Reversible nitrous oxide myelopathy and a polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase

Pontifical Catholic University of Chile, CiudadSantiago, Santiago Metropolitan, Chile
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 03/2006; 96(2):222-5. DOI: 10.1093/bja/aei300
Source: PubMed


We present a case of a patient who received nitrous oxide on two occasions within a period of 8 weeks and who subsequently
developed a diffuse myelopathy, characterized by upper extremity paresis, lower extremity paraplegia and neurogenic bladder.
Laboratory testing revealed hyperhomocysteinaemia and low levels of vitamin B12. Because of this uncommon clinical presentation, we analysed the patient's DNA, and found a polymorphism in the MTHFR gene
that is associated with the thermolabile isoform of the 5,10-methylenetetrahydrofolate reductase enzyme, which explained the
myelopathy experienced by the patient after being exposed to nitrous oxide. Soon after initiating supplementary therapy with
folic acid and vitamin B12, the neurological symptoms subsided.

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    • "However, there are unwanted side effects such as bowel distension, postoperative nausea and vomiting [1]. Although rare, N2O has also been associated with serious complications such as myelopathy, megaloblastic anemia and vitamin B12 deficiency [2], as it inactivates vitamin B12, a key enzyme for methionine synthase. In addition, N2O may be harmful to the developing brain in animal study [3]. "
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    ABSTRACT: Remifentanil can be an alternative to N(2)O in general anesthesia. Intraoperative remifentanil may lead to acute opioid tolerance. This study aims to assess the effect of remifentanil substituted for 70% N(2)O on postoperative pain in children undergoing tonsillectomy/adenoidectomy. In addition, we evaluated the effect of remifentanil infusion on incidence of emergence agitation in these patients. Eighty children, aged 2-12 years, undergoing tonsillectomy/adenoidectomy were randomly allocated to the N(2)O group (Group N; n = 40, sevoflurane and 70% N(2)O) or remifentanil group (Group R; n = 40, sevoflurane with remifentanil infusion at the rate of 0.17 µg/kg/min). In the recovery room, severity of pain and agitation were assessed by an investigator blinded to the assigned group. Time to eye opening and incidence of severe pain and agitation were compared between groups. Logistic regression was used to identify factors related to occurrence of severe pain and agitation. Number of patients with severe postoperative pain was 6 and 16 in groups N and R, respectively (P = 0.012). Incidence of emergence agitation was not significantly different between groups. Remifentanil infusion was a significant factor related to the occurrence of severe postoperative pain (P = 0.015), and age was inversely related to occurrence of emergence agitation (P = 0.001). In children undergoing tonsillectomy/adenoidectomy, intraoperative remifentanil infusion may increase incidence of severe postoperative pain compared to N(2)O, but it may not affect incidence of emergence agitation.
    Full-text · Article · Aug 2011 · Korean journal of anesthesiology
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    ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR) deficiency is an autosomal recessive disorder with a spectrum of manifestations including neurological symptoms, premature arteriosclerosis, and venous and arterial thrombosis. Most patients are heterozygous for multiple MTHFR substitutions; small minorities are homozygous for mutations at this locus. Among these mutations, the C677T polymorphism is the most deleterious. Nitrous oxide use in anesthesia leads to significant increases in plasma homocysteine. We present a patient undergoing urgent surgery with a preoperative diagnosis of homozygous MTHFR deficiency.
    No preview · Article · Feb 2007 · Journal of Anesthesia
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