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Epilepsy

Vagal nerve stimulation device: its role in medically refractory partial epilepsy and reports of weight loss

 

Virginia Thornley, Neurologist, Epileptologist

@VThornleyMD

April 15, 2018

Introduction

The vagal nerve stimulation device is an implanted device that exerts its effort by pulses of electrical activity that stimulates the vagal nerve or cranial nerve X. It had initially been found to work in animal studies in the 1990’s then later applied in clinical studies.

Mechanism of action 

For years, the mechanism was unknown and was used rather effectively in the clinical realm. The elucidated mechanisms were thought to be that the vagal nerve stimulator modifies the highly synchronized electrical activity that occurs in epilepsy through desynchronization via the vagal nerve. In addition, there is increased regional cerebral perfusion, and there is increased GABA neurotransmitters which are inhibitory towards electrical activity causing seizures and a decrease in glutamate which is known to increase excitation with the brain. There are GABA-A receptor increases, an increase in locus ceruleus produced noradrenergic substances which are released through the vagal nerve and an increase in serotonin transmissions through the raphe nucleus.

Role in controlling seizures

In the original open-label trial in 5 clinical trials, the vagal nerve stimulation device was found to be effective in reducing seizures by 50%. 454 patients had the implanted device and clinical information was obtained from 440. A cardiac stimulation device was implanted along with a coil in the ipsilateral vagal nerve. At 1 year of implantation, more than 50% of reduction of seizures occurred in 36.8% of patients at year 1, 43.2% year 2, and 42.7% at year 3.  The most common side effect at year 2 was hoarseness of about 9.8% and headache in 4.5% and at 3 years there was shortness of breath in 3% (4).

In one retrospective study from 1997 to 2008, 436 patients were found with implanted vagal nerve stimulation devices from ages 1-76, 220 were women and 216 were men. 33 had poor follow-up and 3 had removal due to infection. The mean frequency of seizures was better at 50% reduction.  There was 90% better control on 90 patients, >75% control in 162 patients and 50% control in 255 patients, <50% control in 145 patients. Permanent damage to the vagal nerve happened in 2.8% or 11 patients out of the 400 patients (after the removal of the ones lost to follow-up and infected) (5).

Long-term value of vagal nerve stimulating device, effectiveness after 5 years

There have been many studies reported that it may be effective short-term. But there was one pediatric study that reported success in seizure control in longer than 5 years. In a study of 56 pediatric patients ages 4-17, >9.8% were seizure free after 9 months, 24% after 2 years, 46.4% after 3 years and 54% after 5 years.11 out of the 56 patients became seizure free. After 5 years 62% of the patients had fewer seizures after 5 years.

What happens from diagnosis to implantation to use

A patient is identified as medically refractory, meaning a patient who has already failed 2 or more agents. Once control is failed after 2 anti-epileptic drugs after an adequate dosage and trial,  the likelihood of being seizure free becomes significantly less.  It is usually applied to patients with partial seizures, the most common being temporal lobe epilepsy. After appropriate identification is done, the patient undergoes a procedure where a cardiac device is implanted under the skin which generates an electrical impulse. A wire or coil is attached to the vagal nerve which reacts to this signal and emits an electrical pulse which inhibits the seizure which is electrical activity in the brain by disrupting this through various mechanisms. The device can be programmed to have a set frequency, amount of power and can be set to automatic with features where the patient can apply a magnet to inhibit the seizure when it is about to occur. The magnet is typically swiped over the cardiac device which was implanted over the left side of the chest. The settings can be changed in the doctor’s office adjusting according to the number and frequency of seizures.

Common side effects

Some of the most common side effects reported include hoarseness, cough, throat irritation, dyspnea, insomnia, dyspepsia, and vomiting. The symptoms are related to the location of the device near the nerve causing local irritation and likely due to the functions subserved by the vagal nerve.

