Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: case report and literature review

A previously healthy 27-year-old woman developed a subacute myeloneuropathy after receiving nitrous oxide anesthesia for dental procedures. Neurologic evaluation revealed that she was vitamin B(12) deficient due to underlying pernicious anemia. Discontinuation of nitrous oxide and supplementation with vitamin B(12) resulted in dramatic clinical improvement, with near-complete normalization of her neurologic examination. This case and published reports reviewed here emphasize that favorable outcomes are possible following prompt recognition and treatment of vitamin B(12) deficiency.     

Reversible myeloneuropathy of nitrous oxide abuse: serial electrophysiological studies

Detailed electrophysiological studies were performed in 4 patients with myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years. All presented with paresthesias, weakness, and Lhermitte's phenomena, and exhibited signs of sensorimotor polyneuropathy, ataxia, and arreflexia. Two had subnormal serum vitamin B12 levels. Baseline electrophysiologic testing revealed reduced motor unit potentials, prolonged F wave latencies, absent H reflexes, denervation potentials, and delays in motor and sensory conduction. Three had peripheral and nuchal delay after median nerve stimulation. All were reevaluated after 3 to 12 months' abstinence and treatment with vitamin B12, and all showed substantial clinical improvement. Parallel improvement in electrophysiologic findings occurred, but residual minor conduction delays, loss of H reflexes, electromyographic evidence of denervation, or abnormalities of posterior tibial SEP were noted. These findings confirm the reversibility of myeloneuropathy of nitrous oxide abuse and describe the profile of electrophysiologic recovery in subjects who abstain from further neurotoxic exposure.     

Nitric-oxide triggered neurological disorders in subjects with vitamin B12 deficiency

INTRODUCTION: Nitrous oxide is frequently used for anesthesia. It may cause spinal cord toxicity. CASE REPORTS: We report two patients who presented gait disorders after nitrous oxide anesthesia. Physical examination revealed arms and legs pyramidal syndrome and abnormal proprioception, consistent with subacute combined degeneration of the spinal cord. Serum vitamin B12 level was extremely low. The patients improved with parenteral treatment with hydroxycobalamin. CONCLUSIONS: The inactivation of methionine synthase and L methylmalonylcoA mutase by nitrous oxide has been previously demonstrated. Anesthesia-related exposure to nitrous oxide may induce neurologic disorders even in patients with no preliminary vitamin B12 deficiency.     

Nitrous oxide myelopathy in an abuser of whipped cream bulbs.

A 23 year old man presented with a severe posterior column myelopathy related to prolonged nitrous oxide abuse obtained from whipped cream bulbs. The site of pathology was identified by magnetic resonance imaging (MRI) and somatosensory evoked potentials. The mechanism of toxicity involves inactivation of vitamin B12 dependent enzymes. Appropriate treatment with methionine and vitamin B12 was instituted quickly with good neurological outcome. There are major concerns regarding the availability of nitrous oxide in supermarkets.     

Myeloneuropathy and macrocytosis associated with nitrous oxide abuse

After four months of excessive nitrous oxide (N2O) exposure, a dentist had myeloneuropathy with spastic paraparesis, Lhermitte's sign, sensory shading, loss of position and vibration sense, ataxia, and impotence. Macrocytosis, hypersegmented neutrophils, and a reduced vitamin B12 level were associated with normal findings on gastric analysis and Schilling test. Complete hematologic and neurologic recovery followed N2O avoidance and vitamin therapy for six months.     

Nitrous oxide-induced vitamin B(12) deficiency

Two patients with asymptomatic vitamin B(12) deficiency developed a peripheral neuropathy 6-7 weeks after exposure to nitrous oxide during general anaesthesia, and 3 and 11 days after receiving cyclophosphamide. The serum B(12) concentration was less than 20 pmol/l and the symptoms resolved after B(12) replacement. We believe that the neurological symptoms were triggered by exposure to nitrous oxide. A possible novel feature in these patients was the close temporal relationship between the onset of the symptoms and cyclophosphamide treatment. It is possible that cyclophosphamide reduced the availability of remaining B(12) stores.     

