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BACKGROUND AND PURPOSE: Isolated rapid eye movement sleep behaviour disorder (iRBD) is a parasomnia, recently recognized as a risk factor for progression to Parkinson's disease, dementia with Lewy body and multiple system atrophy. Biomarker studies in iRBD are relevant due to lack of evidence in this condition. The identification of biomarkers able to predict progression to synucleinopathy diseases is critical for iRBD. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging might provide information about ongoing neurodegenerative processes. In the present study, we tested for presence of brain hypometabolism patterns as biomarkers of neurodegeneration in single iRBD individuals. METHODS: We recruited 37 subjects with polysomnography-confirmed iRBD, with neuropsychological assessment and available FDG-PET scan. Images were analysed with a validated statistical parametric mapping procedure, providing individual hypometabolism maps. RESULTS: According to the neuropsychological evaluation, 22 subjects with iRBD had normal cognition and 15 subjects showed impairments, particularly in visuoperceptive/visuospatial and memory domains. One-fifth of the cases were impaired on the Qualitative Scoring of Pentagon Test. In 32 iRBD cases, FDG-PET statistical parametric maps revealed significant cerebral hypometabolism, namely in the occipital lobes (n = 5), occipital and cerebellar regions (n = 13), occipitoparietal regions (n = 13) and a selective cerebellar hypometabolism (n = 1). Five cases had normal FDG-PET scans. CONCLUSIONS: These imaging findings indicate that brain neurodegenerative processes are present and already detectable in iRBD. The different hypometabolism patterns in the single individuals may reflect specific early pathophysiological events due to the underlying synucleinopathy, with a specific neural vulnerability for the occipital cortex that might pre-date a risk of progression towards dementia with Lewy body.
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Transtorno do Comportamento do Sono REM , Encéfalo , Fluordesoxiglucose F18 , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Transtorno do Comportamento do Sono REM/diagnóstico por imagemRESUMO
BACKGROUND: Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. AIM: Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy. MATERIALS AND METHODS: Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice. RESULTS: Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce. DISCUSSION/CONCLUSION: Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.
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Síndrome das Pernas Inquietas , Apneia Obstrutiva do Sono , Acidente Vascular Cerebral , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Pessoa de Meia-Idade , Prevalência , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
Insomnia is a frequent symptom in depressed patients. It can present with difficulty in initiating and/or maintaining sleep. We retrospectively evaluated a group of 15 patients affected by major depressive disorder and complaining of insomnia, who started vortioxetine (VOR) treatment for their depressive symptoms. The following questionnaires were captured at baseline and follow-up: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Beck Depression Inventory. Pittsburgh Sleep Quality Index total score significantly decreased between follow-up and baseline (P < 0.01), and in several subitems related to sleep quality and continuity. Moreover, Epworth Sleepiness Scale decreased between follow-up and baseline (P < 0.01). Finally, Beck Depression Inventory reduction was also evident between follow-up and baseline (P < 0.01). This retrospective analysis showing the significant effect of VOR on both depressive symptoms and insomnia in patients showing comorbid major depressive disorder and insomnia invites further research in order to confirm this preliminary evidence. We hypothesize that the VOR mechanism of action may explain the improvement of subjective sleep, other than depressive symptoms.
