Validation of the RBD Symptom Severity Scale in the North American Prodromal Synucleinopathy Consortium.

BACKGROUND AND OBJECTIVES: REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD. METHODS: NAPS participants, who have polysomnogram-confirmed RBD, and their bedpartners completed the RBDSSS (participant and bedpartner versions). The RBDSSS contains 8 questions to assess the frequency and severity/impact of (1) dream content, (2) vocalizations, (3) movements, and (4) injuries associated with RBD. Total scores for participant (maximum score = 54) and bedpartner (maximum score = 38) questionnaires were derived by multiplying frequency and severity scores for each question. The Clinical Global Impression Scale of Severity (CGI-S) and RBD symptom frequency were assessed by a physician during a semistructured clinical interview with participants and, if available, bedpartners. Descriptive analyses, correlations between overall scores, and subitems were assessed, and item response analysis was performed to determine the scale's validity. RESULTS: Among 261 study participants, the median (interquartile range) score for the RBDSSS-PT (participant) was 10 (4-18) and that for the RBDSSS-BP (bedpartner) was 8 (4-15). The median CGI-S was 3 (3-4), indicating moderate severity. RBDSSS-BP scores were significantly lower in women with RBD (6 vs 9, p = 0.02), while there were no sex differences in RBDSSS-PT scores (8 vs 10.5, p = 0.615). Positive correlations were found between RBDSSS-PT vs RBDSSS-BP (Spearman rs = 0.561), RBDSSS-PT vs CGI-S (rs = 0.556), and RBDSSS-BP vs CGI-S (rs = 0.491, all p < 0.0001). Item response analysis showed a high discriminatory value (range 1.40-2.12) for the RBDSSS-PT and RBDSSS-BP (1.29-3.47). DISCUSSION: We describe the RBDSSS with adequate psychometric and clinimetric properties to quantify RBD symptom severity and good concordance between participant and bedpartner questionnaires and between RBDSSS scores and clinician-assessed global severity.

Psychobehavioural profile in narcolepsy type 1 with and without REM sleep behaviour disorder.

REM sleep behaviour disorder (RBD) is common in narcolepsy type 1 (NT1). Abnormalities in the reward system have been observed in NT1, possibly related to impaired orexin projections towards the mesolimbic reward system, but also in RBD when associated with Parkinson's disease. Our study aimed to explore the psychobehavioural profile of NT1 patients with and without RBD compared with healthy controls (HC). Forty patients with NT1 were compared with 20 sex- and age-matched HC. All patients with NT1 underwent a video-polysomnography including a measure of REM sleep without atonia (RSWA). The following neuropsychobehavioural variables were assessed: apathy, impulsivity, depression, cognition, subjective and objective attention, sensation-seeking, and behavioural addictions. The patient population included 22 patients with NT1-RBD and 18 patients with NT1-noRBD. Compared with the healthy controls, patients with NT1 had higher scores of apathy, impulsivity, and depression; a lower score on global cognition, and poorer self-perceived attention. No differences were found between patients with NT1 with and without RBD in all neuropsychological variables, except for impaired objective attention in patients with NT1-RBD. In patients with NT1, a positive correlation was observed between RSWA and both apathy and impulsivity subscale. Moreover, in patients with NT1-RBD, RSWA was positively correlated with depression. Patients with NT1 showed higher depression, apathy, and impulsivity compared with controls. These measures correlate with the severity of RSWA, suggesting a transdiagnostic association between RBD and abnormalities of the reward system at least for patients with NT1.

Volumetric changes and clinical trajectories in Parkinson's disease: a prospective multicentric study.

