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New treatments for epilepsy

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https://www.readbyqxmd.com/read/28917501/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-i-clinical-and-network-analysis-approaches
#1
REVIEW
Felix Rosenow, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Sebastian Bauer
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28917498/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-ii-experimental-and-translational-approaches
#2
REVIEW
Sebastian Bauer, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Felix Rosenow
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28904570/bone-mineral-status-in-children-with-epilepsy-biochemical-and-radiologic-markers
#3
Bothina Hasaneen, Riad Moustafa Elsayed, Nanees Salem, Ashraf Elsharkawy, Noha Tharwat, Khaled Fathy, Amany El-Hawary, Hadil M Aboelenin
OBJECTIVE: The aim of this study is to assess bone mineral status in children with epilepsy, on different antiepileptic drugs (AEDs) regimen, using dual-energy X-ray absorptiometry (DXA) and routine biochemical bone markers. PATIENTS AND METHODS: This is observational prospective controlled cohort study, conducted at Mansoura University Children Hospital, from January 2014 to June 2015. In this study, we had 152 participants with ages 3-13 years, 70 children diagnosed with epilepsy and 82 were controls...
April 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/28895591/development-of-drug-loaded-polymer-microcapsules-for-treatment-of-epilepsy
#4
Yu Chen, Qi Gu, Zhilian Yue, Jeremy M Crook, Simon E Moulton, Mark J Cook, Gordon G Wallace
Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles...
September 12, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28894217/the-faah-inhibitor-urb597-suppresses-hippocampal-maximal-dentate-afterdischarges-and-restores-seizure-induced-impairment-of-short-and-long-term-synaptic-plasticity
#5
Roberto Colangeli, Massimo Pierucci, Arcangelo Benigno, Giuseppe Campiani, Sefania Butini, Giuseppe Di Giovanni
Synthetic cannabinoids and phytocannabinoids have been shown to suppress seizures both in humans and experimental models of epilepsy. However, they generally have a detrimental effect on memory and memory-related processes. Here we compared the effect of the inhibition of the endocannabinoid (eCB) degradation versus synthetic CB agonist on limbic seizures induced by maximal dentate activation (MDA) acute kindling. Moreover, we investigated the dentate gyrus (DG) granule cell reactivity and synaptic plasticity in naïve and in MDA-kindled anaesthetised rats...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891449/role-of-pharmacogenomics-in-antiepileptic-drug-therapy-current-status-and-future-perspectives
#6
Antonio Gambardella, Angelo Labate, Laura Mumoli, Iscia Lopes-Cendes, Fernando Cendes
BACKGROUND: Growing evidence indicates that pharmacogenomics will positively impact treatment for patients with epilepsy in the near future, leading to the implementation of a precision-based use of antiepileptic drug (AED) therapy, thereby providing a cornerstone for precision medicine. OBJECTIVE: In this review, we briefly summarize the studies of pharmacogenomics in epilepsy, recent advances, and how it may progress in the future. METHODS: We subdivided the review into two main sections: genetic variants that may modulate response to AEDs through pharmacokinetics or pharmacodynamics mechanisms; and gene variants that may affect tolerability and safety of AEDs...
September 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28888969/mtor-related-neuropathology-in-mutant-tsc2-zebrafish-phenotypic-transcriptomic-and-pharmacological-analysis
#7
Chloë Scheldeman, James D Mills, Aleksandra Siekierska, Ines Serra, Daniëlle Copmans, Anand M Iyer, Benjamin J Whalley, Jan Maes, Anna C Jansen, Lieven Lagae, Eleonora Aronica, Peter A M de Witte
Tuberous sclerosis complex (TSC) is a rare, genetic disease caused by loss-of-function mutations in either TSC1 or TSC2. Patients with TSC are neurologically characterized by the presence of abnormal brain structure, intractable epilepsy and TSC-associated neuropsychiatric disorders. Given the lack of effective long-term treatments for TSC, there is a need to gain greater insight into TSC-related pathophysiology and to identify and develop new treatments. In this work we show that homozygous tsc2(-/-) mutant zebrafish larvae, but not tsc2(+/-) and WT larvae, display enlarged brains, reduced locomotor behavior and epileptiform discharges at 7dpf...
