Wednesday July 5, 200615:00–17:00Hall 5ADiscussion Group SessionMagnetoencephalography: its contribution for detection of epileptogenicity and functional important cortex

¹ S. Rampp (   ¹ Epilepsycenter (ZEE)–Department of Neurology, University Erlangen-Nuremberg, Germany )
The detection of epileptiform discharges in electroencephalography recordings (EEG) is a crucial part in diagnosing epilepsy. Thorough electrophysiologic evaluation yields information that allows for tailored surgical therapy in many cases, and thus improves treatment outcome. In recent years, the existence of oscillations in frequency bands >60–80 Hz (ripple activity) has been demonstrated in the animal and human brain. It was shown that these high frequency oscillations are highly significant for epileptic network function. Analysis of high frequency activity might provide valuable information for localization of epileptic networks and understanding of their dynamics. While initial research concentrated on the investigation of these basic mechanisms, clinical applications, especially the diagnostic value beyond the information yielded by well-known patterns such as epileptic transients, are increasingly coming into focus.
While investigations regarding pathological high frequency activity have mostly been performed using intracerebral depth electrodes and subdural EEG, magnetoencephalography (MEG) and surface EEG might offer noninvasive alternatives. However, small and highly localized signal generating neuronal populations and consequently very low signal-to-noise ratios pose difficult problems for these modalities. Nevertheless, new methods for the analysis of oscillations, such as beamformer algorithms, are becoming available and might offer solutions.
An overview concering recent findings on high frequency activity and clinical applications is given. The use of MEG for noninvasive detection and analysis of high-frequency activity in patients with epilepsy is discussed, including methods, challenges and preliminary results.     

Saturday, December 1, 2007Broad-Band Intracranial EEG in Patients with Epilepsy: A Window to Human Networks6:00 p.m.-7:30 p.m.

Gregory A. Worrell ¹ and Brian Litt ² (   ¹ Neurology, Mayo Clinic, Rochester, MN and   ² Neurology, University of Pennsylvania, Philadelphi, PA )
Summary: In recent years efforts to understand brain function and progress in neural devices has generated tremendous interest in human intracranial recordings. These broad-band data sets spanning single units to large scale networks now enable us to investigate hypotheses related to normal network function, such as memory, cognition, and motor control, as well as pathologic processes such as seizure generation, movement disorders and psychiatric disease. Patients implanted with intracranial electrodes during evaluation for epilepsy surgery provide unprecedented access to the brain for this research. This workshop reviews some of the advances in large scale electrophysiology and the application to human studies.     

Wednesday July 5, 200615:00–17:00Ballroom 1Discussion Group SessionThe occipital lobe and how to see it

¹ S. Seri (   ¹ Birmingham Children's Hospital, Birmingham, UK )
No abstract received.     

Monday July 3, 200612:00–13:30Hall 5BPlatform SessionEpilepsy Surgery I

¹ G. Dorfmüller , ¹ C. Bulteau , ¹ M. Fohlen , ¹ C. Jalin , and ¹ O. Delalande (   ¹ Fondation A. de Rothschild, Paris, France )
Purpose: To present our experience with frameless stereotactically placed depth electrodes in presurgical evaluation of children with drug-resistant partial seizures.
Method: A total of 738 multilead electrodes were placed with the aid of a Robot-guided MRI-based stereotactic system (Schaerer-Mayfield Neuromate) in 83 children (2.8 to 18 years, mean 9.4). Each monitoring included 6 to 14 electrodes (mean 9) for a period of 2 to 17 days (mean 7).
Results: Twelve children underwent monitoring of a single lobe, 43 of 2, 26 of 3, and 2 children of 4 lobes; 6 had a bilateral recording. MRI was negative in 8 patients (10%). Further studies (PET, SPECT, fMRI, WADA testing, foramen ovale recording) were performed prior to the stereoelectroencephalography (S-EEG) in several cases. We performed electrode stimulations in order to map motor and/or language cortex, and in order to induce seizures. Beside 3 electrode breaks during removal, there were no other surgery-related complications. Having identified the epileptogenic zone, we proposed tailored resection in 69 cases, 1 child had a hemispherotomy instead. In 13 children (16%), SEEG results precluded resective surgery. To date, 57 children underwent surgery; histopathology revealed cortical developmental malformation in 29, glioneural tumour in 13, hippocampal sclerosis in 7 (+ neocortical dysplasia in 5), ischemic alteration in 3, and was negative in 5 cases.
Conclusion: Depth recording remains essential in evaluating the indication and extension of focal resection, particularly in children. Our frameless technique is safe and well tolerated, with no related morbidity in this large series.     

