REM Sleep Behavior Disorder Symptoms Research Articles

Sleep Disturbances and Phenoconversion in Patients with REM Sleep Behavior Disorder.

Objective: We aimed to investigate relationships between sleep disturbances and phenoconversion to neurodegenerative diseases in patients with REM sleep behavior disorder (RBD). Method: Using a comprehensive sleep database in a university-affiliated hospital between December 2014 and March 2021, we reviewed the data of 226 patients with RBD (182 patients with idiopathic RBD (iRBD) and 44 patients with symptomatic RBD (sRBD) with a neurodegenerative disease). Results: Among 226 patients with RBD (male, 61.5%), the mean age at RBD onset and mean disease duration were 59.4 ± 10.5 and 5.9 ± 5.6 years, respectively. Further, 111 (49.1%) patients had periodic limb movements during sleep (PLMS, PLM index ≥ 15/h), while 110 patients (48.7%) had comorbid obstructive sleep apnea (OSA, respiratory disturbance index ≥ 15/h). There was a positive correlation between age at RBD onset and the apnea-hypopnea index and Pittsburgh Sleep Quality Index. Compared to patients with iRBD, patients with sRBD showed a lower N3 sleep (3.3 ± 5.0 vs. 1.6 ± 3.1%, p = 0.004) and higher periodic limb movement index (36.3 ± 31.8 vs. 56.9 ± 47.5/h, p = 0.021) at the baseline. Among the 186 patients with iRBD, 18 (8.0%) developed neurodegenerative diseases (converters, mean follow-up duration: 2.5 ± 1.6 years) and 164 did not (non-converters, mean follow-up 2.4 ± 2.2 years). There was no significant between-group difference in the demographics and baseline clinical features. Continuous positive airway pressure (CPAP) therapy was prescribed in 101 patients with OSA; among them, 71 (70%) patients agreed to use it. CPAP improved dream enactment behaviors. Conclusion: In our study, 8.0% of patients with iRBD showed phenoconversion within a mean follow-up duration of 2.5 years. Polysomnographic parameters could not predict phenoconversion to neurodegenerative disease. However, approximately half of the patients with RBD presented with significant sleep disorders, including OSA or PLMS. CPAP therapy may alleviate RBD symptoms in patients with RBD-OSA.

Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson's Disease.

BackgroundClinical observations reveal that rapid eye movement (REM) sleep behavior disorder (RBD) often develops prior to alpha-synucleinopathies including Parkinson’s disease (PD). However, a causal relationship between alpha-synucleinopathy and Parkinsonian neurodegeneration has not been delineated.MethodsRats were chronically treated with rotenone and EEG and EMG signals were recorded for analysis of sleep behavior, assisted by video recording of body movements. C-fos expression and TUNEL staining were used to assess neuronal activation and apoptosis, respectively. Chemogenetic manipulation of brain stem nuclei was conducted to ameliorate RBD symptoms in rotenone-treated rats.ResultsRats chronically exposed to rotenone exhibited progressive RBD features, from EEG slowing to REM sleep motor behavior and NREM muscle activities. Temporally, these phenomena correlated well with progressive alpha-synuclein aggregation and neuronal apoptosis in the sublaterodorsal tegmental nucleus (SLD) and gigantocellular ventricular reticular nucleus in the brainstem. Chemogenetic activation of glutamatergic neurons in SLD alleviated RBD symptoms in the rotenone model.ConclusionTaken together, these results are consistent with a progressive degeneration in the REM sleep promoting and atonia circuit in early Parkinsonism that underlies the emergence of RBD symptoms, and demonstrate that the rotenone model is useful for further studies into RBD and its relationship to PD.

