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.

Nitrous-oxide-induced polyneuropathy and subacute combined degeneration of the spine: clinical and diagnostic characteristics in 70 patients, with focus on electrodiagnostic studies.

BACKGROUND AND PURPOSE: Nitrous oxide (N2 O) induced neurological symptoms are increasingly encountered. Our aim is to provide clinical and diagnostic characteristics with a focus on electrodiagnostic studies. METHODS: Patients with neurological sequelae due to N2 O presenting in our hospital between November 2018 and December 2021 reporting clinical and diagnostic data were retrospectively reviewed. RESULTS: Seventy patients (median 22 years) were included. Median N2 O usage was 4 kg/week during 12 months. Patients' history revealed a higher rate of sensory symptoms compared to motor (97% vs. 57%) and 77% walking difficulties. Clinical diagnosis was polyneuropathy (PNP) in 44%, subacute combined degeneration (SCD) of the spine in 19%, both in 37%. Median vitamin B12 level was low (159 pmol/L), normal in 16%. The median methylmalonic acid was increased (2.66 µmol/L). Electrodiagnostic abnormalities were observed in 91%, with 72% fulfilling axonal PNP criteria, 20% showing mild to intermediate slowing. One patient fulfilled demyelinating PNP criteria not related to N2 O abuse (Charcot-Marie-Tooth type 1a). More prominent motor nerve conduction abnormalities were found; lower limbs were more affected. In 64% with normal conduction, myography showed signs of axonal loss. Magnetic resonance imaging showed cervical myelopathy in 58% involving generally five to six segments. CONCLUSIONS: Nitrous oxide (N2 O) leads to neurological symptoms by causing PNP and/or SCD primarily involving the legs. Distinguishing PNP and SCD clinically was shown to be insufficient. Electrodiagnostic studies showed axonal PNP. Demyelinating PNP due to N2 O abuse was not present in our cohort. Therefore, further diagnostic work-up is warranted if demyelinating features are present.

Nitrous oxide-induced subacute combined degeneration of the cord: diagnosis and treatment.

Recreational use of nitrous oxide (N2O) has increased rapidly in recent years and is now the second most commonly used recreational drug among young people in the UK. There has been a corresponding rise in cases of nitrous oxide-induced subacute combined degeneration of the cord (N2O-SACD), a pattern of myeloneuropathy usually associated with severe vitamin B12 deficiency. This can cause serious and permanent disability in young people but, if recognised early, may be effectively treated. All neurologists should be aware of N2O-SACD and its treatment; however, there are currently no agreed guidelines. Based on our experience in East London, an area of high N2O use, we provide practical advice on its recognition, investigation and treatment.

Coexistence of Primary Sjögren's Syndrome and Autoimmune Gastritis With Pernicious Anemia and Subacute Combined Degeneration of the Spinal Cord: Case Report and Literature Review.

Background: Autoimmune gastritis (AIG) and Primary Sjögren's syndrome (pSS) are both autoimmune diseases with low prevalence in China. Subacute combined degeneration (SCD) of the spinal cord is the most common neurological manifestation of vitamin B12 deficiency. Until now, a patient with pSS and complications of AIG including SCD has not been reported. Case Presentation: A 69-year-old woman presented with palpitations and symmetrical and progressive numbness in her hands and feet. The patient had a sense of stepping on cotton and could not write or walk without help. We reviewed the patient's history and analyzed her blood tests, imaging, gastroscopic findings, and pathological results. The patient fulfilled the criteria of AIG, pSS, spinal cord SCD and early pernicious anemia (PA) simultaneously. Although pSS can lead to reduction of vitamin B12, this is the first overlapping case of pSS with spinal cord SCD. After symptomatic treatment, the patient returned to a normal life. Conclusions: This first report about the coexistence of pSS and complications of AIG including SCD and PA will promote a better understanding of the relationship between these diseases.

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.

Autoimmune polyglandular syndrome type II presenting as subacute combined degeneration of spinal cord: a neuroendocrinology crossroad.

Introduction: Autoimmune polyglandular syndrome (APS) is a condition having multiple endocrine abnormalities. It is divided into three types depending on the involvement of various endocrinopathies. It is also associated with other systemic involvement. The basic pathophysiology of this syndrome revolves around autoimmunity.Case presentation: We discuss the case of a 50-year-old gentleman who presented to us in emergency with subacute onset progressive weakness of both lower limbs followed by upper limbs. On examination, patient was confused and disoriented. General examination findings include hypotension, pallor, facial puffiness and vitiligo. Neurological examination revealed spasticity and motor weakness in all four limbs with extensor planter response. Sensory examination during hospital course revealed posterior column involvement. Laboratory and radiological investigations confirmed subacute combined degeneration of spinal cord secondary to pernicious anaemia, Addison's disease and autoimmune thyroid disease. The final diagnosis of autoimmune polyglandular syndrome type II was made after fulfilment of the required criteria.Conclusion: Autoimmune polyglandular syndrome type II can rarely present to neurologist as subacute combined degeneration of spinal cord. This syndrome and its systemic association should be kept in mind in order to reach the final diagnosis.

Subacute combined degeneration of the spinal cord with concomitant autoimmune disease: report of 2 cases.

The etiology of subacute combined degeneration (SCD) of the spinal cord is closely associated with vitamin B12 (VitB12) deficiency. The clinical manifestations of SCD are complex and vary substantially. Due to some SCD patients with atypical manifestations and concomitant autoimmune disorders, the probability of misdiagnosis and missed diagnosis is still relatively high in the early stage. We report the cases of two patients who were missed or misdiagnosed at another hospital because of the normal initial VitB12 level and partial overlap of clinical manifestations, finally diagnosed as SCD with atypical manifestations and concomitant autoimmune disorders, pharyngeal-cervical-brachial Guillain-Barre syndrome in Case 1 and SCD with autoimmune thyroiditis in Case 2. After undergoing corresponding treatment, death was reported in Case 1 and improvement in Case 2. Analysis of the clinical manifestations and investigation of the underlying pathogenesis in such patients could help improve the rate of early diagnosis and allow timely treatment of SCD, thereby preventing disease progression and poor clinical outcomes.

[An adult case of Hashimoto's thyroiditis accompanying pernicious anemia and subacute combined degeneration].

A 66-year old man presented to our hospital due to gait disturbance. He was unable to stand or walk without assistance. Laboratory tests revealed macrocytic anemia and an extremely low serum vitamin B12 level. MRI showed high- intensity signals in the posterior and lateral column of the cervical and thoracic region of the spinal cord in T2 weighted image. Other significant laboratory results were an increased and/or positive anti-thyroid peroxidase antibody, anti-gastric parietal cell antibody and anti-intrinsic factor antibody. He was diagnosed with a combination of Hashimoto's thyroiditis, pernicious anemia and subacute combined degeneration of the spinal cord (SCD). The patient's condition was autoimmune polyglandular syndrome type3B. The association of thyroid and gastric autoimmune disorders is a unique syndrome that tend to be complicated by vitamin B12 deficiency.

Subacute combined degeneration of the spinal cord concurrent with acute pulmonary embolism: a case report.

A 58-year-old male vegetarian presented with progressive numbness and weakness in the lower extremities. Laboratory examinations showed reduced vitamin B12 level with megaloblastic anaemia. Spinal magnetic resonance imaging (MRI) revealed hyperintensity within the posterior and lateral columns on T2-weighted imaging. The diagnosis of subacute combined degeneration (SCD) of the spinal cord was established. Unexpectedly, the patient developed transitory syncope on the second day after hospitalization. The diagnostic computed tomography pulmonary angiography (CTPA) confirmed multiple small pulmonary emboli. An isolated significantly elevated level of homocysteine (117.1 µmol/l) was documented when screening for hypercoagulable markers. Except for a long-term vegetarian diet, no other risk factors for hyperhomocysteinaemia (such as a family history of homocysteinuria) was found. The severity of the hyperhomocysteinaemia found in this current patient was unusual for patients with an insufficient intake of vitamin B12. In SCD patients, elevated homocysteine may increase the risk of thrombosis, which may exacerbate existing problems. Knowing the risk factors should help physicians choose appropriate diagnostic and therapeutic strategies.

Subacute combined degeneration of the spinal cord with concomitant autoimmune disease: report of 2 cases

The etiology of subacute combined degeneration (SCD) of the spinal cord is closely associated with vitamin B12 (VitB12) deficiency. The clinical manifestations of SCD are complex and vary substantially. Due to some SCD patients with atypical manifestations and concomitant autoimmune disorders, the probability of misdiagnosis and missed diagnosis is still relatively high in the early stage. We report the cases of two patients who were missed or misdiagnosed at another hospital because of the normal initial VitB12 level and partial overlap of clinical manifestations, finally diagnosed as SCD with atypical manifestations and concomitant autoimmune disorders, pharyngeal-cervical-brachial Guillain-Barre syndrome in Case 1 and SCD with autoimmune thyroiditis in Case 2. After undergoing corresponding treatment, death was reported in Case 1 and improvement in Case 2. Analysis of the clinical manifestations and investigation of the underlying pathogenesis in such patients could help improve the rate of early diagnosis and allow timely treatment of SCD, thereby preventing disease progression and poor clinical outcomes.

Correlation between anemia and clinical severity in subacute combined degeneration patients.

OBJECTIVES: Subacute combined degeneration (SCD) is a demyelinating disease commonly caused by vitamin B12 deficiency. Several studies have been reported SCD could be accompanied by anemia. However, the correlation between anemia and clinical severity of SCD patients is unclear. In this study, we aim to analyze the clinical characteristics of SCD concomitant with anemia, and investigate the effect of anemia in predicting the severity of SCD. METHODS: A total 42 patients were included in the study. Clinical, laboratory, radiological findings, and outcomes from the patients were analyzed. All patients were treated with vitamin B12 for no less than 6 months and a functional disability rating scale was used to evaluate severity of neurological impairment at the time of admission and 3 and 6 months after admission in our study. RESULTS: 85.7% patients had macrocytosis. Decreased serum vitamin B12 levels were found in 27 patients (64.3%). MRI showed long-segment abnormality on the spinal cord in 22 patients. No differences in rating score were found in patients grouped by sex, age, clinical course, serum vitamin B12, or MRI manifestations at the time of admission or at the follow-up visits. Negative correlation was seen between hemoglobin levels and the clinical severity scores on admission. CONCLUSION: Not all patients with SCD concomitant with anemia had decreased serum vitamin B12 level. The inverse correlation between hemoglobin level and clinical severity suggests the degree of anemia can help in evaluating the extent of neurologic impairment.

Degeneración combinada subaguda de la médula espinal por deficiencia de vitamina B12 / Subacute combined degeneration of the spinal cord due to vitamin B12 deficiency

