Neuropsychological symptoms and subclinical disease activity in multiple sclerosis patients receiving high-efficacy...

Previous studies indicated that psychological distress increases the risk for disability progression in people with multiple sclerosis (PwMS). It remains unclear whether psychological distress is immune-mediated, and thus, an expression of MS or independent thereof.

In our prospective cohort of PwMS receiving HE-DMT, we invited all patients with "no evidence of disease activity" (NEDA) to fill out the PHQ-ADS questionnaire. We stratified patients according to severity of psychological symptoms and assessed clinical courses including serum neurofilament light-chain (NfL) levels.

Among 748 patients, 298 were eligible. 197 patients participated in this analysis. 28.4% showed mild and 22.8% showed clinically significant psychological distress. Psychological distress was associated with confirmed disability worsening (CDW; p = 0.040). NfL assessment showed that patients with distress but normal NfL had no significantly increased hazard for disability worsening (HR:2.2(95%:0.5-9.2)). Conversely, patients with distress and elevated NfL had a high hazard for disability worsening (HR:18.2(95%:4.4-76.3)) even surpassing patients with elevated NfL but without distress (HR:4.1(95%:1.2-14.1)).

Psychological distress was again common among PwMS and we found that distress increased the risk of disability progression in PwMS and was associated with subclinical activity in several patients. Screening for distress appears warranted to identify these patients at risk.