• Alvino Bisecco, Giuseppina Caiazzo, Alessandro d'Ambrosio, Rosaria Sacco, Simona Bonavita, Renato Docimo, Mario Cirillo, Elisabetta Pagani, Massimo Filippi, Fabrizio Esposito, Gioacchino Tedeschi, and Antonio Gallo.
• I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy/ MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte," Naples, Italy.
• Mult. Scler. 2016 Nov 1; 22 (13): 1676-1684.

BackgroundA functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity.ObjectivesTo assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS.MethodsSixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group.ResultsThirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain.ConclusionsFatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.© The Author(s), 2016.

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