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Pediatric neurotoxicity

Richard B Parad
On Dec. 16, 2016, the U.S. Food and Drug Administration (FDA) released a warning regarding the potential neurotoxicity of anesthesia and sedation agents on the developing brain in children younger than 3 years and in women during their 3rd trimester of pregnancy. These concerns have relevance to the pediatric radiologist who must take into consideration how the child's state might impact image quality. In this review the author provides background on the special concerns in the potentially highest-risk group, pre-term and term neonates, and provides guidance and rationale for the avoidance of sedation in procedural imaging of the newborn...
April 2018: Pediatric Radiology
Cheng Wang, Xianlin Han, Fang Liu, Tucker A Patterson, Joseph P Hanig, Merle G Paule, William Slikker
Adverse effects related to central nervous system (CNS) function in pediatric populations may, at times, be difficult, if not impossible to evaluate. Prolonged anesthetic exposure affects brain excitability and anesthesia during the most sensitive developmental stages and has been associated with mitochondrial dysfunction, aberrant lipid metabolism and synaptogenesis, subsequent neuronal damage, as well as long-term behavioral deficits. There has been limited research evaluating whether and how anesthetic agents affect cellular lipids, the most abundant components of the brain other than water...
March 14, 2018: Toxicology and Applied Pharmacology
Nikhat Saba, Alpana Seal
Vinca alkaloids are chemotherapeutic agents used in the treatment of both pediatric and adult cancer patients. Cytochrome P450 3A5 (CYP3A5) is 9- to 14-fold more efficient at clearing vincristine than cytochrome P450 3A4 (CYP3A4) is. However, patients who express an inactive form of the polymorphic CYP3A5 enzyme suffer from severe neurotoxicity during vincristine treatment, resulting in chemotherapy failure. Previous studies have found that the addition of new features to the parent drug can enhance its binding affinity to tubulin manyfold and could therefore yield novel anticancer drugs...
March 4, 2018: Journal of Molecular Modeling
Sufang Jiang, Xuze Li, Wei Jin, Xiaofeng Duan, Lijun Bo, Jiangli Wu, Rui Zhang, Ying Wang, Rongtian Kang, Lining Huang
Ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. However, prolonged exposure to ketamine results in widespread anesthetic neurotoxicity and long-term neurocognitive deficits. The molecular mechanisms that underlie this important event are poorly understood. We investigated effects of anesthetic ketamine on neuroapoptosis and further explored role of NMDA receptors in ketamine-induced neurotoxicity. Here we demonstrate that ketamine induces activation of cell cycle entry, resulting in cycle-related neuronal apoptosis...
March 1, 2018: Neuroscience Letters
Laura S Gilchrist, Lynn R Tanner
PURPOSE: To describe the incidence and short-term recovery of balance control in children and adolescents receiving neurotoxic treatment for noncentral nervous system cancers and to investigate the association of chemotherapy-induced peripheral neuropathy and balance control. METHODS: Sixty-five children and adolescents diagnosed with leukemia, lymphoma, or other solid tumors were tested 3 to 6 months into treatment and 3 and 6 months following treatment using the Bruininks-Oseretsky Balance Subscale and Pediatric Modified Total Neuropathy Scale scores of chemotherapy-induced peripheral neuropathy (CIPN)...
March 1, 2018: Pediatric Physical Therapy
Anne Duffy, Paul Grof
INTRODUCTION: There is a resurgence of interest in lithium treatment of bipolar disorders in part related to its unique anti-suicidal and neuroprotective effects. METHODS: This is a narrative review of key studies pertaining to the effectiveness and tolerability of lithium treatment in pediatric populations. RESULTS: Evidence supports that lithium is an effective and generally well-tolerated acute treatment for pediatric mania compared to placebo...
February 28, 2018: Pharmacopsychiatry
Serkan Kırık, Olcay Güngör, Sedat Işıkay, Can Acıpayam, Yasemin Çoban, Emre Çelik
Decreased height of the eyelid or the narrowing of the lid is called ptosis. Ptosis has several causes. Malignancy-related conditions such as Horner's syndrome, which causes unilateral ptosis in the pediatric age group, and patients with malignancy receiving chemotherapeutic treatment, are often secondary to these drugs and ptosis is a clue of underlying diseases. Underlying pathologies can lead to different clinical conditions such as cognitive impairment from coma, the presence of ptosis should be cautionary...
December 2017: Türk Pediatri Arşivi
Efe Serinan, Zekiye Altun, Safiye Aktaş, Emre Çeçen, Nur Olgun
OBJECTIVE: Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. MATERIALS AND METHODS: House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study...
February 20, 2018: Journal of International Advanced Otology
Change Zhu, Saiji Zhang, Zhiqing Gu, Yiru Tong, Rong Wei
BACKGROUND: Dexamethasone has become a popular additive for regional anesthesia. The aim of this meta-analysis was to assess the effectiveness of this additive on the duration of postoperative analgesia, postoperative vomiting, and possible adverse events in pediatrics. METHODS: We searched databases, conference records, and registered trials for randomized controlled trials. The databases included the Cochrane Library, JBI Database of Systematic Reviews, PubMed, ISI Web of Knowledge, Science-Direct, and Embase...
March 2018: Paediatric Anaesthesia
Beverley A Orser, Santhanam Suresh, Alex S Evers
SmartTots ( represents a public-private partnership between the International Anesthesia Research Society and the US Food and Drug Administration. Over the past 7 years, SmartTots has worked in collaboration with various stakeholders to determine whether anesthetic drugs have detrimental effects on the developing brain. SmartTots has funded clinical and preclinical studies, organized meetings, served as a repository of peer-reviewed information, and facilitated the development of consensus-based statements...
