Difference in severity of sleep apnea in patients with rapid eye movement sleep behavior disorder with or without parkinsonism

ObjectiveRapid eye movement sleep behavior disorder (RBD) is a common sleep disturbance in patients with neurodegenerative disorders. We aimed to compare sleep parameters among the different types of RBD patients.MethodsA total of 122 patients with dream enactment behavior were screened. Of these, 92 patients who were diagnosed with RBD by polysomnography were included in this study. Enrolled patients with RBD were classified into four groups based on the following diagnoses: idiopathic RBD (iRBD); RBD with Parkinson disease (PD-RBD); multiple system atrophy (MSA) with RBD (MSA-RBD); and dementia with Lewy bodies (DLB) with RBD (DLB-RBD). Various clinical and polysomnographic parameters were compared.ResultsAmong the 92 patients with RBD, 35 had iRBD, 25 had PD-RBD, 17 had MSA-RBD, and 15 had DLB-RBD. The mean apnea−hypopnea index of atypical parkinsonism with RBD (AP-RBD) group was 16.2 ± 17.7 events/h (MSA-RBD, 14.0 ± 16.6; DLB-RBD, 18.8 ± 19.1), which was significantly higher than the other groups (p < 0.05). The proportion of patients with 100% supine sleep in the AP-RBD group (44%) was higher than that in the iRBD group (14%; p = 0.030). The proportion of OSA with 100% supine sleep position was significantly higher in the MSA-RBD and DLB-RBD groups than in the iRBD group (p = 0.042 and p = 0.029, respectively).ConclusionOur study demonstrated that patients in the MSA-RBD and DLB-RBD groups had a tendency to sleeping in the supine position and a higher vulnerability to OSA compared to other RBD groups. Further cohort studies are needed to evaluate the influence of these factors on the development of parkinsonism.     

Severity of idiopathic rapid eye movement sleep behavior disorder correlates with depression and alexithymia

BackgroundDepression and alexithymia often accompany early stages of Parkinson's disease (PD). However, these symptoms in idiopathic rapid eye movement sleep behavior disorder (iRBD) remain incompletely understood. The aim of this study was to compare depression and alexithymia between iRBD patients and healthy controls, and to evaluate the association between clinical RBD severity and severity of depression and alexithymia.MethodsPolysomnography-confirmed iRBD patients (n = 86) and healthy controls (n = 74) were enrolled. Clinical RBD severity was assessed using the RBD questionnaire-Hong Kong (RBDQ-HK). Depression and alexithymia were evaluated by the Beck Depression Inventory (BDI) and the 20-item Toronto Alexithymia Scale (TAS-20), respectively. Multivariate linear regression analysis was performed with adjustments for several covariates to determine the correlations between RBD severity and severity of depression and alexithymia.ResultsBDI scores were significantly higher in the iRBD group (10.6 ± 7.3) than in healthy controls (8.2 ± 6.0, p = 0.024). Higher total RBDQ-HK scores were associated with more severe depression in iRBD patients, even after controlling for confounding variables. iRBD patients exhibited significantly higher TAS-20 scores (45.7 ± 10.4) than healthy controls (42.1 ± 9.8, p = 0.026). Total RBDQ-HK scores were positively correlated with TAS-20 scores independent of BDI scores.ConclusionsPatients with iRBD were more depressed and had more severe alexithymia than healthy controls. Notably, as the clinical severity of RBD increased, both depression and alexithymia worsened.     

Treatment outcomes in REM sleep behavior disorder

ObjectiveREM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam.MethodsWe surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008–2010 to describe RBD-related injury frequency–severity as well as RBD visual analog scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency.ResultsForty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and two received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (p_m = 0.0001, p_c = 0.0005). Melatonin-treated patients reported significantly reduced injuries (p_m = 0.001, p_c = 0.06) and fewer adverse effects (p = 0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9 ± 29.5 months, and for melatonin 27.4 ± 24 months, p = 0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p = 0.43).ConclusionsMelatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed.     

Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00983-7.Key Words: REM sleep behavior disorder, disease-modifying, treatment, neurodegeneration, sleep     

Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity

ObjectivesOver 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity.MethodsIn a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics.ResultsAmong 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities.ConclusionSurface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury.     

Caring burden of REM sleep behavior disorder – spouses' health and marital relationship

ObjectivesIdiopathic REM sleep behavior disorder (iRBD) is noxious due to the high prevalence of sleep-related injuries to patients and their bed-partners. In this study, we aimed to investigate the impact of patients' RBD symptoms on their spouses, in terms of the quality of sleep, and physical, mental and marital aspects.MethodA cross-sectional study comparing spouses of iRBD patients to the spouses of the age-and-sex-matched OSAS patients.Results40 iRBD patients and their spouses (patients' age 66.6 ± 9.1, male 90%; spouses' age 62.9 ± 7.5), and 35 OSAS patients and their spouses (patients' age 67.8 ± 8.7 years old, male 80%; spouses' age 64.1 ± 9.1) were recruited. Almost all iRBD spouses (90%) reported disturbances by the nocturnal RBD behavioral symptoms of their bedpartners. About two-thirds (62.5%, N = 25) of the iRBD spouses reported a history of being injured during sleep. Spouses of both iRBD and OSAS patients reported a comparably high prevalence of insomnia, anxiety and depressive symptoms. Spouses of iRBD patients, however, reported more impaired quality of life and marital relationship. Nearly two-thirds of RBD couples continued co-sleeping, despite the risk of sleep-related injuries and nocturnal disturbances.ConclusionsBoth iRBD and OSAS spouses exhibited a high prevalence of insomnia and mood problems. In particular, iRBD significantly and negatively affect the spouses' quality of life and the marital relationship. Optimization of iRBD treatment, proper diagnosis, and management of sleep and mental health aspects of spouses may help to lessen the caring burden.     

A prospective,naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder

BackgroundRapid eye movement sleep behavior disorder (RBD) is characterized by prominent dream-enacting behaviors, often resulting in sleep-related injuries.ObjectivesThis study aimed to prospectively examine the treatment response of people with RBD treated with clonazepam, by quantitatively delineating the characteristic changes in the clinical and polysomnographic features, and to explore the factors associated with this response.MethodsPatients diagnosed with idiopathic RBD (iRBD) were consecutively recruited and invited to complete clinical and polysomnographic (PSG) assessments and self-administered questionnaires (including the modified REM Sleep Behavior Questionnaire, RBDQ-3M) before and after the initiation of treatment with clonazepam.ResultsThirty-nine iRBD patients (male: 74.4%, mean age at diagnosis: 68.3 ± 7.8 years) were recruited with a follow-up duration of 28.8 ± 13.3 months. Clonazepam was offered as the first-line treatment (starting dose: 0.43 ± 0.16 mg, range: 0.125–1.00; dose at follow-up: 0.98 ± 0.63 mg, range: 0.125–3). Treatment response, as defined by a complete elimination of sleep-related injuries and potentially injurious behaviors to self and/or to bed partner, at follow-up was reported in 66.7% of the overall study subjects. Frequency of disturbing dreams with violent and frightening content and vigorous behavioral RBD symptoms was significantly reduced, while residual nocturnal symptoms and an increase in REM-related EMG activities were observed at follow-up. Less optimal treatment outcomes were found to be associated with the presence of comorbid obstructive sleep apnea and earlier onset of RBD.ConclusionsClonazepam differentially changes dream affect and content, as well as reduces vigorous verbal and motor behaviors. Residual RBD symptoms are common, despite treatment. Other more effective alternative or adjunctive interventions are needed for better clinical management of RBD.     

