Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease

Background: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. Methodology/Principal Findings: To this end, we conducted 18 FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucos

Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2

Objective: To delineate the natural history, diagnosis, and treatment response of Parkinson disease (PD) in individuals with 22q11.2 deletion syndrome (22q11.2DS), and to determine if these patients differ from those with idiopathic PD. Methods: In this international observational study, we characterized the clinical and neuroimaging features of 45 individuals with 22q11.2DS and PD (mean follow-up 7.5 ± 4.1 years). Results: 22q11.2DS PD had a typical male excess (32 male, 71.1%), presentation and progression of hallmark motor symptoms, reduced striatal dopamine transporter binding with molecular imaging, and initial positive response to levodopa (93.3%). Mean age at motor symptom onset was relatively young (39.5 ± 8.5 years); 71.4% of cases had early-onset PD (<45 years). Despite having a similar age at onset, the diagnosis of PD was delayed in patients with a history of antipsychotic treatment compared with antipsychotic-naive patients (median 5 vs 1 year, p = 0.001). Preexisting psychotic disorders (24.5%) and mood or anxiety disorders (31.1%) were common, as were early dystonia (19.4%) and a history of seizures (33.3%). Conclusions: Major clinical characteristics and response to standard treatments appear comparable in 22q11.2DS-associated PD to those in idiopathic PD, although the average age at onset is earlier. Importantly, treatment of preexisting psychotic illness may delay diagnosis of PD in 22q11.DS patients. An index of suspicion and vigilance for complex comorbidity may assist in identifying patients to prioritize for genetic testing

Can Monkeys Make Investments Based on Maximized Pay-off?

Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella) and thirteen macaques (Macaca fascicularis, Macaca tonkeana) in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible

Place de la pompe à apomorphine dans la maladie de Parkinson (Efficacité et tolérance cognitivo-comportementale chez les patients récusés pour la stimulation cérébrale profonde)

RENNES1-BU Santé (352382103) / SudocSudocFranceF

LA STIMULATION DU NOYAU SOUS-THALAMIQUE DANS LA MALADIE DE PARKINSON (L'EXPERIENCE BRETONNE)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La stimulation du noyau sous-thalamique entraîne des symptômes d'apathie, des troubles de la mémoire de travail, de baisse de libido qui pourraient évoquer un hypogonadisme induit par la stimulation

L'augmentation de l'espérance de vie est responsable de l'émergence de nouvelles pathologies chroniques et notamment les maladies neurodégénératives comme la maladie de Parkinson. L'inefficacité des traitements médicamenteux chez les patients Parkinsoniens à long terme ont amené les chercheurs a trouvé d'autres solutions et notamment la stimulation cérébral profonde. Outre son véritable effet bénéfique sur les symptômes de la maladie, on observe une diminution de la mémoire de travail, une baisse de la libido et un état apathique. Dans cette étude, nous avons essayé de démontré que ces troubles pourraient être dû à un hypogonadisme induit par la stimulation du noyau sous thalamique. La population étudiée étant restreinte, l'étude ne permet pas de conclure précisément sur ce phénomène mais permet d'ouvrir la porte à des études de plus grandes ampleurs et d'étudier l'évolution de ces troubles après l'instauration de traitement hormonal substitutif.In our society, medical advances and changes in health and quality of care have increased the life expectancy. But this increase in life is responsible for the emergence of new chronic diseases, including neurodegenerative diseases such as Parkinson's. The ineffectiveness of drug therapy with long term Parkinson patients has brought researchers to look for other solutions, including deep brain stimulation. Besides the true beneficial effect on symptoms of the disease, there is a decrease in working memory, a decreased libido and an apathetic state. In this study, we tried to show that these disorders could be due to hypogonadism induced by the sub thalamic nucleus stimulation. The study population was limited, the study does not conclude precisely on this phenomenon, but opens the door to studies of larger magnitudes and to study the evolution of these disorders after initiation of hormone replacement therapy .LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Implication de la reconnaissance des expressions faciales sur la qualité de vie des patients parkinsoniens stimulés dans le noyau sous-thalamique

