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: M R Pranzatelli, E Tate, Y Huang, R H Haas, J Bodensteiner, S Ashwal, D Franz
• Journal: Epilepsia (Epilepsia) Vol. 36 Issue 8 Pg. 783-91 (Aug 1995) ISSN: 0013-9580 [Print] United States
• PMID: 7543407 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Serotonin
• Hydroxyindoleacetic Acid
• 5-Hydroxytryptophan
• Carbidopa

Topics

• 5-Hydroxytryptophan (therapeutic use)
• Adolescent
• Adult
• Carbidopa (therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Drug Therapy, Combination
• Epilepsies, Myoclonic (cerebrospinal fluid, drug therapy, metabolism)
• Female
• Humans
• Hydroxyindoleacetic Acid (cerebrospinal fluid)
• Male
• Mitochondrial Encephalomyopathies (cerebrospinal fluid, drug therapy, metabolism)
• Pilot Projects
• Serotonin (metabolism)