Early Hyperglycemia Is Associated With Poor Gross Motor Outcome in Asphyxiated Term Newborns
asphyxia; blood-glucose; cell membrane-function; cerebral-palsy; glucose level; hyperglycemia; hypoxia-ischemia; injury; ischemic brain-damage; metabolism; motor development; Neurosciences & Neurology; newborn full term; outcome; Pediatrics; perinatal asphyxia; stroke
BACKGROUND: Hyperglycemia after ischemic stroke in adults and after near-drowning in children is associated with a poor neurological outcome. Anaerobic metabolism of glucose leads to buildup of lactic acid, free radical production, mitochondrial failure, and ultimately an increase in neurological injury. In asphyxiated infants, high lactate peaks are seen in the basal ganglia with magnetic resonance spectroscopy. Because motor disability in asphyxiated full-term newborns often relates to injury in the basal ganglia, we hypothesized that hyperglycemia and associated buildup of lactic acid may lead to worse gross motor outcome. METHODS: Glucose, blood gas values, and demographic data were abstracted from the medical records of 41 term infants with asphyxia and without confounding diagnoses. Their Gross Motor Function Classification System scores were determined from the medical record or by structured telephone interviews. RESULTS: The outcomes of 14 infants were considered poor on the basis of death within the first 6 months or moderate-to-severe cerebral palsy (Gross Motor Function Classification System score 1-5). The other 27 infants had no gross motor disability (Gross Motor Function Classification System score 0). The highest recorded blood glucose correlated with poor outcome (P = 0.046 by logistic regression). Infants with hyperglycemia (blood glucose > 150 mg/dL) were more likely to have poor outcome (P = 0.017; odds ratio: 5.9; 95% confidence interval: 1.4-24.7). CONCLUSIONS: High blood glucose in the first 12 hours is associated with poor gross motor outcome in this cohort of asphyxiated term infants. Clinicians should avoid hyperglycemia in managing term infants with asphyxia.
Spies E E; Lababidi S L; McBride M C
Pediatric Neurology
2014
2014-06
Journal Article
<a href="http://doi.org/10.1016/j.pediatrneurol.2014.01.043" target="_blank" rel="noreferrer noopener">10.1016/j.pediatrneurol.2014.01.043</a>
Pilot Study of Intensive Chemotherapy With Peripheral Hematopoietic Cell Support for Children Less Than 3 Years of Age With Malignant Brain Tumors, the CCG-99703 Phase I/II Study. A Report From the Children's Oncology Group.
*Hematopoietic Stem Cell Transplantation/adverse effects; Antineoplastic Agents/administration & dosage/adverse effects; Brain Neoplasms/*therapy; Carboplatin/administration & dosage/adverse effects; Child; Children's Oncology Group; Cisplatin/administration & dosage/adverse effects; Combined Modality Therapy/adverse effects/methods; Consolidation Chemotherapy; Cyclophosphamide/administration & dosage/adverse effects/therapeutic use; Etoposide/administration & dosage/adverse effects; Feasibility Studies; Female; high-dose chemotherapy; Humans; Induction Chemotherapy; Infant; infant brain tumor; Male; Pilot Projects; Preschool; stem-cell support; Thiotepa/administration & dosage/adverse effects; Treatment Outcome; Vincristine/adverse effects/therapeutic use
BACKGROUND: The primary goals of the Children's Cancer Group 99703 study were to assess the feasibility and tolerability of-as well as the response rate to-a novel dose-intensive chemotherapy regimen. METHODS: Between March 1998 and October 2004, 92 eligible patients were enrolled. Following biopsy/resection, patients received three identical cycles of Induction chemotherapy (vincristine, cyclophosphamide, etoposide, and cisplatin) administered every 21-28 days. Patients without tumor progression then received three consolidation cycles of marrow-ablative chemotherapy (thiotepa and carboplatin) followed by autologous