Categories
Multiple sclerosis

How long can the pre-symptomatic phase of MS last?

Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis.

Bjornevik K, Munger KL, Cortese M, et al.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Unrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease.

OBJECTIVE:

To assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset.

METHODS:

Nested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding.

RESULTS:

Mean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009).

CONCLUSIONS:

The levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): non-modifiable risk factors

By GerryShaw – Standard tissue culture and immunofluorescencePreviously published: Unpublished, CC BY-SA 3.0, Link

Abstract link

By Ibrahim Imam

I am a UK Neurologist keen on general neurology, but with an interest in neuromuscular diseases. I maintain the neurology searchable database, www.neurochecklists.com. I also blog at www.theneurologylounge.com. I share and discuss current issues around clinical neurology. I hope you find my blogs enlightening, practical, and even entertaining.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s