Vagus nerve stimulation (VNS) is FDA approved for the treatment of medically intractable partial onset epilepsy in patients over 12 years of age. Efficacy and safety issues have been addressed in several large clinical trials. The current device is manufactured by Cyberonics (Houston, TX) and includes a pair of helical electrodes (2mm or 3mm diameter), a battery powered generator (models 101/102), a tunneling tool, software and programming tools, and supplies for the patient. The model 102 generator is smaller and incorporates a single pin electrode design to avoid incorrect lead connections.
Indications for vagus nerve stimulation include patients with medically intractable partial epilepsy without resective surgical options or those where surgery is contraindicated for medical reasons. Contraindications include patients with history of previous left neck surgery or prior cervical vagotomy. Relative contraindications may include pregnancy, asthma, chronic pulmonary disease, active peptic ulcer disease, and insulin dependent diabetes mellitus. Common adverse effects include coughing, hoarseness, dyspnea, and headache. These effects are seen during vagus nerve stimulation and tend to habituate with time. Serious adverse effects have been reported and include vocal cord paralysis, infection, Horner's syndrome, lower facial muscle paresis, and cardiac arrest. Sudden unexplained death has also occurred, but not at a rate different than the epileptic population. Other mechanical complications can occur such as lead fracture or generator malfunction.
Patient Selection
Patients with epilepsy uncontrolled by anticonvulsant medications may be candidates for vagus nerve stimulation. The definition of medically intractable generally includes a description of an adequate drug trial without unacceptable side effects. The exact definition of an adequate drug trial is not clear. At our institution, most candidates for vagus nerve stimulation have been on many medications without appreciable benefit. Because the efficacy of vagus nerve stimulation is not much higher than a new medication trial, it is the author's opinion that vagus nerve stimulation candidates should exhaust medication options prior to consideration for vagus nerve stimulation therapy.
Although not FDA approved for treatment in the pediatric population, there is growing evidence that vagus nerve stimulation is safe and similarly effective in this population.
Anatomy
The vagus nerve is a mixed cranial nerve containing approximately 80% sensory fibers. Efferent fibers innervate the larynx and provide parasympathetic control to the heart, lungs, and abdominal viscera. The right vagus nerve innervates the sinoatrial node of the heart while the left innervates the atrioventricular node. In the dog model, vagus nerve stimulation of the right vagus nerve caused more cardiac slowing then the left. For this reason, the left human vagus nerve is implanted. Adverse cardiac complications have not been seen, perhaps because vagus nerve stimulation of the nerve can be done on a segment away from the origin of the cardiac branches.
Vagus Nerve Stimulation Surgical Technique
The vagus nerve stimulation procedure itself is straight forward and could be done by any surgeon familiar with neck anatomy. Neurosurgeons are ideally suited because of the familiarity with epilepsy and their active roles in comprehensive epilepsy centers.
On the day of vagus nerve stimulation surgery, the electrode and generator are inspected and tested. A spare generator and electrode should be available in case the primary device fails. Once verified that the equipment is functioning, pre-operative antibiotics are given and the patient undergoes a general anesthetic prior to the vague nerve stimulation.
A primary surgeon and assistant participate in the vagus nerve stimulation procedure. The vagus nerve stimulation patient is positioned supine on the table with the anesthesia team at the head. The primary surgeon stands at the left side of the neck, his assistant opposite him. The patient's head is positioned on a donut and slightly extended and turned to the right. The surgeon may use a roll under the scapula to help extend the neck. After preoperative antibiotics are given, the neck and chest is prepped with betadine scrub and paint solutions. The electrodes for the vagus nerve stimulation are implanted in the left neck by either a "carotid" incision or a transverse "collar" incision. A 3-4 cm incision should be centered at mid-neck level (cricothyroid interval) and on the anterior border of the sternocleidomastoid muscle. The skin is incised with a #10 scalpel and the skin edges undermined with Metzenbaum scissors. The platysma muscle is divided in the direction of its fibers and the deep cervical fascia is opened to identify the sternocleidomastoid muscle. This muscle is mobilized and retracted laterally to expose the neurovascular bundle. This bundle is then incised to expose the carotid artery and jugular vein. The vein is retracted laterally and the main trunk of the vagus nerve is usually found deep between the artery and vein. Approximately 3-4cm of nerve should be mobilized from surrounding adventitia. Stay sutures in the carotid sheath can be utilized to deliver the nerve towards the surgeon. Mobilization and handling of the nerve should be done with fine forceps. Care must be taken to avoid injuring the main trunk or one of the branches.
Once the nerve dissection has been completed, the left chest incision is marked along the anterior axillary line and opened with a #10 scalpel. A subcutaneous pocket over the pectoralis fascia is created with sharp and blunt dissection. The pocket must be large enough to accommodate the generator for vagus nerve stimulation while avoiding strain on the incision line.
