REM sleep behavior disorder: update on diagnosis and management / Transtorno comportamental do sono REM: atualização no diagnóstico e manejo

Abstract REM sleep behavior disorder (RBD) is characterized by a loss of atonia of skeletal muscles during REM sleep, associated with acting out behaviors during dreams. Knowledge of this pathology is important to predict neurodegenerative diseases since there is a strong association of RBD with diseases caused by the deposition of alpha-synuclein in neurons (synucleinopathies), such as Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Proper diagnosis of this condition will enable the use of future neuroprotective strategies before motor and cognitive symptoms. Diagnostic assessment should begin with a detailed clinical history with the patient and bed partner or roommate and the examination of any recorded home videos. Polysomnography (PSG) is necessary to verify the loss of sleep atonia and, when documented, the behaviors during sleep. Technical recommendations for PSG acquisition and analysis are defined in the AASM Manual for the scoring of sleep and associated events, and the PSG report should describe the percentage of REM sleep epochs that meet the criteria for RWA (REM without atonia) to better distinguish patients with and without RBD. Additionally, PSG helps rule out conditions that may mimic RBD, such as obstructive sleep apnea, non-REM sleep parasomnias, nocturnal epileptic seizures, periodic limb movements, and psychiatric disorders. Treatment of RBD involves guidance on protecting the environment and avoiding injuries to the patient and bed partner/roommate. Use of medications are also reviewed in the article. The development of neuroprotective medications will be crucial for future RBD therapy.

Resumo O transtorno comportamental do sono REM (TCSREM) é caracterizado por uma perda de atonia dos músculos esqueléticos durante o sono REM, associada a comportamentos de atuação durante os sonhos. O conhecimento desse transtorno é importante como preditor de doenças neurodegenerativas, uma vez que existe uma forte associação de TCSREM com doenças causadas pela deposição de alfa-sinucleína nos neurônios, como a doença de Parkinson (DP), atrofia de múltiplos sistemas (MSA) e demência com corpos de Lewy (DLB). O diagnóstico adequado dessa condição permitirá o uso de futuras estratégias neuroprotetoras antes do aparecimento dos sintomas motores e cognitivos. A avaliação diagnóstica deve começar com uma história clínica detalhada com o paciente e acompanhante, além de exame de vídeos. A polissonografia (PSG) é necessária para verificar a perda da atonia do sono e, quando documentados, os comportamentos durante o sono. As recomendações técnicas para aquisição e análise de PSG são definidas no Manual da AASM (Scoring of sleep and associated events) e o relatório de PSG deve descrever a porcentagem de períodos de sono REM que atendem aos critérios para REM sem atonia. Além disso, a PSG ajuda a descartar condições que podem mimetizar o TCSREM, como apneia obstrutiva do sono, parassonias do sono não REM, crises epilépticas noturnas, movimentos periódicos dos membros e transtornos psiquiátricos. O tratamento do TCSREM envolve orientações sobre adaptações do ambiente para evitar lesões ao paciente e ao colega de quarto. Medicamentos utilizados são revistos no artigo, assim como o crucial desenvolvimento de medicamentos neuroprotetores.

Role of Cannabinoid CB1 Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats / 中国医学科学杂志(英文版)

Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB1R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory.

Effect of the association of amantadine and quetiapine in the treatment of rem sleep behavior disorder: case report / Efeito da associação de amantadina e quetiapina no tratamento do distúrbio do comportamento do sono rem: relato de caso / Efecto de la asociación de amantadina y quetiapina en el tratamiento del trastorno del comportamiento del sueño rem: reporte de un caso

