SleepWell24, a Smartphone Application to Promote Adherence to Positive Airway Pressure Therapy: Feasibility and Acceptability in a Randomized Controlled Trial.

OBJECTIVE: To investigate the feasibility and acceptability of SleepWell24, a multicomponent, evidence-based smartphone application, to improve positive airway pressure therapy (PAP) adherence, among patients with obstructive sleep apnea (OSA) naive to PAP. METHODS: In a single-blind randomized controlled trial, SleepWell24, with a companion activity monitor was compared to usual care plus the activity monitor and its associated app. SleepWell24 provides objective feedback on PAP usage and sleep/physical activity patterns, and chronic disease management. Patients were recruited from two sleep medicine centers and followed over the first 60 days of PAP. Feasibility and acceptability were measured by recruitment/retention rates, app usage, differences in post-trial Treatment Evaluation Questionnaire (TEQ) scores, and patient interviews. Exploratory, intent-to-treat logistic and linear mixed models estimated PAP adherence and clinical outcomes. RESULTS: Of 103 eligible participants, 87 were enrolled (SleepWell24 n = 40, control n = 47; mean 57.6y [SD = 12.3], 44.8% female). Retention was ≥95% across arms. There were no significant differences in TEQ scores. SleepWell24 participants engaged with the app on 62.9% of trial days. PAP use was high across both arms (SleepWell24 vs. Control: mean hours 5.98 vs. 5.86). There were no differences in PAP adherence or clinical outcomes. CONCLUSIONS: SleepWell24 was feasible and acceptable among PAP-naive patients with OSA. CLINICAL TRIAL REGISTRATION: NCT03156283https://www.clinicaltrials.gov/study/NCT03156283.

Clinical considerations in the treatment of idiopathic hypersomnia.

Idiopathic hypersomnia typically is a chronic and potentially debilitating neurologic sleep disorder, and is characterized by excessive daytime sleepiness. In addition to excessive daytime sleepiness, idiopathic hypersomnia symptoms can include severe sleep inertia; long, unrefreshing naps; long sleep time; and cognitive dysfunction. Patients with idiopathic hypersomnia may experience a significant impact on their quality of life, work or school performance, earnings, employment, and overall health. Given the complex range of symptoms associated with idiopathic hypersomnia and the array of treatments available, there is a need to provide guidance on the treatment of idiopathic hypersomnia and the clinically relevant recommendations that enhance effective disease management. Identifying appropriate treatment options for idiopathic hypersomnia requires timely and accurate diagnosis, consideration of individual patient factors, and frequent reassessment of symptom severity. In 2021, low-sodium oxybate was the first treatment to receive approval by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. However, many off-label treatments continue to be used. Adjunct nonpharmacologic therapies, including good sleep hygiene, patient education and counseling, and use of support groups, should be recognized and recommended when appropriate. This narrative review describes optimal treatment strategies that take into account patient-specific factors, as well as the unique characteristics of each medication and the evolution of a patient's response to treatment. Perspectives on appropriate symptom measurement and management, and potential future therapies, are also offered.

Interaction between alcohol consumption and use of peripheral arterial tone home sleep apnea tests for sleep apnea evaluation.

OBJECTIVE/BACKGROUND: Home sleep apnea tests utilizing peripheral arterial tone (PAT HSAT) detect sleep disordered breathing by measuring various physiologic measures including changes in arterial volume in the finger. Validation tests comparing PAT HSAT to simultaneous polysomnography (PSG) have demonstrated a high correlation. Alcohol increases peripheral vasodilation, which may alter arterial tone in the finger. Validation studies have not evaluated for an interaction between alcohol consumption and PAT HSAT measures. PATIENTS/METHODS: We describe an in-depth evaluation of a 53-year-old man who consumes alcohol on nightly basis. He underwent a series of 5 diagnostic studies under different conditions: three PAT HSATs (two nights with and another without alcohol) and two polysomnograms (one night with and another without alcohol). RESULTS: Obstructive sleep apnea (OSA) was found on both polysomnograms but only on the PAT HSAT without alcohol, raising the possibility of two false negative PAT HSAT results after alcohol consumption. CONCLUSIONS: This report demonstrates the need for further investigations into the performance of PAT HSATs with and without alcohol. In the meantime we recommend that testing be done without alcohol and over the course of multiple nights.