Gender differences in REM sleep behavior disorder: a clinical and polysomnographic study in China

ObjectiveRapid eye movement (REM) sleep behavior disorder (RBD) has been considered a male-predominant parasomnia, and there is little comparative data on potential differences between males and females. Therefore, the aim of our study was to examine and characterize gender difference in RBD.MethodsNinety patients diagnosed with RBD were consecutively recruited from a sleep medicine clinic. All patients were assessed by a RBD questionnaire and overnight video polysomnography. Demographic, clinical data, presence of dreams and dream-enacting behaviors, sleep parameters and electromyographic (EMG) activity were compared for male and female patients with RBD.ResultsFemales were significantly younger than males, both in the mean age of RBD onset (45.3 ± 19.3 vs. 56.2 ± 14.1; p = 0.027) and the mean age at diagnosis (50.4 ± 18.2 vs. 61.1 ± 14.1; p = 0.022). Secondary RBD was 21% in males and 44% in females (p = 0.021). Antidepressant use was more common among females (22%) than males (2%; p = 0.003). There was no significant gender difference in dream content (eg, violent and frightening dreams) of RBD patients. However, females had less dream-enacting behaviors, especially in movement related dreams and falling out of bed. Interestingly, no significant difference was found in the quantification of EMG activity during REM sleep between male and female patients.ConclusionsWe found significant gender differences in demographics, associated comorbidities, and dream-related behaviors in patients with RBD. Female RBD patients reported significantly less behavior during dreams, but there was no significant gender difference in EMG activity during REM sleep.     

Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease

IntroductionLoss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD.MethodsWe conducted overnight polysomnography in 145 patients with PD. DEB (motor behaviors and/or vocalizations during REM) and increased RWA (IRWA; tonic and phasic chin EMG density ≥ 30% and ≥15%, respectively) were identified. Patients were categorized as clinical RBD (DEB and IRWA), sub-DEB positive (DEB only), subclinical RBD (IRWA only), or normal REM sleep.ResultsPatients with DEB had higher Hoehn and Yahr (H&Y) stage, Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent dose(LEDs), and worse cognition. RWA was associated with H&Y stage, LEDs, cognition, and sleep structure in all patients. PD duration was associated with RWA, but not DEB. The PD patients who exhibited clinical or subclinical RBD, compared to sub-DEB positive, had higher H&Y stage, UPDRS III score and LEDs, lower cognitive score, worse sleep structure than the PD + cREM group.ConclusionBoth DEB and RWA were associated with severity of PD illness. Subclinical RBD might have different disease progression from sub-DEB positive. DEB symptoms may fluctuate or disappear whereas RWA may continue to develop as PD progresses. Differences in the course of DEB and RWA may reflect the difference in the degeneration process of neurodegenerative disorders.     

Loss of REM sleep features across nighttime in REM sleep behavior disorder

ObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.     

Factors associated with the effect of pramipexole on symptoms of idiopathic REM sleep behavior disorder

BackgroundThe clinical effectiveness of pramipexole (PPX), a candidate treatment for idiopathic rapid eye movement sleep behavior disorder (iRBD), varies among individuals. This study investigates factors associated with PPX effectiveness for treating RBD symptoms.MethodsNinety-eight consecutive patients with RBD who had taken PPX or clonazepam (CNZP) for more than three months were enrolled. Factors associated with PPX effectiveness were examined: the ratio of REM sleep without atonia to total REM sleep (RWA/REM), length of RBD morbidity, frequency of vocalization or abnormal behavior, and Sniffin' Stick Test scores. These factors were also compared among the responders to PPX monotherapy, CNZP monotherapy, and PPX + CNZP combined therapy.ResultsPPX was efficacious in 61.7% (50/81) of the subject patients. RWA/REM was associated with PPX effectiveness. The cut-off rate of RWA/REM for predicting PPX effectiveness was estimated as 16.8%. Responders to PPX + CNZP combined therapy showed significantly higher RWA/REM and frequency of vocalization or dream enactment behavior than either responders to monotherapy with PPX or to CNZP.ConclusionPPX is probably applicable as an alternative to CNZP, especially for mild iRBD cases with a lower rate of RWA. Results of this study suggest that dopaminergic dysfunction can play a role in iRBD pathophysiology.     