Pharmacological Treatment for Rapid Eye Movement Sleep Behavior Disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by abnormal movement during REM sleep. Violent motor behaviors correlated with dreams commonly result in sleep-related injuries, which are sometimes life-threatening, to patients and their bed partners. The current guidelines for RBD treatment include counseling, modifying the sleep environment to prevent sleep-related injury, and pharmacological therapy. This paper focuses on current pharmacotherapy options for the treatment of RBD, including clonazepam and melatonin, which represent the mainstay of RBD therapy. Acetylcholinesterase inhibitors and dopamine-agonists have been used, as RBD is usually associated with other neurodegenerative diseases, with encouraging results in preliminary clinical trials. More randomized controlled trials with objective outcome measures are needed to assess both short-term and long-term effects of these medications and their efficacy in RBD. Understanding the exact mechanisms involved in decreasing RBD symptoms could provide future approaches in new drug development.

Sleep quality, REM sleep behavior disorder and daytime sleepiness in adults with and without Parkinson's

In Parkinson's disease (PD), poor sleep quality and sleep disorders are central part of the non-motor symptoms. The aim was to compare sleep quality (SQ), REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) among adults with and without Parkinson's disease (PD). A second objective was to know the relationship of SQ and RBD with EDS in patients with PD. Method. sixty adults (38 % women, mean age 66.7 ± 8.11 years), 50 % with PD diagnosis and 50 % healthy controls, Instruments: Epworth Sleepiness Scale, Sleep Quality Pittsburgh Index and REM Behavioral Disorder Sleep Questionnaire, which was designed for this study. Results. Differences were found in SQ (PD = 9.90 ±4.47 vs Control group = 7.23 ±4.71, t = 2.25, p = .028), and the percentage of cases with symptoms of RBD (PD = 30%, control group = 6.7%, ji2 = 5.455, p = .020). No differences were found in EDS (PD = 7.43 ± 5.46 vs Control group = 6.50 ± 5.28, t = .673, p = .504). According to the linear regression analysis, the increase in EDS was not associated with SQ, EDS was only associated with RBD. Conclusion, the PD group presents a poor sleep quality and a higher prevalence of RBD symptoms. EDS did not differ between adults with and without PD. However, RBD was associated with an increase in EDS in the PD group.

Sleep quality, REM sleep behavior disorder and daytime sleepiness in adults with and without Parkinson's

In Parkinson's disease (PD), poor sleep quality and sleep disorders are central part of the non-motor symptoms. The aim was to compare sleep quality (SQ), REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) among adults with and without Parkinson's disease (PD). A second objective was to know the relationship of SQ and RBD with EDS in patients with PD. Method. sixty adults (38 % women, mean age 66.7 ± 8.11 years), 50 % with PD diagnosis and 50 % healthy controls, Instruments: Epworth Sleepiness Scale, Sleep Quality Pittsburgh Index and REM Behavioral Disorder Sleep Questionnaire, which was designed for this study. Results. Differences were found in SQ (PD = 9.90 ±4.47 vs Control group = 7.23 ±4.71, t = 2.25, p = .028), and the percentage of cases with symptoms of RBD (PD = 30%, control group = 6.7%, ji2 = 5.455, p = .020). No differences were found in EDS (PD = 7.43 ± 5.46 vs Control group = 6.50 ± 5.28, t = .673, p = .504). According to the linear regression analysis, the increase in EDS was not associated with SQ, EDS was only associated with RBD. Conclusion, the PD group presents a poor sleep quality and a higher prevalence of RBD symptoms. EDS did not differ between adults with and without PD. However, RBD was associated with an increase in EDS in the PD group.

