Diffusion tensor imaging in SPG11- and SPG4-linked hereditary spastic paraplegia

The aim of this study was to identify potential diagnostic markers of Hereditary Spastic Paraplegia (HSP). We investigated the white matter features of spastic gait (SPG)11- and SPG4-linked HSP, using diffusion tensor imaging performed with a 3-Tesla (3T) scanner. We examined four patients with SPG11 mutations, three with SPG4 mutations, and 26 healthy controls. We obtained maps of fractional anisotropy (FA) and mean diffusivity (MD), which we analyzed through both region of interest -based approach and tract-based spatial statistics (TBSS). Compared with healthy controls, SPG11 patients presented increased MD and decreased FA in the semioval centers, frontal and peritrigonal white matter, posterior limb of the internal capsule, and throughout the corpus callosum. Similar alterations were seen in the SPG4 patients at the levels of the semioval centers, the posterior limb of the internal capsule, the left cerebral pedicle, the genu and trunk of the corpus callosum, and the peritrigonal white matter on the left. No MD or FA alterations were observed in the cerebellar white matter. In a direct comparison, white matter alterations were more pronounced and widespread in HSP-SPG11 than in HSP-SPG4 patients. Joint TBSS analysis of all three groups confirmed significant widespread alterations of FA and MD values in the supratentorial white matter. This noninvasive study documented the presence of altered diffusivity in white matter in both forms of HSP, which could represent an important diagnostic marker of HSP. The association of reduced FA and increased MD in this patient population supports the interpretation of HPG as a neurodegenerative disorder.