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Brain Damage and Gene Expression Across Hereditary Spastic Paraplegia Subtypes
Author(s) -
Servelhere Katiane R.,
Rezende Thiago Junqueira Ribeiro,
Lima Fabrício Diniz,
Brito Mariana Rabelo,
França Nunes Renan Flávio,
Casseb Raphael F.,
Pedroso José Luiz,
Barsottini Orlando Graziani P.,
Cendes Fernando,
França Marcondes C.
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28519
Subject(s) - hereditary spastic paraplegia , cerebellum , white matter , pathology , neuroscience , atrophy , biology , medicine , gene , genetics , phenotype , magnetic resonance imaging , radiology
Background Spinal cord has been considered the main target of damage in hereditary spastic paraplegias (HSPs), but mounting evidence indicates that the brain is also affected. Despite this, little is known about the brain signature of HSPs, in particular regarding stratification for specific genetic subtypes. Objective We aimed to characterize cerebral and cerebellar damage in five HSP subtypes (9 SPG3A, 27 SPG4, 10 SPG7, 9 SPG8, and 29 SPG11) and to uncover the clinical and gene expression correlates. Methods We obtained high‐resolution brain T1 and diffusion tensor image (DTI) datasets in this cross‐sectional case–control study (n = 84). The MRICloud, FreeSurfer, and CERES‐SUIT pipelines were employed to assess cerebral gray (GM) and white matter (WM) as well as the cerebellum. Results Brain abnormalities were found in all but one HSP group (SPG3A), but the patterns were gene‐specific: basal ganglia, thalamic, and posterior WM involvement in SPG4; diffuse WM and cerebellar involvement in SPG7; cortical thinning at the motor cortices and pallidal atrophy in SPG8; and widespread GM, WM, and deep cerebellar nuclei damage in SPG11. Abnormal regions in SPG4 and SPG8 matched those with higher SPAST and WASHC5 expression, whereas in SPG7 and SPG11 this concordance was only noticed in the cerebellum. Conclusions Brain damage is a conspicuous feature of HSPs (even for pure subtypes), but the pattern of abnormalities is genotype‐specific. Correlation between brain structural damage and gene expression maps is different for autosomal dominant and recessive HSPs, pointing to distinct pathophysiological mechanisms underlying brain damage in these subgroups of the disease. © 2021 International Parkinson and Movement Disorder Society