title: Fatigue in multiple sclerosis: The contribution of occult white matter damage.
abstract: A 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.
  
  
  
  To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS.
  
  
  
  Sixty 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.
  
  
  
  Thirty 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.
  
  
  
  Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.
authors: 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.
authors: Alvino
authors: A
authors: Bisecco
authors: MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte," Naples, Italy.
authors: Giuseppina
authors: G
authors: Caiazzo
authors: I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
authors: Alessandro
authors: A
authors: d'Ambrosio
authors: 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.
authors: Rosaria
authors: R
authors: Sacco
authors: 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.
authors: Simona
authors: S
authors: Bonavita
authors: I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
authors: Renato
authors: R
authors: Docimo
authors: MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte," Naples, Italy/ Neuroradiology Service, Department of Radiology, Second University of Naples, Naples, Italy.
authors: Mario
authors: M
authors: Cirillo
authors: Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: Elisabetta
authors: E
authors: Pagani
authors: Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: Massimo
authors: M
authors: Filippi
authors: MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte," Naples, Italy/ Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors: Fabrizio
authors: F
authors: Esposito
authors: 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.
authors: Gioacchino
authors: G
authors: Tedeschi
authors: 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 antonio.gallo@unina2.it.
authors: Antonio
authors: A
authors: Gallo
mesh_terms: D000328:Adult; D056324:Diffusion Tensor Imaging / Q000379:methods; D005221:Fatigue / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D055815:Young Adult
keywords: Multiple sclerosis; diffusion tensor imaging; fatigue; magnetic resonance imaging; normal appearing white matter; tract-based spatial statistics