Article
Clinical Neurology
Phat Chang, Hua Xie, Venkata Sita Priyanka Illapani, Xiaozhen You, Tayyba Anwar, Archana Pasupuleti, Thuy-Anh Vu, L. Gilbert Vezina, Taha Gholipour, Chima O. Oluigbo, Anqing Zhang, William Davis Gaillard, Nathan T. T. Cohen
Summary: This study found that children with FCD-related epilepsy and FTBTC seizures are more likely to develop pharmacoresistant epilepsy. The presence of FTBTC seizures is associated with worse surgical outcomes, possibly due to interactions between the lesion and restricted cortical neural networks. These findings are significant for identifying children with FCD-related epilepsy at high risk of PRE and considering potentially curative surgery earlier.
Article
Clinical Neurology
John M. Bernabei, Nishant Sinha, T. Campbell Arnold, Erin Conrad, Ian Ong, Akash R. Pattnaik, Joel M. Stein, Russell T. Shinohara, Timothy H. Lucas, Dani S. Bassett, Kathryn A. Davis, Brian Litt
Summary: Bernabei et al. constructed an atlas of normative interictal intracranial EEG recordings and found that brain regions generating spikes and seizures have different patterns of activity and connectivity compared to the atlas. Comparing EEG recordings to the atlas can reliably identify abnormal regions and guide invasive treatment for epilepsy.
Article
Behavioral Sciences
George Francisco S. Santos, Luan Oliveira Ferreira, Bruna Gerrits Mattos, Eliniete J. Fidelis, Alisson S. de Souza, Paula S. Batista, Cecilia A. F. Manoel, Diego Arthur C. Cabral, Vanessa Joia de Mello, Dielly Catrina Favacho Lopes, Moises Hamoy
Summary: Local anesthetics can cause potentially lethal seizures, and in this study, acute lidocaine toxicity-induced seizures in adult male Wistar rats were investigated using electrocorticographic and electromyographic patterns. The study found that while anticonvulsant drugs reduced the power of brainwaves, only diazepam was able to decrease the intensity of the seizures.
BRAIN AND BEHAVIOR
(2021)
Article
Behavioral Sciences
Yunling Wang, Chenmin He, Cong Chen, Zhongjin Wang, Wenjie Ming, Jingjing Qiu, Meiping Ying, Wei Chen, Bo Jin, Hong Li, Meiping Ding, Shuang Wang
Summary: The study found that focal cortical dysplasia (FCD) is a significantly independent risk factor associated with sleep-related epilepsy (SRE), with the highest incidence of SRE in the FCD group. A small lesion size of FCD further increased the risk of SRE.
EPILEPSY & BEHAVIOR
(2022)
Article
Neurosciences
Lorna Bryant, Emilie T. McKinnon, James A. Taylor, Jens H. Jensen, Leonardo Bonilha, Christophe de Bezenac, Barbara A. K. Kreilkamp, Guleed Adan, Udo C. Wieshmann, Shubhabrata Biswas, Anthony G. Marson, Simon S. Keller
Summary: This study utilized FBI and FBWM to evaluate the diffusion properties of white matter tracts in patients with epilepsy. It was found that patients with chronic epilepsy had a widespread distribution of extra-axonal diffusivity, and those with refractory epilepsy exhibited significantly greater markers of extra-axonal diffusivity compared to nonrefractory epilepsy patients. These findings suggest that extra-axonal diffusivity alterations may serve as biomarkers of neuroinflammatory processes or reduced axonal density in epilepsy.
HUMAN BRAIN MAPPING
(2021)
Article
Behavioral Sciences
Masa Kovacevic, Milena Jankovic, Marija Brankovic, Ognjen Milicevic, Ivana Novakovic, Dragoslav Sokic, Aleksandar Ristic, Jannah Shamsani, Nikola Vojvodic
Summary: Variants in GATOR1 genes are associated with focal epilepsy syndromes and may lead to drug-resistant epilepsy and increased risk of sudden unexplained death. GATOR1 gene sequencing was able to diagnose 3.1% of the patients and identified three likely pathogenic variants and one variant of unknown significance. Further research is needed to understand the clinical implications of GATOR1 gene-associated epilepsy.
