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1.
BMC Psychiatry ; 24(1): 252, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566068

RESUMO

BACKGROUND: Prior studies have identified a correlation between breakfast skipping and a heightened risk of mental health issues. This investigation aimed to employ a Two-Sample Mendelian Randomization (MR) approach to explore the potential causal links between breakfast skipping and various psychiatric, neurological disorders, cognitive performance, and frailty. METHODS: Utilizing data from genome-wide association studies within European demographics, this research scrutinized the association between breakfast habits and several neuropsychiatric conditions and physical health outcomes, including Alzheimer's disease (AD), Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), Major Depressive Disorder (MDD), Narcolepsy, Insomnia, cognitive performance, and frailty. In this MR analysis, the Inverse Variance Weighted (IVW) method was primarily utilized for evaluation. Outcomes were reported as Odds Ratios (OR) and regression coefficients (ß), and underwent validation through False Discovery Rate (FDR) corrections, thereby offering a rigorous evaluation of the effects of breakfast habits on both mental and physical health dimensions. RESULTS: Findings demonstrate a significant causal link between skipping breakfast and an increased risk of ADHD (OR = 2.74, 95%CI: 1.54-4.88, PFDR = 0.003) and MDD (OR = 1.7, 95%CI: 1.22-2.37, PFDR = 0.005). Conversely, no substantial causal associations were identified between breakfast skipping and AD, BD, narcolepsy, or insomnia (PFDR > 0.05). Moreover, a notable causal relationship was established between skipping breakfast and a reduction in cognitive performance (ß = -0.16, 95%CI: -0.29-0.04, PFDR = 0.024) and an increase in frailty (ß = 0.29, 95%CI: 0.12-0.45, PFDR = 0.003). CONCLUSION: The MR analysis reveals that skipping breakfast is associated with an increased risk of ADHD, MDD, decreased cognitive performance, and greater frailty, while showing no associations were found with AD, BD, narcolepsy, or insomnia. These findings warrant further investigation into the underlying mechanisms and emphasize the importance of regular breakfast consumption for mental and physical well-being.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Transtorno Depressivo Maior , Fragilidade , Narcolepsia , Distúrbios do Início e da Manutenção do Sono , Humanos , Desjejum , Estudo de Associação Genômica Ampla , Jejum Intermitente , Análise da Randomização Mendeliana
2.
Arq Neuropsiquiatr ; 82(6): 1-9, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565187

RESUMO

Narcolepsy is a primary disorder of the central nervous system resulting from genetic, environmental, and immunological interactions defined as excessive daytime sleepiness plus cataplexy, hallucinations, sleep paralysis, and sleep fragmentation. The pathophysiology is not entirely known, but the interaction among genetic predisposition, environmental exposition, and immune component with consequent hypocretin-1 deficiency is the model to explain narcolepsy type I. The mechanism of narcolepsy type II is less understood. There is a delay of over ten years for the diagnosis of narcolepsy around the world. Patients with narcolepsy have many comorbidities with a negative impact on quality of life. The treatment of narcolepsy must contain an educational approach for the family, coworkers, and patients. Scheduled naps and sleep hygiene are essential to minimize the dose of medications. Much progress has been seen in the pharmacological treatment of narcolepsy with new stimulants, different presentations of oxybate, and recent studies with orexin agonists. Narcolepsy is a rare disease that needs to be more understood and highlighted to avoid delayed diagnosis and severe disabilities in patients.