BACKGROUND: Longitudinal measures of structural brain changes using MRI in relation to clinical features and progression patterns in PD have been assessed in previous studies, but few were conducted in well-defined and large cohorts, including prospective clinical assessments of both motor and non-motor symptoms. OBJECTIVE: We aimed to identify brain volumetric changes characterizing PD patients, and determine whether regional brain volumetric characteristics at baseline can predict motor, psycho-behavioral and cognitive evolution at one year in a prospective cohort of PD patients. METHODS: In this multicentric 1 year longitudinal study, PD patients and healthy controls from the MPI-R2* cohort were assessed for demographical, clinical and brain volumetric characteristics. Distinct subgroups of PD patients according to motor, cognitive and psycho-behavioral evolution were identified at the end of follow-up. RESULTS: One hundred and fifty PD patients and 73 control subjects were included in our analysis. Over one year, there was no significant difference in volume variations between PD and control subjects, regardless of the brain region considered. However, we observed a reduction in posterior cingulate cortex volume at baseline in PD patients with motor deterioration at one year (p = 0.017). We also observed a bilateral reduction of the volume of the amygdala (p = 0.015 and p = 0.041) and hippocampus (p = 0.015 and p = 0.053) at baseline in patients with psycho-behavioral deterioration, regardless of age, dopaminergic treatment and center. CONCLUSION: Brain volumetric characteristics at baseline may predict clinical trajectories at 1 year in PD as posterior cingulate cortex atrophy was associated with motor decline, while amygdala and hippocampus atrophy were associated with psycho-behavioral decline.

Anti-LGI1 Encephalitis With Co-occurring IgLON5 Antibodies: Clinical Features and Human Leukocyte Antigen Haplotypes.

OBJECTIVES: Autoimmune encephalitis (AE) with antibodies against LGI1 and IgLON5 are clinically distinctive but share some particularities such as a strong association with specific human leukocyte antigen (HLA) class II alleles. METHODS: We clinically describe a patient with double positivity for LGI1 and IgLON5 antibodies. In addition, we conducted specific immunodepletion with the patient's serum and HLA typing and investigated the presence of serum IgLON5 antibodies in a cohort of 23 anti-LGI1 patients carrying the HLA predisposing for anti-IgLON5 encephalitis. RESULTS: A 70-year-old woman with a history of lymphoepithelial thymoma presented with subacute cognitive impairment and seizures. Investigations included MRI and EEG showing medial temporal involvement, increased CSF protein content, and polysomnography with REM and non-REM motor activity, along with obstructive apnea. Neural antibody testing revealed both LGI1 and IgLON5 antibodies in serum and CSF, and serum immunodepletion ruled out cross-reactivity. The patient carried DRB1*07:01 and DQA1*01:01∼DQB1*05:01, but no other IgLON5-positive case was identified in a cohort of anti-LGI1 patients carrying DQA1*01∼DQB1*05. Nearly full therapeutic response was obtained after intensified immunosuppressive treatment. DISCUSSION: We present a case of anti-LGI1 encephalitis with concomitant IgLON5 antibodies. Co-occurring IgLON5 antibodies in anti-LGI1 encephalitis are exceptional, but may appear in genetically predisposed individuals.

Severity of REM sleep without atonia correlates with measures of cognitive impairment and depressive symptoms in REM sleep behaviour disorder.

This study aimed to correlate REM sleep without atonia (RSWA) and neuropsychological data in patients with idiopathic/isolated REM sleep behaviour disorder (iRBD) and those with RBD associated with Parkinson's disease (PDRBD), in order to assess whether higher degrees of RSWA are related to poorer cognitive performance. A total of 142 subjects were enrolled: 48 with iRBD, 55 with PDRBD, and 39 PD without RBD (PDnoRBD). All participants underwent video-polysomnographic recording, clinical and neuropsychological assessment. RSWA was quantified according to two manual scoring methods (Montréal, SINBAR) and one automated (REM atonia index, RAI). Mild cognitive impairment (MCI) was diagnosed according to diagnostic criteria for MCI in Parkinson's disease. The relationship between neuropsychological scores and RSWA metrics was explored by multiple linear regression analysis and logistic regression models. Patients with iRBD showed significantly lower visuospatial functions and working memory, compared with the others. More severe RSWA was associated with a higher risk of reduced visuospatial abilities (OR 0.15), working memory (OR 2.48), attention (OR 2.53), and semantic fluency (OR 0.15) in the iRBD. In the whole group, a greater RSWA was associated with an increased risk for depressive symptoms (OR 3.6). A total of 57(40%) MCI subjects were found (17 iRBD, 26 PDRBD, and 14 PDnoRBD). Preserved REM-atonia was associated with a reduced odds of multi-domain MCI in the whole study population (OR 0.54). In conclusion, a greater severity of RSWA was associated with an increased risk for poor cognitive performance and depressive mood in patients with RBD. Moreover, higher RAI was associated with a lower risk of multi-domain MCI.

