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Independent Component Analysis and Graph Theoretical Analysis in Patients with narcolepsy

Neuroscience Bulletin 2019年第4期35卷 743-755页

作者： Fulong Xiao Chao Lu Dianjiang Zhao Qihong Zou Liyue Xu Jing Li Jun Zhang Fang Han Sleep Medicine Center Department of Respiratory and Critical Care Medicine Peking University People's Hospital Beijing 100044 China Department of Radiology Peking University International Hospital Beijing 102206 China Center for MRI Research Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China PKU-UPenn Sleep Center Peking University International Hospital Beijing 102206 China Department of Neurology Peking University People's Hospital Beijing 100044 China

The present study was aimed to evaluate restingstate functional connectivity and topological properties of brain networks in narcolepsy patients compared with healthy controls.Resting-state fMRI was performed in 26 adult narcolepsy patients and 30 matched healthy controls.MRI data were first analyzed by group independent component analysis,then a graph theoretical method was applied to evaluate the topological properties in the whole brain.Small-world network parameters and nodal topological properties were measured.Altered topological properties in brain areas between groups were selected as regionof-interest seeds,then the functional connectivity among these seeds was compared between groups.Partial correlation analysis was performed to evaluate the relationship between the severity of sleepiness and functional connectivity or topological properties in the narcolepsy patients.Twenty-one independent components out of 48 were obtained.Compared with healthy controls,the narcolepsy patients exhibited significantly decreased functional connectivity within the executive and salience networks,along with increased functional connectivity in the bilateral frontal lobes within the executive network.There were no differences in small-world network properties between patients and controls.The altered brain areas in nodal topological properties between groups were mainly in the inferior frontal cortex,basal ganglia,anterior cingulate,sensory cortex,supplementary motor cortex,and visual cortex.In the partial correlation analysis,nodal topological properties in the putamen,anterior cingulate,and sensory cortex as well as functional connectivity between these regions were correlated with the severity of sleepiness(sleep latency,REM sleep latency,and Epworth sleepiness score)among narcolepsy patients.Altered connectivity within the executive and salience networks was found in narcolepsy patients.Functional connection changes between the left frontal cortex and left caudate nucleus may be one of the parameters describing the sev

关键词： narcolepsy Functional connectivity Independent component analysis Graph theory

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Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1

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Chinese Medical Journal 2019年第15期132卷 1796-1801页

作者： Hui Ouyang Fang Han Ze-Chen Zhou Qi-Wen Zheng Yang-Yang Wang Jun Zhang Department of Clinical Neurology Peking University People's Hospital Beijing 100044 China Department of Clinical Pulmonology Peking University People's Hospital Beijing 100044 China Department of Epidemiology and Biostatistics School of Public Health Peking University Health Science Center Beijing 100191 China

Background:Recent genome-wide association studies have identified an important role of T-cell receptor α(TRA) gene in the development of narcolepsy type 1.However,the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear.This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy.Methods:Totally,903 patients with narcolepsy type 1 were included in the study.Patients were divided into different groups according to their symptoms.First,13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy.We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy.Further,we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model.Results:According to the results of the logistic regression,TRA haplotypes TG and CT were significantly associated with auditory hallucination,with odds ratios of 1.235 (95% confidence interval [CI],1.012-1.507) and 1.236 (95% CI,1.012-1.511),respectively (P narcolepsy type 1.However,further studies are needed to confirm our results and explore the underlying mechanisms.

