Deterioration in gait and functional ambulation in children and adolescents with Charcot–Marie–Tooth disease over 12 months

https://doi.org/10.1016/j.nmd.2017.04.005Get rights and content

Highlights

  • Deterioration in normalised gait speed and 6MWD reflect disease progression in CMT.

  • Deterioration was most notable when normalised for physical growth in children.

  • Normalised stride length decreased but normalised cadence remained stable.

  • Increasing calf weakness may contribute to reduced stride length and gait speed.

  • Gait assessment can screen for functional decline, informing management in CMT.

Abstract

Children and adolescents with Charcot–Marie–Tooth disease (CMT) report problems with gait. Little is known about gait changes over time in children with this degenerative disease. This prospective longitudinal study investigated change in spatio-temporal gait parameters and functional ambulation. Two assessments were conducted 12 months apart. Assessments included: barefoot gait on an electronic walkway; functional ambulation with a six minute walk test and the Functional Mobility Scale; and disease severity with the CMT Pediatric Scale. Gait and strength data were normalised to body anthropometrics. Twenty-seven children (mean age 12.2, SD 3.7 years) with various CMT subtypes (CMT1A 52%) were evaluated. Over 12 months, normalised variables of gait speed, stride length and six minute walk distance significantly decreased. The CMT Pediatric Scale increased 0.7 points, indicating marginal but not significant worsening of disease; notably calf strength decreased significantly over 12 months. Baseline maximum ankle dorsiflexion angle, gastrocnemius and hamstrings length, and calf strength correlated with decline in gait speed, with maximum ankle dorsiflexion angle as the strongest predictor. Deterioration over one year in normalised variables of gait speed, stride length and distance walked in six minutes are indicators of functional decline and disease progression in children and adolescents with CMT.

Introduction

Children and adolescents (“children”) with Charcot–Marie–Tooth disease (CMT) commonly report gait difficulties including reduced endurance [1], [2]. A heterogeneous group of inherited peripheral neuropathies, CMT affects 1:2500 people worldwide, is typically diagnosed in childhood or adolescence and is associated with life-long impairment [3]. Mutations in more than 80 genes cause CMT [4], with marked variability in clinical phenotype and disease progression between and within subtypes [5]. Progressive degeneration of the peripheral nerves in the lower limbs is most notable with reported foot and ankle impairments [6].

Muscle weakness in the feet and ankles is the primary lower limb impairment in CMT, emerging during early childhood [7]. Imbalance between agonists and antagonists is commonly reported, with ankle dorsiflexor and evertor muscle groups typically being weaker than plantar flexor and invertor muscle groups [8]. This imbalance contributes to muscle shortening and contractures, causing foot deformity [9]. Foot and ankle weakness and deformity are associated with gait difficulties in CMT [1]. Functional ambulation is the ability to walk safely and sufficiently to carry out mobility-related activities throughout the day [10]. Long distance walking at school and in community environments is often restricted in children affected by CMT. Physical limitations such as these have been found to be the most significant contributor to reduced quality of life in children with CMT [11].

Although CMT is widely considered degenerative, there is little evidence describing the magnitude or rate of change over time in gait and functional ambulation in children. No studies have evaluated the relationship between gait deterioration and CMT sub-type. Only one previous study examined longitudinal changes in gait, finding that normalised stride length reduced over 18 months in 16 children with CMT1A [12]. Several longitudinal studies in adults have described variable, generally mild disease progression over time, but have not specifically studied gait parameters [13], [14], [15], [16].

As CMT first manifests in childhood, an understanding of gait changes over time is needed for paediatric clinicians to monitor and predict the functional impact of disease progression [3]. This knowledge may inform development of targeted therapies, including pharmacological agents and physiotherapeutic techniques such as strengthening exercises and functional training. The aim of this study was to describe changes in gait and functional ambulation in children with CMT over a 12 month period. We hypothesised that children with CMT would walk with slower gait speed, shortened stride length and reduced distance after 12 months. Furthermore we aimed to identify and explore if clinical or functional measures were predictive of change in gait speed over 12 months.

Section snippets

Study design and participants

Approvals from The Royal Children's Hospital (HREC 33272) and The University of Melbourne (1441639) Human Research Ethics Committees were obtained for this longitudinal prospective study in a tertiary paediatric hospital outpatient clinic. Thirty ambulant children aged 4–18 years with a confirmed genetic or clinical diagnosis of CMT were recruited; participant assent and parental informed consent were obtained for all participants. Additional inclusion criteria included the ability to walk more

Results

Twenty-seven children (18 males, mean age 12.2, SD 3.7 years at 12 month assessment) with a mix of CMT subtypes (CMT1A 51.9%, CMT unknown 18.5%, CMT2 14.8%, CMTX1 7.4%, CMTX3 3.7%, CMTDIB 3.7%) were assessed twice 12 months apart (mean 378 days, SD 41). Table 1 describes the characteristics of the children. Two children were excluded from the 12 month assessment due to foot surgery in the intervening period between assessments. A third could not be contacted at follow-up.

Discussion

The findings support our hypothesis that children with CMT demonstrate significant deterioration in gait and functional ambulation over 12 months. Importantly, in this longitudinal study, the robust findings account for growth in children, with compelling evidence of slowing of Nspeed, shortening of Nstridelength and a decrease in N6MWD over 12 months. Younger children (<12 years) walked faster and with a longer stride length (Nspeed and Nstridelength) but displayed greater deterioration in

Acknowledgements

We are grateful for statistical advice from Assoc Prof Susan Donath, Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute; and to Dr Eppie Yiu, Assoc Prof Andrew Kornberg, Katy de Valle, Robin Forbes and the Neuromuscular team at The Royal Children's Hospital for their assistance with recruitment, genetic diagnoses and assessment.

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