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epilepsy pathophysiology

Doodipala Samba Reddy
Neurosteroids like allopregnanolone (AP) are positive allosteric modulators of synaptic and extrasynaptic GABA-A receptors. AP and related neurosteroids exhibit a greater potency for δ-containing extrasynaptic receptors. The δGABA-A receptors, which are expressed extrasynaptically in the dentate gyrus and other regions, contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. Levels of endogenous neurosteroids fluctuate with ovarian cycle. Natural and synthetic neurosteroids maximally potentiate tonic inhibition in the hippocampus and provide robust protection against a variety of limbic seizures and status epilepticus...
2018: Vitamins and Hormones
S Liyanagedera, R P Williams
The International League Against Epilepsy Classification of the Epilepsies, first presented in 1981, has been widely adopted across the globe. In 2017 it was revised to allow for more robust, specific, flexible and logical classification of seizures. A number of new seizure types are recognised. Classification should be timely as it plays a vital role in the diagnosis and management of patients with epilepsy. Accurate classification also underpins epilepsy research from pathophysiology to public health. Here we review the basic and extended forms of the classification...
December 2017: Journal of the Royal College of Physicians of Edinburgh
Thomas Møhl, Maria J Miranda
Ketogenic diet (KD) has for a long time been known as an effective treatment for medically intractable epilepsy. However, the underlying mechanism is still unknown. Recent work indicates, that several mechanisms exist for KD, including neurotransmitter regulation, glucose restriction, effects of fatty acids, altered mitochondrial function and mammalian target of rapamycin pathway. Revealing the mechanisms of KD provides a better insight in the pathophysiology of epilepsy and helps the development of new treatments of epilepsy and other neurological disorders...
March 5, 2018: Ugeskrift for Laeger
James A Roberts, Karl J Friston, Michael Breakspear
Brain activity derives from intrinsic dynamics (due to neurophysiology and anatomical connectivity) in concert with stochastic effects that arise from sensory fluctuations, brainstem discharges, and random microscopic states such as thermal noise. The dynamic evolution of systems composed of both dynamic and random fluctuations can be studied with stochastic dynamic models (SDMs). This article, Part II of a two-part series, reviews applications of SDMs to large-scale neural systems in health and disease. Stochastic models have already elucidated a number of pathophysiological phenomena, such as epilepsy and hypoxic ischemic encephalopathy, although their use in biological psychiatry remains rather nascent...
April 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Stefania Evangelisti, Claudia Testa, Lorenzo Ferri, Laura Ludovica Gramegna, David Neil Manners, Giovanni Rizzo, Daniel Remondini, Gastone Castellani, Ilaria Naldi, Francesca Bisulli, Caterina Tonon, Paolo Tinuper, Raffaele Lodi
Objectives: To evaluate functional connectivity (FC) in patients with sleep-related hypermotor epilepsy (SHE) compared to healthy controls. Methods: Resting state fMRI was performed in 13 patients with a clinical diagnosis of SHE (age = 38.3 ± 11.8 years, 6 M) and 13 matched healthy controls (age = 38.5 ± 10.8 years, 6 M).Data were first analysed using probabilistic independent component analysis (ICA), then a graph theoretical approach was applied to assess topological and organizational properties at the whole brain level...
2018: NeuroImage: Clinical
Arturo Carpio, Agnès Fleury, Matthew L Romo, Ronaldo Abraham
Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countries due to migration. Many advances have been made in understanding NC, but unanswered questions remain Areas covered: This review discusses the epidemiology, pathophysiology, immunology, diagnosis, treatment, and eradication of NC. Expert commentary: The global NC prevalence remains unknown and needs proper ascertainment. Further understanding of the pathophysiology of extraparenchymally located cysts is needed to improve management...
