In people with MS, neurofilament light chain elevation can be detected as a sign of accelerated neuroaxonal injury up to two years in advance of disability worsening events, a study has shown.

The findings, from a collaboration between US and Swiss researchers, suggest that NfL may be a biomarker to identify neuroaxonal damage preceding disability and define a potential window of dynamic CNS pathology that can be targeted with abortive therapies.

In the study, publishing in JAMA Neurology (link here) researchers from the University of California at San Francisco and University of Basel looked at the incidence of disability worsening, defined as six months or more of increased impairment reflected in a higher score on the Expanded Disability Status Scale, in almost 1900 MS patients.

They distinguished between disability worsening with relapse and gradual progression of symptoms without relapse.

In patients with confirmed disability worsening with relapse, NfL z scores were 0.71 and 0.32 units higher at the preceding visit compared with stable MS samples.

NfL elevation could also be detected preceding confirmed disability worsening without relapse with values of 0.23 and 0.28; at two preceding visits up to two years previously, the study showed. These findings were replicated in a subgroup with relapsing-remitting MS.

Time-to-event analysis confirmed the association between NfL levels and future disability worsening with relapse within approximately one year and disability worsening without relapse in   approximately one to two years.

“We think that NfL elevation occurs earlier in disability worsening without relapse,” said lead author Dr Ahmed Abdelhak of the Weill Institute for Neurosciences, Department of Neurology, UCSF.

“This different pattern may indicate “a more prolonged process that decreases in intensity in advance of increased impairment,” said co-senior author Professor Ari Green, MD, medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center.

“This aligns with recognition that death of nerve cells is a slow process that builds toward permanent disability and means that interventions to protect nerve cells might have time to also stop disability,” he said.

“In addition to the groundbreaking findings on the temporal relationship between NfL increases and gradual disease progression in MS, the study supports the important role of NfL as an early marker of nerve damage,” said co-senior author Dr Jens Kuhle, who led the Swiss cohort and is head of the Multiple Sclerosis Centre at University Hospital and University of Basel, Switzerland.

“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” he said.

Future investigation will look into therapies that can stop progression during this period of elevated NfL.