Introduction: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a complicated form of autosomal-recessive hereditary spastic paraplegia. Characteristic clinical features comprise progressive spastic gait, cognitive impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus callosum and non-progressive white matter (WM) alterations.
Methods: To study the extent of axonal involvement, we performed localized proton magnetic resonance spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient with HSP-TCC at 20 and 25 years of age. The second investigation included diffusion tensor imaging (DTI).
Results: While MRS of the GM was normal, affected WM was characterized by major metabolic alterations such as reduced concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and phosphocreatine, and choline-containing compounds as well as elevated levels of myo-inositol. These abnormalities showed progression over a period of 5 years. DTI revealed increased mean diffusivity as well as reduced fractional anisotropy in periventricular WM. The metabolic and structural findings are consistent with progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation-histopathological changes known to occur in HSP-TCC.
Conclusion: Our results are in agreement with the hypothesis that the primary pathological process in HSP-TCC affects the axon, possibly due to impaired axonal trafficking.