Long-term vagus nerve stimulation in the treatment of Lennox–Gastaut syndrome

doi:10.1016/j.yebeh.2009.07.038

Epilepsy & Behavior

Volume 16, Issue 2, October 2009, Pages 321-324

https://doi.org/10.1016/j.yebeh.2009.07.038 Get rights and content

Abstract

The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 30 patients with Lennox–Gastaut syndrome. Median observation time was 52 months (17–123). The effect parameters investigated were total number of seizures and different seizure types. The median reduction in number of seizures was 60.6%. The effects of VNS varied considerably between seizure types. Best effects were observed with atonic seizures (80.8% median reduction, number of responders: 8/12), followed closely by tonic seizures (73.3% median reduction, number of responders: 8/13). Least effects were with generalized tonic–clonic seizures (median reduction 57.4%, number of responders: 11/20). Additional positive effects included milder or shorter ictal or postictal phase in 16 patients. Improved alertness was reported in 76.7%. Adverse effects, of which drooling and voice alteration were most frequent, were reported in 20 patients. There was a statistically significant reduction in the median number of antiepileptic drugs used. The discontinuation rate was 16.7%.

Introduction

Vagus nerve stimulation (VNS) is a relatively new nonpharmacological treatment for epilepsy. It was commercially introduced in the United States in 1997 as an adjunctive therapy ‘‘in adults and adolescents over 12 years of age with partial onset seizures, which are refractory to antiepileptic medications’’ [1].

The device offers an alternative treatment for patients with pharmacoresistant epilepsy. It has been tried on several different patient groups [2], [3], [4], [5], [6], and its effect has been shown to be comparable to that of newer antiepileptic drugs (AEDs); VNS has been demonstrated to be as effective as gabapentin, and slightly less effective than lamotrigine and tiagabine [7].

Lennox–Gastaut syndrome (LGS) is one of the most severe and prognostically unfavorable epileptic encephalopathies, and patients with this syndrome respond poorly to AEDs. Because of the multifocal character of LGS, resective surgery is unsuitable for patients with this syndrome. Nonpharmacological treatment methods include ketogenic diet, corpus callosotomy, and VNS. Several studies have evaluated the short-term effect of VNS on seizure frequency in patients with LGS [2], [3], [4], [5], [6]. Earlier studies focused solely on the reduction in total number of seizures, with the exception of one study in which the effects of VNS on drop attacks, complex partial seizures (CPS), and atypical absences were assessed [8].

The purpose of this study was to evaluate retrospectively the long-term effects of VNS on patients with pharmacoresistant LGS, with special emphasis on different seizure types and adverse effects.

Section snippets

Patient selection

Data were collected from the medical records of 30 patients who were implanted with a VNS generator in the period 1997–2007 at Oslo University Hospital—Rikshospitalet, Norway. All patients had been followed up at the National Centre for Epilepsy. The inclusion criteria in this open retrospective study were a confirmed electroclinical diagnosis of LGS according to the criteria of the International League Against Epilepsy [9] and an observation time of more than 12 months.

Diagnosis

The diagnosis was

Population

The study population consisted of 17 males and 13 females, 18 of whom were under 18 years. The median age at implantation was 13.0 years (4.0–52.0 years). Median age at onset of epilepsy was 1.1 years (0.1–7.0 years), and median duration of epilepsy before implantation was 11.9 years. The patients were observed for a median of 52 months (17–123 months).

Antiepileptic drugs

The median number of AEDs in use before implantation was 3.0 (2–4) and the patients had tried a median of 10.5 AEDs. The most frequently used

Discussion

The most important finding in this study was the overall positive effect and tolerability of VNS in patients with LGS. The strengths of this study are the relatively large population sample compared with other studies of LGS and the long follow-up time (median = 52 months). Other studies have indicated that the positive effects of VNS increase with time [2], [13], [14], and this is supported by the results of our study with a very high responder rate even after several years. These results are

Acknowledgments

The authors gratefully thank Karl Otto Nakken and Leif Gjerstad for their valuable comments on the article.

References (16)

E.S. Tecoma et al.
Vagus nerve stimulation use and effect in epilepsy: what have we learned?
Epilepsy Behav
(2006)
A.V. Alexopoulos et al.
Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy
Seizure
(2006)
D. Labar
Vagus nerve stimulation for 1 year in 269 patients on unchanged antiepileptic drugs
Seizure
(2004)
H.J.M. Majoie et al.
Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study
Seizure
(2005)
J.A. Cramer et al.
Review of treatment options for refractory epilepsy: new medications and vagal stimulation
Epilepsy Res
(2001)
A. Handforth et al.
Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial
Neurology
(1998)
S.L. Helmers et al.
Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study
J Child Neurol
(2001)
M. Frost et al.
Vagus nerve stimulation in children with refractory seizures associated with Lennox–Gastaut syndrome
Epilepsia
(2001)

There are more references available in the full text version of this article.

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We designed a prospective, individual-controlled study to evaluate the effect of cardiac-based VNS (cbVNS) in a cohort of patients with generalized epilepsy (GE).
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Lennox-Gastaut syndrome (LGS) is a childhood-onset epileptic encephalopathy characterized by multiple types of medically intractable seizures, cognitive impairment, and generalized slow spike-wave discharges in electroencephalography (EEG). Although the onset of this epileptic syndrome occurs typically before eight years of age with a peak age between 3 and 5 years, lifelong persistence of the syndrome is usual. The evolution of clinical features, EEG findings, and paucity of knowledge about LGS among adult health care providers can make LGS significantly underdiagnosed in the adult population. Management of LGS remains problematic beyond childhood due to intractable seizures, the difficult transition from pediatric to adult neurologists, challenging behaviors, impaired cognition, poor quality of life, and disabled social life. In focusing on the management of LGS beyond childhood, this narrative review describes medical and surgical management of epilepsy, the transition from pediatric to adult care, and management of other common comorbidities associated with LGS. Several antiepileptic drugs (AEDs) such as lamotrigine, topiramate, felbamate, rufinamide, clobazam, and Epidiolex (pure pharmaceutical grade cannabidiol (CBD) oil) have been noted to be effective in well-designed, randomized controlled trials. Other non-pharmacological therapies, such as vagus nerve stimulation, ketogenic diet, and epilepsy surgery, have been frequently utilized in the management of intractable seizures associated with LGS. However, effective management of LGS requires a broader perspective to not only control seizures but improve the quality of life by addressing cognitive and behavioral problems, sleep disturbances, physical disability, social disability, and educational and employment challenges.
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Long-term vagus nerve stimulation in the treatment of Lennox–Gastaut syndrome

Abstract

Introduction

Section snippets

Patient selection

Diagnosis

Population

Antiepileptic drugs

Discussion

Acknowledgments

Epilepsy Behav

Seizure

Seizure

Seizure

Epilepsy Res

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial

Neurology

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study

J Child Neurol

Vagus nerve stimulation in children with refractory seizures associated with Lennox–Gastaut syndrome

Epilepsia