Regional brain atrophy in primary fatigued patients with multiple sclerosis

Objective: To examine the relationship between fatigue, regional brain atrophy and normal appearing white matter damage in patients with multiple sclerosis. Methods: Primary fatigued (PF) (n, 17) and non-fatigued (NF) (n, 17) patients with relapsing remitting multiple sclerosis and moderate disability were grouped according to their subjective fatigue score. Also, they were examined with respect to processing speed and central motor activation during isometric contraction. Using 3 Tesla MRI quantitative analyses were performed on normal appearing brain tissue and of brain structure volumes with tensor based morphometry. Results: Between the PF and NF patients there was no significant differences in brain parenchymal fraction (81.5% vs. 82.4%) lesion load (0.53% vs. 0.36%) and NAA/Cr ratio (1.29 vs. 1.32 respectively). Eleven clusters of atrophy in PF versus NF involved gray and nearby white matter, the majority being located in areas functionally related to attentional control. Central motor activation was associated with atrophy in five regions in PF patients, three clusters involving the premotor and primary motor cortex. Normal appearing white matter did not differ between groups. Conclusion: Primary fatigued patients with multiple sclerosis have extended regional atrophy of supratentorial brain parenchyma, involving the cerebral cortex, nearby white matter and the caudate head, areas which are functionally related to attentional control. We suggest that impaired central motor activation is due to interruption of the cortico-subcortical motor circuits involving the motor cortex. (C) 2010 Elsevier Inc. All rights reserved.