JCSM Articles

Sleep Medicine: Strategies for Change

The Future Of Sleep Medicine: Will You Be A Part Of It?

Health Disparities in Sleep Medicine: Responses to the American Sleep Medicine Foundation Humanitarian Projects Award Program

Psychiatric Comorbidity in Children and Adolescents with Restless Legs Syndrome: A Retrospective Study

Objective:

Children and adolescents with restless legs syndrome (RLS) are commonly diagnosed with comorbid attention deficit hyperactivity disorder and behavioral disturbances. Uncertainty exists over the significance of other co-occurring psychiatric disorders and their pharmacologic management in children with RLS. The purpose of this study was to determine the prevalence and nature of psychiatric disorders in children with RLS and to describe the use of psychotropic medications in our study cohort.

Methods:

The electronic medical records of children younger than 18 years of age who had been diagnosed with RLS between January 1, 2003, and December 31, 2009, were reviewed. Only those patients whose findings were consistent with the 2003 NIH workshop diagnostic criteria for probable or definite restless legs syndrome were included in this study. The medical records were cross-referenced for encounters with a child psychiatrist or psychologist. Likewise, only psychiatric diagnoses whose medical records explicitly reflected DSM-IV diagnostic criteria for psychiatric disorder(s) were included. Demographic data, serum ferritin, psychotropic medications, and in some cases, the results of pharmacogenomic testing were included in the data analysis in an ad hoc fashion.

Results:

We found 374/922 patients who met diagnostic criteria for childhood onset RLS. The mean age of the subjects was 10.6 years (range 0 to 18) and the male to female ratio was approximately 1:1. Overall, 239/374 (64%) patients with RLS had one or more comorbid psychiatric disorders. Attention deficit hyperactivity disorder was found in 94/374 (25%) patients, mood disturbances were found in 109/374 (29.1%) patients, anxiety disorders in 43/374 (11.5%) patients, and behavioral disturbances in 40/374 (10.9%) patients. Attention deficit hyperactivity disorder and disruptive behavior disorders were more common in males (OR = 1.94 for both), whereas mood disturbances and anxiety disorders were more common in females (OR = 1.6 and 1.26, respectively).

Mean serum ferritin levels derived from all patients without any psychiatric disorder were compared to all patients with one or more psychiatric disorder. No differences were found. The number of new psychotropic medication trials increased significantly with increase in patient age. Stimulants and antidepressant medications were the most commonly prescribed agents. As a part of clinical care, 15 of these patients underwent pharmacogenomic testing. Metabolic abnormalities were predicted by genotyping in 12/15 (80%) patients.

Conclusion:

Comorbid psychiatric conditions occurred in two-thirds of children with RLS, underscoring the need for multidisciplinary management of this condition. An important relationship might exist between psychotropic medication, and possibly pharmacogenomic factors, in children and adolescents with symptoms of restless legs syndrome. These findings are consistent and build on those reported in the adult literature.

Citation:

Pullen SJ; Wall CA; Angstman ER; Munitz GE; Kotagal S. Psychiatric comorbidity in children and adolescents with restless legs syndrome: a retrospective study. J Clin Sleep Med 2011;7(6):587-596.

Periodic Limb Movements during Sleep in Children with Narcolepsy

Study Objectives:

In adults with narcolepsy, periodic limb movements of sleep (PLMS) occur more frequently than in control population, and presence of increased PLMS is associated with greater sleep disruption and shorter mean sleep latency. This study was performed to determine whether PLMS are common in children with narcolepsy, and whether the presence of PLMS is associated with greater sleep disruption.

Design:

Demographic and polysomnographic information were collected from consecutive patients diagnosed with narcolepsy identified retrospectively by diagnosis-based search. Descriptive data were compiled, and sleep characteristics of children with and without PLMS were compared.

Setting:

Sleep disorders center in a children's hospital.

Patients:

44 patients, 6-19 years old (mean 13 years, SD 3.57), were identified. Twenty-eight were African American.

Interventions:

None.

Measurements and Results:

Four patients had a PLMS index (PLMI) ≥ 5/h (considered abnormal in literature). Sixteen (36%) had “any PLMS” (PLMI > 0/h). The mean PLMI was 1.3/h (SD 2.5). Sleep was significantly more disrupted, and the mean sleep latency was shorter in patients with “any PLMS” as compared to those with no PLMS. There was no correlation between the PLMI and other diagnostic criteria for narcolepsy. “Any PLMS” were present equally in children of African American and Caucasian heritage, 35.7% vs. 37.5%.

