XML Template (2015) [25.4.2015–11:26am] [1–7] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/NEUJ/Vol00000/150036/APPFile/SG-NEUJ150036.3d (NEU) [INVALID Stage] Original article Brain MR diffusion tensor imaging in Kennedy’s disease Francesco Garaci 1,2 , Nicola Toschi 2,3 , Simona Lanzafame 2 , Girolama A Marfia 4 , Simone Marziali 1 , Alessandro Meschini 1 , Francesca Di Giuliano 1 , Giovanni Simonetti 1,2 , Maria Guerrisi 2 , Roberto Massa 4 and Roberto Floris 1,2 Abstract Introduction: Kennedy’s disease (KD) is a progressive degenerative disorder affecting lower motor neurons. We investigated the correlation between disease severity and whole brain white matter microstructure, including upper motor neuron tracts, by using diffusion-tensor imaging (DTI) in eight patients with KD in whom disease severity was evaluated using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS). Methods: From DTI acquisitions we obtained maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1) and radial diffusivities (L2, L3). We then employed tract-based spatial statistics (TBSS) to investigate within-patient correl- ations of DTI invariants with ALSFRS and disease duration (DD). Results: We found a significant correlation between low ALSFRS and 1) low FA values in association commissural and projection fibers, and 2) high L3 values in commissural tracts and fronto-parietal white matter. Additionally, we found a significant association between longer DD and 1) low FA in the genu and body of corpus callosum, association fibers and midbrain and 2) high L1 in projection and association tracts. Conclusions: The associations between clinical variables and white matter microstructural changes in areas thought to be spared by the disease process support the hypothesis of a multisystem involvement in the complex pathogenic mechanisms responsible for the clinical disability of these patients. Keywords Kennedy’s disease, fractional anisotropy, mean diffusivity, DTI, TBSS, ALSFRS, disease duration Background Spino-bulbar muscular atrophy (SBMA), or Kennedy’s disease (KD), is a rare adult-onset, progressive neuro- degenerative disease, caused by the expansion of a poly- glutamine (CAG) triplet repeat in the androgen receptor (AR) gene, transmitted with an X-linked reces- sive modality. The prevalence is low (of the order of 1/ 400,000) and affects exclusively males, whereas female carriers are usually asymptomatic. 1 The clinical fea- tures of this disease include progressive weakness with muscular atrophy localized in hips and shoulders, which gradually extends to muscles with bulbar innerv- ation, resulting in interference with routine physical activities such as walking, climbing up and down stairs as well as difficulties swallowing, chewing and articulating speech. 2 Electrophysiological studies suggest that muscle atrophy in KD is caused by a progressive loss of motor axons and cell bodies, resulting in denervation atrophy. Almost always a loss of sensory fibers—espe- cially of type IA, which inform the motoneuron about the state of muscular tension—is present and respon- sible for a reduction of deep tendon reflexes. 2 Also, histopathological studies have documented the loss of motor fibers with depletion of cell bodies of motor neurons at both the spinal and bulbar level, resulting in a reduced volume of the ventral horns of the spinal cord and in muscle fiber atrophy and degeneration. 2 The amount of brain involvement in KD has not yet 1 Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, University Hospital Tor Vergata, Italy 2 Department of Biomedicine and Prevention, Faculty of Medicine, University of Rome Tor Vergata, Italy 3 Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, USA and Harvard Medical School, USA 4 Department of Systems Medicine, Section Neurology, University of Rome Tor Vergata, Italy Corresponding author: Nicola Toschi, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome (Italy). Email: toschi@med.uniroma2.it The Neuroradiology Journal 0(00) 1–7 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1971400915581740 neu.sagepub.com