Index of 2009 Hallway Conversation Podcasts

Nov. 16, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Joyce Cramer, President, Epilepsy Therapy Project, on the new online Medication Compliance CME.
Nov. 12, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Dan Lowenstein, MD, PhD, Professor of Neurology, University of California, San Francisco on Post-traumatic Epilepsy.
Oct. 14, 2009	In this episode of Hallway Conversations, Dr. Joseph Sirven, Editor-in-Chief of Epilepsy.com/Professionals, interviewed Dona Locke, PhD and Kristin Kirlin, PhD on Diagnosis and Therapy for Nonepileptic Events: Psychological Perspectives. Click on arrow to listen.
Oct. 5, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Robert Fisher, Editor-in-Chief of epilepsy.com and Director of the Stanford Epilepsy Center about My Epilepsy Diary. Click on arrow to listen.
Oct. 5, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Joseph Drazkowski, MD, Mayo Clinic Arizona and Korwyn Williams, MD of Phoenix Children's Hospital on Epilepsy Monitoring for Adults and Children. Click on arrow to listen.
Sept. 25, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Dr. Steve Chung, Director Epilepsy Monitoring, Neurology Residency Director, Barrow Neurological Institute on New AEDS for Epilepsy. Click on arrow to listen.
Sept. 17, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Hemant Kudrimoti, Arizona Comprehensive Epilepsy Program, Director, Residency Training Program on Generic Anti-seizure Medications. Click on arrow to listen.
Sept. 14, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Katherine Noe, Assistant Professor of Neurology, Mayo Clinic on Women's Issues and Epilepsy. Click on arrow to listen.
August 13, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Scott Mintzer, Associate Professor of Neurology, Director, Epilepsy Monitoring Unit and Epilepsy Surgery Program, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University on Antiseizure medications and Metabolism: Can seizure medications impact cholesterol levels? Click on the arrow to listen.
August 5, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Lawrence Hirsch, Associate Clinical Professor of Neurology, Comprehensive Epilepsy Center, Columbia University on the latest management of Status Epilepticus. Click on the arrow to listen.
July 13, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Selim Benbadis, Professor of Neurology, University of South Florida on Nonepileptic seizures: Diagnosis and Treatment. Click on the arrow to listen.
July 13, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Katherine Noe, Assistant Professor of Neurology, Mayo Clinic on Safety Issues as it pertains to Epilepsy Monitoring Units and her newly published research on the topic. Click on the arrow to listen.
July 6, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Alison Pack, Associate Professor of Neurology, Columbia University on Bone Health and Epilepsy. Click on the arrow to listen.
June 22, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Gregory Worrell, Associate Professor of Neurology at Mayo Clinic Rochester about Seizure Prediction: Science, Reality and the Future for Devices. Click on the arrow to listen.
June 18, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Martha Morrell, Chief Science Officer of Neuropace, Inc. The topic was Responsive Neurostimulation System: Preliminary Results. Click on the arrow to listen.
June 15, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Christopher DeGiorgio, a professor in residence at UCLA in the Department of Neurology. The topic is Trigeminal and Vagus Nerve Stimulation therapy for epilepsy. Click on the arrow to listen.
May 20, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Jack Hastings, Chief Neurological Consultant to the FAA about flying and epilepsy. Click on the arrow to listen.
May 13, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Joseph Drazkowski about driving laws and epilepsy. Dr. Drazkowski is Associate Professor of Neurology at Mayo Clinic Arizona. Click on the arrow to listen.
May 6, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Allan Krumholz from the University of Maryland. Dr. Krumholz discusses driving and epilepsy. Click on the arrow to listen.
April 23, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Greg Cascino from Mayo Clinic Rochester. Dr. Cascino discusses epilepsy surgery for adults. Click on the arrow to listen.
April 23, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Dr. Kimford Meador from Emory University. Dr. Meador discusses a recently published study in The New England Journal of Medicine on the topic of valproate (Depakote) taken during pregnancy and its link to lower IQs in children. Click on the arrow to listen.
April 20, 2009	In this episode of Hallway Conversations, Dr. Joe Sirven, Editor-in-Chief of epilepsy.com/Professionals interviewed Warren Lammert, Chairman and founder of Epilepsy Therapy Project, Joyce Cramer, President of Epilepsy Therapy Project, and Dr. Jackie French, professor in the Department of Neurology NYU, in the comprehensive Epilepsy Center, and Director of the Clinical Trials Consortium. Click on the arrow to listen.
April 16, 2009	In this episode of Hallway Conversations Dr. Sirven interviewed Dr. Paul Garcia from University California San Francisco. Dr. Garcia discussed radiosurgery for epilepsy. Click on the arrow to listen.
April 9, 2009	In this episode of Hallway Conversations Dr. Sirven interviewed Dr. Jeffrey Buchhalter from Phoenix Children's Hospital. Dr. Buchhalter discussed epilepsy surgery for children. Click on the arrow to listen.
March 26, 2009	In this episode of Hallway Conversations Dr. Sirven interviewed Dr. Brien Smith from Henry Ford Medical Center. Dr. Smith discuss how we can best advocate for your patient with seizures. What to do about disability and other advice for patients. Click on the arrow to listen.
March 18, 2009	In this episode of Hallway Conversations Dr. Sirven interviewed Dr. David Labiner from the University of Arizona in Tucson to discuss the American with Disabilities Act and how to best inform our patients with regards to this law and its impact. Click on the arrow to listen.
March 13, 2009	In this episode of Hallway Conversations Dr. Sirven interviewed Dr. Brian Alldredge, Pharm D, from the University of California San Francisco on the pros and cons of status epilepticus therapy and the latest clinical research on the topic. Click on the arrow to listen.
March 4, 2009	In this episode of Hallway Conversations Dr. Sirven interviewed Dr. Blanca Vazquez from New York University School of Medicine. Dr. Vazquez spoke about epilepsy treatments and her role in advocacy for patients. The interview was conducted in Spanish. Click on the arrow to listen.
Feb. 19, 2009	Dr. Sirven interviewed Dr. Nathan Fountain from the University of Virginia and co- Chair of the American Academy of Neurology Committee for the Development of Quality Metrics for Epilepsy Care discusses the 8 proposed Quality Metrics for caring for Patients with epilepsy. Please take a listen as public comment on these measures has just started. Click on the arrow to listen.
Feb. 12, 2009	Dr. Sirven interviewed Dr. Jacqueline French of New York University School of Medicine. Dr. French, an internationally renowned epilepsy specialist about the issues surrounding the use of generic seizure medications. Click on the arrow to listen.
Feb. 4, 2009	Dr. Sirven interviewed Greg Krauss, MD, Associate Professor of Neurology at Johns Hopkins University about Rufinamide, a new medication recently approved for epilepsy. Click on the arrow to listen.
Jan. 29, 2009	Dr. Sirven interviewed Elaine Wirrell, Professor in the Division of Child and Adolescent Neurology, Mayo Clinic Rochester about infantile spasms, its diagnosis, prognosis and treatment. Click on the arrow to listen.
Jan. 22, 2009	Dr. Sirven interviewed Elinor Ben-Menachem, Professor of Neurology at the Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenberg, Gothenberg, Sweden about Lacosamide, the newly approved medication for seizures and epilepsy. Click on the arrow to listen.
Jan. 15, 2009	Dr. Sirven interviewed Joyce Cramer, President of the Epilepsy Therapy Project. Joyce gives us a perpective on testifying to the FDA Advisory Panel on Vigabatrin and the role of the Epilepsy Therapy Project on getting new treatments to the patient. Click on the arrow to listen.
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Jan. 9, 2009	Dr. Sirven interviewed Dr. Edward Faught for an opinion regarding news of the FDA Advisory Panel recommending approval for Sabril, Vigabatrin for Infantile Spasms and Refractory Complex Partial seizures. Listen here (MP3) Disclosure: Dr. Faught has been a consultant for Ovation Pharma, makers of Sabril.
Jan. 7, 2009	Dr. Elson So, Professor of Neurology, Mayo Clinic in Rochester, Minnesota talks about SUDEP in this week's edition of Hallway Conversations. Dr. So is Co-Chair of the Joint Taskforce on SUDEP for the Epilepsy Foundation of America and the American Epilepsy Society. Listen here (MP3)

Dr. Benbadis is a French citizen, born in Paris. He obtained his MD at the University of Nice (Nice, France), where he completed a residency in Family Medicine. He then moved to the United States and completed his neurology residency at the Cleveland Clinic Foundation where he stayed an additional two years to complete a fellowship in epilepsy, EEG, and sleep medicine. He is board-certified in neurology, epilepsy & clinical neurophysiology, and sleep medicine.

Dr. Benbadis is currently Professor of Neurology in the departments of Neurology and Neurosurgery at the University of South Florida. He is Director of the University of South Florida /Tampa General Hospital Comprehensive Epilepsy Program. His interests are in the diagnosis and management of difficult-to-control epilepsy, and he has authored over 90 articles and book chapters.

Dr. Burack was born in Montreal, Canada. After completing his residency in Primary Care Internal Medicine at the University of California, San Francisco in 1991, Dr. Burack worked as a clinical and research faculty member in UCSF’s AIDS Program at the San Francisco General Hospital. He pursued additional training in biomedical ethics and general internal medicine as a National Research Service Award Fellow at the University of Washington, and was awarded the Mack Lipkin Sr. Research Award by the Society of General Internal Medicine. In 1996 he was jointly appointed as Associate Clinical Professor of Bioethics and Medical Humanities at the UC Berkeley School of Public Health and as Associate Clinical Professor of Medicine at UCSF. Dr. Burack is Co-Medical Director of the East Bay AIDS Center in Berkeley, CA, providing comprehensive medical care to a diverse population of patients with HIV/AIDS

What was the initial opposition to the use of provocative tests to diagnose PNES?

Dr. Benbadis: In the old days we used an intravenous (IV) placebo and this presented the element of deception. You had to induce a seizure, even though patients were given a placebo with a saline solution. Because of the element of deception, and because we told patients that they were getting a drug that could induce a seizure, some people objected.

Dr. Burack: What makes a practice deceptive is when we undertake to create a false belief in someone else. By giving the patient IV saline you are hoping the patient will come to believe that something is happening that isn’t. Your intent is that the patient will believe that he or she is getting an active drug that causes seizures. By not saying words that aren’t true you may not actually be lying -- according to a literal definition of lying – but your intent is to deceive by not sharing the truth.

What is the procedure that is used today?

Dr. Benbadis: Today we use hyperventilation, photic stimulation, and verbal suggestion – with the same yield; that is, we can trigger a seizure using these methods as often as we were able to by using the IV saline method.

How do you weigh the benefits of the procedure and ethical considerations?

Dr. Benbadis: The benefits strongly outweigh ethical concerns. It is extremely useful for a variety of reasons. Oftentimes you cannot record seizures spontaneously. You can have a patient in the hospital for several days and nights and nothing will happen. So when we do an activation and record information that gives us a clear diagnosis, it is beneficial. With a diagnosis we have the enormous advantage in that we can now provide appropriate treatment. Basically those who object to this actually are concerned with the diagnosis of psychogenic episodes – it is the label.