Effect of low-intensity pure tone auditory stimulation on patients with rapid eye movement sleep behavior disorder

Objective: This study aimed to investigate the influence of low-intensity pure tone auditory stimulation on patients with rapid eye movement (REM), sleep behavior disorder (RBD), and attempt to identify a new method of RBD intervention.

Methods: Patients diagnosed with idiopathic RBD (iRBD) or symptomatic RBD (sRBD) were given auditory stimulation of low-intensity pure tones during their REM sleep. Sleep parameters including sleep process, sleep architecture as well as eye movements (EMs) frequency, and amplitude were recorded by polysomnography monitoring at pre-, intra-, and post-stimulation.

Results: Thirteen iRBD and 18 sRBD patients completed this study. Auditory stimulation significantly reduced the EMs frequency and amplitude in iRBD and sRBD patients (p < 0.05). In the iRBD group, the intra-stimulated FSL increased significantly than the pre-stimulated FSL (p < 0.05). After stimulation, patients had similar sleep latency (FSL), rapid eye movement sleep latency (RSL) and periodic limb movements in sleep (PLMS) compared with control. In the sRBD group, the intra-stimulated total sleep time, sleep efficiency was significantly increased, whereas the RSL and PLMS were significantly reduced compared with the pre-stimulated ones (all p < 0.05). The sRBD patients had similar time in bed, FSL and RBD episodes compared with control (all p < 0.05) in spite of significant difference before stimulation (all p < 0.05). However, the sleep architecture was not influenced by the stimulation despite the decrease in N3% in iRBD group (p < 0.05).

Conclusion: Low-intensity pure tone auditory stimulation may be a potentially effective intervention for RBD, especially for sRBD.     

Impaired decision-making in idiopathic REM sleep behavior disorder

BackgroundPatients with REM sleep behavior disorder (RBD) frequently develop Parkinson’s disease (PD), which can impair decision-making ability. This study was undertaken to investigate decision-making ability and its relation to olfactory function in patients with idiopathic RBD.MethodsThis study used the Iowa Gambling Task (IGT) and the Sniffin’ Stick Test for examination of 38 patients with idiopathic RBD (iRBD) and 34 age-matched healthy control subjects (HC). Associations between these test results and other clinical RBD variables were also assessed.ResultsTotal IGT score and Sniffin’ Stick Test scores were significantly lower in the iRBD group than in the HC group. The iRBD group IGT scores in the first, third, and final blocks were significantly lower than those of the HC group. In the iRBD group, no association was found between the total IGT score and the Sniffin’ Stick Test score or any clinical RBD variable.ConclusionsImpaired decision-making associated with iRBD can herald PD. However, decision-making disability is thought to appear irrespective of olfactory dysfunction and progression of RBD pathology.     

Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder – A PET study

IntroductionNoradrenergic denervation is thought to aggravate motor dysfunction in Parkinson's disease (PD). In a previous PET study with the norepinephrine transporter (NART) ligand ¹¹C-MeNER, we detected reduced NART binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using ¹¹C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether ¹¹C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with ¹⁸F-DOPA PET were correlated.Methods17 iRBD patients, 16 PD patients with (PD^RBD+) and 14 without RBD (PD^RBD−), and 25 control subjects underwent ¹¹C-MeNER PET. iRBD patients also had ¹⁸F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed.ResultsPartial-volume corrected ¹¹C-MeNER binding potential (BP^ND) values in M1S1 differed across the groups (P = 0.022) with the iRBD and PD^RBD+ groups showing significant reductions (controls vs. iRBD P = 0.007; control vs. PD^RBD+ P = 0.008). Voxel-wise comparisons confirmed reductions of M1S1 ¹¹C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal ¹⁸F-DOPA uptake and thalamic ¹¹C-MeNER binding in iRBD patients (r² = 0.343, P = 0.013).ConclusionsThis study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 ¹¹C-MeNER binding in iRBD may represent noradrenergic terminal degeneration or physiological down-regulation of NARTs in this prodromal phenotype of PD. The correlation between thalamic ¹¹C-MeNER binding and putaminal ¹⁸F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.     