Introducción: la degeneración combinada subaguda de la médula espinal es una mielopatía inducida por deficiencia de vitamina B12. Produce disestesias simétricas, alteraciones de la sensibilidad superficial y vibratoria. En estadios avanzados causa defectos de la memoria, el aprendizaje, comportamiento, gusto y olfato.Objetivo: presentar el caso de una paciente diagnosticada y tratada por degeneración combinada subaguda de la médula espinal, afección rara en Cuba.Presentación del caso: paciente femenina, de 50 años de edad. Refirió que dos años antes del ingreso presentó debilidad progresiva en los miembros inferiores, añadiéndose frialdad y adormecimiento de las cuatro extremidades, marcha tambaleante, palpitaciones, fatiga, cefalea, disnea de esfuerzo y tinte de la piel de color amarillo limón. Se le realizaron exámenes complementarios de laboratorio, imagenológicos e histológicos. La lámina periférica mostró anisocitosis y macrocitosis marcadas, presencia de poiquilocitos y policromatofilia. A la paciente se le administró diariamente, en dosis única, 100 mg de vitamina B12 durante 10 días, con recuento leucocitario diario. Fue egresada a los 15 días, con indicaciones para seguir el tratamiento. Transcurridos tres meses recuperó 70 por ciento de sus capacidades cognitivas y motoras, con movilidad de las cuatro extremidades.Conclusiones: el diagnóstico de esta enfermedad precisa de una correcta aplicación del método clínico, y la realización de exámenes de laboratorio, imagenológicos e histológicos. Ello fue posible por la atención multidisciplinaria entre los especialistas de medicina interna, hematología, imagenología y gastroenterología. En este caso la edad de la paciente no estaba comprendida en el rango de presentación de la enfermedad(AU)

Introduction: subacute combined degeneration of the spinal cord is a myelopathy induced by vitamin B12 deficiency. It produces symmetric dysesthesias, alterations of superficial and vibratory sensitivity. In advanced stages it causes defects of memory, learning, behavior, taste and smell.Objective: to present the case of a patient diagnosed and treated by subacute combined degeneration of the spinal cord, a rare condition in Cuba.Case presentation: female patient, 50 years old. She reported that two years before admission she presented progressive weakness in the lower limbs, adding coldness and numbness of the four limbs, wobbly march, palpitations, fatigue, headache, dyspnea and lemon yellow skin tint. She was given complementary laboratory, imaging and histological exams. The peripheral lamina showed marked anisocytosis and macrocytosis, presence of poikilocytes and polychromatofilia. The patient was given daily, in a single dose, 100 mg of vitamin B12 for 10 days, with daily white blood cell count. She was discharged 15 days after, with instructions to continue the treatment. After three months she recovered 70 percent of her cognitive and motor skills, with mobility of the four limbs.Conclusions: the diagnosis of this disease requires a correct application of the clinical method, and the realization of laboratory, imaging and histological exams. This was possible due to the multidisciplinary care among specialists in internal medicine, hematology, imaging and gastroenterology. In this case, the age of the patient was not included in the range of presentation of the disease(AU)

Clinical and imaging characteristics of subacute combined degeneration complicated with white matter lesions in the brain: a report of five cases.

PURPOSE: To report five cases of subacute combined degeneration (SCD) with brain involvement and explore its clinical and imaging characteristics. METHODS: A retrospective study was performed on the clinical data and brain MRI of five patients with subacute combined degeneration with brain involvement (out of 107 cases with SCD in total). White matter lesions (WML) assessment was performed qualitatively using Fazekas scale score. RESULTS: The main symptoms in four patients were weakness in both lower extremities and unstable walking (limb weakness in three patients, dizziness in three patients, and blurred vision in one patient). One patient had memory loss and cognitive dysfunction. The MMSE scale indicated mild dementia in one patient. On head MRI (Magnetic Resonance Imaging), multifocal and symmetrical high signals of T2WI and FLAIR were observed in the frontal lobe and periventricular white matter in four patients, while another patient showed preferential atrophy in frontal regions. Fazekas scale scores ranged from 1-6. CONCLUSION: Adult subacute combined degeneration seldom involves the brain. Multifocal and symmetrical high signal white matter lesions can be found on FLAIR and T2WI, as well as frontal atrophy on head MRI.

Subacute combined degeneration of the spinal cord following nitrous oxide anesthesia: A systematic review of cases.

