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Wiley InterScience | |||||||||
  EpilepsiaVolume 47 Issue 2, Pages 228 - 232 Published Online: 24 Feb 2006 © 2010 International League Against Epilepsy Published on behalf of the International League Against Epilepsy (ILAE)
Abstract | Full Text: PDF (Size: 146K) | Related Articles | Citation Tracking  Clinical Science Copyright 2006 International League Against Epilepsy Vigabatrin Retinopathy in an Irish Cohort: Lack of Correlation with Dose Epilepsia 2006;47(2). ABSTRACTPeter Kinirons, Gianpiero L Cavalleri, Deirdre O'Rourke, Colin P. Doherty, Irene Reid, Patricia Logan, Brenda Liggan, and Norman Delanty Vigabatrin (VGB) is a effective medication used to treat epilepsy. However, it causes irreversible constriction of vision as a side effect in about 40% of individuals. It is unclear whether the development of this relates to the amount of the drug taken over time. We conducted an analysis of patients taking long-term VGB treatment to examine whether toxicity is related to the daily dose, duration of therapy, or cumulative dose taken. Information from 93 patients receiving long-term, stable VGB therapy was analyzed. We recorded patient demographics, how much VGB they had taken and for how long, and the results of all visual field assessments. We then compared the amount of visual field constriction with the daily dose, duration of therapy, and cumulative dose of VGB. Our results show that in 53% of patients, visual field constriction developed. Male and female subjects were affected equally. We found no correlation between the amount of visual field constriction and either the maximum dose of VGB taken, the duration of exposure, or the cumulative dose. The shortest exposure time to development of constriction was 1.1 years. All patients with normal fields on initial assessment continued to have normal fields on follow-up. Most patients who had evidence of constriction on initial assessment and continued to take VGB showed no progression on follow-up. One patient had substantial recovery of vision after discontinuation of VGB. In conclusion, development of visual constriction in patients taking long-term, standard doses of VGB does not depend on the daily dose, duration of exposure, or cumulative dose. Our data suggest that field defects may develop within the first few years of therapy and possibly remain stable thereafter. Predictors of Lamotrigine-associated Rash Epilepsia 2006;47(2). ABSTRACTLawrence J. Hirsch, David B. Weintraub, Richard Buchsbaum, Hilary T. Spencer, Tara Straka, Melissa Hager, and Stanley R. Resor Lamotrigine (LTG) is an antiepileptic drug (AED) approved in the Unites States in 1994. It is effective for multiple types of seizures and is well tolerated overall. Rash is one of the known adverse effects. However, which patients are at particularly high or low risk of rash is unclear. Therefore we performed this study to determine the predictors of LTG-associated rash (LTG-rash) to individualize risk assessment in a given patient. We reviewed the charts of all 988 outpatients seen at the Columbia Comprehensive Epilepsy Center between January 1, 2000, and December 31, 2003, who received LTG. Charts were reviewed for documentation of rash developing from any medication, including antiepileptic drugs (AEDs) and non-AEDs, and including remote histories of drug-related rashes. Demographics, medical history, and medication variables were tested as potential predictors of LTG-rash. Fifty-six (5.7%) of 988 patients experienced rash attributed to LTG, and 39 (3.9%) of 988 discontinued LTG because of rash. No patients required hospitalization because of LTG-rash. A history of rash with another AED was the strongest predictor of LTG-rash, with children younger than 13 years also experiencing significantly more LTG-rash. In children with a rash with another AED, 18% experienced LTG-rash, whereas in adults without a rash with another AED, 3% experienced LTG-rash. Based on this retrospective analysis, a history of another AED-related rash is the greatest risk factor for developing rash to LTG; age younger than 13 years also is a risk factor. Severe rash is rare when using the currently recommended titration rate. Ginkgo biloba Use in Nursing Home Elderly with Epilepsy or Seizure Disorder Epilepsia 2006;47(2). ABSTRACTSusan L. Harms, Judith Garrard, Paul Schwinghammer, Lynn E. Eberly, Yanping Chang, and Ilo E. Leppik The purpose of this study was to discuss how ginkgo, commonly used to treat memory