B-12

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Folate, vitamin B12, and neuropsychiatric disorders.

Bottiglieri T

H. Courtwright and ph W. Summers Institute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas, USA.

Folate and vitamin B12 are required both in the methylation of homocysteine to methionine and in the synthesis of S-adenosylmethionine. S-adenosylmethionine is involved in numerous methylation reactions involving proteins, phospholipids, DNA, and neurotransmitter metabolism. Both folate and vitamin B12 deficiency may cause similar neurologic and psychiatric disturbances including depression, dementia, and a demyelinating myelopathy. A current theory proposes that a defect in methylation processes is central to the biochemical basis of the neuropsychiatry of these vitamin deficiencies. Folate deficiency may specifically affect central monoamine metabolism and aggravate depressive disorders. In addition, the neurotoxic effects of homocysteine may also play a role in the neurologic and psychiatric disturbances that are associated with folate and vitamin B12 deficiency.

Gen Hosp Psychiatry 1994 May;16(3):224-228

Dietary vitamin B12 deficiency in a patient with multiple sclerosis.

Gruener DM, Kunkel EJ, Snyderman DA, Infante MR, Rodgers C, Field HL

Department of Psychiatry and Human Behavior, Jefferson Medical College, Philadelphia, PA.

The authors present a case of dietary vitamin B12 deficiency in a patient with multiple sclerosis. A simple schemata for evaluating patients for vitamin B12 deficiency is included as a clinical aid for physicians.

Ger J Ophthalmol 1993 Aug;2(4-5):234-240

Uncommon chiasmal lesions: demyelinating disease, vasculitis, and cobalamin deficiency.

Wilhelm H, Grodd W, Schiefer U, Zrenner E

Universitats-Augenklinik Tubingen, Abteilung fur Pathophysiologie des Sehens and Neuroophthalmologie, Germany.

We report on eight patients who presented for evaluation of unexplained visual loss. They all showed a typical chiasmal visual field defect (bitemporal hemianopia, junction scotoma). In all patients, high-resolution computer-assisted tomographic (CT) scans of the sellar region were normal, and neither the medical history nor additional ophthalmological findings pointed to any explanation for the underlying disease. Six patients seemed to have suffered from chiasmal optic neuritis. Magnetic resonance imaging (MRI) scans could elucidate the diagnosis in five cases: white-matter lesions typical of multiple sclerosis (MS) were found and, additionally, in four cases an enlargement of the chiasm or barrier defect was revealed in post-gadolinium MRI. In one patient, MRI was normal. He recovered completely after megadose steroid therapy. One patient developed motoric symptoms of MS during the following year, another patient had mild sensory symptoms and recurrence of severe optic neuritis. An MR-proven chiasmal lesion due to a leukocytoclastic immunovasculitis combined with small subcortical white-matter lesions was diagnosed in another patient. The field defects disappeared spontaneously. In a 28-year-old woman a low vitamin B12 level was found in routine blood samples. Parenteral vitamin B12 substitution led to an almost complete recovery of the visual field defects. Chiasmal optic neuritis may occur isolated or during the course of MS. Megadose steroids may be of value if contraindications have been ruled out. A chiasmal visual field defect caused by vitamin B12 deficiency is very uncommon. A similar case was reported in 1961.

Int J Neurosci 1993 Jul;71(1-4):93-99

Vitamin B12 and its relationship to age of onset of multiple sclerosis.

Sandyk R, Awerbuch GI

NeuroCommunication Research Laboratories, Danbury, CT 06811.

Attention has been focused recently on the association between vitamin B12 metabolism and the pathogenesis of multiple sclerosis (MS). Several recent reports have documented vitamin B12 deficiency in patients with MS. The etiology of this deficiency in MS is unknown. The majority of these patients do not have pernicious anemia and serum levels of the vitamin are unrelated to the course or chronicity of the disease. Moreover, vitamin B12 does not reverse the associated macrocytic anemia nor are the neurological deficits of MS improved following supplementation with vitamin B12. It has been suggested that vitamin B12 deficiency may render the patient more vulnerable to the putative viral and/or immunologic mechanisms widely suspected in MS. In the present communication, we report that serum vitamin B12 levels in MS patients are related to the age of onset of the disease. Specifically, we found in 45 MS patients that vitamin B12 levels were significantly lower in those who experienced the onset of first neurological symptoms prior to age 18 years (N = 10) compared to patients in whom the disease first manifested after age 18 (N = 35). In contrast, serum folate levels were unrelated to age of onset of the disease. As vitamin B12 levels were statistically unrelated to chronicity of illness, these findings suggest a specific association between the timing of onset of first neurological symptoms of MS and vitamin B12 metabolism. In addition, since vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of critical pathogenetic significance.

J Neurol 1993 May;240(5):305-308

Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone.

Frequin ST, Wevers RA, Braam M, Barkhof F, Hommes OR

Department of Neurology, University Hospital Nijmegen, The Netherlands.

Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59, P = 0.0084) between serum vitamin B12 and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of vitamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B12 and folate were below the reference medians. We hypothesize that low or reduced vitamin B12/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low vitamin B12/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B12 and folate metabolism in patients with MS.

