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Pediatric neurotoxicity

Riva R Ko, Teeda Pinyavat, Steven Stylianos, Sarah M Lambert, Richard C Anderson, Pamela F Gallin, Lynne G Maxwell, Christopher G Ward, Jayant K Deshpande, Constance S Houck
The Pediatric Anesthesia Neuro Development Assessment (PANDA) team at the Anesthesiology Department at Columbia University Medical Center held its fifth biennial symposium to discuss issues regarding potential neurotoxicity of anesthetic agents in pediatric patients. Overall optimal surgical timing as well as a "critical window" for surgery on a specialty specific basis are areas of focus for the American Academy of Pediatrics Surgical Advisory Panel. An ad hoc panel of pediatric surgical experts representing general surgery, urology, neurosurgery, and ophthalmology was assembled for this meeting and provided a dialogue focused on the benefits of early intervention versus potential anesthetic risk, addressing parental concerns, and the need for continued interdisciplinary collaboration in this area...
October 2016: Journal of Neurosurgical Anesthesiology
Teeda Pinyavat, David O Warner, Randall P Flick, Mary Ellen McCann, Dean B Andropoulos, Danquig Hu, Jeffrey W Sall, Marisa N Spann, Caleb Ing
During the Fifth Pediatric Anesthesia Neurodevelopmental Assessment Symposium, experts and stakeholders met to present and discuss recent advances made in the study of neurodevelopmental outcomes after exposure to anesthetic drugs in infants and children. This article summarizes the update of 5 ongoing clinical studies: General Anesthesia compared to Spinal Anesthesia, Toxicity of Remifentanil and Dexmedetomidine, Mayo Anesthesia Safety in Kids, the University of California San Francisco human cohort study, and Columbia University Medical Center Neonatal Magnetic Resonance Imaging study...
October 2016: Journal of Neurosurgical Anesthesiology
Tonya L K Miller, Raymond Park, Lena S Sun
On April 16 and 17, 2016, the Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study held its fifth biennial symposium at the Morgan Stanley Children's Hospital of New York. The PANDA symposium has served as a key forum for clinicians, researchers, and other major stakeholders to gather and review the current state of preclinical and clinical research related to anesthetic neurotoxicity in children. Goals of the meeting included assessing how current knowledge has translated and impacted clinical care of patients who may be at risk, and future directions for research and policy...
October 2016: Journal of Neurosurgical Anesthesiology
Madhumita Sinha, Dan Quan, Fred W McDonald, André Valdez
OBJECTIVE: Scorpion antivenom was recently approved for use in patients with clinically significant scorpion envenomation in the United States; no formal economic analysis on its impact on cost of management has been performed. METHODS: Three different strategies of management of scorpion envenomation with systemic neurotoxic symptoms in children were compared for cost minimization from a societal perspective. In strategy I, patients were managed with supportive care only without antivenom...
October 4, 2016: Pediatric Emergency Care
Kenneth Habetz, Raghu Ramakrishnaiah, Sunil Kumar Raina, Ryan T Fitzgerald, Archana Hinduja
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that, although characteristically reversible, can result in long-term disability. Our aim was to identify the clinical and radiological factors that are unique to children with PRES compared with adults with the syndrome in a single center. METHODS: We retrospectively reviewed the clinical and radiological records of all patients with PRES admitted at a tertiary care medical center from 2007 to 2014...
September 13, 2016: Pediatric Neurology
Krishnan N Subrahmanian, Young H Shim, Mona D Shah, Brandon H Tran, Alexandra M Stevens, Andrea T Cruz
Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new-onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis...
September 23, 2016: Pediatric Emergency Care
Tejaswi Kandula, Susanna B Park, Richard J Cohn, Arun V Krishnan, Michelle A Farrar
BACKGROUND: The dramatic increase in the number of childhood cancer survivors over the last 60years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches...
September 10, 2016: Cancer Treatment Reviews
Victoria J Forster, Frederik W van Delft, Susan F Baird, Shona Mair, Roderick Skinner, Christina Halsey
PURPOSE: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. METHODS: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy...
