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https://www.readbyqxmd.com/read/29782051/the-novel-sodium-channel-modulator-gs-458967-gs967-is-an-effective-treatment-in-a-mouse-model-of-scn8a-encephalopathy
#1
Erin M Baker, Christopher H Thompson, Nicole A Hawkins, Jacy L Wagnon, Eric R Wengert, Manoj K Patel, Alfred L George, Miriam H Meisler, Jennifer A Kearney
OBJECTIVE: De novo mutations of SCN8A, encoding the voltage-gated sodium channel NaV 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity...
May 21, 2018: Epilepsia
https://www.readbyqxmd.com/read/29766822/2-5-disubstituted-phthalimides-design-synthesis-and-anticonvulsant-activity-in-scptz-and-mes-models
#2
Atefeh Saadabadi, Babak Kohen, Maryam Irandoust, Hamed Shafaroudi, Tara Mohammadpour, Mahdi Rezayat, Asghar Davood
In this study, fifteenth new 2,5-disubstituted analgouges of phthalimide were designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) compare to phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FT-IR, H-NMR, C-NMR and MASS spectroscopy. All the tested compounds were found to be effective in the PTZ model at the dose of 60 mg/kg and most of the compounds showed protection against MES test indicative of their ability to inhibit the seizure spread at the all dose ranges...
May 15, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29766538/chronic-exposure-to-cannabidiol-induces-reproductive-toxicity-in-male-swiss-mice
#3
Renata K Carvalho, Monaliza L Santos, Maingredy R Souza, Thiago L Rocha, Francisco S Guimarães, Janete A Anselmo-Franci, Renata Mazaro-Costa
Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. CBD was orally administered to 21-day-old male Swiss mice at doses of 15 and 30 mg kg-1 daily (CBD 15 and 30 groups, respectively), with a control group receiving sunflower oil, for 34 consecutive days...
May 16, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29761006/sodium-valproate-compared-to-phenytoin-in-treatment-of-status-epilepticus
#4
Mohammad Reza Amiri-Nikpour, Surena Nazarbaghi, Parisa Eftekhari, Sedra Mohammadi, Sina Dindarian, Mahdi Bagheri, Hozan Mohammadi
Background: Status epilepticus (SE) is a neurological emergency which can be life-threatening. Several medical regimens are used in order to control it. In this study, we intended to evaluate the clinical efficacy and tolerability of sodium valproate and intravenous phenytoin (IV PHT) in the control of SE. Methods: One hundred and ten consecutive patients suffering from benzodiazepine refractory SE who were referred to the emergency ward from March 2014 to March 2015 were randomly divided into two groups...
May 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29754109/improving-effect-of-mild-foot-electrical-stimulation-on-pentylenetetrazole-induced-impairment-of-learning-and-memory
#5
Monir Abasi-Moghadam, Arefe Ghasemi-Dehno, Mehdi Sadegh, Mohammad Reza Palizvan
Epilepsy is a common neurological disorder that affects learning and memory. Recently it has been shown that mild foot electrical stimulation (MFES) can increase learning and memory in normal rats. Pentylenetetrazole (PTZ) kindling is a model of human epilepsy. As with human epilepsy, PTZ kindling impairs learning and memory in rats. The purpose of this study was to investigate the effect MFES on kindling-induced learning and memory deficits in rats. Forty-nine male Wistar rats weighting 200 to 250 g were divided into the following seven groups: PTZ only, phenytoin only, MFES only, PTZ plus phenytoin, PTZ plus MFES, phenytoin plus MFES, and saline (control), with the treatments administered for 26 days...
May 10, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29750337/lamotrigine-resistant-corneal-kindled-mice-a-model-of-pharmacoresistant-partial-epilepsy-for-moderate-throughput-drug-discovery
#6
Zachery Koneval, Kevin M Knox, H Steve White, Melissa Barker-Haliski
OBJECTIVE: Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs (ASDs). Thus, there is a strong need for more effective ASDs for these individuals. Early ASD discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy. Etiologically relevant rodent models of pharmacoresistant epilepsy exist (eg, phenytoin (PHT)- and lamotrigine (LTG)-resistant amygdala-kindled rat and focal kainic acid mouse), but these models are resource- and labor-intensive and thus unsuitable for frontline ASD discovery...
May 11, 2018: Epilepsia
https://www.readbyqxmd.com/read/29746397/impact-of-drug-interactions-on-clobazam-and-n-desmethylclobazam-concentrations-in-pediatric-patients-with-epilepsy
#7
Gabrielle R Russell, Stephanie J Phelps, Chasity M Shelton, James W Wheless
BACKGROUND: Clobazam (CLB) is approved as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in patients ≥2 years of age. It is converted to an active metabolite N-desmethylclobazam (NCLB) by CYP3A4, which is then broken down to an inactive metabolite by CYP2C19. This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy. METHODS: This was a retrospective chart review including patients >1 month of age, who received CLB between April 2012 and March 2017...
May 4, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29744790/comparative-efficacy-of-antiepileptic-drugs-for-patients-with-generalized-epileptic-seizures-systematic-review-and-network-meta-analyses
#8
Marília Silveira de Almeida Campos, Lorena Rocha Ayres, Manuela Roque Siane Morelo, Fabiana Angelo Marques Carizio, Leonardo Régis Leira Pereira
Background Valproate is a widely prescribed antiepileptic drug for generalized epilepsies, due to the extensive knowledge on its efficacy since it is on the market for many decades. However, a large number of new antiepileptic medicines was introduced into clinical practice and may be better options for treatment, considering that these medicines differ in terms of efficacy spectrum. Despite extensive research, questions regarding which medicine would constitute the first option for the monotherapy treatment of generalized epilepsy remain...
May 9, 2018: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/29737274/antiepileptic-drug-monitoring-in-pregnancy-empire-a-double-blind-randomised-trial-on-effectiveness-and-acceptability-of-monitoring-strategies
#9
Shakila Thangaratinam, Nadine Marlin, Sian Newton, Annalise Weckesser, Manny Bagary, Lynette Greenhill, Rachel Rikunenko, Maria D'Amico, Ewelina Rogozińska, Andrew Kelso, Kelly Hard, Jamie Coleman, Ngawai Moss, Tracy Roberts, Lee Middleton, Julie Dodds, Angela Pullen, Sandra Eldridge, Alexander Pirie, Elaine Denny, Doug McCorry, Khalid S Khan
BACKGROUND: Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control. OBJECTIVE: To determine if, in pregnant women with epilepsy on AEDs, additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels. DESIGN: A double-blind, randomised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken...
May 2018: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/29730499/the-effects-of-ethosuximide-on-aversive-instrumental-learning-in-adult-rats
#10
John J Orczyk, Preston E Garraghty
Antiepileptic medications are the frontline treatment for seizure conditions but are not without cognitive side effects. Previously, our laboratory reported learning deficits in phenytoin-, carbamazepine-, valproic acid-, and felbamate-treated rats. In this experiment, the effects found in ethosuximide (ETH)-treated rats have been compared with those in water-treated controls (controls) using the same instrumental training tasks. Rats treated with ETH did not display any performance deficits in any of the conditions tested relative to controls...
May 3, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29730273/differences-in-associations-of-antiepileptic-drugs-and-hospitalization-due-to-hyponatremia-a-population-based-case-control-study
#11
Henrik Falhammar, Jonatan D Lindh, Jan Calissendorff, Shermineh Farmand, Jakob Skov, David Nathanson, Buster Mannheimer
PURPOSE: Hyponatremia induced by antiepileptic drugs is common, but detailed evidence is lacking. This can be problematic for the treating neurologist confronted with a patient with severe hyponatremia in need of an alternative drug. The objective of this study was to examine the association between individual antiepileptic drugs and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of patients in the general Swedish population...
April 30, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29725188/beware-of-phenytoin-self-harm-in-children
#12
Varun Kumar Singh, Jayantee Kalita, Usha Kant Misra
No abstract text is available yet for this article.
April 2018: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/29714095/impact-of-obesity-on-fosphenytoin-volume-of-distribution-in-pediatric-patients
#13
Ashley B Prusakov, Anup D Patel, Justin W Cole
The impact of body habitus on fosphenytoin pharmacokinetics is poorly understood in pediatric patients. This retrospective, single-center review examined differences in fosphenytoin volume of distribution (VD ) between children with normal and obese body habitus. From 2013 to 2015, patients 2 to 18 years of age who received a loading dose of fosphenytoin were identified. Thirty-seven patients met inclusion criteria. Mean total serum phenytoin concentration was 25.3 ± 6.5 μg/mL in the nonobese group and 29...
January 1, 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29702046/are-excipients-inert-phenytoin-pharmaceutical-investigations-with-new-incompatibility-insights
#14
Daniela Amaral Silva, Raimar Löbenberg, Neal Davies
PURPOSE: The U.S. Pharmacopeia defines excipients as substances other than the active pharmaceutic ingredient (API) that are added in a drug delivery system in order to aid in the manufacturing process and enhance stability, bioavailability, safety, effectiveness and delivery of the drug. The 1968 phenytoin intoxication outbreak in Brisbane, Australia, is a classic example of an API-excipient interaction. When administered with CaSO4 the absorption of phenytoin was reduced due to an interaction between the API and the excipient...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29700277/prophylactic-anticonvulsants-in-patients-undergoing-craniotomy-a-single-center-experience
#15
Aydemir Kale
BACKGROUND There is no consensus on the efficacy of seizure prophylaxis in patients undergoing craniotomy. Some studies show that antiepileptic use decreases the risk of seizures, but other studies do not support this. The present study investigated the role of antiepileptic drugs in patient undergoing craniotomy due to various intracranial pathologies. MATERIAL AND METHODS A retrospective review was performed in adult patients undergoing craniotomy between January 2013 and June 2017. Results of 282 patients who did not have a history of seizures and had craniotomies for various reasons were included...
April 27, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29699863/two-japanese-cases-of-epileptic-encephalopathy-associated-with-an-fgf12-mutation
#16
Ryo Takeguchi, Kazuhiro Haginoya, Yuri Uchiyama, Atsushi Fujita, Michiaki Nagura, Eri Takeshita, Takehiko Inui, Yukimune Okubo, Ryo Sato, Takuya Miyabayashi, Noriko Togashi, Takashi Saito, Eiji Nakagawa, Kenji Sugai, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto, Masayuki Sasaki
A heterozygous mutation in the fibroblast growth factor 12 (FGF12) gene, which elevates the voltage dependence of neuronal sodium channel fast inactivation, was recently identified in some patients with epileptic encephalopathy. Here we report 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). These 2 patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12 , which was identified with whole-exome sequencing...
April 23, 2018: Brain & Development
https://www.readbyqxmd.com/read/29697464/incidence-and-risk-factors-for-intraoperative-seizures-during-elective-craniotomy
#17
Rachel Kutteruf, Jen-Ting Yang, James G Hecker, Gregory A Kinney, Michele A Furman, Deepak Sharma
BACKGROUND: Perioperative seizures may affect 1% to 50% of patients undergoing craniotomy and adversely impact outcomes. However, data on intraoperative seizures are limited. This retrospective case-control study investigated the incidence and risk factors for intraoperative seizures during elective supratentorial craniotomy involving evoked potential monitoring. MATERIALS AND METHODS: Patients aged 18 years or above undergoing elective supratentorial craniotomy with evoked potential monitoring who experienced intraoperative seizures at our institution between December 2008 and March 2014 were compared with a control group generated using a random number generator...
April 24, 2018: Journal of Neurosurgical Anesthesiology
https://www.readbyqxmd.com/read/29689312/wound-healing-property-of-milk-in-full-thickness-wound-model-of-rabbit
#18
Ali Asghar Hemmati, Anahita Rezaei, Amir Larki-Harchegani, Gholamreza Housmand, Somayeh Shabib, Amir Jalali
OBJECTIVE: Wound healing consists of several continuous phases in which various cells and chemical intermediates are involved. Milk as a rich source of nutrition elements has proved to have potential benefits of treatment of various diseases. The present study was designed to investigate the healing effect of low-fat cow's milk on an open skin wound model in rabbits. METHODS: The 2%, 5%, and 10% (w/w) ointments of lyophilized powder of low-fat milk were prepared ineucerin base and were applied twice daily in the treatment groups...
April 21, 2018: International Journal of Surgery
https://www.readbyqxmd.com/read/29688078/a-systemic-review-of-levetiracetam-versus-phenytoin-in-the-prevention-of-late-post-traumatic-seizures-and-survey-of-uk-neurosurgical-prescribing-practice-of-antiepileptic-medication-in-acute-traumatic-brain-injury
#19
Ahmed Bakr, Antonio Belli
BACKGROUND: Guidelines recommend 1 week of prophylactic phenytoin for post-traumatic seizures (PTS). Levetiracetam is gaining popularity as an alternative with a superior side-effect profile and may be suitable for extended use. We performed a systematic review comparing the efficacy of levetiracetam and phenytoin in reducing the incidence of late PTS. The secondary objectives were to compare their effects on the Extended Glasgow Outcome Scale (GOS-E) and length of stay. We also aimed to survey current prophylaxis prescribing practices...
April 24, 2018: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/29683874/time-dependent-decline-in-serum-phenytoin-concentration-with-heightened-convulsive-seizure-risk-by-prolonged-administration-of-fosphenytoin-in-japanese-a-retrospective-study
#20
Yuta Ohno, Takashi Niwa, Keita Hirai, Keiko Suzuki, Yuto Yamada, Yuichi Hayashi, Hideki Hayashi, Akio Suzuki, Yoshinori Itoh
BACKGROUND: Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. METHODS: Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled...
April 20, 2018: Therapeutic Drug Monitoring
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