Clinical Research News
Orrin Devinsky, M.D., J. Helen Cross, Ph.D., F.R.C.P.C.H., Linda Laux, M.D., Eric Marsh, M.D., Ian Miller, M.D., Rima Nabbout, M.D., Ingrid E. Scheffer, M.B., B.S., Ph.D., Elizabeth A. Thiele, M.D., Ph.D., and Stephen Wright, M.D., for the Cannabidiol in Dravet Syndrome Study Group
Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)
Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.
Lamberink HJ, Otte WM, Geerts AT, Pavlovic M, Ramos-Lizana J, Marson AG, Overweg J, Sauma L, Specchio LM, Tennison M, Cardoso TMO, Shinnar S, Schmidt D, Geleijns K, Braun KPJ.
The paper proposes a web-based tool to calculate the risk of seizure relapse after withdrawal of antiepileptic medication.
Tory P. Johnson, Richa Tyagi, Paul R. Lee, Myoung-Hwa Lee, Kory R. Johnson, Jeffrey Kowalak, Abdel Elkahloun, Marie Medynets, Alina Hategan, Joseph Kubofcik, James Sejvar, Jeffrey Ratto, Sudhir Bunga, Issa Makumbi, Jane R. Aceng, Thomas B. Nutman, Scott F. Dowell and Avindra Nath
Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. … This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.
Tracy A. Glauser, Katherine Holland, Valerie P. O'Brien, Mehdi Keddache, Lisa J. Martin, Peggy O. Clark, Avital Cnaan, Dennis Dlugos, Deborah G. Hirtz, Shlomo Shinnar, Gregory Grabowski and for the Childhood Absence Epilepsy Study Group
Objective: Determine if common polymorphisms in CACNA1G, CACNA1H, CACNA1I, and ABCB1 are associated with differential short term seizure outcome in Childhood Absence Epilepsy (CAE).
Interpretation: Four T-type calcium channel variants and one ABCB1 transporter variant were associated with differential drug response in CAE. The in vivo P640L variant's ethosuximide effect was confirmed by in vitro electrophysiological studies. This suggests genetic variation plays a role in differential CAE drug response. This article is protected by copyright. All rights reserved.
Laura Licchetta, MD, Francesca Bisulli, MD, PhD, Luca Vignatelli, MD, PhD, Corrado Zenesini, MSc, Lidia Di Vito, MD, Barbara Mostacci, MD, PhD, Claudia Rinaldi, MD, Irene Trippi, MD, Ilaria Naldi, MD, PhD, Giuseppe Plazzi, MD, PhD, Federica Provini, MD, PhD and Paolo Tinuper, MD
The objective was to assess the long-term outcome of sleep-related hypermotor epilepsy (SHE). We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.
Vincent Alvarez, MD, Jong Woo Lee, MD, PhD, M. Brandon Westover, MD, PhD, Frank W. Drislane, MD, Jan Novy, MD, PhD, Mohamed Faouzi, PhD, Nicola A. Marchi, MD, Barbara A. Dworetzky, MD, and Andrea O. Rossetti, MD
Our aim was to analyze and compare the use of therapeutic coma (TC) for refractory status epilepticus (SE) across different centers and its effect on outcome. Use of TC for SE treatment seems markedly different between centers from the United States and Europe, and did not affect mortality considering the whole cohort. However, TC may increase length of hospital stay and related costs.
Genevieve Rayner, PhD, Graeme D. Jackson, MD and Sarah J. Wilson, PhD
This study reveals that memory deficits in people with focal epilepsy have differing antecedents depending on the timing of the disease onset. While neurobiological factors strongly underpin reduced autobiographic function in patients with early-onset epilepsy, psychological maladjustment gives rise to the impairments seen in patients with late-onset epilepsy. More broadly, these findings support the practice of subtyping patients according to distinct clinical characteristics to find individualized predictors of cognitive dysfunction.
Rahul S. Desikan and A. James Barkovich
Malformations of cortical development (MCDs) compose a diverse range of disorders that are common causes of neurodevelopmental delay and epilepsy. With improved imaging and genetic methodologies, the underlying molecular and pathobiological characteristics of several MCDs have been recently elucidated. In this review, we discuss genetic and molecular alterations that disrupt normal cortical development, with emphasis on recent discoveries, and provide detailed radiological features of the most common and important MCDs.
Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: a retrospective study
Markus Leitinger, MD, Prof Eugen Trinka, MD, Elena Gardella, MD, Alexandra Rohracher, MD, Gudrun Kalss, MD, Erisela Qerama, MD, Julia HÃ¶fler, MD, Alexander Hess, MD, Georg Zimmermann, MSc, Giorgi Kuchukhidze, MD, Judith Dobesberger, MD, Patrick B Langthaler, BSc, Dr SÃ¡ndor Beniczky, MD
Background: Several EEG criteria have been proposed for diagnosis of non-convulsive status epilepticus (NCSE), but none have been clinically validated. We aimed to assess the diagnostic accuracy of the EEG criteria proposed by a panel of experts at the fourth London-Innsbruck Colloquium on Status Epilepticus in Salzburg, 2013 (henceforth called the Salzburg criteria).
Interpretation: The Salzburg criteria for diagnosis of NCSE have high diagnostic accuracy and excellent inter-rater agreement, making them suitable for implementation in clinical practice.
Kari Modalsli Aaberg, Inger Johanne Bakken, Morten I. Lossius, Camilla Lund Søraas, Siri Eldevik Håberg, Camilla Stoltenberg, Pål Surén, Richard Chin
Background and Objective: Children with epilepsy are at increased risk of other disorders and difficulties, preceding, cooccurring with, or after the diagnosis of epilepsy. Risk estimates vary, few studies are population-based, and few provide comprehensive assessments of comorbidities. We used nationwide registry data to describe frequencies of medical, neurologic, developmental, and psychiatric conditions occurring before and after children are diagnosed with childhood epilepsy.
Conclusions: The overall frequency of comorbid disease is high in children with epilepsy, including children with presumably uncomplicated epilepsies.
Ziyi Chen, Ana Lusicic, Terence J. O’Brien, Dennis Velakoulis, Sophia J. Adams, Patrick Kwan
Antiepileptic drug treatment can induce psychosis in some patients. However, there are no agreed definitions or diagnostic criteria for antiepileptic drug-induced psychotic disorder in the classification systems of either epileptology or psychiatry. In this study we investigated the clinical spectrum of antiepileptic drug-induced psychotic disorder in patients with epilepsy. The medical records of all patients with epilepsy who were diagnosed by a neuropsychiatrist as having a psychotic disorder at the Royal Melbourne Hospital from January 1993 to June 2015 were reviewed .… Our findings indicated that one in seven patients with epilepsy who developed psychosis had antiepileptic drug-induced psychotic disorder. In these patients, female gender, temporal lobe involvement and current use of levetiracetam were significantly associated with antiepileptic drug induced psychotic disorder compared to other types of psychosis, while carbamazepine had a negative association. Disorganized behaviours and thinking were predominant in antiepileptic drug-induced psychotic disorder. Patients with antiepileptic drug-induced psychotic disorder differed from non-antiepileptic drug-induced psychotic disorders in having better outcome.
Gregory L. Krauss and Michael Privitera
Seizures come out of the blue; people with epilepsy find themselves on classroom floors, on sidewalks, or in the emergency department (ED) after seizures and seek explanations for these sudden “breakthroughs.” A pharmacy replaces an effective white tablet with a blue one, leaving the patient anxious and uneasy—especially when the new tablet dissolves slightly more rapidly than the old one. And when the patient suddenly has a seizure, he or she concludes that switching between generic products is responsible.
Deb K. Pal, Colin Ferrie, Laura Addis, Tomoyuki Akiyama, Giuseppe Capovilla, Roberto Caraballo, Anne de Saint-Martin, Natalio Fejerman, Renzo Guerrini, Khalid Hamandi, Ingo Helbig, Andreas A. Ioannides, Katsuhiro Kobayashi, Dennis Lal, Gaetan Lesca, Hiltrud Muhle, Bernd A. Neubauer, Tiziana Pisano, Gabrielle Rudolf, Caroline Seegmuller, Takashi Shibata, Anna Smith, Pasquale Striano, Lisa J. Strug, Pierre Szepetowski, Thalia Valeta, Harumi Yoshinaga, Michalis Koutroumanidis
The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many “treats” for both clinicians and researchers.
In June 2012, an international group of clinical and basic science resear-chers met in London under the auspices of the Waterloo Foundation to discuss and debate issues in relation to IFEs. The symposium led to the formation of international working groups under the umbrella of “Luke‘s Idiopathic Focal Epilepsy Project” to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see www.childhood-epilepsy.org). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.
Hye Eun Kwon, MD, Soyong Eom, PhD, Hoon-Chul Kang, MD, PhD, Joon Soo Lee, MD, PhD, Se Hoon Kim, MD, PhD, Dong Seok Kim, MD, PhD and Heung Dong Kim, MD, PhD
Objective: To analyze the clinical presentation and outcomes of surgically treated focal cortical dysplasia (FCD) in children. We reviewed 75 cases of confirmed FCD by pathology after resective surgery. We used the pathologic classification proposed by the International League Against Epilepsy and included clinical profile and seizure and neurodevelopmental outcomes in analyses.