A data-driven approach to neuropsychological features in isolated REM behaviour disorder: A latent class analysis.

Recent evidence demonstrated that neuropsychological assessment may be considered a valid marker of neurodegeneration in idiopathic REM sleep behaviour disorder (iRBD). However, little is known about the possible neuropsychological heterogeneity within the iRBD population. This retrospective study aimed to identify and describe different neuropsychological phenotypes in iRBD patients by means of a data-driven approach using latent class analysis. A total of 289 iRBD patients underwent a neuropsychological assessment evaluating cognitive domains: global cognition, language, short- and long-term memory, executive functions and visuospatial abilities. The presence of mild cognitive impairment (MCI) was also assessed. Latent class analysis was carried out to identify iRBD subtypes according to neuropsychological scores. The most parsimonious model identified three latent classes. Groups were labelled as follows: Class 2 "severely impaired" (n = 83/289): mean pathological scores in different tests, a high percentage of MCI multiple-domain and impairment in all neuropsychological domains. Class 1 "moderately impaired" (n = 44/289): mean neuropsychological score within the normal value, a high percentage of MCI (high risk to phenoconversion) and great impairment in the visuospatial domain. Class 3 "slightly impaired" (n = 162/289): no deficit worthy of attention except for short- and long-term memory. Our results suggest three different clinical phenotypes within the iRBD population. These findings may be relevant in the future for predicting the clinical trajectories of phenoconversion in iRBD.

Screening and management of sleep disorders in patients with fibromyalgia syndrome: a French multicentred, prospective, observational study protocol (FIBOBS).

INTRODUCTION: Sleep disorders are still often underestimated in patient care management even though they are present in the criteria of the American College of Rheumatology for the diagnosis of fibromyalgia syndrome (FMS). The objective of this study will be to assess the current situation of sleep disorders in patients with FMS in France and to estimate its prevalence. METHODS AND ANALYSIS: The FIBOBS study is a multicentred, prospective, observational trial performed by 46 specialised chronic pain structures in France. Patients with FMS visiting for a first consultation or follow-up (if they have already been followed up for less than a year with a pain management service) will be included after giving their informed consent. Data will be collected through the physician questionnaire filled during the inclusion visit. Patient self-questionnaires will be completed from home. The primary outcome of the study will be to estimate the prevalence of sleep disorders classified into three categories: (a) poor sleep quality in general, (b) sleep apnoea syndrome and (c) restless legs syndrome, using self-administered questionnaires. ETHICS AND DISSEMINATION: This protocol is approved by the ethics committee Comité de Protection des Personnes 'Ile de France II' in accordance with French regulations. The results will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT04775368.

Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study.

BACKGROUND: Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia. METHODS: We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912. FINDINGS: Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041). INTERPRETATION: Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia. FUNDING: Orkyn and Aguettant Pharma. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: guidelines from the International RBD Study Group.

Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.

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.

Effects of a Short Daytime Nap on the Cognitive Performance: A Systematic Review and Meta-Analysis.

BACKGROUND: Napping in the workplace is under debate, with interesting results on work efficiency and well-being of workers. In this systematic review and meta-analysis, we aimed to assess the benefits of a short daytime nap on cognitive performance. METHODS: PubMed, Cochrane Library, ScienceDirect and PsycInfo databases were searched until 19 August 2021. Cognitive performance in working-aged adults, both before and following a daytime nap or under control conditions (no nap), was analysed by time and by type of cognitive function (alertness, executive function and memory). RESULTS: We included 11 studies (all in laboratory conditions including one with a subgroup in working conditions) for a total of 381 participants. Mean duration of nap was 55.4 ± 29.4 min. Overall cognitive performance did not differ at baseline (t0) between groups (effect size -0.03, 95% CI -0.14 to 0.07), and improved in the nap group following the nap (t1) (0.18, 0.09 to 0.27), especially for alertness (0.29, 0.10 to 0.48). Sensitivity analyses gave similar results comparing only randomized controlled trials, and after exclusion of outliers. Whatever the model used, performance mainly improved until 120 min after nap, with conflicting results during the sleep inertia period. Early naps in the afternoon (before 1.00 p.m.) gave better cognitive performance (0.24, -0.07 to 0.34). The benefits of napping were independent of sex and age. Duration of nap and time between nap and t1 did not influence cognitive performance. CONCLUSIONS: Despite the fact that our meta-analyses included almost exclusively laboratory studies, daytime napping in the afternoon improved cognitive performance with beneficial effects of early nap. More studies in real work condition are warranted before implementing daytime napping at work as a preventive measure to improve work efficiency.

