CHRONIC CYANIDE INTOXICATION AND A DEGENERATIVE NEUROPATHY IN NIGERIA

Abstract

The relevant literature on nutritional neuropathies described mainly in tropical countries, and in prisoners of war is reviewed. An account is given of the history of thoughts on the possible aetiological factors involved in the pathogenesis of an ataxic neuropathy described from Nigeria. A dietary toxin such as cyanide from cyanogenetic glycosides, which are widely distributed in tropical countries is implicated as the most important factor. The biological and neuropathological effects of cyanide and methods of investigating and determining the degree of exposure to cyanide are outlined. A detailed account of the ataxic neuropathy as found in 320 patients encountered in this study is presented. It is established that other systemic neurological degenerations may coexist with the ataxic neuropathy. Evidence is produced to show that protein - calorie deficiency, and deficiency of water-soluble. vitamins are not important factors in the aetiology of the disease. It is possible that riboflavin intake is low in patient, but riboflavin intake appears to be low in most Nigerians. Histological examination of peripheral nerves of patients with ataxic neuropathy showed demyelination. The finding of reduced motor nerve conduction velocity even in patients who have no clinical evidence of polyneuropathy supports the histological finding. Biochemical evidence of increased exposure to cyanide of dietary origin, is presented. The plasma thiocyanate, cyanide and urinary excretion of thiocyanate are raised in patient, compared with controls, and fall when patients are fed on diets free of cassava. The levels rise again when the patients, return to cassava diet. Serum hydroxo-cobalamin level is reduced in patients. Serum cyanocohalamin is raised. There is reduced level or absence of the sulphur-containing amino acids in the plasma. Rhodanese activity in the liver in patients is normal. Cyanide is released from cassava derivative on acid hydrolysis with dilute hydrochloric acid in vitro as well as in vitro (intragastric). Epidemiological data show a positive correlation between the prevalence of the disease and consumption of cassava meals. Cassava processers and farmers who grow and handle cassava may be at special risk to develop the disease. There is no evidence at the moment of genetical factors in determining susceptibility to the disease. The evidence suggests a common environmental factor responsible for the disease in multiple familial or conjugal cases. This appears to be diet. There is higher prevalence of goitre in patients than in normals. This may be due to raised plasma thiocyanate which inhibits uptake of iodine by thyroid cells. The endemic belt for ataxic neuropathy is geographically the same southern belt for goitre in Western Nigeria. Therapeutic trial of hydroxoccbalamin and riboflavin over a period of twelve months showed no beneficial effects of the drug used. In Wistar rats fed on cassava diet for varying period, (between 6 -18 months), plasma thiocyanate is raised and rhodanese activity in various tissues is normal. Two rats maintained on cassava diet for 18 months developed ataxia. Histological examination of sciatic nerves of these rats, as well as six other rats maintained on cassava diet for eighteen months, showed diffuse as well as segmental demyelination. It is concluded that in the aetiology of the ataxic neuropathy as defined in this study, chronic cyanide intoxication of dietary origin is the most important factor. The main source of cyanide is cassava. However, it is likely that other factors, such as lack of first class protein and riboflavin deficiency may summate with the neuropathological effects of chronic cyanide poisoning of dietary origin.