Ictal direct current shifts contribute to defining the core ictal focus in epilepsy surgery.

Identifying the minimal and optimal epileptogenic area to resect and cure is the goal of epilepsy surgery. To achieve this, EEG analysis is recognized as the most direct way to detect epileptogenic lesions from spatiotemporal perspectives. Although ictal direct-current shifts (below 1 Hz) and ictal high-frequency oscillations (above 80 Hz) have received increasing attention as good indicators that can add more specific information to the conventionally defined seizure-onset zone, large cohort studies on postoperative outcomes are still lacking. This work aimed to clarify whether this additional information, particularly ictal direct-current shifts which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG data sets recorded with a longer time constant of 10 s using an alternate current amplifier. Sixty-one patients (15 with mesial temporal lobe epilepsy and 46 with neocortical epilepsy) who had undergone invasive presurgical evaluation for medically refractory seizures at five institutes in Japan were retrospectively enrolled in this study. Among intracranially implanted electrodes, the two core electrodes of both ictal direct-current shifts and ictal high-frequency oscillations were independently identified by board-certified clinicians based on unified methods. The occurrence patterns, such as their onset time, duration, and amplitude (power) were evaluated to extract the features of both ictal direct-current shifts and ictal high-frequency oscillations. Additionally, we examined whether the resection ratio of the core electrodes of ictal direct-current shifts and ictal high-frequency oscillations independently correlated with favourable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. Ictal direct-current shifts were detected in the seizure-onset zone more frequently than ictal high-frequency oscillations among both patients (92% versus 71%) and seizures (86% versus 62%). Additionally, ictal direct-current shifts significantly preceded ictal high-frequency oscillations in patients exhibiting both biomarkers, and ictal direct-current shifts occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for ictal direct-current shifts and ictal high-frequency oscillations (39%) at the electrode level, complete resection of the core area of ictal direct-current shifts significantly correlated with favourable outcomes, similar to ictal high-frequency oscillation outcomes. Our results provide a proof of concept that the independent significance of ictal direct-current shifts from ictal high-frequency oscillations should be considered as reliable biomarkers to achieve favourable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of ictal direct-current shifts and ictal high-frequency oscillations may provide new insights into the underlying mechanisms of epilepsy, in which not only neurons but also glial cells may be actively involved via extracellular potassium levels.

[A case of Creutzfeldt-Jakob disease presenting with nonconvulsive status epilepticus in the early stages].

A 64-year-old Japanese woman presented with 1 week of recurrent convulsive seizures. At the time of admission, she was in a coma and did not present with convulsions. Intravenous diazepam administration improved her consciousness, although severe psychomotor excitement developed. Brain MRI demonstrated diffusion restriction in the cerebral cortex of the right hemisphere. Electroencephalography (EEG) showed periodic discharges centered around the parietal regions with right-sided dominance. Nonconvulsive status epilepticus (NCSE) was suspected, and the patient was actively treated with anti-epileptic drugs. She developed akinetic mutism and generalized myoclonus 1 month after admission. Follow-up EEG studies disclosed periodic synchronous discharges. Abnormal prion protein in the cerebral fluid was detected using a real-time quaking-induced conversion assay. The clinical diagnosis in the present case was sporadic Creutzfeldt-Jakob disease (CJD). Seizures as an initial symptom in patients with CJD are relatively rare. Our case suggests that CJD should be considered as a differential diagnosis when a patient presents with refractory NCSE.

Enhanced phase-amplitude coupling of human electrocorticography selectively in the posterior cortical region during rapid eye movement sleep.

The spatiotemporal dynamics of interaction between slow (delta or infraslow) waves and fast (gamma) activities during wakefulness and sleep are yet to be elucidated in human electrocorticography (ECoG). We evaluated phase-amplitude coupling (PAC), which reflects neuronal coding in information processing, using ECoG in 11 patients with intractable focal epilepsy. PAC was observed between slow waves of 0.5-0.6 Hz and gamma activities, not only during light sleep and slow-wave sleep (SWS) but even during wakefulness and rapid eye movement (REM) sleep. While PAC was high over a large region during SWS, it was stronger in the posterior cortical region around the temporoparietal junction than in the frontal cortical region during REM sleep. PAC tended to be higher in the posterior cortical region than in the frontal cortical region even during wakefulness. Our findings suggest that the posterior cortical region has a functional role in REM sleep and may contribute to the maintenance of the dreaming experience.

