المؤلفون: In Goo Lee, Chung Joon Moon, In Kyung Sung, Young-Ah Youn, Ji Yoon Han

المصدر: BMC Pediatrics, Vol 18, Iss 1, Pp 1-6 (2018)
BMC Pediatrics

مصطلحات موضوعية: Male, Pediatrics, medicine.medical_specialty, Levetiracetam, Birth weight, Gestational Age, Infant, Premature, Diseases, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Seizures, 030225 pediatrics, medicine, Birth Weight, Humans, Adverse effect, Retrospective Studies, Maintenance dose, business.industry, Infant, Newborn, lcsh:RJ1-570, Brain, Gestational age, Preterm infants, Retrospective cohort study, lcsh:Pediatrics, Neonatal seizures, Magnetic Resonance Imaging, Phenobarbital, Pediatrics, Perinatology and Child Health, Anticonvulsants, Female, business, Infant, Premature, 030217 neurology & neurosurgery, Research Article, medicine.drug

الوصف: Background Neonatal seizures remain a significant clinical problem, and therapeutic options are still not diverse with limited efficacy. Levetiracetam (LEV) is a relatively new and wide spectrum anti-seizure medication with favorable pharmacokinetics and safety profile. In the recent decades, LEV has been increasingly used for the treatment of neonatal seizures. The aim of this study was to describe the experience of using LEV as the first line anti-seizure medication for preterm infants. Methods A retrospective analysis of 37 preterm infants who were treated with LEV as the first-line anti-seizure medication was performed. Results Mean gestational age of the 37 preterm infants was 31.5 ± 1.9 weeks (range, 26 to 36+ 6 weeks). Twenty-one infants (57%) were seizure-free while given LEV at the end of the first week, and no additional anti-seizure medication was required. Loading doses of LEV ranged from 40 to 60 mg/kg (mean 56 mg/kg) and the maintenance dose ranged from 20 to 30 mg/kg (mean 23 mg/kg). No adverse effect was observed. Conclusions Levetiracetam can be a good and safe choice for treatment of neonatal seizures in preterm infants. Prospective double blind controlled studies are needed in the future.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13b770497760faf615e36e7df78030c8Test
http://link.springer.com/article/10.1186/s12887-018-1103-1Test

المؤلفون: Kai Kaila, Kerstin Römermann, Pauliina Paavilainen, Trine Lisberg Toft-Bertelsen, Andi Kipper, Peter W. Feit, Inkeri Spoljaric, Wolfgang Löscher, Martin Puskarjov, Patricia Seja, Nanna MacAulay, Kathrin Töllner, Markus Kalesse, Philip Hampel, Claudia Brandt, Kasper Lykke

المساهمون: Laboratory of Neurobiology, Neuroscience Center, University of Helsinki, Helsinki Institute of Life Science HiLIFE, Physiology and Neuroscience (-2020), Molecular and Integrative Biosciences Research Programme, Kai Kaila / Principal Investigator

مصطلحات موضوعية: 0301 basic medicine, Benzylamines, medicine.medical_treatment, Drug Evaluation, Preclinical, Pharmacology, Hippocampal formation, Tissue Culture Techniques, Epilepsy, Mice, Xenopus laevis, GABA, 0302 clinical medicine, Sodium Potassium Chloride Symporter Inhibitors, AQUAPORIN 4, Solute Carrier Family 12, Member 2, KINDLED RATS, Bumetanide, PILOCARPINE MODEL, Chemistry, 1184 Genetics, developmental biology, physiology, Brain, Drug Synergism, PYRAMIDAL NEURONS, Loop diuretic, 3. Good health, ANIMAL-MODELS, Pilocarpine, Phenobarbital, Anticonvulsants, Female, CATION-CHLORIDE COTRANSPORTERS, medicine.drug, medicine.drug_class, 03 medical and health sciences, Cellular and Molecular Neuroscience, Giant depolarizing potentials, Seizures, medicine, Animals, Rats, Wistar, GIANT DEPOLARIZING POTENTIALS, 3112 Neurosciences, WATER PERMEABILITY, Neonatal seizures, medicine.disease, DRUG DISCOVERY, 030104 developmental biology, Anticonvulsant, GABA ACTIONS, Oocytes, 030217 neurology & neurosurgery, Anti-seizure drugs

