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1.
Lancet Neurol ; 19(3): 226-233, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32085836

RESUMO

BACKGROUND: S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. METHODS: RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18-85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7-20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0-1 versus 2-6 and 0-2 versus 3-6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615. FINDINGS: Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64-1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81-1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0-2 vs 3-6 or mRS 0-1 vs 2-6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2-8] in 150 mg S44819 group, 4 [2-7] in 300 mg S44819 group, and 4 [2-6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0-26·0] in 150 mg S44819 group, 23·0 [19·0-26·5] in 300 mg S44819 group, and 22·0 [17·0-26·0] in placebo group), time needed to complete parts A (50 s [IQR 42-68] in 150 mg S44819 group, 49 s [36-63] in 300 mg S44819 group, and 50 s [38-68] in placebo group) and B (107 s [81-144] in 150 mg S44819 group, 121 s [76-159] in 300 mg S44819 group, and 130 s [86-175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60-100] in 150 mg S44819 group, 90 [70-100] in 300 mg S44819 group, and 90 [70-100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. INTERPRETATION: There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. FUNDING: Servier.

2.
Trials ; 21(1): 136, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014032

RESUMO

BACKGROUND: The GABAA-α5 receptor antagonist S44819 is a promising candidate to enhance functional recovery after acute ischemic stroke (IS). S44819 is currently evaluated in this indication; RESTORE brain study started in Dec 2016 and was completed in March 2019. METHODS/DESIGN: The study is a 3-month international, randomized, double-blind, parallel group, placebo-controlled phase II multicentre study. Patients in 14 countries who suffered an IS leading to a moderate or severe deficit defined by NIHSS score ranging from 7 to 20 and are aged between 18 to 85 years are included between 3 and 8 days after the stroke onset. Approximately 580 patients are to be included. The primary objective of the study is to demonstrate the superiority of at least one of the two doses of S44819 (150 or 300 mg bid) compared to placebo on top of usual care on functional recovery measured with the modified Rankin scale at 3 months. Comparisons between two doses of S44819 and placebo are assessed with ordinal logistic regression evaluating the odds of shifting from one category to the next in the direction of a better outcome at day 90. Secondary objectives include the evaluation of S44819 effects on neurological examination using the National Institute of Health Stroke Scale total score, activities of daily living using the Barthel Index total score, and cognitive performance using the Montreal Cognitive Assessment scale total score and Trail Making Test times. Safety and tolerability of the two doses of S44819 will also be analyzed. DISCUSSION: The RESTORE BRAIN study might represent the first proof of concept study of an innovative therapeutic approach that is primarily based on enhancing functional recovery after IS. TRIAL REGISTRATION: Randomized Efficacy and Safety Trial with Oral S 44819 after Recent ischemic cerebral Event, an international, multi-centre, randomized, double-blind placebo-controlled phase II study. ClinicalTrials.gov, NCT02877615; Eudract 2016-001005-16. Registered 24 August 2016.

3.
Postgrad Med ; 132(1): 72-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760836

RESUMO

Parasomnias are abnormal behaviors that occur during sleep and can be associated, in particular during adulthood, with impaired sleep quality, daytime dysfunction, and occasionally with violent and harmful nocturnal behaviors. In these cases, therapies are often considered. Longterm pharmacological treatments are not always well tolerated and often have limited efficacy. Therefore, behavioral approaches remain an important treatment option for several types of parasomnias. However, the evidence-based approaches are limited. In the current review, we highlight results from various nonpharmacological techniques on different types of parasomnias and provide a glimpse into the future of nonpharmacological treatments in this field.