J Neuroimmunol 1992 Oct;40(2-3):225-230

Multiple sclerosis and vitamin B12 metabolism.

Reynolds EH

Maudsley Hospital, London, UK.

Multiple sclerosis (MS) is occasionally associated with vitamin B12 deficiency. Recent studies have shown an increased risk of macrocytosis, low serum and/or CSF vitamin B12 levels, raised plasma homocysteine and raised unsaturated R-binder capacity in MS. The aetiology of the vitamin B12 deficiency in MS is often uncertain and a disorder of vitamin B12 binding or transport is suspected. The nature of the association of vitamin B12 deficiency and MS is unclear but is likely to be more than coincidental. There is a remarkable similarity in the epidemiology of MS and pernicious anaemia. Vitamin B12 deficiency should always be looked for in MS. The deficiency may aggravate MS or impair recovery. There is evidence that vitamin B12 is important for myelin synthesis and integrity but further basic studies are required.

Arch Neurol 1992 Jul;49(7):683-684

Biologically significant serum vitamin B12 deficiency in multiple sclerosis inadequately documented.

[LETTER]

Goodkin DE, sen DW, Green R

Vitamin B12 metabolism in multiple sclerosis.

Reynolds EH, Bottiglieri T, Laundy M, Crellin RF, Kirker SG

Department of Neurology, King's College Hospital, London, England.

We have previously described 10 patients with multiple sclerosis (MS) and unusual vitamin B12 deficiency. We have therefore studied vitamin B12 metabolism in 29 consecutive cases of MS, 17 neurological controls, and 31 normal subjects. Patients with MS had significantly lower serum vitamin B12 levels and significantly higher unsaturated R-binder capacities than neurological and normal controls, and they were significantly macrocytic compared with normal controls. Nine patients with MS had serum vitamin B12 levels less than 147 pmol/L and, in the absence of anemia, this subgroup was significantly macrocytic and had significantly lower red blood cell folate levels than neurological and normal controls. Nine patients with MS had raised plasma unsaturated R-binder capacities, including three patients with very high values. There is a significant association between MS and disturbed vitamin B12 metabolism. Vitamin B12 deficiency should always be looked for in patients with MS. The cause of the vitamin B12 disorder and the nature of the overlap with MS deserve further investigation. Coexisting vitamin B12 deficiency might aggravate MS or impair recovery from MS.

J Neurol Neurosurg Psychiatry 1992 May;55(5):339-340

Multiple sclerosis and vitamin B12 metabolism.

[EDITORIAL]

Reynolds EH

Arch Neurol 1991 Aug;48(8):808-811

Multiple sclerosis associated with vitamin B12 deficiency.

Reynolds EH, Linnell JC, Faludy JE

Department of Neurology, King's College Hospital, London, England.

We describe 10 patients with a previously unreported, to our knowledge, association of multiple sclerosis and unusual vitamin B12 deficiency. The clinical features and the age at presentation were typical of multiple sclerosis, with eight cases occurring before age 40 years, which is a rare age for vitamin B12 deficiency. Nine patients had hematologic abnormalities, but only two were anemic. All six patients examined had low erythrocyte cobalamin levels. Only two patients had pernicious anemia; in the remaining patients the vitamin B12 deficiency was unexplained. A vitamin B12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder.

J Neurol Neurosurg Psychiatry 1990 Nov;53(11):951-954

Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia.

Nijst TQ, Wevers RA, Schoonderwaldt HC, Hommes OR, de Haan AF

Institute of Neurology, University Hospital, Nijmegen, The Netherlands.

Vitamin B12 and folate concentrations were measured in serum and cerebrospinal fluid (CSF) in 293 neurological patients. Serum and CSF vitamin B12 concentrations showed a positive correlation. In individual patients CSF B12 concentrations varied considerably for a given serum concentration. The median serum vitamin B12 concentration of the Alzheimer's type dementia group was significantly lower compared with that of a control group. Lower median CSF vitamin B12 concentrations were found in groups of patients with multiple sclerosis and Alzheimer's type dementia. Five patients with heterogeneous clinical pictures had unexplained low serum and CSF B12 concentrations without macrocytosis. Two patients had very high serum B12 and low-normal CSF concentrations which could be explained by a blood-brain barrier transport defect. Serum and CSF folate concentrations did not show significant differences between the various groups.

Lancet 1990 May 26;335(8700):1285-1286

Vitamin B12 deficiency and multiple sclerosis.

[LETTER]

Ransohoff RM, sen DW, Green R

Acta Neurol Scand 1990 May;81(5):388-391

Multiple sclerosis and macrocytosis.

Crellin RF, Bottiglieri T, Reynolds EH

Department of Neurology, King's College Hospital London, England.

Twenty-seven patients with multiple sclerosis had mild but significant macrocytosis when compared with an individually matched neurological control group and the normal laboratory reference range. The cause of the macrocytosis is unknown, but our recent clinical observations implicate a possible disturbance in vitamin B12 metabolism, binding or transport.