vitamin-b-12 and Demyelinating-Diseases

Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.

Topics: Animals; Demyelinating Diseases; Humans; Models, Biological; Multiple Sclerosis; Myelin Sheath; Vitamin B 12; Vitamin B 12 Deficiency; Wound Healing

Topics: Animals; Demyelinating Diseases; Humans; Vitamin B 12

Combined medullary sclerosis developed suddenly postoperatively in a patient with unknown Biermer's disease. The neurological lesions were undoubtedly induced by nitrogen protoxide via an inactivation of vitamin B12.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Abscess; Aged; Anemia, Pernicious; Anesthetics, Inhalation; Arthroplasty, Replacement, Hip; Atrophy; Autoantibodies; Autoimmune Diseases; Demyelinating Diseases; Female; Gastric Mucosa; Humans; Intestinal Absorption; Intrinsic Factor; Nitrous Oxide; Oxidation-Reduction; Paresthesia; Postoperative Complications; Proprioception; S-Adenosylmethionine; Sclerosis; Spinal Cord; Spinal Cord Diseases; Surgical Wound Infection; Vitamin B 12

Indistinguishable hematologic abnormalities are seen in most patients with cobalamin (Cbl, vitamin B12) or folate deficiency. Approximately one third of Cbl-deficient patients develop a wide variety of non-focal neuropsychiatric abnormalities that are not seen in folate deficiency. Serum levels of homocysteine are elevated to a similar degree in Cbl-deficient patients with and without neuropsychiatric abnormalities, and in folate-deficient patients. Serum levels of eight other metabolites including methylmalonic acid also fail to elucidate the biochemical basis for the neuropsychiatric abnormalities. Levels of homocysteine and methylmalonic acid are often only slightly elevated in Cbl-deficient patients who have significant neuropsychiatric defects. Moderate elevations of homocysteine and methylmalonic acid occur in 20%-30% of various elderly populations (mean age 80) and may play a role in the similar neuropsychiatric abnormalities that occur increasingly with aging. Taken together, these studies suggest that an important unknown Cbl-dependent enzyme, metabolic abnormality, environmental factor, or genetic factor may play a major role in the pathophysiology of the neuropsychiatric abnormalities caused by Cbl deficiency.

Topics: Central Nervous System Diseases; Citrates; Demyelinating Diseases; Folic Acid; Homocysteine; Humans; Mental Disorders; Methionine; Methylmalonic Acid; Vitamin B 12

Certain aspects of the clinical syndrome of dementia, cerebral atrophy, predominantly sensory neuropathy, and vacuolar myelopathy in AIDS resemble those seen in vitamin B12 deficiency. Pathologically, there are similarities not only in the changes in the spinal cord, but also in the brain and peripheral nerves. The pathogenesis of vacuolar myelopathy may be secondary to a combination of immune mediated myelin and oligodendrocyte injury, and simultaneous impairment of repair mechanisms due to a deficiency of S-adenosylmethionine (SAM). Products derived from macrophages may interfere directly with the methyl transfer cycle through the generation of reactive oxygen intermediates and reactions involving nitric oxide and peroxynitrite which may limit the supply of methionine for conversion to SAM, both by direct interaction as well as through inhibition of methionine synthase. Macrophage activation with secretion of cytokines and other biologically reactive substances within the nervous system is sustained in the late stages of HIV infection by the general effects of immune depletion, including loss of T cells (with concomitant reduction of macrophage regulatory molecules) and recurrent opportunistic infections, and may be further augmented by the local presence of the virus itself (or its surface glycoprotein gp120). This would account for the common, but not exclusive, occurrence of vacuolar myelopathy in AIDS. The ability of the virus and its products to stimulate macrophage and microglial activation may also explain the association between severity of vacuolar myelopathy and the presence of HIV encephalitis. A similar mechanism may underlie the pathogenesis of dementia, cerebral atrophy, and peripheral neuropathy. Local factors or differential susceptibility between the central and peripheral nervous system may determine whether myelinotoxic or neurotoxic processes predominate; the prominence of myelin involvement in the spinal cord, and axonal involvement peripherally may reflect both ends of this range, with the brain manifesting a more equal balance of both processes.

