, retrospective, observational cohort study within the ASPERA-R initiative. Methods Consecutive adults admitted between February 2020 and February 2025 with IS occurring during continuous oral anticoagulation for AF were included. Time-to-event analyses were landmarked at discharge to minimize immortal-time bias. Secondary outcomes were a composite vascular outcome (recurrent IS, transient ischemic attack (TIA), or vascular death) and recurrent IS/TIA; moderate-to-severe bleeding and intracranial hemorrhage (ICH) were assessed for safety. Inverse probability weighting (IPW) on a prespecified propensity score addressed confounding by indication, and weighted Cox models were fitted, with sensitivity analyses for the primary outcome. Results Among 1,442 patients discharged alive, 1,016 (70.5%) received statins at discharge. After weighting, propensity-score covariates were balanced. Over 90 days, statin therapy was associated with lower all-cause mortality (9.6% vs. 19.2%; HR 0.55, 95% CI 0.39-0.79). The composite vascular outcome showed a directionally similar but borderline association (HR 0.63, 95% CI 0.40-1.00); recurrent IS/TIA was not associated. Moderate-to-severe bleeding and ICH were rare and did not differ between groups. The mortality association was consistent across sensitivity analyses. Conclusion In AF patients with IS despite oral anticoagulation, statin therapy at discharge was associated with lower 90-day all-cause mortality, without increased short-term bleeding. Given the observational design, these hypothesis-generating findings support prospective evaluation of statins in this population.
Background The short-term efficacy and safety of intensive statin therapy in critically ill patients with acute ischemic stroke (AIS) remain unclear. Objectives To evaluate the association between intensive statin therapy and in-hospital mortality in critically ill patients with AIS, and to characterize the timing of statin initiation. Design A matched nested case-control study within a retrospective, multicenter cohort. Methods We used clinical data from three neurocritical care units between January 2019 and December 2024. In-hospital deaths (cases) were matched to survivors (controls) at a ratio of up to 1:3 using nearest-neighbor propensity score matching, with prespecified calipers of ±5 years for age, ±5 points for initial National Institutes of Health Stroke Scale score, and ±365 days for admission date. Conditional logistic regression stratified by matched sets was used to estimate the association, with sequential adjustment for potential confounders. Results A total of 169 matched strata were established, comprising 169 cases and 455 controls. In the matched cohort, the median time from admission to the first statin dose was 10.8 hours (interquartile range 5.4-25.5), and 93.9% of treated patients received their first dose within 48 hours. In the primary analysis, intensive statin therapy was associated with lower in-hospital mortality (adjusted odds ratio [aOR] 0.52; 95% confidence interval [CI] 0.31-0.87; P = 0.013). This association remained consistent after further adjustment for post-stroke complications including pneumonia and hemorrhagic transformation (aOR 0.47; 95% CI 0.27-0.82; P = 0.007). No significant increase in severe hemorrhagic transformation (Heidelberg class 2-3d) was observed with intensive statin therapy (11.4% vs 10.5%, P = 0.767). Conclusion Intensive statin therapy was associated with lower in-hospital mortality in critically ill patients with AIS, without an apparent increase in severe hemorrhagic transformation. These findings support the need for prospective studies to confirm the observed associations and to define the optimal timing of statin therapy in this population.
Background Highly active Generalised myasthenia gravis (gMG) represents a group of patients with substantial disability and recurrent, life-threatening exacerbations. The recent emergence of targeted biologics has created new therapeutic opportunities, yet the potential of dual targeting complement C5 and B-cell signaling, such as B cell activating factor (BAFF)/proliferation-inducing ligand (APRIL), has not been thoroughly explored in these patients. Objectives To explore the efficacy and safety of combined therapies with eculizumab (C5 complement inhibitor) and telitacicept (BAFF/APRIL inhibitor) in acetylcholine receptor antibody (AChR-ab)+ gMG patients who had high disease activity. Design Single-centre, prospective, observational case series. Methods Patients with highly active gMG despite advanced immunotherapies were enrolled in a neuromuscular reference centre for treatment with eculizumab and telitacicept. The primary endpoint was the change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Minimal Symptom Expression (MSE), Clinically Meaningful Improvement (CMI), oral corticosteroid dose, serum IgG, and the incidence of treatment-emergent adverse events (TEAEs) were assessed. Results Among the 22 patients ultimately enrolled, 16 (72.7%) had a history of myasthenic crisis (MC). Previously administered immunomodulatory therapies included intravenous immunoglobulin (IVIG) (16/22, 72.7%), efgartigimod (14/22, 63.6%), and plasma exchange (PE) (13/22, 59.1%). At Week 12 after initiation of eculizumab and telitacicept, significant improvements were observed: the MG-ADL score decreased substantially from a baseline value of 8.0 (IQR 5.0–10.0) to 1.0 (IQR 0.0–2.8) (p < 0.001), with all participants achieving CMI and 54.5% (12/22, 95% CI 32.2–75.6) achieving MSE. Concurrently, the daily oral prednisone dose was significantly reduced by 33% (from 22.5 mg to 15.0 mg; p < 0.001), and serum IgG levels declined markedly from 11.86 g/L to 7.14 g/L (p < 0.001). Notably, no meningococcal infections or other serious adverse events were reported. Conclusion In highly active AChR-ab+ gMG requiring rapid disease control, simultaneous targeting of complement C5 and B cell activating pathway achieved clinical improvement, corticosteroid sparing, and reduced serum IgG, with an acceptable short-term safety profile. These proof-of-concept findings require confirmation in controlled trials with a mono-targeting therapy regimen and longer follow-up.