Clinician Preferences for Oxybate Treatment for Narcolepsy: Survey and Discrete Choice Experiment.

INTRODUCTION: Immediate-release sodium oxybate (SXB) has been Food and Drug Administration (FDA)-approved to treat narcolepsy since 2002; in 2020, a mixed-salt oxybates formulation was also approved. Both are taken at bedtime with a second dose taken 2.5-4 h later. A third oxybate option, an investigational extended-release SXB, may soon be available. This study was undertaken to understand clinicians' preferences between these 3 different oxybate treatments. METHODS: Clinicians in active clinical practice for 3-35 years and experience treating patients with narcolepsy were recruited. A 30-min web-based survey quantified narcolepsy disease-state attitudes, treatment perceptions, and satisfaction with oxybates on 9-point scales. A discrete choice experiment (DCE) of 12 choice sets, with 2 hypothetical treatment profiles in each, was used to capture clinician preferences about overall oxybate therapy preference, impact on patient quality of life (QoL), and patient anxiety/stress. Attributes associated with current therapies and those expected to be available in the near future were included in the design. RESULTS: The clinicians surveyed (n = 100) indicated that narcolepsy has a negative impact on patient QoL (mean rating, 7.7) and rated impact on QoL and treatment efficacy as the most important aspects of a narcolepsy treatment (mean rating, 7.3-7.7). Clinicians with experience prescribing oxybates had moderately high satisfaction with SXB and mixed-salt oxybates efficacy (mean ratings, 6.5-6.9) and safety (mean ratings, 6.1-6.7) and lower satisfaction with nightly dosing frequency (mean rating, 5.9 and 6.3, respectively). In the DCE, dosing frequency was the most important attribute driving overall product choice, patient QoL, and reducing patient anxiety/stress (relative attribute importance, 46.1, 41.7, and 44.0, respectively), with once nightly preferred over twice nightly. CONCLUSION: Clinicians indicated a significantly higher preference for the once-at-bedtime dosing schedule versus twice nightly in selecting oxybate therapies overall and when aiming to improve patient QoL or reduce patient anxiety.

Current medications for narcolepsy include immediate-release sodium oxybate and mixed-salt oxybates. People taking these oxybates for narcolepsy take 1 dose at bedtime and must wake up 2.5­4 h later for the second dose. An investigational sodium oxybate, designed as a single bedtime dose, has been tentatively approved by the US Food and Drug Administration. This study used a 30-min web-based survey to learn what clinicians think about narcolepsy and narcolepsy medicines. A discrete choice experiment was used to identify which properties of current/future oxybate medicines are most important in a narcolepsy treatment. In this exercise, relevant properties of current/future oxybate medicines were mixed and matched to create hypothetical medicine profiles. Clinicians selected from these profiles which medication they preferred overall, which would improve patient quality of life, and which would reduce patient anxiety when thinking about taking the treatment. Clinicians were moderately satisfied with the effectiveness and safety of current narcolepsy medications. They strongly preferred oxybate treatments with fewer nightly doses and agreed that waking up for the second oxybate dose causes stress for patients. In the discrete choice experiment, the number of doses each night was the product characteristic that had the biggest impact on clinicians picking a medicine for narcolepsy. This was true for overall medicine choice, choosing a medicine that would improve patient quality of life, and choosing one that would reduce patient anxiety/stress. If granted marketing approval, extended-release sodium oxybate will be a once-at-bedtime option that may overcome challenges with current oxybate therapies.

Interaction of positive airway pressure mask magnets with cardiac implantable electronic devices.

