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Background and Objectives: Cognitive impairment, fatigue, and mood disorders are common in multiple sclerosis (MS), but their interplay and neurologic substrates are not well understood. This study aims to identify atrophy patterns in patients with MS with varying levels of cognitive impairment, fatigue, anxiety, and depression., Methods: A cross-sectional cohort study enrolling patients with relapsing-remitting MS meeting the 2017 McDonald criteria and healthy controls (HCs), with similar age, sex, and education, was conducted. Participants completed cognitive assessments across 5 domains and inventories for fatigue, anxiety, and depression. Disability was quantified using the Expanded Disability Status Scale (EDSS). K-means clustering grouped patients with MS based on cognitive performance, fatigue, anxiety, and depression, accounting for disability. Group surface analysis from FreeSurfer, corrected for multiple comparisons, was used to assess cortical atrophy ( p < 0.05). Deep gray matter and infratentorial atrophy were defined by a regional volumetric z -score <-1.5, with intergroup comparisons using Bayesian multinomial logistic regression (95% CI)., Results: One hundred and two patients with relapsing-remitting MS (67 women; mean age 37 ± 10 years; mean disease duration 9.8 ± 6.5 years; mean EDSS score 2.2 ± 1.73) and 98 HCs (63 women; mean age 36 ± 12 years) were included. K-means clustering identified 4 MS patient clusters: K1 (n = 26): cognitively preserved (CP) without fatigue, anxiety, and depression; K2 (n = 31): CP with fatigue, anxiety, and depression; K3 (n = 18): cognitively impaired (CI) without fatigue, anxiety, and depression; K4 (n = 27): CI with fatigue, anxiety, and depression. Dimension-1 (cognitive tests) explained 34.7% of the variability; Dimension-2 (fatigue, anxiety, and depression) explained 18.7%. EDSS score correlated more with Dimension-2 (loading = 0.32) and was higher in K2 and K4 ( p < 0.05). K2 and K3 had similar cortical atrophy, but K3 showed more unilateral hippocampus (log odds = 2.47, p = 0.023) and amygdala (log odds = 1.79, p = 0.003) atrophy, compared with K1. K4 had widespread bilateral cortical atrophy, with more bilateral thalamus (log odds = 1.28, p = 0.023), amygdala (log odds = 2.57, p = 0.003), and basal ganglia (log odds = 1.44, p = 0.01) atrophies. Cerebellar atrophy was significant in K2 (log odds = 17.68, p < 0.001) and K4 (log odds = 18.05, p < 0.001), compared with K1., Discussion: Cognitive impairment, fatigue, anxiety, and depression in patients with MS can coexist or present independently. Our findings suggest a stronger association between cognitive impairment and deep gray matter atrophy while fatigue, anxiety, and depression are more strongly associated with cerebellar atrophy. The accumulation of cognitive impairment, fatigue, anxiety, and depression is associated with increasing global cortical and deep gray matter atrophy.

Objective: A 4.5-year follow-up study was conducted to characterize baseline verbal episodic memory (VEM) and its behavior and to assess the effects of relapsing-remitting multiple sclerosis (RRMS) on this domain., Methods: Twenty-nine patients with RRMS underwent two neuropsychological assessments performed an average of 4.5 years apart. Twenty-six control participants underwent a single neuropsychological assessment. A significance level of p < 0.005 was adopted to denote a significant difference between the groups on the Mann Whitney and Wilcoxon paired statistical analyses., Results: No statistical difference was found in the results of the VEM tests between the first and second neuropsychological assessments of the patients. However, a statistical difference was evident between the patient and control groups in the results of the VEM tests., Conclusion: The patient group showed changes in the VEM relative to the control group. After approximately 4.5 years of disease, the patient performance on the VEM stabilized or improved.

Objective: The aim of this study was to characterize the microscopic damage to the corpus callosum in relapsing-remitting multiple sclerosis (RRMS) with diffusion tensor imaging and to investigate the correlation of this damage with disability. The diffusion tensor imaging parameters of fractional anisotropy and mean diffusivity provide information about the integrity of cell membranes, offering two more specific indices, namely the axial and radial diffusivities, which are useful for discriminating axon loss from demyelination., Method: Brain magnetic resonance imaging exams of 30 relapsing-remitting multiple sclerosis patients and 30 age- and sex-matched healthy controls were acquired in a 3T scanner. The axial diffusivities, radial diffusivities, fractional anisotropy, and mean diffusivity of five segments of the corpus callosum, correlated to the Expanded Disability Status Scale score, were obtained., Results: All corpus callosum segments showed increased radial diffusivities and mean diffusivity, as well as decreased fractional anisotropy, in the relapsing-remitting multiple sclerosis group. The axial diffusivity was increased in the posterior midbody and splenium. The Expanded Disability Status Scale scores correlated more strongly with axial diffusivities and mean diffusivity, with an isolated correlation with radial diffusivities in the posterior midbody of the corpus callosum. There was no significant correlation with lesion loads., Conclusion: Neurological dysfunction in relapsing-remitting multiple sclerosis can be influenced by commissural disconnection, and the diffusion indices of diffusion tensor imaging are potential biomarkers of disability that can be assessed during follow-up.