Topics: Acquired Immunodeficiency Syndrome; AIDS Dementia Complex; Cytokines; Demyelinating Diseases; Folic Acid; Glutathione; Humans; Macrophage Activation; Oligodendroglia; Peripheral Nervous System Diseases; S-Adenosylmethionine; Spinal Cord Diseases; Vacuoles; Vitamin B 12

In humans, subacute combined degeneration of the spinal cord and brain, a primary demyelinating disease, is caused by cobalamin or methyltetrahydrofolate deficiency. Experimental studies into its pathogenesis suggest that dysfunction of the methyl-transfer pathway may be the cause. Compelling evidence for this comes from the study of inborn errors of cobalamin metabolism where deficiency of methylcobalamin, but not deoxyadenosylcobalamin, is associated with demyelination. Recent studies have focused upon inborn errors of the methyl-transfer pathway. Cerebrospinal fluid concentrations of metabolites of the methyl-transfer pathway have been measured in humans with sequential errors of the pathway and correlated with demyelination demonstrated on magnetic resonance imaging of the brain. This has provided new data suggesting that deficiency of S-adenosylmethionine is critical to the development of demyelination in cobalamin deficiency.

Topics: Brain Diseases; Demyelinating Diseases; Humans; Metabolism, Inborn Errors; Methylation; Nerve Degeneration; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Child; Child, Preschool; Demyelinating Diseases; Diagnosis, Differential; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Middle Aged; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Antiviral Agents; Demyelinating Diseases; Glutens; Humans; Immunosuppressive Agents; Linoleic Acids; Multiple Sclerosis; Palliative Care; Transfer Factor; Vitamin B 12

Topics: Anemia, Pernicious; Animal Nutritional Physiological Phenomena; Animals; Ataxia; Behavior, Animal; Central Nervous System Diseases; Chiroptera; Demyelinating Diseases; Disease Models, Animal; Flight, Animal; Humans; Species Specificity; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Irradiation of food at 50-55 kGy results in a profound, chronic demyelinating-remyelinating disease of the entire central nervous system (CNS) in cats, named Feline Irradiated Diet-Induced Demyelination (FIDID). This study examines the early stages of demyelination and long-term consequences of demyelination and remyelination on axon survival or loss. Myelin vacuolation is the primary defect leading to myelin breakdown, demyelination then prompt remyelination in the spinal cord and brain. There is no evidence of oligodendrocyte death. The spinal cord dorsal column is initially spared yet eventually becomes severely demyelinated with subsequent loss of axons in the core and then surface of the fasciculus gracilis. However remyelination of the sub-pial axons in the dorsal column results in their protection. While there was a lack of biochemical evidence of Vitamin B12 deficiency, the pathological similarities of FIDID with sub-acute combined degeneration (SCD) led us to explore treatment with Vitamin B12. Treatment led to recovery or improvement in some cats and neurologic relapse on cessation of B12 therapy. While the reason that irradiated food is myelinotoxic in the cat remains unresolved, nonetheless the neuropathological changes match exactly what is seen in SCD and its models and provide an ideal model to study the cellular and molecular basis of remyelination.

Topics: Acute Disease; Animals; Axons; Cats; Chronic Disease; Demyelinating Diseases; Diet; Disease Models, Animal; Female; Macrophages; Male; Metabolome; Microglia; Myelin Sheath; Nerve Degeneration; Neuropathology; Radiation; Remyelination; Spinal Cord; Time Factors; Vitamin B 12

Recreational use of nitrous oxide (NO) in the general public has led to increasing reports of NO-induced demyelination (NOID). We describe the varying clinical presentations and pathophysiology, and offer a treatment paradigm.. A literature search of MEDLINE and EMBASE resulted in 42 publications with 37 studies meeting the inclusion criteria, for a total of 51 patients. Our case series included 5 patients seen from 2014 to 2018 followed over 3-60 months.. Those with sensory symptoms and subjective weakness were categorized as having "mild" symptoms (25%). Symptoms indicating involvement outside the dorsal columns such as observer-graded weakness were categorized as "moderate" (61%). Patients with the aforementioned plus cognitive effects were categorized as "severe" (12%). There was no dose-dependent relationship between the amount of NO used and clinical impairment. There was a trend between the severity of neurologic impairment and serum levels of B12. Two patients were noncompliant. One initiated only oral therapy and did not improve. One received injections a month apart and worsened.. Patients with NOID tend to have worse symptoms when presenting with lower serum vitamin B12 levels and have good recovery rates when treated with intramuscular B12 and oral supplementation.

