Clinical Research News
Prognosis of juvenile myoclonic epilepsy 45 years after onset
Philine Senf, MD,
Bettina Schmitz, PhD,
Martin Holtkamp, PhD and
Dieter Janz, PhD, FANA
Objectives: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy subsyndrome, contributing to approximately 3% to 11% of adolescent and adult cases of epilepsy... The aim of this study was to analyze long-term outcome in a clinically well-defined series of patients with JME for seizure evolution and predictors of seizure outcome.
Conclusions: A significant proportion of patients with JME were seizure-free and off antiepileptic drug therapy in the later course of their disorder. Patients with JME and additional absence seizures might represent a different JME subtype with a worse outcome.
Epilepsia Editor's Choice: Reviews on reflex epilepsy and on resting state networks
Epilepsia Editor's Choice: Bone loss in epilepsy & guidelines for psychogenic seizures
Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy
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
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.
Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies
Simon D. Shorvon and David M. G. Goodridge
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.
Cavernoma-related epilepsy: Review and recommendations for management—Report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies
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
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.
New book: Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H. M.
Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach
W. Curt LaFrance Jr., Gus A. Baker, Rod Duncan, Laura H. Goldstein, Markus Reuber
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.
Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study
Dr Seena Fazel, Achim Wolf MSc, Prof Niklas Långström PhD, Prof Charles R Newton MD, Prof Paul Lichtenstein, PhD
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.
Epilepsy informatics and an ontology-driven infrastructure for large database research and patient care in epilepsy
Sahoo SS, Zhang G-Q, Lhatoo SD
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.
International consensus classification of hippocampal sclerosis in temporal lobe epilepsy
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
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.
Seizure control and treatment changes in pregnancy: Observations from the EURAP epilepsy pregnancy registry
Dina Battino, Torbjörn Tomson, Erminio Bonizzoni, John Craig, Dick Lindhout, Anne Sabers, Emilio Perucca and Frank Vajda, EURAP Study Group
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.
Assessment of antiepileptic drugs usage in a South Indian tertiary care teaching hospital
J Sebastian, R Adepu, BS Keshava, S Harsha
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...
July Epilepsia Editor's Choice
Incidence and prevalence of treated epilepsy among poor health and low-income Americans
Kitti Kaiboriboon, MD, Paul M. Bakaki, MD, Samden D. Lhatoo, MD and Siran Koroukian, PhD
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.
Postictal psychosis in temporal lobe epilepsy: a case–control study
E. Hilger, F. Zimprich, R. Jung, E. Pataraia, C. Baumgartner, S. Bonelli
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
Progress in gene therapy for neurological disorders
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
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.
Mutations of DEPDC5 - Two articles
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.
Mutations of DEPDC5 cause autosomal dominant focal epilepsies
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.
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.
Mutations in DEPDC5 cause familial focal epilepsy with variable foci
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.
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.
Standardized computer-based organized reporting of EEG: SCORE
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
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.
New Book: Handbook of ICU EEG Monitoring
Author/Editor: Suzette LaRoche, MD
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.
Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes
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
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.
Long-tem followup of hemispherectomy
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.
PRRT2 mutations: From familial infantile convulsions/seizures to paroxysmal dyskinesia, episodic ataxia, and hemiplegic migraine
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).
Neurology October 9, 2012 79:1548-1555; published ahead of print September 26, 2012
Ilo E Leppik, Thaddeus S Walczak, Angela K Birnbaum
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.
Antiepileptic drugs and suicidality: An expert consensus statement from the Task Force on Therapeutic strategies of the ILAE Commission on Neuropsychobiology
Marco Mula, Andres M. Kanner, Bettina Schmitz and Steven Schachter
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
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
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.
Seizure risk with AVM treatment or conservative management