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

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.

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

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.

Bibliometric and visual study of narcolepsy from 2000 to 2023

BACKGROUND More studies explored the prevalence,causes,associated conditions,and therapeutic strategies of narcolepsy.With an increasing focus on understanding narcolepsy’s prevalence,associated conditions,and therapeutic strategies,there’s a notable absence of bibliometric analyses summarizing trends in research and identifying emerging areas of focus within this field.AIM To conduct a bibliometric analysis to investigate the current status and frontiers of narcolepsy.METHODS The documents related to narcolepsy are obtained from the Web of Science Core Collection database(WoSCC)from January 1,2000,to December 31,2023,and VOS viewer 1.6.16,and the WoSCC’s literature analysis wire were used to conduct the bibliometric analysis.RESULTS A total of 4672 publications related to narcolepsy were included,and 16182 authors across 4397 institutions and 96 countries/regions contributed to these documents in 1131 different journals.The most productive author,institution,country and journal were Yves Dauvilliers,Stanford University,United States,and Sleep Medicine,respectively.The first high-cited document was published in Nature in 2005 by Saper et al,and this research underscores the role of certain neurons in ensuring the stability of sleep-wake transitions,offering insights into narcolepsy’s pathophysiology.CONCLUSION In conclusion,the main research hotspots and frontiers in the field of narcolepsy are the diagnosis of narcolepsy,pathological mechanism of narcolepsy and the treatment of narcolepsy.More studies are needed to explore effective strategies for the diagnosis and treatment of narcolepsy.

Independent Component Analysis and Graph Theoretical Analysis in Patients with Narcolepsy

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 severity of narcolepsy.Changes in the nodal topological properties in the left putamen and left posterior cingulate,changes in functional connectivity between the left supplementary motor area and right occipital as well as in functional connectivity between the left anterior cingulate gyrus and bilateral postcentral gyrus can be considered as a specific indicator for evaluating the severity of narcolepsy.

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

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 < 0.05).Contusions:The patterns of haplotype in TRA (haplotypes TG and CT) are associated with hypnagogic auditory hallucination in patients with narcolepsy type 1.However,further studies are needed to confirm our results and explore the underlying mechanisms.

Predictive value of typical cataplexy+DQB1~* 0602 positive to hypocretin-1 reduction in cerebrospinal fluid in patients with narcolepsy

Objective To discusses the predictive value of typical cataplexy + HLA-DQB1 * 0602 positive to hypocretin-1(HCRT-1)reduction in cerebrospinal fluid(CSF)in patients with narcolepsy.Methods A total of 165 narcoleptic patients,who were diagnosed at the Sleep Center of Peking University People's Hospital and Peking University International Hospital from March 2003 to March 2017,were recruited.The CSF HCRT-1 level and DQB1* 0602 were measured in all the subjects.The narcoleptic patients were divided into two groups:typical cataplexy + DQB1 * 0602 positive CH group,and untypical cataplexy and DQB1 * 0602 negative simultaneously NCH group.The HCRT-1 level in CSF was declared to have a serious reduction when HCRT-1≤110 ng/L.According to this standard,the CH group and the NCH group were subdivided into sub-groups and the data was analyzed to investigate the predictive value of typical cataplexy + HLA-DQB1 * 0602 positive to HCRT-1 reduction.Results There were 142 patients in CH group,including 137 patients with HCRT-1 reduction and 5 patients without.There were 23 patients in NCH group,including 15 patients with HCRT-1 reduction and 8 patients without.The positive predictive value of typical cataplexy + DQB1* 0602 positive for the reduction of HCRT-1 in CSF was 96.5%.Typical cataplexy + DQB1* 0602 positive had a good consistency with the HCRT-1 reduction in CSF(X^2=26.7,P<0.001).Conclusion Typical cataplexy + DQB1 * 0602 positive has a good predictive value to the HCRT-1 reduction in CSF in patients with narcolepsy.

Treatment Based on Narcolepsy Promote Sleep in Insomniacs

瑞士Actelion制药公司的研究人员在新一期《自然医学》杂志上报告说,他们新发现一种可以阻止大脑激素神经肤活动的化学物质,可以帮助白天昏昏欲睡但夜间无法入睡的人摆脱痛苦。神经肽与睡眠有关,这种激素在有嗜睡症的人体内含量较低,使他们习惯性地昏昏欲睡,甚至会在工作时或驾车时入睡。研究人员称,现有的大多数治疗失眠药物都有一些副作用,会导致服用者第二天出现记忆损失和头昏等症状,但新发现的化学物质基本没有这类副作用。

Reduced Cataplexy Symptoms While on Suboxone: A Case Report

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.

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

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.

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

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.

Xingshentongqiao Decoction Mediates Proliferation, Apoptosis, Orexin-A Receptor and Orexin-B Receptor Messenger Ribonucleic Acid Expression and Represses Mitogen-activated Protein Kinase Signaling

Background：Hypocretin （HCRT） signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy.Our previous study showed that xingshentongqiao decoction （XSTQ） is clinically effective for the treatment of narcolepsy.To determine whether XSTQ improves narcolepsy by modulating HCRT signaling,we investigated its effects on SH-SY5Y cell proliferation,apoptosis,and HCRT receptor 1/2 （orexin receptor 1 [OXl R] and orexin receptor 2 [OX2R]） expression.The signaling pathways involved in these processes were also assessed.Methods：The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays.OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis.Western blotting for mitogen-activated protein kinase （MAPK） pathway activation was performed to further assess the signaling mechanism of XSTQ.Results：XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells.This effect was accompanied by the upregulation of OX 1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase （Erk） 1/2,p38 MAPK and c-Jun N-terminal kinase （JNK）.Conclusions：XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells.XSTQ also promotes OX1R and OX2R expression.These effects are associated with the repression of the Erkl/2,p38 MAPK,and JNK signaling pathways.These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation,which may explain its ability to treat narcolepsy.