Résumé: Le but de cette étude fut d'évaluer la corrélation entre la reconnaissance des expressions faciales par le test Ekman et la qualité de vie des patients parkinsoniens, mesurée par 2 auto-questionnaires SF36 et PDQ39 . Pour cela, nous avons suivi un groupe de 47 patients au CHU Rennes. Les résultats ont été recueillis avant et après la SCP du NST. Une analyse statistique a alors été réalisée en deux temps. Premièrement, nous avons comparé les résultats post-opératoires et pré-opératoires, pour ensuite établir des corrélations entre les variations de la qualité de vie et les variations de reconnaissance des expressions faciales. L'ensemble des variations a été obtenu en soustrayant les résultats recueillis en post-opératoire des résultats en pré-opératoire. Nous avons ainsi observé une moins bonne reconnaissance de la peur et des expressions faciales en général, et ce, après l'implantation des électrodes. La qualité de vie a été améliorée sur le plan moteur mais pas sur le plan mental. Nous avons vu qu'il existe une corrélation entre le déficit de reconnaissance de la peur et la qualité de vie. Ainsi, nous avons pu conclure qu'il existe un lien étroit entre le défaut de reconnaissance de la peur et l'amélioration des fonctions motrices après la SCP du NST.Summary: The object of this study was to evaluate the correlation between the recognition of facial expressions by the test Ekman and the quality of life of parkinsonian's patients, which are measured by two questionnaires SF36 and PDQ39 . To do that, we followed a group of 47 patients at CHU Rennes. The results were collected before and after the DBS of the STN. A statistical analysis was then performed in two stages. First, we compared the post-operative results and the pre-operative results, and after that we correlated the variations of the quality of life and the changements of the facial emotions recognition. The set of variations was obtain by subtracting the results whose resulted of the post-operative outcomes before surgery. We observed a poorer recognition of facial expressions of fear in general, and after implantation of electrodes. The quality of life was improved physically but not mentally. We have noted a correlation between the quality of life and the deficit of recognition of fear. That way, we could conclude that there is link between the lack of recognition of fear and improvement of motor functions after the DBS of the STN.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

The Many Faces of Apomorphine Lessons from the Past and Challenges for the Future

International audienceApomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges. From shamanic rituals in ancient Egypt and Mesoamerica, to the treatment of erectile dysfunction, from being discarded as a pharmacological tool to becoming an essential antiparkinsonian drug, the path of apomorphine in the therapeutic armamentarium has been tortuous and punctuated by setbacks and groundbreaking discoveries. Throughout history, three main clinical indications stood out: emetic (gastric emptying, respiratory disorders, aversive conditioning), sedative (mental disorders, clinical anesthesia, alcoholism), and antiparkinsonian (fluctuations). New indications may arise in the future, both in PD (palliative care, nonmotor symptoms, withdrawal of oral dopaminergic medication), and outside PD, with promising work in neuroprotection or addiction

Pharmacological Insights into the Use of Apomorphine in Parkinson's Disease Clinical Relevance

International audienceThe present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson's disease (PD). The chemistry, structure-activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic. Its pharmacokinetics and pharmacodynamics are complex and subject to interindividual variability, particularly for subcutaneous absorption and metabolism. Subcutaneous apomorphine, either as injections or infusion, is particularly useful for the treatment of PD motor symptoms and growing evidence supports its clinical value for nonmotor disorders. Owing to interindividual variability and sensitivity, apomorphine treatment must be tailored to each patient. While the subcutaneous route has been the gold standard for decades, the search for alternative routes is ongoing, with promising results from studies of pulmonary, sublingual and transdermal routes. In addition, the potential of apomorphine as a disease-modifying therapy deserves to be investigated, as well as its ability to induce brain plasticity through chronic infusion. Moreover, the ongoing progress in the development of analytical methods should be accompanied by new pharmacokinetic and pharmacodynamic studies of apomorphine metabolism and sites of action in humans, as its biochemistry has yet to be fully described

The Many Faces of Apomorphine Lessons from the Past and Challenges for the Future (vol 18, pg 91, 2018)

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