Wednesday July 5, 2006Wednesday July 5, 20067:30–9:00Hall 5ATeaching SessionEpileptic syndromes: from childhood to adulthood

¹ B. Dalla Bernardina (   ¹ Clin. Ped. Università-Borgo Roma, Verona, Italy )
No abstract received.     

FTY720 attenuates lesional interleukin-17+ cell accumulation in rat experimental autoimmune neuritis

Aims : Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies. Here we have studied the spatiotemporal accumulation of interleukin (IL)-17⁺ cells in sciatic nerves of EAN rats and effects of FTY720, an agonist of sphingosine-1-phosphate (S1P) receptors. Methods : In this study, we examined the spatiotemporal expression of IL-17 using immunohistochemistry and RT-PCR, and analysed the IL-17⁺ cell proportion in blood and lymph nodes using flow cytometry. Results : In sciatic nerves of EAN rats, IL-17⁺ cells were mainly found to concentrate around blood vessels and IL-17⁺ cell accumulation was temporally correlated with severity of neurological signs. FTY720, which has been shown to reduce severity of EAN, attenuated accumulation of IL-17⁺ cells in sciatic nerves, decreased IL-17⁺ cell proportion in peripheral blood, but increased IL-17⁺ cell proportion in lymph nodes, suggesting the involvement of S1P signal pathway in regulating IL-17⁺ cell trafficking. Conclusions : our data are consistent with the possibility that IL-17⁺ cells might contribute to the pathogenesis of EAN and the S1P signal pathway may be involved in the in vivo trafficking of IL-17⁺ cells.     

Tuesday July 4, 200615:00–17:00Hall 1Discussion Group SessionNeurostimulation for epilepsy

¹ P. Boon (   ¹ Laboratory for Clinical and Experimental Neurophysiology (LCEN) and Department of Neuology, Ghent University Hospital, Belgium )
Acute deep brain stimulation (DBS) in various thalamic nuclei and medial temporal lobe structures has recently been shown to be efficacious in small pilot studies of patients with medically refractory epilepsy. Only limited data on chronic thalamic and amygdalohippocampal stimulation are available. Chronic DBS in these structures requires resolving many conceptual and technical issues. There is little evidence based information on rational targets and stimulation parameters. Currently available depth EEG recording electrodes are unsuitable for chronic use. Inversely, the use of DBS electrodes for intracranial EEG recording and localization of the ictal onset zone prior to stimulation has only been reported by a few groups. Results from feasibility and pilot studies in the most recent literature will be presented. The experience with DBS in temporal lobe epilepsy using quadripolar DBS electrodes bilaterally implanted in the amygdalohippocampal region to identify and subsequently stimulate the ictal onset zone will be described. This work has yielded a significant decrease of seizure counts and interictal EEG abnormalities during long-term follow-up. Various hypotheses on the possible mechanism(s) of action of DBS for epilepsy using EEG, cerebral blood flow and metabolic measures including results from animal experiments have recently been developed. Data from open pilot studies suggests that chronic DBS for epilepsy may be a feasible, effective and safe procedure that reduces interictal EEG abnormalities and seizures. Further trials with larger patient populations, controlled and randomised designs should be initiated.     

