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Naltrexone therapy of apnea in children with elevated cerebrospinal fluid beta-endorphin
E C Myer1, D L Morris, D A Brase
1Department of Child Neurology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0211.
Insights
Opioid antagonist naltrexone effectively treated apnea in infants and children with elevated beta-endorphin levels. This suggests endogenous opioids play a role in childhood apnea, potentially leading to physical dependence.
Area of Science:
- Neuroscience
- Pediatrics
- Pharmacology
Background:
- Elevated beta-endorphin immunoreactivity in cerebrospinal fluid (CSF) is observed in infants with apnea.
- The role of endogenous opioids in the pathogenesis of childhood apnea requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of the opioid antagonist naltrexone in treating apnea in children with elevated CSF immunoreactive beta-endorphin (i-BE).
Main Methods:
- Oral naltrexone treatment was administered to apneic infants and older children with elevated CSF i-BE.
- CSF i-BE levels were measured and compared to age-matched controls.
- Apneic events were monitored during naltrexone therapy and after attempts to discontinue treatment.
Main Results:
- Naltrexone therapy eliminated apnea in 8 infants and 5 older children with elevated CSF i-BE.
- Apnea recurred in some patients upon naltrexone discontinuation.
- Three children with Leigh's syndrome and elevated CSF i-BE also showed a positive response to naltrexone.
Conclusions:
- Elevated endogenous opioids contribute to the pathogenesis of apnea in children.
- Naltrexone is an effective treatment for certain types of childhood apnea.
- Childhood apnea associated with elevated endogenous opioids may lead to physical dependence.
Abstract:
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.