Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation.

Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease is considered to be the result of the selective disruption of neuronal cells in the lateral hypothalamus expressing the neuropeptide hypocretin, which controls the sleep-wake cycle. Diagnosis and management of narcolepsy represent still a substantial medical challenge due to the large heterogeneity in the clinical manifestation of the disease as well as to the lack of understanding of the underlying pathophysiological mechanisms. However, significant advances have been made in the last years, thus opening new perspective in the field. This review describes the current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management. Recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are also highlighted

Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation.

Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease is considered to be the result of the selective disruption of neuronal cells in the lateral hypothalamus expressing the neuropeptide hypocretin, which controls the sleep-wake cycle. Diagnosis and management of narcolepsy represent still a substantial medical challenge due to the large heterogeneity in the clinical manifestation of the disease as well as to the lack of understanding of the underlying pathophysiological mechanisms. However, significant advances have been made in the last years, thus opening new perspective in the field. This review describes the current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management. Recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are also highlighted

Correction to: Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation.

Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease is considered to be the result of the selective disruption of neuronal cells in the lateral hypothalamus expressing the neuropeptide hypocretin, which controls the sleep-wake cycle. Diagnosis and management of narcolepsy represent still a substantial medical challenge due to the large heterogeneity in the clinical manifestation of the disease as well as to the lack of understanding of the underlying pathophysiological mechanisms. However, significant advances have been made in the last years, thus opening new perspective in the field. This review describes the current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management. Recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are also highlighted.ISSN:1863-2297ISSN:1863-230

Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts

Summary The aim of this European initiative is to facilitate a structured discussion to improve the next edition of the International Classification of Sleep Disorders (ICSD), particularly the chapter on central disorders of hypersomnolence. The ultimate goal for a sleep disorders classification is to be based on the underlying neurobiological causes of the disorders with clear implication for treatment or, ideally, prevention and or healing. The current ICSD classification, published in 2014, inevitably has important shortcomings, largely reflecting the lack of knowledge about the precise neurobiological mechanisms underlying the majority of sleep disorders we currently delineate. Despite a clear rationale for the present structure, there remain important limitations that make it difficult to apply in routine clinical practice. Moreover, there are indications that the current structure may even prevent us from gaining relevant new knowledge to better understand certain sleep disorders and their neurobiological causes. We suggest the creation of a new consistent, complaint driven, hierarchical classification for central disorders of hypersomnolence; containing levels of certainty, and giving diagnostic tests, particularly the MSLT, a weighting based on its specificity and sensitivity in the diagnostic context. We propose and define three diagnostic categories (with levels of certainty): 1/“Narcolepsy” 2/“Idiopathic hypersomnia”, 3/“Idiopathic excessive sleepiness” (with subtypes)Peer reviewe

European guideline and expert statements on the management of narcolepsy in adults and children

Background and purpose: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. Methods: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. Results: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. Conclusion: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.Peer reviewe

Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines – Multi-country assessment

Background: In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines. Methods: We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009. Results: No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03. Conclusions: Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study

Pharmacological management of narcolepsy with and without cataplexy.

INTRODUCTION Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies

Patient-Reported Measures of Narcolepsy: The Need for Better Assessment.

STUDY OBJECTIVES Narcolepsy, a chronic disorder of the central nervous system, is clinically characterized by a symptom pentad that includes excessive daytime sleepiness, cataplexy, sleep paralysis, hypnopompic/hypnagogic hallucinations, and disrupted nighttime sleep. Ideally, screening and diagnosis instruments that assist physicians in evaluating a patient for type 1 or type 2 narcolepsy would be brief, easy for patients to understand and physicians to score, and would identify or rule out the need for electrophysiological testing. METHODS A search of the literature was conducted to review patient-reported measures used for the assessment of narcolepsy, mainly in clinical trials, with the goal of summarizing existing scales and identifying areas that may require additional screening questions and clinical practice scales. RESULTS Of the seven scales reviewed, the Epworth Sleepiness Scale continues to be an important outcome measure to screen adults for excessive daytime sleepiness, which may be associated with narcolepsy. Several narcolepsy-specific scales have demonstrated utility, such as the Ullanlinna Narcolepsy Scale, Swiss Narcolepsy Scale, and Narcolepsy Symptom Assessment Questionnaire, but further validation is required. CONCLUSIONS Although the narcolepsy-specific scales currently in use may identify type 1 narcolepsy, there are no validated questionnaires to identify type 2 narcolepsy. Thus, there remains a need for short, easily understood, and well-validated instruments that can be readily used in clinical practice to distinguish narcolepsy subtypes, as well as other hypersomnias, and for assessing symptoms of these conditions during treatment

'Sleepiness' in obstructive sleep apnea : getting into deep water

Paroxysmal Cerebral Disorder