A narcolepsia é um distúrbio primário do sistema nervoso central resultante das interações genéticas, ambientais e imunológicas definidas como sonolência diurna excessiva mais cataplexia, alucinações, paralisia do sono e fragmentação do sono. A fisiopatologia não é completamente conhecida, mas a interação entre predisposição genética, exposição ambiental e componente imunológico com consequente deficiência de hipocretina-1 é o modelo para explicar a narcolepsia tipo I. O mecanismo da narcolepsia tipo II é menos compreendido. Há um atraso de mais de dez anos para o diagnóstico da narcolepsia em todo o mundo. Pacientes com narcolepsia apresentam muitas comorbidades com impacto negativo na qualidade de vida. O tratamento da narcolepsia deve conter uma abordagem educativa para a família, colegas de trabalho e pacientes. Cochilos programados e higiene do sono são importantes para minimizar a dose dos medicamentos. Muito progresso foi observado no tratamento farmacológico da narcolepsia com novos estimulantes, diferentes apresentações de oxibato e estudos recentes com agonistas de orexina. A narcolepsia é uma doença rara que precisa ser mais compreendida e destacada para evitar atrasos no diagnóstico e incapacidades graves nos pacientes.


Assuntos
Cataplexia , Narcolepsia , Neurologia , Humanos , Qualidade de Vida , Narcolepsia/tratamento farmacológico , Narcolepsia/genética , Narcolepsia/diagnóstico , Cataplexia/tratamento farmacológico , Cataplexia/genética , Cataplexia/diagnóstico , Sono
3.
PLoS One ; 19(3): e0297625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442093

RESUMO

Narcolepsy type 1 (NT1) is an enigmatic sleep disorder characterized by the selective loss of neurons producing orexin (also named hypocretin) in the lateral hypothalamus. Although NT1 is believed to be an autoimmune disease, the orexinergic neuron-specific antigens targeted by the pathogenic immune response remain elusive. In this study, we evaluated the differential binding capacity of various peptides to serum immunoglobin G from patients with NT1 and other hypersomnolence complaints (OHCs). These peptides were selected using an unbiased phage display technology or based on their significant presence in the serum of NT1 patients as identified from previous studies. Although the subtractive biopanning strategy successfully enriched phage clones with high reactivity against NT1 serum IgG, the 101 randomly selected individual phage clones could not differentiate the sera from NT1 and OHC. Compared to the OHC control group, serum from several NT1 patients exhibited increased reactivity to the 12-mer peptides derived from TRBV7, BCL-6, NRXN1, RXRG, HCRT, and RTN4 proteins, although not statistically significant. Collectively, employing both unbiased and targeted methodologies, we were unable to detect the presence of specific autoantibodies in our NT1 patient cohort. This further supports the hypothesis that the autoimmune response in NT1 patients likely stems primarily from T cell-mediated immunity rather than humoral immunity.


Assuntos
Doenças Autoimunes , Bacteriófagos , Narcolepsia , Humanos , Autoanticorpos , Peptídeos , Narcolepsia/diagnóstico
4.
Sleep Med ; 116: 62-70, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430792

RESUMO

INTRODUCTION: Understanding how persons with narcolepsy conceptualize symptoms, daily impact and illness experience is key to facilitating dialogue between patients and healthcare professionals. These concepts are usually explored from the perspective of healthcare professionals/researchers and rarely from the perspective of those with narcolepsy. METHODS: 127 self-reported persons with narcolepsy were recruited from an Australian patient support group. A short demographic survey was completed. All agreed to participate in a subsequent 1:1 semi-structured interview. Saturation was reached after 24 interviews (mean age = 33 years (SD 11) with 44% reporting cataplexy). A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. RESULTS: Participants perceived physical fatigue, sleepiness, and two separate experiences of 'falling asleep/sleep attacks' as distinct symptoms rather than a multidimensional construct (i.e. excessive daytime sleepiness). We also identified two experiences of cataplexy, one triggered by acute emotion and another by a stressor. Participants determined their narcolepsy to be 'well-managed' by the level of functional impairment rather than the frequency of any symptom. Almost all participants described experiencing anticipated stigma and internalized or 'self-' stigma, likely stemming from societal devaluation of sleep and the conflation of sleepiness with laziness. CONCLUSION: Descriptions of common symptoms often differed between participants and the existing literature. These differences likely impact patient-physician communication, with both parties utilizing the same terminology to communicate different concepts. The characterization of stigma in narcolepsy presents opportunities for future research exploring the impact and possible development of interventions to reduce the substantial psychological comorbidity in persons with narcolepsy.


