Clete A. Kushida, M.D., Ph.D.

Journal Articles

• Improved sleep MRI at 3 tesla in patients with obstructive sleep apnea. Journal of magnetic resonance imaging Shin, L. K., Holbrook, A. B., Capasso, R., Kushida, C. A., Powell, N. B., Fischbein, N. J., Pauly, K. B. 2013; 38 (5): 1261-1266

  Abstract

  PURPOSE: To describe a real-time MR imaging platform for synchronous, multi-planar visualization of upper airway collapse in obstructive sleep apnea at 3 Tesla (T) to promote natural sleep with an emphasis on lateral wall visualization. MATERIALS AND METHODS: A real-time imaging platform was configured for sleep MR imaging which used a cartesian, partial k-space gradient-echo sequence with an inherent temporal resolution of 3 independent slices every 2 s. Combinations of axial, mid-sagittal, and coronal scan planes were acquired. The system was tested in five subjects with polysomnography-proven obstructive sleep apnea during sleep, with synchronous acquisition of respiratory effort and combined oral-nasal airflow data. RESULTS: Sleep was initiated and maintained to allow demonstration of sleep-induced, upper airway collapse as illustrated in two subjects when using a real-time, sleep MR imaging platform at 3T. Lateral wall collapse could not be visualized on mid-sagittal imaging alone and was best characterized on multiplanar coronal and axial imaging planes. CONCLUSION: Our dedicated sleep MR imaging platform permitted an acoustic environment of constant "white noise" which was conducive to sleep onset and sleep maintenance in obstructive sleep apnea patients at 3T. Apneic episodes, specifically the lateral walls, were more accurately characterized with synchronous, multiplanar acquisitions. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24029

  View details for PubMedID 23390078

• Habitual shortened sleep and insulin resistance: An independent relationship in obese individuals. Metabolism Liu, A., Kushida, C. A., Reaven, G. M. 2013; 62 (11): 1553-1556

  Abstract

  Short sleep duration has been reported to be associated with obesity, type 2 diabetes, and pre-diabetes. Since excess weight, glucose abnormalities, and insulin resistance tend to cluster, the individual role insulin resistance may have in habitual shortened sleep is unclear. The study purpose was to assess whether habitual sleep curtailment is independently related to insulin resistance in obese individuals.Non-diabetic, overweight/obese individuals from the community were stratified as insulin-resistant (n=35) or insulin-sensitive (n=21) based on steady-state plasma glucose concentrations (SSPG) during the insulin suppression test. Seventy-five gram oral glucose tolerance tests were performed. Participants were asked, "On average, how many hours of sleep do you get per night?" Shortened sleep duration was defined as less than 7h of sleep per night.SSPG concentrations differed 2.5-fold (P<0.001) between insulin-resistant and insulin-sensitive individuals. Impaired fasting glucose and glucose intolerance were prevalent in both groups (>40%); however, body mass index, waist circumference, mean fasting or 2-h post-glucola glucose concentrations were not significantly different. Insulin-resistant individuals reported (mean±SD) fewer hours of sleep than did insulin-sensitive individuals (6.53±1.1 vs 7.24±0.9h, P<0.05). Shortened sleep duration was more prevalent among insulin-resistant as compared with insulin-sensitive individuals (60% vs 24%, P<0.05).Non-diabetic, insulin-resistant individuals averaged fewer hours of sleep and were more likely to report shortened sleep duration as compared with similarly obese insulin-sensitive individuals. There appears to be an independent association between habitual shortened sleep and insulin resistance among obese, dysglycemic adults without diabetes.

  View details for DOI 10.1016/j.metabol.2013.06.003

  View details for PubMedID 23849514

• Risk for obstructive sleep apnea in obese, nondiabetic adults varies with insulin resistance status SLEEP AND BREATHING Liu, A., Kushida, C. A., Reaven, G. M. 2013; 17 (1): 333-338

  Abstract

  Obstructive sleep apnea (OSA) is an increasingly common sleep disorder, especially among obese adults. Early identification of adults at risk for OSA would be of substantial benefit; however, the magnitude of the obesity epidemic requires that screening be performed judiciously. The study's aim was to utilize questionnaires that assess OSA risk and symptoms to test the hypothesis that the most insulin-resistant subset of obese individuals is at highest risk for OSA.Nondiabetic, overweight to obese volunteers underwent direct quantification of insulin sensitivity by measuring steady-state plasma glucose concentrations during the insulin suppression test. Insulin-sensitive and insulin-resistant individuals were administered the Berlin and STOP questionnaires to determine OSA risk status, and Epworth Sleepiness Scale (ESS) to evaluate daytime sleepiness. Fasting insulin and lipid/lipoprotein measurements were performed.Insulin-mediated glucose disposal differed threefold (p?

  View details for DOI 10.1007/s11325-012-0696-0

  View details for Web of Science ID 000315167200052

  View details for PubMedID 22481243

• Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) SLEEP Kushida, C. A., Nichols, D. A., Holmes, T. H., Quan, S. F., Walsh, J. K., Gottlieb, D. J., Simon, R. D., Guilleminault, C., White, D. P., Goodwin, J. L., Schweitzer, P. K., Leary, E. B., Hyde, P. R., Hirshkowitz, M., Green, S., McEvoy, L. K., Chan, C., Gevins, A., Kay, G. G., Bloch, D. A., Crabtree, T., Dement, W. C. 2012; 35 (12): 1593-U40

  Abstract

  To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA).The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures.Active or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F])The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test.CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.Registered at clinicaltrials.gov. Identifier: NCT00051363. CITATION: Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

  View details for DOI 10.5665/sleep.2226

  View details for Web of Science ID 000313000600005

  View details for PubMedID 23204602

• Strategies for De-identification and Anonymization of Electronic Health Record Data for Use in Multicenter Research Studies MEDICAL CARE Kushida, C. A., Nichols, D. A., Jadrnicek, R., Miller, R., Walsh, J. K., Griffin, K. 2012; 50 (7): S82-S101

  Abstract

  De-identification and anonymization are strategies that are used to remove patient identifiers in electronic health record data. The use of these strategies in multicenter research studies is paramount in importance, given the need to share electronic health record data across multiple environments and institutions while safeguarding patient privacy.Systematic literature search using keywords of de-identify, deidentify, de-identification, deidentification, anonymize, anonymization, data scrubbing, and text scrubbing. Search was conducted up to June 30, 2011 and involved 6 different common literature databases. A total of 1798 prospective citations were identified, and 94 full-text articles met the criteria for review and the corresponding articles were obtained. Search results were supplemented by review of 26 additional full-text articles; a total of 120 full-text articles were reviewed.A final sample of 45 articles met inclusion criteria for review and discussion. Articles were grouped into text, images, and biological sample categories. For text-based strategies, the approaches were segregated into heuristic, lexical, and pattern-based systems versus statistical learning-based systems. For images, approaches that de-identified photographic facial images and magnetic resonance image data were described. For biological samples, approaches that managed the identifiers linked with these samples were discussed, particularly with respect to meeting the anonymization requirements needed for Institutional Review Board exemption under the Common Rule.Current de-identification strategies have their limitations, and statistical learning-based systems have distinct advantages over other approaches for the de-identification of free text. True anonymization is challenging, and further work is needed in the areas of de-identification of datasets and protection of genetic information.

  View details for DOI 10.1097/MLR.0b013e3182585355

  View details for Web of Science ID 000314235100016

  View details for PubMedID 22692265

• A method for estimating normative distributions for study-specific populations of clinical trials CONTEMPORARY CLINICAL TRIALS Holmes, T. H., Nichols, D. A., Thomander, D., Kushida, C. A. 2012; 33 (2): 445-449

  Abstract

  For any particular psychological instrument, published normative distributions have been derived in one to at most a few specific "reference" populations. Here a method is provided for estimating a normative distribution pertinent to the specific population being evaluated in a randomized clinical trial. Normative quantiles are obtained using quantile regression, a method chosen for its flexibility in that no assumptions are made about the parametric form (e.g., Gaussian) of the normative distribution to be estimated. Outcome is regressed on disease severity for the ?th quantile using that sample of consented participants who were not randomized because they fell below the trial's disease severity entry criterion. The ?th quantile of the normative distribution is then estimated by the intercept of this fitted regression function, which corresponds to severity of zero. Additional covariates that explain variation in outcome may be included to permit adjustment for shifts in their distributions between the randomized and non-randomized samples. The method is illustrated using data on a depression instrument (GRID Hamilton Rating Scale for Depression) and a neurocognitive instrument (CogScreen Pathfinder Number) from a multicenter clinical trial in sleep apnea patients.

  View details for DOI 10.1016/j.cct.2011.11.014

  View details for Web of Science ID 000300962000025

  View details for PubMedID 22138103

• Positive Airway Pressure Initiation: A Randomized Controlled Trial to Assess the Impact of Therapy Mode and Titration Process on Efficacy, Adherence, and Outcomes SLEEP Kushida, C. A., Berry, R. B., Blau, A., Crabtree, T., Fietze, I., Kryger, M. H., Kuna, S. T., Pegram, G. V., Penzel, T. 2011; 34 (8): 1083-1092

  Abstract

  (1) To determine the efficacy of automatically adjusted positive airway pressure (APAP) with a comfort feature (A-Flex) at reducing apneas and hypopneas in participants with moderate to severe OSA. (2) To determine the relative difference between A-Flex, continuous positive airway pressure (CPAP), and APAP-derived optimal pressure for CPAP (CPAP(APAP)) on adherence to treatment. (3) To determine the relative difference between APAP with A-Flex, CPAP, and CPAP(APAP) on long-term change in functional outcomes.Randomized, double-blinded, 3-arm, multicenter trial.University and Veterans Affairs medical centers.168 participants were randomized, and 140 completed the 180-day study.(1) A-Flex; (2) CPAP; (3) APAP for 14 days and then switched to CPAP at a fixed pressure.Apnea-hypopnea indices, average and minimum oxygen saturation, time spent < 90% were significantly poorer for A-Flex vs. CPAP at the initiation of study treatment; with the exception of minimum oxygen saturation, these differences were absent at 180 days. A-Flex had lower average leak values at both 3 and 6 months. There were no significant differences between groups in major efficacy, adherence, and outcome (subjective sleepiness, objective vigilance, blood pressure, quality of life) measures. No differences between groups in attitudes toward use were observed at 3 or 6 months; participant ratings for CPAP were significantly higher than A-Flex on treatment satisfaction and benefit, but not different for sleep quality and mask comfort.We found that A-Flex shows equivalency, but non-superiority (except for average leak values), in efficacy, adherence, and functional outcomes compared to CPAP after either 3 or 6 months. CLINICAL TRIAL REGISTRY: Positive Pressure Treatment of Obstructive Sleep Apnea, http://www.clinicaltrials.gov, NCT00636181.

  View details for DOI 10.5665/SLEEP.1166

  View details for Web of Science ID 000293466200013

  View details for PubMedID 21804670

• Reliability and validity of two self-administered questionnaires for screening restless legs syndrome in population-based studies SLEEP MEDICINE Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Kushida, C. A., Rama, A. N., Black, J. E., Bernstein, A., Kasten, M., Chade, A., Leimpeter, A., Cassidy, J., McGuire, V., Nelson, L. M. 2010; 11 (2): 154-160

  Abstract

  A reliable and valid questionnaire for screening restless legs syndrome (RLS) is essential for determining accurate estimates of disease frequency. In a 2002 NIH-sponsored workshop, experts suggested three mandatory questions for identifying RLS in epidemiologic studies. We evaluated the reliability and validity of this RLS-NIH questionnaire in a community-based sample and concurrently developed and evaluated the utility of an expanded screening questionnaire, the RLS-EXP.The study was conducted at Kaiser Permanente of Northern California and the Stanford University Sleep Clinic. We evaluated test-retest reliability in a random sample of subjects with prior physician-assigned RLS (n=87), subjects with conditions frequently misclassified as RLS (n=31), and healthy subjects (n=9). Validity of both instruments was evaluated in a random sample of 32 subjects, and in-person examination by two RLS specialists was used as the gold standard.For the first three RLS-NIH questions, the kappa statistic for test-retest reliability ranged from 0.5 to 1.0, and sensitivity and specificity was 86% and 45%, respectively. For the subset of five questions on RLS-EXP that encompassed cardinal features for diagnosing RLS, kappas were 0.4-0.8, and sensitivity and specificity were 81% and 73%, respectively.Sensitivity of RLS-NIH is good; however, the specificity of the instrument is poor when examined in a sample that over-represents subjects with conditions that are commonly misclassified as RLS. Specificity can be improved by including separate questions on cardinal features, as used in the RLS-EXP, and by including a few questions that identify RLS mimics, thereby reducing false positives.

  View details for DOI 10.1016/j.sleep.2009.01.012

  View details for Web of Science ID 000275584500009

  View details for PubMedID 20089446

• Gabapentin Enacarbil in Restless Legs Syndrome: A Phase 2b, 2-Week, Randomized, Double-Blind, Placebo-Controlled Trial CLINICAL NEUROPHARMACOLOGY Walters, A. S., Ondo, W. G., Kushida, C. A., Becker, P. M., Ellenbogen, A. L., Canafax, D. M., Barrett, R. W. 2009; 32 (6): 311-320

  Abstract

  Assess the efficacy and tolerability of gabapentin enacarbil (GEn), a transported prodrug of gabapentin with improved gabapentin exposure, in adults with moderate-to-severe primary restless legs syndrome.This 14-day, double-blind, randomized, controlled trial of GEn at 1200 or 600 mg or placebo taken once daily, evaluated the mean change from baseline International Restless Legs Scale (IRLS) total score at end of treatment (day 14:primary comparison, GEn at 1200 mg vs placebo). Secondary end points included Clinical Global Impression-Improvement scale outcomes at day 14.Ninety-five subjects were randomized (GEn: 1200 mg, n = 33 and 600 mg, n = 29; placebo, n = 33); 2 subjects (GEn at 1200 mg) withdrew because of adverse events. At day 14,the mean (SD) change from baseline IRLS total score was significantly greater with GEn at 1200 mg (-16.1 [7.93]) compared with placebo (-8.9 [7.72]; adjusted mean treatment difference, -7.2; P < 0.0001). Investigator-rated Clinical Global Impression-Improvement scale responses also significantly favored GEn at 1200 mg compared with placebo (P G 0.0001).The mean (SD) change from baseline IRLS total score with GEn at 600 mg at day 14 was -9.1 (5.95), similar to placebo. The most commonly reported treatment-emergent adverse events were somnolence (GEn: 1200 mg, 36% and 600 mg, 14%; placebo,15%) and dizziness (GEn: 1200 mg, 18% and 600 mg, 14%; placebo, 3%), most of which were rated mild or moderate in intensity.Gabapentin enacarbil at 1200 mg significantly improved restless legs syndrome symptoms compared with placebo. Efficacy outcomes for GEn at 600 mg were similar to placebo. Both GEn doses were generally well tolerated.

  View details for DOI 10.1097/WNF.0b013e3181b3ab16

  View details for Web of Science ID 000272362900002

  View details for PubMedID 19667976

• Primary Hypersomnias of Central Origin SEMINARS IN NEUROLOGY Frenette, E., Kushida, C. A. 2009; 29 (4): 354-367

  Abstract

  Hypersomnia is a frequently encountered symptom in clinical practice. The cardinal manifestation is inappropriate daytime sleepiness, common to all types of hypersomnias. Hypersomnias of central origin are a rare cause of excessive daytime sleepiness, much rarer than the hypersomnia related to other pathologies, such as sleep-disordered breathing. Narcolepsy, with or without cataplexy, remains the most well studied of the primary hypersomnias. Although recognized more than a century ago, it was not until the end of the 20th century that major breakthroughs led to a better understanding of the disease, with hope of more specific therapies. The authors review the major aspects of this disorder, including the newer treatment modalities. Idiopathic hypersomnia is also part of the primary hypersomnias. Although difficult to diagnose, certain peculiarities stand out to help us differentiate it from the more commonly seen narcolepsy. The recurrent hypersomnias, particularly the Kleine-Levin syndrome, will be discussed. This rare disorder has been studied more closely in the last few years with abundant epidemiologic data assembled through literature and worldwide case reviews. Understanding the primary central hypersomnias warrants a thorough look from the original description, as well as a peek at the future, while more efficacious diagnostic and therapeutic interventions are currently being developed.

  View details for DOI 10.1055/s-0029-1237114

  View details for Web of Science ID 000269984500008

  View details for PubMedID 19742411

• Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS NEUROLOGY Kushida, C. A., Becker, P. M., Ellenbogen, A. L., Canafax, D. M., Barrett, R. W. 2009; 72 (5): 439-446

  Abstract

  To assess the efficacy and tolerability of the nondopaminergic agent XP13512/GSK1838262 in adults with moderate to severe primary restless legs syndrome (RLS).Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 pm with food. Coprimary endpoints were mean change from baseline International Restless Legs Scale (IRLS) total score and proportion of investigator-rated responders (very much improved or much improved on the Clinical Global Impression-Improvement scale) at week 12 (last observation carried forward). Tolerability was assessed using adverse events, vital signs, and clinical laboratory parameters.A total of 222 patients were randomized (XP13512 = 114, placebo = 108) and 192 patients (XP13512 = 100, placebo = 92) completed the study. At week 12, the mean change from baseline IRLS total score was greater with XP13512 (-13.2) compared with placebo (-8.8). Analysis of covariance, adjusted for baseline score and pooled site, demonstrated a mean treatment difference of -4.0 (95% confidence interval [CI], -6.2 to -1.9; p = 0.0003). More patients treated with XP13512 (76.1%) were responders compared with placebo (38.9%; adjusted OR 5.1; 95% CI, 2.8 to 9.2; p < 0.0001). Significant treatment effects for both coprimary measures were identified at week 1, the earliest time point measured. The most commonly reported adverse events were somnolence (XP13512 27%, placebo 7%) and dizziness (XP13512 20%, placebo 5%), which were mild to moderate in intensity and generally remitted.XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS.

  View details for Web of Science ID 000263188200009

  View details for PubMedID 19188575

• A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of XP13512/GSK1838262 in the Treatment of Patients With Primary Restless Legs Syndrome SLEEP Kushida, C. A., Walters, A. S., Becker, P., Thein, S. G., Perkins, T., Roth, T., Canafax, D., Barrett, R. W. 2009; 32 (2): 159-168

  Abstract

  To evaluate the efficacy and tolerability of XP13512/ GSK1838262, an investigational nondopaminergic agent for the treatment of moderate-to-severe primary restless legs syndrome (RLS).Randomized, double-blind, placebo-controlled, crossover trial.Nine US clinical sites.Thirty-eight treatment-naive subjects with RLS (mean +/- SD age 50.1 +/- 13.2 years).XP13512 1800 mg/day followed by placebo or placebo followed by XP13512 1800 mg/day for 14 days, with a 7-day washout between treatment periods.The primary endpoint was mean change from baseline International RLS Study Group rating scale (IRLS) total score on Day 14, analyzed using analysis of variance with sequence, period, and treatment as fixed effects and subjects within sequence as a random effect. XP13512 significantly reduced IRLS total score on Day 14 compared with placebo (mean +/- SD: XP13512 -12.1 +/-6.5, placebo -1.9 +/- 6.3; P < 0.0001). Polysomnographic data showed that XP13512 significantly improved sleep architecture on Day 14 compared with placebo (mean +/- SD change from baseline sleep time [minutes]: stage 1: XP13512 -9.8 +/- 23.9, placebo 0.4 +/-23.2; adjusted P<0.0054, nominal P<0.0001; stage 3/4 (slow-wave sleep): XP13512 22.8 +/- 40.8, placebo 1.4 +/- 34.3; adjusted P=0.0092, nominal P=0.0002). The most frequently reported adverse events were somnolence (XP13512 30.6%, placebo 2.8%) and dizziness (XP13512 27.8%, placebo 5.6%).XP13512 1800 mg/day significantly reduced RLS symptoms, improved sleep, and was generally well tolerated in subjects with moderate-to-severe primary RLS across 14 days of treatment.

