CSF-G

Integrated Blood Inflammatory Ratios and Cerebrospinal Fluid Blood‒Brain Barrier Dysfunction Predict Relapse Risk in Neuromyelitis Optica Spectrum Disorder.

Zheng Xingyue X, Shi Jing J, Yin Hao H, Song Huiqun H et al.

Relapse is the primary driver of irreversible disability accumulation in neuromyelitis optica spectrum disorder (NMOSD). Although aquaporin-4 immunoglobulin G (AQP4-IgG) is central to disease diagnosis and pathogenesis, reliable tools for individualized relapse risk stratification remain limited. Given emerging evidence that blood-brain barrier (BBB) dysfunction and systemic immune activation play key and interconnected roles in NMOSD pathophysiology, we aimed to develop and internally validate an integrated prognostic model incorporating these dimensions to predict relapse risk. In this retrospective cohort study, 152 patients with NMOSD were enrolled and followed longitudinally for time to first relapse. Baseline peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), as well as cerebrospinal fluid (CSF) parameters reflecting BBB integrity, were collected at study entry. Independent predictors of time to first relapse were identified using multivariable Cox proportional hazards regression. Three hierarchical prognostic models were constructed and compared: a clinical model, a clinical-CSF model, and an integrated clinical-CSF-blood inflammatory model. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis. Internal validation was performed using 1000 bootstrap resamples, and clinical utility was assessed by decision curve analysis (DCA). Patients who experienced relapse exhibited more pronounced BBB dysfunction and higher systemic inflammatory activation at baseline. Model discrimination improved with the sequential incorporation of CSF indices and inflammatory markers, with AUCs of 0.693 for the clinical model, 0.744 for the clinical-CSF model, and 0.850 for the integrated model. The final nomogram demonstrated good discrimination (bootstrap-corrected C-index 0.811), good calibration, and favorable clinical utility. AQP4-IgG seropositive patients had a higher relapse risk; importantly, the integrated model retained predictive performance in this subgroup, indicating added prognostic value beyond serological status. Exploratory analyses further suggested that higher AQP4-IgG titers were associated with increased relapse risk. An integrated nomogram incorporating peripheral inflammatory ratios and BBB-related CSF indices enables individualized relapse risk prediction in NMOSD. The model provides incremental prognostic value beyond AQP4-IgG serostatus and may support risk-adapted clinical management.

Cerebrospinal fluid tap test in normal pressure hydrocephalus.

Schena Josephine J, Burns Harvey H, Hayes Alexander A, Cossou Graeme G et al.

Normal pressure hydrocephalus (NPH) is a common cause of gait apraxia, cognitive impairment and urinary incontinence in older adults and can respond to cerebrospinal fluid (CSF) shunting. It can be challenging to select optimal candidates for CSF shunting given that communicating hydrocephalus is common in the normal ageing population as are the clinical symptoms of NPH. Large-volume lumbar puncture or CSF tap test can identify good candidates for CSF shunting. While neurologists are familiar with and have access to routine lumbar punctures, there are nuances about the CSF tap test for NPH to consider in clinical practice. In this article, we describe our practice for CSF tap tests with reference to the current evidence and common pitfalls while accepting the limitation of the test itself.

Correction: How well do plasma Alzheimer's disease biomarkers reflect the CSF amyloid status?

Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of Central Nervous System Infections: a Subgroup Analysis from the FORTRESS Study.

Jarczak Dominik D, Kluge Stefan S, Kieninger Martin M, Hagel Stefan S et al.

Central nervous system (CNS) infections are associated with high morbidity and mortality, and their management is challenged by antimicrobial resistance and limited cerebrospinal fluid (CSF) penetration of many antibiotics. Intravenous fosfomycin (FOS) offers broad-spectrum activity, favourable pharmacokinetics and reliable CSF penetration, making it a potential partner in combination therapy for severe CNS infections. This interim subgroup analysis of the prospective FORTRESS study evaluated real-world treatment patterns, effectiveness and safety of FOS in patients with CNS infections. FORTRESS is an ongoing multicentre, non-interventional, international study enrolling patients receiving FOS for severe infections. We analysed patients with documented CNS infections among 1019 enrolled up to June 2025. Effectiveness endpoints at end of treatment (EOT) included clinical success (composite endpoint defined as successful clinical response plus concomitant microbiological cure), successful clinical response (defined as complete or partial resolution of signs and symptoms), microbiological cure, clinical failure and in-hospital mortality. Safety outcomes included adverse drug reactions (ADRs; including serious ADRs) and laboratory parameters. A total of 64 patients with CNS infections were included, of which most were critically ill at baseline, with high rates of ICU admission (90.6%), sepsis (42.2%) and mechanical ventilation (35.9%). Included patients were treated for ventriculitis (53.1%), brain abscess/empyema (26.6%), bacterial meningitis (26.6%) and shunt infections (18.8%), mainly caused by Staphylococcus spp. (48.8%). FOS was administered exclusively in combination regimens, generally as second- or third-line therapy, at high daily doses (median 22.1 g/day). At EOT, clinical success was achieved in 82.8% of patients, a successful clinical response in 92.2% and microbiological cure in 85.9%. All-cause in-hospital mortality was 12.5%. Outcomes were especially favourable in bacterial meningitis (94.1% clinical success) and Gram-positive infections (96.6% clinical success). FOS was generally well tolerated. Electrolyte imbalances were the most common ADRs but were mainly mild and did not require treatment modification. These interim real-world data suggest that FOS, used in combination with other antimicrobial agents, is an effective and well-tolerated treatment option for severely ill patients with CNS infections. ClinicalTrials.gov identifier, NCT02979951.