March 14, 2018: Expert Review of Neurotherapeutics
Anne T Berg, Samya Chakravorty, Sookyong Koh, Zachary M Grinspan, Renée A Shellhaas, Russell P Saneto, Elaine C Wirrell, Jason Coryell, Catherine J Chu, John R Mytinger, William D Gaillard, Ignacio Valencia, Kelly G Knupp, Tobias Loddenkemper, Joseph E Sullivan, Annapurna Poduri, John J Millichap, Cynthia Keator, Courtney Wusthoff, Nicole Ryan, William B Dobyns, Madhuri Hegde
Infantile spasms are the defining seizures of West syndrome, a severe form of early life epilepsy with poorly-understood pathophysiology. We present a novel comparative analysis of infants with spasms versus other seizure-types and identify clinical, etiological, and molecular-genetic factors preferentially predisposing to spasms. We compared ages, clinical etiologies, and associated-genes between spasms and non-spasms groups in a multicenter cohort of 509 infants (<12months) with newly-diagnosed epilepsy...
2018: PloS One
Arjune Sen, Valentina Capelli, Masud Husain
With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia...
February 28, 2018: Brain: a Journal of Neurology
Mohamed Almuqbil, Michael J Rivkin, Masanori Takeoka, Edward Yang, Lance H Rodan
GLUT1 deficiency syndrome (GLUT1DS) is a well described neurometabolic disorder that results from impaired glucose transport into the central nervous system. GLUT1DS classically presents with infantile-onset epilepsy, progressive microcephaly, developmental delay, ataxia, dystonia, and spasticity, but a minority of patients may manifest with paroxysmal non-epileptic phenomena including hemiparesis (Wang et al., 2002). We report for the first time cerebral perfusion changes during an acute episode of hemiparesis in a 9 year old child with GLUT1DS...
February 19, 2018: European Journal of Paediatric Neurology: EJPN
Dan Xu, Andrew P Robinson, Toshiyuki Ishii, D'Anne S Duncan, Tord D Alden, Gwendolyn E Goings, Igal Ifergan, Joseph R Podojil, Pablo Penaloza-MacMaster, Jennifer A Kearney, Geoffrey T Swanson, Stephen D Miller, Sookyong Koh
The pathophysiology of drug-resistant pediatric epilepsy is unknown. Flow cytometric analysis of inflammatory leukocytes in resected brain tissues from 29 pediatric patients with genetic (focal cortical dysplasia) or acquired (encephalomalacia) epilepsy demonstrated significant brain infiltration of blood-borne inflammatory myeloid cells and memory CD4+ and CD8+ T cells. Significantly, proinflammatory (IL-17- and GM-CSF-producing) γδ T cells were concentrated in epileptogenic lesions, and their numbers positively correlated with disease severity...
February 27, 2018: Journal of Experimental Medicine
W O Tatum, G Rubboli, P W Kaplan, S M Mirsatari, K Radhakrishnan, D Gloss, L O Caboclo, F W Drislane, M Koutroumanidis, D L Schomer, D Kastelijn-Nolst Trenite, Mark Cook, S Beniczky
Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline...
February 1, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Christina Möller, Fabio Wolf, R Maarten van Dijk, Valentina Di Liberto, Vera Russmann, Michael Keck, Rupert Palme, Rainer Hellweg, Peter Gass, Christiane Otzdorff, Heidrun Potschka
OBJECTIVE: Rodent epilepsy models can significantly contribute to our understanding of pathophysiological mechanisms and to validation of biomarker and target candidates. Evidence-based severity assessment is a presupposition for the ethical evaluation of animal experimentation allowances as well as for the development of efficacious refinement concepts. METHODS: Aiming to improve our understanding of the impact of experimental procedures and repeated seizures, we have completed a comprehensive behavioral and biochemical analysis assessing various parameters that can inform about the influence of an electrical kindling paradigm on well-being in rats...
February 26, 2018: Epilepsia
Hiroki Kitaura, Hiroshi Shirozu, Hiroshi Masuda, Masafumi Fukuda, Yukihiko Fujii, Akiyoshi Kakita
Mesial temporal lobe epilepsy (MTLE) is the most frequent focal epileptic syndrome in adults, and the majority of seizures originate primarily from the hippocampus. The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis (HS). In order to understand hippocampal epileptogenesis in MTLE, it seems important to clarify any discrepancies between the clinical and pathological features of affected patients. Here we investigated epileptiform activities ex vivo using living hippocampal tissue taken from patients with MTLE...
