title: Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences.
abstract: 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.
authors.affiliation: Clinical Ageing Research Unit, Campus for Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, UK, brook.galna@ncl.ac.uk.
authors.forename: Brook
authors.initials: B
authors.lastname: Galna
authors.forename: Jane
authors.initials: J
authors.lastname: Newman
authors.forename: Djordje G
authors.initials: DG
authors.lastname: Jakovljevic
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Bates
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Schaefer
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Michael I
authors.initials: MI
authors.lastname: Trenell
authors.forename: Gráinne S
authors.initials: GS
authors.lastname: Gorman
authors.forename: Lynn
authors.initials: L
authors.lastname: Rochester
mesh_terms: D000293:Adolescent; D000328:Adult; D002531:Cerebellum / Q000002:abnormalities / Q000473:pathology; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial