ABSTRACT
We assessed the relationship between key trace elements and neurocognitive and motor impairments observed in konzo, a motor neuron disease associated with cassava cyanogenic exposure in nutritionally challenged African children. Serum concentrations of iron, copper, zinc, selenium, and neurotoxic lead, mercury, manganese, cadmium, and cobalt were measured in 123 konzo children (mean age 8.53 years) and 87 non-konzo children (mean age 9.07 years) using inductively coupled plasma mass spectrometry (ICPMS). Concentrations of trace elements were compared and related to performance scores on the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) for cognition and Bruininks-Oseretsky Test, 2nd edition (BOT-2) for motor proficiency. Children with konzo had low levels of selenium, copper, and zinc relative to controls. Selenium concentration significantly correlated with serum 8,12-iso-iPF2α-VI isoprostane (Spearman r=0.75, p<0.01) and BOT-2 scores (r=0.31, p=0.00) in children with konzo. Elemental deficiency was not associated with poor cognition. Mean (SD) urinary level of thiocyanate was 388.03 (221.75) µmol/l in non-konzo compared to 518.59 (354.19) µmol/l in konzo children (p<0.01). Motor deficits associated with konzo may possibly be driven by the combined effects of cyanide toxicity and Se deficiency on prooxidant mechanisms. Strategies to prevent konzo may include dietary supplementation with trace elements, preferentially, those with antioxidant and cyanide-scavenging properties.
Subject(s)
Cognition , Copper/blood , Motor Neuron Disease/blood , Motor Neuron Disease/physiopathology , Selenium/blood , Zinc/blood , Africa , Child , Child, Preschool , Cyanides/blood , Dinoprost/analogs & derivatives , Dinoprost/blood , Female , Humans , Male , Mass Spectrometry , Motor Neuron Disease/diagnosis , Motor Neuron Disease/urine , Neuropsychological Tests , Oxidative Stress , Thiocyanates/urineABSTRACT
While risk factors for konzo are known, determinants of cognitive impairment in konzo-affected children remain unknown. We anchored cognitive performance (KABC-II scores) to serum levels of free-thyroxine (free-T4), thyroid-stimulating hormone (TSH), albumin, and motor proficiency (BOT-2 scores) in 40 children including 21 with konzo (median age: 9 years) and 19 without konzo (median age: 8 years). A multiple regression model was used to determine variables associated with changes in KABC-II scores. Age (ß: -0.818, 95% CI: -1.48, -0.152) (p = 0.018), gender (ß: -5.72; 95% CI: -9.87, -1.57 for females) (p = 0.009), BOT-2 score (ß: 0.390; 95% CI: 0.113, 0.667) (p = 0.008), and free-T4 (ß: 1.88; 95% CI: 0.009, 3.74) (p = 0.049) explained 61.1 % of variation in KABC-II scores. Subclinical hypothyroidism was not associated with poor cognition. A crude association was found between serum albumin and KABC-II scores (ß: 1.26; 95 % CI: 0.136, 2.39) (p = 0.029). On spot urinary thiocyanate reached 688 µmol/l in children without konzo and 1,032 µmol/L in those with konzo. Female gender and low serum albumin are risk factors common to cognitive and proportionally associated motor deficits in children exposed to cassava cyanogens. The two types of deficits may share common mechanisms.