Clinical Research News
Lauren E. Walker, Damir Janigro, Uwe Heinemann, Raili Riikonen, Christophe Bernard and Manisha Patel
Peripheral biomarkers have myriad potential uses for treatment, prediction, prognostication, and pharmacovigilance in epilepsy. To date, no single peripheral biomarker has demonstrated proven effectiveness, although multiple candidates are in development. In this review, we discuss the major areas of focus including inflammation, blood-brain barrier dysfunction, redox alterations, metabolism, hormones and growth factors.
Eissa TL, Tryba AK, Marcuccilli CJ, Ben-Mabrouk F, Smith EH, Lew SM, Goodman RR, McKhann GM Jr, Frim DM,
High gamma (HG; 80-150 Hz) activity has been linked to seizures, but how seizure activity influences HG is not well understood. In a recent study, the authors used tissue obtained from resection of people with intractable epilepsy, microelectrode recordings from in vivo seizures and modeling to see if HG activity could be a (better) indicator of the seizure onset zone (SOZ). Currently, low frequency local field potentials (LFPs) are used as a biomarker for the SOZ. The authors found that HG activity on a network level was correlated with paroxysmal depolarizing shifts (PDSs) that are seen on a neuronal level. Also, greater HG was found in the core as opposed to the penumbra, indicating that looking at HG may be a better way to demarcate the SOZ.
High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (no= 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales.
Michael R. Sperling, Suzanne Barshow, Maromi Nei, and Ali A. Asadi-Pooya
A total of 1,110 patients were evaluated (1,006 surgically and 104 nonsurgically treated) for a total follow-up of 8,126.62 person-years from 1986 to 2013. Brain surgery is associated with a reduction in mortality rate in drug-resistant epilepsy, both when seizures are abolished and when it results in significant palliation of tonic-clonic seizure frequency. These observations provide further rationale for earlier consideration of epilepsy surgery.
Editorial: Refractory epilepsy is a life-threatening disease: Lest we forget
Raoul Sutter, Saskia Semmlack & Peter W. Kaplan
Nonconvulsive status epilepticus has subtle symptoms and can be difficult to treat, meaning it is associated with considerable morbidity and mortality. In this review, Sutter and colleagues discuss the epidemiology, clinical features and diagnosis of nonconvulsive status epilepticus, and discuss current recommendations for treatment.
Epilepsy surgery is the standard of care for focal drug-resistant epilepsy, but it is underutilized. Knowledge gaps and attitudes toward epilepsy surgery are partly responsible, and a new study explores whether the health-care infrastructure in developed countries influences access to and utilization of epilepsy surgery.
Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction
Kuo J, Zhao W, Li CS, Kennedy JD, Seyal M
Sudden unexpected death in epilepsy (SUDEP) is a phenomenon for which the mechanisms are not yet understood. The role of postictal generalized EEG suppression (PGES), postictal immobility and respiratory dysfunction has been suggested, but not confirmed. The authors of a recent paper investigated correlations between postictal immobility, PGES and respiratory dysfunction (measured by SpO2 and end-tidal CO2) and seizure parameters. Correlations of postictal immobility with PGES and respiratory dysfunction were found, but not with seizure characteristics. This study suggests the possible sequence of events that may lead to SUDEP with possible ways of intervening to reduce its incidence.
Nina Dupuis, Niccolo Curatolo, Jean-François Benoist and Stéphane Auvin
Dietary therapies like the ketogenic diet have been shown to be beneficial in epilepsy. In a recent study, scientists hypothesized that efficacy of the ketogenic diet is due to a decrease in inflammation. After being administered a regular diet or the ketogenic diet, rats were injected lipopolysaccharide (LPS) and downstream reactions were measured. Rats on the normal diet showed an increase in body temperature, whereas those on the ketogenic diet did not. Rats on the ketogenic diet also showed a decrease in proinflammatory cytokines in the blood (e.g TNFÎ± and IL-1Î²) and brain in response to LPS.
Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John J. Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V. Thomas, Frank Vajda, and For the EURAP Study Group
Objective: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). Conclusions: The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents.
Comment: Stillbirths and spontaneous abortions in women with epilepsy on AEDs
Jolien S. van Campen, Floor E. Jansen, Milou A. Pet, Willem M. Otte, Manon H. J. Hillegers, Marian Joels, and Kees P. J. Braun
Patients with epilepsy often report that stress can trigger seizures, but many physicians interpret this as recall bias. Van Campen et al. show that stress-sensitivity of seizures, determined either retrospectively or prospectively, correlates with a blunted cortisol response. This may suggest incomplete containment of effects of stress on neurotransmission.
Robert J. Lamberts, Marieke T. Blom, Merel Wassenaar, Abdennasser Bardai, Frans S. Leijten, Gerrit-Jan de Haan, Josemir W. Sander, Roland D. Thijs, and Hanno L. Tan
Objective: Ascertain whether characteristics of ventricular tachycardia/fibrillation (VT/VF) differed between people with epilepsy and those without and which individuals with epilepsy were at highest risk. Results: Cardiovascular disease rather than epilepsy characteristics is the main determinant of VT/VF in people with epilepsy in the community. SCA and SUDEP are partially overlapping disease entities.
Editorial: Sudden death in epilepsy: Where is the “heart” of the problem?
Lara Jehi and Stephan Schuele
A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy
Chiara Luoni, Maria Paola Canevini, Giuseppe Capovilla, Giovambattista De Sarro, Carlo Andrea Galimberti, Giuliana Gatti, Renzo Guerrini, Angela La Neve, Iolanda Mazzucchelli, Eleonora Rosati, Luigi Maria Specchio, Salvatore Striano, Paolo Tinuper, Emilio Perucca and Study of Outcome of PHarmacoresistance In Epilepsy (SOPHIE) collaborators
Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.
