Combined degeneration of spinal cord

R12. Ross, J. F., Belding, H. W., and Paegel, B. L., Development and progression of subacute combined degeneration of spinal cord in patients with pernicious anemia treated with synthetic pteroyl glutamic (folic) acid. Blood 3, 68-90 (1948). 

Deficiency symptoms are glossitis, GIT disturbances, megaloblastic anaemia, subacute combined degeneration of spinal cord, peripheral neuritis, poor memory, mood changes and hallucinations. 

Many cases are refractory to vitamin B12 (Israels and Sharp, 1950 Tuck and Whittaker, 1950). Some of the cases studied by Cox et al. (unpublished) have responded poorly or not at all to vitamin B12 (Fig. 9). In all the refractory cases so far reported, the patients have responded to folic acid or to the citrovorum factor, but not all attained normal blood values, even after prolonged treatment. In patients undergoing treatment with folic acid, cerebral, spinal, or neural disorders occasionally develop sometimes these can be arrested or alleviated by administering vitamin Bi2. Cloake et al. (1954) describe 18 patients with a variety of neurological disorders associated with steatorrhea. None had all the essential characteristics of true subacute combined degeneration of the cord. Results of treatment with vitamin B12 or other B vitamins varied unaccountably. 

The chemistry, metabolism, and clinical importance of folic acid have been the subject of many excellent reviews (A7, Gil, H14, H20, Rl). Folic acid deficiency leads to a macrocytic anemia and leucopenia. These symptoms are due to inadequate synthesis of nucleic acid. The synthesis of purine bases and of thymine, required for nucleic acid synthesis, is impaired in folic acid deficiency. Detection of folic acid activity in biologic fluids and tissues is of the utmost importance it distinguishes between the various anemias, e.g., those due to vitamin Bi2 or folic acid deficiency. Because morphology of the abnormal red cell does not help in diagnosing vitamin deficiency, one must rely on assay methods for differential diagnosis. Treatment of pernicious anemia with folic acid has led to subacute combined degeneration of the spinal cord despite... 

Vitamin B12 deficiency is accompanied by neurological degeneration in about two-thirds of cases - either peripheral neuropathy or subacute combined degeneration of the spinal cord. Folic acid deficiency is only rarely associated with similar neurological damage. 

Subacute combined degeneration of the spinal cord is from demyelination of the corticospinal tracts and posterior columns of the spinal cord, leading to gait ataxia and loss of position sense and vibratory sense. Peripheral neuropathy leads to loss of cutaneous sensation and tendon reflexes (Savage and Lindenbaum, 1995). 

Agamanolis DP, Victor M, Harris JW, Hines JD, Chester EM, Kark JA (1978) An ultrastructural study of subacute combined degeneration of the spinal cord in vitamin B12-deficient rhesus monkeys. J Neuropathol Exp Neurol 37(3) 273-299... 

One of the biochemical adverse effects of nitric oxide is inactivation of vitamin B12, with subsequent potentiation of folate deficiency (19). This effect is mediated by irreversible oxidation of the cobalt residue in vitamin B12 to its Co++ and Co forms. This leads to a reduction in methionine synthetase activity, with downstream effects on DNA synthesis. Previous studies have identified five patients with unsuspected vitamin B12 deficiency who developed subacute combined degeneration of the spinal cord following inhalation anesthesia with nitrous oxide... 

Victor, M., and Lear, A. A., 1956, Subacute combined degeneration of the spinal cord— Current concepts of the disease process. Value of serum vitamin Bjj determinations in clarifying some of the common clinical problems. Am. J. Med. 20 896. 

The patient frequently has severe glossitis, gastrointestinal complaints, and may develop neurologic lesions which include subacute combined degeneration of the spinal cord and peripheral neuritis. 

Vitamin 8,2 deficiency results in pernicious anaemia. In this condition there is a delayed maturation of erythrocytes due to the impairment of DNA synthesis. This results in the appearance of megaloblasts in the blood. Deficiency of vitamin 8,2 also results in a neurological condition (subacute combined degeneration of the spinal cord). 

Prescribing perspective is vital so that, if there is any doubt as to whether the macrocytic anaemia is due to shortage of folate acid or vitamin B12, then 1000 mg of the latter must be given by intramuscular injection prior to starting the oral replacement. This will protect the patient from inadvertent precipitation of irreversible damage to the spinal cord known as subacute combined degeneration. 

Degeneration of the brain, spinal cord (subacute combined degeneration) and peripheral nerves symptoms may be psychiatric and physical... 

HIV leukoencephalopathy is characterized by diffuse damage to the white matter with loss of myelin, reactive astrogliosis, multinucleated cells, and macrophages. IHC or ISH helps confirm the association of HIV with the process. Leukoencephalopathy occasionally manifests as marked vacuolar myelin swelling. This finding is more common in the spinal cord, however, where it forms multiple foci of vacuolar myelopathy that resemble combined systems degeneration without pernicious anemia. 

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