Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1.

BACKGROUND: Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides. METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1. Patients with confirmed narcolepsy type 1 according to clinical criteria were randomly assigned to receive twice-daily oral TAK-994 (30 mg, 90 mg, or 180 mg) or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (range, 0 to 40 minutes; normal ability to stay awake, ≥20 minutes). Secondary end points included the change in the Epworth Sleepiness Scale (ESS) score (range, 0 to 24, with higher scores indicating greater daytime sleepiness; normal, <10) and the weekly cataplexy rate. RESULTS: Of the 73 patients, 17 received TAK-994 at a dose of 30 mg twice daily, 20 received 90 mg twice daily, 19 received 180 mg twice daily, and 17 received placebo. The phase 2 trial and an extension trial were terminated early owing to hepatic adverse events. Primary end-point data were available for 41 patients (56%); the main reason for missing data was early trial termination. Least-squares mean changes to week 8 in average sleep latency on the MWT were 23.9 minutes in the 30-mg group, 27.4 minutes in the 90-mg group, 32.6 minutes in the 180-mg group, and -2.5 minutes in the placebo group (difference vs. placebo, 26.4 minutes in the 30-mg group, 29.9 minutes in the 90-mg group, and 35.0 minutes the 180-mg group; P<0.001 for all comparisons). Least-squares mean changes to week 8 in the ESS score were -12.2 in the 30-mg group, -13.5 in the 90-mg group, -15.1 in the 180-mg group, and -2.1 in the placebo group (difference vs. placebo, -10.1 in the 30-mg group, -11.4 in the 90-mg group, and -13.0 in the 180-mg group). Weekly incidences of cataplexy at week 8 were 0.27 in the 30-mg group, 1.14 in the 90-mg group, 0.88 in the 180-mg group, and 5.83 in the placebo group (rate ratio vs. placebo, 0.05 in the 30-mg group, 0.20 in the 90-mg group, and 0.15 in the 180-mg group). A total of 44 of 56 patients (79%) receiving TAK-994 had adverse events, most commonly urinary urgency or frequency. Clinically important elevations in liver-enzyme levels occurred in 5 patients, and drug-induced liver injury meeting Hy's law criteria occurred in 3 patients. CONCLUSIONS: In a phase 2 trial involving patients with narcolepsy type 1, an orexin receptor 2 agonist resulted in greater improvements on measures of sleepiness and cataplexy than placebo over a period of 8 weeks but was associated with hepatotoxic effects. (Funded by Takeda Development Center Americas; TAK-994-1501 and TAK-994-1504 ClinicalTrials.gov numbers, NCT04096560 and NCT04820842.).

Psychobehavioural profile in narcolepsy type 1 with and without REM sleep behaviour disorder.

REM sleep behaviour disorder (RBD) is common in narcolepsy type 1 (NT1). Abnormalities in the reward system have been observed in NT1, possibly related to impaired orexin projections towards the mesolimbic reward system, but also in RBD when associated with Parkinson's disease. Our study aimed to explore the psychobehavioural profile of NT1 patients with and without RBD compared with healthy controls (HC). Forty patients with NT1 were compared with 20 sex- and age-matched HC. All patients with NT1 underwent a video-polysomnography including a measure of REM sleep without atonia (RSWA). The following neuropsychobehavioural variables were assessed: apathy, impulsivity, depression, cognition, subjective and objective attention, sensation-seeking, and behavioural addictions. The patient population included 22 patients with NT1-RBD and 18 patients with NT1-noRBD. Compared with the healthy controls, patients with NT1 had higher scores of apathy, impulsivity, and depression; a lower score on global cognition, and poorer self-perceived attention. No differences were found between patients with NT1 with and without RBD in all neuropsychological variables, except for impaired objective attention in patients with NT1-RBD. In patients with NT1, a positive correlation was observed between RSWA and both apathy and impulsivity subscale. Moreover, in patients with NT1-RBD, RSWA was positively correlated with depression. Patients with NT1 showed higher depression, apathy, and impulsivity compared with controls. These measures correlate with the severity of RSWA, suggesting a transdiagnostic association between RBD and abnormalities of the reward system at least for patients with NT1.

Hyperhidrosis in sleep disorders - A narrative review of mechanisms and clinical significance.