STUDY OBJECTIVES: To evaluate for potential interactions between magnetic positive airway pressure (mPAP) masks and cardiac implantable electronic devices (CIEDs) for patients with sleep apnea. METHODS: Adult patients with a CIED who used an mPAP mask were recruited from our sleep clinic to undergo a safety visit at our pacemaker clinic. We tested whether the mPAP interacted with the implanted device at home during normal use and in the clinic during simulated normal use and with direct contact. The magnetic field strength of 6 mPAP masks was tested with a gaussmeter. RESULTS: Of 13 patients tested, 1 (8%), wearing a full face mask (ResMed AirFit F30 [ResMed, San Diego, California]), had a magnet response event (interaction) with direct contact, but no interactions were identified during normal or simulated normal use in any patient. The magnetic field strength of the mPAP masks increased the closer the mask got to the CIED, from 0.4 mT (4 G) at the mask manufacturer's recommended 5.1-cm (2-inch) distance from an implanted medical device up to 291 mT (2,910 G) at 0 cm (0 inches; direct contact). CONCLUSIONS: An mPAP mask may interact with a CIED if placed directly on the skin overlying the CIED. The use of Philips Respironics (Philips, Cambridge, Massachusetts) mPAP masks is now contraindicated in patients with a CIED. Until additional studies are conducted to better document the risks and benefits of mPAP masks, we recommend discouraging patients with CIEDs from using any mPAP mask. CITATION: Ruoff CM, Tashman YS, Cheema KPK, et al. Interaction of positive airway pressure mask magnets with cardiac implantable electronic devices. J Clin Sleep Med. 2023;19(5):941-946.

Current Understanding of Narcolepsy 1 and its Comorbidities: What Clinicians Need to Know.

Narcolepsy is a chronic neurologic disorder associated with the dysregulation of the sleep-wake cycle that often leads to a decreased quality of life and results in a considerable health burden. There is often a delay to diagnosis of narcolepsy, mainly due to the lack of recognition of this disorder. One of the main factors hindering the diagnosis of narcolepsy is the association of comorbidities, which include other sleep disorders, psychiatric disorders, cardiovascular disorders, and metabolic disorders. The signs and symptoms of these comorbidities often overlap with those of narcolepsy, and some of the medications used for their treatment may obscure the symptoms of narcolepsy, leading to a delay in diagnosis. This review is targeted to clinicians unaccustomed to working with sleep disorders and aims to increase recognition and improve the management of narcolepsy.

Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine.

This article updates the American Academy of Sleep Medicine protocols for the administration of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. The American Academy of Sleep Medicine commissioned a task force of clinical experts in sleep medicine to review published literature on the performance of these tests since the publication of the 2005 American Academy of Sleep Medicine practice parameter paper. Although no evidence-based changes to the protocols were warranted, the task force made several changes based on consensus. These changes included guidance on patient preparation, medication and substance use, sleep before testing, test scheduling, optimum test conditions, and documentation. This article provides guidance to providers who order and administer the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. CITATION: Krahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2021;17(12):2489-2498.

Efficacy of pitolisant in patients with high burden of narcolepsy symptoms: pooled analysis of short-term, placebo-controlled studies.

STUDY OBJECTIVE: To evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms. METHODS: Data were pooled from two randomized, placebo-controlled, 7- or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6 mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score ≥16, Maintenance of Wakefulness Test (MWT) sleep latency ≤8 min, and ≥15 cataplexy attacks per week. RESULTS: The analysis populations included 118 patients for ESS (pitolisant, n = 60; placebo, n = 58), 105 for MWT (pitolisant, n = 59; placebo, n = 46), and 31 for cataplexy (pitolisant, n = 20; placebo, n = 11). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.3; P < 0.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction ≥3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P = 0.001); final ESS score ≤10, 36.2% versus 10.5%, respectively (P = 0.005). On the MWT, mean sleep latency increased from 3.5 min to 10.4 min with pitolisant and from 3.4 min to 6.8 min with placebo (P = 0.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) compared with placebo (-0.1; baseline, 23.1; final, 23.0; P = 0.004). Headache was the most common adverse event with pitolisant. CONCLUSIONS: Pitolisant, at once-daily doses up to 35.6 mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden.

