March 2006
Hypersalivation in Temporal Lobe Epilepsy
Jagdish Shah, Huifang Zhai, Darren Fuerst, and Craig Watson

Several clinical signs and symptoms, which help lateralize seizure onset, have been reported in temporal lobe epilepsy (TLE). Increased salivation has only occasionally been reported as a manifestation of partial epilepsy. We studied 590 consecutive patients admitted for EEG/Video monitoring and identified 10 patients with increased salivation or drooling as a prominent manifestation of their complex partial seizures. We reviewed the clinical features, scalp-sphenoidal EEG/Video monitoring, intracarotid amytal (Wada) testing, hippocampal volumetric MRI, and FDG-PET scans of these patients. Of the 10 patients with increased salivation during their seizures, 7 patients had nondominant/right TLE, and 3 patients had dominant/left TLE. All patients had hippocampal atrophy on volumetric MRI. Eight of the 10 patients underwent standard temporal lobectomy with removal of the amygdala and hippocampus (6 right, 2 left). All of the operated patients had a seizure free outcome, and their increased salivation resolved. Two patients, who did not undergo surgical treatment, continue to have complex partial seizures with increased salivation. We conclude that increased salivation as a prominent finding during complex partial seizures of temporal lobe origin is rare and may more likely be of nondominant temporal lobe origin. Further studies with larger numbers of patients are needed to replicate this finding and to determine if it is a statistically significant finding. Epilepsia 2006;47(3).

Effects of Temporal Lobe Epilepsy on Retrograde Memory

Suncica Lah, Teresa Lee, Sandra Grayson, and Laurie Miller

Patients with epilepsy often experience difficulties with short-term memory (learning and retention of information). These difficulties are most noticeable in patients whose seizures emanate from the temporal lobes, as these parts of the brain are essential for memory formation. Problems with long-term memory were also noticed in patients with epilepsy. It was proposed that they could be simply secondary to poor learning. In addition, seizures themselves may disrupt formation of memory traces or even interfere with memory storage. We examined 15 patients whose seizures were coming from the left temporal lobe, 14 whose seizures were coming from the right temporal lobe and 15 healthy control subjects. Information about medical history and current status was collected during an interview. All participants were given a number of long-term memory tests that involved recall of public and personal facts and events alongside other cognitive tests of short term memory (verbal and visual), language and mental flexibility. The results confirmed that patients with temporal lobe epilepsy had difficulties with long-term memory. Interestingly, word finding deficits had greater impact on long-term memory than short-term memory skills. The side of seizure focus also played a significant role; patients whose epilepsy emanated from the left temporal lobe had low scores on many long-term memory tests. Patients whose epilepsy focus was in the right temporal lobe had mild, circumscribed long-term memory difficulties. Early age of epilepsy onset (<14 years) and taking more then one antiepileptic drug further increased the risk of difficulties in long-term memory. Epilepsia 2006;47(3).

Functional MRI Shows Atypical Language Lateralization in Pediatric Epilepsy Patients

Weihong Yuan, Jerzy P. Szaflarski, Vincent J. Schmithorst, Mark Schapiro, Anna W. Byars, Richard H. Strawsburg, and Scott K. Holland

Left hemisphere is dominant for language function in the vast majority of adult population. In children, language function distribution starts from being relatively bilateral and becomes increasingly left-side dominant, indicating an increasing specialization of language functions to the left hemisphere as age increases. However, the brain development is usually very vulnerable to various neuro-disorders or pathologies. In the present study, we used functional magnetic resonance imaging (fMRI), a neuro-imaging technique that takes advantage of the correlation between neuronal function and corresponding hemodynamics to localize brain function, to investigate if and to what extent epilepsy alters the normal language development. We studied the incidence of left dominant (the so called “typical” hemispheric dominance) and non-left dominant language distribution in a group of children with epilepsy (n=18, age 8-18 years). When compared to age-gender-handedness matched healthy children, a much higher percentage of children with epilepsy were found to have atypical (right or bilateral) language dominance. The mean value of lateralization index (LI, an parameter describing the degree of left hemispheric dominance) was significantly different in the two cohorts. The correlation between LI and age during normal development did not exist in pediatric epilepsy patients. We also found that the degree of left-dominance was significantly correlated with the duration of epilepsy. These findings show that epilepsy during childhood is significantly associated with redistribution of language function in the developing brain to compensate for injury to traditionally left dominant language areas. Epilepsia 2006;47(3).

Role of SOX2 Mutations in Human Hippocampal Malformations and Epilepsy

Sanjay M. Sisodiya, Nicola K. Ragge, Gianpiero L. Cavalleri, Ann Hever, Birgit Lorenz, Adele Schneider, Kathleen A. Williamson, John M. Stevens, Samantha L. Free, Pamela J. Thompson, Veronica van Heyningen, and David R. Fitzpatrick

The search continues for genes mutations that might either directly cause epilepsy, or cause abnormalities of the structure of the brain that in turn lead to epilepsy. Most gene mutations causing epilepsy have been found through the careful genetic study of families in whom many members may have epilepsy. We have used another approach. We have scanned the brain in people who are known to have a mutation in a gene that is active both in the eye and the brain, and in whom the mutation has caused severe developmental eye defects. We proposed that because in these people the mutation would also very probably affect the action of the same gene in the brain, these people might also be found to have developmental brain defects, some of which might be like those seen in people with epilepsy. If this were the case, then other “milder” mutations in that gene might be responsible for some cases of epilepsy without eye disease. In this study, we examined people who were known to have mutations in a gene called SOX2. These mutations caused severe eye defects seen from birth. Some of these people also had epilepsy. Detailed brain scans showed that people with mutation in SOX2 had brain malformations, affecting the hippocampus and nearby structures. We then went on to search for subtle changes in SOX2 in people with epilepsy, but did not find any. Nevertheless, SOX2 is a candidate gene for hippocampal malformation in people with epilepsy without eye disease. Epilepsia 2006;47(3).

February 2006
Defining Intractability: Comparisons Among Published Definitions
Anne T. Berg and Molly Kelly

Although most epilepsy is well-controlled by available medications, intractable epilepsy affects a substantial minority of patients and accounts for a disproportionate amount of resources devoted to care of people with epilepsy. There is no single definition of intractability, and different authors have used different definitions. This creates difficulties for comparing results across studies and synthesizing the literature. In this study, we performed a head-to-head comparison of six different published definitions within a single prospective study of 613 children with newly diagnosed epilepsy. We examined the extent of agreement or disagreement among the definitions and the longer term implications of meeting each definition. The definitions were assessed at various times within the first five years after diagnosis with the exact timing reflecting how they were originally reported. Observed and agreement adjusted for chance were computed. The associations of each definition with remission status 7-10 years after diagnosis were quantified. The different definitions classified 9-24% of children as intractable. Observed agreements among the definitions ranged from a low of 83% to a high of 96%. Agreement adjusted for chance ranged from low of 45% to 79%. All definitions were strongly associated with remission status as of last follow-up. Agreement among the different definitions is strong but imperfect. All definitions were significantly associated with longer term outcome. There is no single preferred definition of intractable epilepsy. Consideration should be given to whether a single definition will suit all purposes or whether different types of definitions are needed for different purposes. Epilepsia 2006;47(2).

Contralateral Smile and Laughter, but no Mirth, Induced by Electrical Stimulation of the Cingulate Cortex

Francesca Sperli, Laurent Spinelli, Claudio Pollo, and Margitta Seeck

The cerebral representation of laughter is dissociated. The emotional aspects seem to be processed in the temporal lobe; whereas, the motor features apparently rely on the frontal cortex. In a few prior studies of patients in whom laughter was elicited by electrical stimulation (ES), it always was associated with mirth. We report a patient in whom ES in the right cingulate gyrus elicited smile and laughter, but no mirth. At low voltages, smiling was seen first contralaterally, and became bilateral with increasing currents. Our observation supports the concept of mesial frontal cortex comprising a motor representation of laughter in the mesial frontal cortex. Epilepsia 2006;47(2).

Linking Generalized Spike and Wave Discharges and Resting State Brain Activity Using EEG/fMRI in a Patient with Absence Seizures

Helmut Laufs, Ulrike Lengler, Khalid Hamandi, Andreas Kleinschmidt, and Karsten Krakow

Epilepsy is a condition of the brain in which the balance between the millions of nerve cells (neuron) is disturbed. This can lead to an epileptic seizure when too many neurons fire at the same time. This can be visualized using an electroencephalogram (EEG, which measures electricity generated by neurons). Synchronous activity can affect most of the brain that on the EEG can appear as a typical pattern of generalized “spike and wave” activity, reflecting the shape of the recorded signal. The associated seizure type is called an absence seizure. During an absence seizure, it appears as if all brain activity comes to a halt, and the patient stops whatever he or she was doing. Afterwards, recollection for the time during the seizure would be lost. In this study, we could show that spike and wave activity lasting at least a second can disrupt brain activity such as spontaneous thought and self-reflection occurring when one is “at rest.” This was possible by combining EEG with functional magnetic resonance imaging that allows to see activity changes in different brain regions. Which function a particular brain area roughly subserves can be looked up in a database containing results of many other research studies. Epilepsia 2006;47(2).