  View details for Web of Science ID 000262890300006

  View details for PubMedID 19238802

• Multiple Sleep Latency Test and Maintenance of Wakefulness Test CHEST Sullivan, S. S., Kushida, C. A. 2008; 134 (4): 854-861

  Abstract

  Excessive daytime sleepiness and fatigue are common complaints in the sleep clinic. The objective evaluation and quantification of these symptoms is important for both the diagnosis of underlying health problems and for gauging treatment response. The multiple sleep latency test measures physiologic sleepiness, whereas the maintenance of wakefulness test (MWT) aims to measure manifest sleepiness. Neither test correlates well with subjective measures of sleep such as the Epworth sleepiness scale and the Stanford sleepiness scale. Although in the past methodological testing differences existed, in 2005 updated practice parameters were published, promoting the standardization of testing procedures. In recent years, there has been an effort to document daytime sleepiness when associated with occupational risk. However, these laboratory-based tests may not reflect or predict real-life experience. Normative data for both tests, particularly the MWT, are limited, and are inadequate for the evaluation of pediatric patients, shift workers, and others.

  View details for DOI 10.1378/chest.08-0822

  View details for Web of Science ID 000260097600032

  View details for PubMedID 18842919

• Patient- and Physician-Rated Measures Demonstrate the Effectiveness of Ropinirole in the Treatment of Restless Legs Syndrome CLINICAL NEUROPHARMACOLOGY Kushida, C. A., Geyer, J., Tolson, J. M., Asgharian, A. 2008; 31 (5): 281-286

  Abstract

  To investigate the effect of twice-daily ropinirole in patients with early evening restless legs syndrome (RLS) symptoms, particularly focusing on the relationship of patient- and physician-rated assessment of treatment outcomes.In this multicenter, double-blind, randomized, 12-week, flexible-dose study, patients with primary RLS, with symptom onset no earlier than 5 PM and a baseline International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score > or = 20 received ropinirole 0.5 to 6.0 mg/d twice daily in equally divided doses, or placebo. First dose was 1 hour before the usual onset of symptoms; second dose was 3 to 8 hours after the first. Primary end point: change from baseline in IRLS total score at week 12 last observation carried forward (LOCF). Key secondary end points: proportion of responders (rated "very much improved" or "much improved") on the Clinical Global Impression-Improvement and the Patient Global Improvement scales.Improvements in IRLS total score were statistically significantly greater for ropinirole (n = 175), compared with placebo (n = 184) at all assessment points beginning at day 3 through to week 12 LOCF (P < 0.001). A statistically significantly greater proportion of patients were classified as responders on the Clinical Global Impression-Improvement scale at all assessment points from day 3 through week 12 LOCF (P < 0.001) and on the Patient Global Improvement scale at all assessment points from day 1 (P = 0.013) through day 7 LOCF (P < or = 0.05 for days 2-7 LOCF) and at week 12 LOCF (P < 0.001).Ropinirole is associated with consistent early and sustained improvements in the symptoms of RLS, as rated by patients and physicians.

  View details for DOI 10.1097/WNF.0B013E31815A3EEC

  View details for Web of Science ID 000260087400005

  View details for PubMedID 18836346

• Clinical presentation, diagnosis, and quality of life issues in restless legs syndrome AMERICAN JOURNAL OF MEDICINE Kushida, C. A. 2007; 120 (1): S4-S12

  Abstract

  Restless legs syndrome (RLS) is a generally underdiagnosed and undertreated condition. It is a common cause of sleep disturbance that can severely disrupt normal life functioning. However, because of the failure to recognize RLS as a distinct disorder, clinicians have minimized the significance of the morbidity experienced by some patients. A positive family history is present in >50% of patients with RLS. Indeed, a person with RLS is 3 to 6 times more likely to have a positive family history of RLS than is an individual who does not have the disease. The differential diagnosis of RLS includes both movement and sleep disorders. Establishing an accurate diagnosis is crucial because effective treatment is available. In 2002, RLS experts revised diagnostic criteria and established 4 essential criteria for the diagnosis. Assessing the most bothersome symptoms and quantifying the severity of RLS are important because not all patients require medical therapy. Moreover, therapy may vary according to which symptom represents the major problem.

  View details for DOI 10.1016/j.amjmed.2006.11.002

  View details for Web of Science ID 000243201800002

  View details for PubMedID 17198769

• Ropinirole for the treatment of restless legs syndrome. Neuropsychiatric disease and treatment Kushida, C. A. 2006; 2 (4): 407-419

  Abstract

  Dopaminergic agents, anticonvulsants, benzodiazepines, opiates, and iron supplementation comprise the classes of medications commonly used to treat restless legs syndrome (RLS), which is a disorder that is estimated to affect about 1 in 10 individuals worldwide and impacts an affected patient's sleep, mood, daytime function, and quality of life. RLS is characterized by an urge to move the legs that is worse at bedtime and at rest; the symptoms are temporarily relieved by leg movement. It is frequently accompanied by periodic limb movements during sleep (PLMS), which may independently disrupt sleep and may cause daytime drowsiness. Dopaminergic agents are considered to be first-line therapy in the management of RLS as well as PLMS. Ropinirole (Requip((R)), GlaxoSmithKline) is a dopamine agonist that was the first medication approved by the US Food and Drug Administration (FDA) for the treatment of moderate-to-severe primary RLS. Based on several large-scale clinical trials and open-label clinical series, this medication has been demonstrated to be effective and safe in treating the motor symptoms of RLS and improving sleep quality.

  View details for PubMedID 19412490

• Efficacy and safety of pramipexole in restless legs syndrome NEUROLOGY Winkelman, J. W., Sethi, K. D., Kushida, C. A., Becker, P. M., Koester, J., Cappola, J. J., Reess, J. 2006; 67 (6): 1034-1039

  Abstract

  To evaluate the efficacy and safety of pramipexole in patients with moderate to severe restless legs syndrome (RLS) METHODS: The authors conducted a 12-week, double-blind, randomized, placebo-controlled trial of fixed doses of pramipexole (0.25, 0.50, and 0.75 mg/day). Patients (N = 344) were up-titrated to their randomized dose over 3 weeks. The primary efficacy endpoints were patient ratings of symptom severity on the International RLS Study Group Rating Scale (IRLS) and clinician ratings of improvement on the Clinical Global Impressions-Improvement (CGI-I) scale. Secondary efficacy endpoints included visual analogue ratings of sleep and quality of life (QOL) RESULTS: By both primary measures, pramipexole was superior to placebo. For IRLS, the adjusted mean (SE) change from baseline to week 12 was -9.3 (1.0) for placebo, -12.8 (1.0) for 0.25 mg/day, -13.8 (1.0) for 0.50 mg/day, and -14.0 (1.0) for 0.75 mg/day (all p < 0.01). Similarly, pramipexole increased the percentage of patients with a CGI-I rating of "very much improved" or "much improved" at the end of the trial (51.2% for placebo and 74.7%, 67.9%, and 72.9% for pramipexole; all p < 0.05). Pramipexole significantly improved ratings of symptom severity, day and night, and also ratings of sleep satisfaction and QOL. Pramipexole was well tolerated: The most frequent adverse events with higher occurrence in the pramipexole group were nausea (19.0% vs 4.7%) and somnolence (10.1% vs 4.7%)As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.

  View details for Web of Science ID 000240749900022

  View details for PubMedID 16931507

• Countermeasures for sleep loss and deprivation. Current treatment options in neurology Kushida, C. A. 2006; 8 (5): 361-366

  Abstract

  Sleep deprivation is ubiquitous and carries profound consequences in terms of personal and public health and safety. There is no substitute for a good night's sleep. Sleep that is optimal in quality and quantity for individuals, factoring in their age and personal sleep requirements, will minimize sleep debt and maximize daytime performance. Therefore, setting aside an adequate amount of time for sleep should be a priority; sleep should not be sacrificed at the expense of other activities of daily living. Nevertheless, there are certain therapeutic countermeasures available for individuals who are unable to obtain adequate sleep because of medical or sleep-related conditions (eg, narcolepsy, obstructive sleep apnea) when excessive daytime sleepiness is the main feature of the condition, or residual sleepiness despite treatment for the main conditions is present. These therapeutic countermeasures may also be considered in situations in which occupational constraints (eg, rotating shift work, military duty) dictate that constant or heightened vigilance is important or critical to work performance, crucial decision making, and/or survival. Exploration of the causes of sleep loss or deprivation, whether it is voluntary, or work or family induced, and/or the effects of a medical or sleep disorder, is a necessary first step in the evaluation of a patient who has significant daytime fatigue or sleepiness. Wake-promoting substances and medications such as caffeine, modafinil, methylphenidate, and dextroamphetamine may be considered in situations in which sleep loss is unavoidable or persists despite treatment of an underlying disorder that is characterized by or associated with daytime fatigue or sleepiness.

  View details for PubMedID 16901375

• The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures. Journal of clinical sleep medicine Kushida, C. A., Nichols, D. A., Quan, S. F., Goodwin, J. L., White, D. P., Gottlieb, D. J., Walsh, J. K., Schweitzer, P. K., Guilleminault, C., Simon, R. D., Leary, E. B., Hyde, P. R., Holmes, T. H., Bloch, D. A., Green, S., McEvoy, L. K., Gevins, A., Dement, W. C. 2006; 2 (3): 288-300

  Abstract

  To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea.Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy.Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. Patients or Participants: Target enrollment is 1100 randomly assigned subjects across 5 clinical centers.Active versus sham (subtherapeutic) CPAP. Measurements and Results: A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life.The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.

