Volume 8, Issue 1 January 2012
One of the most often asked questions by other physicians and all of my patients is in regards to vagus nerve stimulation. Almost everyone has a curiosity about this therapy and more importantly does it work and what does it mean to me in terms of potential benefits or problems. I hope to clear up some of these issues today.
Vagus nerve stimulation was approved in 1997 by the U.S. Food and Drug Administration as add-on treatment to medication for refractory partial onset seizures in patients who are 12 years of age and older. Moreover, the device was also approved for the treatment of depression as well. The therapy is available in several dozen countries and has been used in more than 50,000 patients around the world. .
Vagus nerve stimulation refers to the fact that the device is attached or looped around the vagus nerve in the neck.
The actual system is made up of a pulse generator somewhat similar to a pacemaker, an electrode or special wire that attaches to the vagus nerve stimulation and then a programming wand that attaches to a computer with software in order for the device to be programmed by the physician. The pacemaker portion, otherwise known as the pulse generator, transmits an electrical signal to the vagus nerve through the wire. The software allows placement of the wand over the pulse generator for reading, changing, stimulation, or for that matter turning off the device. When the device is turned on, each stimulation can last anywhere from 30 seconds or longer. The actual pacemaker or pulse generator device is quite small; it is made out of titanium, a metal that is usable with magnetic resonance imaging (MRI). The device itself is implanted on the left side and the reason for this is because the right vagus nerve, as there is one on each side of the neck, has more of a direct input to the heart and could potentially slow down the heart if it was implanted on the right. Therefore, all vagus nerve stimulation is done on the left. The actual device is placed in a pocket of tissue under the arm with another incision in the neck. The best way to understand how this device works is to look at the diagram above.
The device has been studied extensively in a number of clinical trials. There were two very important clinical trials that were conducted in the late 1980s early 1990s which led to the ultimate approval of the device by the U.S. FDA. These studies revealed that there was a 24% -28% reduction in seizures per day. The responder rate --patients who had a 50% or more reduction in seizure frequency-- after three months of treatment was between 23-31%. The device has been studied extensively over the long term. It appears that individuals have improved seizure control over time. At two years some studies have reported up to 40-50% of patients having a marked seizure reduction of 50% or more compared to seizures before treatment. Therefore, the device seems to benefit individuals over time as opposed to a fast benefit.
The efficacy of lacosamide was established in three 12-week randomized, double-blind, multi-center studied enrolling adult patients. Patients enrolled in these studies exclusively had partial-onset seizures with or without secondary generalization that were not adequately controlled on one to three other antiepileptic drugs. The patient that would typically enroll in these trials tended to have somewhat severe epilepsy, with an average of four or more partial-onset seizures every 28 days, and no seizure-free period exceeding more than 21 days.
The studies found that at its best, the median percentage reduction of seizure frequency was 35%; 37.3%; and 39% in the 3 studies. Fifty percent (50%) reduction seizure frequency was achieved in 33%-35% who received 200 mg of the pill; 38.3%-41% with those taking 400 mg. Although lacosamide was tested at doses higher than 400 mg, the FDA approved the drug up to a dose of 400 mg, due to the fact that higher doses produced more side effects than benefits.
How does the device stop seizures?
The mechanism by which vagus nerve stimulation reduces seizures is unknown despite numerous studies. The vagus nerve in the human body influences numerous areas in the brain and other organs. It is believed because the vagus nerve has such broad connections throughout the entire nervous system that the stimulation has been able to improve or reduce the abnormal electrical signals which cause seizures. The method by which this occurs is unclear. It may cause a release of certain neurotransmitters ( brain chemicals) which help to quiet the brain. Despite the numerous studies that have been looked at to assess how the device works, to this date, it is still not certain the effect by which it seems to produce benefit.
Although the device clearly has shown effect benefits, it is important to note this is not a cure for epilepsy. Rather, vagus nerve stimulation is a way to help control seizures but does not in any way completely stop seizures except in very rare instances.
The type of seizures that vagus nerve stimulation helps is also uncertain. Almost all seizure types have improved with the use of vagus nerve stimulation. However, some studies have suggested that specific seizure types such as atonic seizures ( drop seizures) may actually be specifically stopped by VNS therapy
Individuals who are offered vagus nerve stimulation and proceed with the operation are typically either hospitalized overnight on the same day as surgery or in some cases have outpatient surgery performed for implantation. Typically a surgeon with experience in operating in that neck region is the one who will implant the device. The patient is typically under general anesthesia although local or regional anesthesia has been used. A test is performed in the operating room to check that the system is indeed working. The other thing that is checked in the operating room is whether there are any sudden effects on the heart. The placement of the electrodes around the vagus nerve is critical to success. This, in fact, is probably the most critical aspect of the procedure so that there can be fewer side effects related to the device after the individual is implanted. Antibiotics to prevent infection may be given to the patient in the operating room or post-operatively. Discharge education will typically include care of the incision and use of a magnet. Swiping a magnet across the device itself will lead to an emergency rescue dose of the stimulation. Taping a magnet over the device itself can actually turn the device off.
The device is typically turned on about two weeks after the implant to allow for sufficient healing around the vagus nerve and also to make certain that there is less chance for problems such as issues where the vocal cord which is typically associated with the vagus nerve has a chance to be less impacted by the device. The device is typically started at a very small electrical current typically measured as 0 .25 milliamps. The device is turned on for 30 seconds at a time and off for 5 minutes. The current is increased over time to make it comfortable. The device can be set on a more rapid cycle of 30 seconds every 1.8 minutes or a shorter if the physician feels that the individual may benefit by this.
