Differences in the Neural Substrate for Physical and Mental Quality of Life in Patients With Multiple Sclerosis

Abstract

Introduction: Identifying patients with multiple sclerosis (PwMS) who primarily experience a gradual decline in mental rather than physical quality of life (QoL) is clinically significant, as QoL worsening may be underestimated. This study aims to compare the clinical characteristics and neural substrates of PwMS with predominantly reduced physical and mental QoL to distinguish between these patients. Methods: This study included 75 PwMS, of whom 56 had relapsing-remitting multiple sclerosis (MS) and 19 had progressive MS. The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and Medical Outcomes Study Short Form-36 Health Survey were used to assess neuropsychological abnormalities and health-related QoL. Results: Physical and mental QoL were not correlated. In a subset of PwMS, cluster analysis revealed that either physical or mental QoL was primarily affected. Patients with reduced physical QoL (n = 9) were generally older, more likely to have a progressive disease course, and had higher EDSS scores. Imaging revealed reduced whole-brain and grey matter volumes, as well as bilateral cortical atrophy in the frontal lobes, specifically in the left rostral middle frontal cortex. In contrast, patients with reduced mental QoL (n = 19) had a relapsing-remitting disease course and elevated MSNQ scores. These patients exhibited an increased lesion load, T1 white matter hypointensity volume, and bilateral cortical atrophy in the temporal lobes, specifically in the right insula and left superior temporal cortex. Conclusion: PwMS with predominantly reduced mental QoL exhibit distinct inflammatory changes that may contribute to disrupted connectivity and cortical atrophy in the lateral postcentral regions.