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Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences

Mitochondrial disease is complex and variable, making diagnosis and management challenging. The situation is complicated by lack of sensitive outcomes of disease severity, progression, contributing pathology and clinical efficacy. Gait is emerging as a sensitive marker of pathology; however, to date...

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Autores principales: Galna, Brook, Newman, Jane, Jakovljevic, Djordje G., Bates, Matthew G., Schaefer, Andrew M., McFarland, Robert, Turnbull, Douglass M., Trenell, Michael I., Gorman, Gráinne S., Rochester, Lynn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895207/
https://www.ncbi.nlm.nih.gov/pubmed/24150688
http://dx.doi.org/10.1007/s00415-013-7129-2
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author Galna, Brook
Newman, Jane
Jakovljevic, Djordje G.
Bates, Matthew G.
Schaefer, Andrew M.
McFarland, Robert
Turnbull, Douglass M.
Trenell, Michael I.
Gorman, Gráinne S.
Rochester, Lynn
author_facet Galna, Brook
Newman, Jane
Jakovljevic, Djordje G.
Bates, Matthew G.
Schaefer, Andrew M.
McFarland, Robert
Turnbull, Douglass M.
Trenell, Michael I.
Gorman, Gráinne S.
Rochester, Lynn
author_sort Galna, Brook
collection PubMed
description Mitochondrial disease is complex and variable, making diagnosis and management challenging. The situation is complicated by lack of sensitive outcomes of disease severity, progression, contributing pathology and clinical efficacy. Gait is emerging as a sensitive marker of pathology; however, to date, no studies have quantified gait in mitochondrial disease. In this cross-sectional study, we quantified gait characteristics in 24 patients with genetically confirmed mitochondrial disease (m.3243A>G and m.8344A>G) and 24 controls. Gait was measured using an instrumented walkway according to a predefined model with five domains hypothesised to reflect independent features of the neural control of gait in mitochondrial disease, including: pace (step velocity and step length); rhythm (step time); variability (step length and step time variability); asymmetry (step time asymmetry); and postural stability (step width, step width variability and step length asymmetry). Gait characteristics were compared with respect to controls and genotype. Additional measures of disease severity, pathophysiology and imaging were also compared to gait to verify the validity of gait characteristics. Discrete gait characteristics differed between controls and mitochondrial disease groups, even in relatively mildly affected patients harbouring the m.3243A>G mutation. The pattern of gait impairment (increased variability and reduced postural control) was supported by significant associations with measures of disease severity, progression, pathophysiology and radiological evidence of cerebellar atrophy. Discrete gait characteristics may help describe functional deficits in mitochondrial disease, enhance measures of disease severity and pathology, and could be used to document treatment effects of novel therapies.
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spelling pubmed-38952072014-01-22 Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences Galna, Brook Newman, Jane Jakovljevic, Djordje G. Bates, Matthew G. Schaefer, Andrew M. McFarland, Robert Turnbull, Douglass M. Trenell, Michael I. Gorman, Gráinne S. Rochester, Lynn J Neurol Original Communication Mitochondrial disease is complex and variable, making diagnosis and management challenging. The situation is complicated by lack of sensitive outcomes of disease severity, progression, contributing pathology and clinical efficacy. Gait is emerging as a sensitive marker of pathology; however, to date, no studies have quantified gait in mitochondrial disease. In this cross-sectional study, we quantified gait characteristics in 24 patients with genetically confirmed mitochondrial disease (m.3243A>G and m.8344A>G) and 24 controls. Gait was measured using an instrumented walkway according to a predefined model with five domains hypothesised to reflect independent features of the neural control of gait in mitochondrial disease, including: pace (step velocity and step length); rhythm (step time); variability (step length and step time variability); asymmetry (step time asymmetry); and postural stability (step width, step width variability and step length asymmetry). Gait characteristics were compared with respect to controls and genotype. Additional measures of disease severity, pathophysiology and imaging were also compared to gait to verify the validity of gait characteristics. Discrete gait characteristics differed between controls and mitochondrial disease groups, even in relatively mildly affected patients harbouring the m.3243A>G mutation. The pattern of gait impairment (increased variability and reduced postural control) was supported by significant associations with measures of disease severity, progression, pathophysiology and radiological evidence of cerebellar atrophy. Discrete gait characteristics may help describe functional deficits in mitochondrial disease, enhance measures of disease severity and pathology, and could be used to document treatment effects of novel therapies. Springer Berlin Heidelberg 2013-10-23 2014 /pmc/articles/PMC3895207/ /pubmed/24150688 http://dx.doi.org/10.1007/s00415-013-7129-2 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Communication
Galna, Brook
Newman, Jane
Jakovljevic, Djordje G.
Bates, Matthew G.
Schaefer, Andrew M.
McFarland, Robert
Turnbull, Douglass M.
Trenell, Michael I.
Gorman, Gráinne S.
Rochester, Lynn
Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences
title Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences
title_full Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences
title_fullStr Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences
title_full_unstemmed Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences
title_short Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences
title_sort discrete gait characteristics are associated with m.3243a>g and m.8344a>g variants of mitochondrial disease and its pathological consequences
topic Original Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895207/
https://www.ncbi.nlm.nih.gov/pubmed/24150688
http://dx.doi.org/10.1007/s00415-013-7129-2
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