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OBJECTIVE: Changes in sleep architecture following ischemic stroke have been poorly investigated. Our objective was to explore changes of sleep structure in patients with ischemic stroke or transient ischemic attack in order to verify a possible predictive value of sleep with respect to clinical outcome. METHODS: Patients recruited in the prospective SAS-CARE study received two polysomnographies (PSG) in the acute and chronic phases after stroke/TIA. Sleep parameters were compared between the two time-points and matched with a non-stroke population randomly selected from the HypnoLaus cohort. RESULTS: Of the 169 patients investigated with PSG in the acute phase, 104 were again studied 3 months after stroke symptom onset and compared with 162 controls. The acute phase of stroke/TIA was associated with sleep disruption, which significantly improved in the chronic phase, but remained worse than controls (total sleep time improve from 318.8 ± 90.8 to 348.4 ± 81.5 min, compared to 388.2 ± 71.3 in controls, sleep latency from 49.9 ± 58.4 to 27.9 min, compared to 20.2 ± 22 in controls, sleep efficiency from 58.2 ± 18.1% to 27.9 ± 36.4 min, compared to 83.4 ± 10.3% in controls, wakefulness after sleep onset percentage from 36.5 ± 17.3 to 29.3 ± 15.6, compared to 13.2 ± 9.2 in controls). The percentage of REM sleep was negatively associated with stroke severity, whereas stroke topography did not correlate with sleep parameters. CONCLUSIONS: This study confirmed a severe sleep disruption in the acute phase of stroke. Although a significant improvement of sleep quality was observed during the three months after stroke, sleep architecture did not normalize. In particular, sleep efficiency and REM sleep seem to be particularly affected by stroke in the acute phase, with a relative preservation of NREM sleep. We suggest that these sleep architecture changes represent a persistent marker of brain damage due to stroke. Further studies are needed to assess the relationship with stroke topographic and outcome.
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Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/complicações , Polissonografia , Estudos Prospectivos , Sono , Acidente Vascular Cerebral/epidemiologiaRESUMO
Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.
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Encéfalo/fisiologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocoagulação/métodos , Terapia por Radiofrequência/métodos , Sono/fisiologia , Vigília/fisiologia , Encéfalo/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Técnicas EstereotáxicasRESUMO
BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.
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Epilepsia Reflexa , Transtornos do Sono-Vigília , Consenso , Humanos , Qualidade de Vida , Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.
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COVID-19 , Doenças do Sistema Nervoso/terapia , Pandemias , Administração dos Cuidados ao Paciente , Consenso , Técnica Delphi , Guias como Assunto , Humanos , NeurologiaRESUMO
Following the first descriptions of narcolepsy with cataplexy by Westphal, Gelineau, and Fischer (1878-1880), Russian authors started to report on "narcolepsy cases" in 1894. It was, however, only in 1925 that Mankovsky reported a (postencephalitic) case, satisfying current diagnostic criteria for the disease. In the following 66 years (the last publication appeared in 1991), Russian authors including Davidenkov, Vein, and Yakhno made interesting contributions on the clinical features, neurophysiological correlates (e.g., sleep states and boundary dyscontrol), pathogenesis (e.g., hypothalamic origin), etiology (e.g., infectious, postvaccinal triggers, focal encephalitis), and treatment (e.g., use of sodium oxybate) of narcolepsy. Until recently, Pavlov's theory of narcolepsy as a "cortical excitatory-inhibitory phenomenon" strongly influenced the Russian view on the disease, contrasting with the current neurobiological insights acknowledged internationally. A Narcolepsy Network, including currently 10 member centers, was recently founded to promote knowledge, awareness, management, and research on this still poorly known disease in Russia.
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Cataplexia , Narcolepsia , Oxibato de Sódio , Humanos , Federação Russa , SonoRESUMO
BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.
