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Antiepileptic drugs

Chinekwu Anyanwu, Gholam K Motamedi
Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory). Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized which might be in part because of the complexity of presurgical evaluation. This process includes classifying the seizure type, lateralizing and localizing the seizure onset focus (epileptogenic zone), confirming the safety of the prospective brain surgery in terms of potential neurocognitive deficits (language and memory functions), before devising a surgical plan...
March 21, 2018: Brain Sciences
Joana Gonçalves, Gilberto Alves, Joana Bicker, Amílcar Falcão, Ana Fortuna
AIM: To implement pharmacokinetic drug monitoring and individualize the posology of new antiepileptic drugs, the first HPLC-diode array detection method was developed and validated to simultaneously quantify lacosamide, levetiracetam and zonisamide in human plasma. MATERIALS & METHODS: Preceded by a reproducible liquid-liquid extraction, chromatographic separation was achieved by using a C18 column of 5 cm length and a mobile phase of water/acetonitrile. Full validation was performed according to international guidelines...
March 21, 2018: Bioanalysis
Chen Jia, Shanshan Han, Liming Wei, Xiangji Dang, Qianqian Niu, Mengyu Chen, Boqun Cao, Yuting Liu, Haisheng Jiao
CONTEXT: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment. OBJECTIVE: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined...
December 2018: Pharmaceutical Biology
Lanlan Zhang, Chengzhong Wang, Wei Li
Objective: To evaluate clinical efficacy, safety, and tolerability of levetiracetam as mono- or adjunctive therapy in the treatment of children and adolescents with epilepsy. Materials and methods: We performed a meta-analysis of randomized controlled trials published from January 2007 to December 2016 in the databases Web of Science, Medline, Embase, Cochrane Library, and PubMed, Bing, Baidu, Google Scholar, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data...
2018: Neuropsychiatric Disease and Treatment
Hua Tao, Xu Zhou, Bin Zhao, Keshen Li
According to an update from the World Health Organization, approximately 50 million people worldwide suffer from epilepsy, and nearly one-third of these individuals are resistant to the currently available antiepileptic drugs, which has resulted in an insistent pursuit of novel strategies for seizure treatment. Recently, methylglyoxal (MG) was demonstrated to serve as a partial agonist of the gamma-aminobutyric acid type A (GABAA ) receptor and to play an inhibitory role in epileptic activities. However, MG is also a substrate in the generation of advanced glycation end products (AGEs) that function by activating the receptor of AGEs (RAGE)...
2018: Frontiers in Molecular Neuroscience
Emily C Mahoney, Andrew Zeng, Wilson Yu, Mackenzie Rowe, Siddhartha Sahai, Paul J Feustel, Adolfo Ramirez-Zamora, Julie G Pilitsis, Damian S Shin
Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged...
March 9, 2018: Epilepsy Research
Barbara Mostacci, Francesca Bisulli, Elisabetta Poluzzi, Guido Cocchi, Carlo Piccinni, Alessandra Curti, Giuliana Simonazzi, Gianni Astolfi, Nicola Rizzo, Corrado Zenesini, Roberto D'Alessandro, Paolo Tinuper
OBJECTIVES: To assess the prevalence of antiepileptic drug (AED) exposure in pregnant women and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirths, major birth defects (MBDs), neonatal distress and small for gestational age (SGA) infants following intrauterine AED exposure in the Emilia Romagna region, Italy (4 459 246 inhabitants on 31 December 2011). METHODS: We identified all deliveries and hospitalised abortions in Emilia Romagna in the period 2009-2011 from the certificate of delivery assistance registry (Certificato di Assistenza al Parto- CedAP) and the hospital discharge card registry, exposure to AEDs from the reimbursed drug prescription registries, MBDs from the regional registry of congenital malformations, and Apgar scores and cases of SGA from the CedAP...
