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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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Autores principales: Lin, Jian-zhong, Zheng, Hong-hua, Ma, Qi-lin, Wang, Chen, Fan, Li-ping, Wu, Han-ming, Wang, Dan-ni, Zhang, Jia-xing, Zhan, Yi-hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267220/
https://www.ncbi.nlm.nih.gov/pubmed/32536902
http://dx.doi.org/10.3389/fneur.2020.00399
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author Lin, Jian-zhong
Zheng, Hong-hua
Ma, Qi-lin
Wang, Chen
Fan, Li-ping
Wu, Han-ming
Wang, Dan-ni
Zhang, Jia-xing
Zhan, Yi-hong
author_facet Lin, Jian-zhong
Zheng, Hong-hua
Ma, Qi-lin
Wang, Chen
Fan, Li-ping
Wu, Han-ming
Wang, Dan-ni
Zhang, Jia-xing
Zhan, Yi-hong
author_sort Lin, Jian-zhong
collection PubMed
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.
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spelling pubmed-72672202020-06-12 Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation Lin, Jian-zhong Zheng, Hong-hua Ma, Qi-lin Wang, Chen Fan, Li-ping Wu, Han-ming Wang, Dan-ni Zhang, Jia-xing Zhan, Yi-hong Front Neurol Neurology 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. Frontiers Media S.A. 2020-05-27 /pmc/articles/PMC7267220/ /pubmed/32536902 http://dx.doi.org/10.3389/fneur.2020.00399 Text en Copyright © 2020 Lin, Zheng, Ma, Wang, Fan, Wu, Wang, Zhang and Zhan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Lin, Jian-zhong
Zheng, Hong-hua
Ma, Qi-lin
Wang, Chen
Fan, Li-ping
Wu, Han-ming
Wang, Dan-ni
Zhang, Jia-xing
Zhan, Yi-hong
Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation
title 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_short 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
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267220/
https://www.ncbi.nlm.nih.gov/pubmed/32536902
http://dx.doi.org/10.3389/fneur.2020.00399
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