On My Mind
Epilepsy Awareness Month
November again is epilepsy awareness month, stimulating reflection on this very distressing disorder; on the progress we have made and how far we have to go.
Epilepsy remains the most prevalent serious disorder that is able to affect people across the full spectrum of ages. Epilepsy is not as common as stroke or dementia, but epilepsy can strike during childhood, mid-life and the senior years. Approximately one of every hundred people will have epilepsy, defined as a condition of spontaneously recurrent seizures. At least 5% of people will have at least one seizure in their life; though not all of these go on to become epilepsy. We have over 20 medications available to treat epilepsy, in addition to vagus nerve stimulation and a variety of surgical procedures. Despite this impressive arsenal, which is larger than those for many other diseases, about 1 of 3 people with epilepsy continue to have uncontrolled seizures, or unacceptable toxicity of medications used to treat their seizures. The answer for these people lies in research, because there is still so much that we do not know.
Research requires support. In the US, the main funding engine for medical research is the National Institute of Health (NIH), which provides research grant funding for basic scientists and clinical researchers working on health problems. Epilepsy research received about $105 million in 2007 (http://www.nih.gov/news/fundingresearchareas.htm). This is a large absolute amount of money, but small in comparison to NIH funding of $20 billion research dollars for 2007 or $1.3 billion for all neurological (NINDS Institute) research. Other organizations, such as the National Science Foundation, Howard Hughes Foundation, the Klingenstein Foundation, the Epilepsy Foundation, the American Epilepsy Society, the CURE Foundation, and many others, including our own organizations, the Epilepsy Therapy Project and FACEs, make vital additional contributions, often igniting lines of research that are too new to draw support from NIH.
Why this mismatch between importance of epilepsy and its relative scarcity of funding? No one really knows the answer to this question, but several contributing factors apply. One is the centuries-old stigma that still attaches to epilepsy. Although epilepsy has great individual spokespeople, it has never achieved the overall star power of other poster diseases. Another reason is a relative scarcity of researchers devoted to epilepsy. We need to encourage bright young researchers to choose epilepsy as a research field. These researchers, who are the future of medicine, need to know that studying seizures will be intellectually rewarding, satisfying in terms of helping people and capable of securing support. In addition, we need to fund the most innovative ideas of experienced researchers. These are key goals of the Epilepsy Therapy Project.
Please be aware of these points. Epilepsy is common. Epilepsy is important. Epilepsy is underfunded. We all know people affected by Epilepsy, and the effects can be devastating. If you can help, that is great! Please click here, call (540) 687-8077 x2 or write to firstname.lastname@example.org. If you are unable to provide research funding support, but you care, then please know that ETP and epilepsy.com are fighting to get epilepsy the respect and support that it deserves.
In this section of the newsletter, I will highlight each month selected research studies on epilepsy that are appearing in recent medical literature or in public news sources. Among the thousands of studies emerging, I will choose a few that seem to be innovative and of potential interest to the readership of the website. Some may be potential breakthroughs, others thoughtful reviews of important topics, and still others simply food for thought. In each case I will try to put the central message in a context and non-technical language that can be understood by the public. Epilepsy.com usually will have the right to link to the abstracts (brief summaries) of the articles, but not to the full original publication, because the publishing Journal typically retains copyright and requires subscription.
