Ann Clin Neurophysiol.  2021 Oct;23(2):108-116. 10.14253/acn.2021.23.2.108.

Spectrum of nitrous oxide intoxication related neurological disorders in Korea: a case series and literature review

• Lee J
• Park Y
• Kim H
• Kim N
• Sung W
• Lee S
• Park J

• KMID: 2521888
• DOI: http://doi.org/10.14253/acn.2021.23.2.108

Abstract

Background
Nitrous oxide (N₂O) is used in surgery and dentistry for its anesthetic and analgesic effects. However, neurological and psychiatric manifestations of N₂O abuse have been increasingly reported among Korean adults. The aim of this study was to demonstrate laboratory findings of N₂O abuse in Korean patients.
Methods
Patients diagnosed with N₂O-induced neuropathy or myelopathy from August 2018 to December 2019 were enrolled. Their clinical presentations and laboratory and imaging findings were analyzed.
Results
Sensory changes and limb weakness were present in nine of the enrolled patients. The laboratory findings revealed that seven patients had high homocysteine levels and five had high methylmalonic acid levels in their blood. Nerve conductions studies indicated that axonal neuropathy was present in four cases and longer F-wave and Hoffman’s-reflex latencies were present in two cases. Signal changes in cervical spine imaging occurred in five patients, while two had normal results.
Conclusions
Chronic N₂O abuse can cause neurological damage or psychiatric problems. Because N₂O is illegal for recreational use in Korea, patients tend to hide their history of use. Even though the spinal imaging results were normal, clinicians should consider the possibility of N₂O use, and further electrophysiological tests should be applied for precise evaluations.

Figure

• 

  Fig. 1. T2-weighted cervical spinal magnetic resonance imaging (patient no. 1). (A) In the sagittal series, abnormal hyperintensities were observed in the dorsal cervical spinal cord (C2-C5) without enhancement. (B) In the axial series, high signal intensity (inverted-V sign) and cord swelling were observed.

• 

  Fig. 2. T2-weighted spinal magnetic resonance imaging (patient no. 9). (A) T2-weighted sagittal image, indicating high signal intensities within the posterior spinal cord from C7 to the conus medullaris. (B) T2-weighted axial image indicating high signal intensities in the anterior, lateral, and posterior spinal column.

Reference

1. Sethi NK, Mullin P, Torgovnick J, Capasso G. Nitrous oxide “whippit” abuse presenting with cobalamin responsive psychosis. J Med Toxicol. 2006; 2:71–74.

2. Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med. 2007; 131:872–884.

3. Dong X, Ba F, Wang R, Zheng D. Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report and review of the literature. Int J Neurosci. 2019; 129:225–229.

4. Lan SY, Kuo CY, Chou CC, Kong SS, Hung PC, Tsai HY, et al. Recreational nitrous oxide abuse related subacute combined degeneration of the spinal cord in adolescents-a case series and literature review. Brain Dev. 2019; 41:428–435.

5. Kwoun YJ, Choi YJ, Oh JY, Park KD, Choi KG. Myeloneuropathy following chronic abuse of nitrous oxide. J Korean Neurol Assoc. 2003; 21:432–435.

6. Sun W, Liao JP, Hu Y, Zhang W, Ma J, Wang GF. Pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: a case report. World J Clin Cases. 2019; 7:4057–4062.

7. Feng LY, Yu WJ, Chang WT, Han E, Chung H, Li JH. Comparison of illegal drug use pattern in Taiwan and Korea from 2006 to 2014. Subst Abuse Treat Prev Policy. 2016; 11:34.

8. American Association of Electrodiagnostic Medicine, Olney RK. Guidelines in electrodiagnostic medicine. Consensus criteria for the diagnosis of partial conduction block. Muscle Nerve Suppl. 1999; 8:S225–S229.

9. Choi C, Kim T, Park KD, Lim OK, Lee JK. Subacute combined degeneration caused by nitrous oxide intoxication: a report of two cases. Ann Rehabil Med. 2019; 43:530–534.

10. Lee HL, Lee SJ, Nam TS, Min SH, Kim JM, Kang KW. Acute cervical myelopathy following laughing gas abuse. Chonnam Med J. 2019; 55:118–119.

11. Richardson PG. Peripheral neuropathy following nitrous oxide abuse. Emerg Med Australas. 2010; 22:88–90.

12. Maler JM, Seifert W, Hüther G, Wiltfang J, Rüther E, Kornhuber J, et al. Homocysteine induces cell death of rat astrocytes in vitro. Neurosci Lett. 2003; 347:85–88.

13. Kölker S, Ahlemeyer B, Krieglstein J, Hoffmann GF. Methylmalonic acid induces excitotoxic neuronal damage in vitro. J Inherit Metab Dis. 2000; 23:355–358.

14. Weimann J. Toxicity of nitrous oxide. Best Pract Res Clin Anaesthesiol. 2003; 17:47–61.

15. Pleasure D. Toxic neuropathies. In : Darras BT, Jones HR, Ryan MM, De Vivo DC, editors. Neuromuscular disorders of infancy, childhood, adolescence: a clin approach. 2nd ed. Oxford: Elsevier;2015. p. 431–437.

16. Tani J, Weng HY, Chen HJ, Chang TS, Sung JY, Lin CS. Elucidating unique axonal dysfunction between nitrous oxide abuse and Vitamin B12 deficiency. Front Neurol. 2019; 10:704.

17. Waclawik AJ, Luzzio CC, Juhasz-Pocsine K, Hamilton V. Myeloneuropathy from nitrous oxide abuse: unusually high methylmalonic acid and homocysteine levels. WMJ. 2003; 102:43–45.

18. Kwon YJ, Rho JH, Hwang J, Baek SH. Unhappy end of ‘happy balloons’: subacute combined degeneration caused by nitrous oxide gas. J Clin Neurol. 2019; 15:118–119.

19. Kang SW, Hong JM, Namgung DW, Choi Y. Neurological manifestations of myeloneuropathy in patients with nitrous oxide intoxication. J Clin Neurol. 2019; 15:116–117.