JCSM Articles

Sleep Medicine and Graduate Medical Education—Prospects for the Future

Modafinil Improves Functional Outcomes in Patients with Residual Excessive Sleepiness Associated with CPAP Treatment

Objectives: The objective of this secondary analysis was to examine the effects of modafinil on the Functional Outcomes of Sleep Questionnaire (FOSQ) in patients with obstructive sleep apnea and residual excessive sleepiness with continuous positive airway pressure (CPAP) use. We also explored the association of improvement of functional status with the presenting level of subjective sleepiness.

Methods: Data were pooled from 2 randomized placebo-controlled studies (4-week and 12-week interventions) of modafinil in patients with residual sleepiness (Epworth Sleepiness Scale score ≥ 10 on CPAP).

Results: The analysis included 480 patients (FOSQ efficacy data n = 442 patients), 292 in the modafinil group and 188 in the placebo group. The mean age (SD) of the analyzed sample was 49.7 (9.2) years; 76% were men. Following administration with modafinil, there were greater improvements from baseline in the Total score (p < 0.0001) as well as 4 of the 5 domains (p < 0.05), compared with placebo. A greater proportion of patients who received modafinil were considered responders, compared with patients who received placebo (45% vs 25%; p < 0.001). Responder analysis based on the individual FOSQ domain items demonstrated that 18 of the 30 FOSQ items increased by at least 1 point for significantly more patients who received modafinil (p < 0.05). Improvements in functional status were not found to depend on patients’ degree of subjective sleepiness at baseline.

Conclusion: In this secondary analysis of data from patients with OSA and excessive sleepiness despite CPAP use, modafinil was associated with improvements in patients’ functional outcomes and their ability to engage in a broad array of everyday activities.

Keywords: Obstructive sleep apnea, OSA, continuous positive airway pressure, CPAP, modafinil, residual excessive sleepiness, persistent sleepiness, Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale

Differences in the Association Between Obesity and Obstructive Sleep Apnea Among Children and Adolescents

Study Objectives: Overweight and obesity are thought to increase the risk of obstructive sleep apnea syndrome (OSAS) among children. However, previous results have been inconsistent and appear to be confounded by both ethnicity and the different ages of children studied. To determine whether the association between excess weight and OSAS varies with age across childhood, we assessed polysomnographic data from a series of Caucasian children and adolescents referred for clinical evaluation of snoring.

Methods: Sleep and OSAS severity were assessed using polysomnography in 234 children aged 2.0 to 18.0 years. All children were referred for overnight evaluation of suspected OSAS. Severity of OSAS as a function of body mass and age were then evaluated.

Results: Risk of OSAS among adolescents (age ≥ 12 years) was increased 3.5 fold with each standard-deviation increase in body mass index z-score. Risk of OSAS was not significantly increased with increasing body mass among younger children.

Conclusions: Similar to adults, adolescent children show an increased risk for having OSAS in association with overweight and obesity. For Caucasian children, overweight and obesity should be considered a significant risk for OSAS among adolescents or from age 12 years, especially when in combination with other established risk factors, including snoring and adenotonsillar hypertrophy.

Keywords: Obesity, OSAS, children, adolescents

Gender Differences in Obstructive Sleep Apnea and Treatment Response to Continuous Positive Airway Pressure

Objectives: Whether gender differences exist in clinical manifestations of obstructive sleep apnea (OSA) and whether women’s responses to continuous positive airway pressure(CPAP) are similar to those of men are critical areas of exploration in sleep disordered breathing. This exploratory analysis addressed these questions by examining gender differences over a wide range of clinical outcomes at baseline and in response to CPAP in participants with severe OSA.

Methods: Data from 152 men and 24 women who participated in a multicenter CPAP effectiveness study were analyzed. Gender differences in functional status (functional outcomes of sleep questionnaire, sickness impact profile), daytime sleepiness (epworth sleepiness scale, multiple sleep latency test), mood disturbance (profile of mood states), apnea symptoms (multivariable apnea prediction index), and neurobehavioral performance (psychomotor vigilance task) were examined. Treatment response was examined by the change in each outcome from baseline to 3 months after treatment.

Results: Despite similar age, body mass index, and apnea-hypopnea index, women reported significantly lower functional status, more subjective daytime sleepiness, higher frequency of apnea symptoms, more mood disturbance, and poorer neurobehavioral performance compared to men at baseline. CPAP treatment significantly improved functional status and relieved symptoms for both genders. The magnitude of improvement in each clinical outcome did not vary by gender.