loss, may affect seizures and to look at how often ginkgo is prescribed to nursing home (NH) residents, particularly those with epilepsy or seizure disorder (Epi/Sz). Ginkgo trees contain certain compounds that may produce seizures. Conversely, they also contain substances that reduce the likelihood of seizures. The seizure-causing compounds are largely found in Ginkgo seeds rather than in leaves. Although most United States ginkgo products do not contain seeds, no federal standards govern ingredients in herb products. No assurance is possible that contamination of ginkgo products with seeds will not occur. Another feature of ginkgo is that its chemical makeup is affected by growing season and age and gender of the tree. Consequently, the amount and types of medically active substances that are present differs between trees. No guarantee is possible that one ginkgo product will have the same affect in the body as another. Although reports of seizures after ginkgo use are rare, consumers and prescribers should be aware that ginkgo could cause seizures and use ginkgo cautiously. This study found that the level of herb use in NHs is well below that of community elderly (0.41% vs. 29–50%). Among NH residents using herbs, ginkgo was the most commonly prescribed herb for those both with Epi/Sz (62%) and without Epi/Sz (58%). Residents without Epi/Sz were prescribed a wide selection of herbs. Among residents with Epi/Sz, physicians prescribed herbs primarily for dementia or depression. AED Availability and Professional Practices in Delivery Outlets in a City Center in Southern Vietnam Epilepsia 2006;47(2). ABSTRACTTu Luong Mac, Van Tuan Le, Anh Nhi Vu, Pierre-Marie Preux, and Voa Ratsimbazafy In developing countries, a multitude of factors such as nonavailability of antiepileptic drugs (AEDs) contributes to the treatment gap in epilepsy. Eighty percent of the people with active epilepsy do not have access to treatment. Our study in southern Vietnam showed that the availability of AEDs is sufficient. A small quantity of older AEDs is available. The pharmacies that delivered these AEDs are located in specific areas like the market area or the hospital area. However, pharmacists could be absent. These conditions do not allow an adequate treatment for a long period. An effort must be made to sensitize professional health workers to decrease the treatment gap in epilepsy. A Controlled Clinical Trial of Cathodal DC Polarization in Patients with Refractory Epilepsy Epilepsia 2006;47(2). ABSTRACTFelipe Fregni, Sigride Thome-Souza, Michael Nitsche, Steven Freedman, Kette Valente, and Alvaro Pascual-Leone Some patients with epilepsy do not have an adequate seizure control with use of medications. For these patients, new therapeutic approaches have been investigated. In this context, brain stimulation might be a good therapeutic option. Therefore we investigated the effects of a novel technique of noninvasive brain stimulation, brain direct current (DC) polarization, in patients with refractory epilepsy. Nineteen patients with refractory seizures and malformations of cortical development participated in this study. DC polarization is a simple technique that induces a continuous (DC) electric current into the brain. In this technique, electric current flows from cathode to anode electrode, and thus its effects depend on the electrode polarity: cathodal stimulation inhibits brain activity, and anodal stimulation facilitates it. Therefore we placed the cathode electrode over the epileptogenic area (that is, the brain area in which seizures are originated) and the anode electrode over the silent area (that is, the brain area with normal brain activity). We measured epileptic activity before and after the treatment by using an electroencephalogram (EEG) and the frequency of seizures. The results of this study showed that active treatment (DC polarization) compared with sham treatment was associated with a significant decrease in the number of epileptiform discharges (abnormal brain activity in the EEG related to seizure activity) and a trend toward a significant decrease in the frequency of actual seizures. This treatment was not associated with detectable adverse effects. The results of this study encourage future investigations of this new method of brain stimulation for epilepsy treatment. Temporal and Extratemporal BOLD Responses to Temporal Lobe Interictal Spikes Epilepsia 2006;47(2). ABSTRACTEliane Kobayashi, Andrew P. Bagshaw, Christian-George Bénar, Yahya