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Clinical Research News

Malformations of cortical development

Rahul S. Desikan and A. James Barkovich
Annals of Neurology 11 NOV 2016 | DOI: 10.1002/ana.24793

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 Höfler, MD, Alexander Hess, MD, Georg Zimmermann, MSc, Giorgi Kuchukhidze, MD, Judith Dobesberger, MD, Patrick B Langthaler, BSc, Dr Sándor Beniczky, MD
Lancet, September 2016, DOI: http://dx.doi.org/10.1016/S1474-4422(16)30137-5

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.

Article


Comorbidity and Childhood Epilepsy: A Nationwide Registry Study

Kari Modalsli Aaberg, Inger Johanne Bakken, Morten I. Lossius, Camilla Lund Søraas, Siri Eldevik Håberg, Camilla Stoltenberg, Pål Surén, Richard Chin
Pediatrics September 2016, volume 138 /issue 3

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.

Article


Psychotic disorders induced by antiepileptic drugs in people with epilepsy

Ziyi Chen, Ana Lusicic, Terence J. O’Brien, Dennis Velakoulis, Sophia J. Adams, Patrick Kwan
Brain. DOI: http://dx.doi.org/10.1093/brain/aww196 2668-2678 First published online: 8 August 2016

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.

Article


More data on the safety of generic substitution: Yes, the blue tablet is OK?

Gregory L. Krauss and Michael Privitera
Neurology October 25, 2016 87:1754-1755; published ahead of print September 28, 2016

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.

Article


Idiopathic focal epilepsies: the “lost tribe”

Epileptic DisordersDeb 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
Epileptic Disorders, Vol 18, No. 3, September 2016, pp 252-288

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.

PDF | Abstract


Surgical treatment of pediatric focal cortical dysplasia:
Clinical spectrum and surgical outcome.

Neurology

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
Neurology August 30, 2016 vol. 87 no. 9 945-951; published ahead of print July 27, 2016.

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.
Conclusion: FCD can cause FE and EE in pediatric age, and resective surgery should be considered as a treatment option for both types of epilepsy.

Abstract


New diagnostic criteria for neurocysticercosis: Reliability and validity

Annals of Neurology

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
Annals of Neurology. Accepted manuscript online: 20 JUL 2016 06:15PM EST | DOI: 10.1002/ana.24732

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.

Abstract


WONOEP appraisal: Molecular and cellular biomarkers for epilepsy

Epilepsia

Lauren E. Walker, Damir Janigro, Uwe Heinemann, Raili Riikonen, Christophe Bernard and Manisha Patel
Epilepsia; Article first published online: 4 JULY 2016. DOI: 10.1111/epi.13460

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.

Abstract

 


Multiscale Aspects of Generation of High-Gamma Activity during Seizures in Human Neocortex

eNeuro

Eissa TL, Tryba AK, Marcuccilli CJ, Ben-Mabrouk F, Smith EH, Lew SM, Goodman RR, McKhann GM Jr, Frim DM,
Contributed by Sloka S. Iyengar, PhD
eNeuro. 2016 May 23;3(2). doi: 10.1523/ENEURO.0141-15.2016.

Summary for non-specialists

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.

Abstract | Article


A reappraisal of mortality after epilepsy surgery

Neurology

Michael R. Sperling, Suzanne Barshow, Maromi Nei, and Ali A. Asadi-Pooya
Neurology May 24, 2016 86:1938-1944; published ahead of print April 27, 2016

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
Nathalie Jette and Jerome Engel, Jr.
Neurology May 24, 2016 86:1932-1933; published ahead of print April 27, 2016

Abstract | Editorial


Nonconvulsive status epilepticus in adults — insights into the invisible

Nature Reviews Neurology

Raoul Sutter, Saskia Semmlack & Peter W. Kaplan
p281 | doi:10.1038/nrneurol.2016.45. Published online: 11 April 2016.

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.

Abstract | Full text


Does access to care influence the use of epilepsy surgery?

Nature Reviews Neurology

Samuel Wiebe
Nature Reviews Neurology 12, 133-134 (2016) doi:10.1038/nrneurol.2016.7
Published online 29 January 2016

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.

Article


Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction

Epilepsia

Kuo J, Zhao W, Li CS, Kennedy JD, Seyal M
Epilepsia; Article first published online: 14 JAN 2016. DOI: 10.1111/epi.13312

Summary for non-specialists

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.

Abstract | PDF


Ketogenic diet exhibits anti-inflammatory properties

Epilepsia

Nina Dupuis, Niccolo Curatolo, Jean-François Benoist and Stéphane Auvin
Epilepsia. Volume 56, Issue 7, pages e95-e98, July 2015. DOI: 10.1111/epi.13038. Article first published online: 23 May 2015

Summary for non-specialists

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 TNFα and IL-1β) and brain in response to LPS.

Abstract | PDF


Antiepileptic drugs and intrauterine death: A prospective observational study from EURAP

Neurology

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
Neurology August 18, 2015 85:580-588; published ahead of print July 17, 2015

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
Nathalie Jetté
Neurology August 18, 2015 85:587; published ahead of print July 17, 2015
Our knowledge about the association between antiepileptic drugs (AEDs) and major congenital malformations (MCMs) or neurodevelopmental outcomes has increased greatly in the past decade. Yet our understanding regarding the occurrence of other important outcomes, such as stillbirths or spontaneous abortions in women with epilepsy, is limited.

Abstract | Full Article | Comment Extract | Full Comment

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