Topics: Demyelinating Diseases; Humans; Injections, Intramuscular; Nitrous Oxide; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anesthetics, Inhalation; Ataxia; Demyelinating Diseases; Female; Humans; Inhalant Abuse; Magnetic Resonance Imaging; Male; Medical Futility; Memory Disorders; Mental Disorders; Mood Disorders; Nitrous Oxide; Psychoses, Substance-Induced; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Young Adult

Nitrous oxide is commonly used as an analgesic and anaesthetic agent. Nitrous oxide is also in use in industry as an aerosol propellant and is now recognised as a recreational drug whose use is growing, especially among the young. Nitrous oxide from whipped cream canisters is inhaled to produce a dissociative, intoxicated state. Nitrous oxide is known to inactivate vitamin B12 via oxidation, which can precipitate a demyelinating myelopathy akin to the classical B12 deficiency syndrome, subacute combined degeneration of the spinal cord. This case describes a young woman with chronic pain and a poor nutritional state who took regular nitrous oxide as an opiate-sparing agent. She developed a progressive subacute myelopathy with a sensory level, profoundly impaired joint position sense, extensor plantars and required a wheelchair. Once diagnosed, she responded well to a regime of nitrous oxide withdrawal, high-dose B12 replacement and physiotherapy. The case illustrates the need for clinical teams to be able to dentify a nitrous oxide-precipitated myelopathy as its use as a drug of abuse increases; particularly in the case of malnourished patients who receive nitrous oxide surgically or obstetrically.

Topics: Accidental Falls; Adult; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Chronic Pain; Demyelinating Diseases; Female; Humans; Nitrous Oxide; Pain Management; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Nitrous oxide (N₂O) toxicity can result in myelin loss and hyperhomocysteinemia similar to cobalamin (Cbl) deficiency. Studies on N₂O exposure can help in understanding the mechanism of demyelination. In view of paucity of studies on N₂O toxicity in rats this study was undertaken. Six male wistar rats were exposed to 1.5L/min N₂O with 1:1 O₂ for 90 min daily for 1 month. After 1-month exposure blood homocysteine (HCY) and oxidative stress parameters glutathione (GSH) and total antioxidant capacity (TAC) were measured. Brain and spinal cord was subjected to histopathological examination. The neurobehavioral changes, oxidative stress parameters and histopathological changes were correlated with serum B12 and HCY level. After 1-month exposure, the rats appeared sluggish, lethargic and developed predominantly hind limb weakness for 1-1.5h. In the exposed group, the total distance traveled (2001.66 ± 118.27 cm; p=0.037), time moving (80.16 ± 5.7s; p=0.028), number of rearing (10.33 ± 1.45; p=0.014) and grip strength (1042.40 ± 51.3N; p=0.041) were significantly decreased whereas, resting time significantly increased (219.83 ± 5.7s; p=0.030) compared to controls. Serum HCY level was significantly increased (20.56 ± 1.296 μm/ml; p=0.0007) in the exposed group. However, serum B12 and folic acid levels were not significantly different. GSH significantly decreased (2.21 ± 0.60 mg/dl; p=0.018) along with TAC (0.76 ± 0.16 Trolox_Eq_mmol/l; p=0.036). The histopathological studies revealed shrinkage and vacuolation of neurons in cerebral cortex, focal myelin loss, vacuolation in subcortical white matter and spinal cord. N₂O exposure results in behavioral alterations, hyperhomocysteinemia, cortical and spinal cord demyelination which were associated with decrease GSH and TAC highlighting pathophysiological role of oxidative stress.