Hyperhidrosis is characterized by excessive sweating beyond thermoregulatory needs that affects patients' quality of life. It results from an excessive stimulation of eccrine sweat glands in the skin by the sympathetic nervous system. Hyperhidrosis may be primary or secondary to an underlying cause. Nocturnal hyperhidrosis is associated with different sleep disorders, such as obstructive sleep apnea, insomnia, restless legs syndrome/periodic limb movement during sleep and narcolepsy. The major cause of the hyperhidrosis is sympathetic overactivity and, in the case of narcolepsy type 1, orexin deficiency may also contribute. In this narrative review, we will provide an outline of the possible mechanisms underlying sudomotor dysfunction and the resulting nocturnal hyperhidrosis in these different sleep disorders and explore its clinical relevance.

Anxiety and depression in patients with narcolepsy.

We analysed the co-existence of psychopathology in patients with narcolepsy at our centre. We performed an observational retrospective descriptive analysis of patients with a diagnosis of narcolepsy, with and without psychopathology, who attended our sleep disorders unit from October 2012 to October 2021. A total of 51patients with narcolepsy (mean [SD] age 41.10 [14.71] years; 23 [45.1%] males and 28 [54.90%] females) were included. In all, 27 patients (52.94%) and 24 patients (47.06%) had narcolepsy with and without cataplexy, respectively. Of the total, 18 (33.33%) had a mood disorder: 18 with anxiety disorder (33.33%). Of these patients 14 (27.45%) had major depression, two (4%) had attempted suicide, one (2%) had manic outbreak, and one (2%) had substance abuse. Of the 18 patients with anxiety and depression, 10 (55.55%) and eight (44.44%) had narcolepsy with and without cataplexy, respectively. In the comparative analysis, a statistically significant relationship was found between younger age and the presence of anxiety. The prevalence of anxiety and depression in patients with narcolepsy was triple that of the general population, especially in younger patients. Psychopathology precedes the diagnosis of narcolepsy in most patients, not being reactive to diagnosis. This high prevalence suggests a possible biological relationship between both disorders, which should be assessed with larger studies.

DNMT1-associated sensory neuropathy and cerebellar ataxia: A novel variant and review of genotype-phenotype correlation.

AIM: Hereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy. METHODS: A 42-year-old man presented with imbalance, lancinating pain, numerous paucisymptomatic injuries, progressive deafness since his mid-20s, mild cognitive decline and apathy. Examination revealed abnormalities of eye movements, distal sensory loss to all modalities, areflexia without weakness and lower limb ataxia. MRI brain and FDG-PET scan demonstrated biparietal and cerebellar atrophy/hypometabolism. Whole exome sequencing detected a heterozygous likely pathogenic missense variant in DNMT1, c.1289G > A, p.Cys430Tyr. Cochlear implant was performed at 44 years for the bilateral high frequency sensorineural hearing loss with improvement in hearing and day-to-day function. RESULTS AND CONCLUSION: We describe a novel variant in DNMT1 and confirm that an overlapping HSN1E-cerebellar phenotype can occur. Only one prior case of cochlear implant in HSN1E has been reported to date but this case adds to that literature, suggesting that cochlear implant can be successful in such patients. We further explore the clinical and radiological signature of the cognitive syndrome associated with this disorder.

Demographic and Clinical Correlates of Narcolepsy in Adolescents Hospitalized with Mood Disorders: A Nationwide Inpatient Sample (NIS) Study.

OBJECTIVES: To discern the differences in demographic, clinical comorbidities, and hospital outcomes associated with narcolepsy in adolescents hospitalized for mood disorders. METHODS: We included 639,064 adolescents hospitalized with mood disorders, that is, major depressive disorder (MDD) and bipolar disorders (BP) from the nationwide inpatient sample. About 0.04% of inpatients had comorbid narcolepsy (N = 267) and we extracted a demographically matched control group (N = 270) for comparison. RESULTS: Mood-disordered adolescents with narcolepsy had a higher prevalence of comorbid obesity (18.5% in BP,14.4% in MDD) and sleep apnea (9.3% in BP, 9.6% in MDD) compared to those without narcolepsy. Obesity and sleep apnea were significantly more prevalent in Black adolescents hospitalized for MDD and BP (P < .001). There was a higher percentage of females with BP and comorbid narcolepsy than males (59.9% vs 40.1%). In comparison, MDD and comorbid narcolepsy were observed more in males (57.1% vs 42.9%). CONCLUSIONS: Our study results suggest a significantly higher prevalence of obesity and sleep apnea comorbidity in mood-disordered adolescents with narcolepsy with an overall negative impact on hospital outcomes.

[Narcolepsy Type 1 With Comorbid Schizophrenia: A Case Report].

