N2O Abuse Research Articles

B-301 Deciphering Neuropathy features in the Context of Nitrous Oxide abuse: An Integrated Analysis of Electrophysiology and Metabolism

Abstract Background Nitrous oxide (N2O), used medically for its analgesic and anxiolytic properties, has emerged as a common recreational substance, leading to a rise in chronic toxicity cases. N2O abuse induces peripheral neurological damage with a spectrum of clinical presentations, ranging from mild sensory disturbances to severe motor deficits. Neurological complications from N2O include axonal and demyelinating neuropathies, leading to diagnostic and prognostic challenges. The pathophysiology of N2O toxicity is linked to functional inactivation of vitamin B12, resulting in biochemical and electrophysiological alterations. This study aims to enhance understanding of N2O pathophysiology by examining metabolic changes in consumers with axonal and demyelinating patterns. Methods This study included 35 patients with recent N2O abuse (last declarative consumption within the past week) who were treated at Lille University Hospital between March 2020 and April 2023 and underwent electromyography. The collected clinical features encompassed sensory symptoms, motor weakness, gait abnormalities and deep tendon reflexes. Patients were classified based on clinical phenotypes, distinguishing between length-dependent and non-length dependent, sensory or sensory-motor involvement and their peripheral neuropathy disability (PND) score (ranging from I to IV). Neurophysiological data analysis followed the criteria of Hadden et al. to identify patients with demyelinating criteria, while those lacking demyelinating criteria were categorized as “axonal” in the neuropathy group. Simultaneously, biochemical evaluations of serum vitamin B12 and B9 by CLIA methods (Roche), along with plasma homocysteine by LC/MS/MS and CLIA methods (Snibe), methylmalonic acid (MMA), and methionine by LC/MS/MS, were systematically performed for all patients. Results 40% of the selected patients exhibited demyelination criteria. The demyelinated group showed a significantly higher disability PND score compared to the axonal group (3.0 and 2.2, respectively; p-value = 0.028). Elevated levels of homocysteine and methylmalonic acid were found in all patients. Interestingly, plasma concentrations of homocysteine were significantly higher in the group of patient with axonal outcomes compared to the demyelinating group (90 µM and 114 µM; p-value = 0.04), suggesting an involvement of homocysteine in the type of lesion related to N2O abuse. Conclusions This study highlights the diverse electrophysiological manifestations of N2O-induced neuropathy and highlight the potential role of metabolic parameters as biomarkers to understand the pathophysiology. Indeed, lower hyperhomocysteinemia levels were observed in demyelinating patterns, highlighting a potentially biochemical difference between the groups: plasma homocysteine could also be used as a marker of neurological severity. The homocysteine assay used in these conditions must enable the patient to be managed rapidly: it would therefore be preferable to use rapid methods such as immunoanalysis. On the other hand, plasma methylmalonic acid did not differ between groups, which also suggests that other mechanisms have yet to be identified in the pathophysiology of N2O abuse.

Frostbite injuries related to recreational nitrous oxide use: incidence, management, and complications in a Swedish case series

Background: Nitrous Oxide (N2O) use in the recreational setting has been increasing in Sweden and Europe and therefore also related injuries. We aimed to investigate incidence, management, and surgical outcomes of frostbite injury (FI) related to N2O use. Material and MethodAll patients in a 22-month period, 2021-2022 presenting with FI related to N2O abuse from two plastic surgery clinics (one national burn centre) were identified. Data regarding patient comorbidity, mechanism of injury, initial management, treatment, and follow up were investigated. Complications following surgery were categorized into minor (treated in outpatient setting), and major (requiring reoperation). Results: In total 9 patients were identified, and 5 patients gave consent and were included. Direct contact with gas canister was the most common injury mechanism (n=4). All but one patient contracted full thickness injuries, and these four patients later required surgical intervention. The medial thigh was the most common area of injury. Outpatient clinic visits were common (mean 4.8 visits/patient). Surgical complications were common, and all operated patients were diagnosed with a minor complication and half of them also with a major complication (wound dehiscence and scar contracture). Conclusion: Frostbite injuries arising from recreational N2O are complex and often requiring surgical intervention and leading to complications. With the increasing incidence of N2O abuse in Sweden, further research is crucial to address emerging public health concerns and optimize treatment strategies for these distinctive injuries.

