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Neonatal encephalopathy

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https://www.readbyqxmd.com/read/29053702/the-effects-of-adding-prophylactic-phenobarbital-to-therapeutic-hypothermia-in-the-term-equivalent-hypoxic-ischemic-rat
#1
Sushma Krishna, Alexandra Hutton, Eric Aronowitz, Holly Moore, Susan J Vannucci
BackgroundHypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Therapeutic hypothermia (TH) is the only available intervention, but neuroprotection is incomplete and variable. Seizures are common in infants with HIE undergoing TH and may worsen outcome. Phenobarbital is sometimes added, although use of prophylactic phenobarbital is controversial in the neonate. We hypothesize that prophylactic phenobarbital (PB) will not reduce, and may enhance, the neuroprotective effects of TH on brain injury and motor outcomes in the postnatal-day 10 (P10) hypoxic-ischemic (HI) rat...
October 20, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29050392/clinical-spectrum-and-genotype-phenotype-associations-of-kcna2-related-encephalopathies
#2
Silvia Masnada, Ulrike B S Hedrich, Elena Gardella, Julian Schubert, Charu Kaiwar, Eric W Klee, Brendan C Lanpher, Ralitza H Gavrilova, Matthis Synofzik, Thomas Bast, Kathleen Gorman, Mary D King, Nicholas M Allen, Judith Conroy, Bruria Ben Zeev, Michal Tzadok, Christian Korff, Fanny Dubois, Keri Ramsey, Vinodh Narayanan, Jose M Serratosa, Beatriz G Giraldez, Ingo Helbig, Eric Marsh, Margaret O'Brien, Christina A Bergqvist, Adrian Binelli, Brenda Porter, Eduardo Zaeyen, Dafne D Horovitz, Markus Wolff, Dragan Marjanovic, Hande S Caglayan, Mutluay Arslan, Sergio D J Pena, Sanjay M Sisodiya, Simona Balestrini, Steffen Syrbe, Pierangelo Veggiotti, Johannes R Lemke, Rikke S Møller, Holger Lerche, Guido Rubboli
Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative loss-of-function or a gain-of-function of the voltage-gated K+ channel Kv1.2, were described to cause a new molecular entity within the epileptic encephalopathies. Here, we report a cohort of 23 patients (eight previously described) with epileptic encephalopathy carrying either novel or known KCNA2 mutations, with the aim to detail the clinical phenotype associated with each of them, to characterize the functional effects of the newly identified mutations, and to assess genotype-phenotype associations...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29048405/cooling-in-neonatal-hypoxic-ischemic-encephalopathy-practices-and-opinions-on-minimum-standards-in-the-state-of-california
#3
C J Wusthoff, C L Clark, H C Glass, T K Shimotake, J Schulman, S L Bonifacio
OBJECTIVE: Although hospitals increasingly offer therapeutic hypothermia (TH), there is variable implementation of related services. We assessed current practices and opinions regarding what services should be required of centers providing TH in California. STUDY DESIGN: We surveyed neonatal intensive care unit physicians statewide regarding practices and opinions about services related to TH. RESULTS: Of the 50 participating centers (47% response rate), 66% offer TH...
October 19, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/29046881/nmnat3-is-protective-against-the-effects-of-neonatal-cerebral-hypoxia-ischemia
#4
Rafael Galindo, Marianne Banks Greenberg, Toshiyuki Araki, Yo Sasaki, Nehali Mehta, Jeffrey Milbrandt, David M Holtzman
OBJECTIVE: To determine whether the NAD+ biosynthetic protein, nicotinamide mononucleotide adenylyltransferase-3 (NMNAT3), is a neuroprotective inducible enzyme capable of decreasing cerebral injury after neonatal hypoxia-ischemia (H-I) and reducing glutamate receptor-mediated excitotoxic neurodegeneration of immature neurons. METHODS: Using NMNAT3-overexpressing mice we investigated whether increases in brain NMNAT3 reduced cerebral tissue loss following H-I. We then employed biochemical methods from injured neonatal brains to examine the inducibility of NMNAT3 and the mechanism of NMNAT3-dependent neuroprotection...
