Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD.

PURPOSE: Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare disorders of autonomic regulation with risk for disrupted neurocognitive development. Our aim is to summarize research on neurocognitive outcomes in these conditions, advance understanding of how to best support these individuals throughout development, and facilitate future research. METHODS: We conducted a narrative review of literature on neurocognitive outcomes in CCHS and ROHHAD, supplemented with previously unpublished data from patients with CCHS and ROHHAD at our Center for Autonomic Medicine in Pediatrics (CAMP). RESULTS: Individuals with CCHS and ROHHAD experience a wide range of neurocognitive functioning ranging from above average to below average, but are at particular risk for difficulties with working memory, processing speed, perceptual reasoning, and visuographic skills. An assessment framework emphasizing fluid cognition seems especially appropriate for these conditions. Owing to small cohorts and varied methods of data collection, it has been difficult to identify associations between disease factors (including CCHS PHOX2B genotypes) and cognitive outcomes. However, results suggest that early childhood is a period of particular vulnerability, perhaps due to the disruptive impact of recurrent intermittent hypoxic episodes on brain and cognitive development. CONCLUSION: Neurocognitive monitoring is recommended as a component of routine clinical care in CCHS and ROHHAD as a marker of disease status and to ensure that educational support and disability accommodations are provided as early as possible. Collaborative efforts will be essential to obtain samples needed to enhance our understanding of neurocognitive outcomes in CCHS and ROHHAD.

Neurocognitive monitoring in congenital central hypoventilation syndrome with the NIH Toolbox®.

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy, caused by mutations in the paired-like homeobox gene PHOX2B, which alters control of breathing and autonomic nervous system regulation, necessitating artificial ventilation as life-support. A broad range of neurocognitive performance has been reported in CCHS, including an array of cognitive deficits. We administered the NIH Toolbox® Cognition Battery (NTCB), a novel technology comprised of seven tasks presented via an interactive computer tablet application, to a CCHS cohort and studied its convergent and divergent validity relative to traditional clinical neurocognitive measures. The NTCB was administered to 51 CCHS participants, including a subcohort of 24 who also received traditional clinical neurocognitive testing (Wechsler Intelligence Scales). Age-corrected NTCB scores from the overall sample and subcohort were compared to population norms. Associations between NTCB indices and Wechsler Intelligence scores were studied to determine the convergent and divergent validity of the NTCB. NTCB test results indicated reduced Fluid Cognition, which measures new learning and speeded information processing (p < 0.001), but intact Crystallized Cognition, which measures past learning, in CCHS relative to population norms. Moderate to strong associations (r > 0.60) were found between age-corrected NTCB Fluid and Crystallized indices and comparable Wechsler indices, supporting the convergent and discriminant validity of the NTCB. Results reveal deficits of Fluid Cognition in individuals with CCHS and indicate that the NTCB is a valid and sensitive measure of cognitive outcomes in this population. Our findings suggest that the NTCB may play a useful role in tracking neurocognition in CCHS.

New-generation positional therapy in patients with positional central sleep apnea.

PURPOSE: To evaluate the effect of a sleep position trainer (SPT) in patients with positional central sleep apnea (PCSA). METHODS: A multicentre cohort study was conducted. Patients with symptomatic PCSA were included. Effectiveness, compliance and quality of life were assessed at 1- and 6-month follow-up. RESULTS: Sixteen patients were included. Median AHI dropped from 23.4/h [12.9-31.2] to 11.5/h [7.2-24.5] (p = 0.044) after 1-month SPT therapy and in patients who continued treatment, median AHI further decreased after 6 months to 9.7/h [3.4-27.6] (p = 0.075). Median percentage of supine sleep decreased significantly from 37.6 [17.2-51.8] to 6.7 [0.7-22.8] (p < 0.001), after 1 month, and to 6.8 [0.7-22.1] (p = 0.001), after 6 months. Mean compliance over 1 and 6 months was 78.6 ± 35.3 and 66.0 ± 33.3%, respectively. Epworth Sleepiness Scale at baseline was 9.5 [3.3-11.8] and did not significantly decrease after 1 month (11.0 [3.0-13.0]) and 6 months (4.0 [3.0-10.5]) follow-up. Functional Outcomes of Sleep Questionnaire remained stable within the first month. However, after 6 months, there was a significant improvement compared to baseline values, 15.9 [11.9-18.4] vs. 17.8 [14.3-19.2]; p = 0.030. CONCLUSION: This is the first study on effects of positional therapy with a new-generation smart device in patients with PCSA after 1 and 6 months of follow-up. Results of this study show that the SPT is effective in reducing AHI and central AI, feasible in PCSA, and is associated with symptomatic improvement. While the working mechanism behind this effect remains speculative, the effect is positive and considerable.

