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Clinical Research News
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 Abstract | Full article | PDF 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 epilepsiesIshida 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 fociDibbens 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. Abstract | Full article | PDF 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. More information | Link to publisher 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). Quality of life in children with new-onset epilepsy: A 2-year prospective cohort study
Neurology October 9, 2012 79:1548-1555; published ahead of print September 26, 2012
Challenges of epilepsy in elderly people 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. New book: Epilepsy and Memory
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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.
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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
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.
GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy
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.
Feasibility of antiepileptic drug withdrawal following extratemporal resective epilepsy surgery
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.
Seizure risk with AVM treatment or conservative management
Prospective, population-based study
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.
The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy
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.
Patterns of treatment response in newly diagnosed epilepsy
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.
Comparative safety of antiepileptic drugs during pregnancy
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.
Autoimmune Epilepsy: Clinical Characteristics and Response to Immunotherapy
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.
The role of magnetic resonance imaging in the follow-up of children with convulsive status epilepticus
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.
Commentary | Abstract | Full Text | PDF
Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.
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.
Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus
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.
Identification of new epilepsy treatments: Issues in preclinical methodology
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.
Methodology of photic stimulation revisited: Updated European algorithm for visual stimulation in the EEG laboratory.
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.
International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy.
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.
Disparities in NIH funding for epilepsy research.
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.
Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials.
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.
Standards for epidemiologic studies and surveillance of epilepsy
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.