Eppie M Yiu1, Cain R Brockley2, Katherine J Lee2, Kate Carroll2, Katy de Valle2, Rachel Kennedy2, Padma Rao2, Martin B Delatycki2, Monique M Ryan2. 1. From the Bruce Lefroy Centre for Genetic Health Research (E.M.Y., M.B.D.), Neurosciences Research (E.M.Y., K.C., K.d.V., R.K., M.M.R.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Childrens Research Institute; the Departments of Neurology (E.M.Y., K.C., K.d.V., R.K., M.M.R.) and Medical Imaging (C.R.B., P.R.), Royal Children's Hospital, Melbourne; the Department of Paediatrics (E.M.Y., K.J.L., P.R., M.B.D., M.M.R.), The University of Melbourne; and the Department of Clinical Genetics (M.B.D.), Austin Health, Heidelberg, Australia. eppie.yiu@rch.org.au. 2. From the Bruce Lefroy Centre for Genetic Health Research (E.M.Y., M.B.D.), Neurosciences Research (E.M.Y., K.C., K.d.V., R.K., M.M.R.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Childrens Research Institute; the Departments of Neurology (E.M.Y., K.C., K.d.V., R.K., M.M.R.) and Medical Imaging (C.R.B., P.R.), Royal Children's Hospital, Melbourne; the Department of Paediatrics (E.M.Y., K.J.L., P.R., M.B.D., M.M.R.), The University of Melbourne; and the Department of Clinical Genetics (M.B.D.), Austin Health, Heidelberg, Australia.
Abstract
OBJECTIVE: To investigate differences in nerve cross-sectional area (CSA) as measured by peripheral nerve ultrasound in children with Charcot-Marie-Tooth disease type 1A (CMT1A) compared to healthy controls. METHODS: This was a cross-sectional, matched, case-control study. CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with CMT1A and controls at each nerve site was determined. The relationship between nerve CSA and age/body metrics, and between nerve CSA and neurologic disability in CMT1A, was also evaluated. RESULTS: Twenty-nine children with CMT1A and 29 age- and sex-matched controls were enrolled. Nerve CSA was significantly increased in children with CMT1A compared to controls (1.9- to 3.5-fold increase, p < 0.001). The increase in nerve CSA with age was disproportionately greater in those with CMT1A. Nerve CSA showed a strong positive linear correlation with age, height, and weight in both the CMT1A and control groups. Disease severity correlated with both nerve CSA and age. CONCLUSIONS: Children with CMT1A have significantly increased nerve CSA compared to controls, and the increase in nerve CSA with age is disproportionately greater in CMT1A, suggesting ongoing nerve hypertrophy throughout childhood. Nerve CSA correlates with neurologic disability. These findings demonstrate the utility of peripheral nerve ultrasound as a diagnostic tool in pediatric neuropathies, and as an outcome measure in natural history studies and clinical trials in CMT1A. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that measurement of nerve CSA by peripheral nerve ultrasound accurately identifies patients with CMT1A.
OBJECTIVE: To investigate differences in nerve cross-sectional area (CSA) as measured by peripheral nerve ultrasound in children with Charcot-Marie-Tooth disease type 1A (CMT1A) compared to healthy controls. METHODS: This was a cross-sectional, matched, case-control study. CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with CMT1A and controls at each nerve site was determined. The relationship between nerve CSA and age/body metrics, and between nerve CSA and neurologic disability in CMT1A, was also evaluated. RESULTS: Twenty-nine children with CMT1A and 29 age- and sex-matched controls were enrolled. Nerve CSA was significantly increased in children with CMT1A compared to controls (1.9- to 3.5-fold increase, p < 0.001). The increase in nerve CSA with age was disproportionately greater in those with CMT1A. Nerve CSA showed a strong positive linear correlation with age, height, and weight in both the CMT1A and control groups. Disease severity correlated with both nerve CSA and age. CONCLUSIONS:Children with CMT1A have significantly increased nerve CSA compared to controls, and the increase in nerve CSA with age is disproportionately greater in CMT1A, suggesting ongoing nerve hypertrophy throughout childhood. Nerve CSA correlates with neurologic disability. These findings demonstrate the utility of peripheral nerve ultrasound as a diagnostic tool in pediatric neuropathies, and as an outcome measure in natural history studies and clinical trials in CMT1A. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that measurement of nerve CSA by peripheral nerve ultrasound accurately identifies patients with CMT1A.
Authors: Alexander Grimm; Maria Rasenack; Ioanna M Athanasopoulou; Nele Maria Dammeier; Christina Lipski; Stefan Wolking; Debora Vittore; Bernhard F Décard; Hubertus Axer Journal: J Neurol Date: 2015-11-11 Impact factor: 4.849
Authors: Sanne M R Hobbelink; Cain R Brockley; Rachel A Kennedy; Kate Carroll; Katy de Valle; Padma Rao; Mark R Davis; Nigel G Laing; Nicol C Voermans; Monique M Ryan; Eppie M Yiu Journal: Brain Behav Date: 2018-02-21 Impact factor: 2.708
Authors: Maria Rasenack; Bernhard F Décard; Sabine Schädelin; Alexander Grimm; Dirk Fischer; Patricia Hafner Journal: BMJ Open Date: 2016-12-09 Impact factor: 2.692