Temporal and Extra-temporal BOLD Responses to Temporal Lobe Interictal Spikes

Eliane Kobayashi, Andrew P. Bagshaw, Christian-George Bénar, Yahya Aghakhani, Frederick Andermann, François Dubeau, and Jean Gotman

Simultaneous EEG and functional MRI (fMRI) allows measuring metabolic changes related to interictal spikes, which are characteristic discharges in the EEG of patients with epilepsy. Our objective was to investigate responses to temporal lobe (TL) spikes using EEG-fMRI recording. We studied 35 patients with a diagnosis of temporal lobe epilepsy (TLE) and active TL spiking on a routine EEG. Two-hour sessions of continuous EEG-fMRI were recorded and spikes were identified after off-line artifact removal and used as events in the fMRI analysis. Each type of spike was analyzed separately, as one EEG-fMRI study. We determined significant positive (activation) and negative (deactivation) fMRI changes for each study. Twenty-seven patients had spikes during scanning (19 unilateral and 8 bilateral). From a total of 35 fMRI studies, 29 (83%) showed changes: 14 had both activations and deactivations, 12 activations only and 3 deactivations only. Six (17%) showed no responses. Nineteen studies had mainly neocortical TL activation: 16/19 (84%) concordant with spikes, 12/16 with concomitant activation of the contralateral TL, and 16/19 with additional extra-temporal activation; few showed exclusively mesial TL activation. Seventeen studies showed deactivation, either extra-temporal plus temporal (n=8) or exclusively extra-temporal (n=9). In conclusion, fMRI responses to TL spikes occurred in 83% of studies, predominated in the spiking temporal lobe, and manifested as activation or deactivation. Responses often involved the contralateral homologous cortex at the time of unilateral spikes and were frequently observed in extra-temporal regions, suggesting that TL epileptic spikes can affect neuronal activity at a distance through synaptic connections. Epilepsia 2006;47(2).

Single and Multiple Clusters of Magnetoencephalographic Dipoles in Neocortical Epilepsy: Significance in Characterizing the Epileptogenic Zone

Makoto Oishi, Shigeki Kameyama, Hiroshi Masuda, Jun Tohyama, Osamu Kanazawa, Mutsuo Sasagawa, and Hiroshi Otsubo

Surgeons must locate the epileptogenic zone that generates seizures in order to surgically eliminate epileptic seizures, One method of localization is invasive subdural electroencephalography (SEEG). A new method using dipoles for epileptogenic source localization is noninvasive magnetoencephalography (MEG). We characterized the relationships of MEG dipoles (sources of epileptic-like activity) with SEEG-defined seizure onset zones (SOZs) and correlated the findings with MRIs, surgical areas, and postsurgical outcomes for 20 patients with drug-resistant neocortical epilepsy who underwent resection. We referred to MEG findings as either single- or multiple-dipole cluster areas. Fourteen patients had single MEG dipole clusters; 6 had multiple clusters. Single MEG clusters coincided with SEEG SOZs in 9 patients; a single cluster was within or partially overlapped the SOZ in 4 patients; multiple-cluster sections overlapped SOZs in 5 patients; and no overlap with the SOZ occurred in 2 patients (1 with single cluster; 1 with multiple). More single clusters than multiple clusters coincided with the SOZ. More patients with single clusters (10 of 14) had seizure-free outcomes than did patients with multiple clusters (1 of 6). Eight of 9 patients with a single cluster that coincided to the SOZ had seizure-free outcomes, while only 3 of the 11 remaining patients were seizure free after surgery. MRI findings had no significant correlation with postsurgical outcomes. We concluded that, in neocortical epilepsy, MEG dipole clusters correlated with SEEG SOZs: single clusters indicated discrete epileptogenic zones for complete resection and seizure-free outcome; multiple clusters indicated multiple or extensive epileptogenic zones that required complete identification and delineation by SEEG for improved seizure control. Epilepsia 2006;47(2).

January 2006
Somatosensory Auras in Refractory Temporal Lobe Epilepsy
Jay C. Erickson, Lawrence E. Clapp, Gwendolyn Ford, and Bahman Jabbari

The temporal lobe is the most common location in the brain for epileptic seizures to occur. The initial symptom of a seizure that happens before the person loses consciousness is called an aura. People with temporal lobe seizures may experience a wide array of auras, including déjà vu, a foul taste, peculiar odor, fear, or a rising sensation in the abdomen. An unusual type of aura in patients with temporal lobe seizures is a somatosensory aura, manifesting as an alteration in the sensation of the skin in a part of the body, such as a tingling feeling. Somatosensory auras usually occur in patients with seizures arising from the parietal lobe or nearby regions, but less is known about this type of aura in seizures arising from the temporal lobe. To better understand somatosensory auras in patients with temporal lobe seizures, the authors describe a group of patients with temporal lobe seizures and somatosensory auras. The authors found that somatosensory auras, previously considered to be extremely rare in patients with temporal lobe seizures, actually occur in about 11% of patients with temporal lobe epilepsy. The somatosensory auras most often affect a limb on one side of the body, usually on the side opposite that of the brain where the seizure started. The somatosensory auras and other aspects of the seizures disappeared when surgery was performed to remove part of the temporal lobe (a standard treatment for seizures resistant to medications). The findings will help epileptologists better understand the implications of somatosensory auras in patients with temporal lobe seizures. Epilepsia 2006;47(1).

Community-based, Prospective, Controlled Study of Obstetric and Neonatal Outcome of 179 Pregnancies in Women with Epilepsy

Katriina Viinikainen, Seppo Heinonen, Kai Eriksson, and Reetta Kälviäinen

This study evaluates obstetric and neonatal outcome in a community-based cohort of women with active epilepsy (WWAE) compared with the general pregnant population receiving modern obstetric care.

We reviewed the total population of women who gave birth between January 1989 and October 2000 at Kuopio University Hospital. Obstetrical, demographical and epilepsy data were collected prospectively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of women without epilepsy (controls). The obstetrical data from the pregnancy register was supplemented with detailed neurological data retrieved from the medical records. The data retrieved was comprehensive due to a follow-up strategy according to a predetermined protocol. During pregnancy, the majority (83%) of the WWAE had the same amount or fewer epileptic seizures than they did before pregnancy. We found no significant differences between WWAE and controls in the incidence of pre-eclampsia, pre-term labor or in the rates of caesarean sections, perinatal mortality, or low birth weight. However, the rate of small-for- gestational-age infants was significantly higher and the head circumference was significantly smaller in WWAE. The frequency of major malformations was 4.8% in the 127 children of WWAE.

In conclusion, the pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predetermined protocol is used for the follow-up of WWAE in antenatal and neurological care. Epilepsia 2006;47(1).

Ictal Brain Hyperperfusion Contralateral to Seizure Onset: The SPECT Mirror Image

Gilles Huberfeld, Marie-Odile Habert, Stéphane Clemenceau, Philippe Maksud, Michel Baulac, and Claude Adam

Ictal SPECT (single photon emitted computerized tomography) may help localize the Seizure Onset Zone (SOZ) by detecting changes in regional cerebral blood flow induced by epileptic discharges. This imaging method also reveals increased blood flow (hyperperfusion) in areas of seizure propagation, including the hemisphere on the opposite side to the SOZ. We have studied the occurrence, the regional distribution and the clinical value of such contralateral ictal hyperperfusion areas (HPA). We examined data from presurgical evaluations of thirty six consecutive patients with pharmaco-resistant partial epilepsy of various localizations. HPAs on the side opposite to the seizure focus were observed in 72% of the patients: 50% of mesial temporal lobe epilepsy cases with scarring of the hippocampus, 85.7% of the other mesial temporal epilepsies, 85.7% of neocortical lateral temporal epilepsies and 87.5% of extratemporal epilepsies. HPAs opposite to the seizure focus were usually symmetrical to the SOZ, forming a mirror image observed in 57.1% of the patients. They could be slightly asymmetrical in mesial temporal epilepsies, perhaps due to the particular anatomical pathways linking the temporal lobes. In neocortical epilepsies, they were located in the region of cortex corresponding to the region of the SOZ. We showed that the symmetrical nature of the mirror image usually does not disturb SPECT interpretation. It can confirm the location of the SOZ (11 patients) and even occasionally improve the precision of its definition (9 patients), by restraining several potential SOZ related HPAs to a single one, or by permitting a restricted localization of the SOZ in a large HPA. Epilepsia 2006;47(1).

