Nitrous oxide induced subacute combined degeneration of the spine cord: A case report.

RATIONALE: In recent years, recreational use of inhaled nitrous oxide (N2O) is on the increase among young people, accompanied by a corresponding rise in reports about its toxicity. Subacute combined degeneration of the spine cord (SCD) is the typical clinical picture of the nervous system disorder caused by N2O intoxication, as a result of metabolic disturbance of vitamin B12. PATIENT CONCERNS, DIAGNOSES, INTERVENTIONS AND OUTCOMES: We report a 28-year-old female of SCD due to prolonged use of N2O, presented with paresthesia and unsteady in walking progressing within 1 month. Symptoms gradually improved with the treatment of intramuscular injections of hydroxocobalamin combined with N2O abstinence, and the patient recovered completely with normal neurological examination after 4 months of follow-up. LESSONS: Clinicians should be aware of the clinical features and pathogenesis of SCD caused by N2O intoxication in order to lead effective treatment as soon as possible. Recreational N2O use should always be considered as an etiology when dealing with patients presented with myelopathy and/or neuropathy suspected of vitamin B12 deficiency.

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.

A case report: subacute combined degeneration of the spinal cord and pernicious anemia caused by autoimmune gastritis.

INTRODUCTION: Autoimmune gastritis causing both subacute combined degeneration of the spinal cord and pernicious anemia is rare in clinical practice. Here, we report a case of subacute combined degeneration of the spinal cord and pernicious anemia resulting from vitamin B12 deficiency due to autoimmune gastritis. PATIENT CONCERNS: A 66-year-old woman presented with a 2-month history of numbness in her extremities. DIAGNOSES: The diagnoses were (1) autoimmune gastritis (2) subacute combined degeneration of the spinal cord (3) pernicious anemia (4) hypergastrinemia (5) chronic lymphocytic thyroiditis. INTERVENTIONS: The patient received intramuscular methylcobalamin treatment for 5 days, followed by oral methylcobalamin daily.Outcomes: Symptoms improved, and anemia recovered in the second month after discharge. She discontinued her medication afterward, and the neurological symptoms recurred. CONCLUSIONS: Autoimmune gastritis can lead to several diseases if not intervened in the early course. Neuropathy and hematopathy recur with treatment discontinuity. Methylcobalamin and adenosylcobalamin are unlikely to be more effective than vitamin B12.

Prognostic indicators of subacute combined degeneration from B12 deficiency: A systematic review.

OBJECTIVE: A systematic review was conducted on published data of subacute combined degeneration (SCD) from B12 deficiency to investigate potential prognostic indicators of final ambulatory function in affected patients. TYPE: Systematic review. LITERATURE SURVEY: Records published from 1999 through 2018 were searched on the electronic databases MEDLINE, PUBMED, and SCOPUS. The publication language was restricted to English and French. METHODOLOGY: Records that described cases of SCD from B12 deficiency in patients ≥16 years of age at onset were included. From a final total of 66 cases of SCD identified, ambulation scores were assigned based on the clinical descriptions reported. Patient characteristics, clinical manifestations, and ambulatory function were reported descriptively. Subanalyses on potential prognostic indicators were performed. SYNTHESIS: Greater ambulatory function at diagnosis was associated with recovery of normal ambulatory function at follow-up (P < .001). Nearly 90% of patients walking unsupported at diagnosis made a complete recovery regardless of etiology. For patients initially walking with support, 22% of cases from impaired B12 digestion/absorption made a complete recovery compared with ≥50% of cases from other etiologies. For patients initially requiring a wheelchair, 33% of cases from impaired digestion/absorption were able to walk with support compared with ≥50% of cases from other etiologies. The total B12 administered over the course of treatment was correlated with improved ambulation (P = .024) for all patients, with a higher B12 replacement regimen associated with better outcomes in patients who were unable to walk unsupported at diagnosis (number needed to treat = 4). CONCLUSIONS: Initial ambulatory function may be a useful clinical marker of the severity of spinal cord dysfunction and final functional outcome. Etiological risk factors influenced both clinical manifestations and final walking ability in SCD, suggesting a distinct pathophysiological mechanism among the causes. In addition, a more intensive B12 replacement regimen may improve ultimate ambulatory function in advanced cases of SCD.

