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Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.
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Isquemia Encefálica , Distúrbios do Sono por Sonolência Excessiva , AVC Isquêmico , Síndrome das Pernas Inquietas , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Distúrbios do Início e da Manutenção do Sono , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Isquemia Encefálica/complicações , Pressão Positiva Contínua nas Vias Aéreas , Distúrbios do Sono por Sonolência Excessiva/complicações , AVC Isquêmico/complicações , Síndrome das Pernas Inquietas/complicações , Sono , Síndromes da Apneia do Sono/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Distúrbios do Início e da Manutenção do Sono/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
To assess the feasibility, the acceptability and the usefulness of home nocturnal infrared video in recording the frequency and the complexity of non-rapid eye movement sleep parasomnias in adults, and in monitoring the treatment response. Twenty adult patients (10 males, median age 27.5 years) with a diagnosis of non-rapid eye movement parasomnia were consecutively enrolled. They had a face-to-face interview, completed self-reported questionnaires to assess clinical characteristics and performed a video-polysomnography in the Sleep Unit. Patients were then monitored at home during at least five consecutive nights using infrared-triggered cameras. They completed a sleep diary and questionnaires to evaluate the number of parasomniac episodes at home and the acceptability of the home nocturnal infrared video recording. Behavioural analyses were performed on home nocturnal infrared video and video-polysomnography recordings. Eight patients treated by clonazepam underwent a second home nocturnal infrared video recording during five consecutive days. All patients had at least one parasomniac episode during the home nocturnal infrared video monitoring, compared with 75% during the video-polysomnography. A minimum of three consecutive nights with home nocturnal infrared video was required to record at least one parasomniac episode. Most patients underestimated the frequency of episodes on the sleep diary compared with home nocturnal infrared video. Episodes recorded at home were often more complex than those recorded during the video-polysomnography. The user-perceived acceptability of the home nocturnal infrared video assessment was excellent. The frequency and the complexity of the parasomniac episodes decreased with clonazepam. Home nocturnal infrared video has good feasibility and acceptability, and may improve the evaluation of the phenotype and severity of the non-rapid eye movement parasomnias and of the treatment response in an ecological setting.
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Movimentos Oculares , Monitorização Ambulatorial , Parassonias , Humanos , Masculino , Clonazepam/uso terapêutico , Parassonias/diagnóstico , Parassonias/tratamento farmacológico , Polissonografia , Sono , Gravação em Vídeo , Feminino , Adulto , Estudos de Viabilidade , Inquéritos e Questionários , Monitorização Ambulatorial/métodosRESUMO
Symptoms of restless legs syndrome are relieved by movement. Whether a cognitive task decreases sensory discomfort remains understudied. We aimed to assess the frequency of patients with restless legs syndrome who report decreased sensory discomfort during cognitive activities, and quantify this decrease during a cognitive task. Three-hundred and fifty-eight consecutive adults with restless legs syndrome (age 55.17 ± 14.62 years; 55.87% women; 27.65% treated) answered the question: "Does the intensity of your restless legs syndrome symptoms decrease when you perform activities other than moving your legs?" rated on a nine-point Likert scale (from fully-agree to totally-disagree). A subgroup of 65 consecutive drug-free patients underwent an 80-min suggested immobilisation test at 20:00â hours to quantify legs discomfort on a visual analogue scale before polysomnography, including 40 patients performing a cognitive task (balloon analogue risk task) from the 60 to 80 min. A total of 130 (36.3%) patients reported a decrease, 158 (44.1%) no decrease, and 70 (19.5%) uncertain changes in severity of restless legs syndrome symptoms during cognitive activities, with a similar proportion whether treated or not. Patients experiencing a decrease had less severe restless legs syndrome symptoms. In the suggested immobilisation test, mixed-effect regression models showed that legs discomfort decreased in patients performing the cognitive task while it continued to increase in those without task, with a larger difference in patients reporting a self-reported decrease in restless legs syndrome during cognitive activities. In conclusion, one-third of patients reported a self-reported decrease of restless legs syndrome symptoms during cognitive activities, this improvement in restless legs syndrome was confirmed during a sustained cognitive task. Cognitive strategies could be implemented for the management of restless legs syndrome.
