vitamin-b-12 and Nervous-System-Diseases

Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) contribute essentially to the maintenance of a healthy nervous system. Their importance is highlighted by many neurological diseases related to deficiencies in one or more of these vitamins, but they can improve certain neurological conditions even without a (proven) deficiency.. This review focuses on the most important biochemical mechanisms, how they are linked with neurological functions and what deficits arise from malfunctioning of these pathways.. We discussed the main role of B Vitamins on several functions in the peripheral and central nervous system (PNS and CNS) including cellular energetic processes, antioxidative and neuroprotective effects, and both myelin and neurotransmitter synthesis. We also provide an overview of possible biochemical synergies between thiamine, pyridoxine, and cobalamin and discuss by which major roles each of them may contribute to the synergy and how these functions are inter-related and complement each other.. Taking into account the current knowledge on the neurotropic vitamins B1, B6, and B12, we conclude that a biochemical synergy becomes apparent in many different pathways in the nervous system, particularly in the PNS as exemplified by their combined use in the treatment of peripheral neuropathy.

Topics: Animals; Central Nervous System; Humans; Nervous System Diseases; Nervous System Physiological Phenomena; Peripheral Nervous System; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex

The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.

Topics: Diabetes Mellitus; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Infertility; Mental Disorders; Methylenetetrahydrofolate Reductase (NADPH2); Neoplasms; Nervous System Diseases; Polymorphism, Genetic; Psoriasis; Vascular Diseases; Vitamin B 12

The literature regarding the vitamin B(12) status of patients with phenylketonuria was reviewed. Adequate amounts of B(12) are provided in products used in dietary treatment; however, a number of case reports and cohort studies document deficiency in those who have discontinued taking amino acid, mineral and vitamin supplements but who continue to eat only very limited amounts of natural protein. Symptoms and signs of B(12) deficiency are variable but severe deficiency may cause serious neurological disease. Nitrous oxide anaesthesia is a particular risk. It is recommended that plasma total homocysteine and plasma or urinary methylmalonate should be routinely measured, as they are more sensitive markers of deficiency than serum B(12) concentrations. Functional B(12) deficiency can occur in the presence of a normal B(12) concentration.

Topics: Humans; Nervous System Diseases; Nitrous Oxide; Phenylketonurias; Vitamin B 12; Vitamin B 12 Deficiency

To review the prevalence, causes and functional significance of vitamin B12 deficiency in vulnerable subpopulations including older adults and the developing embryo.. It is becoming increasingly recognized that the susceptibility to vitamin B12 deficiency may change throughout the life cycle, with the developing embryo and older adults exhibiting elevated risk. Recent data implicate low vitamin B12 status as a risk factor for birth defects resulting from improper neural tube development. The potential for vitamin supplementation and/or food fortification to ameliorate the risk of deficiency in these subpopulations is discussed.. The prevalence and impact of vitamin B12 deficiency varies throughout the life cycle, with older adults and potentially the developing embryo having the greatest risk and susceptibility. Additional research is needed to develop effective public health interventions that address the unique causes of this nutritional deficiency, which differ among at-risk subpopulations.

Topics: Age Factors; Aged; Anemia, Pernicious; Diet; Dietary Supplements; Female; Food, Fortified; Humans; Intestinal Absorption; Nervous System Diseases; Neural Tube; Pregnancy; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

To address controversial issues surrounding the use of nitrous oxide as a component of anesthesia in neurosurgical and neurologically at-risk patients.. Nitrous oxide has been used as a component of general anesthesia for over 160 years and has contributed to countless apparently uneventful anesthetics in neurologically at-risk patients. Avoidance of nitrous oxide in specific circumstances, such as pre-existing pneumocephalus, during acute venous air embolism, and in patients with disorders of folate metabolism, is warranted. However, various controversies exist regarding the use of this drug in the general neurosurgical population. Specifically, some suggest a possible association between nitrous oxide and the postoperative development of tension pneumocephalus despite lack of data to support this notion. Additionally, data describing alterations of cerebral hemodynamics and metabolism and exacerbation of ischemic neurologic injury by nitrous oxide are inconsistent. Recent data derived from humans having cerebral aneurysm clipping failed to show any long-term adverse effect from the use of nitrous oxide on gross neurologic or cognitive function.. Except in a few specific circumstances, there exists no conclusive evidence to support the dogmatic avoidance of nitrous oxide in neurosurgical patients.

Topics: Anesthesia, General; Anesthetics, Inhalation; Blood Volume; Cerebrovascular Circulation; Electroencephalography; Humans; Metabolism; Monitoring, Intraoperative; Nervous System Diseases; Neurosurgical Procedures; Nitrous Oxide; Risk; Vitamin B 12

In Europe, neuropsychiatric diseases currently make up approximately a third of the total burden of disease. In 2004, 27% of the overall population was affected by at least one of the most frequent neuropsychiatric diseases such as Alzheimer's dementia, Parkinson's disease, stroke or depression. The annual costs of care exceed those of cancer, cardiovascular conditions and diabetes. In order to delay the onset or course of neurodegenerative diseases, the available potential should be utilized. As well as improving quality of life of patients and relatives, this may reduce the great financial burden caused by neurodegenerative disorders. However, the availability of established drugs or therapeutic agents is very limited. This paper reviews the state of current knowledge as to how homocysteine metabolism is relevant for neurodegenerative and other neuropsychiatric diseases, with particular emphasis on the evidence for prophylactic and therapeutic strategies. In the European countries, many people do not take the recommended daily minimum amount of folate and vitamin B12. Deficiency of these vitamins and secondary changes in the concentrations of associated metabolites, such as methylmalonic acid and homocysteine, may contribute to the onset and progression of neuropsychiatric diseases. This paper reviews the evidence regarding whether substitution of folate and vitamin B12 is beneficial, for example, in cerebrovascular disease, dementia and depression.

Topics: Folic Acid; Homocysteine; Humans; Mental Disorders; Nervous System Diseases; Vitamin B 12

Severe vitamin B(12) deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B(12) deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.

Topics: Adult; Anemia, Pernicious; Brain; Developmental Disabilities; Diet, Vegetarian; Failure to Thrive; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Male; Mothers; Nervous System Diseases; Pregnancy; Psychomotor Disorders; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Although cobalamin (vitamin B12) was isolated almost 60 years ago, its biochemical, physiologic and neurologic effects remain incompletely defined. New observations suggest renal regulation of cobalamin metabolism; actions of cobalamin on nucleic acid and protein function; and a role for cobalamin in cytokine and growth factor regulation. Clinically, no gold standard has emerged for the diagnosis of cobalamin deficiency. Moreover, cobalamin resistance may occur in diabetes, renal insufficiency and advanced age, leading to functional cobalamin deficiency despite adequate cobalamin nutriture. Finally, high-dose cobalamin therapy may have salutary pharmacologic effects on neurologic function in a variety of disorders. Many studies lacked appropriate control groups. However, at this time, therapeutic trials with pharmacologic doses of cobalamin are suggested when findings consistent with cobalamin deficiency are present regardless of the results of diagnostic tests. While oral cobalamin immediate-release is adequate for many patients, its effectiveness in reversing neurologic abnormalities has yet to be established.

Topics: Humans; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Elevated concentration of total homocysteine (Hcy) in plasma (> 12 micromol/l) is a risk factor for several diseases of the central nervous system. Epidemiological studies have shown a dose-dependent relationship between concentrations of Hcy and the risk for neurodegenerative diseases. Hcy is a marker for B-vitamin deficiency (folate, B12, B6). Hyperhomocysteinemia (HHcy) causes hypomethylation which is an important mechanism that links Hcy to dementia. Supplementation with vitamins B aims at reducing the risk of neurodegenerative diseases. Current evidence suggests that Hcy-lowering treatment has a positive effect for the secondary and primary prevention of stroke. HHcy is very common in patients with Parkinson disease particularly those who receive L-dopa treatment. Furthermore, a positive association has been reported between HHcy and multiple sclerosis. Moreover, HHcy and vitamin B deficiency are reported to have a causal role in depression, and epilepsy. In addition several anti-epileptic drugs cause secondary HHcy. Therefore, sufficient intakes of the vitamins are recommended for patients who have already developed neuropsychiatric diseases. Vitamin B deficiency should be suspected in children with development disorders, failure to thrive and unexplained neurological manifestations. Elderly people are also an important at-risk group where vitamin B deficiency and HHcy have been linked to neurodegenerative diseases. Treatment with folate, B12, and B6 can improve cerebral function. Preventive vitamin B supplementation and sufficient intake seem very important for secondary and primary prevention of neuropsychiatric disorders, especially in subjects with a low intake or status of the vitamins.

Topics: Aged; Central Nervous System; Child; Dietary Supplements; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Mental Disorders; Nervous System Diseases; Parkinson Disease; Risk Factors; Vitamin B 12; Vitamin B Deficiency

A majority of patients with neurological disorders with chronic exposures to toxigenic molds and mycotoxins has vitamin B12 deficiency that is unrelated to dietary insufficiency. Vitamin B12 is a source of coenzymes, and participates in intracellular recycling of methionine, and in methionine synthase reactions. The biochemical processes that lead to B12 depletion and deficiency are not fully understood. This paper examines and assesses various most likely biochemical reasons that could impede upon the normal intracellular functions of vitamin B12 that lead to neurological manifestations. By biochemical implications and derivations, it is most likely that mycotoxins interrupt the structure and function of vitamin B12 through reactive interference with the normal One-Carbon metabolism leading to the observed clinical neurological manifestations such as nerve damage and, demyelination, degeneration of PNS leading to paralysis, progressive peripheral neuropathy, and spinal degeneration.

Topics: Animals; Carbon; Fungi; Humans; Mycotoxins; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Disorders of cobalamin metabolism include defects of absorption, transport and intracellular metabolism of cobalamin. Most of the patients present in the first years of life with haematological abnormalities and feeding difficulties but some of them have later onset form and can present with pure neurological manifestations.. The suggestive clinical picture is a subacute neurological disorder similar to those observed in case of insufficient B12 intake or Biermer disease. In this frame, additional diagnosis clues could be associated megaloblastic anemia, previous history of venous thrombosis, association with psychiatric disturbances, involvement of both central and peripheral nervous system. The key investigations are measurement of plasma amino acid levels and urinary organic acid, which allow to detect abnormalities consistent with intracellular cobalamin deficiency. Treatment depends on the metabolic defect but usually consist in intramuscular cobalamin supplementation. It results in stabilization or improvement in most cases.. Because this treatable condition can lead to death or irreversible neurological damage, we recommend that disorder of the cobalamin metabolism should be consider in all young adults with unexplained consistent neurological manifestations.

Topics: Adult; Animals; Humans; Metabolism, Inborn Errors; Nervous System Diseases; Prognosis; Vitamin B 12

Multifunctional systems must maintain homeostasis. Man is an ideal example of a system that constantly aspires to attain optimal regulation, even under the stress of severe disease. We assume that there are universal, interchangeable (as required) biologically active substances that regulate the system and try to keep it in balance. We propose that one of these substances is vitamin B12. Why vitamin B12? The list of organs and body systems in which vitamin B12 plays a functional role is constantly being added to. Vitamin B12 affects the normal growth of children, the peripheral and central nervous systems, bone marrow, skin, mucous membranes, bones, and vessels. It is possible that even when the serum cobalamin level is normal, treatment with vitamin B12 could correct defects caused by other biologically active substances. We call this phenomenon the "Master Key" effect. We suggest that this "Master Key" concept can be tested by treating diseases, such as recurrent stomatitis, various forms of hyperpigmentation, trophic ulcers, and burns, with vitamin B12, even if the B12 serum level is normal.

Topics: Animals; Avitaminosis; Cardiovascular Diseases; Dogs; Growth; Humans; Infant; Male; Nervous System Diseases; Skin Diseases; Vitamin B 12

Cobalamin deficiency is a common finding. In the elderly the prevalence is 10-20%, but only 5-10% of these are clinically symptomatic. Typical clinical symptoms include macrocytic anemia, neuropsychiatric symptoms and glossitis. In many cases this triad is lacking, however. The serum cobalamin assay is the best first line test, but the results must be carefully interpreted, since a normal level does not exclude deficiency. Markers of cobalamin activity, such as serum homocysteine or methylmalonic acid may be helpful in this situation. The main cause of cobalamin deficiency is atrophic gastritis. It is either caused by an autoimmune process which leads to achlorhydria and severe intrinsic factor deficiency ("classical pernicious anemia") or by atrophic gastritis from other causes, in particular helicobacter pylori infection. In the latter cases the lack of gastric acid does not allow separation of cobalamin from proteins, but intrinsic factor, although low, is sufficient for cobalamin protection (food cobalamin malabsorption). Helicobacter pylori eradication may cure some of these patients. While in food cobalamin malabsorption syndrome small doses of oral cobalamin are effective, parenteral therapy or high oral doses are required for treatment of pernicious anemia. While almost all patients respond hematologically, only half of the patients with neurological signs, and a small minority of psychiatric patients respond to treatment. Patients with pernicious anemia and atrophic gastritis have a greatly increased long-term risk for gastric carcinoids.

Topics: Clinical Trials as Topic; Evidence-Based Medicine; Humans; Mental Disorders; Nervous System Diseases; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prognosis; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

This paper evaluates the possible reasons for consistent vitamin B12 deficiency in chronic toxigenic mold exposures and the synergistic relationships with the possible mycotoxic effects on one-carbon metabolism that lead to the manifestations of clinical neuropathological symptomology. Vitamins are first defined in general and the nutritional sources of vitamin B12 are evaluated in particular. Since patients with chronic exposures to toxigenic molds manifest vitamin B12 deficiencies, the role of mycotoxins in vitamin B12 metabolism is assessed, and since vitamin B12 plays important biochemical roles in one-carbon metabolism, the synergistic effects with mycotoxins on humans are reviewed. An outline of the proposed mechanism by which mycotoxins disrupt or interfere with the normal functions of vitamin B12 on one-carbon metabolism is proposed. The overall functions of vitamin B12 as a source of coenzymes, in intracellular recycling of methionine, in methionine synthase reaction, in the prevention of chromosome breakage, in methylation, and in maintaining a one-carbon metabolic balance are reviewed. Signs, symptoms, and clinical neurological indications of vitamin B12 deficiency are also cited. By implication and derivation, it is likely that the interruption of the structure and function of vitamin B12 would in turn interfere with the one-carbon metabolism leading to the neurological manifestations. This review is an attempt to formulate a basis for an ongoing research investigation on the subject.

Topics: Animals; Chronic Disease; Environmental Exposure; Fungi; Humans; Intracellular Space; Mycotoxins; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.

Topics: Humans; Malabsorption Syndromes; Mental Disorders; Methylmalonic Acid; Nervous System Diseases; Practice Guidelines as Topic; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Nitrous oxide interacts with vitamin B12 resulting in selective inhibition of methionine synthase, a key enzyme in methionine and folate metabolism. Thus, nitrous oxide may alter one-carbon and methyl-group transfer most important for DNA, purine and thymidylate synthesis. Long-term exposure to high concentrations of nitrous oxide may cause megaloblastic bone-marrow depression and neurological symptoms. Exposure to higher doses for less than 6 hours, as in clinical anaesthesia, are considered harmless. Recent studies seem to suggest a correlation between nitrous oxide anaesthesia and hyperhomocysteinaemia which is accepted to be an independent risk factor for coronary artery disease. As for today, available data do not support the notion that exposure to trace amounts of nitrous oxide is associated with impaired fertility or an increased risk of developing cancer. Emission of nitrous oxide from medical use is estimated to contribute less than 0.05% to total annual greenhouse gas emission.

Topics: Animals; Bone Marrow; Folic Acid Deficiency; Humans; Methionine; Nervous System Diseases; Nitrous Oxide; Occupational Exposure; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Biotin; Diagnosis, Differential; Folic Acid; Humans; Metabolism, Inborn Errors; Nervous System Diseases; Prognosis; Pyridoxine; Syndrome; Thiamine; Vitamin B 12; Vitamin D; Vitamin E Deficiency

In response to research findings that 10% to 30% of people aged 51 years and older may have protein-bound vitamin B-12 malabsorption, the National Academy of Sciences' Institute of Medicine recommends that these people consume a majority of the new Recommended Dietary Allowance (RDA) of 2.4 micrograms/day in its synthetic form rather than in its food form. Protein-bound vitamin B-12 malabsorption in older adults has been attributed to reduced pepsin activity and gastric acid secretion, which interfere with cleavage of vitamin B-12 from dietary protein before absorption. Unlike patients with pernicious anemia, most people with protein-bound vitamin B-12 malabsorption produce intrinsic factor and have the ability to absorb synthetic vitamin B-12 normally. Early diagnosis is necessary to prevent the untoward effects of vitamin B-12 deficiency. A thorough assessment of vitamin B-12 status entails measurement of multiple biochemical assessment indexes, including serum vitamin B-12, methylmalonic acid, and homocysteine concentrations. Dietitians and other health care professionals should be aware of the prevalence of vitamin B-12 deficiency in older adults and be familiar with sources of synthetic vitamin B-12 to facilitate implementation of the new RDA.

Topics: Absorption; Age Factors; Aged; Dietary Proteins; Hematologic Diseases; Humans; Malabsorption Syndromes; Middle Aged; Nervous System Diseases; Nutrition Policy; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

At one time, the diagnosis of a deficiency of vitamin B12 or folate was considered to be relatively straightforward. As knowledge has accumulated, the limitations of such tests as serum vitamin level measurements and the Schilling test have become apparent. With the development of newer tests, atypical and subclinical deficiency states have been recognized. In this review, available tests used in the diagnosis of vitamin B12 and folate deficiency are discussed, and a rational approach to the diagnosis of these deficiency states is presented.

Topics: Antibodies; Clinical Laboratory Techniques; Clinical Trials as Topic; Decision Trees; Diagnosis, Differential; Erythrocytes; Folic Acid Deficiency; Hematologic Diseases; Homocysteine; Humans; Intrinsic Factor; Methylmalonic Acid; Nervous System Diseases; Parietal Cells, Gastric; Primary Health Care; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 (cobalamin) deficiency associated neuropathy, originally called subacute combined degeneration, is particularly common in the elderly. The potential danger today is that with supplementation with folic acid of dietary staples such as flour, that the incidence of this disease could rise as folic acid, as opposed to natural folate (N5CH3HFGlu1), enters the cell and the metabolic cycle by a cobalamin independent pathway. This chapter briefly describes the clinical presentation of the disease, which unless treated will induce permanent CNS damage. The biochemical basis of the interrelationship between folate and cobalamin is the maintenance of two functions, nucleic acid synthesis and the methylation reactions. The latter is particularly important in the brain and relies especially on maintaining the concentration of S-adenosylmethionine (SAM) which, in turn, maintains the methylation reactions whose inhibition is considered to cause cobalamin deficiency associated neuropathy. SAM mediated methylation reactions are inhibited by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin is deficient and, as a result, methionine synthase is inhibited causing a rise of both homocysteine and SAH. Other potential pathogenic processes related to the toxic effects of homocysteine are direct damage to the vascular endothelium and inhibition of N-methyl-D-aspartate receptors.

Topics: Aged; DNA; Folic Acid; Folic Acid Deficiency; Humans; Methylation; Nervous System Diseases; S-Adenosylmethionine; Vitamin B 12; Vitamin B 12 Deficiency

A 69-year-old woman reported marked restriction of voluntary movements of the hands in the preceding 6 months. She had also experienced loss of motivation, memory and concentration. Her skin was pale yellow, and scratches on her skin indicated marked pruritus.. Neurological examination revealed decreased vibratory sense in both legs. Haemoglobin concentration was 8.3 g/dl, mean corpuscular volume 114 fl, vitamin B12 level < 100 ng/l, folic acid level normal. Antibody titre against parietal cells was increased, vitamin B12 resorption diminished. Gastroscopy revealed small raised lesions, made up of hyperplastic cells which stained with chromogranin, indicating a diagnosis of microcarcinoid of the gastric mucosa.. On administration of cobalamine (1,000 micrograms i.m. daily for 2 weeks, twice weekly for 6 weeks, then once per week for the last 7 months) the blood picture returned to normal, but the microcarcinoids, the psychological symptoms and the apraxia of the hands were unchanged.

Topics: Aged; Carcinoid Tumor; Chronic Disease; Female; Gastritis, Atrophic; Hematinics; Humans; Memory Disorders; Nervous System Diseases; Psychopathology; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

In summary, we have shown that there is a high prevalence of Cbl deficiency in the elderly. This observation is based on an increase in the number of low and low normal serum Cbl levels, an increase in elevated serum total homocysteine levels that correct with Cbl therapy, and an increase in elevated serum methylmalonic acid levels that also correct with Cbl therapy. These observations may be of great clinical importance since Cbl deficiency may be a common and treatable cause of vascular disease.

Topics: Aged; Hematologic Diseases; Homocysteine; Humans; Mental Disorders; Methylmalonic Acid; Nervous System Diseases; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

In this report, our goal was to summarize the current knowledge of the biochemical basis for the impaired DNA synthesis and neuropathy associated with vitamin B12 deficiency.. We reviewed the pertinent literature and our clinical experience with cobalamin deficiency.. Studies have established that the megaloblastic hematopoiesis associated with vitamin B12 and folate deficiency is secondary to impaired DNA synthesis. Two mechanisms of impairment of DNA synthesis have been proposed: the "methylfolate trap hypothesis" and the "formate starvation hypothesis." One possibility is that both hypotheses may be contributory--that is, incoming dietary folate may be inaccessible for polyglutamation in accordance with the methylfolate trap hypothesis, whereas the formate starvation hypothesis may explain the failure to use already polyglutamated forms of folate.. Although the pathophysiologic mechanisms of vitamin B12 and folate deficiency are not completely understood, nutritional anemias offer suitable models for the study of the biochemical basis of disease.

Topics: DNA; Folic Acid; Humans; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Neuropathy commonly complicates cobalamin (Cb1) deficiency in humans, monkeys, fruit bats, and pigs. The neuropathy is characterized by demyelination of the posterolateral columns of the spinal cord (subacute combined degeneration). The lesion was thought to arise primarily from impairment of the adenosylcobalamin-dependent methylmalonyl CoA mutase reaction, leading to the formation of abnormal odd-chain and branched-chain fatty acids and their incorporation into myelin with resultant demyelination. Data from recently developed animal models of the Cb1 neuropathy induced by exposure to nitrous oxide do not substantiate this hypothesis, but rather identify impairment of the methylcobalamin-dependent methionine synthetase reaction as the more important basic defect. The key evidence for this hypothesis is the ability of methionine to delay the onset of Cb1 neuropathy in experimental Cb1 deficiency. In the Cb1-deficient pig, adenosylhomocysteine accumulates in neural tissue, presumably owing to the inability to recycle homocysteine via the defective methionine synthetase reaction. Accumulation of adenosylhomocysteine results in a fall in the adenosylmethionine:adenosylhomocysteine methylation ratio, and this change is believed to cause defective methylation and demyelination in the nervous system. However, in the Cb1 neuropathy in the fruit bat, adenosylhomocysteine does not accumulate in the nervous system, the methylation ratio does not change, and no defect can be demonstrated in the methylation of myelin lipid or basic protein. Although a central role for methionine in the pathogenesis of the Cb1 neuropathy has been established, defective methylation attendant upon impairment of the methionine synthetase reaction may not be the universal defect underlying the Cb1 neuropathy. This would suggest that the methionine effect could be mediated via its role in formate metabolism or polyamine synthesis, or by some as yet unidentified pathway.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Animals; Disease Models, Animal; Humans; Methylation; Methylmalonyl-CoA Mutase; Nervous System Diseases; Nitrous Oxide; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Humans; Intrinsic Factor; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl-dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near-normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Anemia, Megaloblastic; Cells, Cultured; Female; Fibroblasts; Genetic Complementation Test; Homocystinuria; Humans; Infant; Infant, Newborn; Male; Methionine; Methyltransferases; Nervous System Diseases; Vitamin B 12

The possible molecular mechanisms potentially inducing occupational disease among operating room personnel were examined; and the really dangerous anaesthetic agents were identified. As concerns the molecular mechanisms of parenchymatous injury, we surveyed: those connected with free radicals and biological reactive intermediates produced during halothane and nitrous oxide biotransformation; those coming from inorganic fluoride produced during biotransformation of any halogenated anaesthetic agent, and from inorganic bromide released during halothane metabolism; and, finally, those linked to vitamin B12 inactivation from nitrous oxide. Halothane and nitrous oxide can be considered as really dangerous anaesthetic agents for operating room personnel, and enflurane as an agent with marginal toxic power. On the contrary, isoflurane is a safe, useful compound, totally devoided of viscerotoxic effects. From data examined it is possible to conclude that an isoflurane-oxygen-air anaesthesia is safe for operating room personnel more than a balanced anaesthesia with intravenous drugs and nitrous oxide as maintenance.

