Atypical Parkinsonism Clinical Trial
Official title:
Epidemiology and Pathophysiology of Parkinsonism in the Caribbeans
The primary aim of this study is to estimate the frequency and to characterize clinically atypical parkinsonism in the French West Indies and Guyana.
An atypical akineto-rigid parkinsonian syndrome, unresponsive to L-dopa has been evidenced in
Guadeloupe. Abnormally frequent, this progressive supranuclear palsy (PSP)-like syndrome
represents a new clinical entity. Unlike in classical PSP 70% of patients have myoclonus, 59%
hallucinations, 78% REM sleep behavior disorders. Oculomotor pattern differs from classical
PSP suggesting that cortical dysfunction predominates over brainstem impairments.
Neuropathological examination in four patients has shown a widespread accumulation of the tau
protein in the basal ganglia, the midbrain and cortical areas.
This syndrome has been associated to the regular consumption of food products derived from
plants of the Annonaceae family, more specifically Annona Muricata (soursop), suggesting a
toxic origin. We have already confirmed the neurotoxic potential of the lipophilic
mitochondrial complex I inhibitor annonacin, the major acetogenin in Annona muricata. This
class of compounds is specific to Annonaceae. Nanomolar concentrations of annonacin induce
the death of dopaminergic neurons in culture, by impairment of energy production. Chronic
systemic intoxication of rats with annonacin causes neuronal damage in the same brain regions
that are damaged in patients with atypical parkinsonism. These results greatly suggest that
the consumption of annonacea might contribute to the pathogenesis of the disease. The H1
subhaplotype in tau gene associated with PSP in Caucasians did not confer risk for PSP-like
atypical parkinsonism in Guadeloupe.
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