CEREBROSPINAL-FLUID 5-HYDROXYINDOLEACETIC ACID AND HOMOVANILLIC-ACID IN THE PEDIATRIC OPSOCLONUS-MYOCLONUS SYNDROME

To study the purported role of central monoamine disturbances in the p athophysiology of the opsoclonus-myoclonus syndrome, the serotonin met abolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovan illic acid were measured in cerebrospinal fluid samples from 27 affect ed children and 47 age- and gender-matched control subjects by high-pr essure liquid chromatography with electrochemical detection. 5-Hydroxy indoleacetic acid and homovanillic acid concentrations in the cerebros pinal fluid were approximately 30 to 40% lower in opsoclonus-myoclonus patients compared to control subjects, and the normal inverse correla tion between age and monoamine metabolite concentrations in the cerebr ospinal fluid of control subjects was not found in opsoclonus-myoclonu s patients. Patients with the lowest values were less than 4 years old , and a subgroup had extremely low levels, but differences in older ch ildren were not significant, Cerebrospinal fluid levels of 5-hydroxyin doleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus-myoclonus patients. None of the patients exhibited high levels of monoamine metabolites, Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patient s receiving corticotropin or steroids at the time of lumbar puncture, Clinical variables that could be excluded were paraneoplastic etiology , anesthetic for lumbar puncture, syndrome duration, age at onset, gen der, response to steroids, length of time until initiation of corticot ropin or steroids, presence of seizures, opsoclonus, and functional im pairment. These data suggest a disturbance and possible altered ontoge ny of serotonin or dopamine neurotransmission in a subpopulation of ch ildren with opsoclonus-myoclonus with low cerebrospinal fluid levels o f 5-hydroxyindoleacetic acid and homovanillic acid. Biochemical hetero geneity for this clinical phenotype may have implications for responsi veness to treatment with serotonergic and other drugs.