It is a difficult phenomenon and one that makes many people uncomfortable. So they may record an episode on video with no associated change on EEG. They conclude that the episode is not epileptic, but they fall short of saying it is psychogenic.

Dr. Burack: Just arriving at a diagnosis does not guarantee clinical benefit. The test has to settle a genuine clinical question, and lead to a change in therapeutic approach that ends by benefiting the patient. With PNES, it’s not clear any of this typically happens. Some patients may have both PNES and epilepsy, so establishing a PNES diagnosis doesn’t even spare them the risks of antiepileptic medications. And if a test is deceptive, it has to not only promise benefit, but do so significantly more than non-deceptive alternatives would. It is hard for us to understand conversion disorders, but PNES is a conversion disorder. And patients don't always want to hear that “either you have epilepsy or some bizarre psychiatric diagnosis.”

What do you see as the greatest advantage and value of these procedures?

Dr. Benbadis: It helps us to diagnose people whom you can otherwise not diagnose even though you might keep them in the hospital for 5 or 6 days. Without it, you may get no information at all. So this makes it very cost effective.

You have to be careful to confirm that what the patient is having at home and in the clinical setting are the same.

As we published, it is so cost effective and the yield is so good as an outpatient that it obviates the need for inpatient care.

Dr. Burack: When we talk about advantages and benefits, we need to ask benefits to whom – the patient or third party payers? You can speed things up with a provocative procedure and reduce costs, but are you then harming the patient to please the payer?

We need to ask whether a test is truly in the patient’s best interest, and whether we are violating ethical principles in performing it. If a diagnosis is made through deception it is tempting to say that it is in the patient’s best interest. It’s certainly difficult to balance ethical harms against clinical benefits. But if there is ethical risk, it’s important at a minimum to take a hard look at whether and to what degree patients really benefit, and whether less deceptive alternatives exist.

How do you answer critics of the test?

Dr. Benbadis: Like any other procedure, it has to be used and interpreted correctly, knowing its limitations. People who are unfamiliar with it say it produces “false positives.” This is completely inaccurate. When we trigger a seizure, we have the EEG so that we know we have just recorded it. They say it is dangerous because you record an episode that the patient does not necessarily have at home. We are well aware of this, and one has to be careful to confirm that what was recorded was similar to the habitual episodes.

Dr. Burack: Tests should only be performed if they add information that is genuinely helpful to the patient. Deceptive tests should be performed, if ever, only if the need is urgent and there is no alternative. Is the patient in immediate danger? Does the test change the way you act therapeutically? Can you offer something beneficial as a result? With a PNES diagnosis, this isn’t clear. Many patients continue to have seizures and do poorly, even after being diagnosed. And even the supposed benefit of stopping epilepsy drugs doesn’t always happen. If you can’t be certain that the patient isn’t also having occasional epileptic seizures, and they stay on drugs anyway, there is no marginal gain to having done the test.

Do you feel that provocative testing could undermine the patient-physician partnership?

Dr. Benbadis: It might, and I agree with the theoretical/philosophical reservations mentioned here. But weigh this against carrying a wrong diagnosis of epilepsy for years. Currently, the average patients with psychogenic non-epileptic episodes carries the wrong diagnosis for 7-10 years, ingesting antiepileptic drugs that do not help, and not addressing the underlying psychological causes.

Dr. Burack: There is certainly risk to the patient-physician partnership. Just imagine performing such a test on your mother. How would you explain afterward what you had done, and why? If doing such a test on your mother would raise qualms for you, then that ought to be a red flag. Even if it gets you a proper diagnosis the doing of the test may undermine future therapy, especially if the patient feels betrayed. He or she might become less trusting of medical personnel, and less likely to follow up with necessary care. Imagine also the public reaction to the news that physicians carry out this type of test on unwitting patients. Finally, we have to think of the physician’s professional integrity: Is this the sort of thing we should be doing?

Russell Katz, MD

Dr. Russell Katz joined the FDA as a medical officer in 1983, where he is currently the Director of the Division of Neurology Products (previously called the Division of Neuropharmacological Drug Products). He has lectured extensively on various aspects of neurologic drug development as well as written numerous articles on the same issues.

He received his BA in mathematics from Queens College in New York City and his medical degree from Albert Einstein College of Medicine in New York City, and completed his residency in Neurology in 1982 at the Einstein affiliated hospitals in New York.

Michael D. Privitera, MD

Dr. Michael Privitera is Professor of Neurology at the University of Cincinnati Medical Center. He is also director of the Cincinnati Epilepsy Center at the Neuroscience Institute at the University of Cincinnati and University Hospital and Medical Director of UC Physicians. He has participated in 55 different research studies in epilepsy sponsored by the National Institutes of Health or the pharmaceutical industry, has authored more than 100 scientific publications and edited the text “Clinician’s Guide to Antiepileptic Drug Use.” He has trained numerous fellows, and has directed the epilepsy course at the American Academy of Neurology and the Annual Course of the American Epilepsy Society. He is a member of the Board of Directors of the American Epilepsy Society.

Generic Substitution: Why the Controversy?

Dr. Privitera: The FDA sets standards for bioequivalence between brand name products and generics and between different generic formulations that they believe are safe for patients including people receiving antiepileptic drugs for epilepsy. These bioequivalence standards may not be appropriate for all classes of medicines, for all diseases, and for all patient populations.