Nitrous oxide abuse direct measurement for diagnosis and follow-up: update on kinetics and impact on metabolic pathways.

Recreational use of nitrous oxide (N2O) has become a major health issue worldwide, with a high number of clinical events, especially in neurology and cardiology. It is essential to be able to detect and monitor N2O abuse to provide effective care and follow-up to these patients. Current recommendations for detecting N2O in cases of recreational misuse and consumption markers are lacking. We aimed to update current knowledge through a review of the literature on N2O measurement and kinetics. We reviewed the outcomes of experiments, whether in preclinical models (in vitro or in vivo), or in humans, with the aim to identify biomarkers of intoxication as well as biomarkers of clinical severity, for laboratory use. Because N2O is eliminated 5 min after inhalation, measuring it in exhaled air is of no value. Many studies have found that urine and blood matrices concentrations are connected to ambient concentrations, but there is no similar data for direct exposure. There have been no studies on N2O measurement in direct consumers. Currently, patients actively abusing N2O are monitored using effect biomarkers (biomarkers related to the effects of N2O on metabolism), such as vitamin B12, homocysteine and methylmalonic acid.

Poūmės kombinuotos nugaros smegenų degeneracijos, sukeltos diazoto monoksido („linksminančių dujų”) vartojimo, klinikinio atvejo aprašymas

Although nitrous oxide (N2O) has long been used as an anesthetic, it’s use as a recreational drug has recently increased. As N2O abuse is associated with a number of adverse health effects, it has become a significant public health issue. Chronic abuse can lead to a number of neurological complications, most commonly related to functional vitamin B12 deficiency. One of the most encountered forms of N2O neurotoxicity is a subacute combined degeneration, which can cause permanent neurological damage. The medical community should therefore be aware of the increasing scale of recreational N2O exposure and the possible complications of this drug abuse. Early recognition and treatment of N2O toxicity are crucial. We present the case of an 18-year-old male who was diagnosed with subacute combined spinal cord degeneration related to N2O abuse.

Nitrous oxide abuse in a 21-year-old female: a case report and review of literature.

The abuse of nitrous oxide (N2O) poses a substantial public health challenge. In many countries, including China, regulations governing the utilization and accessibility to N2O remain ambiguous, particularly within the food industry. Here, we report a case of a 21-year-old female who presented with symptoms of subacute combined degeneration (SCD) of the spinal cord due to N2O abuse. The patient exhibited bilateral lower limb numbness and weakness, low serum vitamin B12 levels with elevated homocysteine levels, and lumbar spine magnetic resonance imaging (MRI) revealed abnormal signals of the spinal cord. Following cessation of N2O and comprehensive therapy including methylcobalamin and nerve growth factor, the symptoms significantly improved. A follow-up examination 3 months later showed good progress in gait stability. At a 5-year follow-up, the patient's previous clinical symptoms had completely disappeared, and her quality of life had returned to normal. This case underscores the urgency of raising awareness and prevention of N2O abuse, emphasizing the importance of timely diagnosis and comprehensive treatment for patient recovery. Clear formulation and enforcement of relevant regulatory measures are equally crucial in reducing instances of abuse.

A recent surge of nitrous oxide misuse around London which merits a public health warning.