March 16, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Bai Hui Chen, Ji Hyeon Ahn, Joon Ha Park, Minah Song, Hyunjung Kim, Tae-Kyeong Lee, Jae Chul Lee, Young-Myeong Kim, In Koo Hwang, Dae Won Kim, Choong-Hyun Lee, Bing Chun Yan, Il Jun Kang, Moo-Ho Won
Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks...
March 13, 2018: Chemico-biological Interactions
Rodrigo Vargas, Lucas Beltrán, Rafael Lizama, Gabriela Reyes Valenzuela, Roberto Caraballo
PURPOSE: To present a retrospective study of 13 children with benign epilepsy with centrotemporal spikes (BECTS), also known as benign rolandic epilepsy (BRE), associated with generalized spikes and waves as the only EEG manifestation at onset. METHOD: Charts of children with typical clinical criteria of BRE electroclinically followed-up between February 2000 and February 2015 were reviewed. RESULTS: Among 309 patients who met the electroclinical criteria of BRE, we identified 13 children who presented with the typical clinical manifestations but who, on the EEG, only had generalized paroxysms at onset that continued along the course of the syndrome...
March 9, 2018: Seizure: the Journal of the British Epilepsy Association
Jingang Zhang, Xinrui Li, Yuanyuan Su, Min Sun, Junbang Wang, Yunhua Hao
The association between cutaneous adverse drug reactions (cADRs) caused by antiepileptic drugs (AEDs) and human leukocyte antigen-A ( HLA-A ) and HLA-B genes in Chinese Han population in Shanghai was investigated. Through the case-control study, 30 child patients with AED-induced cADRs (cADRs group), 60 AED-tolerant child patients (AED-tolerant group) and 60 normal children not taking AEDs (normal group) were collected. The HLA-B*15:02 and HLA-A*31:01 genotypes were detected using the polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) probe method, and the correlation of HLA-B*15:02 and HLA-A*31:01 genes with the incidence of cADRs was analyzed...
April 2018: Experimental and Therapeutic Medicine
Philippe Desmarais, Catherine Miville, Ángela Milán-Tomás, Quoc Dinh Nguyen, Carmen Ojeda-López, Mario Masellis, Sandra E Black, Danielle Molinari Andrade, Nathan Herrmann
OBJECTIVES: To analyze age representation trends over time in antiepileptic drug (AED) trials and to assess trial design elements as possible barriers to enrollment of elderly patients. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and PsycINFO, and meta-analyzed demographic data of cohorts enrolled in randomized controlled trials (RCTs) of AEDs published since 1991. Data analysis included trends of age representation over time and trial design elements associated with average age of enrolled cohorts...
March 6, 2018: Epilepsy Research
Vanessa Lin Lin Lee, Brandon Kar Meng Choo, Yin-Sir Chung, Uday P Kundap, Yatinesh Kumari, Mohd Farooq Shaikh
Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect...
March 15, 2018: International Journal of Molecular Sciences
Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville
OBJECTIVE: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. METHODS: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol)...
March 14, 2018: Neurology
Piero Perucca, Ingrid E Scheffer, Michelle Kiley
The International League Against Epilepsy has recently published a new classification of epileptic seizures and epilepsies to reflect the major scientific advances in our understanding of the epilepsies since the last formal classification 28 years ago. The classification emphasises the importance of aetiology, which allows the optimisation of management. Antiepileptic drugs (AEDs) are the main approach to epilepsy treatment and achieve seizure freedom in about two-thirds of patients. More than 15 second generation AEDs have been introduced since the 1990s, expanding opportunities to tailor treatment for each patient...
March 19, 2018: Medical Journal of Australia
Jovana Kovacevic, Gregoire Maroteaux, Desiree Schut, Maarten Loos, Mohit Dubey, Julika Pitsch, Esther Remmelink, Bastijn Koopmans, James Crowley, L Niels Cornelisse, Patrick F Sullivan, Susanne Schoch, Ruud F Toonen, Oliver Stiedl, Matthijs Verhage
De novo heterozygous mutations in STXBP1/Munc18-1 cause early infantile epileptic encephalopathies (EIEE4, OMIM #612164) characterized by infantile epilepsy, developmental delay, intellectual disability, and can include autistic features. We characterized the cellular deficits for an allelic series of seven STXBP1 mutations and developed four mouse models that recapitulate the abnormal EEG activity and cognitive aspects of human STXBP1-encephalopathy. Disease-causing STXBP1 variants supported synaptic transmission to a variable extent on a null background, but had no effect when overexpressed on a heterozygous background...