Conclusions:

As in adults, children with PLMS and narcolepsy have more sleep disruption and shorter mean sleep latencies than those with narcolepsy but without PLMS. Our findings also suggest that the use of adult criteria for diagnosis of “significant” PLMS in children may not be sufficiently sensitive.

Citation:

Jambhekar SK; Com G; Jones E; Jackson R; Castro MM; Knight F; Carroll JL; Griebel ML. Periodic limb movements during sleep in children with narcolepsy. J Clin Sleep Med 2011;7(6):597–601.

Pediatric Periodic Limb Movement Disorder: Sleep Symptom and Polysomnographic Correlates Compared to Obstructive Sleep Apnea

Study Objectives:

Although periodic limb movements in sleep (PLMS) have been described in multiple pediatric publications, periodic limb movement disorder (PLMD) has not. The aims of this study were to describe the prevalence, sleep-related correlates, and polysomnographic correlates of PLMD in a large pediatric case series, and compare these to pediatric obstructive sleep apnea (OSA).

Methods:

All PLMD cases (defined by International Classification of Sleep Disorders, 2nd edition criteria + respiratory disturbance index [RDI] < 3) and OSA cases (defined by RDI ≥ 3 + PLMS < 5), from a single pediatric sleep practice, over a 2-year time span, were included. Chart, questionnaire, and polysomnographic data were compiled. Of 468 referred children, 66 PLMD cases were identified (14%).

Results:

The PLMD cases, mean age 8.1 years (range 1-17), were clinically characterized by frequent sleep onset and maintenance problems, difficulty awakening, restless sleep, leg pain/discomfort at night, and parasomnias. Compared to 90 OSA children, those with PLMD had a history of significantly more sleep onset and maintenance problems, leg pain/discomfort at night, parasomnias, getting out of bed at night, and family history of restless legs syndrome. Polysomnographically, PLMD cases had more awakenings, stage 1 sleep, stage shifts, and spontaneous arousals.

Conclusions:

These data indicate that pediatric PLMD has important clinical and polysomnographic correlates. In addition, PLMD has many characteristics that are different from pediatric OSA, suggesting that PLMD is a distinct pediatric sleep disorder, of which clinicians should be aware.

Citation:

Gingras JL; Gaultney JF; Picchietti DL. Pediatric periodic limb movement disorder: sleep symptom and polysomnographic correlates compared to obstructive sleep apnea. J Clin Sleep Med 2011;7(6):603-609.

The Effects of Altitude Associated Central Apnea on the Diagnosis and Treatment of Obstructive Sleep Apnea: Comparative Data from Three Different Altitude Locations in the Mountain West

Study Objectives:

This study documents both the incidence and effects of central apnea on diagnosis and treatment of OSA at different altitudes in the Mountain West and substantiates the clinical impression that individuals living at altitude with moderate to severe OSA are significantly more difficult to treat with PAP.

Methods:

Split-night polysomnography was compared between sites for patients with a diagnostic AHI > 15 living at 1421 meters (Site 1; N = 150), at 1808 m (Site 2; N = 150) and at 2165 m (Site 3; N = 142). The quality of PAP titration obtained was rated, based on AASM clinical guidelines, from 1 = optimal to 4 = unacceptable. Patients developing central apneas during PAP therapy (CAI > 5.0) were titrated with an alternative O₂ > CPAP/Bilevel PAP protocol.

Results:

The mean number of central apneas in the diagnostic portion of studies was significantly higher (p < 0.01) at Sites 2 (19.26) and 3 (12.36) than at Site 1 (3.11). Mean numbers of central apneas/h developing on treatment with PAP varied from 4.8/h at Site 1, to 9.79/h at Site 2, to 19.25/h at Site 3 (p < 0.001). At Site 1, 10.6% had a central apnea index (CAI) > 5.0, while 22% met this criterion at Site 2 and 38.7% at Site 3 (Site 3 vs Site 1, p = 0.01; Site 2 vs Site 1, p = 0.02). Rated titration quality varied significantly between sites. At Site 1, mean titration quality was 1.437 (SD 0.821); for Site 2, 1.569 (SD 0.96), and for Site 3, 1.772 (SD 1.025). Titration quality at Site 3 was significantly worse than at Site 1 (t = 3.22, p < 0.01) and at Site 2 (t = 2.55, p < 0.02). Repeat titration requirement differed significantly (p = 0.025). Analysis of covariance comparing titration across 3 altitude levels, controlling for age, was significant for the effect of altitude (p = 0.017). Utilizing the alternative O₂ > C-PAP/Bi-PAP protocol in patients with CAI > 5.0 developing on PAP treatment, an overall optimal or good titration (AASM criteria) was attained in 75/79 (95%) of titrated patients.

