Compulsive eating behaviors in Parkinson's disease.

PURPOSE: Eating disorders are common in Parkinson's disease (PD) patients and often class in Impulse control disorders, however, little is known about their phenomenology. Specific symptoms and comorbidities were described in a group of PD patients in this preliminary study. METHODS: Over a period of 6 months, 51 PD patients who experienced significant changes in eating habits following diagnosis of PD and were interviewed during regularly scheduled follow-up visits. We assessed each patient's height and weight, impulsivity, psychological distress, current eating disorder symptoms, food addiction, food habits and craving. RESULTS: Among the PD patients who experienced modified dietary habits following diagnosis, few exhibited binge eating disorders (BED) full criteria (3.9%). However, 21.6% of patients experienced episodes of out-of-control eating with a large quantity of food in short time and 39.2% satisfied food addiction (FA) criteria without binge eating disorder. Food cravings more than once a week were experienced in approximately half of the population including all FA patients. Regarding comorbidities, FA PD patients present impulsive features and anxiety. CONCLUSIONS: This study confirms the existence of FA profile in PD patients. Eating disorders even in PD are complex and have a cross-cutting criteria related to out-of-control eating, FA, and BED. The association of anxiety with PD-related food addiction, contrary to L-dopa equivalent daily dose mean score or the presence of dopamine agonists, underline the complex sustainability of the dopaminergic brainstem support. A study on their detailed prevalence in this population could be helpful to better understand unspecified feeding or eating disorder. CLINICAL TRIAL NUMBER: DR-2012-007. NAME OF THE REGISTRY: French Committee for the Protection of Persons (CPP) & French National Commission on Computing and Liberty (CNIL). LEVEL OF EVIDENCE: Level V, descriptive study.

Hypersexuality and pathological gambling in Parkinson's disease: A cross-sectional case-control study.

BACKGROUND: Substance and behavioral addictions have already been described separately or in combination in Parkinson's disease. However, no comparisons of the prevalence of addictive behaviors in patients with Parkinson's disease and the general population have been published. The objective of this study was to compare the prevalence and characteristics of addictions (gambling, hypersexuality, tobacco, and alcohol) in patients with Parkinson's disease and in a matched, paired sample from the general population. METHODS: After matching for age, sex, and complete field questionnaires on addictions, we had 115 data sets. RESULTS: No difference was observed between Parkinson's disease and control populations concerning pathological gambling (0.87% vs 0.87%, P = .99), tobacco addiction (1.7% vs 1.7%, P = .99), and alcohol dependence (2.6% vs 3.5%, P = .71). The Parkinson's disease group showed 2 cases of sexual addiction (1.7% vs 0, P = .15). CONCLUSIONS: Our results indicate that patients with Parkinson's disease do not have specific profiles for tobacco or alcohol addiction and pathological gambling compared with the general population.

Preoperative REM Sleep Behavior Disorder and Subthalamic Nucleus Deep Brain Stimulation Outcome in Parkinson Disease 1 Year After Surgery.

BACKGROUND AND OBJECTIVES: To determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD. METHODS: We analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBD-) probable RBD preoperatively. RESULTS: At preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Society-sponsored version of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] III "off": 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaire-39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBD- patients. Both pre-opRBD+ and pre-opRBD- patients had significant MDS-UPDRS IV score decrease (-37% and -33%, respectively), MDS-UPDRS III "med 'off'/stim 'on'" score decrease (-52% and -54%), and dopaminergic treatment decrease (-52% and -49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes. CONCLUSIONS: In patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery. TRIAL REGISTRATION INFORMATION: NCT02360683. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery.

Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.

S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single-dose double-blind double-placebo 3 x 3 cross-over study. Optimal tested doses were determined during a previous open-label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (Delta UPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 +/- 8 years, PD duration: 12 +/- 6 years, UPDRS III OFF: 37 +/- 15) participated. S90049 was superior to placebo on Delta UPDRS III (-13 +/- 12 versus -7 +/- 9 respectively; estimated difference -5.2, 95% Confidence Interval (CI)[-10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, Delta UPDRS III was similar on S90049 (-21.2 +/- 10.1) and apomorphine (-23.6 +/- 14.1) (estimated difference: 4.0 95% CI [-2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate.

Visual hallucinations and illusions in Parkinson's disease: the role of ocular pathology.

