Double seronegative NMOSD (DS-NMOSD) lacks approved disease-modifying treatments, and limited data exist on optimal relapse-prevention strategies. In this multicenter, international, retrospective cohort study, we sought to compare the real-world effectiveness of anti-CD20 agents vs nonspecific immunosuppressants as disease-modifying strategies for relapse prevention in DS-NMOSD. A retrospective cohort database was constructed using standardized data collection from medical records across collaborating centers in the United States, Brazil, the United Kingdom, Thailand, Turkiye, and China. Patients meeting IPND-2015 NMOSD criteria with negative serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibody testing via cell-based assays and at least 12 months of follow-up were reviewed. The primary outcome was the incidence rate ratio (IRR) of relapses; secondary outcomes included the annualized relapse rate (ARR) and time to relapse. A total of 103 patients with DS-NMOSD met study criteria, with a median follow-up of 6 years. Anti-CD20 therapy was associated with a significantly lower IRR (0.02, 95% CI 0.01-0.04) and ARR (0.17, 95% CI 0.07-0.40) compared with nonspecific immunosuppressants (0.76, 95% CI 0.40-1.43) after adjusting for covariates. Survival analysis demonstrated a prolonged relapse-free interval with anti-CD20 agents. Our findings support the use of B-cell depletion as a potentially superior relapse-prevention strategy in DS-NMOSD, highlighting its potential as a first-line therapy. This study provides Class IV evidence that, in patients with DS-NMOSD, treatment with a DMT reduces relapse incidence rate ratio compared with no treatment and anti-CD20 DMTs are associated with a lower relapse incidence rate ratio compared with nonspecific immunosuppressants.

Background: Large B-cell lymphoma of immune-privileged sites (LBCL-IP) is a rare subtype characterized by immune evasion properties. Primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL) are examples of LBCL-IP associated with programmed cell death protein 1 (PD-1). Few studies have investigated the use of PD-1 inhibitors in patients with relapsed PCNSL and PTL. Objective: To conduct a systematic review evaluating the efficacy and safety of PD-1 inhibitors in patients with relapsed PCNSL and PTL. Methods: We searched the PubMed, Embase, and Scopus databases for relevant studies. The inclusion criteria focused on adult patients diagnosed with relapsed PCNSL or PTL who were treated with PD-1 inhibitors. We excluded case reports or series with fewer than five participants, review articles, and animal studies. A random-effects model with the DerSimonian‒Laird method analyzed the pooled complete response rate (CRR), partial response rate (PRR), overall response rate (ORR), and progression-free survival (PFS) rate. Results: Seven studies comprising 127 patients (124 with relapsed PCNSL and 3 with PTL) were included. All patients were treated with either nivolumab or pembrolizumab. The pooled CRR was 42.8% (95% CI, 25.7%‒60.0%; I² = 75.25%; p < 0.001), indicating high heterogeneity. The pooled PRR was 17.1% (95% CI, 9.5%‒24.7%; I² = 18.71%; p = 0.287), with nonsignificant heterogeneity. The pooled ORR was 67.1% (95% CI, 44.9%‒89.4%; I² = 88.64%; p < 0.001), indicating high heterogeneity. The 6-month PFS rate was 34.8% (95% CI, 18.1%‒51.5%; I² = 27%; p = 0.242), with low heterogeneity. Thirty-eight adverse events were reported. The most common were skin reactions (14 events; 36.8%), fatigue (11 events; 28.9%), and nausea (6 events; 15.8%). Conclusions: Our study demonstrates that PD-1 inhibitors show promising efficacy in relapsed PCNSL and PTL, with significant responses observed. The adverse effects were mild, with the most common being skin reactions. Therefore, PD1 inhibitors have the potential to drive advancements in treatment strategies for relapsed PCNSL and PTL.