Response to oral supplementation in copper deficiency myeloneuropathy

Neurological manifestations due to copper deficiency include ataxic myeloneuropathy that resembles subacute combined degeneration due to B12 deficiency. We report our experience in the treatment of 10 patients with copper deficiency myeloneuropathy and conclude that copper supplementation leads to stabilization rather than improvement in the neurological deficits.     

Approach to a case of myeloneuropathy

Myeloneuropathy is a frequently encountered condition and often poses a diagnostic challenge. A variety of nutritional, toxic, metabolic, infective, inflammatory, and paraneoplastic disorders can present with myeloneuropathy. Deficiencies of vitamin B12, folic acid, copper, and vitamin E may lead to myeloneuropathy with a clinical picture of subacute combined degeneration of the spinal cord. Among infective causes, chikungunya virus has been shown to produce a syndrome similar to myeloneuropathy. Vacuolar myelopathy seen in human immunodeficiency virus (HIV) infection is clinically very similar to subacute combined degeneration. A paraneoplastic myeloneuropathy, an immune-mediated disorder associated with an underlying malignancy, may rarely be seen with breast cancer. Tropical myeloneuropathies are classified into two overlapping clinical entities — tropical ataxic neuropathy and tropical spastic paraparesis. Tropical spastic paraparesis, a chronic noncompressive myelopathy, has frequently been reported from South India. Establishing the correct diagnosis of myeloneuropathy is important because compressive myelopathies may pose diagnostic confusion. Magnetic resonance imaging (MRI) in subacute combined degeneration of the spinal cord typically reveals characteristic signal changes on T2-weighted images of the cervical spinal cord. Once the presence of myeloneuropathy is established, all these patients should be subjected to a battery of tests. Blood levels of vitamin B12, folic acid, vitamins A, D, E, and K, along with levels of iron, methylmalonic acid, homocysteine, and calcium should be assessed. The pattern of neurologic involvement and results obtained from a battery of biochemical tests often help in establishing the correct diagnosis.     

Pernicious azotaemia? A case series of subacute combined degeneration of the cord secondary to nitrous oxide abuse

Nitrous oxide abuse is a rare cause of vitamin B12 deficiency and consequent subacute combined degeneration of the spinal cord. Worldwide and Australian statistics indicate that recreational use of nitrous oxide is increasing. We report four cases of females aged 18–24 years presenting with clinical symptoms of subacute combined degeneration of the spinal cord. MRI during admission demonstrated the classic findings of T2 hyperintensity, predominantly within the dorsal columns of the spinal cord, with variable involvement of the lateral corticospinal tracts. These cases highlight the ready availability of nitrous oxide and the fact that heavy prolonged recreational use is occurring in the community. It is important that clinicians in emergency and community settings are alerted to this unusual cause of subacute combined degeneration of the spinal cord because early aggressive vitamin B12 replacement together with behavioural change can reverse this disabling neurological syndrome.     

笑气滥用导致神经功能缺损的临床特点

目的探讨笑气滥用导致神经功能缺损的临床特点。方法回顾性分析2例笑气滥用导致神经功能缺损患者的临床资料,并对相关文献资料进行复习。结果 1例以模拟格林-巴利综合征的症状发病,表现为四肢对称性的麻木无力,脊椎横断面T2WI显示颈髓后索倒"V"形高信号,EMG呈多发性周围神经脱髓鞘和轴索损伤。另1例以模拟急性脊髓炎症状起病,表现为双下肢无力伴小便潴留,EMG呈脊髓损害表现,但脊椎MRI未发现明显病灶。2例患者血同型半胱氨酸水平均明显升高,伴或不伴维生素B12缺乏,停止吸食笑气并补充维生素B12后症状逐渐好转。结论当健康青年人出现维生素B12缺乏的神经系统症状,如表现为亚急性联合变性、周围神经病等,应考虑笑气中毒的可能。