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Sarah F Pollack, Olivia R Grocott, Kimberly A Parkin, Anna M Larson, Ronald L Thibert
Angelman syndrome (AS) is a neurogenetic imprinting disorder caused by loss of the maternally inherited Ube3a gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Myoclonic seizures are often the first seizure type to appear, and myoclonic status, associated with developmental regression, may occur in the first few years of life. Additionally, there have been rare reports of prolonged episodes of myoclonus without electrographic correlate in adults with AS...
March 16, 2018: Epilepsy & Behavior: E&B
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
Rachel Huddart, J Steven Leeder, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
April 2018: Pharmacogenetics and Genomics
M Crettenand, A O Rossetti, T Buclin, U Winterfeld
BACKGROUND: Knowledge about the passage of various antiepileptic drugs into breast milk and its consequences for the infant is limited. Faced with this uncertainty, breastfeeding is often discouraged for these patients. The aim of this study was to comprehensively review the available data regarding antiepileptic drugs during breastfeeding, to compare these data with information provided by the summary of product characteristics (SmPCs), and to provide recommendations for the use of these drugs in breastfeeding women...
February 27, 2018: Der Nervenarzt
Karen S Ho, Leah M Markham, Hope Twede, Amanda Lortz, Lenora M Olson, Xiaoming Sheng, Cindy Weng, E Robert Wassman, Tara Newcomb, E Robert Wassman, John C Carey, Agatino Battaglia
Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged...
February 22, 2018: Epilepsy & Behavior: E&B
Giulia S Porcari, Cary Fu, Emily D Doll, Emma G Carter, Robert P Carson
Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population...
February 8, 2018: Epilepsy & Behavior: E&B
J Schliessbach, A Siegenthaler, L Bütikofer, P Vuilleumier, P Jüni, U Stamer, L Arendt-Nielsen, M Curatolo
BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain...
January 23, 2018: European Journal of Pain: EJP
Emilio Perucca
The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years. Marijuana and other cannabis products with high content in Δ(9) - tetrahydrocannabinol (THC), utilized primarily for recreational purposes, are generally unsuitable for this indication, primarily because THC is associated with many undesired effects. Compared with THC, cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models and is largely devoid of adverse psychoactive effects and abuse liability...
December 2017: Journal of Epilepsy Research
Szu-Ying Chen, Wen-Chi Chen, Sarah Y Chang
A new version of dispersive liquid-liquid microextraction, namely, cyclodextrin-assisted dispersive liquid-liquid microextraction, with subsequent sweeping micellar electrokinetic chromatography has been developed for the preconcentration and sensitive detection of carbamazepine and clobazam. α-Cyclodextrin and chloroform were used as the dispersive agent and extraction solvent, respectively. After the extraction, carbamazepine and clobazam were analyzed using micellar electrokinetic chromatography with ultraviolet detection...
January 13, 2018: Journal of Separation Science
Naoko Sekiya, Midori Awazu
We report a case of nephrogenic syndrome of inappropriate antidiuresis caused by carbamazepine (CBZ). CBZ, an antiepileptic drug, is known to cause hyponatremia. The mechanism is generally considered to be inappropriate secretion of antidiuretic hormone, whereas an experimental study suggests a direct effect of CBZ on the kidney by stimulating vasopressin receptor. An 18-year-old male with atypical autism and epilepsy has been treated with CBZ and clobazam since age 9 and 10 years, respectively. At age 11, he was found to have asymptomatic hyponatremia...
December 27, 2017: CEN Case Reports
Sara Lukmanji, Khara M Sauro, Colin B Josephson, K Chelsea Altura, Samuel Wiebe, Nathalie Jetté
OBJECTIVE: Drug shortages are occurring at an increasing rate. From May to October 2016, there was a shortage of a level I critical antiepileptic drug, clobazam. We aimed to study the impact of this shortage on patients with epilepsy. METHODS: Adult patients from Calgary's Comprehensive Epilepsy Program who were taking clobazam were approached to participate in the study. Baseline data from the clinic prospective registry included clinical variables and presurvey patient-reported outcomes (PROs) such as the Global Assessment of Severity of Epilepsy, the Global Assessment of Disability Associated with Seizures, and the Quality of Life in Epilepsy questionnaire...
February 2018: Epilepsia
Jouko Isojarvi, Barry E Gidal, Steve Chung, Robert T Wechsler
Given the complexities managing Lennox-Gastaut syndrome (LGS)-comorbid conditions, multiple associated seizure types that tend to be refractory to treatment-dosage optimization of antiepileptic drug (AED) treatment is a challenge. In the absence of clinical trial data on optimization of AED dosage in patients with LGS, dose titration is guided by personal experience, anecdotal evidence, and specific patient factors (age, comorbid conditions and medications, seizure types, etc.). The goal of this study was to determine whether a 20% increase in adjunctive clobazam was a reasonable benchmark for improved seizure response in patients with LGS who had responded to adjunctive clobazam treatment during a 12-week lead-in trial...