February 21, 2018: EBioMedicine
Nicolas Gaspard, Lawrence J Hirsch, Claudine Sculier, Tobias Loddenkemper, Andreas van Baalen, Judette Lancrenon, Michel Emmery, Nicola Specchio, Raquel Farias-Moeller, Nora Wong, Rima Nabbout
We report the proceedings of the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. To promote awareness of this condition and foster research efforts, we conveyed the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. The conference was supported by The NORSE Institute ( This article summarizes the discussions that were held during the Symposium and presents our strategy to unravel the cause of these disorders and to improve patient care...
February 24, 2018: Epilepsia
Stuart M Cain, John R Tyson, Hyun-Beom Choi, Rebecca Ko, Paulo J C Lin, Jeffrey M LeDue, Kim L Powell, Louis-Philippe Bernier, Ravi L Rungta, Yi Yang, Pieter R Cullis, Terence J O'Brien, Brian A MacVicar, Terrance P Snutch
OBJECTIVE: Genetic alterations have been identified in the CACNA1H gene, encoding the CaV 3.2 T-type calcium channel in patients with absence epilepsy, yet the precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD) pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN) express high levels of CaV 3.2 calcium channels, and we investigated whether a gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the TRN...
February 21, 2018: Epilepsia
Jason A Justice, Russell M Sanchez
Hypoxic-ischemic encephalopathy (HIE) refers to acute brain injury that results from perinatal asphyxia. HIE is a major cause of neonatal seizures, and outcomes can range from apparent recovery to severe cognitive impairment, cerebral palsy, and epilepsy. Acute partial seizures frequently aid in indicating the severity and localization of brain injury. However, evidence also suggests that the occurrence of seizures further increases the likelihood of epilepsy in later life regardless of the severity of the initial injury...
2018: Methods in Molecular Biology
Zong-Wei Yue, Ye-Lan Wang, Bo Xiao, Li Feng
Cortical dysplasia is the most common etiology of intractable epilepsy. Both excitability changes in cortical neurons and neural network reconstitution play a role in cortical dysplasia epileptogenesis. Recent research shows that the axon initial segment, a subcompartment of the neuron important to the shaping of action potentials, adjusts its position in response to changes in input, which contributes to neuronal excitability and local circuit balance. It is unknown whether axon initial segment plasticity occurs in neurons involved in seizure susceptibility in cortical dysplasia...
February 21, 2018: Neurochemical Research
Yoshihiko Yu, Daisuke Hasegawa, Yuji Hamamoto, Shunta Mizoguchi, Takayuki Kuwabara, Aki Fujiwara-Igarashi, Masaya Tsuboi, James Ken Chambers, Michio Fujita, Kazuyuki Uchida
OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2 nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs. PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes. Values were compared between FSECs and control cats...
March 2018: American Journal of Veterinary Research
Hülya Olgun Yazar, Günay Gül, Tamer Yazar, Fulya Eren, Demet-Yandım Kuscu, Dursun Kirbas
Background and purpose: Epilepsy with photosensitivity (PSE) is one of the reflex epilepsy types with pathophysiology still unexplained. In our study we aimed to evaluate the clinical, electroencephalogram (EEG) and prognosis of patients with PSE diagnosis. Methods: A total of 44 patients with PSE diagnosis according to international classification were included in this retrospective and cross-sectional study. The age, gender, syndrome, clinical and EEG characteristics of patients, and treatment response were investigated...
January 30, 2018: Ideggyógyászati Szemle
A V Sergeev
Differential diagnosis of migraine, can be difficult, especially of migraine with aura. On the one hand, some diseases can produce symptoms similar to migraine (cerebral aneurysm before rupture, reversible cerebral vasoconstriction syndrome). On the other hand, migraine with aura and some other disorders are conditions that have common pathophysiological mechanisms (e.g., CADASIL and MELAS syndrome, antiphospholipid syndrome). Thirdly, clinical presentations of migraine are often difficult to distinguish from features of other headache conditions (migraine with aura - transient ischemic attack, migraine with visual aura - occipital epilepsy)...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
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