Articles científics - CEMCAT

Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis

2025-11-19T03:00:59Z

Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis Deisenhammer, Florian; Arrambide, Georgina; Banwell, Brenda Louise; Coetzee, Timothy; Gnanapavan, Sharmilee; Hegen, Harald; Montalban, Xavier Cerebrospinal fluid; Criteria; Diagnosis; Líquido cefalorraquídeo; Criterios; Diagnóstico; Líquid cefaloraquidi; Criteris; Diagnòstic; The 2024 McDonald diagnostic criteria for Multiple Sclerosis (MS) introduce kappa free light chains (κ-FLC) detection in cerebrospinal fluid (CSF) which can be used interchangeably with oligoclonal IgG bands (OCB) to demonstrate intrathecal immunoglobulin synthesis. Diagnostic sensitivity and specificity of κ-FLC is equal to OCB on a 95% confidence level. In rare cases determination of both, κ-FLC and OCB should be considered as the concordance rate is around 90%. We recommend calculating the κ-FLC index with values of ≥6.1 performing best for diagnosing MS. Validated turbidimetric or nephelometric assays should be applied for which proficiency testing programs are available. There is some prognostic use of the κ-FLC index with higher values predicting higher disease activity. Neurofilament light (NfL) should not be used for diagnostic purposes although it might be useful for prognosis and disease monitoring. All recommendations apply to paediatric and adult relapsing as well as progressive onset MS.

Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis

2025-10-31T04:42:53Z

Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis Rodero-Romero, Alexander; Fernández Velasco, José Ignacio; Sainz-Amo, Raquel; Alvarez-Lafuente, Roberto; Montalban, Xavier; Monreal, Enric; Comabella Lopez, Manuel Cellular phenotype and function; Demyelinating disease of central nervous system; Glial fibrillary acidic protein; Fenotip i funció cel·lular; Malaltia desmielinitzant del sistema nerviós central; Proteïna àcida fibril·lar glial; Fenotipo y función celular; Enfermedad desmielinizante del sistema nervioso central; Proteína ácida fibrilar glial; Background: Serum biomarkers as neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enabled early identification of multiple sclerosis (MS) patients at risk of relapse-associated worsening (RAW) or progression independent of relapses (PIRA). However, the immunological mechanisms underlying these clinical phenotypes remain unclear. Methods: We conducted a cross-sectional study including 117 MS patients and 84 healthy controls (HC). Patients were stratified as NLGL (low sNfL and sGFAP), NH (high sNfL at different levels of sGFAP), and NLGH (low sNfL and high sGFAP). Percentages of blood and cerebrospinal fluid (CSF) mononuclear cells, and intracellular production of cytokines by T and B cells after “in vitro” stimulation were analyzed by flow cytometry. Results: We identified a common inflammatory profile present in the blood of all MS groups comprising significant increases of effector CD4+ and CD8+ T cells, of memory and antigen-presenting B cells, of CD4+ and CD8+ T cells producing interferon-gamma, interleukin-17 and tumor necrosis factor-alpha (TNF-α) and of B cells producing TNF-α. Additionally, the highly inflammatory NH group showed lower frequencies of different regulatory subsets (transitional B cells, PDL1+ monocytes and Treg cells) compared to HC and increased percentages of CD4+ and CD8+ T cells producing granulocyte-macrophage colony-stimulating factor and of effector CD56dim NK cells. They also showed lower percentages of Treg in blood and CSF compared to the low inflammatory NLGL group, which also displayed higher frequencies of regulatory CD56dim, NKG2A+ cells. Conclusion: All MS patients share increased inflammatory B and T cells, but differ in regulatory or NK subsets, which identify highly inflammatory or benign disease courses.; The authors declare financial support was received for the research, authorship, and/or publication of this article. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “PI21/00828” and by grant RD21/0002/0053 from La Red Española de Enfermedades Inflamatorias and cofunded by the European Union.

Unemployment, work hour reduction, and income loss: An international, multicentered, cross-sectional study of neuromyelitis optica spectrum disorder

2025-10-25T08:59:19Z

Unemployment, work hour reduction, and income loss: An international, multicentered, cross-sectional study of neuromyelitis optica spectrum disorder Ham, Andrew Siyoon; Gomez Hjerthen, Isabella; Tian, Decai; Gu, Hongfei; Gao, Wen; Sudhir, Akshatha; Arrambide, Georgina; Cobo-Calvo, Alvaro; Villacieros-Álvarez, Javier Employment; Income; Neurology; Ocupació; Ingressos; Neurologia; Empleo; Ingresos; Neurología; Objectives: To assess loss of employment, work hours, and wages of people with aquaporin-4 antibody-positive or double-seronegative/antibody status unknown neuromyelitis optica spectrum disorder (NMOSD) internationally. Methods: An investigator-designed survey was administered to adults ages 18–70 years with NMOSD and distributed by neurologists in 23 countries, July 2022 to September 2023. Results: There were 897 participants (635 aquaporin-4 antibody positive, 262 double-seronegative/untested; 81.4% female, average age 42.5 years, average disease duration 7.6 years, median 2 disease attacks since diagnosis). NMOSD impact was visual loss (34.0% unilateral; 28.2% bilateral), 61.8% with spinal cord disease, 55.6% with pain, 43.6% with fatigue, 38.2% with depressed mood, and 25.0% with gait aid use. In total, 92.6% took immunosuppressive therapy. Employment rates were 62.6% before and 36.3% after NMOSD diagnosis. In a multivariable model, statistically significant independent associations with unemployment in NMOSD were older age (odds ratio (OR) = 0.97, p < 0.001), being female (OR = 0.48, p < 0.001), bilateral visual loss (OR = 0.61, p = 0.02), highest frequency of depressed mood (OR = 0.29, p < 0.001), and walking aid use (OR = 0.38, p < 0.001). Discussion: Approximately 1/3 of people living with NMOSD of potential working age are in the workforce. Unemployment in NMOSD is associated with previously recognized factors but also self-reported low mood, gait aid use, and bilateral visual loss.; The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding sources for this project include the Sumaira Foundation and an investigatorinitiated grant from Amgen. Both sponsors had no role in the study concept, design, analysis, or decision to submit the work for publication. The authors are grateful to the American Academy of Neurology’s Neuroscience is Rewarding program for an internship scholarship to I.G.H.

