Not a Laughing Matter: When Nitrous Oxide Causes Functional Vitamin B12 Deficiency.

Subacute combined degeneration (SCD) is an acquired neurologic complication from prolonged vitamin B12 deficiency. As a result of dorsal and lateral spinal cord column degeneration, patients present with a range of neurological symptoms, including paresthesias, ataxia, and muscle weakness. Without prompt treatment, irreversible nerve damage occurs. Here we present a young man who developed progressive ascending paresthesias and lower extremity weakness after escalated nitrous oxide use. This case highlights the importance of considering SCD from nitrous oxide toxicity when patients present with progressive ataxia, paresthesia, and lower extremity weakness.

Subacute Combined Degeneration of the Spinal Cord Induced by Nitrous Oxide Abuse: A Rare Patient Presentation to a Spine Surgery Clinic: Illustrative Case.

Subacute combined degeneration (SCD) of the spinal cord is a disease involving the lateral and posterior columns of the spinal cord that can manifest in patients with vitamin B12 deficiency. Nitrous oxide (N2O)-induced SCD of the spinal cord is a result of N2O interfering with the metabolism of vitamin B12 and results in nervous system demyelination. This is an infrequent complication of N2O anesthesia; however, cases are rising with recreational N2O use. This case report describes a patient with SCD of the spinal cord induced by recreational N2O abuse. The patient presented to a spine surgery clinic with a 3-week history of progressive global weakness and paresthesias. After a detailed history and physical examination, the diagnosis was made and supported by various tests and imaging findings. Despite marked neurologic deficits, the patient's symptoms improved markedly with therapy and vitamin B12 supplementation. Spine surgery clinicians may be confronted with these cases and should be aware of this atypical presentation of SCD. As in our case, patients may present with neurologic deficits of unclear etiology. Neurologic dysfunction may be irreversible; therefore, accurate diagnosis, medical treatment, and complete neurologic evaluation are of the utmost importance to prevent additional progression.

Neurological complications of excessive recreational nitrous oxide use: a case series based on a text mining algorithm.

BACKGROUND: The recreational use of nitrous oxide (N2O) has gained popularity over recent years. We present a case series of excessive N2O users with neurological complications. METHODS: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N2O recreationally and visited a neurologist. RESULTS: We identified 251 patients. The median duration of N2O use was 11 months (interquartile range [IQR], 3-24) and the median amount of N2O used per occasion 1.6 kg (IQR 0.5-4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery. CONCLUSIONS: In this case series of excessive N2O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N2O use.

Neurological Manifestations Induced by Nitrous Oxide Abuse: A Case Series and Review of Literature.

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 B 12 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 B 12 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.

Neuropsychiatric disorders associated with recreational nitrous oxide use.

BACKGROUND: Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. PURPOSE: This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. METHODS: We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. RESULTS: There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. CONCLUSION: Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

Analgesic effect of nitrous oxide during manual therapy after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial.

BACKGROUND: Many patients during manual therapy after anterior ligament reconstruction will experience severe pain, which has a negative impact on their rehabilitation. However, there is rarely an analgesic method for these patients during rehabilitation. Nitrous oxide with rapid analgesic and sedative effects is often used to relieve pain in minor procedures. The purpose of this study is to determine whether or not nitrous oxide analgesia decreases pain compared to oxygen during manual therapy after anterior ligament reconstruction. METHODS/DESIGN: This single-center, randomized, double-blind and controlled trial will recruit 120 patients. Patients ≥ 18 years old undergoing manual therapy after anterior ligament reconstruction (1 month post-operative) with acute pain (VAS ≥ 4) are included. The main exclusion criteria included the following: pulmonary embolism, intestinal obstruction, pneumothorax. Patients will be randomly allocated to the intervention group (A) and the control group (B) in a ratio of 1:1. Doctors, therapists, patients, and data collectors are all blind to the study. The manual therapy will be performed by therapists. Nurses who implemented the intervention handed the doctors envelopes containing the patients' codes and allocation of A or B. Group A will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesic) given as 30-min treatment sessions, once daily, and group B will receive oxygen plus conventional treatment (no analgesic) under the same conditions. Assessments will be taken 2 min before the intervention (T0), 5 min after the beginning of the intervention (T1), and 5 min after the intervention finished (T2). The primary outcome is pain score. Secondary outcomes include vital signs, side effects, joint range of motion, adjuvant analgesia need, therapist and patient satisfaction, and whether willing to receive the same gas again. EXPECTED OUTCOMES: We expect nitrous oxide inhalation to have a beneficial effect on the pain of patients who receive manual therapy after anterior ligament reconstruction. DISCUSSION: If this treatment appears beneficial, it could improve patients' satisfaction and quality of life potentially and even be implemented widely in hospital and rehabilitation settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR2200061175 (Version 2.0 June 15, 2022), https://www.chictr.org.cn .

