Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures

E. Ben-Menachem, A. Hamberger, T. Hedner, E. J. Hammond, B. M. Uthman, J. Slater, T. Treig, H. Stefan, R. E. Ramsay, J. F. Wernicke, B. J. Wilder

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276 Scopus citations


Electrical stimulation of the vagus nerve (VNS) is a new method for the treatment of patients with medically intractable epilepsy. Sixteen patients, ten of whom participated in a larger multicenter double-blind trial on the efficacy of VNS in epilepsy, and six who participated in pilot studies, consented to participate in the present study. Ten patients received HIGH stimulation and six patients LOW stimulation for the 3-month trial. Cerebrospinal fluid (CSF) samples (16 ml) were collected both before and after 3 months of VNS. Amino acid and neurotransmitter metabolites were analyzed. Four patients responded to VS with more than a 25% seizure reduction after 3 months. Mean and median concentrations of phosphoethanolamine (PEA) increased in responders and decreased in nonresponders. Free GABA increased in both groups but more so in the nonresponders. After 9 months of VS (6-9 months on HIGH stimulation) 4 of 15 patients had more than 40% seizure reduction. There were significant correlations between seizure reduction and increases in asparagine, phenylalanine, PEA, alanine and tryptophan concentrations. Comparison between patients with HIGH or LOW stimulation showed a significant increase in ethanolamine (EA) in the HIGH group and a decrease in glutamine in the LOW group. All patients regardless of response or stimulation intensity showed significantly increased total and free GABA levels. A decrease in CSF aspartate was marginally significant. Other trends were decreases in glutamate and increases in 5-hydroxyindoleacetic acid. Chronic VNS appears to have an effect on various amino acids pools in the brain. Most interesting are the decreases in aspartate, an excitatory amino acid, increases in GABA, an inhibitory amino acid, and increases in EA, a membrane lipid precursor.

Original languageEnglish (US)
Pages (from-to)221-227
Number of pages7
JournalEpilepsy Research
Issue number3
StatePublished - Mar 1995
Externally publishedYes


  • Amino acids
  • Cerebrospinal fluid
  • Neurotransmitter metabolites
  • Vagus stimulation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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