Article
Clinical Neurology
Jessie De Ridder, Birgit Verhelle, Jan Vervisch, Katrien Lemmens, Katarzyna Kotulska, Romina Moavero, Paolo Curatolo, Bernhard Weschke, Kate Riney, Martha Feucht, Pavel Krsek, Rima Nabbout, Anna C. Jansen, Konrad Wojdan, Dorota Domanska-Pakiela, Magdalena Kaczorowska-Frontczak, Christoph Hertzberg, Cyrille H. Ferrier, Sharon Samueli, Barbora Benova, Eleonora Aronica, David J. Kwiatkowski, Floor E. Jansen, Sergiusz Jozwiak, Lieven Lagae
Summary: The timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) are associated with epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). Early recording of ED-EEG can help identify TSC infants at risk of severe epilepsy and those who may benefit from preventive treatment with vigabatrin.
Article
Clinical Neurology
David K. Park, Woojoong Kim, Olivia S. Thornburg, Danielle K. McBrian, Guy M. McKhann, Neil A. Feldstein, Alexis B. Maddocks, Elena Gonzalez, Min Y. Shen, Cigdem Akman, Frank A. Provenzano
Summary: This study demonstrates the feasibility of automatic segmentation of tubers and derivation of tuber burden across brain lobes, providing crucial insights for the treatment and outcome of TSC patients.
Article
Clinical Neurology
Krzysztof Sadowski, Kamil Sijko, Dorota Domanska-Pakiela, Julita Borkowska, Dariusz Chmielewski, Agata Ulatowska, Sergiusz Jozwiak, Katarzyna Kotulska
Summary: Rapamycin can be used to treat drug-resistant epilepsy in children with TSC, and can effectively reduce the frequency of seizures at a certain dosage. The combination with vigabatrin has better efficacy.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yang Zheng, Cenglin Xu, Jinyi Sun, Wenjie Ming, Sijie Dai, Yuying Shao, Xiaoyun Qiu, Menghan Li, Chunhong Shen, Jinghong Xu, Fan Fei, Jiajia Fang, Xuhong Jiang, Guoqing Zheng, Weiwei Hu, Yi Wang, Shuang Wang, Meiping Ding, Zhong Chen
Summary: This study demonstrates the epileptogenic role of the hippocampus in patients with late-stage cortical dysplasia and identifies the involvement of somatostatin-positive interneurons in seizure generalization. This findings provide new insights into the cellular basis of cortical dysplasia-related seizures.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Ekaterina Bychkova, Marina Dorofeeva, Aleksandr Levov, Alexey Kislyakov, Kristina Karandasheva, Vladimir Strelnikov, Kirill Anoshkin
Summary: Patients with tuberous sclerosis complex display cognitive, behavioral, and psychiatric impairments linked to cortical tubers. These tubers are caused by mutations in TSC1 or TSC2 genes, resulting in overactivation of the mTOR pathway. However, the formation of cortical tubers may involve more complex molecular mechanisms that require further investigation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Clinical Neurology
Romina Moavero, Alessandra Voci, Francesca La Briola, Sara Matricardi, Irene Toldo, Maria Margherita Mancardi, Susanna Negrin, Tullio Messana, Luigi Mazzone, Massimiliano Valeriani, Paolo Curatolo, Oliviero Bruni
Summary: The study aimed to assess the prevalence of sleep disorders (SD) in children with Tuberous Sclerosis Complex (TSC), and to evaluate the relationship between sleep, epilepsy, and TSC-associated neuropsychiatric disorders (TAND). The results revealed a high prevalence of SD in children with TSC, with epilepsy not increasing the risk for SD, while TAND showed a strong association with SD.
Article
Neurosciences
Yangshuo Wang, Liu Yuan, Shaohui Zhang, Shuangshuang Liang, Xiaoman Yu, Tinghong Liu, Xiaofeng Yang, Shuli Liang
Summary: FRs can be extensively detected in TSC patients using SEEG, and high FR rate contacts are mostly localized in the junction region of the epileptogenic tuber, aiding in the localization of epileptogenic tubers.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Review
Clinical Neurology
Eleonora Aronica, Nicola Specchio, Mark J. Luinenburg, Paolo Curatolo
Summary: Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, and several mechanisms, including mTOR dysregulation and GABAergic dysfunction, contribute to this process. Antiseizure medications and drugs targeting the mTOR pathway have been effective in treating TSC-associated epilepsy. Early administration of GABAergic drug vigabatrin delays seizure onset, while mTOR inhibitor everolimus reduces seizure frequency. Further trials are needed to optimize the use of everolimus and evaluate other potential antiseizure drugs. Understanding the complex mechanisms of TSC-related epileptogenesis is crucial for prevention and treatment.
