Medication-Resistant Epilepsy and SUDEP

By David Ficker, MD, professor and associate director, and
Brian Moseley, MD, assistant professor and epileptologist, at the
UC Epilepsy Center, a comprehensive, Level IV epilepsy center


Q: What is medication-resistant epilepsy?

A: Medication-resistant epilepsy is also known as intractable epilepsy or refractory epilepsy. We say that a patient has medication-resistant epilepsy when he or she continues to have seizures after trying at least two different antiepileptic medications, taken alone or in combination. About 30 percent of people with epilepsy have the medication-resistant kind.

Q: There are more than a dozen antiepileptic medications. If two medications fail, shouldn’t a patient try the others?

A: Statistics show that once a patient has tried two medications without success, the chances are slim that another medication will work. Only 5 percent of patients will become seizure-free when trying a third, fourth, fifth, or sixth medication. It would take a lifetime for a patient to test all of the available medications, either alone or in combination. Only a very small minority of patients will find a medication that works after the first two have failed.

Q: What are the long-term risks of having continued, poorly controlled seizures?

A: The risks are underappreciated and should be recognized. The most important and obvious risk is something we call SUDEP, which stands for sudden unexpected death in epilepsy. SUDEP is a sudden death in a person known to have epilepsy when no other reason for the death exists. The death rate for all people with epilepsy is about one in 1,000. But for people with refractory epilepsy, the rate is far higher. For every 1,000 people with refractory, or medication-resistant, epilepsy, six will die each year.  The death rate is similar to – and slightly higher than – the death rate for people with average-size brain aneurysms.

Q: How and why does death from SUDEP occur?

A: One theory is that strong electrical charges in the brain can impact the heart, causing a cardiac arrest. A violent seizure also can interrupt breathing. It is possible that a combination of heart and breathing dysfunction caused by a seizure, coming together in a perfect storm, results in sudden death.

Risk factors for SUDEP are a diagnosis of medication-resistant epilepsy, a high frequency of seizures, a high number of anti-epileptic medications taken, frequent changes in anti-epileptic medications, and the age of onset of epilepsy — all of which are consistent with medication-resistant epilepsy. Although all seizures that impair consciousness can increase a person’s risk of SUDEP, generalized tonic clonic (or grand mal convulsive) seizures put people at greatest risk of sudden death.

It is important to note that some deaths from SUDEP are potentially avoidable. The National Sentinel Clinical Audit of Epilepsy-Related Death, published in 2002, reported that as many as 39 percent of SUDEP deaths were avoidable in adults and 59 percent in children. It is important for patients to take their antiepileptic drugs as prescribed by their doctor. If side effects from these medications arise, it is important that patients communicate those to their doctor before lowering or stopping the drugs on their own. We know that missing or skipping medications put people at risk for breakthrough seizures, including grand mal seizures. This puts people at greater risk for SUDEP.

Q: Are there other, less dramatic, risks of having uncontrolled seizures?

A: Imaging studies of patients with medication-resistant epilepsy have shown ongoing loss of brain cells in the hippocampus and increased memory impairment. Other studies, including our own, show an increased likelihood of depression in patients with medication-resistant epilepsy. In addition, people with uncontrolled seizures are more likely to suffer injuries. Many studies have shown a reduced quality of life in people with epilepsy, often as a result of limitations in driving, working, and social interaction.

Q: Can patients with medication-resistant epilepsy be helped by surgery?

A: All patients with medication-resistant epilepsy should undergo a comprehensive evaluation to see if they could benefit from epilepsy surgery. Studies have shown that 80 percent of carefully selected people who undergo surgery for epilepsy experience a significant reduction or complete elimination of their seizures.

Unfortunately, many people who would benefit from epilepsy surgery are given the opportunity only as a last resort. Although an estimated 100,000 to 200,000 Americans are candidates for surgery, only 2,000 to 3,000 epilepsy surgery cases are performed in the United States each year. The typical patient we see has had epilepsy for 15 years, has several seizures a month, and has tried at least four medications without success.

Q: How do you know whether a person with medication-resistant epilepsy is a candidate for surgery?

A:  Patients undergo careful testing and monitoring at a comprehensive epilepsy center. The four main tests that are used for screening are PET and MRI imaging exams, extended monitoring with simultaneous video and EEG in an epilepsy monitoring unit, and a neuro-psychological (memory) exam. Specialists also may request functional MRI scans, a SPECT blood flow test during the seizure and additional tests. The tests are used to confirm that surgery will not harm the patient’s ability to speak, think or function.

Q: What are the risks of epilepsy surgery?

A: All surgeries involve a risk of complications, such as infection or hemorrhage. Epilepsy surgery carries a risk of disability of 2 to 5 percent. The risk of dying from the surgery itself has been less than 1 percent at the UC Epilepsy Center over the last 26 years. However, these risks are generally outweighed by the potential benefits of achieving complete seizure control, including greater independence and a lower risk of death.

Q: What do you recommend for patients who have medication-resistant epilepsy and who are not candidates for surgery?

A: First, I try to minimize the number of antiepileptic medications they are taking. I try not to prescribe more than two for a patient at any given time. Second, we can continue trying new antiepileptic medications. It is important to match the antiepileptic medication to the patient to minimize or avoid unacceptable side effects. Thirdly, there are now devices that can help reduce the burden of seizures in people who are not candidates for traditional epilepsy surgery. These include vagus nerve stimulation (VNS) and responsive neurostimulation (RNS). There are also special diets that can be helpful in some patients at reducing the burden of seizures. These include the ketogenic diet and a modified Atkins diet. Finally, we can take a holistic approach and try to minimize risk factors as best we can through adherence to a healthy lifestyle, including the adoption of good sleep habits and the minimization or elimination of alcohol.