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Anosmia/etiologia , COVID-19/complicações , Cefaleia/etiologia , Mialgia/etiologia , Agitação Psicomotora/etiologia , Europa (Continente) , Inquéritos Epidemiológicos , Humanos , NeurologiaRESUMO
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
OBJECTIVE/BACKGROUND: The benefit of Continuous Positive Airway Pressure (CPAP) treatment following ischemic stroke in patients with obstructive sleep-disordered breathing (SDB) is unclear. We set out to investigate this open question in a randomized controlled trial as part of the SAS-CARE study. PATIENTS/METHODS: Non-sleepy patients (ESS < 10) with ischemic stroke or transient ischemic attack (TIA) and obstructive SDB (AHI ≥ 20) 3 months post-stroke were randomized 1:1 to CPAP treatment (CPAP+) or standard care. Primary outcome was the occurrence of vascular events (TIA/stroke, myocardial infarction/revascularization, hospitalization for heart failure or unstable angina) or death within 24 months post-stroke. Secondary outcomes included Modified Rankin Scale (mRS) and Barthel Index. RESULTS: Among 238 SAS-CARE patients 41 (17%) non-sleepy obstructive SDB patients were randomized to CPAP (n = 19) or standard care (n = 22). Most patients (80%) had stroke and were males (78%), mean age was 64 ± 7 years and mean NIHSS score 0.6 ± 1.0 (range: 0-5). The primary endpoint was met by one patient in the standard care arm (a new stroke). In an intent-to treat analysis disregarding adherence, this corresponds to an absolute risk difference of 4.5% or an NNT = 22. mRS and Barthel Index were stable and similar between arms. CPAP adherence was sufficient in 60% of evaluable patients at month 24. CONCLUSION: No benefit of CPAP started three months post-stroke was found in terms of new cardio- and cerebrovascular events over 2 years. This may be related to the small size of this study, the mild stoke severity, the exclusion of sleepy patients, the delayed start of treatment, and the overall low event rate.
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Sleep spindles are thalamocortical oscillations associated with several behavioural and clinical phenomena. In clinical populations, spindle activity has been shown to be reduced in schizophrenia, as well as after thalamic stroke. Automatic spindle detection algorithms present the only feasible way to systematically examine individual spindle characteristics. We took an established algorithm for spindle detection, and adapted it to high-density EEG sleep recordings. To illustrate the detection and analysis procedure, we examined how spindle characteristics changed across the night and introduced a linear mixed model approach applied to individual spindles in adults (n = 9). Next we examined spindle characteristics between a group of paramedian thalamic stroke patients (n = 9) and matched controls. We found a high spindle incidence rate and that, from early to late in the night, individual spindle power increased with the duration and globality of spindles; despite decreases in spindle incidence and peak-to-peak amplitude. In stroke patients, we found that only left-sided damage reduced individual spindle power. Furthermore, reduction was specific to posterior/fast spindles. Altogether, we demonstrate how state-of-the-art spindle detection techniques, applied to high-density recordings, and analysed using advanced statistical approaches can yield novel insights into how both normal and pathological circumstances affect sleep.
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Eletroencefalografia/métodos , Fenômenos Eletrofisiológicos , Sono , Acidente Vascular Cerebral/patologia , Tálamo/patologia , Adulto , Algoritmos , Bioestatística , Humanos , MasculinoRESUMO
This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).
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Humanos , Adulto , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia , Fototerapia , Antipsicóticos/uso terapêutico , Terapias Complementares , Terapia Cognitivo-Comportamental , Polissonografia , Receptores de GABA-A/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antidepressivos/uso terapêuticoRESUMO
Headache is one of the most frequent symptoms leading to visits at the emergency department. Here, we aim at presenting a pragmatic algorithm for headache patients at the emergency department. The basic principle is taking a detailed history of the current headache with a focus on dynamics, phenotype and trigger factors as well as a possible preexisting headache. "Red flags" should be interrogated specifically. Hypotheses of the etiology of the headache should be generated in combination with the clinical examination (vital signs, neurological exam, otorhinolaryngological and ophthalmological exams) and should be tested appropriately with imaging, laboratory, cerebral spinal fluid studies and ultrasound. Secondary headache have to be treated with a causal approach, if necessary also symptomatically. When a secondary headache can be excluded, we recommend aiming for a primary headache diagnosis with subsequent specific therapy. When a headache patient can be discharged, we recommend scheduling a follow-up appointment to understand the development of a secondary headache and its cause. In case of a primary headache, optimizing prophylaxis and acute therapy is important to prevent future emergency department visits.