Topics: Air Pollutants, Occupational; Biodegradation, Environmental; Bromides; Chemical and Drug Induced Liver Injury; Fluorides; Free Radicals; Halothane; Humans; Kidney Diseases; Nervous System Diseases; Nitrous Oxide; Occupational Diseases; Vitamin B 12

Recent developments in our knowledge of the biochemistry and metabolism of cobalamin have given us some insight into clinical disorders. N2O, which easily induces cobalamin deficiency, both in vivo and in vitro, has greatly contributed to the investigation of the cobalamin deficient state, especially in relation to folate and amino acid metabolism. Demonstration of the cobalamin analog in human serum and a new enzyme which requires cobalamin as a coenzyme has led to recent increased interest in this field. The disorders of cobalamin metabolism will be summarized briefly as well as those areas currently of particular interest.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Amino Acid Isomerases; Anemia, Pernicious; Animals; Diphyllobothriasis; DNA; Folic Acid; Humans; Intestinal Absorption; Intestinal Mucosa; Intramolecular Transferases; Malabsorption Syndromes; Methylmalonyl-CoA Mutase; Methyltransferases; Nervous System Diseases; Nitrous Oxide; Pancreatic Diseases; Thymidine Monophosphate; Vitamin B 12; Zollinger-Ellison Syndrome

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Pernicious; Child, Preschool; Europe; Female; History, 19th Century; History, 20th Century; Humans; Infant; Intrinsic Factor; Male; Middle Aged; Nervous System Diseases; United States; Vitamin B 12

Topics: Adult; Aged; Anemia, Megaloblastic; Anticonvulsants; Blood-Brain Barrier; Brain; Brain Diseases; Child; Epilepsy; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Humans; Intellectual Disability; Male; Mental Disorders; Metabolism, Inborn Errors; Methotrexate; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Amino Acids, Sulfur; Bone Diseases; Cystathionine beta-Synthase; Eye Diseases; Homocysteine; Homocystine; Homocystinuria; Humans; Intestinal Absorption; Methyltransferases; Nervous System Diseases; Skin Diseases; Tetrahydrofolate Dehydrogenase; Thrombosis; Vitamin B 12

Topics: Aged; Anemia, Pernicious; Animals; Female; Folic Acid; Humans; Male; Middle Aged; Nervous System Diseases; Neurologic Manifestations; Rats; Spinal Cord Diseases; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Alcoholism; Anticonvulsants; Cyanides; Deficiency Diseases; Electroencephalography; Erythrocytes; Folic Acid Deficiency; Humans; Isoniazid; Nervous System Diseases; Neurocognitive Disorders; Pellagra; Polyneuropathies; Schilling Test; Spinal Cord Diseases; Thiamine Deficiency; Transketolase; Tryptophan; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency; Vitamin B Deficiency; Wernicke Encephalopathy

Topics: Anemia, Macrocytic; Deoxyuridine; DNA; Erythrocytes, Abnormal; FIGLU Test; Folic Acid Deficiency; Homocysteine; Humans; Methionine; Nervous System Diseases; Tetrahydrofolate Dehydrogenase; Tetrahydrofolates; Thymine Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Beriberi; Child; Cyanides; Environmental Exposure; Female; Foodborne Diseases; Humans; Jamaica; Lathyrism; Leprosy; Male; Manihot; Nervous System Diseases; Nigeria; Nutrition Disorders; Pregnancy; Racial Groups; Senegal; Syphilis; Tropical Medicine; Vitamin B 12

Structural imaging of the brain does not demonstrate any changes in a vast majority of patients with vitamin B12 deficiency, even in advanced stages. In this study, we aimed to assess and correlate the functional integrity of the brain fiber tracts using diffusion tensor tractography with neuropsychological examination in patients with vitamin B12 deficiency.. The study was conducted at two tertiary care centers. Thirty-two patients with vitamin B12 deficiency were enrolled and subjected to diffusion tensor tractography, as an extension of diffusion tensor imaging, and neuropsychological assessment. Tests of significance were done to detect changes, pre- and post-vitamin B12 supplementation in the diffusivity parameters (fractional anisotropy and mean diffusivity) and the neuropsychological test scores.. Statistically significant changes were observed in the diffusivity parameters and the neuropsychological test scores between the controls and the patients with vitamin B12deficiency in the pre- and post-treatment phases.. This is the first study to evaluate the diffusion tensor tractography (DTT) parameters in the light of clinical neuropsychological assessment in patients with vitamin B12 deficiency. Utilization of DTT parameters may antedate structural changes and may quantify the neurocognitive deficits.

Topics: Adolescent; Adult; Brain; Dietary Supplements; Diffusion Tensor Imaging; Humans; Male; Middle Aged; Nerve Fibers, Myelinated; Nervous System Diseases; Neuropsychological Tests; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients.. Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design.. The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was 2.7 ± 2.2. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was 4.9 ± 2.4.. Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.

Topics: Adult; Aged; Breast Neoplasms; Docetaxel; Drugs, Chinese Herbal; Female; Humans; Medicine, Kampo; Middle Aged; Nervous System Diseases; Taxoids; Vitamin B 12

Combined methylmalonic aciduria and homocystinuria cobalamin C type (cobalamin C disease) is an inborn metabolic disorder consisting of an impaired intracellular synthesis of the 2 active forms of vitamin B12 (cobalamin), namely, adenosylcobalamin and methylcobalamin, that results in increased levels of methylmalonic acid and homocysteine in the blood and urine. Most patients present in the first year of life with systemic, hematological, and neurological abnormalities. Late-onset forms are rare and had not been comprehensively characterized. They could be easily misdiagnosed.. To describe clinical and biochemical features of the disease in 2 siblings affected with presumed late-onset cobalamin C disease.. Case report and review of the literature.. Neurological intensive care unit of a university hospital.. We describe 2 patients with neurological deterioration due to presumed cobalamin C disease. A 16-year-old girl was initially seen with psychosis and severe progressive neuropathy requiring mechanical ventilatory support and her 24-year-old sister had a 2-year disease course of subacute combined degeneration of the spinal cord. A metabolic workup displayed increased methylmalonic acid levels, severe hyperhomocysteinemia, and low plasma methionine levels. The diagnosis was then confirmed by demonstration of impaired synthesis of adenosylcobalamin and methylcobalamin in cultured skin fibroblasts and Epstein-Barr virus-infected lymphocytes. Under specific treatment the younger sister's condition dramatically improved.. Although complementation studies have not been conducted, it is most likely these patients had cobalamin C disease. This study emphasizes the possibility of late-onset disease with purely neurological manifestations. Left untreated, this treatable condition can lead to death or irreversible damage to the nervous system. Screening for intracellular vitamin B12 dysmetabolism should, therefore, be considered in the investigation of adults with unexplained neurological disease, particularly when they are initially seen with a clinical picture suggestive of vitamin B12 deficiency.

Topics: Adolescent; Adult; Brain; Cobamides; Female; Fibroblasts; Homocysteine; Humans; Mental Disorders; Metabolism, Inborn Errors; Methylmalonic Acid; Nervous System Diseases; Sural Nerve; Vitamin B 12

Topics: Aged; Arginine; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Female; Glutamine; Humans; Male; Mental Disorders; Middle Aged; Nervous System Diseases; Organophosphorus Compounds; Serine; Threonine; Tryptophan; Vitamin B 12

Topics: Action Potentials; Adult; Anabolic Agents; Androstanes; Attention; Blood Pressure; Cerebral Hemorrhage; Clinical Trials as Topic; Depression, Chemical; Electrocardiography; Electroencephalography; Female; Folic Acid; Heart Rate; Humans; Hydroxocobalamin; Male; Middle Aged; Multiple Sclerosis; Nervous System Diseases; Niacinamide; Placebos; Psychopharmacology; Pyridoxine; Sleep; Vitamin B 12; Vitamin B Complex

The results are presented of a double-blind therapeutic trial of hydroxocobalamin and riboflavine in Nigerian patients suffering from a degenerative neuropathy. Although no benefit from either vitamin was demonstrated, this may reflect the inadequacy of the dosages used. The results are discussed in relation to the hypothesis that dietary cyanide and cyanogens are responsible, at least in part, for the occurrence of this disease in a malnourished population.

Topics: Ataxia; Clinical Trials as Topic; Female; Humans; Hydroxocobalamin; Male; Manihot; Nervous System Diseases; Nigeria; Placebos; Riboflavin; Thiocyanates; Vitamin B 12

Although several case series have described nitrous-oxide-associated neurological disorders, a comprehensive assessment of exposure characteristics (e.g., time to onset, level of exposure) in substance abusers has not been performed. The aim of this study was to describe the onset patterns of recreational use of nitrous-oxide-induced neurological disorders.. All cases of neurological disorders related to nitrous oxide recreational use reported to the Hauts-de-France addictovigilance center between January 2019 and August 2020 were selected. Only cases requiring hospitalization with informative data to perform the nitrous oxide causality assessment were included.. A total of 20 cases from five hospitals were included. The male-to-female ratio was 6:1 and the median age was 19 years (range 16-34). The neurological presentation (myeloneuropathy 64%, 7/11; sensorimotor neuropathy 36%, 4/11) included for all patients gait disorders due to proprioceptive ataxia and limb hypoesthesia. The median dose used per occasion was 100 cartridges (range 5-960; n = 19). The median time from the start of nitrous oxide use to the onset of neurological symptoms was 6 months (range 0.7-54; n = 16). The cumulative dose was significantly higher in patients with damage to all four limbs than in patients with lower limb symptoms only (p = 0.042).. A low intermittent exposure may be sufficient to cause neurological damage in some subjects, suggesting that, at the population level, there is no safe exposure to nitrous oxide in recreational settings. The severity of neurological impairment could increase once used at high doses and for prolonged durations of nitrous oxide.

Topics: Adolescent; Adult; Ataxia; Female; Humans; Male; Nervous System Diseases; Nitrous Oxide; Peripheral Nervous System Diseases; Substance-Related Disorders; Vitamin B 12; Young Adult

Vitamin B12 deficiency can present with neurologic and psychiatric symptoms without macrocytic anaemia. We describe a case of late-onset cobalamin C deficiency which typically presents with normal serum vitamin B12 concentrations, posing an additional diagnostic challenge. A 23-year-old woman with decreased muscle strength and hallucinations was diagnosed with 'catatonic depression' and admitted to a residential mental health facility. She was referred to our hospital for further investigation 3 months later. Heteroanamnesis revealed that the symptoms had been evolving progressively over several months. Magnetic resonance imaging (MRI) of the brain showed diffuse symmetrical white matter lesions in both hemispheres. Routine laboratory tests including vitamin B12 and folic acid were normal except for a slight normocytic, normochromic anaemia. Over the next 6 weeks her symptoms deteriorated, and she became unresponsive to stimuli. A new MRI scan showed progression of the white matter lesions. The neurologist requested plasma homocysteine (Hcys) which was more than 8 times the upper limit of normal. Further testing revealed increased methylmalonic acid and the patient was diagnosed with adult-onset cobalamin C deficiency. This case illustrates that Hcys and/or methylmalonic acid should be determined in patients presenting with neuropsychiatric symptoms suggestive of vitamin B12 deficiency with a normal serum vitamin B12 to rule out a late-onset cobalamin C deficiency.

Topics: Adult; Female; Folic Acid; Humans; Methylmalonic Acid; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Vitamin B12 is a water-soluble vitamin that plays a fundamental role as an essential cofactor for two enzymes responsible for the production of succinyl-CoA and methionine. Vitamin B12 deficiency can occur in infants and may be related to the breastfeeding mother's adherence to a vegan diet or somatic diseases in the mother. It should be differentiated from inborn errors of vitamin B12 metabolism. Herein, we report the cases of three infants with West syndrome; all three were breastfed by mothers who followed a strict vegan diet. In one of the three infants, West syndrome developed during treatment with vitamin B12 and normalization of the vitamin B12 level. Early treatment and replacement therapy are worthwhile to prevent serious neurological problems and to improve the patient's clinical course.