Topics: Animals; Antioxidants; Behavior, Animal; Brain; Demyelinating Diseases; Disease Models, Animal; Glutathione; Homocysteine; Hyperhomocysteinemia; Male; Motor Activity; Muscle Strength; Nitrous Oxide; Oxidative Stress; Rats, Wistar; Spinal Cord; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Herein, we report a case of a 20-year-old (ethnicity not reported) woman with a history of nitrous oxide abuse and clinical symptoms consistent with spinal cord subacute combined degeneration with associated low serum concentrations of vitamin B12, elevated methylmalonic acid levels, and radiologic evidence of demyelination of the dorsal region of the spinal column. The health of the patient improved dramatically with B12 supplementation. In this case, we discuss the interaction of nitrous oxide with the enzymatic pathways involved in the biochemistry of vitamin B12.

Topics: Adult; Demyelinating Diseases; Female; Humans; Methylmalonic Acid; Nitrous Oxide; Paresthesia; Spinal Cord Diseases; Substance-Related Disorders; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS.

Topics: Animals; Antineoplastic Agents, Phytogenic; Autoimmune Diseases; Demyelinating Diseases; Drug Synergism; Gliosis; Methylation; Mice; Mice, Inbred Strains; Mice, Transgenic; Myelin Basic Protein; Nerve Fibers, Myelinated; Nerve Regeneration; Paclitaxel; STAT1 Transcription Factor; T-Lymphocytes; Vitamin B 12; Vitamin B Complex

Topics: Cervical Vertebrae; Demyelinating Diseases; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Nerve Fibers, Myelinated; Neural Pathways; Neurodegenerative Diseases; Spinal Cord; Spinal Cord Diseases; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Demyelinating Diseases; Diagnosis, Differential; Diet, Vegetarian; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Neurologic Examination; Peripheral Nervous System Diseases; Spinal Cord; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Interferon-beta is a mainstay therapy of demyelinating diseases, but its effects are incomplete in human multiple sclerosis and several of its animal models. In this study, we demonstrate dramatic improvements of clinical, histological, and laboratory parameters in in vivo mouse models of demyelinating disease through combination therapy with IFN-beta plus vitamin B(12) cyanocobalamin (B(12)CN) in nonautoimmune primary demyelinating ND4 (DM20) transgenics, and in acute and chronic experimental autoimmune encephalomyelitis in SJL mice. Clinical improvement (p values <0.0001) was paralleled by near normal motor function, reduced astrocytosis, and reduced demyelination. IFN-beta plus B(12)CN enhanced in vivo and in vitro oligodendrocyte maturation. In vivo and in vitro altered expression patterns of reduced Notch-1 and enhanced expression of sonic hedgehog and its receptor were consistent with oligodendrocyte maturation and remyelination. IFN-beta-B(12)CN combination therapy may be promising for the treatment of multiple sclerosis.

Topics: Acute Disease; Animals; Brain; Cell Line; Chronic Disease; Demyelinating Diseases; Drug Synergism; Drug Therapy, Combination; Encephalomyelitis, Autoimmune, Experimental; Female; Hedgehog Proteins; Humans; Interferon-beta; Mice; Mice, Inbred Strains; Mice, Transgenic; Oligodendroglia; Peptide Fragments; Receptor, Notch1; Receptors, Cell Surface; Stem Cells; Trans-Activators; Transcription Factors; Vitamin B 12

Topics: Aged; Demyelinating Diseases; Female; Humans; Magnetic Resonance Imaging; Nerve Degeneration; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Deficiency of vitamin B12 may produce neuropsychiatric disturbances. In the CNS the disease affects mainly myelin sheaths, and the spongy degeneration and diffuse demyelination of the posterior and lateral columns of the spinal cord are the classical pathological changes in patients with subacute combined degeneration. Similar changes also occur in cerebral hemispheres and MRI abnormalities in brain of such patients could be expected, but have received little attention. We report a case of pernicious anemia with neurological manifestations and brain MRI abnormalities. We discuss the neuropathological aspects and we suggest that pernicious anemia is a differential diagnosis to consider in central demyelinating lesions at MRI.