Assuntos
Parassonias/terapia , Terapia Comportamental , Humanos , Terrores Noturnos/terapia , Transtorno do Comportamento do Sono REM/terapia , Transtornos do Despertar do Sono/terapia , Sonambulismo/terapia
4.
J Neuropsychiatry Clin Neurosci ; 32(1): 79-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31587627

RESUMO

OBJECTIVE: A growing interest in functional neurological disorders (FND) has led to the development of specialized clinics. This study aimed to better understand the structure and role of such clinics. METHODS: Data were retrospectively collected from clinical records at three national referral centers, two specifically for motor FND and one for FND in general. Data were for 492 consecutive patients referred over a 9- to 15-month period: 100 from the United Kingdom clinic, 302 from the Swiss clinic, and 90 from the Canadian clinic. Data included symptom subtype and duration, comorbid pain and fatigue, disability, and treatment recommendations. RESULTS: The mean age of the 492 patients was 44 years, and most (73%) were female. Most had a prolonged motor FND (mean symptom duration of 6 years); 35% were not working because of ill health, 26% received disability benefits, and up to 38% required a care giver for personal care. In the Swiss cohort, 39% were given a diagnosis of another somatic symptom disorder rather than an FND diagnosis. Pain was common in the United Kingdom (79%) and Canada (56%), as was fatigue (48% and 47%, respectively). Most patients (61%) were offered physiotherapy; referral to neuropsychiatry or psychology differed across centers (32%-100%). CONCLUSIONS: FND specialty clinics have an important role in ensuring correct diagnosis and appropriate treatment. Most patients with motor FND require specialized neurophysiotherapy. Patients readily accepted an integrated neuropsychiatric approach. Close collaboration between FND clinics and acute neurology facilities might improve early detection of FND and could improve outcomes.

6.
J Neurol ; 266(12): 3076-3086, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531764

RESUMO

OBJECTIVE: We aimed to determine the incidence of all vestibular symptoms in a large interdisciplinary tertiary emergency department (ED) and to assess stroke prevalence, and frequency of other life-threatening aetiologies. METHODS: In this 1-year retrospective study, we manually screened all medical records of 23,608 ED visits for descriptions of vestibular symptoms. Symptoms were classified according to the International Classification of Vestibular Disorders of the Bárány Society. We evaluated all patients older than 16 years in whom vestibular symptoms were the main or accompanying complaint. We extracted clinical, radiological, and laboratory findings as well as aetiologies from medical records. RESULTS: We identified a total of 2596 visits by 2464 patients (11% of ED visits) who reported at least one vestibular symptom. In 1677/2596 visits (64.6%), vestibular symptoms were the main reason for the ED consultation. Vestibular symptoms were classified as dizziness (43.8%), vertigo (33.9%), postural symptoms (6.5%), or more than one symptom (15.8%). In 324/2596 visits (12.5%), cerebrovascular events were the aetiology of vestibular symptoms, and in 355/2596 visits (13.7%), no diagnosis could be established. In 23.8% of visits with vestibular symptoms as the main complaint, the underlying condition was life-threatening. CONCLUSION: Frequency and impact of vestibular symptoms in patients visiting the ED were higher than previously reported, and life-threatening aetiologies such as strokes are common. Therefore, awareness among physicians regarding the importance of vestibular symptoms has to be improved.

7.
Sleep Med Rev ; 48: 101204, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31491655

RESUMO

Clinical sleep scoring involves a tedious visual review of overnight polysomnograms by a human expert, according to official standards. It could appear then a suitable task for modern artificial intelligence algorithms. Indeed, machine learning algorithms have been applied to sleep scoring for many years. As a result, several software products offer nowadays automated or semi-automated scoring services. However, the vast majority of the sleep physicians do not use them. Very recently, thanks to the increased computational power, deep learning has also been employed with promising results. Machine learning algorithms can undoubtedly reach a high accuracy in specific situations, but there are many difficulties in their introduction in the daily routine. In this review, the latest approaches that are applying deep learning for facilitating and accelerating sleep scoring are thoroughly analyzed and compared with the state of the art methods. Then the obstacles in introducing automated sleep scoring in the clinical practice are examined. Deep learning algorithm capabilities of learning from a highly heterogeneous dataset, in terms both of human data and of scorers, are very promising and should be further investigated.