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Síndrome das Pernas Inquietas , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Síndrome das Pernas Inquietas/diagnóstico , Polissonografia , Autorrelato , Movimento , CogniçãoRESUMO
BACKGROUND: Whether depression and suicide thoughts relate to restless legs syndrome (RLS) or comorbidities associated with RLS remain unclear. OBJECTIVES: To determine frequency of depressive symptoms and suicidal thoughts in patients with RLS and their change after RLS treatment, associated clinical and polysomnographic factors, and current major depressive episode (MDE) frequency and suicide risk in RLS. METHODS: Overall, 549 untreated patients with RLS and 549 age-, sex-, and education level-matched controls completed a standardized evaluation, including the Beck Depression Inventory-II that has one item on suicide thoughts. Patients underwent a polysomnographic recording and completed the Urgency, Premeditation, Perseverance, Sensation Seeking Impulsive Behavior scale. In a subgroup of 153 patients, current MDE and suicide risk were assessed with the face-to-face Mini-International Neuropsychiatric Interview (MINI). A subgroup of 152 patients were evaluated in untreated and treated conditions. RESULTS: The frequency of depressive symptoms (32.5%) and suicidal thoughts (28%) was 10-fold and 3-fold higher, respectively, in patients with RLS than controls. Current MDE (10.5%) and suicidal risk (19.9%) (MINI) were also high. Moderate-to-severe depressive symptoms were associated with young age, female sex, insomnia symptoms, and urgency dimension. The suicide risk was associated with depression, impulsiveness, and RLS severity. RLS treatment improved depressive symptoms but not suicidal thoughts. CONCLUSION: The rate of depressive symptoms, depression, and suicidal thoughts/risk was higher in patients with RLS, with key associations with insomnia symptoms, urgency dimension, and RLS severity. These results emphasize the importance of detecting these symptoms in current practice and of evaluating their change after treatment, especially in young women, to improve RLS management. © 2022 International Parkinson and Movement Disorder Society.
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Transtorno Depressivo Maior , Síndrome das Pernas Inquietas , Distúrbios do Início e da Manutenção do Sono , Depressão/epidemiologia , Depressão/etiologia , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Síndrome das Pernas Inquietas/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/complicações , Ideação SuicidaRESUMO
OBJECTIVE: The objective of this study was to assess the rotigotine effect on the nocturnal blood pressure (BP) dip by 24-hour ambulatory BP monitoring and on endothelial function in patients with restless legs syndrome (RLS) compared with placebo. METHODS: In this double-blind, placebo-controlled trial, 76 adult patients with moderate to severe RLS and periodic legs movements in sleep index ≥10/hour were randomized to rotigotine at optimal dose of 3 mg per day or placebo for 6 weeks. A total of 6 patients had a major protocol deviation. Polysomnography, ambulatory BP monitoring, and endothelial function were assessed at baseline and end point. The primary outcome was the between-group difference in the percentage of BP nondipper profiles at end point. The main secondary outcomes were the mean BP dip, periodic legs movements in sleep index, and endothelial function. RESULTS: Of the 70 patients (age, 59.4 ± 11.40; 43 women) randomized to rotigotine (n = 34) and placebo (n = 36), 66 (33 rotigotine, 33 placebo) completed the study. The percentage of BP nondippers at end point was higher in the placebo than in the rotigotine group (systolic BP, 72.22% vs 47.06%; diastolic BP, 47.22% vs 20.59%; P < 0.05). Mean BP dip at end point was higher in the rotigotine than in the placebo group (systolic BP, 11.24 ± 6.15 vs 6.12 ± 7.98; diastolic BP, 15.12 ± 7.09 vs 9.36 ± 10.23; P < 0.05). Endothelial function was comparable between the groups. No significant safety concerns were reported with similar incidences of adverse events between groups. CONCLUSION: Rotigotine increased the percentage of BP dipper profiles and the BP dip in patients with RLS. Future studies should assess whether this change is associated with a reduction in the long-term cardiovascular risk in RLS. © 2020 International Parkinson and Movement Disorder Society.