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients

BackgroundWe evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS).MethodsIS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity.ResultsAmong the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages.ConclusionImpaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.     

Voxel-based magnetic resonance imaging study of structural brain changes in patients with idiopathic REM sleep behavior disorder

PurposeRapid eye movement (REM) sleep behavior disorder (RBD) is considered to result from dysfunction of the brain stem structures that regulate REM sleep. In this study, we investigated structural brain changes using magnetic resonance imaging (MRI) in patients with idiopathic RBD (iRBD) to determine structural brain alterations associated with the disorder.MethodsVoxel-based MRI morphometry was applied to 20 patients with iRBD and findings were compared with those from 18 age-matched controls.ResultsCompared with the controls, the patients with iRBD had significant gray matter volume reduction in the anterior lobes of the right and left cerebellum, tegmental portion of the pons, and left parahippocampal gyrus.ConclusionThe present study provides in vivo evidence suggesting that structural lesions of the brain stem are responsible for the occurrence of iRBD. In addition, the pattern of gray matter loss is consistent with morphological changes commonly observed in patients with Lewy body disease and multiple system atrophy, indicating that iRBD can share a common morphological abnormality with alpha-synucleinopathies.     

Impact of the Coronavirus Disease Pandemic on Patients with Head Injuries in South Korea

ObjectiveThe coronavirus disease 2019 (COVID-19) pandemic is affecting the characteristics of patients with head injuries. This study aimed to evaluate the effect of the COVID-19 pandemic on patients with head injuries at a regional emergency medical center in South Korea. MethodsFrom April 2019 to November 2020, 350 patients with head injuries were admitted to our hospital. The study period was divided into the pre-COVID-19 (n=169) and COVID-19 (n=181) eras (10 months each). Patients with severe head injuries requiring surgery (n=74) were categorized into those who underwent surgery (n=41) and those who refused surgery (n=33). ResultsHead injuries in pediatric patients (<3 years) were more frequent in the COVID-19 era than in the pre-COVID-19 era (8.8% vs. 3.6%, p=0.048). More patients refused surgery in the COVID-19 era than in the pre-COVID-19 era (57.9% vs. 30.6%, p=0.021). Refusal of surgery was associated with old age (67.7±14.5 vs. 52.4±19.1, p<0.001), marital status (married, 84.8% vs. 61.0%, p=0.037), unemployment (42.4% vs. 68.3%, p=0.034), COVID-19 era (66.7% vs. 39.0%, p=0.021), and lower Glasgow coma scale scores (6.12±3.08 vs. 10.6±3.80, p<0.001). Multivariable logistic regression analysis revealed that refusal of surgery was independently associated with old age (adjusted odds ratio [OR], 1.084; 95% confidence interval [CI], 1.030–1.140; p=0.002), COVID-19 era (adjusted OR, 6.869; 95% CI, 1.624–29.054; p=0.009), and lower Glasgow coma scale scores (adjusted OR, 0.694; 95% CI, 0.568–0.848; p<0.001). ConclusionWe observed an increased prevalence of head injuries in pediatric patients (<3 years) during the COVID-19 pandemic. Additionally, among patients with severe head injuries requiring surgery, more patients refused to undergo surgery during the COVID-19 pandemic.     