Tuesday July 4, 200613:30–15:00Poster Session 2Neuropsychology

¹ W. Alpherts , ¹ J. Vermeulen , and ² P. Van Rijen (   ¹ Department of Psychology, Epilepsy Centre of The Netherlands (SEIN), Heemstede, The Netherlands ,   ² Rudolf Magnus Institute For Neurosciences, University of Utrecht, Utrecht, The Netherlands )
Purpose: Growing evidence suggests that the cerebral hemispheres are asymmetric in the role they play in sustained attention. Studies have suggested that parietal, temporal and prefrontal regions may be involved in the maintenance of a state of vigilance. The present study investigates the effect of left (LTL) vs. right temporal lobectomy (RTL) on a computerised vigilance task (part of the FePsy battery).
Method: The 188 subjects (86 LTL, 102 RTL) were tested before and 6 months after epilepsy surgery. They were presented with 450 stimuli in a signal detection paradigm, equally divided into "signal" (XXXXXXX) or "noise" (XXXAXXX). Duration of the stimuli was 100 msecs, Inter Stimulus Interval 4 secs. The task lasted for 30 minutes. Dependent variables were d' (perceptual sensitivity) as a measure of vigilance and ß (response bias, employing a lax or a conservative criterion).
Results: The LTL group showed a gain in d': before surgery of 2.05 (SD 0.94), and after of 2.17 (SD 1.15) whereas the RTL group showed a decline: 2.23 (SD 1.01) before and 2.03 (SD 0.98) after surgery. This interaction effect is significant, p = .016. No difference was found in betas in either group: LTL group 0.60 (SD .40) pre surgery vs. 0.69 (SD 0.49) post and the RTL group 0.63 (SD .54) pre vs. 0.66 (SD .54) post.
Conclusion: The RTL group cannot profit from a retest effect. These results suggest a strong involvement of the right temporal lobe in vigilance, i.e., sustained attention and the disruption of this mechanism after RTL.     

Monday July 3, 200615:00–17:00Ballroom 1Discussion Group SessionBlood–brain barrier and epilepsy

¹ I. Blasig (   ¹ FMP, Berlin-Buch, Germany )
No abstract received.     

Neuroscience Session

Role of Neurotrophic Factors during Epileptogenesis in the Brain of EL Mice.
¹ Yoshiya L. Murashima , ¹ Jiro Suzuki , and ¹ Mitsunobu Yoshii (   ¹ Department of Neural Plasticity, Tokyo Institute of Psychiatry, Tokyo, Japan ).
Purpose: We have recently observed that the immediate early gene (IEG) c-fos is unusually expressed in the parietal cortex of EL mouse brains during the interictal period, suggesting activation of the protein cascades associated with epileptogenesis. Furthermore, DNA fragmentation has been detected preferentially in the hippocampus CA1 and the parietal cortex. It remains to be seen, however, how these abnormalities are related to DNA fragmentation, and whether or not neuronal cell loss is involved. The present study was designed to address these issues.
Methods: Neurotrophic factors (brain-derived neurotrophic factor, BDNF; neurotrophin-3, NT-3; and fibroblast growth factor-2, FGF-2) were determined by immunoblotting using the EL mouse brain at various developmental stages.
Results: In the EL mouse brain, a marked increase of BDNF was detected temporarily during ictogenesis and epileptogenesis in the early periods. Unexpectedly, no cell loss was found in the hippocampus.
Conclusion: DNA fragmentation without cell loss observed in EL mouse brain appears to result from the initial activation and later inactivation of the apoptotic process. Neurotrophic factors may play a role in the ictogenesis and the epileptogenesis during early development. These gene expressions are closely related to the periods critical for ictogenesis and epileptogenesis, and may be of particular importance in the development of antiepileptic drugs with novel mechanisms.     

