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epilepsy pathophysiology

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https://www.readbyqxmd.com/read/28799512/modulation-of-gabaa-receptors-in-the-treatment-of-epilepsy
#1
Eleonora Palma, Gabriele Ruffolo, Pierangelo Cifelli, Cristina Roseti, Erwin A van Vliet, Eleonora Aronica
BACKGROUND: A variety of evidence suggested that an imbalance in excitatory and inhibitory neurotransmission could be one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Understanding the causes of this imbalance may provide essential insight into the basic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Accordingly, GABA is the most important inhibitory neurotransmitter in the CNS and its receptors (e.g., GABAARs) can still be relevant targets of new antiepileptic drugs (AEDs)...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28794080/the-immune-system-in-pediatric-seizures-and-epilepsies
#2
REVIEW
Christian M Korff, Russell C Dale
The relation between the immune system and epilepsy has been studied for a long time. Immune activation may precede or follow the appearance of seizures. Depending on the situation, the innate and acquired immunity may be involved to various degrees. The intense, ongoing research has opened encouraging management and therapeutic perspectives for a significant number of patients suffering from seizures. These include the use of various drugs and less conventional approaches with anti-inflammatory or immunomodulatory properties...
August 9, 2017: Pediatrics
https://www.readbyqxmd.com/read/28779863/neurological-complications-of-cardiac-disease
#3
Nandini Madan, Karen S Carvalho
This article focuses on the complex interactions between the cardiovascular and neurologic systems. Initially, we focus on neurological complications in children with congenital heart disease both secondary to the underlying cardiac disease and complications of interventions. We later discuss diagnosis and management of common syncope syndromes with emphasis on vasovagal syncope. We also review the diagnosis, classification, and management of children and adolescents with postural orthostatic tachycardia syndrome...
February 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28762469/impairment-of-gabaergic-system-contributes-to-epileptogenesis-in-glutaric-acidemia-type-i
#4
Mayara Vendramin Pasquetti, Letícia Meier, Samanta Loureiro, Marcelo Ganzella, Bernardo Junges, Letícia Barbieri Caus, Alexandre Umpierrez Amaral, David M Koeller, Stephen Goodman, Michael Woontner, Diogo Onofre Gomes de Souza, Moacir Wajner, Maria Elisa Calcagnotto
OBJECTIVES: Glutaric acidemia type I (GA-I) is an inherited neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) and characterized by increased levels of glutaric, 3-OH-glutaric, and glutaconic acids in the brain parenchyma. The increment of these organic acids inhibits glutamate decarboxylase (GAD) and consequently lowers the γ-aminobutyric acid (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during development, including epilepsy, especially following an acute encephalopathy outbreak...
August 1, 2017: Epilepsia
https://www.readbyqxmd.com/read/28755452/extrapolating-evidence-of-antiepileptic-drug-efficacy-in-adults-to-children-%C3%A2-2%C3%A2-years-of-age-with-focal-seizures-the-case-for-disease-similarity
#5
John M Pellock, Alexis Arzimanoglou, O'Neill D'Cruz, Gregory L Holmes, Douglas Nordli, Shlomo Shinnar
Expediting pediatric access to new antiseizure drugs is particularly compelling, because epileptic seizures are the most common serious neurological symptom in children. Analysis of antiepileptic drug (AED) efficacy outcomes of randomized controlled trials, conducted during the past 20 years in different populations and a broad range of study sites and countries, has shown considerable consistency for each drug between adult and pediatric populations. Historically, the majority of regulatory approvals for AEDs have been for seizure types and not for specific epilepsy syndromes...
July 29, 2017: Epilepsia
https://www.readbyqxmd.com/read/28752060/sleep-onset-uncovers-thalamic-abnormalities-in-patients-with-idiopathic-generalised-epilepsy
#6
Andrew P Bagshaw, Joanne R Hale, Brunno M Campos, David T Rollings, Rebecca S Wilson, Marina K M Alvim, Ana Carolina Coan, Fernando Cendes
The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28747448/movement-disorder-in-gnao1-encephalopathy-associated-with-gain-of-function-mutations
#7
Huijie Feng, Benita Sjögren, Behirda Karaj, Vincent Shaw, Aysegul Gezer, Richard R Neubig
OBJECTIVE: To define molecular mechanisms underlying the clinical spectrum of epilepsy and movement disorder in individuals with de novo mutations in the GNAO1 gene. METHODS: We identified all GNAO1 mutations reported in individuals with epilepsy (early infantile epileptiform encephalopathy 17) or movement disorders through April 2016; 15 de novo mutant alleles from 25 individuals were introduced into the Gαo subunit by site-directed mutagenesis in a mammalian expression plasmid...
