Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation
To determine the cortical mechanism that underlies the cognitive impairment and motor disability in hereditary spastic paraplegia (HSP), nine HSP patients from a Chinese family were examined using clinical evaluation, cognitive screening, and genetic testing. Controls were matched healthy subjects....
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doaj-6f0f4f331be643359e58c13b1b7edba42020-11-25T02:21:24ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-05-011110.3389/fneur.2020.00399507813Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST MutationJian-zhong Lin0Hong-hua Zheng1Qi-lin Ma2Chen Wang3Li-ping Fan4Han-ming Wu5Dan-ni Wang6Jia-xing Zhang7Yi-hong Zhan8Magnetic Resonance Center, The Affiliated Zhongshan Hospital of Xiamen University, Xiamen, ChinaFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaInstitute of Brain Diseases and Cognition, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaTo determine the cortical mechanism that underlies the cognitive impairment and motor disability in hereditary spastic paraplegia (HSP), nine HSP patients from a Chinese family were examined using clinical evaluation, cognitive screening, and genetic testing. Controls were matched healthy subjects. White-matter fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD; tract-based spatial statistics), cortical thickness (FreeSurfer), and subcortical gray matter (FIRST) based on T1-weighted MRI and diffusion tensor imaging were analyzed. A novel mutation in the SPAST gene (NM_014946.3, c.1321+2T>C) was detected. Patients had motor disability and low Montreal Cognitive Assessment (MoCA) scores. Patients showed significantly decreased total gray- and white-matter volumes, corpus callosum volume, cortical thickness, and subcortical gray-matter volume as well as significantly lower FA and AD values and significantly higher MD and RD values in the corpus callosum and corticospinal tract. Cortical thickness, subcortical gray-matter volume, and MoCA score were negatively correlated with disease duration. Cortical thickness in the right inferior frontal cortex was negatively correlated with Spastic Paraplegia Rating Scale score. Cortical thickness and right hippocampus volume were positively correlated with the MoCA score and subscores. In conclusion, brain damage is not restricted to the white matter in SPG4-HSP patients, and widespread gray-matter damage may account for the disease progression, cognitive impairment, and disease severity in SPG4-HSP.https://www.frontiersin.org/article/10.3389/fneur.2020.00399/fullSPAST gene mutationSPG4-hereditary spastic paraplegiaMRIbraingray-matter changes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian-zhong Lin Hong-hua Zheng Qi-lin Ma Chen Wang Li-ping Fan Han-ming Wu Dan-ni Wang Jia-xing Zhang Yi-hong Zhan |
spellingShingle |
Jian-zhong Lin Hong-hua Zheng Qi-lin Ma Chen Wang Li-ping Fan Han-ming Wu Dan-ni Wang Jia-xing Zhang Yi-hong Zhan Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation Frontiers in Neurology SPAST gene mutation SPG4-hereditary spastic paraplegia MRI brain gray-matter changes |
author_facet |
Jian-zhong Lin Hong-hua Zheng Qi-lin Ma Chen Wang Li-ping Fan Han-ming Wu Dan-ni Wang Jia-xing Zhang Yi-hong Zhan |
author_sort |
Jian-zhong Lin |
title |
Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation |
title_short |
Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation |
title_full |
Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation |
title_fullStr |
Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation |
title_full_unstemmed |
Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation |
title_sort |
cortical damage associated with cognitive and motor impairment in hereditary spastic paraplegia: evidence of a novel spast mutation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2020-05-01 |
description |
To determine the cortical mechanism that underlies the cognitive impairment and motor disability in hereditary spastic paraplegia (HSP), nine HSP patients from a Chinese family were examined using clinical evaluation, cognitive screening, and genetic testing. Controls were matched healthy subjects. White-matter fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD; tract-based spatial statistics), cortical thickness (FreeSurfer), and subcortical gray matter (FIRST) based on T1-weighted MRI and diffusion tensor imaging were analyzed. A novel mutation in the SPAST gene (NM_014946.3, c.1321+2T>C) was detected. Patients had motor disability and low Montreal Cognitive Assessment (MoCA) scores. Patients showed significantly decreased total gray- and white-matter volumes, corpus callosum volume, cortical thickness, and subcortical gray-matter volume as well as significantly lower FA and AD values and significantly higher MD and RD values in the corpus callosum and corticospinal tract. Cortical thickness, subcortical gray-matter volume, and MoCA score were negatively correlated with disease duration. Cortical thickness in the right inferior frontal cortex was negatively correlated with Spastic Paraplegia Rating Scale score. Cortical thickness and right hippocampus volume were positively correlated with the MoCA score and subscores. In conclusion, brain damage is not restricted to the white matter in SPG4-HSP patients, and widespread gray-matter damage may account for the disease progression, cognitive impairment, and disease severity in SPG4-HSP. |
topic |
SPAST gene mutation SPG4-hereditary spastic paraplegia MRI brain gray-matter changes |
url |
https://www.frontiersin.org/article/10.3389/fneur.2020.00399/full |
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