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.

Myeloradiculoneuropathy due to vitamin B12 deficiency: an unusual clinical and radiological presentation.

A 42-year-old man from rural India presented with asymmetric progressive paraparesis mimicking compressive dorsal myelopathy, followed by distal upper limb, truncal and neck-flexor weakness, further complicated by acute urinary retention. His sensory deficits were marked by loss of joint position sense (JPS) and graded loss of vibration sense, along with a definite sensory level. Deep tendon jerks were hypo-to-areflexic, plantar was bilaterally extensor. He had become less attentive and occasionally failed to keep track with conversations. A syndromic diagnosis of myeloradiculoneuropathy with cognitive impairments was made. Further tailored investigations revealed vitamin B12 deficiency with positive anti-parietal cell antibody. Diagnosis of subacute combined cord degeneration (SACD) was confirmed. Neuro-imaging revealed intramedullary intensity changes only along lateral aspect of spinal cord instead of characteristic posterior involvement. Following parenteral vitamin B12 supplementation, patient started showing improvement in motor power and subjective sensory symptoms. His bladder symptoms persisted initially, however recovered finally after 6 months.

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.

Of dots and levels: a case of partial subacute combined degeneration.

Subacute combined degeneration of the spinal cord is a typical clinical syndrome due to vitamin B12 deficiency, characterised by the involvement of the posterior column and corticospinal tracts. Occasionally, it may present with atypical features such as a sensory level and Lhermitte's sign, both traditionally considered to be a feature of compressive myelopathy. Spinal magnetic resonance imaging strongly augments the diagnosis by exhibiting changes in the posterior column in the form of a 'dot'. We describe such a patient who responded to therapy.

Tumors masquerading as neurological diseases: A caution for clinicians in planning diagnosis and treatment.

INTRODUCTION: Neurological diseases can be due to direct diseases of the central nervous system (CNS) or peripheral nervous system (PNS) or be a bystander syndrome of systemic diseases. Treatment options depend on the cause. Toxic, metabolic and nutritional, and immune-mediated consequences of clinically occult neoplasms produce a spectrum of neurological diseases, recognition of which has therapeutic and prognostic importance. PATIENTS AND METHODS: Children, as well as adults who presented to the authors in the last 5 years with neurological diseases and later their diseases could be diagnosed or attributed to neoplasms which were occult, were included for the study. OBSERVATION: 28 patients were seen by the authors in the last 5 years with neurological manifestation and hidden tumor. Maximum incidence was in the age of above 60 years followed by the age group of 21-40 years. The commonest neurological presentation was muscle and nerve in adults and seizure in children. DISCUSSION: Short duration, rapid progression, severe weight loss, and poor response to treatment given for nontumor associated neurological syndrome are the red flags which point to the diagnosis. CONCLUSION: Seizures and psychosis formed the commonest features in children, muscle and nerve in adults. Short duration, rapid progression, and resistance to treatment are the markers for possible underlying neoplasm.

Is serum vitamin B12 decrease a necessity for the diagnosis of subacute combined degeneration?: A meta-analysis.

BACKGROUND: To determine the prevalence of subacute combined degeneration (SCD) patients with normal or elevated serum vitamin B12 level and to identify clinical characteristics of these patients. METHODS: We searched PubMed, EMBASE, and Cochrane library, without language restriction up to June 2019 and included studies with SCD patients who were diagnosed with normal or elevated serum vitamin B12 levels. Meta-analysis was performed to estimate the prevalence of SCD in patients with normal or elevated serum vitamin B12 levels and compare the differences of clinical data between patients with low and no-low serum vitamin B12 level. RESULTS: Six studies were included in our analysis, with a total number of 181 patients involved. The pooled proportion in patients with no-low serum vitamin B12 level was 31.0% (95% confidence interval [CI]: 22.5-40.8). There was no significant difference in the level of hemoglobin (Mean difference (MD): -3.05, 95% CI: -12.42 to 6.33. P = 0.52) and erythrocyte mean corpuscular volume (MD: -2.37, 95% CI: -11.17 to 6.43, P = 0.60) between SCD patients with no-low and those with low serum vitamin B12 levels. The meta-analysis showed that the functional disability rating scale on admission in patients with low serum vitamin B12 level was no worse than that with normal or elevated serum vitamin B12 level (MD: 0.29, 95% CI: -0.58 to 1.16, P = 0.51). CONCLUSION: Decreased level of serum vitamin B12 may not be a necessity for the diagnosis of SCD. Approximately one third of the SCD patients have normal or elevated serum vitamin B12 level. No differences were found in clinical severity between patients with normal or elevated serum vitamin B12 level and those with low level of serum vitamin B12 on admission.

Subacute combined degeneration of the spinal cord masking motor neuron disease: a case report.

BACKGROUND: Subacute combined degeneration of the spinal cord is a potentially reversible myelopathy typically associated with vitamin B12 deficiency. There is predominant involvement of spinal cord posterior and lateral tracts, and manifestations include peripheral paraesthesia, impaired proprioception, gait disturbance, neuropathy and cognitive changes. Motor neuron disease (MND) is an unremittingly progressive neurodegenerative disorder involving upper and lower motor neurons with an average prognosis of 2-3 years. The diagnosis is clinical and may be supported by electromyography. A subset of MND occurs concurrently with frontotemporal dementia (FTD-MND) and may be initially misdiagnosed as a primary psychotic disorder. CASE PRESENTATION: We describe a 57-year-old Caucasian woman who presented with confusion and dysarthria. Low vitamin B12 levels and MRI findings led to an initial diagnosis of subacute combined degeneration of the spinal cord. Despite treatment, persistent dysarthria and presence of both upper and lower motor neuron signs on clinical examination prompted further assessment. Electromyography supported the diagnosis of MND. Comorbid chronic paranoid schizophrenia complicated the diagnostic process. We discuss overlapping features between B12 deficiency and MND as well as the neuropsychiatric overlap of B12 deficiency, FTD-MND and chronic schizophrenia. CONCLUSIONS: Firstly, variability in neurocognitive and imaging manifestations of B12 deficiency can limit delineation of other pathologies. Failure to improve following correction of nutritional deficiencies warrants further investigation for an alternate diagnosis. Secondly, re-evaluation of patients with comorbid mental health conditions is important in reaching timely and accurate diagnoses.

Isolated subacute combined degeneration in late-onset cobalamin C deficiency in children: Two case reports and literature review.

RATIONALE: Subacute combined degeneration (SCD) is a disease caused by decreased vitamin B12 intake or metabolic disorders. It is more common in the elderly and rarely seen in children. Here, we report 2 pediatric cases of SCD in late-onset cobalamin C (CblC) deficiency. PATIENT CONCERNS: The patients complained of unsteady gait. Their physical examination showed sensory ataxia. Magnetic resonance imaging showed classic manifestations of SCD. The serum vitamin B12 level was normal, but urine methylmalonic acid and serum homocysteine levels were high. DIAGNOSIS: The pathogenic gene was confirmed as MMACHC. The 2 patients each had 2 pathogenic mutations C.482 G>A and C.271dupA and C.365A>T and C.609G>A in this gene. They were diagnosed with combined methylmalonic acidemia and homocysteinemia-CblC subtype. INTERVENTIONS: The patients were treated with methylcobalamin 500 µg intravenous injection daily after being admitted. After the diagnosis, levocarnitine, betaine, and vitamin B12 were added to the treatment. OUTCOMES: Twelve days after treatment, the boy could walk normally, and his tendon reflex and sense of position returned to normal. The abnormal gait seemed to have become permanent in the girl and she walked with her legs raised higher than normal. LESSONS: To the best of our knowledge, this is the first report of 2 cases of isolated SCD in children with late-onset CblC disorder. Doctors should consider that SCD could be an isolated symptom of CblC disorder. The earlier the treatment, the lower the likelihood of sequelae.

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)

Idiopathic Copper Deficiency Myeloneuropathy Resulting in Paraparesis: A Case Report.

Atraumatic spinal cord injuries can be due to inflammatory, vascular, and nutritional etiologies. Due to progression from these causes, the identification and initiation of appropriate treatment are of significant importance. This article explores a case of copper deficiency myeloneuropathy in a patient initially thought to have an inflammatory transverse myelitis. The lack of response to antirheumatologic interventions prompted an extensive workup consistent with copper deficiency. This case stresses the importance of evaluating nutritional causes of myeloneuropathy. LEVEL OF EVIDENCE: V.

Subacute Progressive Myelopathy: Transverse Myelitis or Subacute Combined Degeneration? A Case Report.

Evolving subacute myelopathies have many possible etiologies. This is a report of a patient who presented with progressive paresthesias, proprioceptive loss, and gait disturbance with acute myelitis seen on magnetic resonance imaging initially concerning for transverse myelitis. However, she also had vitamin B12 deficiency, and her clinical course ultimately suggested a diagnosis more compatible with subacute combined degeneration. The clinical features, laboratory, and imaging findings and prognosis of the 2 disorders are compared. LEVEL OF EVIDENCE: V.

When the Laughing Stops: Subacute Combined Spinal Cord Degeneration Caused by Laughing Gas Use.

: Here we describe a case of subacute combined spinal cord degeneration caused by nitrous oxide (N2O, laughing gas) use. Because of its euphoric effects, the use of N2O has become increasingly popular in recent years. Unfortunately, the use of N2O leads to inactivation of vitamin B12. Vitamin B12 plays an essential role in the synthesis and maintenance of myelin, a fatty substance that surrounds nerve cells and is crucial for their functioning. Deficiency of vitamin B12 could typically result in degeneration of posterior and lateral columns of the spinal cord. Treatment with intramuscular vitamin B12 injections and abstinence of N2O generally leads to gradual improvement of symptoms. Our case demonstrates the importance of the methyl malonic acid test to detect early or mild vitamin B12 deficiency as a cause of myelopathy while serum vitamin B12 level may be normal. Written consent was obtained from our patient to publish the details of this individual case.

Dorsal column myelopathy after intrathecal chemotherapy for leukemia.

Intrathecal chemotherapy with methotrexate, a folate antagonist, is widely used to treat central nervous system malignancies. The mechanisms underlying methotrexate-induced neurotoxicity are unclear but may be related to increased homocysteine levels. Intrathecal methotrexate-induced myelopathy mimicking subacute combined degeneration, with normal B12 levels, has been documented. We examined treatment and magnetic resonance imaging (MRI) characteristics of 13 patients with leukemia who received intrathecal methotrexate and developed urinary and bowel incontinence, ascending motor weakness, and sensory loss with dorsal column hyperintensity on MRI between 2000 and 2016. Cerebrospinal fluid evaluation was negative for leukemia in all patients and positive for elevated protein in 12 patients. Seven of eight patients with available data had reduced serum folate, increased serum homocysteine, or both, implicating methotrexate as the cause of neurotoxicity. Autopsy of one patient revealed loss of myelinated axons in the posterior columns. These findings suggest that methotrexate neurotoxicity may be mediated by folate antagonism. Awareness and a high index of suspicion of these characteristic clinical and radiographic features in patients who develop myelopathy after intrathecal methotrexate may help to avoid additional neurotoxic therapy in such patients.