Sunday July 2, 200612:00–14:00Hall 5BNeurobiology SymposiumIn vivo imaging of neurobiology of epileptogenesis

¹ D. Gadian (   ¹ UCL Institute of Child Health, UK )
Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques have found widespread application in the investigation of patients with epilepsy. Applications in animal models of epilepsy are perhaps less well established, but they provide important opportunities for probing pathophysiological changes that may be difficult to characterise in humans. A key feature of animal studies is that they enable us to carry out longitudinal examinations, from prior to the onset of seizures onwards. Comparisons of data obtained before, during and after seizures can greatly facilitate the detection of brain abnormalities that may be functionally important and yet cause only subtle changes in magnetic resonance characteristics. Moreover, the longitudinal magnetic resonance data can be correlated with end-point histopathology.
This presentation will report on our ongoing clinical and experimental magnetic resonance studies of status epilepticus. Convulsive status epilepticus (CSE) is the most common medical neurological emergency in childhood, and is associated with significant morbidity and mortality. Although many patients will have no obvious sequelae, possible outcomes from childhood CSE include epilepsy as well as permanent neurological or cognitive deficits. However, much remains to be learned about the pathophysiology associated with CSE and about the relationship between CSE and subsequent epilepsy. Modern magnetic resonance methods, applied both in patients and in experimental models, provide an opportunity to understand in more detail the temporal evolution of brain abnormalities associated with CSE. This may in due course lead to the development of new therapeutic approaches.     

Monday July 3, 2006 7:30–9:00Hall 5C Teaching SessionDiagnostic methods in presurgical workup—what's new?

¹ M. Scherg (   ¹ University Hospital Heidelberg, Germany )
No abstract received.     

Monday July 3, 200615:00–17:00Hall 3ADiscussion Group SessionCognitive dysfunction in children with temporal lobe epilepsy

¹ F. Vargha-Khadem (   ¹ Institute of Child Health, Development Cognitive Neuroscience Unit, London, UK )
No abstract received.     

Tuesday July 4, 200612:00–13:30Hall 1Platform SessionDrug Therapy II

¹ P. Williamson , ¹ C. Tudur Smith , ² J. Sander , and ¹ A. Marson (   ¹ University of Liverpool, Liverpool, UK   ² University College London, UK )
Purpose: Retention time (time to treatment failure) is a commonly used outcome in antiepileptic drug studies. In this paper we present the issues involved and demonstrate the importance of a full investigation of this outcome.
Method: Fifteen antiepileptic drug monotherapy trials and an add-on therapy clinic cohort are used to illustrate both design and analysis issues. Cumulative incidence analysis is described and applied to a dataset comparing lamotrigine and topiramate. The results are compared to the more common approach using standard survival analysis methods.
Results: A nonsignificant difference in overall retention between lamotrigine and topiramate (logrank test statistic = 2.58, 1 degree of freedom, p = 0.108) masked highly significant differences in opposite directions between the drugs with respect to withdrawals due to side effects (Gray's test statistic = 12.26, 1 degree of freedom, p = 0.0005) and poor seizure control (Gray's test statistic = 34.58, 1 degree of freedom, p < 0.0001).
Conclusion: Retention time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of antiepileptic drugs may be missed unless appropriate statistical methods are used to fully investigate retention time. Cumulative incidence rather than logrank analysis is likely to be a more powerful approach for comparison of standard and new antiepileptic drugs.     

Monday July 3, 200615:00–17:00Hall 3DDiscussion Group SessionProgrammed cell death pathways in seizure-induced neuronal injury and epileptogenesis: human and animal data

¹ D. Lindholm (   ¹ Uppsala University, Department of Neuroscience, Sweden )
No abstract received.     

Monday July 3, 2006 7:30–9:00Hall 5B Teaching SessionTo treat or not to treat the EEG in paediatric epilepsy syndromes

¹ U. Brandl (   ¹ Friedrich-Schiller-Universität, Jena, Germany )
No abstract received.     

