Abstract

Background Identifying the differences between healthy versus pathological classes is essential for diagnostic tests. A current barrier to use of nerve excitability as a routine electrodiagnostic test is the lack of substantive normative control values to compare to patient data. In this study we examine whether it is statistically acceptable to combine normative control data from three centers or if site-specific technical heterogeneity precludes simple data pooling. Materials and methods Secondary data analysis of motor axon excitability tests (median nerve) from three sites: Canada (N = 120 (57 male), ages 18–70), Japan (N = 85 (50 male), ages 19–86) and Portugal (N = 42 (14 male), ages 22–84). Site-specific differences were assessed using ‘batch-effect’ algorithms developed for proteomics data: adjusted rand index (ARI) and normalized mutual information (NMI). ARI and NMI values near 1 indicate problematic heterogeneity (mean ± sd). Regression analysis was used to detect age-related differences in pooled versus site-specific data. Results Site-specific heterogeneity is small, but present at the 99% confidence level for one measure (NMI 0.039 ± 0.007) and absent in the other (ARI 0.027 ± 0.008). Previously reported age-dependent changes in excitability indices were still present in the pooled data. Conclusions There are detectable differences between sites generating control nerve excitability data. However, these differences are very small and do not obscure age-dependent associations. The source of the differences, technical versus biological, is yet to be determined. We are optimistic that an international normative database is feasible.

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