Reliability of self-reported nicotine use as determined by serum cotinine levels in patients referred for liver transplantation.

BACKGROUND: Smoking has been associated with a higher incidence of post-hepatic transplantation de novo noncutaneous neoplasms and vascular complications. There are conflicting reports regarding increased posttransplant mortality. OBJECTIVE: The authors sought to determine the reliability of patient-reported nicotine product use (NPU) in candidates for hepatic transplantation. METHOD: The authors performed a retrospective chart review of all patients referred for liver transplantation in a 12-month period. Each patient's report of recent or current nicotine product use through smoking, chewing tobacco, or nicotine replacement products, as obtained in interviews, was compared with the quantitative result of serum cotinine levels. RESULTS: Of 171 patients referred for liver transplant evaluation during a 12-month period, 17% reported ongoing NPU, and 83% denied it. Of the patients who denied recent NPU, 11% had serum cotinine levels reflective of active use. Of the patients reporting active NPU, 97% had positive cotinine levels. CONCLUSION: There was a high degree of reliability of patient self-reported NPU, but detecting deceptive reporting is important in the selection of patients who will have long-term success with liver transplantation.

Rationale, design, and development of SleepWell24: A smartphone application to promote adherence to positive airway pressure therapy among patients with obstructive sleep apnea.

BACKGROUND: Positive airway pressure (PAP) therapy is the gold standard treatment for obstructive sleep apnea (OSA), a chronic disorder that affects 6-13% of the adult population. However, adherence to PAP therapy is challenging, and current approaches to improve adherence have limited efficacy and scalability. METHODS/DESIGN: To promote PAP adherence, we developed SleepWell24, a multicomponent, evidence-based smartphone application that delivers objective biofeedback concerning PAP use and sleep/physical activity patterns via cloud-based PAP machine and wearable sensor data, and behavior change strategies and troubleshooting of PAP therapy interface use. This randomized controlled trial will evaluate the feasibility, acceptability, and initial efficacy of SleepWell24 compared to a usual care control condition during the first 60 days of PAP therapy among patients newly diagnosed with OSA. DISCUSSION: SleepWell24 is an innovative, multi-component behavior change intervention, designed as a self-management approach to addressing the psychosocial determinants of adherence to PAP therapy among new users. The results will guide lengthier future trials that assess numerous patient-centered and clinical outcomes.

Individuals With Scleroderma May Have Increased Risk of Sleep-Disordered Breathing.

STUDY OBJECTIVES: Scleroderma is associated with abnormal skin thickening, interstitial lung disease, pulmonary hypertension, and abnormalities of the upper airway. These changes can cause cardiopulmonary complications, potentially including sleep-disordered breathing. The objective of this study is to examine the risk of sleep-disordered breathing in patients with scleroderma. METHODS: We retrospectively identified patients with documented scleroderma. We abstracted data from their electronic health records, including findings from antibody tests, serial pulmonary function tests, transthoracic echocardiography, high-resolution computed tomography, and overnight forehead oximetry. RESULTS: We identified 171 patients with scleroderma. Mean age at the time of initial consult was 56.5 years (range, 18-96 years), and 150 (86.7%) were women. Scleroderma was categorized as limited disease for 108 (62.4%), diffuse disease for 59 (34.1%), and mixed connective tissue disease for 6 (3.5%). Fifty-four patients (31.2%) had abnormal overnight forehead oximetry results, defined as an oxygen desaturation index greater than 5 or a baseline mean arterial oxygen saturation level less than 90%. CONCLUSIONS: Cardiopulmonary complications are common in patients with scleroderma, one of which may be sleep-disordered breathing. In our cohort, approximately one-third of individuals with scleroderma had evidence of sleep-disordered breathing. Moreover, the rate of sleep-disordered breathing in our population of scleroderma patients was twice the rate of pulmonary hypertension and was approximately the same as the rate of interstitial lung disease. Future prospective studies are needed to further assess the role of sleep-disordered breathing in scleroderma clinical outcomes.

Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome.