Assuntos
Cataplexia , Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Humanos , Adulto , Cataplexia/diagnóstico , Sonolência , Austrália , Narcolepsia/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/diagnóstico
5.
Sleep Med ; 116: 81-89, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432031

RESUMO

OBJECTIVE: There was more than a 10-fold increase in the incidence of narcolepsy type 1 (NT1) after the H1N1 mass vaccination in 2009/2010 in several countries. NT1 is associated with loss and increase of cell groups in the hypothalamus which may be associated with secondary affected sub-cortical and cortical gray matter. We performed a case-control comparison of MRI-based global and sub-cortical volume and cortical thickness in post-H1N1 NT1 patients compared with controls. METHODS: We included 54 post-H1N1 NT1 patients (51 with confirmed hypocretin-deficiency; 48 H1N1-vaccinated with Pandemrix®; 39 females, mean age 21.8 ± 11.0 years) and 114 healthy controls (77 females, mean age 23.2 ± 9.0 years). 3T MRI brain scans were obtained, and the T1-weighted MRI data were processed using FreeSurfer. Group differences among three global, 10 sub-cortical volume measures and 34 cortical thickness measures for bilateral brain regions were tested using general linear models with permutation testing. RESULTS: Patients had significantly thinner brain cortex bilaterally in the temporal poles (Cohen's d = 0.68, p = 0.00080), entorhinal cortex (d = 0.60, p = 0.0018) and superior temporal gyrus (d = 0.60, p = 0.0020) compared to healthy controls. The analysis revealed no significant group differences for sub-cortical volumes. CONCLUSIONS: Post-H1N1(largely Pandemrix®-vaccinated) NT1 patients have significantly thinner cortex in temporal brain regions compared to controls. We speculate that this effect can be partly attributed to the hypothalamic neuronal change in NT1, including loss of function of the widely projecting hypocretin-producing neurons and secondary effects of the abnormal sleep-wake pattern in NT1 or could be specific for post-H1N1 (largely Pandemrix®-vaccinated) NT1 patients.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Narcolepsia , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Orexinas , Estudos de Casos e Controles , Narcolepsia/etiologia , Imageamento por Ressonância Magnética , Encéfalo
6.
Sleep Med ; 116: 105-114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442518

RESUMO

OBJECTIVE: It is hypothesized that narcolepsy type 1 (NT1) develops in genetically susceptible people who encounter environmental triggers leading to immune-mediated hypocretin-1 deficiency. The pathophysiologies of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remain unknown. The main aim of this study was to collect all reported immunological events before onset of a central disorder of hypersomnolence. METHODS: Medical records of 290 people with NT1, and 115 with NT2 or IH were retrospectively reviewed to extract infection and influenza vaccination history. Prevalence, distribution of immunological events, and time until hypersomnolence onset were compared between NT1 and the combined group of NT2 and IH. RESULTS: Immunological events were frequently reported before hypersomnolence disorder onset across groups. Flu and H1N1 influenza vaccination were more common in NT1, and Epstein-Barr virus and other respiratory and non-respiratory infections in NT2 and IH. Distributions of events were comparable between NT2 and IH. Rapid symptom onset within one month of infection was frequent across groups, especially after flu infection in NT1. Hypersomnolence disorder progression after an immunological event was reported in ten individuals. CONCLUSIONS: Our findings suggest a variety of immunological triggers potentially related to NT1, including H1N1 influenza infection or vaccination, infection with other flu types, and other respiratory and non-respiratory infections. Frequent reports of immunological events (other than those reported in NT1) immediately prior to the development of NT2 and IH support the specificity of triggers for NT1, and open important new research avenues into possible underlying immunological mechanisms in NT2 and IH.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Infecções por Vírus Epstein-Barr , Hipersonia Idiopática , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Narcolepsia , Humanos , Hipersonia Idiopática/diagnóstico , Estudos Retrospectivos , Influenza Humana/complicações , Influenza Humana/prevenção & controle , Herpesvirus Humano 4 , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Narcolepsia/diagnóstico
7.
Sleep Med ; 116: 138-146, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460419