hematopoietic cell rescue. RESULTS: The maximum tolerated dose of thiotepa was 10 mg/kg/day x 2 days per cycle. The toxic mortality rate was zero during induction and 2.6% during consolidation. Centrally evaluated response rates to induction and consolidation in evaluable patients with residual tumor were 73.3% and 66.7%, respectively. Disease progression rates on induction and consolidation were 4%. Five-year event-free survival and overall survival were 43.9 +/- 5.2% and 63.6 +/- 5% respectively. Gross total resection versus less than gross total resection were the only significant outcome comparisons: 5-year maximum tolerated dose and overall survival of 54.4 +/- 7% versus 28.9 +/- 7% (P = 0.0065) and 75.9 +/- 8% versus 48.7 +/- 8% (P = 0.0034), respectively. The 5-year maximum tolerated dose for localized (M0) versus metastatic (M1+) medulloblastoma was 67.5 +/- 9.5% versus 30 +/- 14.5% (P = 0.007). The 5-year maximum tolerated dose and overall survival for desmoplastic medulloblastoma patients versus other medulloblastoma were 78.6 +/- 11% versus 50.5 +/- 12% (P = 0.038) and 85.7 +/- 9.4% versus 60.6 +/- 11.6% (P = 0.046), respectively. CONCLUSIONS: This phase I dose-escalation study of marrow-ablative thiotepa regimen determined a maximum tolerated dose that had acceptable toxicity. Overall survival data justify this strategy for current Children's Oncology Group studies.
Cohen Bruce H; Geyer J Russell; Miller Douglas C; Curran John G; Zhou Tianni; Holmes Emi; Ingles Sue Ann; Dunkel Ira J; Hilden Joanne; Packer Roger J; Pollack Ian F; Gajjar Amar; Finlay Jonathan L
Pediatric neurology
2015
2015-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.pediatrneurol.2015.03.019" target="_blank" rel="noreferrer noopener">10.1016/j.pediatrneurol.2015.03.019</a>
Use of next-generation sequencing as a diagnostic tool for congenital myasthenic syndrome.
congenital myasthenic syndrome; Congenital/*genetics/therapy; Continuous Positive Airway Pressure/methods; Humans; Infant; Male; Muscle Proteins/*genetics; Mutation/*genetics; Myasthenic Syndromes; next-generation sequencing; pyridostigmine; rapsyn
BACKGROUND: The clinical presentation of congenital myasthenic syndromes is similar to many other neuromuscular disorders of infancy, and with 12 known discrete genetic forms of congenital myasthenic syndromes, both the diagnosis and treatment decisions present clinical challenges. PATIENT DESCRIPTION: We report a
Das Alvin S; Agamanolis Dimitri P; Cohen Bruce H
Pediatric neurology
2014
2014-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.pediatrneurol.2014.07.032" target="_blank" rel="noreferrer noopener">10.1016/j.pediatrneurol.2014.07.032</a>
Neonatal glycine encephalopathy: biochemical and neuropathologic findings.
Adolescent; Amino Acid Metabolism; Amino Acids/blood; Brain Diseases; Brain/pathology; Calcium Oxalate/blood; Child; Crystallization; Follow-Up Studies; Glycine/*blood; Humans; Inborn Errors/genetics/*pathology; Infant; Male; Metabolic/genetics/*pathology; Myelin Sheath/*pathology; Newborn; Preschool; Spinal Cord/pathology
A patient with neonatal glycine encephalopathy who had severe neurologic retardation, spasticity, and seizures died at 17 years of age. Glycine concentration was markedly elevated in brain tissue, especially in the cerebellum. Neuropathologic study revealed spongy myelinopathy throughout the central nervous system and calcium oxalate crystals in the cerebellum, which are probably derived from degradation of glycine. Myelinopathy appeared to be static compared to neonatal patients. The neurologic manifestations of neonatal glycine encephalopathy are probably due to neurotransmitter abnormalities, not to myelin damage.
Agamanolis D P; Potter J L; Lundgren D W
Pediatric neurology
1993
1993-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0887-8994(93)90051-d" target="_blank" rel="noreferrer noopener">10.1016/0887-8994(93)90051-d</a>