Article
Clinical Neurology
Fuyi Zhang, Lingling Xie, Xiaoya He, Xiaojie Song, Helin Zheng, Longlun Wang, Li Jiang
Summary: This study found that increasing abnormality of the cerebral hemispheres, as shown by quantitative MRI analysis including tuber brain proportion (TBP), cortical cyst-like tubers, and diffuse lesions, is associated with more severe epilepsy in patients with tuberous sclerosis complex (TSC). TBP demonstrates strong significance for early-onset epilepsy.
PEDIATRIC NEUROLOGY
(2022)
Article
Clinical Neurology
Victoria-Elisabeth Gruber, Mark J. Luinenburg, Katrin Colleselli, Verena Endmayr, Jasper J. Anink, Till S. Zimmer, Floor Jansen, Peter Gosselaar, Roland Coras, Theresa Scholl, Ingmar Blumcke, Jose Pimentel, Johannes A. Hainfellner, Romana Hoeftberger, Karl Roessler, Martha Feucht, Jackelien Scheppingen, Eleonora Aronica, Angelika Muehlebner
Summary: This study found that C3 protein expression was significantly upregulated in white and gray matter lesions of TSC and FCD2B, while synaptophysin showed a remarkable increase in the white matter of both diseases. Confocal imaging revealed colocalization of complement factors with various cell types, suggesting that complement pathway overactivation may play a role in the pathogenesis of TSC and FCD2B.
Review
Clinical Neurology
Susanne Schubert-Bast, Adam Strzelczyk
Summary: Tuberous sclerosis complex is a rare genetic disorder caused by mutations in TSC1 or TSC2 genes, characterized by benign tumors in multiple organs and neurological manifestations. Epilepsy is a common symptom with significant morbidity and mortality; preventative treatment is crucial, with drugs like vigabatrin possibly reducing the risk of seizures.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2021)
Article
Clinical Neurology
Thomas Larrew, Jesse Skoch, S. Katie Z. Ihnen, Ravindra Arya, Katherine D. Holland, Jeffrey R. Tenney, Paul S. Horn, James L. Leach, Darcy A. Krueger, Hansel M. Greiner, Francesco T. Mangano
Summary: In comparison between SDG and SEEG cohorts, the SEEG group appeared to receive more aggressive management with higher multifocality, prior surgical interventions, baseline AEDs, and bilateral invasive monitoring. Despite this, the SEEG cohort showed similar seizure outcomes and a trend towards increased safety, making it a potential option for a wide range of TSC patients.
NEUROSURGICAL FOCUS
(2022)
Article
Clinical Neurology
Charlotte Tye, Fiona S. McEwen, Holan Liang, Emma Woodhouse, Lisa Underwood, Elizabeth Shephard, Edward D. Barker, Fintan Sheerin, Nicholas Higgins, Juul Steenbruggen, Patrick Bolton
Summary: This study found an association between attention-deficit/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC), which may be mediated by epilepsy. The researchers also identified a developmental pathway from genetic mutation to cortical tuber load to epileptic spasm severity in infancy, ultimately leading to ADHD symptoms in middle childhood and adolescence.
Article
Neurosciences
Kefu Wu, Jiong Yue, Kaifeng Shen, Jiaojiang He, Gang Zhu, Shiyong Liu, Hui Yang, Chun-Qing Zhang
Summary: The study found that the mRNA and protein levels of FGF13 were significantly higher in cortical tubers from patients with TSC compared to control cortices. Immunohistochemical results showed strong FGF13 immunoreactivity in abnormal cells, and double-label immunofluorescence analyses confirmed that FGF13 was mainly localized in neurons in the TSC samples. The overexpression and distribution pattern of FGF13 may be related to intractable epilepsy caused by TSC.
NEUROSCIENCE LETTERS
(2021)
Article
Clinical Neurology
Till S. Zimmer, Anatoly Korotkov, Susan Zwakenberg, Floor E. Jansen, Fried J. T. Zwartkruis, Nicholas R. Rensing, Michael Wong, Angelika Muhlebner, Erwin A. van Vliet, Eleonora Aronica, James D. Mills
Summary: This study identified a novel transcription factor, SPI1/PU.1, which is involved in the pro-inflammatory gene expression in malformed cells in TSC and FCD 2b. The expression of SPI1/PU.1 is associated with mTOR activation, oxidative stress, and seizure development, providing potential therapeutic targets for genetic epilepsies.
Article
Clinical Neurology
Smriti Patodia, Alyma Somani, Joan Liu, Alice Cattaneo, Beatrice Paradiso, Maria Garcia, Muhammad Othman, Beate Diehl, Orrin Devinsky, James D. Mills, Jackie Foong, Maria Thom
Summary: Multiple lines of evidence suggest a link between deficient serotonin function and SUDEP, with chronic treatment using serotonin reuptake inhibitors shown to reduce the risk factors associated with SUDEP. Decreased medullary serotonergic neurons, which regulate respiration in response to hypercapnia, have been found in post-mortem SUDEP cases. Additionally, the high innervation of serotonergic neurons in the amygdala and hippocampus, regions involved in seizure-related respiratory dysregulation, further supports the potential involvement of altered serotonergic networks in SUDEP.
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
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.