NCT03368300

Epidemiology and Pathophysiology of Parkinsonism in the Caribbeans

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 550 (estimated)
• Sponsor: Centre Hospitalier Universitaire de la Guadeloupe · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Accepted

Summary

The primary aim of this study is to estimate the frequency and to characterize clinically atypical parkinsonism in the French West Indies and Guyana.

Detailed description

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.

Conditions

• Atypical Parkinsonism

Interventions

Type	Name	Description
OTHER	Clinical and biological exam	The study will include a clinical, neuropsychological, oculomotor, food intake and environmental exposure assessment. Blood samples will be taken to constitute a library of plasma, DNA and serum. The harvesting of samples will be part of a subsequent study. Consent for possible post-mortem neuropathological analysis will be proposed. All the patients accepting it will be followed by a 5-year longitudinal follow-up. The longitudinal follow-up bi-annual and then annual will include a clinical evaluation, a questionnaire of dependence and a questionnaire of monitoring of exposure to certain environmental factors All controls must answer a questionnaire of environmental exposure factors, oculomotor test, and blood sample (3 collections: DNA, serum, plasma).

Timeline

• Start date: 2012-08-03
• Primary completion: 2018-08-03
• Completion: 2023-08-03
• First posted: 2017-12-11
• Last updated: 2017-12-11

Locations

2 sites across 2 countries: French Guiana, Martinique