The Experts below are selected from a list of 17556 Experts worldwide ranked by ideXlab platform
Christian Guilleminault - One of the best experts on this subject based on the ideXlab platform.
-
neurocognition sleep and pet findings in type 2 vs type 1 Narcolepsy
Neurology, 2018Co-Authors: Yushu Huang, Ingtsung Hsiao, Fengyuan Liu, Fangming Hwang, Kuanglin Lin, Wencheng Huang, Christian GuilleminaultAbstract:Objective To analyze differences in functional brain images collected in patients with type 2 and type 1 Narcolepsy compared to normal controls and the relationship among brain images, objective neuropsychologic tests, and sleep findings. Methods Data collection included comprehensive clinical investigation, study of sleep/wake with actigraphy, polysomnography, Multiple Sleep Latency Test, human leukocyte antigen typing, 18 F-fluorodeoxyglucose PET, and cognitive tests obtained from 29 patients with type 2 Narcolepsy, 104 patients with type 1 Narcolepsy, and 26 sex- and age-matched normal control individuals. Conners’ Continuous Performance Test (CPT II) and Wisconsin Card-Sorting Task were performed simultaneously with the FDG-PET examination. After analyses of variance, data between patients with type 1 and type 2 Narcolepsy were compared by post hoc analysis, and correlation between functional brain imaging findings and results of neurocognitive tests was obtained. Results All patients with Narcolepsy presented with at least 2 sleep-onset REM periods (SOREMP) and subjective sleepiness. Patients with type 2 Narcolepsy compared to patients with type 1 Narcolepsy had significantly less SOREMP, longer mean sleep latencies, and lower body mass indexes, apnea-hypopnea indexes, and frequency of human leukocyte antigen DQ-Beta1*0602. In patients with type 2 Narcolepsy, FDG-PET studies showed significantly less hypermetabolism in the fusiform gyrus, striatum, hippocampus, thalamus, basal ganglia, and cerebellum than in patients with type 1 Narcolepsy, and significantly less hypometabolism in the regions of frontal lobe, posterior cingulum, angular gyrus, and part of the parietal lobe; these changes were associated with fewer errors on the CPT. Conclusion Young patients with type 2 Narcolepsy have fewer clinical impairments and less distinct brain functional abnormalities than patients with type 1 Narcolepsy, who are significantly more affected.
-
high rates of psychiatric comorbidity in Narcolepsy findings from the burden of Narcolepsy disease bond study of 9 312 patients in the united states
The Journal of Clinical Psychiatry, 2017Co-Authors: Chad Ruoff, Christian Guilleminault, Maurice M. Ohayon, Nancy L Reaven, Susan E Funk, Karen Mcgaughey, Jed BlackAbstract:OBJECTIVE To evaluate psychiatric comorbidity patterns in patients with a Narcolepsy diagnosis in the United States. METHODS Truven Health Analytics MarketScan Research Databases were accessed to identify individuals ≥ 18 years of age with ≥ 1 ICD-9 diagnosis code(s) for Narcolepsy continuously insured between 2006 and 2010 and non-Narcolepsy controls matched 5:1 (age, gender, region, payer). Extensive subanalyses were conducted to confirm the validity of Narcolepsy definitions. Narcolepsy subjects and controls were compared for frequency of psychiatric comorbid conditions (based on ICD-9 codes/Clinical Classification Software [CCS] level 2 categories) and psychiatric medication use. RESULTS The final population included 9,312 Narcolepsy subjects and 46,559 controls (each group, mean age = 46.1 years; 59% female). All categories of mental illness were significantly more prevalent in patients with Narcolepsy versus controls, with the highest excess prevalence noted for CCS 5.8 Mood disorders (37.9% vs 13.8%; odds ratio [OR] = 4.0; 95% CI, 3.8-4.2), CCS 5.8.2 Depressive disorders (35.8% vs 13.0%; OR = 3.9; 95% CI, 3.7-4.1), and CCS 5.2 Anxiety disorders (25.1% vs 11.9%; OR = 2.5; 95% CI, 2.4-2.7). Excess prevalence of anxiety and mood disorders (Narcolepsy vs controls) was higher in younger age groups versus older age groups. Psychiatric medication usage was higher in the Narcolepsy group versus controls in the following categories: selective serotonin reuptake inhibitors (36% vs 17%), anxiolytic benzodiazepines (34% vs 19%), hypnotics (29% vs 13%), serotonin-norepinephrine reuptake inhibitors (21% vs 6%), and tricyclic antidepressants (13% vs 4%) (all P values < .0001). CONCLUSIONS Narcolepsy is associated with significant comorbid psychiatric illness burden and higher psychiatric medication usage compared with the non-Narcolepsy population.
-
Medical comorbidity in Narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study.
