Vagus nerve stimulation for induced spinal cord seizures: insights into seizure cessation

R. Shane Tubbs PA-C, Ph.D.1, Cheryl R. Killingsworth D.V.M., Ph.D.1, Dennis L. Rollins1, William M. Smith Ph.D.1, Raymond E. Ideker M.D.1, John C. Wellons III M.D.1, Jeffrey P. Blount M.D.1, and W. Jerry Oakes M.D.1
View More View Less
  • 1 Departments of Cell Biology and Surgery, Division of Pediatric Neurosurgery, and Cardiac Rhythm Management Laboratory, University of Alabama at Birmingham, Alabama
Page Range:
213–217
Volume/Issue:
Volume 102: Issue 2
DOI link:
https://doi.org/10.3171/ped.2005.102.2.0213
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Click here for subscription options

  • Purchase Now

    USD  $45.00

  • JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

    USD  $515.00

  • JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

    USD  $612.00
Print or Print + Online Sign in

Object. Vagus nerve stimulation is known to decrease the frequency, duration, and intensity of some types of intracranial seizures in both humans and animals. Although many theories abound concerning the mechanism for this action, the true cause remains speculative. To potentially elucidate a pathway in which vagus nerve stimulation aborts seizure activity, seizures were initiated not in the cerebral cortex but in the spinal cord and then vagus nerve stimulation was performed.

Methods. Ten pigs were anesthetized and placed in the lateral position, and a small laminectomy was performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was applied to the dorsal surface of the exposed cord. With the exception of two animals that were used as controls, once seizure activity was discernible via motor convulsion or increased electrical activity the left vagus nerve, which had been previously isolated in the neck, was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation was performed.

Vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all (87.5%) but one experimented animal. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation to cause cessation of seizure activity in all study animals.

Conclusions. The effects of vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. The authors believe that this experiment is the first to demonstrate that spinal cord neuronal hyperactivity can be suppressed by stimulation of a cranial nerve. These data may aid in the development of alternative mechanisms for electrical stimulation in patients with medically intractable seizures. Further studies are now necessary to isolate which specific tracts, nuclei, and neurotransmitters are involved in this process.

Volume 102: Issue 2 (Mar 2005)

in Journal of Neurosurgery: Pediatrics
Cover Journal of Neurosurgery: Pediatrics

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Click here for subscription options

  • JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

    USD  $515.00

  • JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

    USD  $612.00
Print or Print + Online

Contributor Notes

Address reprint requests to: R. Shane Tubbs, Ph.D., Pediatric Neurosurgery, 1600 7th Avenue South ACC 400, Birmingham, Alabama 35233. email: richard.tubbs@uab.edu.
  • 1.

    Amar AP, , Heck CN, , Levy ML, , Smith T, , De Giorgio CM, & Oviedo S, et al: An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery 43:1265–1280, 1998 Amar AP, Heck CN, Levy ML, Smith T, De Giorgio CM, Oviedo S, et al: An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery 43:1265–1280, 1998

    • Search Google Scholar
    • Export Citation
  • 2.

    Bailey P, & Bremer F: A sensory cortical representation of the vagus nerve. J Neurophysiol 1:405–412, 1938 Bailey P, Bremer F: A sensory cortical representation of the vagus nerve. J Neurophysiol 1:405–412, 1938

    • Search Google Scholar
    • Export Citation
  • 3.

    Ben-Menachem E, , Manon-Espaillat R, , Ristanovic R, , Wilder BJ, , Stefan H, & Mirza W, et al: Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 35:616–626, 1994 Ben-Menachem E, Manon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W, et al: Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 35:616–626, 1994

    • Search Google Scholar
    • Export Citation
  • 4.

    Bertram EH, , Zhang DX, , Mangan P, , Fountain N, & Rempe D: Functional anatomy of limbic epilepsy: a proposal for central synchronization of a diffusely hyperexcitable network. Epilepsy Res 32:194–205, 1998 Bertram EH, Zhang DX, Mangan P, Fountain N, Rempe D: Functional anatomy of limbic epilepsy: a proposal for central synchronization of a diffusely hyperexcitable network. Epilepsy Res 32:194–205, 1998

    • Search Google Scholar
    • Export Citation
  • 5.

    Bordbar A, & Beheshti M: Post-operative convulsions due to penicillin applied to the spinal theca. Anaesthesia 30:56–58, 1975 Bordbar A, Beheshti M: Post-operative convulsions due to penicillin applied to the spinal theca. Anaesthesia 30:56–58, 1975

    • Search Google Scholar
    • Export Citation
  • 6.