March 12, 2018: Brain: a Journal of Neurology
M Marin-Gracia, D Cantero-Lozano, E Garces-Anton, A Lopez-Bravo, A Garrido-Fernandez, M P Navarro-Perez, S Santos-Lasaosa, M Garces-Redondo
INTRODUCTION: Lacosamide is an antiepileptic drug whose exact mechanism of action remains unknown. It acts by increasing the slow inactivation of the voltage-dependent sodium channels of the cell membranes. It is indicated in the treatment of focal seizures with or without secondary generalisation and is occasionally used as adjunct treatment in neuropathic pain. Although the most frequent side effects are mild (dizziness, diplopia, blurred vision, headache, tremor, etc.), others such as supraventricular tachyarrhythmias, changes in repolarisation, atrioventricular blocks and even cardiac arrest or sudden death have been reported...
March 16, 2018: Revista de Neurologia
Mohammed Basith, Andrew Francis, Alfredo Bellon
Gabapentin has become increasingly used in psychiatric practice specifically for anxiety disorders. Even though gabapentin is not approved by the US Food and Drug Administration to treat anxiety, physicians sometimes use it as an alternative to benzodiazepines in patients with a history of substance abuse. Gabapentin is also prescribed when individuals are at risk of thrombocytopenia which is not considered a side effect. Among patients at risk of thrombocytopenia are those positive for human immunodeficiency virus (HIV)...
2018: Case Reports in Psychiatry
Shengdong Wang, Hengyuan Li, Chenyi Ye, Peng Lin, Binghao Li, Wei Zhang, Lingling Sun, Zhan Wang, Deting Xue, Wangsiyuan Teng, Xingzhi Zhou, Nong Lin, Zhaoming Ye
The long-term survival of osteosarcoma has remained unchanged in the last several decades. Immunotherapy is proved to be a promising therapeutic strategy against osteosarcoma, especially for those with metastasis. Our previous study explored the sensibilization of zoledronate (ZOL) in γδ T cell-mediated cytotoxicity against osteosarcoma, but we have not yet elucidated the specific mechanism. Besides, high concentration is required to achieve these effects, whereas plasma ZOL concentration declines rapidly in the circulation...
2018: Frontiers in Immunology
Sandra Ventura, Márcio Rodrigues, Amílcar Falcão, Gilberto Alves
Paullinia cupana-containing preparations are being consumed worldwide for weight reduction. As obesity and epilepsy are common comorbidities and lamotrigine (LTG) is a broad-spectrum antiepileptic drug, it is likely to find epilepsy patients taking P. cupana and LTG simultaneously. Thus, this work aimed to investigate the potential interaction between P. cupana extract and LTG in rats. In a study, rats were orally co-administered with a single-dose of P. cupana extract (821 mg/kg) and LTG (10 mg/kg). In another study, rats were orally pre-treated for 14 days with P...
March 10, 2018: Food and Chemical Toxicology
J M Mercadé Cerdá, F J López Gonzalez, P Serrano Castro, M D Castro Vilanova, D M Campos Blanco, M R Querol Pascual
INTRODUCTION: The study aims to quantify the types of antiepileptic drugs (AED) prescribed in neurology consultations. MATERIAL AND METHOD: This descriptive, observational study included a sample of 559 patients older than 14 years, diagnosed with epilepsy, and receiving pharmacological treatment. Data were collected at outpatient consultations by 47 Spanish neurologists in May 2016. Epilepsy was defined based on the International League Against Epilepsy classification...
March 9, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
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