vitamin-b-12 and AIDS-Dementia-Complex

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

There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology. The Cobalamin deficiency could be either a consequence or cause of amyloidogenesis. Cobalamin deficiency is also associated with the acquired immunodeficiency syndrome (AIDS). A common pathogenic mechanism may exist for AIDS dementia complex (ADC) and AD, but there is no explanation at present for these associations. This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Topics: AIDS Dementia Complex; Alzheimer Disease; Humans; Models, Biological; Trypsin; Trypsin Inhibitors; Vitamin B 12; Vitamin B 12 Deficiency

The human immunodeficiency virus (HIV)-associated dementia complex is characterized by difficulties in concentration and memory followed by apathy, social withdrawal and motor dysfunction. Decreased serum vitamin B12 levels occur in up to 20% of patients with acquired immune deficiency syndrome (AIDS) and may adversely contribute to the haematologic and neurologic dysfunction which is frequently attributed to the human immunodeficiency virus. We describe a patient with AIDS who presented with an apparent advanced AIDS dementia complex. There was an associated low serum vitamin B12 resulting from malabsorption due to low gastric intrinsic factor secretion. Following treatment with vitamin B12 the symptoms resolved over a 2-month period. We believe that the AIDS dementia complex represented a reversible adverse synergistic interaction between the human immunodeficiency virus and vitamin B12 deficiency.

Topics: Adult; AIDS Dementia Complex; HIV-1; Humans; Male; Remission Induction; Substance Abuse, Intravenous; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency