11th European Congress on Epileptology

Close to 2,500 delegates from 91 countries gathered in Stockholm from June 29th through July 3rd for the 11th European Congress on Epileptology. Delegates were welcomed by singers from the world renowned Swedish Choir Orphei Drängar. The opening ceremony also introduced the Nobel Prize Theme of the Congress, the host city being the home of the great donor Alfred Nobel. Dr Olov Amelin, Director of the Nobel Museum in Stockholm, presented the exciting story of the man behind the Prize and its history. The City of Stockholm hosted a much appreciated reception in the magnificent City Hall, venue for the Nobel Prize banquet. To further celebrate the significance of the Prize an exhibition of selected Nobel Laureates in medicine or physiology with links to the most relevant scientific sessions was on display throughout the congress. Delegates were invited to vote for the Laureate that had made the most significant contribution to epileptology. The winner, Golgi, was announced at the closing Highlights session.

Inspired by the bridges connecting the islands of Stockholm, "Building Bridges" was the general philosophy of the scientific programme: Bridges between basic and clinical science; between research and clinical practice; between delegates and the ILAE leadership in interactive sessions on classification and definitions; between ILAE/CEA and other relevant organizations through joint sessions with European Sleep Research Society, with the ILAE North American Commission, with the European Medicines Agency, and with IBE.

Special efforts were made to bridge the generation gap, giving young delegates more visibility and attention. Hence, more space was given to platform presentations, in total 114, and presenters of all 653 posters were given the opportunity of discussing their results with peers in guided poster tours.

In accordance with current health care priorities, the topic selected for the Chairs’ symposium wasPrevention in Epileptology, in its broadest sense ranging from opportunities for primary prevention of the development of epilepsy to prevention of the adverse consequences of epilepsy and the treatment. The four main scientific themes of the Congress, basic science, pharmacology, paediatrics and epilepsy surgery, were each featured in one main topic session and four additional related sessions, and complemented by other sessions and free communications. Penetrating through all basic science presentations was the issue of translation, highlighted in the main session "Changing epileptic brain: translational challenges and opportunities." Questions specifically addressed included: Matching animal models to efficacy in humans: We need to know how predictive the animal models are in terms of overall efficacy and tolerability (including different syndromes); The need of biomarkers: Biomarkers will be essential both in preclinical and clinical research; The need for improved methodological and reporting practices; The importance of using clinically relevant treatment protocols and outcome measures concerning the tolerability of the treatment and other endpoints, in addition to seizures; The issue of statistical power: Proposals were made for Phase II preclinical trial (multi-center studies designed along the lines of Phase II/III clinical studies.

Gene therapy emerged as one of the main translational possibilities in epilepsy. This research area includes not only single or combination gene therapy approaches, but also advanced strategies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and optogenetics. One novel development in basic science approach is addressing alterations in epigenetics, adding another level of complexity to gene regulation that seems to be important for epileptogenesis and ictogenesis. Overall, there seems to be a trend in basic research of shifting the emphasis towards novel, unconventional, and various mechanism-targeting tailored approaches and their combinations, to affect epileptogenesis and prevent epilepsy. However, for translating these findings, we need reliable biomarkers to identify patients that are at risk of developing epilepsy, in particular after brain insults.

Another main topic was "Pharmacotherapy of the future: New molecules, new targets, new goals" where new avenues for pharmacological prevention and treatment of epilepsy were explored, including the potential role of drugs established for other indications and purposes such as ketamine, bumetamide and SSRIs. Long-term effects of the novel everolimus treatment was evaluated in patients with tuberous sclerosis and sub-ependymal giant-cell astrocytoma (SEGA) demonstrating stable effectiveness over 4 years of treatment regarding size of SEGA as well as of reduction of seizure frequency.

Another session that attracted much attention reviewed the possibilities and consequences including risks associated with withdrawal of antiepileptic drugs. Reducing AED load following successful epilepsy surgery in children was associated with increased postoperative IQ in the cohort of 301 patients included in the Time-to-Stop study.

Another study demonstrated that AEDs might have a distinct impact on catastrophic infantile epilepsies as a function of the underlying gene mutation. SCN1A mutations are associated with high rate of AED-triggered aggravation, primarily due to sodium-channel blockers, while such aggravation is rare in PCDH19 mutations. In both mutations, clobazam appeared to be the most effective AED.

The paediatric main topic session focused on Epilepsy syndromes: From infancy to adulthood. Epileptic Encephalopathies (EE) was the topic that received most attention. Thanks to the new genetic techniques such as Next Generation Sequencing, the use of targeted panels, and the Whole Exome Sequencing (WES) there has been an explosion of genetic findings in EE. These techniques have led to the identification of several new genetic mutations that have been classified as ion channel genes and non-ion channel gene mutations.