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Síndrome das Pernas Inquietas , Adulto , Idoso , Pressão Sanguínea , Agonistas de Dopamina , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome das Pernas Inquietas/tratamento farmacológico , Tetra-Hidronaftalenos , Tiofenos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the diagnostic value of extended sleep duration on a controlled 32-hour bed rest protocol in idiopathic hypersomnia (IH). METHODS: One hundred sixteen patients with high suspicion of IH (37 clear-cut IH according to multiple sleep latency test criteria and 79 probable IH), 32 with hypersomnolence associated with a comorbid disorder (non-IH), and 21 controls underwent polysomnography, modified sleep latency tests, and a 32-hour bed rest protocol. Receiver operating characteristic curves were used to find optimal total sleep time (TST) cutoff values on various periods that discriminate patients from controls. RESULTS: TST was longer in patients with clear-cut IH than other groups (probable IH, non-IH, and controls) and in patients with probable IH than non-IH and controls. The TST cutoff best discriminating clear-cut IH and controls was 19 hours for the 32-hour recording (sensitivity = 91.9%, specificity = 85.7%) and 12 hours (100%, 85.7%) for the first 24 hours. The 19-hour cutoff displayed a specificity and sensitivity of 91.9% and 81.2% between IH and non-IH patients. Patients with IH above the 19-hour cutoff were overweight, had more sleep inertia, and had higher TST on all periods compared to patients below 19 hours, whereas no differences were found for the 12-hour cutoff. An inverse correlation was found between the mean sleep latency and TST during 32-hour recording in IH patients. INTERPRETATION: In standardized and controlled stringent conditions, the optimal cutoff best discriminating patients from controls was 19 hours over 32 hours, allowing a clear-cut phenotypical characterization of major interest for research purposes. Sleepier patients on the multiple sleep latency test were also the more severe in terms of extended sleep. Ann Neurol 2018;83:235-247.
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Hipersonia Idiopática/diagnóstico , Adulto , Área Sob a Curva , Feminino , Humanos , Masculino , Curva ROC , Sensibilidade e Especificidade , Sono/fisiologia , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To assess video-polysomnographic (vPSG) criteria and their cutoff values for the diagnosis of disorders of arousal (DOAs; sleepwalking, sleep terror). METHODS: One hundred sixty adult patients with DOAs and 50 sex- and age-matched healthy participants underwent a clinical evaluation and vPSG assessment to quantify slow wave sleep (SWS) interruptions (SWS fragmentation index, slow/mixed and fast arousal ratios, and indexes per hour) and the associated behaviors. First, a case-control analysis was performed in 100 patients and the 50 controls to define the optimal cutoff values using receiver operating characteristic curves. Their sensitivity was then assessed in the other 60 patients with DOAs. RESULTS: The SWS fragmentation index and the mixed, slow, and slow/mixed arousal indexes and ratios were higher in patients with DOAs than controls. The highest area under the curve (AUC) values were obtained for the SWS fragmentation and slow/mixed arousal indexes (AUC = 0.88 and 0.90, respectively). The SWS fragmentation index cutoff value of 6.8/h reached a sensitivity of 79% and a specificity of 82%. The slow/mixed arousal index had a sensitivity of 94% for the 2.5/h cutoff, and 100% specificity for 6/h. Both parameters showed good interrater agreement, and their sensitivities were confirmed in the second group of patients. Combining electroencephalographic parameters and video-based behavioral analyses increased the correct classification rate up to 91.3%. INTERPRETATION: Frequent slow/mixed arousals in SWS and complex behaviors during vPSG are strongly associated with DOAs, and could be promising biomarkers for the diagnosis of non-rapid eye movement parasomnias. Ann Neurol 2018;83:341-351.
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Terrores Noturnos/diagnóstico , Polissonografia/métodos , Sonambulismo/diagnóstico , Adolescente , Adulto , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Gravação em Vídeo/métodos , Adulto JovemRESUMO
BACKGROUND: To better understand the role of iron homeostasis dysregulation in restless legs syndrome, we compared serum hepcidin and ferritin levels in drug-free patients with primary restless legs syndrome and healthy controls and studied the relationship between hepcidin level and restless legs syndrome severity. METHODS: One hundred and eight drug-free patients with primary restless legs syndrome (65 women; median age, 61.5 years) and 45 controls (28 women; median age, 53.9 years) were enrolled. Inclusion criteria were: normal ferritin level (>50 ng/mL) and absence of iron disorders, chronic renal or liver failure, and inflammatory or neurological diseases. Each subject underwent a thorough clinical examination and a polysomnography assessment. Serum hepcidin-25 was quantified using a validated mass spectrometry method. Restless legs syndrome severity was evaluated according to the International Restless Legs Syndrome Study Group. RESULTS: Despite no group difference between normal ferritin levels and demographic features, serum hepcidin level and hepcidin/ferritin ratio were higher in patients than in controls. Hepcidin level and hepcidin/ferritin ratio, but not ferritin level, were positively correlated with periodic leg movements during sleep and wakefulness in the whole sample. Hepcidin level seem to be associated with restless legs syndrome severity in a complex U-shaped relationship, without relationship with age at restless legs syndrome onset, positive family history, sleep and depressive symptoms, genetic background, and polysomnographic measurements. No relationship was found between ferritin level and restless legs syndrome severity. CONCLUSION: In drug-free patients with primary restless legs syndrome, hepcidin level is higher than in controls and may be associated with restless legs syndrome clinical severity. This result emphasizes the complex peripheral iron metabolism deregulation in restless legs syndrome, opening potential perspectives for a personalized approach with a hepcidin antagonist. © 2018 International Parkinson and Movement Disorder Society.