EPILEPSY & BEHAVIOR
(2023)
Article
Clinical Neurology
Violeta Contreras Ramirez, Aparna Vaddiparti, Hal Blumenfeld
Summary: The study investigated how clinicians assess seizure awareness and found that most respondents use both responsiveness and recall to evaluate patients' awareness. Using both measures could provide a more practical classification of impaired consciousness in focal seizures.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Review
Neurosciences
Elena Dossi, Gilles Huberfeld
Summary: Epilepsy is characterized by abnormal neuronal activities, which have traditionally been attributed to a defect in inhibition and excessive excitation. However, recent findings suggest that GABAergic signaling is not impaired, but instead may contribute to seizure generation. This indicates the importance of GABAergic signaling in the onset of seizures.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Amanda Almacellas Barbanoj, Robert T. Graham, Benito Maffei, Jenna C. Carpenter, Marco Leite, Justin Hoke, Felisia Hardjo, James Scott-Solache, Christos Chimonides, Stephanie Schorge, Dimitri M. Kullmann, Vincent Magloire, Gabriele Lignani
Summary: Focal cortical dysplasias are a common type of cortical development abnormality that often leads to cognitive and behavioral abnormalities as well as drug-resistant epilepsy. A gene therapy approach targeting the overexpression of the Kv1.1 potassium channel has shown promising results in reducing seizures in a mouse model of frontal lobe focal cortical dysplasia.
Article
Clinical Neurology
Marienke A. A. M. de Bruijn, Anna E. M. Bastiaansen, Hana Mojzisova, Agnes van Sonderen, Roland D. Thijs, Marian J. M. Majoie, Rob P. W. Rouhl, Marleen H. van Coevorden-Hameete, Juna M. de Vries, Amaia Munoz Lopetegi, Bob Roozenbeek, Marco W. J. Schreurs, Peter A. E. Sillevis Smitt, Maarten J. Titulaer
Summary: Diagnosing autoimmune encephalitis in patients with less fulminant diseases such as epilepsy is difficult, but recognition is crucial as these patients may require immunotherapy. This study identified antibodies in patients with focal epilepsy of unknown etiology and created a score to preselect patients for testing. The ACES score effectively identified patients with autoimmune epilepsy signs and symptoms.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Erin M. Triplet, Katherine Nickels, Lily Wong-Kisiel, Anthony Fine, Elaine C. Wirrell
Summary: This study characterized the etiology and natural history of infantile-onset focal epilepsy. Results showed a high incidence of infantile-onset focal epilepsy, often caused by known etiologies, and a high rate of drug-resistant epilepsy. However, infants without a known cause and with normal development tend to have a favorable course.
Review
Clinical Neurology
Thandar Aung, Jeffrey R. Tenney, Anto I. Bagic
Summary: According to the 2017 ILAE classification, generalized epileptic seizures originate from bilateral networks, while focal epileptic seizures are limited to one hemisphere. The main difference between generalized and focal epilepsy lies in the simultaneous bilateral origin and synchronous tonic discharge seen in the former. Recent literature on generalized epilepsy supports the concept of a cortical epileptogenic focus triggering rapidly generalized epileptic discharges, while focal epilepsy with rich connectivity can give rise to widespread bilateral synchronization of spike and wave discharges.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Heiko J. Luhmann
Summary: This review article provides an overview of the molecular, cellular, and network mechanisms underlying focal seizures in neocortical networks with developmental malformations. Neocortical malformations are a large variety of structural abnormalities associated with epilepsy and other neurological and psychiatric disorders. Animal models and state-of-the-art techniques have contributed to our understanding of neocortical hyperexcitability in developmental disorders. Additionally, molecular biological and electro-physiological techniques have provided insights into the subcellular, cellular, and network mechanisms of focal seizures.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Benjamin Edmonds, Makoto Miyakoshi, Luigi Gianmaria Remore, Samuel Ahn, H. Westley Phillips, Atsuro Daida, Noriko Salamon, Ausaf Bari, Raman Sankar, Joyce H. Matsumoto, Aria Fallah, Hiroki Nariai
Summary: This study aimed to characterize the ictal EEG changes in the CM and AN of the thalamus using SEEG recordings in pediatric-onset neocortical drug-resistant epilepsy patients. Visual and quantitative analysis showed consistent detection of ictal EEG changes in both CM and AN, with low-voltage fast activity being the most common pattern. The results suggest the feasibility of using a closed-loop system in the thalamus for detecting and modulating seizure activity in neocortical epilepsy.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
Joshua M. Diamond, Benjamin E. Diamond, Michael S. Trotta, Kate Dembny, Sara K. Inati, Kareem A. Zaghloul
Summary: Our study suggests that ictal activity observed by intracranial EEG may reflect propagated activity from a relatively focal seizure source, even during later time points when ictal activity is more widespread. By analyzing the time differences between ictal discharges in adjacent electrodes, we were able to estimate the location of the hypothesized focal source, which was found to closely match the clinically and neurophysiologically determined brain region giving rise to seizures. Furthermore, we found that this focal source is a dynamic entity that moves and evolves over the time course of a seizure, challenging the traditional conceptualization of the seizure source.