October 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29038971/the-implementation-of-targeted-temperature-management-an-evidence-based-guideline-from-the-neurocritical-care-society
#5
Lori Kennedy Madden, Michelle Hill, Teresa L May, Theresa Human, Mary McKenna Guanci, Judith Jacobi, Melissa V Moreda, Neeraj Badjatia
BACKGROUND: Targeted temperature management (TTM) is often used in neurocritical care to minimize secondary neurologic injury and improve outcomes. TTM encompasses therapeutic hypothermia, controlled normothermia, and treatment of fever. TTM is best supported by evidence from neonatal hypoxic-ischemic encephalopathy and out-of-hospital cardiac arrest, although it has also been explored in ischemic stroke, traumatic brain injury, and intracranial hemorrhage patients. Critical care clinicians using TTM must select appropriate cooling techniques, provide a reasonable rate of cooling, manage shivering, and ensure adequate patient monitoring among other challenges...
October 16, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/29031613/pathogenic-mutations-of-the-human-mitochondrial-citrate-carrier-slc25a1-lead-to-impaired-citrate-export-required-for-lipid-dolichol-ubiquinone-and-sterol-synthesis
#6
Homa Majd, Martin S King, Anthony C Smith, Edmund R S Kunji
Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by more than 70%, indicating that impaired citrate transport is the most likely primary cause of the disease...
October 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29025962/therapeutic-hypothermia-in-acute-traumatic-spinal-cord-injury
#7
James Collis
Therapeutic hypothermia is already widely acknowledged as an effective neuroprotective intervention, especially within the acute care setting in relation to conditions such as cardiac arrest and neonatal encephalopathy. Its multifactorial mechanisms of action, including lowering metabolic rate and reducing acute inflammatory cellular processes, ultimately provide protection for central nervous tissue from continuing injury following ischaemic or traumatic insult. Its clinical application within acute traumatic spinal cord injury would therefore seem very plausible, it having the potential to combat the pathophysiological secondary injury processes that can develop in the proceeding hours to days following the initial injury...
October 12, 2017: Journal of the Royal Army Medical Corps
https://www.readbyqxmd.com/read/29016557/future-perspectives-of-cell-therapy-for-neonatal-hypoxic-ischemic-encephalopathy
#8
REVIEW
Makoto Nabetani, Haruo Shintaku, Takashi Hamazaki
Neonatal ischemic brain injury causes permanent motor-deficit cerebral palsy. Hypoxic-ischemic encephalopathy (HIE) is a very serious condition that can result in death and disability. In 1997, we reported that irreversible neuronal cell damage is induced by the elevation of intracellular Ca ion concentration that has occurred in sequence after excess accumulation of the excitatory neurotransmitter glutamate during ischemia. We also reported that hypothermia was effective in treating ischemic brain damage in rats by suppressing energy loss and raising intracellular Ca ion concentration...
October 10, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28993251/hypoxia-ischemia-modifies-postsynaptic-glun2b-containing-nmda-receptor-complexes-in-the-neonatal-mouse-brain
#9
Fuxin Lu, Guo Shao, Yongqiang Wang, Shenheng Guan, Alma L Burlingame, Xuemei Liu, Xiao Liang, Renatta Knox, Donna M Ferriero, Xiangning Jiang
The N-methyl-d-aspartate-type glutamate receptor (NMDAR)-associated multiprotein complexes are indispensable for synaptic plasticity and cognitive functions. While purification and proteomic analyses of these signaling complexes have been performed in adult rodent and human brain, much less is known about the protein composition of NMDAR complexes in the developing brain and their modifications by neonatal hypoxic-ischemic (HI) brain injury. In this study, the postsynaptic density proteins were prepared from postnatal day 9 naïve, sham-operated and HI-injured mouse cortex...
