特发性快速眼球运动睡眠行为障碍患者认知脑区灰质体积的改变

目的 通过对特发性快速眼球运动睡眠行为障碍(iRBD)患者认知脑区改变的探索,寻找其与帕金森病(PD)患者大脑形态改变的异同,为两者的联系提供依据.方法 对14例iRBD患者、12例PD患者及8名健康人(CON组)进行认知心理测评(复杂图形测试、临摹及回忆、符号-数字转换测试、连线测试、画钟测试、数字广度测验)及磁共振检查,采用基于体素形态学的研究技术进行分析.结果 iRBD组及PD组患者的数字符号转换测试、连线测验测试2与CON组之间的差异均有统计学意义(P<0.05),iRBD组与PD组间的差异无统计学意义(P>0.05);与CON组比较,iRBD组与PD组患者的右顶叶及左枕叶体积均缩小(P<0.05),但iRBD组与PD组间的差异无统计学意义(P>0.05);PD组右枕叶较CON组体积减小(P<0.05).结论 iRBD患者及PD患者均出现注意力及执行功能等认知能力下降,并且都出现右顶叶和枕叶萎缩,提示两者的认知损害存在相似的病理基础.     

Assessing cerebral glucose metabolism in patients with idiopathic rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement sleep behavior disorder (RBD) is a risk marker for subsequent development of neurodegenerative parkinsonism. In this study, we aimed to investigate whether regional cerebral metabolism is altered in patients with RBD and whether regional metabolic activities are associated with clinical measurements in individual patients. Twenty-one patients with polysomnogram-confirmed RBD and 21 age-matched healthy controls were recruited to undertake positron emission tomography imaging with [¹⁸F]fluorodeoxyglucose. Differences in normalized regional metabolism and correlations between metabolic activity and clinical indices in RBD patients were evaluated on a voxel basis using statistic parametric mapping analysis. Compared with controls, patients with RBD showed increased metabolism in the hippocampus/parahippocampus, cingulate, supplementary motor area, and pons, but decreased metabolism in the occipital cortex/lingual gyrus (P<0.001). RBD duration correlated with metabolism positively in the anterior vermis (r=0.55, P=0.01), but negatively in the medial frontal gyrus (r=−0.59, P=0.005). In addition, chin electromyographic activity presented a positive metabolic correlation in the hippocampus/parahippocampus (r=0.48, P=0.02), but a negative metabolic correlation in the posterior cingulate (r=−0.61, P=0.002). This study has suggested that region-specific metabolic abnormalities exist in RBD patients and regional metabolic activities are associated with clinical measures such as RBD duration and chin electromyographic activity.     

特发性快速眼动睡眠期行为障碍经颅脑实质超声研究

目的探讨快速眼动睡眠期行为障碍患者经颅脑实质超声改变。方法符合睡眠障碍国际分类第2版快速眼动睡眠期行为障碍诊断标准的15例患者(RBD组)和15例正常对照受试者,于多导睡眠图监测后通过经颅脑实质超声检查并测量中脑黑质高回声、基底节高回声、第三脑室宽度;简易智能状态检查量表(MMSE)和蒙特利尔认知评价量表(MoCA)评价认知功能。结果快速眼动睡眠期行为障碍患者具有典型的临床表现和电生理学改变。RBD组黑质高回声(6/15)、基底节高回声(7/15)阳性检出率,与正常对照组(1/15和2/15)之间差异无统计学意义(P=0.080,0.109)。RBD组伴与不伴黑质高回声患者MoCA评分差异无统计学意义(P=0.075);但RBD组伴基底节高回声患者MMSE评分高于不伴基底节高回声患者(P=0.021)。结论快速眼动睡眠期行为障碍作为突触共核蛋白病前驱期,经颅脑实质超声可表现为黑质和基底节高回声,且伴不同结局。经颅脑实质超声可以检测出脑亚临床改变,评价突触共核蛋白病风险。     

Structural and functional brain alterations in patients with idiopathic rapid eye movement sleep behavior disorder