Randomized Double-Blind Controlled Trial on the Effect of Proteins with Different Tryptophan/Large Neutral Amino Acid Ratios on Sleep in Adolescents: The PROTMORPHEUS Study.

Disturbed sleep is common in adolescents. Ingested nutrients help regulate the internal clock and influence sleep quality. The purpose of this clinical trial is to assess the effect of protein tryptophan (Trp)/large neutral amino acids (LNAAs) ratio on sleep and circadian rhythm. Ingested Trp is involved in the regulation of the sleep/wake cycle and improvement of sleep quality. Since Trp transport through the blood-brain barrier is competing with LNAAs, protein with higher Trp/LNAAs were expected to increase sleep efficiency. This randomized double-blind controlled trial will enroll two samples of male adolescents predisposed to sleep disturbances: elite rugby players (n = 24) and youths with obesity (n = 24). They will take part randomly in three sessions each held over a week. They will undergo a washout period, when dietary intake will be calibrated (three days), followed by an intervention period (three days), when their diet will be supplemented with three proteins with different Trp/LNAAs ratios. Physical, cognitive, dietary intake, appetite, and sleepiness evaluations will be made on the last day of each session. The primary outcome is sleep efficiency measured through in-home electroencephalogram recordings. Secondary outcomes include sleep staging, circadian phase, and sleep-, food intake-, metabolism-, and inflammation-related biochemical markers. A fuller understanding of the effect of protein Trp/LNAAs ratio on sleep could help in developing nutritional strategies addressing sleep disturbances.

Napping and cognitive performance during night shifts: a systematic review and meta-analysis.

STUDY OBJECTIVES: To examine the benefits of napping during night shifts on cognitive performance. METHODS: Medline, Cochrane Library, Science direct, and Embase databases were searched up to July 1, 2019. Cognitive performance during night shifts, both before and following napping or under control conditions (no nap), in working-aged adults, were analyzed by time and by type of cognitive function (executive function, attention, instrumental function, and memory). Estimates were pooled using random-effects meta-analysis. RESULTS: A total of 18 articles (6 in real-work and 12 in laboratory) with a total of 494 participants were included. The mean nap duration was 41.6 ± 28.3 min, occurring between 12.00 am and 4.10 am, with a mean time set at 2.12 am. Cognitive performance did not differ at baseline between the groups (effect size 0.02, 95% CI -0.09 to 0.13). There was an overall improvement in performance following a nap compared to the control condition without a nap (0.25, 0.10 to 0.41). Positioning naps early in the night and activity (simulated work tasks) tended to improve cognitive performance (-0.57, -1.16 to 0.002, and 0.082, -0.04 to 0.33, respectively). The improvements were primarily seen 30 min after awakening. Only memory deteriorated immediately after awakening without an overall change in global cognitive performance. CONCLUSION: Napping during night shifts seems to improve cognitive performance. Napping early in the night and activity may benefit cognitive performance over time. Considering lack of data in real work environments, further studies are warranted before preconizing napping during night shifts as a preventive strategy (safety, health, and economic outcomes).

Is Rapid Eye Movement Sleep Behavior Disorder a Risk Factor for Impulse Control Disorder in Parkinson Disease?