We present the case of an 18-year-old male patient who had narcolepsy type 1 and comorbid schizophrenia. The patient's first symptom was mainly excessive daytime sleepiness, which was followed by psychotic symptoms, including hallucinations, delusions, and abnormal speech and behaviors. After admission to the hospital, the patient underwent a number of ancillary tests. Multiple sleep latency test (MSLT) showed that the mean sleep latency was 2 min and the hypocretin-1 was found to be 90.56 pg/mL. The patient was diagnosed with: 1) schizophrenia; 2) narcolepsy. After receiving antipsychotic drugs and behavioral therapy, the patient's hallucinations and abnormal speech and behaviors disappeared, and delusions and excessive daytime sleepiness decreased significantly. The symptoms and manifestations of narcolepsy type 1 overlaps with those of schizophrenia, which may lead to misdiagnosis and underdiagnosis in clinical practice. The case is presented with a view to providing a reference for the clinical diagnosis and treatment of narcolepsy type 1 with comorbid schizophrenia.

Test-retest reliability of the Epworth Sleepiness Scale in clinical trial settings.

The present analysis examined the test-retest reliability of the Epworth Sleepiness Scale in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea in three clinical trials. Intraclass correlation coefficient estimates for Epworth Sleepiness Scale scores from two solriamfetol 12-week placebo-controlled trials (one narcolepsy, one obstructive sleep apnea) and one long-term open-label extension trial (narcolepsy or obstructive sleep apnea) were calculated using postbaseline time-point pairs for the overall population in each trial, by treatment, and by primary obstructive sleep apnea therapy adherence. In the 12-week narcolepsy trial, intraclass correlation coefficients (95% confidence intervals) were 0.83 (0.79, 0.87) for weeks 4 and 8 (n = 199), 0.87 (0.83, 0.90) for weeks 8 and 12 (n = 196), and 0.81 (0.76, 0.85) for weeks 4 and 12 (n = 196). In the 12-week obstructive sleep apnea trial, intraclass correlation coefficients (95% confidence intervals) were 0.74 (0.69, 0.78) (n = 416), 0.80 (0.76, 0.83) (n = 405), and 0.74 (0.69, 0.78) (n = 405), respectively. In the open-label extension trial, intraclass correlation coefficients (95% confidence intervals) were 0.82 (0.79, 0.85) for weeks 14 and 26/27 (n = 495), 0.85 (0.82, 0.87) for weeks 26/27 and 39/40 (n = 463), and 0.78 (0.74, 0.81) for weeks 14 and 39/40 (n = 463). Placebo/solriamfetol treatment or adherence to primary obstructive sleep apnea therapy did not affect reliability. In conclusion, across three large clinical trials of participants with narcolepsy or obstructive sleep apnea, Epworth Sleepiness Scale scores demonstrated a robust acceptable level of test-retest reliability in evaluating treatment response over time.

Paediatric Acute onset Neuropsychiatric Syndrome: Exploratory study finds no evidence of HLA class II association but high rate of autoimmunity in first-degree relatives.

AIM: Paediatric acute-onset neuropsychiatric syndrome (PANS) is defined by an acute onset of obsessive-compulsive disorder and/or eating restrictions and at least two other severe neuropsychiatric symptoms. The condition is suspected to have an immune-mediated pathophysiology, but reliable biomarkers have not been identified. METHODS: We hypothesised that PANS, like narcolepsy, might have a human leucocyte antigen (HLA) association, as found in 95% of children developing narcolepsy after H1N1 immunisation. Low resolution genotyping of the MHC class II antigens HLA-DRB1 and HLA-DQB1 was performed using two different PCR-based methods. In addition, parents were interviewed regarding a detailed family history of autoimmune diseases in first-degree relatives. A total of 18 children, aged 5-14 (mean 8.2) years at onset of PANS met symptom criteria. RESULTS: No evident association between PANS and the specific HLA alleles examined was observed. In first-degree relatives of 10 of the 18 children, an autoimmune disease had been diagnosed, and three of the 18 children themselves had an autoimmune disease. CONCLUSION: No HLA allele association such as seen in children with narcolepsy after H1N1 immunisation could be confirmed in this group of children with PANS. However, more than half the group had a first-degree relative with a diagnosed autoimmune disease.

Dissociative Symptoms are Highly Prevalent in Adults with Narcolepsy Type 1.

