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1.
Ann Clin Transl Neurol ; 10(1): 84-97, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36427295

RESUMO

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. INTERPRETATION: Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.


Assuntos
Encéfalo , Humanos , Masculino , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Atrofia/patologia , Europa (Continente)
2.
Curr Opin Neurol ; 34(3): 312-321, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33709974

RESUMO

PURPOSE OF REVIEW: Multiple sclerosis (MS) is a clinically heterogeneous disease, which complicates expectant management as well as treatment decisions. This review provides an overview of both well established and emerging predictors of disability worsening, including clinical factors, imaging factors, biomarkers and treatment strategies. RECENT FINDINGS: In addition to well known clinical predictors (age, male sex, clinical presentation, relapse behaviour), smoking, obesity, vascular and psychiatric comorbidities are associated with subsequent disability worsening in persons with MS. A number of imaging features are predictive of disability worsening and are present to varying degrees in relapsing and progressive forms of MS. These include brain volumes, spinal cord atrophy, lesion volumes and optical coherence tomography features. Cerebrospinal and more recently blood biomarkers including neurofilament light show promise as more easily attainable biomarkers of future disability accumulation. Importantly, recent observational studies suggest that initiation of early-intensive therapy, as opposed to escalation based on breakthrough disease, is associated with decreased accumulation of disability overall, although randomized controlled trials investigating this question are underway. SUMMARY: Understanding risk factors associated with disability progression can help to both counsel patients and enhance the clinician's availability to provide evidence-based treatment recommendations.


Assuntos
Esclerose Múltipla Crônica Progressiva , Atrofia , Avaliação da Deficiência , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente , Malformações do Sistema Nervoso , Recidiva
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