Diagnosis Of Narcolepsy Research Articles

The Lehigh Valley Health Network narcolepsy cohort: clinical and polysomnographic analysis of 304 cases.

We aimed to characterize clinical features, comorbidities and polysomnographic characteristics of a large cohort of patients with narcolepsy. We undertook a retrospective chart and polysomnographic review of all patients with a diagnosis of narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) seen within the Lehigh Valley Health Network between 2000 and 2022. We found 304 cases with a diagnosis of narcolepsy (52 NT1, 252 NT2), based on International Classification of Sleep Disorders, third edition criteria. Compared to NT2, patients with NT1 had younger diagnosis age (24.5 versus 27.4 years, p=0.03), shorter diagnostic gap (3.0 versus 4.6 years, p=0.002), more frequent sleep paralysis (55.8% versus 19.4%, p<0.0001) and hypnagogic hallucinations (46.2% versus 25.4%, p=0.003), and higher Epworth Sleepiness Scale (ESS) scores (17.8 versus 16.7, p=0.02). The most common comorbid sleep disorders were breathing disorders (17.4%) and insomnia (15.5%). Migraine was the most common neurological disorder. Depression was more common in NT2 than NT1 [12 (23.1%) versus 94 (37.3%), p=0.05]. On the Multiple Sleep Latency Test, patients with NT1 had more sleep onset REM periods (SOREMPs) than patients with NT2 (≥3 SOREMPs in 59.2% versus 26.9%, p<0.0001). Only in NT2, hypnagogic hallucinations and higher ESS scores were associated with higher numbers of SOREMPs (p=0.0277 and p=0.0179 respectively). This is one of the largest monocentric studies to date of patients with narcolepsy and confirms the frequent comorbidities of narcolepsy. Specific clinical characteristics and comorbidities may help differentiate NT1 from NT2.

Opinion About Narcolepsy and Disability Diagnosis

Opinion About Narcolepsy and Disability Diagnosis

Loss of rapid eye movement atonia in rapid eye movement sleep behaviour disorder and narcolepsy.

A reduction of physiological muscle atonia during rapid eye movement sleep is characteristic in patients with rapid eye movement sleep behaviour disorder, however, it can also be found in narcolepsy patients. We evaluated rapid eye movement sleep associated electromyographic activity to set cut-off values of rapid eye movement sleep without atonia, differentiating rapid eye movement sleep behaviour disorder and narcolepsy patients from controls to enable more precise future diagnostic criteria for these disorders. We retrospectively analysed polysomnography recordings of 16 rapid eye movement sleep behaviour disorder patients, 15 narcolepsy patients, and 19 controls. The combination of phasic and tonic electromyographic activity was recorded in the mentalis and tibialis anterior muscles and analysed in 3 second miniepochs. The cut-off value for a diagnosis of rapid eye movement sleep behaviour disorder was 17.07% (100% sensitivity, 94.7% specificity, area under the curve 0.997). For the diagnosis of narcolepsy, we yielded a cut-off value of 8.4% (86.4% sensitivity, 68.4% specificity, area under the curve 0.850). Rapid eye movement sleep without atonia significantly (p = 0.046) increased in the second night half in rapid eye movement sleep behaviour disorder patients, while it remained moderately increased in the narcolepsy group. Polysomnographic evaluation proves significantly higher rates of rapid eye movement sleep without atonia in rapid eye movement sleep behaviour disorder than in narcolepsy patients, allowing differentiation from controls with high sensitivity and specificity. An increase throughout the night is characteristic for rapid eye movement sleep behaviour disorder, whereas a consistent elevation is typical in narcolepsy patients.

The value of using ELISA to detect orexin-A in cerebrospinal fluid in the diagnosis of narcolepsy.

Orexin in cerebrospinal fluid (CSF) is a neuropeptide synthesized by a cluster of neurons in the lateral hypothalamus. It mainly functions to maintain arousal, regulate feeding, and participate in reward mechanisms. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) can detect CSF orexin. At present, RIA is widely used but is limited by various conditions, which is not conducive to its widespread development. We aimed to determine whether ELISA can replace RIA in detecting orexin in CSF. We investigated the results of 20 patients with central disorders of hypersomnolence, including 11 with narcolepsy type 1, 2 with narcolepsy type 2, 5 with idiopathic hypersomnia, and 2 with other causes of somnolence. RIA and ELISA were used to detect CSF orexin, and P values <.05 were considered to be significant. In the narcolepsy and non-narcolepsy type 1 groups, there was no correlation between the RIA and ELISA results (P > .05). In the narcolepsy type 1 group, the ELISA and RIA results were significantly different (P < .05), but this was not observed in the non-narcolepsy type 1 group (P > .05). The accuracy of ELISA to detect CSF orexin was lower than that of RIA (P < .05). ELISA cannot replace RIA in the measurement of CSF orexin, and RIA is recommended as the first choice when narcolepsy is suspected.

