Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : Protection by methionine and aggravation by folates

1. Long-term exposure of the fruit bat Rousettus aegyptiacus to nitrous oxide, which inactivates methylco balamin, leads to neurological impairment and ataxia.2. In N2, O-exposed animals, liver concentrations of total folates and methyl folates decreased to less than one fifth that of control animals. Pediococcus cerevisiue-active folates were also reduced.3. In brain, there were no changes in total or methyl folates, but P.cerevisiae-active folates were lower in N2, O-exposed animals.4. Supplementation with methionine retarded the development of neurological impairment and the fall in liver total and methyl folates, but not that in P. cerevisiae-active folates.5. Supplementation with serine failed to retard the development of neurological impairment or fall in hepatic folates.6. The present results suggest that the N2O-induced neurological impairment in the bat is not related to depletion of cerebral folates, but do not exclude changes in the subcellular distribution of folates.

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Severe Neurological Impairment in an Infant after Nitrous Oxide Anesthesia

Anesthesiology ◽

10.1097/00000542-200012000-00036 ◽

2000 ◽

Vol 93 (6) ◽

pp. 1549-1550 ◽

Cited By ~ 22

Author(s):

James K. McNeely ◽

Bogdan Buczulinski ◽

Diane R. Rosner

Keyword(s):

Nitrous Oxide ◽

Neurological Impairment ◽

Severe Neurological Impairment ◽

Oxide Anesthesia

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Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency

British Journal Of Nutrition ◽

10.1079/bjn19850075 ◽

1985 ◽

Vol 53 (3) ◽

pp. 657-662 ◽

Cited By ~ 13

Author(s):

Justin Van Der Westhuyzen ◽

Suasn V. Van Tonder ◽

Jayne E. Gibson ◽

Terence A. Kilroe-smith ◽

Jack Metz

Keyword(s):

Nitrous Oxide ◽

Vitamin B12 Deficiency ◽

Dietary Supplementation ◽

Basal Diet ◽

Neurological Impairment ◽

Vitamin B ◽

Muscular Weakness ◽

Fruit Bats ◽

B12 Deficiency ◽

Methionine Synthesis

1. The effect of methylcobalamin inactivation by the gas nitrous oxide on plasma amino acid and tissue methionine levels in fruit bats (Rousettus aegyptiacus) was examined.2. Animals exposed to N2O-oxygen (1:1, v/v) for 90 min daily received a fruit diet with or without methionine or betaine supplements. Exposure and diets were continued for up to 17 weeks or until neurological impairment and muscular weakness was established.3. All the groups exposed to N2O had significantly lower liver, brain and plasma methionine concentrations except the methionine-supplemented animals which showed significantly raised levels. Plasma homocysteine, which was absent in controls, was present in all the N2O-exposed groups.4. Betaine supplementation resulted in reduced accumulation of homocysteine in plasma. However, plasma and liver methionine levels were only slightly increased compared with animals on the basal diet, and brain methionine levels were the lowest of all the groups studied.5. These results support the hypothesis that reduced methionine synthesis is an important contributor to the development of neurological impairment in this species and suggest that dietary supplementation with the methionine precursor betaine cannot replace the loss of vitamin B12-dependent methionine synthesis.

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Opioid-Induced Respiratory Depression in Pediatric Palliative Care Patients with Severe Neurological Impairment—A Scoping Literature Review and Case Reports

Children ◽

10.3390/children7120312 ◽

2020 ◽

Vol 7 (12) ◽

pp. 312

Author(s):

Maximilian David Mauritz ◽

Carola Hasan ◽

Larissa Alice Dreier ◽

Pia Schmidt ◽

Boris Zernikow

Keyword(s):

Risk Factors ◽

Palliative Care ◽

Young Adults ◽

Scoping Review ◽

Pediatric Patients ◽

Case Reports ◽

Neurological Impairment ◽

Opioid Therapy ◽

Pediatric Palliative Care ◽

Severe Neurological Impairment

Pediatric Palliative Care (PPC) addresses children, adolescents, and young adults with a broad spectrum of underlying diseases. A substantial proportion of these patients have irreversible conditions accompanied by Severe Neurological Impairment (SNI). For the treatment of pain and dyspnea, strong opioids are widely used in PPC. Nonetheless, there is considerable uncertainty regarding the opioid-related side effects in pediatric patients with SNI, particularly concerning Opioid-Induced Respiratory Depression (OIRD). Research on pain and OIRD in pediatric patients with SNI is limited. Using scoping review methodology, we performed a systematic literature search for OIRD in pediatric patients with SNI. Out of n = 521 identified articles, n = 6 studies were included in the review. Most studies examined the effects of short-term intravenous opioid therapy. The incidence of OIRD varied between 0.13% and 4.6%; besides SNI, comorbidities, and polypharmacy were the most relevant risk factors. Additionally, three clinical cases of OIRD in PPC patients receiving oral or transdermal opioids are presented and discussed. The case reports indicate that the risk factors identified in the scoping review also apply to adolescents and young adults with SNI receiving low-dose oral or transdermal opioid therapy. However, the risk of OIRD should never be a barrier to adequate symptom relief. We recommend careful consideration and systematic observation of opioid therapy in this population of patients.

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Development and psychometric validation of the family-centered multidimensional outcome measure for pediatric palliative care targeted to children with severe neurological impairmentis—A multicenter prospective study

Palliative Medicine ◽

10.1177/0269216320975626 ◽

2020 ◽

pp. 026921632097562

Author(s):

Sophie Pelke ◽

Julia Wager ◽

Benedikt B. Claus ◽

Boris Zernikow ◽

Mandira Reuther

Keyword(s):

Palliative Care ◽

Factor Analysis ◽

Prospective Study ◽

Outcome Measure ◽

Neurological Impairment ◽

Pediatric Palliative Care ◽

Confirmatory Factor ◽

Multicenter Prospective Study ◽

Family Centered ◽

Severe Neurological Impairment

Background: Comprehensive outcome measurement in pediatric palliative care focusing on the entire unit of care, that is, the affected child and its family, is crucial to depict treatment effects. Despite its increasing relevance, no appropriate multidimensional outcome measures exist for the largest patient group in this field, namely children with severe neurological impairments. Aim: The aim of this study was to develop and validate a family-centered multidimensional outcome measure for pediatric palliative care patients with severe neurological impairment that encompasses the entire unit of care. Design: Based on results of a qualitative study, the questionnaire was developed by consensus-based generation of questions. It was validated in a multicenter prospective study employing exploratory and confirmatory factor analyses as well as reliability and item analyses. Setting: A total of 11 pediatric palliative care teams across Germany aided in the recruitment of study participants. Questionnaires were answered by 149 parents of children with severe neurological impairment and 157 professional caregivers. Results: The exploratory factor analysis of parent data revealed a 6-factor structure of the questionnaire representing: symptoms, the child’s social participation, normalcy, social support, coping with the disease and caregiver’s competencies. This structure was verified by a confirmatory factor analysis of professional caregiver data. Five separate items regarding siblings, partners, and further symptoms not applicable for all patients were added to ensure full multidimensionality. Conclusion: A validated outcome tool for severely neurologically impaired pediatric palliative care patients, the FACETS-OF-PPC, now exists. Due to its concise length and appropriate psychometric properties, it is well suited for clinical application.

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