Effects of long-term use of clonazepam on nonrapid eye movement sleep patterns in rapid eye movement sleep behavior disorder

ObjectiveWe aim to analyze in detail the characteristics of nonrapid eye movement (NREM) sleep in drug-free patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). We compare drug-free iRBD patients to both normal controls and drug-free patients with narcolepsy/RBD and evaluate the changes following the long-term use of bedtime clonazepam.Participants and methodsForty-six participants were recruited: 15 with iRBD (13 men, 2 women; mean age, 65.8 ± 4.39 years), 13 with narcolepsy/RBD (10 men, 3 women; mean age, 63.0 ± 6.73 years), and 18 normal controls (10 men, 8 women; mean age 69.4 ± 7.72 years). Sleep was video polysomnographically recorded and the RBD severity scale (RBDSS) was obtained. Chin electromyography (EMG) amplitude was quantitatively assessed and the atonia index was computed. Additionally, NREM sleep instability was evaluated using an automatic quantitative analysis. Participants with iRBD were re-evaluated after 2.75 ± 1.62 years of regular therapy with 0.5 to 1-mg clonazepam at bedtime.ResultsSlow transient electroencephalography (EEG) events were increased in iRBD and decreased in narcolepsy/RBD, while fast transient events decreased in iRBD and increased in narcolepsy/RBD. During rapid eye movement (REM) sleep the atonia index was reduced in both iRBD and narcolepsy/RBD groups and during NREM sleep atonia index was increased in iRBD participants, remaining low in narcolepsy/RBD participants. After long-term therapy with clonazepam, wakefulness after sleep onset was decreased together with an increase in both slow-wave sleep (SWS) and sleep stage 2, in which the latter reached statistical significance; sleep stages 1 and 2 instability significantly decreased and the duration of EEG transients also slightly but significantly decreased. Finally, chin tone was not modified by clonazepam.ConclusionsOur study confirms that clonazepam modifies some aspects of NREM sleep in iRBD participants with a decrease in its instability. Moreover, we also show that a complex modification of sleep chin atonia exists in these participants, which also involves NREM sleep; for iRBD more complex neuropathologic models encompassing REM sleep and NREM sleep mechanisms are needed.     

Gender differences in clinical findings and α-synucleiopathy-related markers in patients with idiopathic REM sleep behavior disorder

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is a male-predominant parasomnia. Earlier clinical RBD patient studies showed gender differences of clinical symptoms and polysomnographic (PSG) findings. However, no previous investigated this issue by means of validated severity scales or by neuropsychological examination related to alpha-synucleinopathy. This study elucidates gender differences in clinical, physiological, and neuropsychological findings in Japanese idiopathic RBD (iRBD) patients.MethodsFrom 220 patients with complaint of sleep-related vocalization or behaviors who visited Yoyogi Sleep Disorder Center from June 2003 through December 2016, 43 female (68.7 ± 7.3 yr) and 141 male patients (66.7 ± 6.7 yr) diagnosed as having iRBD by video-polysomnography (v-PSG) were selected. All subjects answered the RBD questionnaire (RBDQ-JP) and underwent olfactory function test (Sniffin' Sticks test) and cognitive function test (MoCA-J).ResultsFemale iRBD patients had later first symptom-witnessed age (sleep-talking 63.2 ± 10.5 yr, behaviors 60.9 ± 8.6 yr) than male patients (sleep-talking 59.1 ± 8.8 yr, behaviors 64.7 ± 8.9 yr). No gender difference was found in age at diagnosis, clinical severity (RBDQ-JP), or olfactory or cognitive function. Regarding electromyogram (EMG) findings during REM sleep, phasic EMG activity was higher in female patients (22.3 ± 17.8% vs. 16.5 ± 16.1%), although no difference was found in tonic EMG activity.ConclusionsAlthough female iRBD patient symptoms were first recognized later than those of male patients, they showed elevated EMG activity during REM sleep and showed deteriorated olfactory and cognitive function similarly to male patients at the first medical consultation. Results suggest that disease progression in female RBD patients is equivalent to that in male patients.