Charlene E. Gamaldo

Update in restless legs syndrome

PURPOSE OF REVIEW Although restless legs syndrome (RLS) is a disorder recognized in the medical literature since the 17th century, there have only recently been significant clinical and scientific advances in diagnosis, epidemiology and understanding the disorder, mainly due to the advent of dopaminergic treatment. RECENT FINDINGS Recent discoveries have uncovered the iron-dopamine connection in RLS and the basic dopaminergic pathology related to the RLS symptoms. These have led to new understanding of the morbidity of RLS and the many conditions associated with RLS, which have also supported new approaches to treatment. These developments are each briefly described here. SUMMARY Although there has been progress in understanding, diagnosing and treating RLS, it remains an underdiagnosed and undertreated condition severely impairing functioning of patients with moderate-to-severe disease. Much work is needed to improve on current, as well as other novel therapies.

Increased synaptic dopamine in the putamen in restless legs syndrome

STUDY OBJECTIVES Prior studies using positron emission tomography (PET) or single-photon emission computed tomography techniques have reported inconsistent findings regarding differences between patients with restless legs syndrome (RLS) and control patients in the striatal dopamine-2 receptor (D2R) binding potentials (BP). D2R-BP does reflect receptor-ligand interactions such as receptor affinity (K(d)) and density (β(max)) or neurotransmitter synaptic concentrations. Thus, differences in D2R-BP reflect changes in these primary factors. PET techniques are currently available to estimate D2R β(max) and K(d). DESIGN Separate morning and evening PET scans were performed. The D2R-BP were measured in basal ganglia using [(11)C]raclopride. SETTING Academic medical center. PATIENTS OR PARTICIPANTS Thirty-one patients with primary RLS and 36 age- and sex-matched control patients completed the study. MEASURES AND RESULTS Patients with RLS had lower D2R-BP in putamen and caudate but not the ventral striatum. A subgroups analysis of those RLS patients who had not previously taken dopaminergic medications continued to show a significantly lower D2R-BP in the posterior putamen. D2R-BP did not differ between night and day for either group. D2R β(max) and K(d) did not differ significantly between patients with RLS and control patients but did show a strong and significant increase at night in the ventral striatum. Primary and secondary clinical measures of disease status failed to show any relation to D2R in any brain region. CONCLUSIONS Given the lack of any difference in either β(max) or K(d) and the prior studies supporting an increase in presynaptic dopaminergic activity, the current changes found in D2R-BP likely reflect an increase in synaptic dopamine.

The Sleep-Immunity Relationship

Research models show a strong interrelationship between sleep quality and immune function. The proinflammatory cytokines, interleukin-1, interleukin-6, and tumor necrosis factor α are classified as official sleep-regulatory substances. However, sleep-promoting properties are also possessed by several other immune and proinflammatory cellular classes. This article reviews the current physiologic evidence for the prominent somnogenic and sleep-regulatory properties inherent to these immune substances. Clinical examples of this relationship are discussed from the perspective of infectious and primarily immune-related conditions associated with significant sleep disruption and from the perspective of immune dysregulation associated with several primary sleep disorders.

AASM Scoring Manual Version 2.2 Updates: New Chapters for Scoring Infant Sleep Staging and Home Sleep Apnea Testing.

