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Monoaminergic effects of high-dose corticotropin in corticotropin-responsive pediatric opsoclonus-myoclonus
M R Pranzatelli1, Y Y Huang, E Tate
1National Pediatric Myoclonus Center, Washington, DC 20036, USA.
Insights
Corticotropin (ACTH) treatment improves childhood opsoclonus-myoclonus syndrome (OMS) but does not normalize cerebrospinal fluid (CSF) homovanillic acid (HVA) or 5-hydroxyindole-acetic acid (5-HIAA) levels. ACTH reduces HVA, suggesting altered catecholamine metabolism in OMS.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Pharmacology
Background:
- Opsoclonus-myoclonus syndrome (OMS) in children typically responds to corticotropin (adrenocorticotrophic hormone, ACTH) treatment.
- The precise mechanism by which ACTH benefits pediatric OMS remains unclear.
- Previous research indicated low cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) in pediatric OMS.
Purpose of the Study:
- To investigate the impact of ACTH treatment on CSF catecholamine metabolites in pediatric OMS.
- To explore potential correlations between dopaminergic, noradrenergic, and serotonergic markers during ACTH therapy.
Main Methods:
- CSF levels of Dopa, catecholamines, deaminated metabolites, HVA, and 5-HIAA were measured in eight pediatric OMS patients.
- Measurements were taken before and during ACTH treatment.
- Clinical response to ACTH was assessed, with 50-70% improvement noted.
Main Results:
- ACTH treatment significantly reduced CSF HVA concentrations by a mean of 21% (p < 0.001).
- Significant correlations were observed between dopaminergic markers (HVA, DOPAC, Dopa) during ACTH treatment.
- CSF levels of noradrenergic markers (norepinephrine, NE; dihydroxyphenylglycol, DHPG) and the serotonergic marker 5-HIAA showed no significant changes.
Conclusions:
- The beneficial effects of ACTH in pediatric OMS are not linked to the normalization of CSF HVA or 5-HIAA levels.
- Decreased HVA with unchanged DOPAC suggests potential alterations in catecholamine metabolism, possibly due to inhibited extraneuronal uptake or 0-methylation by steroids.
- ACTH's mechanism in OMS may involve modulating catecholamine pathways rather than restoring baseline metabolite levels.
Abstract:
Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5-HIAA in eight patients before and during treatment with ACTH. All the children were ACTH-responsive with 50-70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa. There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are not associated with normalization of HVA or 5-HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased 0-methylation of catecholamines in nonneuronal cells.