Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains.

BACKGROUND: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. OBJECTIVE: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. METHODS: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). RESULTS: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). CONCLUSIONS: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

A preliminary study on the relationship between sleep, depression and cardiovascular dysfunction in a 4 sample population.

BACKGROUND: Major Depressive Disorder (MDD) has been linked in the literature to poorer prognosis in patients with cardiovascular dysfunction, although the mechanisms of this relationship remain unclear. Underlying Sleep Disordered Breathing (SDB) serves as a potential candidate to explain this effect due to its downstream effects on inflammatory activation and decreased nitric oxide (NO) bioavailability, both of which have been shown to contribute to the pathophysiology of both MDD and cardiovascular disease (CVD). METHODS: This study utilizes overnight polysomnography and an inflammation panel to examine the links between cardiovascular dysfunction and sleep difficulties in control participants and patients diagnosed with SDB only, MDD only, and both SDB and MDD. RESULTS: Results demonstrate a strong positive relationship between sleep dysfunction and the nitric oxide synthesis inhibitor Symmetric Dimethyl Arginine (SDMA) in the MDD-only cohort, suggesting a link between SDMA-mediated NO dysregulation and CVD pathogenesis in individuals with MDD. Additionally, hypopneas, a form of sleep impairment characterized by partial reduction of airflow, were found to play a significant role in the relationship between SDB and cardiovascular dysfunction in MDD-only patients. CONCLUSIONS: Results of this study demonstrate the need for widespread screening for SDB in MDD populations to detect predisposition to CVD, and also offer SDMA as a new potential target for CVD treatment in individuals with MDD.

Hypoglossal Nerve Stimulator: A Novel Treatment Approach for OSA - Overview of Treatment, Including Diagnostic and Patient Criteria and Procedural Terminology Codes.

Unilateral stimulation of the hypoglossal nerve may result in clinically valuable patency of the upper airway in well-selected patients for treatment of OSA. The Food and Drug Administration has established stringent criteria for the placement of this medical device. The treatment is a consideration among patients who have been nonadherent or intolerant of positive airway pressure therapy, with moderate to severe OSA, and a BMI of ≤ 32 kg/m2. Some of the insurance providers have lowered BMI guidelines to allow implantation in patients with a BMI of < 35 kg/m2. Further, a clinical assessment with sleep endoscopy is available to define proper anatomic features and to determine, based on the results, if the patients are appropriate surgical candidates. Current Procedural Terminology codes that are specific to the placement as well as removal or replacement of the device, or both, are discussed, as well as sleep medicine-related evaluation and management.

Sleep-related (psychogenic) dissociative disorders as parasomnias associated with a psychiatric disorder: update on reported cases.

STUDY OBJECTIVES: To update the literature on the diagnostic category of sleep-related dissociative disorders (SRDDs), involving psychogenic dissociation, since the time of their inclusion in the parasomnias section of the International Classification of Sleep Disorders, second edition, in 2005; to summarize the most salient clinical and video-polysomnographic (vPSG) findings and typical clinical profile from all reported cases; and to provide the rationale for the re-inclusion of the group of SRDDs in future editions of the International Classification of Sleep Disorders. METHODS: A systematic computerized literature search was conducted searching for SRDDs, nocturnal dissociative disorders, and nocturnal dissociation. RESULTS: Nine additional cases were identified, with sufficient clinical history and vPSG findings to justify the diagnosis of SRDDs, supplementing the 11 cases cited in the International Classification of Sleep Disorders, second edition, for a total of 20 cases. Twenty-six other cases with vPSG testing were found, with 18 cases reported in abstracts and 8 cases reported in a publication with compelling histories of SRDDs and 2 consecutive vPSG studies, but without the vPSG findings explicitly reported for any case. In more than half of all reported cases, there was objective diagnostic confirmation for SRDDs consisting of the hallmark finding of abnormal nocturnal behaviors arising from sustained electroencephalography wakefulness, or during wake-sleep transitions, without epileptiform activity. These nocturnal behaviors often replicated daytime psychogenic dissociative behaviors. A history of trauma (physical, sexual, emotional) was an almost universal finding, along with major psychopathology. All patients, except for one, had prominent histories of daytime dissociative disorders. Many of the patients were referred on account of a presumed parasomnia. CONCLUSIONS: Cases of SRDDs continue to be reported, often as a "parasomnia mimic," with psychogenic dissociation being clearly distinguished from physiologic sleep-wake dissociation as found in primary sleep disorders such as narcolepsy, rapid eye movement sleep behavior disorder, etc. Eleven reasons are provided for why the category of SRDDs should be re-included in future editions of the International Classification of Sleep Disorders, and in the parasomnias section.

Meta-analysis of Usefulness of Phrenic Nerve Stimulation in Central Sleep Apnea.

Transvenous neurostimulation of the phrenic nerve (PNS) is a potentially improved and unique approach to the treatment of central sleep apnea (CSA). There have been multiple studies with limited individuals evaluating the efficacy of PNS. Our aim was to review and pool those studies to better understand whether phrenic nerve stimulation is efficacious in the treatment of CSA. The initial search on Pubmed retrieved a total of 97 articles and after screening all articles, only 5 could be included in our quantitative analysis. Pooling of data from 5 studies with a total of 204 patients demonstrated a reduction of mean apnea hypopnea index with PNS compared to controls by -26.7 events/hour with 95% confidence interval and P value of [CI (-31.99, -21.46), I2 85, p 0.00]. The mean difference in central apnea index was -22.47 [CI (-25.19, -19.76), I2 0, p 0.00]. The mean reduction in the oxygen desaturation index of 4% or more demonstrated a decrease in PNS group by -24.16 events/hour [(CI -26.20, -22.12), I2 0, p 0.00] compared with controls. PNS resulted in mean reduction in arousal index of -13.77 [CI (-16.15, -11.40), I2 0, p 0.00]. The mean change in percent of time spent in rapid eye movement sleep demonstrated a nonsignificant increase in PNS group by 1.01 % [CI (-5.67, 7.86), I293, p 0.75]. In conclusion, PNS therapy for treating CSA demonstrated positive outcomes but larger randomized studies are needed to evaluate the safety and clinical outcomes.

