The 2005 Michael Prize was awarded to
School of Veterinary Medicine, Hanover, Germany
Prof. Dr. Heidrun Potschka
Neurologiai Klinika Pecs
Prof. Dr. Heidrun Potschka has been performing her research since 1997 at the Institute for pharmacology, toxicology and pharmacy in Hannover (director Prof. Dr. W.Löscher). In May 2004 she was appointed as junior professor. In August 2004 she completed her Habilitation and was promoted to the position of Privatdozentin.
Her scientific work is dedicated to the mechanisms of drug-resistance in epilepsy with the aim to find new therapeutic strategies for this group of epileptic patients. Her publications, including her award winning work “Multidrug resistant protein MRP2 contributes to blood-brain barrier function and restricts antiepileptic drug activity”, form the scientific basis of the “multidrug transporter hypothesis” of drug-resistance.
At present two hypotheses are discussed as possible mechanisms: An altered pharmaco-resistance of target tissue (target hypothesis) and the multidrug transporter hypothesis studied by Dr. Potschka. The latter hypothesis postulates that an over-expression of multi-drug transporters limits the concentration of antiepileptic drugs at the blood brain barrier of the epileptogenic focus. This hypothesis has been proved by her work. Antiepileptic drugs are substrates of the transporters. In MRP2-deficient rats (transporter negative TR-rats) it could be shown for the first time that a deficiency of outbound transporters (ABCC2) leads to an increased transport of the anticonvulsant phenytoin into the brain. Experiments with the amygdalae-kindling model demonstrated the functional relevance of this discovery: The combination of the multidrug transporter inhibitor probenicide with phenytoin led to the same increase of the anticonvulsive effect of phenytoin as observed in the animal model of genetic MRP2 deficiency. She has demonstrated similar mechanisms for carbamacepine, but not for phenobarbitone, lamotrigin, and felbamate. The penetration of the latter anticonvulsants into the brain are probably modulated by P-glycoprotein. Only levetiracetam seems not to be a substrate for P-glycoprotein.
A probably seizure-induced upregulation of the expression of the multidrug transporter P-glycoprotein has been observed in endothelial cells of the blood brain barrier but also in neurons and astrocytes in different models for epilepsy.
Dr. Potschka’s scientific work consitutes an important contribution to the understanding of the drug-resistance in epilepsies and enables a new approach for the treatment of people with epilepsy.
Dr. Jozsef Janszky works at present as Head of the section for video-EEG and presurgical diagnostic in the department of neurology of the University of Pecs in Hungary. After profound clinical and neurological training he worked between 2002 and 2004 as research fellow and guest physician at the Epilepsy Centre Bethel. From this time four publications have been presented for this award, which all are published in high-ranking international journals.
Based on the results of the presurgical investigations he analysed the influence of epileptic activity on the organisation of speech in medial temporal lobe epilepsy (MTLE). The lateralisation of speech follows in principle a genetically determined time schedule during the first five years of live. Lesions during this vulnerable period can cause atypical lateralisation of speech, what is often observed in people with epilepsy. Patients with MTLE and hippocampal sclerosis (HS) but no other epileptic lesion present a unique homogeneous epilepsy syndrome. They have the same pathology, which is however spatially separated from the speech area. Therefore it is possible to study the effect of the epileptic activity on the speech organisation not effected by lesions. An atypical representation of speech in left MTLE has been associated with higher spike frequency and sensory aureas. Psychic aureas have been associated significantly with left-sided speech dominance. These findings provide further ev idence for the importance of functional factors for the organisation of speech in the brain.
By his accurate analysis of clinical and paraclinical data of patients with temporal lobe epilepsy and hippocampal sclerosis Dr. Janszky found predictors of long-term surgical outcome. He could demonstrate that the two-year outcome was predicted by the occurrence of secondarily generalised seizures and/or limb dystonia. Duration of epilepsy is the most important predictor for long-term (five years) surgical outcome. These observations suggest that surgery for MTLE-HS should be performed as early as possible.
Dr. Janszky’s research is characterised by great originality and critical reflections. Through the analysis of individual patients he succeeded in the identification of basic mechanisms of neuronal organisation and plasticity. In this way he has successfully bridged the gap between basic and clinical science.
Prof. Dr. Heidrun Potschka
Dr. Jozsef Janszky
The Michael Prize with an amount of € 12.500.- was awarded at the 26th International Epilepsy Congress in Paris.