Abstract
The objective of this study is to evaluate the safety and efficacy of vagus nerve stimulation (VNS) in very young children suffering from catastrophic epilepsy and status epilepticus. We reviewed files of 60 VNS-implanted children at our institution and we selected six very young patients, less than 3 years old (mean age at implant 1.6 years). All patients suffered from severe cognitive impairment and catastrophic epilepsy with underlying diagnosis of hemimegalencephaly (1), hypoxic-ischemic encephalopathy (1), tuberous sclerosis complex (1), and malignant migrating partial epilepsy of infancy (3). Three patients were VNS-implanted during admission at intensive care unit (ICU) after developing life-threatening status epilepticus. The mean follow-up time was 41.6 months. The VNS was implanted using a single cervical incision. No surgery-related complications were observed. Four of six children have shown a significant, persistent improvement in seizure control (range, 60–90%). In patients with status, insertion of the vagal nerve stimulator allowed early cessation of status and discharge from ICU. Quality of life and parental satisfaction improved and for three children there was some milestone evolution. Catastrophic epilepsy in infancy can be devastating and difficult to treat with drugs and surgery. If resective surgery is inappropriate or refused, VNS can be considered as a well-tolerated and effective procedure even in toddlers affected by severe epilepsy and multiple developmental disabilities.
Similar content being viewed by others
References
Aldenkamp AP, Majoie HJ, Berfelo MW et al (2002) Long-term effects of 24-month treatment with vagus nerve stimulation on behaviour in children with Lennox-Gastaut syndrome. Epilepsy Behav 3(5):475–479 Oct
Alexopulos AV, Kotagal P, Loddenkemper T, Hamel J, Bingaman W E (2006) Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy. Seizure 15(7):491–503 Oct
Benifla M, Rutka JT, Logan W (2006) Vagal nerve stimulation for refractory epilepsy in children: indications and experience at The Hospital for Sick Children. Childs Nerv Syst 22(8):1018–1026
Blount Jp, Tubbs RS, Kankiravatana P, Kiel S et al (2006) Vagus nerve stimulation in children less than 5 years old. Childs Nerv Syst 22:1167–1169
Hallbok T, Lundgren J, Stjernqvist K et al (2005) Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behaviour and mood. Seizure 14(7):504–513 Oct
Hirshberg LM, Chiu S, Frazier LA (2005) Emerging brain-based interventions for children and adolescents: overview and clinical perspective. Child Adolesc Psychiatr Clin N Am 14(1):1–19 Jan
Kosoff EH, Pyzik PL (2004) Improvement in alertness and behavior in children treated with combination topiramate and vagus nerve stimulation. Epilepsy Behav 5(2):256–259
Loddenkamper T, Holland KD, Stanford LD, Kotagal P, Bingman W, Willie E (2007) Developmental outcome after surgery in infancy. Pediatrics 119(5):930–935 May
Majoie Hj, Berfelo MW, Aldenkamp AP, Renier WO, Kessels AG (2005) Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study. Seizure 14(1):10–18 Jan
Murphy Jv, Torkelson R, Dowler I et al (2003) Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center. Arch Pediatr Adolesc Med 157(6):560–564
Patwardhan RU, Dellabadia J, Grier L, Nanda A (2005) Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report. Surg Neurol 64(2):170–173 Aug
Renfroe JB, Wehless JW (2002) Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy. Neurology 59(6 Suppl 4):S26–S30 24
Ryclicki F, Zamponi N, Trignani R et al (2006) Vagus nerve stimulation: clinical experience in drug-resistant pediatric epileptic patients. Seizure 15(7):483–490 Oct
Rychlicki F, Zamponi N, Cesaroni E et al (2006) Complications of vagal nerve stimulation for epilespy in children. Neurosurg Rev 29(2):103–107 Apr
Saneto RP, Sotero de Menezes MA, Ojemann JC et al (2006) Vagus nerve stimulation for intractable seizures in children. Pediatr Neurol 35(5):323–326 Nov
Smyth MD, Tubbs RS, Bebin EM et al (2003) Complications of chronic vagus nerve stimulation for epilepsy in children. J Neurosurg (99):500–503 Sep
Sparrow S, Cicchetti DV (1985) Diagnostic use of vineland adaptive behavior scales. J Pediatr Psychol 10(2):215–225
Tecoma Es, Iragui VJ (2006) Vagus Nerve stimulation use and effect in epilepsy: what have we learned? Epilepsy Behav 8(1):127–136 Feb
Vitale SA, Andriola MA, Gabis L et al (2001) Vagus nerve stimulation in the toddler age group. Epilepsia 42(suppl 7)
Wheless JW (2004) Nonpharmacological treatment of the catastrophic epilepsies of childhood. Epilepsia 45(5):17–22
Winston Kr, Levishon P, Miller BR et al (2001) Vagal nerve stimulation for status epilepticus. Pediat Neurosurg 3484:190–192
Author information
Authors and Affiliations
Corresponding author
Additional information
Comments
Dominik Zumsteg and Heinz Gregor Wieser, Zürich, Switzerland
Vagus nerve stimulation (VNS) was the first adjunctive treatment for epilepsy using electrical stimulation that has been approved by the FDA in 1997 for the treatment of medically intractable epilepsy in patients over age 12. The VNS device provides chronic intermittent stimulation to the left vagus nerve through a surgically implanted circumneural bipolar cuff electrode. Premarketing trials have shown that 30 to 40% of individuals with medically intractable partial seizures had a significant improvement, defined as a seizure reduction of ≥50% [1]. Postmarketing experience suggested that the device may also be effective in the treatment of generalized seizures [2]. The initiation of extra cycles by the patient by placing a magnet over the device has been shown to abort or ameliorate seizures in about a third [3].
