Organic arsenic‐induced Guillain‐Barré‐like syndrome due to melarsoprol: A clinical, electrophysiological, and pathological study

Abstract

A young woman suffering from sleeping sickness was treated with melarsoprol. Thirty-eight days after the first administration of this organo-arsenic compound, myalgias, distal paresthesias and rapidly progressive weakness developed in all four limbs. Electrophysiological studies were misleading for Guillain-Barré syndrome. Neuropathological data included massive distal wallerian degeneration in peripheral nerves and abnormalities in dorsal ganglia and spinal cord where vacuolation of anterior horn cells and axonal neurofilamentous masses were observed. Very high concentrations of arsenic were found in the spinal cord, contrasting with undetectable levels in peripheral nerves. Our findings are consistent with an arsenic neuronopathy manifested by initial proximal demyelination and delayed distal axonal damage. Renal and hepatic dysfunctions, which were implicated in the toxic arsenic accumulation, should be systematically detected before administration of melarsoprol. The diagnosis of Guillain-Barré syndrome must be considered with caution in patients treated with this compound.

Pharmacokinetics and tissue distribution of the antileukaemic organoarsenicals arsthinol and melarsoprol in mice

“…5 inset; EI: 1.34 ± 0.60 for melarsoprol vs 1.37 ± 0.49 for arsthinol; NS). This fact is in very good accordance with the observation that the brain is mainly involved in the acute toxicity of trivalent organoarsenicals characterized by a major encephalopathy [18,19]. Thus, the modest brain exposure after arsthinol administration could explain its lower acute toxicity as compared to melarsoprol.…”

Differential Diagnosis of Acute Flaccid Paralysis and its Role in Poliomyelitis Surveillance

“…Arsenic-containing compounds such as melarsoprol are still being used in developing countries for the treatment Epidemiol Rev Vol. 22 of African trypanosomiasis (sleeping sickness) and may cause Guillain-Barre syndrome-like AFP (120).…”

Scientific Opinion on Arsenic in Food

“…Organic arsenic compounds were used -by injection -in the past to treat syphilis (3,3'-diamino-4,4'-dihydroxy-arsenobenzene; arsphenamine) while to date human African trypanosomiasis (sleeping sickness) is treated by another organic arsenic compound melarsoprol ((2-(4-(4,6-diamino-1,3,5-triazin-2-ylamino)phenyl)-1,3,2-dithiarsolan-4-yl) methanol). Both of these compounds are notorious for their acute central arsenic toxicity (see below) while peripheral neuropathies in syphilitic and trypanosomiasis patients are only occasionally reported (Gherardi et al, 1990). Human pathology can not as yet distinguish between the inorganic and organic arsenic induced types of peripheral neurotoxicity.…”