The aim was to report the case of a patient with REM sleep behavior disorder, unresponsive to standard treatment and with complete control of the condition after association of amantadine. Female patient, 45 years old, with systemic arterial hypertension and hypothyroidism, referred to neurological care, reporting frequent episodes of nocturnal agitation in the first hours of sleep, with walking and vocalization, waking up easily if called. She complains of drowsiness and anxiety, secondary to the impact of the RBD on her personal life. She mentions previous attempts at drug treatment with benzodiazepines (Bromazepam and Clonazepam), Zolpidem and Trazodone, all without clinical improvement, with Quetiapine being introduced at a low dose (not yet tried) 25mg, with a therapeutic target of 50mg with partial improvement only with 25mg. When trying 50mg, presenting a worsening of the picture. In a new follow-up, therapy with Amantadine 50 mg/day associated with Quetiapine 25 mg/day was started. The patient returned reporting a significant improvement in the condition, less frequent episodes associated with reduced nocturnal movement. After adaptation of the combined therapy, with adjustments in the dose of Amantadine, an increase of 50mg every 14 days up to 200 mg/day, with the possibility of using quetiapine 50mg (balance between the drugs), the patient evolved stable, with a great improvement in the quality of life and absence of new episodes of the sleep disorder.

O objetivo foi relatar o caso de uma paciente com transtorno comportamental do sono REM, sem resposta ao tratamento padrão e com completo controle do quadro após associação de amantadina. Paciente do sexo feminino, 45 anos, com hipertensão arterial sistêmica e hipotireoidismo, encaminhada a atendimento neurológico relatando episódios frequentes de agitação noturna nas primeiras horas de sono, com deambulo e vocalização, despertava facilmente se chamada. Queixa-se de sonolência e ansiedade, secundárias ao impacto do TCSREM em sua vida pessoal. Menciona tentativas prévias de tratamento medicamentoso com benzodiazepínicos (Bromazepam e Clonazepam), Zolpidem e Trazodona, todos sem melhora clínica, sendo introduzido Quetiapina em dose baixa (ainda não tentado) 25mg, com alvo terapêutico de 50mg com melhora parcial apenas com 25mg. Ao tentar 50mg, apresentando piora do quadro. Em novo retorno, iniciou-se terapia com Amantadina 50 mg/dia associada a Quetiapina 25 mg/dia. A paciente retornou referindo melhora significativa do quadro, episódios em menor frequência associados a redução na movimentação noturna. Após adaptação da terapia combinada, com ajustes da dose de Amantadina, aumento de 50mg a cada 14 dias até 200 mg/dia, sendo possível o uso da quetiapina 50mg (equilíbrio entre os fármacos) a paciente evoluiu estável, com grande melhora da qualidade de vida e ausência de novos episódios do distúrbio de sono.

El objetivo fue reportar el caso de un paciente con trastorno de conducta del sueño REM, que no responde al tratamiento estándar y con un control completo de la condición después de la asociación de amantadina. Paciente femenina, de 45 años de edad, con hipertensión arterial sistémica e hipotiroidismo, referida a atención neurológica, reportando episodios frecuentes de agitación nocturna en las primeras horas de sueño, con marcha y vocalización, despertándose fácilmente si se le llama. Se queja de somnolencia y ansiedad, secundarias al impacto de la RBD en su vida personal. Menciona intentos previos de tratamiento farmacológico con benzodiazepinas (Bromazepam y Clonazepam), Zolpidem y Trazodona, todos sin mejoría clínica, con la introducción de quetiapina a una dosis baja (aún no probada) de 25mg, con un objetivo terapéutico de 50mg con mejoría parcial solo con 25mg. Al intentar 50mg, presentando un empeoramiento de la imagen. En un nuevo seguimiento se inició tratamiento con 50 mg/día de amantadina asociado a 25 mg/día de quetiapina. El paciente retornó reportando una mejoría significativa en la condición, episodios menos frecuentes asociados a reducción del movimiento nocturno. Después de la adaptación de la terapia combinada, con ajustes en la dosis de Amantadina, un aumento de 50mg cada 14 días hasta 200 mg/día, con la posibilidad de utilizar quetiapina 50mg (equilibrio entre los fármacos), el paciente evolucionó estable, con una gran mejoría en la calidad de vida y ausencia de nuevos episodios del trastorno del sueño.