[Paradoxical effect of levetiracetam on seizure suppression: three cases showing U curve association between dose and effect].

We experienced 3 adult patients with intractable focal epilepsy treated by levetiracetam (LEV) as polytherapy, who showed paradoxical effect (PE). Starting dose of LEV was small (62.5, 250 mg/day) and we gradually increased by less than 250 mg/day, every more than 2 weeks. Within 6 months after LEV was added, LEV of 750 to 1,000 mg/day brought reduction of seizure frequency. Serum concentration of LEV was 13.3 and 14.0 µg/ml. In order to obtain better seizure control, LEV was increased up to 1,000-2,500 mg/day (19.3-35.0 µg/ml) within one year, and they developed PE. They all showed increased habitual seizures, occurring in cluster. Once dose of LEV deceased down to what produced the maximum seizure suppression, all of the patients regained the better seizure control. It is most likely that at least in some patients like present 3 cases, PE of LEV may express U curve association between dose and effect and that it was only delineated by slow titration.

Engagement of cortico-cortical and cortico-subcortical networks in a patient with epileptic spasms: An integrated neurophysiological study.

OBJECTIVE: We aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques. METHODS: Seventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks. RESULTS: Ictal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain. CONCLUSIONS: In this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient. SIGNIFICANCE: Cortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.

Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci.

OBJECTIVE: Using interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci. METHODS: We recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30-50 Hz) activities. RESULTS: SOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200-300 Hz) and ripple (80-150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient. CONCLUSIONS: ECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS. SIGNIFICANCE: IED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.

[A case of refractory generalized atonic seizure and hemifacial spasm with the possible causative pontocerebellar lesion].

The patient was a 35-year-old woman. At the age of 1, she had undergone resection and radiation therapy for neoplastic lesions in the pons. She had a history of gelastic seizures when she was in elementary school, and brief lapses of the neck and truncal muscular tone and convulsions on the left face occurred at the age of 23. After a generalized sharp wave in the ictal electroencephalogram and electromyogram recording, left orbicularis oris muscle contraction was observed followed by sudden cervical extensor atonia. Seizure propagation was noted in the cerebral cortex, left facial nerve nucleus, and brainstem reticular formation. In a simultaneous electroencephalography with functional MRI, the blood oxygen level-dependent effect related to generalized sharp waves was observed in the vicinity of brainstem lesions in addition to a decrease in bilateral frontal and parietal lobes signals, as detected in generalized seizures. These findings suggest that the lesion could be a part of the epilepsy network. Although most epileptic seizures are derived from the cerebral cortex, it is important to note that brainstem lesions are involved in seizures in the patient presented in this study.

Adrenal gland size in obstructive sleep apnea: Morphological assessment of hypothalamic pituitary adrenal axis activity.

OBJECTIVES: The association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA. METHODS: We retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT. RESULTS: Adrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (ß = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width. CONCLUSIONS: Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation.

Sleep is associated with reduction of epileptiform discharges in benign adult familial myoclonus epilepsy.

To clarify the effects of sleep on cortical irritability in benign adult familial myoclonus epilepsy (BAFME), we retrospectively compared epileptiform discharges of electroencephalographies (EEGs) between awake and sleep periods in 5 patients (mean age: 49.6 ±â€¯20.3 years). We also analyzed polysomnography (PSG) of 1 patient. Epileptiform discharges were significantly more frequent during the awake period (1.3 ±â€¯1.2/min) than those during light sleep stages (0.02 ±â€¯0.04/min) (P < 0.05). Regarding PSG analysis, epileptiform discharges were also reduced during all sleep stages compared to those during awake periods. Our study suggests a relative reduction in cortical irritability during sleep in BAFME.