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Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Sono/efeitos dos fármacos , Vortioxetina/farmacologia , Adulto , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/etiologia , Inquéritos e Questionários/estatística & dados numéricos , Vortioxetina/uso terapêuticoRESUMO
OBJECTIVE: Narcolepsy is a lifelong disease, manifesting with excessive daytime sleepiness and cataplexy, arising between childhood and young adulthood. The diagnosis is typically made after a long delay that burdens the disease severity. The aim of the project, promoted by the "Associazione Italiana Narcolettici e Ipersonni" is to develop Red Flags to detect symptoms for early referral, targeting non-sleep medicine specialists, general practitioners, and pediatricians. MATERIALS AND METHODS: A multidisciplinary panel, including patients, public institutions, and representatives of national scientific societies of specialties possibly involved in the diagnostic process of suspected narcolepsy, was convened. The project was accomplished in three phases. Phase 1: Sleep experts shaped clinical pictures of narcolepsy in pediatric and adult patients. On the basis of these pictures, Red Flags were drafted. Phase 2: Representatives of the scientific societies and patients filled in a form to identify barriers to the diagnosis of narcolepsy. Phase 3: The panel produced suggestions for the implementation of Red Flags. RESULTS: Red Flags were produced representing three clinical pictures of narcolepsy in pediatric patients ((1) usual sleep symptoms, (2) unusual sleep symptoms, (3) endocrinological signs) and two in adult patients ((1) usual sleep symptoms, (2) unusual sleep symptoms). Inadequate knowledge of symptoms at onset by medical doctors turned out to be the main reported barrier to diagnosis. CONCLUSIONS: This report will hopefully enhance knowledge and awareness of narcolepsy among non-specialists in sleep medicine in order to reduce the diagnostic delay that burdens patients in Italy. Similar initiatives could be promoted across Europe.
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Comunicação Interdisciplinar , Narcolepsia/diagnóstico , Narcolepsia/epidemiologia , Encaminhamento e Consulta/normas , Adulto , Fatores Etários , Criança , Diagnóstico Tardio/estatística & dados numéricos , Diagnóstico Diferencial , Humanos , Itália , Narcolepsia/fisiopatologia , MédicosRESUMO
In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.
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Pesquisa Biomédica/tendências , Neurologia/tendências , Psiquiatria/tendências , Transtornos do Sono-Vigília/fisiopatologia , Sono/fisiologia , HumanosRESUMO
Rapid eye movement (REM) sleep behavior disorder (RBD) can occur in the absence of any other obvious associated neurologic disorder or in association with a neurodegenerative disease, in which case it is considered as symptomatic RBD. RBD is frequently associated with Parkinson's disease (PD), Lewy body dementia or multiple system atrophy (MSA), and in several cases may even antedate the occurrence of motor symptoms by decades. When no neurologic disorder is obvious, RBD can be considered as idiopathic (iRBD). Several studies have looked at neurophysiologic and neuropsychological functions in iRBD and have found evidence of CNS dysfunction during both wakefulness and sleep in a variable proportion of these patients, challenging the concept of iRBD. Identifying subjects with a high risk of developing a neurodegenerative process may be crucial in order to develop early intervention strategies. Some prospective results in iRBD showed that potential markers of neurodegeneration are the following: 1) marked EEG slowing on spectral analysis; 2) decreased striatal 123I-FPCIT; 3) impaired color vision.
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Encéfalo/fisiopatologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Encéfalo/diagnóstico por imagem , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico , Transtornos Parkinsonianos/diagnóstico , Transtorno do Comportamento do Sono REM/diagnóstico , Cintilografia , SensaçãoRESUMO
Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.
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Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , ObservaçãoRESUMO
Sleep bruxism (SB) is a sleep-related movement disorder, characterized by tooth grinding and/or clenching. The causes of SB range from psychosocial factors to an excessive sleep arousal response. Some studies showed that SB episodes during sleep are under the influences of transient activity of the brainstem arousal. Nocturnal groaning (NG) is a parasomnia characterized by an expiratory monotonous vocalization occurring during sleep, especially in REM sleep and during the second half of the night. The pathogenesis of NG remains still unclear and many hypotheses arose, ranging from the persistence of a vestigial ventilatory pattern rather than an expiratory upper airways' obstruction. Sleep microstructure fluctuation might modulate the NG, since the end of the NG episode usually is synchronized with a cortical arousal and an autonomic activation. Further studies should clarify the pathophysiology of SB and NG, especially when the two phenomena are associated.
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Fonação , Bruxismo do Sono/fisiopatologia , Sono REM/fisiologia , Catatonia/complicações , Humanos , Bruxismo do Sono/diagnóstico , Bruxismo do Sono/epidemiologia , Comportamento EstereotipadoRESUMO
OBJECTIVE/METHODS: Phosphorylated alpha-synuclein (p-syn) in dermal nerves of patients with isolated REM sleep behavior disorder (iRBD) is detectable by immunofluorescence-labeling. Skin-biopsy-p-syn-positivity was recently postulated to be a prodromal marker of Parkinson's disease (PD) or related synucleinopathies. Here, we provide two-to four-year clinical and skin biopsy follow-up data of 33 iRBD patients, whose skin biopsy findings at baseline were reported in 2017. RESULTS: Follow-up biopsies were available from 25 patients (18 positive at baseline) and showed consistent findings over time in 24 patients. One patient converted from skin-biopsy-negativity to -positivity. P-syn-positivity was observed in iRBD patients who still had a normal FP-CIT-SPECT two years later. Clinically, five of the 23 at baseline skin-biopsy-positive patients (21.7%) had converted to PD or dementia with Lewy bodies at follow-up, but none of the skin-biopsy-negative patients. CONCLUSIONS: Dermal p-syn in iRBD is most probably an early consistent marker of synucleinopathy and may support other indicators of conversion to manifest disease state.
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Nervos Periféricos/patologia , Sintomas Prodrômicos , Transtorno do Comportamento do Sono REM/patologia , Pele/patologia , alfa-Sinucleína/metabolismo , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Doença por Corpos de Lewy/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologiaRESUMO
BACKGROUND: Sleep complaints are common health issues in the general population. These conditions are associated with poorer physical and psychological activity, and they may have important social, economic, and personal consequences. In the last years, several food supplements with different plant extracts have been developed and are currently taken for improving sleep. Study Objectives. The aim of this study is to systematically review recent literature on oral plant extracts acting on sleep disorders distinguishing their action on the different symptoms of sleep complaints: difficulty in initiating or maintaining sleep, waking up too early, and quality of sleep. METHODS: We searched the PubMed database up to 05/03/2020 based on data from randomized, double-blind, placebo-controlled trials, noncontrolled trials, and cohort studies conducted in children and adult subjects. The search words used contained the following terms: oral food supplement and sleep disorders and the like. The most studied compounds were further analyzed with a second search using the following terms: name of the compound and sleep disorders. We selected 7 emerging compounds and 38 relevant reports. RESULTS: Although nutraceutical natural products have been used for sleep empirically, there is a scarcity of evidence on the efficacy of each product in clinical studies. Valerian and lavender were the most frequently studied plant extracts, and their use has been associated (with conflicting results) with anxiolytic effects and improvements in quality and duration of sleep. CONCLUSIONS: Sleep aids based on plant extracts are generally safe and well tolerated by the population. More high-quality research is needed to confirm the effectiveness of food supplements containing plant extracts in sleep complaints; in particular, it would be interesting to evaluate the association between plant extracts and sleep hygiene guidelines and to identify the optimal products to be used in a specific symptom of sleep complaint, giving more appropriate tools to the medical doctor.
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Sleep disordered breathing (SDB) is a prevalent, important nontraditional cardiovascular (CV) risk factor in end-stage renal disease patients. The prevalence of SDB in renal transplant patients is unknown. We compared polysomnographic studies in 163 transplant patients with matched samples in the general population and explored longitudinally the effect of return to dialysis after graft failure on SDB in three consecutive cases. Episodes of nocturnal hypoxemia, average and minimal O(2) saturation overnight in transplant patients did not differ from those in individuals in the general population matched for age, gender and body mass index (BMI). The prevalence of moderate-to-severe SBD in these patients did not exceed the estimated prevalence of the same disturbance in the general population. The respiratory disturbance index in transplant patients was directly associated with BMI (p < 0.001). In the longitudinal study all indicators of SDB coherently increased after transplant failure. The prevalence of SDB in transplant patients does not differ from that in well-matched individuals in the general population. The favorable effect of renal transplantation on CV risk may be at least partially explained by the lack of risk excess for SDB in this population. Longitudinal observations after transplant failure are compatible with the hypothesis that renal transplantation reverses SDB.
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Síndromes da Apneia do Sono/terapia , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Feminino , Rejeição de Enxerto , Humanos , Falência Renal Crônica/complicações , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Oximetria , Polissonografia , Análise de Regressão , Diálise Renal , Fatores de Risco , Síndromes da Apneia do Sono/etiologiaRESUMO
Sleep-related disorders have been reported to have a higher prevalence in multiple sclerosis (MS) than in the general population. They are often undervalued for the presence of more severe physical problems and the occurrence at night, without a direct observation in common clinical practice, but if not recognized and treated they can negatively affect the quality of life causing daytime drowsiness and worsening fatigue. Sleep related disorders most commonly reported in MS are as follows: insomnia, sleep-related breathing disorders (SRBD), restless legs syndrome (RLS) and periodic limb movement disorders (PLMD). Secondary narcolepsy, REM sleep behavior disorder (RBD) and propriospinal myoclonus have been also described in some case reports or series. The purpose of this review is to correlate the more common sleep disturbances in MS patients to the involvement of specific brain regions, analyzing their relationship with MRI findings. While insomnia is usually secondary to other disabling symptoms such as nocturia or pain, SRBD, RLS, narcolepsy, RBD and propriospinal myoclonus in MS patients can be the consequence of an injury of specific central nervous system (CNS) areas. Lesions in the pontine tegmentum and the dorsal medulla have been associated with SRBD, spinal cord lesions or atrophy with RLS, bilateral lesions in the lateral hypothalamus with narcolepsy-like symptoms, lesions in the dorsal pontine tegmentum with RBD and intramedullary demyelinating plaques in spinal cord with propriospinal myoclonus. MS specialists and general neurologists should be aware of these comorbidities since neuroimaging, which is routinely performed in MS, could provide helpful clinical indications on patients with secondary sleep-related disorders and to categorize symptomatic patients who need to underdo more in-depth sleep studies.
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Tronco Encefálico/patologia , Comorbidade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/patologia , Síndromes da Apneia do Sono/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Medula Espinal/patologia , Tronco Encefálico/diagnóstico por imagem , Humanos , Esclerose Múltipla/diagnóstico por imagem , Transtornos do Sono-Vigília/patologia , Medula Espinal/diagnóstico por imagemRESUMO
Periodic leg movements during sleep (PLMS) are repetitive jerks of the lower limbs. Their occurrence can be isolated or part of various sleep disorders, such as restless legs syndrome (RLS), narcolepsy and obstructive sleep apnoea. Dopamine agonists are very effective in suppressing PLMS in RLS from the first night of administration. PLMS are often associated with cortical and autonomic arousals and may contribute to sleep disruption. Herein, a case of association between PLMS, Cheyne-Stokes respiration (CSR) and severe insomnia is described. Repeated polysomnographic studies demonstrated a clear synchronisation between PLMS and hyperventilation episodes, and the complete recovery of CSR, sleep quality and PLMS during nocturnal ventilation. In the same patient, pharmacological treatment with a dopamine agonist was ineffective on both PLMS and CSR. These results suggest that periodic leg movements during sleep coupled with central breathing events, similar to those observed in conjunction with obstructive events, may have a different origin in terms of neurotransmitter and pathway implicated, compared with periodic leg movements during sleep in restless legs syndrome, and are resolved by treatment of the respiratory abnormalities.
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Respiração de Cheyne-Stokes/fisiopatologia , Perna (Membro)/fisiopatologia , Movimento , Síndrome das Pernas Inquietas/fisiopatologia , Agonistas de Dopamina/metabolismo , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Polissonografia/métodos , Sono , Distúrbios do Início e da Manutenção do Sono/patologiaAssuntos
Benzotiazóis/farmacologia , Agonistas de Dopamina/farmacologia , Síndrome das Pernas Inquietas/complicações , Bexiga Urinaria Neurogênica/etiologia , Adulto , Benzotiazóis/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Feminino , Humanos , Pramipexol , Síndrome das Pernas Inquietas/tratamento farmacológico , Bexiga Urinaria Neurogênica/tratamento farmacológicoRESUMO
Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS prevalence in a large population of MS patients, comparing clinical and MRI findings between patients with and without RLS. Each of the 156 MS patients (100 females, 56 males, mean age 40.7 +/- 10.4) enrolled in a prospective study underwent a medical history interview, a neurological examination with the assessment of the Expanded Disability Status Scale (EDSS), and a structured questionnaire to verify the presence and features of RLS. Conventional brain-spinal MRIs of 99 subjects were also evaluated and compared between patients with and without RLS. Fifty-one subjects (32.7%) (mean age 43.8 +/- 12.8) met the criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset, whilst in the remaining cases the RLS was followed by or was simultaneous with clinical MS onset. Comparing the RLS group with the group without RLS, no significant differences were found in MS duration, gender, and referred sleep habits. The primary progressive MS course was more represented in the RLS group, which also showed a higher EDSS score. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability.
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Esclerose Múltipla/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Idade de Início , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Comorbidade , Estudos Transversais , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Crônica Progressiva/epidemiologia , Exame Neurológico , Prevalência , Estudos Prospectivos , Síndrome das Pernas Inquietas/fisiopatologia , Distribuição por Sexo , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e QuestionáriosRESUMO
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by elaborate behaviours during REM sleep usually associated with action-filled dreams. Typical behaviours are screaming, grasping, punching, kicking and occasionally jumping out of bed, which are potentially harmful for the patient and their bed partner. Polysomnographic (PSG) recording reveals a loss of atonia and an excessive phasic motor activity during REM sleep. RBD affects mainly men over 50 years and its prevalence in the general population is estimated around 0.5%. It may occur in acute or chronic forms. The latter may be isolated (idiopathic RBD), or associated with other neurological diseases (symptomatic RBD), especially with a group of neurodegenerative disease called alpha-synucleinopathies, which includes Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy. The idiopathic form accounts for up to 60% of the cases reported in the literature. Small clinical follow-up studies revealed that a proportion of these patients will eventually develop a parkinsonian syndrome and/or a DLB in the years following the RBD diagnosis, while some patients will remain idiopathic for decades. Recent studies found evidence of neural dysfunction during both wakefulness and sleep in iRBD, such as an impairment of the cortical activity, specific neuropsychological deficits, signs of autonomic dysfunction, deficit of colour discrimination, subtle abnormalities in quantitative measures of motor and gait speed and an olfactory impairment. The notion of "idiopathic" RBD is currently challenged and the use of a more conservative term of "cryptogenic" RBD has been suggested.
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Restless legs syndrome (RLS) is a chronic sleep motor disorder that affects up to 10% of the general population. Except for periodic leg movements (PLM), which can be found in the great majority of RLS patients, no objective hematochimic or neurophysiological markers are available to prove the diagnosis, which is based on clinical standard criteria. Nowadays, the aetiopathogenesis of the syndrome is unknown. In a consistent sample of patients affected by the idiopathic form, the disease is inherited as an autosomal dominant trait related to an unidentified locus, while each symptomatic form is probably linked to a specific cause. Although of possible different origins, both the primary and secondary forms may share the same pathogenetic mechanism, which, even if unclear, could be characterised by a neurological dysfunction of the dopaminergic system. Several issues, including strong efficacy of dopamine-agonist treatments, support this theory, which is currently considered the main pathogenetic hypothesis. Most of the past studies tried to clarify the RLS mechanism using the neurophysiological, biochemical and neuroimaging techniques applied to the field of human research. Now the time has come to accept the challenge in creating an animal model of RLS, which may emerge as a decisive step in understanding RLS pathogenesis, and to develop and test new therapies. Even though there have been a few significant efforts, a valid animal model of RLS still does not exist. In past pioneering studies, the authors attempted to induce restless motor behaviour in animals by different strategies: antidopaminergic pharmacological interventions, spinal or cerebral lesions of specific regions involved in the motor control and in dopamine regulation, and selective deletion of genes coding for dopamine receptors. Rodents (mice and rats) were always chosen by the authors as the animals for their experiments. The current tendency in achieving an RLS model is generally represented by simulation of a symptomatic condition of RLS or by a direct interference of the dopaminergic system. In this regard, the pharmacological method had the intention to reproduce the neuroleptic-induced acathisia, the spinal lesional model was based on the hypothesis of myelopathic- related PLM, and the hypothalamic lesion tested the motor consequence of A11 dopaminergic neurons. Preliminary studies are underway to replicate the pregnancy-related form of RLS by using a hormonal intervention, and the iron-deficiency secondary form by using specific iron-free diets. Today, modern technologies are available to easily replicate in animals most of the symptomatic RLS conditions. In addition, more than a few well validated animal models of different diseases known to be related to RLS or PLM, for instance, Parkinson's disease, rheumatoid arthritis and renal failure, could also be exploited in addressing this topic. The real obstacle in achieving an RLS model is the absence of a certain diagnostic marker to recognise if the animal that underwent the different experimental procedures has developed the RLS condition or not. Concerning this issue, possible specific endpoints are represented by the increase in locomotor activity, which are ascertainable by different techniques, such as openfield or run-wheel activity, or by sleep fragmentation, in which the circadian shift can be verified by applying polysomnography on the animal. PLM are probably the only specific and reliable markers available to recognise and quantify experimentally induced RLS. Despite a few authors who reported the presence of limb-phasic, pseudoperiodic activity during sleep in old or in lesioned rats, the existence of spontaneous or provoked PLM in animals is still debated. Eventually, the PLM features in an animal could be markedly different compared to human ones. To recognise and characterise PLM in animals, three more essential steps are required: a method to record directly, as in humans, the activity of the tibialis anterior (TA) muscles, a consistent amount of normative control data on the TA activity in healthy animals, and reliable analysis to distinguish the generic phasic muscular activity to a possible unambiguous PLM pattern. This review includes a summary and a critical discussion of the previous tentative RLS models, proposals for other possible animal models, and firstly the preliminary normative data on TA activity during sleep in normal rodents.
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The pathogenesis of restless legs syndrome (RLS) is not yet completely understood. However, recent research addressed the hypothesis that dopaminergic pathways are involved in the mechanisms responsible for the syndrome both for sensory and motor symptoms. Different aspects of RLS physiopathogenesis are discussed: the genetic components indicating different chromosomes are responsible for the heterogeneity in the phenotypic expression of the familial forms of RLS; the neurophysiologic data showing the hyperexcitability of the cortico-motor efferents at supraspinal level, with spinal cord involvement leading to a definition of RLS as a syndrome of somatosensory misperception, disturbed gain regulation and/or a shifted threshold; the paucity of neuroimaging data, which do not definitively clarify the eventual dopaminergic dysfunction in RLS patients, at least at the basal ganglia level; an illustration of the iposideremic hypothesis starting from the therapeutic effect of iron, although not for all patients, and based on some neurophysiologic and neuropathologic results both in humans and animal models; and finally the role of the opioid system, suggesting an imbalance of dopamine-opiate system inputs to brain regions involved in motor responses and pain perception, and representing an aberrant behavioural response to sensory inputs. All these theories may have a final common pathway in the dopaminergic system, reinforcing the empirical results of benefit with dopamine or dopamine-agonist treatments in RLS.
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This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM (PLM) are now defined by runs of at least four consecutive CLM with an intermovement interval ≥10 and ≤ 90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining CLM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoringof LM has only been altered by the new standards to require accepting all LM > 0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.
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Movimento/fisiologia , Síndrome da Mioclonia Noturna/diagnóstico , Polissonografia/normas , Síndrome das Pernas Inquietas/diagnóstico , Comitês Consultivos , Algoritmos , Eletromiografia , Humanos , Índice de Gravidade de Doença , Sociedades Médicas/normasRESUMO
The sleep parameters of never-depressed borderline subjects and age- and sex-matched normal controls were compared by continuous 48-hr ambulatory electroencephalographic (EEG) monitoring. Borderline subjects had a significantly shorter rapid eye movement latency, normal architecture of rapid eye movements sleep, and had familial risks for mood disorders four times greater than in the families of controls. Reduced latency of rapid eye movement can be a trait indicator of liability to depression, present before the clinical appearance of the disorder, and demonstrable in a putative high-risk population.