In Vivo Profiling of Focal Cortical Dysplasia on High-resolution MRI Using Computational Models

Olivier Colliot, Samson Antel, Veronique B. Naessens, Neda Bernasconi, and Andrea Bernasconi

Focal cortical dysplasia (FCD), a malformation of brain development, is a frequent cause of severe, medically-ntractable epilepsy. The use of magnetic resonance imaging (MRI) has allowed the identification of FCD in an increasing number of patients. On MRI, FCD is characterized by a combination of increased grey matter (GM) thickness, high signal and blurred transition between GM and white matter (WM). The visual identification of these abnormal FCD characteristics on MRI may be difficult. Moreover, it is unclear to which degree these features occur among different FCD lesions. We investigated the pattern of occurrence of these three abnormal MRI characteristics using a set of computational models that were applied to the MRI of 23 FCD patients and 39 healthy controls. In 78% of the patients, simultaneous cortical thickening, hyperintense signal and blurring characterized FCD lesions. The three features were found not only in large FCD lesions, but also subtle ones that had been overlooked by conventional radiological inspection prior to surgery. We believe that this new finding is relevant for clinical practice because it could influence the way that clinicians evaluate visually the MRI in patients in whom FCD is the suspected cause for intractable seizures. Epilepsia 2006;47(1).

Quantitative MRI Biomarkers of Cognitive Morbidity in Temporal Lobe Epilepsy

Tayo Oyegbile, Abvik Bhattacharya, Michael Seidenberg, and Bruce P. Hermann

We studied the relationship between neuropsychological morbidity, quantitative magnetic resonance imaging (MRI) measures of whole brain structure, and clinical seizure factors reflecting epilepsy cause, course, and treatment. Quantitative MRI measurements of total (whole brain) cerebrospinal fluid (CSF) and gray and white matter volumes and clinical seizure features were examined in relation to summary indices of cognitive morbidity in 96 patients with temporal lobe epilepsy. MRI volumes were adjusted for ICV and cognitive scores were adjusted for age, education and gender based on a sample of 81 healthy controls.

Whole brain volumes (gray, white and CSF) were abnormal in chronic temporal lobe epilepsy patients compared to controls and were related significantly to neuropsychological morbidity, especially total CSF. Statistical modeling demonstrated that markers of total atrophy (seen as increased cerebrospinal fluid around the brain tissue) was the primary mediator of the relationship between clinical seizure variables to neuropsychological morbidity. Quantitative measurements of overall brain abnormality (atrophy) in temporal lobe epilepsy are clinically meaningful markers that are associated with increased cognitive morbidity. These biomarkers appear to mediate the adverse effects of some clinical seizure variables on cognition. Epilepsia 2006;47(1).

Cognitive Functions in Juvenile and Adult Patients with Gelastic Epilepsy due to Hypothalamic Hamartoma

Ansgar Quiske, Lars Frings, Kathrin Wagner, Josef Unterrainer, and Andreas Schulze-Bonhage

Gelastic epilepsy (GE) is a rare but often severe epileptic syndrome characterized by recurrent brief seizures, with initial laughter or grimacing, sometimes followed by more disabling partial or generalized seizures. The most common underlying cause of GE are benign congenital malformations, called hamartomas of the hypothalamus (HH). These growths consist of atypically differentiated neuronal tissue located within or close to the hypothalamus at the base of the third ventricle. This epileptic syndrome typically manifests in early childhood, does not respond to medical therapy, and many patients have additional symptoms like precocious puberty, behavioral disturbances and cognitive deficits. Earlier reports on children with gelastic epilepsy had found particular difficulties in language and memory functions. We here assessed cognitive functions (IQ, attention, memory functions, etc.) in a group of thirteen juvenile and adult patients with GE and HH using a comprehensive neuropsychological test battery. More than half of the patients displayed deficits in a broad range of cognitive functions that were most severe with regard to visual and verbal learning and memory. The reasons for such cognitive dysfunctions are so far poorly understood. In our patients, reduced cognitive flexibility and difficulties in mental rotation correlated to the frequency of partial seizures. Longitudinal investigations on the development of such cognitive impairments over time will be necessary to achieve a more complete understanding of the mechanisms involved. Epilepsia 2006;47(1).

Periventricular Nodular Heterotopia: Classification, Epileptic History, and Genesis of Epileptic Discharges

Giorgio Battaglia, Luisa Chiapparini, Silvana Franceschetti, Elena Freri, Laura Tassi, Stefania Bassanini, Flavio Villani, Roberto Spreafico, Ludovico D’Incerti, and Tiziana Granata

Periventricular nodular heterotopia (PNH) are brain malformations determined by impairment of mechanisms governing brain cell migration prior to birth. They are frequently encountered in clinical practice, and they are made up of nodules of grey matter (brain cells) located along the borders of the cerebral ventricles. Affected patients are frequently characterized by focal drug-resistant epilepsy. In this study, we have analyzed the MRI, EEG and clinical findings in a large cohort of PNH patients followed for prolonged time at the Epilepsy Center of our institute. Our goal was to re-evaluate the classification of PNH and relate the anatomical features to outcome of the epilepsy. We intended also to verify the contribution of PNH nodules to the onset of epileptic discharges by analyzing interictal and ictal abnormalities with EEG and stereo-EEG recordings. Based on imaging and clinical data, we have subdivided the patients into 5 PNH groups: 1) bilateral and symmetrical; 2) bilateral single-noduled; 3) bilateral and asymmetrical; 4) unilateral; 5) unilateral with extension to neocortex. This classification may be used in future genetic studies of PNH patients and it may also prove valuable for clinicians, since distinctive clinical features and epileptic outcomes characterize each group of patients. Our EEG analysis has demonstrated that in all patients abnormalities both between and during seizures always are related to the location of PNH. More importantly, we have clarified the still debated issue of seizure onset in PNH, by demonstrating that seizures are generated by abnormal anatomical circuitries including the heterotopic nodules and adjacent cortical areas. Epilepsia 2006;47(1).

Involvement of Medial Pulvinar Thalamic Nucleus in Human Temporal Lobe Seizures

Dominique Sarah Rosenberg, François Mauguière, Geneviève Demarquay, Philippe Ryvlin, Jean Isnard, Catherine Fischer, Marc Guénot, and Michel Magnin

Several animal studies suggest that the thalamus might be involved in the maintenance and propagation of epileptic seizures. However, electrophysiological (EEG) evidence in human partial epileptic seizures for this hypothesis is still lacking. Considering the rich and reciprocal connectivity of the Medial Pulvinar (PuM) with the temporal lobe, we evaluated a potential participation of this thalamic nucleus in temporal lobe epilepsy (TLE). The electrophysiological activity of PuM was recorded during EEGs recorded by surgically-implanted electrodes into brain during exploration of spontaneous temporal lobe seizures in 14 patients referred for presurgical assessment of refractory TLE. We recorded PuM ictal activity in 80% of the 74 seizures that we analyzed. This activity was characterized by rhythmic slow-waves and/or rhythmic spikes (RSW-RS) or by low-voltage fast activity (LVFA) in 64% and 36% of seizures, respectively. RSW-RS occurred mostly in seizures arising from inner temporal structures; whereas, LVFA was more frequently observed in seizures of neocortical origin. In the 15 seizures without PuM ictal activity, spreading of the seizure outside the onset zone never occurred, while it did in 78% of seizures with PuM ictal involvement. Discharge propagation was systematic when PuM involvement corresponded to LVFA, whatever the seizure onset zone was, while it represented only 66% of the seizures when PuM exhibited RSW-RS. This study shows that ictal changes in PuM activity are frequently observed during temporal lobe seizures and suggests that this thalamic nucleus might participate in their propagation. Epilepsia 2006;47(1).

Identification of the Epileptogenic Tuber in Patients with Tuberous Sclerosis: A Comparison of High-resolution EEG and MEG

Floor E. Jansen, Geertjan Huiskamp, Alexander C. van Huffelen, Mireille Bourez-Swart, Elvire Boere, Tineke Gebbink, Koen L Vincken, and Onno van Nieuwenhuizen

Tuberous Sclerosis Complex (TSC) is an inheritable syndrome involving multiple organs, including the brain. The typical brain lesion, the so-called tubers, can give rise to a variety of neurological symptoms such as epilepsy. Seizures often do not respond to anti-epileptic drugs in patients with TSC. In these patients epilepsy surgery, with resection of the tuber causing the seizures, should be considered. However, tubers are often numerous and widespread, so identification of the tuber causing the seizures can be difficult. We compared epileptiform (EEG activity associated with increased risk for underlying epilepsy) activity recorded with electroencephalography (EEG) and magnetoencephalography (MEG) in 19 patients with tuberous sclerosis (TSC) and epilepsy. EEG, MEG, and MRI scans were performed in all patients. Epileptiform activity was identified in EEG and MEG recordings offline by three observers. When there was a consensus regarding the localization of epileptiform activity (spikes) source localization was performed, meaning that the localization of the epileptiform activity was plotted in the MRI scan. The MRI scan visualizes the tubers. The distance between the localization of epileptiform activity (source), determined from EEG and MEG recordings, and the border of the closest tuber was calculated and compared in each patient. MEG sources were closer to tubers in all but one patient. Three patients underwent epilepsy surgery, two of whom are seizure-free following complete resection of the tuber. Our results show that the epileptogenic source identified on MEG recordings was closer to the presumed epileptogenic tuber than the source identified on EEG recordings from the same patients with TSC. Especially in patients with numerous tubers MEG recordings are valuable to delineate the source of the epileptiform activity and define the relation to the closest tubers. Hence, MEG is a useful technique and should be used to evaluate TSC patients considered for epilepsy surgery. Epilepsia 2006;47(1).

