Blood Test Could Predict Multiple Sclerosis Progression

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), with a highly variable inter-individual disease course. As a result, even if using existing clinical prognostic factors, the forecasting of long-term prognosis is often unreliable and imprecise.

Neurofilaments provide structural support to axons as the main component of the neuronal cytoskeleton. Elevated levels of these proteins have been observed in several neurodegenerative diseases. In persons with MS, elevated CSF levels of neurofilament light chain (NfL) or heavy chain have been associated with brain atrophy and long-term outcome.

Neurologists at the Karolinska Institutet (Stockholm, Sweden) and their associates investigated the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening. They enrolled 4,385 individuals with MS and randomly selecting 1,026 people matched for age and sex who did not have MS.

The team used the highly sensitive Single Molecule Array (Simoa, Billerica, MA, USA) NF-Light Advantage Kit, with antibodies from UmanDiagnostics (Umeå, Sweden). They 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 investigators reported that the participants were followed for a total of five years to see if they developed increased levels of disability. They also looked to see if individuals with high NfL levels developed secondary progressive multiple sclerosis (SPMS). MS patients had an average NfL level of 11.4 pg/mL compared to 7.5 pg/mL in the non-MS patients.

Overall, investigators determined that high plasma NfL correlated with sustained EDSS scores 3.0 and 4.0. MS patients were 40% to 70% more likely to have worsening disability during the following year and 50% more likely to reach a level of moderate disability that affected daily activities. The results reflect other variables that could affect the risk of poorer outcomes in the MS patients, such as rate of relapse and longevity of disease. A total of 525 MS patients (16%) reached the moderate level of disability, and 352 patients (9%) reached significant disability.

Ali Manouchehrinia, PhD, an assistant professor and first author of the study, said, “These results suggest that elevated levels of these nerve proteins biomarkers measured early on in the course of the disease may help us to predict how the disease will develop and monitor how treatment is working. In a disease like MS that is so unpredictable and varies so much from one person to the next, having a noninvasive blood test like this could be very valuable, especially since treatments are most effective in the earliest stages of the disease.”

The authors concluded that elevated pNfL levels measured early on in the disease course are associated with an increased risk of reaching sustained disability milestones. Hence, pNfL may serve as a prognostic and treatment monitoring tool to assess the risk of developing permanent disability in MS as part of a more standardized, noninvasive, longitudinally accessible, and generalizable approach. The study was published on June 9, 2020 in the journal Neurology.

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Karolinska Institutet
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