CSF Biomarker for MS Not Ready for Primetime
High neurofilament levels (specifically those of heavy-chain subunits [NfH]) in CSF appear to be significant indicators of active neurodegeneration in the most common forms of established multiple sclerosis. This conclusion is based on newly published data from a medium-sized European study, in the latest issue of Neurology, which included 73 healthy controls, 63 patients with clinically isolated syndrome (CIS), and others with relapsing-remitting (n = 39), secondary-progressive (n = 25), or primary-progressive (n = 23) MS.
The data, which also demonstrate the importance of controlling for age-related changes in CSF Nf levels, appear to confirm the potential utility of this diagnostic and prognostic biomarker in MS and other neurodegenerative disorders (like Alzheimer disease and ALS). Nfs are structural proteins of axons and dendrites, and their release into the CSF is considered a sign of neuroaxonal damage.
However, the use of CSF Nf levels—for instance, to aid diagnosis or treatment decisions—is not ready for primetime practice. In an accompanying editorial, neuroscientists Giovanni and Nath recognize that "[t]he need to measure Nf in CSF [meaning the necessity of lumbar puncture] is a major hurdle to widespread application as an MS biomarker." They predict that the assay (which, given age-related increases in Nf levels, must be interpreted in the context of control values) will or should be adopted as surrogate endpoints in MS neuroprotective trials and "to enrich" these trials. So-called enrichment, in this case, would be realized by using CSF Nf levels to preferentially enroll patients with higher levels and who are, therefore, more likely to benefit from neuroprotective (eg, immunomodulatory) therapy.
CSF = cerebrospinal fluid.
T2-weighted supraventricular horizontal MR image from Harvard's Whole Brain Atlas. Multiple subcortical MS lesions are evident, including a very prominent lesion in the frontal area. The web site also offers a very cool time-lapsed movie of developing MS lesions.
