Correlated with disease duration and severity
This German study used advanced neuro-imaging to establish that:
widespread changes to different parts of the brain occur with SPG4 HSP
longer duration and severity of HSP correlates with higher levels of change in the brain, and also confirmed that
SPG4 HSP is associated with axonal rather than demyelinating damage.
Changes to the brain included volume loss of both grey and white matter in the corpus callosum, part of the thalamus, parieto-occipital regions, upper brainstem, cerebellum and corticospinal tract.
Hereditary spastic paraplegias (HSP) are a group of clinically and genetically heterogeneous disorders with the hallmark of progressive spastic gait disturbance.
We used advanced neuro-imaging to identify brain regions involved in SPG4, the most common HSP genotype. Additionally, we analyzed correlations between imaging and clinical findings. We performed 3T MRI (Magnetic Resonance Imaging) scans including isotropic high-resolution 3D T1, T2-FLAIR, and DTI (Diffusion Tensor Imaging) sequences in 15 adult patients with genetically confirmed SPG4 and 15 age- and sex-matched healthy controls.
Brain volume loss of gray and white matter was evaluated through voxel-based morphometry (VBM) for supra- and infra-tentorial regions separately. DTI maps of axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), and measured anisotropy (MA1) were analyzed through tract-based special statistics (TBSS).
VBM and TBSS revealed a widespread affection of gray and white matter in SPG4 including the corpus callosum, medio-dorsal thalamus, parieto-occipital regions, upper brainstem, cerebellum, and corticospinal tract. Significant correlations with correlation coefficients r > 0.6 between clinical data and DTI findings could be demonstrated for disease duration and disease severity as assessed by the spastic paraplegia rating scale for the pontine crossing tract (AD) and the corpus callosum (RD and FA).
Imaging also provided evidence that SPG4 underlies a primarily axonal rather than demyelinating damage in accordance with post-mortem data.
DTI is an attractive tool to assess subclinical affection in SPG4. The correlation of imaging findings with disease duration and severity suggests AD, RD, and FA as potential progression markers in interventional studies.
SOURCE: J Neurol. 2015 Aug;262(8):1961-71. doi: 10.1007/s00415-015-7791-7. Epub 2015 Jun 9. PMID: 26050637 [PubMed – in process]
Gray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations.
- 1Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany, [email protected]