Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Oligoclonal IgM bands are a promising biomarker for long-term cognitive outcomes in multiple sclerosis.

BACKGROUND: The presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid is associated with a more severe clinical multiple sclerosis (MS) course. OBJECTIVE: To investigate LS-OCMB as a prognostic biomarker of cognitive long-term outcomes in MS. METHODS: Ninety-nine patients underwent neuropsychological assessment. Cognitive performance between LS-OCMB- and LS-OCMB+ patients was compared adjusting by age, education, anxiety-depression, disease duration, and disability. RESULTS: LS-OCMB+ patients of ∼13 years of disease duration performed worse on Symbol Digit Modalities Test (SDMT) (p = 0.005). CONCLUSION: LS-OCMB+ perform worse on information processing speed and working memory (SDMT), suggesting that LS-OCMB could be a useful biomarker for long-term cognitive outcomes.

Isolation and Quantification of Blood Apoptotic Bodies, a Non-invasive Tool to Evaluate Apoptosis in Patients with Ischemic Stroke and Neurodegenerative Diseases.

BACKGROUND: Improper regulation of apoptosis has been postulated as one of the main factors that contributes to the etiology and/or progression of several prevalent diseases, including ischemic stroke and neurodegenerative pathologies. Consequently, in the last few years, there has been an ever-growing interest in the in vivo study of apoptosis. The clinical application of the tissue sampling and imaging approaches to analyze apoptosis in neurological diseases is, however, limited. Since apoptotic bodies are membrane vesicles that are released from fragmented apoptotic cells, it follows that the presence of these vesicles in the bloodstream is likely due to the apoptotic death of cells in tissues. We therefore propose to use circulating apoptotic bodies as biomarkers for measuring apoptotic death in patients with ischemic stroke and neurodegenerative diseases. RESULTS: Since there is no scientific literature establishing the most appropriate method for collecting and enumerating apoptotic bodies from human blood samples. Authors, here, describe a reproducible centrifugation-based method combined with flow cytometry analysis to isolate and quantify plasma apoptotic bodies of patients with ischemic stroke, multiple sclerosis, Parkinson's disease and also in healthy controls. Electron microscopy, dynamic light scattering and proteomic characterization in combination with flow cytometry studies revealed that our isolation method achieves notable recovery rates of highly-purified intact apoptotic bodies. CONCLUSIONS: This easy, minimally time consuming and effective procedure for isolating and quantifying plasma apoptotic bodies could help physicians to implement the use of such vesicles as a non-invasive tool to monitor apoptosis in patients with cerebrovascular and neurodegenerative diseases for prognostic purposes and for monitoring disease activity.

UHPH-processed O/W submicron emulsions stabilised with a lipid-based surfactant: physicochemical characteristics and behaviour on in vitro TC7-cell monolayers and ex vivo pig's ear skin.

Submicron O/W emulsions formulated with sesame oil plus a lipid-base surfactant, and with or without retinyl acetate (RAC) as a model hydrophobic biomolecule, were prepared by single-pass homogenisation at ≥ 200 MPa (UHPH) and an initial fluid temperature (Tin) of 24°C. These emulsions were characterised by a monomodal distribution (peak maximum at 260 nm) and a 2-year potential physical stability at ambient temperature. Submicron droplets were investigated in term of (i) physicochemical characteristics (size distribution curves; ζ-potential value), and (ii) impact on TC7-cell monolayers (MTT-assay and cell LDH-leakage). Submicron droplets ± RAC did not affect or increased significantly (p=0.05) TC7-cell metabolic activity after 4-24h of exposure indicating absence of cellular impairment, except when high amounts of droplets were deposed on TC7-cells. Indeed, the lipid-based surfactant deposed alone on TC7-cells at high concentration, induced some significant (p=0.05) cell LDH-leakage, and therefore cell-membrane damage. Cellular uptake experiments revealed a significant (p=0.05) time-dependent internalisation of RAC from submicron droplets, and cellular transformation of RAC into retinol. The turnover of RAC into retinol and therefore RAC bioaccessibility appeared faster for RAC-micelles of similar size-range and prepared at atmospheric pressure with polysorbate 80, than for submicron O/W emulsions. Permeation experiments using pig's ear skin mounted on Franz-type diffusion cells, revealed RAC in dermis-epidermis, in significantly (p=0.05) higher amounts for submicron than coarse pre-emulsions. However, RAC amounts remained low for both emulsion-types and RAC was not detected in the receptor medium of Franz-type diffusion cells.