December 2005
Employers’ Attitudes to Employment of People with Epilepsy: Still the Same Old Story?
Ann Jacoby, Joanne Gorr, and Gus A. Baker

One area of life quality known to be compromised by having epilepsy is employment; and one factor contributing to the employment problems of people with epilepsy (PWE) is employer attitudes. Much of the research that has been done on this topic is now outdated and given the changing legal, medical and social contexts in which PWE live, we decided to re-examine employer attitudes in the UK. We conducted a mail survey of a random sample of UK companies selected to be representative of the 14 UK economic regions and proportional to the number of employees. The overall response rate to our survey was 41% (n=204). Twenty-six percent of respondents reported having experience of employing PWE. Sixteen percent considered that there were no jobs in their company suitable for PWE; and 21% thought employing PWE would be ‘a major issue.’ Employers uniformly were of the view that PWE, even when in remission, should disclose their condition to a prospective employer. Seizure severity, frequency and controllability were all considered important features of epilepsy in the context of employment. Epilepsy created high concern for around half of employers, including over the likelihood of it being linked to a work-related accident. Employers were willing to make accommodations for PWE, in particular job sharing, temporary re-assignment of duties and flexible working hours. Attitudes to employment of PWE were influenced by company size and type and previous experience of doing so. We conclude that with regard to employers’ attitudes toward people with epilepsy, it is still the same old story, though happily with some room for optimism. Epilepsia 2005;46(12).

Prevalence of Active Epilepsy in a Rural Area in South-Tanzania: A Door-to-door Survey

Wolfgang Dent, Raimund Helbok, William Bahati Pungu Matuja, Sönke Scheunemann, and Erich Schmutzhard

This study provides baseline data about the prevalence of active epilepsy in a rural African population. Compared to western countries, our study confirmed a pattern towards higher prevalence of epilepsy in tropical countries. A door-to-door survey was carried out to assess the prevalence of active epilepsy in a rural population in Southern Tanzania. A total of 4,905 individuals living in 1047 households were enrolled in the study, consisting of a screening dialog with a representative family member followed by a face-to-face interview with the affected subject. Diagnosis of epilepsy followed clinical guidelines proposed by the International League Against Epilepsy. We detected forty-two cases (21 males, 21 females) of active epilepsy. Thirty of them met the case definitions of generalized seizures; whereas, twelve patients reported partial seizures. The peak prevalence was found in both sexes in the second decade of life with a second peak in the group aged 30-39 years. Eleven patients (26.2%) were classified as “strongly suspected of symptomatic” epilepsy, the remaining 31 patients (73.8%) as possible being idiopathic, symptomatic or cryptogenic epilepsy cases. As shown in previous studies, we observed a higher prevalence of epilepsy in children and adolescents, followed by a steady decline with increasing age. Reasons for this type of frequency could be ascribed to malnutrition, trauma, genetic conditions, antenatal and prenatal care, diseases resulting in febrile convulsions and cerebral infections. Frequent seizures could even result in death in specifically diseased individuals. Epilepsia 2005;46(12).

Brain Perfusion following Single Seizures

Georg Leonhardt, Armin de Greiff, Johannes Weber, Tanja Ludwig, Helmut Wiedemayer, Michael Forsting, and Andreas Hufnagel

A certain number of patients with epilepsy cannot be treated adequately with anticonvulsive drugs and are candidates for surgery to treat their epilepsy. Investigations of brain morphology with MRI and of brain function with electroencephalography (EEG) are well established methods for identification of the epileptic focus. To avoid the invasiveness and high costs of implanted recording EEG electrodes, other functional methods, such as measurements of brain blood flow (perfusion), are desirable. We investigated six patients with temporal lobe epilepsy with MRI perfusion measurements before and after a seizure. We used the bolus-to-peak ratio that gives information on the relative blood flow changes of one side of the brain in comparison to the other, instead of absolute values, which are subject to numerous restrictions and bias. We found increased blood perfusion in the hippocampus of the affected side in the period between seizures, and a decrease after seizures. Later, the perfusion increased. In the neighboring parahippocampal gyrus perfusion showed an opposite pattern, with an initial increase and a subsequent decrease. In the thalamus changes were small at times between or after seizures. Perfusion measurements in the cortex and in the white matter showed equivocal results. Our results are different from those of a number of previous studies that have shown decreased perfusion between seizures, and increased perfusion after seizures in the hippocampus and the surroundings areas. We believe that the better spatial resolution of our MRI techniques and a different time schedule account for these differences. However, this technique currently is far from being suitable for routine diagnosis of epilepsy patients with drug resistant epilepsy. Epilepsia 2005;46(12).

November 2005
Cognitive Decline in Severe Intractable Epilepsy
Pamela J. Thompson and John S. Duncan

Decline in memory and other cognitive abilities is known to occur in people with severe epilepsy and is a cause of concern. Cognitive difficulties can have a negative impact on school and work performance but also on social functioning and self-esteem. A number of factors have been identified as causing this decline including brain abnormalities, medication and seizures. Animal studies suggest a major role for seizure frequency but studies with humans do not indicate a large effect. The aim of this study was to explore further the relationship between seizures and cognitive change in severe epilepsy. Cognitive test results were available for 136 people seen twice at an interval of at least ten years. Cognitive decline was marked and occurred for a range of functions. A high frequency of tonic-clonic seizures and seizure related head injuries were associated with the greatest declines in ability. The performance on tests of memory declined in people with frequent complex partial seizures. On the other hand good seizure control was associated with a better outcome suggesting that achieving complete seizure freedom even after years of poor control can have a beneficial effect on cognition. Epilepsia 2005;46(11).

Ictal Ipsilateral Head Deviation in Frontal Lobe Seizures

Sylvain Rheims, Geneviève Demarquay, Jean Isnard, Marc Guenot, Catherine Fischer, Marc Sindou, François Mauguiere, and Philippe Ryvlin

Drug resistant frontal lobe epilepsy (FLE) remains a difficult therapeutic challenge, with low rate of patients rendered seizure-free by surgery. This partly reflects the difficulty of precisely determining the seizure onset zone in patients with FLE, and argues for a better understanding of the brain regions subserving the various ictal signs associated with this condition. Head deviation (HD) is one of the most frequent motor signs observed during seizures arising from the frontal lobe. It has been typically described as a sustained turning opposite to the side of seizure onset in the brain. However, frontal lobe seizures might also be associated with HD toward the seizure onset zone, blurring the overall lateralizing value of HD in FLE. To address these various clinical issues, we have studied the relation between HD and the localization of the seizure onset zone in 13 consecutive patients who underwent a successful surgery for FLE. HD to the same side as the seizure focus was observed in four patients (30%), whereas opposite turning occurred in five patients (38%). Same-side HD always occurred at or immediately after seizure onset, and was never associated with clonic manifestations (rhythmic jerking). Conversely, opposite HD occurred later during the course of seizure, always involved stiffening of the involved part, or unnatural jerking of half of the face. When both directions of HD were observed during the same seizure, the same side always preceded that to the side opposite the brain seizure focus. Thus the timing and type of ictal HD might help to better lateralize the side of seizure onset in FLE. Epilepsia 2005;46(11).

Hippocampal Involvement in a Language Activation Task in Patients with Mesial Temporal Lobe Epilepsy

Lisa Bartha, Peter Mariën, Christian Brenneis, Thomas Trieb, Christian Kremser, Martin Ortler, Gerald Walser, Judith Dobesberger, Norbert Embacher, Thaddäus Gotwald, Elfriede Karner, Buelent Köylü, Gerhard Bauer, Eugen Trinka, and Thomas Benke

Recent studies suggest that the hippocampal formation is part of the language comprehension network in healthy subjects. We aimed to explore the contribution of the hippocampal formation to the retained language comprehension network in patients with unilateral (single sided) mesial (inner, middle) temporal lobe epilepsy (TLE). We therefore performed a functional MRI study based on a language comprehension paradigm in 45 right-handed patients with unilateral mesial TLE and 35 healthy control subjects. In sum, 82% of TLE patients displayed hippocampal activations. A significant difference in hippocampal activation between left and right TLE was found: Right TLE patients showed increased activity in the left hippocampal formation compared to left TLE patients. In contrast, patients with left TLE did not show increased activity in the right hippocampal formation compared to right TLE patients. In comparison to a healthy control group, right TLE patients activated the left hippocampal formation to a greater extent, whereas patients with left TLE did not activate the right hippocampal formation to a greater degree. These findings point to an increased involvement of the left hippocampal formation during a language comprehension task in right TLE patients. In contrast, left TLE in right-handed patients seems not associated with an enhanced involvement of the right hippocampal formation in retained language comprehension. These findings suggest that effective language comprehension in right-handed subjects with TLE depends on the involvement of the left hippocampal formation and underline the risks of postoperative language decline in patients with left TLE. Epilepsia 2005;46(11).

