Isolated REM Sleep Behavior Disorder Research Articles

Fasting gallbladder volume is increased in patients with Parkinson's disease

IntroductionAutonomic denervation in patients with Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) could impede gallbladder function leading to increased fasting gallbladder volume (fGBV) and higher risk of gallstones. We aimed to determine fGBV in patients with PD, iRBD, and healthy controls (HCs). MethodsWe included 189 subjects; 100 patients with PD, 21 with iRBD, and 68 HCs. fGBV was determined from abdominal CT scans, and radiopaque gallstone frequency was evaluated. ResultsMedian fGBV was 35.7 ml in patients with PD, 31.8 ml in iRBD, and 27.8 ml in HCs (Kruskal-Wallis test: P = 0.0055). Post-tests adjusted for multiple comparison revealed a significant group difference between patients with PD and HCs (P = 0.0038). In the PD group, 23% had enlarged fGBV (cut-off at mean + 2 x standard deviation (SD) in the HC group). No difference in fGBV was observed between iRBD and the other two groups. The total prevalence of gallstones was 6.4% with no differences between the three groups. ConclusionAlmost a quarter of patients with PD in our cohort exhibited increased fGBV. This study illuminates a potentially overlooked topic in PD research and calls for more studies on biliary dysfunction.

Consistent skin α-synuclein positivity in REM sleep behavior disorder – A two center two-to-four-year follow-up study

Objective/methodsPhosphorylated alpha-synuclein (p-syn) in dermal nerves of patients with isolated REM sleep behavior disorder (iRBD) is detectable by immunofluorescence-labeling. Skin-biopsy-p-syn-positivity was recently postulated to be a prodromal marker of Parkinson's disease (PD) or related synucleinopathies. Here, we provide two-to four-year clinical and skin biopsy follow-up data of 33 iRBD patients, whose skin biopsy findings at baseline were reported in 2017. ResultsFollow-up biopsies were available from 25 patients (18 positive at baseline) and showed consistent findings over time in 24 patients. One patient converted from skin-biopsy-negativity to -positivity. P-syn-positivity was observed in iRBD patients who still had a normal FP-CIT-SPECT two years later. Clinically, five of the 23 at baseline skin-biopsy-positive patients (21.7%) had converted to PD or dementia with Lewy bodies at follow-up, but none of the skin-biopsy-negative patients. ConclusionsDermal p-syn in iRBD is most probably an early consistent marker of synucleinopathy and may support other indicators of conversion to manifest disease state.

Cutaneous Alpha-Synuclein is Correlated with Autonomic Impairment in Isolated REM Sleep Behavior Disorder (5128)

Cutaneous Alpha-Synuclein is Correlated with Autonomic Impairment in Isolated REM Sleep Behavior Disorder (5128)

Olfactory Testing in Parkinson Disease and REM Behavior Disorder: A Machine Learning Approach.

We sought to identify an abbreviated test of impaired olfaction amenable for use in busy clinical environments in prodromal (isolated REM sleep behavior disorder [iRBD]) and manifest Parkinson disease (PD). Eight hundred ninety individuals with PD and 313 controls in the Discovery cohort study underwent Sniffin' Stick odor identification assessment. Random forests were initially trained to distinguish individuals with poor (functional anosmia/hyposmia) and good (normosmia/super-smeller) smell ability using all 16 Sniffin' Sticks. Models were retrained using the top 3 sticks ranked by order of predictor importance. One randomly selected 3-stick model was tested in a second independent PD dataset (n = 452) and in 2 iRBD datasets (Discovery n = 241, Marburg n = 37) before being compared to previously described abbreviated Sniffin' Stick combinations. In differentiating poor from good smell ability, the overall area under the curve (AUC) value associated with the top 3 sticks (anise/licorice/banana) was 0.95 in the Development dataset (sensitivity 90%, specificity 92%, positive predictive value 92%, negative predictive value 90%). Internal and external validation confirmed AUCs ≥0.90. The combination of the 3-stick model determined poor smell, and an RBD screening questionnaire score of ≥5 separated those with iRBD from controls with a sensitivity, specificity, positive predictive value, and negative predictive value of 65%, 100%, 100%, and 30%. Our 3-Sniffin'-Stick model holds potential utility as a brief screening test in the stratification of individuals with PD and iRBD according to olfactory dysfunction. This study provides Class III evidence that a 3-Sniffin'-Stick model distinguishes individuals with poor and good smell ability and can be used to screen for individuals with iRBD.

