Neuromodulation Therapy with Vagus Nerve Stimulation for Intractable Epilepsy: A 2-Year Efficacy Analysis Study in Patients under 12 Years of Age

To study the efficacy of vagus nerve stimulation (VNS) therapy as an adjunctive treatment for intractable epilepsy in patients under 12 years of age, we analyzed 2-year postimplant data of 35 consecutive patients. Of the 35 patients, 18 (51.4%) at 6 months, 18 (51.4%) at 12 months, and 21 (60.1%) at 24 months showed ≥50% reduction in seizure frequency (responders). Although incremental seizure freedom was noted, no patient remained seizure-free throughout the 3 study periods. Partial response (≥50% seizure reduction in 2 or less study periods) was seen in 8 (22.9%) patients. Twelve patients (34.3%) were nonresponders. Out of 29 patients with primary generalized epilepsy, 20 (68.9%) and, out of 6 patients with focal epilepsy, 3 (50%) had ≥50% seizure control in at least one study period. No major complications or side effects requiring discontinuation of VNS therapy were encountered. We conclude that (1) patients with intractable primary generalized epilepsy respond better to VNS therapy, (2) cumulative effect of neuromodulation with improving responder rate to seizure freedom with continuation of VNS therapy is noted, and (3) VNS therapy is safe and is well tolerated in children receiving implant under 12 years of age.

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Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy

Neurosurgery ◽

10.1227/neu.0000000000001165 ◽

2015 ◽

Vol 79 (3) ◽

pp. 345-353 ◽

Cited By ~ 78

Author(s):

Dario J. Englot ◽

John D. Rolston ◽

Clinton W. Wright ◽

Kevin H. Hassnain ◽

Edward F. Chang

Keyword(s):

Vagus Nerve ◽

Seizure Frequency ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Intractable Epilepsy ◽

Progressive Increase ◽

Seizure Type ◽

Seizure Freedom ◽

Outcome Registry ◽

Over Time

AbstractBACKGROUND:Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response.OBJECTIVE:To elucidate rates and predictors of seizure freedom with VNS.METHODS:We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies.RESULTS:Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio “OR”, 1.89; 95% confidence interval “CI”, 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom.CONCLUSION:Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients.

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A.6 Vagus Nerve Stimulation in patients with therapy resistant generalized epilepsy

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.268 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S15-S15

Author(s):

AS Suller Marti ◽

SM Mirsattari ◽

KW MacDougall ◽

D Steven ◽

A Parrent ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Hospital Admissions ◽

Focal Epilepsy ◽

Limited Information ◽

Best Response ◽

History Of ◽

Generalized Epilepsy

Background: For patients with generalized epilepsy who do not respond to anti-seizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox Gastaut Syndrome(LGS) and genetic generalized epilepsy(GGE). Methods: We identified patients with a diagnosis of Lennox-Gastaut Syndrome or Genetic Generalized Epilepsy, who underwent VNS implantation, between1997 and July 2018. Results: A total of 46 patients were included in this study with a history of therapy resistant generalized epilepsy. The mean age at implantation was 24 years(IQR= 17.8-31 years) and 50%(n=23) were female. The most common etiologies were GGE in 37%(n=17) and LGS in 63%(n=29). Median follow-up since VNS implantation was 63 months(IQR:31-112.8months). 41.7%(n=12) of the LGS group became responders, and 64.7%(n=11) in the GGE group. The best response in seizure reduction was seen in generalized tonic-clonic seizures. There was a reduction of seizure-related hospital admissions from 89.7%(N=26) pre-implantation, to 41.4%(N=12) post-implantation (p<0.0001). The frequency of side effects due to the stimulation was similar in both groups(62.1% in LGS and 61.1% in GGE). Conclusions: VNS is an effective treatment in patients with therapy resistant generalized epilepsy, especially GGE.

