Neuropsychiatric symptoms and reduced health-related quality of life (HRQoL) are frequent in multiple sclerosis, where they are associated with structural brain changes, but have been less studied in clinically isolated syndrome (CIS).

Objective: To characterize HRQoL, neuropsychiatric symptoms (depressive symptoms, anxiety, apathy and fatigue), their interrelations and associations with structural brain changes in CIS.

Methods: Patients with CIS (n=67) and demographically-matched healthy controls (n=46) underwent neurological and psychological examinations including questionnaires of HRQoL, neuropsychiatric symptoms and cognitive functioning, and MRI brain scan with global, regional and lesion load volume measurement.

Results: The CIS group had more depressive symptoms, anxiety and lower HRQoL physical and social scores (p≤0.037). Neuropsychiatric symptoms were associated with lower HRQoL scores (β≤-0.34, p≤0.005). Lower cognitive functioning unlike clinical disability was associated with depressive symptoms, anxiety and lower HRQoL emotional scores (β≤-0.39, p≤0.001). Severity of depressive symptoms, apathy and anxiety was associated with higher right temporal, left insular, right occipital lesion load (ß≥0.29, p≤0.032) and lower white matter volume (ß=-0.25, p=0.045).

Conclusion: Depressive symptoms, anxiety and decreased HRQoL are present in patients with CIS. Neuropsychiatric symptoms contributing to decreased HRQoL are related to structural brain changes and should require complex therapeutic approach in patients with CIS.