849 REM Behavioral Disorder as a Predictor of Lewy body Dementia- A Case Report

Abstract Introduction Dementia with Lewy bodies (DLB) is one of the most common types of degenerative dementia after Alzheimer’s dementia. The core clinical features for diagnosis includes cognitive fluctuations, visual hallucinations, rapid eye movement (REM) sleep behavior disorder (RBD), and parkinsonism. Other symptoms include daytime drowsiness, longer daytime naps, prolonged staring spells, and episodes of disorganized speech. REM behavioral disorder (RBD) is commonly associated with DLB, occurring in 85 percent of individuals, often early in the course of the disease. It can precede the clinical diagnosis of DLB by up to 20 years. Report of case(s) A seventy-six-year-old female with a history of well controlled obstructive sleep apnea was diagnosed with REM behavioral disorder in 2012. She had presented with episodes of screaming, attempt to ambulate during sleep, resulting in injury. Her polysomnogram revealed evidence of REM without atonia and a screaming episode during REM. Her RBD symptoms were controlled with clonazepam and melatonin with less frequency of the RBD episodes. The patient gradually started noticing memory issues and by January 2020 she was diagnosed with dementia and was initiated on Aricept. Within 7 months of diagnosis of dementia, she started reporting vivid hallucinations that were not threatening or violent compared to her violent content of RBD. Physical exam revealed impaired cognitive function and mild intermittent resting tremor of the right hand. The neurological exam was normal including normal tone, strength, and gait. She also reported repeated falls and fractures. The diagnosis of Lewy body dementia was made based on the presence of 2 core clinical features. Conclusion The current management of these conditions is mainly symptomatic. In the evolution of neurodegenerative disorder, RBD precedes other conditions like LBD, parkinsonism, etc. Research suggests that alpha-synuclein neurodegeneration is the common pathology behind these conditions. The understanding that RBD presents at the beginning of the evolution, provides us with a unique opportunity for preemptive treatment to prevent further degeneration in turn preventing the debilitation consequence like dementia, parkinsonism, neuroleptic sensitivity, and dysautonomia. Further research is needed for developing these early interventional strategies. Support (if any) NOne

Dynamic functional connectivity changes in Parkinson’s disease patients with REM sleep behavior disorder

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is one of the common nonmotor symptoms of Parkinson’s disease (PD), characterized by frequently occurring REM sleep without muscle atonia. Our aim was to explore dynamic network connection changes in PD patients with RBD. MethodOn the basis of RBD screening questionnaire (RBDSQ), 126 PD patients were classified into those with probable RBD symptoms (PD-pRBD) and without probable RBD (PD-npRBD). We applied independent component analysis, sliding window approach and k-means clustering methods to clarify dynamic functional connectivity alterations. ResultsIn contrast to PD-npRBD, PD-pRBD patients were liable to engage in a brain pattern mainly marked by weaker positive couplings between visual network (VIS) and default mode network (DMN), DMN and basal ganglia network (BG), and within DMN (State IV). In addition, we discovered that both PD patients with or without pRBD had shorter dwell time and fewer occurrences in State III, characterized by positive correlations between VIS and DMN, BG and DMN, and positive within-network coupling of sensorimotor network (SMN), relative to healthy controls. ConclusionsOur study suggested that the weaker positive couplings between VIS and DMN, DMN and BG, and within DMN in State IV could be involved in the pathogenesis of PD patients with probable RBD on an overall level.

Probable REM sleep behavior disorder is associated with longitudinal cortical thinning in Parkinson\u2019s disease

REM sleep behavior disorder (RBD) has a poor prognostic implication in both motor and non-motor functions in Parkinson’s disease (PD) patients. However, to the best of our knowledge no study to date investigated the longitudinal cerebral changes underlying RBD symptoms in PD. We performed the longitudinal study to investigate the association between probable RBD and cortical and subcortical changes in early, de novo PD patients. We studied 78 participants from the Parkinson’s Progression Marker Initiative who underwent structural MRI at baseline and after 2 years. The presence of probable RBD (pRBD) was evaluated using the RBD screening questionnaire. We compared the cross-sectional and longitudinal cortical thickness and subcortical volume changes, between PD patients with and without pRBD. At baseline, we found bilateral inferior temporal cortex thinning in the PD-pRBD group compared with the PD-noRBD group. Longitudinally, the PD-pRBD group revealed a significant increase in the rate of thinning in the left insula compared with the PD-noRBD group, and the increased thinning correlated with decreased cognitive performance. In subcortical volume analyses, the presence of pRBD was linked with volume decrease over time in the left caudate nucleus, pallidum and amygdala. The volume changes in the left caudate nucleus revealed correlations with global cognition. These results support the idea that RBD is an important marker of rapid progression in PD motor and non-motor symptoms and suggest that the atrophy in the left insula and caudate nucleus might be the underlying neurobiological mechanisms of the poorer prognosis in PD patients with RBD.

