Masaoki Iwanami

The REM sleep behavior disorder screening questionnaire: validation study of a Japanese version.

BACKGROUND REM sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal skeletal muscle atonia during REM sleep and elaborate motor activity associated with dream mentation. Idiopathic RBD (iRBD) has a known association with neurodegenerative diseases such as synucleinopathies. Recently, a specific screening scale for assessment of REM sleep behavior disorder (RBDSQ) was validated. Detection of RBD using a Japanese version of the RBDSQ would be useful in the stepwise diagnostic process. We investigated the validity and reliability of a Japanese version of this instrument, the RBDSQ-J. METHODS Subjects were 52 patients with iRBD diagnosed according to criteria in the International Classification of sleep disorders, second edition, 55 obstructive sleep apnea syndrome (OSAS) patients who responded well to CPAP therapy after a diagnosis of RBD was ruled out by history and polysomnography (PSG) and 65 healthy subjects. RESULTS An RBDSQ-J score cut-off of 5.0 was considered useful for differentiating the iRBD group from the healthy subjects or the OSAS group. Cronbachs alpha for the entire RBDSQ-J was 0.866. CONCLUSION The RBDSQ-J had high sensitivity, specificity, and reliability and would be applicable as a screening method for iRBD in the elderly Japanese population.

Relevance of substantia nigra hyperechogenicity and reduced odor identification in idiopathic REM sleep behavior disorder

BACKGROUND Substantia nigra (SN) hyperechogenicity determined by transcranial sonography (TCS) and olfactory dysfunction are common findings in Parkinson disease (PD), which may reveal a prodromal synucleinopathy in idiopathic REM sleep behavior disorder (iRBD). METHODS TCS and the Odor Stick Identification Test for Japanese (OSIT-J) were performed in 34 consecutive patients with iRBD (67.9+/-6.1years), 17 consecutive patients with PD (66.4+/-6.7years), and 21 control group subjects (64.4+/-5.8years). RESULTS There was a significantly increased area of echogenicity in the SN in the iRBD group (0.20+/-0.13cm2) and PD group (0.22+/-0.11cm2) compared with the control group (0.06+/-0.06cm(2)). We found pathological SN hyperechogenicity (0.20cm2) in 41.2% of the iRBD group, 52.6% of the PD group, and 9.5% of the control group. Further, there were abnormal findings of both pathological SN hyperechogenicity (0.20cm2) and functional anosmia or hyposmia in 4 (11.8%) or 9 (26.5%) of the iRBD group subjects, respectively, and 7 (57.9%) or 2 (11.8%) of the PD group subjects, respectively. CONCLUSION Pathological SN hyperechogenic abnormality and functional anosmia in iRBD may be a disease state in the transition to a neurodegenerative disease.

Nocturnal disturbances and restlessness in Parkinson's disease: Using the Japanese version of the Parkinson's disease sleep scale-2

OBJECTIVE The aim of this study was to assess the validity and the reliability of the Japanese version of the Parkinsons disease sleep scale (PDSS)-2 and to use this scale to identify nocturnal symptoms and their impact on patients quality of life. METHODS A cross-sectional, case-controlled study was conducted consisting of 93 patients with Parkinsons disease (PD) and 93 age- and gender-matched control subjects. The Japanese version of the PDSS-2 was used for the evaluation of nocturnal disturbances. The patients quality of life was evaluated with the Parkinsons Disease Quality of Life questionnaire (PDQ-39) and their depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II), respectively. In addition, the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Parkinson Fatigue Scale (PFS) were administered. RESULTS As assessed using the PDSS-2, PD patients had significantly impaired scores compared with control subjects (15.0±9.7 vs. 9.1±6.6, p<0.001). The ESS, BDI-II and PFS scores were significantly impaired in PD patients compared with controls. A satisfactory internal consistency and test-retest reliability score were obtained for the PDSS-2 total score (Cronbachs alpha=0.86). The PDSS-2 was correlated with the PSQI, ESS, BDI-II, PFS, PDQ-39 summary index, all of the PDQ-39 domains and Unified Parkinsons Disease Rating Scale part III. The frequency of restless legs syndrome (RLS) was not significantly different between PD patients and controls (5.5% vs. 2.2%), but nocturnal restlessness was significantly more frequent in PD patients than controls. Stepwise linear regression analyses revealed the PDQ-39 summary index and the PSQI global score as significant predictors for the PDSS-2 total score. CONCLUSIONS Our study confirmed the usefulness of the Japanese version of the PDSS-2 that enables the comprehensive assessment of nocturnal disturbances in PD. The association between RLS and nocturnal restlessness in PD requires further study.