Incidental weight loss effect

Vagal nerve stimulation device was applied to treatment-resistant patients with depression where an incidental effect on weight loss was found. One study in 33 patients showed that the vagal nerve stimulator implanted in patients seemed to alter cravings for sweet food which may play a part in weight loss (2). There have been some conflicting studies proving that there is no weight loss in vagal nerve stimulating device at the settings recommended in epilepsy in 21 patients (3). In a large study of 503 patients from 15 study centers, vagal nerve blockade was applied intrabdominally. 294 patients were randomized to treated (192) and to control groups (102). Therapy involved electrical stimulation through an external power source to the vagal nerves in the subdiaphragm which inhibits afferent and efferent vagal transmission. At 12 months, the excess weight loss in the treated group was 17% and in the control group, it was 16%. There was no statistic difference between the two groups, however, the post-study analysis demonstrated a possible result in weight loss related to the system check of the devices using low charges which may have caused weight loss in the control group (6).

In conclusion

There is strong evidence that the vagal nerve stimulation device is effective at reducing seizures of >50% of the medication-resistant epilepsy patient. It is effective even after 5 years of implantation. There are very little side effects which are mild to moderate. In addition, it can cause weight loss.

References:

  1. Serdaroglu, et al, “Long-term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up,” Child’s Nervous System, 2016, 32 (4):641-646.
  2. Bodenlos, “Vagus nerve stimulation acutely alters food craving in adults with depression,” Appetite, 2007, 48: 145-153.
  3. Koren, et al, “Vagus nerve stimulation does not lead to significant changes in body weight in patients with epilepsy,” Epilepsy Behav. 2006;8:246–249.
  4. Morris, et al, “Long-term treatment with vagus nerve stimulation with refractory epilepsy,” Neurology, 1999, 53 (8):1731-1735.
  5. Elliot, et al, “Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response,” Epilepsy Behavior, 2011, Jan., 20(1):57-83.
  6. Sarr, et al, “The EMPOWER study:randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity,” Obes. Surg., 2012, Nov., 22 (11):1771-82.

 

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ketogenic diet, Uncategorized

Ketogenic diet, modified Atkins diet and what is in them: used in seizure control, can these be a weight loss solution to morbid obesity, a risk factor for cerebrovascular and cardiovascular disease?

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD

March 29, 2018

Introduction

Ketogenic diet has been used for seizure control when physicians started to notice a reduction of seizures in patients with a high ketone laden diet. This fell out of favor in the 1920’s with the onset of newer agents. As a side note, weight loss has been noted in those on a ketogenic diet.

Previously, guidelines have recommended a reduction in saturated fat which was thought to be the cause of the growing morbid obesity epidemic. Currently, it has been found that carbohydrates which are rich and refined may contribute towards the obesity epidemic. Sugar-laden sodas, the white bread which has refined flour, pizza batter made out of refined flour, all these food which are popular in theIt is no Western culture contribute to the morbid obesity as it is looming today.

How current culture sets the perfect stage for morbid obesity

The current western diet is about 50% carbohydrates. In addition, physical activity is at an all-time low compared to other eras. The current culture is designed as a sedentary and carbohydrate-rich eating culture. Everything nowadays is rapid pace. There are drive-through banks, drive-through pharmacies. Rather than having to physically go to a shop or order things in person,  many things can be done online or by phone reducing the daily need to exert physical activity. There is less time spent on physical activity compared to 100 years ago. If you go to neighborhoods, sidewalks no longer exist. Unless one lives in an urban environment where you are forced to walk to the bus station or live in cities amenable to walking or biking, the car is the mode of transport. Food is rich in carbohydrate, such hamburger buns, pizza dough, white bread or rolls. It is little wonder that morbid obesity abounds.  Food rich in sugar is abundant in grocery store aisles including donuts, cookies, baking packets. The colorful rich in anti-oxidant fresh fruits and vegetables are usually on the sides of the grocery shops, the food that is actually good for you and you need to take time out of your schedule to cook.

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Living a healthy diet is not just staying active but also eating the proper diet. Food that is closest to their original source are richest in nutrients. In short, the colorful vegetables you have to cook without any of the processing that takes place are the food richest in nutrients and have high anti-oxidant properties. Anti-oxidation is important in helping to combat a wide variety of diseases. Colorful fruits and vegetables are rich in fiber and more difficult to digest, hence, uses up more calories. Those which are high in refined carbohydrates are easily digested and contributes more towards obesity.

Components of the ketogenic diet and ketogenic diet variants

Ketogenic diet variants include modified Atkins diet, low glycemic index treatment, and medium chain diet. The ketogenic diet consists of 4:1 ratio of fat to carbohydrates shifting metabolism to the use of ketone bodies as a source of energy. A lower ratio is sometimes employed called the modified ketogenic diet with a 3:1 or 2:1 ratio of fat to carbohydrates. In the modified ketogenic diet, the palatability is improved and avoids the gastrointestinal symptoms associated with the ketogenic diet such as nausea. With the modified Atkins diet, carbohydrates are restricted to 10-20 grams a day, or a 1-2:1 ratio of protein to fat plus carbohydrates. In the low glycemic index treatment, carbohydrates are limited to 40-60 grams while 50-60% of the diet is fat and 20-30% is from protein. The medium-chain triglyceride diet employs oils as a supplement such as coconut oil. The palatability of these diets improve patient compliance and lessen the side effects of the ketogenic diet. Some patients also used the diets to incidentally lose weight in addition to treating seizures.

Ketogenic diet and evidence it works in losing weight

The ketogenic diet has a carbohydrate component of about 20-50 grams a day. It is not so much the restriction of the carbohydrates but the quality of carbohydrates that are ingested that causes people to shed pounds. High fiber, wheat, and whole grain carbohydrates portend a healthier diet as opposed to just restricting carbohydrates in general. In some clinical studies, it was found that weight loss was higher in those with a low carbohydrate diet compared to a low-fat diet (1).

Will the high fat cause me to have heart disease?

In one study where ketogenic diet was used in glucose transporter deficiency, a pediatric epileptic syndrome with encephalopathy, 10 patients were followed for 10 years. After 10 years on ketogenic therapies, there was no evidence of increased cardiovascular risk. While it is a small study, it shows evidence that eating a low carbohydrate diet did not appear to contribute towards heart disease. Larger clinical trials are needed (3).

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How obesity relates to other diseases

It is not uncommon to see patients who come into the ER or the doctor’s office with a history of hypertension, diabetes mellitus type II, hypercholesterolemia and obesity all related to one common denominator-obesity. Take away the obesity, the bad cholesterol or the LDL values go down, glucose goes down and hypertension resolves. When these risk factors are reduced early enough in your life, the odds of cerebrovascular disease or strokes and cardiovascular diseases or heart attacks vastly diminish. If, however, obesity is long-standing, while it is definitely good to reduce risk factors, once atherosclerosis is present in the blood vessels, there is no magic pill to reverse that.

Early identification and reduction of obesity as a contributor towards many health problems is key. Ketogenic diet may play a role in weight reduction. A small case series did not show any risk of heart disease while on the ketogenic diet long-term, over a span of 10 years. Larger clinical trials are needed to support this.

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Reference

  1. Giugliano, et al, “More sugar? No thank you! The elusive nature of low carbohydrate diets,” Endocrine, 2018, Mar, 19. doi: 10.1007/s12020-018-1580-X (Epub ahead of print)
  2. McDonald, et al, “Ketogenic diets for adults with highly refractory epilepsy,” Epilepsy Currents, 2017, Nov.-Dec., 17 (6):346-350.
  3. Heussinger, et al, “10 patients, 10 years-Long-term follow-up of cardiovascular risk factors in Glut1 deficiency treared with ketogenic diet therapies: a prospective , multicenter case series,” Clin. Nut., 2017, Nov, pil:S0261-5614 (17)31399-7.

 

 

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