Conclusions:

This study demonstrates that central apnea becomes significantly more common at increasing altitude in both diagnostic and treatment portions of split-night polysomnography in patients with significant OSA. An apparent exponential increase in the percentage of OSA patients with a CAI > 5.0 occurs with increasing altitude. Altitude associated central apnea has a significant negative effect on the quality of OSA treatment obtained during PAP titration for patients living at the altitudes addressed in this study.

Citation:

Pagel JF; Kwiatkowski C; Parnes B. The effects of altitude associated central apnea on the diagnosis and treatment of obstructive sleep apnea: comparative data from three different altitude locations in the Mountain West. J Clin Sleep Med 2011;7(6):610-615.

Severe Obstructive Sleep Apnea and Outcomes Following Myocardial Infarction

Study Objective:

We sought to determine the effect of severe obstructive sleep apnea (OSA) on long-term outcomes after myocardial infarction. We hypothesized that severe OSA was associated with lower event-free survival rate after ST-segment elevation myocardial infarction (STEMI).

Methods:

A total of 120 patients underwent an overnight sleep study during index admission for STEMI. Severe OSA was defined as apnea hypopnea index (AHI) ≥ 30, and non-severe OSA defined as AHI < 30.

Results:

Among the 105 patients who completed the study, 44 (42%) had severe OSA and 61 (58%) non-severe OSA. The median creatine kinase level and mean left ventricular systolic function were similar between the 2 groups. None of the 105 study patients had received treatments for OSA. Between 1- and 18-month follow-up, the severe OSA group incurred 1 death, 2 reinfarctions, 1 stroke, 6 unplanned target vessel revascularizations, and 1 heart failure hospitalization. In contrast, there were only 2 unplanned target vessel revascularizations in the non-severe OSA group. The incidence of major adverse events was significantly higher in the severe OSA group (15.9% versus 3.3%, adjusted hazard ratios: 5.36, 95% CI: 1.01 to 28.53, p = 0.049). Kaplan-Meier event-free survival curves showed the event-free survival rates in the severe OSA group was significantly worse than that in the non-severe OSA group (p = 0.021, log-rank test).

Conclusion:

42% of the patients admitted with STEMI have undiagnosed severe OSA. Severe OSA carries a negative prognostic impact for this group of patients. It is associated with a lower event-free survival rate at 18-month follow-up.

Citation:

Lee CH; Khoo SM; Chan MY; Wong HB; Low AF; Phua QH; Richards AM; Tan HC; Yeo TC. Severe obstructive sleep apnea and outcomes following myocardial infarction. J Clin Sleep Med 2011;7(6):616–621.

Physiological Predictors of Response to Exposure, Relaxation, and Rescripting Therapy for Chronic Nightmares in a Randomized Clinical Trial

Study Objectives:

Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy(ERRT) and extended prior research by including broad measures of mental health difficulties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined.

Methods:

Forty-seven individuals were randomized to treatment or waitlist control.

Results:

The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, significant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health.

Conclusions:

Findings provide additional support for the use of ERRT in treating nightmares and related difficulties and improving sleep.

Citation:

Davis JL; Rhudy JL; Pruiksma KE; Byrd P; Williams AE; McCabe KM; Bartley EJ. Physiological predictors of response to exposure, relaxation, and rescripting therapy for chronic nightmares in a randomized clinical trial. J Clin Sleep Med 2011;7(6):622-631.

Zolpidem Ingestion, Automatisms, and Sleep Driving: A Clinical and Legal Case Series

Study Objectives:

To describe zolpidem-associated complex behaviors, including both daytime automatisms and sleep-related parasomnias.

Methods:

A case series of eight clinical patients and six legal defendants is presented. Patients presented to the author after an episode of confusion, amnesia, or somnambulism. Legal defendants were being prosecuted for driving under the influence, and the author reviewed the cases as expert witness for the defense. Potential predisposing factors including comorbidities, social situation, physician instruction, concomitant medications, and patterns of medication management were considered.