Arturo Carpio, Agnès Fleury, Matthew L. Romo PharmD, Ronaldo Abraham, Jaime Fandiño, Juan C. Durán, Graciela Cárdenas, Jorge Moncayo, Cleonísio Leite Rodrigues, Daniel San-Juan, Marcos Serrano-Dueñas, Oswaldo Takayanagui and Josemir W. Sander
The diagnosis of neurocysticercosis (NCC) remains problematic due to the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease. A group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. These criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers.
Lauren E. Walker, Damir Janigro, Uwe Heinemann, Raili Riikonen, Christophe Bernard and Manisha Patel
Peripheral biomarkers have myriad potential uses for treatment, prediction, prognostication, and pharmacovigilance in epilepsy. To date, no single peripheral biomarker has demonstrated proven effectiveness, although multiple candidates are in development. In this review, we discuss the major areas of focus including inflammation, blood-brain barrier dysfunction, redox alterations, metabolism, hormones and growth factors.
Eissa TL, Tryba AK, Marcuccilli CJ, Ben-Mabrouk F, Smith EH, Lew SM, Goodman RR, McKhann GM Jr, Frim DM,
High gamma (HG; 80-150 Hz) activity has been linked to seizures, but how seizure activity influences HG is not well understood. In a recent study, the authors used tissue obtained from resection of people with intractable epilepsy, microelectrode recordings from in vivo seizures and modeling to see if HG activity could be a (better) indicator of the seizure onset zone (SOZ). Currently, low frequency local field potentials (LFPs) are used as a biomarker for the SOZ. The authors found that HG activity on a network level was correlated with paroxysmal depolarizing shifts (PDSs) that are seen on a neuronal level. Also, greater HG was found in the core as opposed to the penumbra, indicating that looking at HG may be a better way to demarcate the SOZ.
High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (no= 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales.
Michael R. Sperling, Suzanne Barshow, Maromi Nei, and Ali A. Asadi-Pooya
A total of 1,110 patients were evaluated (1,006 surgically and 104 nonsurgically treated) for a total follow-up of 8,126.62 person-years from 1986 to 2013. Brain surgery is associated with a reduction in mortality rate in drug-resistant epilepsy, both when seizures are abolished and when it results in significant palliation of tonic-clonic seizure frequency. These observations provide further rationale for earlier consideration of epilepsy surgery.
Editorial: Refractory epilepsy is a life-threatening disease: Lest we forget
Raoul Sutter, Saskia Semmlack & Peter W. Kaplan
Nonconvulsive status epilepticus has subtle symptoms and can be difficult to treat, meaning it is associated with considerable morbidity and mortality. In this review, Sutter and colleagues discuss the epidemiology, clinical features and diagnosis of nonconvulsive status epilepticus, and discuss current recommendations for treatment.
Epilepsy surgery is the standard of care for focal drug-resistant epilepsy, but it is underutilized. Knowledge gaps and attitudes toward epilepsy surgery are partly responsible, and a new study explores whether the health-care infrastructure in developed countries influences access to and utilization of epilepsy surgery.
Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction
Kuo J, Zhao W, Li CS, Kennedy JD, Seyal M
Sudden unexpected death in epilepsy (SUDEP) is a phenomenon for which the mechanisms are not yet understood. The role of postictal generalized EEG suppression (PGES), postictal immobility and respiratory dysfunction has been suggested, but not confirmed. The authors of a recent paper investigated correlations between postictal immobility, PGES and respiratory dysfunction (measured by SpO2 and end-tidal CO2) and seizure parameters. Correlations of postictal immobility with PGES and respiratory dysfunction were found, but not with seizure characteristics. This study suggests the possible sequence of events that may lead to SUDEP with possible ways of intervening to reduce its incidence.
Nina Dupuis, Niccolo Curatolo, Jean-François Benoist and Stéphane Auvin
Dietary therapies like the ketogenic diet have been shown to be beneficial in epilepsy. In a recent study, scientists hypothesized that efficacy of the ketogenic diet is due to a decrease in inflammation. After being administered a regular diet or the ketogenic diet, rats were injected lipopolysaccharide (LPS) and downstream reactions were measured. Rats on the normal diet showed an increase in body temperature, whereas those on the ketogenic diet did not. Rats on the ketogenic diet also showed a decrease in proinflammatory cytokines in the blood (e.g TNFÎ± and IL-1Î²) and brain in response to LPS.
Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John J. Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V. Thomas, Frank Vajda, and For the EURAP Study Group
Objective: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). Conclusions: The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents.
Comment: Stillbirths and spontaneous abortions in women with epilepsy on AEDs
Read older Clinical Research News items here.