September 22, 2016: Cancer Chemotherapy and Pharmacology
Allison M Bradbury, Jessica H Bagel, Xuntian Jiang, Gary P Swain, Maria L Prociuk, Caitlin A Fitzgerald, Patricia A O'Donnell, Kyle G Braund, Daniel S Ory, Charles H Vite
Globoid cell leukodystrophy (GLD), or Krabbe's disease, is a debilitating and always fatal pediatric neurodegenerative disease caused by a mutation in the gene encoding the hydrolytic enzyme galactosylceramidase (GALC). In the absence of GALC, progressive loss of myelin and accumulation of a neurotoxic substrate lead to incapacitating loss of motor and cognitive function and death, typically by 2 years of age. Currently, there is no cure. Recent convincing evidence of the therapeutic potential of combining gene and cell therapies in the murine model of GLD has accelerated the requirement for validated markers of disease to evaluate therapeutic efficacy...
November 2016: Journal of Neuroscience Research
Wen Wee Ma, Muhammad Wasif Saif, Bassel F El-Rayes, Marwan G Fakih, Thomas H Cartwright, James A Posey, Thomas R King, Reid W von Borstel, Michael K Bamat
BACKGROUND: Increased susceptibility to 5-fluorouracil (5-FU)/capecitabine can lead to rapidly occurring toxicity caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, and other genetic variations in the enzymes that metabolize 5-FU. Life-threatening 5-FU overdoses occur because of infusion pump errors, dosage miscalculations, and accidental or suicidal ingestion of capecitabine. Uridine triacetate (Vistogard) was approved in 2015 for adult and pediatric patients who exhibit early-onset severe or life-threatening 5-FU/capecitabine toxicities or present with an overdose...
September 13, 2016: Cancer
Yi Wei, Junhua Hu, Yubing Liang, Yuling Zhong, Dan He, Yi Qin, Li Li, Jing Chen, Qiang Xiao, Yubo Xie
Propofol is widely used for the induction and maintenance of pediatric anesthesia. Previous studies have indicated that propofol can induce apoptosis, and damage cognitive and memory functions. Dexmedetomidine is a potent α‑2 adrenoceptor agonist with high selectivity. Previous observations have shown that dexmedetomidine exhibits anti‑apoptotic qualities. The present study evaluated the neuroprotective effects of dexmedetomidine pretreatment against propofol‑induced neurotoxicity in immature hippocampal neurons...
October 2016: Molecular Medicine Reports
Caleb Ing, Virginia A Rauh, David O Warner, Lena S Sun
On April 16 and 17, 2016, the Fifth biennial Pediatric Anesthesia & Neurodevelopment Assessment (PANDA) symposium was convened at the Morgan Stanley Children's Hospital of New York at Columbia University Medical Center. During the symposium, experts in the fields of anesthesiology, neuropsychology, and epidemiology were convened in a small group session to determine the level of confidence in the current clinical evidence and the next steps in anesthetic neurotoxicity clinical research. Among the participants in the discussion, there remained a lack of consensus on whether anesthetic exposure causes long-term neurodevelopmental deficits in children based on the current evidence...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Yolanda Y Huang, Lucy Li, Matthew Monteleone, Lynne Ferrari, Lisa J States, James J Riviello, Steven G Kernie, Ali A Mencin, Sumit Gupta, Lena S Sun
Ongoing investigation from the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study hopes to examine the long-term effect on cognitive and language development of a single anesthetic exposure in children undergoing inguinal hernia repair. The fifth PANDA Symposium, held in April 2016, continued the mission of previous symposia to examine evidence from basic science and clinical studies on potential neurotoxic effects of anesthetics on developing brain. At the 2016 Symposium, a panel of specialists from nonsurgical pediatric disciplines including anesthesiology, radiology, neurology, gastroenterology, oncology, cardiology, and critical care reviewed use of anesthesia in their practices, including how concern over possible neurodevelopmental effects of early childhood anesthetic exposure has changed discussion with patients and families regarding risks and benefits of imaging studies and interventional procedures involving sedation or anesthesia...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Yolanda Y Huang, Caleb Ing, Gouhua Li, Lena S Sun