Topics: Breast Feeding; Female; Humans; Infant; Nervous System Diseases; Spasms, Infantile; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Clinical Audit; Female; Guideline Adherence; Humans; Male; Middle Aged; Nervous System Diseases; Neurology; New Zealand; Practice Guidelines as Topic; Practice Patterns, Physicians'; Tertiary Care Centers; Vitamin B 12; Vitamin B 12 Deficiency

Topics: China; Female; Humans; Hyperpigmentation; Illicit Drugs; Male; Nervous System Diseases; Nitrous Oxide; Retrospective Studies; Substance-Related Disorders; Vitamin B 12; Young Adult

The aim of this retrospective study was to search for risk factors for neurological adverse events in gastrointestinal cancer patients receiving chemotherapy and analyze the relationship between thiamine serum levels and neurological adverse events.. This is a single-center retrospective observational study. We enrolled patients who were diagnosed with gastrointestinal cancer at our hospital, for whom we measured the thiamine serum levels. We then performed a multivariate analysis (logistic regression) to identify risk factors for the neurological symptoms in our cohort. We then divided the patients into two groups, with and without neurological symptoms, based on their electronic medical records. By using the Mann-Whitney U-test, we performed a comparative analysis of the thiamine serum levels between the two groups. We also used descriptive statistics to examine the presence/absence of neurological symptoms or other potentially related clinical features in patients with decreased thiamine serum levels.. The logistic regression analysis detected the decrease in thiamine serum levels as a statistically significant risk factor for neurological symptoms. The analysis of the relationship between the presence/absence of neurological symptoms and thiamine serum levels showed that the thiamine serum levels were significantly lower in the group presenting neurological symptoms. Descriptive statistics showed that all the patients with decreased thiamine serum levels had either cognitive decline, attention decline, or depression symptoms, and most of them were receiving the 5-fluorouracil anticancer drug and showing decreased serum albumin levels. We also observed a slight decrease in serum sodium, vitamin B12, and folate levels.. When neurological symptoms occur in patients receiving chemotherapy for gastrointestinal cancer, the measurement of thiamine serum levels may become a standard reference for treatment indication.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Female; Fluorouracil; Folic Acid; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Nervous System Diseases; Retrospective Studies; Risk Factors; Sodium; Thiamine; Thiamine Deficiency; Vitamin B 12; Young Adult

Vitamin B12 is one of the essential vitamins that affect various systems in the body, including the central nervous system. Vitamin B12 plays an important part in the metabolism of the nervous system, although its exact role under pathological conditions is not fully understood. The purpose of this study was to emphasize the importance of early diagnosis of vitamin B12 deficiency in the light of the characteristics of the patients enrolled. This retrospective, clinical study included 38 children with neurological symptoms of vitamin B12 deficiency. Records of 38 patients referred to a single center of the university hospital outpatient child neurology clinic due to neurological symptoms of vitamin B12 deficiency between February 2012 and December 2013 were evaluated retrospectively. Patients aged 0-18 years with symptoms including syncope, dizziness, convulsion, hypotonia, developmental retardation, tremor, ataxia, tingling sensations and paresthesia, blurring of vision, fatigue and concentration difficulty caused by vitamin B12 deficiency were included in the study. Patient neurological findings included syncope (n=6), dizziness (n=4), hypotonia (n=9), inability to sit or walk without support, or gait ataxia (n=2), convulsion (n=4), hand tremor (n=1), tingling sensations and paresthesia (n=3), vision blurring (n=1), fatigue and concentration difficulty (n=8). All patients with neurological symptoms of vitamin B12 deficiency recovered within one month after vitamin B12 supplementation. In conclusion, clinical characteristics of vitamin B12 deficiency are broad and nonspecific and may not be associated with anemia and increased mean corpuscular volume. Since different clinical characteristics can be seen without anemia, awareness and cautious approach are essential in order to avoid severe clinical disease, especially in children from underdeveloped countries.

Topics: Adolescent; Child; Child, Preschool; Developmental Disabilities; Dizziness; Early Diagnosis; Fatigue; Female; Humans; Infant; Male; Nervous System Diseases; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Neurological disorders secondary to vitamin B12 deficiency are polymorphic and diverse. There have been very few studies conducted in the Moroccan as well as in the African population. This study aims to describe the clinical, paraclinical, evolutionary features of neurological manifestations in patients with vitamin B12 deficiency within the Department of Neurology at the Moulay Ismail Military Hospital, Meknes over a period of 18 years (1999-2017). The study involved 06 women and 23 men, with an average age of 57 years. The mean time between symptom onset and diagnosis was 3 months. Neurological manifestation was indicative of vitamin B12 deficiency in 100% of cases. The average hemoglobin level was 10 g/dl, the mean corpuscular volume was 115 fl. Medullary megaloblastosis and atrophic gastritis were found in 95% and 90% of cases respectively. Regular electromyography (EMG), electroencephalography (EEG) and visual evoked potentials (VEP) showed subclinical peripheral and optic neuropathies. In 20 cases they were caused by Biermer's anemia. All the patients received parenteral Vitamin B12 with good outcome. These results demonstrate the importance of early diagnosis in patients with a potentially serious neuropsychiatric condition as well as of rapid substitution treatment which is the only therapeutic option to secure a good outcome.

Topics: Aged; Anemia, Pernicious; Electroencephalography; Electromyography; Evoked Potentials, Visual; Female; Humans; Male; Middle Aged; Morocco; Nervous System Diseases; Optic Nerve Diseases; Retrospective Studies; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

The rising rates of bariatric surgery (BS) are accompanied by neurological complications related to nutrient deficiencies. One of the risk factors for neurological complications in BS patients is poor vitamin and mineral supplementation. Prevention, diagnosis and treatment of these disorders are necessary parts of lifelong care after BS. Particularly important for optimal functioning of the nervous system are vitamin B

Topics: Adult; Anemia; Dietary Supplements; Female; Folic Acid; Gastric Bypass; Humans; Minerals; Nervous System Diseases; Obesity, Morbid; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Neuropathies often accompany vitamin B12 deficiency. Since many neuropathies are linked to oxidative stress and since B12 has both antioxidant and neurotrophic properties, B12 may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B12-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined.. Retrospective review of 78 subjects with neurological abnormalities treated with B12 and evaluated by the measurement of B12 and the B12-dependent metabolites, methylmalonic acid (MMA), and homocysteine.. Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B12-responsive macrocytosis. Pretherapy B12, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B12 therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable non-responders. At least one oxidant risk was present in 41 of the 46 responders with normal B12 levels (89%). Oral therapy was effective, but parenteral B12 improved responses in four subjects.. B12-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B12-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B12 levels are normal. Since no predictors of responses to B12 therapy were identified, empiric trials with parenteral B12 should be considered in appropriate subjects.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antioxidants; Biotransformation; Female; Homocysteine; Humans; Injections, Intramuscular; Male; Medical Records; Methylmalonic Acid; Middle Aged; Nervous System Diseases; Nutritional Status; Oxidative Stress; Retrospective Studies; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 (cobalamin, Cbl) deficiency can cause metabolic, hematological, and neurological abnormalities. Adequate levels of succinyl-coenzyme A (CoA) cannot be synthesized from methylmalonyl-CoA because of the decreased activity of the methylmalonyl-CoA mutase enzyme that uses Cbl as the cofactor. Succinyl-CoA synthesis deficiency leads to decreased heme synthesis and gluconeogenesis. The reason of growth retardation can be gluconeogenesis deficiency together with heme synthesis deficiency whereas the reason of the neurological abnormalities can be glycine increase in the tissue due to decreased heme synthesis. We present 7 infants diagnosed with severe nutritional Cbl deficiency and discuss the role of succinyl-CoA and glycine in the possible pathogenesis in this article. Patients brought to our clinic with a complaint of growth retardation and diagnosed with nutritional Cbl deficiency were included in the study. There were 5 females and 2 males. The mean age was 11 ± 2.30 (range 6-13) months. All patients had general muscular hypotonia and 4 had growth retardation. Neuromotor growth retardation was found in 4 of the children who had previously shown normal neuromotor development for age. The mean Cbl level was 83.8 ± 27.6 (45.6-114) pg/mL. The mean Cbl level of the mothers was 155 ± 56.6 (88-258) pg/mL. Six of the patients had anemia and 1 had thrombocytopenia. Mean corpuscular volume value was 91.5 ± 12.2 fL. Following treatment, the muscle tonus of the patients improved, the anemia and growth retardation decreased, and the lost neuromotor abilities were recovered. Severe nutritional Cbl deficiency is an important nutritional disease where complications can be prevented with early treatment. When evaluating the pathogenesis, it should be noted that nutritional Cbl deficiency is a succinyl-CoA synthesis deficiency.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Acyl Coenzyme A; Amino Acid Metabolism, Inborn Errors; Anemia; Female; Gluconeogenesis; Glycine; Growth Disorders; Hematopoiesis; Humans; Infant; Male; Mothers; Motor Skills; Muscle Hypotonia; Nervous System Diseases; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin B 12 Deficiency

The frequency and type of neuropathy in vitamin B12 deficiency neurological syndrome (VBDNS) is controversial. This study reports the frequency and type of nerve dysfunction in VBDNS using nerve conduction and sural nerve biopsy and its response to treatment.. Sixty-six patients with VBDNS diagnosed on the basis of low serum vitamin B12 level and/or megaloblastic bone marrow were subjected to clinical evaluation, hemoglobin, mean corpuscular volume, thyroid function test, HIV serology, and vasculitic profile. Peroneal motor and sural sensory nerve conduction studies were done. Sural nerve biopsy was done in six patients. The patients were treated with cyanocobalamin injection and followed up clinically and with nerve conduction study at 3 and 6 months.. The median age of the patients was 46 (12-80) years and 11 patients were females. The duration of symptoms was 1-96 (median 7) months. Clinical features of neuropathy were present in 46 (69.7%) patients and nerve conduction was abnormal in 36 (54.5%) patients. On nerve conduction study, 8 (22.2%) patients had axonal, 4 (11.1%) had demyelinating, and 24 (66.7%) had mixed features. Nerve biopsy revealed acute axonal degeneration in early stage and chronic axonopathy with demyelination in the late stages of disease. The nerve conduction parameters improved at 6 months along with clinical recovery.. Nearly 70% patients with VBDNS had evidence of neuropathy which is mainly axonal with some demyelinating features.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Child; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nervous System Diseases; Neural Conduction; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Vitamin B12 (Cbl) deficiency may cause hematologic and neurologic dysfunction. Replacement therapy is effective in correcting hematologic abnormalities and improving neurologic symptoms. Cbl is known to have antioxidant activity. This antioxidant activity may antagonize the effects of chemotherapeutics (i.e. genotoxic effects of paclitaxel) on tumor DNA. We claim that Cbl replacement should be done more cautiously in patients receiving cytotoxic chemotherapy.

Topics: Antineoplastic Agents; Antioxidants; DNA, Neoplasm; Drug Interactions; Free Radicals; Humans; Neoplasms; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Higher prevalence of neuropathy has been described in patients with Parkinson's disease (PD) in comparison with age and gender-matched controls. The cause of neuropathy may be levodopa-induced impairment of vitamin B12 metabolism, suggesting levodopa-naïve subjects should be unaffected. There may, however, be other yet unidentified determinants of neuropathy in PD. We screened 33 consecutive levodopa-naïve PD patients for neuropathy. Demographics, vitamin B12 and folate levels were studied. Findings were analyzed in the light of our previous available data on levodopa-treated PD patients. Four of 33 (12.1 %) levodopa-naïve PD patients were diagnosed with neuropathy. This compared to 13/36 (36.1 %) previously evaluated levodopa-treated patients (p = 0.027) and 3/37 controls (p = 0.7). Analysis of our whole PD cohort consisting of a total of 70 subjects, including levodopa-naïve and levodopa-treated patients, revealed that neuropathy correlated with use of levodopa (p = 0.041), cumulative levodopa exposure (p = 0.046), age at time of study (p = 0.005) and serum folate levels <10 μg/L (p = 0.003). There was no association of neuropathy with PD duration. Multivariate regression analysis showed that neuropathy was only independently associated with age (p = 0.016) and serum folate levels <10 μg/L (p = 0.012). We conclude that this study confirms the roles of levodopa usage and cumulative levodopa exposure in the neuropathy of PD. However, the effects of levodopa only appear contributory and are surpassed by age and lower folate levels. In view of the independent implication of lower folate levels, the need for preventative/protective supplementation including folate in addition to vitamin B12, probably irrespective of levodopa use, may deserve consideration in patients with PD.