1. A new epilepsy medicine, lacosamide, recommended for approval in the US and Europe.
From news sources: Lacosamide, brand name Vimpat™, was recommended for approval in the United Kingdom and Germany on September 3, 2008, and for the US on September 29. Vimpat™ is produced by the company UCB Pharma, Inc, a company that also makes Keppra™. Such approval is a prelude to medication becoming available in pharmacies for use by prescription. Lacosamide soon will be available as an add-on treatment of partial onset seizures with or without secondary generalization in people with epilepsy, aged 16 years (Europe) or 17 years (US) and older. Lacosamide has a mechanism of action different from all other currently available anitiepileptic drugs. The drug acts on sodium channels, which affect excitability of brain cells. Other medications, such as phenytoin (Dilantin™) and carbamazepine (Tegretol™) also act on sodium channels, but on a different aspect of the channels. Lacosamide also acts on a protein in brain cells called collapsin response mediator protein-2 (CRMP-2), which affects long-term growth of nerve cells. The medication comes in the form of an oral tablet or syrup, to be given twice a day in daily doses ranging from 200 to 600 mg, and also as an intravenous injection. Recommended starting dose is 50 mg twice a day, with slow buildup to a full dose. Specific details about use will be available in the package insert by time of drug availability in pharmacies. Studies of the safety and tolerability of lacosamide come from three clinical trials in over 1300 patients with seizures. Over half of the people in the trial had significant improvement in their seizures, above and beyond the improvement from their baseline ongoing antiepileptic medications. The most common side effects were dizziness, nausea, double vision and headache. Fainting has occurred on the medication and caution is advised for people with cardiac rhythm problems. Availability of lacosamide is targeted in the US for early 2009.
2. Improvements in memory after temporal lobe epilepsy surgery.
Published article: Baxendale S, Thompson PJ, Duncan JS. Improvements in memory function following anterior temporal lobe resection for epilepsy. Neurology. 2008; volume 71; pages 1319-25.
Faulty memory is one of the most common complaints voiced by people with epilepsy. Memory difficulties results from a combination of factors, including seizures that disrupt memory formation circuits in the brain, negative effects of some seizure medicines on memory and underlying injuries to the brain that can cause both seizures and memory problems. Patients who are thinking of having epilepsy surgery to help their seizures may wonder, will this also help my memory? The usual answer to this question up to now has been no, but a new study from the National Hospital at Queen Square in London suggests that the answer may sometimes be yes: memory can improve
The study was done on 230 patients who had a type of scarring in their temporal lobe called hippocampal sclerosis. This condition can be seen on the preoperative MRI, and is commonly associated with the place of origin in the brain where seizures arise (the so-called seizure focus). The left temporal lobe, which is more usually involved with word and number memory, was involved in 132 patients. The right temporal lobe, which typically mediates picture, map, and face memory, was involved in 105 patients. Postoperatively, 22% of people with right temporal lobe surgery and 9% of people with left temporal lobe surgery showed improvement in memory with their partial temporal lobectomy. Those with shorter durations of epilepsy tended to improve more. Previous experience from several studies have suggested that secondary improvement in memory may result from successful surgery if surgery eliminates or reduces numbers of seizures and therefore allows reduction in seizure medications. Other individuals, however, have a decrease in memory function after epilepsy surgery. A post-surgical memory decrease may recover after a few months, but sometimes the decrease in memory is lasting. Such a decline does not result in loss of specific memories, but rather the ability to retain new memories: basically, a form of absent-mindedness. So now we have a study with a little more optimism, raising the possibility that epilepsy surgery sometimes makes memory better, and not always worse or unchanged.
3. Risks of antiepileptic drugs during pregnancy.
Published article: Meador KJ, Pennell PB, Harden CL, Gordon JC, Tomson T, Kaplan PW, Holmes GL, French JA, Hauser WA, Wells PG, Cramer JA and HOPE Work Group Collaborators. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology. 2008;71:1109-17.
The Epilepsy Therapy Project established the HOPE group, standing for Health Outcomes in Pregnancy and Epilepsy, comprising nine international groups with input from six pregnancy registries. A consensus view of HOPE was published in the September, 2008 issue of the journal Neurology. The article points out that about 25,000 children are born each year to women with epilepsy. Most children are born normal, but about 4.5% born to women taking one antiepileptic drug (AED) have a birth defect. This compares to 8.1% for women taking more than one AED and to a background population birth defect rate of 1.6-2.1%. Birth defects can include minor or sometimes major problems with heart, face, fingers, genitals, bones or brain. Much of the increased risk for birth defects in children of women with epilepsy comes from effects of AEDs on the fetus. However, women with epilepsy should not stop their AEDs before or during pregnancy, without having detailed discussions with their seizure doctor and obstetrician. Stopping AEDs can lead to uncontrolled seizures, which can be harmful to both the mother and the future baby. The article recommends using the minimum amount of and smallest number of medications that is still therapeutic and able to control serious seizures.