Dr. Katz: With regard to the bioequivalence standard – there is a 90 percent confidence interval of 80-125% for the ratio of test/reference on log transformed data. In order for this standard to be met, the ratio has to be (and essentially always has been in thousands of studies) very close to one. Manufacturing standards for generic drugs are essentially identical to those for New Chemical Entities; that is, there are the same quantitative requirements for active substances.

What is the concern regarding breakthrough seizures?

Dr. Privitera: Physicians and other professionals caring for people with epilepsy believe that people with epilepsy have an unacceptable incidence of seizures or side effects when switching formulations. A single seizure can cause physical injury or have a dramatic impact on a patient’s quality of life and on activities such as working or driving. These are critical to their well being -- especially if they have had seizure control for many years. But we don’t know what the acceptable bioequivalence range is that would sufficiently protect patients from seizure risk and toxicity.

Dr. Katz: We are, of course, aware that there are reports of breakthrough seizures and adverse reactions in association with the use of generics. However, we have seen no credible evidence that the drugs are responsible. All of the support for these claims arises from patient and physician reports, either anecdotally or through surveys, which have used flawed methodologies. These sorts of reports cannot establish that the drugs caused the adverse outcomes.

If there is concern that generic drugs do not perform optimally, what is their value?

Dr. Privitera: Generic drugs are less expensive and everyone wants to reduce health care costs and the costs of medicines. However, our role as physicians is primum non nocere – first do no harm. We need to be assured that the generic drugs are absolutely safe. When someone with epilepsy is affected by an unexpected seizure that can cause loss of driving privileges, loss of job, or severe injury, once again this can dramatically impact their quality of life.

Dr. Katz: As I noted, the belief that generic drugs perform inadequately derives from anecdotal reports or flawed surveys by physicians. It is, of course, natural that when a patient receives a pill that differs in appearance from their previous pill (as when they receive a generic) and an adverse event occurs sometime after that (for example, a seizure), they and perhaps their physician would attribute that adverse event to the new pill. However, we know that patients with epilepsy have breakthrough seizures for many reasons, and even when their blood levels of drug are fine. So, it is not easy or even possible to tell whether that adverse event is related to the treatment or not, and such reports are certainly not evidence of generic failure. Evidence requires adequately designed and conducted trials. Although we are not convinced, at this time, that there are real problems with generic drugs, we of course acknowledge that there is a perceived problem, and we are currently working with the epilepsy community to design studies to address this perceived problem.

What suggestions do you have to the public with regard to generic drugs?

Dr. Privitera: Physicians and patients should be adequately informed before a pharmacy switches a patient to a generic equivalent. When patients call and say they are having increased frequency with seizures, we ask about the usual triggers. Then the next question we often ask is about medication – “Did the pills you took look the same as the ones you have been taking?” That gives us an answer.

Dr. Katz: As I described above, the FDA believes that generic drugs perform perfectly adequately, but we are attempting to design studies to address the questions that have been raised about them.

Page Pennell, MD, is Director of The Emory Epilepsy Program and Associate Professor, Department of Neurology, Emory University School. She completed her medical school and Internal Medicine Internship at the University of Florida Health Sciences Center and her Neurology Residency and epilepsy/clinical neurophysiology fellowship at the University of Michigan Medical Center, Ann Arbor. Dr. Pennell holds professional memberships with numerous organizations including the American Academy of Neurology, the American Epilepsy Society, and the American Clinical Neurophysiology Society. Dr. Pennell's area of particular interest and expertise is women's health and epilepsy. She is the recipient of numerous academic and professional honors, and has frequently been published in peer-reviewed journals.

Andre Lagrange, MD, PhD, is Assistant Professor of Neurology at Vanderbilt University. He studied Physiology/Pharmacology, Neuroscience at Oregon Health Sciences University, Portland, Oregon and attended the University of Michigan, Ann Arbor for both his residency in neurology and his fellowship in clinical neurphysiology. He holds board certifications with the American Board of Psychiatry and Neurology with an added qualification in neurophysiology, and the American Board of Clinical Neurophysiology. Currently a member of the Society for Neuroscience, the American Academy of Neurology and the American Epilepsy Society among others, he regularly contributes to peer-reviewed publications in addition to writing chapters for books, reviewing publications and writing abstracts in his area of expertise.

How do the available findings from pregnancy registries influence your decision?

Page Pennell: I use the information from pregnancy registries to identify which medications have enough data to provide us a reasonable idea about the differential risks of that particular AED compared to other AEDs. I consider whether the fetal risk for that particular AED is clearly higher than other medication choices. Given the findings in several registries, I now avoid the use of valproic acid in women of childbearing age, unless they have failed other treatment options or have an extremely low chance of becoming pregnant (sexually inactive, have an IUD, or have had tubal ligation or hysterectomy). In addition to a higher risk for birth defects, valproic acid has also been shown to carry a higher risk for neurodevelopmental delays in the children exposed to valproic acid in utero. I try to choose a medication for which we have substantial information that its risk is not particularly high compared to other medication choices.

Andre Lagrange: With more than 10,000 patients enrolled from nearly 50 countries, the ongoing pregnancy registries have provided invaluable information for the treatment of women with epilepsy.

The first question I would ask is whether this patient needs an antiepileptic medication (AED). This can be a complex decision, which may be further compounded by the reproductive repercussions of these medications. While the pregnancy registries have confirmed the teratogenic potential of the older AEDs, we now have a better understanding of the magnitude of those risks, thereby allowing us to make more well-informed choices in considering the risk-to-benefit ratio of instituting AEDs. Moreover, if medical treatment is instituted, we now also have a better sense for which AEDs are relatively safe in pregnancy.

Prospective parents are often worried that epilepsy will hamper their ability to raise a healthy baby. Thanks to the pregnancy registries, we can now allay some of those fears by telling the parents that having epilepsy per se does not seem to increase the risk of birth defects over the general population.

These studies have also helped improve the care of pregnant women. While most women have no change in their seizure frequency during pregnancy, approximately 20% have increased seizure frequency, especially if they are taking one of the newer AEDs. The registries have helped cast a spotlight on the effects of hormones on AED pharmacokinetics. Armed with this information, we can use frequent blood levels and appropriate dose adjustments to help minimize seizures in our patients during their pregnancies.

Do you discuss all of the available medications with the patient that are appropriate for her seizure type?

Page Pennell: Yes, but part of that discussion is based upon what information we have on specific risks during pregnancy. However, there must also be a decision regarding the need for medication. Most women with epilepsy will need medication during pregnancy, but there will be a small minority of women who can forego starting medication or taper existing medication prior to conception. Since you posed the question – as to “treating a woman with newly diagnosed partial epilepsy, not yet started on medication” – I would presume that she has had a recent seizure. If her seizures have been very rare, isolated events, or if they are only simple partial seizures, then there may be an opportunity to hold off on starting medication. Although the risk for birth defects is only in the first trimester, we also consider medication exposure throughout the entire pregnancy and particularly the third trimester for possible neurodevelopmental consequences.

Andre Lagrange: With the number of AEDs currently available, it is not practical to discuss every type of medication. I usually mention valproate as a particularly problematic AED. I also mention that the older AEDs, while much less expensive, do pose a small risk to the infant. However, I tend to focus on the newer AEDs that seem to be safer in pregnancy.

Among the newer medications, lamotrigine and oxcarbazepine seem to have the lowest risk of birth defects. However, the discussion should be tempered by some of the possible problems associated with these medications. For example, in patients with some forms of idiopathic generalized epilepsy, lamotrigine may not be as effective as valproate and I generally avoid oxcarbazepine altogether. Secondly, while these drugs may be safer for the developing baby, increased metabolism can lead to subtherapeutic blood levels that put the patient at increased risk for breakthrough seizures.

In fact, there is some concern that the apparent safety of lamotrigine and oxcarbazepine in pregnancy may actually be due to subtherapeutic drug levels during pregnancy; an idea that was supported by recent data from the UK registry that showed an increased fetal risk in pregnant women with epilepsy taking > 200 mg per day of lamotrigine monotherapy. However, the other registries have not replicated that finding.

How do you discuss the risks and benefits of AEDs with the patient?

Page Pennell: With all available medications, we need to look at seizure types. Although we can not perform randomized trials of women treated with AEDs versus women not treated and allowed to have seizures during pregnancy, there is general consensus that generalized tonic-clonic seizures should be avoided to the best extent possible. I have concerns about convulsive seizures during pregnancy because of maternal and fetal hypoxia and risk of trauma with the fall. Although rare, I do discuss the possibility of fetal death. Another consideration is the risk for status epilepticus in some patients.

For women who have any type of seizure that impairs awareness, there are additional risks of accidents including motor vehicle accidents, blunt trauma, and drowning. I discuss tub baths in particular, as pregnancy and postpartum is often a time that women will take baths. This will affect many aspects of their daily lives including the ability to drive. They may rely on driving for work or for caring for other children. Although there are risks of AEDs, using them will often outweigh the risk of continued seizures, which can negatively impact maternal medical and social well-being.

Andre Lagrange: The decision of whether to institute AED therapy entails a frank discussion weighing the risks of medication against the potential adverse outcomes of not treating the patient. It is important to remind patients that convulsions can result in premature labor, as well as trauma to the mother and baby. Furthermore, complex partial seizures can lead to self-injury and even partial seizures may be associated with autonomic changes that alter uterine blood flow.

Most patients have already heard of the potential teratogenicity of AEDs. It helps to put things into perspective by telling patients that the absolute risk of birth defects in the general population is as high as 2-4%. The older AEDs, especially valproate, may increase this risk to about 5-15%. However, even with valproate, women with epilepsy have an 85-90% chance of having a perfectly normal baby. Lamotrigine and oxcarbazepine do not consistently raise the risk of birth defects.

What AED would you prescribe and why?

Page Pennell: Since we are discussing partial epilepsy in this case, we have information that the relative risk is fairly low with lamotrigine and carbamazepine. Carbamazepine is the only AED that has evidence for a statistically significant lower risk than valproic acid for both birth defects and for neurodevelopmental consequences.

And we are quickly gathering information on levetiracetam and oxcarbazepine – but we do not have the number of monotherapy cases reported in the literature yet to have a clear idea of the level of risk for each of these medications. I believe that we will have this information in the near future. Other newer medications have even less information from prospective studies, and thus I do not use them as first-line treatment in a woman who states that she is planning a pregnancy in the near future, or in a woman who is at high risk of unplanned pregnancy, perhaps due to inconsistent use of birth control. The newer medications that lack adequate information at this time include topiramate, zonisamide, tiagabine, and pregabalin.

If pregnancy is very unlikely to occur in the next three years, then I will more readily consider these medications and counsel the patient about the need for planned pregnancy and with repeat preconception counseling in the future. It is likely we will have information on these other medications before she actively pursues conception.

Andre Lagrange: The older AEDs increase the risk of major malformations two-fold to three-fold, while the risk is even higher with valproate. In contrast, among the newer AEDs, lamotrigine and oxcarbazepine do not seem to increase the risk of birth defects. Preliminary data from the UK registry suggests that levetiracetam may be safe as well, but the jury is still out. I tend toward recommending lamotrigine and oxcarbazepine, although it is important to discuss the fact that frequent blood tests will probably need to be drawn and there may be small increased risk of breakthrough seizures during pregnancy.

Since our hypothetical patient has partial seizures, I would tend to favor oxcarbazepine because of the rapid titration. In women with idiopathic generalized epilepsy (IGE), I use lamotrigine with the explanation that this drug may be less effective for myoclonic seizures.

Valproate is the AED with the strongest association with birth defects and impaired childhood cognitive development, so I generally avoid this drug in women who may become pregnant. This is not to say that valproate should never be used in women with epilepsy. With our hypothetical patient who has partial seizures, the recently published SANDAT trial and years of experience with valproate indicates that this drug can be very effective in patients with IGE; it is possibly the most effective drug available.

While somewhat safer, the other older AEDs (phenytoin, carbamazepine, and phenobarbital) also have an increased risk of birth defects, along with the same problems affecting all patients with epilepsy, such as drug interactions and long-term side effects. I generally avoid starting patients on these medications, unless these are all that the patient can afford. When patients are on these drugs, it is important to aim for monotherapy, since polytherapy can greatly increase the risk of congenital malformation.

How do you select the daily dose?

Page Pennell: I use two principles. One is that we want to use the lowest dose that will control seizures. We don’t have clear evidence-based information for all medications, but we do have information about a dose-related risk for valproate and possibly for lamotrigine. I still apply this principle to all medications used during pregnancy.

The other principle is to avoid high peak levels of the medication. I use an extended formulation of the medication when available, and I try to spread out the doses, when possible, into 2 or 3 times per day depending upon the medication.

Andre Lagrange: The dose-dependent teratogenicity of valproate has been well-documented in a number of studies and the risk to the fetus may be reduced by using lower doses (< 1100-1500 mg per day). One registry suggested that high doses of lamotrigine may also increase the risk of malformations. While this association has not be found by the other registries, it is still probably prudent to use the lowest effective dose when prescribing AEDs to women with epilepsy.

While determining the dose is based mostly on seizure control, this is one situation in which I rely more heavily on blood levels. Since levels can decline during pregnancy, I generally aim for blood levels in the low therapeutic range and then adjust the dose during the pregnancy to maintain this level.

How do you monitor for seizures and medication dosages through the course of the pregnancy?

Page Pennell: I perform monthly measurements of the AED level and make changes according to that particular woman’s individual target concentration. In a recent study we did see a substantial difference when we took a therapeutic drug monitoring approach to the use of lamotrigine, with only a small portion of women experiencing seizure worsening in comparison to previous studies of seizure frequency in women on lamotrigine. Although a lot has been written about lamotrigine recently, it is important to remember that almost all AEDs decrease in concentration during pregnancy and often in an unpredictable way for each patient.

The individual target concentration for any AED varies between patients according to seizure type, epilepsy syndrome and other personal factors. I try to establish this prior to conception and make sure they have a measurement within the year prior to conception. I then try to maintain that concentration during pregnancy. I think the bigger disservice we can do to our patients, once they decide to use AEDs during their pregnancy, is to inadequately treat their epilepsy, and cause fetal exposure to both antiepileptic drugs and maternal seizures.

Andre Lagrange: If the patient was seizure-free prior to pregnancy, I aim to keep drug concentrations around the pre-pregnancy level. Since pregnancy may alter the volume of distribution and protein binding of some drugs, it is best to follow free levels, when available. Given the variability among laboratories, using the same one throughout the pregnancy is probably a good idea. Depending on the patient, I generally check levels every four to six weeks in patients taking lamotrigine, oxcarbazepine or levetiracetam. For other AEDs, an interval of every 2-3 months is probably sufficient.

In addition to medication therapy is there something else that you would recommend before and during the pregnancy?

Page Pennell: I do recommend the benefits of folic acid as a way to mitigate the possibility of neural tube defects, oral clefts, and possibly other birth defects. Although the benefits of folic acid in women with epilepsy are not clear, the benefits in both the general population and in other groups at high risk are clearly proven. I recommend one milligram of folic acid daily and sometimes will increase the daily folate dose to 4 milligrams, especially if the woman in on carbamazepine or valproate. I also reinforce that they take a prenatal vitamin prior to and during pregnancy, as various theories relate insufficient vitamin intake to AED-induced teratogenicity. It is also important that we establish close contact with her obstetrician and recommend that she gets an ultrasound by a perinatologist at 18 to 22 weeks gestational age.

Andre Lagrange: Folate has clearly been shown to reduce the risk of neural tube defects in the general population. Neural tube defects are one of the more common birth defects in women taking valproate or carbamazepine. Furthermore, AEDs can negatively impact folate metabolism. Given the low cost and risk of folate supplementation, it is reasonable to add 2-5 mg folate to the regimen of women taking AEDs. Having said that, the optimum folate dose is unknown and none of the registries have shown that folate supplementation actually reduces the risk of birth defects in children of women taking AEDs during pregnancy.

Hemorrhagic disease of the newborn is a potentially neurologically devastating condition in which previously normal neonates suffer spontaneous intracerebral hemorrhages. The risk of this condition is increased in the children of mothers taking enzyme-inducing AEDs, especially phenytoin. The increased risk is thought to involve AED-induced changes in Vitamin K metabolism, and the American Academy of Neurology recommends supplementing 10 mg daily of Vitamin K in the last trimester of pregnancy in women taking phenytoin. However, as with folate in pregnancy, there is no study that actually shows that supplementation reduces the risk in these babies.

While most women with epilepsy have normal, vaginal deliveries, I recommend that my patients are followed by a high-risk pregnancy service. As part of their obstetric care, it is also recommended that these women undergo more rigorous prenatal testing. This testing should also be offered to women who would never consider terminating a pregnancy, in that identifying congenital anomalies will allow planning appropriate post-natal care, if any is needed.

Finally, many obstetricians are unfamiliar with the sudden changes in AED metabolism that occur after parturition. When a patient has substantially increased her dose of lamotrigine or oxcarbazepine during the pregnancy, I let both the patient and their physicians know that the dose should be decreased halfway back to their pre-pregnancy dose at the time of delivery. Depending on the patient, I usually titrate the AED back to the pre-pregnancy dose over the next two to three weeks, followed by checking blood levels.

What most concerns you when prescribing medication to a woman who has seizures and who also wishes to start a family?

Page Pennell: I am most concerned about the health of the mother and child. Although there are risks, we can do several things to reduce these risks to a level that is not much higher than the risks of any pregnancy. Guiding principles include use of monotherapy with an AED that has substantial safety information during pregnancy, avoidance of valproate in monotherapy or polytherapy, supplemental folic acid and a prenatal vitamin, and maintaining adequate AED dosages to prevent seizure worsening or at least convulsive seizures or status epilepticus. I provide both counseling at the visit and written materials to assure that the patient and her spouse or partner understand the latest information available, so she can actively participate in making an informed decision about use of AEDs during her pregnancy.

Andre Lagrange: I try to remind patients that the vast majority of women with epilepsy deliver perfectly normal infants and that all of this preceding discussion is simply helping her to further optimize her chances. For most women, adequately treating her epilepsy needs to be the primary goal. Unfortunately, it is all too common for a woman to discontinue her AED upon discovering that she is pregnant, in the mistaken belief that this will be good for her developing baby.

I try to remind each woman about the risks that subsequent seizures pose her and her baby. Furthermore, organogenesis is largely complete before women even are aware of the pregnancy. Since nearly 50% of all pregnancies in the U.S. are unplanned, it is important to have this discussion early. I generally bring it up during the first visit.

Dr. Meador is presently the Melvin Greer Professor of Neurology at the University of Florida, where he serves as Director of Epilepsy Program and Director of Clinical Alzheimer Program. Dr. Meador graduated from Georgia Institute of Technology in Applied Biology and received his MD from Medical College of Georgia. After an internship at University of Virginia and service as an officer in Public Health Corps, he completed a residency in Neurology at Medical College of Georgia and a fellowship in Behavioral Neurology at University of Florida. Dr. Meador joined the faculty at Medical College of Georgia (1984-2002) where he became the Charbonnier Professor of Neurology. He was Chair of Neurology at Georgetown University (2002-2004) and joined the faculty of University of Florida in 2004. Dr. Meador has authored over 200 publications and serves on multiple journal editorial boards. His areas of research include cerebral lateralization, dementia, epilepsy, mechanisms of attention and memory, neglect syndrome, psychoimmunology, and the pharmacology and physiology of cognition.  

Michael E. Clark is a partner at Hamel Bowers & Clark LLP in Houston, TX. Mr. Clark is the Chair of the Publications Committee for the ABA Health Law Section (and a Vice Chair of its Health Care Litigation and Risk Management Interest Group), and is also the Chair of the Criminal Laws Committee for the ABA Business Law Section. Mr. Clark is a Fellow of the American Bar Foundation and a Life Fellow of the Houston Bar Foundation. He is Board Certified in Criminal Law by the Texas Board of Legal Specialization and by the National Board of Trial Advocacy. Mr. Clark is AV® rated by Martindale Hubbell, and a member of the National Arbitration Forum Panel.

He has served as an Adjunct Professor at the University of Houston Law Center, where he has taught Antitrust and Health Care, and has co-taught Regulation of Biomedical Research, Civil Trial Advocacy, and Criminal Trial Advocacy. In addition to his JD from South Texas College of Law, Mr. Clark has obtained two LLM degrees, one in Taxation and the other in Health Law, from the University of Houston Law Center.

What is your opinion on optional versus mandatory reporting?

Michael Clark: While I am reluctant to recommend imposing additional, government-mandated duties on healthcare professionals, for various reasons it appears that a mandatory reporting system is more workable.When viewed from a liability standpoint, having a clearly-expressed and mandatory reporting obligation will establish a standard of conduct and a baseline for measuring a physician’s conduct. This is preferable to having a hazy or discretionary suggestion of when a physician may report. In addition, having a mandated duty will likely help physicians to realize the importance of becoming more knowledgeable about the issues.

An optional regime appears far more likely to put physicians in untenable situations that can only harm the physician-patient relationship. If, in the exercise of professional judgment, a physician reports a patient (because the patient’s condition poses a high risk to the general public if s/he continues to operate a motor vehicle without any conditions or restrictions), the patient could hold the physician responsible since the physician chose to report the patient.

Kim Meador: I don’t think that physicians should be obligated to report. I have seen no data that says it helps in any way. In states where reporting is mandated, there are no studies that prove that this has been effective. But there are data that indicate that reporting disrupts the patient-physician partnership. I do think physicians should talk to the patient about this and document the conversation in the charts. All of this should be within the context of state law.

For physicians, it is a medical, legal, and moral issue. But they don’t have an obligation to track down and find out what a patient is really doing. Physicians are not here to enforce the law. If you find that patients are still driving after you informed them not to drive, then you should be able to freely report them. But here is the next problem. If reporting is codified, and it is mandatory, then the patient might lie.

One irony as I see it is that these reporting laws are made by lawyers, who still maintain their client-laywer confidentiality. I find that to be hypocritical because the law expects us, as physicians, to compromise the patient-physician relationship.

Should there be more clear-cut guidelines that mandate reporting?

Michael Clark: Yes. Clearer guidelines will not only protect physicians from legal liability, but should also protect patients who suffer from such conditions from being unfairly treated since a large number of them should be allowed to drive since they can do so safely and without imposing broadly-based restrictions.

Kimford Meador: Patients whose medical condition compromises their driving pose a risk to themselves and the public. This is one of those situations where there is a conflict of civil liberties verses the public good. It is important that state laws are clear – and many set time limits such as 3 months to 2 years during which a patient has to have no seizures before being able to drive. The timelines are related to relative risks, but as the variance in state laws exhibit, the timelines are somewhat arbitrary.

Variance in state laws is a problem. A state that has a mandate makes the reporting issue pretty clear cut. Some states have no guidelines at all. When you have a state that has clear cut guidelines and a patient with uncontrolled epilepsy, then it has to be reported. However, in those states where the guidelines do not mandate reporting, the physician has a moral and legal responsibility to talk to the patient about their risks and the local driving laws. The physician should document this discussion. Overall, I think physicians have an obligation to advise their patient, and patients have an obligation to follow the law.

How should the issue of the non-compliant patient be handled?

Michael Clark: I advise lawyers who encounter problem clients who fail to follow their advice that the lawyers need to consider whether this is a client who they should continue to represent since, from a legal liability perspective, this is a major warning sign. While physicians face different duties and pressures (compared to lawyers) in their practices, this advice holds true since having a non-compliant patient can increase a physician’s legal liability. Physicians should determine the reasons for the patient’s non-compliance, such as whether he or she failed to understand what was required, or understood what was required but did not want to follow the instructions given. Patients in the latter category likely should be fast-tracked to the status of former patients. Finally, to ensure that such recalcitrant patients are not allowed to pose systemic harm, there should be a mechanism in place that physicians can report to when they have encountered such patients.

Kim Meador: If we are talking about non-compliance with regard to medication, that is one issue. Non-compliance in terms of driving against medical advice is another.

If a person is not taking medication as prescribed, they compromise their own health and possibly the safety of others if they drive. If a person’s medication is being changed because, for example, a woman is pregnant – this could trigger a seizure. Guidelines for a seizure free patient who is changing medications are unclear.

What about the patient who is non-compliant with medication, but is not having seizures? They didn’t break the state law by stopping their medication.But they do risk harming themselves and others if they have a seizure.

But one who is non-compliant with medication imposes the greatest risk which moves from civil liberties to public safety. We saw one study in which 54% of patients with epilepsy involved in an accident while driving were doing so illegally. If a person is non-compliant with respect to driving against medical advice after you told that person the law, then in my opinion, that’s a problem.And the patient should be reported.

What responsibility does the physician have with regard to patients with active seizures that are still driving?

Michael Clark: If the seizures are reasonably foreseeable in light of the patient’s known condition, then a physician’s obligations are heightened not only to protect the patient, but also the general public. Patients who are experiencing active seizures that may not be controllable pose such dangers and the (in)action of caregivers who had an opportunity to prevent a foreseeable bad result could be measured in a courtroom with a jury that is being asked to award damages. Physicians can expect that plaintiffs’ counsel will be arguing that they failed to adhere to the standard of care and should be held liable. This is again why it seems important for a clear legal standard to be mandated since juries can be emotionally swayed when they must decide liability or award damages when faced with bad outcomes.

Kimford Meador: Physician responsibility for reporting in California and some other states is mandated – although it is not clear in most states. However, what happens when you have specifically told a patient not to drive? If the patient continues to drive, and you know for a fact that the patient is driving, then you should report because it is a legal liability if you do not and can be dangerous to others.

Oftentimes you don’t know whether or not a patient is driving against medical advice. Most patients don’t tell. However, many live in places that do not have good public transportation. So if you ask about driving, they may well lie to you. The physician must document their conversation including information given by the patient. Otherwise the physician may be legally liable.

What happens in the case where a patient is non-compliant and a family member asks me to intervene? I will sit and talk with the patient and explain that driving while their seizures are not under control is very serious and if they have an accident and someone dies, that they can be charged with manslaughter. If after that conversation I find out that they are still driving, I would report them. Sometimes you can reason with a patient, and sometimes, you cannot, especially if the patient has a cognitive impairment. However, it should be noted that a physician’s knowledge of patient driving is almost entirely based on self-report and family reporting.

We are trying to balance these issues without evidence-based medicine. So we see variance across states. We would like the laws to be more uniform, but more actual data is needed to make laws that balance individual rights and public safety. Unfortunately, a great deal of health policy is not evidence-based.

Are you satisfied that the American Academy of Neurology is supporting stricter driving and reporting standards for public transportation drivers, professional driving services, or hazardous-material drivers, or should the AAN be taking a more active role?

Michael Clark: A more active role is needed for all of the reasons expressed above. Optional reporting regimes are impractical, unworkable, and generally a bad idea.

Kimford Meador: I think that these standards should be much stricter. Such individuals spend more time on the road and transport than other people. The standards should be even higher for those who pilot a plane, a school bus or a tanker full of gasoline or other dangerous materials. With these types of drivers, the public health risks are higher.