Aghakhani, Frederick Andermann, François Dubeau, and Jean Gotman Simultaneous EEG and functional magnetic resonance imaging (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 by 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 eight bilateral). From a total of 35 fMRI studies, 29 (83%) showed changes: 14 had both activations and deactivations, 12 activations only, and three deactivations only. Six (17%) showed no responses. Nineteen studies had mainly neocortical TL activation: 16 (84%) of 19 concordant with spikes, 12 of 16 with concomitant activation of the contralateral TL, and 16 of 19 with additional extratemporal activation; few showed exclusively mesial TL activation. Seventeen studies showed deactivation, either extratemporal plus temporal (n = 8) or exclusively extratemporal (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 extratemporal regions, suggesting that TL epileptic spikes can affect neuronal activity at a distance through synaptic connections. Single and Multiple Clusters of Magnetoencephalographic Dipoles in Neocortical Epilepsy: Significance in Characterizing the Epileptogenic Zone Epilepsia 2006;47(2). ABSTRACTMakoto Oishi, Shigeki Kameyama, Hiroshi Masuda, Jun Tohyama, Osamu Kanazawa, Mutsuo Sasagawa, and Hiroshi Otsubo Surgeons must locate the epileptogenic zone that generates seizures to eliminate epileptic seizures surgically. 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 relations of MEG dipoles (sources of epileptic discharges) 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; six had multiple clusters. Single MEG clusters coincided with SEEG SOZs in nine patients; a single cluster was within or partially overlapped the SOZ in four patients; multiple-cluster sections overlapped SOZs in five patients; and no overlap with the SOZ occurred in two patients (one with single cluster; one 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 (one of six). Eight of nine patients with a single cluster that coincided to the SOZ had seizure-free outcomes, whereas only three 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. Epileptogenicity of Supratentorial Medullary Venous Malformation Epilepsia 2006;47(2). ABSTRACTTakato Morioka, Kimiaki Hashiguchi, Shinji Nagata, Yasushi Miyagi, Fumiaki Yoshida, Futoshi Mihara, Ayumi Sakata, and Tomio Sasaki Abnormal blood vessels in the brain, called vascular malformations, are common causes of epilepsy. Vascular malformations come in several types. Arteriovenous malformations (made of arteries and veins) and cavernous angiomas (made of capillaries) are known to produce seizures. The role of venous malformations is less clear. The purpose of this study was to evaluate the epileptogenicity of a type of venous malformation called a medullary venous malformations (MVM). Special consideration was given to any associations with intracerebral hemorrhage with or without other vascular malformations, including cavernous angioma (CA). In total, 10 patients with angiographically or histologically verified MVM were examined. The patients were divided into two groups with or without intracerebral hemorrhage, and their clinical, neuroradiologic, and interictal and ictal EEG findings were reviewed retrospectively. Although three of five patients in the nonhemorrhagic group had epilepsy, no concordance was found between the location of the MVM location and the EEG seizure focus. On the contrary, in four of five patients in the hemorrhagic group, epilepsy developed, and concordance between the hemorrhagic MVM location and the EEG focus was noted. One patient with a hemorrhagic MVM and an associated CA in the hippocampus had an electroclinical picture of intractable medial temporal lobe epilepsy on this side. Although a supratentorial MVM itself is not epileptogenic, the development of an intracerebral hemorrhage may cause epilepsy. In particular, an associated CA may be highly epileptogenic. Extended, One-stage Callosal Section for Treatment of Refractory Secondary Generalized Epilepsy in Patients with Lennox–Gastaut and Lennox-like Syndromes Epilepsia 2006;47(2). ABSTRACTArthur Cukiert, Jose Augusto Burattini, Pedro Paulo Mariani, Ródio Brandão Câmara, Lauro Seda, Cristine Mella Baldauf, Meire Argentoni, Carla Baise-Zung, Cássio Roberto Forster, and Valeria Antakli Mello Epilepsy surgery is an accepted treatment modality for patients with refractory epilepsy. Usually these patients are evaluated by a multiprofessional team, and resective, disconnective, and stimulatory procedures are used