Smaller pineal gland is associated with rapid eye movement sleep behavior disorder in Alzheimer\u2019s disease

BackgroundTo investigate the association between pineal gland volume and symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) in Alzheimer’s disease (AD) patients without any feature of dementia with Lewy bodies.MethodsWe enrolled 296 community-dwelling probable AD patients who did not meet the diagnostic criteria for possible or probable dementia with Lewy bodies. Among them, 93 were amyloid beta (Aβ) positive on 18F-florbetaben amyloid brain positron emission tomography. We measured RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as the RBDSQ of 5 or higher. We manually segmented pineal gland on 3T structural T1-weighted brain magnetic resonance imaging.ResultsThe participants with pRBD had smaller pineal parenchyma volume (VPP) than those without pRBD (p < 0.001). The smaller the VPP, the more severe the RBD symptoms (p < 0.001). VPP was inversely associated with risk of prevalent pRBD (odds ratio = 0.909, 95% confidence interval [CI] = 0.878–0.942, p < 0.001). Area under the receiver operator characteristic curve for pRBD of VPP was 0.80 (95% CI = 0.750–0.844, p < 0.0001). These results were not changed when we analyzed the 93 participants with Aβ-positive AD separately.ConclusionsIn AD patients, reduced pineal gland volume may be associated with RBD.

Non-motor symptoms and striatal dopamine transporter binding in early Parkinson's disease

BackgroundNon-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored. MethodsWe evaluated 18 NMS scores covering 5 major domains in relation to concurrent and future dopamine transporter (DAT) imaging in 344 PD patients from the Parkinson's Progression and Markers Initiative (PPMI). We standardized NMS assessments into z-scores for side-by-side comparisons. Patients underwent sequential DaTSCAN imaging at enrollment and at months 12, 24, and 48. Specific binding ratios (SBR) were calculated using the occipital lobe reference region. We evaluated the association of striatal DAT binding at the four time points with each baseline NMS using mixed-effects regression models. ResultsMultiple baseline NMS were significantly associated with DAT binding at baseline and at follow-up scans. REM sleep behavior disorder (RBD) symptoms showed the strongest association – mean striatal SBR declined with increasing RBD symptom z-score (average of time-point-specific slopes per unit change in z-score: βAVG = −0.083, SE = 0.017; p < 0.0001). In addition, striatal DAT binding was linearly associated with increasing baseline z-scores: positively for the memory (βAVG=0.055, SE = 0.022; p = 0.01) and visuospatial (βAVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (βAVG= −0.059, SE = 0.018; p = 0.001). Striatal DAT binding showed curvilinear associations with odor identification, verbal discrimination recognition, and autonomic dysfunction z-scores (p = 0.001, p = 0.0009, and p = 0.0002, respectively). Other NMS were not associated with DAT binding. ConclusionsMultiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD. Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years. ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04). ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.

Pineal gland volume is associated with prevalent and incident isolated rapid eye movement sleep behavior disorder.

We aimed to investigate the association of pineal gland volume with the risk of isolated rapid eye movement (REM) sleep behavior disorder (RBD). We enrolled 245 community-dwelling cognitively normal elderly individuals without major psychiatric or neurological disorders at the baseline evaluation, of whom 146 completed the 2-year follow-up evaluation. We assessed RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as an RBDSQ score of ≥ 5. We manually segmented the pineal gland on 3T T1-weighted brain magnetic resonance imaging and estimated its volume. The smaller the baseline pineal gland volume, the more severe the RBD symptoms at baseline. The individuals with isolated pRBD showed smaller pineal gland volumes than those without isolated pRBD. The larger the baseline pineal gland volume, the lower the risks of prevalent isolated pRBD at the baseline evaluation and incident isolated pRBD at the 2-year follow-up evaluation. Pineal gland volume showed good diagnostic accuracy for prevalent isolated pRBD and predictive accuracy for incident isolated pRBD in the receiver operator characteristic analysis. Our findings suggest that pineal gland volume may be associated with the severity of RBD symptoms and the risk of isolated RBD in cognitively normal elderly individuals.