September 2005
Cerebral Damage in Epilepsy: A Population-based Longitudinal Quantitative MRI Study
Rebecca S.N. Liu, Louis Lemieux, Gail S. Bell, Sanjay M. Sisodiya, Philippa A. Bartlett, Simon D. Shorvon, Josemir W.A.S. Sander, and John S. Duncan

There have been concerns that epileptic seizures may cause brain damage. Studies in animals have shown that even a small number of relatively mild seizures may damage brain structures such as the hippocampus, which is important for memory function. Only recently have researchers performed repeated magnetic resonance imaging (MRI) brain scans on individuals with epilepsy to determine whether seizures cause brain damage in humans, shown as loss in brain volume.In the largest MRI study investigating whether seizures damage the brain, we performed brain scans on 190 patients of different ages, 3.5 years apart. We measured the whole brain and specific structures within the brain, and compared changes in their brains, with those seen in healthy control subjects of similar ages.Previous brain injuries, such as convulsions related to high temperatures in early childhood were associated with lower brain volumes at the start of the study. The overall rates of brain volume loss were similar in individuals with and without epilepsy, and amongst patients with different kinds of epilepsy. The main factor influencing the rate of volume loss was the age of the patient and not the number of seizures. There was significant shrinkage of a part of the brain in 17% of those with epilepsy, compared with 7% of those without epilepsy. We concluded that epilepsy is associated with brain shrinkage in only a minority of those with the condition. More studies are needed to identify who is at particular risk of this occurring, and how this may be prevented. Epilepsia 2005;46(9).

Unusual Findings In Brain Biopsies of Two Patients with Acute Magnetic Resonance Imaging Lesions Associated with Focal Seizures

Shearwood McClelland III, Jenny M. Libien, Steven S. Chin, David J. Adams, Stanley R. Resor, Jr., Stephen Chan, and Robert R. Goodman

Patients with focal seizures often have MRI abnormalities in the brain region of their presumed seizure focus. Neoplasms, ischemic infarctions, inflammatory processes, and other specific pathologic entities have been diagnosed by biopsies of such MRI abnormalities. Two patients with this presentation had brain lesion biopsies with a leading presumptive diagnosis of glial neoplasm but were found to have indistinct histopathology. Each patient presented with focal seizures (right parietal region, right hippocampus) corresponding with focally increased T2 signal on MRI. In both patients, the preoperative clinical suspicion was for neoplastic or inflammatory processes. Several weeks after seizure onset, craniotomy in patient 1 and stereotactic needle biopsy in patient 2 revealed mild gliosis with reactive vascular changes and perivascular hemosiderin deposition, not diagnostic of but compatible with venous congestion (or possibly venous thrombosis). Postoperatively, patient 1 had brief sensory seizures that stopped 5 months after surgery, while patient 2 did not develop subsequent seizures. Both patients had normalization of their MRI (except for postoperative changes) and have remained seizure-free. We describe two patients who had brain biopsies of striking focal increased T2 signal MRI abnormalities associated with seizures. Pathologic findings contradicted our preoperative suspicions (neoplasm or inflammatory process), compatible with (but not conclusive for) subacute venous congestion/thrombosis. These findings indicate that patients with seizures may have an associated discrete intra-axial MRI lesion that is not neoplastic. To our knowledge, this is the first report of focal seizure-associated MRI lesions with biopsy findings compatible with venous congestion/thrombosis. Epilepsia 2005;46(9).

Intellectual Prognosis of Status Epilepticus in Adult Epilepsy Patients: Analysis with Wechsler Adult Intelligence Scale-Revised

Naoto Adachi, Kousuke Kanemoto, Reimi Muramatsu, Masaaki Kato, Nozomi Akanuma, Masumi Ito, Jun Kawasaki, and Teiichi Onuma

Various systemic and brain condition can cause prolonged seizures, termed status epilepticus (SE). After recovering from an episode of SE, some patients suffer from cognitive dysfunction as well as other serious neurological symptoms. However, it has not been well studied whether and to what extent SE could lead to an intellectual deterioration in epilepsy patients who have already been treated with antiepileptic drugs (AED). To investigate this issue, we tested intellectual function before and after an episode of SE in 15 adult epilepsy patients. As an index of intellectual function, we used full scale IQ of the Wechsler Adult Intelligence Scale-Revised. The change of FIQ before and after the SE was compared with the differences between the two test trials performed in an equivalent interval in 40 clinically matched patients without SE. We found no significant changes, either increase or decrease, in intellectual ability as a consequences of SE. Furthermore, there were no significant associations between FIQ changes and SE-related variables, i.e., age at the episode of SE, duration of SE, type of SE. Our findings suggest that in epilepsy patients, SE per se does not often result in long-lasting intellectual dysfunction. Epilepsia 2005;46(9).

Characteristics of Male Veterans with Nonepileptic Seizures

Barbara A. Dworetzky, Andreja Strahonja-Packard, Christopher W. Shanahan, Jeanette Paz, Barbara Schauble, and Edward B. Bromfield

In the population of patients referred to epilepsy centers with seizures that are not adequately controlled by medications, 10-58 % do not turn out to have epilepsy, and instead have psychologically based spells referred to as psychogenic nonepileptic seizures (PNES). These patients are usually young women, by a ratio of 3 to 1. Male Veterans with PNES were compared to those with a definite history of epileptic seizures. A small number of patients who may have had both types of seizures were excluded from analysis. All patients were evaluated between 1997 and 2000 and were asked questions about whether they had ever experienced a traumatic brain injury, whether they had taken anti-seizure medications (and if so, how many), if they experienced depression, anxiety, or used alcohol or illicit drugs, or had chronic pain or post-traumatic stress disorder. In addition, the medical chart was reviewed to confirm whether they received compensation from the Veteran’s Administration for their diagnosis, or had normal or abnormal neuroimaging, neurological examinations, or electroencephalograms (brain waves). Men with PNES were significantly younger, reported more frequent events, and were more likely to report chronic pain, anxiety, and post-traumatic stress disorder than patients with epileptic seizures. They did not differ with respect to whether they reported the loss of bladder control during a seizure, or whether they received disability compensation from the Veteran’s Administration. Epilepsia 2005;46(9).

August 2005
Management of Women with Epilepsy: Are Guidelines Being Followed?
Margitta T. Kampman, Stein-Vegar Johansen, Helge Stenvold, and Ganesh Acharya

Several international guidelines for the management of women with epilepsy (WWE) have been developed since 1989. We aimed to determine whether guidelines for the management of WWE are followed in our Department and whether active implementation of such guidelines makes a difference to clinical practice.

The study covered a two-year period of “passive dissemination” of guidelines, followed by a two-year period of “active implementation.” Case-notes on 215 WWE aged 16-42 years were reviewed for documentation that the guidelines were followed. Data abstracted from case-notes included: counseling on contraception and pregnancy-related issues, follow-up during pregnancy, advice on supplementation of folic acid, calcium and vitamin D, and serum folate measurements. A questionnaire assessing the knowledge of WWE-issues was completed by 112/157 (71%) patients. Documentation that WWE-issues had been addressed was found in approximately one third of medical case-records in both study periods. Active implementation of guidelines had no measurable effect on clinical practice. Only the follow-up during pregnancy seemed to have improved. However, patients’ knowledge of WWE-issues compared favorably with published studies. Better strategies are needed to secure successful implementation of guidelines. Epilepsia 2005;46(8).

Application of Magnetoencephalography in Epileptic Patients with Widespread Spike or Slow Wave Activity

Hideaki Shiraishi, Seppo P. Ahlfors, Steven M. Stufflebeam, Kyoko Takano, Maki Okajima, Susanne Knake, Keisaku Hatanaka, Shinobu Kohsaka, Shinji Saitoh, Anders M. Dale, and Eric Halgren

Recently magnetoencephalography (MEG) has become an important evaluative tool for patients with epilepsy. We introduce a new analyzing method: dynamic statistical parametric mapping (dSPM) that can show the change of epileptic activities more directly and clearly. We investigated two epileptic patients. Case 1 had a brain tumor and showed widespread spikes in the EEG. Case 2 had sensory auras and showed hemispheric slow-wave activity in the EEG. MEG was collected with a 204-channel helmet-shaped sensor array. dSPM was constructed to estimate the cortical position of the places in cortex that the epileptic-like spikes originated. Conventional presentation of magnetic source: equivalent current dipoles (ECDs) were also calculated for comparison with the results of dSPM. In Case 1, dSPM presented the major activity in the vicinity of the region of tumor and surgery in the left frontal lobe. Later in the time course of the epileptic-like spikes, some activity appeared in the left temporal lobe. In Case 2, with hemispheric slow waves, the most active area was located in the left parietal lobe and additional activity was seen at the temporal and frontal lobes on the same side in dSPM. The source estimates correlated well with the results of single-photon-emission-CT (SPECT) and the manifestations of epileptic seizures. Regarding the results of ECDs, ECDs could not model well the MEG data in both cases. We believe that the new technique dSPM coupled with magnetic brain recordings, can show patterns of brain activity more clearly than conventional methods, thereby extending the applicability of MEG to a larger population of people with epilepsy. Epilepsia 2005;46(8).

