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Cyanide and the human brain: perspectives from a model of food (cassava) poisoning - PubMed

Review

. 2016 Aug;1378(1):50-57.

doi: 10.1111/nyas.13159. Epub 2016 Jul 23.

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Review

Cyanide and the human brain: perspectives from a model of food (cassava) poisoning

Desire D Tshala-Katumbay et al. Ann N Y Acad Sci. 2016 Aug.

Abstract

Threats by fundamentalist leaders to use chemical weapons have resulted in renewed interest in cyanide toxicity. Relevant insights may be gained from studies on cyanide mass intoxication in populations relying on cyanogenic cassava as the main source of food. In these populations, sublethal concentrations (up to 80 μmol/l) of cyanide in the blood are commonplace and lead to signs of acute toxicity. Long-term toxicity signs include a distinct and irreversible spastic paralysis, known as konzo, and cognition deficits, mainly in sequential processing (visual-spatial analysis) domains. Toxic culprits include cyanide (mitochondrial toxicant), thiocyanate (AMPA-receptor chaotropic cyanide metabolite), cyanate (protein-carbamoylating cyanide metabolite), and 2-iminothiazolidine-4-carboxylic acid (seizure inducer). Factors of susceptibility include younger age, female gender, protein-deficient diet, and, possibly, the gut functional metagenome. The existence of uniquely exposed and neurologically affected populations offers invaluable research opportunities to develop a comprehensive understanding of cyanide toxicity and test or validate point-of-care diagnostic tools and treatment options to be included in preparedness kits in response to cyanide-related threats.

Keywords: cassava; cyanide; neurocognition; paralysis; warfare.

© 2016 New York Academy of Sciences.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1

Metabolic fate of linamarin and cyanide during cassava processing and after ingestion of poorly processed cassava foodstuffs. Once the physical integrity of the cassava tissue is disrupted, linamarin is hydrolyzed to glucose and cyanohydrins. At pH > 5, the cyanohydrins spontaneously break down into ketones, and hydrogen cyanide (HCN) gas escapes. Lower pH leads to persistence of cyanohydrins in the finished food product, with the result that cyanide may be released by bacterial enzymatic cleavage in the gastrointestinal tract and enter the bloodstream. Once in the bloodstream, cyanide is either trapped by methemoglobin (MetHB–CN) or converted into thiocyanate (SCN). The human body may then excrete either intact linamarin or reportedly less toxic SCN in urine.

Figure 2
Figure 2

Spastic stance in a child severely affected by the cassava-associated spastic paraparesis known as konzo (child left) and a woman with a moderate form of the disease (woman with walking stick).

Figure 3
Figure 3

Low motor or cognition performance scores significantly correlate with high serum concentrations of 8,12-iso-iPF2α-VI isoprostane. Neuropsychological assessments were done using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) for cognition and the Bruininks/Oseretsky Test, 2nd Edition (BOT-2) measure for motor proficiency. (A) MPI (KABC-II) scores relative to serum concentration of 8,12-iso-iPF2α-VI isoprostane (triangles = konzo children, r = −0.78, P = 0.00; circles = non-konzo children, r = −0.24, P = 0.47). (B) BOT-2 scores relative to serum level of 8,12-iso-iPF2α-VI isoprostane (triangles = konzo children, r = −0.63, P < 0.01; circles = non-konzo children, r = −0.06, P = 0.86).

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