RESUMO

OBJECTIVES: Physical activity (PA) is recommended as part of the management of narcolepsy type 1 (NT1). This study aimed at 1) characterizing PA in children and adolescents treated for NT1 using objective and subjective measurements, 2) evaluating how PA is associated with NT1 symptoms and comorbidities, and 3) evaluating the effects of an Adapted Physical Activity (APA) program on PA and clinical characteristics. PATIENTS/METHODS: Patients with NT1 from the National Reference Center of Narcolepsy (Lyon, France) were consecutively included in an APA intervention protocol. Narcolepsy symptoms and comorbidities were collected using standardized questionnaires and sustained attention was evaluated using the Bron-Lyon Attention Stability Test before and after the four-week APA intervention. PA was measured objectively using actigraphy throughout the study. RESULTS: Twenty-seven NT1 patients were included (median age 14.7 years [8.3-18.4], cataplexy 88.9%, obesity 37.0%). At baseline, 52.4% of the patients had satisfactory PA levels according to international recommendations. Patients with leisure-time PA (LTPA) showed higher quality of life than patients without. 45% of the patients increased PA during the intervention compared to baseline. These responsive patients had more depressive feelings and tended to have lower objective PA than non-responsive patients at baseline. No significant correlation was found between PA levels before and during the intervention and other clinical data. CONCLUSIONS: Most children with NT1 showed satisfying PA levels despite their daytime sleepiness. LTPA engagement was associated with higher quality of life. An APA intervention could be effective in children with narcolepsy, especially for those with depressive feelings.


Assuntos
Narcolepsia , Qualidade de Vida , Criança , Adolescente , Humanos , Narcolepsia/diagnóstico , Actigrafia/métodos , Obesidade/complicações , Exercício Físico
8.
Curr Biol ; 34(7): 1532-1540.e4, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38490200

RESUMO

The Hypocretin/Orexin signaling pathway suppresses sleep and promotes arousal, whereas the loss of Hypocretin/Orexin results in narcolepsy, including the involuntary loss of muscle tone (cataplexy).1 Here, we show that the South Asian fish species Chromobotia macracanthus exhibits a sleep-like state during which individuals stop swimming and rest on their side. Strikingly, we discovered that the Hypocretin/Orexin system is pseudogenized in C. macracanthus, but in contrast to Hypocretin-deficient mammals, C. macracanthus does not suffer from sudden behavioral arrests. Similarly, zebrafish mutations in hypocretin/orexin show no evident signs of cataplectic-like episodes. Notably, four additional species in the Botiidae family also lack a functional Hypocretin/Orexin system. These findings identify the first vertebrate family that does not rely on a functional Hypocretin/Orexin system for the regulation of sleep and arousal.


Assuntos
Cataplexia , Narcolepsia , Neuropeptídeos , Animais , Orexinas/genética , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Nível de Alerta/fisiologia , Mamíferos
9.
Pediatr Neurol ; 153: 56-64, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38320459