Addressing gaps between payer policies and AASM clinical practice guidelines using scorecards.

None: The Payer Policy Review Committee of the American Academy of Sleep Medicine launched an initiative to assess the alignment between clinical practice guidelines and private payer medical policies. This article summarizes the importance of the initiative, details the scorecard development process, including an analysis of policy scores and subsequent revisions, and discusses the impact of the scorecards particularly as related to the scorecards on the clinical practice guideline for diagnosis of obstructive sleep apnea in adults. This initiative has increased communication and engagement among members of the Payer Policy Review Committee and private payers, creating opportunities to advocate on behalf of sleep medicine providers and patients with sleep disorders, encouraging payers to modify existing policies so that evidence-based care is provided to patients with sleep disorders.

A randomized, subject and rater-blinded, placebo-controlled trial of dimethyl fumarate for obstructive sleep apnea.

Study Objectives: To investigate the therapeutic effect of dimethyl fumarate (DMF, an immunomodulatory agent) on obstructive sleep apnea (OSA), and potential influence of any such effect by selected proinflammatory molecules. Methods: Patients with OSA who deferred positive airway pressure therapy were randomized (2:1) to receive DMF or placebo for 4 months. Participants underwent polysomnography before randomization and at 4 months. Blood was collected monthly. The primary outcome was the mean group change in respiratory disturbance index (δ-RDI). Secondary analyses focused on the association between treatment effect of DMF (on RDI) and expression of plasma cytokines and chemokines, or nuclear factor κ-B (NFκB) signaling molecules in peripheral blood mononuclear cells. Results: N = 65 participants were randomized. N = 50 participants (DMF = 35, placebo = 15) had complete data for final analyses. The mean difference in δ-RDI between groups was 13.3 respiratory events/hour of sleep: -3.1+/-12.9 vs. 10.2+/-13.1 in DMF and placebo groups, respectively (mixed-effects model treatment effect: ß = -0.14, SE = 0.062, p = 0.033). Plasma levels of TNF-α showed only nonsignificant decreases, and IL-10 and IL-13 only nonsignificant increases, in DMF-treated participants compared with placebo. No significant interaction or main effect on RDI for selected cytokines and chemokines was found. Participants with a therapeutic response to DMF did experience significant reductions in intracellular NFκB signaling molecules at 4 months. Overall, DMF was well-tolerated. Conclusions: The immunomodulatory drug DMF partially ameliorates OSA severity. Suppression of systemic inflammation through reduction of NFκB signaling may mediate this effect. Clinical Trials: ClinicalTrials.gov, NCT02438137, https://clinicaltrials.gov/ct2/show/NCT02438137?term=NCT02438137&rank=1.

Sleep and Cognitive Function in Multiple Sclerosis.

STUDY OBJECTIVES: To examine associations between cognitive performance and polysomnographic measures of obstructive sleep apnea in patients with multiple sclerosis (MS). METHODS: Participants underwent a comprehensive MS-specific cognitive testing battery (the Minimal Assessment of Cognitive Function in MS, or MACFIMS) and in-laboratory overnight PSG. RESULTS: In adjusted linear regression models, the oxygen desaturation index (ODI) and minimum oxygen saturation (MinO2) were significantly associated with performance on multiple MACFIMS measures, including the Paced Auditory Serial Addition Test (PASAT; 2-sec and 3-sec versions), which assesses working memory, processing speed, and attention, and on the Brief Visuospatial Memory Test-Revised, a test of delayed visual memory. The respiratory disturbance index (RDI) was also significantly associated with PASAT-3 scores as well as the California Verbal Learning Test-II (CVLT-II) Discriminability Index, a test of verbal memory and response inhibition. Among these associations, apnea severity measures accounted for between 12% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation (as reflected by the total arousal index) and total sleep time also showed significant associations with a component of the CVLT-II that assesses response inhibition, explaining 18% and 27% of the variance in performance. CONCLUSIONS: Among patients with MS, obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function (as reflected by response inhibition), attention, processing speed, and working memory. If sleep disorders degrade these cognitive functions, effective treatment could offer new opportunities to improve cognitive functioning in patients with MS. COMMENTARY: A commentary on this article appears in this issue on page 1489.

The parasomnias: epidemiology, clinical features, and diagnostic approach.

Parasomnias are a group of disorders exclusive to sleep and wake-to-sleep transition that encompass arousals with abnormal motor, behavioral, or sensory experiences. Sensory experiences often involve but are not limited to perceptions, dreamlike hallucinatory experiences, and autonomic symptoms. When accompanied with excessive motoric activity and other complex motor behaviors, these parasomnnias can be disruptive to the patient and bed partners. Motor behaviors may or may not be restricted to bed but can become dangerous when the subject ambulates or is agitated. The behaviors are inappropriate for the time of occurrence but may seem purposeful or goal directed. Most parasomnias are more common in children and decrease in frequency as they get older. Parasomnias have been reported in approximately 4% of the adult population.