INTRODUCTION: Whether different mechanisms, particularly ocular pathology, could lead to the emergence of visual hallucinations (VH) (defined as false perceptions with no external stimulus) versus visual illusions (VI) (defined as a misperception of a real stimulus) in Parkinson's disease (PD) remains debated. We assessed retinal, clinical and structural brain characteristics depending on the presence of VH or VI in PD. METHODS: In this case-control study, we compared retinal thickness using optical coherence tomography (OCT), between PD patients with: VI (PD-I; n = 26), VH (PD-H; n = 28), and without VI or VH (PD-C; n = 28), and assessed demographic data, disease severity, treatment, anatomical and functional visual complaints, cognitive and visuo-perceptive functions and MRI brain volumetry for each group of PD patients. RESULTS: Parafoveal retina was thinner in PD-H compared to PD-C (p = 0.005) and PD-I (p = 0.009) but did not differ between PD-I and PD-C (p = 0.85). Multivariate analysis showed that 1/retinal parafoveal thinning and total brain gray matter atrophy were independently associated with the presence of VH compared to PD-I; 2/retinal parafoveal thickness, PD duration, sleep quality impairment and total brain gray matter volume were independent factors associated with the presence of VH compared to PD-C; 3/anterior ocular abnormalities were the only factor independently associated with the presence of illusions compared to PD-C. CONCLUSION: These findings reinforce the hypothesis that there may be different mechanisms contributing to VH and VI in PD, suggesting that these two entities may also have a different prognosis rather than simply lying along a continuous spectrum. REGISTRATION NUMBER: Clinicaltrials.gov number NCT01114321.

Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized controlled trial.

INTRODUCTION: There is an unmet need to better control motor complications in Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of PD and in a clinical proof of concept study. METHODS: We conducted a double-blind randomized placebo-controlled cross-over trial in PD patients with motor fluctuations and dyskinesia testing naftazone 160 mg/day versus placebo for 14 days. The two co-primary endpoints were the area under curve (AUC) of motor (MDS-UPDRS part III) and dyskinesia (AIMS) scores during an acute levodopa challenge performed at the end of each period. Secondary endpoints were UDysRS and axial symptoms scores during the challenge; AIMS, UDysRS, and time spent with or without dyskinesia the day before the challenge. The primary analysis was performed in the per protocol population. RESULTS: Sixteen patients were included in the analysis. There was no difference between naftazone and placebo for the AUC of MDS-UPDRS III (-89, 95%CI[-1071; 893], p = 0.85), and AIMS (70, 95%CI[-192; 332], p = 0.57). At the end of treatment periods, AIMS score tended to be lower with naftazone than placebo (4.4 ±â€¯3.4 versus 6.7 ±â€¯4.4, p = 0.07), but UDysRS scores and other secondary outcomes were not different. Naftazone was safe and well tolerated. CONCLUSIONS: This study did not confirm previous results on the efficacy of naftazone on dyskinesia nor motor fluctuations highlighting the problem of translating results obtained in preclinical models into clinical trials. Further investigation of naftazone may be conducted in PD with longer treatment duration.

Impulse control disorders in Parkinson's disease patients with RLS: a cross sectional-study.

BACKGROUND: Although dopamine replacement therapy is the main risk factor for the occurrence of Impulse Control Disorders (ICDs) in Parkinson's disease (PD), non-pharmacological risk factors for have also been identified in that population and sleep disorders could be part of them. Our objective is to determine whether Restless Legs Syndrome (RLS), that has been associated with more impulsive choices in general population regardless of dopaminergic therapy, could be associated with a specific psycho-behavioral profile and ICDs in PD. METHODS: Eighty consecutive PD patients were screened for the presence of RLS in a cross-sectional study. Sleep features were evaluated during one video-polysomnography. The frequency of ICDs, according to standard criteria, together with a broad range of psycho-behavioral features using the Ardouin Scale of Behavior in PD, were compared in patients with RLS (PD-RLS, n = 30) versus without RLS (PD-nRLS, n = 50). RESULTS: PD patients with RLS reported significantly more ICDs than those without RLS (50% versus 26%, p = 0.03), especially compulsive eating disorders, and a different psycho-behavioral profile with more hyperdopaminergic behaviors. There was no between group difference for total and dopamine agonists levodopa equivalent doses. However, age and durations of both disease and dopaminergic treatment were greater in the RLS group. Multivariate and propensity score analyses controlling for age, gender, total sleep time, disease severity, dose and duration of treatment, anxiety and depression showed that RLS was an independent predictor of ICDs in PD (OR = 5.91 [1.63; 22.1] and OR = 2.89 [1.63; 6.67] respectively). CONCLUSION: RLS per se could be a risk factor for impulsive behaviors in PD.

Emergence of restless legs syndrome after subthalamic stimulation in Parkinson's disease: a dopaminergic overstimulation?

