Selective Neuromodulation of the Vagus Nerve

Vagus nerve stimulation (VNS) is an effective technique for the treatment of refractory epilepsy and shows potential for the treatment of a range of other serious conditions. However, until now stimulation has generally been supramaximal and non-selective, resulting in a range of side effects. Selective VNS (sVNS) aims to mitigate this by targeting specific fiber types within the nerve to produce functionally specific effects. In recent years, several key paradigms of sVNS have been developed—spatially selective, fiber-selective, anodal block, neural titration, and kilohertz electrical stimulation block—as well as various stimulation pulse parameters and electrode array geometries. sVNS can significantly reduce the severity of side effects, and in some cases increase efficacy of the treatment. While most studies have focused on fiber-selective sVNS, spatially selective sVNS has demonstrated comparable mitigation of side-effects. It has the potential to achieve greater specificity and provide crucial information about vagal nerve physiology. Anodal block achieves strong side-effect mitigation too, but is much less specific than fiber- and spatially selective paradigms. The major hurdle to achieving better selectivity of VNS is a limited knowledge of functional anatomical organization of vagus nerve. It is also crucial to optimize electrode array geometry and pulse shape, as well as expand the applications of sVNS beyond the current focus on cardiovascular disease.

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Cognition-enhancing effect of vagus nerve stimulation on refractory epilepsy secondary to lissencephaly: A case report.

Psychology & Neuroscience ◽

10.1037/pne0000120 ◽

2018 ◽

Vol 11 (1) ◽

pp. 80-85

Author(s):

Rodrigo Marmo da Costa e Souza ◽

Felipe Ricardo Pereira Vasconcelos De Arruda ◽

Jose Anderson Galdino Santos ◽

Jamerson De Carvalho Andrade ◽

Suellen Mary Marinho Dos Santos Andrade ◽

...

Keyword(s):

Case Report ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Refractory Epilepsy ◽

Enhancing Effect

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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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Ictal heart rate changes and the effects of vagus nerve stimulation for patients with refractory epilepsy

Neuropsychiatric Disease and Treatment ◽

10.2147/ndt.s142714 ◽

2017 ◽

Vol Volume 13 ◽

pp. 2351-2356 ◽

Cited By ~ 6

Author(s):

Wei Chen ◽

Fangang Meng

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Refractory Epilepsy

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Vagus Nerve Stimulation (VNS) in Super Refractory New Onset Refractory Status Epilepticus (NORSE)

Case Reports in Neurological Medicine ◽

10.1155/2019/7852017 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Mohankumar Kurukumbi ◽

James Leiphart ◽

Anam Asif ◽

Jing Wang

Keyword(s):

Status Epilepticus ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Refractory Epilepsy ◽

Refractory Status Epilepticus ◽

Refractory Status ◽

History Of ◽

Electrographic Seizures ◽

New Onset

The treatment protocol of status epilepticus has many associated toxicities so there is interest in alternate nonmedicinal therapies for managing New Onset Refractory Status Epilepticus (NORSE) patients. Vagus nerve stimulation (VNS) is an FDA-approved therapy for refractory epilepsy that has been shown to decrease the frequency and severity of seizures. We present the case of a patient with new-onset refractory status epilepticus (NORSE) whose seizures were successfully treated with vagus nerve stimulation. A 25-year-old male with no history of epilepsy or other neurological disorders presented with altered mental status and generalized tonic-clonic seizures following a two-week history of an upper respiratory tract infection. Lumbar puncture showed neutrophilic pleocytosis, and he was treated for bacterial and viral meningoencephalitis. In spite of treatment, his seizures began increasing in frequency. On day three, the patient entered status epilepticus (SE) refractory to intensive pharmacotherapy with maximal doses of valproate, levetiracetam, and propofol. On day four, SE remained refractory, so pentobarbital was introduced with targeted burst suppression pattern on electroencephalography (EEG). Patient continued to be refractory to these measures, so a vagus nerve stimulator (VNS) was implanted (day eight). Following VNS implantation, EEG demonstrated significant reduction of seizure activity and subsequent magnet swiping continued aborting electrographic seizures. No SE or electrographic seizures were reported for seventy-two hours, but few occasional discharges were reported. Seizures eventually recurred on day fourteen and the patient succumbed to his multiple comorbidities on day seventeen. Due to the efficacy of VNS in refractory epilepsy, there was interest in using it in refractory status epilepticus. Multiple case reports have described a benefit from implantation of VNS in the treatment of SE. The successful use of VNS to acutely terminate status epilepticus for seventy-two hours in this critically ill patient adds to current evidence that there is utility in using VNS for refractory status epilepticus.

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Vagus nerve stimulation may be a sound therapeutic option in the treatment of refractory epilepsy

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2013000100006 ◽

2013 ◽

Vol 71 (1) ◽

pp. 25-30 ◽

Cited By ~ 4

Author(s):

Murilo S. Meneses ◽

Samanta F. B. Rocha ◽

Cristiane Simão ◽

Heraldo Nei Hardt Laroca dos Santos ◽

Cleudi Pereira ◽

...

Keyword(s):

Vagus Nerve ◽

Seizure Frequency ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Palliative Treatment ◽

Refractory Epilepsy ◽

Therapeutic Option ◽

Treatment Objective

INTRODUCTION: Refractory epilepsy accounts for 20 to 30% of epilepsy cases and remains a challenge for neurologists. Vagus nerve stimulation (VNS) is an option for palliative treatment. OBJECTIVE: It was to study the efficacy and tolerability of VNS in patients implanted with a stimulator at the Curitiba Institute of Neurology (INC). METHODS: A case study of six patients with refractory epilepsy submitted to a VNS procedure at the INC in the last four years was described and discussed. RESULTS: Mean age at time of implantation was 29 years. Mean follow-up was 26.6 months. Seizure frequency decreased in all patients (40-50% (n=2) and >80% (n=4)). Three patients no longer required frequent hospitalizations. Two patients previously restricted to wheelchairs started to walk, probably because of improved mood. CONCLUSION: In this population, VNS proved to be a sound therapeutic option for treating refractory epilepsy.

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