Clinical Research News
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 Långström 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, Torbjörn 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. Hernández-Díaz, 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, Moshé SL, Perucca E, Engel J Jr, Löscher W, Noebels JL, Pitkänen 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 Trenité, 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.