Sex-Specific Differences in Life Span Brain Volumes in Multiple Sclerosis.

Abstract

Numerous sex-specific differences in multiple sclerosis (MS) susceptibility, disease manifestation, disability progression, inflammation, and neurodegeneration have been previously reported. Previous magnetic resonance imaging (MRI) studies have shown structural differences between female and male MS brain volumes. To determine sex-specific global and tissue-specific brain volume throughout the MS life span in a real-world large MRI database. A total of 2,199 MS patients (female/male ratio of 1,651/548) underwent structural MRI imaging on either a 1.5-T or 3-T scanner. Global and tissue-specific volumes of whole brain (WBV), white matter, and gray matter (GMV) were determined by utilizing Structural Image Evaluation using Normalisation of Atrophy Cross-sectional (SIENAX). Lateral ventricular volume (LVV) was determined with the Neurological Software Tool for REliable Atrophy Measurement (NeuroSTREAM). General linear models investigated sex and age interactions, and post hoc comparative sex analyses were performed. Despite being age-matched with female MS patents, a greater proportion of male MS patients were diagnosed with progressive MS and had lower normalized WBV (P<.001), GMV (P <.001), and greater LVV (P <.001). In addition to significant stand-alone main effects, an interaction between sex and age had an additional effect on the LVV (F-statistics = 4.53, P = .033) and GMV (F-statistics = 4.59, P = .032). The sex and age interaction was retained in both models of LVV (F-statistics = 3.31, P = .069) and GMV (F-statistics = 6.1, P = .003) when disease subtype and disease-modifying treatment (DMT) were also included. Although male MS patients presented with significantly greater LVV and lower GMV during the early and midlife period when compared to their female counterparts (P <.001 for LVV and P <.019 for GMV), these differences were nullified in 60+ years old patients. Similar findings were seen within a subanalysis of MS patients that were not on any DMT at the time of enrollment. There are sex-specific differences in the LVV and GMV over the MS life span.