关键词： narcolepsy T-cell receptor α gene Symptomatic subtype Haplotype Precision medicine

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Ventricular Tachycardia during Treatment with Modafinil for narcolepsy: A Case Report

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International Journal of Clinical Medicine 2012年第6期3卷 513-517页

作者： Heleen Binnenmars Herman H. D. Idzerda Hanno L. Tan Gerard C. M. Linssen Department of Cardiology Academic Medical Center Amsterdam The Netherlands Department of Cardiology Hospital Group Twente Almelo The Netherlands

Pharmacological treatment of narcolepsy is complex. We reported a case of recurrent episodes of polymorphic ventricular tachycardia attributed to the use of modafinil, a recently approved wake-promoting agent for narcolepsy and shift work sleep disorder. Modafinil is also approved as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. While the exact mechanism of action for modafinil is not known, central dopamine receptors seem to play an essential role. Adverse influences on the electrocardiogram (ECG) or drug-related cardiac arrhythmias are rarely reported, but are considered as clinically important.

关键词： Modafinil narcolepsy Ventricular Tachycardia

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Zolpidem-Induced narcolepsy, Faint, Seizure or Coma? A Case Report

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Case Reports in Clinical Medicine 2017年第2期6卷 31-35页

作者： Abdolhamid Parsa Amir Mohammadkhan Mohammad Babaeian School of Pharmacy Shahid Beheshti University of Medical Sciences Tehran Iran

Zolpidem, as an imidazopyridine agent, is a widely prescribed drug among practitioners for short-term treatment of insomnia. Nevertheless, there have been a number of cases associated with the adverse effects of the stated drug recently. Many cases of serious complications induced by high dose of zolpidem have been reported. Further to the existing reports of adverse reactions to zolpidem, throughout the current manuscript, another case of zolpidem-induced loss of consciousness is going to be presented. The case had taken 100 mg of zolpidem and afterwards, went into an unknown status of narcolepsy, faint, seizure or transient coma. Overdosing zolpidem and being affected by its central effects, he performed risky actions such as cooking by a gas oven and eating meal while intoxicated. The current case suggests that zolpidem overdose might contribute to loss of consciousness and exhibition of high-risk behaviors.

关键词： Zolpidem Eating Behavior Faint narcolepsy Seizure Coma

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Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction

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Cellular & Molecular Immunology 2018年第6期15卷 586-594页

作者： Yahel Segal Yehuda Shoenfeld Department of Medicine B Zabludowicz Center for Autoimmune DiseasesSheba Medical CenterTel-Hashomeraffiliated with the Sackler Faculty of MedicineTel Aviv UniversityRamat Gan 52621Israel Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases Sackler Faculty of MedicineTel Aviv UniversityRamat GanIsrael

Since the early 1800s vaccines have saved numerous lives by preventing lethal infections.However,during the past two decades,there has been growing awareness of possible adverse events associated with vaccinations,cultivating heated debates and leading to significant fluctuations in vaccination rates.It is therefore pertinent for the scientific community to seriously address public concern of adverse effects of vaccines to regain public trust in these important medical interventions.Such adverse reactions to vaccines may be viewed as a result of the interaction between susceptibility of the vaccinated subject and various vaccine components.Among the implicated mechanisms for these reactions is molecular mimicry.Molecular mimicry refers to a significant similarity between certain pathogenic elements contained in the vaccine and specific human proteins.This similarity may lead to immune crossreactivity,wherein the reaction of the immune system towards the pathogenic antigens may harm the similar human proteins,essentially causing autoimmune disease.In this review,we address the concept of molecular mimicry and its application in explaining post vaccination autoimmune phenomena.We further review the principal examples of the influenza,hepatitis B,and human papilloma virus vaccines,all suspected to induce autoimmunity via molecular mimicry.Finally,we refer to possible implications on the potential future development of better,safer vaccines.

