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epilepsy pathophysiology

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https://www.readbyqxmd.com/read/28334922/scn2a-deletion-improves-survival-and-brain-heart-dynamics-in-the-kcna1-null-mouse-model-of-sudden-unexpected-death-in-epilepsy-sudep
#1
Vikas Mishra, Bharat K Karumuri, Nicole M Gautier, Rui Liu, Timothy N Hutson, Stephanie L Vanhoof-Villalba, Ioannis Vlachos, Leonidas Iasemidis, Edward Glasscock
People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology, and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28316319/epileptic-spasms-in-paediatric-post-traumatic-epilepsy-at-a-tertiary-referral-centre
#2
Jun T Park, Harry T Chugani
To recognize epileptic spasms (ES) as a seizure type after traumatic brain injury (TBI), accidental or non-accidental, in infants and children. In the process, we aim to gain some insight into the mechanisms of epileptogenesis in ES. A retrospective electronic chart review was performed at the Children's Hospital of Michigan from 2002 to 2012. Electronic charts of 321 patients were reviewed for evidence of post-traumatic epilepsy. Various clinical variables were collected including age at TBI, mechanism of trauma, severity of brain injury, electroencephalography/neuroimaging data, and seizure semiology...
March 17, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/28306623/risk-of-epilepsy-in-individuals-with-posttraumatic-stress-disorder-a-nationwide-longitudinal-study
#3
Yu-Hsiung Chen, Han-Ting Wei, Ya-Mei Bai, Ju-Wei Hsu, Kai-Lin Huang, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Yi-Hui Wu, Tai-Long Pan, Tzeng-Ji Chen, Shih-Jen Tsai, Mu-Hong Chen
OBJECTIVE: Several cross-sectional studies reported a relationship between post-traumatic stress disorder (PTSD) and epilepsy. However, the temporal association between PTSD and epilepsy has rarely been investigated. We hypothesized that the risk of developing epilepsy later in life would be higher in patients with PTSD than in those without PTSD. METHODS: Using the Taiwan National Health Insurance Research Database, 6425 individuals with PTSD and 24,980 age-/sex-matched controls were enrolled between 2002 and 2009 in our study, and followed up to the end of 2011...
March 17, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28293101/new-developments-in-the-management-of-partial-onset-epilepsy-role-of-brivaracetam
#4
REVIEW
Giangennaro Coppola, Giulia Iapadre, Francesca Felicia Operto, Alberto Verrotti
Currently, a number of novel anticonvulsant drugs, the so-called third generation, are in various stages of development. Several of them are already available or in ongoing clinical trials. These new compounds should take advantage of new insights into the basic pathophysiology of epileptogenesis, drug metabolism and drug interactions. Many of them still need to be further evaluated mainly in real-world observational trials and registries. Among newer anticonvulsant drugs for partial-onset seizures (POSs), rufinamide, lacosamide, eslicarbazepine and perampanel are those new treatment options for which more substantial clinical evidence is currently available, both in adults and, to some extent, in children...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28290248/the-%C3%AE-2%C3%AE-subunit-and-absence-epilepsy-beyond-calcium-channels
#5
Roberta Celli, Ines Santolini, Michela Guiducci, Gilles van Luijtelaar, Pasquale Parisi, Pasquale Striano, Roberto Gradini, Giuseppe Battaglia, Richard T Ngomba, Ferdinando Nicoletti
Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The α2δ subunit is a component of high voltage-activated VSCCs (i...
March 8, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28286918/altered-effective-connectivity-network-in-childhood-absence-epilepsy-a-multi-frequency-meg-study
#6
Caiyun Wu, Jing Xiang, Wenwen Jiang, Shuyang Huang, Yuan Gao, Lu Tang, Yuchen Zhou, Di Wu, Qiqi Chen, Zheng Hu, Xiaoshan Wang
Using multi-frequency magnetoencephalography (MEG) data, we investigated whether the effective connectivity (EC) network of patients with childhood absence epilepsy (CAE) is altered during the inter-ictal period in comparison with healthy controls. MEG data from 13 untreated CAE patients and 10 healthy controls were recorded. Correlation analysis and Granger causality analysis were used to construct an EC network at the source level in eight frequency bands. Alterations in the spatial pattern and topology of the network in CAE were investigated by comparing the patients with the controls...
March 12, 2017: Brain Topography
https://www.readbyqxmd.com/read/28284396/pyridoxal-phosphate-supplementation-in-neuropediatric-disorders
#7
Elisenda Cortès-Saladelafont, Marta Molero-Luis, Hsjd Working Group, Rafael Artuch, Àngels García-Cazorla
Pyridoxal phosphate (PLP) is the active form of vitamin B6 and a cofactor in many enzyme reactions including neurotransmitter metabolism. PLP metabolism disturbances may mostly lead to refractory seizures. In this report, we review the main pathophysiological factors related with PLP deficiency and our experience in PLP treatment in pediatric patients with low-normal cerebrospinal fluid PLP values who presented epilepsy. Only one case had a definite diagnosis (Phelan-McDermid syndrome). The results of extensive metabolic workups and targeted genetic studies were normal for all patients...