Results:

Patients and defendants exhibited abnormal behavior characterized by poor motor control and confusion. Although remaining apparently interactive with the environment, all reported amnesia for 3 to 5 hours. In some cases, the episodes began during daytime wakefulness because of accidental or purposeful ingestion of the zolpidem and are considered automatisms. Other cases began after ingestion of zolpidem at the time of going to bed and are considered parasomnias. Risk factors for both wake and sleep-related automatic complex behaviors include the concomitant ingestion of other sedating drugs, a higher dose of zolpidem, a history of parasomnia, ingestion at times other than bedtime or when sleep is unlikely, poor management of pill bottles, and living alone. In addition, similar size and shape of two medications contributed to accidental ingestion in at least one case.

Conclusions:

Sleep driving and other complex behaviors can occur after zolpidem ingestion. Physicians should assess patients for potential risk factors and inquire about parasomnias. Serious legal and medical complications can occur as a result of these forms of automatic complex behaviors.

Citation:

Poceta JS. Zolpidem ingestion, automatisms, and sleep driving: a clinical and legal case series. J Clin Sleep Med 2011;7(6):632-638.

A Novel Therapy for REM Sleep Behavior Disorder (RBD)

Study Objectives:

RBD may result in sleep related injury (SRI) particularly if a patient exits the bed during dream enactment behavior (DEB). The complex auditory processing and low arousal threshold of REM sleep offers a therapeutic window to halt behavior prior to SRI. We evaluated whether a recorded message prevents SRI in medically refractory RBD.

Design:

Case Series.

Setting:

Sleep disorders center.

Patients:

Four consecutive RBD patients with continued SRI despite both clonazepam and melatonin therapy.

Intervention:

A pressurized bed alarm customized with a familiar voice to deliver a calming message during vigorous DEB.

Measurements and Results:

The RBDQ-HK evaluated RBD symptoms, and SRI was further quantified with a new clinical tool, the Minnesota Parasomnia Injury Scale. All patients reported a decrease in RBD symptoms and SRI. No injuries occurred post-intervention. Pre-treatment: 5 serious events (SE), 80 minor events (ME), and 193 near events (NE) were noted over 66 patient-months (4.21 events/pt-mo). Post-treatment: 0 SE, 0 ME, and 3 NE were noted after a follow up period of 63 pt-months (0.05 event/pt-mo). There were 176 total bed alarm interventions (2.79 interventions/pt-mo). No adverse effects were reported, and all 4 patients described a minimal burden of treatment. RBD symptoms improved as the average RBDQ-HK score decreased from 68 (range: 53-80) to 54 (range 42-65).

Conclusion:

A customized bed alarm may be an effective method to prevent SRI in RBD. This intervention is most suitable for cases of medically refractory RBD and/or for those patients who are unable to tolerate medical therapy.

Citation:

Howell MJ; Arneson PA; Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med 2011;7(6):639-644.

CBT for Insomnia in Patients with High and Low Depressive Symptom Severity: Adherence and Clinical Outcomes

Study Objectives:

To evaluate whether depressive symptom severity leads to poorer response and perceived adherence to cognitive behavioral therapy for insomnia (CBTI) and to examine the impact of CBTI on well-being, depressive symptom severity, and suicidal ideation.

Design:

Pre- to posttreatment case replication series comparing low depression (LowDep) and high depression (HiDep) groups (based on a cutoff of 14 on the Beck Depression Inventory [BDI]).

Participants:

127 men and 174 women referred for the treatment of insomnia.

Interventions:

Seven sessions of group CBTI.

Measurements and Results:

Improvement in the insomnia severity, perceived energy, productivity, self-esteem, other aspects of wellbeing, and overall treatment satisfaction did not differ between the HiDep and LowDep groups (p > 0.14). HiDep patients reported lower adherence to a fixed rise time, restricting time in bed, and changing expectations about sleep (p < 0.05). HiDep participants experienced significant reductions in BDI, after removing the sleep item. Levels of suicidal ideation dropped significantly among patients with pretreatment elevations (p < 0.0001).

Conclusion:

Results suggest that pre- to post CBTI improvements in insomnia symptoms, perceived energy, productivity, self-esteem, and other aspects of well-being were similar among patients with and without elevation in depressive symptom severity. Thus, the benefits of CBTI extend beyond insomnia and include improvements in non-sleep outcomes, such as overall well-being and depressive symptom severity, including suicidal ideation, among patients with baseline elevations. Results identify aspects of CBTI that may merit additional attention to further improve outcomes among patients with insomnia and elevated depressive symptom severity.

Citation:

Manber R; Bernert RA; Suh S; Nowakowski S; Siebern AT; Ong JC. Cbt for insomnia in patients with high and low depressive symptom severity: adherence and clinical outcomes. J Clin Sleep Med 2011;7(6):645-652.