Research progress on the common pathogenesis of Parkinson′s disease and rapid eye movement sleep behavior disorder / 中华神经科杂志

Parkinson′s disease (PD) is one of the neurodegenerative diseases with high incidence in middle-aged and elderly people, and its prodromal stage lasts for several years to decades, markers of disease progression in prodromal stage are important basis for early recognition and diagnosis of PD. Current studies have shown that rapid eye movement sleep behavior disorder (RBD) is the specific clinical prodromal symptoms of PD, and has some of the same mechanisms as PD. Part of the same mechanisms develop regularly in the process of RBD converting to PD, which may produce valuable prodromal markers of PD. This paper reviews the common mechanisms of PD and RBD, in order to provide some ideas for the early clinical diagnosis and treatment of PD.

Impact of rapid eye movement sleep behavior disorder and autonomic disorders on Parkinson's disease: a review / Impacto do transtorno comportamental do sono REM e doenças autonômicas na doença de Parkinson: uma revisão

ABSTRACT Parkinson's disease (PD) has heterogeneous clinical manifestations and prognoses. It is accompanied by a group of motor and non-motor symptoms ranging from independence to total disability, limiting work and personal care activities. Currently, disease subtype markers for informing prognosis remain elusive. However, some studies have reported an association between rapid eye movement (REM) sleep behavior disorder (RBD) and faster motor and non-motor symptom progression, including autonomic dysfunction and cognitive decline. Moreover, since autonomic dysfunction has been described in idiopathic forms of RBD, and they share some central regulatory pathways, it remains unclear whether they have a primary association or if they are more severe in patients with PD and RBD, and thus are a disease subtype marker. This article aimed at critically reviewing the literature on the controversies about the prevalence of RBD in PD, the higher incidence of PD non-motor symptoms associated with RBD, the evidence of faster motor worsening in parkinsonian patients with this parasomnia, and the main pathophysiological hypotheses that support these findings.

RESUMO A doença de Parkinson (DP) apresenta variadas manifestações clínicas e distintos prognósticos. É caracterizada por um conjunto de sintomas motores e não motores que podem variar desde um quadro de independência até a completa incapacidade laborativa e de cuidados pessoais. Até o momento, não está claro quais seriam os marcadores de subtipos da doença que poderiam alertar para formas de prognóstico. Porém existem alguns estudos que mostram que a presença do transtorno comportamental do sono REM pode estar associada à progressão mais rápida dos sintomas motores e não motores, como disfunção autonômica e declínio cognitivo. Questiona-se ainda se a disautonomia está primariamente associada ao transtorno do sono REM, já que são relatadas nas formas idiopáticas deste transtorno de sono e compartilham alguns núcleos reguladores centrais. Ou se são mais graves nos pacientes com diagnóstico de DP e transtorno comportamental do sono REM, marcando assim um subtipo da doença. Esta revisão teve como objetivo revisar criticamente os principais estudos publicados envolvendo as controvérsias sobre a prevalência do transtorno comportamental do sono REM na DP, a maior incidência de sintomas não motores da DP associados ao transtorno do sono REM, as evidências de piora motora mais rápida nos pacientes parkinsonianos que apresentam este transtorno do sono e as principais hipóteses fisiopatológicas que justificam esses achados.

Progress in sleep disorders in multiple system atrophy / 中华神经科杂志

Multiple system atrophy can have various forms of sleep disorders, including insomnia, rapid eye movement sleep behavior disorder, sleep-disordered breathing, periodic leg movements during sleep and excessive daytime sleepiness. This article will focus on the concept, classification, pathogenesis, clinical features, diagnosis and treatment, aiming to deepen clinicians′ understanding of the disease, which will be helpful for early diagnosis and treatment.