  View details for PubMedID 17561541

• Botulinum toxin A: new hope for RLS? Journal of clinical sleep medicine Kushida, C. A. 2006; 2 (3): 279-280

  View details for PubMedID 17561539

• Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders SLEEP Kushida, C. A., Littner, M. R., Hirshkowitz, M., Morgenthaler, T. I., Alessi, C. A., Bailey, D., Boehlecke, B., Brown, T. M., Coleman, J., Friedman, L., Kapen, S., Kapur, V. K., Kramer, M., Lee-Chiong, T., Owens, J., Pancer, J. P., Swick, T. J., Wise, M. S. 2006; 29 (3): 375-380

  Abstract

  Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBD) including obstructive sleep apnea (OSA). Currently, PAP devices come in three forms: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) automatic self-adjusting positive airway pressure (APAP). After a patient is diagnosed with OSA, the current standard of practice involves performing full, attended polysomnography during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guideline for using CPAP and BPAP appropriately (an earlier review and practice parameters for APAP was published in 2002). Major conclusions and current recommendations are as follows: 1) A diagnosis of OSA must be established by an acceptable method. 2) CPAP is effective for treating OSA. 3) Full-night, attended studies performed in the laboratory are the preferred approach for titration to determine optimal pressure; however, split-night, diagnostic-titration studies are usually adequate. 4) CPAP usage should be monitored objectively to help assure utilization. 5) Initial CPAP follow-up is recommended during the first few weeks to establish utilization pattern and provide remediation if needed. 6) Longer-term follow-up is recommended yearly or as needed to address mask, machine, or usage problems. 7) Heated humidification and a systematic educational program are recommended to improve CPAP utilization. 8) Some functional outcomes such as subjective sleepiness improve with positive pressure treatment in patients with OSA. 9) CPAP and BPAP therapy are safe; side effects and adverse events are mainly minor and reversible. 10) BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with hypercapnia.

  View details for Web of Science ID 000240123600014

  View details for PubMedID 16553024

• Pramipexole for the treatment of restless legs syndrome EXPERT OPINION ON PHARMACOTHERAPY Kushida, C. A. 2006; 7 (4): 441-451

  Abstract

  Restless legs syndrome (RLS) is a common disorder that is estimated to affect 10% of Americans. However, it remains largely undiagnosed and untreated by clinicians. The primary symptoms of this condition are leg discomfort or an urge to move that is temporarily relieved by movement and is worse at rest and at bedtime. RLS impacts the quality of life of the sufferer by disrupting sleep and disturbing or curtailing work and social activities. Approximately 80% of RLS sufferers also have periodic limb movements during sleep, in which repetitive leg movements fragment sleep and may result in daytime drowsiness. RLS may be treated by dopaminergic agents, benzodiazepines, anticonvulsants and opiates; dopamine agonists are currently considered first-line therapy for this condition. Pramipexole has been studied in the treatment of RLS since 1998. This article reviews the role of this medication in the management of this serious neurological disorder.

  View details for DOI 10.1517/14656566.7.4.441

  View details for Web of Science ID 000235822800008

  View details for PubMedID 16503816

• Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances: An update for 2005 SLEEP Kushida, C. A., Morgenthaler, T. I., Littner, M. R., Alessi, C. A., Bailey, D., Coleman, J., Friedman, L., Hirshkowitz, M., Kapen, S., Kramer, M., Lee-Chiong, T., Owens, J., Pancer, J. P. 2006; 29 (2): 240-243

  Abstract

  These practice parameters are an update of the previously published recommendations regarding use of oral appliances in the treatment of snoring and Obstructive Sleep Apnea (OSA). Oral appliances (OAs) are indicated for use in patients with mild to moderate OSA who prefer them to continuous positive airway pressure (CPAP) therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP. Until there is higher quality evidence to suggest efficacy, CPAP is indicated whenever possible for patients with severe OSA before considering OAs. Oral appliances should be fitted by qualified dental personnel who are trained and experienced in the overall care of oral health, the temporomandibular joint, dental occlusion and associated oral structures. Follow-up polysomnography or an attended cardiorespiratory (Type 3) sleep study is needed to verify efficacy, and may be needed when symptoms of OSA worsen or recur. Patients with OSA who are treated with oral appliances should return for follow-up office visits with the dental specialist at regular intervals to monitor patient adherence, evaluate device deterioration or maladjustment, and to evaluate the health of the oral structures and integrity of the occlusion. Regular follow up is also needed to assess the patient for signs and symptoms of worsening OSA. Research to define patient characteristics more clearly for OA acceptance, success, and adherence is needed.

  View details for Web of Science ID 000240123500016

  View details for PubMedID 16494092

• Practice parameters for the indications for polysomnography and related procedures: An update for 2005 SLEEP Kushida, C. A., Littner, M. R., Morgenthaler, T., Alessi, C. A., Bailey, D., Coleman, J., Friedman, L., Hirshkowitz, M., Kapen, S., Kramer, M., Lee-Chiong, T., Loube, D. L., Owens, J., Pancer, J. P., Wise, M. 2005; 28 (4): 499-521

  Abstract

  These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders. Diagnostic categories include the following: sleep related breathing disorders, other respiratory disorders, narcolepsy, parasomnias, sleep related seizure disorders, restless legs syndrome, periodic limb movement sleep disorder, depression with insomnia, and circadian rhythm sleep disorders. Polysomnography is routinely indicated for the diagnosis of sleep related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep related breathing disorders; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep related symptoms; to assist in the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure related; in a presumed parasomnia or sleep related seizure disorder that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement sleep disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with seizures who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression.

  View details for Web of Science ID 000228134900015

  View details for PubMedID 16171294

• Practice Parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test - An American Academy of Sleep Medicine Report - Standards of practice committee of the American Academy of Sleep Medicine SLEEP Littner, M. R., Kushida, C., Wise, M., Davila, D. G., Morgenthaler, T., Lee-Chiong, T., Hirshkowitz, M., Loube, D. L., Bailey, D., Berry, R. B., Kapen, S., Kramer, M. 2005; 28 (1): 113-121

  Abstract

  Characterization of excessive sleepiness is an important task for the sleep clinician, and assessment requires a thorough history and in many cases, objective assessment in the sleep laboratory. These practice parameters were developed to guide the sleep clinician on appropriate clinical use of the Multiple Sleep Latency Test (MSLT), and the Maintenance of Wakefulness Test (MWT). These recommendations replace those published in 1992 in a position paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature and grade the evidence regarding the clinical use of the MSLT and the MWT. Practice parameters were developed based on this review and in most cases evidence based methods were used to support recommendations. When data were insufficient or inconclusive, the collective opinion of experts was used to support recommendations. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The MSLT is indicated as part of the evaluation of patients with suspected narcolepsy and may be useful in the evaluation of patients with suspected idiopathic hypersomnia. The MSLT is not routinely indicated in the initial evaluation and diagnosis of obstructive sleep apnea syndrome, or in assessment of change following treatment with nasal continuous positive airway pressure (CPAP). The MSLT is not routinely indicated for evaluation of sleepiness in medical and neurological disorders (other than narcolepsy), insomnia, or circadian rhythm disorders. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on the MWT with risk of accidents in real world circumstances. For this reason, the sleep clinician should not rely solely on mean sleep latency as a single indicator of impairment or risk for accidents, but should also rely on clinical judgment. Assessment should involve integration of findings from the clinical history, compliance with treatment, and, in some cases, objective testing using the MWT. These practice parameters also include recommendations for the MSLT and MWT protocols, a discussion of the normative data available for both tests, and a description of issues that need further study.

  View details for Web of Science ID 000228028000016

  View details for PubMedID 15700727

• Ropinirole in the treatment of restless legs syndrome. Expert review of neurotherapeutics Kakar, R. S., Kushida, C. A. 2005; 5 (1): 35-42

  Abstract

  Ropinirole is an original nonergoline dopamine agonist indicated for the treatment of Parkinson's disease. However, recent developments in the study of restless legs syndrome have demonstrated another role for this drug. The symptoms of restless legs syndrome are responsive to dopaminergic agents such as ropinirole. The dosage of ropinirole needed to treat the symptoms of restless legs syndrome appears to be much smaller than what is necessary for Parkinson's disease therapy. The liver is primarily responsible for the metabolism of ropinirole, which has an elimination half-life of approximately 6 h. Ropinirole is generally well tolerated, with no serious adverse effects. Clinical studies have indicated that ropinirole can effectively reduce the motor symptoms of restless legs syndrome and improve overall sleep quality.

  View details for PubMedID 15853472

• Modeling the causal relationships between symptoms associated with restless legs syndrome and the patient-reported impact of RLS SLEEP MEDICINE Kushida, C. A., Allen, R. P., Atkinson, M. J. 2004; 5 (5): 485-488

  Abstract

  The objective of this study is to examine the causal relationships between the symptoms of restless legs syndrome (RLS) and specific clinical and subjective health-related, quality of life consequences. Structural equation modeling was applied to data from a questionnaire-based observational study. The RLS morbidities of decreased functional alertness and emotional distress in our sample of patients appear to be mostly secondary to the sleep disturbance associated with RLS. There was no clear indication of any other feature of RLS affecting these two aspects of RLS morbidity. A primary treatment goal should be the reduction of the sleep disturbance of RLS, both to decrease the RLS-related nocturnal distress and to improve daytime functioning.

  View details for DOI 10.1016/j.sleep.2004.04.004

  View details for Web of Science ID 000224018100010

  View details for PubMedID 15341894

• Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome SLEEP Allen, R., Becker, P. M., Bogan, R., Schmidt, M., Kushida, C. A., Fry, J. M., Poceta, J. S., Winslow, D. 2004; 27 (5): 907-914

  Abstract

  Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS).Double-blinded, placebo-controlled, parallel-group study.15 tertiary referral centers in the USA. Participants: 65 patients with RLS and PLMS.Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks.Data from 59 patients were included in the primary endpoint analysis. PLMS per hour decreased more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2; adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4; P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5; 95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep compared with placebo (P < .001). There were also non-significant trends toward increases in total sleep time and sleep efficiency. Sleep adequacy (measured on the subjective Medical Outcomes Study sleep scale) was significantly improved with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1, 23.1; P = .0316). In contrast, the placebo group showed a greater increase in Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group.Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.