0663 Assessing the Predictive Accuracy of Quantitative Electroencephalography in the Diagnosis of Narcolepsy

0663 Assessing the Predictive Accuracy of Quantitative Electroencephalography in the Diagnosis of Narcolepsy

Narcolepsy: an interface among neurology, immunology, sleep, and genetics.

Narcolepsy is a primary disorder of the central nervous system resulting from genetic, environmental, and immunological interactions defined as excessive daytime sleepiness plus cataplexy, hallucinations, sleep paralysis, and sleep fragmentation. The pathophysiology is not entirely known, but the interaction among genetic predisposition, environmental exposition, and immune component with consequent hypocretin-1 deficiency is the model to explain narcolepsy type I. The mechanism of narcolepsy type II is less understood. There is a delay of over ten years for the diagnosis of narcolepsy around the world. Patients with narcolepsy have many comorbidities with a negative impact on quality of life. The treatment of narcolepsy must contain an educational approach for the family, coworkers, and patients. Scheduled naps and sleep hygiene are essential to minimize the dose of medications. Much progress has been seen in the pharmacological treatment of narcolepsy with new stimulants, different presentations of oxybate, and recent studies with orexin agonists. Narcolepsy is a rare disease that needs to be more understood and highlighted to avoid delayed diagnosis and severe disabilities in patients.

Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data.

The purpose of this study was to characterize the incidence of pediatric narcolepsy diagnosis, subsequent care, and potential sociodemographic disparities in a large US claims database. Merative MarketScan insurance claims (n = 12,394,902) were used to identify youth (6-17 years of age) newly diagnosed with narcolepsy (International Classification of Diseases, 10th revision codes). Narcolepsy diagnosis and care 1 year postdiagnosis included polysomnography with Multiple Sleep Latency Test, pharmacological care, and clinical visits. Potential disparities were examined by insurance coverage and child race and ethnicity (Medicaid-insured only). The incidence of narcolepsy diagnosis was 10:100,000, primarily type 2 (69.9%). Most diagnoses occurred in adolescents with no sex differences, but higher rates in Black vs White youth with Medicaid. Two thirds had a prior sleep disorder diagnosis and 21-36% had other co-occurring diagnoses. Only half (46.6%) had polysomnography with Multiple Sleep Latency Test (± 1 year postdiagnosis). Specialty care (18.9% pulmonary, 26.9% neurology) and behavioral health visits were rare (34.4%), although half were prescribed stimulant medications (51.0%). Medicaid-insured were 86% less likely than commercially insured youth to have any clinical care and 33% less likely to have polysomnography with Multiple Sleep Latency Test. Narcolepsy diagnoses occurred in 0.01% of youth, primarily during adolescence, and at higher rates for Black vs White children with Medicaid. Only half overall had evidence of a diagnostically required polysomnography with Multiple Sleep Latency Test, underscoring potential misdiagnosis. Many patients had co-occurring conditions, but specialty and behavioral health care were limited. Results suggest misdiagnosis, underdiagnosis, and limited narcolepsy treatment, as well as possible disparities. Results highlight the need to identify determinants of evidence-based pediatric narcolepsy diagnosis and management. Tang SH, Min J, Zhang X, etal. Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data. J Clin Sleep Med. 2024;20(7):1141-1151.

Path to diagnosis and impact of narcolepsy on quality of life: a survey of people living with narcolepsy

Path to diagnosis and impact of narcolepsy on quality of life: a survey of people living with narcolepsy

Diagnosis and symptoms of narcolepsy from the patient perspective: results from in-depth qualitative interviews

Diagnosis and symptoms of narcolepsy from the patient perspective: results from in-depth qualitative interviews

Sleep Stage Transition of Sleep Onset Rapid Eye Movement Periods Suggesting REM Dysregulation in Narcolepsy