    Cherrick AA, & Ellenberg M: Spinal cord seizures in transverse myelopathy: report of two cases. Arch Phys Med Rehabil 67:129–131, 1986 Cherrick AA, Ellenberg M: Spinal cord seizures in transverse myelopathy: report of two cases. Arch Phys Med Rehabil 67:129–131, 1986

    • Search Google Scholar
    • Export Citation
  • 7.

    Davenport J, , Schwindt PC, & Crill WE: Penicillin-induced spinal seizures: selective effects on synaptic transmission. Exp Neurol 56:132–150, 1977 Davenport J, Schwindt PC, Crill WE: Penicillin-induced spinal seizures: selective effects on synaptic transmission. Exp Neurol 56:132–150, 1977

    • Search Google Scholar
    • Export Citation
  • 8.

    Davenport J, , Schwindt PC, & Crill WE: Presynaptic and long-lasting postsynaptic inhibition during penicillin-induced spinal seizures. Neurology 28:592–597, 1978 Davenport J, Schwindt PC, Crill WE: Presynaptic and long-lasting postsynaptic inhibition during penicillin-induced spinal seizures. Neurology 28:592–597, 1978

    • Search Google Scholar
    • Export Citation
  • 9.

    Garnett ES, , Nahmias C, , Scheffel A, , Firnan Gamma, & Upton AR: Regional cerebral blood flow in man manipulated by direct vagal stimulation. Pacing Clin Electrophysiol 15:1579–1580, 1992 Garnett ES, Nahmias C, Scheffel A, Firnan Gamma, Upton AR: Regional cerebral blood flow in man manipulated by direct vagal stimulation. Pacing Clin Electrophysiol 15:1579–1580, 1992

    • Search Google Scholar
    • Export Citation
  • 10.

    Hammond EJ, , Uthman BM, , Reid SA, & Wilder BJ: Electrophysiological studies of cervical vagus nerve stimulation in humans: I. EEG effects. Epilepsia 33:1013–1020, 1992 Hammond EJ, Uthman BM, Reid SA, Wilder BJ: Electrophysiological studies of cervical vagus nerve stimulation in humans: I. EEG effects. Epilepsia 33:1013–1020, 1992

    • Search Google Scholar
    • Export Citation
  • 11.

    Hammond EJ, , Uthman BM, , Wilder BJ, , Ben-Menachem E, & Hamberger A, et al: Neurochemical effects of vagus nerve stimulation in humans. Brain Res 583:300–303, 1992 Hammond EJ, Uthman BM, Wilder BJ, Ben-Menachem E, Hamberger A, et al: Neurochemical effects of vagus nerve stimulation in humans. Brain Res 583:300–303, 1992

    • Search Google Scholar
    • Export Citation
  • 12.

    Handforth A, , DeGirogio CM, , Schachter SC, , Uthman BM, , Naritoku DK, & Tecoma ES, et al: Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51:48–55, 1998 Handforth A, DeGirogio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, et al: Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51:48–55, 1998

    • Search Google Scholar
    • Export Citation
  • 13.

    Henry TR, , Bakay RAE, , Votaw JR, , Pennell PB, , Epstein CM, & Faber TL, et al: Acute vagus nerve stimulation selectively alters blood flow in somatosensory and limbic cortex and the cerebellum of patients with complex partial seizures. Epilepsia 38 (Suppl 8):144, 1997 (Abstract) Henry TR, Bakay RAE, Votaw JR, Pennell PB, Epstein CM, Faber TL, et al: Acute vagus nerve stimulation selectively alters blood flow in somatosensory and limbic cortex and the cerebellum of patients with complex partial seizures. Epilepsia 38 (Suppl 8):144, 1997 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 14.

    Holder LK, , Wernicke JF, & Tarver WB: Treatment of refractory partial seizures: preliminary results of a controlled study. Pacing Clin Electrophysiol 15:1557–1571, 1992 Holder LK, Wernicke JF, Tarver WB: Treatment of refractory partial seizures: preliminary results of a controlled study. Pacing Clin Electrophysiol 15:1557–1571, 1992

    • Search Google Scholar
    • Export Citation
  • 15.

    Kamath MV, , Upton ARM, , Talalla A, & Fallen EL: Neurocardiac responses to vagoafferent electrostimulation in humans. Pacing Clin Electrophysiol 15:1581–1587, 1992 Kamath MV, Upton ARM, Talalla A, Fallen EL: Neurocardiac responses to vagoafferent electrostimulation in humans. Pacing Clin Electrophysiol 15:1581–1587, 1992

    • Search Google Scholar
    • Export Citation
  • 16.

    Kao LI, & Crill WE: Penicillin-induced segmental myoclonus. I. Motor responses and intracellular recording from motorneurons. Arch Neurol 26:156–161, 1972 Kao LI, Crill WE: Penicillin-induced segmental myoclonus. I. Motor responses and intracellular recording from motorneurons. Arch Neurol 26:156–161, 1972

    • Search Google Scholar
    • Export Citation
  • 17.

