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https://www.readbyqxmd.com/read/29338461/mtor-dysregulation-and-tuberous-sclerosis-related-epilepsy
#1
Paolo Curatolo, Romina Moavero, Jackelien van Scheppingen, Eleonora Aronica
The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for proper neural network development, and it is involved in epileptogenesis triggered by both genetic or acquired factors. Areas covered. The robust mTOR signaling deregulation observed in a large spectrum of epileptogenic developmental pathologies, such as focal cortical dysplasias and tuberous sclerosis complex (TSC), has been linked to germline and somatic mutations in mTOR pathway regulatory genes, increasing the spectrum of "mTORopathies"...
January 17, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29331315/ethnobotany-phytochemistry-and-pharmacology-of-arctotis-arctotoides-l-f-o-hoffm-a-review
#2
REVIEW
Md Moshfekus Saleh-E-In, Johannes Van Staden
ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the genus Arctotis. Arctotis is an African genus of approximately 70 species that occur widely in the African continent with diverse medicinal values. This plant is used for the treatment of indigestion and catarrh of the stomach, epilepsy, topical wounds and skin disorders among the ethnic groups in South Africa and reported to have a wide spectrum of pharmacological properties. AIM OF THE REVIEW: The aim of the present review is to appraise the botany, traditional uses, phytochemistry, pharmacological potential, analytical methods and safety issues of A...
January 10, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29331082/mechanistic-target-of-rapamycin-complex-1-and-2-in-human-temporal-lobe-epilepsy
#3
Delia M Talos, Leah M Jacobs, Sarah Gourmaud, Carlos A Coto, Hongyu Sun, Kuei-Cheng Lim, Timothy H Lucas, Kathryn A Davis, Maria Martinez-Lage, Frances E Jensen
OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) Complex 1 (mTORC1) and Complex 2 (mTORC2) activities in the brain, as both pathways may represent unique targets for treatment. METHODS: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by Western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29320603/drug-management-for-acute-tonic-clonic-convulsions-including-convulsive-status-epilepticus-in-children
#4
REVIEW
Amy McTague, Timothy Martland, Richard Appleton
BACKGROUND: Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and require urgent and appropriate anticonvulsant treatment. International consensus is that an anticonvulsant drug should be administered for any tonic-clonic convulsion that has been continuing for at least five minutes. Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line drugs...
January 10, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29317649/synchrotron-generated-microbeams-induce-hippocampal-transections-in-rats
#5
Erminia Fardone, Benoît Pouyatos, Elke Bräuer-Krisch, Stefan Bartzsch, Hervè Mathieu, Herwig Requardt, Domenico Bucci, Giacomo Barbone, Paola Coan, Giuseppe Battaglia, Geraldine Le Duc, Alberto Bravin, Pantaleo Romanelli
Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29291240/meta-analysis-of-micrornas-dysregulated-in-the-hippocampal-dentate-gyrus-of-animal-models-of-epilepsy
#6
Prashant K Srivastava, Paolo Roncon, Katarzyna Lukasiuk, Jan A Gorter, Eleonora Aronica, Asla Pitkänen, Enrico Petretto, Michael R Johnson, Michele Simonato
The identification of mechanisms transforming normal to seizure-generating tissue after brain injury is key to developing new antiepileptogenic treatments. MicroRNAs (miRNAs) may act as regulators and potential treatment targets for epileptogenesis. Here, we undertook a meta-analysis of changes in miRNA expression in the hippocampal dentate gyrus (DG) following an epileptogenic insult in three epilepsy models. We identified 26 miRNAs significantly differentially expressed during epileptogenesis, and five differentially expressed in chronic epilepsy...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29279892/treatment-outcomes-in-patients-with-newly-diagnosed-epilepsy-treated-with-established-and-new-antiepileptic-drugs-a-30-year-longitudinal-cohort-study
#7
Zhibin Chen, Martin J Brodie, Danny Liew, Patrick Kwan
Importance: A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades. Objective: To assess long-term treatment outcome in patients with newly diagnosed and treated epilepsy. Design, Setting, and Participants: This longitudinal observational cohort study was conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland...
December 26, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29249551/validation-of-a-clinical-prediction-model-for-the-development-of-neuromuscular-scoliosis-a-multinational-study
#8
Carlo M Bertoncelli, Domenico Bertoncelli, Leonard Elbaum, Michal Latalski, Paola Altamura, Charles Musoff, Virginie Rampal, Federico Solla
BACKGROUND: The objective of this study was to evaluate the performance of a clinical prediction model of neuromuscular scoliosis via external validation. METHODS: We analyzed a series of 120 patients (mean age ± standard deviation, 15.7 ± 1.8 years; range: 12 to 18 years) with cerebral palsy, severe motor disorders, and cognitive impairment with and without neuromuscular scoliosis treated in two specialized units (70 patients from Nice, France, and 50 patients from Lublin, Poland) in a cross-sectional, double-blind study...