Cerebrospinal Fluid Hypocretin 1 Deficiency, Overweight, and Metabolic Dysregulation in Patients with Narcolepsy

Study Objectives:

The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls.

Patients:

26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls.

Measurements and Results:

Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p < 0.001 and 0.011, respectively). The number of obese patients (BMI > 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups.

Conclusions:

The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms.

Citation:

Heier MS; Jansson TS; Gautvik KM. Cerebrospinal fluid hypocretin 1 deficiency, overweight, and metabolic dysregulation in patients with narcolepsy. J Clin Sleep Med 2011;7(6):653-658.

Relationship between Food Intake and Sleep Pattern in Healthy Individuals

Study Objectives:

The purpose of this study was to analyze the relationship between food intake and sleep patterns in healthy individuals.

Methods:

Fifty-two healthy volunteers (27 women and 25 men) were recruited to participate in the study. Volunteers underwent sleep evaluation through nocturnal polysomnography and completed a 3-day food diary to evaluate food intake.

Results:

No differences in sleep patterns were observed in either gender, except in the percentage of stage 1 sleep, which was greater in men. Different correlations were observed between sleep and dietary variables according to gender. The correlation between dietary and sleep variables in men indicated a negative relationship between nocturnal fat intake and the sleep latency, including REM sleep. The percentage of nocturnal fat intake correlated with sleep efficiency, sleep latency, REM latency, stage 2 sleep, REM sleep, and wake after sleep onset (WASO) in women. The percentage of nocturnal caloric intake correlated with sleep latency and efficiency in women.

Conclusions:

We conclude that food intake during the nocturnal period is correlated with negative effects on the sleep quality of healthy individuals. Indeed, food intake near the sleeping period (dinner and late night snack) was negatively associated with sleep quality variables. More studies are necessary to elucidate the real effect of food intake on sleep.

Citation:

Crispim CA; Zimberg IZ; dos Reis BG; Diniz RM; Tufik S; de Mello MT. Relationship between food intake and sleep pattern in healthy individuals. J Clin Sleep Med 2011;7(6):659-664.

Psychosis in the Context of Sodium Oxybate Therapy

Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medication, as well as withdrawal symptoms, even at clinical doses.

Citation:

Langford J; Gross WL. Psychosis in the context of sodium oxybate therapy. J Clin Sleep Med 2011;7(6):665-666.

Sodium Oxybate and Sleep Apnea: A Clinical Case

Sodium oxybate (GHB, Xyrem, Jazz Pharmaceuticals) is used to treat cataplexy in patients with narcolepsy. We report the case of a middle aged, normo-ponderal narcoleptic woman without risk factors who developed reversible sleep apnea and objective sleepiness when treated by sodium oxybate, with an apnea-hypopnea index (AHI) of 19.7 on sodium oxybate and AHI 4.8 without treatment. Despite a subjective improvement in vigilance, mean sleep latency on MWT decreased from 21 minutes to 8 minutes on sodium oxybate.

Citation:

Hartley S; Quera-Salva MA; Machou M. Sodium oxybate and sleep apnea: a clinical case. J Clin Sleep Med 2011;7(6):667-668.

Chronic Cough and OSA: A New Association?

Chronic cough is defined as cough lasting more than 2 months. Common causes for chronic cough in nonsmokers with normal chest radiographs and pulmonary functions include gastroesophageal reflux disease (GERD), cough-variant asthma (CVA), and upper airway cough syndrome (UACS). Current guidelines recommend diagnosing the etiology of chronic cough based upon the results of therapy for suspected GERD, CVA, and UACS. Despite following current recommendations for diagnosis and treatment, the cause for a significant proportion of chronic cough remains unexplained.

Recent reports indicate the resolution of chronic cough following treatment of concomitantly diagnosed obstructive sleep apnea (OSA). Whether this represents a co-occurrence of two commonly prevalent disorders or a pathophysiologic relationship between OSA and cough remains unknown. This review offers insights into a pathophysiologic link between OSA and the commonly purported etiologies for cough, namely, GERD, UACS, and CVA. In addition, evidence for a relationship between airway inflammation that can trigger or perpetuate cough and OSA is discussed. This review explores mechanisms by which nocturnal continuous positive airway therapy resolves cough by improving underlying airway inflammation secondary to OSA and impacts upon GERD, CVA, and UACS.

Citation:

Sundar KM; Daly SE. Chronic cough and OSA: a new association? J Clin Sleep Med 2011;7(6):669-677.

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