Treatment of infants with epilepsy: Common practices around the world
Jo M. Wilmshurst, Richard Burman, William D. Gaillard and J. Helen Cross
Objective: High quality data to guide recommendations for infants with epilepsy are lacking. This study aimed to develop an understanding of common practice and regional variations in the treatment interventions of infants with epilepsy, and also to identify areas for further study and to highlight where common practice occurs without sound evidence.
Significance: More randomized controlled trials in infants with seizures are needed to permit useful recommendations. The survey identified widespread use of levetiracetam in North America, which may be the result of effective marketing or based on good clinical practice. The widespread use of valproate may have safety implications. The lack of access to care in the African region highlighted the need for more sustained resources. Although the survey was not evidence based, the findings could be useful to support additional well-designed studies.
IQ improves after antiepileptic drug withdrawal following pediatric epilepsy surgery
K Boshuisen, MMJ van Schooneveld, CSPM Uiterwaal, Prof JH Cross, S Harrison, T Polster, M Daehn, S Djimjadi, D Yalnizoglu, Prof G Turanli, R Sassen, C Hoppe, S Kuczaty, C Barba, P Kahane, S Schubert-Bast, G Reuner, T Bast, K Strobl, H Mayer, A de Saint-Martin, C Seegmuller, A Laurent, A Arzimanoglou, Prof KPJ. Braun and for the TimeToStopcognitive outcome study group
Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative IQ, and change in IQ (delta IQ) following pediatric epilepsy surgery. Start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome. This article is protected by copyright. All rights reserved.
The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma
Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, Scheck AC
The usefulness of the ketogenic diet has been shown in refractory epilepsy, but its use in brain tumors is still being investigated. This study showed that in mice with glioma, the ketogenic diet along with radiation was effective in shrinking tumor volume. The effect of the ketogenic diet along with radiation on seizure frequency would be interesting to observe.
IQ at 6 years after in utero exposure to antiepileptic drugs: A controlled cohort study
Gus A. Baker PhD, Rebecca L. Bromley PhD, Maria Briggs RGN, Christopher P. Cheyne PhD, Morris J. Cohen EdD, Marta García-Fiñana PhD, Alison Gummery BSc, Rachel Kneen MD, David W. Loring PhD, George Mawer PhD, FRCP, Kimford J. Meador MD, Rebekah Shallcross PhD and Jill Clayton-Smith MD on behalf of the Liverpool and Manchester Neurodevelopment Group
Neurology, January 27, 2015 vol 84 no. 4 382-390; published ahead of print December 24, 2014 1526-632X
Conclusions: Consistent with data from younger cohorts, school-aged children exposed to valproate at maternal doses more than 800 mg daily continue to experience significantly poorer cognitive development than control children or children exposed to lamotrigine and carbamazepine.
Editorial: Fine-tuning risk assessment with antiepileptic drug use in pregnancy
Torbjörn Tomson, MD, PhD and Pavel Klein, MB, BChir
Excerpt: Approximately 15 million women with epilepsy worldwide are of childbearing age, making management of epilepsy in pregnancy a global public health issue. The possibility of harmful effects of exposure to antiepileptic drugs (AEDs) in fetal life is a major concern for women with epilepsy, their families, and their physicians. However, uncontrolled major seizures during pregnancy can also have devastating consequences. A recent survey in the United Kingdom suggested a 10-fold increase in mortality in pregnancy in women with epilepsy compared to women without epilepsy, mostly due to sudden unexpected death, highlighting the importance of effective seizure control during pregnancy. Thus, consideration should be given to potential adverse effects of both treatment and seizures on the fetus as well as the mother. The challenge is to select effective treatment while minimizing risk to both the fetus and the mother.
No evidence for human papillomavirus infection in focal cortical dysplasia IIb
Roland Coras MD, Klaus Korn MD, Christian G. Bien MD, Thilo Kalbhenn MD, Karl RÃ¶ssler MD, Katja Kobow PhD, Johannes Gied MD, Bernhard Fleckenstein MD, PhD, and Ingmar Blümcke MD
The aetiology of Focal Cortical Dysplasia Type IIb (FCDIIb) remains enigmatic in patients suffering from drug-resistant epilepsy, and an aberrant activation of the mammalian target of rapamycin complex 1 signalling pathway (mTORC1) was detectedin this developmental brain malformation. Recently, the human papillomavirus (HPV) oncoprotein E6 has been identified as a potent activator of mTORC1, and HPV16 E6 described to persist in balloon cells obtained from surgical FCDIIb specimens. In this study, the authors tried to confirm two previous reports of HPV16 E6 infection using an independent series of 14 surgical specimens with histopathologically confirmed FCDIIb.
Complete remission of childhood-onset epilepsy: stability and prediction over two decades
Anne T. Berg, Karen Rychlik, Susan R. Levy, and Francine M. Testa
The ultimate seizure outcome of childhood epilepsy is complete resolution of all seizures without further treatment. How often this happens and how well it can be predicted early in the course of epilepsy could be valuable in helping families understand the nature of childhood epilepsy and what to expect over time. In the Connecticut study of epilepsy, a prospective cohort of 613 children with newly-diagnosed epilepsy (onset age 0-15 years), complete remission, ≥5 years both seizure-free and medication-free, was examined as a proxy of complete seizure resolution.
Berg et al. report that complete remission of paediatric epilepsy occurs in about 60% of patients over the course of 20 years. This outcome can be predicted with fair accuracy based on initial clinical factors, and good accuracy based on early seizure outcomes over the first 2-5 years.
Epilepsy: Pregnancy in women with epilepsy — risks and management
Kimford J. Meador
The risks of seizures and antiepileptic drug (AED) teratogenicity must be balanced when treating pregnant women with epilepsy. Two recent articles address these risks for newer AEDs. Lamotrigine and levetiracetam carried low risks of malformations, and topiramate exhibited a dose-dependent risk. Levetiracetam controlled seizures more effectively than lamotrigine and topiramate.
