Vagus nerve stimulation

  • The text on this page is abstracted from Cyberonics physician and patient information as well as published reviews and clinical studies. Photographs reproduced with permission from Cyberonics and patients.

    What is vagus nerve stimulation?

    Vagus nerve stimulation (VNS) is a treatment for uncontrolled epilepsy. VNS reduces the frequency and severity of epileptic seizures in some children. VNS involves insertion of a pulse generator, similar to a heart pacemaker, under the skin on the chest that sends intermittent electrical signals to the brain by stimulating the left vagus nerve in the neck. The pulse generator is programmed to stimulate in two ways. It is individually programmed to automatically stimulate in the background, typically ON for 30 seconds and OFF for 3 minutes. In addition, the pulse generator can be manually activated in between programmed stimulation times by the child or caregiver, by placing a provided magnet over the pulse generator and then removing it.  This gives extra stimulation at pre-programmed settings.

    It is not fully understood how VNS works, but the theory is that the VNS over time modulates nerve pathways involved in seizures.  VNS works differently to antiepileptic medications and dietary treatments.

    Who is suitable for vagus nerve stimulation?

    VNS is generally considered for children with epilepsy which significantly affects the life of the child and family, is not adequately controlled by antiepileptic medication, and is not treatable with surgery. Assessment by a paediatric neurologist experienced in comprehensive epilepsy management, including surgery, and VNS therapy is a prerequisite.

    What does the vagus nerve do?

    The vagus nerve is one of the cranial nerves, meaning a nerve that is connected directly to the brain. Output nerve fibres control muscles responsible for swallowing, coughing and voice sounds. Input nerve fibres transmit sensations and electrical feedback from the heart, lung, stomach and upper bowel to the brain. About 80% of the nerve fibres in the left vagus nerve are input fibres transmitting, from the body to the brain, and the output fibres have minimal heart connections, making the left vagus nerve a suitable "wire" into the brain.

    History of vagus nerve stimulation

    The first VNS device was implanted in 1988 in the United States of America. Regulatory approval as an adjunct therapy in reducing seizure frequency was granted in 1994 in Europe and 1997 in USA. The first implant in Australia was in 1994 and regulatory approval by the Therapeutic Goods Administration (Australia) was granted in April 2000. More than 20,000 people worldwide have had a VNS implanted, 5,500 of this number being under 18 years of age. In Australia since 1994, a total of 146 people have had a VNS implant, 66 of this number being children. The device has been replaced in 13 adults and 5 children following battery end of life.

    What does a vagus nerve stimulator look like?

    VNS image 2 front view

    VNS image 1 side view

    What is involved prior to vagus nerve stimulation?

    Children require referral from their neurologist or paediatrician to an epileptologist at the RCH for assessment of suitability. The child's seizure history, prior and current treatments, behaviour and past medical problems need to be reviewed. Alternative treatments are also discussed.

    Families are fully informed about VNS before embarking on this form of treatment. The epileptologist and the epilepsy nurse specialist discuss realistic expectations of VNS, how VNS works, the surgical procedure, post operative care, advantages and disadvantages, continuing medication, the admission process and precautions. Families will meet with the neurosurgeon prior to planned surgery.

    What happens during the admission for insertion?

    The child and family present to the Surgical Admissions reception on the 3rd floor on the morning of surgery. Usual medications are taken unless otherwise instructed by the neurologist. The anaesthetist assesses the child and routine blood tests are performed. Post-operative care is discussed with medical and nursing teams, particularly relating to pain management, oral intake, seizure management, antiepileptic medications and wound care. Parents may accompany their child to the pre-theatre waiting area.