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Técnicas de Diagnóstico Neurológico , Serviços Médicos de Emergência/métodos , Cefaleia/diagnóstico , Cefaleia/terapia , Exame Físico/métodos , Diagnóstico Diferencial , Serviço Hospitalar de Emergência/organização & administração , Cefaleia/etiologia , HumanosRESUMO
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
OBJECTIVES: Animal and human studies have shown that sleep may have an impact on functional recovery after brain damage. Baclofen (Bac) and gamma-hydroxybutyrate (GHB) have been shown to induce physiological sleep in humans, however, their effects in rodents are unclear. The aim of this study is to characterize sleep and electroencelphalogram (EEG) after Bac and GHB administration in rats. We hypothesized that both drugs would induce physiological sleep. METHODS: Adult male Sprague-Dawley rats were implanted with EEG/electromyogram (EMG) electrodes for sleep recordings. Bac (10 or 20 mg/kg), GHB (150 or 300 mg/kg) or saline were injected 1 h after light and dark onset to evaluate time of day effect of the drugs. Vigilance states and EEG spectra were quantified. RESULTS: Bac and GHB induced a non-physiological state characterized by atypical behavior and an abnormal EEG pattern. After termination of this state, Bac was found to increase the duration of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep (â¼90 and 10 min, respectively), reduce sleep fragmentation and affect NREM sleep episode frequency and duration (p<0.05). GHB had no major effect on vigilance states. Bac drastically increased EEG power density in NREM sleep in the frequencies 1.5-6.5 and 9.5-21.5 Hz compared to saline (p<0.05), while GHB enhanced power in the 1-5-Hz frequency band and reduced it in the 7-9-Hz band. Slow-wave activity in NREM sleep was enhanced 1.5-3-fold during the first 1-2 h following termination of the non-physiological state. The magnitude of drug effects was stronger during the dark phase. CONCLUSION: While both Bac and GHB induced a non-physiological resting state, only Bac facilitated and consolidated sleep, and promoted EEG delta oscillations thereafter. Hence, Bac can be considered a sleep-promoting drug and its effects on functional recovery after stroke can be evaluated both in humans and rats.
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Adjuvantes Anestésicos/farmacologia , Baclofeno/farmacologia , Comportamento Animal/efeitos dos fármacos , Ondas Encefálicas/efeitos dos fármacos , Agonistas dos Receptores de GABA-B/farmacologia , Sono/efeitos dos fármacos , Oxibato de Sódio/farmacologia , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Eletroencefalografia , Eletromiografia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Restless legs syndrome (RLS) is a common neurologic disorder. Secondary RLS includes pregnancy and iron deficiency. Prevalence of RLS in pregnancy ranges from 11% to 27%. We aimed to assess the frequency and characteristics of RLS in pregnancy in a Peruvian population and to evaluate the possible pregnancy or delivery complications due to RLS. METHODS: We assessed 218 consecutive expectant mothers at the inpatient clinic of the Hospital San Bartolome in Lima, Peru. Assessment was performed by using the standard diagnostic criteria for RLS and by using a clinical and diagnostic interview. Questionnaires for RLS severity, idiopathic RLS (IRLS), and excessive daytime sleepiness (EDS) according to the Epworth sleepiness scale (ESS) were used. Blood examination was performed for hemoglobin and hematocrit. For comparison, RLS patients were matched for age and body mass index (BMI) with pregnant women without RLS. RESULTS: Out of 218 patients, 40 (18.4%) fulfilled diagnostic criteria for RLS. In RLS patients, prophylactic iron supplementation therapy during pregnancy was less frequently taken (P=.02). Pregnant women with RLS had a higher ESS score than pregnant controls (10.6 +/- 3.1 vs 7.6. +/- 3.6; P<.001). Preeclampsia was more frequent in RLS (7/40 vs 1/39; P=.03). CONCLUSIONS: In our study, RLS was frequent in pregnant Peruvian women, especially in those without prophylactic iron supplementation. RLS patients described more EDS. Preeclampsia was more common in RLS. Our study is the first study to indicate a possible association between RLS and preeclampsia.