This systematic review aims to analyze the clinical, laboratory, and imaging characteristics of GFAP astrocytopathy, with attention to differences between Asian and non-Asian populations. We searched PubMed, Embase, and Scopus from inception through June 2025 for case reports, case series, and observational studies involving adult patients with GFAP astrocytopathy. Fifteen studies, including 538 patients, were analyzed. Data on clinical presentations, MRI findings, and laboratory results were extracted and compared across regions. We identified a total of 2,272 studies, of which 15 were included in our final analysis, comprising 538 patients. Our analysis identified three main clinical phenotypes: meningoencephalitis (164/371, 44.2%), meningoencephalomyelitis (94/371, 25.3%), and myelitis (26/371, 7.0%). The most common clinical symptoms were headache (186/470, 39.6%), abnormal movements (160/473, 33.8%), fever (172/538, 32.0%), and psychiatric symptoms (111/471, 23.6%). MRI findings frequently showed lesions in the periventricular (85/434, 19.6%) and subcortical regions (80/432, 18.5%). Perivascular and meningeal enhancements represented the most common radiological findings. Laboratory findings revealed positive GFAP antibodies in either serum or CSF. Co-existence of other antibodies in CSF and serum was also observed, most notably anti-AQP4, anti-MOG, and anti-NMDAR. GFAP astrocytopathy is characterized by a wide range of clinical and radiological manifestations, most commonly presenting as meningoencephalitis, meningoencephalomyelitis, or myelitis, with meningoencephalitis being the most prevalent clinical syndrome observed in this study. Commonly reported symptoms include headache, fever, abnormal movements, and psychiatric symptoms. The disease exhibits diverse neurological and imaging features. Regional differences suggest that genetics, diagnostic practices, and cultural factors may influence symptom profiles. These findings highlight the need for standardized diagnostic criteria and further research across diverse populations.

Objective: This study aimed to elucidate the clinical manifestations, laboratory findings and outcomes of patients with intravascular large B cell lymphoma (IVLBCL) with neurological involvement and to differentiate IVLBCL with and without neurological involvement.Methods: A cohort study was conducted at Siriraj Hospital, Mahidol University, Thailand, between January 2005 and September 2024. Clinical data, laboratory values and central nervous system imaging results were analysed. Categorical variables were compared using the χ² or Fisher’s exact test, while continuous variables were analysed with the Mann-Whitney U test, as appropriate.Results: Of the 30 patients with IVLBCL, 10 had neurological involvement and 20 without neurological symptoms, including myelopathy (5 patients, 50%); cognitive impairment (3 patients, 30%); seizures (2 patients, 20%); optic neuropathy, hemiparesis, homonymous hemianopia, vertigo and global aphasia (each affecting 1 patient, 10%). 60% of IVLBCL with neurological involvement had systemic symptoms, including prolonged fever, anaemia, anorexia and weight loss. MRI showed hyperintense lesions in the supratentorial, infratentorial and spinal cord with the prominent findings being longitudinally extensive cord lesions (four patients, 40.0%). The median survival time of the IVLBCL with neurological involvement was 4.1 months (95% CI: 0.0 to 17.1 months), with a 1-year survival rate of 37.5% and a 2-year survival rate of 25.0%.Interpretation: This study highlights the distinct clinical, laboratory features and imaging of IVLBCL with neurological involvement and compares it to IVLBCL without neurological involvement. Early recognition of these findings is crucial for accurate diagnosis and improved patient outcomes despite the aggressive nature of IVLBCL.

Background/Objective: Clostridioides difficile infection (CDI) is a common healthcare-associated ailment, presenting major health and economic challenges, especially for the elderly. Despite its prevalence, comprehensive data about CDI’s impact on the elderly are limited. Methods: This study used the Global Burden of Disease Study 2019 data to analyze CDI trends from 2000 to 2019, considering factors like sex, region, and sociodemographic index (SDI). Results: This study revealed that CDI caused approximately 18,181 deaths and 252,709 disability-adjusted life years (DALYs) among the elderly worldwide. The Americas showed the highest CDI burden, while the Eastern Mediterranean saw the steepest rate increase from 2000 to 2019. Regions with a high SDI also displayed substantial CDI impact. Conclusions: The escalating burden of CDI in the elderly, especially in high-SDI areas and the Americas, emphasizes an urgent need for targeted public health strategies.