The role of pedunculopontine nucleus in isolated REM sleep behavior disorder and REM sleep without atonia

IntroductionThe aim of this study was to analyze the functions of pedunculopontine nucleus (PPN) in isolated REM sleep behavior disorder (iRBD) and REM sleep without atonia (RSWA) to investigate the role of PPN in dream-enacting motor behaviors in RBD. We evaluated the activity of PPN through the prepulse modulation (PPM) together with other brainstem reflexes to investigate the differences in changes at brainstem. MethodsWe included nine patients with isolated RSWA and 10 patients with iRBD. For diagnosis, all patients underwent polysomnography. None of the patients had parkinsonism or dementia. We also included 17 healthy participants with similar age and sex. Blink reflex (BR), PPM of BR, recovery excitability of BR, and auditory startle reflex (ASR) were recorded in all participants. ResultsThere was a prepulse inhibition deficit in iRBD and RSWA groups compared to healthy subjects. The BR-R2 recovery at 200 ms interval was also higher in patients with iRBD and RSWA. In ASR recordings, the response probabilities were higher in the RBD group compared to RSWA and control groups. ConclusionThe PPM was abnormal in both iRBD and RSWA whereas ASR was enhanced in iRBD. We suggest that there are certain similarities and differences in the pathophysiologies of iRBD and RSWA.

Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder.

ObjectiveTo examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD).MethodsWe fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests. The contribution of biallelic variants was further tested. To examine the potential effect of rare nonsynonymous BST1 variants on the protein structure, we performed in silico structural analysis. Finally, we examined the association of common variants using logistic regression adjusted for age and sex.ResultsWe found an association between rare heterozygous nonsynonymous variants in BST1 and iRBD (p = 0.0003 at coverage >50× and 0.0004 at >30×), driven mainly by 3 nonsynonymous variants (p.V85M, p.I101V, and p.V272M) found in 22 (1.2%) controls vs 2 (0.2%) patients. All 3 variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare noncoding heterozygous variants in LAMP3 were also associated with iRBD (p = 0.0006 at >30×). We found no association between rare heterozygous variants in the rest of genes and iRBD. Several carriers of biallelic variants were identified, yet there was no overrepresentation in iRBD.ConclusionOur results suggest that rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and to examine whether loss of function of BST1 could be a therapeutic target.

Altered insular functional connectivity in isolated REM sleep behavior disorder: a data-driven functional MRI study

ObjectiveFunctional connectivity (FC) changes can occur prior to structural changes. This study aimed to evaluate data-driven whole-brain FC associated with isolated rapid eye movement sleep behavior disorder (iRBD) using multivariate pattern analysis (MVPA). MethodsThis was a cross-sectional study of 50 polysomnography-confirmed iRBD patients and 20 age- and sex-matched controls. We used MVPA implemented in the connectome-MVPA CONN toolbox to identify data-driven seed regions for post hoc seed-to-voxel connectivity analysis. The association between FC changes and clinical characteristics, including cognition, depression, autonomic function, and daytime sleepiness, was evaluated. ResultsMVPA revealed one significant cluster located in the left posterior insular cortex. Seed-to-voxel FC analysis using the cluster as a seed showed significantly reduced FC with two clusters located in the precuneus in iRBD patients compared to the controls. The degree of FC was associated with the Montreal Cognitive Assessment-Korean version scores (r = 0.317, p = 0.025). ConclusionThis study emphasizes the insula as an important neural correlate associated with iRBD that was associated with cognitive function.

