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.

A Brief Review on Vitamin B12 Deficiency Looking at Some Case Study Reports in Adults.

In the era of evidence-based medicine, the randomized clinical trial corresponds to the top step in the qualitative scale of the evidence available in the literature, while small series of cases or the description of individual cases occupy the last place. However, the latter represent an important part of clinical practice and have significantly influenced the evolution of medicine, contributing significantly to the advancement of scientific knowledge. Vitamin B12 deficiency shares several common symptoms that affect several tissues and organs with health aliments, so its diagnosis could be unobvious for the broad array of its effects and investigation methods used. In this review, we focused our attention on some case reports related to the vitamin B12 deficiency associated to anemia, neurologic disorders, and hyperhomocysteinemia. B12 deficiency reversal is simply achieved by prompt therapy, even though it is not the same for several disorders.

Pseudomicroangiopatía trombótica por deficiencia de vitamina B12 en un lactante / Pseudo-thrombotic microangiopathy due to vitamin B12 deficiency in an infant

La seudomicroangiopatía trombótica o síndrome de Moschcowitz es una manifestación infrecuente del déficit de vitamina B12. Se caracteriza por anemia hemolítica con características microangiopáticas, reticulocitos e índices hematimétricos normales o con ligera megaloblastosis, asociados a manifestaciones neurológicas. La vitamina B12 está presente en alimentos proteicos de origen animal. La lactancia materna es una fuente adecuada para los niños cuando los niveles maternos son normales. Se presenta a una paciente de 16 meses que se internó por anemia hemolítica con requerimiento transfusional, plaquetopenia, mal progreso pondoestatural y retraso neuromadurativo. Durante su internación se arribó al diagnóstico de seudomicroangiopatía trombótica secundaria a déficit de vitamina B12.

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods. Breastfeeding is an adequate source of this vitamin for children, when maternal serum levels are normal. The case of a 16-month-old infant is presented. She was admitted for hemolytic anemia with transfusion requirement, thrombocytopenia, failure to thrive and developmental delay. During her hospitalization, she was diagnosed with pseudothrombotic microangiopathy caused by vitamin B12 deficiency.

Enteral Vitamin B12 Supplementation Is Effective for Improving Anemia in Patients Who Underwent Total Gastrectomy.

BACKGROUND: This study aimed to investigate the efficacy of enteral supplementation of vitamin B12 for vitamin B12 deficiency in patients who underwent total gastrectomy for gastric cancer. METHODS: The study enrolled 133 patients who underwent total gastrectomy for gastric cancer at Kochi Medical School. Clinical data were obtained to investigate associations between vitamin B12 supplementation and vitamin B12 levels. Vitamin B12 deficiency was defined as serum vitamin B12 less than 200 pg/mL. Baseline characteristics and changes in hematological variables, including vitamin B12 levels, were examined. RESULTS: Vitamin B12 deficiency was present in 71.4% of the 133 patients. Vitamin B12 levels at 3, 6, and 12 months after enteral supplementation were 306 pg/mL, 294 pg/mL, and 367 pg/mL, respectively, which were all significantly higher than those before supplementation (p < 0.001 for all comparisons). The median red blood cell count at 3, 6, and 12 months after enteral supplementation were 380 × 104/mm3, 394 × 104/mm3, and 395 × 104/mm3, respectively, which were all significantly higher than those before supplementation (p = 0.020, p = 0.001, and p = 0.003, respectively). Vitamin B12 levels at 3, 6, and 12 months after supplementation were significantly higher in patients supplemented enterally than those supplemented parenterally (p < 0.001 for all comparisons). CONCLUSIONS: Vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.

Metabolic and Toxic Myelopathies.

PURPOSE OF REVIEW: This article describes the clinical presentation, relevant diagnostic investigations, and treatment of metabolic and toxic myelopathies. RECENT FINDINGS: Metabolic myelopathies, including those due to deficiency of vitamin B12, folate, copper, or vitamin E, are preventable and typically respond to supplementation. In metabolic myelopathy, early recognition and treatment are important to reduce morbidity, particularly due to subacute combined degeneration of the spinal cord. Toxic myelopathies, including those due to medical interventions (eg, methotrexate, radiation), dietary toxins (eg, lathyrism, konzo), and drugs of abuse (eg, heroin), typically result in permanent neurologic deficits. Toxic myelopathy due to hepatic dysfunction may be reversible if patients receive early intervention, whereas nitrous oxide myelopathy responds to vitamin B12 replacement and cessation of exposure. In toxic myelopathy, it is best to avoid the provoking factor when possible or attempt to mitigate risk by identifying risk factors for developing myelopathy. SUMMARY: Metabolic and toxic myelopathies are important causes of morbidity that require a high index of suspicion for diagnosis.