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

BACKGROUND: Nitrous 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 REPORT: A 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. CONCLUSION: This 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.

Experiences of frostbite injury from recreational use of nitrous oxide canisters in a UK burns center: Not a laughing matter.

Nitrous oxide is used as a recreational drug. Contact frostbite injury from compressed gas canisters has previously been described in the literature, but an increased number of such cases has been noted in our busy regional burns center in the UK. A single-center prospective case series of all patients referred and treated for frostbite injury secondary to misuse of nitrous oxide compressed gas canisters between January and December 2022 is presented. Data collection was performed through a referral database and patient case notes. Sixteen patients, of which 7 were male and 9 were female, satisfied the inclusion criteria. Mean patient age was 22.5 years. The median TBSA was 1%. In total, 50% of patients in the cohort had a delayed initial presentation to A&E of greater than 5 days. Eleven patients were reviewed at our burns center for further assessment and management. In total, 11 patients had bilateral inner thigh frostbite injuries, of which 8 had necrotic full-thickness injury, including subcutaneous fat. Seven patients were reviewed at our burns center and offered excision and split-thickness skin graft. Four patients presented with contact frostbite injury to the hand and one patient to the lower lip. This subgroup was managed successfully with conservative management alone. The reproducible pattern of frostbite injury secondary to the abuse of nitrous oxide compressed gas canisters is demonstrated in our case series. The distinct pattern of injury, patient cohort, and anatomical area affected presents an opportunity for targeted public health intervention in this group.

Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro.

Age-related decrements in the central nervous system (CNS) are thought to result from: (1) increased susceptibility to and accumulating effects of free radicals and inflammation; and (2) dysregulation in Ca2+ homeostasis, which affects numerous signaling pathways. Certain bioactive phytochemicals exhibit potent anti-inflammatory activities which may mitigate these age-related CNS decrements. This study investigated the individual and combination effects of green tea catechin (epigallocatechin gallate, EGCG), curcumin from turmeric, and broccoli sprouts which contain the isothiocyanate sulforaphane on inflammation and dysregulation in Ca2+ homeostasis to determine if the individual compounds were working synergistically and/or through independent mechanisms. Rat hippocampal neurons or highly aggressive proliferating immortalized (HAPI) microglial cells were pre-treated for a week with either the individual components or all in combination before inducing Ca2+ buffering deficits with dopamine (DA, 0.1 µM for 2 h) or inflammation using lipopolysaccharide (LPS, 100 ng/mL for 18 h), respectively. The EGCG (3 µM) and combination protected against DA-induced deficits in Ca2+ buffering (both % of cells that recovered and recovery time, p < 0.05). Additionally, the EGCG and combination reduced stress-mediated inflammation in HAPI rat microglial cells by attenuating LPS-induced nitrite release, inducible nitrous oxide synthase (iNOS) expression, and tumor necrosis factor-alpha (TNF-α) release (p < 0.05), but not cyclooxygenase-2 (COX-2) expression. Overall, broccoli sprouts (2 µM) and curcumin (1 µM) were not as effective as the EGCG or combination. Further research is needed to determine if dietary intervention with a variety of foods containing compounds such as those found in green tea, turmeric, or broccoli sprouts can play a role in reducing age-related CNS inflammation, microglial activation, and downstream signaling pathways that can lead to neuronal dysfunction.

An unusual case of subacute combined degeneration due to nitrous oxide abuse, which relapsed after bariatric surgery: A case report.

RATIONALE: Several studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, few studies have reported that N2O-induced SCD recurred because of sleeve gastrectomy after neurological symptoms improved. PATIENT CONCERNS: We report the case of an 18-year-old woman who developed paresthesia, weakness in 4 limbs, and an unstable gait after frequent, excessive N2O inhalation. DIAGNOSIS: The patient was diagnosed as having SCD. INTERVENTIONS AND OUTCOMES: Nineteen days after intravenous mecobalamin and supplementation with other kinds of vitamin B, her weakness and paresthesia resolved. However, 7 months after discharge, the patient experienced recurrence following sleeve gastrectomy. Blood biochemistry revealed low vitamin B12 levels. After a 22-day treatment, similar to the first hospitalization, her residual numbness and unsteady gait improved. LESSONS: This case highlights that patients, especially those at high risk of vitamin B12 deficiency, undergoing sleeve gastrectomy require careful nutritional follow-up and routine monitoring of micronutrients such as vitamin B12 and homocysteine. Continuous vigilance is essential for patients with common and rare neurological complications.

Thrombosis within the left anterior descending coronary artery and left ventricle after high-dose nitrous oxide use.

We present a man in his 30s with acute anterior myocardial infarction due to thrombotic occlusion of the left anterior descending artery and subsequent left ventricular thrombus formation after high-dose recreational use of nitrous oxide (N2O). Initial questioning for use of illicit substances was negative, but low vitamin B12 levels and severely elevated homocysteine levels prompted us to interrogate for the use of laughing gas. On questioning, the patient admitted to have used this substance, which he presumed to be innocent. Neither percutaneous coronary intervention with balloon dilatation nor intravenous glycoprotein IIb/IIIa receptor antagonist, nor continuous use of anticoagulation and double antiplatelet therapy resulted in thrombus resolution. Due to a severely reduced left ventricular function, despite 3 months on heart failure therapy, the patient is being counselled for intracardiac defibrillator implantation. We conclude that N2O, notably when consumed in conjunction with other proatherogenic substances, is associated with thrombosis: a relation possibly mediated by severe hyperhomocysteinaemia.

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

PURPOSE: To review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2 O) abuse, and analyze the factors that affect outcomes. METHODS: Patients with N2 O 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. RESULTS: The average age of the 110 patients with N2 O 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 N2 O 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. CONCLUSION: The recreational use of N2 O 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 N2 O abuse. The therapeutic administration of vitamin B12 supplementation and N2 O withdrawal can make the overall prognosis good, especially for female patients.

Nitrous oxide abuse induced subacute combined degeneration despite patient initiated B12 supplementation.

INTRODUCTION: Nitrous oxide (N2O) is a commonly used inhaled anesthetic that is legal to purchase as a food additive and is popular as a recreational euphoric drug. Abuse causes a functional B12 deficiency, leading to clinical features and imaging consistent with subacute combined spinal cord degeneration (SCD). CASES: Poison Center medical records from four patients are reviewed in this series. Four patients presented with lower extremity weakness, paresthesias and gait abnormalities in the setting of chronic N2O abuse. Each reported using 50-150 N2O cartridges ("whippets") almost daily for months to years, and reported supplementing with oral B12 at the recommendation of other users and online forums. None reported prior B12 deficiency or dietary restrictions, and none exhibited hematologic abnormalities. RESULTS: All patients had clinical signs of neurotoxicity including weakness and ataxia. Additionally, all had elevated methylmalonic acid and homocysteine concentrations with normal B12 indicating a functional B12 deficiency. Three had imaging consistent with SCD despite home supplementation The MRI in the fourth case was inconclusive due to movement artifact. CONCLUSION: We report four cases of subacute combined degeneration induced by recreational nitrous oxide abuse despite self-administered vitamin B12 supplementation.

Vitamin B12 deficiency in the setting of nitrous oxide abuse: diagnostic challenges and treatment options in patients presenting with subacute neurological complications.

OBJECTIVE: It is well recognized that nitrous oxide abuse can lead to vitamin B12 deficiency presenting with neurological complications. Nevertheless, establishing this diagnosis can be challenging, and treatment guidelines are lacking. METHODS: In this paper, we present a case series of eight patients and discuss the diagnostic challenges and treatment options for vitamin B12 deficiency due to nitrous oxide abuse presenting with neurologic complications. RESULTS: Biochemical findings are not always straightforward and complementary testing is often necessary. Magnetic Resonance Imaging (MRI) revealed a longitudinally myelopathy extending over a long segment typically involving the dorsal columns of the cervical cord. To increase the lesion conspicuity, dedicated MRI sequences are needed. In our practice, we recommend the use of T2-weighted images (WI) with fat suppression (FS). Treatment consists of cessation of nitrous oxide abuse and supplementation with intramuscular injections of cobalamin. Due to a lack of treatment guidelines, we also describe the treatment schedule used in our neurology clinic and give a brief overview of treatment options suggested in the literature. CONCLUSION: We described diagnostic steps en treatment plans in patients presenting with subacute neurological complications due to nitrous oxide abuse. ABBREVIATIONS: crea: creatinine; HCy: homocysteine; MCA: 2-methylcitric acid; MMA: methylmalonic acid; MRI: magnetic resonance imaging; SEP: somatosensory evoked potentials.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: Seven patients aged 18-30, consuming more than 140 gas-filled balloons (one balloon is filled with approximately 8 g of N2O) per week for over a month, developed a severe, predominantly motor, length-dependent, progressive neuropathy over 3 to 6 weeks. 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 9.2 months, IQR 7.5-10.75), mean ONLS was 2.0 (IQR 2.0-2.0). DISCUSSION: Young patients, with induced N2O motor neuropathy remain disabled after 5 to 14.5 months of gas withdrawal, despite vitamin B12 supplementation. A longer follow-up is needed to fully appraise the severity of these toxic neuropathies.

Just 'nanging' around - harmful nitrous oxide use: a retrospective case series and review of Internet searches, social media posts and the coroner's database.

BACKGROUND: The chronic recreational inhalation of nitrous oxide (N2 O) 'nanging', can have adverse neurological and psychiatric effects. AIM: To evaluate cases of chronic N2 O use presenting to two hospitals, as well as to evaluate nationally N2 O deaths reported to the coroner and trends in Internet searches and social media posts related to N2 O. METHODS: Retrospective review of two toxicology units, from July 2017 to October 2020, of patients presenting with chronic N2 O use and neurological and/or psychiatric symptoms. We evaluated 10 years (2010-2019) of Internet search and social media trends involving N2 O and the National Coronial Information System (NCIS) database for deaths across Australia. RESULTS: Twenty-two patients were identified: median age 22 years, half female, 17 Asian background and 15 students. Presentations included decreased mobility or unsteady gait (n = 15) and psychiatric symptoms (n = 5). The median reported bulb use/day was 300 (interquartile range (IQR): 200-370), for a median of 6 months (IQR: 3-24). On magnetic resonance imaging, 10/18 had subacute combined degeneration of the spinal cord and 7/7 sensorimotor neuropathy on nerve conduction studies. All received high-dose intramuscular vitamin B12 and 11 methionine. Despite prolonged rehabilitation, nine required walking aids on discharge. Since 2017, social media posts and Internet searches for N2 O increased rapidly, the latter mostly directed at obtaining N2 O canisters. From the NCIS, 36 deaths were identified, 12 unintentional (recreational drug use), 20 intentional self-harm and 4 traumatic. CONCLUSION: We report a case series of symptomatic chronic N2 O use, many with ongoing neurological sequelae. Furthermore, a sharp increase in Internet searches to obtain N2 O cannisters was noted. Education of high-risk student groups on the long-term sequelae is important.

A rise in cases of nitrous oxide abuse: neurological complications and biological findings.

BACKGROUND: The 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. METHODS: We 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. RESULTS: Our 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. CONCLUSION: We 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.

Extensive Cerebral Venous Thrombosis Secondary to Recreational Nitrous Oxide Abuse.

Nitrous oxide, colloquially known as "whippets," is a commonly abused inhalant by adolescents and young adults. There are limited data describing the adverse effects of this abuse. We present a 16-year-old girl with no medical history who presented to the emergency department for confusion, hallucinations, weakness, and headaches. Imaging revealed extensive cerebral thrombosis. She had no prior history of venous or arterial thrombosis. Hypercoagulability workup demonstrated an elevated homocysteine level. She was treated with effective anticoagulation and vitamin B12 folate supplementation. To our knowledge, there are a very few cases in the medical literature of cerebral venous thrombosis following the use of nitrous oxide. The pathophysiology of the disorder appears to be linked to the metabolism of vitamin B12 inducing hyperhomocysteinemia and a procoagulant state.