Longitudinal associations between brain structural changes and fatigue in early MS.

BACKGROUND: Fatigue is a common and disabling symptom of multiple sclerosis (MS) patients. Structural changes in several brain areas have been reported to correlate with fatigue in MS patients but none consistently. OBJECTIVE: To study the association between global and regional measures of brain atrophy and fatigue in patients with early relapsing MS. METHODS: Clinically isolated syndrome and relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included brain volumes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). Cortical thickness, thalamic volume and cerebellar cortical volume were measured using Freesurfer's longitudinal pipeline (v5.3) and a lesion inpainting approach. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS). Mixed model regression measured time trends and associations between imaging and fatigue severity, adjusting for age and sex. RESULTS: Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5 ± 4.9 months of symptom onset. Baseline and change over baseline in lesion volumes, grey matter, white matter, basal ganglia and total parenchymal volumes were not associated with change in MFIS score over time. Lower thalamic volume at baseline predicted increasing physical subscale of MFIS score during the study (p=0.017). There was a trend toward baseline thalamic volume and cerebellar cortical volume predicting subsequent change in total MFIS score (p=0.055 and 0.082 respectively). On-study change in thalamic or cerebellar cortical volume was not associated with on-study change in MFIS score. CONCLUSION: Global measures of tissue loss are not strongly associated with fatigue in patients with early MS. However, thalamic and cerebellar cortical atrophy may be predictive of subsequent changes in fatigue in these patients.

Longitudinal associations between MRI and cognitive changes in very early MS.

OBJECTIVES: Cognitive dysfunction in multiple sclerosis (MS) has been primarily examined in patients with advanced disease. Our objective was to study the longitudinal associations between brain magnetic resonance imaging (MRI) metrics and neuropsychological outcomes in patients with early MS. METHODS: Relapsing MS patients within 12 months of onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included percent brain volume changes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). A neuropsychological battery was performed annually. Mixed model regression measured time trends and associations between imaging and neuropsychological outcomes, adjusting for sex, age and education level. RESULTS: Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5 ± 4.9 months of disease onset. 11.6% of patients with baseline cognitive assessment met conservative criteria for cognitive impairment. Compared to placebo, riluzole had no significant effect on neuropsychological performance; thus, both groups were combined for the association analyses. Baseline T2LV predicted subsequent changes in PASAT (p=0.006) and SDMT (p=0.002) scores. Longitudinal changes of T2LV were associated with changes in CVLT-II (p<0.001). CONCLUSION: These findings suggest that cognitive impairment is relatively common in patients with very early MS. Baseline and longitudinal changes in the lesion load may be associated with some of the most frequently identified changes in cognitive function in MS.

Neuropsychological correlates of multiple sclerosis across the lifespan.

Multiple sclerosis can adversely affect cognitive functioning whether the disease has an adult or pediatric onset. The research thus far suggests that pediatric MS shares many features with adult MS but is also unique in several respects. One particular characteristic of pediatric MS is that, while physical disability develops more slowly as compared with adult patients, the impact of cognitive deficits in children may be more substantial as they are in a period of life during which they acquire many skills that are needed to transition into independently functioning adults. Our review takes a lifespan approach to MS, comparing and contrasting the neuropsychology (i.e., cognitive, psychological, and psychosocial factors) of these two populations. Understanding how MS manifests across the lifespan has important implications for tailoring assessment and treatment for individuals with MS as they transition from childhood to adulthood, and later life.