Leonard et al. reply

Abstract

SIR–We thank Dr Whitehouse for his interest in our paper on metabolic testing in children with cerebral palsy (CP) and normal brain imaging,1 and for his constructive comments on the interpretation and implications of the results of our study. His suggested methods for providing an upper confidence limit in the circumstance where there were no positive results were most helpful. Our study was certainly limited by its small sample size, and was probably not originally designed to answer the study question definitively. Rather, our project had the objective of highlighting an under-researched area that has important clinical implications. We had hoped that positive results would help clinicians decide when to engage in the process of testing, but in the end our negative results left the issue open for debate. An important part of our interest in doing the study related to the process itself. This involved reviewing the status of all eligible children and contemplating a practical process for deciding which children should be investigated further, and what testing might be performed. In the end we could not ethically justify performing costly, time-consuming, or invasive procedures in children exhibiting a typical pattern of spasticity of a mild severity, or in those with an already established causal pathway. If we had included all children with CP and normal imaging, our sample size would have been larger, and presuming we obtained the same diagnostic yield, the upper confidence interval would have been lower. Clearly our negative findings should be treated with caution. We definitely concur with Dr Whitehouse in his assertion that children with abnormal imaging suggestive of an inherited metabolic disorder should undergo metabolic testing, as should those with other features consistent with inherited metabolic disorders. These children are not eligible for inclusion on the Victorian Cerebral Palsy Register, and were not included in our study. On the other hand, the Victorian Cerebral Palsy Register includes some children with hypotonic CP, a motor type that is not accepted under the CP banner in many parts of the world. Three children with hypotonic CP underwent further testing for inherited metabolic disorders as part of our study. We also agree with Dr Whitehouse that the likely diagnostic yield of further investigation of children with magnetic resonance imaging in the setting of non-progressive motor impairment is still unclear. We suggest that larger, possibly multicentre, studies would provide better power to answer the study question and, hopefully, produce stronger evidence to assist clinicians in the management of these diagnostically difficult cases.1