Use of nitrous oxide (N2O) gas for recreational purposes by young people is increasingly recognized as a public health hazard in the UK. We looked at the hospital records of patients admitted over the last 4years to a single neurological centre in Essex to determine the demographics, presentation, and management of patients presenting with symptoms of N2O toxicity from its recreational use. Of the 17 patients (mean age = 22.9 ± 3years) admitted between September 2018 and October 2022, 70% were admitted between January and October 2022. All patients reported limb paraesthesiae and 16/17 reported (95%) imbalance; 11/17 (65%) showed objective limb weakness. Serum B12 concentration was low in 9/17 (53%). Plasma methylmalonic acid (n = 7) and homocysteine (n = 8) levels were elevated in all patients tested. Spinal cord Magnetic Resonance Imaging (MRI) imaging was abnormal in 10/17 (59%) patients. Nerve conduction studies were abnormal in 10/13 (77%) patients, with evidence of a symmetric, length-dependent, large fibre neuropathy. There has been a recent surge of cases with neurological complications of recreational N2O abuse in the UK, with a relatively greater rate in 2022. Greater awareness of this condition amongst clinicians and health regulators is urgently required to prevent harm from N2O misuse in young people.

Biomarkers for the diagnosis and monitoring of nitrous oxide intoxication: objectives and methodology of the SFBC Working Group.

The recreational use of nitrous oxide (N2O) is an emerging public health issue. Chronic N2O abuse may result in various clinical symptoms, encompassing neurological, psychiatric and cardiovascular outcomes. Despite the difficulties for the laboratory investigation of N2O intoxication, there is currently no guidelines in France to help both clinicians and biologists use appropriate biomarkers for the diagnosis and monitoring of patients with clinical symptoms potentially related to N2O intoxication. Amulti-disciplinary Working Group, carried out under the auspices of the French Society of Clinical Biology (SFBC) and in collaboration with the French Societies of Emergency Medicine (SFMU), Analytical Toxicology (SFTA), Hemostasis and Thrombosis (SFTH), Vitamins and Biofactors (SFVB), and the French Federation of Neurology (FFN), was recently implemented to elaborate practical guidelines. The methodology of the Working Group is based on the critical analysis of the literature, and raising concerns and objectives are grouped into five working packages. The present manuscript primarily aims to expound upon the methodology and objectives of the ongoing SFBC Working Group on N2O.

Nitrous Oxide Inhalant Abuse: Preliminary Results from a Cross-Sectional Study on Knowledge, Attitudes, and Practices of Italian Physicians (2023).

Background and Objectives: Nitrous oxide (N2O) has recently emerged as a cheap alternative to other recreational substances. Although legally available, its chronic use is associated with severe neurological and hematological complications due to the irreversible inactivation of vitamin B12. While no reliable data on abuse of N2O in Italy have been provided to date, we assessed the knowledge, attitudes, and practices of Italian medical professionals on the management of N2O abuse cases. Materials and Methods: A cross-sectional study was performed as a web-based survey through a series of Facebook discussion groups (targeted medical professionals: 12,103), and participants were specifically asked about their previous understanding of N2O abuse and whether they had or not any previous experience in this topic. Results: A total 396 medical professionals participated in the survey. Overall, 115 participants had previous knowledge about N2O abuse (29.04%), with higher odds for professionals with a background in emergency medicine (adjusted odds ratio (aOR) 3.075; 95% confidence intervals (95%CI) 1.071 to 8.828) and lower for specialists in psychiatry (aOR 0.328; 95%CI 0.130 to 0.825). Knowledge status on N2O abuse was largely unsatisfying, as knowledge status, reported as a percent value, was estimated to 45.33% ± 24.71. Having previously managed a case of N2O abuse was associated with higher risk perception of the actual severity of this condition (aOR 5.070; 95%CI 1.520 to 16.980). Conclusions: Our study suggests that N2O poisoning cases are occurring in Italian settings but are not reasonably reported to national authorities. As substantial knowledge gaps of Italian medical workforces were identified, we cannot rule out that the actual abuse of N2O in the population may be far larger than currently suspected.

Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report

BackgroundNitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature.Case reportA 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected.ConclusionThis case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.

Nitrous oxide-induced myeloneuropathy: a case series

BackgroundNitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but...

A Suspected Link Between Recreational Nitrous Oxide Use and Papilloedema

Herein, we present a case report of a young male with worsening headaches and visual disturbance who was found to have papilloedema. Through exclusion, there is a high index of suspicion that this was related to N2O abuse. Therefore, we hope clinicians will adopt a low threshold for taking a detailed drug history and investigation for raised intracranial pressure (ICP) in this patient population, including ophthalmological assessment.

Comparison of biomarker for diagnosis of nitrous oxide abuse: challenge of cobalamin metabolic parameters, a retrospective study.

Recreational use of nitrous oxide (N2O) leads to neurological disorders including combined subacute degeneration of spinal cord, psychological disorders, and thrombosis. Serum or urine N2O assays could not be routinely performed. Hence, it is necessary to investigate other biological markers such as metabolic markers. We aimed here to challenge the three main biological markers used for the diagnosis of nitrous oxide abuse as total vitamin B12, homocysteine, and methylmalonic acid. We retrospectively collected clinical and biological data from 52 patients with known, documented chronic N2O abuse and associated clinical signs (peripheral neuropathy disability score or thrombosis event). Sera and plasma total vitamin B12, methylmalonic acid (MMA), and homocysteine were performed to identify the most specific marker of chronic N2O intoxication and related clinical outcomes. Plasma homocysteine was almost consistently increased in case of N2O chronic consumption, whereas MMA increase and total vitamin B12 decrease are not systematically found. Our results showed that none of the markers are correlated with levels of N2O consumptions. However, homocysteine and MMA are correlated with clinical severity, but MMA seems to be a better marker of clinical severity. There is no specific marker of nitrous oxide abuse according to levels of consumption, total vitamin B12 decrease could not be used either as consumption or as severity marker. However, we showed that homocysteine is consistently increased and could be used as marker of recent N2O consumption. On the other hand, we showed that MMA could be used as a marker of clinical gravity.

Electrophysiologic Characteristics of Nitrous-Oxide-Associated Peripheral Neuropathy: A Retrospective Study of 76 Patients

The electrophysiologic characteristics of peripheral neuropathy secondary to nitrous oxide (N2O) abuse remain unclear. The paper therefore aimed to summarize the electrophysiologic characteristics of N2O-associated peripheral neuropathy and identify the risk factors of severe nerve injury. The electrophysiologic results and clinical data of patients with peripheral neuropathy secondary to N2O abuse at our hospital between 2018 and 2020 were analyzed retrospectively, and their electrophysiologic changes were summarized. Most patients exhibited decreased sensory and motor nerve conduction velocities (75% and 76%), decreased sensory nerve and compound motor action potentials (57% and 59%), and prolonged distal motor latency (59%), while a response was absent in 36%. These findings indicate that N2O abuse can result in generalized injury to sensory and motor nerves. Electrophysiologic results indicated axonal neuropathy in 37 cases (49%), demyelinating peripheral neuropathy in 4 (5%), and mixed neuropathy in 12 (16%). Peripheral nerve injury was more common in the lower limbs (72%) than in the upper limbs (42%, p<0.0001). The upper and lower limbs were primarily affected by sensory nerve demyelination (35%) and motor axonal injury (67%), respectively. Subgroup analysis indicated that longer N2O exposure and longer disease course were associated with more-severe motor axonal injury in the lower limbs. N2O-associated peripheral neuropathy can lead to sensory and motor nerve injury, with axonal injury being the most common. Injuries were more severe in the lower limbs. Prolonged N2O exposure and disease course increased the severity of motor axonal injury in the lower limbs.

SPECT findings on neuropsychiatric symptoms caused by nitrous oxide abuse.

The aim of the study was to investigate the clinical, neuropsychological, and regional cerebral blood flow (rCBF) perfusion changes in patients with neuropsychiatric symptoms caused by nitrous oxide (N2O) abuse. A total of 16 patients with neuropsychiatric symptoms caused by nitrous oxide abuse were recruited for this study. The study was carried out in the withdrawal phase of N2O abuse. A 925-1110 MBq 99mTc-ECD was administered intravenously. SPECT/CT images were collected with a low-energy and high-resolution collimator. The region uptake statistics of different brain regions of interest between patients with N2O abuse and normal people of the databases for younger subjects from the Scenium DB Comparison software were calculated automatically. The clinical manifestations of the 16 patients with neuropsychiatric symptoms were mood lability, anxiety, hallucination, delusion, agitation, confusion, and other psychiatric symptoms. In addition, 15 of the patients also complained of memory decline; 14 patients manifested numbness or paresthesia; 14 patients developed limb weakness, and their motor impairments were more severe in the lower limbs than in the upper limbs; and eight patients had urinary and defecation disturbances. In the neuropsychological examination, the BPRS score was 54.69 ± 11.48, the HAMD score was 30.00 ± 11.06, the HAMA score was 18.06 ± 5.77, the MMSE score was 28.06 ± 2.29, and the MoCA score was 25.06 ± 3.40. SPECT showed hypoperfusion in the frontal and temporal lobes, which is consistent with the clinical findings. This was the first study to demonstrate the obvious effect of N2O abuse on CBF in patients with neuropsychiatric symptoms. CBF perfusion imaging is helpful to detect the changes in the local brain functional activity in patients with N2O abuse.

Severe Isolated Peripheral Polyneuropathy without Myelopathy after Nitrous Oxide Abuse: A Case Report

Nitrous oxide (N2O) abuse induces vitamin B12 deficiency, resulting in complications in the central and peripheral nervous systems. Some cases related to subacute combined degeneration or myeloneuropathy after N2O abuse have been reported. However, isolated peripheral polyneuropathy without spinal cord involvement has rarely been reported in South Korea. We describe a 29-year-old woman who had inhaled “happy balloons” daily (1,000 balloons/day) for recreational purposes over 3-month period, and presented with acute symmetrical hypoesthesia, paresthesia, and motor weakness on the bilateral lower limbs. Serologic tests showed megaloblastic anemia and vitamin B12 deficiency. Magnetic resonance imaging of the brain and spine showed no abnormalities. An electrodiagnostic study confirmed lower limb-dominant axonal sensorimotor polyneuropathy due to vitamin B12 deficiency from N2O abuse. The patient was treated with intramuscular vitamin B12 replacement. A follow-up electrodiagnostic study 4 months after the initial study showed only partial improvement. Despite the legal efforts of the Korean government to ban the use of N2O other than for medical purposes, cases of complications from its abuse are on the rise, especially among young adults. Physicians should recognize the strong possibility of N2O abuse as an underlying cause of vitamin B12 responsive polyneuropathy with or without spinal cord involvement.

Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse.

PurposeTo review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2O) abuse, and analyze the factors that affect outcomes.MethodsPatients with N2O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow‐up was conducted to determine the outcomes.ResultsThe average age of the 110 patients with N2O abuse was 21.4 ± 4.2 years (range: 14–33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow‐up was completed for 51 patients. Thirty‐four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients.ConclusionThe recreational use of N2O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2O abuse. The therapeutic administration of vitamin B12 supplementation and N2O withdrawal can make the overall prognosis good, especially for female patients.

Nitrous oxide abuse in the emergency practice, and Review of toxicity mechanisms and potential markers

Nitrous oxide (N2O) toxicity is a concern common to several medical fields. Here, retrospective study of four N2O abuses with neurological signs in the emergency practice provides a preliminary basis for a metabolic Discussion/Review. This latter highlights N2O abuse as pathology of DNA/RNA/protein methylations, for instance consistent with impairments of protein arginine methyltransferases involved in myelinogenesis and myelopathy in patients. Basically, pathogenesis starts with oxidation by N2O of coordinated cobalamine cobalt ions at enzyme sites with impairments of vitamin-B12-dependent pathways. Methionine synthase (methylcobalamine) and methymalonyl-CoA mutase (adenosylcobalamine) are inactivated and cofactor-depleted, respectively. The number of impacted pathways (folate cycle, methylation cycle, S-adenosylmethionine-dependent methyltransferases, transulfuration pathway, Krebs cycle fueling by methylmalonyl-CoA, glutathione synthesis) explains the variety of potential research/laboratory markers, and may provide new clues and future angles to explore N2O toxicity. Overall, homocysteine measurements obviously help diagnosis of N2O abuses. Additional markers may include vitamin-B12, methionine, methylmalonate, dimethylglycine, sarcosine, S-adenosylmethionine to S-adenosylhomocysteine ratio, various S-adenosylamino acids, S-adenosylmethionine-dependent cellular methylations, and additional analytes (propionylcarnitine, propionylglycine, cystathionine and derived metabolites, methylated amino acids [eg arginine], betaine).

Polyneuropathy Following Nitrous Oxide Abuse

Nitrous oxide (N2O), an anesthetic gas, has been abused by some people for entertainment purposes. Recently, N2O (under the name of "Happy Balloon") abuse has become problematic among young people in Korea. N2O intoxication can develop a neuropathy, as well as other systemic disorders, either by inactivating vitamin B12 or by a direct neurotoxic mechanism. Here, we report a case of peripheral neuropathy with possible coexisting myelopathy following N2O abuse.

Serum copper decrease and cerebellar atrophy in patients with nitrous oxide-induced subacute combined degeneration: two cases report

BackgroundSubacute combined degeneration (SCD) is a neurological complication commonly associated with vitamin B12 deficiency. It can result from nitrous oxide (N2O) abuse and cause neuropsychiatric symptoms. However, there has been no literature regarding alterations of serum copper and cerebellum in SCD patients.Case presentationWe reported two cases of young SCD patients with histories of N2O abuse. In these cases, elevated homocysteine, macrocytic anemia, spinal cord abnormalities, and peripheral nerve injuries were detected. In addition, decreased serum copper level and cerebellar atrophy were reported for the first time. The patients’ symptoms improved after withdrawal of N2O exposure and vitamin B12 supplements.ConclusionWe reported two SCD cases with serum copper alteration and cerebellar atrophy after N2O abuse for the first time. These might be crucial complements to the diagnosis of SCD.

Nitrous oxide-induced predominantly motor neuropathies: a follow-up study.

Recreational nitrous oxide (N2O) abuse is increasingly popular among youth. We report a systematic clinical, electrophysiological and biological follow-up of patients with neuropathy caused by N2O. We retrospectively report seven patients with neuropathy attributed to N2O abuse and their comprehensive follow-up. Demographic, toxicological, clinical, biological and electrophysiological data were collected at first and second examination. Functional data were collected at the last evaluation. Seven patients aged 18-30, consuming more than 140 gas-filled balloons (one balloon is filled with approximately 8g of N2O) per week for over a month, developed a severe, predominantly motor, length-dependent, progressive neuropathy over 3 to 6weeks. Two-thirds presented associated signs of myelopathy. Distal lower limbs motor deficit and ataxia led to moderate disability. Spinal cord imaging was frequently normal. Nerve conduction studies disclosed an almost exclusively motor axonal neuropathy affecting the lower limbs with active denervation. Homocysteine plasma level was systematically elevated, whereas cobalamin plasma levels were normal in almost all patients. At short-term follow-up after intoxication discontinuation, ataxia and motor deficit only partially resolved despite vitamin B12 supplementation, while active denervation and homocysteinemia decreased. At last follow-up (median 9.2months, IQR 7.5-10.75), mean ONLS was 2.0 (IQR 2.0-2.0). Young patients, with induced N2O motor neuropathy remain disabled after 5 to 14.5months of gas withdrawal, despite vitamin B12 supplementation. A longer follow-up is needed to fully appraise the severity of these toxic neuropathies.