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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Atypical unclassifiable parkinsonism on Guadeloupe: an environmental toxic hypothesis.
We characterize the clinical features of Parkinson's syndrome on Guadeloupe and describe possible environmental causes. Consecutive patients who were referred to the University Hospital at Pointe a Pitre with parkinsonism from September 1996 to May 2002 were included. All cases were examined in a standardized manner by a neurologist with a special interest in movement disorders and independently by 3 external movement disorders specialists, using standard operational clinical diagnostic criteria. The subjects were 265 patients with Parkinson's syndrome living on Guadeloupe, four fifths of whom had been referred by primary care physicians and one fifth by neurologists. The levodopa response was assessed after a minimum period of 1 month of continuous treatment. All patients had brain computed tomography or brain magnetic resonance imaging scans and detailed neuropsychological examinations. Of 265 patients, only 66 were classified as Parkinson's disease, whereas 58 fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) and Society for Progressive Supranuclear Palsy (SPSP) criteria for progressive supranuclear palsy, 100 had unclassifiable parkinsonism, characterized by dopa-unresponsiveness, marked axial rigidity, relative symmetry of parkinsonian features, early dysarthria, and frontolimbic cognitive impairment. Within this group, early postural instability, dysarthria, a frontal behavior disorder, cortical or subcortical atrophy, pyramidal signs, axial rigidity, and family history of neurodegenerative disorders were associated with poorer prognosis. A very large number of unclassifiable cases of atypical parkinsonism that do not fulfill operational criteria for Parkinson's disease or other defined motor neurodegenerations has been observed on Guadeloupe. Most patients closely resemble descriptions of bodig from Guam. In both geographic isolates, an environmental cause has been discussed. Annonaceae fruits and herbal teas are consumed on both islands. These plants contain several neurotoxins, particularly acetogenins, which induce dopaminergic neuron loss in animals. Neuronal death involves cholinergic and dopaminergic cells of the substantia nigra and GABAergic neurons of the striatum, associated with microglial proliferation. The development of atypical parkinsonism in Guadeloupe and probably elsewhere, could result from synergistic toxicity, but acetogenins are probably the most potent neurotoxin, acting as mitochondrial complex I inhibitor.
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