Prolonged Epileptic Seizures: Identification and Rescue Treatment Strategies
Alexis Arzimanoglou, Thomas Bast, Jaume Campistol, Richard Chin, Aristea Galanopoulou, Lieven Lagae
The majority of convulsive generalized tonic-clonic seizures terminate prior to two minutes with a small percentage prolonged up to five and occasionally ten minutes. Which are the factors leading to an occasional seizure prolongation? Which factors involved to seizure termination fail, consequently allowing some of the seizures to continue and develop into status epilepticus? What are the mechanisms involved? How can children at risk for prolonged seizures can be identified and treated? Can we agree upon an operational definition of prolonged seizures to determine optimal timing of treatment to prevent established status epilepticus?
Understanding of the mechanisms underlying the predisposition for prolonged seizures may lead to improved management pathways. The contributions published in this supplement of Epileptic Disorders are the final product of constructive debates held during an international experts workshop devoted to the topic of prolonged seizures, particularly in children.
The international incidence and prevalence of neurologic conditions: How common are they?
Tamara Pringsheim, MD, MSc, Kirsten Fiest, PhD and Nathalie Jette, MD, MSc
In an effort to better understand the global burden of neurologic conditions, the Public Health Agency of Canada launched the National Population Health Study of Neurological Conditions (NPHSNC) in 2009. One of the many aims of the NPHSNC was to examine the epidemiology, including the incidence and prevalence, of 15 neurologic conditions: Alzheimer disease (AD) and related dementia, amyotrophic lateral sclerosis (ALS), brain tumors, cerebral palsy, dystonia, epilepsy, Huntington disease (HD), hydrocephalus, multiple sclerosis, muscular dystrophy, Parkinson disease (PD), spina bifida, spinal cord injury (SCI), Tourette syndrome, and traumatic brain injury (TBI). In addition to performing systematic reviews on the worldwide incidence and prevalence of these neurologic conditions, we examined issues arising as a result of heterogeneity in the conduct of international epidemiologic studies in neurology.
WONOEP appraisal: Optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis
Laura Mantoan Ritter, Peyman Golshani, Koji Takahashi, Suzie Dufour, Taufik Valiante and Merab Kokaia
Optogenetics is a novel technology that combines optics and genetics by optical control of microbial opsins, targeted to living cell membranes. The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization. This review outlines the most recent advances achieved with optogenetic techniques in the field of epilepsy by summarizing the presentations contributed to the 13th ILAE WONOEP meeting held in the Laurentian Mountains, Quebec, in June 2013.
Several studies now show great heterogeneity in mutations discovered by whole exome sequencing in epileptic encephalopathies
De novo KCNB1 mutations in epileptic encephalopathy
Whole-exome sequencing broadens the phenotypic spectrum of rare pediatricepilepsy: a retrospective study
De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause EpilepticEncephalopathies
Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life
Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy
Nicola Vanni PhD, Floriana Fruscione PhD, Edoardo Ferlazzo MD, Pasquale Striano MD, PhD, Angela Robbiano PhD, Monica Traverso PhD, Thomas Sander MD, Antonio Falace PhD, Elisabetta Gazzerro MD, Placido Bramanti MD, Jacek Bielawski PhD, Anna Fassio PhD, Carlo Minetti MD, Pierre Genton MD, and Federico Zara PhD
Objective: Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders.
Early predictors of refractory status epilepticus: an international two-center study
R. Sutter, P. W. Kaplan, S. Marsch, E. M. Hammel, S. RÃ¼egg, and W. C. Ziai.
Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE) – an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults.
This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.
The wide phenotypic spectrum of patients with DEPDC5 mutations encompasses many electroclinical epilepsy syndroms and levels of severity.
Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations (pages 782–787)
DEPDC5 mutations in genetic focal epilepsies of childhood (pages 788–792)
DEPDC5 does it all: Shared genetics for diverse epilepsy syndromes (pages 631–633)
Nature Reviews Neurology: Special Focus on Epilepsy
Treatment-resistant epilepsy remains a major burden at both global and individual levels. About 1% of individuals have epilepsy and, in almost one-third of patients, antiseizure medications do not provide sufficient seizure control, which can result in dramatically impaired quality of life and increased mortality.
Nature Reviews Neurology special Focus on Epilepsy highlights the important challenges and progress in epilepsy research and clinical practice. This focus issue brings together an ensemble of cutting-edge investigators from leading research institutes around the world.
The topics in this issue include global challenges in paediatric epilepsy, the genetic background of the epilepsies and its implications for genetic diagnosis and personalized medicine, prospects for gene therapy in epilepsy, brain stimulation in refractory epilepsy, and mechanisms of sudden unexpected death in epilepsy. (doi:10.1038/nrneurol.2014)
Rolandic epilepsy has little effect on adult life 30 years later
Carol S. Camfield, MD and Peter R. Camfield, MD
Objective: To establish the adult social outcome for childhood-onset rolandic epilepsy.
Conclusions: The adult social outcome for children with rolandic epilepsy is remarkably better than for those with other major epilepsies and normal intelligence
Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study
Darrell V. Lewis MD, Shlomo Shinnar MD, PhD, Dale C. Hesdorffer PhD, Emilia Bagiella PhD, Jacqueline A. Bello MD, Stephen Chan MD, Yuan Xu BS, James MacFall PhD, William A. Gomes MD, PhD, Solomon L. Moshé MD, Gary W. Mathern MD, John M. Pellock MD, Douglas R. Nordli Jr MD, L. Matthew Frank MD, James Provenzale MD, Ruth C. Shinnar RN, MSN, Leon G. Epstein MD, David Masur PhD, Claire Litherland MS, Shumei Sun PhD, and the FEBSTAT Study Team
Objective: Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute hippocampal injury that evolves to HS.
