Correspondence

www.thelancet.com/neurology Vol 8 October 2009 881

is clinically meaningful in this context is unclear. Correlation with associated motor tests and function, as studied by Burns and colleagues, might not capture aspects of CMT indicated in the QOL score. Third, the data from Burns and colleagues will be useful for planning future studies of CMT1A in children, which should include a QOL measure. Careful consideration must be given to sample size calculations if such QOL outcome measures are to be used. Given the sample size of 35 patients receiving ascorbic acid and 34 controls in the fi nal analysis of Burns and colleagues, a 15-point diff erence in QOL scores would have been necessary for a p value of 0·05 and a power of 90%. This requirement is three-times greater than the fi ve-point diff erences that have been reported to be clinically important for the CHQ.6 Such large diff erences are more likely to be apparent in studies of longer duration (ie, more than 1 year); alternatively, larger sample sizes are needed to detect smaller, yet still important, diff erences. Lastly, the sensitivity of the CHQ (ie, its ability to indicate disease progression in children with CMT) is unknown. Disease-specifi c measures might be more sensitive to change and, therefore, more useful for clinical trials.7 A direct head-to-head com parison of generic and disease-specifi c QOL instruments in children with CMT will be necessary to identify which will be a more sensitive outcome measure for clinical trials. We have no confl icts of interest.

Sindhu Ramchandren, Michael E Shy, Richard S Finkelsramchan@med.wayne.edu

Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI 48201, USA (SR, MES); and Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA (RSF)

1 Burns J, Ouvrier RA, Yiu EM, et al. Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and effi cacy trial. Lancet Neurol 2009; 8: 537–44.

2 Padua L, Schenone A, Aprile I, et al; the Italian NEUROPA study group. Quality of life and disability assessment in neuropathy: a multicentre study. J Peripher Nerv Syst 2005; 10: 3–10.

3 Vinci P, Serrao M, Millul A, et al. Quality of life in patients with Charcot-Marie-Tooth disease. Neurology 2005; 65: 922–24.

4 Waters E, Salmon L, Wake M, Hesketh K, Wright M. The Child Health Questionnaire in Australia: reliability, validity and population means. Aust N Z J Public Health 2000; 24: 207–10.

5 Gutiérrez-Suárez R, Pistorio A, Cespedes Cruz A, et al; the Pediatric Rheumatology International Trials Organisation (PRINTO). Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 diff erent geographic areas. The PRINTO multinational quality of life cohort study. Rheumatology 2007; 46: 314–20.

6 Landgraf JM, Abetz L, Ware JE. Child Health Questionnaire (CHQ): a user’s manual. Boston, MA: The Health Institute, New England Medical Center, 1996.

7 Hays R. Developing and evaluating questionnaires. In: Fayers P, Hays R, eds. Assessing quality of life in clinical trials. Oxford: Oxford University Press, 2005; 3–8.

Author’s replyI thank Ramchandren and colleagues for highlighting the disparity in quality of life scores between children with Charcot–Marie–Tooth disease type 1A (CMT1A) and age-matched population norms. Their analysis confi rms our previous work showing that quality of life is negatively aff ected by many types of CMT in

childhood and adolescence.1,2 Such early involvement is consistent with changes in foot and ankle strength, problems with motor function and walking ability, and hand dysfunction in children with CMT1A.3,4

There is a need to understand what really aff ects quality of life in children with CMT, to help interpret natural history data and investigate alternative strategies to improve quality of life and disability in these patients. This need is particularly important in trials in which the primary endpoint might be one that does not have obvious relevance to a child’s day-to-day experiences, such as nerve conduction studies, muscle weakness scores, or sensory defi cit. Therefore, the next important step is to identify and understand the factors associated with impaired quality of life in children with CMT.I have no confl icts of interest.

Joshua Burnsjoshuab2@chw.edu.au

Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Australia; and Institute for Neuroscience and Muscle Research, Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia

1 Burns J, Ryan MM, Ouvrier RA. Quality of life in children with Charcot-Marie-Tooth disease. J Child Neurol (in press).

2 Burns J, Ryan MM, Ouvrier RA. Impact of Charcot-Marie-Tooth disease on quality of life in children. J Peripheral Nerv Syst 2007; 12 (suppl 1): 13.

3 Burns J, Ryan MM, Ouvrier RA. Evolution of foot and ankle manifestations in children with CMT1A. Muscle Nerve 2009; 39: 158–66.

4 Burns J, Bray P, Cross L, North KN, Ryan MM, Ouvrier RA. Hand involvement in children with Charcot-Marie-Tooth disease type 1A. Neuromuscul Disord 2008; 18: 970–73.