INTRODUCTION: Although animal studies have consistently demonstrated long-term neurocognitive deficits following early anesthetic exposure under certain conditions, risk in human children remains unknown. Magnetic resonance imaging (MRI) in young patients often requires anesthesia to facilitate image acquisition. We studied MRI utilization in a pediatric population, and associated use of anesthesia for ambulatory MRI. MATERIALS AND METHODS: Data were obtained from the New York State Inpatient Database and State Ambulatory Surgery and Services Database on MRI performed in children under the age of 18 years from 2005 to 2011...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Richard J Levy, Julie B Herbstman, Zeljko J Bosnjak, Andreas W Loepke, Francis X McGowan
Exposure to commonly used anesthetic agents causes widespread neuronal degeneration in the developing mammalian brain and has been shown to impair neurodevelopment in a variety of newborn vertebrate animal species. Although retrospective studies have suggested an association between anesthesia exposure in childhood and subsequent neurodevelopmental abnormalities, a causal relationship in humans has yet to be demonstrated. Unfortunately, translation of findings from bench to bedside is limited by several factors and histologic assessment in healthy children following exposure to anesthesia is not possible...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Zeljko J Bosnjak, Sarah Logan, Yanan Liu, Xiaowen Bai
Mounting evidence has demonstrated that general anesthetics could induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long-term memory and learning abnormalities. Propofol is a commonly used intravenous anesthetic agent for the induction and maintenance of anesthesia and procedural and critical care sedation in children. Compared with other anesthetic drugs, little information is available on its potential contributions to neurotoxicity. Growing evidence from multiple experimental models showed a similar neurotoxic effect of propofol as observed in other anesthetic drugs, raising serious concerns regarding pediatric propofol anesthesia...
August 22, 2016: Anesthesia and Analgesia
Catherine E Creeley
The fetal and neonatal periods are critical and sensitive periods for neurodevelopment, and involve rapid brain growth in addition to natural programmed cell death (i.e., apoptosis) and synaptic pruning. Apoptosis is an important process for neurodevelopment, preventing redundant, faulty, or unused neurons from cluttering the developing brain. However, animal studies have shown massive neuronal cell death by apoptosis can also be caused by exposure to several classes of drugs, namely gamma-aminobutyric acid (GABA) agonists and N-methyl-d-aspartate (NMDA) antagonists that are commonly used in pediatric anesthesia...
August 16, 2016: Brain Sciences
Li-Yan Wang, Zhi-Jun Tang, Yu-Zeng Han
Millions of infants and children are exposed to anesthesia every year during medical care. Sevoflurane is a volatile anesthetic that is frequently used for pediatric anesthesia. However, previous reports have suggested that the administration of sevoflurane promotes neurodegeneration, raising concerns regarding the safety of its usage. The present study aimed to investigate caffeic acid phenethyl ester (CAPE) and its protective effect against sevoflurane‑induced neurotoxicity in neonatal rats. Rat pups were administered with CAPE at 10, 20 or 40 mg/kg body weight from postnatal day 1 (P1) to P15...
October 2016: Molecular Medicine Reports
Hui Zhang, Xiao-Ru Sun, Jing Wang, Zhen-Zhen Zhang, Hong-Ting Zhao, Hui-Hui Li, Mu-Huo Ji, Kuan-Yu Li, Jian-Jun Yang
Ketamine, a common anesthetic used for pediatric patients, has been shown to induce neurotoxicity and alter adolescent behaviors in rats when administered during neonatal period. However, the mechanisms underlying this kind of neurotoxicity remain largely to be determined. Herein, we studied whether the reactive oxygen species (ROS) due to the increased NOX2 mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Sprague-Dawley male rat pups received a daily administration of ketamine intraperitoneally (75 mg/kg) from postnatal day 6 (P6) to P8 for three consecutive days...
November 2016: Neurotoxicity Research
Shin-Ichi Tsujimoto, Masakatsu Yanagimachi, Reo Tanoshima, Kevin Y Urayama, Fumiko Tanaka, Noriko Aida, Hiroaki Goto, Shuichi Ito
BACKGROUND: Methotrexate (MTX) can lead to neurotoxicity and asymptomatic leukoencephalopathy. However, the mechanism of MTX-related leukoencephalopathy is obscure. MTX and its metabolites inhibit 5-aminoimidazole-4-carboxamide ribonucleotide formiltransferase (ATIC) and promote adenosine release. Recently, it has been reported that adenosine and its receptor are related to certain central nervous system diseases. We investigated whether adenosine pathway gene polymorphisms and clinical factors were related to MTX-related leukoencephalopathy in pediatric patients affected by hematological malignancies...
November 2016: Pediatric Blood & Cancer
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