Specialist approaches to prognostic counseling in isolated REM sleep behavior disorder

Objectives/backgroundMost middle-aged and older adult patients with isolated (idiopathic) REM sleep behavior disorder (RBD) eventually develop parkinsonism, dementia with Lewy bodies, or multiple system atrophy. We aimed to describe the current sleep medicine specialist approach toward RBD prognostic counseling, and to determine physician beliefs and characteristics that impact provision of counseling. Patients/methodsWe surveyed 70 sleep medicine physicians with RBD expertise for demographic information, counseling practices, and their beliefs and understandings concerning the association between RBD and synucleinopathies, among other questions. Responses were summarized by descriptive statistics. ResultsAmong the 44 respondents (63% response rate), 41 (93.2%) regularly provided prognostic counseling for most RBD patients, but only 31.8% routinely asked about patient preferences on receiving counseling. 41.8% believed that the risk for developing overt synucleinopathy following RBD diagnosis was >80%, but only 15.9% routinely provided this detailed phenoconversion risk estimate to their patients. Most respondents were concerned that RBD prognostic counseling could adversely impact on the patient's and family's mental health. ConclusionsMost expert RBD sleep clinicians routinely counsel their patients regarding the high risk for phenoconversion to parkinsonism or dementia, yet relatively few routinely ask patients about their preferences for receiving this information, and fewer provide details concerning the known high risk estimates for developing a synucleinopathy. Future research should analyze patients’ values and preferences in RBD populations to inform approaches toward shared decision making for RBD prognostic counseling.

Cortical cholinergic dysfunction correlates with microglial activation in the substantia innominata in REM sleep behavior disorder

IntroductionIn vivo PET studies in patients with isolated REM sleep behavior disorder (iRBD) have shown presence of neuroinflammation (microglial activation) in the substantia nigra, and reduced cortical acetylcholinesterase activity, suggestive of cholinergic dysfunction, that was more widespread in patients with poorer cognitive performances. This study aimed to explore whether reduced cortical acetylcholinesterase activity in iRBD is linked to microglial activation in the substantia innominata (SI), the major source of cholinergic input to the cortex. MethodsWe used 11C(R)-PK11195 and 11C-Donepezil PET to assess levels of activated microglia and cholinergic function, respectively, in 19 iRBD patients. 11C(R)-PK11195 binding potential (BPND) and 11C-Donepezil distribution volume ratio (DVR) values were correlated using the Pearson statistic. ResultsWe found that a lower cortical 11C-Donepezil DVR correlated with a higher 11C(R)-PK11195 BPND in the SI (r = −0.48, p = 0.04). At a voxel level, the strongest negative correlations were found in the frontal and temporal lobes. ConclusionOur results suggest that reduced cortical acetylcholinesterase activity observed in our iRBD patients could be linked to the occurrence of neuroinflammation in the SI. Early modulation of microglial activation might therefore preserve cortical cholinergic functions in these patients.

Serum TNF-α and neurodegeneration in isolated REM sleep behavior disorder

ObjectiveTo investigate serum inflammatory cytokine profiles in patients with isolated REM sleep behavior disorder (iRBD) and to explore whether these markers are associated with phenoconversion risk to α-synucleinopathies. MethodsIn this prospective cohort study, we analyzed serum samples from patients with polysomnography-confirmed iRBD (n = 30) and healthy controls (n = 12). We measured the following cytokines: interleukin (IL)-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-α (TNF-α). All patients underwent motor and non-motor evaluations and dopamine transporter imaging at baseline for predicting the phenoconversion risk. We followed the patients quarterly over up to 6 years to identify disease conversion. We also assessed longitudinal changes in cytokine levels from baseline at the 2- and 4-year follow-up visits. ResultsThe baseline cytokine levels did not differ between the patients and controls. However, the TNF-α levels were significantly increased in a subgroup of the patients with multiple markers (≥3) for phenoconversion risk compared to those without (p = 0.008) and controls (p = 0.003). At longitudinal analyses, patients with TNF-α levels above the median showed a higher incidence of phenoconversion than those with lower TNF-α levels (47% vs. 7%; p = 0.008), and this significant association persisted after adjusting for covariates (p = 0.026). The cytokine levels over 4 years of follow-up period did not change significantly. ConclusionsOur data suggest a possible link between serum TNF-α and phenoconversion risk in iRBD. Further studies are warranted to confirm the role of peripheral TNF-α in the pathogenesis of neurodegeneration in this disorder.