关键词： autoimmunity Guillain-Barre syndrome human papilloma virus influenza molecular mimicry narcolepsy systemic lupus erythematosus vaccines

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Physiology of gangliosides and the role of antiganglioside antibodies in human diseases

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Cellular & Molecular Immunology 2020年第4期17卷 313-322页

作者： Gianni Cutillo Anna-Helena Saariaho Seppo Meri Translational Immunology Research Program and the Department of Bacteriology and Immunology University of HelsinkiHelsinkiFinland Humanitas University MilanRozzanoItaly Helsinki University Hospital Laboratory(HUSLAB) HelsinkiFinland

Gangliosides are structurally and functionally polymorphic sialic acid containing glycosphingolipids that are widely distributed in the human body.They play important roles in protecting us against immune attacks,yet they can become targets for autoimmunity and act as receptors for microbes,like the influenza viruses,and toxins,such as the cholera toxin.The expression patterns of gangliosides vary in different tissues,during different life periods,as well as in different animals.Antibodies against gangliosides(AGA)can target immune attack e.g.,against neuronal cells and neutralize their complement inhibitory activity.AGAs are important especially in acquired demyelinating immune-mediated neuropathies,like Guillain–Barrésyndrome(GBS)and its variant,the Miller–Fisher syndrome(MFS).They can emerge in response to different microbial agents and immunological insults.Thereby,they can be involved in a variety of diseases.In addition,antibodies against GM3 were found in the sera of patients vaccinated with Pandemrix®,who developed secondary narcolepsy,strongly supporting the autoimmune etiology of the disease.

关键词： ganglioside Guillain-Barre syndrome complement narcolepsy sialic acid

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Reduced Cataplexy Symptoms While on Suboxone: A Case Report

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Journal of Behavioral and Brain Science 2022年第11期12卷 548-551页

作者： Nathan B. Omari Ngugi M. Kinyungu University of Houston-Downtown Houston USA ITAV Pain Management Donald and Barbara Zucker School of Medicine at Hofstra/Northwell New York USA

Background: narcolepsy type 1 is a sleep disorder characterized by excessive sleepiness along with cataplexy and/or hypocretin deficiency. We present a case of narcolepsy type 1 in which the cataplexy symptoms were reduced while on suboxone. Aim: This case report aims to note the reduction of cataplexy symptoms with suboxone. Case Presentation: A 39-year-old female patient with narcolepsy type 1 was referred to our pain clinic for management with suboxone. The patient had tried various other medications for the management of narcolepsy. With opioid management, the patient reported reduced cataplexy symptoms. Conclusion: The case illustrates the scientific thought that opioids could increase hypocretin and reduce symptoms in narcolepsy type 1.

关键词： narcolepsy Cataplexy Suboxone Sleep Muscle Tone

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Comorbid attention-deficit/hyperactivity disorder impact clinical expression and response to methylphenidate treatment in children and adolescents patients with narcolepsy

Comorbid attention-deficit/hyperactivity disorder impact cli...

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中国睡眠研究会第十届全国学术年会

作者： Peipei Wang Shan Qu Fang Han

Objective: To investigate the prevalence of core Attention-Deficit/Hyperactivity Disorder（ADHD） symptoms in narcolepsy patients and the response to methylphenidate hydrochloride treatment in narcolepsy patients with or without ADHD.Method: 277 pediatric narcolepsy patients with cataplexy（NC,205 males and 72 females,5 to17 years old） were evaluated for ADHD symptoms by a psychiatrist using DSM-IV diagnostic criteria of the Mini International Neuropsychiatric Interview for children and adolescents（MINI Kid）,from Feb 2011 to Jul 2013 at Peking University People’s Hospital.All patients underwent a polysomnography followed by multiple sleep latency tests（MSLT） before methylphenidate hydrochloride（MPH） treatment.Neuropsychological evaluations,including Inventory of subjective life quality（ISLQ）,depression self-reating scale for Children（DSRS-C）,screen for child anxiety related emotional disorders（SCARED） and barratt impulsiveness scale（BIS） were performed before and after 16-week MPH（9-18 mg） treatment.Executive abilities were assessed by behavior rating inventory of executive function—parent’s version（BRIEF-P）.Result: 79 of 277（28.5%） NC had clinical significant ADHD symptoms,with 75 cases being inattentive type（ADHD-I） and 4 cases being combined type（ADHD-C）.46.8% of these 79 patients（37） had ADHD symptoms before the diagnosis of narcolepsy.In spit of similar objective daytime sleepiness and number of sleep onset REM periods（SOREMPs）,NC with ADHD symptoms experienced higher anxiety level,more impulsive behaviors,lower health-related quality of life and executive functions compared to those without ADHD（p＜0.05）.16-week MPH treatment were effective in improving daytime sleepiness in NC with ADHD,reducing PSQ from 13.5 ± 2.0 to 16.7± 2.1（p＜0.001）,but had little influence on ADHD-RS（25.3 ± 9.1 vs 24.7 ± 9.3）,ISLQ,DSRS-C,SCARED or BIS.Conclusion: High prevalence of ADHD（28.5%） was identified in children and adolescents with narcolepsy.Comorbid ADHD symptoms were associated with increased levels of mood disorders and lower

关键词： attention deficit hyperactivity disorder narcolepsy methylphenidate comorbidity

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发作性嗜睡病(narcolepsy)二例报告

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山西医学杂志 1958年第3期 63-64页

作者：王子玉山西省大同市第二人民医院

发作性嗜睡病较为少見。1877年Westphal首次报告,国内郑氏首先发現一例,最近吳逊氏报告37例,并詳加分析。作者最近在大同曾发現两例,均为閉鎖性头顱外伤引起者,特报告如下: 例一病历摘要患者男性,45岁,煤矿工人,住院号167,于1956年元月... 详细信息

发作性嗜睡病较为少見。1877年Westphal首次报告,国内郑氏首先发現一例,最近吳逊氏报告37例,并詳加分析。作者最近在大同曾发現两例,均为閉鎖性头顱外伤引起者,特报告如下: 例一病历摘要患者男性,45岁,煤矿工人,住院号167,于1956年元月9日入院。主訴为两个月来有嗜睡发作。患者两个月前,在矿井下劳作,頂煤堕落,轟击后头頂部,瞬間人事不省,将其移运坑外約一小时逐漸清醒,但未見头皮破損。于当地休养之第六天晚六时,

关键词：发作性嗜睡病外伤 narcolepsy 发作性睡眠麻黄素麻黄碱

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Independent components analysis and graph theoretical analysis in adult narcolepsy compared with healthy controls

Independent components analysis and graph theoretical analys...

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中国睡眠研究会第十一届全国学术年会

作者： Fulong Xiao Fang Han Peking University People’s Hospital

Objective To evaluate resting state functional connectivity and topological properties of complex network in adult narcolepsy compared with healthy controls.Methods Resting state f MRI was performed in 26 adult narcolepsy patients and 30 matched healthy controls. MRI data was analyzed by group independent component analysis, then a graph theoretical method was applied to evaluate topological properties within whole brain. Global measures, such as small-world network parameters and nodal measures, including Degree centrality, between centrality, nodal clustering coefficient and nodal efficiency were measured in the graph theoretical analysis. Partial correlation analysis was performed to evaluate the relationship between sleepiness severity in narcolepsy and functional connectivity or topological properties in the narcolepsy patients. Results 21 independent components out of 48 components were obtained. Compared with healthy controls, narcolepsy exhibited a significant decreased functional connectivity within the executive and salience network, while increased functional connectivity in bilateral frontal lobe within executive network can be detected in narcolepsy. There was no differences in small-world network properties between narcolepsy and healthy controls. Many brain nodes were shown altered topological properties between narcolepsy and healthy controls. Correlations between ICA results and sleepiness severity lead to no significant results. In the graph theoretical analysis results, local topological properties in some nodes were correlated with the severity of sleepiness among narcolepsy.Conclusions As for some nodes, altered topological properties were associated with severity of sleepiness among narcolepsy. Variations in resting state FC and nodal topological properties in adult narcolepsy may be related to reduced hypocretin, severity of sleepiness（REM sleep latency and ESS） and subjective effort to maintain wakefulness and alertness.

关键词： narcolepsy functional connectivity independent component analysis graph theory

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