Micro-structural cerebral damage in hereditary spastic paraplegia caused by SPG4 mutations (SPG4-HSP)

Abstract

Hereditary spastic paraplegia caused by SPG4 mutations is the most frequent form of the disease and classically considered a spinal disorder. Little is known about encephalic damage in SPG4-HSP. This study was then carried out to identify micro-structural white matter (WM) damage in SPG4-HSP patients. We selected 11 patients with molecular confirmation of the disease and 23 healthy controls matched by age and gender. These subjects underwent magnetic ressonance imaging (MRI) on a 3T Achieva-Intera PHILLIPS scan. Diffusion tensor images (DTI) were obtained using a specific Spin echo DTI sequence. Fractional anisotropy (FA) and axial (AD), radial (RD) and mean difusivity (MD) maps were then created using the FMRIB tool on FSL v.4.1.4 software. These maps were used to search for damage in patients when compared to controls. This comparison was performed using TBSS, a algorithm in FSL v.4.1.4. A two sample t-test (p-value <0.05) was used to identify differences between the two groups. TBSS analysis revealed micro-structural impairment in patients, with FA reduction and AD and RD increase in corticospinal tracts, posterior cyngulate gyri and the splenium of the corpus callosum. We conclude that SPG4-HSP patients present micro-structural damage in motor and non-motor areas of the brain. Diffusion tensor imaging, spastic paraplegia, Neurogenetics.