    Implantation of the VNS pulse generator and lead wire requires an operation, which usually takes two hours. Children require a general anaesthetic and at least an overnight stay in hospital. Two incisions are made to implant the pulse generator and lead wire, one horizontally on the left side of the chest below the collar bone (clavicle) and one vertically in a skin fold on the left side of the neck. The stimulator with lead wire connection is inserted under the skin on the upper left chest wall. The lead wire is passed under the skin and the contacts are wrapped around the left vagus nerve.  The VNS unit is tested prior to skin closure but then left off.

    vns_line

    Diagrammatic View of insertion of VNS

    vns_scar

    Post-operative VNS insertion scars

    Children are admitted to the Cockatoo Ward following surgery and usually stay in hospital for one or two nights. Fluids and antibiotics are given by intravenous drip for at least 24 hours.  Regular assessment of the child's comfort continues throughout the hospital stay and oral pain killers are administered as required. Most children have minimal pain that is controlled by paracetamol. Oral pain killers continues at home as necessary.

    The two wound sites are covered with a clear waterproof dressing which allows for normal bathing and easy assessment of the wounds. No stich removal is required, as all stitches dissolve under the skin.

    Antiepileptic medications remain unchanged.

    The VNS is turned on 10 days post insertion.

    The scars will be quite reddened initially and will fade to white with time, depending on individual healing processes. In some people, scars on the chest remain red and may thicken and become raised.

    002.jpgNeurosurgical follow up occurs shortly after discharge from hospital and assessment of wound site will occur at this visit.  Regular appointments are scheduled with the neurologist, usually every 4 weeks initially. During these visits, the functioning of the VNS is checked, seizure history noted and the stimulating parameters increased, as tolerated, towards settings which are usually effective.

    Does vagus nerve stimulation work?

    VNS has been extensively studied in clinical trials around the world, including in children. The results vary depending on the patients studied and the design of the trial.

    The following is our summary of the available data:

    • About 30-50% of children gain a significant improvement in seizure control, with reduced seizure frequency or severity
    • Less than 10% of children become seizure free and most continue taking antiepileptic medication
    • Results are similar across all seizure types and syndromes, although there is some suggestion that children with Lennox-Gastaut syndrome and other severe epilepsies may respond better
    • Children with recurrent bouts of seizures that escalate to hospitalisation often benefit from VNS
    • Termination of prolonged seizures or seizure clusters is possible in some children
    • Currently there is no way to predict response to VNS
    • Many children have improvements in mood, alertness and overall quality of life, even in the absence of significant seizure improvement
    • Seizure reduction is often not evident for several months
    • Over time there may be a continued decline in seizures in many patients. 25% may have a reduction in seizure frequency at 3 months, increasing to 50% after 2 years

    What side effects or problems can occur?

    • The most common side effects reported with VNS are hoarse voice, pain or tingling in the throat or neck, cough, headache and ear pain. These effects are generally related to stimulation settings and settle over time or after reduction of stimulation settings.
    • Less common side effects of VNS are difficulty sleeping, weight loss, shortness of breath, reduced exercise tolerance, snoring and apnnoea during sleep, vomiting, facial flushing, dizziness and irritability
    • Swallowing problems and rarely aspiration may occur in some children with disablilities, feeding difficulties and reflux
    • Wound breakdown, wound infection and device damage are rare but potentially serious complications
    • Cessation of heart beat has been rarely reported in adults undergoing VNS implantation, during the intraoperative lead test, but this has not been reported in children

    Our experience with VNS at the Royal Children's Hospital

    We reviewed the outcome of VNS in 12 children aged 6-16 years who were implanted with VNS devices between 1998-2000.  Duration of VNS therapy was 2.6 to 5.3 years.  Eight children had multiple-daily seizures, including 4 with drop attacks and 3 with recurrent bouts of status requiring hospitalisation.

    VNS was removed in 2 children because of behaviour disturbance in one and weight loss and discomfort in another.  Of the 10 patients who continue with VNS therapy 4 have had >50% seizure reduction, 3 have had 30-40% seizure reduction, and 3 have had no real change in seizures.  Drop attacks ceased in 2 and status requiring hospitalisation ceased in 3.  No child is totally seizure-free and only 1 had medication reduced.  All five NCP100 devices were replaced at 3 years for diminished efficacy. 

    Precautions with vagus nerve stimulation

    VNS Magnet

     Physical trauma to the pulse generator or lead wire, such as with rough sport or neck manipulation, can damage the device.

