Endemic ataxic polyneuropathy in Nigeria

Abstract: Ataxic polyneuropathy is a neurological syndrome that was described from an endemic area in south-western Nigeria in the 1950s and 1960s. The major clinical features are sensory polyneuropathy, sensory gait ataxia, optic atrophy, and nerve deafness. Although cases with similar clinical features have been described from other parts of the world, their distribution and natural history are not identical with cases from Nigeria. Exposure to cyanide from cassava foods was proposed as the major causal factor. However, occurrence of ataxic polyneuropathy is rare in many parts of the tropics where cassava foods are the major source of calories. The objective of this thesis was to determine if occurrence of ataxic polyneuropathy in Nigeria is associated with cyanide from cassava foods. The prevalence of ataxic polyneuropathy in Ososa, a community in the endemic area was compared with the prevalence of ataxic polyneuropathy in Jobele, a community in the non-endemic area. A case-referent study was nested in an incidence study of ataxic polyneuropathy in Ososa. Intake of cassava foods and of protein, levels of thiocyanate in plasma and urine, and levels of low molecular weight thiols in the plasma were measured in cases and referents. Cohorts of subjects were followed in Ososa and Jobele to compare mortality. 150 g of gari from which 128 µmol of cyanide could be released was given to 12 healthy volunteers to determine if gari is a source of exposure to cyanide. Consumption of cassava foods and exposure to cyanide from cassava foods were compared in the endemic and non-endemic areas. Efficiencies of the methods of processing cassava roots to gari and lafun, two common cassava foods in Nigeria, were compared, and changes in the level of cyanogenic compounds in gari during storage were studied. The prevalence of ataxic polyneuropathy was 490 per 10 000 in Ososa compared with 17 per 10 000 in Jobele. The age standardised prevalence ratio between Jobele and Ososa was 4 % (95 % Cl 0 - 9). The incidence of ataxic polyneuropathy in Ososa was 63 per 10 000 personyears, 27 for males and 93 for females. The adjusted odds ratios (95 % CI) were 0.44 (0.09 2.26) for the intake of cassava foods, and 1.74 (0.48- 6.28) for exposure to cyanide. The concentrations of thiols were within the reference limits in cases and referents. The adjusted relative risk of death in Jobele, compared with Ososa, was 0.43 (95 % CI 0.25 - 0.76). The mean amount of cyanide absorbed into the plasma from gari was 13 µmol (SD 12), and the mean transit time of absorbed cyanide in the plasma was 7.3 hours (SD 2. 1). The mean number of times cassava foods were eaten per person per week (95 % Cl) were 17 (16- 17) in the endemic area, and 10 (9 - 10) in the non-endemic area in southwestern Nigeria, while the geometrical mean thiocyanate (95 % Cl) were 73 µmol/l (66 - 80) in the endemic area, and 51 µmol/l (48 -54) in the non-endemic area in southwest Nigeria. Mean levels of cyanogenic compounds in mg HCN eq/kg dry weight (95 % Cl) were 18.0 (15.9 -20.1), and 7.0 (4.3 - 9.7) in gari, which were processed using two different methods from cassava roots that contained 313.7 mg HCN eq/kg dry weight. Mean level of cyanogenic compounds dropped from 15 mg HCN eq/kg dry weight to 7 mg HCN eq/kg dry weight in gari after four weeks of storage. The studies in this thesis do not show association of occurrence of ataxic polyneuropathy and exposure to cyanide from cassava foods. The finding of comparable levels of thiols and thiocyanate in the plasma of cases and referents suggests that detoxification of cyanide is not impaired in cases of ataxic polyneuropathy. Although cassava foods are consumed in most communities in Nigeria, exposure to cyanide from cassava foods varies widely, due largely to differences in the frequency of intake of cassava foods and the amount of cyanogenic compounds in cassava foods. The studies in this thesis show that the method of processing cassava roots, the duration of storage of the foods before being prepared to meals, and the method of preparation of the meals determine the amount of cyanide that consumers are exposed to. Since all possible adverse effects of a toxicant on health were not studied in this thesis, reduction of exposure to cyanide from cassava foods is recommended in communities where cassava foods are eaten.