Epidemiology and Pathophysiology of Parkinsonism in the Caribbeans

Not Applicable

• Conditions: Atypical Parkinsonism
• Interventions: Other: Clinical and biological exam

• Registration Number: NCT03368300
• Lead Sponsor: Centre Hospitalier Universitaire de Pointe-a-Pitre

Brief 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.

Study Timeline

• Study Start: 2012-08-03
• Status Verified: 2017-11
• Study First Submitted: 2017-11-24
• Study First Submitted QC: 2017-12-05
• Last Update Submitted: 2017-12-05
• Study First Posted: 2017-12-11
• Last Update Posted: 2017-12-11
• Primary Completion: 2018-08-03
• Study Completion: 2023-08-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

• Pour les patients :

  1. Patient ou tiers responsable ayant reçu une information sur l'étude et ayant signé le consentement éclairé

  2. Patient âgé de plus de 18 ans

  3. Patient consultant en neurologie ou en gériatrie pour symptomatologie parkinsonienne ou pour troubles cognitifs évocateurs d'une démence à corps de Lewy

  4. Patient domicilié aux Antilles-Guyane

     Pour les témoins :

  5. Conjoint ou accompagnant ayant reçu une information sur l'étude et ayant signé le consentement éclairé

  6. Personne âgée de plus de 18 ans

  7. Personne ne présentant pas de pathologie d'allure neurodégénérative (Parkinson, démence notamment)

  8. Personne domiciliée aux Antilles-Guyane

Exclusion Criteria

Pour les patients :

1. Syndrome parkinsonien secondaire (post-traumatique, vasculaire, iatrogène, post encéphalitique)
2. Patient non affilié au régime de sécurité sociale
3. En cas de difficulté de suivi le patient sera exclu de l'étude longitudinale

Pour les témoins :

1. Personnes présentant des troubles cognitifs ou un syndrome parkinsonien diagnostiqué.
2. Patient non affilié au régime de sécurité sociale -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients	Clinical and biological exam	Parkinson's patient
witnesses: without parkinson's disease	Clinical and biological exam	Subjects without parkinson's disease

Primary Outcome Measures

Name	Time	Method
to estimate the frequency and to characterize clinically atypical parkinsonism in the French West Indies and Guyana	At the end of the Period of inclusion, around 5-6 years	Collection of : administrative and socioeconomic data, medical consultation with video recording , recording oculomotor to the atypical

Secondary Outcome Measures

Name	Time	Method
to compare the proportion of atypical forms within parkinsonian syndromes;	At the end of the Period of inclusion, around 5-6 years	Collection of : administrative and socioeconomic data, medical consultation with video recording , recording oculomotor to the atypical neuropsychological balance assessment ,; 1. Clinical diagnostic criteria; 2. Compilation of functional indicators of motor and cognitive autonomy and Collection of intercurrent medical events; 3. Food and exposure questionnaire; 4. Neuropsychological assessment; 5. Recording of oculomotor movements and Post-mortem analysis; 6. biological collection (plasma, DNA, serum)
to characterize the entity "Parkinson-dementia complex" described in Guadeloupe ; to characterize the entity "Parkinson-dementia complex" described in Guadeloupe ;	Through study completion, an average of 11 years	Compilation of functional indicators of motor and cognitive autonomy and Collection of intercurrent medical events.; Collection of : administrative and socioeconomic data, medical consultation with video recording , recording oculomotor to the atypical neuropsychological balance assessment ,
to determine the implication of a toxic alimentary factor in the etiopathogenesis of atypical forms and compare the results in the 3 areas (Guadeloupe, Guyane, Martinique);	Through study completion, an average of 11 years	Neuropsychological assessment Food and exposure survey
to determine the latency of cognitive decline in idiopathic Parkinson's disease in the 3 areas ;	Through study completion, an average of 11 years, post-mortem analysis after death if applicable	Recording of oculomotor movements and Post-mortem analysis (sampling of blood and cutaneous biopsy to establish a collection of biological samples)
to constitute a biological collection (plasma, DNA, serum).	At the end of the Period of inclusion, around 5-6 years	biological collection (plasma, DNA, serum)
to determine the natural history of typical and atypical forms of parkinsonism by following a cohort of the incident cases only;	Through study completion, an average of 11 years	Neuropsychological assessment Food and exposure survey

Trial Locations

Locations (2)

University Hospital of Martinique; 🇲🇶 Fort-de-France, Martinique

University Hospital of Guyana; 🇬🇫 Cayenne, French Guiana