Edward H. Bertram 1 , Gary Mathern 2 , Helen Cross 3 and Maria Thom 4 ( 1 Department of Neurology, University of Virginia, Charlottesville, VA ; 2 Department of Neurosurgery, UCLA, Los Angeles, CA ; 3 Institute of Child Health, University College London, London, United Kingdom and 4 Institute of Neurology, University College London, London, United Kingdom ) Summary: Mesial temporal lobe epilepsy (MTLE) has been synonymous with hippocampal sclerosis, such that the consensus is that the removal of the latter cures the former. There is increasing information, including recent epidemiological data regarding the long term outcomes of surgery, that suggests that the underlying basis for the disorder is more extensive than originally thought. The ultimate question for improving outcomes is “What is the true focus for MTLE?” Although our understanding of what constitutes the focus remains limited, there is evidence from surgical outcome, pathology, imaging and animal studies that the hippocampus alone is not the answer. Outcome studies show that only a small percentage of patients who are seizure free following surgery for MTLE can successfully stop medications and remain seizure free. Further there is evidence that the number of patients in remission falls steadily, even after a period of seizure freedom. These observations suggest that the seizure focus has not been completely removed. Studies of the temporal lobe pathology demonstrate changes that are variable but which extend beyond the hippocampus. Imaging has been a key factor in identifying structural abnormalities, but we may be missing key pieces of information that could identify the focus more precisely. Animal studies indicate that the ictal onset zone may be extensive and extend well beyond the hippocampus, but a true understanding of the physical substrate for seizure initiation still eludes us. This session is asking questions for which we only have partial answers. What do we know now about the seizure focus in MTLE? What do we need to know to have better outcomes? We don't have any good answers for either question other than a) not enough and b) a lot more. We hope this session will stimulate the participants to fill in the many gaps that now exist.