Sleep medicine, 2016Co-Authors: Jed Black, Christian Guilleminault, Maurice M. Ohayon, Nancy L Reaven, Susan E Funk, Karen Mcgaughey, Chad RuoffAbstract:Abstract Objective/Background The objective of this study was to evaluate medical comorbidity patterns in patients with a Narcolepsy diagnosis in the United States. Patients/Methods This was a retrospective medical claims data analysis. Truven Health Analytics MarketScan® Research Databases were accessed to identify individuals ≥18 years of age with ≥1 diagnosis code for Narcolepsy (International Classification of Diseases (ICD)-9, 347.0, 347.00, 347.01, 347.1, 347.10, or 347.11) continuously insured between 2006 and 2010, and controls without Narcolepsy matched 5:1 on age, gender, region, and payer. Narcolepsy and control subjects were compared for frequency of comorbid conditions, identified by the appearance of >1 diagnosis code(s) mapped to a Clinical Classification System (CCS) level 1 category any time during the study period, and on specific subcategories, including recognized Narcolepsy comorbidities of obstructive sleep apnea (OSA) and depression. Results The final study group included 9312 subjects with Narcolepsy and 46,559 controls (each group: average age, 46.1 years; 59% female). As compared with controls, patients with Narcolepsy showed a statistically significant excess prevalence in all the CCS multilevel categories, the only exceptions being conditions originating in the perinatal period and pregnancy/childbirth complications. The greatest excess prevalence in the Narcolepsy cohort was seen for mental illness (31.1% excess prevalence; odds ratio (OR) 3.8, 95% confidence interval (CI) 3.6, 4.0), followed by diseases of the digestive system (21.4% excess prevalence; OR 2.7, 95% CI 2.5, 2.8) and nervous system/sense organs (excluding Narcolepsy; 20.7% excess prevalence; OR 3.7, 95% CI 3.4, 3.9). Conclusions In this claims analysis, a Narcolepsy diagnosis was associated with a wide range of comorbid medical illness claims, at significantly higher rates than matched controls.
-
Emerging Treatments for Narcolepsy
Narcolepsy, 2008Co-Authors: Meredith Broderick, Christian GuilleminaultAbstract:The current treatments for Narcolepsy are aimed primarily at treating symptoms. Even in the best cases, this method is only partially effective. To date, there are no comprehensive treatments addressing the underlying causes of Narcolepsy. Instead, the treatments are aimed at the classic tetrad of daytime sleepiness, cataplexy, sleep paralysis, hypnagogic and hypnopompic hallucinations. For these reasons, a more advanced treatment for Narcolepsy is sought. Significant advances in elucidating the pathophysiology of Narcolepsy have been made in the last decade. One of the most important is the relationship of hypocretin deficiency to Narcolepsy–cataplexy and the description of animal models of Narcolepsy. These advances are leading to new possibilities in the development of treatment modalities with the mission of offering a more effective and comprehensive treatment strategy aimed at the underlying cause of Narcolepsy. The new approaches being investigated are predominantly related to drug development, although some of the newer treatments are improvements made to existing therapies. The emerging treatments for Narcolepsy can be classified into five broad categories which include: hypocretin-based treatments, immunotherapy, thyrotrophin (TRH) analogs and promoters, histamine (H3) antagonists, combinations or variations of currently used therapies and other therapies. Within each of those five categories are subcategories with specifically aimed mechanisms of action targeted at the known pathophysiological mechanisms involved in the etiology of Narcolepsy. The potential to combine each of these theoretical approaches for a potent treatment with minimal side effects is even more exciting. This chapter will review the current literature on the emerging treatments for Narcolepsy.
-
Emerging Treatments for Narcolepsy
Narcolepsy, 2008Co-Authors: Meredith Broderick, Christian GuilleminaultAbstract:The current treatments for Narcolepsy are aimed primarily at treating symptoms. Even in the best cases, this method is only partially effective. To date, there are no comprehensive treatments addressing the underlying causes of Narcolepsy. Instead, the treatments are aimed at the classic tetrad of daytime sleepiness, cataplexy, sleep paralysis, hypnagogic and hypnopompic hallucinations. For these reasons, a more advanced treatment for Narcolepsy is sought. Significant advances in elucidating the pathophysiology of Narcolepsy have been made in the last decade. One of the most important is the relationship of hypocretin deficiency to Narcolepsy–cataplexy and the description of animal models of Narcolepsy. These advances are leading to new possibilities in the development of treatment modalities with the mission of offering a more effective and comprehensive treatment strategy aimed at the underlying cause of Narcolepsy. The new approaches being investigated are predominantly related to drug development, although some of the newer treatments are improvements made to existing therapies. The emerging treatments for Narcolepsy can be classified into five broad categories which include: hypocretin-based treatments, immunotherapy, thyrotrophin (TRH) analogs and promoters, histamine (H3) antagonists, combinations or variations of currently used therapies and other therapies. Within each of those five categories are subcategories with specifically aimed mechanisms of action targeted at the known pathophysiological mechanisms involved in the etiology of Narcolepsy. The potential to combine each of these theoretical approaches for a potent treatment with minimal side effects is even more exciting. This chapter will review the current literature on the emerging treatments for Narcolepsy.
Emmanuel Mignot - One of the best experts on this subject based on the ideXlab platform.
-
Knowledge Gaps in the Perioperative Management of Adults With Narcolepsy
Anesthesia and Analgesia, 2019Co-Authors: Shelley Hershner, Yves Dauvilliers, Emmanuel Mignot, Frances Chung, Mandeep Singh, Jean Wong, Bhargavi Gali, Rahul Kakkar, Michael Thorpy, Dennis AuckleyAbstract:There is increasing awareness that sleep disorders may be associated with increased perioperative risk. The Society of Anesthesia and Sleep Medicine created the Narcolepsy Perioperative Task Force: (1) to investigate the current state of knowledge of the perioperative risk for patients with Narcolepsy, (2) to determine the viability of developing perioperative guidelines for the management of patients with Narcolepsy, and (3) to delineate future research goals and clinically relevant outcomes. The Narcolepsy Perioperative Task Force established that there is evidence for increased perioperative risk in patients with Narcolepsy; however, this evidence is sparse and based on case reviews, case series, and retrospective reviews. Mechanistically, there are a number of potential mechanisms by which patients with Narcolepsy could be at increased risk for perioperative complications. These include aggravation of the disease itself, dysautonomia, Narcolepsy-related medications, anesthesia interactions, and withdrawal of Narcolepsy-related medications. At this time, there is inadequate research to develop an expert consensus or guidelines for the perioperative management of patients with Narcolepsy. The paucity of available literature highlights the critical need to determine if patients with Narcolepsy are at an increased perioperative risk and to establish appropriate research protocols and clearly delineated patient-centered outcomes. There is a real need for collaborative research among sleep medicine specialists, surgeons, anesthesiologists, and perioperative providers. This future research will become the foundation for the development of guidelines, or at a minimum, a better understanding how to optimize the perioperative care of patients with Narcolepsy.
-
genetics of vaccination related Narcolepsy
bioRxiv, 2017Co-Authors: Hanna M Ollila, Emmanuel Mignot, Markku Partinen, C Hublin, Annika Wennerstrom, Janna Saarela, Turkka Kirjavainen, Logan Schneider, Sarileena Himanen, Outi SaarenpaaheikkilaAbstract:Narcolepsy type 1 is a severe hypersomnia affecting 1/3000 individuals. It is caused by a loss of neurons producing hypocretin/orexin in the hypothalamus. In 2009/2010, an immunization campaign directed towards the new pandemic H1N1 Influenza-A strain was launched and increased risk of Narcolepsy reported in Northern European countries following vaccination with Pandemrix, an adjuvanted H1N1 vaccine resulting in ~250 vaccination-related cases in Finland alone. Using whole genome sequencing data of 2000 controls, exome sequencing data of 5000 controls and HumanCoreExome chip genotypes of 81 cases with vaccination-related Narcolepsy and 2796 controls, we, built a multilocus genetic risk score with established Narcolepsy risk variants. We also analyzed, whether novel risk variants would explain vaccine-related Narcolepsy. We found that previously discovered risk variants had strong predictive power (accuracy of 73% and P<2.2*10-16; and ROC curve AUC 0.88) in vaccine-related Narcolepsy cases with only 4.9% of cases being assigned to the low risk category. Our findings indicate genetic predisposition to vaccine-triggered Narcolepsy, with the possibility of identifying 95% of people at risk.
-
challenges in diagnosing Narcolepsy without cataplexy a consensus statement
Sleep, 2014Co-Authors: Judith A Owens, Christian R Baumann, Gert Jan Lammers, Yves Dauvilliers, Emmanuel Mignot, Isabelle Arnulf, Sebastiaan Overeem, Makoto Honda, Giuseppe PlazziAbstract:BACKGROUND: Diagnosing Narcolepsy without cataplexy is often a challenge as the symptoms are nonspecific, current diagnostic tests are limited, and there are no useful biomarkers. In this report, we review the clinical and physiological aspects of Narcolepsy without cataplexy, the limitations of available diagnostic procedures, and the differential diagnoses, and we propose an approach for more accurate diagnosis of Narcolepsy without cataplexy. METHODS: A group of clinician-scientists experienced in Narcolepsy reviewed the literature and convened to discuss current diagnostic tools, and to map out directions for research that should lead to a better understanding and more accurate diagnosis of Narcolepsy without cataplexy. RECOMMENDATIONS: To aid in the identification of Narcolepsy without cataplexy, we review key indicators of Narcolepsy and present a diagnostic algorithm. A detailed clinical history is mainly helpful to rule out other possible causes of chronic sleepiness. The multiple sleep latency test remains the most important measure, and prior sleep deprivation, shift work, or circadian disorders should be excluded by actigraphy or sleep logs. A short REM sleep latency (Narcolepsy without cataplexy, although sensitivity is low. Finally, measurement of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30% of Narcolepsy without cataplexy patients. CITATION: Baumann CR, Mignot E, Lammers GJ, Overeem S, Arnulf I, Rye D, Dauvilliers Y, Honda M, Owens JA, Plazzi G, Scammell TE. Challenges in diagnosing Narcolepsy without cataplexy: a consensus statement. SLEEP 2014;37(6):1035-1042.
-
Etiology and Genetics of Human Narcolepsy
Narcolepsy, 2011Co-Authors: Emmanuel MignotAbstract:Low levels of the neuropeptide hypocretin-1 (hcrt-1, also called orexin-A) are found in the cerebrospinal fluid (CSF) of most people with Narcolepsy with cataplexy and in some without cataplexy [1–6]. As a result, in the most recent revision of the International Classification of Sleep Disorders (ICSD), Narcolepsy with cataplexy and Narcolepsy without cataplexy have been separated [7]. In this chapter, we will discuss the etiology of Narcolepsy/hcrt deficiency, as there is a strong suggestion of homogeneity based on the very high association with human leukocyte antigen (HLA) DQB1*0602 and low CSF hcrt-1. References to Narcolepsy without cataplexy, defined by sleepiness and a positive multiple sleep latency test (MSLT), will also be made, although the condition likely represents a constellation of problems and pathologies. We will also briefly discuss secondary Narcolepsy cases.
-
Narcolepsy and cataplexy
Handbook of clinical neurology, 2011Co-Authors: Seiji Nishino, Emmanuel MignotAbstract:Abstract The term “Narcolepsy” was first coined by Gelineau in 1880 with the complete description of a patient with excessive daytime sleepiness (EDS), sleep attacks, and episodes of muscle weakness triggered by emotions. In the current international classification, Narcolepsy is characterized by “excessive daytime sleepiness that is typically associated with cataplexy and abnormal REM (rapid eye movement) sleep phenomena such as sleep paralysis and hypnagogic hallucinations”. Narcolepsy is a chronic neurological condition, but is not a progressive disorder. The major pathophysiology of human Narcolepsy has been elucidated recently based on the discovery of Narcolepsy genes (hypocretin/orexin ligand and its receptor) in animals. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in many cases. This recent discovery is likely to lead to the development of new diagnostic tests and targeted treatments. As hypocretins are involved various hypothalamic functions, hypocretin-deficient Narcolepsy appears now to be a more complex condition than just a simple sleep disorder. This chapter starts with an overview of the clinical aspects of Narcolepsy, followed by an update on the pathophysiology. Finally, we discuss the expectations from future Narcolepsy research.
Jed Black - One of the best experts on this subject based on the ideXlab platform.
-
high rates of psychiatric comorbidity in Narcolepsy findings from the burden of Narcolepsy disease bond study of 9 312 patients in the united states
The Journal of Clinical Psychiatry, 2017Co-Authors: Chad Ruoff, Christian Guilleminault, Maurice M. Ohayon, Nancy L Reaven, Susan E Funk, Karen Mcgaughey, Jed BlackAbstract:OBJECTIVE To evaluate psychiatric comorbidity patterns in patients with a Narcolepsy diagnosis in the United States. METHODS Truven Health Analytics MarketScan Research Databases were accessed to identify individuals ≥ 18 years of age with ≥ 1 ICD-9 diagnosis code(s) for Narcolepsy continuously insured between 2006 and 2010 and non-Narcolepsy controls matched 5:1 (age, gender, region, payer). Extensive subanalyses were conducted to confirm the validity of Narcolepsy definitions. Narcolepsy subjects and controls were compared for frequency of psychiatric comorbid conditions (based on ICD-9 codes/Clinical Classification Software [CCS] level 2 categories) and psychiatric medication use. RESULTS The final population included 9,312 Narcolepsy subjects and 46,559 controls (each group, mean age = 46.1 years; 59% female). All categories of mental illness were significantly more prevalent in patients with Narcolepsy versus controls, with the highest excess prevalence noted for CCS 5.8 Mood disorders (37.9% vs 13.8%; odds ratio [OR] = 4.0; 95% CI, 3.8-4.2), CCS 5.8.2 Depressive disorders (35.8% vs 13.0%; OR = 3.9; 95% CI, 3.7-4.1), and CCS 5.2 Anxiety disorders (25.1% vs 11.9%; OR = 2.5; 95% CI, 2.4-2.7). Excess prevalence of anxiety and mood disorders (Narcolepsy vs controls) was higher in younger age groups versus older age groups. Psychiatric medication usage was higher in the Narcolepsy group versus controls in the following categories: selective serotonin reuptake inhibitors (36% vs 17%), anxiolytic benzodiazepines (34% vs 19%), hypnotics (29% vs 13%), serotonin-norepinephrine reuptake inhibitors (21% vs 6%), and tricyclic antidepressants (13% vs 4%) (all P values < .0001). CONCLUSIONS Narcolepsy is associated with significant comorbid psychiatric illness burden and higher psychiatric medication usage compared with the non-Narcolepsy population.
-
Medical comorbidity in Narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study.
Sleep medicine, 2016Co-Authors: Jed Black, Christian Guilleminault, Maurice M. Ohayon, Nancy L Reaven, Susan E Funk, Karen Mcgaughey, Chad RuoffAbstract:Abstract Objective/Background The objective of this study was to evaluate medical comorbidity patterns in patients with a Narcolepsy diagnosis in the United States. Patients/Methods This was a retrospective medical claims data analysis. Truven Health Analytics MarketScan® Research Databases were accessed to identify individuals ≥18 years of age with ≥1 diagnosis code for Narcolepsy (International Classification of Diseases (ICD)-9, 347.0, 347.00, 347.01, 347.1, 347.10, or 347.11) continuously insured between 2006 and 2010, and controls without Narcolepsy matched 5:1 on age, gender, region, and payer. Narcolepsy and control subjects were compared for frequency of comorbid conditions, identified by the appearance of >1 diagnosis code(s) mapped to a Clinical Classification System (CCS) level 1 category any time during the study period, and on specific subcategories, including recognized Narcolepsy comorbidities of obstructive sleep apnea (OSA) and depression. Results The final study group included 9312 subjects with Narcolepsy and 46,559 controls (each group: average age, 46.1 years; 59% female). As compared with controls, patients with Narcolepsy showed a statistically significant excess prevalence in all the CCS multilevel categories, the only exceptions being conditions originating in the perinatal period and pregnancy/childbirth complications. The greatest excess prevalence in the Narcolepsy cohort was seen for mental illness (31.1% excess prevalence; odds ratio (OR) 3.8, 95% confidence interval (CI) 3.6, 4.0), followed by diseases of the digestive system (21.4% excess prevalence; OR 2.7, 95% CI 2.5, 2.8) and nervous system/sense organs (excluding Narcolepsy; 20.7% excess prevalence; OR 3.7, 95% CI 3.4, 3.9). Conclusions In this claims analysis, a Narcolepsy diagnosis was associated with a wide range of comorbid medical illness claims, at significantly higher rates than matched controls.
-
Increased Mortality in Narcolepsy
Sleep, 2014Co-Authors: Maurice M. Ohayon, Jed Black, Chinglin Lai, Mark Eller, Diane Guinta, Arun BhattacharyyaAbstract:Objective To evaluate the mortality rate in patients with Narcolepsy. Design Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. Setting Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. Patients/participants All records of patients registered in the SHS database between 2008 and 2010. Interventions None. Measurements and results Identification of patients with Narcolepsy was based on ≥ 1 medical claim with the diagnosis of Narcolepsy (ICD-9 347.xx) from 2002 to 2012. Dates of death were acquired from the Social Security Administration via a third party; the third party information was encrypted in the same manner as the claims data such that anonymity is ensured prior to receipt by SHS. Annual all-cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively for patients with Narcolepsy and patients without Narcolepsy in the database, and standardized mortality ratios (SMR) were calculated. Mortality rates were also compared with the general US population (Centers for Disease Control data). SMRs of the Narcolepsy population were consistent over the 3-year period and showed an approximate 1.5-fold excess mortality relative to those without Narcolepsy. The Narcolepsy population had consistently higher mortality rates relative to those without Narcolepsy across all age groups, stratified by age decile, from 25-34 years to 75+ years of age. The SMR for females with Narcolepsy was lower than for males with Narcolepsy. Conclusions Narcolepsy was associated with approximately 1.5-fold excess mortality relative to those without Narcolepsy. While the cause of this increased mortality is unknown, these findings warrant further investigation.
-
Increased Mortality in Narcolepsy
Sleep, 2014Co-Authors: Maurice M. Ohayon, Jed Black, Chinglin Lai, Mark Eller, Diane Guinta, Arun BhattacharyyaAbstract:To evaluate the mortality rate in patients with Narcolepsy. Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. All records of patients registered in the SHS database between 2008 and 2010. None. Identification of patients with Narcolepsy was based on ≥ 1 medical claim with the diagnosis of Narcolepsy (ICD-9 347.xx) from 2002 to 2012. Dates of death were acquired from the Social Security Administration via a third party; the third party information was encrypted in the same manner as the claims data such that anonymity is ensured prior to receipt by SHS. Annual all-cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively for patients with Narcolepsy and patients without Narcolepsy in the database, and standardized mortality ratios (SMR) were calculated. Mortality rates were also compared with the general US population (Centers for Disease Control data). SMRs of the Narcolepsy population were consistent over the 3-year period and showed an approximate 1.5-fold excess mortality relative to those without Narcolepsy. The Narcolepsy population had consistently higher mortality rates relative to those without Narcolepsy across all age groups, stratified by age decile, from 25-34 years to 75+ years of age. The SMR for females with Narcolepsy was lower than for males with Narcolepsy. Narcolepsy was associated with approximately 1.5-fold excess mortality relative to those without Narcolepsy. While the cause of this increased mortality is unknown, these findings warrant further investigation.
-
Narcolepsy-cataplexy: How does recent understanding help in evaluation and treatment
Current Treatment Options in Neurology, 2005Co-Authors: Mujahid Mahmood, Jed BlackAbstract:Narcolepsy is a substantially disabling disease with profound physical, mental, and social effects. The burden on patients is compounded by delayed and missed diagnoses and by the subsequent undertreatment of Narcolepsy and associated symptoms such as cataplexy. The recent advances in the elucidation of the genetics of canine Narcolepsy and the pathophysiologic role of hypocretin, in animals and humans, enhances current diagnostic capability and will provide better treatment modalities in the future. The varied symptoms of Narcolepsy are challenging to manage and may require treatment with a combination of agents. The recent development of a markedly enhanced characterization of sodium oxybate in the treatment of the excessive daytime sleepiness, nocturnal sleep fragmentation, and cataplexy of Narcolepsy offers the potential of treating multiple symptoms simultaneously and marks a dramatic advance in the treatment of Narcolepsy.
Yves Dauvilliers - One of the best experts on this subject based on the ideXlab platform.
-
Knowledge Gaps in the Perioperative Management of Adults With Narcolepsy
Anesthesia and Analgesia, 2019Co-Authors: Shelley Hershner, Yves Dauvilliers, Emmanuel Mignot, Frances Chung, Mandeep Singh, Jean Wong, Bhargavi Gali, Rahul Kakkar, Michael Thorpy, Dennis AuckleyAbstract:There is increasing awareness that sleep disorders may be associated with increased perioperative risk. The Society of Anesthesia and Sleep Medicine created the Narcolepsy Perioperative Task Force: (1) to investigate the current state of knowledge of the perioperative risk for patients with Narcolepsy, (2) to determine the viability of developing perioperative guidelines for the management of patients with Narcolepsy, and (3) to delineate future research goals and clinically relevant outcomes. The Narcolepsy Perioperative Task Force established that there is evidence for increased perioperative risk in patients with Narcolepsy; however, this evidence is sparse and based on case reviews, case series, and retrospective reviews. Mechanistically, there are a number of potential mechanisms by which patients with Narcolepsy could be at increased risk for perioperative complications. These include aggravation of the disease itself, dysautonomia, Narcolepsy-related medications, anesthesia interactions, and withdrawal of Narcolepsy-related medications. At this time, there is inadequate research to develop an expert consensus or guidelines for the perioperative management of patients with Narcolepsy. The paucity of available literature highlights the critical need to determine if patients with Narcolepsy are at an increased perioperative risk and to establish appropriate research protocols and clearly delineated patient-centered outcomes. There is a real need for collaborative research among sleep medicine specialists, surgeons, anesthesiologists, and perioperative providers. This future research will become the foundation for the development of guidelines, or at a minimum, a better understanding how to optimize the perioperative care of patients with Narcolepsy.
-
Narcolepsy.
Nature reviews. Disease primers, 2017Co-Authors: Birgitte R Kornum, Yves Dauvilliers, Fabio Pizza, Stine Knudsen, Hanna M Ollila, Poul J Jennum, Sebastiaan OvereemAbstract:Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with Narcolepsy include social stigma associated with this disease, difficulties in obtaining an education and keeping a job, a reduced quality of life and socioeconomic consequences. Two subtypes of Narcolepsy have been described (Narcolepsy type 1 and Narcolepsy type 2), both of which have similar clinical profiles, except for the presence of cataplexy, which occurs only in patients with Narcolepsy type 1. The pathogenesis of Narcolepsy type 1 is hypothesized to be the autoimmune destruction of the hypocretin-producing neurons in the hypothalamus; this hypothesis is supported by immune-related genetic and environmental factors associated with the disease. However, direct evidence in support of the autoimmune hypothesis is currently unavailable. Diagnosis of Narcolepsy encompasses clinical, electrophysiological and biological evaluations, but simpler and faster procedures are needed. Several medications are available for the symptomatic treatment of Narcolepsy, all of which have quite good efficacy and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of Narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions.
-
Narcolepsy
Nature Reviews Disease Primers, 2017Co-Authors: Birgitte R Kornum, Yves Dauvilliers, Fabio Pizza, Stine Knudsen, Hanna M Ollila, Poul J Jennum, Sebastiaan OvereemAbstract:Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with Narcolepsy include social stigma associated with this disease, difficulties in obtaining an education and keeping a job, a reduced quality of life and socioeconomic consequences. Two subtypes of Narcolepsy have been described (Narcolepsy type 1 and Narcolepsy type 2), both of which have similar clinical profiles, except for the presence of cataplexy, which occurs only in patients with Narcolepsy type 1. The pathogenesis of Narcolepsy type 1 is hypothesized to be the autoimmune destruction of the hypocretin-producing neurons in the hypothalamus; this hypothesis is supported by immune-related genetic and environmental factors associated with the disease. However, direct evidence in support of the autoimmune hypothesis is currently unavailable. Diagnosis of Narcolepsy encompasses clinical, electrophysiological and biological evaluations, but simpler and faster procedures are needed. Several medications are available for the symptomatic treatment of Narcolepsy, all of which have quite good efficacy and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of Narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions. Narcolepsy is a sleep disorder that is characterized by excessive daytime sleepiness. This Primer by Kornum and colleagues primarily focuses on Narcolepsy type 1 (also known as Narcolepsy with cataplexy), which is believed to be caused by the autoimmune-mediated loss of hypocretin neurons in the lateral hypothalamus.
-
The European Narcolepsy Network (EU-NN) database
Journal of Sleep Research, 2016Co-Authors: Ramin Khatami, Gianina Luca, Claudio Bassetti, Rafael Del Rio-villegas, Eva Feketeova, Oliviero Bruni, Christian Baumann, Yves Dauvilliers, Ferra Cañellas, Raffaele FerriAbstract:Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered Narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on Narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European Narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of Narcolepsy and related disorders, including clear phenotype characterization of subtypes of Narcolepsy, more precise epidemiological data and knowledge on the natural history of Narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.
-
Interactions of the histamine and hypocretin systems in CNS disorders
Nature Reviews Neurology, 2015Co-Authors: Ling Shan, Yves Dauvilliers, Jerome M. SiegelAbstract:Over-the-counter histamine H_1 receptor antagonists (antihistamines) block the effects of histamine, have sedating properties and are commonly used to treat insomnia A large increase in the number of histamine neurons is seen in type 1 Narcolepsy (Narcolepsy with cataplexy), but not in animal models of Narcolepsy Low levels of cerebrospinal fluid (CSF) hypocretin are characteristic of type 1 Narcolepsy; changes in CSF histamine levels are small and variable in this disorder In several neurological disorders including Parkinson and Alzheimer diseases, hypocretin-containing cells degenerate while the number of histamine cells and histamine levels are in the normal range Histamine H_3 receptor antagonists and inverse agonists promote histamine release and are a promising class of drugs for the promotion of wakefulness, as has been shown in patients with Narcolepsy Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as Narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In Narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with Narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep–wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in Narcolepsy and discuss the possibility that Narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system. Loss of hypocretin neurons is a hallmark finding in Narcolepsy; recent findings have implicated also increased number of histamine neurons in this disorder. This Review provides an overview of coregulation of sleep and wakefulness by hypocretin and histamine. The authors also review the changes in hypocretin and histamine systems in Narcolepsy and neurodegenerative diseases (such as Alzheimer disease, Parkinson disease and Huntington disease) and discuss novel therapeutic approaches for manipulation of the histamine system in these diseases.
Ahmed S. Bahammam - One of the best experts on this subject based on the ideXlab platform.
-
Neuropsychiatric Correlates of Narcolepsy.
Current psychiatry reports, 2020Co-Authors: Ahmed S. Bahammam, Kholoud Alnakshabandi, S. R. Pandi-perumalAbstract:The complex nature of Narcolepsy symptoms, along with the use of stimulants and anticataplectic medications, poses diagnostic difficulties in terms of underlying neuropsychiatric comorbidities. This study reviews recent evidence for the association between Narcolepsy and neuropsychiatric disorders. We also critically analyze studies that have addressed the neuropsychiatric correlates of patients with Narcolepsy, with a discussion of the possible pathophysiological mechanisms linking Narcolepsy and neuropsychiatric disorders. Neuropsychiatric manifestations are common among patients with Narcolepsy as Narcolepsy and some neuropsychiatric disorders share common clinical features. This may create challenges in making the correct diagnosis, and hence result in a delay in starting appropriate treatment. Comorbid neuropsychiatric manifestations in patients with Narcolepsy include depression, anxiety, psychosis, rapid eye movement (REM) sleep behavior disorder, and cognitive impairment. Although hypocretin deficiency has been proposed as a pathophysiological mechanism underlying both Narcolepsy and neuropsychiatric disorders, further research is necessary to identify the exact mechanisms. Narcolepsy patients often manifest comorbid neuropsychiatric symptoms, which makes the diagnosis difficult. Therefore, it is essential to address neuropsychiatric symptoms in the clinical care of patients with Narcolepsy.
-
Neuropsychiatric Correlates of Narcolepsy.
Current psychiatry reports, 2020Co-Authors: Ahmed S. Bahammam, Kholoud Alnakshabandi, S. R. Pandi-perumalAbstract:Purpose of review The complex nature of Narcolepsy symptoms, along with the use of stimulants and anticataplectic medications, poses diagnostic difficulties in terms of underlying neuropsychiatric comorbidities. This study reviews recent evidence for the association between Narcolepsy and neuropsychiatric disorders. We also critically analyze studies that have addressed the neuropsychiatric correlates of patients with Narcolepsy, with a discussion of the possible pathophysiological mechanisms linking Narcolepsy and neuropsychiatric disorders. Recent findings Neuropsychiatric manifestations are common among patients with Narcolepsy as Narcolepsy and some neuropsychiatric disorders share common clinical features. This may create challenges in making the correct diagnosis, and hence result in a delay in starting appropriate treatment. Comorbid neuropsychiatric manifestations in patients with Narcolepsy include depression, anxiety, psychosis, rapid eye movement (REM) sleep behavior disorder, and cognitive impairment. Although hypocretin deficiency has been proposed as a pathophysiological mechanism underlying both Narcolepsy and neuropsychiatric disorders, further research is necessary to identify the exact mechanisms. Narcolepsy patients often manifest comorbid neuropsychiatric symptoms, which makes the diagnosis difficult. Therefore, it is essential to address neuropsychiatric symptoms in the clinical care of patients with Narcolepsy.
-
Comorbid psychiatric disorders among patients with Narcolepsy
Sleep and Breathing, 2019Co-Authors: Haithm Alasim, Aljohara S. Almeneessier, Salman Alqazlan, Saleh Albanyan, Abdulaziz Alsalhi, Alwalid Buraik, Awad H. Olaish, Fahad D. Alosaimi, Ahmad Alhadi, Ahmed S. BahammamAbstract:Purpose This case-control study assessed the prevalence of psychiatric disorders in Arab (Saudi) patients with Narcolepsy using a structured clinical interview. Methods The study included 74 adult patients with Narcolepsy and 265 controls matched for age and sex. Narcolepsy diagnosis was made according to the International Classification of Sleep Disorders-Third Edition. Psychiatric disorders were diagnosed via using a validated Arabic version of the Mini International Neuropsychiatric Interview DSM-IV (MINI version 6). A multivariate logistic regression model was used to assess the potential influence of Narcolepsy on the comorbidity of psychiatric disorders. Results The mean age of the patients was 29.4 ± 10.2 years, and males accounted for 81% of the study sample. Forty-four patients (60%) were diagnosed with Narcolepsy type-1 (NT1) and 30 (40%) with Narcolepsy type-2 (NT2). Psychiatric disorders were diagnosed in 45% of patients with Narcolepsy compared with 15% of the controls ( p
-
Medical specialty visits and diagnoses received by Saudi patients prior to a diagnosis of Narcolepsy
Sleep and Breathing, 2019Co-Authors: Aljohara S. Almeneessier, Sara Al-jebrin, Reem Labani, Hussain Alkaff, Omar Al-rahbeeni, Musab Alageel, Awad Olaish, Ahmed S. BahammamAbstract:Purpose Narcolepsy is an uncommon neurological disorder characterized by excessive daytime sleepiness (EDS) and multiple other symptoms. Due to the under-recognition of Narcolepsy symptoms, patients are often misdiagnosed. This study aimed to assess the types of specialties visited and the diagnoses received by Saudi patients prior to their Narcolepsy diagnosis. Methods The study included 55 consecutive patients with type-1 and type-2 Narcolepsy who attended the Narcolepsy clinic between August 2017 and December 2017. Narcolepsy was diagnosed according to the International Classification of Sleep Disorders–third edition criteria. We evaluated sociodemographic data, the specialties visited, and diagnoses and treatments received prior to visiting a sleep specialist. Results The mean diagnostic delay was 9.1 ± 8.4 years (1–43 years). Multiple linear regression analysis identified early onset as the only predictor of a delayed diagnosis ( β coefficient = − 0.262, p = 0.03). EDS was the main symptom that prompted patients to seek medical consultation, and only one patient had been (1.8%) referred with the diagnosis of Narcolepsy. In the study group, 82% of the patients were misdiagnosed with a mental or neurological disorder or were thought to be afflicted by “envy,” “evil eye,” or “black magic” before receiving a correct diagnosis. No significant differences were detected between patients with Narcolepsy type-1 and Narcolepsy type-2. Conclusions Delays in diagnosing Narcolepsy remain a major problem for Saudi patients with this disorder. We found that Saudi patients with Narcolepsy had visited several medical specialists and faith healers and were misdiagnosed prior to visiting a sleep specialist.
