Gait and functional ambulation in children and adolescents with Charcot-Marie-Tooth disease

© 2018 Dr. Rachel Alexandra KennedyChildren and adolescents (“children”) with Charcot-Marie-Tooth disease (CMT) have progressive weakness of the lower limbs causing problems with gait and function. This thesis examined the nature and impact of gait dysfunction in children with CMT, with consideration of the typical everyday environments in which children function. Little is known about the effect of this degenerative peripheral neuropathy on gait and functional ambulation over time in children. Gait dysfunction may contribute to retrospective reports of frequent trips and falls in children with CMT, yet there are no studies of falls in this population. Children with CMT often report reduced physical endurance, yet no studies have investigated physical endurance, and more generally functional ambulation and physical activity. Six studies were designed to address these knowledge gaps, with comparison to typically developing peers (TD) to place gait dysfunction within the context of typical growth and development. A systematic review of gait in paediatric CMT found only a few studies with small sample sizes, examining barefoot gait in clinical and laboratory settings and providing limited comparison to TD databases. Gait was slower, most likely due to shorter stride length, with foot drop, reduced calf push-off power and proximal lower limb compensatory strategies. Two cross-sectional, case controlled studies utilising spatio-temporal gait analysis, one in different footwear and the other during a six-minute walk test, confirmed that gait in 30 children with CMT was slower, with shorter and wider steps, and greater step-to-step variability compared to TD children. Increased barefoot base of support variability was associated with poorer balance. Suboptimal footwear negatively affected gait in all children, irrespective of disease, which has clinical implications for children with CMT who have weak feet and ankles and poor balance. Reduced six-minute walk distance (6MWD) was an indicator of reduced physical endurance, and increased step-to-step variability was moderately associated with reduced 6MWD and increased perceived exertion. A longitudinal study of gait in 27 children with CMT over 12-months highlighted the importance of normalising gait data in children. Over 12-months, children with CMT were found to have reduced walking speed and endurance, and older children (≥ 12 years) exhibited greater disease progression and decline in functional ambulatory capacity than younger children. A novel six-month prospective cohort study of falls identified a markedly higher incidence of falls in children with CMT, with concerningly high numbers of injurious falls compared to TD children. Tripping was the most common mechanism of falls and all children under the age of 7 years fell, irrespective of disease. Age and balance were the strongest predictors of falls. A cross-sectional, case controlled study of functional ambulation and physical activity in 50 children with CMT across two paediatric centres found that functional ambulation was limited on all measures, including capacity, performance in every day environments, and the child’s perception of gait-related disease limitations. Children with CMT were less physically active than their TD peers with greater disease severity associated with lower physical activity. This thesis delivers important information to healthcare providers and families of children with CMT, and highlights the degree to which gait dysfunction impacts everyday activities. Gait dysfunction can be used as a biomarker of disease severity and progression in CMT. These findings will inform management of children with CMT, development of clinical practice guidelines and educational resources, and influence future research, including exercise interventions