Melatonin as a Chronobiotic/Cytoprotective Agent in REM Sleep Behavior Disorder.

Dream-enactment behavior that emerges during episodes of rapid eye movement (REM) sleep without muscle atonia is a parasomnia known as REM sleep behavior disorder (RBD). RBD constitutes a prodromal marker of α-synucleinopathies and serves as one of the best biomarkers available to predict diseases such as Parkinson disease, multiple system atrophy and dementia with Lewy bodies. Most patients showing RBD will convert to an α-synucleinopathy about 10 years after diagnosis. The diagnostic advantage of RBD relies on the prolonged prodromal time, its predictive power and the absence of disease-related treatments that could act as confounders. Therefore, patients with RBD are candidates for neuroprotection trials that delay or prevent conversion to a pathology with abnormal α-synuclein metabolism. The administration of melatonin in doses exhibiting a chronobiotic/hypnotic effect (less than 10 mg daily) is commonly used as a first line treatment (together with clonazepam) of RBD. At a higher dose, melatonin may also be an effective cytoprotector to halt α-synucleinopathy progression. However, allometric conversion doses derived from animal studies (in the 100 mg/day range) are rarely employed clinically regardless of the demonstrated absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers. This review discusses the application of melatonin in RBD: (a) as a symptomatic treatment in RBD; (b) as a possible disease-modifying treatment in α-synucleinopathies. To what degree melatonin has therapeutic efficacy in the prevention of α-synucleinopathies awaits further investigation, in particular multicenter double-blind trials.

Dysfunction of the cardiac parasympathetic system in fatal familial insomnia: a heart rate variability study.

STUDY OBJECTIVES: Although sympathetic hyperactivity with preserved parasympathetic activity has been extensively recognized in fatal familial insomnia (FFI), the symptoms of parasympathetic nervous system failure observed in some patients are difficult to explain. Using heart rate variability (HRV), this study aimed to discover evidence of parasympathetic dysfunction in patients with FFI and the difference of parasympathetic activity between patients with FFI and Creutzfeldt-Jakob disease (CJD). METHODS: This study enrolled nine patients with FFI, eight patients with CJD and 18 healthy controls (HCs) from May 2013 to August 2020. All participants underwent a nocturnal video-polysomnography with lead II electrocardiography, and the data were analyzed using linear and nonlinear indices of HRV during both wake and sleep states. RESULTS: Compared to the HC and CJD groups, the FFI group had a continuously higher heart rate with a lower amplitude of oscillations. The low frequency (LF)/high frequency (HF) ratio and ratio of SD1 to SD2 and correlation dimension D2 (CD2) were significantly different in the FFI group compared to the HC group. The root mean square of successive differences (RMSSD), HF and SD1 in the FFI group were significantly lower than in the HC group. RMSSD, SD1, and CD2 in the FFI group were all significantly lower than in the CJD group. CONCLUSIONS: Cardiovascular dysautonomia in FFI may be partly attributable to parasympathetic abnormalities, not just sympathetic activation. HRV may be helpful as a noninvasive, quantitative, and effective autonomic function test for FFI diagnosis.

Analysis of Sleep Quality, Mood Alterations and modifications of some Habits/Behavior during two different Periods of the COVID-19 Pandemic in Argentina / Análisis de la calidad del sueño, alteraciones del humor y modificaciones de algunos hábitos y conductas durante dos diferentes períodos de la pandemia por COVID-19 en Argentina.

The pandemic caused by COVID-19 in the world, in its different periods, produced many changes in sleep and in various areas of mental health. Objectives: To evaluate and to compare sleep quality and aspects of mental health during two different periods of the COVID-19 pandemic, as well as to analyze some changes in habits/behaviors. Subjects and methods: A cross-sectional study was carried out, through an anonymous survey. Demographic information, sleep quality, depressive and anxiety symptoms were analyzed. Of the total, 998 surveys were selected. The survey focused on 2 time periods, from March to July 2020 and from March to July 2021. Results: When sleep quality was compared during the 2020 versus 2021 periods, the percentage of poor sleepers went from 51% to 59% in the second period. Regarding depressive symptoms, it went from 21.1 to 16.3% and the percentage of anxiety symptoms went from 59.5 to 47.6%. Poor sleep quality affected more people in 2021 compared to 2020. The percentage of participants with symptoms of anxiety and depression decreased in 2021. People changed some habits/behaviors, such as: changing routine schedules, acquiring pets, sharing their dreams more, and remembering them more frequently. This article contributes to knowing various aspects of sleep, mood swings and changes in habits/behaviors that occurred during the pandemic in Argentina.