Sleep Disturbances Associated with Parkinson's Disease

Sleep disturbances are common problems affecting the quality life of Parkinsons disease (PD) patients and are often underestimated. The causes of sleep disturbances are multifactorial and include nocturnal motor disturbances, nocturia, depressive symptoms, and medication use. Comorbidity of PD with sleep apnea syndrome, restless legs syndrome, rapid eye movement sleep behavior disorder, or circadian cycle disruption also results in impaired sleep. In addition, the involvement of serotoninergic, noradrenergic, and cholinergic neurons in the brainstem as a disease-related change contributes to impaired sleep structures. Excessive daytime sleepiness is not only secondary to nocturnal disturbances or dopaminergic medication but may also be due to independent mechanisms related to impairments in ascending arousal system and the orexin system. Notably, several recent lines of evidence suggest a strong link between rapid eye movement sleep behavior disorder and the risk of neurodegenerative diseases such as PD. In the present paper, we review the current literature concerning sleep disorders in PD.

Odor identification test as an indicator of idiopathic REM sleep behavior disorder

Reduction of olfactory function in idiopathic rapid‐eye‐movement (REM) sleep behavior disorder (iRBD) is of the same magnitude as that found in patients with Parkinsons disease (PD) and dementia with Lewy bodies (DLB). We assessed olfactory function using the Odor Stick Identification Test for Japanese (OSIT‐J) in 48 Japanese patients with iRBD, 21 with PD, and 34 with obstructive sleep apnea syndrome (OSAS). Possible score of the OSIT‐J ranges from 0 to 12. OSIT‐J scores were 4.9 ± 2.8 in patients with iRBD, 4.8 ± 2.8 in patients with PD, and 9.9 ± 1.4 in OSAS patients. An OSIT‐J score of 8.5 was associated with a sensitivity of 88.2 and 85.3%, respectively, and specificity of 83.3 and 85.7%, respectively, in differentiating iRBD or PD patients from OSAS patients. Odor identification is impaired in Japanese patients with iRBD and PD. The results suggest that OSIT‐J, which is a short and simple nonlexical olfactory identification test, can be useful as a clinical indicator for iRBD with Lewy body formation and is appropriate in the Japanese elderly population.

Preclinical substantia nigra dysfunction in rapid eye movement sleep behaviour disorder.

OBJECTIVES Transcranial sonography (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in people with Parkinsons disease and in approximately 10% of healthy subjects. It is hypothesized that SN hyperechogenicity in healthy subjects and patients with idiopathic rapid eye movement (REM) sleep behaviour disorder (iRBD) patients is a marker of vulnerability for Parkinsons disease. METHODS TCS and positron emission tomography (PET) with 6-[(18)F] fluoro-meta-tyrosine (FMT), which can assess the level of the presynaptic dopaminergic nerve, were performed in 19 male patients with iRBD, mean age 66.4 (standard deviation [SD] 4.9) years, to assess nigrostriatal function. RESULTS Nine patients had pathological SN hyperechogenicity (mean age 66.8 [SD 3.9] years; 0.31 [SD 0.12] cm(2)) and 10 patients did not have SN hyperechogenicity (mean age 66.0 [SD 5.8] years; 0.11 [SD 0.06] cm(2)). FMT uptake at the putamen and caudate was significantly lower in iRBD patients with pathological SN hyperechogenicity compared with those without SN hyperechogenicity. However, no correlation was found between SN echogenicity and FMT uptake. This is in conflict with previous findings which showed that subjects with hyperechogenicity had lower FMT uptake in the striatum. CONCLUSION Pathological hyperechogenic alterations in the SN in patients with iRBD may suggest the existence of preclinical SN dysfunction as determined by FMT-PET.

Probable rapid eye movement sleep behavior disorder, nocturnal disturbances and quality of life in patients with Parkinson's disease: a case-controlled study using the rapid eye movement sleep behavior disorder screening questionnaire

BackgroundIncreasing evidence provides a clear association between rapid eye movement sleep behavior disorders (RBD) and Parkinson’s disease (PD), but the clinical features that determine the co-morbidity of RBD and PD are not yet fully understood.MethodsWe evaluated the characteristics of nocturnal disturbances and other motor and non-motor features related to RBD in patients with PD and the impact of RBD on their quality of life. Probable RBD (pRBD) was evaluated using the Japanese version of the RBD screening questionnaire (RBDSQ-J).ResultsA significantly higher frequency of pRBD was observed in PD patients than in the controls (RBDSQ-J ≥ 5 or ≥ 6: 29.0% vs. 8.6%; 17.2% vs. 2.2%, respectively). After excluding restless legs syndrome and snorers in the PD patients, the pRBD group (RBDSQ-J≥5) showed higher scores compared with the non-pRBD group on the Parkinson’s disease sleep scale-2 (PDSS-2) total and three-domain scores. Early morning dystonia was more frequent in the pRBD group. The Parkinson’s Disease Questionnaire (PDQ-39) domain scores for cognition and emotional well-being were higher in the patients with pRBD than in the patients without pRBD. There were no differences between these two groups with respect to the clinical subtype, disease severity or motor function. When using a cut-off of RBDSQ-J = 6, a similar trend was observed for the PDSS-2 and PDQ-39 scores. Patients with PD and pRBD had frequent sleep onset insomnia, distressing dreams and hallucinations. The stepwise linear regression analysis showed that the PDSS-2 domain “motor symptoms at night”, particularly the PDSS sub-item 6 “distressing dreams”, was the only predictor of RBDSQ-J in PD.ConclusionOur results indicate a significant impact of RBD co-morbidity on night-time disturbances and quality of life in PD, particularly on cognition and emotional well-being. RBDSQ may be a useful tool for not only screening RBD in PD patients but also predicting diffuse and complex clinical PD phenotypes associated with RBD, cognitive impairment and hallucinations.

