ONE SIDE OR TWO? Morgan Sangeux, MSc, PhD. Senior Biomedical Engineer2,3,4. Rory Wolfe, BSc, PhD. Statistician5, H. Kerr Graham MD, FRCS (Ed), FRACS, Professor of Orthopaedic Surgery1,2,3,4 1
Orthopaedic Department, The Royal Children’s Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia 2
Hugh Williamson Gait Analysis Laboratory, The Royal Children’s Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia 3
Murdoch Childrens Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia
4
The University of Melbourne, Parkville 3050, Victoria, Australia
5
School of Public Health and preventive Medicine, Monash University, The Alfred Centre, Commercial Road, Melbourne, Victoria 3004, Australia
Corresponding Author Morgan Sangeux Hugh Williamson Gait Analysis Laboratory The Royal Children’s Hospital 50 Flemington Road Parkville, Victoria, 3052 Australia Telephone:
61 3 9345 6792
E-mail:
[email protected]
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Journals such as Developmental Medicine and Child Neurology publish increasing numbers of papers reporting gait analysis data as a primary outcome measure in intervention studies for children with cerebral palsy. Despite increasing standardization of the formatting of gait data and improved reliability, a wide variety of statistical approaches to data analysis and presentation have been taken. A recurrent question raised by clinical and statistical reviewers is the inclusion of data from both lower limbs. The variability in the approach taken by authors and the response by reviewers can lead to frustrating delays or even the rejection of some studies by this and other journals. Ambulant children with cerebral palsy have two lower limbs with one affected (hemiplegia) or both affected (diplegia). In spastic diplegia gait pathology may be symmetric or asymmetric. What is usually unclear is the problem of the “non-independence of the two lower limbs” i.e. how much does one limb affect the other in gait? Starting at the top of the skeletal chain for gait, there is one pelvis, it can be viewed morphologically as a semi-rigid bony box or ring, and it is modelled as rigid in instrumented gait analysis. Therefore whatever the right side of the pelvis does during gait, the left side must do the same (for pelvic tilt) or the exact opposite (for pelvic rotation or obliquity) at exactly the same time. In hemiplegia if the right side is retracted, the left side will be protracted by the same amount. In spastic hemiplegia, even when there is clearly neurologic involvement on only one side, there are well known compensatory changes in gait pattern on the unaffected side. Most intervention studies on hemiplegic patients concern a unilateral procedure on the involved side. Data is therefore presented from this side and pre- to post-intervention changes can reasonably be attributed to the intervention. Now that the use of summary statistics of gait, such as the Gait Profile Score (GPS1) and the Gait Deviation Index (GDI2) are more widely used, it should be remembered that these are derived from multiple parameters, from multiple levels and from both lower limbs. Therefore an improvement in the Gait Profile Score after an intervention on the hemiplegic limb, receives contributions directly from the effects on the affected limb and also from resolution of compensatory gait deviations on the unaffected limb. For example, some children with equinus gait secondary to hemiplegia choose to adopt an equinus pattern on the unaffected side (vaulting) to improve clearance. Correction of the equinus deformity on the affected side usually leads to resolution of the compensatory equinus on the unaffected side. The complexity of the inter-relationship of the two lower limbs in spastic diplegia is an order of magnitude more complex. In children with symmetric diplegia, the gait pathology may be symmetric, the fixed musculoskeletal deformities may be symmetric and symmetric interventions may be advised during multilevel surgery. However, many children with diplegia have asymmetric neurological involvement, asymmetric gait pathology and asymmetric musculoskeletal pathology. Such children have complex interactions between levels of the same lower limb and between the two lower limbs. Surgical prescriptions are therefore often asymmetric. For example, there may be a decision to perform a procedure on one side only or to use a different “surgical dose”. Bilateral femoral derotations are commonly performed and just as commonly, asymmetric degrees of rotation are required and performed. In children with asymmetric equinus deformities, asymmetric surgery is often required, for example a gastrocnemius recession on one side and a gastrocsoleus recession on the other side.
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In summary, interventions may be unilateral, bilateral but asymmetric or bilateral and symmetric and a study cohort may include subjects belonging to more than one category. There are currently no widely agreed methods on how to deal with these complexities in study design, data analysis or data presentation. A distinction should be made as to whether the outcome measure is a summary statistic of gait (involving both sides, GPS or GDI) or whether the outcome measure is the direct effect (involving one level for one side, a Gait Variable Score1, GVS for example), such as ankle dorsiflexion GVS for gastrocsoleus lengthening. If the primary outcome measure is a summary statistic of gait, then this will be calculated from the multiple parameters in both lower limbs according to the description by the creators of these indices1,2. In this case, cohorts composed of only unilateral or only bilateral and symmetric procedures do not present major difficulties. In principle, unilateral and bilateral procedures and individuals with hemiplegia and diplegia should not be mixed together. If they are mixed, the statistical analysis should still only include the one gait summary statistic per subject but distinguish between individuals who have had a unilateral procedure and individuals who have had bilateral procedures and estimate the effects separately. If the outcome of a procedure is the direct effect at a single level then researchers have several options. Two simple approaches would be to either report the effect on both sides mixed together A1, or report only one side, even when bilateral procedures have been performed, A2. Given that for example, 10 children with spastic diplegia have 20 lower limbs, it is obvious that approach A2 halves the sample size and “wastes” information with the consequence of less precise estimates of effect. Approach A2 may also introduce bias to the estimated effect if the chosen side has not been selected either randomly or according to a clear rule determined prior to data collection. Many authors reporting small data sets are keen to report data from both sides, i.e. take approach A1. However, analysing data from both sides without taking care of correlation between the two lower limbs of an individual study participant falsely narrows confidence intervals and may lead to incorrect conclusions. Another approach is to recognize that the two lower limbs are not independent, and to make a statistical adjustment to take into account correlations between the lower limbs of the same patient. Such adjustment may use one of the two following options; a marginal approach, with generalised estimating equations and robust standard error calculations to allow for excess correlation between outcomes in the two sides of the same individual, or a conditional approach with a mixed effect model containing a random effect for study participant. There remains the problem that the degree of inter-dependence or dependence between the two sides has usually not been studied nor is it clearly known. Studies in which the non-independence of the two lower limbs is recognized, explicitly stated and in which a statistical adjustment has been made, are likely to be more favourably reviewed than those studies which simply ignore the problem. However this is clearly an avenue for further research. Given the number of new reporting tools including the Movement Analysis Profile, and Gait Variable Scores, it should be possible to gain insight to the relative dependence/inter-dependence of the two sides and the multiple levels in children with asymmetric spastic diplegia. Certainly better estimates of effect will be obtained from larger studies, use of all available data, in the light of a more informed understanding of inter-limb dependence in gait. 3
References 1. Baker R, McGinley JL, Schwartz MH, Beynon S, Rozumalski A, Graham HK, et al. The Gait Profile Score and Movement Analysis Profile. Gait & Posture. 2009;30(3):265-9. 2. Schwartz MH, Rozumalski A. The gait deviation index: A new comprehensive index of gait pathology. Gait & Posture. 2008;28(3):351-7.
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