September 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28886982/management-of-epilepsy-due-to-hypothalamic-hamartomas
#8
REVIEW
Ayaz M Khawaja, Sandipan Pati, Yu-Tze Ng
A hypothalamic hamartoma consists of hyperplastic heterotopic tissue growing in a disorganized fashion. These lesions occur in about one per 50,000 to 100,000 people. Hypothalamic hamartomas can cause intrinsic epileptogenesis leading to gelastic seizures. Surrounding cortical structures may also develop secondary epileptogenesis. Persistent seizures caused by hypothalamic hamartomas can be debilitating and result in significant cognitive and behavioral impairment. Early recognition and treatment is important in controlling seizures and in preventing further cognitive deterioration...
July 5, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28886496/convulsive-status-epilepticus-in-a-quaternary-hospital-paediatric-intensive-care-unit-picu-in-south-africa-an-8-year-review
#9
Yavini Reddy, Yusentha Balakrishna, Lawrence Mubaiwa
PURPOSE: Convulsive status epilepticus (CSE) is associated with a high morbidity and mortality. This study aimed to describe the clinical profile, aetiology, neuroimaging and EEG findings as well as outcome of children with CSE in Sub-Saharan Africa. METHODS: This was a retrospective analysis of electronic records of children with CSE admitted to the Paediatric Intensive Care Unit (PICU) over an 8-year period from January 2007 to December 2014. RESULTS: Seventy six patients were admitted to the PICU with CSE and 55(72%) had refractory status epilepticus...
August 2, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28885567/metabolic-and-homeostatic-changes-in-seizures-and-acquired-epilepsy-mitochondria-calcium-dynamics-and-reactive-oxygen-species
#10
REVIEW
Stjepana Kovac, Albena T Dinkova Kostova, Alexander M Herrmann, Nico Melzer, Sven G Meuth, Ali Gorji
Acquired epilepsies can arise as a consequence of brain injury and result in unprovoked seizures that emerge after a latent period of epileptogenesis. These epilepsies pose a major challenge to clinicians as they are present in the majority of patients seen in a common outpatient epilepsy clinic and are prone to pharmacoresistance, highlighting an unmet need for new treatment strategies. Metabolic and homeostatic changes are closely linked to seizures and epilepsy, although, surprisingly, no potential treatment targets to date have been translated into clinical practice...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28885121/epilepsy-headache-and-abdominal-pain-after-shunt-surgery-for-idiopathic-normal-pressure-hydrocephalus-the-inph-crash-study
#11
Jenny Larsson, Hanna Israelsson, Anders Eklund, Jan Malm
OBJECTIVE Adverse events related to shunt surgery are common and might have a negative effect on outcome in patients with idiopathic normal pressure hydrocephalus (INPH). The authors' objectives were to establish the frequencies of epilepsy, headache, and abdominal pain and determine their impact on patient quality of life (QOL), in long-term follow-up after shunt surgery for INPH. METHODS One hundred seventy-six shunt-treated patients with INPH (mean age 74 years) and 368 age- and sex-matched controls from the population were included...
September 8, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28880996/dravet-syndrome-and-its-mimics-beyond-scn1a
#12
REVIEW
Dora Steel, Joseph D Symonds, Sameer M Zuberi, Andreas Brunklaus
OBJECTIVE: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy, and evolving to drug-resistant epilepsy with accompanying cognitive, behavioral, and motor impairment. Most cases are now known to be caused by pathogenic variants in the sodium channel gene SCN1A, but several other genes have also been implicated. This review examines current understanding of the role of non-SCN1A genes in DS, and what is known about phenotypic similarities and differences...
September 7, 2017: Epilepsia
https://www.readbyqxmd.com/read/28878622/ganaxolone-a-new-treatment-for-neonatal-seizures
#13
REVIEW
Tamara Yawno, Suzie L Miller, Laura Bennet, Flora Wong, Jonathan J Hirst, Michael Fahey, David W Walker
Neonatal seizures are amongst the most common neurologic conditions managed by a neonatal care service. Seizures can exacerbate existing brain injury, induce "de novo" injury, and are associated with neurodevelopmental disabilities in post-neonatal life. In this mini-review, we present evidence in support of the use of ganaxolone, a GABA(A) agonist neurosteroid, as a novel neonatal therapy. We discuss evidence that ganaxolone can provide both seizure control and neuroprotection with a high safety profile when administered early following birth-related hypoxia, and show evidence that it is likely to prevent or reduce the incidence of the enduring disabilities associated with preterm birth, cerebral palsy, and epilepsy...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28870844/inhibitory-synapse-deficits-caused-by-familial-%C3%AE-1-gabaa-receptor-mutations-in-epilepsy
#14
Xiumin Chen, Nela Durisic, Joseph W Lynch, Angelo Keramidas
Epilepsy is a spectrum of neurological disorders with many causal factors. The GABA type-A receptor (GABAAR) is a major genetic target for heritable human epilepsies. Here we examine the functional effects of three epilepsy-causing mutations to the α1 subunit (α1(T10'I), α1(D192N) and α1(A295D)) on inhibitory postsynaptic currents (IPSCs) mediated by the major synaptic GABAAR isoform, α1β2γ2L. We employed a neuron - HEK293 cell heterosynapse preparation to record IPSCs mediated by mutant-containing GABAARs in isolation from other GABAAR isoforms...