Review of Vitamin B12 deficiency in pregnancy: a diagnosis not to miss as veganism and vegetarianism become more prevalent.

Vegetarianism and veganism are increasingly popular. The Food Standards Agency, biennial Food and You Survey of adults aged 16 years and over living in the UK, found that between 2012 and 2018 the proportion of people who reported never consuming dairy products had increased from 2% to 5%. However, veganism risks development of vitamin B12 deficiency as it is not available from plant sources. Moreover, its impact may be slow to be detected because body stores of vitamin B12 can last years. There is currently no published guidance on antenatal diagnosis and management of vitamin B12 deficiency. This paper reviews the metabolism, diagnosis and treatment of vitamin B12 in pregnancy. It concludes that national screening policymakers should consider introducing screening for B12 deficiency into the Antenatal and Newborn Screening Programmes for mothers and their infants if at risk of vitamin B12 deficiency. In the interim, national policy should be developed for prophylactic vitamin B12 supplementation in high-risk groups around the time of pregnancy.

Encefalopatía grave y deficiencia de vitamina B12: reversibilidad tras la terapia nutricional / Severe encephalopathy and vitamin B12 deficiency: reversibility after nutritional therapy

INTRODUCCIÓN: la vitamina cobalamina es esencial para el buen funcionamiento del SNC, la hematopoyesis y la síntesis de ADN. Su déficit es frecuentemente secundario a la anemia perniciosa o a las dietas vegetarianas estrictas. CASO CLÍNICO: lactante varón de 18 meses con disminución del nivel de conciencia y trastorno del movimiento (temblor y movimientos coreiformes) de horas de duración. Como antecedentes, presenta retraso de la adquisición de los hitos motores (no bipedestación, lenguaje monosilábico) y pérdida progresiva de los mismos en las últimas semanas (sostén cefálico y sedestación). Alimentado mediante lactancia materna desde el nacimiento. La familia sigue una alimentación vegetariana. En las pruebas de neuroimagen, la TC y la RM craneales muestran atrofia supratentorial generalizada de ambas sustancias y de los ganglios basales. Se inicia tratamiento con vitamina B12 intramuscular, aumentando sus niveles. Posteriormente se procede a la diversificación alimentaria y la administración de cianocobalamina oral, con normalización clínica al cabo de 6 meses y radiológica al cabo de 7 meses. DISCUSIÓN: recalcamos la importancia de la suplementación con B12 durante el embarazo y la lactancia tanto en la mujer como en el lactante

INTRODUCTION: the vitamin cobalamin is essential for a proper functioning of the CNS, hematopoiesis, and DNA synthesis. Its deficiency is frequently secondary to pernicious anemia or strict vegetarian diets. CASE REPORT: an 18-month-old male infant presented with a decreased level of consciousness and movement disorder (tremor and choreiform movements) of several hours' standing. He had a history of delayed acquisition of motor milestones (not standing, monosyllabic language), and progressive loss of these over the last few weeks (head support and sitting). He had been breastfed from birth. His family has a vegetarian diet. In neuroimages, cranial CT and MRI scans showed generalized supratentorial atrophy involving both matters and the basal ganglia. Treatment was started with intramuscular vitamin B12, which increased its levels. Subsequently, the patient was subjected to dietary diversification and oral cyanocobalamin, with clinical normalization after 6 months and radiological normalization after 7 months. DISCUSSION: we emphasize the importance of vitamin B12 supplementation during pregnancy and lactation in vegetarian mothers and their infants

[Severe encephalopathy and vitamin B12 deficiency: reversibility after nutritional therapy]. / Encefalopatía grave y deficiencia de vitamina B12: reversibilidad tras la terapia nutricional.