OBJECTIVES: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease. METHODS: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors. RESULTS: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits. CONCLUSIONS: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.

The Effect of Dogs on Human Sleep in the Home Sleep Environment.

OBJECTIVE: To objectively assess whether a dog in the bedroom or bed disturbs sleep. PARTICIPANTS AND METHODS: From August 1, 2015, through December 31, 2015, we evaluated the sleep of humans and dogs occupying the same bedroom to determine whether this arrangement was conducive to sleep. The study included 40 healthy adults without sleep disorders and their dogs (no dogs <6 months old). Each participant wore an accelerometer and their dog a validated dog accelerometer for 7 nights. RESULTS: The mean ± SD age of the participants (88% women) was 44±14 years and body mass index was 25±6. The mean ± SD age of the dogs was 5±3 years and weight was 15±13 kg. Mean ± SD actigraphy data showed 475±101 minutes in bed, 404±99 minutes total sleep time, 81%±7% sleep efficiency, and 71±35 minutes wake time after sleep onset. The dogs' accelerometer activity during the corresponding human sleep period was characterized as mean ± SD minutes at rest, active, and at play of 413±102, 62±43, and 2±4. The dogs had mean ± SD 85%±15% sleep efficiency. Human sleep efficiency was lower if the dog was on the bed as opposed to simply in the room (P=.003). CONCLUSION: Humans with a single dog in their bedroom maintained good sleep efficiency; however, the dog's position on/off the bed made a difference. A dog's presence in the bedroom may not be disruptive to human sleep, as was previously suspected.

A preliminary fluorodeoxyglucose positron emission tomography study in healthy adults reporting dream-enactment behavior.

STUDY OBJECTIVES: To test the hypothesis that healthy adults reporting dream-enactment behavior (DEB+) have reduced cerebral metabolic rate for glucose (CMRgl) in regions preferentially affected in patients with dementia with Lewy bodies (DLB). DESIGN: Automated brain-mapping algorithms were used to compare regional fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements from previously evaluated DEB cases and controls. SETTING: Tertiary-care academic medical centers. PARTICIPANTS: Seventeen cognitively normal patients with DEB+ and 17 control subjects (DEB-) who were individually matched for age (59 +/- 11 years), education level (16 +/- 4 years), sex (67% women), body mass index (26 +/- 4.8 kg/m2), first-degree relative with dementia (85%), and proportion of apolipoprotein E (APOE) e4 carriers (13 e4 carriers, 4 noncarriers). INTERVENTIONS: FDG-PET. MEASUREMENTS AND RESULTS: DEB was associated with significantly lower CMRgl in several brain regions known to be preferentially affected in both DLB and Alzheimer disease (parietal, temporal, and posterior cingulate cortexes) and in several other regions, including the anterior cingulate cortex (p < .001, uncorrected for multiple comparisons). The DEB-associated CMRgl reductions were significantly greater in the APOE e4 noncarriers than in the carriers. CONCLUSIONS: These preliminary findings suggest that cognitively normal persons with DEB have reduced CMRgl in brain regions known to be metabolically affected by DLB, supporting further study of DEB as a possible risk factor for the development of DLB.

Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy.

BACKGROUND: Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. METHODS: Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. RESULTS: There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. CONCLUSIONS: The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.

Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study.