RESUMO

BACKGROUND: In 2010, the H1N1 Pandemrix vaccination campaign was followed by a sudden increase in narcolepsy type 1 (NT1). We investigated the brain white matter microstructure in children with onset of NT1 within two years after the Pandemrix vaccination. METHODS: We performed diffusion-weighted magnetic resonance imaging (MRI) on 19 children and adolescents with NT1 and 19 healthy controls. Imaging was performed at a median of 4 years after the diagnosis at a median age of 16 years. For the MRI, we used whole-brain tractography and tract-based spatial statistics (TBSS). We compared these results with medical records and questionnaire data. RESULTS: Narcoleptic children showed a global decrease in mean, axial, and radial diffusivity and an increase in planarity coefficient in the white matter TBSS skeleton and tractography. These differences were widespread, and there was an increased asymmetry of the mean diffusivity in children with NT1. The global microstructural metrics were reflected in behavior, and especially the axial diffusion levels correlated with anxiety and depression symptoms and social and behavioral problems. CONCLUSIONS: In pediatric patients with Pandemrix-associated NT1, several global changes in the brain white matter network skeleton were observed within five years after the onset of NT1. The degree of changes correlates with behavioral problems.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Narcolepsia , Substância Branca , Humanos , Adolescente , Criança , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Narcolepsia/diagnóstico por imagem
11.
PLoS One ; 19(2): e0288216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38319900

RESUMO

The 176-item Sleep Disorders Questionnaire (SDQ) was initially developed using canonical discriminant function analysis on 4 groups of sleep disorder patients, but it was never studied by factor analysis in its entirety. Several authors have criticized 2 of its subscales as being confounded with each other, and its narcolepsy scale as substantially over-diagnosing narcolepsy. This study describes its first exploratory factor analysis (EFA), the intent of which was to reassess item membership on the 4 existing subscales and to derive new scales to improve differential diagnosis between patient groups. It was also hoped that EFA could reduce the total number of questions, to increase speed of completion. The EFA was performed on the anonymized SDQ results from a retrospective review of the charts of 2131 persons from 7 sleep disorders clinics and research centers. Factors were assessed via scree plots and eigenvalues. The EFA identified four main factors: insomnia, daytime sleepiness, substance use, and sleep-disordered breathing. The insomnia factor had 3 subfactors: psychological symptoms of insomnia, subjective description of insomnia, and insomnia due to periodic limb movements. The sleepiness factor had two subfactors: daytime sleepiness and neurological symptoms of narcolepsy. The novel substance use factor was homogeneous, as was the sleep-disordered breathing factor. Importantly, the EFA reassigned items from the original SDQ's NAR, PSY, and PLM subscales to five of the new subscales. The Sleep Apnea (SA) subscale emerged mostly unchanged. The 7 resulting factors comprised only 66 items of the original 176-item SDQ. These results have allowed the creation of a new shorter questionnaire, to be called the SDQ-2. External validation of the SDQ-2 is currently underway. It will likely prove to be a superior differential diagnostic instrument for sleep disorders clinics, compared to the original SDQ.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Síndromes da Apneia do Sono , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Transtornos Relacionados ao Uso de Substâncias , Humanos , Polissonografia/métodos , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Inquéritos e Questionários , Narcolepsia/diagnóstico
12.
Brain Stimul ; 17(1): 83-88, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38184192

RESUMO

BACKGROUND AND OBJECTIVE: No study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. METHODS: In our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. RESULTS: Compared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. CONCLUSION: In this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.


Assuntos
Cataplexia , Epilepsia , Narcolepsia , Estimulação do Nervo Vago , Humanos , Cataplexia/terapia , Epilepsia/terapia , Narcolepsia/terapia , Estudos Prospectivos , Sonolência , Resultado do Tratamento , Nervo Vago/fisiologia , Adulto
13.
Sleep Med ; 115: 1-4, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286043

