Nitrous Oxide-Associated Myelopolyneuropathy-A Case Series.
Nitrous oxide is a multipurpose gas that has recently gained attention because of its use as a recreational drug and the associated neurological complications of abuse. Seven patients were included, and clinical, electrodiagnostic, imaging, and serological data were retrospectively analyzed. All patients presented with various degrees of sensory impairment, gait disorder, muscle weakness, or ataxia, mainly involving the lower limbs. Electrodiagnostic studies showed a predominantly motor neuropathy, with axonal, demyelinating, or mixed features. Spinal magnetic resonance imaging showed posterior cord lesions in cervical regions, with 2 patients presenting concomitant thoracic cord lesions. Homocysteine levels were elevated in all patients. Nitrous oxide abuse is known to be connected to the development of both polyneuropathy and myelopathy. Better understanding of the physiological, clinical, and paraclinical aspects of this pathology is needed to make a correct differential diagnosis and conduct and adequate treatment.
- Research Article
1
- 10.1212/wnl.0000000000203416
- Apr 25, 2023
- Neurology
<h3>Objective:</h3> To report laboratory, radiologic, and clinical findings in a case series of patients hospitalized with subacute combined degeneration (SCD) caused by nitrous oxide (NO) abuse. <h3>Background:</h3> NO is legal and widely available as a food additive, making it an easily accessible recreational drug. NO inhibits methionine synthase and inactivates vitamin B12. Prolonged use can lead to B12 deficiency and SCD. <h3>Design/Methods:</h3> We reviewed hospital records from March 2016 until August 2022 and found three cases of SCD associated with NO abuse. <h3>Results:</h3> One 43-year-old male and two females, 27 and 44 years old, had SCD in the setting of NO abuse. All had numbness, weakness, and ataxia. Cognitive and behavioral changes with loss of vibratory sensation and proprioception were not universal. MRI of the cervical cord in all patients demonstrated T2 hyperintensity of the posterior columns in the classic “inverted V” shape consistent with SCD. B12 levels in two patients were 0.54 and 0.73X lower limit of normal (LLN), while in the third patient it was 2.3X the LLN. Methylmalonic acid (MMA) and homocysteine levels were elevated in all patients up to 34X the upper limit of normal. All patients were treated with high-dose B12 repletion, physical therapy, and counseled on nitrous oxide cessation. Two patients were discharged home, while one was discharged to a skilled facility for further rehabilitation. <h3>Conclusions:</h3> NO abuse can induce SCD. Patients may have a normal B12 level but still be functionally B12 deficient because NO inactivates the B12 molecule. Elevated MMA and homocysteine levels are consistent with B12 inactivation as well as deficiency, illustrating the utility of these additional diagnostic tests when B12 deficiency is suspected. Profound neurological deficits can persist at the time of hospital discharge in NO-related SCD. <b>Disclosure:</b> Dr. Warren has nothing to disclose. Dr. Taylor has nothing to disclose. Dr. Savage has nothing to disclose.
- Research Article
- 10.3290/j.qi.b6444238
- Oct 21, 2025
- Quintessence international (Berlin, Germany : 1985)
The objectives of this article were to provide a review of published cases of frostbite injuries of the head and neck associated with abuse of nitrous oxide (NO) and to summarize other pathophysiologic consequences. A literature search was undertaken for articles on the development of frostbite injuries to the head and neck from recreational use of NO, including review papers, clinical investigations, case reports, case series, cohort studies, and letters to the editor. Relevant articles were attained from the electronic databases of PubMed and Google Scholar from 1 January 1985 through 5 July 2025 and from references cited within culled sources. The search identified 13 articles, involving 16 patients, with NO-related frostbite injuries to the head and neck. Commonly affected sites included the face, palate, lips, and oropharynx. Six patients required hospital admission, including three who were referred to the intensive care unit. Oral health care practitioners should be aware of contemporary modalities of substance abuse, particularly from the recreational use of NO and the consequent risk of frostbite to the mucocutaneous structures of the head and neck. Attending clinicians are advised to educate their patients about the potential for these injuries from recreational NO abuse.
- Research Article
1
- 10.1212/wnl.0000000000203384
- Apr 25, 2023
- Neurology
<h3>Objective:</h3> We present a unique case of nitrous oxide abuse presented with B12 deficiency symptoms and cerebral venous thrombosis. <h3>Background:</h3> Nitrous oxide is being used as a recreational drug. It’s unknown side effects and low-price account for its rising popularity. In the paper, we discuss the link between nitrous oxide, vitamin B12 deficiency, and the development of cerebral venous thrombosis. <h3>Design/Methods:</h3> A 33-year-old female, with a past medical history of anxiety, presented to the emergency department with a five-day history of BLE weakness, generalized numbness, and confusion. The patient appeared lethargic, disoriented, and confused. Gait evaluation showed sensory ataxia with a positive Romberg sign. No other neurological deficits were elicited. Patient denied usage of drugs or alcohol. A head CT showed a possible thrombus in the left transverse and sigmoid sinuses. This was confirmed by a computed tomography angiography (CTA) of the head and neck. Lab results showed elevated homocysteine and methylmalonic acid levels with decreased B12. Upon further discussion with the patient, she disclosed the use of Nitrous Oxide recreationally for about six months. Treatment included IM B12 1,000 mcg daily for 4 weeks, then monthly until future follow up. Patient was advised to avoid further use of Nitrous oxide. <h3>Results:</h3> Chronic Nitrous oxide abuse can present as cerebral venous thrombosis (CVT). Though unusual, it needs to be included among possible complications/ presentations. <h3>Conclusions:</h3> We recommend conducting an extensive workup on CVT, which includes homocysteine and B12 levels. <b>Disclosure:</b> Ms. AlNaser has nothing to disclose. Dr. Kebbeh has nothing to disclose. Shauna Cheung, MD has nothing to disclose.
- Research Article
- 10.7759/cureus.91279
- Aug 1, 2025
- Cureus
Nitrous oxide, commonly known as "laughing gas," has been widely used as a medical and dental sedative for centuries. Despite its recognized therapeutic applications, there has been a concerning rise in its recreational use, particularly among young adults. This trend has led to an increase in associated toxicities, including neurological, hematological, and psychiatric complications.This is a case report of a young adult presenting with neurological and hematological symptoms following chronic recreational nitrous oxide use. The patient exhibited diffuse abdominal pain, vomiting, nausea, confusion, and radicular pain in her upper extremities upon initial exam, which prompted an extensive diagnostic evaluation. These findings evolved during her hospital course, including the development of depressive symptoms, insomnia, and ataxia. Laboratory findings revealed evidence of severe neutropenia, pancytopenia, and vitamin B12 deficiency, supporting a diagnosis of nitrous oxide-induced neurotoxicity. Management included cessation of nitrous oxide exposure, vitamin B12 supplementation, psychiatric intervention, and supportive therapy, leading to gradual symptom improvement, which will hopefully continue in the outpatient setting.This case highlights the growing public health concern surrounding nitrous oxide abuse. Its recreational use can result in severe and potentially irreversible neurological impairment, often linked to its association with vitamin B12 deficiency. Increased awareness among healthcare providers is crucial for early recognition and intervention. Additionally, preventive measures, including public education and regulatory policies, may help curb the rising trend of nitrous oxide abuse. It is an emerging public health issue with significant consequences, and this case highlights the importance of early diagnosis and treatment, as well as the need for increased awareness to mitigate long-term complications.
- Research Article
31
- 10.1002/brb3.2533
- Mar 20, 2022
- Brain and Behavior
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.
- Research Article
32
- 10.1007/s11239-019-02010-9
- Dec 9, 2019
- Journal of Thrombosis and Thrombolysis
Nitrous oxide is a commonly abused inhalant by adolescents and young adults. There is limited data describing the adverse effects of nitrous oxide abuse, known colloquially as "whippets". We present a 21-year-old female with no medical history who presented to the emergency department for confusion, hallucinations, weakness, and falls. She was accompanied by her roommates, who endorsed significant nitrous oxide abuse. Imaging revealed a large cerebral sinus venous thrombus with extension into the transverse sinus, sigmoid sinus and internal jugular vein. She had no prior history of venous or arterial thrombosis. Hypercoagulability workup demonstrated an elevated homocysteine level, elevated methylmalonic acid level, and normal cobalamin and folate levels. Additionally, she was found to be 11weeks pregnant, with no prior spontaneous abortions. Genetic testing was significant for methylenetetrahydrofolate reductase polymorphisms. She was managed with enoxaparin, cobalamin and folate supplementation. Homocysteine and methylmalonic acid levels normalized after cessation of nitrous oxide use, with no recurrence of venous thrombosis. This case represents the first reported patient with a venous thrombus associated with nitrous oxide abuse.
- Research Article
17
- 10.1080/15563650.2021.1938107
- Aug 2, 2021
- Clinical Toxicology
Background Recreational use of nitrous oxide (N2O) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms. Aims To explore the relationship among the occurrence of recreational nitrous oxide-induced psychiatric symptoms, accompanying neurological symptoms, vitamin B12 status and choice of treatment. Methods A retrospective search for case reports was conducted across multiple databases (Pubmed, Embase, Web of Science, PsycINFO and CINAHL). Keywords included variants of “nitrous oxide”, “case report” and “abuse”. No restrictions to language or publication date were applied. Results The search retrieved 372 articles. A total of 25 case reports were included, representing 31 patients with psychiatric complications following nitrous oxide abuse. The most often reported symptoms were: hallucinations (n = 16), delusions (n = 11), and paranoia (n = 11). When neurological symptoms were present, patients were treated more frequently with vitamin B12 supplementation. Conclusions This review highlights the need to recognize that psychiatric symptoms may appear in association with nitrous oxide use. Approximately half of the cases that presented with nitrous oxide-induced psychiatric complaints did not show neurological symptoms, and their vitamin B12 concentration was often within the hospital's reference range. Psychiatrists and emergency physicians should be aware of isolated psychiatric symptoms caused by recreational nitrous oxide abuse. We suggest asking all patients with new psychiatric symptoms about nitrous oxide use and protocolizing the management of nitrous oxide-induced psychiatric symptoms.
- Research Article
2
- 10.1186/s12883-024-03966-9
- Nov 26, 2024
- BMC Neurology
ObjectivesNitrous oxide has long been used as an anesthetic agent. The recreational use and abuse are rapidly increased in Western countries and lead to many neurological complications.MethodsRetrospectively review of seven patients.ResultsSeven patients aged 19–32 years, mean 22.6 years. They inhaled nitrous oxide between 1 month to 1 year prior to the symptom onset. They all presented with acute or subacute ataxia or motor, and sensory dysfunction. The two had coexisting encephalopathy. Electrodiagnosis showed sensorimotor axonal polyneuropathy. All patients had borderline or low serum vitamin B12 level. Two had high serum homocysteine or methylmalonic acid levels. Cervical spine MRI in two patients showed posterior column lesion. At average 2 month-follow up, all patients had minimal improvement. While at more than 6 month-follow up, most patients had moderate to complete recovery.ConclusionSeven patients with nitrous oxide induced neurological disease are reported. All patients present with acute myelopathy and sensorimotor polyneuropathy. Short term outcome is generally not favorable while long term outcome shows remarkable improvement.
- Research Article
1
- 10.3390/jox14040075
- Sep 27, 2024
- Journal of Xenobiotics
Background: Historically used as a marker for inherited disorders, the current interest in plasma homocysteine measurement lies in its ability to provide valuable information about the metabolic and nutritional status of patients. Specifically, nitrous oxide (N2O) abuse can lead to functional vitamin B12 deficiency by oxidation and increase oxidative stress, resulting in elevated plasma homocysteine levels, which mimic neurological conditions such as Guillain–Barré syndrome. Rapid identification of hyperhomocysteinemia is crucial for timely intervention and avoiding costly, unnecessary treatments. Objective: This study evaluates the performance of a rapid immunoassay technique (Snibe) compared to mass spectrometry (LC-MS/MS) for measuring plasma homocysteine levels in patients with nitrous oxide abuse and non-inherited caused of elevated homocysteine, aiming to enhance differential diagnosis related to oxidative stress. Methods: 235 patients from Lille University Hospital were included. EDTA blood samples were collected and analyzed using both rapid immunoassay (Snibe) and LC-MS/MS. Neurological assessment was performed using the peripheral neuropathy disability (PND) score. Results: Firstly, significant elevations in plasma homocysteine levels were observed in patients abusing nitrous oxide measured by LC-MS/MS. Secondly, the immunoassay provided rapid results, essential for early clinical decision-making, but tended to underestimate high values compared to LC-MS/MS. A good correlation was found between the methods for low and moderate values. Conclusion: The immunoassay tended to underestimate high-value samples compared to LC-MS/MS, which is a common problem with the competitive methodology. The rapid immunoassay technique is effective for initial screening and early intervention, aiding in the differential diagnosis of conditions related to oxidative stress. Therefore, it is recommended to use the CLIA method for initial screening and confirm with mass spectrometry if there are abnormal samples. Integrating both techniques can enhance diagnostic accuracy and improve patient outcomes.
- Research Article
21
- 10.1093/omcr/omw012
- Mar 1, 2016
- Oxford Medical Case Reports
Nitrous oxide is increasingly used as a recreational drug that is easily and legally available worldwide. Occasional nitrous oxide use has been considered relatively safe without the development of addiction or major adverse effects. However, heavy long-term nitrous oxide abuse can be associated with severe neurological complications, and even deaths have been described. The characteristic presentation is myeloneuropathy with dorsal column degeneration and demyelinating sensory polyneuropathy related to vitamin B12 deficiency. Described is a 23-year-old male who developed recurrent paraparesis related to nitrous oxide abuse. A second, more severe, episode of paraparesis was associated with predominantly lower motor neuron damage. A partial recovery was achieved by discontinuation of nitrous oxide use and initiation of vitamin B12 supplementation. However, the patient relapsed and ultimately died while being intoxicated with several abusive substances. The case adds to the cumulative literature about the clinical phenomenology and dangers of nitrous oxide abuse.
- Abstract
- 10.1136/jnnp-2017-abn.46
- Nov 20, 2017
- Journal of Neurology, Neurosurgery & Psychiatry
Nitrous oxide (NO) is an increasingly used recreational drug amongst the young. Six patients presented to our unit with varying neurological presentations ranging from acute AIDP to a pure cord...
- Research Article
6
- 10.1002/ccr3.6881
- Feb 1, 2023
- Clinical Case Reports
Nitrous oxide abuse can have detrimental effects on the central and peripheral nervous systems. This case study report aims to demonstrate a combination of severe generalized sensorimotor polyneuropathy and cervical myelopathy related to vitamin B12 deficiency following nitrous oxide abuse. We present a clinical case study and literature review examining primary research—published between 2012 and 2022—reporting nitrous oxide abuse affecting the spinal cord (myelopathy) and peripheral nerves (polyneuropathy); 35 articles were included in the review with a total of 96 patients, where the mean “patients” age was 23.9 years and were in a 2:1 male/female ratio. Of the 96 cases, within the review, 56% of patients were diagnosed with polyneuropathy, most commonly impacting the nerves of the lower limb (62%), while 70% of patients were diagnosed with myelopathy, most commonly impacting the cervical region (78%) on the spinal cord. In our clinical case study, a 28‐year‐old male underwent a multitude of diagnostic investigations for bilateral “foot drop” and sense of lower limb stiffness as ongoing complications of a vitamin B12 deficiency secondary to recreational nitrous oxide abuse. Both the literature review and our case report emphasize the dangers of recreational nitrous oxide inhalation, colloquially termed “nanging” and the risks it presents to both the central and peripheral nervous systems, which is erroneously considered by many recreational drug users to be less harmful than other illicit substances.
- Research Article
11
- 10.3389/fpubh.2022.854977
- Jun 2, 2022
- Frontiers in Public Health
BackgroundThe COVID-19 pandemic has a serious impact on the mental health of the public due to its economic and social impact. And psychological effects have led to drug and alcohol abuse. After the city lifted the lockdown, we consecutively encountered several young nitrous oxide abusers admitted to hospital for neurological treatment.PurposeTo inform physician decisions and social intervention, this observational study aimed at investigating the neurological and psychological characteristics of nitrous oxide abusers and its underlying causes during the COVID-19 lockdown.MethodsThe nitrous oxide abusers who sought neurological treatment at our hospital between May 2020 and June 2020 were enrolled. Clinical data including socio-demographic, physical examination, laboratory examination, electromyography and neuroimaging were collected. Their motivations for inhaling nitrous oxide, knowledge about the nitrous oxide abuse and the accompanying of family were investigated face to face. Psychological status was assessed by the Symptom Checklist 90 (SCL-90) psychological evaluation.ResultsSix nitrous oxide abusers were enrolled and the age was 22 ± 4.3. Clinical presentations included varying degrees of limb numbness and an ataxic gait. Laboratory examination revealed that all the patients did not have pernicious anemia, 4 patients had decreased vitamin B12 while 3 patients exhibited elevated homocysteine levels. MR of the spinal cord revealed that 4 patients had abnormal signals in the cervical spinal cord of high symmetry with splayed or inverted V sign after T2WI. Electromyogram (EMG) test showed 5 patients had peripheral nerve damage. The SCL-90 psychological evaluation results indicated that all patients had severe anxiety, depression and psychosis and they had severer psychological problems than ordinary citizens. Their motives for inhaling nitrous oxide are to relieve boredom, curiosity and buddy pressure. Their family spent <1 day per week to stay with them during city lockdown.ConclusionThe enrolled patients caused by abuse of nitrous oxide presented with symptoms of subacute combined with spinal degeneration. They had more serious psychological problems related to the COVID-19 pandemic. These cases make us value the psychological problems of young people under the outbreak and take multi-layered measures from families, schools (companies), hospitals, and governments to address it.
- Research Article
9
- 10.1136/bcr-2021-244478
- Aug 1, 2021
- BMJ Case Reports
Nitrous oxide (NO) is an inhalant that has become increasingly popular as a recreational drug. While it is presumed to be harmless, a number of adverse effects of NO have...
- Research Article
36
- 10.1007/s00415-021-10702-7
- Jul 10, 2021
- Journal of Neurology
BackgroundThe recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent.MethodsWe report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse.ResultsOur patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients.ConclusionWe report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.
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