Axonal injury may occur up to 9 years prior to symptom onset in multiple sclerosis

1. Multiple sclerosis patients can sustain axonal injury up to 9 years before symptom onset.

2. Until symptom onset, physical and mental well-being are comparable between affected and unaffected individuals.

Evidence Rating Level: 3 (Average)

Multiple sclerosis (MS) has an unclear mechanism and onset with physiological changes occurring well before symptom onset. A prodromal phase of MS has been described and includes inflammatory activity, fatigue, cognitive impairment, depression, and increased utilization of healthcare resources. One method of monitoring MS disease activity is neurofilament light chain (NfL) which is a component of the neuroaxonal skeleton. NfL levels have been shown to be increased in patients up to 10 years before symptom onset. However, no study has shown if the level of NfL reflects the time to symptom onset in patients. This study aimed to investigate the intraindividual NfL dynamics in the presymptomatic phase of MS. Plasma samples from blood donors who were subsequently diagnosed with MS were analyzed. 64 donors developed MS and were compared to 138 healthy donors. A highly significant, positive, linear association between log(NfL) and age (p = 0.0001), indicating that NfL increased by 1.4% (95% CI 1.0%–2.1%) with each additional year of age. Storage time showed a 0.3% reduction in NfL with each year of storage (95% CI 0.1%–0.5%). Intraindividual analysis showed most of the presymptomatic MS donors had low baseline NfL levels comparable to healthy donors. Increased NfL levels were seen up to 9 years before initial demyelinating symptoms. Bayesian analysis showed a higher proportion of extreme NfL values in presymptomatic MS group compared to the healthy group. All groups (healthy, MS-no NfL change, and MS-elevated NfL) reported equally high physical and mental well-being before symptom onset. Unfortunately, there was inadequate sample frequency to identify intraindividual trends in NfL before symptom onset which should be elucidated as it can provide prognostic information and could identify a therapeutic window.  

Click to read the study in Neurology

Image: PD

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