Conclusions: Women with OSA showed greater impairment in daytime functioning and symptoms than men. Both genders benefit from CPAP treatment. Adequately powered studies considering possible referral and response bias are necessary to examine gender differences in OSA clinical manifestations and response to CPAP treatment.

Keywords: Obstructive sleep apnea, CPAP, gender differences, functional status, daytime sleepiness, treatment response

Marked Reduction in Obstructive Sleep Apnea Severity in Slow Wave Sleep

Introduction: Obstructive sleep apnea (OSA) is widely accepted to improve during slow wave sleep (SWS) compared to lighter stages of NREM sleep. However, supporting data to establish the magnitude and prevalence of this effect is lacking. Consequently, we examined this phenomenon, controlling for posture, in a large group of patients investigated for OSA at an academic clinical sleep service.

Methods: A detailed retrospective analysis was conducted on data obtained from each 30-sec epoch of sleep in 253 consecutive full-night diagnostic polysomnography studies performed over a 3-month period. Respiratory and arousal event rates were calculated within each stage of sleep, in the supine and lateral postures, and across the whole night, with OSA patients classified on the basis of an overall apnea-hypopnea index (AHI) ≥ 15 events/h. Central sleep apnea (CSA) patients were defined by a central apnea index ≥ 5/h. Sleep latency and time, and respiratory and arousal event rates in OSA, CSA, and non-OSA patients were compared between sleep stages and postures using linear mixed model analysis. The numbers of patients achieving reduced event rates in SWS and in the lateral posture were also examined.

Results: There were 171 patients with OSA, 14 with CSA, and 68 non-OSA patients. OSA patients took significantly longer to achieve slow wave and REM sleep (p < 0.001) than non-OSA patients and had less stage 4 sleep (p = 0.037). There were striking improvements in AHI and arousal index (AI) from stage 1 to 4 NREM sleep (p < 0.001), with intermediate levels in REM sleep. AHI and AI were also markedly reduced in lateral versus supine sleep in all sleep stages (p < 0.001), with an effect size comparable to that of the slow wave sleep effect. The majority of OSA patients achieved low respiratory event rates in SWS. Eighty-two percent of patients achieved an AHI < 15 and 57% < 5 events/hour during stage 4 sleep.

Conclusion: Although OSA patients demonstrate both a delayed and reduced proportion of SWS compared to non-OSA subjects, once they achieved SWS, AHI, and AI markedly improved in most patients.

Keywords: Obstructive sleep apnea, slow wave sleep, ventilatory control, posture, delta sleep, arousal, sleep stage

Iron Stores, Periodic Leg Movements, and Sleepiness in Obstructive Sleep Apnea

Study Objectives: Most clinical sleep studies are performed for suspected obstructive sleep apnea (OSA), yet one-quarter to one-half show periodic leg movements (PLMs), for reasons that remain unknown. Several other disparate sleep disorders also increase the risk for PLMs. We examined the novel hypotheses that OSA as a representative sleep disorder could promote lower body iron stores, as reflected by serum ferritin levels, and, through downstream effects on dopaminergic transmission, increase PLMs and daytime sleepiness.

Methods: Subjects were recruited as they underwent laboratory-based polysomnography for suspected OSA. Serum ferritin levels were measured the next morning. Each subject completed an Epworth Sleepiness Scale and a brief questionnaire to assess for restless legs syndrome (RLS).

Results: The frequency of apneic events showed no association with serum ferritin levels, before or after adjustment for age, sex, body mass index, and likely RLS (each p value > 0.3). Serum ferritin levels did not predict the frequency of PLMs (p = 0.7) or Epworth scores (p = 0.8). Iron deficiency as a dichotomous variable, determined by ferritin levels less than < 50µg/L or in combination with low transferrin saturation or mean corpuscular volume, showed similar results. In exploratory analyses, contrary to expectations, lower minimum oxygen saturation and increased sleep-stage shifts predicted increased rather than decreased ferritin levels (p = 0.03 and p = 0.02, respectively).

Conclusions: Results of this study, powered to detect small to moderate effect sizes, strongly suggest that OSA does not cause lower serum ferritin levels, which, in turn, cannot explain PLMs or daytime sleepiness in these patients.

Keywords: Ferritin, PLMs, sleepiness, OSA, iron

A Multicenter, Prospective Study of a Novel Nasal EPAP Device in the Treatment of Obstructive Sleep Apnea: Efficacy and 30-Day Adherence

Study Objectives: Evaluate the efficacy of a novel device placed in the nares that imposes an expiratory resistance for the treatment of obstructive sleep apnea (OSA) and evaluate adherence to the device over a 30-day in-home trial period.