V 2.2 of the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events was released on July 1, 2015. The Scoring Manual Editorial Board (previously the Scoring Manual Committee) would like to call attention to the most important changes. As discussed below, there are two new major chapters providing rules for the staging of infant sleep and scoring respiratory events in home sleep apnea testing (HSAT) studies. The new chapters were approved by the AASM Board of Directors to fi ll two obvious gaps in the Scoring Manual. The Scoring Manual Editorial Board would like to emphasize that any changes in the manual are instituted after long deliberation and consultation with area content experts. Version 2.2 of the Scoring Manual, for the fi rst time, includes rules for scoring sleep studies in term infants less than two months of age. This milestone acknowledges the importance of studying sleep across the lifespan, beginning with our youngest patients. The new scoring rules address sleep staging in infants and are based on the classic infant scoring rules of Anders et al.1 Development of these new rules benefi tted from expert consultation from Madeleine Grigg-Damberger, MD, and Mark Scher, MD. One important difference between the current manual and Anders is that sleep is now classifi ed into three stages: REM, NREM and transitional, as compared to the Anders classifi cation of active, quiet and indeterminate sleep. This new classifi cation was based on the physiologic similarities between active and REM sleep, and quiet and NREM sleep. Further, it was realized that young infants have stages of sleep that manifest elements of both REM and NREM sleep; hence, the term “transitional” rather than “indeterminate.” Note that respiratory events in infants should be scored using the standard AASM pediatric scoring criteria. Version 2.2 of the AASM Scoring Manual now also includes scoring rules for adult Home Sleep Apnea Testing (HSAT; chapter IX). The foundation for the development of these rules includes the work of the 2010 AASM Out-of-Center Task Force who developed the SCOPER (Sleep, Cardiovascular, Oximetry, Position, Effort, Respiratory) classifi cation system.2 This classifi cation system systematically evaluated available technology and evidence for diagnosing obstructive sleep apnea using portable devices. These new HSAT scoring rules allow for standardization of scoring and reporting data generated from HSAT AASM Scoring Manual Version 2.2 Updates: New Chapters for Scoring Infant Sleep Staging and Home Sleep Apnea Testing Richard B. Berry, MD1; Charlene E. Gamaldo, MD2; Susan M. Harding, MD3; Rita Brooks, MEd, RST, RPSGT4; Robin M. Lloyd, MD5; Bradley V. Vaughn, MD6; Carole L. Marcus, MBBCh7 1University of Florida, Gainesville, FL; 2Johns Hopkins University, Baltimore, MD; 3University of Alabama, Birmingham, AL; 4Capital Health, Hamilton, NJ; 5Mayo Clinic, Rochester, MN; 6University of North Carolina, Chapel Hill, NC; 7Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA

Polysomnogram changes in marijuana users who report sleep disturbances during prior abstinence

BACKGROUND Abrupt discontinuation of heavy marijuana (MJ) use is associated with self-reports of sleep difficulty. Disturbed sleep is clinically important because MJ users experiencing sleep problems may relapse to MJ use to improve their sleep quality. Few studies have used polysomnography (PSG) to characterize changes in sleep architecture during abrupt abstinence from heavy MJ use. METHODS We recorded PSG measures on nights 1, 2, 7, 8, and 13 after abrupt MJ discontinuation in 18 heavy MJ users residing in an inpatient unit. RESULTS Across abstinence, Total Sleep Time (TST), Sleep Efficiency (SEff), and amount of REM sleep declined, while Wake after Sleep Onset (WASO) and Periodic Limb Movements (PLM) increased. Furthermore, quantity (joints/week) and duration (years) of MJ use were positively associated with more PLMs. CONCLUSION The treatment of sleep disturbance is a potential target for the management of cannabis use disorders since poor sleep could contribute to treatment failure in heavy MJ users.

Evaluating daytime alertness in individuals with restless legs syndrome (RLS) compared to sleep restricted controls

BACKGROUND AND PURPOSE Restless Legs Syndrome (RLS) is a common sensorimotor disorder often associated with significant chronic sleep loss. Previous studies looking at the effects of sleep loss on daytime function in RLS individuals, using subjective reporting techniques have yielded mixed results. In this study we used more objective measures of alertness and compared RLS subjects who are off treatments and chronically sleep restricted to chronic sleep-restricted controls. SUBJECTS AND METHODS The final sample consisted of 20 RLS subjects (10 male and 10 female) and 13 sleep-restricted controls (seven male and six female). Thirteen controls underwent a 14-day chronic partial sleep-restriction protocol in order to closely match the degree of chronic sleep loss reportedly experienced by untreated RLS patients. On the final day of the protocol each subject performed a morning and evening Suggested Immobilization Test (SIT) which served as a modified Maintenance of Wakefulness Test (MWT). RLS and control groups were compared for differences in alertness as measured objectively by the sleep latency on the morning and evening SITs. RESULTS The RLS subjects had a longer sleep latency on the morning and evening SIT than controls (t=3.80, p=0.001, U=31.0, p<0.001, respectively). Even after controlling for the potential arousal impact associated with increased leg activity, RLS individuals still demonstrated a higher degree of objective alertness (p=0.023, p=0.006, Fishers exact test). CONCLUSIONS RLS subjects, despite having, if anything, greater sleep loss, displayed greater sustained alertness than sleep-restricted controls. Thus, the heightened degree of alertness demonstrated by RLS patients may be in contrast to the perceived impairment in mood, vigor, and vigilance commonly reported in previous studies.