ObjectiveTo investigate structural and functional alterations in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with healthy controls.MethodsTwenty-seven patients with polysomnography-confirmed iRBD and 33 healthy subjects were recruited. All subjects underwent a 3-tesla structural and resting-state functional magnetic resonance imaging (fMRI) examination. Voxel-based morphometry (VBM) analysis was performed to assess grey matter alterations between groups. The amplitude of low-frequency fluctuations (ALFF) was calculated and then compared to measure differences in spontaneous brain activity. Correlations were performed to explore associations between imaging metrics and clinical characteristics in iRBD patients.ResultsCompared with healthy controls, patients with iRBD had decreased grey matter volume in the frontal, temporal, parietal, occipital cortices as well as increased grey matter volume in cerebellum posterior lobe, putamen, and thalamus. Patients with iRBD also exhibited increased ALFF values in the right parahippocampal gyrus. Olfaction correlated with ALFF value changes in occipital cortices.ConclusionsPatients with iRBD had widespread decreases of grey matter volume. Increases of grey matter volume in cerebellum, putamen, and thalamus may suggest a compensatory effect, while the altered ALFF values in parahippocampal gyrus and occipital cortices may play a role in the underlying process of neurodegeneration in this disorder.     

Dynamic functional connectivity impairments in idiopathic rapid eye movement sleep behavior disorder

IntroductionPrevious functional magnetic resonance imaging (fMRI) studies typically analyzed static functional connectivity (sFC) to reveal the pathophysiology of iRBD and overlooked the dynamic nature of brain activity. Thus, we aimed to explore whether iRBD showed abnormalities of brain network dynamics using the dynamic functional connectivity (dFC) approach.MethodsResting-state fMRI data from 33 iRBD patients and 38 matched healthy controls were analyzed using an independent component analysis, sliding window correlation and k-means clustering. Relationships between clinical symptoms and abnormal dFC were evaluated using Spearman's correlation analysis.ResultsFour distinct connectivity states were identified to characterize and compare dFC patterns. We demonstrated that iRBD had fewer occurrences and a shorter dwell time in the infrequent and strongly connected State 1, but with more occurrences and a longer dwell time in the frequent and sparsely connected State 2. In addition, iRBD patients showed significantly decreased FC in certain dFC states compared to healthy controls. More importantly, the impairments in the temporal properties of State 2 were found to be associated RBDSQ scores in the patient group.ConclusionsThis study detected dFC impairments in iRBD patients and provided new insights into the pathophysiology of iRBD, which might contribute to the development of disease-modifying drugs in future clinical trials.     

Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement sleep behavior disorder is a parasomnia that is a risk factor for dementia with Lewy bodies and Parkinson's disease. Brain function impairments have been identified in this disorder, mainly in the frontal and posterior cortical regions. However, the anatomical support for these dysfunctions remains poorly understood. We investigated gray matter thickness, gray matter volume, and white matter integrity in patients with idiopathic rapid eye movement sleep behavior disorder. Twenty‐four patients with polysomnography‐confirmed idiopathic rapid eye movement sleep behavior disorder and 42 healthy individuals underwent a 3‐tesla structural and diffusion magnetic resonance imaging examination using corticometry, voxel‐based morphometry, and diffusion tensor imaging. In the patients with idiopathic rapid eye movement sleep behavior disorder, decreased cortical thickness was observed in the frontal cortex, the lingual gyrus, and the fusiform gyrus. Gray matter volume was reduced in the superior frontal sulcus only. Patients showed no increased gray matter thickness or volume. Diffusion tensor imaging analyses revealed no significant white matter differences between groups. Using corticometry in patients with idiopathic rapid eye movement sleep behavior disorder, several new cortical regions with gray matter alterations were identified, similar to those reported in dementia with Lewy bodies and Parkinson's disease. These findings provide some anatomical support for previously identified brain function impairments in this disorder. © 2014 International Parkinson and Movement Disorder Society     

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord.     

Morbidities in rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, RBD without any obvious comorbid major neurological disease), is strongly associated with numerous comorbid conditions. The most prominent is that with neurodegenerative disorders, especially synuclein-mediated disorders, above all Parkinson disease (PD). Idiopathic RBD is an important risk factor for the development of synucleinopathies. Comorbidity studies suggest that iRBD is associated with a number of other potential pre-motor manifestations of synucleinopathies such as, cognitive and olfactory impairment, reduced autonomic function, neuropsychiatric manifestations and sleep complaints. Furthermore, patients with PD and RBD may have worse prognosis in terms of impaired cognitive function and overall morbidity/mortality; in dementia, the presence of RBD is strongly associated with clinical hallmarks and pathological findings of dementia with Lewy bodies. These findings underline the progressive disease process, suggesting involvement of more brain regions in patients with a more advanced disease stage. RBD is also associated with narcolepsy, and it is likely that RBD associated with narcolepsy is a distinct subtype associated with different comorbidities. RBD is also associated with antidepressant medications, autoimmune conditions, and, in rare cases, brainstem lesions.     

Increased neural motor activation and functional reorganization in patients with idiopathic rapid eye movement sleep behavior disorder

IntroductionAltered brain activity and functional reorganization patterns during self-initiated movements have been reported in early pre-motor and motor stages of Parkinson's disease. The aim of this study was to investigate whether similar alterations can be observed in patients with idiopathic REM-sleep behavior disorder (RBD).Methods13 polysomnography-confirmed male and right-handed RBD patients and 13 healthy controls underwent a bilateral hand-movement fMRI task including internally selected (INT) and externally-guided (EXT) movement conditions for each hand. We examined functional activity and connectivity differences between groups and task-conditions, structural differences using voxel-based morphometry, as well as associations between functional activity and clinical variables.ResultsNo group differences were observed in fMRI-task performance or in voxel-based morphometry. Both groups showed faster reaction times and exhibited greater neural activation when movements were internally selected compared to externally-guided tasks. Compared to controls, RBD patients displayed stronger activation in the dorsolateral prefrontal cortex and primary somatosensory cortex during INT-tasks, and in the right fronto-insular cortex during EXT-tasks performed with the non-dominant hand. Stronger activation in RBD patients was associated with cognitive and olfactory impairment. Connectivity analysis demonstrated overall less interregional coupling in patients compared to controls. In particular, patients showed reduced temporo-cerebellar, occipito-cerebellar and intra-cerebellar connectivity, but stronger connectivity in fronto-cerebellar and fronto-occipital pathways.ConclusionThe observed stronger activation during hand-movement tasks and connectivity changes in RBD may reflect early compensatory and reorganization patterns in order to preserve motor functioning. Our findings may contribute to a better understanding and prognosis of prodromal stages of α-synucleinopathies.     

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.     

Non-rapid eye movement sleep characteristics in idiopathic REM sleep behavior disorder

This study investigated slow waves (SW; >75μV and <4Hz) characteristics in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Thirty patients with iRBD and 30 age- and sex-matched healthy subjects underwent one polysomnographic (PSG) nocturnal sleep recording. SW automatic detection was performed on F3, C3, P3, and O1 leads and SW characteristics were derived (SW density, amplitude, frequency, slope, and duration of negative and positive phases). We also compared iRBD patients and control subjects on PSG variables and delta (0.25-4.0Hz) spectral power. No between-group differences were found on PSG variables, delta spectral power, or SW characteristics. Results show no SW abnormalities in iRBD patients compared to healthy participants, which suggests similar level of synchronization of thalamo-cortical neurons during N-REM sleep.     

Clinical markers of early nigrostriatal neurodegeneration in idiopathic rapid eye movement sleep behavior disorder

Background

Rapid eye movement sleep behavior disorder (RBD) is an early feature in α synucleinopathies and may precede other clinical manifestations of disease for several years. Olfactory dysfunction and mild motor abnormalities (MMAs) are highly prevalent in prodromal α synucleinopathies such as RBD and are suspected to be predictive neurodegenerative markers. Because both markers also are highly prevalent in the healthy elderly population, the discriminative value to detect an early neurodegenerative process is unclear.

Methods

We examined 28 patients with idiopathic RBD (iRBD) without manifest neurodegenerative disease to determine diagnostic accuracy of MMAs and olfactory dysfunction in identifying patients with early nigrostriatal degeneration in transcranial sonography (TCS) and ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography (¹²³I-FP-CIT-SPECT).

Results

Sixty-three percent of our participants showed MMAs which were strongly associated with abnormal TCS and ¹²³I-FP-CIT-SPECT findings. The discriminative value in detecting participants with early nigrostriatal degeneration was excellent (area under the receiver operating characteristic [ROC] curve, 0.84 [P ? .003] for TCS and 0.79 [P ? .066] for ¹²³I-FP-CIT-SPECT). Olfactory dysfunction was present in 78% of iRBD participants, but it was not linked with neuroimaging abnormalities or MMAs. Olfactory dysfunction did not discriminate participants with early nigrostriatal degeneration (area under the ROC curve, 0.54 [P ? .747] for TCS and 0.31 [P ? .225] for ¹²³I-FP-CIT-SPECT). Early RBD manifestation but no demographic (e.g., age, gender) or clinical characteristics of RBD (e.g., duration, severity of RBD) were associated with neuroimaging abnormalities in TCS and ¹²³I-FP-CIT-SPECT.

Conclusions

Unlike olfactory dysfunction, MMAs discriminate patients with early nigrostriatal degeneration in iRBD. Early RBD manifestation seems to be an additional risk factor which aggravates neurodegenerative risk.