OBJECTIVE: To assess the association between rapid eye movement sleep behavior disorder (RBD) and other determinants and incident impulse control disorder behaviors (ICBs) in patients with early Parkinson disease (PD) using longitudinal data from the Parkinson's Progression Markers Initiative. METHODS: Four hundred one newly diagnosed PD patients were prospectively evaluated at baseline (BL), month 6, and annually for 5 years. Probable RBD (pRBD) was assessed with the RBD Screening Questionnaire (RBDSQ) and dichotomized using a cutoff value of ≥6. The association of BL and time-dependent (TD) pRBD and other covariates with the development of ICB symptoms was evaluated using Cox proportional hazards regression and general estimating equation logistic regression. Models considered adjustment for age, sex, Movement Disorders Society Unified Parkinson's Disease Rating Scale part III, Geriatric Depression Scale (GDS-15), RBD medication use, total levodopa equivalent daily dose, and dopamine agonist (DA) and antidepressant medication use. RESULTS: Both BL pRBD and TD pRBD were not associated with an increased risk for incident ICB symptoms after adjustment for covariates (adjusted hazard ratio [HR] = 1.17, p = 0.458 and HR = 1.27, p = 0.257, respectively). In a modified TD pRBD model (ie, considering subjects as pRBD onward from the first time point with RBDSQ score ≥ 6), the risk for incident ICB symptoms was higher in pRBD in unadjusted (HR = 1.48, p = 0.038) but not adjusted (HR = 1.29, p = 0.203) models. TD DA use (HR = 1.64, p = 0.039), TD GDS-15 score (HR = 1.12, p < 0.001), and male sex (year 3: HR = 2.10, p = 0.009; year 4: HR = 3.04, p = 0.006; year 5: HR = 4.40, p = 0.007) were associated with increased ICB symptom risk. INTERPRETATION: pRBD is not clearly associated with ICB symptom development in early PD, in contrast to DA use, depression, and male sex. ANN NEUROL 2020;88:759-770.

REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder.

STUDY OBJECTIVES: The neurophysiological hallmark of REM sleep behavior disorder (RBD) is loss of atonia during REM sleep. Indeed, signs and symptoms of neurodegeneration can occur after years, even decades, from its beginning. This study aimed to measure neurophysiological alterations of the brainstem that potentially correlate with the severity of atonia loss, and determining whether a prodromal neurodegenerative disorder underlines this condition when it occurs as an isolated condition (iRBD). METHODS: Subjects with iRBD and matched healthy controls were recruited. The study included the recording of one-night polysomnography, vestibular-evoked myogenic potentials (VEMPs), and a [123I]-FP-CIT dopamine transporter (DAT) scan. The quantification of REM sleep without atonia (RSWA) was made according to two previously published manual methods and one automated method. RESULTS: The rate of alteration of VEMPs and VEMP score were significantly higher in iRBD patients than controls. Moreover, VEMP score was negatively correlated with the automated REM atonia index; a marginal statistical significance was also reached for the positive correlation with the visual tonic electromyographic parameter, while the other correlations, including that with DAT-scan score were not statistically significant. CONCLUSIONS: Brainstem neurophysiology in iRBD can be assessed by VEMPs and their alterations may possibly indicate an early expression of the neurodegenerative process underlying this disorder at the brainstem level, which awaits future longitudinal confirmation. The correlation between RSWA and VEMP alteration might also represent a prodromal aspect anticipating the possible evolution from iRBD to neurodegeneration, whereas DAT-scan abnormalities might represent a later step in this evolution.

Impulse Control Disorders in REM Sleep Behavior Disorder.

PURPOSE OF REVIEW: This paper reviews clinical and pathophysiological features of both impulse control disorders (ICDs) and REM sleep behavior disorder (RBD) in Parkinson's disease (PD), as well as current evidences of their association. Then, we suggest recommendations to manage PD patients with RBD in order to prevent this potentially devastating psychiatric complication. RECENT FINDINGS: ICDs are psychiatric complications occurring in patients with Parkinson's disease (PD) treated with dopaminergic replacement therapies (DRT). Besides DRT, risk factors for ICDs are poorly known. We recently showed an association between ICDs and RBD in PD. Detecting RBD in PD may provide clinician the opportunity to identify patients at higher risk to develop ICDs. In PD patients with either a video-polysomnographic (v-PSG) diagnosis of RBD or a typical history of RBD when v-PSG is not available, dopamine agonists should be avoided whenever possible, or be prescribed at the lowest effective dose. Furthermore, gradual tapering of dopamine agonist would be recommended, due to the potential increased risk of dopamine withdrawal syndrome in these patients. Increased surveillance, implying patients and caregiver education to recognize early changes in behavior and in mood possibly related to a hyperdopaminergic status, should be part of the preventive strategies.

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.

Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

OBJECTIVE: To detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. METHODS: Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). RESULTS: Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ±â€¯229 vs 1101 ±â€¯201 mmol min.l-1; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p < 0.001), female gender (p < 0.033), longer duration of PD (p = 0.001), lower dose of dopaminergic treatment (p = 0.023), and higher score of dysautonomia (p = 0.017). CONCLUSION: Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia.