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Background  Fatigue is a disabling syndrome in multiple sclerosis (MS), which may be associated with inflammation and faster disease progression.    Objective  To analyze the significance of cognitive fatigue for subsequent disease progression.    Method  We followed 46 MS patients and 14 healthy controls in a study over 17 months. At the beginning (t1) and at the end (t2) of the study participants scored their fatigue, performed the Multiple Sclerosis Functional Composite and received MRI scanning, encompassing MPR T1, FLAIR, and DTI sequences. At t1, MS patients were divided into those with and those without cognitive fatigue (cut-off score for moderate cognitive fatigue of the Fatigue Scale for Motor and Cognition). We calculated ANCOVAs for repeated measurement to analyze the relevance of cognitive fatigue status for the number of relapses and for MRI parameters.    Results  At t1, but not at t2, patients with cognitive fatigue showed increased axial and radial diffusivity of corpus callosum fibers. At t2, these patients showed significantly more loss of brain parenchyma and greater enlargement of lateral ventricles. Moreover, they developed more relapses, but there was no difference in lesion load or in performance deterioration. Additional analyses showed that only cognitive fatigue but not a more general score for fatigue (Fatigue Severity Scale) had an impact on the worsening of the disease status.    Conclusion  Patients with cognitive fatigue may develop more brain atrophy and relapses during the next 17 months than patients without cognitive fatigue. Hence, experiencing cognitive fatigue might indicate more aggressive inflammatory processes and subsequent neurodegeneration.

The Impact of MS-Related Cognitive Fatigue on Future Brain Parenchymal Loss and Relapse: A 17-Month Follow-up Study