Factors Influencing the Presentation of REM Sleep Behavior Disorder: The Relative Importance of Sex, Associated Neurological Disorder, and Context of Referral to Polysomnography.

To identify the interrelation and relative influence of sex, associated neurological disorder, and polysomnography (PSG) context on the manifestations of rapid eye movement (REM) sleep behavior disorder (RBD). Fifty-seven patients with RBD were assessed with video PSG regarding sleep structure, muscular activity, and motor events (ME) during REM sleep. Patients were categorized according to sex, associated neurological disorder (clinically isolated RBD [iRBD] versus RBD associated with an overt α-synucleinopathy [sRBD]) and motive for PSG (direct referral due to RBD symptoms [First, n = 14]; referred after screening procedures [Screening, n = 13]; referred during clinical follow-up for other disorders [Follow-up, n = 22]; referred for symptoms other than RBD [Incidental, n = 8]). Phasic muscular activity index and the relative number of myoclonic and trunk ME were significantly higher in males and segmental ME in female patients. sRBD was associated with Screening and iRBD with First categories. There was a higher severity of ME in patients with iRBD. Global motor severity of ME was significantly higher in the First category. In multivariate analysis, both motive for PSG and associated neurological disorder had a significant and independent influence in the global severity of ME. Associated neurological disorder and motive for PSG can significantly influence RBD presentation. Male sex is related with higher muscular phasic activity and a different pattern of ME, which could contribute to prevalence variations across studies. Having iRBD and being directly referred for a first consultation because of complaints compatible with RBD are interrelated and contribute independently to a higher severity of ME.

Tract-Based Spatial Statistics Reveal Lower White Matter Integrity Specific to Idiopathic Rapid Eye Movement Sleep Behavior Disorder as a Proxy for Prodromal Parkinson's Disease.

Parkinson's disease (PD) is characterized by distinct motor symptoms which do not manifest until significant neurodegeneration has already occurred. Therefore, preventative treatments depend on PD being detected in a prodromal phase. To date, prodromal PD (pPD) has been conceptualized based on conditions such as REM Sleep Behavior Disorder (RBD), which has a high conversion rate to clinical PD (cPD). However, few studies have examined microstructural differences between healthy controls (HC), pPD, and cPD. The current study examined white matter microstructure in different phases of PD progression. Participants included 21 HC, 20 pPD (14 with RBD and 6 with hyposmia), and 17 cPD from the Parkinson's Progression Markers Initiative database. Tract-based spatial statistics were used to determine between group differences in fractional anisotropy (FA) and mean diffusivity (MD). Mean diffusivity was significantly increased in pPD relative to cPD in widespread, but mostly right lateralized regions. Post-hoc analyses indicated that this pattern was particular to individuals with RBD. There were no microstructural differences between HC and pPD or cPD. The pPD group had significantly higher RBD symptoms and the cPD group had significantly higher motor symptoms. Observed microstructural deterioration in individuals with RBD relative to cPD may indicate an altered pattern of neurodegeneration associated with RBD as a prodromal symptom of PD. Future studies should aim to further characterize possible differential patterns of progression from various non-motor symptoms (e.g., RBD, hyposmia) to cPD using longitudinal designs.

Motor and non-motor function predictors of mortality in Parkinson's disease.

