As I reflect back on the 64th annual meeting of the American Epilepsy Society, I am still very energized about all that I have learned at this meeting. The meeting in early December had over 1200 presentations and 4500 attendees. The following is a summary of the some of the research highlights from the meeting.

• There are many myths about the co-existence of epilepsy in people with psychogenic non-epileptic seizures (PNES). Although some studies had indicated a prevalence of 30-60% of epilepsy in PNES, more recent studies have demonstrated an incidence of 9-13% suggesting that discontinuation of AEDs in a patient with no significant risk factors for epilepsy might be a reasonable course of action. About 98% of patients with PNES have an affective disorder during their lifetime. There are also similar high rates for other psychiatric co-morbidities such as dissociative disorder (93%), somatoform disorder (98%) and PTSD (58%). Results from the randomized controlled trial of sertraline for people with PNES (LaFrance et al., 2010), where flexible titration doses up to 200 mg showed a potential benefit for frequency of spells was a surprising find. However, the study was designed as a pilot and the
  results need to be replicated.
• The Presidential Symposium with its analogy about how to identify aconductor in the neuronal orchestra, just find where the GABA cells are was especially illuminating. The music analogy is fairly powerful as inhibitory cells are responsible for the tempo in the circuitry. I also finally understood why benzodiazepines which work great for Status Epilepticus early, lose their efficacy late in SE. The explanation has to do with the turnover of GABA-A receptors, the internalization of receptors with selective subunit composition, leading to a progressive use-dependant reduction of GABA-A mediated inhibition (Goodkin et al., 2008, Goodkin & Kapur, 2009).
• At the Antiepileptic Therapy symposium, the emphasis was on the KCNQ1 channel that is expressed in heart and CNS, and a loss of function mutation of KCNQ1 results in prolonged QT syndrome and seizures in mice (Goldman et al., 2009; Glasscock et al., 2010).
• At the annual course, I learned more about the pro-convulsant functional interaction between Interleukin 1-beta and NMDA receptors (Balosso et al., 2008), which might explain in part, why our epilepsy patients often have exacerbations of seizures during minor systemic illnesses. Although I knew about the role of Interleukin 1-beta, I was unaware of its interaction with NMDA receptors, and I met another inflammatory family, the Toll-like receptors which are also upregulated in human epileptic brain and their activation by HMGB1 appears also pro-convulsant (Maroso et al., 2010). I then learned that the alleged vaccine encephalopathy was truly the unmasking of a genetic mutation of the SCNA1 (sodium) channel with a phenotype of Dravet syndrome (Berkovic et al. 2006; McIntosh et al., 2010). Tallie Baram presented a series of elegant experiments demonstrating that Interleukin 1-beta levels after a febrile seizure were predictive of developing subsequent epilepsy in her experimental model of febrile convulsions (Dube et al., 2010).
• There were so many other important symposia, that it is almost impossible to attend them all. Fortunately, before the end of February, I expect that the major symposia of the 2010 annual meeting of the American Epilepsy Society will be available on the AES website with slide presentation, the MP3 audio file, and a transcription. The link of the archived symposia since the 2004 annual meeting is at: http://www.aesnet.org/go/professional-development/educational-opportunities/archived-aes-symposia . You can also find the handouts from the major symposia already at the AES at this link: http://www.aesnet.org/syllabus-handouts/2010-handouts .
• On Monday, I was the main presenter of a poster from my research laboratory where we demonstrated with electrophysiological recordings in the Kainic Acid rat model that the epileptic hippocampus no longer works in discrete lamellas (or slices), but that there is translamellar hyperconnectivity and hyperexcitability. In essence, the reason why we need to excise the epileptic hippocampus in human mesial TLE is because the wiring has become an amplifier of epileptic activity and it is the cause of the intractability of mTLE. Our laboratory also presented patch clamp recordings of KCNQ channels in the brainstem, which might be an area to examine further in the attempt to explain SUDEP. We also had two clinical research posters on Sunday.

Highlights from the platform sessions included:

• Camfield and colleagues examined whether children with intractable focal epilepsy experienced a substantial period of remission at 10-30 years of follow-up.
• Hesdorffer and colleagues discussed a meta-analysis of pooled data from several epidemiological studies on SUDEP extracting the most powerful risk factors.
• Christensen and colleagues presented mortality data in a large Danish cohort of people with epilepsy, and Meador and colleagues (C.08) revealed the age 4.5 year results of the NIH study on cognitive functions of children exposed in utero to antiepileptic drugs.

Lastly, the ILAE symposium addressed differences in clinical trials for seizure drugs across the world. Two issues were discussed: approach for randomized control trials for regulatory approval of antiepileptic drugs in Europe (pragmatic comparative trials) as compared to the United States (placebo controlled trials), and 2) doing epilepsy surgery with fewer diagnostic tests as compared to multiple tests. Although the first topic is of great clinical significance, I plan to discuss what goes on within a FDA advisory panel in a future column. The presentation on epilepsy surgery with a shoe-string approach gave me great hope for many patients with intractable epilepsy in the countries with few resources. A pilot study in Uganda (Boling et al., 2009), a country with a GDP of $1,200 per capita (207 out of 227 countries), life expectancy of 52 years, and 7% health expenditure of GDP, a consortium was able to perform standard anterior temporal lobectomy at a cost of $100 dollars. The consortium placed one video EEG bed in a pediatric hospital and trained nurses. The patients had stringent inclusion criteria and underwent a fine cut head CT. The video EEG study was interpreted in the US or Canada, and the local Ugandan physician and neurosurgeon received several weeks of training. Out of 10 cases operated, 60% were seizure-free and 20% had >90% improvement in seizure frequency. These results appear comparable to the full-dress approach that might cost several thousands of dollars.

The AES meeting is always a great meeting and an opportunity to network with new collaborations. I hope to see you in Baltimore for the 75th anniversary of our society. I hope this summary helps to distill the essence of some of the important discoveries that occurred at the AES meeting.

Jose E. Cavazos, M.D., Ph.D.
Last Reviewed: 1/15/11