It is hard to specify a single “best” AED during pregnancy. The article reviews data collected from six pregnancy registries, with over 20,000 enrolled pregnancies. Because the groups using one drug versus another are not always comparable in terms of seizure characteristics and other health factors, registries only give clues to problem drugs, not proof. Treatment with valproic acid (Depakote™) or phenobarbital during pregnancy appeared potentially problematic. The malformation rate with valproate varied in different registries from 6.2 - 13.3%. The rate with phenobarbital was approximately 6% for malformations, but an earlier study suggested additional risk for lower intelligence in the offspring when phenobarbital was used during pregnancy. Malformation rates with carbamazepine (Tegretol™, Carbatrol™) ranged from 2.2 -4.0%, and with lamotrigine (Lamictal™) from 1.4 - 3.2%. Individual cases of cleft lip and cleft palate occurred with carbamazepine or lamotrigine. Numbers of pregnancies with single drug therapy with other AEDs was too low for firm conclusions.
Although not part of the article, it is worth remembering this: women with epilepsy who are planning to have children should plan ahead and optimize medications before pregnancy. Potential mothers should confer with their doctors about taking folic acid (folate), a vitamin that may reduce the risk for birth defects.
Take a Look
A New Type of Newsletter: Each month, we will produce an epilepsy.com newsletter with three sections. The first section will be a column called "On My Mind" with a discussion topic by
myself, Dr. Robert S. Fisher, the new Editor-In-Chief of the website. The second section will be a segment called "What's New," in which selected interesting topics from medical literature or news sources will be reviewed for the readership. The third section of the newsletter will be called "Take a Look." This section will highlight new or interesting features of the website itself. Newsletters can be read online at the site, and also will be made available in PDF format for archiving, for those who wish to read the older newsletters.
New Educational Videos: The staff of epilepsy.com believes that different people prefer different forms of media for education, and as many as possible should be available to help educate about epilepsy. This month, we are introducing to the site 23 new educational videos about topics in epilepsy, written by myself, Dr. Robert Fisher, and Dr. Orrin Devinsky, produced by FullTurn Media, sponsored by the Chairman of the Epilepsy Therapy Project, Warren Lammert. Dozens of other excellent educational videos have been available on the site, but it has been hard to find them. This month, we are initiating a reorganization of navigation to the videos. Clicking on the videos button on the homepage will now take the reader to a table of contents of videos group by subjects. Over the next few months, we will add links to other portions of the website. The person reading, for example, about epilepsy surgery in the “Epilepsy 101” text-based portion of the website will then be able to jump easily to several videos discussing epilepsy surgery. Please take a look at the videos, and if you feel so moved, provide feedback, comments for improvement and possible topics for future videos in the forum section of the website.
Managing Seizure Triggers: Seizures sometime seem to come "out of the blue." At other times they can be triggered by various factors, for example, missing medications, missing sleep, physical illness, emotional stress, the menstrual cycle in women, certain over-the-counter, prescription medications or recreational drugs, or environmental stimuli like flashing lights. Epilepsy.com, through the efforts of Steven Schachter and Patricia Shafer have added a section to the site called "Managing Seizure Triggers." The section can be accessed from the left column of the home page via this heading "Seizure Preparedness.” Take a look, and begin to think about whether there are triggers for your seizures that can be avoided.
Ketogenic News: This month Dr. Eric Kossoff summarizes results of a study by the group at Johns Hopkins which was published in the journal, Epilepsia. The study evaluated use of the ketogenic diet in 13 babies, with infantile spasms, a form of tonic seizures. Effectiveness of the diet was at least as good as that of the standard medication, ACTH. In the words of Dr. Kossoff, "it is now certainly no longer acceptable to think of the ketogenic diet as a treatment of last resort."
Robert Fisher, MD, PhD