8.
Sleep ; 42(12)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31410477

RESUMO

Theta phase modulates gamma amplitude in hippocampal networks during spatial navigation and rapid eye movement (REM) sleep. This cross-frequency coupling has been linked to working memory and spatial memory consolidation; however, its spatial and temporal dynamics remains unclear. Here, we first investigate the dynamics of theta-gamma interactions using multiple frequency and temporal scales in simultaneous recordings from hippocampal CA3, CA1, subiculum, and parietal cortex in freely moving mice. We found that theta phase dynamically modulates distinct gamma bands during REM sleep. Interestingly, we further show that theta-gamma coupling switches between recorded brain structures during REM sleep and progressively increases over a single REM sleep episode. Finally, we show that optogenetic silencing of septohippocampal GABAergic projections significantly impedes both theta-gamma coupling and theta phase coherence. Collectively, our study shows that phase-space (i.e. cross-frequency coupling) coding of information during REM sleep is orchestrated across time and space consistent with region-specific processing of information during REM sleep including learning and memory.

9.
J Neurol Neurosurg Psychiatry ; 90(12): 1310-1316, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31422368

RESUMO

BACKGROUND: Although rapid eye movement sleep behaviour disorder (RBD) in Parkinson's disease (PD) is associated with increased non-motor symptoms, its impact on the deep brain stimulation (DBS) outcome remains unclear. This is the first study to compare the post-DBS outcome between PD patients with RBD (PD-RBD+) and without (PD-RBD-). METHODS: We analysed data from PD patients who were treated with bilateral DBS in the nucleus subthalamicus. Assessments included night-polysomnography (only pre-DBS), and motor and non-motor assessments pre-DBS and post-DBS. RESULTS: Among 50 PD patients (29 males, mean age 62.5 years, 11.8 mean PD years), 24 (48%) had RBD. Pre-DBS, the two groups were equal in respect to sociodemographic features, disease duration and PD medications. A multivariate analysis showed that the clinical profile linked to motor, non-motor and quality of life features differed significantly between PD patients with and without RBD. The most discriminative elements were Unified Parkinson's Disease Rating Scale (UPDRS)-III, apathy and depression scores. Post-DBS, UPDRS-III, Epworth sleepiness scale and PD questionnaire improved significantly in both groups. UPDRS-II scores significantly improved in the PD-RBD+ group (-45%) but remained unchanged in the PD-RBD- group (-14%). The depression score improved significantly in the PD-RBD+ (-34%) and remained unchanged in the PD-RBD- group. The apathy score remained unchanged in the PD-RBD+ group but increased significantly in the PD-RBD- group (+33%). CONCLUSION: While pre-DBS, PD patients with and without RBD showed different clinical profiles, post-DBS, the clinical profiles were comparable between the two groups. In respect to depressive symptoms, apathy and activities of daily living, PD-RBD+ patients show favourable post-DBS outcome. These findings highlight the importance of RBD assessment prior to DBS surgery.

10.
Nat Rev Neurol ; 15(9): 519-539, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324898

RESUMO

Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.


Assuntos
Encéfalo/fisiopatologia , Narcolepsia , Orexinas/fisiologia , Humanos , Hipotálamo/fisiopatologia , Narcolepsia/diagnóstico , Narcolepsia/etiologia , Narcolepsia/fisiopatologia , Narcolepsia/terapia
11.
J Sleep Res ; : e12878, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31192512

RESUMO

Ischaemic stroke is accompanied by important alterations of cardiac autonomic control, which have an impact on stroke outcome. In sleep, cardiac autonomic control oscillates with a predominant sympathetic modulation during REM sleep. We aimed to assess cardiac autonomic control in different sleep stages in patients with ischaemic stroke. Forty-five patients enrolled in the prospective, multicentre SAS-CARE study but without significant sleep-disordered breathing (apnea-hypopnea index < 15/hr) and without atrial fibrillation were included in this analysis. The mean age was 56 years, 68% were male, 76% had a stroke (n = 34, mean National Institutes of Health Stroke Scale [NIHSS] score of 5, 11 involving the insula) and 24% (n = 11) had a transitory ischaemic attack. Cardiac autonomic control was evaluated using three different tools (spectral, symbolic and entropy analysis) according to sleep stages on short segments of 250 beats in all patients. Polysomnographic studies were performed within 7 days and 3 months after the ischaemic event. No significant differences in cardiac autonomic control between sleep stages were observed in the acute phase and after 3 months. Predominant vagal modulation and decreased sympathetic modulation were observed across all sleep stages in ischaemic stroke involving the insula. Patients with ischaemic stroke and transitory ischaemic attack present a loss of cardiac autonomic dynamics during sleep in the first 3 months after the ischaemic event. This change could represent an adaptive phenomenon, protecting the cardiovascular system from the instabilities of autonomic control, or a risk factor for stroke, which precedes the ischaemic event.