The electrode array is removed from the sterile package and brought onto the surgical field. Skin edges should be isolated with sterile gauze and the electrode tunneling device passed from the neck incision to the chest incision in a plane just above the sternocleidomastoid muscle and the clavicle. Once the tunneler is passed, the metal rod is removed leaving the plastic sheath in place. The electrode cables are then inserted into the plastic sheath and the sheath pulled through to the chest. The ends of the cable are wrapped in a sterile towel until connected to the generator.
The electrodes are implanted on the vagus nerve by gently winding the electrode spirals around the nerve. The electrode array consists of three spiral coils. The first is not an electrode but a tethering coil. The next is the cathode electrode and the most distal is the anode electrode. The actual electrode coils should be handled with care to prevent electrode breakage. Each coil has a small string attached, which is useful for deploying it around the nerve. The deployment of the electrode coils should be done with the primary surgeon and assistant surgeon working together to pass the electrode spirals around the nerve without placing undue tension on the electrodes or the nerve. Fine jeweler's forceps work well during this stage of the procedure. Once coiled properly around the nerve, a strain relief loop should be created above the carotid sheath with excess electrode cable. The loop is tied down with silicone ties provided in the electrode kit. These ties should be sutured in place to cervical fascia deep to the platysma muscle. Avoid tying to muscle as the electrode may shift position when the patient moves their neck.
The pins are then connected to the generator. The following procedure is correct for the model 101 (the model 102 generator has only one pin to connect to the generator). The positive electrode connector is marked with a white stripe on the lead. The end of this connector should slide into the generator receptor marked positive. Make sure to slide the connector all the way in and then tighten it with the wrench provided. This wrench will give way when the appropriate torque is reached. Repeat the same procedure for the negative electrode and then prepare to test the system.
The neurologist or intra-operative neurophysiologist may assist you at this stage. The computer and hand-held wand are powered up. Make sure the batteries in the hand-held wand are new. Place the hand-held wand in a sterile drape and place it over the generator in the surgical field. During this programming, lead impedance and all connections are tested to verify integrity of the system. A one minute lead test is then performed with a stimulus delivered at 20 Hz frequency, output current of 1 mA, and a pulse width of 500 microseconds. During this test, the patient's vital signs and EKG are monitored for bradycardia. Some centers will then turn on the system at the lowest setting, while most prefer to wait one or two weeks before initiating stimulation therapy.
Once the system is tested, the generator is internalized and sewn to the pectoralis fascia with a permanent suture (prevents generator migration). Both incisions are then irrigated with antibiotic solution and closed anatomically with self-absorbing skin sutures. The patient is then discharged to home after 4-6 hours of observation in the recovery room. Prior to discharge following vagus nerve stimulation, the patient should be assessed for vocal cord function.
Post-operative Management
Patients should be counseled to observe the wound for signs of infection following the vagus nerve stimulation procedure. The sutures are self-absorbing and need not be removed. Return to normal pre-operative activities is all owed after 48 hours. Patients should be warned that this therapy will not result in cessation of seizures and they should continue to practice seizure precautions. A return to care in two weeks with the treating neurologist is indicated to begin or increase vagus nerve stimulation.
References
1. The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for the treatment of medically intractable seizures. Neurology 1995; 45:224-230.
2. Morris GL, Mueller WM, and the Vagus Nerve Stimulation Study Group E01-E05. Long term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 1999; 53:1731-1735.
3. Amar AP, DeGiorgio CM, Tarver WB, et al. Long term multicenter experience with vagus nerve stimulation for intractable partial seizures. Stereotact Funct Neurosurg 1999; 73: 104-108.
4. Fisher RS, Handforth A. Reassessment: vagus nerve stimulation for epilepsy. Neurology 1999; 53:666-669.
5. Amar AP, Heck CN, Levy ML, et al. An institutional experience with cervical vagus nerve trunk stimulation for medically intractable epilepsy: rationale, technique, and outcome. Neurosurgery 1998; 43: 1265-1280.
6. Farooqui S, Boswell W, Hemphill JM, et al. Vagus nerve stimulation in pediatric patients with intractable epilepsy: case series and operative technique. American Surgeon 2001; 67: 119-121.
7. Murphy JV and the Pediatric VNS Study Group. Left vagal nerve stimulation in children with medically refractory epilepsy. J Pediatr 1999; 134: 563-6.
8. Valencia I, Holder DL, Helmers SL, et al. Vagus nerve stimulation in pediatric epilepsy: a review. Pediatr Neurol 2001; 25: 368-376.
9. Rutecki P. Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia 1990; 31: S1-6.