July 26, 2017: Neurology
https://www.readbyqxmd.com/read/28729114/altered-intrinsic-functional-connectivity-in-the-latent-period-of-epileptogenesis-in-a-temporal-lobe-epilepsy-model
#8
Hyoin Lee, Seungmoon Jung, Peter Lee, Yong Jeong
The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition...
July 17, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28719803/elevated-sterol-regulatory-elementary-binding-protein-1-and-glua2-levels-in-the-hippocampal-nuclear-fraction-of-genetic-absence-epilepsy-rats-from-strasbourg
#9
Sathiya Sekar, Entesar Omran, Venkat Gopalakrishnan, John G Howland, Terrance P Snutch, Changiz Taghibiglou
Studies in animal models and human tissues show that nuclear translocation of sterol regulatory element binding protein 1 (SREBP1) and glutamate A2 subunit (GluA2) of cell-surface AMPA receptor (AMPAR) trigger neuronal excitotoxicity-induced apoptosis in stroke. However, it is not known whether a similar type of underlying pathophysiology occurs in absence epilepsy. To explore this issue, we examined the levels of mature SREBP1, GluA2, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), p53, and activated to total caspase 3 ratio in nuclear fractions (NF) of hippocampal homogenate from 8 to 10 week old male Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and non-epileptic control (NEC) strains...
July 12, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28699523/altered-homeostatic-functions-in-reactive-astrocytes-and-their-potential-as-a-therapeutic-target-after-brain-ischemic-injury
#10
Helena Pivonkova, Miroslava Anderova
Brain ischemic injury represents one of the greatest medical challenges for the aging population in developed countries, yet despite strong efforts, possibilities to treat ischemic injury still remain poor. Stroke, the most common type of brain ischemic injury in humans, is caused by brain artery occlusion, and represents a focal form of ischemia, which leads to neuronal loss in the ischemic core, and glial scar formation in the penumbral region around the core. Such glial scar mainly comprises reactive astrocytes, reactive NG2 glia and activated microglia...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28688882/neuroimaging-in-animal-models-of-epilepsy
#11
REVIEW
Daniele Bertoglio, Jeroen Verhaeghe, Stefanie Dedeurwaerdere, Olli Gröhn
Epilepsy is one of the most common chronic neurological conditions worldwide. The current poor understanding and lack of reliable biomarkers of the epileptogenic process are the major limitations in the development of anti-epileptic drugs that are able to prevent or modify the underlying disease. The rapid progress in advanced imaging technologies has expanded our opportunities to study the disease in animal models of epilepsy by means of non-invasive research tools. Here we review the advances of different in vivo imaging techniques, including magnetic resonance-based and nuclear imaging-based modalities, in animal models of epilepsy...
July 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28688606/a-clinical-and-neurophysiological-motor-signature-of-unverricht-lundborg-disease
#12
E Hainque, A Blancher, V Mesnage, S Rivaud-Pechoux, A Bertrand, S Dupont, V Navarro, E Roze, I Gourfinkel-An, E Apartis
OBJECTIVES: Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time, contributing along with myoclonus to motor disability. The purpose of the present work was to clarify the motor and neurophysiological characteristics of ULD patients. METHODS: Nine patients with genetically proven ULD were evaluated clinically (medical history collected from patient charts, the Scale for the Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale)...
July 5, 2017: Revue Neurologique
https://www.readbyqxmd.com/read/28682842/dual-isotope-spect-study-with-epilepsy-patients-using-semiconductor-spect-system
#13
Tohru Shiga, Atsuro Suzuki, Kotarou Sakurai, Tsugiko Kurita, Wataru Takeuchi, Takuya Toyonaga, Kenji Hirata, Keiji Kobashi, Chietsugu Katoh, Naoki Kubo, Nagara Tamaki
PURPOSE: We developed a prototype CdTe SPECT system with 4-pixel matched collimator for brain study. This system provides high-energy-resolution (6.6%), high-sensitivity (220 cps/MBq/head), and high-spatial-resolution images. The aim of this study was to evaluate dual-isotope study of CBF and central benzodiazepine receptor (BZR) images using Tc-ECD and I-IMZ with the new SPECT system in patients with epilepsy comparing with single-isotope study using the conventional scintillation gamma camera...
