title: Neuropharmacology of progressive myoclonus epilepsy: response to 5-hydroxy-L-tryptophan.
abstract: Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) of patients with progressive myoclonus epilepsy (PME) suggest hypofunctional serotonergic neurotransmission. To study this hypothesis, we enrolled 6 patients with PME [Unverricht-Lündborg disease (U-L), mitochondrial encephalomyopathy, or Lafora disease] in a controlled, double-blinded, dose-ranging, cross-over add-on pilot clinical trial of 5-hydroxy-L-tryptophan (L-5-HTP) plus carbidopa after 2 other patients had received open-label L-5-HTP for compassionate use. Prestudy CSF 5-HIAA concentrations were low (< 20 ng/ml) in 6 patients regardless of the etiology of PME. One patient with U-L disease showed clinical improvement and a fivefold increase in CSF 5-HIAA, and 1 with Lafora disease showed a twofold increase in CSF 5-HIAA without improvement. A patient with Lafora disease reported enough improvement in myoclonus-evoked convulsions to continue chronic use of the drug. One patient with mitochondrial encephalomyopathy developed status epilepticus during treatment with L-5-HTP. As a group, patients had no statistically significant changes in myoclonus evaluation scale scores, subjective and objective measures of ataxia, seizure frequency, antiepileptic drug (AED) levels, or routine blood tests. These data suggest a serotonergic abnormality regardless of the underlying etiology of PME, but one that seldom responds to acute treatment with L-5-HTP.
authors.affiliation: Department of Neurology, George Washington University, Washington, D.C., USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Pranzatelli
authors.forename: E
authors.initials: E
authors.lastname: Tate
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: R H
authors.initials: RH
authors.lastname: Haas
authors.forename: J
authors.initials: J
authors.lastname: Bodensteiner
authors.forename: S
authors.initials: S
authors.lastname: Ashwal
authors.forename: D
authors.initials: D
authors.lastname: Franz
mesh_terms: D006916:5-Hydroxytryptophan / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D002230:Carbidopa / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004831:Epilepsies, Myoclonic / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism; D010865:Pilot Projects; D012701:Serotonin / Q000378:metabolism
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D002230:Carbidopa