STUDY OBJECTIVES: To ascertain complications associated with high-dose stimulant therapy in patients with narcolepsy or idiopathic hypersomnia. DESIGN: Case-control, retrospective chart review. SETTING: Sleep center in an academic hospital. PATIENTS: 116 patients with narcolepsy or idiopathic hypersomnia were individually matched by sex, diagnosis, age of onset, and duration of follow-up from both onset and diagnosis. Members of the high-dose group (n = 58) had received at least 1 stimulant at a dosage > or = 120% of the maximum recommended by the American Academy of Sleep Medicine Standards of Practice Committee. The standard-dose control group (n = 58) had received stimulants at a dosage < or = 100% of the American Academy of Sleep Medicine guidelines. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The prevalence of psychosis (odds ratio = 12.0 [1.6-92.0]), alcohol or polysubstance misuse (odds ratio = 4.3 [1.2-15.2]), and psychiatric hospitalization (odds ratio = 3.2 [1.1-10.0]) was significantly increased in the high-dose group. More high-dose patients also experienced tachyarrhythmias (odds ratio = 3.3 [0.92-12.1] and anorexia or weight loss (odds ratio = 11.0 [1.4-85.2]). The frequency of physician-diagnosed depression, drug-seeking and suicide-related behaviors, hypertension, and cardiovascular disease did not differ significantly between the groups. CONCLUSIONS: This study demonstrated a significantly higher occurrence of psychosis, substance misuse, and psychiatric hospitalizations in patients using high-dose stimulants compared to those using standard doses. Tachyarrhythmias and anorexia or weight loss were also more common in this group as compared with controls. Clinicians should be very cautious in prescribing dosages that exceed maximum guidelines.

Analysis of hypocretin (orexin) antibodies in patients with narcolepsy.

STUDY OBJECTIVES: We tested the hypothesis that patients with narcolepsy have serum antibodies specific for preprohypocretin and its derivatives. DESIGN: We tested sera from strictly diagnosed HLA DQB1*0602-positive narcoleptic patients with cataplexy for evidence of autoantibodies against human preprohypocretin, hypocretin 1 and 2, N-terminal leader and C-terminal peptides of preprohypocretin using enzyme-linked immunosorbent assays (ELISA). These results were compared to samples from nonnarcoleptic psychiatric and sleep apnea controls. Laboratory personnel were blinded to subject status. SETTING: Narcoleptic patients and nonnarcoleptic controls were recruited from the Mayo Clinic facilities in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. Laboratory testing was conducted in the Mayo Psychogenomic Laboratory at the Rochester Mayo Clinic. PARTICIPANTS: A sample of 34 narcoleptic patients and 49 nonnarcoleptic controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: ELISA measurements were in optical density. Primary analyses were of the entire narcoleptic and control groups for each potential antigen, and none of the differences reached P values required for significance after Bonferroni adjustment. Secondary analyses by age and sex yielded P values that were significant after Bonferroni adjustment in only 2 cases, but further statistical analyses cast doubt on the veracity of these differences. In all cases where a significant difference was recorded, the hypothesis was not supported because the control optical density reading was higher than the narcoleptic values. CONCLUSIONS: These ELISA assay results do not support the hypothesis that HLA DQB1*0602-positive narcolepsy with cataplexy is associated with serum antibodies against preprohypocretin or its cleavage products.

Reevaluating spells initially identified as cataplexy.

BACKGROUND AND PURPOSE: Cataplexy, transient episodes of bilateral muscle weakness with areflexia provoked by emotions, is a state highly specific to narcolepsy. Cataplexy is diagnosed based on clinical interview. Two screening tools have been developed recently but their usefulness has been limited because of length or current lack of psychometric data. Used effectively even these screening tests require the interpreting physician to have an understanding of the typical features of cataplexy. Most physicians encounter patients with cataplexy fairly infrequently, making it difficult to gain proficiency in detecting cataplexy based on clinical interview alone. Relatively little attention has been given to the differential diagnosis of cataplexy, which increases the likelihood of unnecessary sleep testing or false positive diagnosis. PATIENTS AND METHODS: This case series describes six cases where cataplexy was initially diagnosed. In all cases the weakness spells were eventually not attributed to cataplexy. The presentation and characteristics of these cases will be presented as a means to discuss the differential diagnosis of cataplexy. RESULTS: These cases represent a diverse set of medical disorders including bradycardia, migraine, delayed sleep phase syndrome, conversion disorder, malingering and a chronic psychotic disorder. CONCLUSIONS: A more in-depth understanding of the classic features of cataplexy should improve recognition of this fascinating state. Improved cataplexy recognition will enhance the appropriate usage of sleep tests and eventually increase the timeliness and accuracy of the diagnosis of narcolepsy with cataplexy.