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Hepcidinas/sangue , Síndrome das Pernas Inquietas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estatísticas não Paramétricas , Espectrometria de Massas em TandemRESUMO
Somnambulism, also called sleepwalking, classified as a non-rapid eye movement sleep parasomnia, encompasses a range of abnormal paroxysmal behaviors, leading to sleepwalking in dissociated sleep in an altered state of consciousness with impaired judgment and configuring a kind of hierarchical continuum with confusional arousal and night terror. Despite being generally regarded as a benign condition, its potential severity entails social, personal, and even forensic consequences. This comprehensive review provides an overview on the current state of knowledge, elucidating the phenomenon of somnambulism and encompassing its clinical manifestations and diagnostic approaches.
Assuntos
Terrores Noturnos , Parassonias , Transtornos do Despertar do Sono , Sonambulismo , Humanos , Sonambulismo/diagnóstico , Sonambulismo/terapia , Terrores Noturnos/diagnóstico , Parassonias/diagnóstico , Transtornos do Despertar do Sono/diagnóstico , SonoRESUMO
STUDY OBJECTIVES: Narcolepsy type 2 (NT2) is an understudied central disorder of hypersomnolence sharing some similarities with narcolepsy type 1 and idiopathic hypersomnia (IH). We aimed: (1) to assess systematically the symptoms in patients with NT2, with self-reported questionnaires: Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), and (2) to evaluate the responsiveness of these scales to treatment. METHODS: One hundred and nine patients with NT2 (31.4â ±â 12.2 years old, 47 untreated) diagnosed according to ICSD-3 were selected in a Reference Center for Narcolepsy. They all completed the ESS, subgroups completed the modified NSS (NSS-2, without cataplexy items) (nâ =â 95) and IHSS (nâ =â 76). Some patients completed the scales twice (before/during treatment): 42 ESS, 26 NSS-2, and 30 IHSS. RESULTS: Based on NSS-2, all untreated patients had sleepiness, 58% disrupted nocturnal sleep, 40% hallucinations, and 28% sleep paralysis. On IHSS, 76% reported a prolonged nocturnal sleep, and 83% sleep inertia. In the independent sample, ESS and NSS-2 scores were lower in treated patients, with same trend for IHSS scores. After treatment, ESS, NSS-2, and IHSS total scores were lower, with a mean difference of 3.7â ±â 4.1, 5.3â ±â 6.7, and 4.1â ±â 6.2, respectively. The minimum clinically important difference between untreated and treated patients were 2.1 for ESS, 3.3 for NSS-2, and 3.1 for IHSS. After treatment, 61.9% of patients decreased their ESSâ >â 2 points, 61.5% their NSS-2â >â 3 points, and 53.3% their IHSSâ >â 3 points. CONCLUSIONS: NSS-2 and IHSS correctly quantified symptoms' severity and consequences in NT2, with good performances to objectify response to medications. These tools are useful for monitoring and optimizing NT2 management, and for use in clinical trials.
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Hipersonia Idiopática , Narcolepsia , Índice de Gravidade de Doença , Humanos , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Narcolepsia/tratamento farmacológico , Masculino , Feminino , Adulto , Hipersonia Idiopática/diagnóstico , Hipersonia Idiopática/fisiopatologia , Inquéritos e Questionários , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Alucinações/diagnóstico , Alucinações/fisiopatologia , Pessoa de Meia-Idade , Modafinila/uso terapêutico , Adulto Jovem , Paralisia do Sono/diagnóstico , Paralisia do Sono/fisiopatologia , Autorrelato , Promotores da Vigília/uso terapêuticoRESUMO
OBJECTIVES: Kleine-Levin syndrome (KLS) is a rare recurrent hypersomnolence disorder associated with cognitive and behavioral disturbances, of unknown origin, but inflammatory mechanisms could be involved. We aimed to explore in vivo microglia activation using [18F]DPA-714 PET imaging in patients with KLS compared with controls, and during symptomatic vs asymptomatic periods. METHODS: Patients with KLS and controls underwent a standardized clinical evaluation and PET imaging, using a radiolabeled ligand specific to the 18 kDa translocator protein. Images were processed on the PMOD (peripheral module) interface using a standard uptake value (SUV). Five regions of interest (ROIs) were analyzed: hypothalamus, thalamus, frontal area, cerebellum, and whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake. RESULTS: Images of 17 consecutive patients with KLS (7 during episodes, 10 out of episodes) and 14 controls were analyzed. We found no SUV/SUVr difference between KLS and controls, between patients in and out episodes in all ROIs, and no correlation between SUVr and episode duration at the time of PET scan. No association was found between SUVr and sex, disease duration, or orexin levels. DISCUSSION: Our findings do not support the presence of neuroinflammation in KLS. Further research is needed to identify relevant biomarkers in KLS.