RESUMO

BACKGROUND: The gold standard investigation for central disorders of hypersomnolence is the Multiple Sleep Latency Test (MSLT). As the clinical features of these disorders of hypersomnolence evolve with time in children, clinicians may consider repeating a previously non-diagnostic MSLT. Currently there are no guidelines available regards the utility and timing of repeating paediatric MSLTs. METHODS: Retrospective review of children aged 3-18years with ≥2MSLTs between 2005 and 2022. Narcolepsy was defined as mean sleep latency (MSL) <8min with ≥2 sleep onset REM (SOREM); idiopathic hypersomnia (IH) was defined as MSL <8min with <2 SOREM. MSLTs not meeting these criteria were labelled non-diagnostic. RESULTS: 19 children (9 female) with initial non-diagnostic MSLT underwent repeat MSLT, with 6 proceeding to a 3rd MSLT following 2 non-diagnostic MSLTs. The 2nd MSLT resulted in diagnosis in 6/19 (32 %) (3 narcolepsy, 3 IH); and 2/6 (33 %) 3rd MSLT were diagnostic (2 IH). Median age at initial MSLT was 7.5y (range 3.4-17.8y), with repeat performed after median of 2.9y (range 0.9-8.2y), and 3rd after a further 1.9 years (range 1.2-4.2y). Mean change in MSL on repeat testing was -2min (range -15.5min to +4.9min, p = 0.18). Of the 8 diagnostic repeat MSLTs, in addition to the MSL falling below 8 min, 2 children also developed ≥2 SOREM that had not been previously present. CONCLUSIONS: A third of repeat MSLTs became diagnostic, suggesting repeat MSLT should be considered in childhood if clinical suspicion persists. Further work needs to address the ideal interval between MSLTs and diagnostic cut-points specific to the paediatric population.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Humanos , Feminino , Criança , Latência do Sono , Sono REM , Narcolepsia/diagnóstico , Polissonografia/métodos , Distúrbios do Sono por Sonolência Excessiva/diagnóstico
14.
J Clin Sleep Med ; 20(4): 643-651, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38217475

RESUMO

Brain fog is an undefined term describing a cluster of symptoms related to fatigue and impaired memory, attention, and concentration. Brain fog or brain fog-like symptoms have been reported in central disorders of hypersomnolence and in a range of seemingly unrelated disorders, including coronavirus disease 2019, major depressive disorder, multiple sclerosis, lupus, and celiac disease. This narrative review summarizes current evidence and proposes a consensus definition for brain fog. Brain fog is prevalent in narcolepsy and idiopathic hypersomnia, with more than three-quarters of patients with either disorder reporting this symptom in a registry study; it has also been reported as particularly difficult to treat in idiopathic hypersomnia. Studies directly evaluating brain fog are rare; tools for evaluating this symptom cluster typically are patient reports, with few objective measures validated in any disorder. Evaluating brain fog is further complicated by confounding symptoms, such as excessive daytime sleepiness, which is a hallmark of hypersomnolence disorders. No treatments specifically address brain fog. The paucity of literature, assessment tools, and medications for brain fog highlights the need for research leading to better disambiguation and treatment. Until a clear consensus definition is established, we propose brain fog in hypersomnia disorders be defined as a cognitive dysfunction that may or may not be linked with excessive sleepiness, related to an underlying neuronal dysfunction, which reduces concentration and impairs information processing, leading to a complaint of lack of clarity of mental thinking and awareness. CITATION: Rosenberg R, Thorpy MJ, Doghramji K, Morse AM. Brain fog in central disorders of hypersomnolence: a review. J Clin Sleep Med. 2024;20(4):643-651.


Assuntos
Transtorno Depressivo Maior , Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Humanos , Hipersonia Idiopática/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/etiologia , Narcolepsia/diagnóstico , Fadiga Mental
15.
Sleep ; 47(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38174762