INTRODUCTION: Introduction: the vitamin cobalamin is essential for a proper functioning of the CNS, hematopoiesis, and DNA synthesis. Its deficiency is frequently secondary to pernicious anemia or strict vegetarian diets. Case report: an 18-month-old male infant presented with a decreased level of consciousness and movement disorder (tremor and choreiform movements) of several hours' standing. He had a history of delayed acquisition of motor milestones (not standing, monosyllabic language), and progressive loss of these over the last few weeks (head support and sitting). He had been breastfed from birth. His family has a vegetarian diet. In neuroimages, cranial CT and MRI scans showed generalized supratentorial atrophy involving both matters and the basal ganglia. Treatment was started with intramuscular vitamin B12, which increased its levels. Subsequently, the patient was subjected to dietary diversification and oral cyanocobalamin, with clinical normalization after 6 months and radiological normalization after 7 months. Conclusions: we emphasize the importance of vitamin B12 supplementation during pregnancy and lactation in vegetarina mothers and their infants.

INTRODUCCIÓN: Introducción: la vitamina cobalamina es esencial para el buen funcionamiento del SNC, la hematopoyesis y la síntesis de ADN. Su déficit es frecuentemente secundario a la anemia perniciosa o a las dietas vegetarianas estrictas. Caso clínico: lactante varón de 18 meses con disminución del nivel de conciencia y trastorno del movimiento (temblor y movimientos coreiformes) de horas de duración. Como antecedentes, presenta retraso de adquisición de hitos motores (no bipedestación, lenguaje monosilábico) y pérdida progresiva de los mismos en lúltimas semanas (sostén cefálico y sedestación). Alimentado mediante lactancia materna desde el nacimiento. La familia sigue una alimentación vegetariana. En las pruebas de neuroimagen, la TC y la RM craneales muestran atrofia supratentorial generalizada de ambas sustancias y de los ganglios basales. Se inicia tratamiento con vitamina B12 intramuscular, aumentando sus niveles. Posteriormente se procede a la diversificación alimentaria y la administración de cianocobalamina oral, con normalización clínica al cabo de 6 meses y radiológica al cabo de 7 meses. Conclusiones: recalcamos la importancia de la suplementación con B12 durante el embarazo y lactancia tanto en la mujer como en el lactante.

Profile of anemia in acute lymphoblastic leukemia patients on maintenance therapy and the effect of micronutrient supplementation.

BACKGROUND: Anemia is a common finding and important cause of morbidity in patients with acute lymphoblastic leukemia (ALL) at diagnosis or during the course of its protracted treatment. We studied profile of anemia in ALL patients on maintenance therapy and evaluated specific micronutrients as cause of this anemia. PATIENTS AND METHODS: ALL patients who were on maintenance therapy and had grade ≥ 2 anemia were recruited for the study. Serum iron studies, folate, and vitamin B12 were done to identify micronutrient deficiency and to initiate supplementation with specific components if found to be deficient. Toxicities, improvement of anemia, micronutrient levels, and disease outcome were studied after 3 months. RESULTS: From March 2015 to September 2016, 105 ALL patients were found to be on maintenance fulfilling the inclusion criteria. Overall, the proportion of anemia was 80%(N = 84). Majority had normocytic normochromic anemia (71%). Macrocytic anemia was seen in 18% and microcytic hypochromic in 9.5%. In patients with anemia of grade ≥ 2 (N = 84), 38 patients (45%) had biochemical deficiency of serum folate, and 7 (8%) had vitamin B12 deficiency. No biochemical evidence of iron deficiency was found. Supplementation of deficient micronutrients improved anemia: mean hemoglobin significantly increased from 8.06 ± 1.63 to 10.78 ± 1.53 (p < 0.001) at 3 months; and reduced treatment toxicities, mean number of febrile neutropenia episodes (p = 0.007), and treatment interruptions of > 2 weeks (p = 0.002) were lowered. Patients with anemia had significantly more relapses (N = 14,64%) compared to patients without anemia (N = 8,36%), (p = 0.040). CONCLUSION: Timely identification and correction of micronutrient deficiencies causing anemia in ALL patients on maintenance can enhance treatment outcomes.

The impact of vitamin B12 deficiency on infant gut microbiota.

