Current Series: Epilepsy Trends Treatments Focal Seizures


Rodney A. Radtke, MD: We’re hearing more and more about Lennox-Gastaut syndrome and Dravet syndrome, which are 2 of the epileptic encephalopathies. Both of these disorders are childhood seizure disorders that have very difficult-to-control epilepsy, and we think that if we’re able to control the seizures sooner, we’re able to protect neurological development more. The outcomes in terms of cognitive and physical development will be better if we’re able to make the proper diagnosis, get the proper treatment, and stop or control the seizures as soon as possible.

I’m not a pediatric neurologist; I’m an adult neurologist. And that job is, for the most part, carried out by the pediatric neurologists who are seeing them in this age-dependent expression of these very syndromes. The tools that they have to use include not only the MRI [magnetic resonance imaging] scan, EEG [electroencephalogram] recording, and physical exam but also more and more the epilepsy panels. There are now epilepsy gene panels that are routinely used in the clinic in pediatric neurology that are very helpful in identifying the specific cause of a disorder such as Dravet or maybe 1 of many contributing causes to a disorder like Lennox-Gastaut.

Many times there are issues with administration of medicine and getting the medicine in the patient. Obviously there’s the reluctant or difficult teenager who’s pushing back against the control of the adult world, but there also are intellectually disabled or physically disabled patients who either don’t understand that they’re supposed to swallow or have difficulty swallowing, and as such other formulations are very important to be able to adequately administer the medicines to these individuals.

The administration of medicine to someone who can’t readily swallow pills frequently is very challenging. You obviously can crush many of the pills and administer them through food or applesauce or whatever, sometimes through a gastrostomy tube if necessary. But it’s certainly advantageous to have the oral preparation where you can more accurately measure and ensure adequate administration of the medicine.

In addition, there are some other routes of administration. One is the early disintegrating tablet, which melts in your mouth and allows even someone with dysphagia and difficulty swallowing to take the medicine effectively and easily. More recently there’s development of a film, and in this case it’s the new preparation for clobazam. It’s a film that I guess many of us think about, like the Listerine melt-in-your-mouth films that were available for bad breath. This is very similar and has the advantage that once it sticks to the mucous membrane of the cheek, it dissolves, and even a difficult patient can’t spit it out or reject it. So it’s really an interesting technology that is going to be extended to other products as well. And the most interesting 1 is diazepam. So the same company is developing diazepam administered by this film that’s placed in the mucosa, in the mouth, and trying to get it approved for the treatment of epilepsy, acute repetitive seizures in a fashion similar to how we use Diastat, or rectal valium. And certainly the administration of film to one’s cheek is a lot more attractive than the rectal administration and would extend the use, under this rescue medicine, to a much larger population of patients, particularly in the adult population.

With the new film technology to administer medicines, it will be an interesting question as to what patients may benefit from its use. I’ve prescribed it a few times so far. I don’t really have enough clinical experience to make a judgment as to how it’s going to work, but clearly it’s very nice to have an easily administered medicine that really cannot be rejected by the patient. Aside from getting your finger bit or something like that, once you can get it in their mouth, it’s going to be absorbed, it’s going to be swallowed, and it’s going to get into the individual.

Another product that’s being developed for the treatment of Dravet syndrome is fenfluramine. Many of you may recognize that as a product that many years ago was in fen-phen, which was a dietary treatment. It was fenfluramine and phentermine. The use of that product was basically brought to a halt by the demonstration of valvular changes in the heart, so the safety got called into question. Fenfluramine is being investigated now for the treatment of Dravet. Recent presentations at the American Epilepsy Society show significant efficacy, really impressive efficacy in the treatment of seizures. And so it’s really an exciting advancement that certainly may be an important part of treating Dravet as we go forward. It’s unclear how it may shake out. There will be some sort of safety monitoring, cardiac echocardiograms to look at cardiac health when the product is used. But the numbers are really impressive and encouraging, so that’s another product that we’re looking at with some expectation for the treatment of Dravet and possibly other similarly affected individuals.