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The emergence of highly effective therapies for multiple sclerosis (MS) has led to heightened attention to finding metrics sensitive to disease progression and activity. The neurologic examination alone cannot reliably assess ongoing MS disease activity, as new clinical findings emerge only with the involvement of eloquent areas of the CNS. Furthermore, multiple studies have shown the ability of MRI to assess MS disease activity and progression1 but at great expense of time and resources. Thus a noninvasive marker of progression and response to therapy remains an unmet need. In recent years, attention has fallen on the potential clinical utility of levels of neurofilaments (Nf), proteins that maintain neuronal caliber as part of the axoskeleton of neurons, and comprise light, medium, and heavy chains. The most abundant of these 3 proteins, Nf light chain (NfL), has emerged as a promising marker of neuroaxonal destruction. Recent technology using the single molecule array (Simoa) platform has allowed for the rapid, sensitive, and reproducible readout of NfL.2 This marker exhibits dynamic changes that correlate with neurodegeneration in diseases such as amyotrophic lateral sclerosis,3 amyotrophic lateral sclerosis–frontotemporal dementia,4 and Alzheimer disease, among others, and may also predict the emergence of Alzheimer disease in presymptomatic individuals.5 In MS, studies have shown an association of serum, plasma, or CSF NfL with disease activity and progression.6 We now face a number of questions: Can this marker be used to assess therapy efficacy in clinical trials? Can it help us in clinical decision-making for individual patients with MS?
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
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