November 20, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/29247482/commonalities-in-epileptogenic-processes-from-different-acute-brain-insults-do-they-translate
#9
REVIEW
Pavel Klein, Raymond Dingledine, Eleonora Aronica, Christophe Bernard, Ingmar Blümcke, Detlev Boison, Martin J Brodie, Amy R Brooks-Kayal, Jerome Engel, Patrick A Forcelli, Lawrence J Hirsch, Rafal M Kaminski, Henrik Klitgaard, Katja Kobow, Daniel H Lowenstein, Phillip L Pearl, Asla Pitkänen, Noora Puhakka, Michael A Rogawski, Dieter Schmidt, Matti Sillanpää, Robert S Sloviter, Christian Steinhäuser, Annamaria Vezzani, Matthew C Walker, Wolfgang Löscher
The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification...
December 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/29246093/targeting-the-mammalian-target-of-rapamycin-for-epileptic-encephalopathies-and-malformations-of-cortical-development
#10
Anna Jeong, Michael Wong
Malformations of cortical development represent a common cause of epileptic encephalopathies and drug-resistant epilepsy in children. As current treatments are often ineffective, new therapeutic targets are needed for epileptic encephalopathies associated with cortical malformations. The mechanistic/mammalian target of rapamycin (mTOR) pathway constitutes a signaling pathway that drives cellular and molecular mechanisms of epileptogenesis in a variety of focal cortical malformations. mTOR inhibitors prevent epilepsy and associated pathogenic mechanisms of epileptogenesis in mouse models of tuberous sclerosis complex and are currently in clinical trials for drug-resistant seizures in these patients...
January 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29246092/improvement-of-self-injury-with-dopamine-and-serotonin-replacement-therapy-in-a-patient-with-a-hemizygous-pak3-mutation-a-new-therapeutic-strategy-for-neuropsychiatric-features-of-an-intellectual-disability-syndrome
#11
Gabriella A Horvath, Maja Tarailo-Graovac, Tanja Bartel, Simone Race, Margot I Van Allen, Ingrid Blydt-Hansen, Colin J Ross, Wyeth W Wasserman, Mary B Connolly, Clara D M van Karnebeek
PAK3-related intellectual disability is caused by mutations in the gene encoding the p21-activated kinase (PAK) protein. It is characterized by mild to moderate cognitive impairment, micro/normocephaly, and a neurobehavioral phenotype characterized by short attention span, anxiety, restlessness, aggression, and self-abusive behaviors. The authors report a patient with a novel PAK3 mutation, who presented with intellectual disability, severe automutilation, and epilepsy. His magnetic resonance imaging changes were most likely secondary to lacerations from parenchymal contusions...
January 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29223050/a-simple-rapid-and-stability-indicating-validated-method-for-quantification-of-lamotrigine-in-human-plasma-and-dry-plasma-spot-using-lc-esi-ms-ms-application-in-clinical-study
#12
Kuldeep Kumar Namdev, Jaya Dwivedi, Deepak Chandra Chilkoti, Swapnil Sharma
Lamotrigine (LTZ) is a phenyltriazine derivative which belongs to anti-epileptic drugs (AEDs) class and prescribed as mono- or adjunctive-therapy in treatment of epilepsy. Therapeutic drug monitoring (TDM) of AEDs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) are suitable alternative to overcome these issues...
December 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29223007/examining-health-service-utilization-hospital-treatment-cost-and-mortality-of-individuals-with-epilepsy-and-status-epilepticus-in-new-south-wales-australia-2012-2016
#13
Rebecca J Mitchell, Geoffrey Herkes, Armin Nikpour, Andrew Bleasel, Patti Shih, Sanjyot Vagholkar, Frances Rapport
This study examined the health service utilization and hospital treatment cost of individuals with epilepsy by age group, mortality within 30days, and surgical outcomes for individuals with refractory epilepsy in New South Wales (NSW), Australia. A retrospective examination of linked hospitalization and mortality data for individuals hospitalized with a diagnosis of epilepsy during 2012-2016. Hospitalized incidence rates per 1000 population were calculated, and negative binomial regression was used to examine temporal trends...