January 2018: Epilepsy & Behavior: E&B
Clemente Vega, Ivan Sánchez Fernández, Jurriaan Peters, Maria S Thome-Souza, Michele Jackson, Masanori Takeoka, Greta N Wilkening, Phillip L Pearl, Kevin Chapman, Tobias Loddenkemper
AIM: To evaluate the efficacy of clobazam treatment in reducing epileptiform discharges and modifying neuropsychological function in continuous spike-wave during slow wave sleep. METHOD: We performed a prospective clinical trial in patients with continuous spike-wave during sleep aged 4 to 10 years. Patients underwent neuropsychological assessment and overnight electroencephalographic monitoring before treatment, and subsequent repeat assessment and overnight electroencephalographic monitoring 3 months after treatment...
March 2018: Developmental Medicine and Child Neurology
Min Jung Cho, Soon Sung Kwon, Ara Ko, Seung Tae Lee, Young Mock Lee, Heung Dong Kim, Hee Jung Chung, Se Hee Kim, Joon Soo Lee, Dae Sung Kim, Hoon Chul Kang
BACKGROUND AND PURPOSE: The aim of this study was to determine the effectiveness of stiripentol (STP) add-on therapy to valproate and clobazam in patients with Dravet syndrome (DS) according to the presence of mutations in the sodium channel alpha-1 subunit gene (SCN1A). METHODS: We performed direct sequencing to analyze SCN1A mutations in 32 patients with clinically confirmed with DS, and classified them into mutation (pathogenic or likely pathogenic) and nonmutation groups based on American College of Medical Genetics and Genomics guidelines...
October 31, 2017: Journal of Clinical Neurology
Nicole A Hawkins, Michael Lewis, Rebecca S Hammond, James J Doherty, Jennifer A Kearney
Dravet syndrome is an infant-onset epileptic encephalopathy with multiple seizure types that are often refractory to conventional therapies. Treatment with standard benzodiazepines like clobazam, in combination with valproate and stiripentol, provides only modest seizure control. While benzodiazepines are a first-line therapy for Dravet syndrome, they are limited by their ability to only modulate synaptic receptors. Unlike benzodiazepines, neuroactive steroids potentiate a wider-range of GABAA receptors. The synthetic neuroactive steroid SGE-516 is a potent positive allosteric modulator of both synaptic and extrasynaptic GABAA receptors...
November 10, 2017: Scientific Reports
Ali A Asadi-Pooya
Lennox-Gastaut syndrome (LGS) is considered an epileptic encephalopathy and is defined by a triad of multiple drug-resistant seizure types, a specific EEG pattern showing bursts of slow spike-wave complexes or generalized paroxysmal fast activity, and intellectual disability. The prevalence of LGS is estimated between 1 and 2% of all patients with epilepsy. The etiology of LGS is often divided into two groups: identifiable (genetic-structural-metabolic) in 65 to 75% of the patients and LGS of unknown cause in others...
November 9, 2017: Neurological Sciences
Maren Cecilie Strand, Jørg Mørland, Lars Slørdal, Bettina Riedel, Cato Innerdal, Trond Aamo, Grete Mathisrud, Vigdis Vindenes
AIMS: Norway has introduced legal concentration limits in blood for 28 non-alcohol drugs in driving under the influence cases. As of 2016 this legislation also regulates the assessment of combined effects of multiple benzodiazepines and opioids. We herein describe the employed methodology for the equivalence tables for concentrations of benzodiazepines/z-hypnotics and opioids implemented in the Norwegian Road Traffic Act. METHODS: Legislative limits corresponding to impairment at blood alcohol concentrations (BAC) of 0...
December 2017: Forensic Science International
Yoshiaki Yamamoto, Naotaka Usui, Takuji Nishida, Miho Mori, Yukitoshi Takahashi, Katsumi Imai, Yoshiyuki Kagawa, Yushi Inoue
BACKGROUND: Several studies have demonstrated that renal impairment not only decreases renal clearance, but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs (AEDs) metabolized by CYP3A4. METHODS: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment...
October 31, 2017: Therapeutic Drug Monitoring
Charles Vecht, Louis Royer-Perron, Caroline Houillier, Gilles Huberfeld
In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDA- and AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Epilepsy as presenting sign is associated with a longer survival in low- and high- grade gliomas, particularly with the IDH1 mutation...
October 27, 2017: Current Pharmaceutical Design
Noel Frey, Michael Bodmer, Andreas Bircher, Stephan Rüegg, Susan S Jick, Christoph R Meier, Julia Spoendlin
OBJECTIVE: Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. METHODS: In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs...
December 2017: Epilepsia
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