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


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.
From the Institute of Life Sciences (G.A.), Scuola Superiore Sant'Anna, Pisa, ItalyNeuroradiology Unit (G.A., F.F., H.H., D.M.), Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
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Aghakhanyan
Medea Scientific Institute (A.M., M.V., G.P.), Conegliano and Bosisio Parini, Treviso, Italy.
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Martinuzzi
Neuroradiology Unit (G.A., F.F., H.H., D.M.), Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
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Frijia
Medea Scientific Institute (A.M., M.V., G.P.), Conegliano and Bosisio Parini, Treviso, Italy.
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Vavla
Neuroradiology Unit (G.A., F.F., H.H., D.M.), Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
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Hlavata
Radiology Unit (A.B., N.M.), MRI Unit, ULSS7, Conegliano, Treviso, Italy.
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Baratto
Radiology Unit (A.B., N.M.), MRI Unit, ULSS7, Conegliano, Treviso, Italy.
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Martino
Medea Scientific Institute (A.M., M.V., G.P.), Conegliano and Bosisio Parini, Treviso, Italy.
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Paparella
Neuroradiology Unit (G.A., F.F., H.H., D.M.), Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy domont@ftgm.it.
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Montanaro
D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D015419:Spastic Paraplegia, Hereditary / Q000473:pathology*; D066127:White Matter / Q000473:pathology*