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Clinical Research News

No evidence for human papillomavirus infection in focal cortical dysplasia IIb

Annals of Neurology

Roland Coras MD, Klaus Korn MD, Christian G. Bien MD, Thilo Kalbhenn MD, Karl Rössler MD, Katja Kobow PhD, Johannes Gied MD, Bernhard Fleckenstein MD, PhD, and Ingmar Blümcke MD
Annals of Neurology DOI: 10.1002/ana.24328

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.

Abstract


Complete remission of childhood-onset epilepsy: stability and prediction over two decades

Anne T. Berg, Karen Rychlik, Susan R. Levy, and Francine M. Testa
Brain 2014 137: 3213-3222

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.

Abstract | Full Article | PDF


Epilepsy: Pregnancy in women with epilepsy—risks and management

Nature Reviews Neurology

Kimford J. Meador
Nature Reviews Neurology 10, 614–616(2014). Published online 30 September 2014
doi:10.1038/nrneurol.2014.179

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.

Article Preview


Prolonged Epileptic Seizures: Identification and Rescue Treatment Strategies

Epileptic Disorders Supplement; Prolonged Epileptic Seizures

Alexis Arzimanoglou, Thomas Bast, Jaume Campistol, Richard Chin, Aristea Galanopoulou, Lieven Lagae
Epileptic Disorders Vol. 16, Supplement 1, October 2014

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.

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The international incidence and prevalence of neurologic conditions: How common are they?

Neurology

Tamara Pringsheim, MD, MSc, Kirsten Fiest, PhD and Nathalie Jette, MD, MSc
Neurology October 28, 2014 vol. 83 no. 18 1661-1664. doi: 10.1212/WNL.0000000000000929.

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.

Abstract | Full text | PDF


WONOEP appraisal: Optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis

Epilepsia

Laura Mantoan Ritter, Peyman Golshani, Koji Takahashi, Suzie Dufour, Taufik Valiante and Merab Kokaia
Epilepsia. Article first published online: 9 OCT 2014 | DOI: 10.1111/epi.12804

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.

Abstract


Several studies now show great heterogeneity in mutations discovered by whole exome sequencing in epileptic encephalopathies

De novo KCNB1 mutations in epileptic encephalopathy
Ali Torkamani, Kevin Bersell, Benjamin S. Jorge, Robert L. Bjork Jr, Jennifer R. Friedman, Cinnamon S. Bloss, Julie Cohen, Siddharth Gupta, Sakkubai Naidu, Carlos G. Vanoye, Alfred L. George Jr and Jennifer A. Kearney
Annals of Neurology, volume 76, issue 4, pages 529-540, October 2014. Article first published online: 19 SEP 2014 | DOI: 10.1002/ana.24263

Whole-exome sequencing broadens the phenotypic spectrum of rare pediatricepilepsy: a retrospective study
Dyment DA, Tétreault M, Beaulieu CL, Hartley T, Ferreira P, Chardon JW, Marcadier J, Sawyer SL, Mosca SJ, Innes AM, Parboosingh JS, Bulman DE, Schwartzentruber J, Majewski J, Tarnopolsky M, Boycott KM; FORGE Canada Consortium; Care4Rare Canada.
Clin Genet. 2014 Jul 21. doi: 10.1111/cge.12464

De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause EpilepticEncephalopathies
EuroEPINOMICS-RES Consortium. Electronic address: euroepinomics-RES@ua.ac.be;Epilepsy Phenome/Genome Project; Epi4K Consortium; EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4K Consortium.
Am J Hum Genet. 2014 Oct 2;95(4):360-70.

Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life
Thevenon J, Milh M, Feillet F, St-Onge J, Duffourd Y, Jugé C, Roubertie A, Héron D, Mignot C, Raffo E, Isidor B, Wahlen S, Sanlaville D, Villeneuve N, Darmency-Stamboul V, Toutain A, Lefebvre M, Chouchane M, Huet F, Lafon A, de Saint Martin A, Lesca G, El Chehadeh S, Thauvin-Robinet C, Masurel-Paulet A, Odent S, Villard L, Philippe C, Faivre L, Rivière JB.
Am J Hum Genet. 2014 Jul 3;95(1):113-20.


Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy

Annals of Neurology

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
Annals of Neurology, Volume 76, Issue 2, pages 206-212, August 2014. Article first published online: 20 MAY 2014. DOI: 10.1002/ana.24170

Objective: Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders.
Results: We demonstrated that the mutation decreases C18-ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways.