Cardiac 123I-MIBG accumulation in Parkinson's disease differs in association with REM sleep behavior disorder.

Nomura et al. [1] recently reported that 123I-MIBG uptake was decreased in non-demented Parkinson’s disease (PD) patients with clinical REM sleep behavior disorder (RBD) and that patients with subclinical RBD did not have significantly reduced 123I-MIBG uptake. Moreover, among the studied variables, the existence of RBD symptoms alone was associated with reduced MIBG uptake among PD patients. PD patients with clinical RBD might suffer from a wider a-synuclein pathology, including reduced cardiac sympathetic ganglia function as reflected by a lowered 123I-MIBG uptake. In another recent report, Kashihara et al. showed that cardiac 123I-MIBG uptake was more markedly reduced in patients with idiopathic RBD (iRBD) than in those with early stage PD [2]. IRBD may not necessarily be a prodromal condition of PD with respect to cardiac 123I-MIBG uptake results. Lesions responsible for RBD are located or linked more closely to the lesion responsible for decreased 123I-MIBG uptake than are lesions in patients with PD. We have reported that cardiac 123I-MIBG accumulation was reduced to about the same degree in iRBD, PD and DLB, which implicates a Lewy body a-synucleinopathy in cardiac postganglionic sympathetic and intrinsic neurons [3]. In most cases, a marked reduction in 123I-MIBG accumulation occurred soon after the onset of iRBD. Therefore, most iRBD patients presumably had cardiac neuronal parkinsonian pathology present around the time that their RBD emerged. We also conducted clinical interviews, such as with caregivers, to assess RBD symptoms in PD patients [4], and a positive diagnosis of clinically probable RBD (cpRBD) was made according to the minimal diagnostic criteria for parasomnias provided in the International Classification of Sleep Disorders-Revised. Cardiac 123IMIBG uptake in patients with polysomnography(PSG) confirmed iRBD (n 1⁄4 59) was compared with that in patients with PD with cpRBD (n 1⁄4 11), with PD without cpRBD (n 1⁄4 27), and control subjects (n 1⁄4 19). This study was performed in accordance with the Declaration of Helsinki. Procedureswere approved by the Ethics Review Committee of Dokkyo Medical University, and informed

Evaluation of cutoff scores for the Parkinson's disease sleep scale-2

The Parkinsons Disease Sleep Scale (PDSS)‐2 is a recently developed tool for evaluating disease‐related nocturnal disturbances in patients with Parkinsons disease (PD). However, its cutoff score has not been clinically assessed. We determined the optimal cutoff score of the Japanese version of the PDSS‐2.

Idiopathic REM Sleep Behavior Disorder: Implications for the Pathogenesis of Lewy Body Diseases

Objectives. Both results of the odor identification and cardiac 123I-metaiodobenzylguanidine accumulation have been investigated for their potential to enhance the detection of pathogenesis resembling that of Lewy body-related α-synucleinopathies in patients clinically diagnosed as having idiopathic REM sleep behavior disorder. Methods. We performed both the Odor Stick Identification Test for Japanese and 123I-metaiodobenzylguanidine scintigraphy in 30 patients with idiopathic REM sleep behavior disorder, 38 patients with Parkinsons disease, and 20 control subjects. Results. In idiopathic REM sleep behavior disorder, reduced odor identification score and an early or delayed heart to mediastinum ratio on 123I-metaiodobenzylguanidine were almost as severe as in Parkinsons disease patients. Delayed cardiac 123I-metaiodobenzylguanidine uptake was even more severe in the idiopathic REM sleep behavior disorder group than in the Parkinsons disease group. Conclusions. Reduced cardiac 123I-metaiodobenzylguanidine uptake, which is independent of parkinsonism, may be more closely associated with idiopathic REM sleep behavior disorder than olfactory impairment.