Reflex Seizures in Patients with Malformations of Cortical Development and Refractory Epilepsy

André Palmini, Peter Halasz, Ingrid E. Scheffer, Yukitoshi Takahashi, Angeles Perez Jimenez, François Dubeau, Frederick Andermann, Eliseu Paglioli-Neto, Jaderson Costa da Costa, Felix Rosenow, and Brita Fritsch

Reflex seizures are epileptic attacks associated with specific stimuli. Reflex seizures are rare. Any type of visual, auditory, tactile, or even motor or cognitive stimulus, such as chewing, swallowing or thinking about something may give rise to an epileptic seizure, providing the cortical region where the stimulus arrives at the brain is, for some reason, hyperexcitable. Malformations of cortical development (MCD) are brain lesions that have been associated with increased levels of excitability, and often coexist with very severe epilepsies. The present study set out to present a series of patients with MCD and reflex seizures. We describe the types of stimuli leading to reflex attacks and the correlation between the stimuli and the brain region where the malformations were localized. Also, we discuss why such seizures are not more frequently found in patients with MCD, given the high degree of epileptogenicity of these types of lesions. In this respect, we put forward a hypothesis proposing that processes occurring within the malformation and other types of inhibitory mechanisms may play a role in the prevention of reflex seizures in many patients with MCD. Epilepsia 2005;46(8).

Hyperorality in Epileptic Seizures: Periictal Incomplete Klüver-Bucy Syndrome

Jozsef Janszky, Andras Fogarasi, Vafa Magalova, Ingrid Tuxhorn, and Alois Ebner

Our study analyzed a particular feature of certain epileptic seizures, called “periictal hyperorality.” This means that the patient suffering from epilepsy puts or unambiguously intends to put non-food items into his or her mouth during or after the seizures. We reviewed video-recordings of 269 patients who had video-EEG recordings during seizures and a brain MRI as part of an evaluation for possible epilepsy surgery. All the patients had epilepsy surgery due to intractable frontal (FLE) or temporal lobe epilepsy (TLE). We identified eight patients who had hyperorality during or after seizures. Three patients exhibited hyperorality during the seizures, five patients after the seizures. EEG during seizures suggested bilateral transient disturbance in brain functions due to epileptic seizures in six cases. In two cases, the disturbance on EEG was seen on only the left side. We concluded that periictal hyperorality is a rare phenomenon occurring in 3% of epileptic seizures. We suggest that periictal hyperorality is a feature of a previously described syndrome of Drs. Klüver and Bucy. The Klüver-Bucy syndrome is characterized by hypersexuality, excessive oral tendencies, dietary changes, loss of normal fear, lack of aggression and excessive attentiveness to visual stimuli. This syndrome can occur after bilateral surgery affecting the temporal lobes but it can also appear after herpes encephalitis, brain trauma, or in Pick’s or Alzheimer diseases. We also concluded that bilateral (both side) seizure activity plays an important role in the hyperorality of most of our patients, but left-sided epileptic activity without right brain involvement sometimes can also cause periictal hyperorality. Epilepsia 2005;46(8).

Characteristics of Headache Associated with Intractable Partial Epilepsy

Alexei E. Yankovsky, Frederick Andermann, and Andrea Bernasconi

The association between headache (HA) and epilepsy is well known. However, there have been few previous studies characterizing HA types and head sensations in large populations of individuals with well-defined forms of epilepsy. To analyze the incidence of HA in such a group, we compared HA and non-HA patients in order to identify special predictive factors for HAs or migraine. We also investigated the pathologically-verified group for possible correlations with HAs or migraine. One hundred consecutive patients undergoing pre-surgical evaluation for partial epilepsy uncontrollable by medications were interviewed. For each HA type, we inquired about lateralization, localization, quality of HA and results of treatment. Headaches occurring around time of the seizure were reported by 47 patients. Of those, 11 had HA before the seizure, and 44 had HA after the seizure. Eight patients had both pre-seizure headaches and post-seizure headaches. HAs occurring at times between seizures were reported by 31 patients. Twenty-nine of 47 patients (62%) had fronto-temporal HAs. Twenty-five patients had migraine-like HA without aura: 18/30 (60%) of patients with temporal lobe epilepsy and 7/17 (41%) of those with extratemporal epilepsy. No correlation between pathology and presence of HA was found in 59 pathologically verified patients, except in four who had arteriovenous malformations: 3 did and one did not have HAs. Eighteen patients had in addition poorly localized and ill described head sensations other than HAs. We confirm that there is an association between focal epilepsy and HAs including migraine without aura. This is true both for temporal lobe and extra-temporal epilepsy. Headaches around the time of seizures and even prodromal HA may be related to the epileptic discharge and may have lateralizing value. This association is not recognized by the current International Headache Society (IHS) classification. The presence of HA and migraine is not related to the underlying pathological cause of epilepsy except in patients with arteriovenous malformations. Epilepsia 2005;46(8).

July 2005
Psychological Distress, Comorbidities, and Health Behaviors Among U.S. Adults with Seizures: Results From the 2002 National Health Interview Survey
Tara W. Strine, Rosemarie Kobau, Daniel P. Chapman, David J. Thurman, Patricia Price, and Lina Balluz

More than 2 million people in the United States have experienced an unprovoked seizure or have been diagnosed with epilepsy. Seizures can result from many different conditions that affect the brain including stroke, complications during childbirth, infections, and head trauma. Seizures can also occur in response to disturbances not directly related to the central nervous system such as hypoxia, toxins, or fever, and may also be due to heredity Findings from this study indicate that adults with seizures were significantly more likely than those without seizures to report lower levels of education and higher levels of unemployment, psychological distress (i.e., feelings of sadness, nervousness, hopelessness, worthlessness, and that everything is an effort), recurrent pain, and sleep disturbance. Adults with seizures were also more likely to report insufficient leisure-time physical activity as well as co-occurring disorders such as cancer, arthritis, heart disease, stroke, asthma, severe headaches, lower back pain, and neck pain. Previous research indicates that persons with epilepsy are at higher risk for depression, anxiety, and suicide. Depression and anxiety, however, are underrecognized and undertreated in this population. Therefore, it is important for healthcare professionals to screen for psychiatric as well as physical problems among patients with a history of seizures in order to improve patient health outcomes. Furthermore, public health surveillance systems should include questions on seizures, epilepsy, and mental health in order to facilitate further examination of the existing associations among these disorders and to better identify populations meriting further assessment and intervention. Epilepsia 2005;46(7).

Hyperglycemia with Occipital Seizures: Images and Visual Evoked Potentials

Chung-Pang Wang, Peiyuan F. Hsieh, Clayton Chi-Chang Chen, Wan-Yu Lin, Wei-Hsiung Hu, Dar-Yu Yang, and Ming-Hong Chang

Nonketotic hyperglycemia (NKH) is defined as a clinical syndrome consisting of severe hyperglycemia, hyperosmolality (excess concentration of electrolytes in the blood), and intracellular dehydration without ketoacidosis. NKH has a convulsive effect but rarely presents with visual seizures. A diabetic woman had complex visual hallucinations and illusions (up to 10 fits per hour) as an initial manifestation of NKH. Neurological examination showed ictal nystagmus (jerky eye movements) to the right and continuous right hemi-visual field defect. During the seizures, single photon emission computed tomography and electroencephalography revealed left occipital hyperperfusion and epileptiform discharges arising in the same region. The seizures gradually subsided over a period of 11 days with medical treatment. Magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery showed left occipital subcortical decreasaed intensity in conjuction with hyperintensity in the cortex of the region. Follow-up MRI showed only minimal hyperintensity at 6 months. The visual evoked potential (VEP) is a gross electrical signal recorded from the occipital cortex in response to a systematic change in some visual event. The occipital equivalent dipole of responses to pattern reversal stimuli projects to the contralateral hemisphere and the maximal representation of the pattern reversal VEP is on the contralateral side. Interestingly, the VEP amplitude of our patient was significantly higher in the right occipital area during seizures, but slightly higher in the left after the patient had been seizure-free for 6 months. This is the first report of NKH-related visual seizures associated with special MRI and VEP features. It also reminds us that visual hallucinations and illusions may be the chief symptoms of hyperglycemic seizures. Epilepsia 2005;46(7).

A Comparison of Two fMRI Protocols for Eliciting Hippocampal Activation

Jeffrey R. Binder, Patrick S.F. Bellgowan, Thomas A. Hammeke, Edward T. Possing, and Julie A. Frost

People with epilepsy may have recurring seizures despite treatment with anti-seizure medications. Surgery to remove the site where seizures originate can cure epilepsy in many patients. The most common epilepsy

surgery involves removing a brain area called the hippocampus. This region is known to play a critical role in forming memories, and patients who undergo such surgery may afterward experience memory impairment. Assessing the functionality of the hippocampus before surgery can help prevent this complication. One promising method for assessing the hippocampus uses functional magnetic resonance imaging, a non-invasive imaging technique that produces 3-dimensional maps of brain activity during performance of cognitive tasks. The optimal cognitive tasks for activating the hippocampus are not yet known. The authors studied brain activity in 32 healthy volunteers during two types of tasks, one emphasizing the novelty of an experience and the other emphasizing the meaningfulness of an experience. In the Novelty study, brain activity produced by visual scenes (color photographs) the participants had never seen before was compared to activity produced by two visual scenes that were repeated many times. In the Relational study, brain activity produced by recognizable visual scenes was compared to activity produced by meaningless visual patterns. Both tasks activated the hippocampus. The Novelty study showed more activation in the back of the hippocampus, while the Relational study showed more activation in the front of the hippocampus. Because epilepsy surgery most often involves the front of the hippocampus, the Relational tasks may be preferable for preoperative evaluation. Epilepsia 2005;46(7).