Review
Clinical Neurology
Johanna W. Bunschoten, Nafisa Husein, Orrin Devinsky, Jacqueline A. French, Josemir W. Sander, Roland D. Thijs, Mark R. Keezer
Summary: There is insufficient evidence to support or refute the association between lamotrigine and sudden death or ECG abnormalities. The high risk of bias in most studies and inconsistency in reported results contribute to the uncertainty of this association.
Article
Multidisciplinary Sciences
Dominique F. Leitner, Evgeny Kanshin, Manor Askenazi, Yik Siu, Daniel Friedman, Sasha Devore, Drew Jones, Beatrix Ueberheide, Thomas Wisniewski, Orrin Devinsky
Summary: This pilot study found that short-term everolimus before epilepsy surgery in TSC and FCD resulted in no adverse events and trending lower mTOR signaling (phospho-S6). Future studies should evaluate implications of our findings, including coagulation system activation and everolimus efficacy in FCD, in larger studies with long-term treatment to better understand molecular and clinical effects.
Article
Clinical Neurology
Orrin Devinsky, Angelica Marmanillo, Theresa Hamlin, Philip Wilken, Daniel Ryan, Conor Anderson, Daniel Friedman, George Todd
Summary: This study examined the safety and efficacy of medical cannabis formulations containing CBD and THC for the treatment of epilepsy. The results showed that there was no significant difference in seizure frequency, duration, postictal duration, or use of rescue medication compared to baseline. There was also no improvement in behavioral disorders or sleep duration. The study found that the medication was generally well tolerated, with few adverse events. However, the doses of CBD used in the study were lower than in previous studies. Larger randomized trials are needed to further investigate the efficacy of CBD:THC products for epilepsy, sleep, and behavior.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Tamar Sapir, Aditya Kshirsagar, Anna Gorelik, Tsviya Olender, Ziv Porat, Ingrid E. Scheffer, David B. Goldstein, Orrin Devinsky, Orly Reiner
Summary: HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with a higher sensitivity of the latter. The expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu's conditional truncation. Pharmaceutical and genetic agents have been identified to partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Abdulwahab Alasfour, Paolo Gabriel, Xi Jiang, Isaac Shamie, Lucia Melloni, Thomas Thesen, Patricia Dugan, Daniel Friedman, Werner Doyle, Orin Devinsky, David Gonda, Shifteh Sattar, Sonya Wang, Eric Halgren, Vikash Gilja
Summary: In this study, the authors analyzed neural activity from two patients using electrocorticography (ECoG) and stereo-electroencephalography (sEEG) recordings. They found multiple neural signal characteristics that discriminate between unstructured and naturalistic behavioral states. The high gamma amplitude and Gaussian process factor analysis (GPFA) were used to demonstrate the discriminability of these features.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Clinical Neurology
Jerzy P. P. Szaflarski, Orrin Devinsky, Merrick Lopez, Yong D. D. Park, Pilar Pichon Zentil, Anup D. D. Patel, Elizabeth A. A. Thiele, Robert T. T. Wechsler, Daniel Checketts, Farhad Sahebkar
Summary: The CBD expanded access program initiated in 2014 provided additional CBD treatment for patients with treatment-resistant epilepsies. The study showed that CBD treatment was effective in reducing seizure frequency and had an acceptable safety profile for long-term use in patients with treatment-resistant epilepsies.
Article
Clinical Neurology
Robert J. Flamini, Anne M. Comi, E. Martina Bebin, Michael G. Chez, Gary Clark, Orrin Devinsky, Shaun A. Hussain, Paul D. Lyons, Anup D. Patel, Jillian L. Rosengard, Farhad Sahebkar, Eric Segal, Laurie Seltzer, Jerzy P. Szaflarski, Arie Weinstock
Summary: The CBD Expanded Access Program provided CBD treatment to patients with treatment-resistant epilepsy and showed a significant reduction in seizure frequency. CBD was well tolerated and effective in treating both convulsive and nonconvulsive seizure types. Controlled trials are needed to further confirm these findings.
Editorial Material
Clinical Neurology
Pavel Klein, Gregory L. Krauss, Bernhard J. Steinhoff, Orrin Devinsky, Michael R. Sperling
Summary: Despite the approval of numerous antiseizure medications (ASMs), a significant number of epilepsy patients still experience seizures. Two new ASMs, cenobamate and fenfluramine, have shown improved efficacy in reducing seizures with sustained results. However, these medications are underutilized, likely due to limited knowledge, access restrictions, and insufficient post-launch information about their efficacy and safety. Addressing these issues can improve seizure control and ultimately reduce morbidity and mortality in epilepsy patients.