Medication use in patients with restless legs syndrome compared with a control population

Primary restless legs syndrome (RLS) is a sensorimotor disorder causing chronic sleep deprivation in those with moderate to severe symptoms. It has been associated with other medical conditions, such as high blood pressure, depression and attention deficit hyperactive disorder (ADHD). If these conditions are more prevalent for RLS patients, then it would be expected RLS patients would use relatively more of the medications treating these conditions. Current medication use was obtained from 110 RLS patients and 54 age, race and gender‐matched local‐community controls. Each subject was diagnosed as primary RLS or having no indications for RLS by a clinician board‐certified in sleep medicine. The RLS group used more medications than the control group even when medications used for treating RLS were excluded. Significantly more of the RLS patients than controls used anti‐depressants, gastro‐intestinal (GI) medications and asthma/allergy medications. RLS patients compared with those without RLS are more likely to use medications not related to treating RLS. Moreover they use medications for conditions that have not previously been considered related to RLS, i.e. GI and asthma/allergy conditions.

Evaluating sleep and cognition in HIV

Objective:To examine the relationship between measures of sleep quality and cognitive performance in HIV-positive individuals stable on combination antiretroviral therapy. Design:Multimethod assessments of sleep quality, patterns, and cognitive performance were assessed in a predominantly black HIV-positive cohort. Methods:Sleep quality and patterns were characterized in 36 subjects by polysomnogram, 2-week actigraphy monitoring, and validated sleep questionnaires. Cognitive performance was assessed with a battery of neuropsychological tests. Results:The majority of participants were cognitively impaired [based on Frascati (75%) criteria]. Self-reported mean scores on the Pittsburgh sleep quality index and the insomnia severity scale suggested poor sleep quality. Better cognitive performance, particularly on tasks of attention, frontal/executive function, and psychomotor/motor speed, was associated with polysomnogram sleep indices (ie, reduced wake after sleep onset, greater sleep efficiency, greater sleep latency, and greater total sleep time). Thirty-seven percent of participants had sleep patterns suggestive of chronic partial sleep deprivation, which was associated with significantly worse performance on the digit symbol test (P = 0.006), nondominant pegboard (P = 0.043), and verbal fluency tests (P = 0.044). Conclusions:Our results suggest that compromised sleep quality and duration may have a significant impact on cognitive performance in HIV-positive individuals. Future studies are warranted to determine the utility of sleep quality and quantity indices as potential predictive biomarkers for development and progression of future HIV-associated neurocognitive disorder.

Sleep Medicine Pharmacotherapeutics Overview: Today, Tomorrow, and the Future (Part 1: Insomnia and Circadian Rhythm Disorders)

Over the past 10 years, significant strides have been made in the understanding, development, and availability of sleep disorder therapeutics. In this review series, we discuss the current evidence surrounding the mechanisms of actions, indications, efficacy, and adverse side effects associated with the available armamentarium of sleep over-the-counter and pharmacotherapeutics. This article is the first of a two-part series that covers the therapeutics for insomnia and circadian rhythm disorders.

All the wrong moves: a clinical review of restless legs syndrome, periodic limb movements of sleep and wake, and periodic limb movement disorder

Restless legs syndrome, periodic limb movements in sleep, and periodic limb movement disorder are a group of conditions that merit awareness from the medical community. These disorders are commonly encountered yet are often confused and misdiagnosed by health care professionals. It is imperative that health care providers are able to recognize these conditions to accurately diagnose, manage, and appropriately refer patients.