OBJECTIVE: Vitamin B12 deficiency can lead to subacute combined degeneration (SCD). Nitrous oxide (N2O) is an anesthetic which oxidizes the cobalt ion of vitamin B12, interfering with its function as a coenzyme. In this study, we conduct a systematic review of reported cases of SCD following nitrous oxide anesthesia. PATIENTS AND METHODS: A comprehensive search of multiple databases was conducted, and information about patient characteristics, symptomatology, clinical work-up, and treatment was extracted from eligible articles. Univariate analyses were performed to identify predictors of poor neurological recovery following SCD. RESULTS: 32 studies, reporting 37 cases of nitrous oxide-induced SCD, were included through the screening process. These cases included 21 male patients and 16 female patients, with an average age of 50.4 years (SD 17.6). An etiology for subclinical B12 deficiency was determined in 30 reports; of these, 25 were due to vitamin malabsorption secondary to a gastrointestinal disorder. Duration of nitrous oxide exposure was described in 19 reports, and ranged from 30 min to 11 h. Univariate analysis failed to find an association between post-operative recovery and age (p = 0.60), sex (p = 0.46), positive MRI findings (p = 0.47), post-operative serum B12 (p = 1.00), post-operative hemoglobin (p = 0.18), type of surgery (p = 0.58), or post-operative high mean corpuscular volume (p = 0.13). CONCLUSION: In patients with postsurgical myelopathy, surgeons should evaluate B12 status and consider the possibility that nitrous oxide could cause a subclinical B12 deficiency to become overt, particularly in patients with malabsorptive GI comorbidities. Treatment with B12 in this population can result in significant improvement of neurological function.

Subacute Combined Degeneration: A Retrospective Study of 68 Cases with Short-Term Follow-Up.

PURPOSE: The study aimed to analyze the clinical characteristics, laboratory test results, neuroimaging findings, and outcomes in patients diagnosed with subacute combined degeneration (SCD). MATERIALS AND METHODS: A total of 68 patients with SCD who had been appropriately treated for no less than 6 months were included in our study. Histories, results of routine blood tests, biochemical indices, serum vitamin B12 levels, and spinal magnetic resonance imaging (MRI) findings from the patients were studied and analyzed. Clinical signs and symptoms, graded using a functional disability rating scale, were scored at the time of admission and 3 and 6 months after admission. RESULTS: Limb numbness, limb weakness, and gait disturbances were the most common symptoms in patients with SCD. All patients showed clinical improvement to different degrees at the follow-up visits after vitamin B12 treatment. No differences in rating score were found in patients grouped by sex, hemoglobin level, serum vitamin B12, or MRI manifestations at the time of admission or at the follow-up visits. Younger patients and those with shorter disease courses had better rating scores at the short-term follow-up visits. CONCLUSION: Anemia, low levels of serum vitamin B12, and MRI abnormalities in the spinal cord are not expected to be associated with worse clinical manifestations. The age of onset and course of disease are important in evaluating the short-term prognosis of patients with SCD.

Prevalence of MR imaging abnormalities in vitamin B12 deficiency patients presenting with clinical features of subacute combined degeneration of the spinal cord.

BACKGROUND AND AIMS: Subacute combined degeneration (SACD) of the spinal cord, characterized by degeneration of lateral and posterior columns, is often found in vitamin B12 deficiency. Our aim was to look for sensitivity of imaging in depicting the spinal cord abnormality in vitamin B12 deficient patients and to find any correlation of vitamin B12 levels with clinical scores/severity at time of presentation. MATERIAL AND METHODS: A total 54 patients with biochemically proven vitamin B12 deficiency were included in the study. In all these patients MR study of cervico-dorsal spine was done. All the patients after initiation of appropriate treatment were followed up for a minimum of two months. RESULTS: MRI showed cord signal abnormality in only 8 patients out of 54 patients with low sensitivity of 14.8%. After appropriate therapy, complete resolution of cord signal abnormalities was observed in all these 8 patients, on follow-up MR imaging. Significant negative correlation (r=-0.503, p<0.000) was seen between the clinical severity scores and initial vitamin B12 levels. CONCLUSION: Conventional MRI may not be a useful tool for the diagnosis of SACD as it has very low sensitivity. Inverse correlation of Vitamin B12 levels with clinical scoring suggests that initial serum vitamin B12 levels may help in predicting the clinical severity.