for seizure control. Although we would always prefer to offer resective procedures, which may ultimately render the patients seizure free, some patients are not candidates for cortical resection, and palliative procedures then might be considered. Callosal section, also known as callosotomy, is the most widely performed disconnective palliative procedure. With callosotomy, the large band of fibers connecting the two halves of the brain is severed. As a result, seizures cannot spread so rapidly through the brain. We analyzed the effect of callosal section on 76 patients with the syndrome called Lennox–Gastaut and Lennox-like secondarily generalized epilepsy. These patients usually have refractory epilepsy, including frequent drop attacks and developmental delay, and their treatment always represents a challenge. We were able to show that extensive callosal section could be safely obtained in a one-stage procedure by means of careful microsurgical techniques and that the clinical outcome regarding seizures was better than that after performing a small callosal section. Patients had an acute disconnection syndrome that lasted for 2 weeks; no other morbidity or mortality was present. Worthwhile improvement (>50%) was noted in 69 of 76 patients; 52 patients had at least a 90% reduction in seizure frequency. Seven patients were seizure free after surgery. The seizure patterns most responsive to surgery were atonic (92%), atypical absence (82%), and tonic–clonic (57%) seizures. Parallel to the seizure-frequency reduction, a consistent increase in attention level was observed postoperatively. Callosal section was found to be a good palliative option for these severely ill patients. It is the only procedure available so far that was capable of disrupting secondary bilateral synchrony, which is the electroencephalographic hallmark of these syndromes. Seizure Recurrence and Risk Factors after Antiepilepsy Drug Withdrawal in Children with Brain Tumors Epilepsia 2006;47(2). ABSTRACTRaja B. Khan and Arzu Onar Brain tumors are the second most common tumor in children, after acute leukemia. In approximately 20% of children with brain tumors, seizures will develop. The majority of these patients will achieve seizure control with appropriate medical therapy. Until now, risk for seizure recurrence was not known after discontinuation of seizure medications in brain tumor patients. We report rate and predictors of seizure recurrence in 62 children with brain tumors, in whom seizure medications were withdrawn. Based on our data, the estimated risk of seizure recurrence is 18% at 2 years and 27% at 5 years. We found that risk of seizure recurrence increased substantially if the child was treated with whole-brain radiation therapy and required more than one brain surgery to treat the tumor. Younger age at tumor diagnosis and initial difficulty in controlling seizures may also increase the risk of seizure recurrence after medication withdrawal. Our data show that the risk of seizure recurrence in childhood brain tumor patients is comparable to that in children with medically controlled seizures without brain tumors. We also show that seizure medications can be successfully discontinued in carefully selected patients with childhood brain tumors and controlled seizures. Epilepsy in Menkes Disease: Analysis of Clinical Stages Epilepsia 2006;47(2). ABSTRACTNadia Bahi-Buisson, Anna Kaminska, Rima Nabbout, Christine Barnerias, Isabelle Desguerre, Pascale De Lonlay, Michele Mayer, Perrine Plouin, Olivier Dulac, and Catherine Chiron Menkes disease (MD) is a rare X-linked recessive disorder with a primary generalized defect in copper transport. It results in a copper deficiency and subsequent impairment of activity of multiple copper-dependent enzymes. Epilepsy is one of the main features of MD. To determine better the spectrum of epilepsy, we retrospectively analyzed the evolution of electroclinical features of 12 patients with confirmed MD based on clinical charts. Epilepsy could be divided into three successive periods. First was an early stage (median age, 3 months) characterized by focal clonic status epilepticus, usually triggered by fever (10 patients). Ictal EEG showed runs of slow spike–waves and slow waves in the posterior regions, and interictal EEG multifocal and polymorphic slow waves (three cases), or mixed slow spike–waves and slow waves (seven cases). Partial seizure control was obtained in nine patients during 5.9 months. The second period or intermediate stage (median