    Equipment that may interfere with the stimulator should be avoided. These include strong magnets, hair clippers and loudspeakers. Some medical tests, such as MRI scans, can interfere with the device.  Always tell health professionals that your child has a VNS implanted.

    The neurologist or epilepsy nurse specialist should always be consulted prior to any medical imaging, diagnostic testing or surgical procedures, to ensure patient safety and device integrity.  The pulse generator may need to be turned off temporarily and special precautions may need to be taken with anaesthesia, surgery or scanning.

    *Always avoid areas where pacemaker warning signs are posted.

    The magnet provided for manual stimulation may damage credit cards, mobile phones, computer disks, televisions and other items affected by strong magnetic fields. Care should be taken to store magnet away from these types of equipment.

    What is the cost of a vagus nerve stimulator?

    Funding for VNS in Australia is complex, and varies between states and centres.  The VNS device and stimulating lead (NeuroCyberonics Prothesis® 102) actual cost is approximately $15,600. The VNS device contains a battery, which lasts between 7-10 years, depending on the programmed output current and frequency of stimulation. The replacement cost of a VNS device with a new battery is approximately $11,600.  Private health insurers should cover the cost of the device, as VNS Therapy is on the Australian Prosthesis List, but not the surgical procedure.  Some public hospitals have allocated funds for VNS therapy in public patients whose epilepsy meets specific criteria. The specific funding issues that apply to families should be discussed with the treating neurologist.

    References and links

    Commercial links

    The following company sites may be useful for further general information regarding VNS.

    Selected references

    Original Controlled Trials of VNS

    • Ben-Menachem E et al. Vagus Nerve Stimulation for Treatment of Partial Seizures: 1. A Controlled Study of Effect on Seizures. Epilepsia 1994; 35: 616-26.  [PubMed]
    • Ramsey RE et al. Vagus Nerve Stimulation for Treatment of Partial Seizures: 2. Safety, Side Effects, and Tolerability. Epilepsia 1994; 35: 627-36.  [PubMed]
    • George R et al. Vagus Nerve Stimulation for Treatment of Partial Seizures: 3. Long-Term Follow-Up on First 67 Patients Exiting a Controlled Study. Epilepsia 1994; 35: 637-43. [PubMed]
    • The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 1995; 45: 224-30.  [PubMed]
    • Ben-Menachem E et al. Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years. Neurology 1999; 52: 1265-7.  [PubMed]

    VNS Studies in Children

    • Murphy JV et al. Adverse Events in Children Receiving Intermittent Left Vagal Nerve Stimulation. Pediatr Neurol 1998;19:42-3.  [PubMed]
    • Parker APJ et al. Vagal Nerve Stimulation in Epileptic Encephalopathies. Pediatrics 1999; 103:778-82.  [PubMed]
    • Murphy JV and the Pediatric VNS Study Group. Left vagal nerve stimulation in children with medically refractory epilepsy. J Pediatrics1999;134:563-6.  [PubMed]
    • Helmers SL et al. Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol2001;16:843-8.  [PubMed]
    • Frost M et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia 2001;42:1148-52.  [PubMed]
    • Nagarajan L et al. VNS therapy in clinical practice in children with refractory epilepsy. Acta Neurol Scand 2002;105:13-7.  [PubMed]
    • Wheless JW and Maggio V. Vagus nerve stimulation therapy in patients younger than 18 years. Neurology 2002;59(Suppl 4):S21-5.  [PubMed]
    • Murphy JV et al. Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center. Arch Pediatr Adolesc Med 2003;157:560-4.  [PubMed]

    Reviews of VNS

    • Boon P et al. Cost-benefit of vagus nerve stimulation for refractory epilepsy. Acta Neurol Belg 1999;99:275-80.  [PubMed]
    • Valencia I et al. Vagus nerve stimulation in pediatric epilepsy: a review. Pediatr Neurol 2001;25:368-76.  [PubMed]
    • Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurology 2002;1:477-82.  [PubMed]