However, with a decade experience in VNS, we know that the level of effectiveness is moderate, leaving many patients with frequent seizures: The device generally reduces rather than eliminates seizures. The experience with VNS in very young children, particularly in children younger than 5 years, is limited. There are only a few uncontrolled studies based on small cohorts, suggesting that VNS may also be safe and moderately effective in the very young [4, 5]. In this article, Zamponi et al. again report on the safety and efficacy of VNS in a small cohort of very young children suffering from catastrophic epilepsy with frequent seizures and severe psychomotor retardation. There were no surgery-related complications. The authors found a 60 to 90% seizure reduction in four of six patients, and a 4-month seizure-free period in a 2.7-year-old girl, subsequent to a 40% seizure reduction during the early course of treatment (however, it is pertinent to note that some of these effects may also have been related to modifications of antiepileptic drug treatment during the study period). Quality of life and parental satisfaction is said to have improved (as assessed by an analog scale), but this improvement was not significant when using the standardized Vineland Adaptive Behavior Scale for quality of life evaluation. Considering that complete seizure control is a key predictor of improved quality of life, the reductions in seizure frequency may not have been great enough to affect quality of life.
Now, does a moderate level of VNS effectiveness affect quality of life in a way that would justify the surgical procedure in toddlers? Would it be good enough for you, if you had seizures? Shouldn’t improvement with VNS be much better than that found with medications to justify the increased risk (and costs) of an invasive procedure? There may be no definite general answers to these questions. What we do know is that VNS in patients with epilepsy, irrespective of age, appears to be less efficacious than had been hoped. Moreover, it is important to bear in mind that surgical sham control in VNS studies is a priori precluded due to unavoidable though usually mild to moderate side effects with VNS, such as hoarseness, discomfort in the throat, cough or swallowing difficulties. In that sense, the investigation of VNS in toddlers is interesting, considering that there is hardly any placebo effect to be expected in very young children. Nevertheless, to truly ascertain how much of any benefit is related to VNS, it would be very informative to know the actual effectiveness of VNS in those 1,450 patients aged 0 to 5 years implanted with the device (the number 1,450 is based on the implant registration cards returned to Cyberonics, mentioned by the authors in this issue). There is not much hope considering the publication bias (that is, the phenomenon that studies with positive results are more likely to be published than studies with negative results).
References
1. The Vagus Nerve Stimulation Study Group (1995) A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 45:224–230
2. Labar D, Murphy J, Tecoma E (1999) Vagus nerve stimulation for medication-resistant generalized epilepsy. E04 VNS Study Group. Neurology 52:1510–1512
3. Morris GL III (2003) A retrospective analysis of the effects of magnet-activated stimulation in conjunction with vagus nerve stimulation therapy. Epilepsy Behav 4:740–745
4. Vitale SA, Andriola MR, Gabis L, Luckow LR (2001) Vagus nerve stimulation in the toddler age group. Epilepsia 42(Suppl.7):175
5. Blount JP, Tubbs RS, Kankirawatana P, Kiel S, Knowlton R, Grabb PA, Bebin M (2006) Vagus nerve stimulation in children less than 5 years old. Childs Nerv Syst 22:1167–1169
Rights and permissions
About this article
Cite this article
Zamponi, N., Rychlicki, F., Corpaci, L. et al. Vagus nerve stimulation (VNS) is effective in treating catastrophic 1 epilepsy in very young children. Neurosurg Rev 31, 291–297 (2008). https://doi.org/10.1007/s10143-008-0134-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10143-008-0134-8