Basic mechanisms of partial epilepsies.
OBJECTIVE
Partial epilepsies are characterized by cell loss with consequences for neuronal organization, excitability, mnestic and cognitive functions and present with pharmaco-resistance and difficulties in clinical management. While mesial temporal lobe epilepsies present frequently with cell loss and neuronal reorganization, neocortical epilepsies frequently involve developmental alterations.


RESULTS
There is increasing evidence that nerve cells in epileptic tissue become more vulnerable to excitotoxic cell death due to impairment of mitochondrial functions and that free radical formation is critically involved in these processes. Whether and to what extent such alterations contribute to pharmaco-resistance is unclear. However, at least three mechanisms may contribute to pharmaco-resistance: changes in target molecules for antiepileptic drugs, upregulation of drug transporters, and potentially reorganization processes in inhibitory networks. Upregulation of drug transporters also seems to be involved in pharmaco-resistance of developmental alterations underlying focal epilepsies. Recent data from the literature suggest that transgenic models for disturbances of cortical development may be useful models for the study of these variable forms of partial epilepsies.


CONCLUSIONS
The data suggest that improvement of therapy could result from free radical scavenging and from manipulation of drug transport into the affected tissue. New models of developmental epilepsies may help us to understand mechanisms underlying increased vulnerability to seizures as well as improving strategies for treatment.
Heinemann
Uwe
U
Johannes Müller Institute of Physiology, University of Medicine Berlin, Germany. uwe.heinemann@charite.de
D000927:Anticonvulsants / Q000627:therapeutic use; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D002648:Child; D004351:Drug Resistance; D004569:Electroencephalography / Q000187:drug effects; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D009415:Nerve Net / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology
D000927:Anticonvulsants