La pandemia provocada por COVID-19 en el mundo, en sus diferentes períodos, produjo muchos cambios en el sueño y en diversas áreas de la salud mental. Objetivos: Evaluar y comparar calidad de sueño y aspectos de la salud mental durante dos períodos diferentes de la pandemia por COVID-19, como así también analizar algunos cambios en hábitos/conductas. Materiales y métodos: Se realizó un estudio de corte transversal, a través de una encuesta anónima de la que participaron 998 personas. La misma se realizó en dos períodos de tiempo. El primer período comprendió de marzo a julio de 2020, el segundo período abarcó de marzo a julio 2021. El análisis consideró: información demográfica, calidad del sueño, síntomas depresivos y de ansiedad. Resultados: Al comparar la calidad de sueño durante los períodos 2020 versus el 2021, el porcentaje de malos dormidores pasó del el 51% al 59% en el segundo período. En cuanto a los síntomas depresivos pasó del 21,1 al 16,3% y el porcentaje de síntomas de ansiedad pasó del 59,5 al 47,6%. La mala calidad del sueño afectó a un número mayor de personas en el 2021 que en el 2020 mientras que el porcentaje de participantes con síntomas de ansiedad y de depresión disminuyó en el año 2021. En la segunda fase de la encuesta las personas modificaron algunos hábitos/conductas como ser: cambiaron horarios de rutina, adquirieron mascotas, compartieron más sus sueños y recordaban con mayor frecuencia los mismos. Este artículo contribuye a conocer diversos aspectos del sueño, los cambios de humor y modificaciones de hábitos/conductas que ocurrieron durante la pandemia en Argentina.

Proposal of new diagnostic criteria for fatal familial insomnia.

BACKGROUND: The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio. METHODS: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with two-round expert consultation: (1) Validation of the 2018 FFI criteria. (2) Diagnostic item selection according to statistical analysis and expert consensus. (3) Validation of the new criteria. RESULTS: The 2018 criteria for possible FFI had a sensitivity of 90.6%, a specificity of 83.3%, with a positive likelihood ratio (PLR) of 5.43, and a negative likelihood ratio (NLR) of 0.11; and the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, with a PLR of 11.77, and a NLR of 0.18. The new criteria included more specific and/or common clinical features, two exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had therefore reached a better sensitivity and specificity (92.2% and 96.1%, respectively), a PLR of 23.64 and a NLR of 0.08, whereas the probable FFI criteria showed a sensitivity of 90.6%, a specificity of 98.2%, with a PLR of 50.33 and a NLR of 0.095. CONCLUSIONS: We propose new clinical diagnostic criteria for FFI, for a better refining of the clinical hallmarks of the disease that ultimately would help an early recognition of FFI and a better differentiation from other prion diseases.

Early impact on sleep and mental health during the mandatory social isolation of COVID-19 outbreak: an obser vational cross-sectional study carried out in Argentina.

Introduction: The mandatory social isolation (MSI) due to the pandemic caused by COVID-19 in the world produced many changes in sleep and different areas of mental health. Objectives: To evaluate the early effects of MSI on sleep, anxiety, and depression in Argentina. Material and Methods: An anonymous observational cross-sectional web-based study was distributed throughout the country and was completed by 2,594 respondents to analyze demographic information, quality of sleep, REM sleep-related events, depressive, and anxiety symptoms. Results: The study revealed that 53, 21, 22, 23, and 16% of people surveyed were poor sleepers, had dream-related behaviors, nightmares, depression, and anxiety symptoms, respectively. Multivariate logistic regression showed a positive correlation between anxiety, being a poor sleeper, and having nightmares. Conclusion: We identified the early effects of MSI on sleep quality, dreaming activity, anxiety, and depression in Argentina during the COVID-19 outbreak. Our findings can be used to formulate sleep and psychological interventions to improve mental health during the pandemic and post-pandemic times.

[Sleep quality, depressive symptoms and generalized anxiety disorders during confinement by COVID-19]. / Calidad de sueño, síntomas depresivos y de ansiedad durante el confinamiento por COVID-19 en Argentina.

The confinement due to the pandemic caused by COVID-19 in Argentina produced many changes. OBJECTIVE: To assess sleep, anxiety disorders, and depression in adults. SUBJECTS AND METHODS: Through an anonymous survey distributed in the country through the web that was completed by 2,594 people (69% women, 32% men). 30% reported working in the health field. Demographic information, quality and other sleep variables, depressive symptoms and anxiety were analyzed. RESULTS: The general prevalence of bad sleepers, depressive symptoms, and anxiety were 53%, 21.1%, and 43.8%, respectively. Those over 65 years of age showed a significantly higher prevalence of going to bed earlier and having a lower sleep onset latency. Multivariate logistic regression showed that age <55 years and being a woman were associated with anxiety and with being a poor sleeper. Sleeping more than 10 hours, going to bed later, being a poor sleeper and anxiety, were associated with depressive symptoms. Being a healthcare worker was associated with more anxiety. CONCLUSIONS: We identified poor sleep quality and alteration mental health in times of confinement. We found that more than half of the evaluated population turned out to be poor sleepers and presented high scores of symptoms related to anxiety and depression. Additionally, health workers presented more anxiety than the rest.

The "respiratory REM sleep without atonia benefit" on coexisting REM sleep behavior disorder - obstructive sleep apnea.