Topics: Adult; Aged; Aging; Antiparkinson Agents; Cross-Sectional Studies; Female; Folic Acid; Humans; Levodopa; Male; Middle Aged; Nervous System Diseases; Parkinson Disease; Vitamin B 12

Folate and vitamin B(12) metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Anemia, Megaloblastic; Bone Marrow Examination; Cardiomyopathies; Combined Modality Therapy; DNA Mutational Analysis; Drug Combinations; Drug Therapy, Combination; Exome; Female; Genetic Carrier Screening; Humans; Hydroxocobalamin; Immunization, Passive; Infant; Infant, Newborn; Leukopenia; Lipid Metabolism, Inborn Errors; Methylenetetrahydrofolate Dehydrogenase (NADP); Minor Histocompatibility Antigens; Mitochondrial Myopathies; Mitochondrial Trifunctional Protein; Nervous System Diseases; Opportunistic Infections; Peripheral Nervous System Diseases; Pneumonia, Pneumocystis; Retinitis Pigmentosa; Rhabdomyolysis; Sequence Analysis, DNA; Severe Combined Immunodeficiency; Sulfadoxine; Trimethoprim; Vitamin B 12

To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B(12) deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

Topics: Adult; Aged; Anemia, Pernicious; Asian People; Autoimmune Diseases; Female; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Isoantibodies; Male; Middle Aged; Nervous System Diseases; Parietal Cells, Gastric; Republic of Korea; Retrospective Studies; Vitamin B 12

A patient developed numbness and tingling in distal extremities with subsequent weakness. Evaluation revealed B12 deficiency. She had evidence of myelopathy on imaging studies and polyneuropathy on electrodiagnostic testing. Treatment with B12 caused remittance of symptoms and resolution/improvement of abnormalities found on the imaging and electrodiagnostic studies. This case demonstrates that early intervention with B12 supplementation can cause reversal of both central and peripheral nervous system dysfunction.

Topics: Adult; Electrodiagnosis; Female; Humans; Magnetic Resonance Imaging; Nervous System Diseases; Neural Conduction; Reaction Time; Recovery of Function; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Brain; Homocysteine; Humans; Nervous System Diseases; Vitamin B 12

Combined medullar sclerosis, together with peripheral sensory neuropathies, is the most common neurological manifestation observed in cobalamin deficiency. Biermer's disease is the predominant cause. Other clinical and etiological aspects are nevertheless frequent, although underestimated.. This retrospective study included patients with neurological symptoms and cobalamin (B12 vitamin) deficiency confirmed by laboratory tests collected over a period of 11 years.. Twenty-seven cases were analyzed. Mean age was 47 years and there were 11 women and 16 men. Distribution of the neurological syndromes was: combined medullar sclerosis in 18 patients (67%), sensory neuropathies in 30% of cases and sensory-motor neuropathies in 15%. One patient had fronto-subcortical dementia with good improvement after vitamin replacement. In addition, autonomic dysfunction was noted in six patients (orthostatic symptomatic hypotension and/or urinary dysfunction and/or erectile failure). Dysautonomia revealed cobalamin deficiency in three patients with a good and fast response to the cobalamin therapy in all cases. Biermer's disease was diagnosed in 17 patients (63%) and a likely syndrome of nondissociation of cobalamin in two patients. One patient had Crohn's disease and no etiology was found in seven patients. In five patients (19%), nitrous oxide undoubtedly induced decompensation of latent cobalamin deficiency; four after a general anesthesia and one by chronic professional exposure. Outcome was very good in 46% of patients after vitamin replacement, particularly if treatment was started rapidly.. The findings in this series highlight the frequency of autonomic dysfunction sometimes revealing cobalamin deficiency with a fast and good response to vitamin replacement and the frequency of neurological disorders following decompensation triggered by general anesthesia using nitrous oxide in patients with latent cobalamin deficiency.

Topics: Adolescent; Adult; Aged; Anesthesia, General; Autonomic Nervous System Diseases; Female; Humans; Male; Medulla Oblongata; Middle Aged; Nervous System Diseases; Retrospective Studies; Sclerosis; Sensation Disorders; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins; Young Adult

Topics: Adult; Ataxia; Dementia; Humans; Jaundice; Male; Nervous System Diseases; Recurrence; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Increased plasma total homocysteine (tHcy) is a risk factor for neurological diseases, but the underlying pathophysiology has not been adequately explained.. We evaluated concentrations of tHcy, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), folate, and vitamin B(12) in cerebrospinal fluid (CSF) and plasma or serum from 182 patients with different neurological disorders. We measured concentrations of phosphorylated tau protein (P-tau)((181P)) and beta-amyloid(1-42) in the CSF.. Aging was associated with higher concentrations of tHcy and SAH in the CSF, in addition to lower concentrations of CSF folate and lower SAM:SAH ratio. Concentrations of CSF SAH and CSF folate correlated significantly with those of P-tau (r = 0.46 and r = -0.28, respectively). Moreover, P-tau correlated negatively with SAM:SAH ratio (r = -0.40, P <0.001). The association between SAH and higher P-tau was observed in 3 age groups (<41, 41-60, and >60 years). CSF tHcy was predicted by concentrations of CSF cystathionine (beta = 0.478), folate (beta = -0.403), albumin (beta = 0.349), and age (beta = 0.298).. tHcy concentration in the brain is related to age, B vitamins, and CSF albumin. Increase of CSF SAH is related to increased CSF P-tau; decreased degradation of P-tau might be a plausible explanation. Disturbed methyl group metabolism may be the link between hyperhomocysteinemia and neurodegeneration. Lowering tHcy and SAH might protect the brain by preventing P-tau accumulation.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amyloid beta-Peptides; Biomarkers; Cysteine; Female; Folic Acid; Humans; Male; Methylation; Middle Aged; Nervous System Diseases; Neurodegenerative Diseases; Peptide Fragments; Phosphorylation; S-Adenosylhomocysteine; tau Proteins; Vitamin B 12

Isolated methylmalonic acidurias comprise a heterogeneous group of inborn errors of metabolism caused by defects of methylmalonyl-CoA mutase (MCM) (mut0, mut-) or deficient synthesis of its cofactor 5'-deoxyadenosylcobalamin (AdoCbl) (cblA, cblB). The aim of this study was to compare the long-term outcome in patients from these four enzymatic subgroups. Eighty-three patients with isolated methylmalonic acidurias (age 7-33 y) born between 1971 and 1997 were enzymatically characterized and prospectively followed to evaluate the long-term outcome (median follow-up period, 18 y). Patients with mut0 (n = 42), mut- (n = 10), cblA (n = 20), and cblB (n = 11) defects were included into the study. Thirty patients (37%) died, and 26 patients survived with a severe or moderate neurologic handicap (31%), whereas 27 patients (32%) remained neurologically uncompromised. Chronic renal failure (CRF) was found most frequently in mut0 (61%) and cblB patients (66%), and was predicted by the urinary excretion of methylmalonic acid (MMA) before CRF. Overall, patients with mut0 and cblB defects had an earlier onset of symptoms, a higher frequency of complications and deaths, and a more pronounced urinary excretion of MMA than those with mut- and cblA defects. In addition, long-term outcome was dependent on the age cohort and cobalamin responsiveness.

Topics: Adolescent; Adult; Age of Onset; Alkyl and Aryl Transferases; Amino Acid Metabolism, Inborn Errors; Child; Cobamides; Disease Progression; Female; Follow-Up Studies; Gastrointestinal Diseases; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Membrane Transport Proteins; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Mitochondrial Membrane Transport Proteins; Mitochondrial Proteins; Mutation; Nervous System Diseases; Prognosis; Prospective Studies; Time Factors; Vitamin B 12; Vitamin B Complex

In order to clarify vitamin E malabsorption after gastric surgery, we evaluated serum vitamin E level and neurological consequences in patients who had undergone gastrectomy for gastric cancer.. We studied forty-eight patients (30 men, 18 women) with a mean age of 68.0 years, who had previously undergone gastrectomy for gastric cancer and had no evidence of recurrence. The types of operation consisted of subtotal gastrectomy in 26 patients and total gastrectomy in 22 patients. We measured postoperative body weight, white blood cells, red blood cells, hemoglobin, hematocrit, platelets, and serum levels of vitamins E, vitamin B12, folic acid, total cholesterol, triglycerides, total protein, and albumin.. Serum vitamin E level was decreased in 7 (14.6%) of the 48 patients. The occurrence of low vitamin E level was significantly more frequent in the total gastrectomy group than in the subtotal gastrectomy group. In relation to reconstruction procedures, the incidence of low vitamin E level was significantly higher in patients without food passage through the duodenum. The low vitamin E level was significantly associated with low total cholesterol level. The incidence of neuropathy was significantly higher in patients with low vitamin E level.. We assume that vitamin E deficiency more likely occurs after the reconstruction procedure in which food does not pass through the duodenum. Transport disturbance with loss of passage through the duodenum consequently may be the major cause of malabsorption. Differential diagnosis of neurological symptoms in post-gastrectomy patients should include hypovitaminosis E.

Topics: Aged; Female; Gastrectomy; Humans; Malabsorption Syndromes; Male; Middle Aged; Nervous System Diseases; Postgastrectomy Syndromes; Postoperative Complications; Regression Analysis; Stomach Neoplasms; Treatment Outcome; Vitamin B 12; Vitamin E

Neurological symptoms of B12 vitamin deficiency are polymorph. Causes are dominated by Biermer's disease and B12 vitamin non dissociation that is frequent in the elderly.. We realized a retrospective study during 11 years. Patients with neurological symptoms associated to megaloblastosis were included. Treatment with B12 vitamin lead to haematological manifestation regression.. 26 cases were analyzed. Mean age was 50+/-14.5 years and there were 11 women and 15 men. Neurological signs included combined medullar sclerosis (N = 10), peripheral neuropathy (N = 10), isolated paresthesia (N = 5) and inferior limb pyramidal syndrome (N = 1). Neurological signs revealed vitamin B12 deficiency in 4 cases. Mean haemoglobin rate was 6.2+/-2.6 g/dl, mean MCV was 109+/-56 fl. Eight patients had macrocytic anaemia, nine bi-cytopenia and eight deep pancytopenia. Electromyography (N = 8) confirmed neuropathy and medullar MRI (N = 2) showed antero-posterior cordonal demyelinisation of cervico-dorsal medulla. Causes of B12 vitamin deficiency were Biermer's disease (N = 11), non dissociation of B12 vitamin's syndrome (N = 8) and partial gastrectomy (N = 1). In 6 patients, no aetiology was found. Treatment with parenteral vitamin B12 induced neurological symptoms regression in 14 cases. Patient with neurological disorder had significantly higher platelet count and haemoglobin level as compared with patients without neurological disorder. Reticulocyte crisis was more precocious in patients with neurological disorders.. Neurological symptoms in vitamin B12 deficiency are frequent. We insist on isolated forms, inaugural forms and on the interest of medullar MRI for early diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Electromyography; Evoked Potentials; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nervous System Diseases; Peripheral Nervous System Diseases; Retrospective Studies; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Antibodies, Antinuclear; Arthralgia; Arthritis; Autoantigens; Female; France; Humans; Male; Mental Disorders; Middle Aged; Nervous System Diseases; Prevalence; Raynaud Disease; Sjogren's Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Brain; Female; Folic Acid; Humans; Magnetic Resonance Imaging; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Ceruloplasmin; Copper; Female; Follow-Up Studies; Hematologic Diseases; Humans; Magnetic Resonance Imaging; Metabolic Diseases; Middle Aged; Nervous System Diseases; Neural Conduction; Neutropenia; Peripheral Nerves; Spinal Cord; Vitamin B 12; Zinc

The unknown biochemical basis for neurologic dysfunction in cobalamin deficiency and the frequent divergence between neurologic and hematologic manifestations led us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet), cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only levels of tHcy and cysteine were increased and only GSH was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels (P =.015) and cysteine only with cys-gly (P =.007) in healthy subjects, but in cobalamin-deficient patients AdoMet correlated instead with cysteine, cys-gly, and folate levels only (P =.008, P =.03, and P =.03, respectively). Significant differences appeared in clinically subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6 nM), cysteine (462 versus 325 microM), and cys-gly (85.0 versus 54.7 microM) than the 11 neurologically unaffected patients. Cobalamin therapy restored all metabolic changes to normal. The results indicate that changes in several metabolic pathways differ in patients with and without neurologic dysfunction. Cysteine levels were the most significant predictors of neurologic dysfunction, but it is unclear if they are direct or indirect indicators of neurotoxicity. The higher AdoMet levels in neurologically affected patients may result from inhibition of glycine N-methyltransferase by those patients' higher folate levels. The origin of the folate differences is unclear and possibly varied. Low AdoMet and GSH levels were independent predictors of anemia.

