Specificity of association and plausibility in paediatric neurodisability

The two review articles concerning gross skeletal muscle morphology are both valuable contributions to the literature. They document comparisons in muscle size and architecture between typically developing individuals and those with cerebral palsy (CP), and the effects of intervention in the affected group. The article by Williams et al. describes the different imaging methodologies used to evaluate muscle morphology (magnetic resonance imaging, and 2D and 3D ultrasound). In individuals with CP classified in Gross Motor Function Classification System (GMFCS) level II and GMFCS level III, there is little doubt that lower limb muscles are smaller than in their typically developing peers. In contrast, evidence for differences in fascicle length and pennation between the groups is not convincing, nor is the effect of intervention on muscle morphology. In these two scoping reviews, cited studies are criticized for having small sample sizes, limited scope (in that they tend to concentrate on the medial gastrocnemius), the moderate precision of the measurement modalities employed, and the lack of inclusion of functional measures. These criticisms are valid but they are not the only ones that could be applied. Since the 1600s, empiricism has become the dominant philosophy for establishing causality in science. In medicine, this view has been formalized within the evidence-based medicine paradigm. The establishment of proof from controlled trials, cohort studies, and cross-sectional studies relies on adequate sample sizes in representative populations in the face of heterogeneity in the characteristics of the patient group, diverse interventional and measurement methodologies, study bias, and generalizability. A strong advocate of empirical evidence, Austin Bradford Hill is famous as being the architect of the first successful randomized controlled trial. In his 1965 address to the Section of Occupational Medicine of the Royal Society of Medicine, he recognized that empirical observations alone may not be sufficient for a causal claim in many cases, especially when the empirical evidence is weak. His guideline for establishing causality included five non-empirical considerations (specificity of association, temporality, plausibility, coherence, and analogy). We could apply two of these guidelines to the studies cited by the ‘morphology’ reviews. First, specificity of association. Shortland et al. observed changes in muscle architecture after muscle lengthening surgery to the medial gastrocnemius. These changes were attributed to the surgery alone but may have been caused by the casting after surgery or to a combination of casting and surgery. Second, plausibility. Variable increases in muscle size in response to strengthening programmes were reported by Walhain et al. A causal claim for the effect of strengthening here would be supported by evidence from histological studies. Do changes in gross morphology correspond with proportionate changes in myocyte cross-sectional area? Based on empirical considerations alone, it may be difficult to develop a case for causality between morphology and functional capacity, or between intervention and changes in morphology. We need to be careful to remove or explain potential confounders when designing studies and may need to support any claim with complementary studies at the molecular and cellular levels.