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Síndrome de Kleine-Levin , Microglia , Tomografia por Emissão de Pósitrons , Humanos , Síndrome de Kleine-Levin/diagnóstico por imagem , Masculino , Feminino , Microglia/metabolismo , Adulto , Adulto Jovem , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: Narcolepsy type 1 (NT1) is due to the loss of hypothalamic neurons that produce orexin (ORX), by a suspected immune-mediated process. Rare postmortem studies are available and failed to detect any inflammation in the hypothalamic region, but these brains were collected years after the first symptoms. In vivo studies close to disease onset are lacking. We aimed to explore microglia density in the hypothalamus and thalamus in NT1 compared with controls using [18F]DPA-714 PET and to study in NT1 the relationships between microglia density in the hypothalamus and in other regions of interest (ROIs) with disease duration, severity, and ORX levels. METHODS: Patients with NT1 and controls underwent a standardized clinical evaluation and [18F]DPA-714 PET imaging using a radiolabeled ligand specific to the 18 kDa translocator protein (TSPO). TSPO genotyping determined receptor affinity. Images were processed on peripheral module interface using standard uptake value (SUV) on ROIs: hypothalamus, thalamus, frontal area, cerebellum, and the whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake. RESULTS: A total of 41 patients with NT1 (21 adults, 20 children, 10 with recent disease onset <1 year) and 35 controls were included, with no significant difference between groups for [18F]DPA-714 binding (SUV/SUVr) in the hypothalamus and thalamus. Unexpectedly, significantly lower SUVr in the whole brain was found in NT1 compared with controls (0.97 ± 0.06 vs 1.08 ± 0.22, p = 0.04). The same finding between NT1 and controls in the whole brain was observed in those with high or mixed TSPO affinity (p = 0.03 and p = 0.04). Similar trend was observed in the frontal area in NT1 (0.96 ± 0.09 vs 1.09 ± 0.25, p = 0.05). In NT1, no association was found between SUVr in different ROIs and age, disease duration, severity, or ORX levels. DISCUSSION: We found no evidence of in vivo increased microglia density in NT1 compared with controls, even close to disease onset, and even unexpectedly a decrease in the whole brain of these patients. These findings do not support the presence of neuroinflammation in the destruction process of ORX neurons. TRIAL REGISTRATION INFORMATION: ClinicalTrials.org NCT03754348.
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Microglia , Narcolepsia , Orexinas , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Feminino , Microglia/metabolismo , Narcolepsia/metabolismo , Narcolepsia/genética , Narcolepsia/diagnóstico por imagem , Orexinas/metabolismo , Adulto , Adulto Jovem , Tálamo/metabolismo , Tálamo/diagnóstico por imagem , Pirazóis , Hipotálamo/metabolismo , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Índice de Gravidade de Doença , Pessoa de Meia-Idade , Pirimidinas , Adolescente , Receptores de GABA/metabolismo , Receptores de GABA/genéticaRESUMO
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome das Pernas Inquietas , Síndrome das Pernas Inquietas/genética , Humanos , Fatores de Risco , Feminino , Masculino , Polimorfismo de Nucleotídeo Único , Análise da Randomização Mendeliana , Aprendizado de MáquinaRESUMO
STUDY OBJECTIVES: To assess the performances of alternative measures of the multiple sleep latency test (MSLT) to identify hypocretin-deficiency in patients with a complaint of hypersomnolence, including patients with narcolepsy. METHODS: MSLT parameters from 374 drug-free patients with hypersomnolence, with complete clinical and polysomnographic (PSG) assessment and cerebrospinal hypocretin-1 measurement were collected. Conventional (sleep latency, number of sleep onset REM-SOREM-periods) and alternative (sleep duration, REM sleep latency and duration, sleep stage transitions) MSLT measures were compared as function of hypocretin-1 levels (≤110 vsâ >â 110 pg/mL). We performed receiver-operating characteristics analyses to determine the best thresholds of MSLT parameters to identify hypocretin-deficiency in the global population and in subgroups of patients with narcolepsy (i.e. typical cataplexy and/or positive PSG/MSLT criteria, nâ =â 223). RESULTS: Patients with hypocretin-deficiency had shorter mean sleep and REM sleep latencies, longer mean sleep and REM sleep durations and more direct REM sleep transitions during the MSLT. The current standards of MSLT/PSG criteria identified hypocretin-deficient patients with a sensitivity of 0.87 and a specificity of 0.69, and 0.81/0.99 when combined with cataplexy. A mean REM sleep durationâ ≥â 4.1 min best identified hypocretin-deficiency in patients with hypersomnolence (AUCâ =â 0.932, sensitivity 0.87, specificity 0.86) andâ ≥â 5.7 min in patients with narcolepsy (AUCâ =â 0.832, sensitivity 0.77, specificity 0.82). CONCLUSION: Compared to the current neurophysiological standard criteria, alternative MSLT parameters would better identify hypocretin-deficiency among patients with hypersomnolence and those with narcolepsy. We highlighted daytime REM sleep duration as a relevant neurophysiological biomarker of hypocretin-deficiency to be used in clinical and research settings.
Assuntos
Cataplexia , Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Humanos , Orexinas , Sono REM/fisiologia , Cataplexia/diagnóstico , Latência do Sono , Duração do Sono , Narcolepsia/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/diagnósticoRESUMO
STUDY OBJECTIVES: To assess the responsiveness of the Idiopathic Hypersomnia Severity Scale (IHSS) to medications and estimate the minimum clinically important difference, to report clinically relevant score ranges, and to confirm its psychometric properties and whether items need to be weighted in drug-free and treated patients with idiopathic hypersomnia (IH). METHODS: Two-hundred twenty-six (166 drug-free and 60 treated) patients with IH (cross-sectional sample) completed the 14-item IHSS to quantify the severity of the 3 major IH symptoms (excessive daytime sleepiness, prolonged nighttime sleep, and sleep inertia) and consequences; 77 untreated patients were evaluated again after treatment (longitudinal sample). Patients filled in the Epworth Sleepiness Scale, Beck Depression Inventory II, and European Quality of Life questionnaires. RESULTS: The IHSS confirmed adequate psychometric properties with a factor analysis indicating a 3-component solution. IHSS total score was lower in treated than untreated patients, with a mean difference of 4-5 points in the cross-sectional and longitudinal samples. Distribution-based methods were used to estimate that 4 points represented the minimum clinically important difference. Four severity levels were defined with between-group differences related to treatment. The probability of having severe sleepiness, depressive symptoms, and low quality of life increased with the severity level. Our results showed that IHSS item-weighting was not necessary. CONCLUSIONS: The IHSS is a valid and reliable tool to quantify IH symptoms, with 4 severity score levels of clinical importance. The IHSS has adequate psychometric properties and can detect symptom changes after treatment. These findings should stimulate its use in clinical settings and in research studies. CITATION: Rassu AL, Evangelista E, Barateau L, et al. Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and their consequences in idiopathic hypersomnia. J Clin Sleep Med. 2022;18(2):617-629.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Estudos Transversais , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Humanos , Hipersonia Idiopática/diagnóstico , Narcolepsia/diagnóstico , Qualidade de VidaRESUMO
STUDY OBJECTIVES: Despite its high frequency in narcolepsy type 1(NT1), disrupted nocturnal sleep (DNS) remains understudied, and its determinants have been poorly assessed. We aimed to determine the clinical, polysomnographic (PSG), and biological variables associated with DNS in a large sample of patients with NT1, and to evaluate the effect of medication on DNS and its severity. METHODS: Two hundred and forty-eight consecutive adult patients with NT1 (145 untreated, 103 treated) were included at the National Reference Center for Narcolepsy-France; 51 drug-free patients were reevaluated during treatment. DNS, assessed with the Narcolepsy Severity Scale (NSS), was categorized in four levels (absent, mild, moderate, severe). Clinical characteristics, validated questionnaires, PSG parameters (sleep fragmentation markers: sleep (SB) and wake bouts (WB), transitions), objective sleepiness, and orexin-A levels were assessed. RESULTS: In drug-free patients, DNS severity was associated with higher scores on NSS, higher sleepiness, anxiety/depressive symptoms, autonomic dysfunction, worse quality of life (QoL). Patients with moderate/severe DNS (59%) had increased sleep onset REM periods, lower sleep efficiency, longer wake after sleep onset, more N1, SB, WB, sleep instability, transitions. In treated patients, DNS was associated with the same clinical data, and antidepressant use; but only with longer REM sleep latency on PSG. During treatment, sleepiness, NSS scores, depressive symptoms decreased, as well as total sleep time, WB, SB, transitions. DNS improved in 55% of patients, without predictors except more baseline anxiety. CONCLUSION: DNS complaint is frequent in NT1, associated with disease severity based on NSS, several PSG parameters, and objective sleepiness in untreated and treated conditions. DNS improves with treatment. We advocate the systematic assessment of this symptom and its inclusion in NT1 management strategy.
