Prediction of Epileptic Seizures for On-Demand Vagus Nerve Stimulation
Abstract
Vagus nerve stimulation (VNS) is a therapy for refractory epilepsy. Typically, VNS is performed for 30 s every 5 min, and the therapeutic effect increases over a time scale of several months. In addition, VNS exerts an immediate seizure suppressing effect. To use this effect, VNS should be done ondemand, before or at the early start of seizures. This requires that seizures can be predicted or detected at an early stage. This study was performed to develop an epilepsy model suitable for identifying seizure predictors for use in an on-demand VNS system.
The present work was performed in 9 rats. Animals were anesthetized by continuous intravenous (I.V.) administration of a mixture of ketamine and xylazine. Seizures were induced by I.V. infusion of 50 mg/kg pentylenetetrazole (PTZ) over a 5 min period. During the experiments EEG, ECG and EMG (one animal) were recorded. Seizures were defined from the EEG activity and RR interval (RRInt) changes were investigated as a seizure predictor.
Four different stages of EEG activity were identified. Stage 2 was associated with the onset of the tonic phase of the seizure. Therefore the start of this EEG stage was defined as the onset of tonic seizure. In 78% of cases, it was possible to predict seizures based on significant changes in the RRInt. Predictions were done 114 ± 29 s (mean ± SD) prior to seizure onset. In 89% of cases tonic seizure was associated with bradycardia.
The results show that the model is suitable for identifying precursors for epileptic seizures. RRInt changes could be used as a predictor in the model, however, further work is needed to clarify if RRInt changes can be used for seizure prediction in other animal models or in human patients.
Keywords
Epilepsy Vagus Nerve Stimulation Animal model RR interval Heart RatePreview
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References
- 1.Groves DA, Bowman EM, Brown VJ (2004) Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat. Neurosci Lett 379: 174–179 DOI:10.1016/j.neulet. 2004.12.055CrossRefGoogle Scholar
- 2.De Herdt V, Boon P, Ceulemans B et al. (2007) Vagus nerve stimulation for refractory epilepsy: A Belgian multicenter study. Eur J Paediatr Neuro l 11(5):261–269 DOI:10.1016/j.ejpn.2007.01.008CrossRefGoogle Scholar
- 3.Zabara J. (1992) Inhibition of experimental seizures in canines by repetitive vagal stimulation. Epilepsia 33(6):1005–12 DOI:10.1111/j.1528-1157.1992.tb01751.xCrossRefGoogle Scholar
- 4.Takaya M, Terry WJ, Naritoku DK. (1996) Vagus nerve stimulation induces a sustained anticonvulsant effect. Epilepsia 37(11):1111–6 DOI:10.1111/j.1528-1157.1996.tb01033.xCrossRefGoogle Scholar
- 5.Labar D, (2004) Vagus nerve stimulation for 1 year in 269 patients on unchanged antiepileptic drugs. Seizure 13(6):392–8 DOI:10.1016/j.seizure.2003.09.009CrossRefGoogle Scholar
- 6.Lehnertz K, Mormann F, Osterhage H et al. (2007) State-of-the-Art of seizure prediction. J Clin Neurophysiol 24(2):147–153MathSciNetCrossRefGoogle Scholar
- 7.Novak V, Reeves AL, Novak P et al.(1999) Time-frequency mapping of R-R interval during complex partial seizures of temporal lobe origin. J Auton Nerv Syst. 77(2–3):195–202 DOI:10.1016/S0165-1838(99)00044-2CrossRefGoogle Scholar
- 8.Ono J, Vieth FR, Walson PD. (1990) Electrocorticographical observation of seizure induced by pentylenetetrazol (PTZ) injected in rats. Funct Neurol 5(4):345–352Google Scholar
- 9.Herink J. (1997) Effect of alprazolam and ketamine on seizures induced by two different convulsants. Acta Medica (Hradec Kralove). 40(1):9–11Google Scholar
- 10.Beiga MI, Bhagata N, Talwara A et al. (2007) Simultaneous recording of electroencephalogram and blood pressure in conscious telemetered rats during ictal state. J Pharmacol Toxicol Methods 56(1):51–57 DOI:10.1016/j.vascn.2006.12.006CrossRefGoogle Scholar
- 11.Lathers CM, Schraeder PL (1982) Autonomic dysfunction in epilepsy: characterization of autonomic cardiac neural discharge associated with pentylenetetrazol-induced epileptogenic activity. Epilepsia. 23(6):633–647CrossRefGoogle Scholar