Clinical,electrophysiological,imaging Characteristic And Mechanism Analysis Of 8 Cases Of Neurological Diseases Caused By N₂O Abuse

Objective:The laughing gas,which is also called nitrous oxide(N2O),is a colorless,slightly sweet and non-inflammable gas.First discovered by British scientist Joseph Priest,it is widely used in clinic as inhaled anesthetic because the mildly analgesia.However,in the last 20 years,several foreign cases reported the neuropathy caused by prolonged exposure of N2O.Then,we began to recognize its harmfulness.The neuropathy caused by N2O included myeloneuropathy,myelopathy,peripheral neurology and subacute combined degeneration(SCD)etc.Some cases maybe lead to emotional,psychological and mental effect.Clinically,it is mainly manifested as acute or subacute onset limb weakness,paresthesia,ataxia and abnormal posture and gait,some of which have autonomic dysfunction,decreased cognition and mental symptoms.Physical examination showed hyporeflexia,Romberg sign,Lhermitte’s sign(an "electric" sensation that travels down the limbs and back upon neck flexion)and decreased sensation.Electrophysiology and spinal magnetic resonance imaging(MRI)can present typical characteristic.The neurotoxicity of N2O is currently thought to be associated with metabolic disorders of cobalamin(vitamin B12).8 cases who are diagnosed as neuropathy caused by N2O abuse are collected in this study.We analyzed the clinical characteristics,laboratory test results,electrophysiological and imaging data of the 8 patients and summarized the diagnosis and treatment of this disease.And further exploration of the pathogenesis need to be discussed through literature review.Material and methods:We collected and retrospectively analyzed 8 cases who are diagnosed as neurological disorder caused by N2O abuse in Qilu hospital of Shandong University from Jan.2016 to Feb.2019.Detailed medical history inquiry and comprehensive neurological examination of every patients were summarized.Electrophysiological examination,spinal MRI and hematology examination included the hemoglobin,homocysteine(HCY),the level of vitamin B12 and folic,CSF examination,methylmalonic acid(MMA)examination in serum and urine,etc.had been analyzed.Some patients were followed up.And we summarized characteristics and prognosis of the patients.Result:Clinical characteristic of 8 patients:There are 5 males and 3 females,with the onset age ranging from 16 to 26 years old.All of them had acute onset and progressive course.The first symptom of 5 patients is numbness of their limbs,while the other 3 complained of psychiatric symptom.All of these 8 patients manifested as muscle weakness,6 of them had subjective paresthesia and 1 case presented with cognition impairment and autonomic dysfunction.Physical examination(PE):6 cases presented distal weakness in their lower extremities,especially dorsal flexion of foot.7 cases had decreased algesthesia.6 cases had reduced pallesthesia of their lower extremities.6 cases had positive Romberg sign.3 cases had deep tendon reflexes in their lower extremities diminished.1 cases had positive Babinski sign and Chaddock sign and 1 case had positive Chaddock sign on her right site only.Laboratory test:1 case had lower vitamin B12 level than normal,the other one case had lower folate than normal.The level of HCY elevated in 4 cases.2 cases had elevated level of MMA in urine.Electrophysiological examination in most patients showed multiple peripheral neuropathy characteristic as symmetry,length dependent and axonal injury.Spinal MRI showed hyperintensity on T2-weighted images of the lateral and posterior columns.The invert V-sign can be seen in typical cases.Cerebrospinal fluid(CSF)examination and brain MRI showed no significant changes.After supplementation of vitamin B12,the level of vitamin B12 and the level of HCY level quickly returned to normal.The clinical manifestations and spinal MRI findings recovered gradually.Electrophysiology indicated that the nerve injury gradually returned to the near normal level after transient aggravation.The overall prognosis of the patient was good.Conclusion:1.N2O abuse mainly affect adolescent.2.Typical clinical manifestations of N2O abuse are numbness and weakness of the limbs and/or mental symptoms,a few accompanied by cognitive dysfunction and autonomic symptoms.Several patients were accompanied by autonomic dysfunction.3.HCY,MMA in blood and urine and cervical spinal MRI play an imperative role in diagnosis,CSF examination,brain MRI and MMA gene detection is of significant importance in differential diagnosis.4.Neuroelectrophysiological examination shows symmetric,length-dependent and axonal damage multiple peripheral neuropathy.5.Avioding exposure of N2O and high-dose of vitamin B12 supplement had a good prognosis.Thus,early diagnosis and treatment of this disease is of great significance.6.Teenagers have poor self-control and some patients relapse.Our nation and society should strengthen the control of N2O and the education of teenagers.