EE is a condition with a wide genetic and phenotypic heterogeneity. To reach a better understanding of this condition, collaborative studies are needed. Several examples of mutations identified through such collaborative efforts were presented: in one study from the EuroEPINOMICS-RES – EPGP/Epi4K consortium of patients with Epileptic Spasms or Lennox Gastaut Syndrome, 429 de novo mutations were identified in 356 patients. By collaborating in consortia, large case series of patients with a defined genetic mutation are collected in which the phenotype can be studied in depth. In one such study the emerging phenotype of SCN8A encephalopathy, based on a case series of 17 cases, was presented.

The association of Epilepsy and Movement Disorders was emphasized. In one study of EE with movement disorder and/or hand stereotypies, mutations were discovered in 8 patients out of 10 (80%). Some affected well-known genes as CDKL5, SCN1A and SCN2A, others affected less known genes as CHD2, TBL1XR1, SETD5 and GRIN1. Therefore involuntary movements or hand stereotypies provide important clues for an appropriate choice of gene test leading to proper diagnostic approach for EE. The expanding phenotype associated with PRRT2 mutation was also pointed out: not only Benign Infantile Familial (and sporadic) Epilepsy and/or Paroxysmal Kinesigenic Choreoathetosis, but also Hemiplegic Migraine, Migraine with aura and Episodic ataxia.

Another topic was the expanding use of the Ketogenic Diet (KD) in drug-resistant epilepsy and in inborn error of metabolism (Glut-1 deficiency, Pyruvate dehydrogenase deficiency, and other mitochondrial diseases), status epilepticus, FIRES, Rett and Dravet syndrome, Tuberous sclerosis complex (TSC), and Myoclonic atonic epilepsy. New diet regimens have been developed with a lower fat percentage therefore having a better taste but shown to be equally effective. After 12 months a good therapeutic outcome is achieved in around the 40% of patients, and 60% are still on KD after 12 months.

Other treatment news included the proposal that sodium channel blockers such as carbamazepine and phenytoin, seem to be particularly effective in KCNQ2 encephalopathy and SCN2A-related epileptic encephalopathies.

Another main topic session took the challenge to explore "Who benefits from epilepsy surgery?" with a post main session discussing the down-sides of epilepsy surgery. In order to counsel patients appropriately and realistically, long-term outcome data are needed. Several recent long-term studies have shown that around 40-50% of patients have over 10 years of sustained seizure freedom after resective epilepsy surgery while the risk of major complications is limited to around 2-3%. Optimism bias and framing of information were pointed out as problems to be aware of when counseling. The importance of a more holistic approach to outcome evaluation was emphasized. We need to identify patients who are at risk of being double losers – i e those who do not achieve seizure freedom after surgery, but who have a memory decline. The need for systematic studies of the poorly studied but important behavioral consequencesof epilepsy surgery was also pointed out. Only if we have a more thorough understanding of the long-term impact of surgery can people with epilepsy be adequately counseled about both the possible gains and risks of epilepsy surgery.

One specific question in the management of epilepsy is whether a genetic basis of epilepsy precludes epilepsy surgery. Intuitively, focal resection may seem inappropriate in genetic epilepsy. However, several studies were reported both of patients with refractory familial mesial TLE and of patients with nocturnal FLE (NFLE), some of which were autosomal dominant, where presurgical evaluation could identify a focal seizure onset and epilepsy surgery was successful. Also, a GEFS+ mutation was shown not to be a contraindication to epilepsy surgery when the epileptogenic zone is well localized like in case of SCN1A/B epilepsy and hippocampal sclerosis. However, not all structural abnormalities seen in the context of genetic epilepsy are necessarily a surgical target and it was emphasized that we need to pay attention to understanding the phenotype.

Finally, E-Pilepsy, the European pilot network of reference centers in refractory epilepsy and epilepsy surgery, was presented. One goal of E-Pilepsy is to harmonize pre-surgical evaluation and optimize the surgical treatment of epilepsy throughout Europe.

In addition to cutting edge scientific sessions, the congress offered highly appreciated teaching sessions and courses targeting clinicians, nurses as well as EEG technicians. Teaching courses as well as scientific sessions were well attended. Discussions were lively and characterized by an informal and friendly atmosphere, and our impression was that indeed many new bridges were established and that the Congress fulfilled its mission.

Torbjörn Tomson, SAC Chair; Kristina Malmgren, IOC Co-Chair;
Merab Kokaia, Reetta Kälviäinen, Philippe Ryvlin, Federico Vigevano, Main Topic Chairs