Optimization of epilepsy treatment with vagus nerve stimulation

Basim Uthman, Michael Bewernitz, Chang Chia Liu, Georges Ghacibeh

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Scopus citations


Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained overtime. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al found no effect of VNS on scalp EEG by spectral analysis, Kuba et al suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the clinical or electroencephalographic seizure onset. It is possible that intermittent VNS maintains chaoticity of brain activity in patients with epilepsy that respond to this therapy. The most optimal stimulation parameters of VNS are not known and further study of nonlinear dynamics of brain activity may shed some light on more effective interception or prevention of seizures. Online real time analysis may allow on-demand stimulation rather than hit-or-miss approach.

Original languageEnglish (US)
Title of host publicationData Mining, Systems Analysis, and Optimization in Biomedicine
Number of pages8
StatePublished - 2007
Externally publishedYes
EventConference on Data Mining, Systems Analysis, and Optimization in Biomedicine, 2007 - Gainesville, FL, United States
Duration: Mar 28 2007Mar 30 2007

Publication series

NameAIP Conference Proceedings
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616


OtherConference on Data Mining, Systems Analysis, and Optimization in Biomedicine, 2007
Country/TerritoryUnited States
CityGainesville, FL


  • Data mining
  • Epilepsy
  • Optimization
  • Quantitative EEG analysis
  • Vagus nerve stimulation

ASJC Scopus subject areas

  • Physics and Astronomy(all)


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