June 2005
Speech-induced Aphasic Seizures in Epilepsy Caused by LGI1 Mutation
Eylert Brodtkorb, Ralf P. Michler, Wenli Gu, and Ortrud K. Steinlein

Autosomal dominant lateral temporal lobe epilepsy is an inherited form of epilepsy, usually with auras in the form of hearing phenomena (humming or buzzing) and sometimes sensory aphasia (lost understanding of words). Seizures can sometimes be precipitated by sound or, in the family studied here, by speech.

The patient was a 23-year-old, right-handed man belonging to a family with a mutation (C46R) in the LGI1 gene. He had experienced short episodes of aphasia in situations where he was suddenly addressed. Voices became distorted and he could not comprehend, despite hearing words. The day after a late party, his girlfriend unexpectedly spoke to him. Her speech became unintelligible to him. He did not reply and had a generalized tonic-clonic seizure. During an EEG, he was suddenly asked for the names of his siblings. He answered, but lost understanding of the further conversation and described how syllables floated together with an echoing character. He turned his head to the right and developed another tonic-clonic seizure. In the EEG, seizure activity built up in the fronto-temporal areas, starting on the left side with spreading to both sides of the brain. To our knowledge, this is the first video-EEG recorded seizure in LGI1-caused epilepsy. The peculiar auras of this patient and the precipitating effect of speech may serve as a marker for identifying further individuals with this particular type of partial epilepsy and may indicate that the mutated gene (LGI1) may have a natural function connected to the human capacity for speech and language. Epilepsia 2005;46(6).

GABA(B) Receptor 1 Polymorphism (G1465A) and Temporal Lobe Epilepsy

Annick Salzmann, Bruno Moulard, Arielle Crespel, Michel Baldy-Moulinier, Catherine Buresi, and Alain Malafosse

Epilepsy is an important worldwide health problem that can affect people of any age, ethnic group and socio-economic background. Our understanding of the genetics of the epilepsies has advanced greatly over the past few years. Discoveries of new mutations responsible for inherited human epilepsies could contribute to enhanced diagnosis, to a better understanding of the mechanisms that produce epilepsy and their inheritance, and to development of novel epilepsy therapies. GABA is the major inhibitory neurotransmitter in the brain, where it acts on two receptor subtypes, named GABA-A (the most important and first known receptor) and GABA-B (a more recently discovered receptor). We studied the role of the GABA-B receptor in the pathogenesis of temporal lobe epilepsy. In order to test the hypothesis that the GABA-B receptor played an important role, a variation of the gene coding for a portion of the GABA-B receptor [GABA(B[1])] was studied in a sample of patients with temporal lobe epilepsy. Our results excluded a major effect of variation in the GABA-B subunit 1 in the susceptibility to temporal lobe epilepsy. Epilepsia 2005;46(6).

Hippocampal Malformations Do Not Necessarily Evolve into Hippocampal Sclerosis

Arjune Sen, Maria Thom, Lillian Martinian, Stephen Dawodu, and Sanjay M. Sisodiya

One of the most common causes of drug-resistant epilepsy is a type of scarring or hardening of the inner temporal lobe, called hippocampal sclerosis (HS). In this condition, the hippocampus shrinks owing to loss of nerve cells, scars and becomes a potential focus from which seizures can originate. Despite extensive research over many years, the exact cause of hippocampal sclerosis is uncertain. It has been suggested that an underlying malformation of the hippocampus may, in time, progress to hippocampal sclerosis and that this process could be accelerated by epileptic seizures. In this report, we describe two patients who suffered from drug-resistant epilepsy for several decades. At post-mortem, both patients were found to have malformations of their hippocampi. However, neither patient exhibited features of HS even when their hippocampi were analyzed using tissue markers that detect subtle signs of hippocampal sclerosis.

A proportion of patients with malformations of their hippocampi might develop hippocampal sclerosis. It is difficult to be sure of the frequency with which this happens, since patients do not come to medical attention until after the onset of their seizures. By that stage, it may be impossible to detect any signs of the pre-existing malformation. However, these two patients demonstrate, at a tissue level, that hippocampal malformations do not necessarily progress to hippocampal sclerosis. It would be worthwhile to study more cases like these to better understand the mechanisms that protect against scarring and the loss of nerve cells in patients with temporal lobe epilepsy. Epilepsia 2005;46(6).

May 2005
Deep EEG Recordings of the Mammillary Body in Epilepsy Patients
Kenou van Rijckevorsel, Basel Abu Serieh, Marianne deTourtchaninoff, and Christian Raftopoulos

The search continues for structures in the brain involved in the generation or spread of epileptic seizures. One structure that may be important, but has not received much attention from clinical epilepsy studies is the hypothalamus, and its posterior segment, called the mammillary bodies (MB). The electrophysiological patterns of MB have been well-documented in laboratory studies with animal models of epilepsy. Other studies have demonstrated the important role played by the MBs in seizure propagation. Our group embarked on a double-blind, cross-over pilot trial to evaluate the therapeutic effect of deep brain stimulation (DBS) of MB and its outflow fibers in patients with uncontrolled epilepsy. Here we aim to report, for the first time, the epileptic and nonepileptic discharges recorded within MB in patients with uncontrolled epilepsy. Three adult males were enrolled after obtaining the ethical committee approval and an informed consent from each. These patients were not believed to be curable by existing medicines or surgical procedures. DBS electrodes were implanted into the left and right MBs, with the patient under general anesthesia. Location was verified by magnetic resonance imaging (MRI). We obtained a surface-depth electroencephalogram (EEG) for a 2-4 day period under vigilant monitoring of the cardio-respiratory and memory functions. The background pattern of EEG recorded from MB was low-amplitude waves with mixed frequencies between 7-12 cycles / sec. We recorded several deep discharges of an epileptic type in each patient, which sometimes did and sometimes did not correlate with behavioral and EEG seizures. Seizure-associated discharges can be observed in human MB and differs from rhythmic EEG activity recorded in animals. These data supplement those available from animal observations. Epilepsia 2005;46(5).

Is Variation in the GABA(B) Receptor 1 Gene Associated with Temporal Lobe Epilepsy?

Nigel C.K. Tan, Sarah E. Heron, Ingrid E. Scheffer, Samuel F. Berkovic, and John C. Mulley

Some genes are believed to influence susceptibility to epilepsy. A gene known as GABA(B) receptor 1 has been linked to temporal lobe epilepsy in a recent genetic study. GABA is important because it is the main inhibitory neurotransmitter in brain. The GABA(B) receptor is one type of receptor site at which GABA binds to neurons to exert its effects. In this study, done in Italy, people who have a rare variant the gene for GABA(B) receptors appeared to have an increased risk of temporal lobe epilepsy. However, results of these types of genetic studies can be affected by the way in which the study was conducted. We therefore performed a similar genetic study in white Australians, adhering to existing guidelines for conducting such studies. We looked at over 200 Australians with temporal lobe epilepsy, but we did not find a similar link between the GABA(B) receptor 1 gene and temporal lobe epilepsy. We believe that our findings either reflect limitations in the way which the first study was conducted, or that different populations from different countries may have different genes influencing epilepsy risk. Further research into this gene and temporal lobe epilepsy is needed. Epilepsia 2005;46(5).

Predictors for Negative Attitudes Towards Subjects with Epilepsy: A Representative Survey in the General Public in Austria

Josef Spatt, Gerhard Bauer, Christoph Baumgartner, Martha Feucht, Martin Graf, Bruno Mamoli, and Eugen Trinka

The quality of life of people with epilepsy is not only determined by the disease itself but also by prejudices and negative attitudes towards the disorder in the general public. In this questionnaire study we asked 2128 Austrian adults about their opinions concerning people with epilepsy, for example, whether they should do the same jobs, whether children suffering from epilepsy should go to regular schools and other similar questions. This was not the first survey of its kind. However, what we tried was to determine was the attributes of respondents that predisposes to negative attitudes. We found that 10% of Austrian adults have negative attitudes towards people with epilepsy – a figure that is similar to studies done in other societies – and that being male, and of low socio-economic background predispose to unfavorable attitudes. In addition, little theoretical knowledge about epilepsy, misconceptions of epilepsy as a form of insanity, and no personal acquaintance with someone with epilepsy independently led to negative attitudes. Information campaigns should try to combine theoretical knowledge about epilepsy with opportunities for personal acquaintance with people suffering from epilepsy. Input from patient interest groups is essential to this regard. Epilepsia 2005;46(5).