Design: One diagnostic and 3 treatment polysomnograms were administered in a Latin-square design to identify the optimal expiratory resistance to be used during the 30-day in-home trial. Subjects had repeat polysomnography with the prescribed device at the end of the 30-day trial.

Setting: Multicenter study.

Participants: Participants (N = 34; age 27 to 67) with a baseline apnea-hypopnea index (AHI) ≥ 5.

Measurements and Results: The AHI was reduced from 24.5 ± 23.6 (mean ± SD) to an average of 13.5 ± 18.7 (p < 0.001) across initial treatment nights. The AHI was 15.5 ± 18.9 (p = 0.001) for the prescribed device at the end of the 30-day trial. Of 24 subjects with an AHI > 10 at baseline, 13 achieved an AHI ≤ 10 on the initial treatment nights; 10 had a similar response on the final treatment night. Percent of the night snoring decreased from 27.5 ± 23.2 to 11.6 ± 13.7 (p < 0.001) on initial treatment nights and 14.6 ± 20.6 (p = 0.013) at the end of the trial; Epworth Sleepiness scores decreased from 8.7 ± 4.0 at baseline to 6.9 ± 4.4 (p < 0.001) at the end of the trial; the Pittsburgh Sleep Quality Index improved from 7.4 ± 3.3 to 6.5 ± 3.6 (p = 0.042). Mean oxygen saturation increased from 94.8 ± 2.0 to 95.2 ± 1.9 (p = 0.023) on initial treatment nights and 95.3 ± 1.9 (p = 0.003) at the end of the trial. Sleep architecture was not affected. Participants reported using the device all night long for 94% of nights during the in-home trial.

Conclusions: Treatment with this novel device was well tolerated and accepted by the participants. An overall reduction in AHI was documented; however, therapeutic response was variable among the participants. Further research is required to identify the ideal candidates for this new therapeutic option in the management of OSA.

Keywords: Sleep apnea, OSA, therapy, CPAP, sleepiness

Auto-PEEP to Treat Obstructive Sleep Apnea

Commentary on Rosenthal et al. A multicenter, prospective study of a novel nasal EPAP device in the treatment of obstructive sleep apnea: efficacy and 30-day adherence. J Clin Sleep Med 2009;5:532-537.

Memory Before and After Sleep in Patients with Moderate Obstructive Sleep Apnea

Objective: The aim of this study was to investigate the effects of obstructive sleep apnea (OSA) on procedural and declarative memory encoding in the evening prior to sleep, on memory consolidation during subsequent sleep, and on retrieval in the morning after sleep.

Methods: Memory performance (procedural mirror-tracing task, declarative visual and verbal memory task) and general neuropsychological performance were assessed before and after one night of polysomnographic monitoring in 15 patients with moderate OSA and 20 age-, sex-, and IQ-matched healthy subjects.

Results: Encoding levels prior to sleep were similar across groups for all tasks. Conventional analyses of averaged mirror tracing performance suggested a significantly reduced overnight improvement in OSA patients. Single trial analyses, however, revealed that this effect was due to significantly flattened learning curves in the evening and morning session in OSA patients. OSA patients showed a significantly lower verbal retention rate and a non-significantly reduced visual retention rate after sleep compared to healthy subjects. Polysomnography revealed a significantly reduced REM density, increased frequency of micro-arousals, elevated apnea-hypopnea index, and subjectively disturbed sleep quality in OSA patients compared to healthy subjects.

Conclusions: The results suggest that moderate OSA is associated with a significant impairment of procedural and verbal declarative memory. Future work is needed to further determine the contribution of structural or functional alterations in brain circuits relevant for memory, and to test whether OSA treatment improves or normalizes the observed deficits in learning.

Keywords: Obstructive sleep apnea, memory, plasticity, procedural, declarative

Medical Complaints Are More Common in Young School-Aged Children with Parent Reported Insomnia Symptoms

Objective: Studies in adults have found significant association between sleep disturbances and various medical symptoms/disorders. However, in children, few studies have explored this complex association in clinical samples. In this study, we examined prevalence of medical complaints in children with insomnia symptoms in a large general population of school aged children.

