On the French West Indian island of Guadeloupe, atypical parkinsonian patients 
represent two-thirds of all cases of parkinsonism, which is exceptionally 
frequent compared to epidemiological data from European countries where atypical 
parkinsonism accounts for only approximately 5% of all cases. The clinical 
entity was a unique combination of levodopa-resistant parkinsonism, tremor, 
myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical 
dementia. Based on the presence or the absence of supranuclear gaze palsy, two 
subgroups of patients were distinguished. In patients with oculomotor signs that 
came to autopsy, neuronal loss was found to predominate in the substantia nigra 
and the striatum but other brain areas were also affected, including the frontal 
cortex. In addition, tau-containing lesions were detected throughout the brain. 
Epidemiological data suggested a close association of the disease with the 
regular consumption of soursop, a tropical annonaceous plant. Experimental 
studies performed in midbrain cell cultures identified annonacin, a selective 
mitochondrial complex I inhibitor contained in the fruit and leaves of soursop, 
as a probable etiological factor. Consistent with this view, chronic 
administration of annonacin to rats through Alzet osmotic minipumps showed that 
annonacin was able to reproduce the brain lesions characteristic of the human 
disease.