Screening for Major Depression in Epilepsy Using Common Self-Report Depression Inventories

Jana E. Jones, Bruce P. Hermann, John Woodard, John J. Barry, Frank Gilliam, Andres M. Kanner, and Kimford J. Meador

Major depression is a common problem for individuals with chronic epilepsy. It is frequently unrecognized and untreated. A variety of self-report questionnaires are available, but their ability to identify major depression in people with epilepsy remains uncertain. The purpose of this study was to determine the ability of two common self report measures of depressive symptoms to identify major depression in people with epilepsy. A total of 174 adults with epilepsy underwent standardized psychiatric interviews to determine the presence of current major depression. Individuals completed two self-report depression questionnaires (Beck Depression Inventory-II [BDI-II] and Center for Epidemiological Study of Depression [CES-D]). The ability of these self-report questionnaires to identify major depression compared to the gold standard structured interviews was examined using diagnostic efficiency statistics. Both the BDI-II and the CES-D exhibited significant ability to identify major depression in individuals with epilepsy. Common self-report depression measures can be used to screen for major depression in clinical settings. Use of these measures will assist in the clinical identification of individuals with major depression so that treatment can be started. Epilepsia 2005;46(5).

Quantitative 1HMRS and MRI Volumetry Indicate Neuronal Damage in the Hippocampus of Children with Focal Epilepsy and Infrequent Seizures

Tarja Varho, Markku Komu, Pirkko Sonninen, Jaana Lähdetie, and Irma E. Holopainen

Seizures can induce structural and functional changes in the brain, in particular in the hippocampus (a key structure in the temporal lobe, often involved with seizures) of adult patients with epilepsy, but whether or not the hippocampus is affected in children with temporal, non-intractable epilepsy is poorly known. Proton magnetic resonance spectroscopy is a relatively new neuroimaging technique, able to track the concentration of certain chemical components of brain, particularly chemicals called N-acetyl group, creatine, phosphocreatine, choline and myo-inositol. We also measured the volume of hippocampus in the MRI to reveal volume changes of eleven pediatric outpatients (10 to 17 years) with non-symptomatic focal epilepsy under antiepileptic medication but still having infrequent seizures. Eight healthy volunteers (9 to 16 years) served as controls. Our results showed that the mean concentration of N-acetyl group was significantly decreased both on the side of the brain giving rise to seizures and also the other side in the patients, compared to the control persons, in particular if the children had a history of generalized tonic-clonic seizures. The mean concentration of choline, creatine and myo-inositol did not differ significantly between the patients and controls. Moreover, the mean volume of the seizure-side hippocampi in patients was significantly reduced compared to that of the controls. The present results suggest that size of the hippocampus and chemical changes in the hippocampus can occur in children with childhood –onset focal epilepsy, even if they have infrequent seizures. Moreover, our results indicate that seizure-induced changes, although less severe, may occur earlier than suggested in children with non-intractable epilepsy. Epilepsia 2005;46(5).

Intracranial EEG Substrates of Scalp EEG Interictal Spikes

James X. Tao, Amit Ray, Susan Hawes-Ebersole, and John S. Ebersole

EEG (electroencephalography, brainwave recordings) is an important test for the diagnosis of epilepsy. Although the EEG can be normal between seizures in people with epilepsy, about half will show brief, abnormal electrical discharges, called interictal (meaning “between seizures”) spikes, This study was performed to better determine what part of the brain gives rise to these interictal spikes. We recorded simultaneously 26 channels of scalp EEG with additional electrodes in the brain in 16 surgery candidates with temporal lobe epilepsy. We reviewed approximately 600 interictal spikes recorded with intracranial EEG. Only a very few of these cortical spikes were associated with scalp recognizable potentials. 90% of cortical spikes with a source area of greater than 10 cm² produced scalp EEG spikes, whereas only 10% of cortical spikes having less than 10 cm² of source area produced scalp potentials. Intracranial spikes with less than 6 cm² of area were never associated with scalp EEG spikes. These data demonstrate that cerebral sources of scalp EEG spikes are larger than commonly thought. Synchronous or at least activation overlapping in time of 10-20 cm² of brain cortex is common. Skull may actually serve a role in filtering out all but the most significant interictal discharges. This study helps us better to understand the likely spatial extent of the abnormal brain region that gives rise to EEG spikes correlated with certain types of epilepsy. Epilepsia 2005;46(5).

Self-Reported Seizure Frequency and Time to First Event in the Seizure Monitoring Unit

Lawrence N. Eisenman, Hrayr Attarian, A. James Fessler, Victoria J. Vahle, and Frank Gilliam

Over the past several years, it has become very clear that for patients with seizures that are not controlled by medications, admission to a hospital in order to record their seizures (video/EEG monitoring) is very helpful for determining the best treatment to stop the seizures. However, some patients have infrequent seizures and many people including the treating physician, the insurer and the patient themselves may be concerned that no seizures will be recorded during a brief hospital stay. For this reason, these patients may not get monitoring. We tested the validity of this concern by looking at our patients who were monitored to see if there was any relationship between the seizure frequency they reported in a clinic visit and the time it took to record a seizure during monitoring. We found there was no meaningful relationship and that most patients had a seizure within seven days. We concluded that even patients with low seizure rates have seizures during monitoring so low seizure rates should not prevent patients from getting monitoring. Epilepsia 2005;46(5).

Biting Behaviour, Aggression, and Seizures

Carlo Alberto Tassinari, Laura Tassi, Giovanna Calandra-Buonaura, Michelangelo Stanzani-Maserati, Nicola Fini, Fabio Pizza, Giorgio Lo Russo, and Stefano Meletti

The study report an original description of behaviors rarely observed as ictal (during the seizure) or postictal (after the seizure) phenomena. Few articles have documented aggressive behaviors related to epileptic seizures by video-EEG recording. The authors discuss the significance of seizure-related aggressive displays, with particular reference to the act of biting another person. The main finding of the study is that seizure-associated violence depends upon two main “conditions”: on one hand seizures with fronto-temporal involvement (may-be encompassing the orbito-medial prefrontal cortex and amygdala) had to be present; on the other hand, an appropriate external stimulus had to violate the patient’s personal space. Triggering stimuli were both visual stimuli (the hand of the examiner) located around the patient’s face and tactile ones applied near the mouth. The findings are discussed in the light of the literature concerning epilepsy and aggression, human aggression. Behavioral data suggest that the biting behavior and related aggressive gestures can be considered as the emergence of instinctive behaviors meant to defend the personal space. Epilepsia 2005;46(5).

April 2005
Atypical Language Representation in Patients with Chronic Seizure Disorder and Achievement Deficits using Magnetoencephalography
Joshua I. Breier, Edwardo M. Castillo, Panagiotis G. Simos, Rebecca L. Billingsley-Marshall, Ekaterina Pataraia, Sharin Sarkari, James W. Wheless, and Andrew C. Papanicolaou

The purpose of the study was to see if patients with chronic complex partial seizures and reading problems have an unusual pattern of language representation in the brain. Thirty-one patients with reading deficits and 52 patients with no reading problems participated. All patients had undergone mapping of receptive language areas (the parts responsible for comprehension) of the brain using magnetoencephalography (MEG) as part of a pre-operative seizure surgery evaluation. MEG is a non-invasive procedure, related to EEG, but using magnetic recording, that is able to provide images of areas of the brain involved in language function by detecting the magnetic energy produced by brain cells when they signal to each other. As expected, patients with no reading/spelling difficulty had a normal pattern of brain activation during the language task: more activity in the left (usually the language-related hemisphere in right-handers) as compared to the right hemisphere. Patients with left hemisphere seizure onset and reading/spelling deficits showed an abnormal pattern of activation consisting of increased activation in the right hemisphere. The findings suggest that reading and spelling achievement deficits in patients with complex partial seizures of left hemisphere origin are associated with atypical language organization, possibly secondary to reorganization of language function to right hemisphere areas that are not as efficient as areas in the left hemisphere in supporting reading and spelling functions. Such results provide additional evidence that brain functions are not fixed in place, but can move to other locations when their primary area is impacted by disorders or injuries, including seizures. Epilepsia 2005;46(4).

Somatosensory Processing is Impaired in Temporal Lobe Epilepsy

Arthur C. Grant, Thomas R. Henry, Raquel Fernandez, MaryAnn Hill, and K. Sathian

There is growing evidence that temporal lobe epilepsy (TLE) is a network disease affecting many brain regions, including areas outside of the temporal lobe. In this view, the seizure focus may impact brain activity not only during seizures, but also in between seizures. We tested whether people with intractable TLE were impaired on a touch sensitivity task called “discrimination of grating orientation”. In this task the blindfolded subject must determine the orientation or direction of a grooved surface applied repeatedly to their index fingertip. Fifteen subjects with TLE and 19 neurologically normal controls were tested. TLE subjects were tested while taking their usual anti-seizure drugs (ASDs), and off ASDs during in-patient video-EEG monitoring. We found that TLE subjects performed substantially worse than controls with both hands. There was no difference in performance between hands, or between baseline and off-ASD testing. These results imply that patients with medically-intractable TLE have impaired touch discrimination in both hands that is not due to non-specific effects of ASDs. The results support the hypothesis that a seizure focus in the temporal lobe can affect the function of other brain regions. Further studies will investigate whether surgical removal of the seizure focus can improve performance on this and other perceptual tasks. Epilepsia 2005;46(4).