Cognitive function and mood at high altitude following acclimatization and use of supplemental oxygen and adaptive servoventilation sleep treatments.

Impairments in cognitive function, mood, and sleep quality occur following ascent to high altitude. Low oxygen (hypoxia) and poor sleep quality are both linked to impaired cognitive performance, but their independent contributions at high altitude remain unknown. Adaptive servoventilation (ASV) improves sleep quality by stabilizing breathing and preventing central apneas without supplemental oxygen. We compared the efficacy of ASV and supplemental oxygen sleep treatments for improving daytime cognitive function and mood in high-altitude visitors (N = 18) during acclimatization to 3,800 m. Each night, subjects were randomly provided with ASV, supplemental oxygen (SpO2 > 95%), or no treatment. Each morning subjects completed a series of cognitive function tests and questionnaires to assess mood and multiple aspects of cognitive performance. We found that both ASV and supplemental oxygen (O2) improved daytime feelings of confusion (ASV: p < 0.01; O2: p < 0.05) and fatigue (ASV: p < 0.01; O2: p < 0.01) but did not improve other measures of cognitive performance at high altitude. However, performance improved on the trail making tests (TMT) A and B (p < 0.001), the balloon analog risk test (p < 0.0001), and the psychomotor vigilance test (p < 0.01) over the course of three days at altitude after controlling for effects of sleep treatments. Compared to sea level, subjects reported higher levels of confusion (p < 0.01) and performed worse on the TMT A (p < 0.05) and the emotion recognition test (p < 0.05) on nights when they received no treatment at high altitude. These results suggest that stabilizing breathing (ASV) or increasing oxygenation (supplemental oxygen) during sleep can reduce feelings of fatigue and confusion, but that daytime hypoxia may play a larger role in other cognitive impairments reported at high altitude. Furthermore, this study provides evidence that some aspects of cognition (executive control, risk inhibition, sustained attention) improve with acclimatization.

Sleepless nights and sleepy days: a qualitative study exploring the experiences of patients with chronic heart failure and newly verified sleep-disordered breathing.

BACKGROUND: Sleep-disordered breathing, including obstructive sleep apnoea and central sleep apnoea, is a common disorder among patients with chronic heart failure. Obstructive sleep apnoea is often treated with continuous positive airway pressure, but central sleep apnoea lacks a clear treatment option. Knowledge of how sleep-disordered breathing is experienced (e.g. difficulties and care needs) and handled (e.g. self-care actions) by the patients is limited, but needed, to provide patient-centred care. AIM: To explore how newly verified sleep-disordered breathing is experienced by patients with chronic heart failure. METHODS: Data were collected through semi-structured interviews and analysed with qualitative content analysis. Seventeen participants (14 men, three women), mean age 60 years (range 41-80) diagnosed with chronic heart failure and objectively verified sleep-disordered breathing (nine obstructive, seven central and one mixed) were strategically selected from heart failure outpatient clinics at two Norwegian university hospitals. RESULTS: Patients with chronic heart failure and newly verified sleep-disordered breathing (SDB) described experiences of poor sleep that had consequences for their daily life and their partners. Different self-care strategies were revealed, but they were based on 'common sense' and were not evidence-based. The awareness of having SDB was varied; for some, it gave an explanation to their trouble while others were surprised by the finding. CONCLUSION: Patients with chronic heart failure and sleep-disordered breathing experienced reduced sleep quality, influencing their daily life. Possible underlying causes of disrupted sleep, such as sleep-disordered breathing, should be identified to establish proper patient-centred treatment strategies. There is a need for new strategies to approach patients with chronic heart failure (i.e. those with central sleep apnoea) who are not subject to continuous positive airway pressure treatment for their sleep-disordered breathing.

[Sleep-disordered breathing in occupational places: from screening to Health and Productivity Management].

BACKGROUND: Sleep-disordered breathing (SDB), represented by sleep apnea, is highly prevalent in the general population and is associated with alcohol intake and obesity. Since SDB is further associated with hypertension, diabetes, and future cardiovascular diseases, as well as accidents and injuries in workplaces, there is a need for complete SDB assessment in workers, including screening and the application of diagnostic and therapeutic approaches. RESULTS: Currently, it appears that SDB assessment is not sufficiently conducted, even among commercial motor vehicle (CMV) drivers, despite CMV drivers with SDB being at a high risk of serious traffic accidents. Based on a discussion conducted in The Study Group for Sleep Disordered Breathing in Work Places, we summarized the current situation in Japan and tried to elucidate the bottleneck of these approaches. Then, the situation in Japan was compared with that in South Korea; Professor Chol Shin substantiated that the situation in South Korea was similar to that in Japan. However, recently published data on CMV drivers in the United States showed that appropriate treatment of SDB reduced the risk of traffic accidents among CMV drivers. This will encourage the implementation of the required processes, from screening to maintenance of treatment. CONCLUSION: We propose a new approach based on "harmonizing work with treatment and prevention" and "Health and Productivity Management (HPM)" as a solution for implementing SDB programs.

[Clinical and neuropsychological characteristics in congenital central hypoventilation syndrome]. / Aspectos clinicos y neuropsicologicos del sindrome de hipoventilacion central congenita.

INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) syndrome is a rare disease caused by mutations in the PHOX2B gene. Patients show a reduced response to hypercapnia and hypoxia accompanied by diffuse disturbances of the autonomic nervous system and occasionaly also disturbances in neuroimaging. A specific neuropsychological profile has not been described in children and adolescents with CCHS. CASE REPORTS: We describe three cases (aged between 4 and 19 years) with different profiles of affectation in cognitive and functionality. These profiles are compared with the features described in the literature about neuropsychology in CCHS. CONCLUSIONS: The profile of functional impairment in the CCHS is variable: in case 1, a severe global developmental delay with autistic features and marked functional involvement is described. In case 2, bilateral atrophy of the hippocampus is associated with involvement in social cognition and in executive functions with moderate functional repercussion. Case 3 shows difficulties in some cognitive executive functions (planning and non-verbal fluency), but without functional repercussion. Neuropsychological assessment can help in the clinical management of these patients by determining and guiding the need for rehabilitation treatments.

TITLE: Aspectos clinicos y neuropsicologicos del sindrome de hipoventilacion central congenita.Introduccion. El sindrome de hipoventilacion central congenita (SHCC) es una enfermedad rara producida por mutaciones en el gen PHOX2B. Los pacientes muestran una reducida respuesta a la hipercapnia e hipoxia acompañada de alteraciones difusas del sistema nervioso autonomo y ocasionalmente alteraciones en neuroimagen. No se ha descrito un perfil neuropsicologico especifico en los niños y adolescentes con SHCC. Casos clinicos. Se presentan tres casos (de edades comprendidas entre 4 y 19 años) con diferente perfil de afectacion cognitiva y funcional. Se comparan los perfiles de los tres casos con los hallazgos descritos en la bibliografia sobre neuropsicologia en el SHCC. Conclusiones. El perfil de afectacion funcional en el SHCC es variable: en el caso 1 se describe un grave retraso global en el desarrollo con rasgos autistas y acusadas implicaciones funcionales. En el caso 2, la atrofia bilateral del hipocampo se asocia a deficit en cognicion social y alteraciones en funciones ejecutivas con moderada repercusion funcional. El caso 3 muestra dificultades en algunas funciones ejecutivas cognitivas (planificacion y fluidez no verbal), pero sin repercusion funcional. La evaluacion neuropsicologica puede ayudar en el manejo clinico de estos pacientes determinando y orientando la necesidad de tratamientos rehabilitadores.

Congenital central hypoventilation syndrome: Broader cognitive deficits revealed by parent controls.

OBJECTIVE: To investigate neurocognitive deficits in children with Congenital Central Hypoventilation Syndrome (CCHS) by comparing them to their parents, since parents comprise a particularly suitable control group matched on disease-extrinsic factors that can influence neurocognitive functioning. We compared CCHS patients to their parents and to population norms, hypothesizing that they would obtain lower intelligence test scores than both groups. We also compared patient-parent differences against patient-normative differences, to determine whether the two analytic approaches would yield different results. METHODS: We administered an intelligence screening, the Shipley-2, to 21 school-aged patients (age 14.2 ± 5.5 years) with PHOX2B mutation-confirmed CCHS and their parents. Patients also received detailed clinical intellectual assessments using the Wechsler scales. RESULTS: CCHS patients scored significantly below parents on Shipley-2 indices of intelligence, vocabulary, and abstraction, with a trend for perceptual reasoning. The CCHS patients scored significantly below population norms on indices of abstraction and perceptual reasoning. Patient-parent differences were significantly larger than patient-normative differences for vocabulary scores. CCHS patients scored significantly below population norms on Wechsler indices of intelligence, perceptual reasoning, working memory, and processing speed. CONCLUSIONS: CCHS may affect a broader range of cognitive abilities than previous research based on comparisons to population norms has indicated. Comparisons of CCHS children to their parents reveal deficits of vocabulary and abstract reasoning which have not been previously identified. A full understanding of the neurocognitive impact of CCHS requires comparisons between patients and other individuals such as friends, parents, or siblings who closely resemble them on disease-extrinsic characteristics.

Neuropsychological profile and social cognition in congenital central hypoventilation syndrome (CCHS): Correlation with neuroimaging in a clinical case.

INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder due to paired-like homeobox gene (PHOX2B) mutations. CCHS patients suffer from dysregulation of the autonomic nervous system characterized by the absence of or extremely reduced response to hypercapnia and hypoxia, with neuropsychological deficits. The aim of this exploratory study is to describe the longitudinal neuropsychological profile and its correlations with magnetic resonance imaging (MRI) of a child with CCHS with a PHOX2B mutation. METHOD: A comprehensive neuropsychological evaluation was conducted serially at age 7 years 4 months and 10 years 3 months, including assessment of intellectual functioning (IQ), motor functioning, perception, attention, executive functions, language, memory, social cognition, academic skills, and psychopathology. Reliable change index (RCI) scores were used to assess changes between assessments. We collected spin lattice relaxation time (T1)-weighted, fluid-attenuated inversion recovery (FLAIR), and spin spin lattice relaxation time (T2)-weighted images from the child at age 10 years 3 months using a 1.5-tesla MRI scanner. RESULTS: IQ, processing speed index (PSI), social cognition (theory of mind and facial emotion recognition), selective attention, naming, academic skills (reading/comprehension), and manual speed with right hand declined in the second evaluation relative to the initial evaluation, while visuoconstructional praxis, receptive vocabulary, working memory, and arithmetic skill improved. The patient showed a remarkable global deterioration in executive functions (planning, task flexibility, behavioral regulation, and metacognition) as revealed by parental report and clinical evaluation. MRI revealed gliosis from the head to tail of the hippocampus and thinning of parahippocampal gyri. CONCLUSIONS: In a clinical case of CCHS, serial evaluation revealed deterioration of executive functions and social cognition over a 3-year interval. These changes corresponded to hippocampal damage as revealed in MRI, which may have affected social cognition through its role in the default mode network. Serial neuropsychological assessment is clinically useful in managing the needs of these patients.

Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children.

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P < .001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P = .001; motor, P = .006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P < .05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.

[Relation between psychological development and respiratory management in patients with congenital central hypoventilation syndrome in Japan].

OBJECTIVE: To evaluate the psychological development of patients with congenital central hypoventilation syndrome (CCHS). METHODS: We performed a questionnaire-based survey of 17 patients with CCHS aged over 7 years and assessed their clinical course, respiratory management, and psychological development. RESULTS: CCHS was present at birth in 15 patients, of which eight presented with respiratory failure with a low Apgar score. Twelve patients required mechanical ventilation with intubation, and five received mask ventilation. All patients with intubation underwent tracheostomy between 1 and 12 months of age (median 5.5 months), and most of them had associated conditions such as Hirschsprung disease. Four of 12 patients with intubation were eventually switched to mask ventilation and one to diaphragm pacing and mask ventilation. The patients undergoing mask ventilation had relatively milder disease severity and had fewer complications than did the patients with intubation. The psychological development of patients who received tracheostomy ranged from normal to severe retardation. Retardation was more likely to be severe in patients who received tracheostomy in late infancy. All patients who received mask ventilation experienced borderline to moderate psychological retardation. This effect could be attributed to poor compliance with mask fitting. CONCLUSION: Our findings suggest that the psychological development of CCHS patients was influenced by hypoxia; tracheostomy and strict respiratory management since the neonatal period were needed for neurological protection.

