Annonaceae Consumption Worsens Disease Severity and Cognitive Deficits in Degenerative Parkinsonism.

BACKGROUND: High consumption of Annona muricata fruit has been previously identified as a risk factor for atypical parkinsonism in the French Caribbean islands. OBJECTIVE: We tested whether consumption of Annonaceae products could worsen the clinical phenotype of patients with any form of degenerative parkinsonism. METHODS: We analyzed neurological data from 180 Caribbean parkinsonian patients and specifically looked for dose effects of lifelong, cumulative Annonaceae consumption on cognitive performance. Using unsupervised clustering, we identified one cluster with mild/moderate symptoms (N = 102) and one with severe symptoms including cognitive impairment (N = 78). RESULTS: We showed that even low cumulative consumption of fruits/juices (>0.2 fruit-years) or any consumption of herbal tea from Annonaceae worsen disease severity and cognitive deficits in degenerative parkinsonism including Parkinson's disease (OR fruits-juices: 3.76 [95% CI: 1.13-15.18]; OR herbal tea: 2.91 [95% CI: 1.34-6.56]). CONCLUSION: We suggest that more restrictive public health preventive recommendations should be made regarding the consumption of Annonaceae products. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Optimized Quantification of Translocator Protein Radioligand ¹8F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers.

UNLABELLED: Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the (18)F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling. METHODS: Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent (18)F-DPA-714 PET with arterial and venous sampling. (18)F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1- and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (V(T)) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples. RESULTS: The distribution pattern of (18)F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of (18)F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation < 5%). For each region of interest, V(T) was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. V(T) calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation. CONCLUSION: Genotyping of subjects is a prerequisite for a reliable quantification of (18)F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate (18)F-DPA-714 V(T) in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.

Outcome of bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease: correlation with intra-operative multi-unit recordings but not with the type of anaesthesia.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) gained general acceptance in the treatment of Parkinson's disease (PD). OBJECTIVE: To study the clinical outcome and the predicting factors of efficacy of chronic STN stimulation, while DBS electrodes were implanted under local or general anaesthesia with intra-operative electrophysiological guidance based on multi-unit recordings. METHODS: We included a large single-centre cohort of 54 patients with advanced PD (mean age: 59 years; disease duration: 14 years). Clinical evaluation was performed by the Unified Parkinson's Disease Rating Scale (UPDRS) before and 1 year after surgical placement of DBS electrodes. RESULTS: In the on-stimulation and off-medication condition, the UPDRS part III score was reduced by 56% compared to the off-stimulation condition or pre-operative off-drug score. In the on-stimulation and on-medication condition, this score was reduced by 73%. The severity of motor fluctuations and dyskinesia (UPDRS part IV) and the activities of daily living (UPDRS part II) were reduced by 65 and 80%, respectively, in the on-stimulation/on-medication condition compared to the pre-operative baseline. The daily dose of antiparkinsonian treatment was diminished by 72%. Among the various pre- and intra-operative data, the most important predictive factor for clinical efficacy of STN stimulation was the length of hyperactivity along the best track observed in intra-operative multi-unit recordings. Other predictive factors included age, disease duration and pre-operative levodopa responsiveness or baseline off-drug values of the Hoehn and Yahr and UPDRS part III scores. In contrast, the type of anaesthesia (local vs. general) did not significantly influence the clinical outcome. CONCLUSION: The present results are in the average of previously published results, but they have been obtained from a large single-centre cohort of patients with important reductions in the daily dose of antiparkinsonian drugs. This study confirmed the efficacy of the STN-DBS technique and emphasized the value of an original intra-operative electrophysiological approach based on multi-unit and not single-unit quantified recordings. This method allows DBS electrode implantation to be safely performed under general anaesthesia without lessening the rate of efficacy of the procedure.

Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior.

Two parkinsonian patients who experienced transient hypomanic states when the subthalamic nucleus (STN) was stimulated during postoperative adjustment of the electrical parameters for antiparkinsonian therapy agreed to have the mood disorder reproduced, in conjunction with motor, cognitive, and behavioral evaluations and concomitant functional neuroimaging. During the experiment, STN stimulation again induced a hypomanic state concomitant with activation of cortical and thalamic regions known to process limbic and associative information. This observation suggests that the STN plays a role in the control of a complex behavior that includes emotional as well as cognitive and motor components. The localization of the four contacts of the quadripolar electrode was determined precisely with an interactive brain atlas. The results showed that (i) the hypomanic state was caused only by stimulation through one contact localized in the anteromedial STN; (ii) both this contact and the contact immediately dorsal to it improved the parkinsonian motor state; (iii) the most dorsal and ventral contacts, located at the boundaries of the STN, neither induced the behavioral disorder nor improved motor performance. Detailed analysis of these data led us to consider a model in which the three functional modalities, emotional, cognitive, and motor, are not processed in a segregated manner but can be subtly combined in the small volume of the STN. This nucleus would thus serve as a nexus that integrates the motor, cognitive, and emotional components of behavior and might consequently be an effective target for the treatment of behavioral disorders that combine emotional, cognitive, and motor impairment.

Subthalamic nucleus stimulation reduces abnormal motor cortical overactivity in Parkinson disease.

BACKGROUND: Based on the basal ganglia model, it has been hypothesized that the efficacy of high-frequency stimulation of the subthalamic nucleus (STN) against parkinsonian symptoms relies on the activation of cortical premotor regions. In previous positron emission tomography activation studies, STN high-frequency stimulation was associated with selective activation of midline premotor areas during hand movements but mainly reduced the regional cerebral blood flow in movement-related areas, peculiarly at rest. OBJECTIVE: To investigate with positron emission tomography the role of regional cerebral blood flow reduction in the clinical improvement provided by STN high-frequency stimulation. METHODS: Seven patients with advanced Parkinson disease, who were markedly improved by bilateral STN high-frequency stimulation, underwent positron emission tomography with H2(15)O while the right STN electrode was turned off. The patients were studied at rest and during right-hand movements in 3 electrode conditions: no stimulation, inefficient low-frequency stimulation, and efficient high-frequency stimulation. RESULTS: The main effect of high-frequency stimulation was to reduce regional cerebral blood flow in the left primary sensorimotor cortex, the lateral premotor cortex, the right cerebellum, and the midline premotor areas. The selective activation of the anterior cingulate cortex and the left primary sensorimotor cortex during hand movement under STN high-frequency stimulation was attributed to decreased regional cerebral blood flow at rest, rather than increased activation induced by STN high-frequency stimulation. Akinesia was correlated with the abnormal overactivity in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. CONCLUSION: High-frequency stimulation of the STN acts through the reduction of abnormal resting overactivity in the motor system, allowing selective cortical activation during movement.