Results: Hippocampal T2 hyperintensity, maximum in Sommer's sector, occurred acutely after FSE in 22 of 226 children in association with increased volume. Follow-up MRI obtained on 14 of the 22 with acute T2 hyperintensity showed HS in 10 and reduced hippocampal volume in 12. In contrast, follow-up of 116 children without acute hyperintensity showed abnormal T2 signal in only 1 (following another episode of FSE). Furthermore, compared to controls with simple febrile seizures, FSE subjects with normal acute MRI had abnormally low right to left hippocampal volume ratios, smaller hippocampi initially, and reduced hippocampal growth.
Editorial: Can febrile status cause hippocampal sclerosis?
Familial risk of epilepsy: a population-based study
Anna L. Peljto, Christie Barker-Cummings, Vincent M. Vasoli, Cynthia L. Leibson, W. Allen Hauser, Jeffrey R. Buchhalter, and Ruth Ottman
Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study.
We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935–94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives’ medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75–5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted ‘prenatal/developmental cause’ (standardized incidence ratio 4.3). …
Anthony K. Ngugi, PhD,
Christian Bottomley, PhD,
Gregory Fegan, PhD,
Eddie Chengo, MSc,
Rachael Odhiambo, BSc,
Evasius Bauni, PhD,
Brian Neville, FRCP,
Immo Kleinschmidt, PhD,
Josemir W. Sander, FRCP and
Charles R. Newton, MD
Objective: We estimated premature mortality and identified causes of death and associated factors in people with active convulsive epilepsy (ACE) in rural Kenya.
Conclusion: Mortality in people with ACE was more than 6-fold greater than expected. This may be reduced by improving treatment adherence and prompt management of prolonged seizures and supporting those with cognitive impairment.
Diagnostic test utilization in evaluation for resective epilepsy surgery in children
Prasanna Jayakar, William D. Gaillard, Manjari Tripathi, Mark H. Libenson, Gary W. Mathern and J. Helen Cross, The Task Force for Paediatric Epilepsy Surgery, Commission for Paediatrics, and the Diagnostic Commission of the International League Against Epilepsy
Epilepsy surgery is highly successful in achieving seizure freedom in carefully selected children with drug-resistant focal epilepsy. Advances in technology have aided presurgical evaluation and increased the number of possible candidates. Many of the tests employed are resource intense, and in specific cases they may be unhelpful or have adverse effects. Some standardization of the evaluation process is thus considered timely. Given the lack of class 1 or 2 evidence defining the relative utility of each test in specific clinicopathologic cohorts, a set of expert recommendations was attempted using consensus among members of the Pediatric Epilepsy Surgery Task Force of the International League Against Epilepsy (ILAE) Commissions of Pediatrics and Diagnostics These recommendations aim to limit fringe over or underutilization of use while retaining substantial flexibility in the use of various tests, in keeping with most standard practices at established pediatric epilepsy centers.
Early Treatment with AED Reduces Duration of Febrile Seizures
Commentaries by Editor-in-Chief Astrid Nehlig on two articles:
Commentaries by Editor-in-Chief Astrid Nehlig on two articles:
David Masur, PhD,
Shlomo Shinnar, MD, PhD,
Avital Cnaan, PhD,
Ruth C. Shinnar, RN, MSN,
Peggy Clark, RN, MSN, CNP,
Jichuan Wang, PhD,
Erica F. Weiss, MS,
Deborah G. Hirtz, MD,
Tracy A. Glauser, MD;
For the Childhood Absence Epilepsy Study Group
Neurology October 29, 2013. vol. 81 no. 18, 1572-1580. Published online before print October 2, 2013
Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine short-term differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine.
Conclusions: Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted.
Classification of evidence: This study provides Class I evidence that valproic acid is associated with more significant attentional dysfunction than ethosuximide or lamotrigine in children with newly diagnosed CAE.
Simon D. Shorvon and David M. G. Goodridge
Brain (2013) 136 (11): 3497-3510. doi: 10.1093/brain/awt223. First published online: September 24, 2013
Longitudinal cohort studies of prognosis in epilepsy have been carried out since the late 1970s and these have transformed our understanding of prognosis in epilepsy. This paper reviews the contribution of such studies and focuses particularly on the National General Practice Study of Epilepsy, a prospective population-based cohort study of 1195 patients that was initiated in 1983. The National General Practice Study of Epilepsy and other studies have shown that: (i) epilepsy has an often good prognosis with 65–85% of cases eventually entering long-term remission, and an even higher proportion of cases entering a short-term remission; (ii) the likelihood of long-term remission of seizures is much better in newly diagnosed cases than in patients with chronic epilepsy; (iii) the early response to treatment is a good guide to longer term prognosis (although not inevitably so, as in a minority of cases seizure remission can develop after prolonged activity); (iv) the longer is the remission (and follow-up), the less likely is subsequent recurrence; (v) the longer an epilepsy is active, the poorer is the longer term outlook; (vi) that delaying treatment, even for many years, does not worsen long-term prognosis; (vii) the ‘continuous’ and ‘burst’ patterns are more common than the ‘intermittent’ seizure pattern; (viii) epilepsy has a mortality that is highest in the early years after diagnosis, and in the early years is largely due to the underlying cause, however, higher mortality rates than expected are observed throughout the course of an epilepsy; (ix) the prognosis of febrile seizures is generally good, with ∼6–7% developing later epilepsy; and (x) clinical factors associated with outcome have been well studied, and those consistently found to predict a worse outcome include: the presence of neurodeficit, high frequency of seizures before therapy (seizure density), poor response to initial therapy, some epilepsy syndromes.
Felix Rosenow, Mario A. Alonso-Vanegas, Christoph Baumgartner, Ingmar Bl&uumcke, Maria Carreño, Elke R. Gizewski, Hajo M. Hamer, Susanne Knake, Philippe Kahane, Hans O. Lüders, Gary W. Mathern, Katja Menzler, Jonathan Miller, Taisuke Otsuki, Cigdem Özkara, Asla Pitkänen, Steven N. Roper, Americo C. Sakamoto, Ulrich Sure, Matthew C. Walker and Bernhard J. Steinhoff, The Surgical Task Force, Commission on Therapeutic Strategies of the ILAE
Epilepsia. Article first published online: 17 OCT 2013 | DOI: 10.1111/epi.12402
Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4 – 0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.
Author: Suzanne Corkin
In 1953, 27-year-old Henry Gustave Molaison underwent an experimental “psychosurgical” procedure – a targeted lobotomy – in an effort to alleviate his debilitating epilepsy. The outcome was unexpected — when Henry awoke, he could no longer form new memories, and for the rest of his life would be trapped in the moment. But Henry's tragedy would prove a gift to humanity. As renowned neuroscientist Suzanne Corkin explains in Permanent Present Tense, she and her colleagues brought to light the sharp contrast between Henry's crippling memory impairment and his preserved intellect. This new insight that the capacity for remembering is housed in a specific brain area revolutionized the science of memory. The case of Henry — known only by his initials H. M. until his death in 2008 — stands as one of the most consequential and widely referenced in the spiraling field of neuroscience.
W. Curt LaFrance Jr., Gus A. Baker, Rod Duncan, Laura H. Goldstein, Markus Reuber
Volume 54, issue 9, September 2013. Article first published online: 20 September 2013
An international consensus group of clinician-researchers in epilepsy, neurology, neuropsychology, and neuropsychiatry collaborated with the aim of developing clear guidance on standards for the diagnosis of psychogenic nonepileptic seizures (PNES). Because the gold standard of video electroencephalography (vEEG) is not available worldwide, or for every patient, the group delineated a staged approach to PNES diagnosis. ...The aim and hope of this report is to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures.
Dr Seena Fazel, Achim Wolf MSc, Prof Niklas LÃ¥ngstrÃ¶m PhD, Prof Charles R Newton MD, Prof Paul Lichtenstein, PhD
The Lancet, Early Online Publication, 22 July 2013 doi:10.1016/S0140-6736(13)60899-5
People with epilepsy are 11 times more likely to die prematurely than the general population, and the risk appears to be much higher for individuals with common co-existing psychiatric illnesses, especially depression and alcohol and drug use disorders, new research published in The Lancet suggests.
Sahoo SS, Zhang G-Q, Lhatoo SD
Volume 54, issue 8, pages 1335-1341, August 2013. Article first published online: 3 MAY 2013
See also Commentaries (in Gray Matters) from P. Bergin and J. Buchhalter (pp.1507-1511)
This review by Sahoo and colleagues is most interesting and adds significantly to the current debate about "classification" in epilepsy. Ontology, as defined in this article in rather obtuse jargon, is "the formal representation of knowledge in a given domain that allows both human users and machines to consistently and accurately interpret terms." The authors make the case for a new approach to the data underpinning classification.
Ingmar Blümcke, Maria Thom, Eleonora Aronica, Dawna D. Armstrong, Fabrice Bartolomei, Andrea Bernasconi, Neda Bernasconi, Christian G. Bien, Fernando Cendes, Roland Coras, J. Helen Cross, Thomas S. Jacques, Philippe Kahane, Gary W. Mathern, Haijme Miyata, Solomon L. Moshé, Buge Oz, Çigdem Özkara, Emilio Perucca, Sanjay Sisodiya, Samuel Wiebe, and Roberto Spreafico
Epilepsia, Volume 54, Issue 7, July 2013. Article first published online: 20 MAY 2013
Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug-resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory.
Dina Battino, TorbjÃ¶rn Tomson, Erminio Bonizzoni, John Craig, Dick Lindhout, Anne Sabers, Emilio Perucca and Frank Vajda, EURAP Study Group
Epilepsia Article first published online: 12 JUL 2013 | DOI: 10.1111/epi.12302
Although the majority of women remain seizure-free throughout pregnancy, our data suggest that a more proactive approach to adjusting the dose of all AEDs in pregnancy should be considered, in particular for those pregnancies with seizures occurring in the first trimester and those exposed to lamotrigine, to reduce the risk of deterioration in seizure control.
J Sebastian, R Adepu, BS Keshava, S Harsha
Neurology Asia, June 2013; 18(2) : 159 – 165
A prospective observational study was conducted to assess the antiepileptic drugs (AEDs) usage, drug related problems and medication adherence behavior among enrolled epileptic patients in a South Indian tertiary care teaching hospital. The prescriptions from 439 patients containing AEDs were analyzed for number of AEDs prescribed and for potential drug related problems. Morisky's Medication adherence scale was applied to study the medication adherence behaviour of enrolled patients and those patients were also monitored to identify the adverse drugs reactions...
This month's Editors' Choice selections focus on structural damage in the epileptic brain.
Kitti Kaiboriboon, MD, Paul M. Bakaki, MD, Samden D. Lhatoo, MD and Siran Koroukian, PhD
Neurology, May 21, 2013. Vol. 80 no. 21 1942-1949. Published online before print April 24, 2013.
Objectives: To determine the incidence and prevalence of treated epilepsy in an adult Medicaid population.