Methods: We conducted a cross sectional study of 700 children, ages 5–12 years, from the Penn State Children’s Cohort. All children underwent a medical and psychiatric history, physical examination, 9-h overnight polysomnography, and neuropsychological testing. Comprehensive sleep and development questionnaires were completed by a parent. We compared 135 (19.3%) children with parent-reported sleep disturbances to 565 (80.7%) children with no parent-reported sleep disturbances.

Results: Insomnia symptoms were significantly associated with gastrointestinal regurgitation and headaches after controlling for demographic variables, apnea hypopnea index, ADHD, learning disorder or other psychiatric/behavioral disorder, socioeconomic status, and minority status. Children with gastrointestinal regurgitation and headaches compared to children without these symptoms were 3.3 times and 2.3 times as likely to suffer from sleep disturbances, respectively. Objectively, sleep latency increased in the sleep disturbance group, and there were significant differences between groups in REM latency, slow wave, and stage 2 sleep.

Discussion: These results underscore the importance of inquiring about insomnia symptoms when children present with medical complaints particularly gastrointestinal regurgitation or headaches and taking a comprehensive medical history when children present with sleep complaints. Future studies are needed to replicate these findings and explore the possible underlying pathophysiological abnormalities of such comorbidity between insomnia symptoms and medical symptoms in children.

Keywords: Insomnia, insomnia symptoms, medical complaints, gastrointestinal regurgitation, headaches, pediatric sleep disorders

Polysomnographic Findings are Associated with Cephalometric Measurements in Mouth-Breathing Children

Objectives: Children with adenotonsillar hypertrophy and those with an abnormal craniofacial morphology are predisposed to having sleep disordered breathing; many of these children are mouth breathers. The aim of this study was to determine whether an association exists between polysomnographic findings and cephalometric measures in mouth-breathing children.

Methods: Twenty-seven children (15 mouth-breathing children and 12 nose-breathing children [control subjects]), aged 7 to 14 years, took part in the study. Polysomnographic variables included sleep efficiency, sleep latency, apnea-hypopnea index, oxygen saturation, arousal index, number of periodic limb movements in sleep, and snoring. Cephalometric measures included maxilla and mandible position, occlusal and mandibular plane inclination, incisor position, pharyngeal airway space width, and hyoid bone position.

Results: As compared with nose-breathing children, mouth breathers were more likely to snore (p < 0.001) and to have an apnea-hypopnea index greater than 1 (p = 0.02). Mouth-breathing children were also more likely to have a retruded mandible, more inclined occlusal and mandibular planes, a smaller airway space, and a smaller superior pharyngeal airway space (p < 0.01). The apnea-hypopnea index increased as the posterior airway space decreased (p = 0.05).

Conclusions: Our study showed an association between polysomnographic data and cephalometric measures in mouth-breathing children. Snoring was the most important variable associated with abnormal craniofacial morphology. Orthodontists should send any mouth-breathing child for an evaluation of sleep if they find that the child has a small superior pharyngeal airway space or an increased ANB (the relationship between the maxilla and mandible), NS.PlO (occlusal plane inclination in relationship to the skull base), or NS.GoGn (the mandibular plane inclination in relation to the skull base), indicating that the child has a steeper mandibular plane.

Keywords: Sleep disordered breathing, polysomnography, lateral radiography, mouth-breathing children

Idiopathic Hypersomnia: Clinical Features and Response to Treatment

Objective: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy.

Methods: A retrospective review of our database initially identified 997 patients, utilizing “idiopathic hypersomnia,” “hypersomnia NOS,” and “primary hypersomnia” as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale.

Results: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a “complete response” to pharmacotherapy as assessed by the authors’ grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of “complete” or “partial” responses than modafinil, although statistical significance was not reached (38/40 [ 95%] vs 22/25 [88%], respectively, p = 0.291).

Conclusions: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

Keywords: Idiopathic hypersomnia, treatment, modafinil, methylphenidate, stimulants

Obstructive Sleep Apnea Syndrome: A Cause of Acute Delirium

Delirium is a transient global disorder of cognition related to a variety of structural or functional neural disorders. Descriptions and characterizations of delirium associated with obstructive sleep apnea syndrome (OSAS) are rare. We describe a 52-year-old man with severe OSAS associated with sudden onset of delirium and with a fluctuating nighttime course, prolonged for several days. The delirium disappeared after treatment with continuous positive airway pressure (CPAP). The patient remained free of symptoms under CPAP during a follow-up of 8 years.