  View details for Web of Science ID 000223451400013

  View details for PubMedID 15453549

• Restless legs syndrome and periodic limb movement disorder MEDICAL CLINICS OF NORTH AMERICA Rama, A. N., Kushida, C. A. 2004; 88 (3): 653-?

  View details for DOI 10.1016/j.mcna.2004.01.004

  View details for Web of Science ID 000221049600007

  View details for PubMedID 15087209

• Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder SLEEP Littner, M. R., Kushida, C., Anderson, W. M., Bailey, D., Berry, R. B., Hirshkowitz, M., Kapen, S., Kramer, M., Lee-Chiong, T., Li, K. K., Loube, D. L., Morgenthaler, T., Wise, M. 2004; 27 (3): 557-559

  Abstract

  Dopaminergic agents, particularly dopamine agonists, have been used with increasing frequency in the treatment of restless legs syndrome and periodic limb movement disorder. These evidence-based practice parameters are complementary to the Practice Parameters for the Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder, published in 1999. These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the dopaminergic treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of dopaminergic agents in the treatment of RLS and PLMD. Levodopa with decarboxylase inhibitor, and the dopaminergic agonists pergolide, pramipexole, and ropinirole are effective in the treatment of RLS and PLMD. Other dopamine agonists (talipexole, cabergoline, piribidel, and alpha-dihydroergocryptine) and the dopaminergic agents amantadine and selegiline may be effective in the treatment of RLS and PLMD, but the level of effectiveness of these medications is not currently established. Lastly, no specific recommendations can be made regarding dopaminergic treatment of children or pregnant women with RLS or PLMD.

  View details for Web of Science ID 000223169000031

  View details for PubMedID 15164914

• The use of esophageal manometry in the diagnosis of sleep-related breathing disorders. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference Kushida, C. A. 2004; 5: 3860-3863

  Abstract

  Esophageal manometry is a technique used to detect abnormal sleep-related respiratory events. One method used to measure and score esophageal pressure during sleep is described. The contraindications for esophageal manometry, the methods for scoring esophageal pressure, the use of esophageal manometry as the "gold standard", and directions for future research are discussed.

  View details for PubMedID 17271138

• Non-Rapid Eye Movement Parasomnias. Current treatment options in neurology Farid, M., Kushida, C. A. 2004; 6 (4): 331-337

  Abstract

  Non-rapid eye movement parasomnias are unique physical or experiential phenomena that disrupt sleep. Non-rapid eye movement parasomnias are common in children, but they typically outgrow them. Sleep-stage shifts caused by sleep-disordered breathing and associated arousals may be precipitating events for episodes of parasomnia. Seizure disorders should always be considered in the differential diagnosis for the evaluation of parasomnias. Violent or injurious sleepwalking should be rapidly evaluated and treated.

  View details for PubMedID 15157410

• Report of a case of immunosuppression with prednisone in an 8-year-old boy with an acute onset of hypocretin-deficiency narcolepsy SLEEP Hecht, M., Lin, L., Kushida, C. A., Umetsu, D. T., Taheri, S., Einen, M., Mignot, E. 2003; 26 (7): 809-810

  Abstract

  To explore whether acute destruction of hypocretin cells in a patient with narcolepsy could be detected and if the course of the disease could be reversed or altered by the use of prednisone for immunosuppression.Case report.A sleep-clinic population in a tertiary-care hospital.An 8-year-old boy with a very acute recent (< 2 month) onset of sleepiness.Sleep studies; fluid-attenuated inversion recovery and gadolinium magnetic resonance imaging studies with a focus on the hypothalamus; examinations of cerebrospinal fluid for cytology, protein, and hypocretin-1 levels; and HLA typing were performed.A 3-week regimen of 1 mg x kg(-1) x day(-1) of prednisone was administered in an attempt to modify the course of the disease.Sleep evaluations were consistent with a diagnosis of narcolepsy. Hypocretin-1 was absent in the cerebrospinal fluid, and HLA-DQB1*0602 was present. All other results were within normal limits, and prednisone did not have any noticeable effects. Clinical manifestation of narcolepsy might occur when the hypocretin cell damage is too advanced to be reversible.

  View details for Web of Science ID 000186745800007

  View details for PubMedID 14655912

• Restless legs syndrome symptoms in primary care - A prevalence study ARCHIVES OF INTERNAL MEDICINE Nichols, D. A., Allen, R. P., Grauke, J. H., Brown, J. B., Rice, M. L., Hyde, P. R., Dement, W. C., Kushida, C. A. 2003; 163 (19): 2323-2329

  Abstract

  There are relatively few studies on the prevalence of restless legs syndrome (RLS) in the general population, even fewer that used diagnostic questions covering all 4 essential diagnostic criteria defining the RLS symptom complex, and none that have reported on the 2 RLS phenotypes for patients seen by family physicians.To determine the prevalence of the symptom complex, diagnostic for RLS in a primary care patient population, a prospective population-based single-center study was performed. Every adult patient presenting for care in a small rural primary care practice with mostly white patients was surveyed for a 1-year period using a validated RLS diagnostic questionnaire.A total of 2099 patients completed the questionnaire. Analysis revealed that 24.0% of these patients were positive for all 4 of the essential symptoms used to make the diagnosis of RLS and 15.3% reported these symptoms at least weekly. In addition, the RLS symptom complex was reported significantly more often by women than men and, as a whole, patients reporting the RLS symptoms were significantly older than patients without symptoms. The prevalence of symptoms increased with age until about 60 years and then showed a steady decrease thereafter. Further, early-onset RLS was significantly more common in women than men.A high prevalence of RLS symptoms was observed in this primary care population. This finding supports the need for heightened awareness in both the medical community and general population regarding this disorder, which can often be effectively treated within the primary care practice.

  View details for Web of Science ID 000186207400009

  View details for PubMedID 14581252

• Anterior cervical spine fusion and sleep disordered breathing NEUROLOGY Guilleminault, C., Li, K. K., Philip, P., Kushida, C. A. 2003; 61 (1): 97-99

  Abstract

  The authors reviewed 12 patients who developed obstructive sleep apnea (OSA) syndrome in association with anterior cervical spine fusion. Four subsequent patients were studied prospectively before C2 to C4 anterior fusion and documented to have OSA by questionnaire, visual analogue scales, polysomnography, and multiple sleep latency tests. The authors found that placement of the anterior cervical plates reduced the size of the upper airway. Symptoms and objective findings were controlled with nasal continuous positive airway pressure.

  View details for Web of Science ID 000183978800020

  View details for PubMedID 12847164

• Nasal obstruction in sleep-disordered breathing OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Chen, W., Kushida, C. A. 2003; 36 (3): 437-?

  Abstract

  It has been 30 years since Cottle suggested that "sleeping patterns are in great measure dependent on good nasal function" [1]. During this time, we have identified the OSAHS and related forms of sleep-disordered breathing such as UARS, and better appreciate the clinical sequelae of recurrent arousals and sleep fragmentation. Yet the exact role that obstructed nasal breathing plays in the pathogenesis of such sleep disorders remains presumptive, and robust clinical studies to corroborate this theory remain elusive; however, patients who may benefit most from correction of nasal obstruction as a sole intervention may be those with the mildest forms of sleep-disordered breathing without other significant predisposing anatomic abnormalities. Clearly, more stringently controlled studies [17,105] are needed, particularly in these types of patients. Until such time, it is reasonable to address issues of nasal obstruction as an adjunct to surgical and nonsurgical treatment in all patients who are diagnosed with a sleep-related breathing disorder.

  View details for DOI 10.1016/S0030-6665(02)00175-5

  View details for Web of Science ID 000183412600004

  View details for PubMedID 12956093

• Practice parameters for the role of actigraphy in the study of sleep and circadian rhythms: An update for 2002 - An American academy of sleep medicine report SLEEP Littner, M., Kushida, C. A., Anderson, M., Bailey, D., Berry, R. B., Davila, D. G., Hirshkowitz, M., Kapen, S., Kramer, M., Loube, D., Wise, M., Johnson, S. F. 2003; 26 (3): 337-341

  Abstract

  Actigraphy is a method used to study sleep-wake patterns and circadian rhythms by assessing movement, most commonly of the wrist. These evidence-based practice parameters are an update to the Practice Parameters for the Use of Actigraphy in the Clinical Assessment of Sleep Disorders, published in 1995. These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the role of actigraphy, which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of actigraphy. Actigraphy is reliable and valid for detecting sleep in normal, healthy populations, but less reliable for detecting disturbed sleep. Although actigraphy is not indicated for the routine diagnosis, assessment, or management of any of the sleep disorders, it may serve as a useful adjunct to routine clinical evaluation of insomnia, circadian-rhythm disorders, and excessive sleepiness, and may be helpful in the assessment of specific aspects of some disorders, such as insomnia and restless legs syndrome/periodic limb movement disorder. The assessment of daytime sleepiness, the demonstration of multiday human-rest activity patterns, and the estimation of sleep-wake patterns are potential uses of actigraphy in clinical situations where other techniques cannot provide similar information (e.g., psychiatric ward patients). Superiority of actigraphy placement on different parts of the body is not currently established. Actigraphy may be useful in characterizing and monitoring circadian rhythm patterns or disturbances in certain special populations (e.g., children, demented individuals), and appears useful as an outcome measure in certain applications and populations. Although actigraphy may be a useful adjunct to portable sleep apnea testing, the use of actigraphy alone in the detection of sleep apnea is not currently established. Specific technical recommendations are discussed, such as using concomitant completion of a sleep log for artifact rejection and timing of lights out and on; conducting actigraphy studies for a minimum of three consecutive 24-hour periods; requiring raw data inspection; permitting some preprocessing of movement counts; stating that epoch lengths up to 1 minute are usually sufficient, except for circadian rhythm assessment; requiring interpretation to be performed manually by visual inspection; and allowing automatic scoring in addition to manual scoring methods.

