Tract-based spatial statistics of diffusion tensor imaging in hereditary spastic paraplegia with thin corpus callosum reveals widespread white matter changes

Abstract

NEURORADIOLOGYORIGINAL ARTICLE PURPOSE We aimed to investigate white matter diffusivity abnormalities in hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) patients in relation with electrophysiological findings. MATERIALS AND METHODSBrain magnetic resonance imaging (MRI) and diffusion tensor imaging were performed on four HSP-TCC patients and 15 age-matched healthy subjects. Voxel-wise statistical analysis of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity maps were carried out using tract-based spatial statistics, and significantly affected voxels were labeled using a human white matter atlas. Conventional nerve conduction studies, cortical and spinal-root motor evoked potentials, and somatosensory evoked potentials were examined in three patients. RESULTSOn MRI, all patients had a thin corpus callosum with mild T2 hyperintensity in the periventricular white matter. Compared to control subjects, we detected widespread significant decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity in structures including in the corpus callosum, motor, and non-motor white matter tracts in HSP-TCC patients. Several different regions showed significant reduction in axial diffusivity. Electrophysiological studies revealed prolonged central motor conduction times and reduced cortical motor evoked potentials and somatosensory evoked potentials amplitudes in all patients. One patient had low sural sensory nerve action potential suggestive of axonal neuropathy. CONCLUSION Tract-based spatial statistics of diffusion tensor imaging revealed a more widespread involvement of white matter in HSP-TCC patients than has previously been detected by conventional MRI. This may explain the broad spectrum of electrophysiological and neurological abnormalities that complicate hereditary spastic paraplegia in these patients. Hereditary spastic paraplegia (HSP) describes a group of neurodegenerative disorders that can either be pure (isolated HSP), with progressive spasticity, or complicated. HSP is classified as "complicated" when it co-occurs with other abnormalities such as mental and cognitive changes, optic atrophy, amyotrophy, ataxia, deafness, ichthyosis, and peripheral neuropathy (1, 2). In autosomal recessive HSP with thin corpus callosum (HSP-TCC), a form of complicated HSP, a patient typically has normal early motor and mental development followed by progressive spastic paraparesis, cognitive impairment, sensory disturbances, and ataxia during the second decade of life (3). First described by Iwabuchi et al. (4), HSP-TCC has been genetically linked to the SPG11 locus 15q13-15 , although some heterogeneity has been described (5).There are a few studies in the published literature describing the morphological, pathological, and imaging features of a limited number of HSP-TCC patients. The main feature of HSP-TCC seen on structural magnetic resonance imaging (MRI) is marked thinning of the corpus callosum; this is especially prominen...

Multiparametric 3T MRI evaluation of hereditary spastic paraplegia: A case report

“…Average MD values were 1.07 and 0.89 × 10 -6 mm 2 /s in the genu and splenium of CC, respectively. [ 7 ] Reported values were similar to that in the present study, with the genu and anterior part of the body being most severely affected. Aghakhanyan et al .…”

“…DTI often shows increased mean diffusivity and reduced fractional anisotropy in the CC and periventricular white matter, compatible with damaged myelinated axons. [ 7 ] Brain MRI and DTI performed on four HSP patients and 15 age-matched healthy subject by Oğuz et al . [ 7 ] reported that average FA values in genu and splenium were 0.55 and 0.72, respectively.…”

“…[ 7 ] Brain MRI and DTI performed on four HSP patients and 15 age-matched healthy subject by Oğuz et al . [ 7 ] reported that average FA values in genu and splenium were 0.55 and 0.72, respectively. In comparison, the values in healthy controls were 0.81 and 0.87.…”

“…reported that the patients with CC hypoplasia showed less severe changes in diffusion parameters (FA ≃ 0.67 and MD ≃ 1.05 × 10 −6 ) as compared to those with dysgenesis or degeneration. [ 7 9 ]…”

Patient-Derived Stem Cell Models in SPAST HSP: Disease Modelling and Drug Discovery

“…The common DTI indices are: fractional anisotropy, a measure of sensitivity to changes in orientation of axons along the tracts; mean diffusivity, a measure of magnitude of water diffusion and the presence of obstacles to diffusion [14,15], and radial diffusion, used to differentiate axonal injury from demyelination [13]. The most common radiological changes in a variety of HSP gene mutations are alterations in the corticospinal tract (70% of all studies, 71% of SPAST studies) and corpus callosum (80% of all studies, 86% of SPAST studies) [16,17,18,19,20,21,22,23,24,25]. Loss or damage to axons in the corticospinal tract are consistent with the motor symptoms of the disease, although white matter disturbances are not confined to the corticospinal tract and corpus callosum with involvement at the whole brain level, frontal and temporal lobes, cerebellum, and other regions.…”