Elucidating Unique Axonal Dysfunction Between Nitrous Oxide Abuse and Vitamin B12 Deficiency

Jowy Tani; Hsing-Yu Weng; Hung-Ju Chen; Tsui-San Chang; Jia-Ying Sung; Cindy Shin-Yi Lin

doi:10.3389/fneur.2019.00704

Elucidating Unique Axonal Dysfunction Between Nitrous Oxide Abuse and Vitamin B12 Deficiency

Front Neurol. 2019 Jul 9:10:704. doi: 10.3389/fneur.2019.00704. eCollection 2019.

Authors

Jowy Tani^{1

2

3}, Hsing-Yu Weng^{1

4}, Hung-Ju Chen¹, Tsui-San Chang⁴, Jia-Ying Sung^{1

3

4}, Cindy Shin-Yi Lin^{5

6}

Affiliations

¹ Department of Neurology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
² Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.
³ Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁶ Faculty of Medicine and Health, Brain and Mind Centre, Central Clinical School, The University of Sydney, Sydney, NSW, Australia.

Abstract

Introduction: Abuse of nitrous oxide (N₂O) has an unusually high lifetime prevalence in developed countries and represents a serious concern worldwide. Myeloneuropathy following the inhalant abuse is commonly attributed to the disturbance of vitamin B12 metabolism, with severe motor deficits are often noted. The present study aims to elucidate its underlying pathophysiology. Methods: Eighteen patients with N₂O abuse or vitamin B12 deficiency were recruited. Comprehensive central and peripheral neuro-diagnostic tests were performed, including whole spine MRI, and thermal quantitative sensory testing (QST). Specifically, paired motor and sensory nerve excitability tests were performed in order to obtain a complete picture of the sensorimotor axonal damage. Results: The mean duration of N₂O exposure for the N₂O abuse patients was 17.13 ± 7.23 months. MRI revealed T2 hyperintensity in 87.5% of the N₂O abuse patients and 50% of the vitamin B12 deficiency patients. In N₂O abuse patients, the motor nerve excitability test showed decreased in peak response (7.08 ± 0.87 mV, P = 0.05), increased latency (7.09 ± 0.28 ms, P < 0.01), increased superexcitability (-32.95 ± 1.74%, P < 0.05), and decreased accommodation to depolarizing current [TEd (40-60 ms) 56.53 ± 0.70%, P < 0.05]; the sensory test showed only decreased peak response (30.54 ± 5.98 μV, P < 0.05). Meanwhile, motor test in vitamin B12 deficiency patients showed only decreased accommodation to depolarizing current [TEd (40-60 ms) 55.72 ± 1.60%, P < 0.01]; the sensory test showed decreased peak response (25.86 ± 3.44 μV, P < 0.05) increased superexcitability (-28.58 ± 3.71%, P < 0.001), increased subexcitability (8.31 ± 1.64%, P < 0.05), and decreased accommodation to depolarizing current [TEd (peak) 67.31 ± 3.35%, P < 0.001]. Conclusion: Compared to vitamin B12 deficiency, N₂O abuse patients showed prominent motor superexcitability changes and less prominent sensory superexcitability changes, hinting a unique pathological process different from that of vitamin B12 deficiency. N₂O abuse might cause axonal dysfunction not only by blocking methionine metabolism but also by toxicity affecting the paranodal region.

Keywords: inhalant; myeloneuropathy; nerve excitability test; nitrous oxide; vitamin B12.