Topics: Acute Disease; Anemia, Pernicious; Brain Diseases; Demyelinating Diseases; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Middle Aged; Spinal Cord Diseases; Vitamin B 12

Topics: Demyelinating Diseases; Homocysteine; Humans; Vitamin B 12; Vitamin B 12 Deficiency

We report a 35-year-old patient with megaloblastic anemia who presented with features of subacute combined degeneration of the cord. Electrophysiological studies showed features of axonal neuropathy. In addition, there was evidence of prominent focal proximal conduction block in several nerves. After treatment with cyanocobalamin the neuropathy improved, and the peripheral nerve conduction block detected earlier disappeared. Reversible nerve conduction block as a feature of vitamin B12 deficiency in man, to our knowledge, has not been reported in literature, so far.

Topics: Adult; Axons; Demyelinating Diseases; Humans; Male; Neural Conduction; Peripheral Nerves; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Subacute combined degeneration is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord and even more rarely of the pyramidal and spinocerebellar tracts and cerebellum. We present the initial and follow-up MRI appearances in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B12 deficiency. The lesions in these structures were demonstrated clearly as pathologically high-signal areas on T2-weighted images. These lesions, except those of the brain stem and cerebellum, disappeared 4 months after therapy. MRI 14 months after the patient's discharge on vitamin B12 therapy showed the same picture.

Topics: Brain Stem; Cerebellum; Demyelinating Diseases; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Lack of vitamin B12 in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. We report the case of a 14(1)/2-month-old child of strictly vegetarian parents who presented with severe psychomotor retardation. This severely hypotonic child had anemia due to insufficient maternal intake of vitamin B12 with associated megaloblastic anemia. MRI of the brain revealed severe brain atrophy with signs of retarded myelination, the frontal and temporal lobes being most severely affected. It was concluded that this myelination retardation was due to insufficient intake of vitamin B12 and vitamin B12 therapy was instituted. The patient responded well with improvement of clinical and imaging abnormalities. We stress the importance of MRI in the diagnosis and follow-up of patients with suspected diseases of myelination.

Topics: Anemia, Megaloblastic; Atrophy; Brain; Demyelinating Diseases; Diet, Vegetarian; Female; Follow-Up Studies; Frontal Lobe; Humans; Infant; Magnetic Resonance Imaging; Muscle Hypotonia; Myelin Sheath; Pregnancy; Prenatal Exposure Delayed Effects; Psychomotor Performance; Temporal Lobe; Vitamin B 12; Vitamin B 12 Deficiency

The catalysis by phosphatidylethanolamine methyltransferase (PEMT) of phosphatidylcholine (PC) synthesis by the successive methylation of phosphatidylethanolamine in the presence of S-adenosylmethionine (AdoMet) as methyl donor, was detected in actively myelinating mouse brains. PEMT activity in the microsome fraction of fetal mouse brain at 17 days of gestation was 253 mu u/mg protein and that of adult brain after 7 days of remyelination following 6 weeks cuprizone administration was 148 mu u/mg. These figures are much higher than found in normal adult brains (1.7 mu u/mg). An increase in PEMT activity was observed in the brains of genetically transmitted diabetic mice, C57BL/KsJ-db/db, and streptozotocin-induced diabetic mice; 16.3 and 9.2 mu u/mg, respectively. The methyl group of mecobalamin was transferred to homocysteine producing AdoMet and was further metabolized into choline and acetylcholine in brain slices. These results suggest that in the diabetic state, an increase in PC synthesis is probably required in order to replace damaged myelin or to supply choline or acetylcholine essential to for nerve functions. Mecobalamin might serve as the source of the methyl group utilized for PC synthesis.

Topics: Animals; Brain; Cuprizone; Demyelinating Diseases; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Humans; Methyltransferases; Mice; Mice, Inbred C57BL; Phosphatidylethanolamine N-Methyltransferase; Vitamin B 12

In a total of 55 samples of cerebrospinal fluid (CSF) and an equal number of serum samples obtained from 45 patients with neurological disorders and 10 controls, folic acid and vitamin B12 were measured. A radioisotopic assay method was used. A significant decrease of CSF folic acid was noted in the group with cerebral tumors.

