The MICHAEL FORUM was initiated in order to enable the MICHAEL PRIZE awardees to discuss their research in an informal setting organized every two years in the proximity of larger European scientific conferences. In these workshops, awardees, trustees of the MICHAEL FOUNDATION, the international jury, as well as representatives of the sponsors meet for two days to have an in-depth and at times controversial discussion of the newest findings illuminating causes, consequences, and the treatment of epileptic seizures.

The speeches given during the forum have been published as a summary article in the journal “EPILEPSIA” for several years.

In 2010, the MICHAEL FORUM took place in Regensburg, Germany, from the 2nd to the 5th of September.

The MICHAEL-FORUM 2010 brought together 22 MICHAEL PRIZE laureates to discuss the latest advancement in epilepsy research.

A broad range of exciting topics was covered which can be subdivided into several research areas:

Heinz Beck reported on the pattern of input integration in granule cells. Two-photon guided dual somatodendritic patch-clamp recording revealed that both excitatory post-synaptic potentials and back-propagating action potentials exhibit strong but uniform attenuation in GC dendrites. The somatic impact of individual spines proved to remain remarkably constant, independent of the number of active input sites and of their localization. The data propose that granule cell dendritic integration is fundamentally different from that observed in other principal neurons.
Rüdieger Köhling presented evidence that functional small-conductance Ca2+-activated K+ channel currents (SK currents) are reduced in chronic epileptic CA1 pyramidal neurons. Both the SK2 channel transcript and protein proved to be down-regulated in the epileptic CA1 region. As a consequence after-hyperpolarization is reduced and the remaining functional SK currents become critical for the network excitability in epileptic tissue.
Jerome Engel explored the occurrence of high frequency oscillations (fast ripples) in human epileptic tissue and rodent models of epilepsy. The occurrence of fast ripples proved to correlate with the degree of hippocampal atrophy in human tissue, with onset of spontaneous seizures and with the development of spontaneous seizures in chronic rodent models. Thus, high frequency oscillations might serve as a biomarker for epileptogenesis, disease progression and ictogenesis.
Gregory L. Holmes discussed the functional consequences of interictal spikes. In a rat model evidence was obtained that early-life interictal spikes can result in impaired hippocampal new cell formation associated with a long-lasting impairment in spatial learning. The findings indicate that suppressing interictal spikes might be as important as treating seizures during brain development.
Jeffrey Noebels described the first viable genetic mouse model of infantile spasms syndrome. The model recapitulates critical phenotypic features of the human triplet-repeat expansion mutation in the Arx gene known to be one cause of the catastrophic pediatric epilepsy syndrome. The respective Arx (GCG)10+7 mouse mutant provides a basis to further examine the abnormal patterns of disinhibition in affected brain regions and explore novel therapeutic strategies for reversing the interneuron migration defect underlying the neurodevelopmental disorder.
Ivan Soltesz investigated the GABAergic control of entorhinal cortex outputs. Cannabinoid type-1 receptor expressing GABAergic basket cells selectively innervate principal cells in layer II of the medial entorhinal cortex that project outside the hippocampus, but avoid the neighboring cells that give rise to the perforant pathway. The new results revealed that the organization of both GABAergic microcircuits reflects the long-distance axonal targets of principal neurons. The findings have significant implications for basic epilepsy research and future treatment strategies aiming to modulate GABAergic targets.
Charles E. Ribak focused on a new type of neuronal death involving microglia in the adult dentate gyrus of normal and epileptic rats. Dying granule cells were found in close contact with Iba1-immunolabeled microglial cell bodies and their processes both at the hilar and the molecular layer borders. Thorough electron microscopic analyses indicated that granule cells are dying by a novel micoglia-associated mechanism involving lysis of their plasma membranes followed by neuronal edema and nuclear phagocytosis.
Jozsef Janzsky examined the reorganization of brain function in epilepsy and neurological injuries by functional MRI. Independent of the lesion a reorganization of language and memory representation can be observed in the epileptic brain. Complex alterations in language representation can also occur in other CNS diseases such as Parkinson’s disease as well as in peripheral nerve injury.
Matthias Koepp investigated the cortical activation patterns and connectivity of the motor cortex and its modulation through cognitive interaction in patients with juvenile myoclonic epilepsy (JME) and healthy controls. An increased coactivation of the motor system was found in JME patients during cognitive functional MRI tasks. The effect appeared only during the more demanding tasks and was more pronounced in patients with more recent seizures.
Ortrud K. Steinlein reviewed the current knowledge on mutations in nicotinic acetylcholine receptors (nAChRs) as a cause of familial nocturnal frontal lobe epilepsy (ADNFLE). Based on recent research it has become obvious that carriers of some ADNFLE mutations are more likely than others to be affected by additional neurological features including cognitive deficits and schizophrenia-like symptoms. Expression experiments in Xenopus oocytes demonstrated that the clinical phenotypes can be matched to biopharmacological profiles being specific for each mutation
Thomas Sander studied genetic factors predisposing to idiopathic generalized epilepsies. Genome-wide linkage and association studies on IGE syndromes performed within a EU-funded research initiative resulted in intriguing insights into the respective complex genetic traits. It was demonstrated that rare recurrent microdeletions collectively account for a significant fraction of the genetic etiology of common IGE syndromes.
Brian Meldrum critically discussed various experimental approaches used to study antiepileptogenic effects in rodent models. Emphasis was made that there is a lack of appropriate and /or practicable animal models reflecting development of seizures due to different clinical conditions including perinatal hypoxia/ischemia and developmental brain disorders. Novel antiepileptogenic strategies were presented such as targeting neurotrophins or their intracellular signaling cascades.
Wolfgang Löscher gave an overview on studies testing disease-modifying and/or antiepileptogenic effects in rodent models. Whereas several experimental investigations explored the efficacy of antiepileptic drugs resulting in clinical testing of selected compounds in preventive approaches, further experimental studies targeted neurodegeneration, inflammation, immune responses and neuronal hyperexcitability. Recent data obtained with a neuromodulation strategy using bumetanide as an inhibitor of the Na+-K+-2Cl– co-transporter NKCC1 were presented.
Alon Friedman focused on blood-brain barrier (BBB) dysfunction as a target for antiepileptogenesis. Human and experimental data substantiating the critical role of BBB disintegrity during epileptogenesis were presented. Targeting TGFb signalling which contributes to the consequences of blood-brain barrier dysfunction counteracted epileptogenesis in a rodent model. Analysis of BBB permeability was suggested as a valuable biomarker for epileptogenesis in patients at risk.
Heidrun Potschka reported on peptide mimetics as a novel strategy for disease modification. Neural cell adhesion molecule- (NCAM-) and erythropoietin-derived peptides showed promising effects on the cellular consequences of a status epilepticus in rodent models. Moreover, an erythropoietin-derived peptide attenuated spatial learning deficits in a post-status epilepticus model.


Alsstrasse 12
53227 Bonn

Phone:   +49 228 - 94 55 45 40
Fax:         +49 228 - 94 55 45 42
E-mail: poststiftung-michael.de