The device is powered by a battery. The typical battery life is 7-10 years and this does require a surgery to change out the battery.
The actual surgical complications of the device are rare. There have been reports of an electrode or wire breaking which can occur but has been improved upon by later versions of the device. Infections at the site of surgery are unusual but may occur. Fluid accumulation around the site can occur in up to 2% of cases. The more concerning and problematic of the side affects are vocal cord paralysis which occurs in 1% of individuals. This may occur because of excessive manipulation of the vagus nerve and subsequent damage to the vagal artery. Other side effects which tend to occur is when the device itself is delivering the stimulation. Typically these include hoarseness of the voice, a gentle cough or a feeling of tightening in the neck. Throat pain has been reported. It is important that if you have these effects that you let your physician know so that they can quickly adjust the device appropriately. It is also important to let the physician know of any problems with gastrointestinal or stomach pain as the vagus nerve influences the gastrointestinal system. There have been clinical studies that have looked to see whether there is the change in how your stomach and digestive system works in relationship to vagus nerve stimulation. However, no problems have been found. Nevertheless, diarrhea and some types of abdominal pain should be reported should they occur.
Death has been reported in very rare instances. There was an analysis performed by the British Medical Journal in which they reported a significant sudden unexplained death in epilepsy patients implanted with the device. However, this study has been refuted by the fact that this seemed to reflect patients with difficult to control seizures that are not completely cured rather than the device itself causing the problem.
There are some positive benefits to the device. As already noted, the device has been studied in individuals with depression and has been noted to have a beneficial response for this. Therefore, one could see potential improvement in mood associated with vagus nerve stimulation. Other reports have suggested improved benefits with memory although this has not been proven to occur.
Advantages and/or Disadvantages
The advantages to vagus nerve stimulation are primarily the fact that it is a new and different way of treating seizures and may be complementary to medications. Therefore, the device is intended to be used with add-on medications. Medications may potentially be lowered over time but that should not be an expectation. Therefore, the biggest advantage is that the device may be combined with medications. However, the converse side of this issue or disadvantage is the fact that the device is not a cure. Another disadvantage is the fact that the device requires surgery for placement. Because surgery is involved there is a potential of infection around the incision and although scars with the device are minimal it needs to be carefully considered particularly for those individuals who are worried about the appearance of a scar in an exposed area. Another potential disadvantage is cost. Because it is an operation, this will clearly have a more expensive price tag associated with it than medications. Most insurance plans, including Medicare, cover the cost of the device. The decision whether to proceed is very important and should be discussed carefully with both the surgeon and the neurologist. The device will require programming over time and you will need to increase visits over the first several months after implantation in order to get the device appropriately adjusted.
One advantage related to this device is the fact that one does not have to remember to take medication or to do anything for that matter. Once the device is turned on, there is nothing more to do. This is perfect for those who do not want to be reminded about their seizures. Another potential advantage is that swiping a magnet across the device, as already noted, releases an urgent electrical stimulation and gives the individual some control particularly when there is a cluster of seizures or an acute seizure occurring. For those who want to turn the device off, the same magnet can be taped onto the chest and can turn the device off until the magnet is taken off the chest. Again this allows some element of independence from the physician for the patient. The last disadvantage associated with the device is that as already noted, this is a battery operated device. Therefore, a battery change will be needed. Currently there is no way to accurately predict when the battery life of the device will cease to work. When seizures unexpectedly increase suddenly after someone has had the device implanted for several years then it is likely the time that one should consider replacing the device.
How can the Epilepsy Therapy Project Help
The Epilepsy Therapy Project is committed to the development of new devices and new treatments for epilepsy and bringing them to the market as soon as it is safe and feasible. By the use of our seizure diary we can help delineate whether a therapy such as vagus nerve stimulation is working. By the information on our epilepsy.com web site we hope to empower all individuals to understand if the vagus nerve stimulator is an appropriate choice of treatment. As they say, information is power and we are here and committed to improve everyone’s knowledge of all the various treatments available for epilepsy in order to provide the best quality of life for the individual with epilepsy.
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HIGHLIGHTS FROM THE AMERICAN EPILEPSY SOCIETY MEETING:
The 2011 Hoyer Lecture on Epilepsy is presented by Dr. Steven C. Schachter, Professor of Neurology at Harvard Medical School. His topic is "Psychosocial Aspects of Epilepsy: State of the Art" and is followed by a special performance of Cynthia Folio's "When the Spirit Catches You" by the Relache Ensemble.
Hallway Conversations, a series of audio podcasts in which Dr. Joseph Sirven, Editor-in-Chief of epilepsy.com, has the pleasure of having a brief conversation with thought leaders and newsmakers in the field of epilepsy on a range of seizure related topics. The series is intended as a second opinion to help clinicians understand the latest research as explained by the investigator or perhaps focus on a clinical issue with the help of a leading epilepsy authority on the topic. The purpose is to frame the latest epilepsy news in the right context so as to better manage patients with seizures and improve quality of life. We hope that you find the series informative and helpful and that you join us in listening on a regular basis.
Listen to the latest podcasts from 2012 in the Hallway Conversations series from:
January 6, 2012
Executive Director, Epilepsy Therapy Project
Web Director, Epilepsy Therapy Project
Topic: The newly redesigned epilepsy.com
November 10, 2011
Christopher de Giorgio, MD
Associate Professor of Neurology
Gregory Worrell, MD
Associate Professor of Neurology
Mayo Clinic in Rochester
Topic: Devices for Epilepsy: Past, Present and Future
Interested In Participating?
If you are interested in participating in a Hallway Conversation interview, please contact ETP at: firstname.lastname@example.org