Neuropharmacology of Progressive Myoclonus Epilepsy: Response to 5-Hydroxy-L-Tryptophan |
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Authors: | M. R. Pranzatelli&dagger ,E. Tate&dagger ,Y. Huang&Dagger ,R.H. Haas§ ,J. Bodensteiner ,S. Ashwal,¶ ,D. Franz |
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Affiliation: | Department of Neurology, Pediatrics, and Pharmacology, The George Washington University, Washington D.C.;The Center for Neurosciences, Children's Research Institute, New York;Department of Psychiatry, Columbia University, and Division of Neuroscience, New York State Psychiatric Institute, New York, New York;Department of Neurosciences, University of California at San Diego, San Diego, California;Neurology and Pediatrics Departments, West Virginia University School of Medicine, Morgantown, West Virginia;Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California;Department of Neurology, University of Cincinnati Children's Hospital, Cincinnati, Ohio, U.S.A. |
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Abstract: | Summary: 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-Lundborg disease (U-L), mitochondria1 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 mitochondria1 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. |
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Keywords: | Myoclonus-5-Hydroxy-tryptophan-5-Hydroxyindoleacetic acid-Serotonin-Unverricht-Lundborg disease-Lafora disease-Mitochondria1 encephalopathy-Progressive my-oclonus epilepsy. |
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