September 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28860984/early-seizure-detection-by-applying-frequency-based-algorithm-derived-from-the-principal-component-analysis
#15
Jiseon Lee, Junhee Park, Sejung Yang, Hani Kim, Yun Seo Choi, Hyeon Jin Kim, Hyang Woon Lee, Byung-Uk Lee
The use of automatic electrical stimulation in response to early seizure detection has been introduced as a new treatment for intractable epilepsy. For the effective application of this method as a successful treatment, improving the accuracy of the early seizure detection is crucial. In this paper, we proposed the application of a frequency-based algorithm derived from principal component analysis (PCA), and demonstrated improved efficacy for early seizure detection in a pilocarpine-induced epilepsy rat model...
2017: Frontiers in Neuroinformatics
https://www.readbyqxmd.com/read/28859565/neuroplasticity-and-the-brain-connectome-what-can-jean-talairach-s-reflections-bring-to-modern-psychosurgery
#16
Pierre Bourdillon, Caroline Apra, Marc Lévêque, Fabien Vinckier
Contrary to common psychosurgical practice in the 1950s, Dr. Jean Talairach had the intuition, based on clinical experience, that the brain connectome and neuroplasticity had a role to play in psychosurgery. Due to the remarkable progress of pharmacology at that time and to the technical limits of neurosurgery, these concepts were not put into practice. Currently, these concepts are being confirmed by modern techniques such as neuroimaging and computational neurosciences, and could pave the way for therapeutic innovation in psychiatry...
September 2017: Neurosurgical Focus
https://www.readbyqxmd.com/read/28845714/the-potential-role-of-cannabinoids-in-epilepsy-treatment
#17
Carmen De Caro, Antonio Leo, Rita Citraro, Caterina De Sarro, Roberto Russo, Antonio Calignano, Emilio Russo
Epilepsy is one of the world's oldest recognized and prevalent neurological diseases. It has a great negative impact on patients' quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs' side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. Areas Covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system...
August 26, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28843069/new-onset-status-epilepticus-in-older-patients-clinical-characteristics-and-outcome
#18
M P Malter, R D Nass, T Kaluschke, G R Fink, L Burghaus, C Dohmen
PURPOSE: We here evaluated (1) the differential characteristics of status epilepticus (SE) in older (≥60 years) compared to younger adults (18-59 years). In particular, we were interested in (2) the proportion and characteristics of new onset SE in patients with no history of epilepsy (NOSE) in older compared to younger adults, and (3) predictive parameters for clinical outcome in older subjects with NOSE. METHODS: We performed a monocentric retrospective analysis of all adult patients (≥18years) admitted with SE to our tertiary care centre over a period of 10 years (2006-2015) to evaluate clinical characteristics and short-time outcome at discharge...
August 18, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28835254/using-routinely-recorded-data-in-the-uk-to-assess-outcomes-in-a-randomised-controlled-trial-the-trials-of-access
#19
G A Powell, L J Bonnett, C Tudur-Smith, D A Hughes, P R Williamson, A G Marson
BACKGROUND: In the UK, routinely recorded data may benefit prospective studies including randomised controlled trials (RCTs). In an on-going study, we aim to assess the feasibility of access and agreement of routinely recorded clinical and non-clinical data compared to data collected during a RCT using standard prospective methods. This paper will summarise available UK routinely recorded data sources and discuss our experience with the feasibility of accessing routinely recorded data for participants of a RCT before finally proposing recommendations for improving the access and implementation of routinely recorded data in RCTs...
August 23, 2017: Trials
https://www.readbyqxmd.com/read/28833036/treatment-with-lacosamide-impedes-generalized-seizures-in-a-rodent-model-of-cortical-dysplasia
#20
Ashley D Nemes, Rebecca O'Dwyer, Imad M Najm, Zhong Ying, Jorge Gonzalez-Martinez, Andreas V Alexopoulos
OBJECTIVE: Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD)...
August 20, 2017: Epilepsia
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