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.

Intelligence-aided diagnosis of Parkinson's disease with rapid eye movement sleep behavior disorder based on few-channel electroencephalogram and time-frequency deep network / 生物医学工程学杂志

Aiming at the limitations of clinical diagnosis of Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD), in order to improve the accuracy of diagnosis, an intelligent-aided diagnosis method based on few-channel electroencephalogram (EEG) and time-frequency deep network is proposed for PD with RBD. Firstly, in order to improve the speed of the operation and robustness of the algorithm, the 6-channel scalp EEG of each subject were segmented with the same time-window. Secondly, the model of time-frequency deep network was constructed and trained with time-window EEG data to obtain the segmentation-based classification result. Finally, the output of time-frequency deep network was postprocessed to obtain the subject-based diagnosis result. Polysomnography (PSG) of 60 patients, including 30 idiopathic PD and 30 PD with RBD, were collected by Nanjing Brain Hospital Affiliated to Nanjing Medical University and the doctor's detection results of PSG were taken as the gold standard in our study. The accuracy of the segmentation-based classification was 0.902 4 in the validation set. The accuracy of the subject-based classification was 0.933 3 in the test set. Compared with the RBD screening questionnaire (RBDSQ), the novel approach has clinical application value.

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.

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.

Fatigue correlates with sleep disturbances in Parkinson disease / 中华医学杂志(英文版)

BACKGROUND@#Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.@*METHODS@#Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.@*RESULTS@#Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.@*CONCLUSION@#Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.

Sleep-related symptoms in multiple system atrophy: determinants and impact on disease severity / 中华医学杂志(英文版)

BACKGROUND@#Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity.@*METHODS@#This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS).@*RESULTS@#The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA.@*CONCLUSIONS@#Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

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.

Transtornos do sono: atualização (parte2/2) / Sleep disorders: up to date (2/2)

Este artigo (2/2) compõe uma revisão sobre fundamentos do sono e transtornos do sono (TS), sendo aqui considerados: 1-Incapacidade de dormir na hora desejada-atraso de fase, avanço de fase, ''jet lag'', ritmo sono-vigília irregular, sono/vigília de livre curso, transtornos dos trabalhadores em turnos; 2-Movimentos ou comportamentos anormais durante o sono. Este segundo grupo é aqui subdividido em: A1-Parassonias relacionadas ao sono NREM (Non-rapid eye movement) ­ despertar confusional, sonambulismo, terror noturno, síndrome da cabeça explosiva, alucinações relacionadas ao sono, enurese noturna e parassonias causadas por doenças e medicações; A2-Parassonias relacionadas ao sono REM (rapid eye movement) - transtorno comportamental do sono REM, pesadelos, paralisias recorrentes isoladas do sono, promulgação sono ''dream enactment behavior"; B-Transtornos do movimento relacionados ao sono-bruxismo, síndrome das pernas inquietas, movimentos periódicos das pernas, câimbras do sono, movimentos rítmicos relacionados ao sono, mioclonias proprioespinhais do início do sono, movimentos relacionados à medicação, mioclonias em doenças sistêmicas e mioclonias benignas do sono em bebês.(AU)

This is the second part (2/2) of an article that intends to review major topics regarding sleep fundamentals and sleep disorders (SD), now considering: 1-Circadian rhythm disorders-delayed onset sleep phase disorder, advanced onset sleep phase disorder, jet lag, irregular sleep-wake rhythm, free-running type, shift work type; 2-Abnormal movements or behaviours during sleep. This second category is divided in two groups: A1-NREM (Non-rapid eye movement) parasomnias ­ confusional awakening, sleepwalking, night terrors, explosive head syndrome, sleep-related hallucinations, nocturnal enuresis and parasomnias related to diseases or medications; A2-REM (Rapid eye movement) parasomnias-REM sleep behaviour disorder, nightmares, recurrent isolated sleep paralysis, dream enactment behaviour; B-Sleep related movement disorders-bruxism, restless legs syndrome, periodical limb movement disorders, nocturnal leg cramps, sleep related rhythmic movement disorder, propriospinal myoclonus, movements related to medication use, myoclonus related to systemic diseases and benign myoclonus of sleep.(AU)

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.

Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson's Disease Patients / 中华医学杂志(英文版)

<p><b>Background</b>Rapid eye movement (REM) sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) are the most common sleep disorders in Parkinson's disease (PD). The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.</p><p><b>Methods</b>From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography (PSG). We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.</p><p><b>Results</b>We grouped participants as follows: PD only (n = 53), PD + OSA (n = 29), PD + RBD (n = 61), and PD + RBD + OSA (n = 31). Minimum oxygen saturation (SaO) during whole sleep and in REM sleep was higher in PD + RBD + OSA patients than that in PD + OSA patients. PD + RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) scores than those in the PD group (P < 0.001), especially in visuospatial/executive, attention, and memory functions. The PD + OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA (β = -0.736, P = 0.043) and RBD (β = -2.575,P < 0.001). The severity of RBD (tonic/phasic electromyography activity) and OSA (apnea-hypopnea index/oxygen desaturation index/minimum SaO) were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.</p><p><b>Conclusions</b>We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.</p>

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment / 中华医学杂志(英文版)

<p><b>Objective</b>Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions.</p><p><b>Data Sources</b>Using the combined keywords: "RBD", "neurodegenerative disease", "Parkinson disease", and "magnetic resonance imaging", the PubMed/MEDLINE literature search was conducted up to January 1, 2018.</p><p><b>Study Selection</b>A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full.</p><p><b>Results</b>Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings.</p><p><b>Conclusions</b>More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases.</p>

Decreased Nocturnal Blood Pressure Dipping in Patients with Periodic Limb Movements in Sleep / 수면정신생리

OBJECTIVES: Previous studies have shown that periodic limb movements in sleep (PLMS) could be one of risk factors for cardiovascular morbidity. The purpose of this study was to investigate the association between PLMS and blood pressure changes during sleep. METHODS: We analyzed data from 358 adults (176 men and 182 women) aged 18 years and older who were free from sleep apnea syndrome (Respiratory Disturbance Index 15)]. Blood pressure change patterns were compared using repeated measures analysis of variance. RESULTS: Systolic blood pressure in the high PLMI group was lower than that in the low PLMI group (p = 0.036). These results were also significant when adjusted for gender and age, but were not statistically significant when adjusted for BMI, alcohol, smoking, anti-hypertension medication use and sleep efficiency (p = 0.098). Systolic blood pressure dropped by 9.7 mm Hg in the low PLMI group, and systolic blood pressure in the high PLMI group dropped by 2.9 mm Hg. There was a significant difference in delta systolic blood pressure after sleep between the two groups in women when adjusted for age, BMI, alcohol, smoking, antihypertensive medication use and sleep efficiency (p = 0.023). CONCLUSION: PLMS was significantly associated with a decreasing pattern in nocturnal BP during sleep, and this association remained significant in women when adjusted for age, BMI, alcohol, smoking, antihypertension medication use and sleep efficiency related to blood pressure. We suggest that PLMS may be associated with cardiovascular morbidity.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Trastornos del sueño en niños y adolescentes con enfermedades neurológicas / Sleep disorders in children and adolescents with neurological diseases

Resumen Los trastornos del ciclo circadiano vigilia-sueño son primarios y secundarios. Los primarios o intrínsecos son menos frecuentes (31%) que los secundarios o extrínsecos pero más rápido diagnosticados y tratados (69%). Los primarios se deben a alteraciones intrínsecas anatómico y/o funcionales del ciclo circadiano sueño-vigilia. Su tratamiento está bien definido en caso de que exista. Los trastornos del sueño secundarios son alteraciones extrínsecas del sueño de origen adquirido cuyo diagnóstico de certeza es más clínico que polisomnográfico y su tratamiento dirigido a la condición asociada así como a la manifestación anormal onírica. Aunque las secundarias son más comunes que las primarias (69% contra 31%) se diagnostican y tratan menos que las primarias. Cuando no se diagnostican y tratan correctamente inducen problemas significativos emocionales, conductuales y cognoscitivos en niños y adolescentes comparados con aquellos sin tales sin trastornos del sueño. El propósito de esta revisión es que los pediatras generales, pediatras neurólogos y paidopsiquiatras tengan en mente la alta incidencia de los trastornos secundarios del sueño en niños con enfermedades neurológicas y que pregunten a los padres y pacientes sobre la calidad del sueño de sus hijos y realicen un diagnóstico y tratamiento precoz para evitar consecuencias en algunos casos fatales.