Design of the remede System Pivotal Trial: A Prospective, Randomized Study in the Use of Respiratory Rhythm Management to Treat Central Sleep Apnea.

BACKGROUND: Central sleep apnea is common in patients with cardiovascular disease and worsens outcomes. There is a lack of established therapies for central sleep apnea, and those available are limited by poor patient adherence and potentially adverse cardiovascular effects, at least in a subset of patients. The remede System (Respicardia, Minnetonka, Minnesota) is a new physiologic treatment that uses transvenous phrenic nerve stimulation to contract the diaphragm, thereby stabilizing gas exchange and restoring normal breathing throughout the sleep period. METHODS: This is a prospective multicenter randomized trial with blinded end points evaluating the safety and efficacy of the remede System. Up to 173 patients with central sleep apnea will be randomized 1:1 to remede System therapy initiated at 1 month after implantation (treatment) or to an implanted remede System that will remain inactive for 6 months (control). Primary efficacy end point is the percentage of patients who experience a reduction in apnea-hypopnea index by a ≥ 50% at 6 months (responder analysis). Primary safety end point is freedom from serious adverse events through 12 months. Secondary end points include sleep-disordered breathing parameters, sleep architecture, Epworth Sleepiness Scale score, and Patient Global Assessment. CONCLUSIONS: This is the 1st randomized controlled trial of the safety and efficacy of the remede System for the treatment of central sleep apnea.

Health-related quality of life in young adults with congenital central hypoventilation syndrome due to PHOX2B mutations: a cross-sectional study.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disease due to PHOX2B mutations. CCHS patients suffer from many autonomic disorders, dominated clinically by defective ventilatory automatisms. From birth, the life of CCHS patients depends on ventilatory support during sleep, involving a high burden of care. Whether or not this impairs the quality of life of these patients during adulthood remains unknown. METHODS: We applied the medical outcome study short form-36 (SF-36) to 12 CCHS patients aged 15-33 (9 women) at the time of their passage from pediatric to adult care. Scores for the SF-36 dimensions were compared to the age- and gender-matched French reference population after transformation into standardized Z-scores. The SF-36 physical component summary score (PCS) and mental component summary score (MCS) were compared to American reference values. RESULTS: Median Z-scores were significantly different from zero for PF (physical functioning, p = 0.020) and GH (general health perception, p = 0.0342) and for PCS (p = 0.020). The other physical dimensions (RP, role limitation due to physical function; BP, bodily pain) and the mental dimensions (VT, vitality; SF, social functioning; RE, role limitation due to emotional function; MH, mental health) and MCS were not altered. CONCLUSIONS: We conclude that, despite the physical constraints imposed by CCHS and its anxiogenic nature, this disease is associated with an impairment of health-related quality of life in young adults that remains moderate. Whatever the underlying explanations, these results convey hope to parents with a child diagnosed with CCHS and for patients themselves.

Sleeping problems in mothers and fathers of patients suffering from congenital central hypoventilation syndrome.

PURPOSE: Advanced medical technology has resulted in an increased survival rate of children suffering from congenital central hypoventilation syndrome. After hospitalization, these technology-dependent patients require special home care for assuring ventilator support and the monitoring of vital parameters mainly during sleep. The daily challenges associated with caring for these children can place primary caregivers under significant stress, especially at night. Our study aimed at investigating how this condition affects mothers and fathers by producing poor sleep quality, high-level diurnal sleepiness, anxiety, and depression. METHODS: The study included parents of 23 subjects with congenital central hypoventilation syndrome and 23 healthy subjects. All parents filled out the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI-II), and Beck Anxiety Inventory (BAI). RESULTS: A comparison between the two groups showed that parents of patients had poorer sleep quality, greater sleepiness, and higher BDI-II scores compared to that of parents of healthy subjects (respectively, PSQI score 6.5 vs 3.8, ESS score 6.2 vs 4.3, BDI-II score 8.4 vs 5.7). Specifically, mothers of patients showed poorer sleep quality and higher BDI-II scores compared to that of mothers of controls (respectively, PSQI score 7.5 vs 3.8, BDI-II score 9.3 vs 5.9), whereas fathers of patients showed greater levels of sleepiness with respect to fathers of healthy children (respectively, ESS score 6.8 vs 4.0). These differences emerged in parents of younger children. CONCLUSIONS: Congenital central hypoventilation syndrome impacts the family with different consequences for mothers and fathers. Indeed, while the patients' sleep is safeguarded, sleeping problems may occur in primary caregivers often associated with other psychological disorders. Specifically, this disease affects sleep quality and mood in the mothers and sleepiness levels in the fathers.