Topics: Anemia; Anemia, Pernicious; Cysteine; Dipeptides; Folic Acid; Glutathione; Homocysteine; Humans; Memory Disorders; Methionine; Movement Disorders; Nervous System Diseases; Retrospective Studies; S-Adenosylmethionine; Sensation Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Celiac Disease; Diet Therapy; Female; Glutens; Humans; Mental Disorders; Nervous System Diseases; Vitamin B 12

Funicular myelosis is considered to be the main neurological syndrome in vitamin B12 deficiency. However, many authors tend to think that sensory neuropathy is the most common neurological manifestation of vitamin B12 deficiency. The aim of this paper was to assess neurological condition of patients with vitamin B12 malabsorption. The absorption of vitamin B-12 was assessed by Schilling's test. Patients with abnormal results of this test underwent neurological and medical examinations as well as series of accessory investigations. 16 cases of deficient vitamin B12 absorption accompanied by neurological symptoms were presented. The results of the investigation showed that the most common clinical manifestation of vitamin B12 deficiency was sensory neuropathy. In over 93% of described cases pathologic changes in gastric mucous membrane were found.

Topics: Adult; Aged; Female; Humans; Malabsorption Syndromes; Male; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Chronic exposure to nitrous oxide (N2O) is known to be associated with hematologic and neurologic abnormalities. When this syndrome occurs, it is generally seen in health care workers, especially dentists and anesthesiologists, who have access to nitrous oxide. Here, however, we report a case of a 55-year-old non-healthcare worker who presented with multiple neurological abnormalities. His serum vitamin B12 level was low but his Shilling test was normal. His neurologic symptoms improved after cessation of inhaling nitrous oxide and starting vitamin B12 therapy. Physicians should consider nitrous oxide abuse in non-healthcare workers presenting with neurologic symptom of unclear cause.

Topics: Humans; Inhalation Exposure; Male; Middle Aged; Nervous System Diseases; Nitrous Oxide; Substance-Related Disorders; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Over a 2-year period, we examined 48 patients with P-cobalamin levels in the difficult "grey zone" at the lower reference limit detected by a competitive protein binding assay using intrinsic factor as binder. In 21 of 30 patients (70%) with low P-cobalamins we could not establish the diagnosis of metabolic cobalamin deficiency, but 1 of 18 patients (6%) with low-normal P-cobalamin values was confirmed metabolically cobalamin-deficient. Half of these 30 patients with low P-cobalamins had neuropsychiatric disorders, but only one-third of the latter patients had metabolic cobalamin deficiency. Ten of the remaining 15 patients (67%) were characterized as non-deficient. In patients with low-normal P-cobalamin level, we found neuropsychiatric disorders in 5 of the 18 (28%), but none of these had metabolic cobalamin deficiency. We conclude that P-cobalamins below the reference interval combined with typical neuropsychiatric symptoms or findings are not diagnostic of cobalamin deficiency and that further analyses are necessary.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anemia, Macrocytic; Female; Humans; Malabsorption Syndromes; Male; Mental Disorders; Middle Aged; Nervous System Diseases; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Serum levels of total homocysteine were studied in the following: 26 healthy adults; 79 hospitalised patients in whom serum cobalamin, serum folate, and erythrocyte folate were greater than 230 pmol/L, 12 nmol/L, and 600 nmol/L, respectively; 32 hospitalised patients whose serum cobalamin was less than 147 pmol/L, compared to 25 patients whose serum cobalamin was greater than 147 pmol/L but unmatched in any other parameter; and 194 patients in whom samples were sent for determination of cobalamin and folate from a neurological service. None of this last group had megaloblastic anaemia. There was a relationship between the elevated concentrations of total homocysteine in serum and low concentrations of serum cobalamin and of erythrocyte folate. This relationship was most evident in samples with serum cobalamin < 86 pmol/L and erythrocyte folate < 335 nmol/L, although elevated homocysteine levels were found in some samples where serum cobalamin and erythrocyte folate levels were greater than these. Serum folate correlated poorly with serum total homocysteine. There was only a poor-to-fair correlation of neutrophil lobe counts to total serum homocysteine.

Topics: Adult; Erythrocytes; Folic Acid; Homocysteine; Hospitalization; Humans; Middle Aged; Nervous System Diseases; Neutrophils; Reference Values; Vitamin B 12

Serum vitamin B12 levels and unsaturated vitamin B12 binding capacities were measured in 24 patients with multiple sclerosis (MS), 73 patients with other neurological disorders and 21 healthy subjects. There was no decrease in the vitamin B12 levels, however, a significant decrease in the unsaturated vitamin B12 binding capacities was observed in patients with MS when compared with other groups. A massive dose of methyl vitamin B12 (60 mg every day for 6 months) was administered to 6 patients with chronic progressive MS, a disease which usually had a morbid prognosis and widespread demyelination in the central nervous system. Although the motor disability did not improve clinically, the abnormalities in both the visual and brainstem auditory evoked potentials improved more frequently during the therapy than in the pre-treatment period. We therefore consider that a massive dose methyl vitamin B12 therapy may be useful as an adjunct to immunosuppressive treatment for chronic progressive MS.

Topics: Adult; Afferent Pathways; Chronic Disease; Drug Evaluation; Evoked Potentials; Female; Humans; Male; Middle Aged; Motor Neurons; Multiple Sclerosis; Muscular Diseases; Nervous System Diseases; Vitamin B 12

An adult male patient of Dutch ancestry has a slowly progressive neurological disease characterised by a cerebellar syndrome, distal spinal muscular atrophy, pyramidal tract dysfunction, and perceptive hearing loss. A severe folate deficiency state was found in CSF in combination with a normal serum and red cell folate state. Two unknown abnormal metabolites were present in CSF. The concentration of immunoreactive folate binding protein in CSF was unusually low, whereas the concentration of the protein measured with radioligand (3H-folate) binding was unusually high. The transfer of folate over the choroid plexus seems to be disturbed, potentially reflecting a defect in the choroid plexus folate binder.

Topics: Adolescent; Carrier Proteins; Central Nervous System; Folate Receptors, GPI-Anchored; Folic Acid; Folic Acid Deficiency; Humans; Male; Nervous System Diseases; Receptors, Cell Surface; Vitamin B 12

Vitamin B12 deficiency may result in a number of neurological and neuropsychiatric disorders. Patients with human immunodeficiency virus type 1 (HIV-1) infection may have a high rate of vitamin B12 deficiency and nervous system disease. Vitamin B12 deficiency may contribute to neurological disease in HIV-1-infected individuals.. To evaluate the possible contribution of vitamin B12 deficiency to neurological disease in HIV-1-infected individuals.. Comparison of serum vitamin B12 levels with neurological, neuropsychological, and mood state abnormalities in 153 HIV-1-positive subjects and 57 high-risk seronegative controls. A subgroup of 67 subjects underwent additional extensive clinical neurophysiological, cerebrospinal fluid, and magnetic resonance imaging evaluations.. No statistically significant relationships were noted between vitamin B12 levels and abnormalities on any of the measures examined.. This study does not indicate an important role for vitamin B12 deficiency in the neurological disease of HIV-1 infection.

Topics: Adult; Female; HIV Infections; HIV-1; Humans; Male; Nervous System Diseases; Neuropsychological Tests; Vitamin B 12; Vitamin B 12 Deficiency

Low levels of cerebrospinal S-adenosylmethionine in association with abnormal myelination in inherited disorders affecting cobalamin and folate metabolism provide new data on a possible mechanism of cobalamin neuropathy.

Topics: Child, Preschool; Folic Acid; Folic Acid Deficiency; Humans; Infant; Infant, Newborn; Metabolism, Inborn Errors; Nervous System Diseases; S-Adenosylmethionine; Vitamin B 12; Vitamin B 12 Deficiency

Two cases of severe myeloneuropathy and macrocytic anemia associated with a low serum level of vitamin B12 after prolonged exposure to nitrous oxide are reported. In both cases, the neurological manifestations worsened initially despite B12 supplementation, although in one case the use of methionine seemed to arrest the progression of the disease and accelerate recovery. This offers further support for the biochemical hypothesis of methionine synthetase inhibition by nitrous oxide and reproduces in man previously reported animal studies with methionine. Methionine may be an important first-line therapy in the initial treatment of neuropathy and myeloneuropathy induced by nitrous oxide, and has a hypothetical role in the treatment of subacute combined degeneration of the cord.

Topics: Adult; Anemia, Macrocytic; Female; Humans; Male; Methionine; Nervous System Diseases; Neuromuscular Diseases; Nitrous Oxide; Sensation Disorders; Vitamin B 12

A review of the clinical findings in six infants with nutritional vitamin B12 deficiency seen during the last 10 years was undertaken and an attempt made to obtain long-term neurologic follow-up. There was a consistent clinical pattern in vitamin B12-deficient infants; irritability, anorexia, and failure to thrive were associated with marked developmental regression and poor brain growth. Two of the four patients who qualified for long-term review had a poor intellectual outcome. Although early response to treatment is satisfying, the long-term consequences of nutritional vitamin B12 deficiency in infants emphasize the need for prevention or early recognition of this syndrome.

Topics: Anemia, Pernicious; Breast Feeding; Child Development; Child, Preschool; Diet, Vegetarian; Female; Follow-Up Studies; Humans; Infant; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Thirty-four symptomatic cases of inherited transcobalamin II (TCII) deficiency were analysed in order to determine the frequency and nature of neurologic manifestations. In no instance was there definite evidence of a neurologic disorder at the time of presentation as a young infant. One child of 2 1/2 years transiently lost deep tendon reflexes at a time of suboptimal treatment. A syndrome of mental retardation and other neurologic manifestations was observed in three cases, all with the following in common: (1) an extended duration of illness of 2-17 years; (2) inadequate or not treatment with Cbl; (3) treatment with folic of folinic acid. TCII deficiency rarely if ever presents with neurologic manifestations. However, neurologic disorders can be produced subsequently by improper treatment.

Topics: Central Nervous System Diseases; Folic Acid; Humans; Infant; Infant, Newborn; Intellectual Disability; Leucovorin; Nervous System Diseases; Time Factors; Transcobalamins; Vitamin B 12

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Ataxia; Evoked Potentials, Somatosensory; Humans; Memory Disorders; Mental Disorders; Middle Aged; Nervous System Diseases; Paresthesia; Peripheral Nervous System Diseases; Reflex, Abnormal; Regression Analysis; Sensation; Spinal Cord Diseases; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

An increased prevalence of vitamin B12 deficiency has been reported in patients infected by the human immunodeficiency virus (HIV). We report an unexpectedly high prevalence (20%) of such abnormal vitamin B12 metabolism in a population of HIV-infected patients referred for neurological evaluation. This abnormality was associated with both peripheral neuropathy and myelopathy. A majority of those treated with cyanocobalamin had a therapeutic response. Selected neuropathological results suggest a relationship between vitamin B12 deficiency and vacuolar myelopathy. Vitamin B12 deficiency may be a frequent and treatable cause of neurological dysfunction in patients with HIV infection.

Topics: HIV Infections; Humans; Nervous System Diseases; Neurologic Examination; Parenteral Nutrition; Peripheral Nervous System Diseases; Spinal Cord; Spinal Cord Diseases; Vitamin B 12

Topics: Hematopoiesis; Humans; Nervous System Diseases; Nitrous Oxide; Students, Dental; Students, Medical; Substance-Related Disorders; United States; Vitamin B 12

We present a 9-month-old exclusively breast-fed baby of a strict vegetarian mother who had excluded all animal proteins from her diet. The patient's symptoms included dystrophy, weakness, muscular atrophy, loss of tendon reflexes, psychomotor regression and haematological abnormalities. Biochemical investigations revealed severe methylmalonic aciduria and homocystinuria in the patient, slight methylmalonic aciduria in the mother and low concentrations of serum vitamin B12 in both patient and mother.

Topics: Adult; Breast Feeding; Diet, Vegetarian; Female; Homocysteine; Humans; Infant; Methionine; Methylmalonic Acid; Milk, Human; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Supplementation of the diet with valine or isoleucine protects the fruit bat from neurological impairment associated with experimentally induced vitamin B12 deficiency. Valine and isoleucine are precursors in the vitamin B12 dependent propionic acid pathway and it is proposed that they exert their protective effect through stimulation of this pathway. This suggests that the previously observed protective effect of methionine may be mediated also through this pathway, since methionine may be metabolised via the transsulfuration pathway to propionyl CoA. The results of this study refocus attention on the propionic acid pathway, and specifically on the methylmalonyl CoA mutase reaction, as central to the biochemical basis of the vitamin B12 neuropathy.

Topics: Animals; Body Weight; Chiroptera; Isoleucine; Nervous System Diseases; Valine; Vitamin B 12; Vitamin B 12 Deficiency

The meaning of a low serum cobalamin level when the classic findings of pernicious anemia are lacking is undergoing reevaluation. We therefore studied the neurologic status of 11 patients who had low cobalamin levels without definite hematologic evidence of deficiency. Neurologic evaluation included pattern-shift visual and median and posterior tibial nerve somatosensory evoked potentials. None of the patients had megaloblastic changes in the blood or bone marrow, although 7 of the 11 had subtle cellular cobalamin disturbances demonstrated by an abnormal deoxyuridine suppression test result. Seven patients had normal Schilling test results and 2 had borderline results; however, 2 of the 5 patients tested further had food-cobalamin malabsorption, while a third had prepernicious anemia. The patients displayed a variety of neurologic problems, including dementia, depression, myelopathy, neuropathy, and seizure disorder; 1 patient was neurologically normal by clinical criteria. Evoked potential abnormalities were demonstrable in 8 of the 9 patients with subtle cobalamin deficiency, and in at least 5 cases the disturbance was central. In contrast, both patients whose low serum cobalamin levels were found on evaluation to be spurious had normal evoked potentials. Evoked potential abnormalities improved in the one patient retested after cobalamin therapy. These findings demonstrate that neurologic deficits occur not only in classic cobalamin deficiency but also in subtle or atypical cobalamin deficiency states in which anemia is absent and Schilling test results are normal. Electrophysiologic evidence of neurologic impairment is often present, even in patients without obvious clinical neurologic abnormalities.

Topics: Absorption; Adult; Aged; Anemia, Megaloblastic; Anemia, Pernicious; Evoked Potentials; Female; Humans; Intestinal Absorption; Male; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Diagnosis, Differential; Female; Homocystinuria; Humans; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Multiple Sclerosis; Mutation; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Pigs were treated with N2O which is known to impair vitamin B12 function in vivo. Such pigs demonstrated an inability to gain weight, progressive ataxia, and spinal neuropathy. The ataxia was totally and the neuropathy partially preventable by dietary methionine supplementation. Methionine synthase activity was inhibited in both the liver and brain. There was a marked elevation of S-adenosylhomocysteine in the neural tissues and a concomitant failure of S-adenosylmethionine to rise and thus maintain the methylation ratio, except when supplementary dietary methionine was added. In contrast, the methylation ratio in the rat was affected to a lesser extent. The neuropathy, it is suggested, is caused by raised S-adenosylhomocysteine levels in neural tissue; as a result, the methylation ratio is inverted and S-adenosylmethionine-dependent methylation reactions are inhibited.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Animals; Homocysteine; Methylation; Nervous System Diseases; Nitrous Oxide; S-Adenosylhomocysteine; S-Adenosylmethionine; Spinal Cord; Swine; Vitamin B 12

Serum cobalamin "analogue" levels were estimated by the discrepancy in cobalamin results with radioassays done with pure intrinsic factor and R binder in 364 patients with low cobalamin levels. No differences were found among the various causes of low cobalamin levels, except for the lower "analogue" levels among pregnant women. However, 76 patients with low cobalamin levels and primarily neurologic (spinal cord, neuropathic, cerebral, or a combination of these) symptoms had significantly higher "analogue" levels than 19 patients with primarily hematologic abnormalities. Moreover, the "analogue" levels correlated with hemoglobin values and were significantly higher in patients without megaloblastic changes in their bone marrow than in patients with megaloblastosis. An analysis limited to 47 patients with pernicious anemia yielded similar findings. The seven patients with only neurologic abnormalities had higher "analogue" levels than did the nine patients with only hematologic abnormalities. Because of the higher "analogue" levels, the assay done with R binder failed to register low cobalamin levels in 33 of 76 patients with low cobalamin levels and primarily neurologic abnormality (compared with only two of 19 with hematologic abnormality) and in 10 of 20 patients with pernicious anemia who had neurologic abnormalities (compared with only two of 12 without such abnormalities). These differences between patients with hematologic disturbances and patients with neurologic disturbances, and the inverse relationship of "analogue" level with severity of anemia, suggest that the disproportionate accumulation of analogues may explain why some patients with cobalamin deficiency display neurologic abnormalities while others do not.

Topics: Adult; Aged; Anemia, Pernicious; Female; Hematologic Diseases; Humans; Middle Aged; Nervous System Diseases; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Megaloblastic; Ataxia; Erythrocyte Indices; Erythrocytes; Female; Hematocrit; Homocysteine; Humans; Hypesthesia; Iron; Male; Methylmalonic Acid; Middle Aged; Nervous System Diseases; Neurocognitive Disorders; Paresthesia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diagnosis, Differential; Humans; Male; Middle Aged; Multiple Sclerosis; Nervous System Diseases; Transcobalamins; Vitamin B 12

Topics: Adult; Biotin; Child; Female; Humans; Infant; Infant, Newborn; Ligases; Male; Metabolism, Inborn Errors; Middle Aged; Nervous System Diseases; Niacinamide; Orthomolecular Therapy; Pedigree; Vitamin B 12

27 patients with pernicious anaemia, followed for a long period, were consecutively treated with 3 different vitamin B12 preparations while, during intervening periods, no therapy was given until signs of B12 deficiency developed. The mean of the vitamin B12-free period lasted 400 d. Some patients were 'short-reactors' whereas others were 'long-reactors'. Some patients repeatedly revealed deficiency signs at cobalamin values greater than 200 pmol/l and others at values less than 50 pmol/l, pointing to individually different cut-off points for appearance of signs of deficiency. Hypersegmentation was the first sign in about 2/3, neuropathy in 1/3 and mucosal changes in about 1/10 of the patients. The same type of deficiency was repeatedly noted in the same patient. The daily decline of plasma cobalamin values decreased during the vitamin B12-free period. In perorally treated patients the unsaturated transcobalamin values showed an inverse relationship to the cobalamin values. Marked increases in unsaturated transcobalamin I values were noted in 4 of 16 patients treated with B12 injections, resulting in prolonged high cobalamin values and prolongation of the vitamin B12-free periods.

Topics: Adult; Aged; Anemia, Pernicious; Diarrhea; Erythrocytes; Female; Humans; Male; Middle Aged; Mucous Membrane; Nervous System Diseases; Pain; Time Factors; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Two women developed significant neurologic dysfunction, consistent with subacute combined degeneration of the spinal cord, within eight weeks of being anesthetized with nitrous oxide. Investigation revealed that each had preclinical or masked vitamin B12 deficiency. The first patient had two previous ileal resections for Crohn's disease and the other had pernicious anemia. It is postulated that nitrous oxide anesthesia may precipitate neurologic disease in people with unrecognized deficiency of vitamin B12.

Topics: Adult; Erythrocyte Indices; Female; Hematocrit; Humans; Leukocyte Count; Middle Aged; Nervous System Diseases; Nitrous Oxide; Platelet Count; Vitamin B 12; Vitamin B 12 Deficiency

A case of giant axonal neuropathy (GAN) in a boy of 4 years and 6 months, is reported. Nerve conduction velocity (NCV), EEG and CT scan indicated both peripheral and central nervous system involvement. Intestinal absorption tests did not reveal vitamin B12 malabsorption; the endocrine situation was found to be substantially normal. The clinical picture was not modified by 18 months cyanocobalamine administration followed by 2 months therapy with prednisone. Electron microscopic (EM) examination revealed longitudinal and opposing grooves (pili canaliculi) in the hair and bundles of neuro-filaments in the myelinated and unmyelinated nerve fibre axons in sural nerve. EM of conjunctiva and skin revealed masses of intermediate-sized filaments within mast cells, fibroblasts, melanocytes, endothelial and Schwann cells. These findings confirm the hypothesis that GAN is a generalised abnormality of cytoplasmic microfilament formation, probably linked to an unknown disorder of protein metabolism.

Topics: Axons; Child, Preschool; Conjunctiva; Electroencephalography; Hair; Humans; Intermediate Filaments; Intestinal Absorption; Male; Microscopy, Electron; Nervous System Diseases; Neural Conduction; Skin; Sural Nerve; Vitamin B 12

Plasma cobalamins (vitamin B12) were determined by a microbiological method in 235 patients with continent ileostomies and postoperative observation times of 3-13 years (mean, 6 years). The influence of the reservoir on the vitamin B12 values could not be evaluated in 22 patients (9%)--because of prophylactic treatment in 6%, subnormal B12 values before the operation in 1%, and 'treatment' of various neurological symptoms not caused by vitamin B12 deficiency in 2%. Fourteen (7%) of the remaining 213 patients had developed subnormal plasma levels of vitamin B12 and another 14 patients (7%) had 'borderline' values (130-200 pmol/l). The median time interval between reservoir operation and the development of subnormal values was 7.5 years (range, 3-11 years). A small-bowel resection had been added to the proctocolectomy in 11 out of 14 patients with subnormal values and in 8 out of 14 patients with borderline values. Subnormal or borderline values were seen in 27% of patients with Crohn's disease and in 12% of patients with ulcerative colitis. No patient had anaemia or neurological symptoms caused by B12 deficiency. The study shows that most patients with continent ileostomies do not develop B12 deficiency, and there is therefore no need for general prophylaxis. Since at least 7% developed subnormal values, the plasma levels of vitamin B12 should, however, be followed up regularly in all patients with continent ileostomies.

Topics: Adolescent; Adult; Aged; Female; Humans; Ileostomy; Male; Middle Aged; Nervous System Diseases; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Folic Acid Deficiency; Humans; Male; Nervous System Diseases; Vitamin B 12

A female patient with subacute neurological deficits secondary to an hereditary vitamin B12 deficiency was repeatedly examined clinically and neurophysiologically. It is concluded that neurological normalization after treatment with vitamin B12 also occurs within the CNS. Such normalization takes place soon after initiating treatment and probably reflects other neuronal mechanisms that remyelination, i.e. recovery from conduction block in fast somatosensory pathways and/or improvement of synaptic transmission.

Topics: Evoked Potentials, Somatosensory; Evoked Potentials, Visual; Female; Humans; Median Nerve; Middle Aged; Motor Neurons; Nerve Degeneration; Nervous System Diseases; Neural Conduction; Sensation; Spinal Cord; Sural Nerve; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Diabetic Neuropathies; Humans; Methionine; Middle Aged; Nervous System Diseases; Neuritis; Peripheral Nervous System Diseases; Physical Therapy Modalities; Polyneuropathies; Thioctic Acid; Transketolase; Vitamin B 12

Topics: Adult; Aged; Asthenia; Calcitonin; Female; Gangliosides; Humans; Kidney Transplantation; Male; Middle Aged; Nervous System Diseases; Paresthesia; Renal Dialysis; Restless Legs Syndrome; Uremia; Vitamin B 12

Topics: Anemia, Pernicious; Humans; Male; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Chiroptera; Nervous System Diseases; Nitrous Oxide; Vitamin B 12

Giant axonal neuropathy in two siblings was reported. The fact that two cases are found in the same family supports this disorder is genetically determined and recessively inherited. These two cases, similar to the cases reported in literature, had chronic peripheral neuropathy and CNS symptoms, and also petit mal absence and mental retardation in elder sister (case 1) and precocious puberty in younger sister (case 2). Sural nerve biopsies in both cases disclosed axonal swellings or giant axons filled with aggregated neurofilaments, and that aggregated intermediate-sized filaments were found within cytoplasm of Schwann cells, endothelial cells of intra and extra-neurial capillaries and of extra-neurial arterioles, perineurial cells and endoneurial fibroblasts. Skin biopsies in both cases disclosed that aggregated intermediate-sized filaments were also found within cytoplasm of fibroblasts, Langerhans' cells, melanocytes and endothelial cells of capillaries, lymphatic vessels and arterioles. The diagnosis of giant axonal neuropathy can be made only by the findings in skin biopsy.

Topics: Adolescent; Axons; Child; Cytoskeleton; Epilepsy, Absence; Female; Humans; Intellectual Disability; Nervous System Diseases; Puberty, Precocious; Schwann Cells; Sural Nerve; Vitamin B 12

Topics: Female; Humans; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

A colony of rhesus monkeys made vitamin B12 deficient through dietary deprivation has been maintained since 1970. Deficient animals regularly develop neurologic lesions histologically, ultrastructurally, and topographically indistinguishable from those of human subacute combined degeneration but have failed to develop overt hematologic changes. No megaloblastic alterations, other evidence of impaired blood cell production, or subtle differences in mean red cell size are found. dU suppression tests on bone marrow were performed to determine whether functional B12 deficiency existed. All B12-deficient monkeys had markedly abnormal dU suppression test results after more than 10 months of B12 depviation, corrected by addition of B12 in vitro, whereas controls remained normal. Reasons for these disparate findings are considered, including species differences in metabolism of cobalamin analogues, cobalamin, and transcobalamins; the sensitivity of the dU test; the fact that ability to utilize preformed nucleotides may be greater in monkeys than in humans.

Topics: Animals; Bone Marrow Cells; Deoxyuridine; Erythrocyte Volume; Folic Acid; Iron; Macaca mulatta; Male; Nervous System Diseases; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

In 42 gastrectomized patients with low serum B12 the vibration perception threshold (VPT) was significantly elevated as compared with a control group. Forty patients were followed up after 6-12 months of intensive vitamin B12 therapy. Within an adequately treated group (25 patients) remission of symptoms and signs of peripheral neuropathy was observed, including a statistically significant reduction of the VPT measured on the medial malleolus and big toe. Such a reduction was not observed in the adequately treated group of patients with myclopathy. Findings in the inadequately treated group were less definite, both as regards remission of clinical findings and VPT. In four untreated patients the neurological symptoms and signs progressed during the follow-up period. On the basis of these findings intensive and long-lasting treatment with vitamin B12 is recommended for gastrectomized patients showing signs of neuropathy.

Topics: Adult; Aged; Electric Stimulation; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Nervous System Diseases; Neurologic Manifestations; Perception; Peripheral Nervous System Diseases; Reflex; Spinal Cord Diseases; Vibration; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. C

Topics: Anemia, Megaloblastic; DNA; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Glycine; Homocysteine; Humans; Methionine; Methylmalonyl-CoA Mutase; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Evaluation Studies as Topic; Humans; Mental Disorders; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Ten patients with severe neurological disease that was clinically indistinguishable from subacute combined degeneration of the spinal cord were found to have normal serum vitamin B12 levels. All were folate deficient. Specific folate treatment led to significant reversal of the neuropathy. These findings indicate the need to review orthodox concepts of the role of folic acid in maintaining the integrity of the nervous system.

Topics: Aged; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Middle Aged; Nervous System Diseases; Vitamin B 12

Topics: Adenosine Monophosphate; Adenosine Triphosphate; Drug Combinations; Drug Evaluation; Female; Humans; Male; Nervous System Diseases; Nucleotides; Pyridoxine; Taurine; Vitamin B 12; Vitamins

Topics: Ataxia; Cyanides; Diet; Humans; Liver; Nervous System Diseases; Nigeria; Vitamin B 12

In a general medical hospital population the neurological status of 24 patients with severe folate deficiency was compared with that of a control group of 21 patients with normal serum folate. A significant increase of organic brain syndrome and pyramidal tract damage was found in the folate-deficient group. These findings were independent of the degree of anaemia or the presence of alcoholism. These data are consistent with the view that severe folate deficiency may cause neurological deficits.

Topics: Alcoholism; Anemia; Brain Diseases; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Middle Aged; Nervous System Diseases; Pyramidal Tracts; Reflex, Abnormal; Vitamin B 12

Topics: Aged; Electroencephalography; Female; Humans; Male; Nervous System Diseases; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diet; Hemoglobins; Humans; Nervous System Diseases; Vitamin B 12

Topics: Anemia, Macrocytic; Humans; Nervous System Diseases; Neurocognitive Disorders; Neurologic Manifestations; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Data on thiocyanate and vitamin B(12) concentrations in plasma from Tanzanian patients with ataxic tropical neuropathy are presented and support the hypothesis that, as in Nigeria, the condition may result from chronic exposure to cyanide or cyanogens from a diet including large amounts of cassava.

Topics: Ataxia; Cyanides; Humans; Manihot; Mental Disorders; Nervous System Diseases; Optic Atrophy; Tanzania; Thiocyanates; Vitamin B 12

Topics: Ataxia; Cyanides; Diet; Foodborne Diseases; Humans; Manihot; Nervous System Diseases; Vitamin B 12

Topics: Analgesics; Antipyrine; Humans; Methylamines; Nervous System Diseases; Pain; Pyridoxine; Sulfonic Acids; Thiamine; Vitamin B 12

Topics: Adult; Chronic Disease; Cyanides; Female; Food Analysis; Humans; Male; Nervous System Diseases; Optic Atrophy; Smoking; Vitamin B 12

Topics: Avitaminosis; Folic Acid; Humans; Nervous System; Nervous System Diseases; Niacinamide; Nicotinic Acids; Nutritional Physiological Phenomena; Pantothenic Acid; Pyridoxine; Riboflavin; Thiamine; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Muscular Diseases; Nervous System Diseases; Thiamine; Uracil Nucleotides; Vitamin B 12

Topics: Folic Acid; Humans; Nervous System Diseases; Statistics as Topic; Vitamin B 12

A survey of neurological abnormalities in two Nigerian villages preselected for their differing consumption of cassava has shown that a degenerative neuropathy occurs with relatively high frequency in the village (Ososa) where cassava consumption was high.It is suggested that eating cassava results in exposure to cyanide, as shown by a raised plasma thiocyanate level, and that the latter, together with other factors, may contribute to the pathogenesis of "tropical neuropathy."

Topics: Biological Assay; Cyanides; Diet; Feeding Behavior; Female; Humans; Lactobacillus; Male; Manihot; Nervous System Diseases; Nigeria; Smoking; Thiocyanates; Tropical Medicine; Vitamin B 12

Topics: Biological Assay; Folic Acid; Humans; Lactobacillus; Nervous System Diseases; Statistics as Topic; Vitamin B 12

Topics: Erythropoiesis; Female; Hemoglobinometry; Humans; Male; Nervous System Diseases; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Investigation of nine patients with tropical ataxic neuropathy showed an absence or diminution of sulphur-containing amino-acids-cysteine and methionine-and a variable concentration of most other essential amino-acids. The pattern was unlike that found in kwashiorkor. The levels of serum cholesterol and total protein were normal, and the serum vitamin B(12) levels were normal or high. Plasma thiocyanate concentration was high.All the patients gave a history of a monotonous diet of cassava derivatives. Cassava contains a cyanogenetic glycoside (linamarin) from which cyanide is released on hydrolysis. The excessive cyanide detoxication may be responsible for the low concentration of the sulphur-containing amino-acids.

Topics: Adult; Amino Acids; Ataxia; Blood Proteins; Cholesterol; Cyanides; Cysteine; Female; Glycoside Hydrolases; Glycosides; Humans; Male; Manihot; Methionine; Middle Aged; Nervous System Diseases; Nigeria; Thiocyanates; Tropical Medicine; Vitamin B 12

Topics: Adolescent; Adult; Age Factors; Aged; Ataxia; Child; Child, Preschool; Cyanides; Deafness; Diet; Electromyography; Female; Folic Acid; Gait; Glucose Tolerance Test; Humans; Infant; Infant, Newborn; Leg; Male; Middle Aged; Motor Neurons; Muscles; Nervous System Diseases; Nigeria; Nutrition Disorders; Reflex, Abnormal; Riboflavin Deficiency; Sensation; Sex Factors; Thiocyanates; Vision Disorders; Vitamin B 12

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Nervous System Diseases; Pyridoxine; Taurine; Vitamin B 12

Topics: Adult; Aged; Anemia, Pernicious; Female; Gastrectomy; Gastrointestinal Diseases; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Male; Mental Disorders; Middle Aged; Nervous System Diseases; Schilling Test; Vitamin B 12

Topics: Blood; Cyanides; Diet; Female; Humans; Male; Nervous System Diseases; Nigeria; Peripheral Nervous System Diseases; Thiocyanates; Vitamin B 12

Topics: Anemia, Pernicious; Humans; Nervous System Diseases; Vitamin B 12

Topics: Humans; Injections, Spinal; Nervous System Diseases; Vitamin B 12

Topics: Adenosine Triphosphate; Corrinoids; Hematinics; Humans; Hydroxocobalamin; Nervous System Diseases; Thiamine; Vitamin B 12; Vitamins

Topics: Folic Acid; Humans; Nervous System Diseases; Pain; Quaternary Ammonium Compounds; Thiamine; Vitamin B 12; Vitamin B Complex

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Humans; Nervous System Diseases; Vitamin B 12

Topics: Drug Therapy; Fatty Acids; Fatty Acids, Essential; Humans; Nervous System Diseases; Niacin; Nicotinic Acids; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Herpes Zoster; Humans; Nervous System Diseases; Neuralgia; Neuritis; Pain; Phantom Limb; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Myelophthisic; Biochemical Phenomena; Gastroenterology; Humans; Nervous System Diseases; Schilling Test; Vitamin B 12

Topics: Adenine Nucleotides; Herpes Zoster; Humans; Multiple Sclerosis; Nervous System Diseases; Neuralgia; Neuritis; Pyridoxine; Thiamine; Vitamin B 12; Vitamins

Topics: Nervous System Diseases; Vitamin B 12

Topics: Corrinoids; Humans; Nervous System Diseases; Vitamin B 12; Vitamin B Complex

Topics: Corrinoids; Hematinics; Nervous System Diseases; Vitamin B 12

Topics: Hematinics; Humans; Nervous System Diseases; Thromboplastin; Vitamin B 12

Topics: Humans; Nervous System Diseases; Spinal Cord Diseases; Vitamin B 12; Vitamin B Complex

Topics: Corrinoids; Hematinics; Humans; Nervous System Diseases; Vitamin B 12; Vitamin B Complex

Topics: Herpes Zoster; Humans; Nervous System Diseases; Neurology; Pain; Phantom Limb; Trigeminal Neuralgia; Vitamin B 12

Topics: Corrinoids; Databases, Genetic; Hematinics; Humans; Nervous System Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Nervous System Diseases; Vitamin B 12; Vitamins

Topics: Corrinoids; Isoniazid; Nervous System Diseases; Niacin; Nicotinic Acids; Vitamin B 12; Vitamin B Complex

Topics: Corrinoids; Fatigue; Hematinics; Humans; Nervous System Diseases; Neurasthenia; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Nervous System Diseases; Vitamin B 12

Topics: Adenosine Triphosphate; Diabetes Complications; Diabetic Neuropathies; Humans; Liver Extracts; Nervous System Diseases; Pantothenic Acid; Thiamine; Vitamin B 12; Vitamin B Complex

Topics: Alcoholism; Humans; Nervous System Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Nervous System Diseases; Vitamin B 12; Vitamin B Complex

Topics: Corrinoids; Hematinics; Humans; Nervous System Diseases; Vitamin B 12; Vitamin B Complex

Topics: Corrinoids; Hematinics; Nervous System Diseases; Neurology; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Nervous System Diseases; Neurology; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Corrinoids; Hematinics; Nervous System Diseases; Vitamin B 12; Vitamin B Complex; Vitamins