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Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Pré-Eclâmpsia/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Sono , Adolescente , Adulto , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Feminino , Humanos , Incidência , Ferro/uso terapêutico , Pessoa de Meia-Idade , Peru/epidemiologia , Gravidez , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.
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Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/prevenção & controle , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Clonazepam/uso terapêutico , Consenso , Moduladores GABAérgicos/uso terapêutico , Humanos , Melatonina/uso terapêutico , Doença de Parkinson/epidemiologia , Transtorno do Comportamento do Sono REM/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND AND AIM: We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after stroke onset aggravates brain damage. Others reported that sleep deprivation prior to stroke is neuroprotective. The main aim of this study was to test the hypothesis that the neuroprotection may be related to an increase in sleep (sleep rebound) during the acute phase of stroke. METHODS: Male Sprague Dawley rats (n=36) were subjected to continuous polygraphic recordings for baseline, total sleep deprivation (TSD), and 24h after ischemia. TSD for 6h was performed by gentle handling and immediately followed by ischemia. Focal cerebral ischemia was induced by permanent occlusion of distal branches of the middle cerebral artery. Control experiments included ischemia without SD (nSD) and sham surgery with TSD (n=6/group). RESULTS: Shortly after stroke, the amount of slow wave sleep (SWS) and paradoxical sleep (PS) increased significantly (p<0.05) in the TSD/ischemia, resulting in an increase in the total sleep time by 30% compared to baseline, or by 20% compared with the nSD/ischemia group. The infarct volume decreased significantly by 50% in the TSD/ischemia compared to nSD group (p<0.02). Removal of sleep rebound by allowing TSD-rats sleep for 24h before ischemia eliminated the reduction in the infarct size. CONCLUSION PRESTROKE: Sleep deprivation results in sleep rebound and reduces brain damage. Sleep rebound may be causally related to the neuroprotection.
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Precondicionamento Isquêmico/métodos , Privação do Sono , Sono/fisiologia , Acidente Vascular Cerebral/prevenção & controle , Análise de Variância , Animais , Infarto Encefálico/etiologia , Infarto Encefálico/prevenção & controle , Contagem de Células , Modelos Animais de Doenças , Eletroencefalografia , Eletromiografia , Masculino , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/complicações , Fatores de TempoRESUMO
This paper is meant to provide guidance to anyone wishing to write a neurological guideline for diagnosis or treatment, and is directed at the Scientist Panels and task forces of the European Federation of Neurological Societies (EFNS). It substitutes the previous guidance paper from 2004. It contains several new aspects: the guidance is now based on a change of the grading system for evidence and for the resulting recommendations, and has adopted The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The process of grading the quality of evidence and strength of recommendations can now be improved and made more transparent. The task forces embarking on the development of a guideline must now make clearer and more transparent choices about outcomes considered most relevant when searching the literature and evaluating their findings. Thus, the outcomes chosen will be more critical, more patient-oriented and easier to translate into simple recommendations. This paper also provides updated practical recommendations for planning a guideline task force within the framework of the EFNS. Finally, this paper hopes to find the approval also by the relevant bodies of our future organization, the European Academy of Neurology.