Practice Parameter: Diagnostic assessment of the child with cerebral palsy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter the authors reviewed available evidence on the assessment of a child suspected of having cerebral palsy (CP), a nonprogressive disorder of posture or movement due to a lesion of the developing brain. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: CP is a common problem, occurring in about 2 to 2.5 per 1,000 live births. In order to establish that a brain abnormality exists in children with CP that may, in turn, suggest an etiology and prognosis, neuroimaging is recommended with MRI preferred to CT (Level A). Metabolic and genetic studies should not be routinely obtained in the evaluation of the child with CP (Level B). If the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination, metabolic and genetic testing should be considered (Level C). Detection of a brain malformation in a child with CP warrants consideration of an underlying genetic or metabolic etiology. Because the incidence of cerebral infarction is high in children with hemiplegic CP, diagnostic testing for coagulation disorders should be considered (Level B). However, there is insufficient evidence at present to be precise as to what studies should be ordered. An EEG is not recommended unless there are features suggestive of epilepsy or a specific epileptic syndrome (Level A). Because children with CP may have associated deficits of mental retardation, ophthalmologic and hearing impairments, speech and language disorders, and oral-motor dysfunction, screening for these conditions should be part of the initial assessment (Level A). CONCLUSIONS: Neuroimaging results in children with CP are commonly abnormal and may help determine the etiology. Screening for associated conditions is warranted as part of the initial evaluation

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible