The 27th International Epilepsy Congress (IEC) was held in Singapore from July 8 to July 12. We added the most recent presentation sent to us on September 7, 2007. The topics focused on:

• Issues in Developing Countries, Treatment of Epilepsy
• Neuropsychological and Psychiatric Aspects
• Men and Women with Epilepsy Throughout Life
• Stigma and Quality of Life
• Epileptogenesis in Relation to Genetic Predisposition in Abnormal Brains
• Epidemiology and Prognosis

Members of the editorial board of epilepsy.com/ professionals and physicians and scientists whose works have appeared on our site submitted the following abstracts:

• Appropriate Management of Women who Become Pregnant while Participating in Clinical Trials of Anti-Epileptic Medications
• Clinical Trials with Brain Stimulation
• Reduced Sexuality in Men with Epilepsy: Multiple Putative Factors
• Seizure Severity Questionnaire (SSQ) As a Patient-reported Outcome in Multi-national Clinical Trials
• What Is the Long Term Outcome in Patients with Intractable Epilepsy? Are There Treatment Options in Addition to Surgery?

Presentation Synopses

Appropriate Management of Women who Become Pregnant while Participating in Clinical Trials of Anti-Epileptic Medications

Roy Beran, MD, a recent contributor to epilepsy.com/professionals, is a consultant neurologist and visiting medical officer at a group of hospitals in Australia. He has a special interest in epilepsy and law. In Singapore he presented “Appropriate Management of Women who become Pregnant while participating in Clinical Trials of Anti-Epileptic Medications”

Dr. Beran noted that most trials do not include “pregnant women or those who wish to become pregnant; are breast-feeding; or who do not practice adequate contraception.” Nonetheless, it does happen that some women do become pregnant during trials of anti-epileptic drugs (AEDs). Usually at that point they are excluded from continued participation. What happens to these women?

“Trial exclusion, irrespective of efficiency or risk of ‘withdrawal seizures’ exposes mother and fetus to potential risks beyond direct AED teratogenicity,” says Dr. Beran. He points out that while it is appropriate to exclude women prior to pregnancy, once inadvertent pregnancy occurs, “these pregnant women deserve the right to self-determination be it: continued trial participation; cessation of trial AED; maintenance of pregnancy; or abortion. Automatic exclusion denies informed consent for the individual and wastes valuable data should the subject decide to persevere with the trial.”

Clinical Trials with Brain Stimulation

Robert S. Fisher, MD, PhD, Stanford University, whose educational videos are slated to appear on epilepsy.com, presented a paper focusing on deep brain stimulation (DBS) for epilepsy, which has been attempted at several sites within the brain.

Dr. Fisher noted that pioneering work was performed by the New York neurosurgeon, Irving Cooper, MD, but initial results were anecdotal. He said, “The success of vagus nerve stimulation and DBS for movement disorders reinvigorated the search for DBS epilepsy therapies. No large controlled study of this therapy has yet been published, although small pilot controlled studies have shown variably positive or negative results. As with medication clinical trials, results with animal models may or may not extend to the human condition; however, laboratory research and scientific underpinnings for DBS deserve much more study and attention.”

He pointed out that two large controlled trials are underway, one investigating anterior thalamus stimulation (sponsored by Medtronic), another testing direct responsive stimulation of the seizure focus (sponsored by NeuroPace). Trials of hippocampus stimulation are in development. Detailed information on safety and efficacy of deep brain stimulation for some types of epilepsy should become available within the next year.

NeuroPace was a presenter at the AED IX Conference sponsored by the Epilepsy Therapy Project this past year, and Dr. Fisher presented preliminary information on the Medtronic study at that meeting.

Reduced Sexuality in Men with Epilepsy: Multiple Putative Factors

Cynthia L. Harden, MD, from Weill Medical College of Cornell University and a member of the editorial board of epilepsy.com/professionals was a co-author on a paper that was presented at the IEC by her colleagues, pointing out that “men with epilepsy are at risk for decreased sexual functioning, including sexual interest and sexual performance.”

Dr. Harden and her colleagues noted that reduced sexual functioning could be due to antiepileptic drugs (AEDs). They also stressed that “Epilepsy itself appears to have the potential to affect sexual function, likely because of irregular gonadotropin secretion due to seizure-related depletion of hypothalamic neurons that secrete gonadotropin releasing hormone. The amygdala is also emerging as a brain structure with significant involvement in sexuality in persons with epilepsy, as shown by alterations in sexual functioning after temporal lobectomy.”

Dr. Harden concluded that epilepsy may compromise sexual development in male adolescents and that both sexual anxiety as well as the stigma of epilepsy “can also affect the sexual life of persons with the disorder.”

Seizure Severity Questionnaire (SSQ) As a Patient-reported Outcome in Multi-national Clinical Trials

Joyce Cramer, President of The Epilepsy Therapy Project and Associate Research Scientist in the Department of Psychiatry at Yale University School of Medicine, in collaboration with colleagues at Yale, presented their ongoing research that will demonstrate the utilization of a questionnaire to assess seizure severity in multi-national clinical trials of carisbamate, an investigational anti-epileptic drug.

Ms. Cramer et al chose the SSQ (Cramer et al, Epil Res 2002; 48:187-97) for their study. The SSQ is a patient report of multiple components of seizures that assesses severity and bothersome aspects of seizures, including seizure warnings, activity, and recovery (physical, emotional, cognitive aspects). Patients also define the most bothersome component of their seizures.

The researchers and their trained study staff will obtain responses to the SSQ at baseline (BL) and follow-up (FU) interviews, using translations of the SSQ to match the primary language of the patients. The team anticipates that “patient-reported outcome information on seizure severity will be collected accurately and completely using the SSQ. Assessments at BL and FU will be compared to determine change with addition of carisbamate versus placebo in multinational clinical trials.

What Is the Long Term Outcome in Patients with Intractable Epilepsy?

Are There Treatment Options in Addition to Surgery?

Jacqueline French, MD, University of Pennsylvania, is the Director of the Penn Epilepsy Center and Assistant Dean for Clinical trials. She is also a member of the executive committee of the Epilepsy Therapy Project. In her abstract she noted that “Much of what is currently known about refractory epilepsy derives from studies in newly diagnosed patients.”

In a paper that points out that this may not be “the optimal population to study, since there is a lot of variability at that stage,” Dr. French says, “Newly diagnosed patients may appear to remit, but later start to have seizures again. Studies indicate that many people will alternate back and forth between periods of seizure activity and periods of remission. On the other hand, patients may take a while to respond, , and spontaneous remissions are not uncommon (1). Rather than identifying patients initiated on therapy to determine who will be refractory, several recent studies have focused on patients who have already stabilized and have established treatment resistance, to see who of these patients will remit.”

In her presentation, she noted that “randomized controlled trials of new AEDs in patients with refractory epilepsy have shown relatively low seizure free rates, even in the short term, ranging from 0-7.9% (2)” This makes it seem as if remission with AEDs is very unlikely. But, several recent studies following people for a longer time have shed more light on the issue.

Recent studies discussed included:

• Short-term seizure freedom with the new drug pregabalin.
  • Estimates of seizure freedom for pregabalin were 5.5%, 1.3%, and 0.4% for baseline seizure frequencies of 5, 10, and 15 respectively.
  • As such this study indicates that “patients with a high baseline seizure frequency were less likely to remit.”
• Seizure freedom for at least six months was demonstrated in 16% of 155 adult patients with therapy-resistant epilepsy treated in a single practice (3).
• The remission rate (at least 12 months) was 5%/year (4) in 246 adult refractory patients studied for 3 years.

Dr. French concluded: “Patients with seemingly refractory epilepsy can, indeed, ultimately respond to therapy. Further study is needed to determine prognostic indicators for remission, and to see whether refractory patients who become seizure free will remain so for the long-term.”

References

1. Sillanpaa M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain. 2006;129:617-24.
2. Gazzola D, Balcer L, JA French. Seizure free Outcome in Randomized add-on Trials of the New Antiepileptic Drugs. Epilepsia 2007 In Press.
3. Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007.
4. Callaghan B, Anand K, Hauser W, French J. The Likelihood of Seizure Remission in an Adult Population with Refractory Epilepsy. Epilepsia. 2005;5(6C)::S594.

We will present other abstracts in the coming weeks.

Edited by Steven C. Schachter, MD 09/7/2007