Background Mutations in SPG11 are the most frequent known cause of autosomal recessive hereditary spastic paraplegia. Corpus callosum thinning is a hallmark of the condition but little is known about damage to other structures in the CNS.
Objective To evaluate in vivo cerebral damage in patients with SPG11 mutations.
Methods 5 patients and 15 age and sex matched healthy controls underwent high resolution diffusion tensor imaging (32 directions) and a T1 volumetric (1 mm slices) acquisition protocol in a 3 T scanner (Philips Achieva). These sequences were then analysed through voxel based morphometry (VBM) and tract based spatial statistics (TBSS).
Results Mean age of the patients was 23.6±4.5 years (range 14–45) and mean duration of disease was 12 years (range 5–15). All patients presented with progressive spastic paraplegia and three were already wheelchair bound when first evaluated. Mutations found were: c.529_533delATATT, c.704_705delAT, c.733_734delAT, c.118C>T and c.7256A>G. VBM identified significant grey matter atrophy in both the thalamus and lentiform nuclei. TBSS analyses revealed reduced fractional anisotropy involving symmetrically subcortical white matter of the temporal and frontal lobes, the cingulated gyrus, cuneus, striatum, corpus callosum and brainstem.
Conclusions Widespread white matter damage in patients with SPG11 mutations has been demonstrated. Grey matter atrophy was prominent in both the thalamus and basal ganglia but not in the cerebral cortex. These findings suggest that neuronal damage/dysfunction is more widespread than previously recognised in this condition.
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Funding MCF received a post-doctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo–FAPESP, São Paulo, Brazil (2008/58605-7). IL-C and FC are supported by FAPESP and Conselho Nacional de Pesquisa (CNPq, Brazil). The funding agencies did not interfere with the design of the study, collection of the data or drafting of the manuscript.
Competing interests None.
Ethics approval Ethics approval was provided by Comitê de Ética da Faculdade de Ciências Médicas (UNICAMP).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement There are no additional unpublished data from this research. All information is included in the manuscript, tables and figures.