110 Vagal Nerve Stimulator

Case 110 Vagal Nerve Stimulator

Nazer H. Qureshi

Clinical Presentation

A 16-year-old boy with cerebral palsy and a long history of seizures is referred to you for a vagal nerve stimulator (VNS) placement.
The mother wishes the generator to be placed on the right side because of flexion contractures in the left upper extremity.

Questions

What is the mechanism of action of VNS?
What is the United States Food and Drug Administration (FDA-) approved indication for VNS in the treatment of epilepsy?
How do you identify the vagal nerve in the neck for implantation?
Where on the vagal nerve should the lead wires be ideally placed and is there any concern regarding VNS placement on the right side?
What are the reported results for VNS use in epilepsy?
What are the usual initial VNS settings for use?
What are the usual side effects of VNS placement?
The patient returns to you a month later with pus draining out from the battery site. What are your options?
Antibiotics and your debridement cleared the infection. What are you going to do next?
A few weeks after reimplantation of the battery at the new site, the patient presents with infection along the leads extending into the neck. What are your options now?
Nine months after all the infection is cleared, the patient is referred to you once more for reimplantation of VNS. What are your options now?
Other than the treatment of seizures, is there any other indication for VNS placement?

Answers

What is the mechanism of action of VNS?

The precise mechanism of action of VNS is unknown.

It has been suggested that VNS has action on various regions of the brain including the locus ceruleus, amygdala, hippocampus, and contralateral somatosensory cortex.

Another proposed mechanism of action is the possibility that VNS increases γ-aminobutyric acid (GABA) and glycine levels in the brain.

Ben-Menachem et al.1 measured amino acid and neurotransmitter metabolite concentrations in cerebrospinal fluid (CSF) samples of patients on clinical trials of VNS before and 3 months after VNS placement.

Their results showed an increase in GABA level among patients that failed to respond to VNS stimulation, those with a lower setting of stimulation, as well as patients who had undergone a long-term VNS stimulation.

Yet others have indicated that VNS decreases cortical epileptiform activity directly and possibly alsoaffects blood flow through different regions of the brain.^2,2
What is the FDA-approved indication for VNS in the treatment of epilepsy?
- In 1997, the FDA approved implantation of VNS as an adjunctive therapeutic modality in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizure that are refractory to antiepileptic medications.⁴
- Although the FDA indication for VNS excludes other types of epilepsies, most epileptologists and neurosurgeons believe the indications for placement of VNS to be more widespread.^5,6
How do you identify the vagal nerve in the neck for implantation?
- The vagal nerve is in the posterior part of carotid sheath between the carotid artery and internal jugular vein.
- Caution is advised to differentiate the vagus from the phrenic nerve, which traverses in the anterior part of the sheath.
Where on the vagal nerve should the lead wires be ideally placed, and is there any concern regarding VNS placement on the right side?
- What the mother wished was for the battery pocket to be placed on the right side secondary to flexion contractures of the left upper extremity. This can be done and should be considered given the contractures.7
- The ideal place for implantation of leads on vagus is in the middle part of the neck proximal to the branches to the cardiac plexus.
- The three lead wires are placed from proximal to distal along the nerve.
What are the reported results for VNS use in epilepsy?
- In the Vagus Nerve Stimulation Study Group E05 trial, the median reduction in seizure frequency at 12 months after completion of the initial double-blind study was 45%.⁸
- Overall, 35% of the patients had a reduction in seizures of at least 50%; 20% of the patients demonstrated a 75% reduction in their seizure frequency.⁸
- Similar results have also been reported in the XE5 trial.⁹
- A 12-year retrospective review of the effectiveness of VNS in 48 patients with intractable partial epilepsy reported a mean decrease in seizure frequency by 26% after 1 year, 30% after 5 years, and 52% after 12 years.¹⁰
What are the usual initial VNS settings for use?
- Although some centers initiate stimulation the day after implantation, usually the generator is kept turned off and an increase in output is advanced by the neurologists after a 2-week postoperative period.
- Typically, the output is adjusted to tolerance, using a 30-Hz signal frequency, with a 500-microsecond pulse width for 30 seconds of “on” time and 5 minutes of “off” time.
- This is not standard and multiple variations exist depending on the clinical situation.
What are the usual side effects of VNS placement?
- The most common side effects of VNS are cough, hoarseness, and throat pain.
- Unlike antiepileptic drugs, VNS has not been associated with adverse effects such as depression, fatigue, confusion or cognitive impairment, etc.
The patient returns to you a month later with pus draining out from the battery site. What are your options?
- Infection at the site of battery would necessitate removal of the battery and treatment with debridement and antibiotics.¹¹
- The lead wire could be left in place and moved away from the infected site.
Antibiotics and your debridement cleared the infection. What are you going to do next?
- Once the infection is cleared, a new battery should be implanted at another site in the anterior chest wall and reconnected to the lead wires.
A few weeks after reimplantation of the battery at the new site, the patient presents with infection along the leads extending into the neck. What are your options now?
- If there is suspicion of infection along the lead wires, then the neck incision should be opened and explored.¹²
- The wires should be cut close to the vagus nerve’s lead implantation site and the leads should be left in situ.
- Attempting to remove the leads from the vagus nerve will result in injury to the nerve.
Nine months after all the infection is cleared, the patient is referred to you once more for reimplantation of VNS. What are your options now?
- The vagus nerve can be explored proximally in the neck and if it is possible to implant another set of leads on the vagus nerve, it should be done proximal to its cardiac branches.
Other than the treatment of seizures, is there any other indication for VNS placement?
- Other indications for use of VNS include refractory depression, and research is being conducted for its use in the treatment of such varied diseases as anxiety disorders, Alzheimer disease, migraines, and fibromyalgia.^13,14