INTRODUCTION: The core symptoms of narcolepsy such as excessive daytime sleepiness and cataplexy are well known. However, there is mounting evidence for a much broader symptom spectrum, including psychiatric symptoms. Disordered sleep has previously been linked with dissociative symptoms, which may imply that patients with narcolepsy are more prone to develop such symptoms. OBJECTIVES: To investigate the frequency of dissociative symptoms in adult patients with narcolepsy type 1 compared to population controls. METHODS: In a retrospective case control study, sixty adult patients fulfilling the criteria for narcolepsy type 1 and 120 matched population control subjects received a structured interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to assess dissociative symptoms and disorders. RESULTS: A majority of narcolepsy patients reported dissociative symptoms, and even fulfilled the DSM-IV-TR criteria of a dissociative disorder (62% vs 1% in controls, p < .001). Most frequently reported symptoms were "dissociative amnesia" (37% vs 1%, p < .001) and "dissociative disorder of voluntary movement" (32% vs 1%, p < .001). CONCLUSION: Dissociative symptoms are strikingly prevalent in adult patients with narcolepsy type 1. Although a formal diagnosis of dissociation disorder should not be made as the symptoms can be explained by narcolepsy as an underlying condition, the findings do illustrate the extent and severity of the dissociative symptoms. As for the pathophysiological mechanism, there may be symptom overlap between narcolepsy and dissociation disorder. However, there may also be a more direct link between disrupted sleep and dissociative symptoms. In either case, the high frequency of occurrence of dissociative symptoms should result in an active inquiry by doctors, to improve therapeutic management and guidance.

Prevalence of Depression or Depressive Symptoms in Patients with Narcolepsy: a Systematic Review and Meta-Analysis.

A meta-analysis was conducted to review the prevalence and associated moderators of depression or depressive symptoms in patients with narcolepsy. An extensive search of the literature yielded 1104 articles and abstracts, of which 31 studies were included in the meta-analysis. Meta-analysis revealed that the overall pooled prevalence of depression or depressive symptoms in patients with narcolepsy was 32% (95% Confidence Interval, 28-36%) with high between-study heterogeneity (Q = 249.77, df = 30, p < 0.001, τ2 = 0.0087, I2 = 88%). An analysis of 13 studies with healthy control groups indicated that narcolepsy was associated with a significantly increased risk of depression or depressive symptoms (Odds Ratio 3.48, 95% Confidence Interval 2.73-4.45; Q = 41.23, df = 12, p < 0.001, τ2 = 0.0087, I2 = 70.9%). The prevalence of depression or depressive symptoms in patients with narcolepsy was significantly affected by study design (Q = 5.05, p = 0.02) and recruitment setting (Q = 5.98, p = 0.01), and was marginally affected by age group (Q = 3.44, p = 0.06). The results indicate that narcolepsy patients should be closely monitored for depression and depressive symptoms and that early screening should be considered. However, these conclusions should be tempered because of high variability between studies. The estimates across studies are very inconsistent, indicating the need for larger, multicenter studies, with stringent case definitions.

Pitolisant versus placebo for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea: A meta-analysis from randomized controlled trials.

Excessive daytime sleepiness is considered as the prominent symptom in narcolepsy and Obstructive Sleep Apnea (OSA). Pitolisant is a novel selective histamine H3 receptor antagonist approved for improving excessive daytime sleepiness. The meta-analysis is conducted to assess the efficacy and safety of pitolisant versus placebo for excessive daytime sleepiness in narcolepsy and OSA. PubMed, Embase and Cochrane Library databases were searched from earliest date to November 2020 for randomized controlled trials (RCTs). The primary outcomes were mean changes in Epworth Sleepiness Scale (ESS), mean sleep latency, European quality-of-life questionnaire (EQ-5D), and risk ratio of treatment-emergent adverse events (TEAEs). We pooled 678 patients from four RCTs and found pitolisant significantly decreased ESS by mean difference (MD) of - 2.86 points (95% CI: -3.75 to -1.96), increased mean sleep latency by MD of 3.14 min (95% CI: 2.18-4.11), and increased EQ-5D by MD of 3.32 points (95% CI: 0.26-6.39) compared with placebo. The risk ratio of TEAE was 1.37 (95% CI: 1.08-1.74). Insomnia was the only TEAE significantly associated with pitolisant treatment. In conclusion, pitolisant showed great efficacy and controllable security versus placebo for excessive daytime sleepiness in narcolepsy and OSA. Compared with narcolepsy, patients with OSA were deemed to benefit more from pitolisant especially in terms of improving mobility and quality of life of patients without continuous positive airway pressure therapy.