Objectives: Narcolepsy diagnosis is often complicated, using relatively simple criteria that rely on sleep onset rapid eye movement periods (SOREMP) and average sleep latency in the multiple sleep latency test (MSLT). Therefore, the main goal of this study was to gain a new perspective on narcolepsy diagnosis and explore the role of rapid eye movement (REM) dysregulation by examining the progression of sleep stage transitions leading to SOREMP.Methods: From 2008 to 2022, 109 patients diagnosed with narcolepsy who underwent polysomnography and MSLT were included. Comprehensive data on clinical features, polysomnography, and MSLT findings were collected. For the MSLT, we not only considered SOREMP and mean sleep latency but also the sleep stage transition preceding SOREMP, the presence of N3, and the average SOREMP duration.Results: Among the 109 patients enrolled in the study, 59 were diagnosed with narcolepsy type 1 (NT1) and 50 with narcolepsy type 2 (NT2). We observed a high frequency of transitions in the MSLT of waking to REM (W-R) in patients with NT1. Moreover, the occurrence of W-R was associated with a higher number of SOREMPs. The temporal distribution of the MSLT results revealed a significant correlation; W-R occurrences were more frequent during the third nap.Conclusions: W-R occurrence was frequent in patients with NT1, indicating more pronounced REM dysregulation than in patients with NT2.

Missed diagnosis of longstanding narcolepsy.

Missed diagnosis of longstanding narcolepsy.

Narcolepsy in a 4-Year-Old

Narcolepsy is a disabling neurodegenerative condition that is characterized by the hallmark of excessive daytime sleepiness. Diagnosis of narcolepsy can be difficult in all aged patients, but especially so in children less than 5 years old. We present a unique case of a 4-year-old girl who presented with slurred speech, behavioral changes, and hypersomnolence. After a thorough evaluation, she was diagnosed with narcolepsy type 1. We provide a literature review about this diagnosis and discuss the signs, symptoms, and workup, with a focus on the challenges associated with determining the definitive diagnosis. The role of obtaining cerebrospinal fluid hypocretin-1 levels in the diagnostic evaluation of patient with suspected narcolepsy is emphasized.

Role of New Drug Delivery System in Brain Disorder: Narcolepsy

Narcolepsy is a chronic neurological disorder that involves a decreased ability to regulate sleep wake cycles. In this review authors highlighted various types of narcolepsy, the most common symptoms of the narcolepsy, symptoms of the narcolepsy in children, various causes of narcolepsy, how it effects, how common is narcolepsy, stages of narcolepsy, diagnosis of narcolepsy, its treatment and cure, complications associated with its treatment. The brain is shielded with blood brain barrier system and the methods that can enhance drug delivery to the brain are of great interest in treatment of various brain related problems. Novel drug delivery specially targeted drug delivery is a method by which localizing and maximizing drugs at their desired site of action to reduce toxicity and increase treatment efficiency. This review intends to detail new drug delivery system over conventional drug delivery system, brain targeted drug delivery, challenges faced while making targeted drug delivery system for brain, various strategies and advances in targeted drug delivery for the treatment of narcolepsy.

Prevalence and incidence of narcolepsy symptoms in the US general population

ObjectiveThe objectives of this study are to evaluate the prevalence and incidence of Narcolepsy type 1 and type 2 and to determine the prevalence of narcolepsy diagnosis criteria in the US general population. MethodsThis longitudinal study was conducted in the adult US general population in two occasions. The initial interviews included 15 states (Arizona, California, Colorado, Florida, Idaho, Missouri, New York, North Carolina, North Dakota, Oregon, Pennsylvania, South Dakota, Texas, Washington, and Wyoming). The follow-up interviews, was done three years later in eight of these states. Of the 19,136 contacted individuals, 15,929 completed the initial interview and 10,931 completed the follow-up. Participants were interviewed using the Sleep-EVAL system, an artificial intelligence tool. Narcolepsy Type 1 (with cataplexy) and Narcolepsy Type 2 (without cataplexy) were defined according to the ICSD-3 classification. Symptoms of narcolepsy were assessed by frequency per week and duration. Medical visits and diagnoses were also collected. ResultsParticipants were aged between 18 and 102 years of age (mean 45.8 ± 17.9 years), 51.3 % were women. The prevalence of narcolepsy with cataplexy was 12.6 per 100,000 individuals (95 % C.I., 0 to 30) and narcolepsy without cataplexy was 25.1 per 100,000. The incidence per year was 2.6 per 100,000 individuals (95 % C.I., 0 to 11). ConclusionsNarcolepsy is a rare condition affecting 37.7/100,000 individuals (126,191 individuals in the current US population). Our US general population prevalence is in line with rates found in community-based studies but lower than what is reported in claim database studies.