Topics: Brain Neoplasms; Central Nervous System Diseases; Demyelinating Diseases; Folic Acid; Humans; Meningitis; Vitamin B 12

Topics: Demyelinating Diseases; DNA; Folic Acid; Humans; Peripheral Nerves; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

To study the cobalamin content of the brains in various clinico-pathologic states in the elderly, the patho-histology and cobalamin content were examined in autopsy brains with special attention to the temporal and frontal lobes. Consequently, a decrease of cobalamin contents and its binding protein (binder) was found in brains with dementia, severe neuronal loss, myelin degeneration, brain atrophy, ventricular dilatation, and vascular lesions in comparison with those in the controls.

Topics: Aged; Brain; Brain Diseases; Dementia; Demyelinating Diseases; Frontal Lobe; Humans; Subcellular Fractions; Temporal Lobe; Transcobalamins; Vitamin B 12

Four pairs of monkeys were maintained in an atmosphere of nitrous oxide under conditions which had previously been shown to produce subacute combined degeneration (SCD) of the spinal cord. The diet of one of each pair was supplemented with methionine. In every case the monkey with the unsupplemented diet became ataxic at around 10 weeks and the disorder progressed over a period of 2-3 weeks until the animal was moribund. During this period there was no detectable clinical change in the monkeys receiving methionine supplementation. Microscopical examination of the spinal cord and peripheral nerves of the unsupplemented monkeys showed the classical changes of SCD. The histological changes correlated with the clinical observations. Sections form the methionine-supplemented monkeys showed no change or only slight changes. These results suggest that, in these animals, inability to resynthesise methionine from homocysteine leads to SCD. It seems probable that the primary lesion producing SCD in human beings with pernicious anaemia is also inability to maintain methionine biosynthesis.

Topics: Animals; Demyelinating Diseases; Disease Models, Animal; Humans; Macaca fascicularis; Methionine; Nitrous Oxide; Spinal Cord; Spinal Cord Diseases; Tetrahydrofolates; Vitamin B 12

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Bone Marrow Cells; Demyelinating Diseases; Disease Models, Animal; Erythrocyte Count; Erythrocytes; Folic Acid; Haplorhini; Hematocrit; Hemoglobins; Leukocyte Count; Liver; Macaca; Male; Malonates; Nervous System; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Atrophy; Autopsy; Blood Vessels; Brain; Brain Chemistry; Cerebrosides; Child; Cholesterol; Chromatography, Thin Layer; Demyelinating Diseases; Esters; Fatty Acids; Fatty Acids, Unsaturated; Female; Galactose; Gliosis; Globus Pallidus; Homocystinuria; Humans; Malonates; Metabolism, Inborn Errors; Phosphatidylcholines; Phospholipids; Sphingomyelins; Sulfoglycosphingolipids; Vitamin B 12

Topics: Animals; Demyelinating Diseases; Diet; Female; Haplorhini; Macaca; Macrophages; Male; Monkey Diseases; Nerve Degeneration; Neurofibrils; Papio; Peripheral Nervous System Diseases; Pregnancy; Ranvier's Nodes; Sciatic Nerve; Tibial Nerve; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Brain; Demyelinating Diseases; Diet; Erythrocyte Count; Haplorhini; Hematocrit; Hemoglobins; Macaca; Monkey Diseases; Nerve Degeneration; Nervous System; Papio; Paralysis; Peripheral Nerves; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Demyelinating Diseases; Haplorhini; Nerve Degeneration; Paralysis; Vitamin B 12

Topics: Adrenocorticotropic Hormone; Demyelinating Diseases; Humans; Spinal Cord Diseases; Vitamin B 12

Topics: Amblyopia; Animals; Cyanides; Demyelinating Diseases; Humans; Hydroxocobalamin; Male; Rats; Smoking; Vitamin B 12