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Brain Damage and Gene Expression Across Hereditary Spastic Paraplegia Subtypes
Katiane R Servelhere1, Thiago Junqueira Ribeiro Rezende1, Fabrício Diniz de Lima1
1Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
Movement Disorders : Official Journal of the Movement Disorder Society
|February 12, 2021
Summary
Brain damage is common in hereditary spastic paraplegias (HSPs), with distinct patterns for each genetic subtype. These findings highlight genotype-specific brain abnormalities and varying pathophysiological mechanisms in HSPs.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Hereditary spastic paraplegias (HSPs) are traditionally associated with spinal cord damage.
- Emerging evidence reveals significant brain involvement in HSPs, yet brain signatures vary by genetic subtype.
- Understanding genotype-specific brain abnormalities is crucial for HSP research.
Purpose of the Study:
- To characterize cerebral and cerebellar damage across five distinct HSP genetic subtypes (SPG3A, SPG4, SPG7, SPG8, SPG11).
- To investigate the clinical and gene expression correlates of observed brain abnormalities.
- To elucidate genotype-specific patterns of brain damage in HSPs.
Main Methods:
- Cross-sectional case-control study involving 84 participants.
- Acquisition of high-resolution brain T1 and diffusion tensor imaging (DTI) datasets.
- Utilized MRICloud, FreeSurfer, and CERES-SUIT for comprehensive analysis of gray matter, white matter, and cerebellar structures.
Main Results:
- Brain abnormalities were identified in all but the SPG3A subtype.
- Observed distinct, gene-specific patterns of damage: SPG4 (basal ganglia, thalamus, posterior white matter), SPG7 (diffuse white matter, cerebellum), SPG8 (motor cortex thinning, pallidal atrophy), and SPG11 (widespread gray/white matter, deep cerebellar nuclei).
- Correlations between structural damage and gene expression (SPAST, WASHC5) varied between autosomal dominant and recessive HSPs, particularly in the cerebellum.
Conclusions:
- Brain damage is a significant feature of HSPs, irrespective of subtype purity.
- The pattern of brain abnormalities is distinctly genotype-specific.
- Differences in structural damage and gene expression correlations suggest distinct pathophysiological mechanisms underlying brain damage in autosomal dominant versus recessive HSPs.