October 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28991764/hypoglycaemia-in-the-newborn
#10
Orhideja Stomnaroska, Elizabeta Petkovska, Sanja Ivanovska, Snezana Jancevska, Dragan Danilovski
AIM: Severe neonatal hypoglycaemia (HG) leads to neurologic damage, mental retardation, epilepsy, impaired cardiac performance and muscle weakness. The aim was to assess the frequency and severity of HG in a population of newborns. PATIENTS AND METHODS: We investigated 739 patients with neonatal hypoglycaemia (HG) (M:F=370:369) born at the University Clinic for Gynaecology and Obstetritics in Skopje in the period 2014-2016 and treated at the neonatal intensive care unit (NICU)...
September 1, 2017: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/28985901/systemic-manifestations-in-pyridox-am-ine-5-phosphate-oxidase-deficiency
#11
Réjean M Guerriero, Archana A Patel, Brian Walsh, Fiona M Baumer, Ankoor S Shah, Jurriaan M Peters, Lance H Rodan, Pankaj B Agrawal, Phillip L Pearl, Masanori Takeoka
OBJECTIVE: Pyridoxine is converted to its biologically active form pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine 5'-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5'-phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5'-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5'-phosphate oxidase deficiency...
June 3, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28982530/variability-in-preferred-management-of-electrographic-seizures-in-neonatal-hypoxic-ischemic-encephalopathy
#12
Melanie A McNally, Adam L Hartman
BACKGROUND: Seizures may cause added harm in neonates with hypoxic-ischemic encephalopathy (HIE). Specific recommendations about seizure treatment in this context are lacking. We sought to determine the scope of practice regarding management of non-status epilepticus electrographic-only seizures in this setting. METHODS: A case-based survey was distributed to members of the Child Neurology Society. Providers were asked about their preferred management strategy for sequential clinical scenarios...
June 15, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28981488/from-cord-to-caudate-characterizing-umbilical-cord-blood-stem-cells-and-their-paracrine-interactions-with-the-injured-brain
#13
REVIEW
Priya F Maillacheruvu, Lauren M Engel, Isaiah T Crum, Devendra K Agrawal, Eric S Peeples
Stem cells are proving to be a promising therapy for a wide range of pediatric disorders, from neonatal hypoxic-ischemic encephalopathy to pediatric leukemia. Due to their low immunogenicity and ease of availability, umbilical cord blood (UCB) progenitor cells are increasingly replacing fetal and adult-derived cells in therapeutic settings. Multiple environmental and demographic factors affect the number and type of stem cells extracted from UCB, and these differences have been associated with disparities in outcomes after transplantation...
October 5, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28980775/long-term-recovery-after-endothelial-colony-forming-cells-or-human-umbilical-cord-blood-cells-administration-in-a-rat-model-of-neonatal-hypoxic-ischemic-encephalopathy
#14
Isabelle Grandvuillemin, Philippe Garrigue, Alaa Ramdani, Farid Boubred, Umberto Simeoni, Françoise Dignat-George, Florence Sabatier, Benjamin Guillet
Neonatal hypoxic-ischemic encephalopathy (NHIE) is a dramatic perinatal complication, associated with poor neurological prognosis despite neuroprotection by therapeutic hypothermia, in the absence of an available curative therapy. We evaluated and compared ready-to-use human umbilical cord blood cells (HUCBC) and bankable but allogeneic endothelial progenitors (ECFC) as cell therapy candidate for NHIE. We compared benefits of HUCBC and ECFC transplantation 48 hours after injury in male rat NHIE model, based on the Rice-Vannucci approach...
October 5, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28972960/strategies-to-enhance-paracrine-potency-of-transplanted-mesenchymal-stem-cells-in-intractable-neonatal-disorders
#15
REVIEW
Won Soon Park, So Yoon Ahn, Se In Sung, Jee-Yin Ahn, Yun Sil Chang
Mesenchymal stem cell (MSC) transplantation represents the next breakthrough in the treatment of currently intractable and devastating neonatal disorders with complex multifactorial etiologies, including bronchopulmonary dysplasia, hypoxic ischemic encephalopathy, and intraventricular hemorrhage. Absent engraftment and direct differentiation of transplanted MSCs, and the 'hit and run' therapeutic effects of these MSCs suggest that their pleiotropic protection might be attributable to paracrine activity via the secretion of various biologic factors rather than to regenerative activity...