February 2, 2018: Anesthesia and Analgesia
Napoleón González Saldaña, Diego Mauricio Galvis Trujillo, Ana Maria Borbolla Pertierra, Ana Ivette Mondragón Pineda, Hugo Juárez Olguín
BACKGROUND: Toxic optic neuropathies are alterations of the optic nerve and can be caused by environmental, pharmacological, or nutritional agents. CASE: It is about a 7-year-old male patient, a native of the State of Mexico, Mexico who was diagnosed with cervical mycobacterial lymphadenitis that required management with linezolid. OBSERVATIONS: After 7 months of treatment, visual acuity of the left eye decreased and was accompanied by headache...
December 2017: Medicine (Baltimore)
Thomas Duflot, Aude Marie-Cardine, Céline Verstuyft, Bruno Filhon, Tony Pereira, Nathalie Massy Guillemant, Robinson Joannidès, Jérémy Bellien, Fabien Lamoureux
Ifosfamide (IFA) is a potent alkylating antitumoral agent but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In 3 consecutive cases of pediatric patients who exhibited ifosfamide-induced encephalopathy (IIE), genotyping of clinically relevant single nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed...
January 10, 2018: Fundamental & Clinical Pharmacology
Robert J Tamai, Brian T Sullivan, Rushyuan J Lee
BACKGROUND: Peripheral nerve blocks (PNBs) provide excellent pain control and reduce the need for systemic analgesics in orthopaedic surgery. PNBs rarely cause complications; however, a few studies of adults have reported neurological complications during the early postoperative period. We investigated complications associated with the use of PNBs during pediatric knee surgery. METHODS: We reviewed the medical records of all 121 children (aged ≤18 y) who underwent knee surgery by 1 orthopaedic surgeon between October 2014 and September 2016...
March 2018: Journal of Pediatric Orthopedics
Monica Guzman-Limon, Subha Amatya, Joshua Samuels, Rita Swinford, Sonal Bhatnagar, Joyce Samuel
Impaired renal function increases the risk for cefepime-induced neurotoxicity. Symptoms include disorientation, myoclonus, status epilepticus, ataxia, gait disturbance, coma, and death. A high index of suspicion and early recognition of symptoms can minimize the risk of progression of symptoms to permanent neurologic impairment or death.
December 2017: Clinical Case Reports
Bonnie L Robinson, Melanie Dumas, Syed F Ali, Merle G Paule, Qiang Gu, Jyotshna Kanungo
Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+ -permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR's protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos...
December 7, 2017: Neurotoxicology and Teratology
Xiaoli Liang, Yi Zhang, Chao Zhang, Chunchun Tang, Yi Wang, Juanjuan Ren, Xi Chen, Yu Zhang, Zhaoqiong Zhu
Currently sevoflurane is the volatile anesthetic most wildly used in pediatric surgery. Whether neonatal exposure to sevoflurane brings about a long-lasting adverse impact even at juvenile and adult age, attracts extensive concerns. However, to date the consensus has not been reached and how exposure to sevoflurane in early life affects long-term ability of learning and memory is not fully elucidated. To obtain further insight into this issue, 32 neonatal SD rats were assigned into control group (group C, n=16) and sevoflurane group (group SEV, n=16)...
2017: American Journal of Translational Research
Diana Cardona-Grau, Christopher E Bayne, Michael H Hsieh
No abstract text is available yet for this article.
October 2017: Journal of Pediatric Urology
Niviann M Blondet, Patrick J Healey, Evelyn Hsu
The field of pediatric solid-organ transplantation has significantly evolved since its beginnings in the early 20th century. As advancements have led to the development of innovative surgical techniques and novel medication regimens, transplantation has now become a routine practice leading to an increase in the rates of organ recipients worldwide. The care of pediatric solid-organ transplant recipients differs from adults in several areas not only due to technically challenging surgeries, but mostly due to the complexity of their immunosuppression management...
August 2017: Seminars in Pediatric Surgery
Zhi Ye, Qing Li, Qulian Guo, Yunchuan Xiong, Dong Guo, Hong Yang, Yan Shu
Ketamine, a pediatric anesthetic, is widely used in clinical practice. There was growing evidence showing that ketamine can promote neuronal death in developing brains of both humans and animals. In this study, we used in vivo neonatal and juvenile mouse models to induce ketamine-related neurotoxicity in the hippocampus. Active caspase-3 and -9 proteins, which are responsible for the release of cytochrome C, and the mitochondrial translocation of p53, which is associated with mitochondrial apoptosis, were found to be significantly up-regulated in the ketamine-induced hippocampal neurotoxicity...
January 2018: Neuropharmacology
Athena F Zuppa, Martha A Q Curley
Sedation is a mainstay of therapy for critically ill children. Although necessary in the care of the critically ill child, sedative drugs are associated with adverse effects, such as disruption of circadian rhythm, altered sleep, delirium, potential neurotoxicity, and immunosuppression. Optimal approaches to the sedation of the critically ill child should include identification of sedation targets and sedation interruptions, allowing for a more individualized approach to sedation. Further research is needed to better understand the relationship between critical illness and sedation pharmacokinetics and pharmacodynamics, the impact of sedation on immune function, and the genetic implications on drug disposition and response...
October 2017: Pediatric Clinics of North America
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