Significance of hyposmia in isolated REM sleep behavior disorder.

To determine if hyposmia in isolated REM sleep behavior disorder (IRBD) predicts short-term conversion to any α-synucleinopathy and declines with time. Olfaction was tested using the University of Pennsylvania Smell Identification Test (UPSIT-40) in 140 consecutive patients with polysomnography-confirmed IRBD and in 77 matched controls. Patients were followed-up during 5.6 ± 3.9 (range 0.2-13) years. Twenty-one patients underwent serial UPSIT-40 evaluations at 1-3 and 4-6years after baseline. UPSIT-40 score was lower in patients than in controls (20.2 ± 6.5 vs. 28.6 ± 5.0; p < 0.001). Hyposmia (UPSIT-40 score < 19 points) occurred in 42.9% patients. Forty-three (30.7%) patients developed Parkinson disease (PD = 27), dementia with Lewy bodies (DLB = 13) and multiple system atrophy (MSA = 3). Kaplan-Meier analysis showed that hyposmics had higher risk than normosmics to develop a synucleinopathy atthe short term (p = 0.030). UPSIT-40 score was similar between patients who developed PD and DLB (p = 0.136). Normal smell occurred in all three (100%) IRBD patients who developed MSA, 12 of 27 (44%) who developed PD, and 4 of 13 (31%) that developed DLB. Serial UPSIT-40 evaluations showed no changes with time (p = 0.518). In IRBD, hyposmia is a short-term risk for synucleinopathies but cannot distinguish underlying PD from DLB. Normosmia not only occurs in latent MSA but also in latent PD and DLB. In future IRBD neuroprotective trails, individuals at entry could be enriched for hyposmia, whereas serial evaluation of smell would not be useful to monitor the efficacy of a therapeutic intervention.

GBA variants in REM sleep behavior disorder: A multicenter study.

ObjectiveTo study the role of GBA variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration.MethodsA total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk of iRBD, age at onset (AAO), and conversion rates.ResultsGBA variants were found in 9.5% of patients with iRBD compared to 4.1% of controls (odds ratio, 2.45; 95% confidence interval [CI], 1.87–3.22; p = 1 × 10−10). The estimated OR for mild p.N370S variant carriers was 3.69 (95% CI, 1.90–7.14; p = 3.5 × 10−5), while for severe variant carriers it was 17.55 (95% CI, 2.11–145.9; p = 0.0015). Carriers of severe GBA variants had an average AAO of 52.8 years, 7–8 years earlier than those with mild variants or noncarriers (p = 0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% of noncarriers (p = 0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be interpreted with caution.ConclusionsGBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.

0814 A New Diagnostic Tool for Isolated REM Sleep Behavior Disorder: Automated 3D Video Analysis of Lower Limb Movements During REM Sleep

Abstract Introduction The differentiation of isolated REM sleep behavior disorder (iRBD) or its prodromal phase (prodromal RBD, pRBD) from other disorders with motor activity during sleep is critical for identifying α-synucleinopathy in an early stage. Currently, definite RBD diagnosis requires video-polysomnography (vPSG). Aim of this study was to evaluate automated 3D video analysis of leg movements during REM sleep as objective diagnostic tool for iRBD. Methods A total of 122 participants (40 iRBD, 18 pRBD, 64 with other disorders with motor activity during sleep) were recruited among patients undergoing vPSG at the Sleep Disorders Unit, Department of Neurology, Medical University of Innsbruck. 3D videos synchronous to vPSG were recorded. Lower limb movements rate, duration, extent and intensity were computed using a newly developed software. Results The analyzed 3D movement features were significantly increased in subjects with iRBD compared to pRBD and other disorders with motor activity during sleep. Minor leg jerks with a duration &amp;lt;2 seconds discriminated with the highest accuracy (90.4%) iRBD from other motor activity during sleep. Automatic 3D analysis did not differentiate between pRBD and other disorders with motor activity during sleep. Conclusion Automated 3D video analysis of leg movements during REM sleep is a promising diagnostic tool for identifying subjects with iRBD in a sleep laboratory population and is able to distinguish iRBD from subjects with other motor activities during sleep. For future application as a screening, further studies should investigate usefulness of this tool when no information about sleep stages from vPSG is available. Support This study was funded by the Austrian Science Fund (FWF), Project KLI 677-B31.