Abstract | Article


Early predictors of refractory status epilepticus: an international two-center study

European Journal of Neurology

R. Sutter, P. W. Kaplan, S. Marsch, E. M. Hammel, S. Rüegg, and W. C. Ziai.
European Journal of Neurology. Article first published online: 7 AUG 2014. DOI: 10.1111/ene.12531

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.

Abstract


The wide phenotypic spectrum of patients with DEPDC5 mutations encompasses many electroclinical epilepsy syndroms and levels of severity.

Annals of Neurology

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations (pages 782–787)
Ingrid E. Scheffer, Sarah E. Heron, Brigid M. Regan, Simone Mandelstam, Douglas E. Crompton, Bree L. Hodgson, Laura Licchetta, Federica Provini, Francesca Bisulli, Lata Vadlamudi, Jozef Gecz, Alan Connelly, Paolo Tinuper, Michael G. Ricos, Samuel F. Berkovic and Leanne M. Dibbens
Article first published online: 14 APR 2014 | DOI: 10.1002/ana.24126

DEPDC5 mutations in genetic focal epilepsies of childhood (pages 788–792)
Dennis Lal, Eva M. Reinthaler, Julian Schubert, Hiltrud Muhle, Erik Riesch, Gerhard Kluger, Kamel Jabbari, Amit Kawalia, Christine Bäumel, Hans Holthausen, Andreas Hahn, Martha Feucht, Birgit Neophytou, Edda Haberlandt, Felicitas Becker, Janine Altmüller, Holger Thiele, Johannes R. Lemke, Holger Lerche, Peter Nürnberg, Thomas Sander, Yvonne Weber, Fritz Zimprich and Bernd A. Neubauer
Article first published online: 14 APR 2014 | DOI: 10.1002/ana.24127

DEPDC5 does it all: Shared genetics for diverse epilepsy syndromes (pages 631–633)
Annapurna Poduri
Article first published online: 8 MAY 2014 | DOI: 10.1002/ana.24160


Nature Reviews Neurology: Special Focus on Epilepsy

Nature Neurology

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)

Article index


Rolandic epilepsy has little effect on adult life 30 years later

Neurology

Carol S. Camfield, MD and Peter R. Camfield, MD
Neurology April 1, 2014 vol. 82 no. 13 1162-1166. Published online before print February 21, 2014
doi: 10.1212/WNL.0000000000000267

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

Abstract | Full text | PDF


Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study

Annals of Neurology

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
Annals of Neurology, vol.75, issue 2 Feb 2014, pp. 1178-185. Article first published online: 1 March 2014
DOI: 10.1002/ana.24081

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?
Jacqueline A. French MD and Ruben Kuzniecky MD (2014), Ann Neurol., 75: 173–174. doi: 10.1002/ana.24109

Abstract | Article | PDF


Familial risk of epilepsy: a population-based study

Brain, A Journal of Neurology

Anna L. Peljto, Christie Barker-Cummings, Vincent M. Vasoli, Cynthia L. Leibson, W. Allen Hauser, Jeffrey R. Buchhalter, and Ruth Ottman
Brain (2014) 137 (3): 795-805. doi: 10.1093/brain/awt368 First published online: January 26, 2014

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). …

Abstract


Premature mortality in active convulsive epilepsy in rural Kenya Free access

Neurology

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
Neurology February 18, 2014 vol. 82 no. 7 582-589. Published online before print January 17, 2014, doi: 10.1212/WNL.0000000000000123

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.

Full article


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
Epilepsia, Article first published online: 11 FEB 2014 | DOI: 10.1111/epi.12544

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.

Abstract | Full Article | PDF


Early Treatment with AED Reduces Duration of Febrile Seizures
- Standard EMS Treatment Policy Needed in U.S.

Epilepsia

New research shows that children with febrile status epilepticus (FSE) who receive earlier treatment with antiepileptic drugs (AEDs) experience a reduction in the duration of the seizure. The study published in Epilepsia, a journal of the International League Against Epilepsy (ILAE), suggests that a standard Emergency Medical Services (EMS) treatment protocol for FSE is needed in the U.S.

“The time from the start of the seizure to treatment is crucial to improving patient outcomes,” said lead author Syndi Seinfeld, DO, with the Neurology Department at Virginia Commonwealth University in Richmond “Our study is the first to examine the treatment of FSE by EMS, which currently does not have a standard therapy protocol for prolonged seizures.” …

… “Our findings clearly show that early AED initiation results in shorter seizure duration,” concludes Dr. Seinfeld. “A standard FSE treatment protocol prior to arrival at the hospital, along with training for EMS staff, is needed across the U.S. to help improve outcomes for children with prolonged seizures.”

