RESUMEN
Cerebral palsy is a clinical diagnosis of a nonprogressive developmental disorder of motor impairment. The scope of the diagnosis of cerebral palsy has been broadening significantly in recent years to include patients with genetic disorders. This article helps clinicians to determine which patients would benefit from a thorough genetic/metabolic evaluation and helps to delineate an approach for the work-up, with an emphasis on newer technologies and the evolving fields of fetal medicine and genetics. It provides guidance to providers to assist in clarifying an cause for some patient's symptoms.
Asunto(s)
Parálisis Cerebral/genética , Pruebas Genéticas , Predisposición Genética a la Enfermedad , Genómica , Humanos , Cariotipificación , Examen Físico , Secuenciación del ExomaRESUMEN
OBJECTIVE: Pediatric patients often require larger doses of antiepileptic drug (AED) than adults in order to attain therapeutic serum concentrations and/or achieve seizure control. Safety and efficacy data are often extrapolated from adult literature; hence, optimal dosage may only be determined anecdotally or based on expert opinion. With limited pediatric dosing guidelines, milligrams per day that are based on weight may exceed the maximum adult dose. The primary objective of this study is to evaluate the safety of exceeding maximum doses as specified by the US Food and Drug Administration or manufacturers of commonly used AEDs in pediatric patients. METHODS: This study is a single-center, retrospective analysis of all pediatric patients seen in the outpatient clinic between October 2010 and October 2014 who were prescribed a dose that exceeds the maximum approved dose of oxcarbazepine, zonisamide, topiramate, levetiracetam, lamotrigine, or clobazam. Baseline demographics (ie, sex, age, race/ethnicity, weight, height, diagnosis), serum drug concentrations, and appropriate laboratory tests were collected. Side effects were reviewed. RESULTS: During the 4-year study period, 41,137 prescriptions were included. A total of 2% of prescriptions exceeded the maximum dose of 1 of the included AEDs. The most common AED prescribed above the maximum dose was levetiracetam (53%), whereas lamotrigine was the least common (6%). The largest doses prescribed exceeded the maximum by 3-fold (i.e., levetiracetam dose of 9000 mg/day). CONCLUSION: It appears safe to use doses exceeding the maximum approved dose of the evaluated AEDs in pediatric patients, with appropriate counseling and monitoring for adverse effects.
RESUMEN
BACKGROUND: Primary amebic meningoencephalitis is a rare, almost uniformly fatal disease of cerebral invasion by Naegleria fowleri, occurring most commonly after swimming in warm fresh water in summer months. Treatment using the experimental medication miltefosine demonstrated improved survival and favorable neurocognitive outcome in a 2013 North American patient. There is little information about the electroencephalographic findings of such patients, and our understanding of factors predicting survival is limited. METHODS AND RESULTS: We describe two children, aged four and 14 years, who both presented with seizures and altered mental status after recent fresh water swimming exposures. With evidence of pyogenic meningitis and examination of cerebrospinal fluid demonstrating motile trophozoites on wet mount, N. fowleri meningoencephalitis was diagnosed. Amebicidal antibiotic regimens with miltefosine were administered. Continuous electroencephalography monitoring demonstrated evolution from diffuse slowing to seizures, status epilepticus, and eventually global attenuation and absence of activity. Both patients ultimately died after complications of progressive increasing intracranial pressure and hemodynamic compromise. CONCLUSIONS: Primary amebic meningoencephalitis is a serious, sporadic infection. We describe two fatal pediatric patients, the evolution of their electroencephalography findings, and compare their findings with the 13 reported pediatric survivors.