Results: There were 9,056 prevalent cases of treated epilepsy in 1992-2006 and 1,608 incident cases in 1997-2006. The prevalence was 13.2/1,000 (95% confidence interval, 13.0 – 13.5/1,000). The incidence was 362/100,000 person-years (95% confidence interval, 344-379/100,000 person-years). The incidence and prevalence were significantly higher in men, in older people, in blacks, and in people with preexisting disability and/or comorbid conditions. The most common preexisting conditions in epilepsy subjects were depression, developmental disorders, and stroke, whereas people with brain tumor, traumatic brain injury, and stroke had the higher risk of developing epilepsy.
Conclusions: The Medicaid population has a high incidence and prevalence of epilepsy, in an order of magnitude greater than that reported in the US general population. This indigent population carries a disproportionate amount of the epilepsy burden and deserves more attention for its health care needs and support services.
E. Hilger, F. Zimprich, R. Jung, E. Pataraia, C. Baumgartner, S. Bonelli
European Journal of Neurology, Article first published online: 16 MAR 2013
Postictal psychosis (PP) is a frequent and potentially dangerous complication within the course of TLE. Bilateral or widespread functional central nervous system disturbances rather than distinct structural brain alterations or certain predisposing aetiologies of epilepsy appear to be a risk factor for the development of PP. Ictal fear may be a predictive clinical variable of PP in TL
Michele Simonato, Jean Bennett, Nicholas M. Boulis, Maria G. Castro, David J. Fink, William F. Goins, Steven J. Gray, Pedro R. Lowenstein, Luk H. Vandenberghe, Thomas J. Wilson, John H. Wolfe & Joseph C. Glorioso
Nature Reviews Neurology 9, 277-291 (May 2013) | doi:10.1038/nrneurol.2013.56
Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes.
Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy.
The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. These two articles explore mutations of DEPDC5.
Ishida S, Picard F, Rudolf G, Noé E, Achaz G, Thomas P, Genton P, Mundwiller E, Wolff M, Marescaux C, Miles R, Baulac M, Hirsch E, Leguern E, Baulac S.
Nature Genetics. 2013 Mar 31. doi: 10.1038/ng.2601. [Epub ahead of print]
Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
Dibbens LM, de Vries B, Donatello S, Heron SE, Hodgson BL, Chintawar S, Crompton DE, Hughes JN, Bellows ST, Klein KM, Callenbach PM, Corbett MA, Gardner AE, Kivity S, Iona X, Regan BM, Weller CM, Crimmins D, O'Brien TJ, Guerrero-López R, Mulley JC, Dubeau F, Licchetta L, Bisulli F, Cossette P, Thomas PQ, Gecz J, Serratosa J, Brouwer OF, Andermann F, Andermann E, van den Maagdenberg AM, Pandolfo M, Berkovic SF, Scheffer IE.
Nature Genetics. 2013 Mar 31. doi: 10.1038/ng.2599. [Epub ahead of print]
Using exome sequencing, we detected DEPDC5 mutations in two affected families. We subsequently identified mutations in five of six additional published large families with FFEVF. Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families (10/82). This high frequency establishes DEPDC5 mutations as a common cause of familial focal epilepsies. Shared homology with G protein signaling molecules and localization in human neurons suggest a role of DEPDC5 in neuronal signal transduction.
Sándor Beniczky, Harald Aurlien, Jan C. Brøgger, Anders Fuglsang-Frederiksen, António Martins-da-Silva, Eugen Trinka, Gerhard Visser, Guido Rubboli, Helle Hjalgrim, Hermann Stefan, Ingmar Rosén, Jana Zarubova, Judith Dobesberger, Jørgen Alving, Kjeld V. Andersen, Martin Fabricius, Mary D. Atkins, Miri Neufeld, Perrine Plouin, Petr Marusic, Ronit Pressler, Ruta Mameniskiene, Rüdiger Hopfengärtner, Walter van Emde Boas, Peter Wolf
Epilepsia, Vol. 54, Issue 3, March 2013; first published online 18 March 2013
The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, “episodes” (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists.
Author/Editor: Suzette LaRoche, MD
Publisher: Demos Medical Publishing
Length: 338 pp Cost: $60 US
The emerging technology of continuous EEG monitoring in intensive care units gives practitioners the ability to identify malignant EEG patterns quickly and provide more effective care. Handbook of ICU EEG Monitoring encompasses the wide range of technical and clinical issues involved in the successful monitoring of critically ill patients to detect significant changes in cerebral function and prevent serious neuronal injury. Divided into five sections, the handbook covers EEG acquisition and other technical considerations, clinical indications, EEG interpretation, appropriate treatment, and practical and administrative concerns.
The book addresses the often overlooked subjects of billing, coding, and generating reports to facilitate communication across the entire ICU team. Written by leading experts in this rapidly evolving field, the chapters are brief and formatted for maximum utility with bulleted text, pearls, and take-home points to reinforce key information. High-quality examples of routine and quantitative EEG findings help users hone their interpretive understanding and build skills for detecting clinically significant EEG changes in the ICU.
Tracy Glauser, Elinor Ben-Menachem, Blaise Bourgeois, Avital Cnaan, Carlos Guerreiro, Reetta Kälviäinen, Richard Mattson, Jacqueline A. French, Emilio Perucca, Torbjorn Tomson, for the ILAE subcommission of AED Guidelines
Epilepsia, Vol. 54, Issue 1, January 2013; first published online 25 January 2013
The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update.
The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup.
Data on longitudinal seizure outcome after hemispherectomy in children are limited. This study explores the posthemispherectomy longitudinal seizure outcome and prognostic predictors after hemispherectomy in 170 children.
Mutations in the PRRT2 gene have been associated with different paroxysmal neurologic disorders, including benig n familial infantile convulsions, paroxysmal kinesigenic dyskinesia, hemiplegic migraine and, rarely, ataxia. (From the Highlights by R. Gross).
See the November 20 issue of Neurology for a series of studies.