September 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28681378/update-on-the-mechanisms-and-roles-of-high-frequency-oscillations-in-seizures-and-epileptic-disorders
#14
REVIEW
Premysl Jiruska, Catalina Alvarado-Rojas, Catherine A Schevon, Richard Staba, William Stacey, Fabrice Wendling, Massimo Avoli
High-frequency oscillations (HFOs) are a type of brain activity that is recorded from brain regions capable of generating seizures. Because of the close association of HFOs with epileptogenic tissue and ictogenesis, understanding their cellular and network mechanisms could provide valuable information about the organization of epileptogenic networks and how seizures emerge from the abnormal activity of these networks. In this review, we summarize the most recent advances in the field of HFOs and provide a critical evaluation of new observations within the context of already established knowledge...
August 2017: Epilepsia
https://www.readbyqxmd.com/read/28675563/neuroinflammatory-targets-and-treatments-for-epilepsy-validated-in-experimental-models
#15
Eleonora Aronica, Sebastian Bauer, Yuri Bozzi, Matteo Caleo, Raymond Dingledine, Jan A Gorter, David C Henshall, Daniela Kaufer, Sookyong Koh, Wolfgang Löscher, Jean-Pierre Louboutin, Michele Mishto, Braxton A Norwood, Eleonora Palma, Michael O Poulter, Gaetano Terrone, Annamaria Vezzani, Rafal M Kaminski
A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets...
July 2017: Epilepsia
https://www.readbyqxmd.com/read/28675258/narcolepsy-cataplexy-and-psychosis-a-case-study
#16
F Canellas-Dols, C Delgado, C Arango-Lopez, R Peraita-Adrados
AIMS: To report a challenging patient a girl who developed narcolepsyy with cataplexy (NT1) and a psychosis during adolescence. To discuss diagnostic and therapeutic challenges of the comorbid cases. CASE REPORT: A 14-year-old girl was referred to Sleep and Epilepsy Unit for excessive daytime sleepiness, impaired nocturnal sleep, binge eating and weight gain, over the last year. After being diagnosed with a NT1 the patient was treated with modafinil and sodium oxybate...
July 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28673685/controversies-in-the-treatment-of-seizures-associated-with-neurocysticercosis
#17
REVIEW
Gagandeep Singh, Ravina Sharma
Seizures are the commonest manifestation of brain parenchymal cysticercosis. In terms of pathophysiological basis and prognostic significance of the seizures, a distinction might be applied between viable cysts, solitary cysticercus granuloma and calcific cysticerci. A number of uncertainties shroud the management of seizures in people with neurocysticercosis (NCC). Although antihelminthic treatment is effective in eliminating viable cysts and possibly cysticercus granulomas, its effect on seizure outcome remains uncertain...
June 30, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28669405/loss-of-function-and-gain-of-function-mutations-in-kcnq5-cause-intellectual-disability-or-epileptic-encephalopathy
#18
Anna Lehman, Samrat Thouta, Grazia M S Mancini, Sakkubai Naidu, Marjon van Slegtenhorst, Kirsty McWalter, Richard Person, Jill Mwenifumbo, Ramona Salvarinova, Ilaria Guella, Marna B McKenzie, Anita Datta, Mary B Connolly, Somayeh Mojard Kalkhoran, Damon Poburko, Jan M Friedman, Matthew J Farrer, Michelle Demos, Sonal Desai, Thomas Claydon
KCNQ5 is a highly conserved gene encoding an important channel for neuronal function; it is widely expressed in the brain and generates M-type current. Exome sequencing identified de novo heterozygous missense mutations in four probands with intellectual disability, abnormal neurological findings, and treatment-resistant epilepsy (in two of four). Comprehensive analysis of this potassium channel for the four variants expressed in frog oocytes revealed shifts in the voltage dependence of activation, including altered activation and deactivation kinetics...
July 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28667575/animal-and-cellular-models-of-familial-dysautonomia
#19
REVIEW
Frances Lefcort, Marc Mergy, Sarah B Ohlen, Yumi Ueki, Lynn George
Since Riley and Day first described the clinical phenotype of patients with familial dysautonomia (FD) over 60 years ago, the field has made considerable progress clinically, scientifically, and translationally in treating and understanding the etiology of FD. FD is classified as a hereditary sensory and autonomic neuropathy (HSAN type III) and is both a developmental and a progressive neurodegenerative condition that results from an autosomal recessive mutation in the gene IKBKAP, also known as ELP1. FD primarily impacts the peripheral nervous system but also manifests in central nervous system disruption, especially in the retina and optic nerve...
August 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/28658047/a-magnetoencephalography-investigation-of-coherence-source-imaging-in-panic-disorder
#20
Nash N Boutros, Seung-Suk Kang, Kathleen M Gustafson, Zach Thomas, Kemal Sagduyu, Jocelyn Pearson, Susan M Bowyer
Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined...
September 6, 2017: Neuroreport
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