Press release | Abstract | Full Article | PDF


Long-term outcome in epilepsy with grand mal on awakening – 40 years of follow-up

Martin Holtkamp, Alexander B. Kowski, Hannah Merkle and Dieter Janz
Annals of Neurology. Accepted manuscript online: 7 JAN 2014 04:15AM EST | DOI: 10.1002/ana.24103

Epilepsy with grand mal on awakening (EGMA) is a well-defined subtype of idiopathic generalized epilepsy. Patients with follow-up of at least 20 years were assessed retrospectively regarding 5-year terminal seizure remission. Forty-two patients were included (mean age, 60±13 years). After follow-up of 40±13 years, 26 patients (62%) were in remission, five without antiepileptic drugs. Age at investigation (OR 0.939; CI95% 0.887-0.994; p=0.029) independently predicted lacking remission. Nineteen patients (45.2%) had withdrawn antiepileptic drugs at least once, 12 of those (63.2%) had seizure relapse. EGMA has a favorable long-term prognosis. With increasing age and treatment duration, antiepileptic drug withdrawal may be justified. ANN NEUROL 2014. © 2014 American Neurological Association

Abstract | PDF


Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy

Veiby G, Engelsen BA, Gilhus NE
JAMA Neurol. 2013 Nov;70(11):1367-74. doi: 10.1001/jamaneurol.2013.4290

Importance:
Exposure to antiepileptic drugs during pregnancy is associated with adverse effects on psychomotor development.

Objectives:
To determine whether signs of impaired development appear already during the first months of life in children exposed prenatally to antiepileptic drugs, and to explore potential adverse effects of antiepileptic drug exposure through breastfeeding.

Conclusions and Relevance:
Prenatal exposure to antiepileptic drugs was associated with impaired fine motor skills already at age 6 months, especially when the child was exposed to multiple drugs. There were no harmful effects of breastfeeding. Women with epilepsy should be encouraged to breastfeed their children irrespective of antiepileptic drug treatment.

Abstract | Commentary


Prognosis of juvenile myoclonic epilepsy 45 years after onset

Neurology Journal

Philine Senf, MD, Bettina Schmitz, PhD, Martin Holtkamp, PhD and Dieter Janz, PhD, FANA
Neurology vol. 81 no. 24 2128-2133. Published online before print November 8, 2013
doi: 10.1212/01.wnl.0000437303.36064.f8

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.

Abstract | Full Text | PDF


Epilepsia Editor's Choice: Reviews on reflex epilepsy and on resting state networks

Epilepsia Editor's Choice

Commentaries by Editor-in-Chief Astrid Nehlig on two articles:

  • Conceptual distinctions between reflex and nonreflex precipitated seizures in the epilepsies: A systematic review of definitions employed in the research literature
  • Resting state networks in temporal lobe epilepsy

Read commentaries


Epilepsia Editor's Choice: Bone loss in epilepsy & guidelines for psychogenic seizures

Epilepsia Editor's Choice

Commentaries by Editor-in-Chief Astrid Nehlig on two articles:

  • Prevention of bone loss and vertebral fractures in chronic epileptic patients - antiepileptic drug and osteoporosis prevention trial (ADOPT)
  • Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach

Read commentaries


Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy

Neurology Journal

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
doi: 10.1212/WNL.0b013e3182a9f3ca

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.

Abstract | Full article | PDF


Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies

Brain

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.

Abstract | Full Article | PDF


Cavernoma-related epilepsy: Review and recommendations for management—Report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies

Epilepsia

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.

Abstract | Article | PDF


New book: Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H. M.

Permanent Present Tense

Author: Suzanne Corkin
Publisher: Basic Books, 2013

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.

Order from publisher (excl UK & Commonwealth) | UK & Commonwealth


Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach

Epilepsia, September 2013

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
DOI: 10.1111/epi.12356

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.

Abstract | Article | PDF


Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study

The Lancet

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.

Abstract


Epilepsy informatics and an ontology-driven infrastructure for large database research and patient care in epilepsy

Epilepsia, Aug 2013

Sahoo SS, Zhang G-Q, Lhatoo SD
Volume 54, issue 8, pages 1335-1341, August 2013. Article first published online: 3 MAY 2013
DOI: 10.1111/epi.12211
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.

Abstract | Article | PDF


International consensus classification of hippocampal sclerosis in temporal lobe epilepsy

Epilepsia - July 2013

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
DOI: 10.1111/epi.12220

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.

