Motor proficiency is dramatically affected, and both children with and without konzo have impaired neurocognition compared with control children from a nonoutbreak area. This may evidence a subclinical neurocognitive form of the disease, extending the human burden of konzo with dramatic public health implications.
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 levels of thiocyanate were 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.
Background
While risk factors for konzo are known, determinants of cognitive impairment in konzo-affected children remain unknown.
Method
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.
Results
Age (β: − 0.818, 95%CI: − 1.48, − 0.152) (p=0.018), gender (β: − 5.72; 95% CI: − 9.87, −1.57 for females) (p=0.009), BOT-2 score (β: 0.390; 95% CI: 0.113, 0.667) (p=0.008), and free-T4 (β: 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 (β: 1.26; 95% CI: 0.136, 2.39) (p=0.029). On spot urinary thiocyanate reached 688 μmol/l in children without konzo and 1032 μmol/L in those with konzo.
Conclusion
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.
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