Assuntos
Narcolepsia , Qualidade de Vida , Adulto , Humanos , Narcolepsia/complicações , Narcolepsia/diagnóstico , Narcolepsia/tratamento farmacológico , Polissonografia , Sono , SonolênciaRESUMO
STUDY OBJECTIVES: To describe the phenotype of narcolepsy with intermediate cerebrospinal fluid hypocretin-1 levels (CSF hcrt-1). METHODS: From 1600 consecutive patients with narcolepsy from Bologna and Montpellier sleep centers, we selected patients with intermediate CSF hcrt-1 levels (110-200 pg/mL). Clinical, neurophysiological, and biological data were contrasted for the presence of cataplexy, human leukocyte haplotype (HLA)-DQB1*06:02, and median CSF hcrt-1 levels (149.34 pg/mL). RESULTS: Forty-five (55% males, aged 35 ± 17 years) patients (2.8% of all cases) were included. Thirty-three (73%) were HLA-DQB1*06:02, 29 (64%) reported cataplexy (21, 72.4% with typical features), and 5 (11%) had presumed secondary etiology. Cataplexy was associated with other core narcolepsy symptoms, increased sleep onset rapid eye movement periods, and nocturnal sleep disruption. Cataplexy and irrepressible daytime sleep were more frequent in HLA-DQB1*06:02 positive patients. Lower CSF hcrt-1 levels were associated with hallucinations. CONCLUSIONS: Narcolepsy with intermediate CSF hcrt-1 level is a rare condition with heterogeneous phenotype. HLA-DQB1*06:02 and lower CSF hcrt-1 were associated with typical narcolepsy features, calling for future research to distinguish incomplete from secondary narcolepsy forms.
Assuntos
Cataplexia , Narcolepsia , Orexinas/líquido cefalorraquidiano , Adolescente , Adulto , Cataplexia/diagnóstico , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: To explore the first coronavirus disease 2019 (COVID-19) lockdown effect on sleep symptoms in patients with narcolepsy, idiopathic hypersomnia (IH), and restless legs syndrome (RLS). METHODS: Between March and May 2020, a sample of adult patients regularly followed up in a Reference Hospital Sleep Unit (299 with narcolepsy, 260 with IH, and 254 with RLS) was offered an online survey assessing their sleep-wake habits, daily activities, medication intake, and validated scales: International RLS Study Group questionnaire, Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Beck Depression Inventory-II, and European Quality of Life (QoL) scale. The survey was proposed once, and the questions were answered for the prelockdown (recall of the month before the confinement) and the lockdown (time of study) periods. RESULTS: Overall, 331 patients completed the survey (response rate 40.7%): 102 with narcolepsy, 81 with IH, and 148 with RLS. All patients reported later bedtimes, with reduced differences for time in bed (TIB) and total sleep time (TST) over 24 hours between weekdays and weekends. Patients with narcolepsy spent more TIB and increased TST overnight, with more daytime napping. They had more awakenings, higher ESS scores, lower QoL, and no NSS changes. Patients with IH also increased their TIB, TST overnight and 24 hours on weekdays. Nocturnal sleep latency and the number of awakenings increased but with no change in ESS, QoL, and IHSS scores. Patients with RLS reported longer nocturnal sleep latency, more awakenings, more naps, decreased TIB, and TST overnight. RLS severity increased while QoL decreased. A significant portion of patients reported disease worsening during the lockdown (narcolepsy: 39.4%, IH: 43.6%, and RLS: 32.8%), and some patients stopped or lowered their medication (narcolepsy: 22.5%, IH: 28%, and RLS: 9.5%). DISCUSSION: During the lockdown, all patients reported later bedtimes; those with narcolepsy and IH extended their sleep duration unlike patients with RLS. These changes were often associated with negative consequences on QoL. In the current context of recurrent COVID-19 waves, the recent development of teleconsultations should enable physicians to monitor patients with chronic sleep disorders more closely and to recommend optimized sleep schedules and duration, in order to prevent psychological problems and improve their QoL.