    Ko D, , Heck C, , Grafton S, , Apuzzo ML, , Couldwell WT, & Chen T, et al: Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2 15O blood flow imaging. Neurosurgery 39:426–431, 1996 Ko D, Heck C, Grafton S, Apuzzo ML, Couldwell WT, Chen T, et al: Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2 15O blood flow imaging. Neurosurgery 39:426–431, 1996

    • Search Google Scholar
    • Export Citation
  • 18.

    Krahl SE, , Clark KB, , Smith DC, & Browning RA: Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia 39:709–714, 1998 Krahl SE, Clark KB, Smith DC, Browning RA: Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia 39:709–714, 1998

    • Search Google Scholar
    • Export Citation
  • 19.

    Lockard JS, , Congdon WC, & DuCharme LL: Feasibility and safety of vagal stimulation in monkey model. Epilepsia 31 (Suppl 2):S20–S26, 1990 Lockard JS, Congdon WC, DuCharme LL: Feasibility and safety of vagal stimulation in monkey model. Epilepsia 31 (Suppl 2):S20–S26, 1990

    • Search Google Scholar
    • Export Citation
  • 20.

    Lothman EW, & Somjen GG: Motor and electrical signs of epileptiform activity induced by penicillin in the spinal cords of decapitated cats. Electroenceph Clin Neurophysiol 41:237–252, 1976 Lothman EW, Somjen GG: Motor and electrical signs of epileptiform activity induced by penicillin in the spinal cords of decapitated cats. Electroenceph Clin Neurophysiol 41:237–252, 1976

    • Search Google Scholar
    • Export Citation
  • 21.

    McLachlan RS: Suppression of interictal spikes and seizures by stimulation of the vagus nerve. Epilepsia 34:918–923, 1993 McLachlan RS: Suppression of interictal spikes and seizures by stimulation of the vagus nerve. Epilepsia 34:918–923, 1993

    • Search Google Scholar
    • Export Citation
  • 22.

    Naritoku DK, , Morales A, , Pencek TL, & Winkler D: Chronic vagus nerve stimulation increases the latency of the thalamocortical somatosensory evoked potential. Pacing Clin Electrophysiol 15:1572–1578, 1992 Naritoku DK, Morales A, Pencek TL, Winkler D: Chronic vagus nerve stimulation increases the latency of the thalamocortical somatosensory evoked potential. Pacing Clin Electrophysiol 15:1572–1578, 1992

    • Search Google Scholar
    • Export Citation
  • 23.

    National Institutes of Health Consensus Conference: Surgery for epilepsy. JAMA 264:729–733, 1990 National Institutes of Health Consensus Conference: Surgery for epilepsy. JAMA 264:729–733, 1990

    • Search Google Scholar
    • Export Citation
  • 24.

    Penry JK, & Dean JC: Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results. Epilepsia 31 (Suppl 2):S40–S43, 1990 Penry JK, Dean JC: Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results. Epilepsia 31 (Suppl 2):S40–S43, 1990

    • Search Google Scholar
    • Export Citation
  • 25.

    Rajna P, & Lona C: Sensory stimulation for inhibition of epileptic seizures. Epilepsia 30:168–174, 1989 Rajna P, Lona C: Sensory stimulation for inhibition of epileptic seizures. Epilepsia 30:168–174, 1989

    • Search Google Scholar
    • Export Citation
  • 26.

    Ricardo JA, & Koh ET: Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res 153:1–26, 1978 Ricardo JA, Koh ET: Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res 153:1–26, 1978

    • Search Google Scholar
    • Export Citation
  • 27.

    Rutecki P: Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia 31 (Suppl 2):S1–S6, 1990 Rutecki P: Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia 31 (Suppl 2):S1–S6, 1990

    • Search Google Scholar
    • Export Citation
  • 28.

    Ryan GP, , Hackman C, & Davidoff RA: Spinal seizures and excitatory amino acid-mediated synaptic transmission. Neurosci Lett 44:161–166, 1984 Ryan GP, Hackman C, Davidoff RA: Spinal seizures and excitatory amino acid-mediated synaptic transmission. Neurosci Lett 44:161–166, 1984

    • Search Google Scholar
    • Export Citation
  • 29.

    Salinsky MC, & Burchiel KJ: Vagus nerve stimulation has no effect on awake EEG rhythms in humans. Epilepsia 34:299–304, 1993 Salinsky MC, Burchiel KJ: Vagus nerve stimulation has no effect on awake EEG rhythms in humans. Epilepsia 34:299–304, 1993

    • Search Google Scholar
    • Export Citation
  • 30.

