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epilepsy pathophysiology

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https://www.readbyqxmd.com/read/28427841/localized-shape-abnormalities-in-the-thalamus-and-pallidum-are-associated-with-secondarily-generalized-seizures-in-mesial-temporal-lobe-epilepsy
#1
Linglin Yang, Hong Li, Lujia Zhu, Xinfeng Yu, Bo Jin, Cong Chen, Shan Wang, Meiping Ding, Minming Zhang, Zhong Chen, Shuang Wang
Mesial temporal lobe epilepsy (mTLE) is a common type of drug-resistant epilepsy and secondarily generalized tonic-clonic seizures (sGTCS) have devastating consequences for patients' safety and quality of life. To probe the mechanism underlying the genesis of sGTCS, we investigated the structural differences between patients with and without sGTCS in a cohort of mTLE with radiologically defined unilateral hippocampal sclerosis. We performed voxel-based morphometric analysis of cortex and vertex-wise shape analysis of subcortical structures (the basal ganglia and thalamus) on MRI of 39 patients (21 with and 18 without sGTCS)...
April 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28427028/terminal-seizure-frequency-and-its-relation-to-sudep
#2
Deng Chen, Yang Si, Jun He, Ying Deng, Tao Chen, Yu-Jin He, Ling Liu, Dong Zhou
BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with epilepsy. Several risk factors have been implicated, including early age of onset, tonic-clonic seizures and antiepileptic drugs. However, whether patients who die from SUDEP have a greater frequency of seizures in the few months before death is unclear. We investigated the terminal seizure frequency and its relation to SUDEP among a large group of patients with tonic-clonic seizures in rural West China...
April 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28427026/epilepsy-and-headaches-further-evidence-of-a-link
#3
Asli Ece Çilliler, Hayat Güven, Selim Selçuk Çomoğlu
OBJECTIVE: Epilepsy and primary headaches are two of the most common neurologic conditions that share some common clinical characteristics, and can affect individuals of all age groups around the world. In recent years, the underlying pathophysiologic mechanisms potentially common to both headaches and epileptic seizures have been the subject of scrutiny. The objective of this study was to determine the frequencies and types of headaches in patients with epilepsy, and evaluate any temporal relationship with epileptic seizures...
April 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28425097/seizure-frequency-correlates-with-loss-of-dentate-gyrus-gabaergic-neurons-in-a-mouse-model-of-temporal-lobe-epilepsy
#4
Paul S Buckmaster, Emily Abrams, Xiling Wen
Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. The present study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31 - 61 d earlier were video-monitored for spontaneous, convulsive seizures 9 h/d every day for 24 - 36 d...
April 20, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28420012/vitamin-b6-responsive-epilepsy-due-to-a-novel-kcnq2-mutation
#5
Kerstin Alexandra Klotz, Johannes R Lemke, Rudolf Korinthenberg, Julia Jacobs
Mutations in KCNQ2, encoding for subunits of potassium channels, are known to cause neonatal epileptic encephalopathy (NEE). Therapeutic options for these children are often limited. Recently, there are indications that some patients with KCNQ2 NEE show seizure response to vitamin B6 (VB6) therapy. We present a young infant with severe KCNQ2 encephalopathy resulting from a novel de novo mutation (c.1023G>C; p.(Gln341His)). In our patient, VB6 responsiveness could be demonstrated clearly by remarkable seizure-response to VB6 therapy and seizure exacerbation to discontinuation of VB6 therapy...
April 18, 2017: Neuropediatrics
https://www.readbyqxmd.com/read/28416445/%C3%AE-o-conotoxin-gexiva-disulfide-bond-isomers-exhibit-differential-sensitivity-for-various-nicotinic-acetylcholine-receptors-but-retain-potency-and-selectivity-for-the-human-%C3%AE-9%C3%AE-10-subtype
#6
REVIEW
Dongting Zhangsun, Xiaopeng Zhu, Quentin Kaas, Yong Wu, David J Craik, J Michael McIntosh, Sulan Luo
Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible isomers...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28410466/history-of-surgery-for-temporal-lobe-epilepsy
#7
REVIEW
Ali A Asadi-Pooya, Cyrus Rostami
The history of epilepsy and its treatment goes back to ancient times when it included medicinal herbs, lifestyle modifications, and even surgery. Trepanation is considered the oldest surgical procedure for the treatment of epilepsy. The first series of temporal lobectomies for the treatment of drug-resistant epilepsy were reported by Penfield and Flanigin (1950). During the years since then, neuroimaging and other technologies have had remarkable and revolutionary progress. This progress has resulted in tremendous advancements in understanding the underlying causes and pathophysiology of epilepsies...