Locus Coeruleus Acid-Sensing Ion Channels Modulate Sleep–Wakefulness and State Transition from NREM to REM Sleep in the Rat / 神经科学通报·英文版

The locus coeruleus (LC) is one of the essential chemoregulatory and sleep–wake (S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement (REM) sleep. LC neurons are also involved in CO

Recent Progress in Non-motor Features of Parkinson’s Disease with a Focus on Circadian Rhythm Dysregulation / 神经科学通报·英文版

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which manifests with both motor and non-motor symptoms. Circadian rhythm dysregulation, as one of the most challenging non-motor features of PD, usually appears long before obvious motor symptoms. Moreover, the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis, and it has emerged as a hot topic in PD research. In this review, we briefly introduce the circadian rhythm and circadian rhythm-related genes, and then summarize recent research progress on the altered circadian rhythm in PD, ranging from clinical features to the possible causes of PD-related circadian disorders. We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD, but also shed light on the better management of PD.

Validation of the Brazilian Portuguese version of the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ-BR) / Validação da Versão Brasileira do Questionário de Triagem do Transtorno Comportamental do Sono REM (QT-TCSREM-BR)

ABSTRACT Introduction: A diagnosis of rapid eye movement sleep behavior disorder (RBD) currently requires confirmation with polysomnography (PSG). However, PSG may not be sufficiently available. In these situations, a clinical diagnostic measure might be useful. Objective: To validate the Brazilian Portuguese version of RBD screening questionnaire (RBDSQ) for patients with Parkinson's disease (PD). Methods: Using detailed clinical interviews and PSG analysis (diagnostic gold standard), a convenience sample of 69 subjects was divided into the following subgroups: patients with PD and RBD (PD+RBD; n=50) and patients with PD alone (PD-RBD; n=19). Results: RBDSQ-BR showed adequate internal consistency (Cronbach's α=0.809) and, except for item 8, adequate item-test correlation. The retest performed in a second sample (n=13, consecutive) showed high agreement for total score (intraclass correlation coefficient, ICC=0.863) and acceptable agreement for items 2, 3, 6.2, 6.3, 7, and 8 (K>0.60). The receiver operating characteristic (ROC) curve analysis had an area under the curve (AUC) of 0.728. A cut-off score of 4 enabled the correct diagnosis of 76.8% subjects and provided the best balance between sensitivity (84%) and specificity (57.9%), with a 2.0 likelihood ratio of a positive result (LR+) and a 0.3 likelihood ratio of a negative result (LR-). Items 2 and 6.2 had 84.2% specificity and 3.2 LR+. Combined items 1+2+6.2, 2+6.1, and 6.1+6.2 increased the specificity to 94.7%, with LR+ ranging from 6.1 to 7.6. Conclusions: RBDSQ-BR is a reliable instrument, which may be useful for RBD diagnosis of Brazilian patients with PD. The instrument is also valid and may help in a better selection of cases for a more detailed clinical evaluation or even PSG analysis.

RESUMO Introdução: O diagnóstico do transtorno comportamental do sono REM (TCSREM) implica na realização da polissonografia (PSG), mas sua disponibilidade pode não ser suficiente. Portanto, meios clínicos para o diagnóstico podem ser úteis. Objetivo: Validar para a língua portuguesa falada no Brasil o questionário de triagem do TCSREM (QT-TCSREM) em pacientes portadores de doença de Parkinson (DP). Métodos: Uma amostra por conveniência composta de 69 indivíduos foi dividida em portadores de DP com TCSREM (n=50) e DP sem TCSREM (n=19) através de entrevista clínica detalhada e análise da PSG. Resultados: QT-TCSREM-BR apresentou consistência interna adequada (α de Cronbach=0,809) e, exceto pelo item 8, correlação item-total adequada. Reteste feito em uma segunda amostra (n=13, consecutivos) evidenciou concordância elevada para o escore total (coeficiente de correlação intraclasse, CCI=0,863) e aceitável para os itens 2, 3, 6.2, 6.3, 7 e 8 (K>0,60). Análise da curva característica de operação do receptor (COR) obteve uma área sob a curva de 0,728. O corte 4 permitiu o diagnóstico correto de 76,8% dos indivíduos e apresentou o melhor equilíbrio entre sensibilidade (84%) e especificidade (57,9%), com uma razão de verossimilhança de um resultado positivo (RV+) 2,0 e de um resultado negativo (RV-) 0,3. Os itens 2 e 6.2 obtiveram especificidade 84,2% e RV+ 3,2. Itens combinados 1+2+6,2, 2+6,1 e 6,1+6,2 aumentaram a especificidade para 94,7%, com RV+ variando de 6,1 até 7,6. Conclusões: O QT-TCSREM-BR é um instrumento confiável que pode ser útil para o diagnóstico do TCSREM em pacientes com DP no Brasil. O instrumento também é válido e pode auxiliar numa melhor seleção de casos a serem submetidos a uma avaliação mais detalhada ou até mesmo a uma análise de PSG.

