Subacute Combined Degeneration from Nitrous Oxide Use

Yoon, Joseph Y.; Klein, Joshua P.

doi:10.1056/nejmicm2119871

Cited by 8 publications

(7 citation statements)

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“…Detailed characterization would be needed to provide more solid evidence, and it would add more value if similar findings could be recapitulated in human spinal cords. Human neurological diseases such as copper deficiency myelopathy and subacute combined degeneration primarily exhibit degenerative pathologies in the dorsal column of the spinal cord [125][126][127][128][129] , with accumulation of foamy microglia 130,131 . It would be of interest to investigate the involvement of dysregulated microglial TGF-β signaling in these human diseases.…”

Section: Discussionmentioning

confidence: 99%

Disrupting microglial TGF-β signaling triggers region-specific pathology in the spinal cord

Zhu

Min

Joshua

et al. 2023

Preprint

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Transforming growth factor-β (TGF-β) signaling is critical for microglial maturation during development and the maintenance of microglial homeostasis in adulthood. It remains unclear whether regional susceptibilities to the loss of TGF-β signaling in microglia also exist, and the contributing factors have yet to be identified. We find that deletion of Tgfbr2 on microglia leads to microglial activation and demyelination in mouse spinal cords, primarily in the dorsal column (DC). Tgfbr2-deficient microglia exhibit distinct transcriptomic changes, and those sorted from the DC display a more proinflammatory profile compared to those from the ventral column (VC) and grey matter (GM). Single nucleus RNA sequencing (snRNA-seq) of the spinal cord uncovers a microglial subtype that emerges exclusively following Tgfbr2 deletion (termed TGFβ signaling-suppressed microglia, TSM), exhibiting high expression of Mmp12, Gpnmb, Lgals3, Mgll, and Alcam, predominantly located in the DC. Phenotypically, disruption of microglial TGF-β signaling results in behavioral deficits that are more severe in female and older mice, whereas young male mice are less affected. Mechanistically, we reveal a significantly higher level of TGF-β1/TGFBR2 in the spinal cords of normal older mice compared to the young mice, with the DC region richer in genes of the TGF-β signaling pathway than the VC and GM regions. This indicates that older mice and the DC region require more TGFβ1 to maintain tissue homeostasis and, reciprocally, are more responsive and sensitive to the disruption of TGF-β signaling in microglia. Herein, we report a demyelinating disease with region-specificity and its susceptibility to the loss of microglial TGF-β signaling with gender and age differences. Our findings contribute valuable information to our understanding of the importance of microglia in regulating myelin health, especially during the aging process.

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Section: Discussionmentioning

confidence: 99%

Disrupting microglial TGF-β signaling triggers region-specific pathology in the spinal cord

Zhu

Min

Joshua

et al. 2023

Preprint

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“…13 16 21 Axial slices are particularly useful to see the classical 'inverted V' or 'rabbit ears' sign (figure 2A). 35 Given the currently high prevalence of N 2 O use, clinicians should be aware that N 2 O users may have an alternative cause for a spinal cord syndrome, including inflammatory processes, cervical cord compression and hereditary syndromes. MRI is particularly useful to look for these other causes, since each has a distinct MRI appearance (described elsewhere).…”

Section: Blood Testingmentioning

confidence: 99%

“…13 16 21 Axial slices are particularly useful to see the classical ‘inverted V’ or ‘rabbit ears’ sign (figure 2A). 35…”

Section: Choosing and Interpreting Investigationsmentioning

confidence: 99%

Nitrous oxide-induced subacute combined degeneration of the cord: diagnosis and treatment

et al. 2023

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Recreational use of nitrous oxide (N2O) has increased rapidly in recent years and is now the second most commonly used recreational drug among young people in the UK. There has been a corresponding rise in cases of nitrous oxide-induced subacute combined degeneration of the cord (N2O-SACD), a pattern of myeloneuropathy usually associated with severe vitamin B12deficiency. This can cause serious and permanent disability in young people but, if recognised early, may be effectively treated. All neurologists should be aware of N2O-SACD and its treatment; however, there are currently no agreed guidelines. Based on our experience in East London, an area of high N2O use, we provide practical advice on its recognition, investigation and treatment.

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“…We identified 154 patients meeting our inclusion criteria after reviewing the literature 5–68 . There was a predominance of males (n=94, 61%), and the median age was 22 [19 to 26] years.…”

Section: Case Seriesmentioning

confidence: 99%

Neurological Manifestations Induced by Nitrous Oxide Abuse

Pichon,

Majhadi,

Menn

2023

The Neurologist

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Introduction: Nitrous oxide (NO) abuse is increasing among young people. This can result in severe neurological disorders such as myelopathy and/or peripheral neuropathy. We report the clinical presentations, biological, radiologic and electrophysiological findings of 5 patients hospitalized with neurological symptoms consecutive to NO abuse. In addition, a literature review was conducted to describe the neurological characteristics and to identify factors associated with a poor recovery. Case report: Among the 5 patients included, 2 had a myeloneuropathy, 2 had a sensorimotor neuropathy, and 1 had a normal spinal cord magnetic resonance imaging and electromyography despite neurological manifestations consistent with myeloneuropathy. After vitamin B12 supplementation, recovery was reported in 4 patients, and 1 was lost to follow-up. From the literature review, 154 patients were included [94 males; median age 22 (19 to 26) y; NO exposure 9 (3 to 18) mo]. A myelopathy was identified in 116 patients (75%) and a peripheral neuropathy was documented in 89 patients (58%). Compared with patients who recovered, those with sequelae were more likely to have a motor deficit at presentation (P<0.001), to use NO regularly (P<0.001), to have a lower vitamin B12 level (P=0.04), and a higher concentration of homocysteine (P=0.04). A less extensive myelopathy was more frequently found in the group with favorable outcomes (P=0.002). Conclusion: Neurological disorders caused by NO may be challenging with severe clinical patterns. We identified several factors associated with a poor recovery, to make clinicians aware of NO-induced neurotoxicity.

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Subacute Combined Degeneration from Nitrous Oxide Use

Cited by 8 publications

References 0 publications

Disrupting microglial TGF-β signaling triggers region-specific pathology in the spinal cord

Disrupting microglial TGF-β signaling triggers region-specific pathology in the spinal cord

Nitrous oxide-induced subacute combined degeneration of the cord: diagnosis and treatment

Neurological Manifestations Induced by Nitrous Oxide Abuse

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