December 6, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29222951/neuronal-pas-domain-protein-4-npas4-controls-neuronal-homeostasis-in-pentylenetetrazole-induced-epilepsy-through-the-induction-of-homer1a
#14
Wei Shan, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Masahiro Sokabe, Kiyofumi Yamada
Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyper-excitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29213042/-new-opportunities-in-the-optimization-of-epilepsy-treatment-in-adolescents
#15
V I Guzeva, I V Okhrim, O V Guzeva, V V Guzeva, N E Maksimova
In the pubertal period, the most severe forms of childhood epilepsy persist and are modified; genetically determined syndromes, atypical for early and late age periods, make their debut. Hereditary predisposition, instability of homeostatic mechanisms, neuroendocrine restructuring at the age of puberty and the influence of factors contributing to the realization of a genetic defect lead to a long-term transformation of mediator systems and formation of epileptic activity in adolescents. The authors present common approaches in the treatment and characterization of the modern antiepileptic drug perampanel, which is highly effective in treatment of patients with resistant forms of epilepsy...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29213041/-perampanel-in-the-treatment-of-patients-with-epilepsy
#16
F K Rider
Development of new antiepileptic drugs (AED) does not stop due to the fact that the number of patients with pharmacoresistant epilepsy remains at about 30%. One of the newest AEDs is perampanel (PER), a selective, non-competitive AMPA receptor antagonist to target post-synaptic glutamate transmission. PER is approved in the Russian Federation as adjunctive treatment for focal seizures with or without secondarily generalized seizures and for primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE) in patients with epilepsy aged ≥12 years...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29213035/-problems-of-juvenile-myoclonic-epilepsy-a-view-through-the-prism-of-time
#17
V A Karlov, V S Zolovkina
The authors present a comparative analysis of the results of the study of 72 adolescent patients with juvenile myoclonic epilepsy (JME), which were published in 2010, and a new sample of patients over the last 5 years with the publications of domestic and foreign authors. Difficult clinical cases are described. These data indicate positive shifts in the diagnosis and treatment of JME. However, the question of diagnosis is still a hard problem for neurologists. The questions to be resolved are: gender aspect of the disease, to what extent levetiracetam could be a drug of first choice and to what extent valproats could be replaced; monitoring of children born to mothers with JME, a role of paternal inheritance...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29198272/paradigm-shifts-in-the-neuropsychology-of-epilepsy
#18
Bruce Hermann, David W Loring, Sarah Wilson
This article reviews the major paradigm shifts that have occurred in the area of the application of clinical and experimental neuropsychology to epilepsy and epilepsy surgery since the founding of the International Neuropsychological Society. The five paradigm shifts discussed include: 1) The neurobiology of cognitive disorders in epilepsy - expanding the landscape of syndrome-specific neuropsychological impairment; 2) pathways to comorbidities: bidirectional relationships and their clinical implications; 3) discovering quality of life: The concept, its quantification and applicability; 4) outcomes of epilepsy surgery: challenging conventional wisdom; and 5) Iatrogenic effects of treatment: cognitive and behavioral effects of antiepilepsy drugs...
October 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/29196247/early-and-late-post-traumatic-epilepsy-in-the-setting-of-traumatic-brain-injury-a-review-of-anti-epileptic-management
#19
Christopher D Wilson, Josh D Burks, Richard B Rodgers, Robert M Evans, Adewale A Bakare, Sam Safavi-Abbasi
INTRODUCTION: Moderate to severe traumatic brain injury confers increased risk of early and late post-traumatic seizures (PTS). Early PTS are diagnosed when seizures develop within 7 days following injury, whereas initial seizures in late PTS occur later. Traditionally, patients have been treated with phenytoin (PHT) to prevent early PTS, and more recently with levetiracetam (LEV). Various regimens have been tried in patients to prevent late PTS with variable success. In this meta-analysis, we assessed and compared effectiveness of these drugs on early and late PTS prevention...
November 28, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29187252/atypical-non-standard-functions-of-the-microtubule-associated-tau-protein
#20
REVIEW
Ioannis Sotiropoulos, Marie-Christine Galas, Joana M Silva, Efthimios Skoulakis, Susanne Wegmann, Mahmoud Bukar Maina, David Blum, Carmen Laura Sayas, Eva-Maria Mandelkow, Eckhard Mandelkow, Maria Grazia Spillantini, Nuno Sousa, Jesus Avila, Miguel Medina, Amrit Mudher, Luc Buee
Since the discovery of the microtubule-associated protein Tau (MAPT) over 40 years ago, most studies have focused on Tau's role in microtubule stability and regulation, as well as on the neuropathological consequences of Tau hyperphosphorylation and aggregation in Alzheimer's disease (AD) brains. In recent years, however, research efforts identified new interaction partners and different sub-cellular localizations for Tau suggesting additional roles beyond its standard function as microtubule regulating protein...
November 29, 2017: Acta Neuropathologica Communications
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