Fatigue, insomnia and daytime sleepiness in multiple sclerosis versus narcolepsy.

OBJECTIVES: In multiple sclerosis (MS), fatigue is the most prevalent cause of impaired ability to work. In narcolepsy, daytime sleepiness is the main symptom but some studies indicate fatigue being present. We aimed to assess fatigue and associated features in patients with MS or narcolepsy and healthy controls and to assess whether clinical parameters separate fatigued (MS-F) and non-fatigued MS patients (MS-NoF). MATERIALS & METHODS: In this non-interventional cross-sectional study, we recruited 34 MS patients, 15 narcolepsy type 1 patients and 17 healthy controls. An interviewer administered the Fatigue Severity Scale (FSS), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale, the Patient Health Questionnaire-9 and the Saltin-Grimby Physical Activity Level Scale. Information about clinical parameters and current treatments was collected. RESULTS: In its fatigue profile, MS-F resembled the narcolepsy group rather than MS-NoF, which resembled the healthy control group. ISI alone was significantly associated with FSS, and only in MS-NoF and healthy controls; in MS-F and the narcolepsy group, no variable was associated with FSS. Months since diagnosis was the only clinical variable significantly separating MS-F from MS-NoF. In MS, disease duration correlated with fatigue. No clinical variables correlated with fatigue in the narcolepsy group. CONCLUSIONS: Fatigued MS patients resemble narcolepsy patients more than they resemble non-fatigued MS patients, who resemble healthy controls. Insomnia is the main factor associated with fatigue in MS, while disease duration is the only clinical variable separating fatigued and non-fatigued MS patients. In fatigued patients, variance in fatigue cannot be explained by insomnia, daytime sleepiness, depression or level of exercise.

Perioperative Management of Insomnia, Restless Legs, Narcolepsy, and Parasomnias.

Obstructive sleep apnea (OSA) has been shown to increase risk of adverse perioperative events. More recently, investigators have begun to examine other common sleep disorders to assess how they may be impacted by the perioperative environment, as well as influence postoperative outcomes. There are a number of mechanisms by which such common sleep disorders (eg, insomnia, restless legs syndrome, narcolepsy, and parasomnias) may have consequences in the perioperative setting, both related to the underlying pathophysiology of the diseases as well as their treatments. This review will highlight the current state of the literature and offer recommendations for management of these conditions during the perioperative journey.

Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea.

OBJECTIVE: The purpose of this article is to review the available clinical trial data that led to the Food and Drug Administration (FDA) approval of solriamfetol as well as its role in clinical practice. DATA SOURCES: A MEDLINE/PubMed search was conducted (January 2000 to February 2020) using the keyword solriamfetol to discover appropriate clinical trials. STUDY SELECTION AND DATA EXTRACTION: Articles were included that were published in the English language and related to the FDA approval of solriamfetol or provided novel information regarding this drug entity. DATA SYNTHESIS: The findings of the review show that solriamfetol may be a safe and effective option for the treatment of excessive sleepiness (ES) related to narcolepsy and obstructive sleep apnea (OSA). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Solriamfetol is distinguished from other stimulants in that it has lower binding affinity to dopamine and norepinephrine transporters and does not have the monoamine-releasing effects of amphetamines at usual therapeutic doses. Because of solriamfetol's unique mechanism of action, there may be a reduction in abuse potential compared with the other currently FDA-approved options. CONCLUSIONS: In clinical trials, solriamfetol has shown dose-dependent improvement in wakefulness over placebo and adds another option for clinicians when treating ES in narcolepsy and OSA.

Chronic pain in narcolepsy type 1 and type 2 - an underestimated reality.

Narcolepsy is a rare sleep disorder classified in types 1 and 2. The co-morbidities of narcolepsy type 1, with hypocretin-1 deficiency, are established. Hypocretin-1 in the central and peripheral nervous systems regulates nociception and pain. However, the patients with narcolepsy type 2 have similar excessive daytime sleepiness and co-morbidities without elucidation. The objective of the study was to determine the frequency and the characteristic of chronic pain according to the type of narcolepsy. We also investigated the effect of the interaction between the nutritional status and the type of narcolepsy. It was a cross-sectional study using self-administered questionnaires. Patients with narcolepsy (33 type 1 and 33 type 2), from Universidade Federal de São Paulo, Brazil, matched by age and gender to 33 control subjects were included. Both types of narcolepsy presented a high frequency of chronic pain (84.84% type 1 versus 75.75% type 2), with indistinct pain characteristics between them. The odds ratio was 20.8 in type 1 and 11.6 in type 2, compared with controls. Obese individuals with narcolepsy type 1 and type 2 did not present a significant difference in pain intensity, compared with obese controls. Patients with narcolepsy type 1 and type 2 were associated with a high frequency of chronic pain. Chronic pain emerged as a co-morbidity never reported before in type 2. Depression possibly influences pain perception in these patients. Obesity might play a role in pain intensity in narcolepsy. The treatment of narcolepsy should take account of chronic pain, depression and obesity management.