12.
Curr Biol ; 29(12): 1976-1987.e4, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31155350

RESUMO

Ambient temperature (Ta) warming toward the high end of the thermoneutral zone (TNZ) preferentially increases rapid eye movement (REM) sleep over non-REM (NREM) sleep across species. The control and function of this temperature-induced REM sleep expression have remained unknown. Melanin-concentrating hormone (MCH) neurons play an important role in REM sleep control. We hypothesize that the MCH system may modulate REM sleep as a function of Ta. Here, we show that wild-type (WT) mice dynamically increased REM sleep durations specifically during warm Ta pulsing within the TNZ, compared to both the TNZ cool and baseline constant Ta conditions, without significantly affecting either wake or NREM sleep durations. However, genetically engineered MCH receptor-1 knockout (MCHR1-KO) mice showed no significant changes in REM sleep as a function of Ta, even with increased sleep pressure following a 4-h sleep deprivation. Using MCH-cre mice transduced with channelrhodopsin, we then optogenetically activated MCH neurons time locked with Ta warming, showing an increase in REM sleep expression beyond what Ta warming in yellow fluorescent protein (YFP) control mice achieved. Finally, in mice transduced with archaerhodopsin-T, semi-chronic optogenetic MCH neuronal silencing during Ta warming completely blocked the increase in REM sleep seen in YFP controls. These data demonstrate a previously unknown role for the MCH system in the dynamic output expression of REM sleep during Ta manipulation. These findings are consistent with the energy allocation hypothesis of sleep function, suggesting that endotherms have evolved neural circuits to opportunistically express REM sleep when the need for thermoregulatory defense is minimized.

15.
J Neurol ; 266(9): 2137-2143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31127382

RESUMO

Previous studies reported high sensitivity and specificity of the Swiss Narcolepsy Scale (SNS) for the diagnosis of narcolepsy type 1. We used data from the Bern Sleep-Wake Database to investigate the discriminating capacity of both the SNS and the Epworth Sleepiness Scale (ESS) to identify narcolepsy type 1 and type 2 in patients with central disorders of hypersomnolence (CDH) or sleepy patients with obstructive sleep apnea (OSA). In addition, we aimed to develop a simplified version of the SNS. We created the two-item short-form SNS (sSNS), based on the discriminative capability of the models including all possible combinations of the five questions of the SNS. Using the previously published co-efficiencies, we confirmed the high capacity of the SNS in identifying narcolepsy type 1. The updated SNS (based on new co-efficiencies and cutoff) and the sSNS showed high capacity and were both superior to ESS in identifying narcolepsy type 1. The sSNS correlated significantly with the SNS (r = - 0.897, p < 0.001). No scale showed sufficient discrimination for narcolepsy type 2. This is the largest cohort study that confirms the discriminating power of SNS for narcolepsy type 1 in patients with hypersomnolence and the first study to assess its discriminative power for narcolepsy type 2. The easy-to-use and easy-to-calculate short-form scale has a high discriminating power for narcolepsy type 1 and may be used as screening tool, especially among general practitioners, to identify patients and accelerate their referral to a center of expertise.


