Brain white matter involvement in hereditary spastic paraplegias: analysis with multiple diffusion tensor indices

Abstract

Background and purpose: The hereditary spastic paraplegias are a group of genetically heterogeneous neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower limbs. Although conventional brain MR imaging findings are normal in patients with pure hereditary spastic paraplegia, microstructural alteration in the cerebral WM can be revealed with DTI. Concomitant investigation of multiple intrinsic diffusivities may shed light on the neurobiologic substrate of the WM degeneration pattern in patients with pure hereditary spastic paraplegia across the whole brain.

Materials and methods: Tract-based spatial statistics analysis was performed to compare fractional anisotropy and mean, axial, and radial diffusivities of the WM skeleton in a group of 12 patients with pure hereditary spastic paraplegia and 12 healthy volunteers. Data were analyzed counting age and sex as nuisance covariates. The threshold-free cluster-enhancement option was applied, and the family-wise error rate was controlled by using permutation tests for nonparametric statistics.

Results: In pure hereditary spastic paraplegia, group widespread fractional anisotropy decreases and radial diffusivity and mean diffusivity increases (P < .05, corrected) were found. No voxelwise difference was observed for the axial diffusivity map. Percentage of voxels within the WM skeleton that passed the significance threshold were 51%, 41.6%, and 11.9%, respectively, for radial diffusivity, fractional anisotropy, and mean diffusivity clusters. An anteroposterior pattern with preferential decrease of fractional anisotropy in the frontal circuitry was detected.

Conclusions: In patients with pure hereditary spastic paraplegia, alterations in multiple DTI indices were found. Radial diffusivity seems more sensitive to hereditary spastic paraplegia-related WM pathology and, in line with the lack of axial diffusivity changes, might indicate a widespread loss of myelin integrity. A decrease of fractional anisotropy alone in the frontal circuitry may reflect subtle disruption of the frontal connections.

Fig 1.

DTI indices maps (P < .05, corrected) are represented in the FMRIB58_FA template on the axial plan with z-axis coordinates (in millimeters) above the upper row images. Green corresponds to the mean white matter skeleton of all participants. A, Red-yellow represents decreased FA. B, Pink-light pink represents increased MD. C, Blue-light blue represents increased RD.

Fig 2.

Conjunction map of spatial differences between reduced FA and increased RD maps, represented in the FMRIB58_FA template on the axial plane with Montreal Neurological Institute 152 coordinates (in millimeters) above each upper row image. Red-yellow represents decreased FA; blue-light blue, increased RD. A decrease in FA alone shows an anterior frontal circuitry pattern, while an increase in RD is more prominent in the posterior supratentorial brain regions and brain stem.