age, 10 months) was characterized by intractable infantile spasms (11 patients) in which interictal EEG demonstrated modified hypsarrhythmia (seven cases), diffuse irregular slow waves, and spike–waves (four cases). Six patients died at the median age of 15 months. The third period or late stage in the six remaining patients (median age, 25 months) was characterized by multifocal seizures, tonic spasms, and myoclonus in four patients, whereas two patients became seizure free. Interictal EEG showed multifocal high-amplitude activity, mixed with irregular slow waves in all six cases. These patients died at the median age of 3.6 years. Based on a relatively large series of MD patients with a quite prolonged survival, we individualized three successive periods in the course of epilepsy: early focal status, followed by infantile spasms, and then myoclonic and multifocal epilepsy after age 2 years. Benign Myoclonic Epilepsy in Infants: Electroclinical Features and Long-term Follow-up of 34 Patients Epilepsia 2006;47(2). ABSTRACTStéphane Auvin, Florence Pandit, Julitta De Bellecize, Nicole Badinand, Hervé Isnard, Jacques Motte, Nathalie Villeneuve, Marie-Dominique Lamblin, Louis Vallée, and the Epilepsy Study Group of the French Pediatric Neurology Society Benign myoclonic epilepsy in infants (BMEI) is a rare epileptic syndrome characterized only by generalized myoclonic seizures (MSs) in normal children during the first 2 years. Our aim was to assess the follow-up of this syndrome. BMEI was confirmed by electroencephalogram (EEG) in four neuropediatric units in France between 1981 and 2002. Clinical and EEG findings at diagnosis and during the follow-up were collected. The Vineland scale or Wechsler scale or both were used to perform neuropsychological evaluations. We report on 34 patients. BMEI is clinically characterized by myoclonic seizures involving the upper part of the body, occurring many times a day. The ictal EEG showed a generalized discharge of polyspike, polyspike and wave, or spike and wave. The interictal EEG was usually normal. Reflex MS were frequently observed and could suggest the diagnosis. A family history of febrile seizures (FSs) or epilepsy was noted in six patients. A history of FS was noted in 11 patients. Monotherapy with valproic acid was effective in 23 of 30 treated patients. Four patients had seizures after the initial symptoms. Juvenile myoclonic epilepsy developed in two patients, and cryptogenic partial epilepsy, in another. Neuropsychological outcome was evaluated in 20 patients (10 with Wechsler scales and 17 with Vineland scale). Cognitive functions were normal in 17 patients, whereas developmental delay was observed in three others. Despite a generally favorable neuropsychological outcome, cognitive impairment and developmental delay can be observed more frequently than in the general population. Further prospective studies are needed to understand the existence of factors that contribute to these conditions. Absence of Seizures Despite High Prevalence of Epileptiform EEG Abnormalities in Children with Autism Monitored in a Tertiary Care Center Epilepsia 2006;47(2). ABSTRACTHoward L. Kim, Joseph H. Donnelly, Anne E. Tournay, Teri M. Book, and Pauline Filipek Seizures and EEG abnormalities are more common in children with autism than in normal children, but the relationship is poorly understood. We studied 32 children with autism by using prolonged video-EEG (VEEG) recording; 22 of these children had recurrent seizures. The VEEG evaluations revealed that the majority of these children had epileptiform EEG abnormalities. These types of abnormalities can occur in children with epilepsy, or in those who have a higher risk for having epileptic seizures. However, in our study, these EEG abnormalities occurred in 60% of children who did not have a history of epileptic seizures. Of the children who had their "seizures" recorded on VEEG, none of them was epileptic, even though 73% of these children had epileptiform EEG abnormalities. Most of the recorded "seizures" were staring spells, resembling absence seizures or bland complex partial seizures. The findings of our study demonstrate the peril of making a clinical diagnosis of epilepsy in children with autism. Our study also highlights the important role of video-EEG monitoring in establishing an accurate diagnosis of epilepsy in these children. Thalamic Atrophy in Childhood Absence Epilepsy Epilepsia 2006;47(2). ABSTRACTChow Huat (Patrick) Chan, Regula S. Briellmann, Gaby S. Pell, Ingrid E. Scheffer, David F. Abbott, and Graeme D. Jackson Childhood absence epilepsy (CAE) is a common childhood epilepsy with frequent, but very short absence seizures. Patients with CAE have no abnormalities of their brain structure. Seizures may be caused by a functional disturbance of brain networks, prominently involving the cortex and the thalamus. We used automated voxel-by-voxel statistical assessment to assess for subtle volume differences of gray and white matter of cortex and thalamus. We recruited 13 patients with a clinical and EEG diagnosis of CAE (mean age at examination, 17 ± 8 years), and compared them with a consecutive series of 109 controls (mean age, 29 ± 9 years). Each subject had a high-resolution magnetic resonance scan, which was analyzed with an optimized protocol for voxel-based volume assessment. Compared with controls, CAE patients showed areas of grey-matter decrease in the thalamus as well as less pronounced decrease in other structures. White-matter decrease was found around the thalamus and in the white matter of the forebrain. Grey- and white-matter increase was restricted to small areas. Therefore evidence exists of thalamic volume reduction in CAE patients. Bilateral thalamic atrophy may be a result of either damage from seizures or a reflection of a primary underlying pathology as the cause of absence seizures. Postsurgical Outcome in Pediatric Patients with Epilepsy: A Comparison of Patients with Intellectual Disabilities, Subaverage Intelligence, and Average-Range Intelligence Epilepsia 2006;47(2). ABSTRACTUlrike Gleissner, Hans Clusmann, Robert Sassen, Christian E. Elger, and Christoph Helmstaedter The chances of becoming seizure free after focal epilepsy surgery are often considered to be worse in developmentally delayed patients because intellectual disabilities frequently are associated with bilateral or diffuse morphologic brain damage, thus increasing the risk of multiple epileptic foci. Moreover, the risk of postoperative cognitive deficits could increase because diffuse brain damage reduces the patient's ability to compensate for surgically induced deficits. Recently several studies in adult patients have indicated that the intelligence quotient (IQ) alone is not a good predictor of postoperative cognitive and seizure outcome, but no study specifically evaluated this subject in children and adolescents. In our study, we compared pediatric patients with intellectual disabilities (IQ ≤70), subaverage intelligence (IQ between 71 and 85), or average-range intelligence (IQ >85) who were matched according to several clinical and etiologic criteria to determine the isolated impact of IQ. The results indicated no dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level. Between 67 and 78% were seizure free 1 year after surgery. School placement remained unchanged for the majority of patients. We conclude that IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average-range intelligence, the decision to operate on intellectually disabled patients should depend on the results of the presurgical diagnostics. Diffuse functional cognitive impairment should not hinder further steps, if all other findings are consistent. School Performance of Nigerian Adolescents with Epilepsy Epilepsia 2006;47(2). ABSTRACTAbiodun O. Adewuya, Saheed B.A. Oseni, and John A.O. Okeniyi This study assessed the school performance, over the past academic year, of 73 Nigerian adolescents with epilepsy, compared with their healthy classmates matched for age, gender, socioeconomic status, and the presence of psychopathology. Results indicated that the mean school grades of adolescents with epilepsy are significantly lower than those of their healthy controls in all the subjects. The variables that significantly predict poor school performance of adolescents with epilepsy include psychopathology in the caretaker; adolescents' perceived poor family functioning; adolescents' attitude toward the illness; adolescents' felt stigma; externalizing symptoms in the adolescents, and duration of illness. It is evident that the determinants of poor school performance in Nigerian adolescents with epilepsy are multivariate, with psychosocial factors most important. These should be noted for early identification and screening of those children at greatest risk for academic failure and the need for appropriate educational remediation services. A Modified Atkins Diet Is Effective for the Treatment of Intractable Pediatric Epilepsy Epilepsia 2006;47(2). ABSTRACTEric