Tuesday July 4, 200615:00–17:00Hall 5ADiscussion Group SessionThe spectrum of temporal "plus" epilepsy

¹ D. Schmidt (   ¹ Epilepsy Research Group, Berlin, Germany )
Temporal lobe surgery is the nonpharmacological treatment of choice for carefully selected patients with drug resistant temporal lobe epilepsy. On average, two of three patients undergoing surgery will become seizure free or nearly seizure free after surgery with continued antiepileptic drug (AED) treatment. We limit our discussion to failure to achieve long term surgical seizure control which can occur in three groups of patients. One, surgery fails with respect to seizure control with continued AEDs in one of three cases who never become seizure free after surgery. Two, a small subgroup of patients who were seizure free after surgery on AEDs will not remain seizure free in the long run. This is another group of patients in whom surgery may be considered to have failed. When AEDs are stopped in patients who have been seizure free after temporal lobe surgery for several years, one in three patients has a seizure recurrence. This is a third subgroup of patients in whom surgery has failed, particularly in a small group in whom reinstitution of AEDs after seizure recurrence fails to regain seizure freedom. Despite all these instances of failure, temporal lobe surgery is a very useful procedure and the only one which achieves seizure freedom in 50% of patients with drug resistant temporal lobe epilepsy, approximately in 20% of patients with AEDs and in 30% without AEDs.     

Tuesday July 4, 200615:00–17:00Hall 3DDiscussion Group SessionLarge scale mRNA and protein expression profiling in epilepsy—where we are and where we are going

¹ M. Majores (   ¹ Department of Neuropathology, University of Bonn Medical Center, Germany )     

Presidential Symposium: Behavioral and Cognitive Comorbidities in Pediatric Epilepsy; Recognition, Mechanisms, Assessment, and Treatment 9:00 a.m.–11:30 a.m.

¹ Joan K. Austin , ¹ David W. Dunn , ¹ Amy Brooks-Kayal , ¹ Gregory L. Holmes , and ¹ Rochelle Caplan (   ¹ School of Nursing, Indiana University, Indianapolis, IN; Child Psychiatry, Indiana University School of Medicine, Indianapolis, IN; Abrahamson Research Center, University of Philadelphia, Philadelphia, PA; Neuroscience Center, Dartmouth Medical School, Lebanon, NH; and Child and Adolescent Psychiatry, UCLA, Los Angeles, CA ,)
The purpose of this symposium is to provide clinicians and epilepsy care professionals a greater understanding of the behavioral and cognitive comorbidities observed in children with seizures and epilepsy. The first presentation will review recent research findings related to the prevalence and nature of behavioral and cognitive comorbidities as well as their risk and protective factors. Two presentations will focus on underlying biological mechanisms related to behavioral and cognitive co-morbidities. The first will discuss the effects of changes associated with epileptogenesis in the developing brain. The second will address the effects of seizures and antiepileptic drugs (AEDs) on cognition with an emphasis on what is happening at the circuit level. Research findings related to remediation of behavioral and cognitive effects in animals will also be discussed. The final presentation will discuss the complexities of addressing behavioral and cognitive problems in the clinical setting and describe strategies for assessing and treating these problems.     

Tuesday, December 4, 2007Subcortical Control of Cortical Excitability11:00 a.m.-12:30 p.m.

Elaine Wyllie ¹ and Michael Duchowny ² (   ¹ Cleveland Clinic Foundation, Cleveland, OH and   ² Brain Institute, Miami Children's Hospital, Miami, FL )
Summary: Epilepsy surgery is accepted as an appropriate intervention for children with medically refractory epilepsy. Key elements for surgical candidacy include a localized epileptogenic zone and a low risk for new postoperative neurological deficits. The strategies for identifying these elements for surgical candidacy are in evolution. This Symposium will examine current worldwide variations in pediatric epilepsy surgical practice, based on an international multicenter survey. Faculty will also examine age-related aspects to selection for surgery including lesion timing and type and functional plasticity, and strategies for surgery when MRI is normal or shows multiple lesions. Pediatric neurology and neurosurgery speakers will emphasize the tactics involved in designing a safe and effective plan for surgery for selected infants and children with intractable epilepsy.