The aetiology of SMON may involve an interaction between clioquinol and environmental metals.

Clioquinol can increase the penetration of metallic cations through cellular membranes by forming lipophilic metal-chelates. It is suggested that the pathogenesis of SMON may involve an accumulation of injurious metals in nervous tissues due to facilitated uptake by complex formation with clioquinol. The Japanese have been more heavily exposed to metals by environmental pollution than the inhabitants of other countries, which may explain the prevalent occurrence of SMON in Japan.