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Patient Characteristics Associated with Seizure Freedom after Vagus Nerve Stimulation in Pediatric Intractable Epilepsy: An Analysis of “Super-Responders”

Journal of Pediatric Epilepsy ◽

10.1055/s-0041-1739489 ◽

2021 ◽

Author(s):

Goichiro Tamura ◽

William B. Lo ◽

Ivanna Yau ◽

Kerry A. Vaughan ◽

Cristina Go ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Intractable Epilepsy ◽

Patient Characteristics ◽

Response To Therapy ◽

The Other ◽

Seizure Freedom ◽

Device Implantation ◽

Exceptional Patient

AbstractClinical responses to vagus nerve stimulation (VNS) therapy for intractable epilepsy can be unpredictable, and factors that predict response to therapy are elusive. Minority of children undergoing VNS achieve seizure freedom. The current study aimed to characterize this exceptional patient population, defined as “super-responders” (SRs). Retrospective data were collected from 150 children who underwent VNS at a single pediatric institution. The patients' mean age at VNS device implantation was 12.0 years (range, 3.09–17.9 years). Ten SRs (6.7%) were identified who achieved and maintained seizure freedom for longer than 1 year following implantation. The interval between epilepsy onset and VNS device implantation was significantly shorter in SRs than in the other children (mean epilepsy duration 5.72 vs. 8.44 years, respectively; p = 0.032). SRs also had a significantly shorter proportion of life with epilepsy compared with the other children (mean ratio of epilepsy duration to age at implantation 0.52 vs. 0.71, respectively; p = 0.023). SRs reported their seizure freedom relatively early (six patients within 6 months and all patients within 12 months after implantation) at relatively low device settings (mean output current 0.81 mA at their last follow-up). Compared with conventional models, responsive VNS models with autostimulation features did not increase the ratio of SRs. No other clinical or imaging characteristic difference between SRs and the other children was found in this cohort. The current study showed a significant association between shorter epilepsy duration and shorter proportion of life with epilepsy and seizure freedom after VNS.

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Implanted vagus nerve stimulation in 126 patients: surgical technique and complications

Perspectives in Surgery ◽

10.33699/pis.2020.99.7.304-310 ◽

2020 ◽

Vol 99 (7) ◽

Keyword(s):

Vagus Nerve ◽

Vocal Cord ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Pulse Generator ◽

Operative Procedure ◽

Intractable Epilepsy ◽

Vagal Nerve ◽

University Hospital ◽

Nerve Stimulator

Introduction: Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy to reduce the frequency and intensity of seizures. A bipolar helical electrode is placed around the left vagus nerve at the cervical level and is connected to the pulse generator placed in a subcutaneous pocket, most commonly in the subclavian region. Methods: Between March 1998 and October 2019, we performed 196 procedures related to the vagal nerve stimulation at the Neurosurgery Department in Motol University Hospital. Of these, 126 patients were vagal nerve stimulator implantation surgeries for intractable epilepsy. The cases included 69 female and 57 male patients with mean age at the time of the implantation surgery 22±12.4 years (range 2.1−58.4 years). Results: Nine patients (7.1%) were afflicted by complications related to implantation. Surgical complications included postoperative infection in 1.6%, VNS-associated arrhythmias in 1.6%, jugular vein bleeding in 0.8% and vocal cord paresis in 2.4%. One patient with vocal cord palsy also suffered from severe dysphagia. One patient (0.8%) did not tolerate extra stimulation with magnet due to a prolonged spasm in his throat. The extra added benefit of vagus stimulation in one patient was a significant reduction of previously regular severe headaches. Conclusion: Vagus nerve stimulation is an appropriate treatment for patients with drug-resistant epilepsy who are not candidates for focal resective surgery. Implantation of the vagus nerve stimulator is a relatively safe operative procedure.

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Impact of Cardiac‐Based Vagus Nerve Stimulation Closed‐Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective, Individual‐Control Study

Neuromodulation Technology at the Neural Interface ◽

10.1111/ner.13290 ◽

2020 ◽

Author(s):

Arthur Cukiert ◽

Cristine Mella Cukiert ◽

Pedro Paulo Mariani ◽

Jose Augusto Burattini

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Closed Loop ◽

Seizure Outcome ◽

Individual Control ◽

Generalized Epilepsy ◽

Control Study ◽

Closed Loop Stimulation

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Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes

Seizure ◽

10.1016/j.seizure.2003.09.002 ◽

2004 ◽

Vol 13 (5) ◽

pp. 340-345 ◽

Cited By ~ 59

Author(s):

Mark D Holmes ◽

Daniel L Silbergeld ◽

Diane Drouhard ◽

Alan J Wilensky ◽

Linda M Ojemann

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Generalized Epilepsy

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Vagus nerve stimulation for partial and generalized epilepsy from infancy to adolescence

Journal of Neurosurgery Pediatrics ◽

10.3171/2012.5.peds11489 ◽

2012 ◽

Vol 10 (3) ◽

pp. 200-205 ◽

Cited By ~ 30

Author(s):

Eric M. Thompson ◽

Susan E. Wozniak ◽

Colin M. Roberts ◽

Amy Kao ◽

Valerie C. Anderson ◽

...

Keyword(s):

Vagus Nerve ◽

Seizure Frequency ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Pediatric Patients ◽

Medication Use ◽

Partial Epilepsy ◽

Seizure Duration ◽

Antiepileptic Medication ◽

Generalized Epilepsy

Object Vagus nerve stimulation (VNS) is approved by the FDA for the treatment of partial epilepsy in patients older than 12 years. Authors of the current study performed a large retrospective analysis and comparison of VNS outcomes in children with an age ≥ and < 12 years, including those with partial and generalized epilepsy. Methods A retrospective review of the records of pediatric patients (age < 18 years) who had undergone primary VNS system implantation between 2001 and 2010 by a single pediatric neurosurgeon was undertaken. Considered data included demographics, epilepsy type (partial vs generalized), seizure frequency, seizure duration, postictal period duration, and antiepileptic medication use. Results One hundred forty-six patients (49% female) were followed up for a mean of 41 months after VNS implantation. Thirty-two percent of patients had partial epilepsy and 68% had generalized epilepsy. After VNS system implantation, seizure frequency was reduced in 91% of patients, seizure duration in 50%, postictal period in 49%, and antiepileptic medication use in 75%. There was no significant difference in age, sex, or duration of follow-up according to epilepsy type. Neither was there any significant difference in seizure frequency reduction, seizure duration, postictal period, medication use, overall clinical improvement, or improvement in quality of life based on an age ≥ or < 12 years or epilepsy type. Conclusions Vagus nerve stimulation reduced both seizure frequency and antiepileptic medication use in the majority of pediatric patients regardless of sex, age cohort, or epilepsy type. Vagus nerve stimulation also reduced seizure duration and postictal period in approximately half of the pediatric patients. Contrary to expectation, children with partial epilepsy do not benefit from VNS at higher rates than those with generalized epilepsy.

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Genetic variations of adenosine kinase as predictable biomarkers of efficacy of vagus nerve stimulation in patients with pharmacoresistant epilepsy

Journal of Neurosurgery ◽

10.3171/2021.3.jns21141 ◽

2021 ◽

pp. 1-10

Author(s):

Yifan Zhang ◽

Xiongfei Wang ◽

Chongyang Tang ◽

Yuguang Guan ◽

Fan Chen ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Refractory Epilepsy ◽

Genetic Variations ◽

Adenosine Kinase ◽

Minor Allele ◽

Seizure Freedom ◽

Seizure Reduction ◽

Genes Encoding

OBJECTIVE Vagus nerve stimulation (VNS) is an alternative treatment option for individuals with refractory epilepsy, with nearly 40% of patients showing no benefit after VNS and only 6%–8% achieving seizure freedom. It is presently unclear why some patients respond to treatment and others do not. Therefore, identification of biomarkers to predict efficacy of VNS is of utmost importance. The objective of this study was to explore whether genetic variations in genes involved in adenosine kinase (ADK), ecto-5′-nucleotidase (NT5E), and adenosine A1 receptor (A1R) are linked to outcome of VNS in patients with refractory epilepsy. METHODS Thirty single-nucleotide polymorphisms (SNPs), including 9 in genes encoding ADK, 3 in genes encoding NT5E, and 18 in genes encoding A1R, were genotyped in 194 refractory epilepsy patients who underwent VNS. The chi-square test and binary logistic regression were used to determine associations between genetic differences and VNS efficacy. RESULTS A significant association between ADK SNPs rs11001109, rs7899674, and rs946185 and seizure reduction with VNS was found. Regardless of sex, age, seizure frequency and type, antiseizure drug use, etiology, and prior surgical history, all patients (10/10 patients [100%]) with minor allele homozygosity at rs11001109 (genotype AA) or rs946185 (AA) achieved > 50% seizure reduction and 4 patients (4/10 [40%]) achieved seizure freedom. VNS therapy demonstrated higher efficacy among carriers of minor allele rs7899674 (CG + GG) (68.3% vs 48.8% for patients with major allele homozygosity). CONCLUSIONS Homozygous ADK SNPs rs11001109 (AA) and rs946185 (AA), as well as minor allele rs7899674 (CG + GG), may serve as useful biomarkers for prediction of VNS therapy outcome.

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