Biomaterial Database

Plasma neurofilament light levels are associated with risk of disability in multiple sclerosis. 2020

Ali Manouchehrinia, and Pernilla Stridh, and Mohsen Khademi, and David Leppert, and Christian Barro, and Zuzanna Michalak, and Pascal Benkert, and Jan Lycke, and Lars Alfredsson, and Ludwig Kappos, and Fredrik Piehl, and Tomas Olsson, and Jens Kuhle, and Ingrid Kockum

From the Department of Clinical Neuroscience (A.M., P.S., M.K., F.P., T.O., I.K.), The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Karolinska Institutet; Centre for Molecular Medicine (A.M., P.S., M.K., F.P., T.O., I.K.), Karolinska University Hospital, Stockholm, Sweden; Departments of Medicine, Biomedicine, and Clinical Research (D.L., C.B., Z.M., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Switzerland; Institution of Neuroscience and Physiology (J.L.), Sahlgrenska Academy, University of Gothenburg, Gothenburg; Institute of Environmental Medicine (L.A.), Karolinska Institutet, Stockholm; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. ali.manouchehrinia@ki.se.

To investigate the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening. Concentrations of pNfL were determined in 4,385 persons with multiple sclerosis (MS) and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive Single Molecule Array (SimoaTM) NF-Light Advantage Kit. We assessed the impact of age-stratified pNfL levels above the 80th, 95th, and 99th percentiles among controls on the risk of Expanded Disability Status Scale (EDSS) worsening within the following year and reaching sustained EDSS scores of 3.0, 4.0, and 6.0 and conversion to secondary progressive multiple sclerosis (SPMS). The median (interquartile range [IQR]) pNfL was 7.5 (4.1) pg/mL in controls and 11.4 (9.6) pg/mL in MS (p < 0.001). The median (IQR) duration of follow-up was 5 (5.1) years. High pNfL was associated with increased adjusted rates of EDSS worsening ranging between 1.4 (95% confidence intervals [CIs]: 1.1-1.8) and 1.7 (95% CI: 1.4-2.3). High pNfL was also associated with the risk of reaching a sustained EDSS score of 3.0, with adjusted rates ranging between 1.5 (95% CI: 1.2-1.8) and 1.55 (95% CI: 1.3-1.8) over all percentile cutoffs (all p < 0.001). Similar increases were observed for the risk of sustained EDSS score 4.0. In contrast, the risk of reaching sustained EDSS score 6.0 and conversion to SPMS was not consistently significant. Elevated pNfL levels at early stages of MS are associated with an increased risk of reaching sustained disability worsening. Hence, pNfL may serve as a prognostic tool to assess the risk of developing permanent disability in MS.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009103	Multiple Sclerosis	An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)	MS (Multiple Sclerosis),Multiple Sclerosis, Acute Fulminating,Sclerosis, Disseminated,Disseminated Sclerosis,Sclerosis, Multiple
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011446	Prospective Studies	Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.	Prospective Study,Studies, Prospective,Study, Prospective
D004185	Disability Evaluation	Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for Social Security and workmen's compensation benefits.	Disability Evaluations,Evaluation, Disability,Evaluations, Disability
D005260	Female		Females
D005500	Follow-Up Studies	Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.	Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths