Special Populations, Future of Epilepsy Discussed at J. Kiffin Penry Briefing

By Adam Modzelesky
EpilepsyUSA staff
Posted: August 3, 2006

Every profession has had its own pioneer, that one person who went a step further than everyone else and reshaped the nature of the business. Some of the people who did this are more commonplace than others, like Albert Einstein and Stephen Hawkings. But those who aren't quite household names, the unsung heroes, are nonetheless revered for the effects of their work. Their dedication and ingenuity still helped bring their respective disciplines to the next level, and for that they'll never be forgotten.

The late J. Kiffin Penry, M.D., is one of those unsung heroes. His medical career spanned 45 years and his then-visionary work in epilepsy resulted in what are now considered ordinary tools in the fight against the condition. Not only did Penry start the Antiepileptic Drug Development Program that's yielded several new antiepileptic agents, he was also responsible for the development of antiepileptic drug monitoring, use of simultaneous, closed-circuit television and EEG monitoring, and the establishment of comprehensive epilepsy centers. He also gained an international reputation for his work on the diagnosis and classification of epileptic seizures and syndromes while at the National Institute of Neurological Disorders and Stroke.

In essence, Penry paved the way for innovative research on how to eliminate the condition in those it most affects. He essentially dared young scientists and physicians to follow in his footsteps and start thinking outside the box, urging them to find those populations most affected by epilepsy and treat them as best as they could. In light of his concerted efforts to focus on those with epilepsy that are most in need, it was fitting that the recent J. Kiffin Penry Media Briefing emphasized these aspects.

Epilepsy in Special Populations

Women, the developmentally delayed and the elderly are some of those most affected by epilepsy. Because each group carries with it a host of issues associated with their epilepsy, they are sometimes particularly difficult patients to treat.

Women's issues in epilepsy include: effects of sex steroid hormones (a.k.a. menstrual cycle and menopause), effects of epilepsy on reproductive health, interactions with oral contraceptives, effects of epilepsy on pregnancy and bone health.

The issue of pregnancy and the affects of medication on a developing fetus is always the most popular. Despite the fact that more than 90 percent of women with epilepsy have normal, healthy outcomes, the idea of taking medication while pregnant – even while under the care of a physician – is terrifying for many women.

Georgia Montouris, M.D., of Boston University Medical Center and a member of the Epilepsy Foundation's professional advisory board, outlined some preventative measures that doctors use to guard against pregnancy complications: use of folic acid pregestationally to prevent spina bifida, use of Vitamin K during last month of pregnancy to prevent hemorrhagic syndrome and the careful selection of antiepileptic drugs. According to her, the latter measure applies to the physician's desire to achieve the necessary level of seizure control without the most side effects.

"Once a woman is pregnant, it's much too risky to make any kind of major changes – I think – because you don't know the reactions they're going to have," Montouris explained. "You don't know how it's going to affect a drug they might already be on. You don't know if they're going to have an allergic reaction.

"There have been times when I've been asked, ‘In the first three months, because that's when the organs are being formed, wouldn't it be better not to give medication during those three months?'" Montouris added. "My answer to that is always, ‘No, we're talking about seizures here.'"

Montouris continued by addressing bone health in epilepsy, which is cause for concern in the three special populations most affected by epilepsy: women, the developmentally delayed and the elderly. According to her, people with epilepsy, especially women, have a high risk of osteoporosis or osteopenia, which is the risk of bone fracture. Certain antiepileptic drugs can cause a Vitamin D deficiency which is what increases the risks of these bone conditions. In developmentally delayed patients, if they are non-ambulatory or institutionalized their risk of osteoporosis is also high.

That being the case, it should come as little surprise that epilepsy is the most common comorbid condition in patients with developmental delay – hence the reason why it's so difficult to treat them. Epilepsy exists in approximately 30 percent of persons with mental retardation, 30 percent of individuals with autism and 28 percent with cerebral palsy that experience chronic seizures.

According to Montouris, these individuals are difficult to treat because they have multiple seizure types and are typically refractory, or difficult to control. In addition, other issues, such as a patient's ability to swallow, affects treatment choices, and these patients also often experience adverse effects.

Of particular difficulty, however, are the behavioral dysfunctions which occur at higher rates in this population. Non-verbal individuals present a unique challenge, and their inability to express themselves often complicates diagnosis of seizure activity, side effects or an underlying brain disorder.

On the other hand, the challenges that come with treating the elderly population are limited mostly to the physiologic changes that normally come with aging. About 1-in-100 people over age 60 have epilepsy, and it is the fastest growing population with over 68,000 new cases being diagnosed each year. Of known causes, which can be identified two-thirds of the time, cerebral vascular disease, such as stroke, hemorrhage, arteriosclerosis and head trauma are most common. Alzheimer's Disease has also been identified as a popular underlying cause.

Great care, according to Montouris, must be taken when selecting treatment for this population.

"Tolerance is different in this age group," she said. "They simply don't tolerate the same medication dosage someone much younger would, and that has to be taken into consideration when selecting treatment. One of the problems over the past few years is that there's been too much ‘one shoe fits all' in the general medical field. Maybe less is good for some people, and that's certainly the case in the older populations."

Not to mention the fact Montouris also said this population already has a reputation for responding best to medication. They tend to be less refractory than anybody else.

"This is an interesting group because in a typical partial seizure, the patient may have a warning – which is known as an aura – they may have some automatisms – which are repetitive movements – and they may come out of it in about 5-to-10 minutes and have a short postictal phase," Montouris said. "In the elderly, however, there are typically no auras, virtually no automatisms, and in the end the patient looks more confused, disoriented or demented. Because they have these episodically confused looks, they are often misdiagnosed."

Misdiagnosis is continuously identified as a problem for all people of all ages with epilepsy, not just special populations.

Future of Epilepsy

With epilepsy research and technology advancing at its current, break-neck speed, it's difficult not to grow increasingly hopeful for a monumental breakthrough. However, Richard Mattson, M.D., of Yale University Medical School, doesn't want to jump on the bandwagon quite yet.

"There are things on the horizon, but I confess that I don't see any overwhelmingly dynamic breakthroughs," he said. "I think one of the best ways of improving the state of things is simply to keep doing what's been going on in the post-Penry era, and that is, we need to increasingly implement what we already know."

By that, Mattson proposes some reflection on current prescription writing practices. He believes physicians should consider rethinking the order in which they prescribe drugs. Currently, phenytoin is the most commonly prescribed drug in America – despite some undesirable properties.

"I use phenytoin a fair amount, but I use it for difficult to control people," Mattson said. "And I think phenytoin should not be a first drug; it ought to be the last drug, because it's very effective at the expense of a lot of side effects. There's a lot of evidence saying it's a good drug, but it'd probably make more sense to prescribe something that's kinder, gentler than these older drugs.

"Interestingly, too, is that phenytoin is the most commonly prescribed drug in America, but it's the fifth most popular in Europe," Mattson added.

Mattson continued by saying one-third of patients remain sub-optimally controlled on present available therapy, and many investigational compounds are in various testing phases. In other words, an increased amount of "designer drugs" are being created to focus on specific, epileptic parts of the brain. This works when a drug is specifically produced with certain structural activity and certain molecular properties targeted.

Mattson is optimistic for what the future holds, but he's cautious in his hopefulness because, as he puts it, "Most of our best drugs have come from serendipitous discovery, and very few, with the exception of Dilantin, were really set out to be antiepileptic drugs. They were accidentally found to work for those purposes."

This isn't to say lightening can't strike, again, however. Epilepsy, in its very nature, has always been unpredictable.