OBJECTIVE: Studies investigating the effects of subthalamic deep-brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) are limited and report conflicting results, with some describing the emergence of RLS after DBS-STN, while others report postoperative improvement of this disorder. Severe decrease in postoperative dopaminergic medications dose, which may unmask RLS symptoms, has been proposed to explain the emergence of RLS after surgery. We aimed to specifically identify factors associated with the risk of developing RLS after DBS-STN in order to enhance our comprehension of the underlying mechanisms contributing to the development of RLS in PD. PATIENTS: In this observational prospective study, we evaluated the occurrence of RLS in 31 patients with PD originally free from RLS symptoms, six months after bilateral chronic DBS-STN, and compared clinical and treatment parameters of patients who developed postoperative RLS with those of patients without postoperative RLS. RESULTS: Six patients out of 31 reported post-operative emergence of RLS. There was no between-group difference in demographic data, pre-operative treatment parameters or clinical improvement measures after DBS-STN. However, PD patients with emergence of RLS after DBS-STN had a higher dose of dopamine agonists at postoperative evaluation compared to PD patients without emergence of RLS (p = 0.040) and a lower percentage of decrease in dopamine agonists (p = 0.043). CONCLUSION: Overstimulation resulting from cumulative effects of dopamine agonists and STN-DBS may induce changes in excitability of the dopaminergic system, leading to an emergence of RLS. Clinicians should take into account this phenomenon while adjusting pharmacological treatment after surgery.

Central pain modulation after subthalamic nucleus stimulation: A crossover randomized trial.

OBJECTIVE: To investigate the acute effect of subthalamic nuclei deep brain stimulation (STN-DBS) and levodopa on pain and tolerance thresholds in patients with Parkinson disease. We hypothesized that a modification of pain threshold after STN-DBS would suggest a central modification of pain perception, whereas the absence of pain threshold change after STN-DBS would correspond to a peripheral mechanism via a decrease of painful stimuli. METHODS: Nineteen patients with Parkinson disease were included in this double-blind, randomized, crossover study. Postoperatively, we evaluated pain thresholds (thermal and mechanical) and motor symptoms under 3 acute conditions: stimulation on/medication off; stimulation off/medication on; and stimulation off/medication off. We also conducted a retrospective analysis of the data prospectively recorded during the follow-up of the cohort pre- and postoperatively (Unified Parkinson's Disease Rating Scale [UPDRS] score, Hoehn and Yahr stage, equivalent levodopa daily dose, and tapping test score). RESULTS: We found a significant increase of pain and tolerance mechanical thresholds not only after acute STN-DBS but also after acute levodopa administration. We did not find any significant correlation between postoperative clinical pain improvement and UPDRS-III improvement after acute levodopa or STN-DBS, nor with motor complications improvement assessed with UPDRS-IV after chronic STN-DBS. No correlation was found between postoperative clinical pain improvement and mechanical pain threshold modification. CONCLUSION: Clinical pain alleviation after STN-DBS cannot be considered merely as a consequence of motor complications improvement and could be attributable to a direct central modulation of pain perception, via increased mechanical pain and tolerance thresholds.

Long-term follow-up of globus pallidus chronic stimulation in advanced Parkinson's disease.

To assess the long-term follow-up of the globus pallidus internus (GPi) stimulation, six patients were evaluated every year by using the Unified Parkinson's Disease Rating Scale (UPDRS). Three years postoperatively, GPi stimulation led to a significant improvement of dyskinesia severity (50%, P = 0.05) and activities of daily living (subscore of quality of life scale, 9%, P = 0.05). However, the improvement induced by chronic pallidal stimulation on the mean daily duration in the off state was lost at the last assessment.

Safety of entacapone and apomorphine coadministration in levodopa-treated Parkinson's disease patients: pharmacokinetic and pharmacodynamic results of a multicenter, double-blind, placebo-controlled, cross-over study.

We investigated whether administration of the catechol-O-methyl transferase (COMT) inhibitor entacapone, at doses of 200 mg and 400 mg, alters the pharmacokinetics of apomorphine in Parkinson's disease patients experiencing severe motor fluctuations. In addition, the pharmacodynamics and safety of entacapone and apomorphine coadministration in these patients were examined. The study followed a three-sequence, three-period, crossover design. Patients were randomly assigned to one of three sequences that included single oral doses of entacapone 200 mg, entacapone 400 mg, and placebo in a predefined order. On 3 separate test days, study treatment was administered before apomorphine. The study evaluations (pharmacokinetics, tapping test, and dyskinesia evaluation [Abnormal Involuntary Movements Scale - AIMS]) were performed on these days. Furthermore, Unified Parkinson Disease Rating Scale (UPDRS) scores were evaluated at baseline and study end. Pharmacokinetic parameters for apomorphine (C(max), AUC, t(max), t(1/2)) were unchanged by the administration of entacapone, and changes in both the tapping test and AIMS score were similar with all treatments (entacapone 200 mg, entacapone 400 mg, and placebo). There was no significant difference in mean total UPDRS scores between baseline and study end. The administration of entacapone did not change the pharmacokinetic or pharmacodynamic effects of apomorphine in these patients or prolong the clinical effect of apomorphine. Thus, apomorphine may be safely administered to patients receiving therapy with levodopa and entacapone, providing a useful addition to treatment for patients with advanced Parkinson's disease.