Neurology October 9, 2012 79:1548-1555; published ahead of print September 26, 2012
Ilo E Leppik, Thaddeus S Walczak, Angela K Birnbaum
The Lancet, Volume 380, Issue 9848, Pages 1128 - 1130, 29 September 2012. doi:10.1016/S0140-6736(12)61517-7
Because elderly people are the most rapidly growing segment of the population and because incidence and prevalence of epilepsy are higher in this age group than in younger people, a marked increase in epilepsy in the elderly is expected over the coming decades. In a US Medicare beneficiary sample, the annual mean incidence and prevalence rates of epilepsy in elderly people were 2.4 per 1000 people and 10.8 per 1000 people, respectively.
Memory problems are extremely common among those suffering from epilepsy, yet until now there has been no book specifically on this topic making it a much-needed resource. Epilepsy and Memory comprehensively reviews all aspects of the relationship between this common and potentially serious neurological disorder and memory, one of the core functions of the human mind. The authors review the history of the subject, the clinical features of memory disorder in epilepsy, neuropsychological, neuroradiological, neuropathological and electrophysiological findings, the roles of anticonvulsant side effects and psychiatric disorder, and the scope for memory support and rehabilitation.
Marco Mula, Andres M. Kanner, Bettina Schmitz and Steven Schachter
Epilepsia. Article first published online: 20 SEP 2012 | DOI: 10.1111/j.1528-1167.2012.03688.x
Although some (but not all) AEDs can be associated with treatment-emergent psychiatric problems that can lead to suicidal ideation and behavior, the actual suicidal risk is yet to be established, but it seems to be very low. The risk of stopping AEDs or refusing to start AEDs is significantly worse and can actually result in serious harm including death to the patient. Suicidality in epilepsy is multifactorial, and different variables are operant. Clinicians should investigate the existence of such risk factors and adopt appropriate screening instruments. If necessary, patients should be referred for a psychiatric evaluation, but AED treatment should not be withheld, even in patients with positive suicidal risks. When starting an AED or switching from one to other AEDs, patients should be advised to report to their treating physician any change in mood and suicidal ideation. Data on treatment-emergent psychiatric adverse events need to be collected, in addition to general safety information, during controlled studies in order to have meaningful information for patients and their relatives when a new drug is marketed.
Ryuta Koyama, Kentaro Tao, Takuya Sasaki, Junya Ichikawa, Daisuke Miyamoto, Rieko Muramatsu, Norio Matsuki, and Yuji Ikegaya
Nature Medicine. 18, 1271-1278 (2012). doi:10.1038/nm.2850. Published online 15 July 2012
Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. This work identifies a previously unknown pathogenic role of excitatory GABAA-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures.
Ramsekhar Menon, MD, Chaturbhuj Rathore, MD, Sankara P. Sarma, PhD and Kurupath Radhakrishnan, M
Neurology. August 21, 2012 vol. 79 no. 8 770-776. Published online before print July 25, 2012, doi: 10.1212/WNL.0b013e3182644f7d
Following resective extratemporal epilepsy surgery, AED can be successfully discontinued in only in a minority of patients. One-third of patients who recur fail to regain seizure control upon AED reintroduction. Longer duration of epilepsy prior to surgery, abnormal postoperative EEG, early postoperative seizures, and focal gliosis or dysplasia as substrate predispose to seizure recurrence.
Colin B. Josephson, MD, MSc, Jo J. Bhattacharya, MSc, FRCR, Carl E. Counsell, MD, MRCP, Vakis Papanastassiou, MD, FRCS(SN), Vaughn Ritchie, MB BS, Richard Roberts, MD, FRCP, Robin Sellar, MBBS, DMRD, FRCP, FRCS, FRCR, Charles P. Warlow, MD, FRCP and Rustam Al-Shahi Salman, MA, PhD, FRCP(Edin) On behalf of the Scottish Audit of Intracranial Vascular Malformations (SAIVMs) steering committee and collaborators
Neurology, August 7, 2012 vol. 79 no. 6 500-507. doi: 10.1212/WNL.0b013e3182635696. Published online before print July 3, 2012.
Objective: To compare the risk of epileptic seizures in adults during conservative management or following invasive treatment for a brain arteriovenous malformation (AVM).
Conclusions: In this observational study, there was no difference in the 5-year risk of seizures with AVM treatment or conservative management, irrespective of whether the AVM had presented with hemorrhage or epileptic seizures.
Simon Shorvon and Monica Ferlisi
Brain, (2012) 135 (8): 2314-2328. doi: 10.1093/brain/aws091; First published online: May 9, 2012
Here we report a review of the outcome of therapies in refractory and super-refractory status epilepticus. Patients (n=1168) are reported who had therapy with: thiopental, pentobarbital, midazolam, propofol, ketamine, inhalational anaesthetics (isoflurane, desflurane), antiepileptic drugs (topiramate, lacosamide, pregabalin, levetiracetam), hypothermia, magnesium, pyridoxine, immunotherapy, ketogenic diet, emergency neurosurgery, electroconvulsive therapy, cerebrospinal fluid drainage, vagal nerve stimulation and deep brain stimulation. The outcome parameters reported include control of status epilepticus, relapse on withdrawal, breakthrough seizures and mortality.
M.J. Brodie, MD, S.J.E. Barry, PhD, G.A. Bamagous, PhD, J.D. Norrie, MSc and P. Kwan, MD, PhD
Neurology, May 15, 2012 vol. 78 no. 20 1548-1554. doi: 10.1212/WNL.0b013e3182563b19. Published online before print May 9, 2012.
Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.
Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.
S. HernÃ¡ndez-DÃaz, MD, DrPH, C.R. Smith, MPH, A. Shen, MPH, R. Mittendorf, MD, DrPH, W.A. Hauser, MD, M. Yerby, MD, and L.B. Holmes, MD
Neurology, May 22, 2012 vol. 78 no. 21 1692-1699. doi: 10.1212/WNL.0b013e3182574f39. Published online before print May 2, 2012.