الوصف: Correction Volume: 143 Pages: 349-350 DOI: 10.1016/j.neuropharm.2018.10.012 Based on the potential role of Na-K-Cl cotransporters (NKCCs) in epileptic seizures, the loop diuretic bumetanide, which blocks the NKCC1 isoforms NKCC1 and NKCC2, has been tested as an adjunct with phenobarbital to suppress seizures. However, because of its physicochemical properties, bumetanide only poorly penetrates through the blood-brain barrier. Thus, concentrations needed to inhibit NKCC1 in hippocampal and neocortical neurons are not reached when using doses (0.1-0.5 mg/kg) in the range of those approved for use as a diuretic in humans. This prompted us to search for a bumetanide derivative that more easily penetrates into the brain. Here we show that bumepamine, a lipophilic benzylamine derivative of bumetanide, exhibits much higher brain penetration than bumetanide and is more potent than the parent drug to potentiate phenobarbital's anticonvulsant effect in two rodent models of chronic difficult-to-treat epilepsy, amygdala kindling in rats and the pilocarpine model in mice. However, bumepamine suppressed NKCC1-dependent giant depolarizing potentials (GDPs) in neonatal rat hippocampal slices much less effectively than bumetanide and did not inhibit GABA-induced Ca2+ transients in the slices, indicating that bumepamine does not inhibit NKCC1. This was substantiated by an oocyte assay, in which bumepamine did not block NKCC1a and NKCC1b after either extra- or intracellular application, whereas bumetanide potently blocked both variants of NKCC1. Experiments with equilibrium dialysis showed high unspecific tissue binding of bumetanide in the brain, which, in addition to its poor brain penetration, further reduces functionally relevant brain concentrations of this drug. These data show that CNS effects of bumetanide previously thought to be mediated by NKCC1 inhibition can also be achieved by a close derivative that does not share this mechanism. Bumepamine has several advantages over bumetanide for CNS targeting, including lower diuretic potency, much higher brain permeability, and higher efficacy to potentiate the anti-seizure effect of phenobarbital.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2eb498b43ac7a92429d3b6c29ccfcc27Test
http://hdl.handle.net/10138/312515Test

المؤلفون: Michael W. Kuzniewicz, Sharon O. Wietstock, Charles E. McCulloch, Hannah C. Glass, Sonia L. Bonifacio

المصدر: Journal of child neurology, vol 30, iss 9
Wietstock, SO; Bonifacio, SL; McCulloch, CE; Kuzniewicz, MW; & Glass, HC. (2015). Neonatal neurocritical care service is associated with decreased administration of seizure medication. Journal of Child Neurology, 30(9), 1135-1141. doi: 10.1177/0883073814553799. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/01810827Test

مصطلحات موضوعية: Male, Pediatrics, neonatal seizures, epilepsy monitoring, Hypothermia, Neurodegenerative, Cohort Studies, Hypothermia, Induced, Neonatal, Hypnotics and Sedatives, hypoxic-ischemic encephalopathy, media_common, Pediatric, Brain, Electroencephalography, Phenobarbital, Anesthesia, Hypoxia-Ischemia, Brain, Female, Cognitive Sciences, medicine.drug, Vigilance (psychology), Cohort study, medicine.medical_specialty, media_common.quotation_subject, Seizure medication, Clinical Sciences, Encephalopathy, Loading dose, Article, Seizures, Hypoxia-Ischemia, medicine, Humans, Epilepsy, Neurology & Neurosurgery, business.industry, Induced, Intensive Care, Neurosciences, Neurointensive care, electroencephalogram, medicine.disease, Confidence interval, Brain Disorders, Good Health and Well Being, Pediatrics, Perinatology and Child Health, Intensive Care, Neonatal, Neurology (clinical), business

الوصف: © The Author(s) 2014. This cohort study examines medication use in term neonates with hypoxic-ischemic encephalopathy and seizures before and after implementation of a Neonatal Neurocritical Care Service (N = 108), which included increased seizure monitoring. Nearly all neonates received phenobarbital (96% pre- vs 95% post-Neonatal Neurocritical Care Service) and total loading dose did not vary among groups (33 [95% confidence interval 29-37] vs 30 [26-34] mg/kg). After adjustment for seizure burden, neonates managed during the Neonatal Neurocritical Care Service era, on average, received 30 mg/kg less cumulative phenobarbital (95% confidence interval 15-46 mg/kg) and were on maintenance 5 fewer days (95% confidence interval 3-8 days) than those who were treated prior to implementation of the service. In spite of the enhanced ability to detect seizures because of improved monitoring and increased vigilance by bedside practitioners, implementation of the Neonatal Neurocritical Care Service was associated with decreased use of potentially harmful phenobarbital treatment among neonates with hypoxic-ischemic encephalopathy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::963447d06a5a4e923c369c89931904aeTest
https://doi.org/10.1177/0883073814553799Test

المؤلفون: Mohamed M. Helmy, Patrick O. Kanold, Paul V. Watkins, Juha Voipio, Eva Ruusuvuori, Kai Kaila

المصدر: Brain

مصطلحات موضوعية: Male, medicine.medical_specialty, Sodium-Hydrogen Exchangers, Alkalosis, Intracellular pH, resuscitation, neonatal seizures, Na/H exchange, birth asphyxia, Blood–brain barrier, Membrane Potentials, Amiloride, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Seizures, Internal medicine, medicine, Extracellular, Animals, Humans, Normocapnia, 030304 developmental biology, Acidosis, Acid-Base Equilibrium, Neurons, Asphyxia, Asphyxia Neonatorum, 0303 health sciences, pH, Chemistry, Infant, Newborn, Brain, Original Articles, Hydrogen-Ion Concentration, medicine.disease, Rats, Disease Models, Animal, medicine.anatomical_structure, Endocrinology, Animals, Newborn, Blood-Brain Barrier, Anesthesia, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery, medicine.drug

الوصف: Birth asphyxia is often associated with a high seizure burden that is predictive of poor neurodevelopmental outcome. The mechanisms underlying birth asphyxia seizures are unknown. Using an animal model of birth asphyxia based on 6-day-old rat pups, we have recently shown that the seizure burden is linked to an increase in brain extracellular pH that consists of the recovery from the asphyxia-induced acidosis, and of a subsequent plateau level well above normal extracellular pH. In the present study, two-photon imaging of intracellular pH in neocortical neurons in vivo showed that pH changes also underwent a biphasic acid-alkaline response, resulting in an alkaline plateau level. The mean alkaline overshoot was strongly suppressed by a graded restoration of normocapnia after asphyxia. The parallel post-asphyxia increase in extra- and intracellular pH levels indicated a net loss of acid equivalents from brain tissue that was not attributable to a disruption of the blood-brain barrier, as demonstrated by a lack of increased sodium fluorescein extravasation into the brain, and by the electrophysiological characteristics of the blood-brain barrier. Indeed, electrode recordings of pH in the brain and trunk demonstrated a net efflux of acid equivalents from the brain across the blood-brain barrier, which was abolished by the Na/H exchange inhibitor, N-methyl-isobutyl amiloride. Pharmacological inhibition of Na/H exchange also suppressed the seizure activity associated with the brain-specific alkalosis. Our findings show that the post-asphyxia seizures are attributable to an enhanced Na/H exchange-dependent net extrusion of acid equivalents across the blood-brain barrier and to consequent brain alkalosis. These results suggest targeting of blood-brain barrier-mediated pH regulation as a novel approach in the prevention and therapy of neonatal seizures.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e44da3c9de3b059ce1cfaacee38ac1fTest
https://doi.org/10.1093Test/brain/aws257

المؤلفون: Mona C. Toet, Vicki Livingstone, Ronit M. Pressler, Barry Mangum, Renate Swarte, Catherine Chiron, Neil Marlow, Sampsa Vanhatalo, Vincent Jullien, Mats Blennow, J. Helen Cross, Linda S. de Vries, Geraldine B. Boylan, Sarah Zohar, Brendan P. Murphy, Boubou Hallberg, Lena Hellström-Westas, Janet M. Rennie, Gérard Pons, Deirdre M. Murray

المساهمون: Pediatrics

المصدر: Lancet Neurology, 14(5), 469-477. Lancet Publishing Group
Lancet Neurology, 14(5), 469. Lancet Publishing Group

مصطلحات موضوعية: Male, Pediatrics, medicine.medical_specialty, OTOTOXICITY, INFANTS, Drug Administration Schedule, Sodium Potassium Chloride Symporter Inhibitors, Pharmacokinetics, Ototoxicity, Seizures, Intensive care, NEONATAL SEIZURES, medicine, NKCC1, Humans, Treatment Failure, BRAIN, Adverse effect, Bumetanide, HYPOTHERMIA, business.industry, Infant, Newborn, Drug Synergism, Hypothermia, medicine.disease, Clinical trial, COTRANSPORTER, Phenobarbital, Anesthesia, Early Termination of Clinical Trials, Hypoxia-Ischemia, Brain, Feasibility Studies, Female, Neurology (clinical), medicine.symptom, business, medicine.drug

الوصف: Summary Background Preclinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding, and feasibility phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic ischaemic encephalopathy and electrographic seizures not responding to a loading-dose of phenobarbital from eight neonatal intensive care units across Europe. Newborn babies were allocated to receive an additional dose of phenobarbital and one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy. We assessed adverse events, pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic seizure burden of more than 80% without the need for rescue antiepileptic drugs in more than 50% of infants. The trial is registered with ClinicalTrials.gov, number NCT01434225. Findings Between Sept 1, 2011, and Sept 28, 2013, we screened 30 infants who had electrographic seizures due to hypoxic ischaemic encephalopathy. 14 of these infants (10 boys) were included in the study (dose allocation: 0·05 mg/kg, n=4; 0·1 mg/kg, n=3; 0·2 mg/kg, n=6; 0·3 mg/kg, n=1). All babies received at least one dose of bumetanide with the second dose of phenobarbital; three were withdrawn for reasons unrelated to bumetanide, and one because of dehydration. All but one infant also received aminoglycosides. Five infants met EEG criteria for seizure reduction (one on 0·05 mg/kg, one on 0·1 mg/kg and three on 0·2 mg/kg), and only two did not need rescue antiepileptic drugs (ie, met rescue criteria; one on 0·05 mg/kg and one on 0·3 mg/kg). We recorded no short-term dose-limiting toxic effects, but three of 11 surviving infants had hearing impairment confirmed on auditory testing between 17 and 108 days of age. The most common non-serious adverse reactions were moderate dehydration in one, mild hypotension in seven, and mild to moderate electrolyte disturbances in 12 infants. The trial was stopped early because of serious adverse reactions and limited evidence for seizure reduction. Interpretation Our findings suggest that bumetanide as an add-on to phenobarbital does not improve seizure control in newborn infants who have hypoxic ischaemic encephalopathy and might increase the risk of hearing loss, highlighting the risks associated with the off-label use of drugs in newborn infants before safety assessment in controlled trials. Funding European Community's Seventh Framework Programme.

وصف الملف: image/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0fa6dfcb17b8378b3635355e3309d96Test
https://dspace.library.uu.nl/handle/1874/333543Test

المؤلفون: Kleopas A. Kleopa, Jérôme Devaux, Steven S. Scherer, Edward C. Cooper

المساهمون: Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Devaux, jérôme

المصدر: Journal of Neuroscience
Journal of Neuroscience, Society for Neuroscience, 2004, 24 (5), pp.1236-1244. ⟨10.1523/JNEUROSCI.4512-03.2004⟩

مصطلحات موضوعية: Potassium Channels, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Linopirdine, chemistry.chemical_compound, Mice, 0302 clinical medicine, M current, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Ankyrin, Benign familial neonatal seizures, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, Chemistry, General Neuroscience, Retigabine, Brain, Immunohistochemistry, Sciatic Nerve, [SDV] Life Sciences [q-bio], Spinal Cord, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Potassium Channels, Voltage-Gated, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, Cellular/Molecular, Ankyrins, Immunoblotting, KCNQ3 Potassium Channel, 03 medical and health sciences, Ranvier's Nodes, medicine, Repolarization, Animals, Humans, KCNQ2 Potassium Channel, Myokymia, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, 030304 developmental biology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Optic Nerve, medicine.disease, Axon initial segment, Precipitin Tests, Rats, nervous system, Amino Acid Substitution, Mutation, Neuroscience, 030217 neurology & neurosurgery, HeLa Cells

الوصف: Mutations in the gene encoding the K+channel KCNQ2 cause neonatal epilepsy and myokymia, indicating that KCNQ2 regulates the excitability of CNS neurons and motor axons, respectively. We show here that KCNQ2 channels are functional components of axon initial segments and nodes of Ranvier, colocalizing with ankyrin-G and voltage-dependent Na+channels throughout the CNS and PNS. Retigabine, which opens KCNQ channels, diminishes axonal excitability. Linopirdine, which blocks KCNQ channels, prolongs the repolarization of the action potential in neonatal nerves. The clustering of KCNQ2 at nodes and initial segments lags that of ankyrin-G during development, and both ankyrin-G and KCNQ2 can be coimmunoprecipitated in the brain. KCNQ3 is also a component of some initial segments and nodes in the brain. The diminished activity of mutant KCNQ2 channels accounts for neonatal epilepsy and myokymia; the cellular locus of these effects may be axonal initial segments and nodes.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6682d1ac2222e899a27af318afa65e8Test
https://hal.archives-ouvertes.fr/hal-02999281Test