November 2016: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28284393/epilepsy-in-inborn-errors-of-metabolism-with-therapeutic-options
#8
Jaume Campistol
Inborn errors of metabolism (IEM) are rare conditions that represent more than 1000 diseases, with a global prevalence of approximately 1:2000 individuals. Approximately, 40%-60% of IEM may present with epilepsy as one of the main neurologic signs. Epilepsy in IEM may appear at any age (fetal, newborn, infant, adolescent, or even adult). Different pathophysiological mechanisms may be responsible for the clinical phenotype, such as disturbances in energy metabolism (mitochondrial and fatty oxidation disorders, GLUT-1, and cerebral creatine deficiency), accumulation of complex molecules (lysosomal storage disorders), toxic mechanisms (organic acidurias and urea cycle disorders), or impairment of neurotransmission...
November 2016: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28279785/epigenetic-interventions-for-epileptogenesis-a-new-frontier-for-curing-epilepsy
#9
REVIEW
Iyan Younus, Doodipala Samba Reddy
This article highlights the emerging therapeutic potential of specific epigenetic modulators as promising antiepileptogenic or disease-modifying agents for curing epilepsy. Currently, there is an unmet need for antiepileptogenic agents that truly prevent the development of epilepsy in people at risk. There is strong evidence that epigenetic signaling, which exerts high fidelity regulation of gene expression, plays a crucial role in the pathophysiology of epileptogenesis and chronic epilepsy. These modifications are not hard-wired into the genome and are constantly reprogrammed by environmental influences...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28272506/a-murine-model-to-study-epilepsy-and-sudep-induced-by-malaria-infection
#10
Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff
One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271336/the-relationship-between-headaches-with-epileptic-and-non-epileptic-seizures-a-narrative-review
#11
REVIEW
William S Kingston, Todd J Schwedt
PURPOSE OF REVIEW: The purpose of this review is to examine the relationship between headaches and epilepsy as well as headaches and psychogenic non-epileptic seizures (PNES). Emphasis was placed on clinical characteristics, pathophysiology, and treatment. RECENT FINDINGS: Epilepsy and headaches are common disorders that co-occur more often than would be expected by chance. There are some overlapping clinical features between migraine and epilepsy as well as evidence for shared underlying mechanisms...
March 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28241168/association-of-depression-and-treated-depression-with-epilepsy-and-seizure-outcomes-a-multicohort-analysis
#12
Colin B Josephson, Mark Lowerison, Isabelle Vallerand, Tolulope T Sajobi, Scott Patten, Nathalie Jette, Samuel Wiebe
Importance: A bidirectional relationship exists between epilepsy and depression. However, any putative biological gradient between depression severity and the risk of epilepsy, and the degree to which depression mediates the influence of independent risk factors for epilepsy, has yet to be examined. Objective: To determine the effect of depression on the risk of epilepsy and seizure outcomes. Design, Setting, and Participants: An observational study of a population-based primary care cohort (all patients free of prevalent depression and epilepsy at 18-90 years of age who were active after the Acceptable Mortality Reporting date in The Health Improvement Network database) and a prospectively collected tertiary care cohort (all patients whose data were prospectively collected from the Calgary Comprehensive Epilepsy Programme)...
February 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28238620/coexistence-of-childhood-absence-epilepsy-and-benign-epilepsy-with-centrotemporal-spikes-a-case-series
#13
Alberto Verrotti, Sara Casciato, Alberto Spalice, Marco Carotenuto, Pasquale Striano, Pasquale Parisi, Nelia Zamponi, Salvatore Savasta, Victoria Elisa Rinaldi, Renato D'Alonzo, Federico Mecarini, Anthony J Ritaccio, Giancarlo Di Gennaro
AIM: Childhood absence epilepsy (CAE) and benign childhood epilepsy with centrotemporal spikes (BECTS) are the most common forms of childhood epilepsy. Recent studies in animal models suggest that the two phenotypes may represent a neurobiological continuum. Although the coexistence of CAE and BECTS has been reported, this issue remains controversial. The purpose of this study was to analyse the electro-clinical characteristics of a group of children with contemporary or subsequent features of absence seizures and focal seizures consistent with BECTS...
February 14, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28237318/strokes-are-possible-complications-of-cannabinoids-use
#14
REVIEW
Valérie Wolff, Emilie Jouanjus
It is critically important to identify all factors that may play a role in the recent increase of the incidence of stroke among the young population. Considering the worldwide use of cannabinoids (cannabis and synthetic cannabinoids), the recent legalization of their consumption in some countries, and their supposed involvement in cardiovascular events, we evaluated their role in the occurrence of neurovascular complications among the young. Ninety-eight patients were described in the literature as having a cannabinoids-related stroke (85 after cannabis use and 13 after synthetic cannabinoids)...