Enfermedad de Willis-Ekbom a propósito de un caso / Willis-Ekbom's disease a case report

Los trastornos del sueño REM, son de alta prevalencia en nuestro medio, se manifiestan por lo general en comorbilidad con trastornos afectivos como la ansiedad y la depresión. Dependiendo de la sintomatología del paciente la afectación puede afectar su calidad de vida, en nuestro medio son frecuentes las crisis de pánico y trastornos del sueño reconocidos culturalmente como provenientes de embrujos o maleficios, que al no ser tratados con buenos resultados, buscan una respuesta en el ámbito médico postergando la intervención en el caso evaluado. El presente caso describe los síntomas experimentados por un adulto de sexo masculino, con un cuadro que impresiona por su descripción sintomatológica de origen netamente urológico, que fue valorado en integridad con sus respectivos resultados laboratoriales y de gabinete es referido a diferentes especialidades y finalmente a psiquiatría donde se llega a la conclusión diagnostica de enfermedad de Willis-Ekbom, trastorno del sueño REM y Trastorno de ansiedad generalizada con crisis de pánico, se realiza tratamiento específico, con resultados favorables y seguimientos periódicos. Se presenta el caso clínico de un paciente de sexo masculino de 61 años como se describe en la presentación.

REM sleep disorders, are of high prevalence in our environment, are usually manifested in comorbidity with affective disorders such as anxiety and depression. Depending on the symptomatology of the patient, the affectation can affect their quality of life, in our environment there are frequent panic crises and sleep disorders culturally recognized as coming from spells or curses, which, when not being treated with good results, seek an answer in the medical field postponing the intervention in the case evaluated. The present case describes the symptoms experienced by a male adult, with a picture that impresses with his symptomatic description of a purely urological origin, which was assessed in integrity with their respective laboratory and laboratory results. It refers to different specialties and finally to psychiatry. where the diagnostic conclusión of Willis-Ekbom disease, REM sleep disorder and generalized anxiety disorder with panic crisis is reached, specific treatment is performed, with favorable results and periodic follow-up.

Unveiling sleep mysteries: neurobiology of dreaming / Revelando mistérios do sono: neurobiologia dos sonhos

Dreaming is the result of the mental activity of rapid eye movement (REM) sleep stage, and less commonly of non-REM sleep. Dreams offer unique insights into the patients' brains, minds, and emotions. Based on neurophysiological and neuroimaging studies, the biological core of dreaming stands on some brain areas activated or inactivated. Dream abnormalities in neurological disorders include a reduction / cessation of dreaming, an increase in dream frequency, changes in dream contents and accompaniments, and the occurrence of dreamlike experiences (hallucinations) mainly during the wake-sleep/sleep-wake transitions. Dream changes can be associated with several neurological conditions, and the unfolding of biological knowledge about dream experiences can also have significance in clinical practice. Regarding the dream importance in clinical neurological management, the aim of this paper encompasses a summary of sleep stages, dreams neurobiology including brain areas involved in the dreams, memory, and dreams, besides Dreams in the aging people and neurodegenerative disorders.

Sonhar é o resultado da atividade mental do estágio do sono de movimento rápido dos olhos (REM) e, menos comumente, do sono não-REM. Os sonhos oferecem informações únicas sobre o cérebro, a mente e as emoções dos pacientes. Com base em estudos neurofisiológicos e de neuroimagem, o núcleo biológico do sonho está em algumas áreas do cérebro ativadas ou inativadas. As anormalidades do sonho nos distúrbios neurológicos incluem uma redução / cessação do sonho, um aumento na frequência do sonho, alterações nos conteúdos e acompanhamentos do sonho e a ocorrência de experiências semelhantes ao sonho (alucinações), principalmente durante as transições de vigília-sono / sono-vigília. As mudanças do sonho podem estar associadas a várias condições neurológicas, e o desenvolvimento do conhecimento biológico sobre as experiências do sonho também pode ter significado na prática clínica. Com relação à importância do sonho no manejo neurológico clínico, o objetivo deste artigo é resumir os estágios do sono, a neurobiologia dos sonhos, incluindo as áreas do cérebro envolvidas nos sonhos, a memória e os sonhos, além dos sonhos nos idosos e nos distúrbios neurodegenerativos.

Abnormal eye movements in patients with idiopathic rapid eye movement sleep behavior disorder / 浙江大学学报·医学版

OBJECTIVE@#To analyze the characteristics of eye movements in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD).@*METHODS@#Twenty two patients with iRBD and 20 controls were enrolled between January 2017 and May 2019 from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Clinical data including polysomnogram (PSG) results were collected. Videonystagmography (VNG) including spontaneous nystagmus, gaze, saccade, tracking and optokinetic test were performed. The difference of VNG results between iRBD patients and controls were analyzed. The factors related to the abnormal VNG results were analyzed by using logistic regression analysis.@*RESULTS@#No significant differences were found between the iRBD and control groups in the spontaneous nystagmus, gaze nystagmus, square wave jerk, involuntary eye movement, saccade and optokinetic nystagmus (all >0.05). In smooth pursuit of 0.4-0.5 Hz and 0.6-0.7 Hz, iRBD patients had more type Ⅲ-Ⅳ curve than controls (=5.177 and 5.301, both <0.05). Logistic regression analysis indicated that less sleep time of N3 stage was related to the abnormal results in smooth pursuit of 0.4-0.5 Hz (=0.963, <0.05). iRBD patients with Ⅲ-Ⅳ type curve in smooth pursuit of 0.4-0.5 Hz had less N3 sleep time than iRBD patients with Ⅰ-Ⅱ type curve (52±28 min vs. 76±23 min, =2.197, <0.05).@*CONCLUSIONS@#Abnormal smooth pursuit was found in iRBD patients, which might be related to the pathological mechanism of iRBD.

A Case of Rapid Eye Movement Sleep-Related Bradyarrhythmia Syndrome with Severe Obstructive Sleep Apnea Syndrome

A close relationship has emerged between obstructive sleep apnea (OSA) and cardiac arrhythmia. However, transient sinus arrest or atrioventricular (AV) conduction disturbance during rapid eye movement (REM) sleep was rarely reported. This sleep stage specific arrhythmia has been referred to as REM sleep-related bradyarrhythmia syndrome. The differential diagnosis between OSA-related arrhythmia and REM sleep-related bradyarrhythmia syndrome is important in determining the treatment strategy for the underlying disease and its complication, especially in patient with a history of OSA. Here, we report a case with both REM sleep-related AV block and severe OSA, whose REM sleep-related AV block was not improved with continuous positive airway pressure treatment.

Nonmotor and Dopamine Transporter Change in REM Sleep Behavior Disorder by Olfactory Impairment

OBJECTIVE: It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss. METHODS: This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson's disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei. RESULTS: Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8. CONCLUSION: There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.

Does Rapid Eye Movement Sleep Aggravate Obstructive Sleep Apnea?

OBJECTIVES.: To investigate the apnea-hypopnea index (AHI) according to the sleep stage in more detail after control of posture. METHODS.: Patients who underwent nocturnal polysomnography between December 2007 and July 2018 were retrospectively evaluated. Inclusion criteria were as follows: age >18 years, sleep efficacy >80%, and patients who underwent polysomnography only in the supine position (100% of the time). Patients were classified into different groups according to the methods: the first, rapid eye movement (REM)-dominant group (AHIREM/AHINREM >2), non-rapid eye movement (NREM)-dominant group (AHINREM/AHIREM >2), and non-dominant group; and the second, light sleep group (AHIN1N2>AHISWS) and slow wave sleep (SWS) group (AHISWS>AHIN1N2). RESULTS.: A total of 234 patients (mean age, 47.4±13.9 years) were included in the study. There were 108 patients (46.2%) in the REM-dominant group, 88 (37.6%) in the non-dominant group, and 38 (16.2%) in the NREM-dominant group. The AHI was significantly higher in the NREM-dominant group than in the REM-dominant group (32.9±22.9 events/hr vs. 18.3±9.5 events/hr, respectively). There were improvements in the AHI from stage 1 to SWS in NREM sleep with the highest level in REM sleep. A higher AHISWS than AHIN1N2 was found in 16 of 234 patients (6.8%); however, there were no significant predictors of these unexpected results except AHI. CONCLUSION.: Our results demonstrated the highest AHI during REM sleep stage in total participants after control of posture. However, there were 16.2% of patients showed NREM-dominant pattern (AHINREM/AHIREM >2) and 6.8% of patients showed higher AHISWS than AHIN1N2. Therefore, each group might have a different pathophysiology of obstructive sleep apnea (OSA), and we need to consider this point when we treat the patients with OSA.

Disrupted network topology in patients with idiopathic rapid eye movement sleep behavior disorder / 中华核医学与分子影像杂志

Objective@#To explore the topological abnormality of brain metabolic network in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and compare it with the topology of brain metabolic network in patients with Parkinson′s disease (PD).@*Methods@#The 18F-fluorodeoxyglucose (FDG) PET brain images of 19 patients with iRBD diagnosed with polysomnography (PSG) (iRBD group; 15 males, 4 females, average age: 64.9 years), 19 patients with PD (PD group; 12 males, 7 females, average age: 62.2 years) and 19 gender and age-matched healthy controls (HC group; 15 males, 4 females, average age: 63.1 years) in Huashan Hospital from September 2014 to June 2015 were retrospectively analyzed. According to the complex brain network method based on graph theory, the brain metabolic networks of each group was constructed and the network parameters (clustering coefficient, characteristic path length, local efficiency, global efficiency and small-world property, etc) were evaluated quantitatively. The 500 times non-parametric permutation test was used to determine the differences in network parameters between groups.@*Results@#The brain metabolic networks of iRBD group and PD group both had abnormal topological structure, which showed that the characteristic path length (for example, when sparsity=34%, HC vs iRBD vs PD groups: 1.517 vs 1.552 vs 1.561) and local efficiency (for example, when sparsity=30%, HC vs iRBD vs PD groups: 0.802 vs 0.824 vs 0.831) were significantly increased (both P<0.05), the global efficiency (for example, when sparsity=36%, HC vs iRBD vs PD groups: 0.672 vs 0.658 vs 0.656) was significantly decreased (P<0.05). The topology was more aggravated in PD group compared with that in iRBD group.@*Conclusion@#The graph-based complex brain network analysis can reveal the abnormal topological structure of the brain metabolic network in which iRBD progresses to PD.

Parkinson's disease and sleep disorders / 中国实用内科杂志

Sleep disorders are very common non-motor symptoms in Parkinson disease(PD) related to the life quality of patients, mainly including insomnia, arousal disorders, restless legs syndrome(RLS), REM sleep behavior disorder(RBD) and sleep disorders breathing(SDB). In this article, the author discusses the causes and the current state of the diagnosis and management of sleep disorders in PD, aiming to increase clinical doctors' attention to it.

Disrupted network topology in patients with idiopathic rapid eye movement sleep behavior disorder / 中华核医学与分子影像杂志

Objective To explore the topological abnormality of brain metabolic network in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and compare it with the topology of brain metabolic network in patients with Parkinson's disease (PD).Methods The 18F-fluorodeoxyglucose (FDG) PET brain images of 19 patients with iRBD diagnosed with polysomnography (PSG) (iRBD group;15 males,4 females,average age:64.9 years),19 patients with PD (PD group;12 males,7 females,average age:62.2 years) and 19 gender and age-matched healthy controls (HC group;15 males,4 females,average age:63.1 years) in Huashan Hospital from September 2014 to June 2015 were retrospectively analyzed.According to the complex brain network method based on graph theory,the brain metabolic networks of each group was constructed and the network parameters (clustering coefficient,characteristic path length,local efficiency,global efficiency and small-world property,etc) were evaluated quantitatively.The 500 times non-parametric permutation test was used to determine the differences in network parameters between groups.Results The brain metabolic networks of iRBD group and PD group both had abnormal topological structure,which showed that the characteristic path length (for example,when sparsity =34％,HC vs iRBD vs PD groups:1.517 vs 1.552 vs 1.561) and local efficiency (for example,when sparsity=30％,HC vs iRBD vs PD groups:0.802 vs 0.824 vs 0.831) were significantly increased (both P＜0.05),the global efficiency (for example,when sparsity =36％,HC vs iRBD vs PD groups:0.672 vs 0.658 vs 0.656) was significantly decreased (P＜0.05).The topology was more aggravated in PD group compared with that in iRBD group.Conclusion The graph-based complex brain network analysis can reveal the abnormal topological structure of the brain metabolic network in which iRBD progresses to PD.

Rapid Eye Movement Sleep Behavior Disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by sleep interruption or trauma due to abnormal behaviors that occur during REM sleep. The pathophysiology of RBD is known to be a dysfunction of brainstem circuit that causes the loss of skeletal muscle atonia during REM sleep. The diagnosis of RBD is needed to confirm REM sleep without atonia in the polysomnography. The management of RBD includes not only drug treatment, but also to prevent injury from RBD and to follow-up on neurodegenerative diseases that may occur later. RBD is thought to be a prodromal stage of neurodegenerative disease associated with α-synucleoinopathy, such as Parkinson's Disease or multiple system atrophy. This article reviews the symptoms, epidemiology, diagnosis and treatment of RBD, the relevance of neurodegenerative diseases, and recent research trends.

Linalool Ameliorates Memory Loss and Behavioral Impairment Induced by REM-Sleep Deprivation through the Serotonergic Pathway

Rapid eye movement (REM) sleep has an essential role in the process of learning and memory in the hippocampus. It has been reported that linalool, a major component of Lavandula angustifolia, has antioxidant, anti-inflammatory, and neuroprotective effects, along with other effects. However, the effect of linalool on the cognitive impairment and behavioral alterations that are induced by REM-sleep deprivation has not yet been elucidated. Several studies have reported that REM-sleep deprivation-induced memory deficits provide a well-known model of behavioral alterations. In the present study, we examined whether linalool elicited an anti-stress effect, reversing the behavioral alterations observed following REM-sleep deprivation in mice. Furthermore, we investigated the underlying mechanism of the effect of linalool. Spatial memory and learning memory were assessed through Y maze and passive avoidance tests, respectively, and the forced swimming test was used to evaluate anti-stress activity. The mechanisms through which linalool improves memory loss and behavioral alterations in sleep-deprived mice appeared to be through an increase in the serotonin levels. Linalool significantly ameliorated the spatial and learning memory deficits, and stress activity observed in sleep-deprived animals. Moreover, linalool led to serotonin release, and cortisol level reduction. Our findings suggest that linalool has beneficial effects on the memory loss and behavioral alterations induced by REM-sleep deprivation through the regulation of serotonin levels.