Neurosurgical aspects of Noonan syndrome.

PURPOSE: Noonan syndrome (NS) is a rare neurodevelopmental syndrome characterized by dysmorphic features, congenital heart defects, neurodevelopmental delay, and bleeding diathesis. Though rare, several neurosurgical manifestations have been associated with NS, such as Chiari malformation (CM-I), syringomyelia, brain tumors, moyamoya, and craniosynostosis. We describe our experience in treating children with NS and various neurosurgical conditions, and review the current literature on neurosurgical aspects of NS. METHODS: Data were retrospectively collected from the medical records of children with NS who were operated at a tertiary pediatric neurosurgery department, between 2014 and 2021. Inclusion criteria were clinical or genetic diagnosis of NS, age < 18 years at treatment, and need for a neurosurgical intervention of any kind. RESULTS: Five cases fulfilled the inclusion criteria. Two had tumors, one underwent surgical resection. Three had CM-I, syringomyelia, and hydrocephalus, of whom one also had craniosynostosis. Comorbidities included pulmonary stenosis in two patients and hypertrophic cardiomyopathy in one. Three patients had bleeding diathesis, two of them with abnormal coagulation tests. Four patients were treated preoperatively with tranexamic acid, and two with Von Willebrand factor or platelets (1 each). One patient with a clinical bleeding predisposition developed hematomyelia following a syringe-subarachnoid shunt revision. CONCLUSIONS: NS is associated with a spectrum of central nervous system abnormalities, some of which with known etiology, while in others a pathophysiological mechanism has been suggested in the literature. When operating on a child with NS, a meticulous anesthetic, hematologic, and cardiac evaluation should be conducted. Neurosurgical interventions should then be planned accordingly.

Extracellular production and degradation of superoxide in the coral Stylophora pistillata and cultured Symbiodinium.

BACKGROUND: Reactive oxygen species (ROS) are thought to play a major role in cell death pathways and bleaching in scleractinian corals. Direct measurements of ROS in corals are conspicuously in short supply, partly due to inherent problems with ROS quantification in cellular systems. METHODOLOGY/PRINCIPAL FINDINGS: In this study we characterized the dynamics of the reactive oxygen species superoxide anion radical (O(2)(-)) in the external milieu of the coral Stylophora pistillata. Using a sensitive, rapid and selective chemiluminescence-based technique, we measured extracellular superoxide production and detoxification activity of symbiont (non-bleached) and aposymbiont (bleached) corals, and of cultured Symbiodinium (from clades A and C). Bleached and non-bleached Stylophora fragments were found to produce superoxide at comparable rates of 10(-11)-10(-9) mol O(2)(-) mg protein(-1) min(-1) in the dark. In the light, a two-fold enhancement in O(2)(-) production rates was observed in non-bleached corals, but not in bleached corals. Cultured Symbiodinium produced superoxide in the dark at a rate of . Light was found to markedly enhance O(2)(-) production. The NADPH Oxidase inhibitor Diphenyleneiodonium chloride (DPI) strongly inhibited O(2)(-) production by corals (and more moderately by algae), possibly suggesting an involvement of NADPH Oxidase in the process. An extracellular O(2)(-) detoxifying activity was found for bleached and non-bleached Stylophora but not for Symbiodinium. The O(2)(-) detoxifying activity was partially characterized and found to resemble that of the enzyme superoxide dismutase (SOD). CONCLUSIONS/SIGNIFICANCE: The findings of substantial extracellular O(2)(-) production as well as extracellular O(2)(-) detoxifying activity may shed light on the chemical interactions between the symbiont and its host and between the coral and its environment. Superoxide production by Symbiodinium possibly implies that algal bearing corals are more susceptible to an internal build-up of O(2)(-), which may in turn be linked to oxidative stress mediated bleaching.