RESUMEN
OBJECTIVE: To characterize the longitudinal clinical and electrophysiological patterns of thalidomide neuropathy in children and adolescents. STUDY DESIGN: Retrospective analysis of clinical records at a tertiary care children's hospital, including serial electrophysiological studies. RESULTS: Sixteen patients aged 6-24 years received thalidomide to treat Crohn's disease from 2002 to 2012. Nine subjects had electrophysiological evidence of sensorimotor axonal polyneuropathy, 8 of whom had sensory and/or motor symptoms. The patients with polyneuropathy received thalidomide for 5 weeks to 52 months, with cumulative doses ranging from 1.4 to 207.7 g. All subjects with cumulative doses greater than 60 g developed polyneuropathy, and 4 of the 5 subjects who received thalidomide for more than 20 months developed polyneuropathy. The 7 subjects who had normal neurophysiological studies received therapy for 1 week to 25 months, with cumulative doses ranging from 0.7 to 47 g. In contrast to some previous reports, several patients had sensorimotor polyneuropathies, rather than pure sensory neuropathies. In patients with neuropathy who received therapy for more than 24 months and had 3 or more electromyography studies, the severity of the neuropathy plateaued. CONCLUSIONS: Factors in addition to the total dose may contribute to the risk profile for thalidomide neuropathy, including pharmacogenetic susceptibilities. The severity of the neuropathy does not worsen relentlessly. Children, adolescents, and young adults receiving thalidomide should undergo regular neurophysiological studies to monitor for neuropathy.
Asunto(s)
Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Talidomida/efectos adversos , Adolescente , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Conducción Nerviosa , Enfermedades del Sistema Nervioso Periférico/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: High reliability is a prerequisite for any test to be useful as a biomarker in a clinical trial. Here we assessed the reproducibility of electrical impedance myography (EIM) in children by comparing data obtained by different evaluators on separate days. METHODS: Healthy boys and boys with Duchenne muscular dystrophy (DMD) aged 2-14 years underwent EIM of multiple muscles performed by two evaluators on two visits separated by 3-7 days. Single and multifrequency data were analyzed. Reliability was assessed via calculation of the percent relative standard deviation (% RSD), Bland-Altman analysis, and the intraclass correlation coefficient (ICC). RESULTS: For both individual muscle data and data averaged across muscles, intra-evaluator measurements showed high repeatability for both 50 kHz phase and 50/200 kHz phase ratio values, with ICCs generally above 0.90 and % RSD below 10%. Inter-evaluator results showed very similar ICC and % RSD values as those obtained by the same evaluator. CONCLUSIONS: Both the 50 kHz phase and 50/200 kHz phase ratio are reliable measures both across time and evaluators and in both health and disease. SIGNIFICANCE: These results support the concept that EIM can serve as a reliable measure in clinical therapeutic trials in a pediatric population.
Asunto(s)
Electromiografía/normas , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/fisiopatología , Adolescente , Niño , Preescolar , Impedancia Eléctrica , Electromiografía/métodos , Femenino , Humanos , Masculino , Miografía/métodos , Miografía/normas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Electrical impedance myography and quantitative ultrasound are two noninvasive, painless, and effort-independent approaches for assessing neuromuscular disease. Both techniques have potential to serve as useful biomarkers in clinical trials in Duchenne muscular dystrophy. However, their comparative sensitivity to disease status and how they relate to one another are unknown. METHODS: We performed a cross-sectional analysis of electrical impedance myography and quantitative ultrasound in 24 healthy boys and 24 with Duchenne muscular dystrophy, aged 2 to 14 years with trained research assistants performing all measurements. Three upper and three lower extremity muscles were studied unilaterally in each child, and the data averaged for each individual. RESULTS: Both electrical impedance myography and quantitative ultrasound differentiated healthy boys from those with Duchenne muscular dystrophy (P < 0.001 for both). Quantitative ultrasound values correlated with age in Duchenne muscular dystrophy boys (rho = 0.45; P = 0.029), whereas electrical impedance myography did not (rho = -0.31; P = 0.14). However, electrical impedance myography phase correlated with age in healthy boys (rho = 0.51; P = 0.012), whereas quantitative ultrasound did not (rho = -0.021; P = 0.92). In Duchenne muscular dystrophy boys, electrical impedance myography phase correlated with the North Star Ambulatory Assessment (rho = 0.65; P = 0.022); quantitative ultrasound revealed a near-significant association (rho = -0.56; P = 0.060). The two technologies trended toward a moderate correlation with one another in the Duchenne muscular dystrophy cohort but not in the healthy group (rho = -0.40; P = 0.054 and rho = -0.32; P = 0.13, respectively). CONCLUSIONS: Electrical impedance myography and quantitative ultrasound are complementary modalities for the assessment of boys with Duchenne muscular dystrophy; further study and application of these two modalities alone or in combination in a longitudinal fashion are warranted.