Naltrexone therapy of apnea in children with elevated cerebrospinal fluid beta-endorphin

Naltrexone therapy of apnea in children with elevated cerebrospinal fluid beta-endorphin

Myer E C; Morris D L; Brase D A; Dewey W L; Zimmerman A W

Annals of Neurology

1990

beta-Endorphin/cerebrospinal fluid; Male; Sleep Apnea Syndromes/cerebrospinal fluid/drug therapy; Infant Newborn; Leigh Disease/cerebrospinal fluid; Child; Humans; Prospective Studies; Naltrexone/therapeutic use; Female; Child Preschool; Infant; Biomarkers of Pain; child; female; male; beta-Endorphin/cerebrospinal fluid; Naltrexone/therapeutic use; Sleep Apnea Syndromes/cerebrospinal fluid/drug therapy; breathing difficulties; Leigh syndrome; pharmacologic intervention; oral naltrexone; naltrexone; sleep apnea

Previous studies have indicated increased immunoreactivity of the endogenous opioid peptide beta-endorphin in the cerebrospinal fluid (CSF) of infants under 2 years of age with apnea. To assess the role of endogenous opioids in the pathogenesis of apnea in children, the effect of oral treatment with the opioid antagonist naltrexone was studied in apneic infants, as well as in older apneic children, with demonstrated increases in CSF immunoreactive beta-endorphin (i-BE). In the 8 apneic infants with elevated i-BE in lumbar CSF (range, 55-155 pg/ml; normal, 17-52 pg/ml), no further apnea occurred during naltrexone therapy (1 mg/kg/day, by mouth). Five children (2-8 years old) with apnea of unknown cause had elevated CSF i-BE (range, 74-276 pg/ml) compared to 6 age-matched nonapneic children (range, 15-48 pg/ml). No apneic events occurred during naltrexone therapy, except in 1 child during stressful events, but apnea recurred in some patients after attempts to discontinue naltrexone treatment. Adverse effects of naltrexone included complaints of headaches in 2 children and symptoms of a narcotic withdrawal syndrome during the first 3 days of treatment in 1 child. Three children with Leigh's syndrome had elevated CSF i-BE (range, 104-291 pg/ml) and their apnea also responded to naltrexone. We conclude that elevated endogenous opioids contribute to the pathogenesis of apnea in children and may even result in physical dependence.

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