Deborah Brauser

September 27, 2016

LONDON — Testing blood samples for levels of neurofilament light chains (NfLs) can identify patients with multiple sclerosis (MS), as well as indicate degree of disease activity, new research suggests.

In a proof-of-concept cohort study of 149 patients with relapsing-remitting MS (RRMS) and 29 healthy control participants, the first group had twice the NfL concentrations that the latter group had.

In addition, higher NfL levels correlated with greater inflammation, more gadolinium-enhancing (Gd+) lesions, greater T2 lesion volume, and higher rates of brain atrophy and relapse.

"These findings support a role of blood NfL as a sensitive peripheral biomarker of neuronal injury in MS," said Jens Kuhle, MD, Neurology Clinic and Policlinic at the University Hospital Basel, Switzerland, during his presentation at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016.

"We have several approved treatments for MS, but we don't really know which patient to treat. A blood-based biomarker could prove very convenient to draw conclusions about treatment response," Dr Kuhle later told Medscape Medical News.

This idea of using blood NfL levels as a biomarker was embraced enthusiastically by Michael Hutchinson, MD, St Vincent's University Hospital, Dublin, Ireland, during his "clinical highlights" session at the end of the meeting.

"Serum NfL will be cheaper, faster, and probably much more reproducible," than other methods, he said. "And it will detect disease activity to which both the clinician and the MRI scanner is blind," added Dr Hutchinson, who was not involved with the research.


NfLs are structural proteins in neurons. Although testing in cerebrospinal fluid (CSF) has suggested that levels of these proteins may be a biomarker for neurodegeneration in various central nervous system diseases, the investigators wanted to test correlations with MS in serial blood samples. These samples are easier to collect and more comfortable for the patient to undergo.

The current RRMS patient cohort was taken from the phase 3 FREEDOMS trial, which was created to evaluate fingolimod vs placebo. The investigators assessed blood samples that were collected 5 days before and 14 days after the patients underwent MRI.

They then placed each participant into one of four disease activity subgroups based on the number of Gd+ lesions found (from none to more than three).

NfL was determined in these patients and in the age-matched healthy controls group by using Single Molecule Array (Simoa) immunoassay technology and antibodies from UmanDiagnostics.

Results showed that the patients with RRMS had a mean blood NfL level of 28.1 pg/mL vs 12.5 pg/mL for the healthy control group (P < .0001).

The patients with no Gd+ lesions had a mean level of 23.9 pg/mL, with levels rising as the number of lesions increased. Those with more than three lesions had an NfL level of 55.9 pg/mL.

Interestingly, "we saw that the patients without any lesions still had twice the levels of NfL as the healthy controls" (P = .0004), Dr Kuhle pointed out.

The blood NfL level also increased with the number of relapses (P < .0001 for two or more relapses) and for higher Expanded Disability Severity Scale scores (P = .0002 for score >3).

In addition, a high level of NfL was significantly associated with greater T2 lesion volume and annualized rates of brain atrophy and relapse (all, P < .0001).

Overall, the NfL blood concentrations were significantly higher in the RRMS group "but also reflected the degree of acute CSN inflammation and correlated with other measures of focal and diffuse damage," summarized Dr Kuhle.

Using in 3 to 4 Years?

"I think this is definitely one of the big highlights of what we've seen at the conference: the introduction of…measuring serum neurofilament light," Dr Hutchinson told meeting attendees.

"This is something we need different centers to try and validate, but I think it's something we'll be using in 3 to 4 years' time."

He said that his take-home messages from ECTRIMS to the MS community includes the recommendation to measure both serum and CSF levels of NfL. "I will be making plans for storing these serum samples for future comparisons in relation to disease activity."

Dr Hutchinson later told Medscape Medical News that "it's all preliminary work, but it proves the principle that it's possible to measure neurofilament light serum."

He noted that "the big block" to measuring NfL before was that it needed lumbar punctures. "That's a big no-no to people with MS. Clearly, other laboratories need to establish that there is a relationship between serum and CSF filament light. And there needs to be prospective studies."

Dr Kuhle reports he or his institution has received "and used exclusively for research support," consulting fees from Biogen, Novartis, and Protagen AG; speaker fees from the Swiss MS Society, Biogen, Genzyme, Merck, Novartis, and Roche; travel expenses from Merck Serono, Novartis, and Roche; and grants from the ECTRIMS Research Fellowship Program, the Swiss MS Society, the Swiss National Research Foundation, Bayer, Genzyme, Novartis, and Roche. Dr Hutchinson has disclosed no relevant financial relationships.

Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016. Parallel Session 14: Late-Breaking News, oral presentation 249; and Plenary Session 2, oral presentation 258. Both presented September 17, 2016.

Follow Deborah Brauser on Twitter: @MedscapeDeb. For more Medscape Neurology news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.