    Schlag MG, , Hopf R, & Redl H: Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model. Neurosurgery 47:1463–1467, 2000 Schlag MG, Hopf R, Redl H: Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model. Neurosurgery 47:1463–1467, 2000

    • Search Google Scholar
    • Export Citation
  • 31.

    Suenaga N, , Oishi R, & Fukuda T: The role of locus coeruleus in decapitation convulsions of rats. Brain Res 177:83–93, 1979 Suenaga N, Oishi R, Fukuda T: The role of locus coeruleus in decapitation convulsions of rats. Brain Res 177:83–93, 1979

    • Search Google Scholar
    • Export Citation
  • 32.

    Tubbs RS, , Wellons JC III, , Patwardhan RV, , Oakes WJ, & Wyss JM: The effectiveness of Hering's nerve stimulation in controlling penicillin-induced seizures in the rat is dependent on the amygdala. Pediatr Neurosurg 37:231–234, 2002 Tubbs RS, Wellons JC III, Patwardhan RV, Oakes WJ, Wyss JM: The effectiveness of Hering's nerve stimulation in controlling penicillin-induced seizures in the rat is dependent on the amygdala. Pediatr Neurosurg 37:231–234, 2002

    • Search Google Scholar
    • Export Citation
  • 33.

    Upton ARM: Editorial. Pacing Clin Electrophysiol 15:1543–1544, 1992 Upton ARM: Editorial. Pacing Clin Electrophysiol 15:1543–1544, 1992

    • Search Google Scholar
    • Export Citation
  • 34.

    Uthman BM, , Wilder BJ, , Hammond EJ, & Reid SA: Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. Epilepsia 31 (Suppl 2):S44–S50, 1990 Uthman BM, Wilder BJ, Hammond EJ, Reid SA: Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. Epilepsia 31 (Suppl 2):S44–S50, 1990

    • Search Google Scholar
    • Export Citation
  • 35.

    Vagus Nerve Stimulation Study Group: A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 45:224–230, 1995 Vagus Nerve Stimulation Study Group: A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 45:224–230, 1995

    • Search Google Scholar
    • Export Citation
  • 36.

    van den Pol AN, , Obrietan K, & Belousov A: Glutamate hyperexcitability and seizure-like activity throughout the brain and spinal cord upon relief from chronic glutamate receptor blockade in culture. Neuroscience 74:653–674, 1996 van den Pol AN, Obrietan K, Belousov A: Glutamate hyperexcitability and seizure-like activity throughout the brain and spinal cord upon relief from chronic glutamate receptor blockade in culture. Neuroscience 74:653–674, 1996

    • Search Google Scholar
    • Export Citation
  • 37.

    Woodbury DM, & Woodbury JW: Effects of vagal nerve stimulation on experimentally induced seizures in rats. Epilepsia 31 (Suppl 2):S7–S19, 1990 Woodbury DM, Woodbury JW: Effects of vagal nerve stimulation on experimentally induced seizures in rats. Epilepsia 31 (Suppl 2):S7–S19, 1990

    • Search Google Scholar
    • Export Citation
  • 38.

    Woodbury JW, & Woodbury DM: Vagal stimulation reduces the severity of maximal electroshock seizures in intact rats: use of a cuff electrode for stimulating and recording. Pacing Clin Electrophysiol 14:94–107, 1991 Woodbury JW, Woodbury DM: Vagal stimulation reduces the severity of maximal electroshock seizures in intact rats: use of a cuff electrode for stimulating and recording. Pacing Clin Electrophysiol 14:94–107, 1991

    • Search Google Scholar
    • Export Citation
  • 39.

    Yu J, , Chambers WW, , Liu CN, , Herdman SJ, & Chen WP: Induction of spinal seizures by natural stimulation in cats. Brain Res 299:323–330, 1984 Yu J, Chambers WW, Liu CN, Herdman SJ, Chen WP: Induction of spinal seizures by natural stimulation in cats. Brain Res 299:323–330, 1984

    • Search Google Scholar
    • Export Citation
  • 40.

    Zabara J: Inhibition of experimental seizures in canines by repetitive vagal stimulation. Epilepsia 33:1005–1012, 1992 Zabara J: Inhibition of experimental seizures in canines by repetitive vagal stimulation. Epilepsia 33:1005–1012, 1992

    • Search Google Scholar
    • Export Citation
  • 41.

    Zanchetti A, , Wang SC, & Moruzzi G: The effect of vagal afferent stimulation on the EEG pattern of the cat. Electroencephalography Clin Neurophysiol 4:357–361, 1952 Zanchetti A, Wang SC, Moruzzi G: The effect of vagal afferent stimulation on the EEG pattern of the cat. Electroencephalography Clin Neurophysiol 4:357–361, 1952

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 121 21 7
Full Text Views 27 1 0
PDF Downloads 48 0 0
EPUB Downloads 0 0 0