February 23, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28236431/catamenial-like-seizure-exacerbation-in-mice-with-targeted-ablation-of-extrasynaptic-%C3%AE-gaba-a-receptors-in-the-brain
#15
Bryan L Clossen, Doodipala Samba Reddy
Neurosteroids play a key role in catamenial epilepsy, a menstrual cycle-related seizure clustering in women with epilepsy. While neurosteroids act on all GABA-A receptor isoforms, they cause greater effects on extrasynaptic δGABA-A receptors that mediate tonic inhibition in the brain. Previously, we identified a potential GABA-A receptor mechanism for catamenial epilepsy. However, the precise functional role of extrasynaptic δGABA-A receptors in the pathophysiology of catamenial epilepsy remains unclear. In this study, we utilized mice lacking extrasynaptic δGABA-A receptors (δKO) to investigate whether reduction of tonic inhibition affects catamenial seizure susceptibility or intensity...
February 25, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28236069/cerebrospinal-fluid-neuron-specific-enolase-interleukin-1%C3%AE-and-erythropoietin-concentrations-in-children-after-seizures
#16
Ling-Min Shi, Rui-Jie Chen, Hui Zhang, Chun-Ming Jiang, Jian Gong
PURPOSE: In the present study, the levels of neuron-specific enolase (NSE), interleukin-1β (IL-1β), and erythropoietin (EPO) in cerebrospinal fluid (CSF) in children with idiopathic epilepsy were measured to illuminate the relationships between these markers with idiopathic epilepsy. METHODS: Eighty-five children from 6 months to 12.5 years of age with single, previously undiagnosed, and untreated idiopathic epilepsy were participated in this study. The concentrations of CSF NSE, 1L-1β, and EPO were measured by specific ELISA methods...
February 24, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28229394/epileptic-encephalopathies-clinical-syndromes-and-pathophysiological-concepts
#17
REVIEW
Markus von Deimling, Ingo Helbig, Eric D Marsh
Epileptic encephalopathies account for a large proportion of the intractable early-onset epilepsies and are characterized by frequent seizures and poor developmental outcome. The epileptic encephalopathies can be loosely divided into two related groups of named syndromes. The first comprises epilepsies where continuous EEG changes directly result in cognitive and developmental dysfunction. The second includes patients where cognitive impairment is present at seizure onset and is due to the underlying etiology but the epileptic activity may then worsen the cognitive abilities over time...
February 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28222432/extracellular-hmgb1-modulates-glutamate-metabolism-associated-with-kainic-acid-induced-epilepsy-like-hyperactivity-in-primary-rat-neural-cells
#18
Yuji Kaneko, Colleen Pappas, Teresita Malapira, Fernando Ĺ Vale, Naoki Tajiri, Cesar V Borlongan
BACKGROUND/AIMS: Neuroinflammatory processes have been implicated in the pathophysiology of seizure/epilepsy. High mobility group box 1 (HMGB1), a non-histone DNA binding protein, behaves like an inflammatory cytokine in response to epileptogenic insults. Kainic acid (KA) is an excitotoxic reagent commonly used to induce epilepsy in rodents. However, the molecular mechanism by which KA-induced HMGB1 affords the initiation of epilepsy, especially the role of extracellular HMGB1 in neurotransmitter expression, remains to be elucidated...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222338/effect-of-synaptic-adhesion-like-molecule-3-on-epileptic-seizures-evidence-from-animal-models
#19
Jie Li, Ling Chen, Na Wang, Guohui Jiang, Yuqing Wu, Yi Zhang
Axonal sprouting and synaptic reorganization are the primary pathophysiological characteristics of epilepsy. Recent studies demonstrated that synaptic adhesion-like molecule 3 (SALM3) is highly expressed in the central nervous system and plays important roles in neurite outgrowth, branching, and axon guidance, mechanisms that are also observed in epilepsy. However, the expression of SALM3 in the epileptic brain and the effect of SALM3 in the pathogenesis of epilepsy remain unclear. The aims of this study were to investigate SALM3 expression in rat models of epilepsy and to explore the functional significance of SALM3 in epilepsy...
February 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28222113/differentially-expressed-proteins-underlying-childhood-cortical-dysplasia-with-epilepsy-identified-by-itraq-proteomic-profiling
#20
Lu Qin, Xi Liu, Shiyong Liu, Yi Liu, Yixuan Yang, Hui Yang, Yangmei Chen, Lifen Chen
Cortical dysplasia accounts for at least 14% of epilepsy cases, and is mostly seen in children. However, the understanding of molecular mechanisms and pathogenesis underlying cortical dysplasia is limited. The aim of this cross-sectional study is to identify potential key molecules in the mechanisms of cortical dysplasia by screening the proteins expressed in brain tissues of childhood cortical dysplasia patients with epilepsy using isobaric tags for relative and absolute quantitation-based tandem mass spectrometry compared to controls, and several differentially expressed proteins that are not reported to be associated with cortical dysplasia previously were selected for validation using real-time polymerase chain reaction, immunoblotting and immunohistochemistry...
2017: PloS One
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