Progressive paranoid psychosis in a 20-year-old with central congenital hypoventilation syndrome.

A 20-year-old man with a history of congenital central hypoventilation syndrome presented with recent-onset psychosis, catatonia, and a diagnosis of schizophrenia. Psychiatric symptoms were resistant to conventional treatment. A fluorodeoxyglucose positron emission tomography scan of the brain obtained during the hospitalization revealed a hypometabolism distribution more consistent with hypoperfusion than with primary central nervous system disease. Increased mechanical ventilation was successfully used to treat the psychiatric symptoms.

The puzzle of apparent life-threatening events in a healthy newborn.

Apneic neonatal seizures can present as apparent life-threatening events. We report a newborn with unexplained episodes of apnea associated with cyanosis and desaturation, starting on the first day postpartum. Biochemical tests were normal. Central nervous system infections as well as abnormalities of upper airways and cardiovascular system were excluded. Brain monitoring using amplitude-integrated electroencephalography (aEEG) was inconclusive. Continuous monitoring using video EEG revealed epileptic seizures originating from the left temporal region as the cause of the apneas. Magnetic resonance imaging (MRI) of the brain showed a developmental malformation of the left frontal and temporal lobes. The patient became seizure free after treatment with antiepileptic medication. This report illustrates that brain monitoring using amplitude-integrated EEG alone could miss focal neonatal seizures. When clinical suspicion of apneic seizures is high in infants with apparent life threatening events, multichannel polygraphic video-EEG monitoring is indicated. Prompt diagnosis and treatment can be life saving.

Relationship between sleep problems and health-related quality of life among pediatric liver transplant recipients.

Among adult liver transplant recipients (LTRs), sleep disturbances and fatigue are common. Sleep problems following pediatric liver transplantation may contribute to daytime fatigue and lower health-related quality of life (HRQOL). The aim of this cross-sectional study was to determine the impact of sleep problems on the HRQOL of pediatric LTRs using validated measures. Participants included 47 LTRs. Mean age of the LTRs was 10.9 ± 4.6 years, and mean time since transplantation was 6.2 ± 3.9 years. The primary indication for transplantation was biliary atresia (51%). According to parent reports, pediatric transplant recipients had symptoms of sleep-disordered breathing, excessive daytime sleepiness, daytime behavior problems, and restless legs; 40.4% of parents and 43.8% of children reported significantly lower total HRQOL for the recipients. Age, time since transplantation, and health status were not significantly related to the quality of life. Hierarchical regression analyses revealed that the sleep-disordered breathing subscale of the Pediatric Sleep Questionnaire accounted for significant variance in parent-proxy reports on the Pediatric Quality of Life (PedsQL) summary scales measuring children's psychosocial health (R(2) = 0.36, P < 0.001), physical health (R(2) = 0.19, P = 0.004), and total HRQOL (R(2) = 0.35, P < 0.001). Also, the sleep-disordered breathing subscale accounted for significant variance in the child self-reported school functioning scale (R(2) = 0.18, P = 0.03). Clinically significant sleep problems were more common among children with low total HRQOL. In conclusion, sleep problems were common in this cohort of pediatric LTRs and predicted significant variance in HRQOL. Prospective larger scale studies are needed to assess factors that contribute to sleep difficulties and low HRQOL in this population. The detection and treatment of significant sleep problems may benefit the HRQOL of pediatric LTRs.

Behavioral correlates of sleep-disordered breathing in older men.

STUDY OBJECTIVES: To examine the association between sleep-disordered breathing (SDB) and subjective measures of daytime sleepiness, sleep quality, and sleep-related quality of life in a large cohort of community-dwelling older men and to determine whether any association remained after adjustment for sleep duration. DESIGN: Cross-sectional. The functional outcome measures of interest were daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep-related symptoms (Pittsburgh Sleep Quality Index, PSQI), and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire, FOSQ). Analysis of variance and adjusted regression analyses examined the association between these outcome measures and SDB severity and actigraphy-determined total sleep time (TST). We then explored whether associations with SDB were confounded by sleep duration by adjusting models for TST. SETTING: Community-based sample in home and research clinic settings. PARTICIPANTS: Two-thousand eight-hundred forty-nine older men from the multicenter Osteoporotic Fractures in Men Study that began in 2000. All participants underwent in-home polysomnography for 1 night and wrist actigraphy for a minimum of 5 consecutive nights. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants were aged 76.4 + 5.5 years and had an apnea-hypopnea index (AHI) of 17.0 + 15.0. AHI and TST were weakly correlated. ESS scores individually were modestly associated with AHI and TST, but the association with AHI was attenuated by adjustment for TST. PSQI and FOSQ scores were largely not associated with measures of SDB severity but were modestly associated with TST. CONCLUSIONS: Daytime sleepiness, nighttime sleep disturbances, and sleep-related quality of life were modestly associated with TST. After adjustment for TST, there was no independent association with SDB severity. These results underscore the potential differences in SDB functional outcomes in older versus young and middle-aged adults.

Subjective daytime sleepiness and daytime function in patients on stable methadone maintenance treatment: possible mechanisms.

INTRODUCTION: Subjects using opioids on a chronic basis have been reported to have a high prevalence of abnormal sleep architecture and central sleep apnea (CSA). The severity of CSA is, in part, related to blood opioid concentration. The aim of this study was to investigate subjective daytime sleepiness and daytime function in patients who are on stable methadone maintenance treatment (MMT) and to assess the possible mechanisms involving abnormal sleep architecture, CSA severity, and blood methadone concentration. METHODS: Fifty patients on MMT and 20 normal control subjects matched for age and body mass index were tested using polysomnography, blood toxicology, Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire (FOSQ), and Beck Depression Inventory (BDI). RESULTS: The patients receiving MMT had significantly worse daytime function, were depressed, and had increased daytime sleepiness when compared with the control subjects (FOSQ 15.47 +/- 3.19 vs 19.4 +/- 0.47, BDI 14.64 +/- 10.58 vs 2.05 +/- 2.46, ESS 7.1 +/- 5 vs 2.05 +/- 1.76; all p values < 0.001). Nevertheless, daytime sleepiness in the patients receiving MMT was, on average, within the normal range (ESS < or = 10). Multiple regression analysis demonstrated that the severity of CSA, blood methadone concentration, and abnormalities in sleep architecture were not significant in predicting the variance of ESS or FOSQ (all p values > 0.05) in these patients receiving MMT. The BDI was the best predictive variable for FOSQ, explaining 16% of the variance (p = 0.004). CONCLUSIONS: Patients on stable MMT have, in general, normal subjective daytime sleepiness but impaired daytime function that partially relates to depression. The changes in sleep architecture, presence of CSA, and blood methadone concentrations do not significantly affect subjective daytime sleepiness and daytime function in these patients.

Quality of life in patients with congestive heart failure and central sleep apnea.

OBJECTIVE: To assess the impact of Cheyne-Stoke respiration-central sleep apnea (CSR-CSA) on quality of life (QOL) in patients with congestive heart failure (CHF). QOL was established using the MLHFQ (Minnesota Living with Heart Failure Questionnaire), and the FOSQ (Functional Outcomes of Sleep Questionnaire). METHODS: We examined 90 patients with CHF. The diagnosis of CSR-CSA was performed by polysomnography. We established a correlation between the apnea-hypopnea index (AHI) and the MLHFQ and FOSQ scores. RESULTS: Five patients were excluded (obstructive sleep apnea). Of the 85 remaining patients, 25 presented CSR-CSA. The mean MLHFQ score was higher in patients with CHF and CSR-CSA (25.8+/-2.97 vs. 16.6+/-2.05; p=0.01), and showed a significant yet moderate correlation with the AHI. A lower mean FOSQ score was obtained for the group of patients with CHF and CSR-CSA (78.4+/-4.31 vs. 88.47+/-2.4; p=0.03), showing weak negative correlation with the AHI. CONCLUSION: According to the MLHFQ scores, it seems that CHF patients with CSR-CSA have a worse QOL than those with CHF alone. Although this could be attributable to a greater impairment of heart function in the former group, the FOSQ scores indicate some influence of their sleep disorder on the impairment of QOL.