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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

Lookup NU author(s): Dr Brook Galna, Jane Newman, Professor Djordje JakovljevicORCiD, Dr Matthew Bates, Dr Andrew Schaefer, Professor Bobby McFarlandORCiD, Emeritus Professor Doug Turnbull, Professor Mike TrenellORCiD, Professor Grainne Gorman, Professor Lynn RochesterORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Galna B, Newman J, Jakovljevic DG, Bates MG, Schaefer AM, McFarland R, Turnbull DM, Trenell MI, Gorman GS, Rochester L

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2014

Volume: 261

Issue: 1

Pages: 73-82

Print publication date: 01/01/2014

Online publication date: 23/10/2013

Acceptance date: 20/09/2013

Date deposited: 22/04/2014

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Springer Berlin Heidelberg


DOI: 10.1007/s00415-013-7129-2


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Funder referenceFunder name
UK National Institute for Health Research Biomedical Research Centre for Ageing and Age-related Diseases award
UK NHS Highly Specialized Services
UK NIHR Biomedical Research Centre for Ageing and Age-Related Disease award
Newcastle upon Tyne Hospitals NHS Foundation Trust
074454/Z/04/ZWellcome Trust
096919Z/11/ZWellcome Trust
BH092142Wellcome Trust
G0601943Medical Research Council
G0800674Medical Research Council