Assuntos
Bases de Dados Factuais/normas , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Narcolepsia/diagnóstico , Sono/fisiologia , Inquéritos e Questionários/normas , Vigília/fisiologia , Adulto , Estudos de Coortes , Diagnóstico Diferencial , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/epidemiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Suíça , Adulto Jovem
16.
J Sleep Res ; 28(5): e12831, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30815913

RESUMO

Neck myoclonus (NM) is a frequent recently described sleep-related motor phenomenon occurring mainly during REM sleep with uncertain effect on sleep continuity. To better describe this phenomenon we studied 11 consecutive drug-free patients undergoing a video-polysomnographic (V-PSG) study who present at least 5 NM events in one single night of recording. All events were measured and checked for their association with rapid eye and leg movements, EEG arousals, awakenings and Bereitschaftspotential. One hundred and eighty-two motor events from 11 subjects were analyzed. Motor events were approximately 0.5 s in duration and occurred during REM sleep in 79.7% of the cases. Only 14.8% of the events were associated with rapid eye movements, 52.2% with leg movements, while approximately 80% of them were accompanied by an arousal or awakening. No EEG abnormalities and Bereitschaftspotential were observed. For its duration and its segregation in sleep, NM could be more appropriately named "sleep-related head jerks" (SRHJ). SRHJ should be recognized and its effect on sleep stability should be re-considered.

17.
J Neurol Sci ; 399: 194-198, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30826716

RESUMO

OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) in patients with Parkinson's disease (PD) is associated with increased risk of non-motor symptoms. However, the association between RBD and apathy in PD remains unclear. AIMS: To compare the prevalence and severity of apathy symptoms in PD patients with RBD (PD-RBD+) and without (PD-RBD-). In addition, we explored the association between apathy, depressive symptoms and RBD, taking into consideration the concomitant influence of demographic, disease- and therapy-associated variables. METHODS: Sixty-four PD patients were evaluated with systematic motor (unified Parkinson's disease rating scale, UPDRS-III) and non-motor assessments. The diagnosis of RBD was based on the international consensus criteria using video-polysomnography. Apathy, sleepiness, depressive symptoms and cognitive performance were assessed using the Starkstein apathy (SAS, cut-off = 14), the Epworth sleepiness (ESS), the Hamilton depression (HAM-D, cut-off = 9) scales and the mini-mental state examination (MMSE), respectively. RESULTS: Among 64 patients, 26 (40%) had RBD. In the PD-RBD+ group, apathy symptoms were more frequent (52% vs 42%) and more severe (14.3 ±â€¯5.8 vs 11.2 ±â€¯4.9, p < 0.05), especially in the females (17.3 ±â€¯6.0 vs 11.4 ±â€¯5.8 in males, p < 0.05) compared to the PD-RBD- group. A high percentage of patients, especially in the PD-RBD+ group (53%), had isolated apathy without increased depressive symptoms. Increased depressive symptoms were also more frequent (50% vs 20%) and more severe in the PD-RBD+ group. The two groups were comparable in respect to demographic and clinical characteristics. CONCLUSIONS: In PD, RBD is associated with isolated apathy and increased severity of depressive symptoms, independent of medication, motor and other non-motor symptoms. Potential mechanisms underlying this association are discussed.

18.
Neurology ; 92(7): e648-e654, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30635478

RESUMO

OBJECTIVE: To perform a systematic review and meta-analysis on the prevalence of sleep-disordered breathing (SDB) after stroke. METHODS: We searched PubMed, Embase (Ovid), the Cochrane Library, and CINAHL (from their commencements to April 7, 2017) for clinical studies reporting prevalence and/or severity of SDB after stroke or TIA. Only sleep apnea tests performed with full polysomnography and diagnostic devices of the American Academy of Sleep Medicine categories I-IV were included. We conducted random-effects meta-analysis. PROSPERO registration number: CRD42017072339. RESULTS: The initial search identified 5,211 publications. Eighty-nine studies (including 7,096 patients) met inclusion criteria. Fifty-four studies were performed in the acute phase after stroke (after less than 1 month), 23 studies in the subacute phase (after 1-3 months), and 12 studies in the chronic phase (after more than 3 months). Mean apnea-hypopnea index was 26.0/h (SD 21.7-31.2). Prevalence of SDB with apnea-hypopnea index greater than 5/h and greater than 30/h was found in 71% (95% confidence interval 66.6%-74.8%) and 30% (95% confidence interval 24.4%-35.5%) of patients, respectively. Severity and prevalence of SDB were similar in all examined phases after stroke, irrespective of the type of sleep apnea test performed. Heterogeneity between studies (I 2) was mostly high. CONCLUSION: The high prevalence of SDB after stroke and TIA, which persists over time, is important in light of recent studies reporting the (1) feasibility and (2) efficacy of SDB treatment in this clinical setting.