Harriet Tubman's Hypersomnia: Insights from Historical and Medical Perspectives.

Harriet Tubman, a hero of the abolitionist movement and early civil rights advocate, suffered a head injury in childhood and subsequently developed sleep attacks associated with visions that were extensively documented in historical accounts. Her contemporaries perceived these visions together with unpredictable and unavoidable urges to sleep as manifestations of her deep faith, rather than as symptoms of an illness. While religious perspectives remain crucial to understanding Tubman's sleep-related experiences, some may consider them insufficient in view of modern medical advances. We propose the parallel explanation that her sleep attacks, usually attributed to temporal lobe epilepsy, actually represent a hypersomnia that is most consistent with the modern diagnosis of post-traumatic narcolepsy. Using historical analysis as well as current understandings of sleep medicine, we aim to shed light on this under-recognized aspect of Tubman's life. In addition, this case study allows us to review the potential long-term effects of severe traumatic brain injuries; consider a differential for excessive daytime sleepiness and hypnagogic hallucinations; and familiarize readers with the pathophysiology, diagnosis, and treatment of narcolepsy. Whether her symptoms are viewed through the lens of the past or measured against current biomedical standards, Tubman demonstrated an inspiring ability to persevere despite intrusive sleep episodes and to realize her dreams for the betterment of others.

Repeated polysomnography and multiple sleep latency test in narcolepsy type 1 and other hypersomnolence disorders

BackgroundThe diagnosis of narcolepsy is based on clinical information, combined with polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT). PSG and the MSLT are moderately reliable at diagnosing narcolepsy type 1 (NT1) but unreliable for diagnosing narcolepsy type 2 (NT2). This is a problem, especially given the increased risk of a false-positive MSLT in the context of circadian misalignment or sleep deprivation, both of which commonly occur in the general population. AimWe aimed to clarify the accuracy of PSG/MSLT testing in diagnosing NT1 versus controls without sleep disorders. Repeatability and reliability of PSG/MSLT testing and temporal changes in clinical findings of patients with NT1 versus patients with hypersomnolence with normal hypocretin-1 were compared. Method84 patients with NT1 and 100 patients with non-NT1-hypersomnolence disorders, all with congruent cerebrospinal fluid hypocretin-1 (CSF-hcrt-1) levels, were included. Twenty-five of the 84 NT1 patients and all the hypersomnolence disorder patients underwent a follow-up evaluation consisting of clinical assessment, PSG, and a modified MSLT. An additional 68 controls with no sleep disorders were assessed at baseline. ConclusionConfirming results from previous studies, we found that PSG and our modified MSLT accurately and reliably diagnosed hypocretin-deficient NT1 (accuracy = 0.88, reliability = 0.80). Patients with NT1 had stable clinical and electrophysiological presentations over time that suggested a stable phenotype. In contrast, the PSG/MSLT results of patients with hypersomnolence, and normal CSF-hcrt-1 had poor reliability (0.32) and low repeatability.

A Turkish Validity and Reliability Study of the Swiss Narcolepsy Scale

Background: The clinical evaluation of a patient complaining of excessive daytime sleepiness is of crucial importance for the diagnosis of narcolepsy. The Swiss Narcolepsy Scale (SNS) was developed in 2004 as a screening tool for patients with narcolepsy and shown in three different studies to have a high sensitivity and specificity for narcolepsy type 1 (NT1). The aim of this study was to assess the validity and reliability of the Turkish version of SNS (SNS-TR). Patients and Methods: Twenty-one healthy controls, 26 patients with idiopathic hypersomnia, and 27 patients with narcolepsy were recruited from five accredited sleep centers in Turkey. Pearson’s correlation coefficient and degree of freedom were used to determine the validity of each question. Cronbach’s alpha was calculated to assess the internal consistency or reliability of Likert-type questions. The inter-rater reliability was tested using Cohen’s kappa analysis, and the intra-class correlation coefficient (ICC) was used to evaluate the validity and reliability between two evaluations with a one-month interval. Results: Sensitivity and specificity of SNS-TR were 90.5% and 100%, respectively, for diagnosing NT1. Cronbach’s alpha was 0.976, showing a highly reliable level of internal consistency. The inter-rater reliability of the questions and the validity and reliability between two evaluations were moderate or above. Conclusion: This study provides evidence for the validity and reliability of SNS-TR in diagnosing and discriminating NT1 from other disorders of hypersomnolence with a very high sensitivity and specificity.

Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study.

Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy. A retrospective cohort study using IBM MarketScan administrative claims data (2014-2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]). Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.

0909 Pitolisant Pregnancy Registry: An Observational Study of the Safety of Pitolisant Exposure in Pregnant Women and Their Offspring

Abstract Introduction WAKIX (pitolisant) is a potent and highly selective histamine 3 receptor antagonist/inverse agonist approved for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy. The safety of pitolisant in pregnant women has not been established. Available case reports from clinical trials and postmarketing experience have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The registry is a prospective, observational cohort study designed to evaluate the association between pitolisant exposure during pregnancy and subsequent maternal, fetal, and infant outcomes. Methods The primary study population consists of 3 cohorts: pregnant women with a diagnosis of narcolepsy who are exposed to pitolisant during pregnancy, pregnant women with narcolepsy who are unexposed to pitolisant but exposed to comparator products during pregnancy, and pregnant women with narcolepsy who are neither exposed to pitolisant nor comparator products. Comparator products include modafinil, armodafinil, sodium oxybate, oxybate mixed salts, solriamfetol, methylphenidate, and amphetamines. Outcomes of interest include major congenital malformation (primary outcome), minor congenital malformation, pre-eclampsia, eclampsia, spontaneous abortion, stillbirth, elective termination, small for gestational age, preterm birth, postnatal growth deficiency, and infant developmental deficiency. Data are collected from enrolled pregnant women and healthcare providers involved in their care or the care of their infants, if applicable. Only data that are routinely documented in patients' medical records during usual care are collected. Participation in the registry is voluntary and participants may withdraw their consent to participate at any time. The registry design follows current FDA guidance for designing and implementing pregnancy exposure registries. Results The registry was initiated in May 2021. Presently, data are insufficient to assess an association between pitolisant exposure and any endpoint of interest. Study completion is planned in 2030. Conclusion Healthcare providers are encouraged to discuss this voluntary pregnancy registry with their eligible patients and assist women who are interested in enrolling. The study is registered on Clinicaltrials.gov (ID# NCT05536011). Support (if any) This study is sponsored by Harmony Biosciences LLC.

0597 Path to Diagnosis and Impact of Narcolepsy on Quality of Life: A Survey of People Living With Narcolepsy

Abstract Introduction Research was undertaken to better understand the path to a narcolepsy diagnosis, common symptoms, and the impact of narcolepsy on work, social interactions, and mental health. Methods In February 2022, an email invitation to an online, 27-question survey was sent to US members of MyNarcolepsyTeam, a social network of &amp;gt;9,800 members. Results In total, 110 members completed the survey. 38% of respondents started to experience symptoms before reaching 16 years of age. Most commonly experienced symptoms included excessive daytime sleepiness (EDS; 93%) and fatigue (84%). In total, 72% were also experiencing some form of sleep disturbance and 67% were already suffering from cognitive/memory challenges. 68% who were eventually diagnosed with narcolepsy type 1 (NT1) had cataplexy attacks. For 31%, getting to a narcolepsy diagnosis took ≥10 years. In fact, 64% were initially under- or misdiagnosed with something other than narcolepsy, including depression (73%), sleep apnea (36%), or attention-deficit/hyperactivity disorder (16%). 74% of patients with NT1 have continued to experience cataplexy, with 46% having some form of a cataplexy episode a few times per week. Cataplexy episodes were triggered by a wide range of emotional situations, including over-tiredness (70%), anger (48%), being startled (46%), laughter (46%), fear (44%), excitement (38%), or crying (33%). 76% of respondents indicated that the impact of narcolepsy on daily life is extremely or very severe. The far-reaching impact on quality of life was evident in that most respondents reported that narcolepsy interfered with work (82%), social life (86%), everyday chores (85%), and exercise (85%) and has limited career options (76%). The emotional toll of narcolepsy manifested in feeling isolated (83%), depressed (81%), anxious (80%), or embarrassed (75%). Conclusion Patients routinely experienced a misdiagnosis or a “missed” diagnosis based on common symptoms experienced. Being able to quickly identify narcolepsy as the root cause for symptoms of EDS, fatigue, and sleep disturbances can lead to getting the patient on the best treatment path as early as possible. Understanding the physical, emotional, and quality-of-life impact of narcolepsy can help clinicians provide a more holistic approach to treating their patients. Support (if any) Avadel Pharmaceuticals