RESUMO

STUDY OBJECTIVES: Narcolepsy type 1 (NT1), characterized by cataplexy and orexin deficiency, is a rare and frequently debilitating neurological disorder. It has been noted to have connections with the gut microbiota, yet the exact causal relationships remain unclear. METHODS: We conducted a comprehensive bidirectional Mendelian randomization (MR) study to rigorously investigate the causal links between the gut microbiota and NT1, utilizing genetic datasets from the MiBioGen consortium and FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was employed to obtain the primary MR estimates, supplemented by several alternative methods as well as sensitivity analyses including Cochran's Q, MR-Egger, MR pleiotropy residual sum and outlier, leave-one-out, and genetic colocalization. RESULTS: Our findings indicated that an increased relative abundance of five genera including Blautia (p = 4.47E-5), Collinsella (p = 0.036), Gordonibacter (p = 0.047), Hungatella (p = 0.015), and Lachnospiraceae UCG010 (p = 0.027) may be associated with a decreased risk of NT1. Conversely, an increased relative abundance of class Betaproteobacteria (p = 0.032), genus Alloprevotella (p = 0.009), and genus Ruminiclostridium6 (p = 0.029) may potentially heighten the risk of NT1. The onset of NT1 may lead to a decrease in the relative abundance of genus Eubacterium eligens group (p = 0.022), while a increase in the family Family XI (p = 0.009), genus Hungatella (p = 0.005), genus Prevotella (p = 0.013), and unknown genus id.2001 (p = 0.019). These findings remained robust under all sensitivity analyses. CONCLUSIONS: Our results offer robust evidence for the bidirectional causal links between particular gut microbial taxa and NT1, underscoring the significance of the microbiota-gut-brain axis in the pathological process of NT1.


Assuntos
Cataplexia , Microbioma Gastrointestinal , Narcolepsia , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Narcolepsia/genética , Estudo de Associação Genômica Ampla
16.
Pharmacol Res Perspect ; 12(1): e1161, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38174838

RESUMO

Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real-world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant-associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant-associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life-threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.


Assuntos
Narcolepsia , Farmacovigilância , Humanos , Estudos Retrospectivos , Narcolepsia/tratamento farmacológico , Piperidinas/efeitos adversos
17.
Neurology ; 102(1): e207815, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38165365

RESUMO

BACKGROUND AND OBJECTIVES: Narcolepsy type 1 (NT1) is still largely underdiagnosed or diagnosed too late in children. Difficulties in obtaining rapid and reliable diagnostic evaluations of the condition in clinical practice partially explain this problem. Predictors of NT1 include cataplexy and sleep-onset REM periods (SOREMPs), documented during nocturnal polysomnography (N-PSG) or through the multiple sleep latency test (MSLT), although low CSF hypocretin-1 (CSF hcrt-1) is the definitive biological disease marker. Obtaining reliable MSLT results is not always feasible in children; therefore, this study aimed to validate daytime continuous polysomnography (D-PSG) as an alternative diagnostic tool. METHODS: Two hundred consecutive patients aged younger than 18 years (112 with NT1; 25 with other hypersomnias, including narcolepsy type 2 and idiopathic hypersomnia; and 63 with subjective excessive daytime sleepiness) were randomly split into 2 groups: group 1 (n = 133) for the identification of diagnostic markers and group 2 (n = 67) for the validation of the detected markers. The D-PSG data collected included the number of spontaneous naps, total sleep time, and the number of daytime SOREMPs (d-SOREMP). D-PSG data were tested against CSF hcrt-1 deficiency (NT1 diagnosis) as the gold standard using receiver operating characteristic (ROC) curve analysis in group 1. ROC diagnostic performances of single and combined D-PSG parameters were tested in group 1 and validated in group 2. RESULTS: In group 1, the areas under the ROC curve (AUCs) were 0.91 (95% CI 0.86-0.96) for d-SOREMPs, 0.81 (95% CI 0.74-0.89) for the number of spontaneous naps, and 0.70 (95% CI 0.60-0.79) for total sleep time. A d-SOREMP count ≥1 (sensitivity of 95% and specificity of 72%), coupled with a diurnal total sleep time above 60 minutes (sensitivity of 89% and specificity of 91%), identified NT1 in group 1 with high reliability (area under the ROC curve of 0.93, 95% CI 0.88-0.97). These results were confirmed in the validation group with an AUC of 0.88 (95% CI 0.79-0.97). DISCUSSION: D-PSG recording is an easily performed, cost-effective, and reliable tool for identifying NT1 in children. Further studies should confirm its validity with home D-PSG monitoring. These alternative procedures could be used to confirm NT1 diagnosis and curtail diagnostic delay.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Humanos , Criança , Idoso , Diagnóstico Tardio , Polissonografia , Reprodutibilidade dos Testes , Narcolepsia/diagnóstico
18.
CMAJ ; 196(1): E17, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38228341
19.
Sleep Med ; 114: 272-278, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244465