  View details for Web of Science ID 000182439100019

  View details for PubMedID 12749556

• Factor analysis of the International Restless Legs Syndrome Study Group's scale for restless legs severity SLEEP MEDICINE Allen, R. P., Kushida, C. A., Atkinson, M. J. 2003; 4 (2): 133-135

  Abstract

  The International Restless Legs Syndrome Study Group has developed and validated a ten-item scale for assessing the severity of the restless legs syndrome. This International Restless Legs Severity Scale (IRLS) is reported to have a high degree of internal consistency and it has generally been used as a single scale. This study uses a factor analytic approach to evaluate the IRLS for possibly useful subscales.A large convenience sample (n=516) of self-identified restless leg syndrome patients completed the IRLS over the Internet. Data were analyzed using principal component analyses.Two primary factors were identified, one with six items related to symptom severity and a second with three items related to impact of the symptoms on life. These accounted for 41.8 and 22.5% of the variance, respectively.The IRLS can be evaluated using separate subscale scores: one for symptoms and the other symptom impact. The relative merits of these subscale scores versus the score for the entire test need to be evaluated in different situations in further studies, in especially the ones involving assessing responsiveness to treatment effects.

  View details for DOI 10.1016/S1389-9457(02)00193-4

  View details for Web of Science ID 000188839100006

  View details for PubMedID 14592343

• Behavioral parasomnias. Current psychiatry reports Brooks, S., Kushida, C. A. 2002; 4 (5): 363-368

  Abstract

  Sleep is not a static state. During the sleep period, physiologic changes occur throughout the body and brain. This complex, dynamic process can, at times, result in episodes of unusual or undesirable behaviors. These phenomena are called parasomnias. The accurate diagnosis of this group of treatable disorders is important, because they can have a negative impact on sleep, health, and social function. In addition, some of the parasomnias may provide clues to the presence of other underlying pathologic conditions. The parasomnias may be categorized in more than one way, but any attempt to classify such a diverse collection of entities is likely to be somewhat arbitrary. This article discusses the parasomnias according to the classification of the International Classification of Sleep Disorders, with emphasis on those characterized by observable behavior. As the understanding of these disorders (and sleep, in general) continues to deepen, new entities and schemes of classification may emerge.

  View details for PubMedID 12230965

• Sites of obstruction in obstructive sleep apnea CHEST Rama, A. N., Tekwani, S. H., Kushida, C. A. 2002; 122 (4): 1139-1147

  Abstract

  The aim of this article was to identify the most common sites of obstruction in patients with obstructive sleep apnea (OSA) by a systematic review of published studies.The review was conducted by a MEDLINE search of the English literature published during the years 1980 to 2002. The inclusion criteria were experiments involving five or more adult subjects, total rather than partial obstruction or narrowing of the upper airway, and techniques that were performed on the subjects while they were asleep.Although there was considerable variability in the techniques and the results, the most common site of obstruction detected by these studies was at the level of the oropharynx, with extension to the laryngopharynx commonly observed.

  View details for Web of Science ID 000178685200010

  View details for PubMedID 12377834

• Practice parameters for the use of auto-titrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome SLEEP Littner, M., Hirshkowitz, M., Davila, D., Anderson, W. M., Kushida, C. A., Woodson, T., Johnson, S. F., Wise, M. S. 2002; 25 (2): 143-147

  Abstract

  Continuous positive airway pressure (CPAP) is used to treat patients with the obstructive sleep apnea syndrome (OSAS). The current standard is for an attendant technician to titrate CPAP during full polysomnography to obtain a fixed single pressure. The patient uses CPAP nightly at this fixed single pressure. Recently, devices using new technology that automatically titrate positive airway pressure (APAP) have become available. Such devices continually adjust pressure, as needed, to maintain airway patency (APAP titration). These adjustments can be made with or without attendant technician intervention. Data obtained during APAP titration can be used to provide a fixed single pressure for subsequent treatment. Alternatively, APAP devices can be used in self-adjusting mode for treatment (APAP treatment). A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guide to the appropriate use of APAP. Recommendations are as follows: 1) A diagnosis of OSAS must be established by an acceptable method. 2) APAP titration and APAP treatment are not currently recommended for patients with congestive heart failure, significant lung disease (e.g., chronic obstructive pulmonary disease), daytime hypoxemia and respiratory failure from any cause, or prominent nocturnal desaturation other than from OSA (e.g., obesity hypoventilation syndrome). In addition, patients who do not snore (either due to palate surgery or naturally) should not be titrated with an APAP device that relies on vibration or sound in the device's algorithm. 3) APAP devices are not currently recommended for split-night studies since none of the reviewed research studies examined this issue. 4) Certain APAP devices may be used during attended titration to identify by polysomnography a single pressure for use with standard CPAP for treatment of OSA. 5) Once an initial successful attended CPAP or APAP titration has been determined by polysomnography, certain APAP devices may be used in the self-adjusting mode for unattended treatment of patients with OSA. 6) Use of unattended APAP to either initially determine pressures for fixed CPAP or for self-adjusting APAP treatment in CPAP naïve patients is not currently established. 7) Patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must be followed to determine treatment effectiveness and safety, and 8) a re-evaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the CPAP or APAP treatment otherwise appears to lack efficacy.

  View details for Web of Science ID 000174275400003

  View details for PubMedID 11902424

• Technical protocol for the use of esophageal manometry in the diagnosis of sleep-related breathing disorders SLEEP MEDICINE Kushida, C. A., Giacomini, A., Lee, M. K., Guilleminault, C., Dement, W. C. 2002; 3 (2): 163-173

  Abstract

  A time-tested protocol for intrathoracic pressure monitoring during sleep is described. This method of esophageal manometry uses a fluid-filled catheter to measure variations in transmitted intrathoracic pressure with respiration. Esophageal manometry is an invaluable tool for the sleep specialist in the diagnosis of sleep-related breathing disorders, especially for detecting cases of upper airway resistance syndrome and for distinguishing subtle central apneas from obstructive events. The methods for scoring esophageal pressure, the indications and contraindications for esophageal manometry, the use of esophageal manometry as the 'gold standard' for the measurement of respiratory effort, and directions for future research are also discussed.

  View details for Web of Science ID 000208301700014

  View details for PubMedID 14592238

• Sleep deprivation in the rat: X. Integration and discussion of the findings. 1989. Sleep Rechtschaffen, A., Bergmann, B. M., Everson, C. A., Kushida, C. A., Gilliland, M. A. 2002; 25 (1): 68-87

  Abstract

  The results of a series of studies on total and selective sleep deprivation in the rat are integrated and discussed. These studies showed that total sleep deprivation, paradoxical sleep deprivation, and disruption and/or deprivation of non-rapid eye movement (NREM) sleep produced a reliable syndrome that included death, debilitated appearance, skin lesions, increased food intake, weight loss, increased energy expenditure, decreased body temperature during the late stages of deprivation, increased plasma norepinephrine, and decreased plasma thyroxine. The significance of this syndrome for the function of sleep is not entirely clear, but several changes suggested that sleep may be necessary for effective thermoregulation.

  View details for PubMedID 11833857

• Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients SLEEP MEDICINE Kushida, C. A., Chang, A., Gadkary, C., Guilleminault, C., Carrillo, O., Dement, W. C. 2001; 2 (5): 389-396

  Abstract

  Comparison of polysomnography (PSG)-derived sleep parameters (total sleep time, sleep efficiency, and number of awakenings) to those derived from actigraphy and subjective questionnaires.Actigraphy is commonly used to assist sleep specialists in the diagnosis of various sleep and circadian-rhythm disorders. However, few validation studies incorporate large sample sizes, typical sleep clinic patients, or comparisons with subjective reports of sleep parameters.Clinical series with 100 consecutive sleep-disordered patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep disorders center. Sensitivity, specificity, and accuracy measures were obtained from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep parameter data were derived from questionnaires given to subjects in the morning following their recording night.We found that total sleep time and sleep efficiency did not significantly differ between PSG data and the combined data obtained from actigraphy and subjective reports. Using a high-threshold (low-wake-sensitivity) actigraphic algorithm, the number of awakenings was not significantly different from those detected by PSG.We recommend the use of subjective data as an adjunct to actigraphic data in estimating total sleep time and sleep efficiency in sleep-disordered patients, especially those with disorders of excessive somnolence.

  View details for Web of Science ID 000208301200003

• Practice parameters for the use of laser-assisted uvulopalatoplasty: An update for 2000 SLEEP Littner, M., Kushida, C. A., Hartse, K., Anderson, W. M., Davila, D., Johnson, S. F., Wise, M. S., Hirshkowitz, M., Woodson, B. T. 2001; 24 (5): 603-619

  Abstract

  Laser-assisted uvulopalatoplasty (LAUP) is an outpatient surgical procedure which is in use as a treatment for snoring. LAUP also has been used as a treatment for sleep-related breathing disorders, including obstructive sleep apnea. The Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature, and developed these practice parameters as a guide to the appropriate use of this surgery. Adequate controlled studies on the LAUP procedure for sleep-related breathing disorders were not found in peer-reviewed journals. This is consistent with findings in the original practice parameters on LAUP published in 1994. The following recommendations are based on the review of the literature: LAUP is not recommended for treatment of sleep-related breathing disorders. However, it does appear to be comparable to uvulopalatopharyngoplasty (UPPP) for treatment of snoring. Individuals who are candidates for LAUP as a treatment for snoring should undergo a polysomnographic or cardiorespiratory evaluation for sleep-related breathing disorders prior to LAUP and periodic postoperative evaluations for the development of same. Patients should be informed of the best available information of the risks, benefits, and complications of the procedure.

  View details for Web of Science ID 000169972400011

  View details for PubMedID 11480657

• Practice parameters for the treatment of narcolepsy: An update for 2000 SLEEP Littner, M., Johnson, S. F., McCall, W. V., Anderson, W. D., Davila, D., Hartse, K., Kushida, C. A., Wise, M. S., Hirshkowitz, M., Woodson, B. T. 2001; 24 (4): 451-466

  Abstract

  Successful treatment of narcolepsy requires an accurate diagnosis to exclude patients with other sleep disorders, which have different treatments, and to avoid unnecessary complications of drug treatment. Treatment objectives should be tailored to individual circumstances. Modafinil, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, selegiline, pemoline, tricyclic antidepressants, and fluoxetine are effective treatments for narcolepsy, but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness, but naps seldom suffice as primary therapy. Regular follow up of patients with narcolepsy is necessary to educate patients and their families, monitor for complications of therapy and emergent of other sleep disorders, and help the patient adapt to the disease.

  View details for Web of Science ID 000169184800011

  View details for PubMedID 11403530

• Cervical positioning for reduction of sleep-disordered breathing in mild-to-moderate OSAS. Sleep & breathing = Schlaf & Atmung Kushida, C. A., Sherrill, C. M., Hong, S. C., Palombini, L., Hyde, P., Dement, W. C. 2001; 5 (2): 71-78

  Abstract

  The objective of this study was to assess whether cervical positioning could improve mild to moderate cases of the obstructive sleep apnea syndrome (OSAS). Eighteen subjects recruited from a tertiary sleep disorders clinic population with mild to moderate cases of OSAS were evaluated using a custom-fitted cervical pillow designed to increase upper airway caliber by promoting head extension. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. They then used the cervical pillow for 5 days at home and returned for 2 consecutive recorded nights at our laboratory to use the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had full polysomnography. The subjects had a significant trend toward improvement in their respiratory disturbance indices with use of the cervical pillow, despite spending more time in the supine position and having similar amounts of REM sleep in the baseline and experimental conditions. They also had nonsignificant trends toward improvements in their sleep efficiency and subjective depth of their sleep as well as significantly fewer arousals and awakenings in the experimental compared with the baseline condition. We propose that cervical positioning (i.e., head extension) with a custom-fitted cervical pillow provides a simple, noninvasive, and comfortable means of reducing sleep-disordered breathing in patients with mild to moderate OSAS.

  View details for PubMedID 11868144

• Symptom-Based Prevalence of Sleep Disorders in an Adult Primary Care Population. Sleep & breathing = Schlaf & Atmung Kushida, C. A., Nichols, D. A., Simon, R. D., Young, T., Grauke, J. H., Britzmann, J. B., Hyde, P. R., Dement, W. C. 2000; 4 (1): 9-14

  Abstract

  The prevalence of sleep disorders in a primary care physician practice in Moscow, Idaho, was studied between February 7, 1997, and February 6, 1998. This primary care clinic visit population was surveyed for this 1-year period. Every patient above the age of 18 years who visited the Moscow Clinic in this time period was either approached by our on-site researcher during the patient's clinic visit or contacted via mail. Out of a total of 1249 adult patients who met with our on-site researcher during their clinic visit, 962 (77.0%) completed questionnaires and were interviewed for symptoms of sleep disorders. An additional 292 patients completed mailed questionnaires, resulting in a total of 1254 participants in the study. The percentages of patients in our sample reporting symptoms of the following sleep disorders were insomnia (32.3%), obstructive sleep apnea syndrome (23.6%), and restless legs syndrome (29.3%). This study demonstrates the need for heightened awareness and subsequent diagnosis and treatment of sleep disorders in the primary care population.

  View details for PubMedID 11894194

• Cervical positional effects on snoring and apneas. Sleep research online : SRO Kushida, C. A., Rao, S., Guilleminault, C., Giraudo, S., Hsieh, J., Hyde, P., Dement, W. C. 1999; 2 (1): 7-10

  Abstract

  We examined the effects of cervical position on the Obstructive Sleep Apnea Syndrome (OSAS) through the use of a custom-designed cervical pillow which promoted neck extension. Twelve subjects with OSAS were recruited from a tertiary sleep disorder clinic population. Of the twelve subjects, three had mild cases of OSAS, four had moderate cases, and the remaining five had severe cases. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. The subjects then used the cervical pillow for five days at home, and returned for two consecutive recorded nights at our laboratory while using the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had their breathing parameters recorded during sleep. Subjects with mild OSAS cases had a non-significant improvement in the severity of their snoring and a significant improvement in their respiratory disturbance index with the cervical pillow, while subjects with moderate OSAS cases showed no improvement in these parameters. Subjects with severe OSAS cases showed slight improvement in some measures of their abnormal respiratory events during the experimental period.

  View details for PubMedID 11382876

• A predictive morphometric model for the obstructive sleep apnea syndrome ANNALS OF INTERNAL MEDICINE Kushida, C. A., Efron, B., Guilleminault, C. 1997; 127 (8): 581-?

  Abstract

  Mathematical formulas have been used to clinically predict whether patients will develop the obstructive sleep apnea syndrome (OSAS). However, these models do not take into account the disproportionate craniofacial anatomy that accompanies OSAS independently of obesity.To determine the accuracy of a morphometric model, which combines measurements of the oral cavity with body mass index and neck circumference, in predicting whether a patient has OSAS.6-month prospective study.University-based tertiary referral sleep clinic and research center.300 consecutive patients evaluated for sleep disorders for the first time.Body mass index, neck circumference, and oral cavity measurements were obtained, and a model value was calculated for each patient. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. Sleep apnea was defined as more than five episodes of apnea or hypopnea per hour of sleep.The morphometric model had a sensitivity of 97.6% (95% CI, 95% to 98.9%), a specificity of 100% (CI 92% to 100%), a positive predictive value of 100% (CI, 98.5% to 100%), and a negative predictive value of 88.5% (CI, 77% to 95%). No significant discrepancies were revealed in tests of intermeasurer and test-retest reliability.The morphometric model provides a rapid, accurate, and reproducible method for predicting whether patients in an ambulatory setting have OSAS. The model may be clinically useful as a screening tool for OSAS rather than as a replacement for polysomnography.

  View details for Web of Science ID A1997YB41900001

  View details for PubMedID 9341055

• Nasal obstruction and obstructive sleep apnea: A review ALLERGY AND ASTHMA PROCEEDINGS Kushida, C. A., Guilleminault, C., Clerk, A. A., Dement, W. C. 1997; 18 (2): 69-71

  Abstract

  Several groups of investigators have assessed the impact of nasal obstruction on the obstructive sleep apnea syndrome. These studies evaluated patients with either naturally occurring partial nasal obstruction (e.g., allergic rhinitis, septal deviation) or experimentally induced nasal occlusion. The results of these studies are summarized and discussed in this article.

  View details for Web of Science ID A1997WW54000003

  View details for PubMedID 9134062

• PROLONGED CONFUSION WITH NOCTURNAL WANDERING ARISING FROM NREM AND REM-SLEEP - A CASE-REPORT SLEEP Kushida, C. A., Clerk, A. A., Kirsch, C. M., Hotson, J. R., Guilleminault, C. 1995; 18 (9): 757-764

  Abstract

  A 51-year-old man with Machado-Joseph disease had a 3-year history of prolonged confusion following nightly nocturnal wandering. Polysomnography with videotape monitoring revealed 19- to 120-minute sleepwalking episodes emerging from non-rapid eye movement (NREM) sleep and occasionally from rapid eye movement (REM) sleep, followed by 22-47 minutes of prolonged confusion and disorientation. The patient also had a periodic limb movement disorder and obstructive sleep apnea syndrome. Excessive daytime sleepiness was evident by results from the Epworth Sleepiness Scale and Multiple Sleep Latency Test. A sleep-deprived electroencephalogram (EEG) and a polysomnogram with an expanded EEG montage before and during these episodes revealed no epileptiform activity. A contrast-enhanced brain magnetic resonance imaging (MRI) scan demonstrated findings consistent only with Machado-Joseph disease. The patient improved with a combination of temazepam and carbidopa-levodopa.

  View details for Web of Science ID A1995TH48600008

  View details for PubMedID 8638068

• THE EXPRESSION OF M1-M3 MUSCARINIC RECEPTOR MESSENGER-RNAS IN RAT-BRAIN FOLLOWING REM-SLEEP DEPRIVATION NEUROREPORT Kushida, C. A., Zoltoski, R. K., Gillin, J. C. 1995; 6 (12): 1705-1708

  Abstract

  We used in situ hybridization histochemistry to study the effects of REM sleep deprivation on m1-m3 muscarinic receptor mRNA expression in the rat brain. REM sleep deprivation for 72 h did not affect m1 receptor mRNA expression. However, we found significantly increased m3 receptor mRNA expression in the pontine nuclei and nucleus accumbens-bed nucleus of the stria terminalis region of REM sleep-deprived rats compared with controls. Paradoxically, we found significantly decreased m2 receptor mRNA expression in the pontine nuclei of REM sleep-derived rats vs controls. The present findings implicate these structures in the cholinergic effector pathways of REM sleep, although the type and magnitude of the effects of these structures on REM sleep may vary with different receptor subtypes.

  View details for Web of Science ID A1995RR26200027

  View details for PubMedID 8527746

• CORTICAL ASYMMETRY OF REM-SLEEP EEG FOLLOWING UNILATERAL PONTINE HEMORRHAGE NEUROLOGY Kushida, C. A., Rye, D. B., NUMMY, D., Milton, J. G., Spire, J. P., Rechtschaffen, A. 1991; 41 (4): 598-601

  Abstract

  A 24-year-old woman with a left pontine hematoma showed marked asymmetry in the EEG of REM sleep, suggesting that a unilateral pontine lesion is sufficient to disrupt normal REM sleep EEG in the ipsilateral hemisphere. Other REM sleep characteristics (rapid eye movements, muscle atonia) were unaffected by this lesion.

