BACKGROUND:Narcolepsy type 1 (NT1) is a sleep disorder characterized by excessive daytime sleepiness accompanied by cataplexy. Sleep disorders have been shown to affect the glymphatic system. This study aimed to evaluate changes in the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus (CP) volume in NT1 participants, and to further explore their clinical significance. METHODS:We prospectively enrolled participants diagnosed with NT1 based on cerebrospinal fluid hypocretin-1 concentration and multiple sleep latency tests at our hospital. All participants underwent MRI to allow analysis of the DTI-ALPS index and CP volume. We subsequently performed correlation analyses between the DTI-ALPS index, CP volume, and important clinical parameters, including the Epworth Sleepiness Scale (ESS) score, Narcolepsy Severity Scale (NSS) score, stage rapid eye movement sleep (REM) ratio, stage 1 non-REM (N1) ratio, stage 2 non-REM (N2) ratio, and stage 3 non-REM (N3) ratio, among the NT1 participants. Inter-group and correlation analyses of DTI-ALPS index and CP volume were performed using age, sex, body mass index, and lateral ventricle volume as covariates. RESULTS:This study enrolled 41 NT1 participants and 42 healthy controls (HC). The DTI-ALPS index of NT1 participants was significantly lower than HC (1.444 ± 0.119 vs.1.661 ± 0.135, P < 0.001), while the CP volume of NT1 participants was significantly larger than those of HC (0.831 ± 0.146 vs. 0.645 ± 0.137, P < 0.001). The DTI-ALPS index was negatively correlated with both the ESS (PFDR-corrected<0.001) and NSS scores (PFDR-corrected = 0.010), but positively correlated with the Stage N3 ratio (PFDR-corrected = 0.033). The CP volume of NT1 participants was positively correlated with ESS (PFDR-corrected = 0.047) and NSS scores (PFDR-corrected = 0.047), but negatively correlated with the stage N3 ratio (PFDR-corrected = 0.047). CONCLUSION:Our study suggests that the DTI-ALPS index was lower and CP volume was larger in NT1 participants. The DTI-ALPS index and CP volume in the NT1 participants were related to disease severity and sleep structure. These findings may provide new insights into the mechanisms underlying NT1.

Background: Symptoms of depression and anxiety are common complications of narcolepsy. Earlier studies have shown that narcolepsy type 1 (NT1) is an autoimmune inflammatory disease and symptoms of depression and anxiety are closely related to fluctuations in inflammatory cytokines. The objective of the current research was to investigate the potential correlation between cytokines and symptoms of depression and anxiety in patients with NT1. Methods: We collected demographic and clinical data and information on cytokine levels from 50 patients with NT1 and used Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) to assess the severity of depression and anxiety symptoms. Patients with SDS scores >= 53 points were defined as depressive narcolepsy type 1 (D-NT1) and those with SDS scores < 53 points as non-depressive narcolepsy type 1 (ND-NT1). Patients with SAS scores >= 50 points were defined as anxious narcolepsy type 1 (A-NT1) and those with SAS scores < 50 points as non-anxious narcolepsy type 1 (NA-NT1). A binary logistic regression model was employed to identify the influencing factors of depressive and anxiety symptoms. Results: Levels of IL-10 (p = 0.02), IL-4 (p = 0.049) and disease duration (p = 0.049) were decreased, while SAS scores (p < 0.001) and total sleep duration (p = 0.03) were increased in D-NT1 relative to ND-NT1 patients. ANT1 patients had higher SDS scores (p < 0.001) compared to NA-NT1 patients. Binary logistic regression analysis revealed associations of longer disease duration (OR=0.83; 95 % CI: 0.70-0.97) and increased IL-10 (OR=0.40; 95 % CI: 0.17-0.90) with reduced risk of depression and worsening anxiety (SAS score; OR=1.17; 95 % CI: 1.06-1.30) with increased risk of depression in patients with NT1. Consistently, worsening depression (SDS score; OR=1.22; 95% CI: 1.07-1.39) was correlated with increased risk of anxiety in the NT1 group. Conclusion: Our finding that higher IL-10 levels correlate with a lower risk of depression in NT1 patients provides a reference for further exploration of the pathophysiological mechanisms of depressive symptoms in NT1 patients.

Narcolepsy type 1 is attributed to a deficiency in cerebrospinal fluid orexin and is considered linked to autoimmunity. The levels of anti-Tribbles homolog 2 (TRIB2) autoantibodies are elevated in the sera of some patients with narcolepsy with cataplexy. Additionally, injecting mice with serum immunoglobulin from patients with narcolepsy with positive anti-TRIB2 antibodies can induce hypothalamic neuron loss and alterations in sleep patterns. Consequently, we hypothesized the existence of a potential association between anti-TRIB2 antibodies and narcolepsy. To test this possibility, we used cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs) to detect the presence of anti-TRIB2 antibodies in Chinese patients with narcolepsy. We included 68 patients with narcolepsy type 1, 39 patients with other central disorders of hypersomnolence, and 43 healthy controls. A CBA and a conventional ELISA were used to detect anti-TRIB2 antibody levels in patients’ sera. CBA was used to detect serum anti-TRIB2 antibodies in Chinese patients with narcolepsy, and the results were negative. However, when the ELISA was used, only 2 patients with narcolepsy type 1 had TRIB2 antibody titers higher than the mean titer plus 2 standard deviations of the healthy controls. In our study, ELISA identified TRIB2 autoantibodies in sera of patients with narcolepsy where CBA failed to demonstrate them. Contrary to our hypothesis, this intriguing finding deserves further research to elucidate the potential association between TRIB2 and narcolepsy type 1. Exploring the implications of TRIB2 autoantibodies in narcolepsy and disparate outcomes between ELISA and CBA could provide crucial insights.

Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography–tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis.

Type 1 narcolepsy is a rare central nervous system disorder that is believed to result from the interaction of environmental and genetic factors. Traumatic brain injury (TBI) is one of the most common causes of secondary narcolepsy. Currently, there are very few reports on post-TBI narcolepsy, and this patient is the first reported case of HLA-DQB1 *06:02-positive type 1 narcolepsy following TBI in China. The clinical data of this patient are retrospectively analyzed to improve the understanding of the diagnosis and pathogenesis of the disease among clinicians.