A data-driven model of disability progression in progressive multiple sclerosis

2025-10-25T08:59:15Z

A data-driven model of disability progression in progressive multiple sclerosis garbarino, sara; Lorenzi, Marco; Pardini, Matteo; PIANA, MICHELE; UCCELLI, Antonio; TUR, CARMEN Bayesian learning; Multimodal data; Primary progressive multiple sclerosis; Aprendizaje bayesiano; Datos multimodales; Esclerosis múltiple progresiva primaria; Aprenentatge bayesià; Dades multimodals; Esclerosi múltiple progressiva primària; This study applies the Gaussian process progression model, a Bayesian data-driven disease progression model, to analyse the evolution of primary progressive multiple sclerosis. Utilizing data from 1521 primary progressive multiple sclerosis participants collected within the International Progressive Multiple Sclerosis Alliance Project, the analysis includes 18 581 longitudinal time-points (average follow-up time: 28.2 months) of disability assessments including the expanded disability status scale, symbol digit modalities, timed 25-foot-walk, 9-hole-peg test and of MRI metrics such as T1 and T2 lesion volume and normalized brain volume. From these data, Gaussian process progression model infers a data-driven description of the progression common to all individuals, alongside scores measuring the individual progression rates relative to the population, spanning ∼50 years of disease duration. Along this timeline, Gaussian process progression model identifies an initial steep worsening of the expanded disability status scale that stabilizes after ∼30 years of disease duration, suggesting its diminished utility in monitoring disease progression beyond this time. Conversely, it underscores the slower evolution of normalized brain volume across the disease duration. The individual progression rates estimated by Gaussian process progression model can be used to identify three distinct sub-groups within the primary progressive multiple sclerosis population: a normative group (76% of the population) and two ‘outlier’ sub-groups displaying either accelerated (13% of the population) or decelerated (11%) progression compared to the normative one. Notably, fast progressors exhibit older age at symptom onset (38.5 versus 35.0, P < 0.0001), a higher prevalence of males (61.1% versus 48.5%, P = 0.013) and a higher lesion volumes both in T1 (4.1 versus 0.6, P < 0.0001) and T2 (16.5 versus 7.9, P < 0.0001) compared to slow progressors. Prognostically, fast progressors demonstrate a significantly worse prognosis, with double the risk of experiencing a 3-month confirmed disease progression on expanded disability status scale compared to the normative population according to Cox proportional hazard modelling (HR = 2.09, 95% CI: 1.66–2.62, P < 0.0001) and a shorter median time from the onset of disease symptoms to reaching a confirmed expanded disability status scale 6 (95% CI: 5.83–7.68 years, P < 0.0001). External validation on a test set comprising 227 primary progressive multiple sclerosis participants from the SPI2 trial produced consistent results, with slow progressors exhibiting a reduced risk of experiencing 3-month confirmed disease progression determined through expanded disability status scale (HR = 0.21), while fast progressors facing an increased risk (HR = 1.45). This study contributes to our understanding of disability accrual in primary progressive multiple sclerosis, integrating diverse disability assessments and MRI measurements. Moreover, the identification of distinct sub-groups underscores the heterogeneity in progression rates among patients, offering invaluable insights for patient stratification and monitoring in clinical trials, potentially facilitating more targeted and personalized interventions.; This investigation was supported by an award from the International Progressive Multiple Sclerosis Alliance (award reference number PA-1412-02420). This work was supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministero dell’Università e delle Ricerca, Italy (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)—A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). The authors acknowledge financial contribution from the Italian Ministry of Health, with the project NeuroArtP3 (NET-2018-12366666). S.G. acknowledges financial contributions from the Istituto Nazionale di Alta Matematica—Gruppo Nazionale di Calcolo Scientifico (INdAM–GNCS) Project (CUP_E53C22001930001). C.T. is currently being funded by a Miguel Servet contract, awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (CP23/00117). She has also received a 2023 FORTALECE grant, awarded by the ISCIII (FORT23/00034) and a 2020 Junior Leader La Caixa Fellowship (fellowship code: LCF/BQ/PI20/11760008), awarded by ‘la Caixa’ Foundation (ID 100010434), a 2021 Merck’s Award for the Investigation in multiple sclerosis, awarded by Fundación Merck Salud (Spain), and a Research Grant awarded by the ISCIII, Ministerio de Ciencia e Innovación de España (PI21/01860). M.L. acknowledges funding from the Michael J. Fox Foundation for Parkinson’s Research (grant ID MJFF-021683). F.B. received the 2022 Biostatistic/Informatics Junior Faculty Award (grant code BI-2107-38160) awarded by the National Multiple Sclerosis Society.