Assuntos
Ataque Isquêmico Transitório/epidemiologia , Síndromes da Apneia do Sono/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Humanos , Polissonografia , Prevalência , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
19.
Sleep ; 42(4)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649557

RESUMO

STUDY OBJECTIVES: The main objective of the study was to assess the prevalence, the severity, and the daytime course of excessive daytime sleepiness (EDS) in advanced Parkinson's disease (PD) and to explore how people with PD perceive the degree and onset of their sleepiness during objective sleepiness tests. In addition, the occurrence of early-onset rapid eye movement (REM) periods (sleep-onset REM periods [SOREMPs]) in PD was assessed. METHODS: We analyzed data from 46 people with PD (26 males, mean age 63.5 years, mean UPDRS-III-OFF 34.7). The sleep-wake assessment included Epworth sleepiness scale (ESS), Karolinska sleepiness scale (KSS), and objective (polysomnography, multiple sleep latency test [MSLT], and maintenance of wakefulness tests [MWT]) measures. RESULTS: Subjective (ESS ≥ 10) and objective (mean sleep latency, MSL < 5 min in MSLT) EDS were present in 43% and 41% of patients, respectively. The MSL in MSLT and MWT remained unchanged throughout the day and significantly correlated with KSS during the trial but not with KSS shortly before it. In MWT, about one-fourth of patients failed to signal their sleepiness before falling asleep. SOREMPs, usually (83%) arising from NREM1 or wake, were recorded in 24% of the patients. People with SOREMPs had significantly lower MSL in MSLT and MWT and higher AHI compared with those without SOREMPs. CONCLUSIONS: Patients with PD exhibit daylong increased EDS but they underestimate its degree and often fail to signal its onset. SOREMPs in PD have a "narcoleptic" character in sleep-stage sequencing and are associated with the presence of sleep-disturbed breathing. These results add to our understanding of sleepiness and sleepiness perception in PD and have important implications for its diagnosis and management.

20.
Stroke ; 49(10): 2495-2503, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30355106

RESUMO

Background and Purpose- Poststroke, neuronal excitability is tonically reduced in peri-infarct tissue via inhibitory influences of extrasynaptic GABAA receptors. We hypothesized that GABAA α5 blockade by the competitive antagonist S44819 enhances postischemic neurological recovery, brain remodeling, and neuroplasticity. Methods- In an explorative study followed by a confirmation study, male C57Bl6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. Starting 72 hours poststroke, vehicle or S44819 (3 or 10 mg/kg, BID) was delivered orally for 28 days. Neurological recovery, perilesional tissue remodeling, and contralesional pyramidal tract plasticity were evaluated for 42 days, that is, 14 days after completion of S44819 delivery. Results- S44819, delivered at 10 but not 3 mg/kg, persistently improved motor coordination and spatial memory in both studies. Striatal atrophy was reduced by 10 mg/kg S44819 at 42 days post-treatment onset, and neuronal long-term survival in the peri-infarct striatum was increased. Delayed neuroprotection was associated with reduced peri-infarct astrogliosis, increased peri-infarct brain capillary density, and increased neural precursor cell proliferation and differentiation in proximity to the ipsilesional subventricular zone. Contralesional pyramidal tract plasticity, evaluated by anterograde tract tracing at the level of the red nucleus, was not influenced by S44819. Concentrations of neurotrophic (brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) and angiogenic (vascular endothelial growth factor and basic fibroblast growth factor) growth factors were elevated by 10 mg/kg S44819 in peri-infarct but not contralesional brain tissue. Conclusions- Our data demonstrate that S44819 enhances neurological recovery and peri-infarct brain remodeling in the postacute stroke phase.


Assuntos
Benzodiazepinas/farmacologia , Antagonistas GABAérgicos/farmacologia , Oxazóis/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Acidente Vascular Cerebral/fisiopatologia
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