Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes?

Abstract

In Guadeloupe, there is an abnormally high frequency of atypical parkinsonism. Only one-third of the patients that develop parkinsonian symptoms were reported to present the classical features of idiopathic Parkinson disease and one-third a syndrome resembling progressive supranuclear palsy (PSP). The others were unclassifiable, according to established criteria. We carried out a cross-sectional study of 160 parkinsonian patients to: (i) define more precisely the clinical phenotypes of the PSP-like syndrome and the parkinsonism that was considered unclassifiable in comparison with previously known disorders; (ii) define the neuropsychological and brain imaging features of these patients; (iii) evaluate to what extent a candidate aetiological factor, the mitochondrial complex I inhibitor annonacin contained in the fruit and leaves of the tropical plant Annona muricata (soursop) plays a role in the neurological syndrome. Neuropsychological tests and MRI were used to classify the patients into those with Parkinson's disease (31%), Guadeloupean PSP-like syndrome (32%), Guadeloupean parkinsonism-dementia complex (PDC, 31%) and other parkinsonism-related disorders (6%). Patients with a PSP-like syndrome developed levodopa-resistant parkinsonism, associated with early postural instability and supranuclear oculomotor dysfunction. They differed, however, from classical PSP patients by the frequency of tremor (>50%), dysautonomia (50%) and the occurrence of hallucinations (59%). PDC patients had levodopa-resistant parkinsonism associated with frontosubcortical dementia, 52% of these patients had hallucinations, but, importantly, none had oculomotor dysfunction. The pattern of neuropsychological deficits was similar in both subgroups. Cerebral atrophy was seen in the majority of the PSP-like and PDC patients, with enlargement of the third ventricle and marked T2-hypointensity in the basal ganglia, particularly the substantia nigra. Consumption of soursop was significantly greater in both PSP-like and PDC patients than in controls and Parkinson's disease patients. In conclusion, atypical Guadeloupean parkinsonism comprises two forms of parkinsonism and dementia that differ clinically by the presence of oculomotor signs, but have similar cognitive profiles and neuroimaging features, suggesting that they may constitute a single disease entity, and both were similarly exposed to annonaceous neurotoxins, notably annonacin.

Investigation of the toxic potential of crude ethanol extract of Annona coriacea (araticum) seeds in acute exposed mice

“…The activities of acetogenins are in agreement with reports from Caparros-Lefebvre (1999, 2002 and Lannuzel et al (2007), correlating the appearance, in a Caribbean population that used tea and fruits of plants from the Annonaceae family, of a atypical Parkinsonian syndrome caused by atrophy in regions of the cerebral cortex, midbrain, cerebellum and corpus callosum.…”

Annonacin, a Natural Mitochondrial Complex I Inhibitor, Causes Tau Pathology in Cultured Neurons

“…Approximately half of the affected patients have clinical manifestations that are strikingly similar to those found in progressive supranuclear palsy (PSP) (CaparrosLefebvre et al, 2002;Lannuzel et al, 2007). Three of the PSP-like patients that came to autopsy also had neuropathological features resembling those of PSP, characterized in particular by an abnormal accumulation of the axonal microtubule-associated protein (MAP) tau in the cell bodies of neurons (Caparros-Lefebvre et al, 2002).…”

“…Three of the PSP-like patients that came to autopsy also had neuropathological features resembling those of PSP, characterized in particular by an abnormal accumulation of the axonal microtubule-associated protein (MAP) tau in the cell bodies of neurons (Caparros-Lefebvre et al, 2002). Clinical and epidemiological studies (Caparros-Lefebvre and Elbaz, 1999;Angibaud et al, 2004;Lannuzel et al, 2007) have found a significant association between atypical parkinsonism, in Guadeloupe and in New Caledonia, and the regular consumption of tropical anonaceous plant products, suggesting that they contain substances that trigger the disease. Anonaceous acetogenins, a large and unique family of lipophilic complex I inhibitors that are produced exclusively by annonaceous plants, appear to be prime candidates (Degli Esposti, 1998;Höglinger et al, 2005b).…”

Atypical parkinsonism in the Caribbean island of Guadeloupe: Etiological role of the mitochondrial complex I inhibitor annonacin

“…The group of patients with oculomotor signs was referred as Gd-PSP and the other group as Gd-parkinsonism dementia complex (PDC). 3 The two groups could not be distinguished on the basis of any other sign, and thus appear to constitute a single disease entity that differs markedly from related syndromes like classical PSP, dementia with Lewy bodies (DLB) or fronto-temporal dementia.…”

“…3 Patients with I-PD had unilateral onset, a good response to levodopa and dopa-induced dyskinesias. Patients with atypical Caribbean parkinsonism developed levodopa-resistant motor symptoms, which is associated with early postural instability and dementia.…”