IX. EFFECTS OF DEFICIENCY 211 



muscular injection is about lifty times as great as when administeicd l)y 

 mouth, wliereas PGA is almost as effective by the oral as by the parenteral 

 route of administration. It was not long before even more convincing evi- 

 dence was at hand clearly distinguishing between PGA and KWY and 

 demonstrating that the former constituted incomplete therapy for per- 

 nicious anemia. The occurrence and progression of subacute combined 

 degeneration of the spinal cord in pernicious anemia patients recei\ing 

 PGA was first reported by Vilter et aU^^ Adchtional reports of similar 

 obser\'ations soon appeared in the literature. '^^-"^ The accumulated ex- 

 perience of these authors as well as that of many other clinical observers 

 enable the following conclusions to be drawn with respect to the effects of 

 PG.V therapy in pernicious anemia. Most, if not all, patients receiving this 

 medication as the only form of specific treatment ultimately develop some 

 degree of relapse. The time required for hematologic abnormaUties to occur 

 varies from a few weeks to one 3'ear or longer. Glossitis may appear during 

 PGA administration, even when the blood values are normal. Paresthesias 

 and evidence of combined system disease may develop insidiously months 

 after PGA therapy is instituted, or rapidly progressive nervous system 

 damage may take place during the initial treatment period while the eryth- 

 rocyte count is rising. Some patients experience glossitis or a fall in blood 

 \'alues after long-continued PGA administration without ever showing evi- 

 dence of peripheral or central neiu'opathy. The mode of action of PGA 

 with reference to nervous S3^stem injury is not well understood. It is the 

 opinion of some observers that the complication is more likely to develop 

 in patients whose diets have been poor. In the writer's experience, no such 

 correlation has been apparent, and the most rapidly progressive cases of 

 ner\'ous system involvement occurred in patients who were not severely ill 

 with anemia and whose dietary histories were good. It is a widely held 

 impression, which the writer shares, that relatively large daily doses of 

 PGA, 10 to 20 mg. or more, are especially likely to be associated with the 

 development of neuropathy. Institution of liver extract or vitamin B12 

 therapy arrests the progress of the condition and, if begun early, reverses 

 much of the functional impairment associated with peripheral and central 

 nervous system disease. There is no e\'idence that PGA is toxic to nerve 



"» C. F. Vilter, R. W. Vilter, and T. D. Spies, Proc. Central Soc. Clin. Research 19, 



26 (1946). 

 '" B. E. Hall and C. H. Watkins, J. Lab. Clin. Med. 32, 622 (1947). 

 "0 L. M. Meyer, Blood 2, 50 (1947). 



"' R. W. Heinle and \. D. Welch, /. Am. Med. Assoc. 133, 749 (1947). 

 "= F. H. Bethell and C. C. Sturgis, Blood 3, 57 (1948). 

 ^o' J. F. Ross, H. Belding, and B. L. Paegel, Blood 3, 6S (1948). 

 •"* S. O. Schwartz, S. R. Kaplan, and B. E. .\rm.strong, /. Lab. Clin. Med. 35, 894 



(1950). 