H. Kossoff, Jane R. McGrogan, Renee M. Bluml, Diana J. Pillas, James E. Rubenstein, and Eileen P. Vining The ketogenic diet has been used since 1921 to treat intractable childhood epilepsy. Over the past 85 years, it has not changed significantly. A modified Atkins diet may similarly induce ketosis without an admission or fasting period and does not restrict protein, fluids, and calories. In a follow-up to our case series from 2003, we report on the first prospective study of a modified Atkins diet. Children ages 3–18 years, with at least three seizures per week, who had been treated with at least two anticonvulsants, were enrolled and received the diet for the 6-month study period. Carbohydrates initially were limited to 10 g/day. All children became ketotic within days. After 6 months, 13 (65%) had >50% improvement, and seven (35%) had >90% improvement. Sixteen (80%) completed the 6-month study; 14 chose to remain on the diet afterward. Side effects were minimal, and weight did not significantly decrease. Children who had their heights and weights remain relatively stable had better seizure control. A modified Atkins diet appears to be an effective and well-tolerated therapy. The Outcome of Children with Intractable Seizures: A 3- to 6-Year Follow-up of 67 Children Who Remained on the Ketogenic Diet Less Than One Year Epilepsia 2006;47(2). ABSTRACTElisabeth B. Marsh, John M. Freeman, Eric H. Kossoff, Eileen P. Vining, James E. Rubenstein, Paula L. Pyzik, and Cheryl Hemingway Children who have epilepsy that have not responded to two appropriately administered medications are termed "difficult-to-control" or "intractable" and are widely believed to have only a 10–30% chance of responding to any additional medication. Our prior study of the effectiveness of the ketogenic diet in 150 children with these seizures documented that after 1 year, more than 25% had a 90% decrease in seizures. Similar seizure control was found 3–6 years later, when most children had discontinued the diet and were off medications. However, in that study, almost half of the children discontinued the diet during the first year, one third within 3 months, and two thirds by 6 months. Discontinuation was usually because of failure of the diet to control their seizures adequately. These children were also assessed by questionnaire 3–6 years later. To our surprise, 22% had become seizure free, and an additional 10% were mostly seizure free (>90% decrease). Half had a greater than 50% reduction in seizures with or without surgery. It was unclear whether this improvement in seizure control was due to the natural history of the conditions causing the seizures or to the use of newer anticonvulsant medications. In either event, the outlook for children with "difficult-to-control" or "intractable" seizures is not as bleak as was once believed. Defining Intractability: Comparisons among Published Definitions Epilepsia 2006;47(2). ABSTRACTAnne T. Berg and Molly M. 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 5 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 a 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. Consideration should be given to whether a single definition will suit all purposes or whether different types of definitions are needed for different purposes. Contralateral Smile and Laughter, but No Mirth, Induced by Electrical Stimulation of the Cingulate Cortex Epilepsia 2006;47(2). ABSTRACTFrancesca 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 a 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 the motor representation of laughter in the mesial frontal cortex. Linking Generalized Spike-and-Wave Discharges and Resting State Brain Activity by Using EEG/fMRI in a Patient with Absence Seizures Epilepsia 2006;47(2). ABSTRACTHelmut 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 (neurons) is disturbed. This can lead to an epileptic seizure when too many neurons fire at the same time. This can be visualized by using an electroencephalogram (EEG, which measures electricity generated by neurons). Synchronous activity can affect most of the brain, which 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. Afterward, recollection for the time during the seizure would be lost. In this study, we showed that spike-and-wave activity—even those lasting not longer than 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, which allows us 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. | 
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