Article
Neurosciences
Carly M. O'Donnell, Sara J. J. Swanson, Chad E. E. Carlson, Manoj Raghavan, Peter A. A. Pahapill, Christopher Todd Anderson
Summary: This study explores the use of responsive thalamic stimulation in patients with drug-resistant genetic generalized epilepsies (GGEs). The results show significant improvement in seizure control for two patients and seizure freedom for one patient. These findings suggest that responsive thalamic stimulation may be an effective treatment option for GGEs.
Article
Clinical Neurology
Joseph Sullivan, Lieven Lagae, J. Helen Cross, Orrin Devinsky, Renzo G. Guerrini, Kelly Knupp, Linda Laux, Marina Nikanorova, Tilman Polster, Dinesh Talwar, Berten Ceulemans, Rima M. Nabbout, Gail S. Farfel, Bradley R. Galer, Arnold Gammaitoni, Michael Lock, Anupam E. Agarwal, Ingrid Scheffer, FAiRE DS Study Grp
Summary: This study examined the safety and effectiveness of fenfluramine in treating convulsive seizures in patients with Dravet syndrome. The results showed that patients treated with fenfluramine had lower seizure frequency and longer interval between seizures compared to the placebo group. Common side effects of fenfluramine were observed, but no evidence of severe cardiac or vascular issues was found.
Review
Clinical Neurology
Laura Gould, Victoria Delavale, Caitlin Plovnick, Thomas Wisniewski, Orrin Devinsky
Summary: Febrile seizures are associated with an increased risk of epilepsy and rare cases of sudden unexplained death. Mortality rates varied in different studies, with some reporting no deaths and others identifying a significant percentage of deaths associated with febrile seizures. Minor hippocampal histopathological anomalies were common in sudden deaths with or without a history of febrile seizures. Most electroencephalography (EEG) studies were normal, and neuroimaging studies suggested increased right hippocampal volumes. Longer-term prospective studies are needed to fully understand the outcomes of simple or brief complex febrile seizures.
Article
Multidisciplinary Sciences
Rodrigo Ordonez Sierra, Lizeth Katherine Pedraza, Livia Barcsai, Andrea Pejin, Qun Li, Gabor Kozak, Yuichi Takeuchi, Anett J. Nagy, Magor L. Lorincz, Orrin Devinsky, Gyoergy Buzsaki, Antal Berenyi
Summary: Dysregulated fear reactions can be caused by maladaptive processing of trauma-related memories. By manipulating hippocampal SWRs and cortical oscillations, fear extinction can be enhanced in male rats. The modified fear memories become resistant to recall and do not spontaneously reemerge. This effect is mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. These findings demonstrate the potential of neuromodulation in augmenting extinction learning and provide a new avenue for anxiety disorder treatments.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Heather E. Olson, Sam Amin, Nadia Bahi-Buisson, Orrin Devinsky, Eric D. Marsh, Elia Pestana-Knight, Rajsekar R. Rajaraman, Alex A. Aimetti, Eva Rybak, Fanhui Kong, Ian Miller, Joseph Hulihan, Scott Demarest
Summary: This study reports the 2-year safety and clinical outcomes of ganaxolone treatment in patients with CDD. The results show that ganaxolone significantly reduces major motor seizure frequency and maintains its efficacy and safety over the long term.
Article
Linguistics
Erik Kaestner, Xiaojing Wu, Daniel Friedman, Patricia Dugan, Orrin Devinsky, Chad Carlson, Werner Doyle, Thomas Thesen, Eric Halgren
Summary: The precentral gyrus, as part of the brain, plays a role in transducing visual signals into auditory codes during silent reading. Other regions like the pars opercularis, supramarginal gyrus, and superior temporal gyrus are also involved.
NEUROBIOLOGY OF LANGUAGE
(2022)
Article
Clinical Neurology
Patricia Dugan, Elizabeth Carroll, Jennifer Thorpe, Nathalie Jette, Parul Agarwal, Samantha Ashby, Jane Hanna, Jacqueline French, Orrin Devinsky, Arjune Sen
Summary: The study aimed to understand the impact of COVID-19 on people with epilepsy (PWE) and their caregivers in the US. Findings showed diverse effects, including changes in health, mental health issues, difficulties in medication management, and variations in discussions with healthcare providers between PWE and caregivers. Additionally, post-vaccine period saw more adverse impacts on health, particularly on mental health, compared to pre-vaccine period, highlighting the need for increased emotional support and effective counseling for PWE during the pandemic.