Abstract The disorders of the circadian cycle sleep-wake are primary and secondary. The primary or intrinsic are less frequent (31%) than the secondary or extrinsic but early diagnosed and treated (69%). The primary intrinsic alterations are due to anatomical and/or functional process circadian rhythm sleep-wake cycle. Its treatment is well defined in case it exists. The secondary sleep alterations are extrinsic and their diagnosis is more clinical than polysomnographic and its treatment directed to the associated condition as well as the manifestation abnormal sleep. Although the secondary are more common than the primary (69% vs. 31%) they are diagnosed and treated less than the primaries. When not properly diagnosed and treated induce significant problems with emotional, behavioral and cognitive changes in children and adolescents compared with those without sleep disorders. The purpose of this review is that the general pediatricians, pediatric neurologists and pediatric psychiatric bear in mind the high incidence of side effects of sleep disorders in children with neurological diseases and to ask parents and patients about the quality of sleep of their children and adolescents and make a diagnosis and early treatment to avoid fatal consequences in some cases.

Uso da actigrafia na avaliação do ritmo atividade-repouso em pacientes com doença de Parkinson / Use of actigraphy on assessment of activity-rest rhythm in patients with Parkinson's disease

Distúrbios do sono são os mais comuns sintomas não-motores encontrados na doença de Parkinson (DP). OBJETIVOS: Avaliar a relação entre actigrafia e distúrbios do sono mais incidentes na DP. MÉTODOS: Pacientes com e sem DP foram avaliados quanto aos sintomas motores, qualidade do sono, cronotipo e objetivamente através do uso do actímetro. RESULTADOS: Encontrou-se uma significante redução da qualidade do sono entre os pacientes com DP (p = 0.0023), uma pior qualidade subjetiva do sono, maior uso de medicamentos para insônia, mais distúrbios do sono e uma maior fragmentação do ritmo atividade-repouso (IV) (p=0.0271). CONCLUSÃO: Pacientes com DP possuem uma pior qualidade de sono e um ritmo atividade-repouso mais fragmentado. A actigrafia pode ser útil na avaliação da qualidade do sono e do ciclo atividade repouso em pacientes com DP, contribuindo para o rastreio e acompanhamento de eventuais distúrbios do ritmo circadiano a esta doença associados. (AU)

Sleep disorders are the most common non-motor symptom found in Parkinson's Disease (PD). OBJECTIVES: To evaluate the relationship between actigraphy and more incidents sleep disorders in PD. METHODS: Patients with and without PD were assessed regarding motor symptoms, sleep quality, chronotype and objectively through the use of an actimeter. RESULTS: It was found a significant reduction of sleep quality among the patients with PD (p = 0.0023), a worse subjective sleep quality, they used more medications to sleep, they had more sleep disorders and a significantly higher fragmentation of pace (IV) (p = 0.0271). CONCLUSION: Patients with PD have a worse sleep quality and a rest-activity rythm fragmented. Actigraphy can be useful for assessing the quality of sleep and activity/rest cycle in patients with PD, contributing to the screening and follow-up of any circadian rhythm disorders associated to this disease. (AU)

The Changes in Polysomnographic Sleep Variables by Periodic Limb Movements During Sleep / 수면정신생리

OBJECTIVES: Periodic limb movement disorder (PLMD) has been debated with regard to its clinical significance and diagnostic criteria. The current diagnostic criterion for PLMD in adults has been changed from periodic limb movement index (PLMI) > 5/ hour to PLMI > 15/hour by the International Classification of Sleep Disorders (ICSD). In this study, we aimed to investigate the changes in polysomnographic sleep variables according to PLMI and to determine the relevance of the diagnostic criterion for PLMD. METHODS: Out of 4195 subjects who underwent standard polysomnography, we selected 666 subjects (370 males and 296 females, aged 47.1 ± 14.8) who were older than 17 years and were not diagnosed with primary insomnia, sleep apnea, narcolepsy, or REM sleep behavior disorder. Subjects were divided into three groups according to PLMI severity: group 1 (PLMI ≤ 5), group 2 (5 15). Demographic and polysomnographic sleep variables and Epworth sleepiness scale (ESS) were compared among the three groups. RESULTS: There were significant differences among the three groups in age and gender. Sleep efficiency (SE) and stage 3 sleep percentage in group 1 were significantly higher than those in groups 2 and 3. The wake after sleep onset (WASO) score in group 1 was significantly lower than those in groups 2 and 3. However, there were no significant differences in SE, stage 3 sleep percentage, or WASO between groups 2 and 3. Sleep latency (SL) in group 1 was significantly lower than that in group 3, but there was no difference in SL between group 2 and group 3. ESS score in group 1 was significantly higher than that in group 3, but there was no difference between group 2 and group 3. Partial correlation analysis adjusted by age showed that PLMI was significantly related to SE and WASO. CONCLUSION: This study suggests that PLMI influences polysomnographic sleep variables. In addition, we found the individuals who did not have PLMD but had PLMI > 5 were not different in polysomnographic sleep variables from the individuals who had PLMD according to the current criterion. These results raise questions about the relevance of the current diagnostic criterion of PLMD.

Dream Recall Frequency and Sleep in Patients with Rapid Eye Movement Sleep Behavior Disorder

OBJECTIVES: The dream recall and sleep of patients with rapid eye movement sleep behavior disorder (RBD) were not sufficiently studied. We hypothesized that RBD patients have frequent dream recall with poor sleep quality, and investigated the relationship between the dream recall frequency and sleep quality in RBD patients compared to controls. METHODS: We analyzed 81 drug naïve patients [RBD (+), 64.6±8.3 y, 57 males] and 81 age and gender matched patients with sleep disturbances without RBD [RBD (−), 63.7±7.3 y, 57 males]. All completed Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), Epworth sleepiness scale and Beck depression inventory. The 5-point rating scale was used to categorize dream recall frequency of most recent month (0=never, 4=very frequent). RESULTS: In RBD (+), dream recall frequency was much higher [frequent dreaming, 77.2% vs. 35.4%], and subjective sleep quality was much better [PSQI, 6.36±3.26 vs. 8.71±4.69]. Insomnia severity was much less in RBD (+) (ISI, 9.13±5.86) than RBD (−) (12.43±7.62). No significant differences were found in sleep parameters except lower N2 sleep % in RBD (+). The relationship between dream recall frequency and sleep was not significant in RBD (+), yet, a positive correlation was noted in RBD (−). CONCLUSIONS: RBD (+) had better sleep quality despite higher frequency of dream recall compared to RBD (−). Also dream recall was not related to their sleep quality in RBD (+), which suggests that RBD patients may have different sleep perception about their sleep and sleep quality.

A Case of Rapid Eye Movement Sleep Behavior Disorder during Continuous Positive Airway Pressure Titration in a Patient with Multiple System Atrophy

Sleep disorders are commonly observed in multiple systemic atrophy (MSA). The rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of normal voluntary muscle atonia during REM sleep. It usually presents during early course, and disappears over the course of disease progression. Sleep-disordered breathing (SDB) is also common sleep disorder in MSA which can be life-threatening, and continuous positive airway pressure (CPAP) treatment is useful in these patients. A 74-year-old woman with MSA presented for nocturnal respiratory disturbance. She had a five-year history of dream enacting behaviors, which had disappeared four months prior. Polysomnography revealed frequent stridor and sleep hypopnea. During the following full nigh CPAP titration for SDB, dream enacting behavior was observed during REM sleep stage. In MSA patients with SDB, CPAP administration may lead to increase REM sleep stage. An increase in REM sleep stage, which previously had been deprived, may have trigger RBD symptoms to reappear. The CPAP treatment should be considered with great caution in these patients.

Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD.</p><p><b>METHODS</b>The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.</p><p><b>RESULTS</b>Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure (copy) results.</p><p><b>CONCLUSIONS</b>When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.</p>