April 11, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28403704/nursing-management-of-reflex-anoxic-seizures-in-children
#8
Neal Patel, Rowan Kerr-Liddell, Louise Challis, Siba Prosad Paul
Children who present with transient loss of consciousness (T-LOC) are often first seen in emergency departments (EDs). Reflex anoxic seizure (RAS), vasovagal syncope and prolonged respiratory apnoea are benign, syncopal events that can be generally managed by explanation and reassurance. RAS is a short, paroxysmal, self-reverting episode of asystole that is triggered by pain, fear or anxiety and is caused by increased vagal response. It is an important differential diagnosis in pre-school age children who present with T-LOC, but is often underdiagnosed and can sometimes be misdiagnosed as epilepsy...
April 13, 2017: Emergency Nurse: the Journal of the RCN Accident and Emergency Nursing Association
https://www.readbyqxmd.com/read/28389651/unique-residues-in-the-atp-gated-human-p2x7-receptor-define-a-novel-allosteric-binding-pocket-for-the-selective-antagonist-az10606120
#9
Rebecca C Allsopp, Sudad Dayl, Ralf Schmid, Richard J Evans
The P2X7 receptor (P2X7R) for ATP is a therapeutic target for pathophysiological states including inflammation, pain management and epilepsy. This is facilitated by the predicted low side effect profile as the high concentrations of ATP required to activate the receptor are usually only found following cell damage/disease and so P2X7Rs respond to a "danger" signal and are not normally active. AZ10606120 is a selective antagonist for P2X7Rs (IC50 of ~10 nM) and ineffective at the P2X1R (at 10 μM). To determine the molecular basis of selectivity we generated a series of P2X7/1R chimeras and mutants...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386848/identification-of-de-novo-dnmt3a-mutations-that-cause-west-syndrome-by-using-whole-exome-sequencing
#10
Zhenwei Liu, Zhongshan Li, Xiao Zhi, Yaoqiang Du, Zhongdong Lin, Jinyu Wu
Epileptic encephalopathies (EEs) are a group of severe neurodevelopmental disorders with extreme genetic heterogeneity. Recent trio-based whole-exome sequencing (WES) studies have demonstrated that de novo mutations (DNMs) play prominent roles in severe EE. In this study, we searched for potential causal DNMs by using high-coverage WES of four unrelated Chinese parent-offspring trios affected by West syndrome. Through extensive bioinformatic analysis, we identified three novel DNMs in DNMT3A, CDKL5, and MAMDC2 in three trios and two compound heterozygous mutations in KMT2A in one trio...
April 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28374921/intracerebral-delivery-of-the-m2-polarizing-cytokine-interleukin-13-using-mesenchymal-stem-cell-implants-in-a-model-of-temporal-lobe-epilepsy-in-mice
#11
Idrish Ali, Stephanie Aertgeerts, Debbie Le Blon, Daniele Bertoglio, Chloe Hoornaert, Peter Ponsaerts, Stefanie Dedeurwaerdere
OBJECTIVES: Neuroinflammation plays a critical role in the pathophysiology of mesial temporal lobe epilepsy. We aimed to evaluate whether intracerebral transplantation of interleukin 13-producing mesenchymal stem cells (IL-13 MSCs) induces an M2 microglia/macrophage activation phenotype in the hippocampus with an epileptogenic insult, thereby providing a neuroprotective environment with reduced epileptogenesis. METHODS: Genetically engineered syngeneic IL-13 MSCs or vehicle was injected within the hippocampus 1 week before the intrahippocampal kainic acid-induced status epilepticus (SE) in C57BL/6J mice...
April 4, 2017: Epilepsia
https://www.readbyqxmd.com/read/28372486/the-effect-of-il-1%C3%AE-on-synaptophysin-expression-and-electrophysiology-of-hippocampal-neurons-through-the-pi3k-akt-mtor-signaling-pathway-in-a-rat-model-of-mesial-temporal-lobe-epilepsy
#12
Zhaohua Xiao, Jing Peng, Liwen Wu, Ahmed Arafat, Fei Yin
BACKGROUND: The inflammation induced by interleukin-1β (IL-1β) is a critical factor in the pathogenesis of mesial temporal lobe epilepsy (MTLE). Synaptophysin (SYN) and other changes, including neuron electrophysiology, participate in the pathophysiological processes of MTLE. Phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling pathway may play a critical role in regulating SYN expression and electrophysiology of hippocampal neurons. METHODS: We used lithium-pilocarpine-treated rats as model of human MTLE, detecting epileptic seizures with digital video-EEG, and evaluating the proteins related to the PI3K/Akt/mTOR signaling pathway by western blot (WB)...
April 4, 2017: Neurological Research
https://www.readbyqxmd.com/read/28364550/individual-brain-structure-and-modelling-predict-seizure-propagation
#13
Timothée Proix, Fabrice Bartolomei, Maxime Guye, Viktor K Jirsa
See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28355243/ketogenic-diet-improves-the-spatial-memory-impairment-caused-by-exposure-to-hypobaric-hypoxia-through-increased-acetylation-of-histones-in-rats
#14
Ming Zhao, Xin Huang, Xiang Cheng, Xiao Lin, Tong Zhao, Liying Wu, Xiaodan Yu, Kuiwu Wu, Ming Fan, Lingling Zhu
Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms...
2017: PloS One
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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