Doubts persist regarding the influence of Parkinson's disease (PD) on mortality. Our objective was to assess mortality rates in a prospectively followed cohort of PD patients and the impact of motor and non-motor symptoms in survival. 130 consecutive PD patients were followed during a 4-year period or until death. Baseline assessment included motor function (UPDRSIII, Hoehn and Yahr-HY), incapacity (Schwab and England-S&E, UPDRS II), Health-Related quality of life (EuroQol), non-motor symptoms (Non-Motor Symptom Scale-NMSS, MoCA, REM sleep behavior disorder symptoms questionnaire) and comorbidity burden (Charlson Comorbidity Index-CCI). These were used as predictor variables. Standardized mortality rates (SMR) were calculated, comparing with the general population. The association between mortality and predictors was tested with univariate and multivariate Cox proportional hazard regression models. Overall and gender-related SMRs were similar to the general population. SMR for pneumonia was five times higher than in the general population. Age, disease duration, CCI, EuroQol, dementia, MoCA, S&E, NMSS Hallucinations, HY, and PIGD motor phenotype were significantly associated with mortality. Adjusting for age, gender and disease duration, S&E remained significantly associated with mortality. In multivariate logistic regression analysis, death was significantly associated with disease duration, CCI and NMSS-mood/cognition scores. PD was not associated with an excess of mortality, but conferred a higher probability of dying from pneumonia. Comorbidity was a major determinant, but disease duration, baseline incapacity, cognition, psychosis, mood complaints and HRQL also contributed significantly to mortality.

REM-Sleep Behavior Disorder in Patients With Essential Tremor: What Is Its Clinical Significance?

Objective: REM sleep behavior disorder (RBD) is an important risk factor for the dementia development and for the deterioration of autonomic functions in patients with Parkinson's Disease. RBD has also been reported in patients with Essential Tremor (ET). However, its clinical significance in ET remains still unknown. We aimed to investigate clinical, neuropsychological and cardiac autonomic scintigraphic differences between ET patients with and without RBD.Methods: To assess RBD symptoms, RBD Single-Question has been administered in a cohort of 55 patients with a clinical diagnosis of ET. Patients with clinical RBD underwent polysomnography (PSG) confirmation. All patients completed a battery of neuropsychological assessment of memory, executive function, attention, language, and visuospatial function. Cardiac MIBG scintigraphy was performed in order to measure the cardiac autonomic innervation.Results: Ten ET patients (18%) had a PSG-confirmed RBD (ETRBD+). Compared to ET patients without RBD (ETRBD−), significantly reduced scores on memory domain tests such as Rey auditory verbal learning test immediate recall (p = 0.015) and Rey auditory verbal learning test delayed recall (p = 0.004) and phonemic fluency test (p = 0.028) were present in ETRBD+. By contrast, no other significant clinical difference has emerged from the comparison between two ET groups. Similarly, ETRBD+ patients have cardiac MIBG tracer uptake in the normal value range as occurred in those with ETRBD−.Conclusions: This study improves the knowledge on clinical significance of RBD symptoms in ET patients. Our preliminary findings demonstrate that presence of RBD in ET is associated with neurocognitive impairment, but not with cardiac autonomic dysfunction. Further longitudinal studies are needed to investigate whether ET patients with RBD will develop a frank dementia over the time.

REM sleep behavior disorder predisposed by neuroleptic malignant syndrome: a case report

A 44-year-old man was confirmed by polysomnography to have rapid eye movement (REM) sleep behavior disorder (RBD) following recovery from haloperidol- and risperidone-induced neuroleptic malignant syndrome (NMS). RBD symptoms persisted for 30 days. Subsequently, no clinical symptoms or polysomnographic findings of RBD have been observed for 3 years. RBD is reported to be associated with Parkinson’s disease and dementia with Lewy bodies, which involve brainstem dopaminergic hypofunction. However, no reports have documented RBD due to drug-induced dopaminergic hypofunction. This appears to be the first observation of RBD in relation to pharmacological dopaminergic dysfunction.