Pareidolias and cognition in isolated REM sleep behavior disorder

BackgroundThough visual illusions and hallucinations are common in dementia with Lewy bodies (DLB) and Parkinson's disease (PD), they are not typically observed clinically in prodromal stages, including isolated REM sleep behavior disorder (iRBD). False-noise errors on the pareidolia test (seeing faces when none are present) may be an effective measure of susceptibility to future hallucinations in iRBD. MethodsOne hundred patients with iRBD underwent the 20-image pareidolia test. Clinical markers were assessed and a neuropsychological battery was administered. An exploratory analysis on the impact of pareidolic errors on phenoconversion was also performed. ResultsIn our cohort, 17 patients (17%) made false-noise pareidolic errors. These patients had significantly lower total Montreal Cognitive Assesment (MoCA) scores (26.7 ± 2.3 vs. 24.4 ± 2.6, B = −1.88, 95% CI: [-3.17, −0.59]), with lower subcomponent MoCA scores on memory and visuospatial-executive sections. Pareidolic errors were also associated with lower visuospatial, attention/executive, and memory scores on the neuropsychological tests. Furthermore, after 1.6 years follow-up, 3/16 (19%) patients making pareidolic errors had phenoconverted at time of publication compared to 6/71 (8%) patients who did not make errors. ConclusionPareidolic errors in patients with iRBD are associated with poorer overall cognition and may indicate higher risk of DLB.

Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies

The clinical diagnosis of synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), is challenging, especially at an early disease stage, due to the heterogeneous and often non-specific clinical manifestations. The discovery of reliable specific markers for synucleinopathies would consequently be of great aid to the diagnosis and management of these disorders. Real-Time Quaking-Induced Conversion (RT-QuIC) is an ultrasensitive technique that has been previously used to detect self-templating amyloidogenic proteins in the cerebrospinal fluid (CSF) and other biospecimens in prion disease and synucleinopathies. Using a wild-type recombinant α-synuclein as a substrate, we applied RT-QuIC to a large cohort of 439 CSF samples from clinically well-characterized, or post-mortem verified patients with parkinsonism or dementia. Of significance, we also studied patients with isolated REM sleep behavior disorder (iRBD) (n = 18) and pure autonomic failure (PAF) (n = 28), representing clinical syndromes that are often caused by a synucleinopathy, and may precede the appearance of parkinsonism or cognitive decline. The results show that our RT-QuIC assay can accurately detect α-synuclein seeding activity across the spectrum of Lewy Body (LB)-related disorders (LBD), including DLB, PD, iRBD, and PAF, with an overall sensitivity of 95.3%. In contrast, all but two patients with MSA showed no α-synuclein seeding activity in the applied experimental setting. The analysis of the fluorescence response reflecting the amount of α-synuclein seeds revealed no significant differences between the clinical syndromes associated with LB pathology. Finally, the assay demonstrated 98% specificity in a neuropathological cohort of 101 cases lacking LB pathology. In conclusion, α-synuclein RT-QuIC provides an accurate marker of synucleinopathies linked to LB pathology and may have a pivotal role in the early discrimination and management of affected patients. The finding of no α-synuclein seeding activity in MSA seems to support the current view that MSA and LBD are associated with different conformational strains of α-synuclein.

Left-hemispheric predominance of nigrostriatal deficit in isolated REM sleep behavior disorder.

Unilateral onset of parkinsonism due to nigrostriatal damage of the contralateral hemisphere is frequent in Parkinson disease (PD). There is evidence for a left-hemispheric bias of motor asymmetry in right-handed patients with PD indicating a hemispheric dominance. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of PD and other synucleinopathies. To test the hypothesis that right-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction, we evaluated this aspect using neuroimaging instruments. In 167 right-handed patients with IRBD without parkinsonism, we evaluated in each hemisphere the integrity of the striatal dopaminergic terminals by dopamine transporter (DAT)-SPECT and the substantia nigra echogenicity by transcranial sonography. DAT-SPECT showed lower specific binding ratio (SBR) in the left striatum and left caudate nucleus than in the right striatum and right caudate nucleus. The percentage of patients with lower SBR was greater in the left striatum and left caudate nucleus than in the right striatum and right caudate nucleus. In those who developed a synucleinopathy in <5 years from DAT-SPECT, there was a lower SBR in the left putamen and left caudate nucleus than in the right putamen and right caudate nucleus. Substantia nigra echogenic size was greater in the left than in the right side in patients with hyperechogenicity and among individuals who phenoconverted in <5 years from transcranial sonography. Right-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction. In premotor PD, the neurodegenerative process begins asymmetrically, initially impairing the nigrostriatal system of the dominant hemisphere.

Prevalence and clinical characteristics of REM sleep behavior disorder in Japanese elderly people.

To evaluate the prevalence and clinical characteristics of isolated REM sleep behavior disorder (iRBD) among a general population of elderly Japanese people. This epidemiological study targeted 2714 elderly residents (76.0 ± 8.0 years, 52.9% female) of a rural community. Questionnaires including the REM sleep behavior disorder single question and demographic information were distributed. All respondents with the question positive were interviewed by telephone. Respondents suspected of having iRBD proceeded to face-to-face interviews and underwent video-polysomnography and neurological/neuropsychological examination. These results were compared to those of previously diagnosed clinical iRBD patients in our sleep clinic. Of 1464 respondents to the questionnaire, 18 respondents were diagnosed as iRBD (1.23 [0.66-1.79]%), including eight respondents who satisfied diagnostic criteria with REM sleep without atonia (RWA) above the cut-off value (0.54 [0.17-0.92]%) and 10 respondents who had clear dream enactment behaviors but not RWA above the cut-off (provisionally diagnosed iRBD; p-iRBD) (0.69 [0.26-1.11]%). Severity of RBD and RWA of the population-based iRBD were compatible with those of the clinical iRBD. Half of the population-based iRBD showed orthostatic hypotension and they showed lower olfactory function than population-based p-iRBD and non-RBD. However, their olfactory and cognitive functions were higher than those in the clinical iRBD patients. Prevalence of iRBD in Japanese elderly people was comparable with the rate reported from other countries. Population-based iRBD/p-iRBD showed lower neurodegenerative loading than clinical iRBD in spite of comparable disease duration of RBD, that may indicate their lower risk of future neurodegeneration.

Quantitative sudomotor abnormalities in clinically isolated rapid eye movement sleep behavior disorder.

Post-ganglionic sudomotor abnormalities are common in Parkinson's disease (PD), however data in clinically isolated REM sleep behavior disorder (iRBD) are limited. To determine the prevalence of sudomotor abnormalities in a cohort of patients with iRBD. We performed a retrospective review of patients seen in our autonomic clinic who underwent testing with the quantitative sudomotor axon reflex test (QSART). We identified three groups for comparison: 1.) iRBD, 2.) PD with RBD (PDwRBD) 3.) PD without RBD (PDwoRBD). PDwRBD (n=27) patients demonstrated the greatest sudomotor abnormalities (sudomotor CASS 1.44±1.24), followed by PDwoRBD (n=23, 0.57±0.5) and iRBD (n=20, 0.55±0.94) (p=0.015). Twenty percent of patients with iRBD had an abnormal result, compared to 67% PDwRBD and 35% PDwoRBD. Sudomotor abnormalities are common in patients with iRBD, supporting the concept that peripheral autonomic impairment occurs early in the course of disease.

Olfaction in patients with isolated REM sleep behavior disorder who eventually develop multiple system atrophy.

Olfaction in patients with isolated REM sleep behavior disorder who eventually develop multiple system atrophy.

Abnormal vestibular evoked myogenic potentials are correlated with REM sleep without atonia in patients with isolated REM sleep behavior disorder

Abnormal vestibular evoked myogenic potentials are correlated with REM sleep without atonia in patients with isolated REM sleep behavior disorder