Vitamin spinal cord degeneration

Pernicious anemia is the megaloblastic anemia due specifically to vitamin B12 deficiency, in which there is also spinal cord degeneration and peripheral neuropathy. It is a disease of later life. Only about 10% of patients are under age 40 by the age of 60, about 1% of the population is affected, rising to 2% to 5% of people over age 65, as a result of atrophic gastritis and thus impaired absorption of vitamin B12 (Section 10.7.1). 

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... 

Vitamin B12 —> megaloblastic anemia, neuropathy, and spinal cord degeneration... 

Dietary deficiency of vitamin B occurs only in strict vegans, as the vitamin is found almost exclusively in animal foods. However, functional deficiency (pernicious anaemia, with spinal cord degeneration), as a result of impaired absorption, is relatively common, especially in elderly people with atrophic gastritis. 

The other clinical feature of vitamin B deficiency, which is very rarely seen in folic acid deficiency, is degeneration of the spinal cord - hence the name pernicious for the anaemia of vitamin B deficiency. The spinal cord degeneration is due to a failure of the methylation of one arginine residue on myelin basic protein and occurs in about one-third of patients with megaloblastic anaemia due to vitamin B deficiency and in about one-third of patients who do not show signs of anaemia. 

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... 

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. 

In >crnicious anemia, the hone marrow fails to produce mature erythrocytes as a result of defective cell division, a consequence of impaired DNA synthesis which requires vitamin BI If the disease goes unlreaietl, extensive neurological damage, c.g.. irreversible degeneration of the spinal cord by deinyeliniralinn. may occur hccausc of faulty fatly acid metabolism. 

High-dose pretreatment with vitamin E (1000IU p.o. once daily for 5 days) has been shown to promote the chronic recovery of spinal-cord injured cats [45]. This is consistent with its ability to prevent post-traumatic spinal-cord hypoperfusion [29] and lipid peroxidation [8] and with the hypothesis that oxygen-radical generation and lipid peroxidation are important mediators of post-traumatic spinal-cord pathophysiology and degeneration. 

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. 

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. 

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). 

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. 

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