  View details for Web of Science ID A1991FG37700029

  View details for PubMedID 2011264

• SLEEP-DEPRIVATION IN THE RAT .5. ENERGY USE AND MEDIATION SLEEP Bergmann, B. M., Everson, C. A., Kushida, C. A., Fang, V. S., Leitch, C. A., Schoeller, D. A., Refetoff, S., Rechtschaffen, A. 1989; 12 (1): 31-41

  Abstract

  We investigated the use and possible mechanisms mediating the increased energy expenditure (EE) previously described for rats subjected to total or paradoxical sleep deprivation. Bomb calorimetry of wastes showed that during deprivation the efficiency of energy utilization was not reduced. Estimates of CO2 production by the doubly labelled water method of indirect calorimetry correlated with EE estimated from the caloric value of food, weight change, and wastes and confirmed an increase in EE during deprivation. Core temperatures decreased during the later stages of deprivation, suggesting the hypothesis that excessive heat loss may have required increased EE to protect body temperature. The increased EE could not be explained by the metabolic cost of increase wakefulness, water exposure, or motor activity; an increase in resting EE was indicated. The contribution of the hypothalamic-pituitary-adrenal axis, thyroid gland, and sympathoadrenal system to the mediation of the EE increases was evaluated by measuring the plasma levels of their hormones. Results appear to rule out the first as a mediator. Evidence for the other two was equivocal.

  View details for Web of Science ID A1989T091200005

  View details for PubMedID 2538910

• SLEEP-DEPRIVATION IN THE RAT .10. INTEGRATION AND DISCUSSION OF THE FINDINGS SLEEP Rechtschaffen, A., Bergmann, B. M., Everson, C. A., Kushida, C. A., Gilliland, M. A. 1989; 12 (1): 68-87

  Abstract

  The results of a series of studies on total and selective sleep deprivation in the rat are integrated and discussed. These studies showed that total sleep deprivation, paradoxical sleep deprivation, and disruption and/or deprivation of non-rapid eye movement (NREM) sleep produced a reliable syndrome that included death, debilitated appearance, skin lesions, increased food intake, weight loss, increased energy expenditure, decreased body temperature during the late stages of deprivation, increased plasma norepinephrine, and decreased plasma thyroxine. The significance of this syndrome for the function of sleep is not entirely clear, but several changes suggested that sleep may be necessary for effective thermoregulation.

  View details for Web of Science ID A1989T091200010

  View details for PubMedID 2648533

• SLEEP-DEPRIVATION IN THE RAT .9. RECOVERY SLEEP Everson, C. A., Gilliland, M. A., Kushida, C. A., Pilcher, J. J., Fang, V. S., Refetoff, S., Bergmann, B. M., Rechtschaffen, A. 1989; 12 (1): 60-67

  Abstract

  Eight rats were subjected to total sleep deprivation, paradoxical sleep deprivation, or high amplitude sleep deprivation until they showed major deprivation-induced changes. Then they were allowed to sleep ad lib. Three rats that had shown the largest temperature declines died within two to six recovery days. During the first 15 days of ad lib sleep, surviving rats showed complete or almost complete reversal of the following deprivation-induced changes: debilitated appearance, lesions on the paws and tail, high energy expenditure, large decreases in peritoneal temperature, high plasma epinephrine and norepinephrine levels, and low thyroxine levels. The most prominent features of recovery sleep in all rats were immediate and large rebounds of paradoxical sleep to far above baseline levels, followed by lesser temporally extended rebounds. Rebounds of high amplitude non-rapid eye movement (NREM) sleep occurred only in some rats and were smaller and less immediate.

  View details for Web of Science ID A1989T091200009

  View details for PubMedID 2538911

• SLEEP-DEPRIVATION IN THE RAT .7. IMMUNE FUNCTION SLEEP Benca, R. M., Kushida, C. A., Everson, C. A., KALSKI, R., Bergmann, B. M., Rechtschaffen, A. 1989; 12 (1): 47-52

  Abstract

  Immune function studies were performed on splenic lymphocytes obtained from rats subjected to total or paradoxical sleep deprivation. Spleen cell counts, in vitro lymphocyte proliferation responses to mitogens, and in vitro and in vivo plaque-forming cell responses to antigens were obtained. Sleep-deprived rats were roughly equivalent to both their yoked controls and home-cage controls in all assays. The results do not support the hypothesis that sleep deprivation results in immune suppression as measured by the above-mentioned parameters.

  View details for Web of Science ID A1989T091200007

  View details for PubMedID 2784583

• SLEEP-DEPRIVATION IN THE RAT .1. CONCEPTUAL ISSUES SLEEP Rechtschaffen, A., Bergmann, B. M., Everson, C. A., Kushida, C. A., Gilliland, M. A. 1989; 12 (1): 1-4

  Abstract

  Sleep deprivation is a potentially powerful strategy for discovering the function(s) of sleep, but the approach has had limited success. Few studies have described serious physiological consequences of sleep deprivation, perhaps because the deprivation has not been maintained long enough. However, prolonging deprivation usually requires sustained, frequently intense stimulation, which makes it difficult to determine whether subsequent impairment resulted from the sleep loss or from the stimulation per se. Accordingly, several older studies that showed severe impairment have been neglected or discounted, because the impairment could have resulted from the stimulation. To evaluate the effects of sleep deprivation independent of the stimulation used to enforce deprivation, we have used an apparatus that can awaken experimental rats while delivering the same gentle stimulation to control rats according to a schedule that only moderately shortens their sleep.

  View details for Web of Science ID A1989T091200001

  View details for PubMedID 2648532

• SLEEP-DEPRIVATION IN THE RAT .2. METHODOLOGY SLEEP Bergmann, B. M., Kushida, C. A., Everson, C. A., Gilliland, M. A., Obermeyer, W., Rechtschaffen, A. 1989; 12 (1): 5-12

  Abstract

  Methods common to several studies in this series are described. A key feature is a sleep deprivation apparatus in which an experimental and a yoked control rat are housed on opposite sides of a divided disk suspended over shallow water. When the experimental rat enters a "forbidden" sleep stage, the disk is automatically rotated, forcing the experimental rat to walk to avoid being carried into the water. The control rat receives the same physical stimulation but can sleep ad lib when the disk is stationary.

  View details for Web of Science ID A1989T091200002

  View details for PubMedID 2928625

• SLEEP-DEPRIVATION IN THE RAT .4. PARADOXICAL SLEEP-DEPRIVATION SLEEP Kushida, C. A., Bergmann, B. M., Rechtschaffen, A. 1989; 12 (1): 22-30

  Abstract

  Twelve rats were subjected to paradoxical sleep deprivation (PSD) by the disk apparatus. All PSD rats died or were sacrificed when death seemed imminent within 16-54 days. No anatomical cause of death was identified. All PSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (PSC) rats remained healthy. Since dehydration was ruled out and several measures indicated normal or accelerated use of nutrients, the food-weight changes in PSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all PSD rats increased EE, with mean levels reaching more than twice baseline values. All of these changes had been observed in rats deprived totally of sleep; the major difference was that they developed more slowly in PSD rats.

  View details for Web of Science ID A1989T091200004

  View details for PubMedID 2928623

• SLEEP-DEPRIVATION IN THE RAT .6. SKIN CHANGES SLEEP Kushida, C. A., Everson, C. A., Suthipinittharm, P., Sloan, J., Soltani, K., BARTNICKE, B., Bergmann, B. M., Rechtschaffen, A. 1989; 12 (1): 42-46

  Abstract

  All rats subjected to total or paradoxical sleep deprivation by the disk apparatus developed severe ulcerative and hyperkeratotic skin lesions localized to the plantar surfaces of their paws and to their tails. Yoked control rats only occasionally developed similar appearing lesions, which were always much less severe than in deprived rats. The deprived rat lesions could not be explained by pressure, disk rotation, water immersion, infection, necrotizing vasculitis, tyrosinemia, protein deficiency, or reduced rates of mitosis. Thus, although paw and tail lesions constitute a very reliable and severe symptom of total or selective sleep deprivation in the rat that potentially could yield insights into the pathogenic mechanisms induced by sleep loss, the mediation of the lesions remains unknown.

  View details for Web of Science ID A1989T091200006

  View details for PubMedID 2928624

• ELECTROENCEPHALOGRAPHIC CORRELATES OF CATAPLECTIC ATTACKS IN NARCOLEPTIC CANINES ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Kushida, C. A., Baker, T. L., Dement, W. C. 1985; 61 (1): 61-70

  Abstract

  Cataplectic attacks were monitored behaviorally and polygraphically in 4 narcoleptic dogs, of which three inherited the disorder. The recorded EEG signals were evaluated by power spectral analysis. We found 3 distinct stages of cataplexy: an initial stage which resembled wakefulness with tonic suppression of EMG activity, a later stage which was highly similar to REM sleep, and a final transitional stage to wakefulness or NREM sleep. The first stage of cataplexy was characterized by full postural collapse, a waking-like EEG spectrum, visual tracking, and a hypotonic EMG. The second stage of cataplexy differed electrographically from the previous stage by the onset of hypersynchronous hippocampal theta activity, a REM-like EEG spectrum, larger amplitude EEG signals, and a higher peak theta frequency. Glazed eyes, sporadic rapid eye movements and muscle twitches were also present. The final stage of cataplexy was characterized by mixed amplitude, mixed frequency EEG activity, and by the absence of rapid eye movements, visual tracking, directed movements, and muscle twitches. The EEG spectra of two other narcoleptic phenomena, sleep-onset REM periods and NREM sleep onsets from cataplexy, were nearly identical to the spectra of the normally occurring REM and NREM sleep periods.

  View details for Web of Science ID A1985AMD8600009

  View details for PubMedID 2408864