Smaller subcortical volume in Parkinson patients with rapid eye movement sleep behavior disorder

Parkinson disease (PD) patients with rapid eye movement (REM) sleep behavior disorder (RBD) have worse motor symptoms and non-motor symptoms than patients without RBD. The aim of this study was to examine underlying differences in brain structure from a network perspective. Baseline data were obtained from Parkinson’s Progression Markers Initiative (PPMI) participants. We divided PD patients and healthy controls (HC) into RBD positive and RBD negative using a cutoff score of ≥5 on the RBD screening questionnaire. HC with probable RBD were excluded. We first carried out a region-of-interest analysis of structural MRIs using voxel-based morphometry to study volumetric differences for the putamen, thalamus and hippocampus in a cross-sectional design. Additionally, an exploratory whole-brain analysis was performed. To study group differences from a network perspective, we then performed a ‘seed-based’ analysis of structural covariance, using the bilateral dorsal-caudal putamen, mediodorsal thalamus and anterior hippocampus as seed regions. The volume of the right putamen was smaller in PD patients with RBD. RBD symptom severity correlated negatively with volume of the right putamen, left hippocampus and left thalamus. We did not find any differences in structural covariance between PD patients with and without RBD. Presence of RBD and severity of RBD symptoms in PD are associated with smaller volumes of the putamen, thalamus and hippocampus.

Microstructural Changes in Patients With Parkinson's Disease Comorbid With REM Sleep Behaviour Disorder and Depressive Symptoms.

The diagnosis of Parkinson's disease (PD) is currently anchored on clinical motor symptoms, which appear more than 20 years after initiation of the neurotoxicity. Extra-nigral involvement in the onset of PD with probable nonmotor manifestations before the development of motor signs, lead us to the preclinical (asymptomatic) or prodromal stages of the disease (various nonmotor or subtle motor signs). REM sleep behavior disorder (RBD) and depression are established prodromal clinical markers of PD and predict worse motor and cognitive outcomes. Nevertheless, taken by themselves, these markers are not yet claimed to be practical in identifying high-risk individuals. Combining promising markers may be helpful in a reliable diagnosis of early PD. Therefore, we aimed to detect neural correlates of RBD and depression in 93 treatment-naïve and non-demented early PD by means of diffusion MRI connectometry. Comparing four groups of PD patients with or without comorbid RBD and/or depressive symptoms with each other and with 31 healthy controls, we found that these two non-motor symptoms are associated with lower connectivity in several white matter tracts including the cerebellar peduncles, corpus callosum and long association fibers such as cingulum, fornix, and inferior longitudinal fasciculus. For the first time, we were able to detect the involvement of short association fibers (U-fibers) in PD neurodegenerative process. Longitudinal studies on larger sample groups are needed to further investigate the reported associations.

Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease.

Determining baseline predictors of future psychosis in Parkinson disease (PD) may identify those at risk for more rapidly progressive disease, i.e., a more malignant PD subtype. This cohort study evaluated 423 patients with newly diagnosed PD collected as part of the Parkinson's Progression Markers Initiative. Psychotic symptoms were assessed with the Movement Disorders Society-Unified Parkinson Disease Rating Scale item 1.2, which assesses hallucinations and psychosis over the past week. At baseline, participants completed the Scales for Outcomes in Parkinson's Disease-Autonomic, the REM Sleep Behavior Disorder (RBD) Screening Questionnaire, and the Epworth Sleepiness Scale. Cholinergic nucleus 4 (Ch4) density was calculated for 228 participants with PD and 101 healthy controls. Multivariate logistic regression adjusted for age and sex found that greater autonomic symptoms (p = 0.002), RBD (p = 0.021), and excessive daytime sleepiness (EDS) (p = 0.003) at baseline were associated with increased risk of reporting psychotic symptoms on ≥2 occasions. Having 2 or 3 of these baseline symptoms was associated with lower Ch4 density (p = 0.007). In a logistic regression model adjusted for age and sex, higher Ch4 gray matter density was associated with lower risk of reporting psychotic symptoms on ≥2 occasions (odds ratio 0.96 [for an increase in density of 1 unit], p = 0.03). This study confirms that RBD, EDS, and greater autonomic symptom burden are associated with greater risk of future psychotic symptoms in PD. Reduced Ch4 density at baseline is associated with future psychotic symptoms and a greater burden of RBD, EDS, and autonomic symptoms.