Narcolepsy, Anesthesia, and Sedation: A Survey of the Perioperative Experience of Patients With Narcolepsy.

BACKGROUND: Patients with narcolepsy may be at increased perioperative risk due to the interactions among anesthesia, narcolepsy, and narcolepsy medications. This study sought to determine the perioperative experience of narcoleptic patients undergoing anesthesia or sedation, the frequency of perioperative counseling, and self-reported surgical complications. METHODS: A 22-question survey was developed by expert consensus and distributed by the Narcolepsy Network. Recruitment was via the Narcolepsy Network's list-serve and a Facebook link to the survey. One thousand and twenty respondents reported a diagnosis of narcolepsy and 1 or more procedures under anesthesia or sedation. Descriptive, comparative statistics and logistic regression were utilized. RESULTS: Respondents were mostly women (79.5%) and Caucasian (84.9%), with a mean age of 45 ± 16 years. Most respondents did not receive counseling regarding the possibility of increased sleepiness (70%), cataplexy (90%), or drowsy driving (59%) postanesthesia. More than half of respondents reported adverse events (medication withdrawal symptoms, inadequate pain relief, increased cataplexy). Subjects with cataplexy more frequently reported surgical complications (70% vs 31%; P = .03) and medication withdrawal symptoms (stimulant medications: odds ratio, 3.0 [95% CI, 1.9, 3.06]; P > .001 and antidepressant medications: odds ratio, 6.5 [95% CI, 2.1-19.5]; P = .001). Of the total sample, 18% indicated surgical complications. Undergoing 5 or more separate surgeries or procedures was associated with a 2-fold increase in self-reported complications (odds ratio, 2.2 [95% CI, 1.3-3.4]; P = .001), difficulty waking (odds ratio, 2.1 [95% CI, 1.45-3.06]; P = .001), and inadequate pain relief (odds ratio, 1.77 [95% CI, 1.01-3.13]; P < .05). CONCLUSIONS: Most narcoleptic patients report not receiving counseling regarding potential worsening of narcolepsy symptoms postanesthesia or an increased risk of drowsy driving. Enhanced education of perioperative providers about potential narcolepsy-related issues is essential. Respondents frequently self-report adverse events in the perioperative period. Future studies should clarify the perioperative risk associated with narcolepsy to optimize the care and safety of narcoleptic patients.

Knowledge Gaps in the Perioperative Management of Adults With Narcolepsy: A Call for Further Research.

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.

Assessing readiness to drive in adolescents with narcolepsy: what are providers doing?

PURPOSE: There are no universally accepted guidelines for assessing driving readiness in adolescents with narcolepsy. The purpose of the present study was to survey pediatric sleep medicine providers regarding their current practice patterns for assessing driving readiness in adolescents with narcolepsy, knowledge of their state laws regarding physician reporting of unsafe drivers, and opinions regarding what physician duty ought to be. METHODS: This was an anonymous web-based survey distributed via the PedSleep listserv, which serves as a hub of communication for pediatric sleep medicine providers. RESULTS: A total of 52 pediatric sleep providers from 25 different states completed the survey. Eighty-eight percent of providers routinely assess driving readiness in adolescents with narcolepsy. Factors rated as "absolutely essential" by at least 50% of respondents included the following: history of previous fall-asleep crash or near miss, sleepiness (reported by patient), sleepiness (reported by caregiver), and cataplexy (reported by patient). Providers included maintenance of wakefulness testing: never (34%), if patient reports no/mild sleepiness (10%), if patient reports moderate/severe sleepiness (25%), or always regardless of patient symptoms (30%), and the median minimally acceptable result was 30 min (25-75th: 20-40 min). There was substantial lack of knowledge regarding legal obligations for reporting. CONCLUSIONS: These results demonstrate great variability in practice patterns among pediatric sleep medicine providers for assessing driving readiness in adolescents with narcolepsy. In addition, it shows limited knowledge of the providers about their respective states' laws. Further studies are required to identify the best approach to assess residual sleepiness in this population.