Objective: To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy.
Conclusion: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population.
Quek AM, Britton JW, McKeon A, So E, Lennon VA, Shin C, Klein CJ, Watson RE Jr, Kotsenas AL, Lagerlund TD, Cascino GD, Worrell GA, Wirrell EC, Nickels KC, Aksamit AJ, Noe KH, Pittock SJ.
Archives of Neurology, 2012 Mar 26. [Epub ahead of print]
Objective: To describe clinical characteristics and immunotherapy responses in patients with autoimmune epilepsy.
Conclusion: When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome.
Yoong M, Madari R, Martinos M, Clark C, Chong K, Neville B, Chin R, Scott R.
Developmental Medicine and Child Neurology 2012 Apr;54(4):328-33. doi: 10.1111/j.1469-8749.2011.04215.x. Epub 2012 Jan 23
The aim of this study was to determine the yield of magnetic resonance imaging (MRI) after an episode of childhood convulsive status epilepticus (CSE) and to identify the clinical predictors of an abnormal brain scan.
Interpretation: Brain MRI should be considered for all children with a history of CSE who have not previously undergone MRI, especially those with non-prolonged febrile seizure CSE, those with persisting neurological abnormalities 2 to 13 weeks after CSE, and those with continuous CSE.
Engel J Jr, McDermott MP, Wiebe S, Langfitt JT, Stern JM, Dewar S, Sperling MR, Gardiner I, Erba G, Fried I, Jacobs M, Vinters HV, Mintzer S, Kieburtz K; Early Randomized Surgical Epilepsy Trial (ERSET) Study Group.
Journal of the American Medical Association 2012; March 7; 307(9):922-30
Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death.
The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation.
Robert Silbergleit, M.D., Valerie Durkalski, Ph.D., Daniel Lowenstein, M.D., Robin Conwit, M.D., Arthur Pancioli, M.D., Yuko Palesch, Ph.D., and William Barsan, M.D. for the NETT Investigators
New England Journal of Medicine 2012; 366:591-600 | February 16, 2012
Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route. This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics.
Galanopoulou AS, Buckmaster PS, Staley KJ, MoshÃ© SL, Perucca E, Engel J Jr, LÃ¶scher W, Noebels JL, PitkÃ¤nen A, Stables J, White HS, O'Brien TJ, Simonato For The American Epilepsy Society Basic Science Committee And The International League Against Epilepsy Working Group On Recommendations For Preclinical Epilepsy Drug Discovery M.
Epilepsia. 2012 Jan 31. doi: 10.1111/j.1528-1167.2011.03391.x. [Epub ahead of print]
Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic antiseizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (2) disease-modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy.
Kasteleijn-Nolst TrenitÃ©, D., Rubboli, G., Hirsch, E., Martins da Silva, A., Seri, S., Wilkins, A., Parra, J., Covanis, A., Elia, M., Capovilla, G., Stephani, U. and Harding, G. (2012)
Epilepsia. 2012 January, 53: 16-24. doi: 10.1111/j.1528-1167.2011.03319.x
Intermittent photic stimulation (IPS) is a common procedure performed in the electroencephalography (EEG) laboratory in children and adults to detect abnormal epileptogenic sensitivity to flickering light (i.e., photosensitivity). In practice, substantial variability in outcome is anecdotally found due to the many different methods used per laboratory and country. We believe that standardization of procedure, based on scientific and clinical data, should permit reproducible identification and quantification of photosensitivity. We hope that the use of our new algorithm will help in standardizing the IPS procedure, which in turn may more clearly identify and assist monitoring of patients with epilepsy and photosensitivity.
Kerr MP, Mensah S, Besag F, de Toffol B, Ettinger A, Kanemoto K, Kanner A, Kemp S, Krishnamoorthy E, Lafrance C Jr, Mula M, Schmitz B, van Elst LT, Trollor J, Wilson SJ.
Epilepsia. 2011 Sep 28. doi: 10.1111/j.1528-1167.2011.03276.x.
In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with the aim of developing clear evidence-based and practice-based statements to provide guidance on the management of these conditions.
Meador KJ, French J, Loring DW, Pennell PB.
Neurology. 2011 Sep 27;77(13):1305-7.
Using data from NIH Research Portfolio Online Reporting Tools (RePORT) and recently assembled prevalence estimates of 6 major neurologic diseases, we compared the relative prevalences and the annual NIH support levels for 6 major neurologic disorders: Alzheimer disease, amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis, Parkinson disease, and stroke.
Philippe Ryvlin, Michel Cucherat, Sylvain Rheims
www.thelancet.com/neurology. Published online September 19, 2011 DOI:10.106/S1474-4422(11)70193-4.
Sudden unexpected death in epilepsy (SUDEP) represents the main cause of death in patients with refractory epilepsy. No evidence-based intervention to prevent SUDEP exists. We postulated that pooling data from randomised placebo-controlled trials in patients with refractory epilepsy might show a lower incidence of SUDEP in patients receiving antiepileptic drugs (AEDs) at effi cacious doses than in those receiving placebo.
Thurman DJ, Beghi E, Begley CE, Berg AT, Buchhalter JR, Ding D, Hesdorffer DC, Hauser WA, Kazis L, Kobau R, Kroner B, Labiner D, Liow K, Logroscino G, Medina MT, Newton CR, Parko K, Paschal A, Preux PM, Sander JW, Selassie A, Theodore W, Tomson T, Wiebe S; ILAE Commission on Epidemiology.
Epilepsia. 2011 Sep;52 Suppl 7:2-26. doi: 10.1111/j.1528-1167.2011.03121.x.
Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy.