Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.

Abstract

SUMMARY An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.

Spinocerebellar degeneration secondary to chronic intestinal malabsorption: A vitamin E deficiency syndrome

“…These clinical findings may be related to a persisting central axonopathy with interruption of the reflex arc at a site proximal to the dorsal root ganglia. A similar explanation has been offered for the reflex depression and sensory loss that occur in clioquinol neurotoxicity [4] and hereditary spastic paraplegia 1291.…”

Comparison of Prophylactic Tetracycline and Clioquinol in a Rabbit Model of Intestinal Infection with <i>Vibrio cholerae </i>and <i>Escherichia coli</i>

“…In many developing countries clioquinol remains a popular drug to treat a variety of acute diarrheal diseases of unknown etiology. Because of its association with an epidemic of sub acute myeloptic neuropathy (SMON) in Japan, clioquinol's use is being discou raged [2,18,20). However, compared to many other antibiotics clioquinol is a rela tively safe drug, since SMON is an ex tremely rare complication of clioquinol [2], The issue regarding clioquinol relates primarily to efficacy rather than safety.…”

“…It therefore serves as an ef fective standard antibiotic against which to measure others. Clioquinol continues to be used widely to prevent and treat bacte rial diarrhea; however, the drug remains controversial because of conflicting re ports of its efficacy in clinical trials [ 15,22] and because of its association with sub acute myeloptic neuropathy [2,18,20].…”

Prevention of Travelers' Diarrhea by Nonantibiotic Drugs

“…Other uncontrolled studies have looked at the effectiveness of iodochlorhydroxyquin in the prevention of travelers' diarrhea [4][5][6][7][8] (table 1). Because of the association of the drug with the syndrome of subacute myelooptic neuropathy (SMON), which occurs primarily in Japan [16] and rarely in other countries [17], use of this agent cannot be recommended.…”