Keywords: Sleep disordered breathing, delirium, neurological symptoms, sleep apnea

A Multigenerational Family with Persistent Sleep Related Rhythmic Movement Disorder (RMD) and Insomnia

In the International Classification of Sleep Disorders 2^nd Edition (ICSD -2), sleep related rhythmic movement disorder (RMD) is classified as a disorder characterized by rhythmic movements of large muscle groups in different parts of the body. These are repetitive, stereotyped, rhythmic motor behaviors that occur predominantly during drowsiness or sleep,and are typically seen in infants and children. Episodes often occur at sleep onset, at any time during the night, and during quiet wakeful activities at a frequency of 0.5–2 sec), lasting < 15 min. The prevalence is high in infants (59%), dropping to 5% at the age of 5 years. When persisting to older childhood or beyond, association with mental retardation, autism, or other significant pathology is reported.¹ Few cases in adults of normal intelligence have been reported in the literature.^2-5 There is a strong association with attention deficit hyperactivity disorder, suggesting a similar pathogenetic mechanism.⁵ There is also one adult case report occurring during strictly REM sleep.⁶ Mayer et al reported 24 subjects with RMD that persisted into adolescence and adulthood. Twenty of the subjects were adults, and 16 of them had the condition since childhood. Of these 20, 16 had no other sleep disorders (but 2 had a family history of RMD), and 4 had obstructive sleep apnea.⁷ This was the first ever report of familial RMD.

Keywords: Sleep related rhythmic movement disorder, adults, insomnia, familial condition

Physician Practice Information: The Practice Expenses and Characteristics of Sleep Medicine as Compared with Other AMA-Recognized Medical Specialties

Summary: This report introduces the Physician Practice Information (PPI) Survey and its findings. Background information on the PPI Survey is explained, as is the Survey’s importance to the field of sleep medicine. Statistics reported by the Survey regarding Practice Expenses per Hour (PE/HR) for various specialties are analyzed in comparison with those reported specifically for sleep medicine. The similarities and differences between sleep medicine and all other medical specialties surveyed in terms of practice characteristics are also discussed.

Analysis of PE/HR data found that sleep medicine payroll practice expenses are closest to those of obstetrics/gynecology, likely due to the employment of technologists in both fields. Regarding supplies and equipment expenses, sleep medicine is most similar to radiology, cardiology, and spine surgery, probably due to the use of disposable medical supplies. In terms of total PE/HR (less separately billable), sleep medicine is most like obstetrics/gynecology, orthopedic surgery, and otolaryngology. The full cause of this is undeterminable from the PPI Survey.

Some areas of dissimilarity in regard to the practice characteristics of sleep physicians and all physicians surveyed across all specialties were found. Most of these fell in the area of “practice size and function of non-physician personnel.” Overall, the results of this section of the PPI Survey show that sleep medicine is practiced in a manner similar to that of the various specialty fields of all physicians surveyed across all specialties but still maintains some unique practice characteristics.

Keywords: Practice expenses; practice characteristics; medical specialties; sleep medicine; practice information

Obstructive Sleep Apnea and Risk of Motor Vehicle Crash: Systematic Review and Meta-Analysis

Study Objectives: We performed a systematic review of the OSA-related risk of crash in commercial motor vehicle (CMV) drivers. The primary objective involved determining whether individuals with obstructive sleep apnea (OSA) are at an increased risk for a motor vehicle crash when compared to comparable individuals who do not have the disorder. A secondary objective involved determining what factors are associated with an increased motor vehicle crash risk among individuals with OSA.

Design/Setting: Seven electronic databases (MEDLINE, PubMed (PreMEDLINE), EMBASE, PsycINFO, CINAHL, TRIS, and the Cochrane library) were searched (through May 27, 2009), as well as the reference lists of all obtained articles. We included controlled studies (case-control or cohort) that evaluated crash risk in individuals with OSA. We evaluated the quality of each study and the interplay between the quality, quantity, robustness, and consistency of the body of evidence, and tested for publication bias. Data were extracted by 2 independent analysts. When appropriate, data from different studies were combined in a fixed- or random-effects meta-analysis.

Results: Individuals with OSA are clearly at increased risk for crash. The mean crash-rate ratio associated with OSA is likely to fall within the range of 1.21 to 4.89. Characteristics that may predict crash in drivers with OSA include BMI, apnea plus hypopnea index, oxygen saturation, and possibly daytime sleepiness.

Conclusions: Untreated sleep apnea is a significant contributor to motor vehicle crashes.

Keywords: Crash, driver, commercial motor vehicle, sleepiness, obesity

Central Alveolar Hypoventilation and Failure to Wean from the Ventilator

Sleep Medicine News and Updates