Correspondence
Ataxia and Slurred Speech after Artesunate Treatment for Falciparum Malaria
N Engl J Med 1997; 336:1328-1329May 1, 1997
- Article
To the Editor:
Artemisinin compounds are used to treat Plasmodium falciparum infections in many countries worldwide.1,2 We describe a patient with acute cerebellar dysfunction that was temporally associated with the ingestion of artesunate.
In July 1996, a 36-year-old American geologist in Ghana had fever and chills without associated neurologic symptoms. His blood smear revealed P. falciparum. He proceeded to a local market and purchased a pack of artesunate tablets manufactured in China. He took two tablets on day 1, followed by one tablet daily for the next four days. He became afebrile on day 2. A blood smear on day 5 contained no malaria parasites.
Two days after completing the artesunate treatment, the patient noted that his gait was unsteady. His electroencephalogram was normal. Over the next week, worsening ataxia and slurred speech developed. Three weeks later, he was evacuated to a London hospital. Magnetic resonance imaging of the brain and a lumbar puncture revealed no abnormalities. He then flew home to California with a nursing escort.
In September 1996, the patient was admitted to a southern California hospital with persistent neurologic symptoms. He had slurred speech; a wide-based, ataxic gait; and impaired heel-to-shin and rapid alternating movements. A peripheral smear was again positive for plasmodium species, but the parasites were too scant to speciate. He was re-treated with oral quinine and doxycycline. In October 1996 he began rehabilitation therapy. One month later, his ataxia was moderately improved, and his speech was nearly normal.
Artesunate is an antimalarial agent derived from the Chinese medicinal plant qinghao (Artemisia annua). Other related agents are artemether, arteether, and artelinic acid.1 These drugs are available primarily in Asia and Africa, where parenteral, oral, and rectal formulations have been used to treat an estimated 1 million patients.2
Although there are no previous clinical reports of artemisinin-related neurotoxic effects, Brewer et al. observed a staggering gait and respiratory arrest in dogs treated with high doses of intramuscular arteether, as well as ataxia and myoclonic activity in rats given intramuscular arteether and artemether.3 In the Gambian children with cerebral malaria described in the Journal by van Hensbroek et al. (July 11 issue),4 intramuscular artemether was associated with more convulsions and more prolonged coma than was intramuscular quinine. In the accompanying editorial, Hoffman expressed concern about the potential neurotoxicity of all artemisinin compounds.5
Our patient had neurologic sequelae over a four-month period immediately after treatment with artesunate for P. falciparum. Since cerebellar dysfunction would be a highly unusual complication of malaria, this case serves as a warning of the need for further attentiveness to the neurotoxic side effects of artemisinin compounds.
5 ReferencesLoren G. Miller, M.D.
Claire B. Panosian, M.D., D.T.M.H.
University of California, Los Angeles, Los Angeles, CA 900951
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Full Text | Web of Science | Medline
- Citing Articles (33)
Citing Articles
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