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. In patients with RBD, obstructive sleep apneas syndrome (OSAS) frequently occurs as a comorbid entity. It has been reported that the presence of muscle tone during REM sleep (REM sleep without atonia-RSWA) could play a protective role in patients with OSAS RBD. In OSAS, recurrent episodes of complete or partial collapse of the upper airway occur during both, NREM and REM sleep. Particularly during sleep, the withdrawal of excitatory noradrenergic and serotoninergic inputs to the upper airway motor neurons deeply reduces the pharyngeal muscle activity, increasing the propensity for superior airway collapse. The present study compared for the first time the impact of OSAS in RBD patients with a subtype of OSAS patients with predominantly or isolated REM sleep-related OSAS (OSAS REM group) in the search of an adequate model to evaluate future therapeutic strategies. Our study found a significant lower nadir of oximetry values in OSAS RBD in comparison with the OSAS REM group. This reduction, that we called the "respiratory RSWA benefit", is in accordance with the decrease of the nadir oximetry values observed in patients with Parkinson disease and OSAS with or without RBD. We suggest that the group of OSAS REM patients is a natural model to evaluate the respiratory protective role of RSWA in patients with coexisting RBD-OSAS and Parkinson's disease.

The endless quarantine: the impact of the COVID-19 outbreak on healthcare workers after three months of mandatory social isolation in Argentina.

OBJECTIVES: At the end of 2019 the SARS-CoV-2 outbreak spread around the globe with a late arrival to South America. The objective of this study was to evaluate the impact of the long period of mandatory social isolation that took place in Argentina on the general psychological well-being of healthcare workers due to the COVID-19 pandemic. METHODS: A survey was conducted during June 2020, in healthcare workers. Pittsburgh Sleep Quality Index, Insomnia Severity Index, Sleepiness-Wakefulness Inability and Fatigue Test, and Goldberg depression and anxiety scale, were used to analyze the effects of the SARS-Cov 2 outbreak after three months of mandatory social isolation. Analyses were performed by logistic regression and a clustering algorithm in order to classify subjects in the function of their outcome's severity. RESULTS: From 1059 surveys, the majority reported symptoms of depression (81.0%), anxiety (76.5%), poor sleep quality (84.7%), and insomnia (73.7%) with 58.9% suffering from nightmares. Logistic regression showed that being in contact with COVID-19 patients, age, gender and the consumption of sleep medication during the mandatory social isolation were relevant predictors for insomnia, anxiety, and depression. Clustering analysis classified healthcare workers in three groups with healthy/mild, moderate, and severe outcomes. The most vulnerable group was composed mainly of younger people, female, non-medical staff, or physicians in training. CONCLUSION: An extremely high proportion of Argentinian healthcare workers suffered from sleep problems, anxiety, and depression symptoms. The clustering algorithm successfully separates vulnerable from non-vulnerable populations suggesting the need to carry out future studies involving resilience and vulnerability factors.

[Kleine Levin syndrome: Review of diagnosed cases of Buenos Aires, Argentina]. / Síndrome de Kleine Levin: reporte de casos de Buenos Aires, Argentina.

Kleine-Levin syndrome is an uncommon disorder with recurrent episodes of hypersomnia, and behavioral abnormalities such as binge-eating and hypersexuality. Our aims were to report cases of the Kleine-Levin syndrome diagnosed in Buenos Aires, Argentina and to characterize the clinical presentation of these patients. We evaluated patients with Kleine-Levin syndrome according to the International Classification of Sleep Disorders. Psychiatric, physical and neurological symptoms were present. Some patients were investigated with brain Magnetic Resonance Imaging, Single Photon Emission Computed Tomography, electroencephalogram and some with polysomnography. Seven patients (2 female, 5 male), ages from 8 to 47 years (median 20.7 years) were included in the study. The duration of symptoms was 1.5-20 days with a mean of 8. The range of interval between episodes: 2.5-24 months, median=13. All seven patients had a history of hypersomnia (one of them post head injury); 5 reported hyperphagia and 2 reduced appetite. Brain MRI was performed in 6 patients: 1 showed non-specific abnormalities and another presented diencephalic hematoma; the rest were normal. Our paper is the first one in Buenos Aires reporting Kleine-Levin syndrome of different ethiologies. The prevalence is difficult to estimate in our country.

Comparison of frequency bands using spectral entropy for epileptic seizure prediction.

Introduction. Under the hypothesis that the uncontrolled neuronal synchronization propagates recruiting more and more neurons, the aim is to detect its onset as early as possible by signal analysis. This synchronization is not noticeable just by looking at the EEG, so mathematical tools are needed for its identification. Objective. The aim of this study is to compare the results of spectral entropies calculated in different frequency bands of the EEG signals to decide which band may be a better tool to predict an epileptic seizure. Materials and Methods. Invasive ictal records were used. We measured the Fourier spectrum entropy of the electroencephalographic signals 4 to 32 minutes before the attack in low, medium and high frequencies. Results. The high-frequency band shows a markedly rate of increase of the entropy, with positive slopes and low correlation coefficient. The entropy rate of growth in the low-frequency band is practically zero, with a correlation around 0.2 and mostly positive slopes. The mid-frequency band showed both positive and negative slopes with low correlation. Conclusions. The entropy in the high frequencies could be predictor, because it shows changes in the previous moments of the attack. Its main problem is the variability, which makes it difficult to set the threshold that ensures an adequate prediction.