October 3, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28962807/targeted-temperature-management-in-brain-injured-patients
#16
REVIEW
Fred Rincon
Evidence from animal models indicates that lowering temperature by a few degrees can produce substantial neuroprotection. In humans, hypothermia has been found to be neuroprotective with a significant impact on mortality and long-term functional outcome only in cardiac arrest and neonatal hypoxic-ischemic encephalopathy. Clinical trials have explored the potential role of maintaining normothermia and treating fever in critically ill brain injured patients. This review concentrates on basic concepts to understand the physiologic interactions of thermoregulation, effects of thermal modulation in critically ill patients, proposed mechanisms of action of temperature modulation, and practical aspects of targeted temperature management...
November 2017: Neurologic Clinics
https://www.readbyqxmd.com/read/28961316/reduced-infancy-and-childhood-epilepsy-following-hypothermia-treated-neonatal-encephalopathy
#17
Xun Liu, Sally Jary, Frances Cowan, Marianne Thoresen
OBJECTIVE: To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age. METHODS: From 2006-2013, 151 infants with perinatal asphyxia underwent 72 h cooling. Clinical and amplitude-integrated electroencepalography (aEEG) with single-channel EEG-verified neonatal seizures were treated with AEDs...
September 29, 2017: Epilepsia
https://www.readbyqxmd.com/read/28960438/evaluating-a-targeted-bedside-measure-of-cerebral-perfusion-in-a-nonhuman-primate-model-of-neonatal-hypoxic-ischemic-encephalopathy
#18
Eric S Peeples, Chikodinaka K Ezeokeke, Sandra E Juul, Pierre D Mourad
OBJECTIVES: To compare ultrasound-derived resistive indices (RIs) obtained at the level of the thalamus via fast Doppler ultrasound with traditional anterior cerebral artery measures in a model of neonatal hypoxic-ischemic encephalopathy and to correlate each with clinical outcomes. METHODS: Nine nonhuman primate neonates underwent no umbilical cord occlusion (n = 3), umbilical cord occlusion without hypothermia (n = 3), or umbilical cord occlusion with hypothermia (n = 3)...
September 29, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28954393/insulin-like-growth-factors-in-the-pathogenesis-of-neurological-diseases-in-children
#19
REVIEW
Raili Riikonen
Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced in the developing brain. In this paper we will try to give an answer to the following questions: Why are studies in children important? What clinical studies in neonatal asphyxia, infantile spasms, progressive encephalopathy-hypsarrhythmia-optical atrophy (PEHO) syndrome, infantile ceroid lipofuscinosis (INCL), autistic spectrum disorders (ASD) and subacute sclerosing encephalopathy (SSPE) have been carried out? What are IGF-based therapeutic strategies? What are the therapeutic approaches? We conclude that there are now great hopes for the therapeutic use of IGF-1 for some neurological disorders (particularly ASD)...
September 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28942555/the-applicability-of-amide-proton-transfer-imaging-in-the-nervous-system-focus-on-hypoxic-ischemic-encephalopathy-in-the-neonate
#20
REVIEW
Yang Zheng, Xiaoming Wang
In recent years, magnetic resonance imaging (MRI) has become more widely used in neonatal hypoxic-ischemic encephalopathy (HIE), involving, for example, evaluation of cerebral edema, white matter fiber bundle tracking, cerebral perfusion status, and assessment of brain metabolites. MRI has many imaging modalities. However, its application for assessing changes in the internal environment at the tissue and cellular level after hypoxia-ischemia remains a challenge and is currently the focus of intense research...
September 23, 2017: Cellular and Molecular Neurobiology
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