Assuntos
COVID-19 , Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Síndrome das Pernas Inquietas , Adulto , Controle de Doenças Transmissíveis , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Humanos , Narcolepsia/complicações , Narcolepsia/epidemiologia , Qualidade de Vida , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/epidemiologia , Índice de Gravidade de Doença , SonoRESUMO
STUDY OBJECTIVES: Sleep inertia is a frequent and disabling symptom in idiopathic hypersomnia (IH), but poorly defined and without objective measures. The study objective was to determine whether the psychomotor vigilance task (PVT) can reliably measure sleep inertia in patients with IH or other sleep disorders (non-IH). METHODS: A total of 62 (51 women, mean age: 27.7 ± 9.2) patients with IH and 140 (71 women, age: 33.3 ± 12.1) with non-IH (narcolepsy = 29, non-specified hypersomnolence [NSH] = 47, obstructive sleep apnea = 39, insomnia = 25) were included. Sleep inertia and sleep drunkenness in the last month (M-sleep inertia) and on PVT day (D-sleep inertia) were assessed with three items of the Idiopathic Hypersomnia Severity Scale (IHSS), in drug-free conditions. The PVT was performed four times (07:00 pm, 07:00 am, 07:30 am, and 11:00 am) and three metrics were used: lapses, mean 1/reaction time (RT), and slowest 10% 1/RT. RESULTS: Sleep inertia was more frequent in patients with IH than non-IH (56.5% and 43.6% with severe sleep inertia in the past month, including 24% and 12% with sleep drunkenness). Lapse number increase and slowest 10% 1/RT decrease, particularly at 07:00 am and 07:30 am, were proportional with M-sleep inertia severity, but regardless of sleep drunkenness and sleep disorders. Similar results were obtained when PVT results were compared in patients with/without D-sleep inertia, with the largest increase of the lapse number at 07:00 am and 07:30 am associated with severe sleep inertia and sleep drunkenness. CONCLUSIONS: PVT is a reliable and objective measure of sleep inertia that might be useful for its characterization, management, and follow-up in patients with IH.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Adolescente , Adulto , Feminino , Humanos , Hipersonia Idiopática/complicações , Hipersonia Idiopática/diagnóstico , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Sono , Vigília , Adulto JovemRESUMO
STUDY OBJECTIVES: Hypersomnolence, defined by excessive daytime sleepiness (EDS) or excessive quantity of sleep (EQS), has been associated with increased morbidity. The aim of this study was to determine the clinical and polysomnographic characteristics associated with EQS and EDS assessed objectively during extended polysomnography recording. METHODS: A total of 266 drug-free subjects (201 women; mean age: 26.5 years [16.08; 60.87]) underwent 32-h bed-rest polysomnography recording preceded by polysomnography and modified multiple sleep latency test (mMSLT). Participants were categorized according to their total sleep time (bed-rest TST ≥19 h, hypersomnia), objective EDS (mean sleep latency on MSLT ≤8 min), and self-reported EDS (Epworth sleepiness scale score >10) and EQS (≥9 h/24 h per week). RESULTS: Subjects with hypersomnia were often younger, with normal sleep architecture, high nighttime sleep efficiency, and severe objective EDS. No association with sex, body mass index, Epworth sleepiness scale, EQS, and depressive symptoms was detected. Subjects with objective EDS had less EQS, higher sleep efficiency, and increased hypersomnia. Discrepancies were observed between objective and self-reported measures of sleep duration and EDS. Finally, 71 subjects were identified who had objective hypersomnia and/or EDS, no medical and psychiatric conditions and normal polysomnography parameters, and therefore met the stringent criteria of idiopathic hypersomnia, an orphan disorder. CONCLUSIONS: Sleep duration and EDS should be quantified using self-reported and objective measures in a controlled procedure to differentiate long sleepers, patients with hypersomnia, and patients with idiopathic hypersomnia. This will help to better understand their biology, to identify specific biomarkers, and to assess related health outcomes.