RESUMO

Excessive daytime sleepiness (EDS) is common in childhood and is currently quantified using adult criteria on a multiple sleep latency test (MSLT). This study aimed to describe paediatric MSLT results, particularly focussing on a previously proposed alternative mean sleep latency (MSL) threshold for children of 12 min, and assess the impact of a 5th nap. We performed a retrospective analysis of MSLTs at a single paediatric centre from 2004 to 2021. Narcolepsy was defined as a mean sleep latency (MSL) ≤8min with ≥2 sleep onset REM (SOREM) periods. Idiopathic Hypersomnia (IH) was defined as a MSL ≤8min with <2 SOREMs. An ambiguous MSLT result was defined as a MSL 8-12min and/or ≥2 SOREM periods. Of 214 MSLTs [50 % female, median age 14.0y (range 3.3-20.1y)], narcolepsy was diagnosed in 48 (22 %), IH in 22 (10 %) and the result was ambiguous in 44 (21 %). Those with ambiguous MSLT results were older (15.6 vs 13.4y, p = 0.006) with a higher proportion of females (61 % vs 35 %, p = 0.01) in comparison to the narcolepsy group. A 5th nap was performed in 60 (28 %) of MSLTs and only changed the outcome in one case. In conclusion, MSLT results are borderline in 21 % of paediatric cases, suggesting that current adult diagnostic criteria may miss narcolepsy and IH in children. A 5th nap usually makes no difference or increases the MSL, suggesting that a four nap MSLT protocol could be used apart from rare cases where the result is borderline after the 4th nap.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Adolescente , Criança , Feminino , Humanos , Masculino , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Narcolepsia/diagnóstico , Polissonografia/métodos , Estudos Retrospectivos , Latência do Sono , Sono REM , Pré-Escolar , Adulto Jovem
20.
J Clin Neurosci ; 120: 102-106, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237487

RESUMO

BACKGROUND: Fatigue is a frequent complaint among patients with narcolepsy. Studies have shown that inflammatory cytokines are associated with fatigue in neurological disorders; however, this association has not been identified in patients with type 1 narcolepsy. The purpose of this study was to investigate the potential relationship between cytokines and fatigue in patients with type 1 narcolepsy. METHODS: We investigated the association between 12 inflammatory cytokines and fatigue in 49 patients with type 1 narcolepsy. The Multidimensional Fatigue Inventory-20 was used to assess the fatigue severity. The associations of fatigue were identified using Spearman and Pearson correlation analyses. A linear regression analysis model was used to adjust the confounding factors and evaluate the associations of fatigue. RESULTS: Correlation analysis showed that the plasma interleukin (IL)-2 level (r = 0.409, p = 0.004) was positively correlated with fatigue in patients with narcolepsy type 1. After adjusting for confounding factors, the linear regression model revealed a positive association between the IL-2 level (ß = 1.148, p = 0.04) and fatigue in individuals diagnosed with type 1 narcolepsy. CONCLUSION: IL-2 levels show a positive correlation with fatigue in type 1 narcolepsy, suggesting its potential role in the pathophysiology of fatigue.


Assuntos
Citocinas , Narcolepsia , Humanos , Interleucina-2 , Narcolepsia/complicações , Fadiga/complicações
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