Abstract | Full Article | PDF


Seizure control and treatment changes in pregnancy: Observations from the EURAP epilepsy pregnancy registry

Epilepsia - July 2013

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.

Abstract | Full article | PDF


Assessment of antiepileptic drugs usage in a South Indian tertiary care teaching hospital

Neurology Asia

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...

Article


July Epilepsia Editor's Choice

Epilepsia - July 2013

This month’s Editors’ Choice selections focus on structural damage in the epileptic brain.

  • Structural correlates of impaired working memory in hippocampal sclerosis.
  • Lacosamide treatment following status epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical status epilepticus model
  • Can structural or functional changes following traumatic brain injury in the rat predict the epileptic outcome?

Read more

 


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
Neurology, May 21, 2013. Vol. 80 no. 21 1942-1949. Published online before print April 24, 2013.
doi: 10.1212/WNL.0b013e318293e1b4

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.

Abstract | Full article


Postictal psychosis in temporal lobe epilepsy: a case–control study

European Neurology Journal - March 2013

E. Hilger, F. Zimprich, R. Jung, E. Pataraia, C. Baumgartner, S. Bonelli
European Journal of Neurology, Article first published online: 16 MAR 2013
DOI: 10.1111/ene.12125

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

NatureReview-May2013

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.

Abstract


Mutations of DEPDC5 - Two articles

NatureGenetics

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.
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.

Abstract | Article

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.
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.

Abstract | Article


Standardized computer-based organized reporting of EEG: SCORE

Epilepsia - March 2013

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
DOI: 10.1111/epi.12135

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

Handbook of ICU EEG Monitoring

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.

More information | Link to publisher


Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes

Epilepsia January 2013 V54 issue 1

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
DOI: 10.1111/epi.12074

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.

Abstract | Article | PDF


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.

Abstract | Paper


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).
See the November 20 issue of Neurology for a series of studies.


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

Article

 


Challenges of epilepsy in elderly people

Lancet

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.

Article


New book: Epilepsy and Memory
Edited by Adam Zeman, Narinder Kapur, and Marilyn Jones-Gotman

Epilepsy & Memory book cover

 

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.

  • Includes editors and contributors at the forefront of research into this area, resulting in a state of the art volume on the topic
  • Explores how epilepsy has been valuable in showing the workings of human memory

Publisher Information


Antiepileptic drugs and suicidality: An expert consensus statement from the Task Force on Therapeutic strategies of the ILAE Commission on Neuropsychobiology

Epilepsia

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.

Abstract | Full Text | PDF


GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy

Nature Medicine

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.

Article | PDF


Feasibility of antiepileptic drug withdrawal following extratemporal resective epilepsy surgery

American Academy of Neurology

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.

Abstract | Full Text | PDF


Seizure risk with AVM treatment or conservative management
Prospective, population-based study

American Academy of Neurology

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.

Abstract | Full Text | PDF


The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy

Brain Journal cover image

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.

Abstract | Full Text | PDF


Patterns of treatment response in newly diagnosed epilepsy

American Academy of Neurology

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.

Abstract | Full Text | PDF


Comparative safety of antiepileptic drugs during pregnancy

American Academy of Neurology

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.

Abstract | Full Text | PDF


Autoimmune Epilepsy: Clinical Characteristics and Response to Immunotherapy

Archives of Neurology cover

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.

Abstract | Full Text | PDF

 


The role of magnetic resonance imaging in the follow-up of children with convulsive status epilepticus

Developmental Medicine & Child Neurology cover

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.

Journal of the Amer. Med. Assoc

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.

Abstract | Full Text | PDF


Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus

New England Journal of Medicine insignia

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.

Abstract | Full Text


Identification of new epilepsy treatments: Issues in preclinical methodology

Epilepsia

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.

Abstract | Full Text | PDF


Methodology of photic stimulation revisited: Updated European algorithm for visual stimulation in the EEG laboratory.

Epilepsia cover - 1-2012

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.

Abstract | Full Text | PDF


International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy.

Epilepsia cover - 9-2011

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.

Abstract | Full Text | PDF

 


Disparities in NIH funding for epilepsy research.

American Academy of Neurology

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.

Abstract | Full Text | PDF


Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials.

The Lancet/Neurology cover

 

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.

Abstract | Full Text | PDF


Standards for epidemiologic studies and surveillance of epilepsy

Epilepsia cover image 9-2011 supplement

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.

Abstract | Full Text | PDF

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