Although physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively, less is known about their impact on developing gut microbiota. Vitamin B12 deficiency is a common micronutrient deficiency in infants. We aimed to analyze the gut microbial composition of exclusively breastfed infants aged between 4 and 6 months with and without vitamin B12 deficiency by 16S rRNA gene sequencing. In a subgroup of infants with vitamin B12 deficiency, stool samples are recollected and reanalyzed after vitamin B12 supplementation. A total of 88 infants' stool samples (median age 4 months [IQR 4-5], 50% males) were analyzed, of which 28 (31.8%) were vitamin B12 sufficient and 60 (68.2%) were vitamin B12 insufficient. Comparisons between vitamin B12-sufficient and vitamin B12-insufficient infants revealed no evidence of differences in the microbiota. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the most abundant phyla in all groups. There was no difference between the pre- and post-treatment composition of gut microbiota.Conclusion: Vitamin B12-deficient infants have similar gut microbial composition as vitamin B12-sufficient infants. Since the samples were collected at an early period of life and the exposure to deficiency was relatively short, it may be possible that the effects were not fully established.What is Known: • Vitamin B12 is an essential vitamin for humans and also a crucial compound for human gut microbiota. • Vitamin B12 deficiency is common in exclusively breastfed infants. • In contrast to the adult gut microbiota, infant gut microbiota has been shown to have decreased capacity for de novo synthesis of vitamin B12 and depend on dietary source of vitamin B12.What is New: • There is no difference in the gut microbial composition of vitamin B12-deficient and vitamin B12-sufficient infants.

Severe Cobalamin Deficiency Disguised as Schistocytes: A Case Report.

BACKGROUND Vitamin B12, also known as cobalamin (Cbl), is a major player in both erythropoiesis and myelination of the central nervous system. The 2 main manifestations of vitamin B12 deficiency are bone marrow failure and demyelinating disease. These manifestations also depend on the severity and duration of the deficiency. In severe cases, ineffective erythropoiesis, with intramedullary destruction of erythrocytes has been reported, and increased homocysteine level was shown to be a cause of this hemolysis, in vitro. CASE REPORT We present the case of a middle-aged man presented with worsening fatigue, pallor, and dyspnea on moderate exertion. He was found to have a macrocytic anemia associated with intravascular hemolysis and clinical hypothyroidism in the setting of Hashimoto's thyroiditis. Vitamin B12 measured as part of his anemia investigation, was found to be markedly deficient (less than 100 pg/mL). Replacement was started and a reversal of his anemia and hemolysis was shown with improvement in his hemoglobin level upon follow-up. CONCLUSIONS Although a rare presentation, severe vitamin B12 deficiency can lead to hemolysis and severe anemia that can be life threatening. Timely and appropriate diagnosis and replacement, lifelong in some cases, in addition to looking for the underlying cause of this deficiency, and excluding other concomitant hemolytic disorders, is crucial for the management of this reversible disease. Despite some in vitro early results, the exact underlying mechanism behind hemolysis is still unclear.

Neurological disorders in vitamin B12 deficiency.

The review discusses thesteps of vitamin B12 metabolism and its role in maintaining of neurological functions. The term "vitamin B12 (cobalamin)" refers to several substances (cobalamins) of a very similar structure. Cobalamin enters the body with animal products. On the peripherу cobalamin circulates only in binding with proteins transcobalamin I and II (complex cobalamin-transcobalamin II is designated as "holotranscobalamin"). Holotranscobalamin is absorbed by different cells, whereas transcobalamin I-binded vitamin B12 - only by liver and kidneys. Two forms of cobalamin were identified as coenzymes of cellular reactions which are methylcobalamin (in cytoplasm) and hydroxyadenosylcobalamin (in mitochondria). The main causes of cobalamin deficiency are related to inadequate intake of animal products, autoimmune gastritis, pancreatic insufficiency, terminal ileum disease, syndrome of intestinal bacterial overgrowth. Relative deficiency may be seen in excessive binding of vitamin B12 to transcobalamin I. Cobalamin deficiency most significantly affects functions of blood, nervous system and inflammatory response. Anemia occurs in 13-15% of cases; macrocytosis is an early sign. The average size of neutrophils and monocytes is the most sensitive marker of megaloblastic hematopoiesis. The demands in vitamin B12 are particularly high in nervous tissue. Hypovitaminosis is accompanied by pathological lesions both in white and gray brain matter. Several types of neurological manifestations are described: subacute combined degeneration of spinal cord (funicular myelinosis), sensomotor polyneuropathy, optic nerve neuropathy, cognitive disorders. The whole range of neuropsychiatric disorders with vitamin B12 deficiency has not been studied well enough. Due to certain diagnostic difficulties they are often regarded as "cryptogenic", "reactive", "vascular¼ origin. Normal or decreased total plasma cobalamin level could not a reliable marker of vitamin deficiency. In difficult cases the content of holotranscobalamin, methylmalonic acid / homocysteine, and folate in the blood serum should be investigated besides carefully analysis of clinical manifestations.