Interictal Slow and High-Frequency Oscillations: Is it an Epileptic Slow or Red Slow?

PURPOSE: We reported the presence of interictal slow and high-frequency oscillations (HFOs) (IIS + HFO) and its temporal change so as to elucidate its clinical usefulness as a surrogate marker of epileptogenic zone in a patient with intractable focal epilepsy. METHODS: We focused on one of the core electrodes of epileptogenicity, and investigated IIS + HFO in the pre- and post-segment of 30 minutes to all the 6 seizures. We adopted interictal slow in duration of 0.33 to 10 seconds, amplitude ≥50 µV and co-occurring with HFOs, and then divided into 5 groups depending on the amplitude of slow wave. RESULTS: Before and after all the 6 seizures, the number of IIS + HFO was 2,890 at one electrode in the core epileptogenic zone. The number of IIS + HFO significantly decreased for 30 minutes after seizures. Furthermore, the number of IIS + HFO with the amplitude of 200 to 399 µV significantly decreased after seizures. CONCLUSIONS: IIS + HFO with the amplitude of 200 to 399 µV was influenced by and decreased after seizures. It may reflect the core part of epileptogenic area as similarly as ictal direct current shifts and ictal HFOs do. IIS + HFO could be called as the term "red slow," which may be useful to delineate at least a part of the epileptogenic zone.

Absence of an Autonomic Sign Assists in the Diagnosis of Extratemporal Lobe Epilepsy Manifesting Generalized Convulsion with Retained Awareness.

We herein report two epilepsy patients with the seizure focus in the non-dominant hemisphere manifesting secondarily generalized convulsion (sGC) with retained awareness characterized by a lack of autonomic signs although GC was complicated by respiratory arrest. Given the semiology and electrophysiological findings, the seizure activity was considered to propagate to the supplementary-motor area and the bilateral primary-motor area, with a clinical manifestation of sGC. The absence of autonomic signs during GC can be a key indicator that the seizure remains in the bilateral suprasylvian area and thus does not involve the region necessary for awareness preservation, which may assist in the diagnosis of this atypical epileptic seizure.

Associations of obstructive sleep apnea with truncal skeletal muscle mass and density.

Sarcopenia has been associated with several conditions relevant to obstructive sleep apnea (OSA), such as aging and obesity, but a direct relationship between OSA and skeletal muscle alterations has not been identified. This study investigated associations between computed tomography (CT)-measured skeletal muscle indices and OSA severity. Analyzed were 334 patients who underwent polysomnography to diagnose OSA. Lumbar skeletal muscles were assessed with CT for the skeletal muscle mass index (SMI, cross-sectional area, normalized for height squared) and skeletal muscle density (SMD, fat infiltration). The apnea-hypopnea index (AHI) correlated positively with the SMI and negatively with SMD in both men and women. The AHI was weakly associated with SMI only in men (ß = 0.11, P = 0.017) after adjustment for the body mass index (BMI) (BMI: ß = 0.61, P < 0.001 in men, ß = 0.65, P < 0.001 in women). The association of AHI and SMD was not significant after adjustment for BMI (BMI: ß = -0.42, P < 0.001 in men, ß = -0.64, P < 0.001 in women). Severity of OSA correlated with increases in skeletal muscle mass rather than muscle depletion and skeletal muscle adiposity. These associations were limited compared with the stronger associations between obesity and skeletal muscles.

Changes in Habitual Sleep Duration after Continuous Positive Airway Pressure for Obstructive Sleep Apnea.

RATIONALE: Obstructive sleep apnea (OSA) can affect not only sleep quality but also sleep duration. Determining the therapeutic effects of continuous positive airway pressure (CPAP) on habitual sleep profiles may shed light on the impact of OSA on sleep duration. OBJECTIVES: To determine whether and how CPAP affects habitual sleep duration in patients with OSA. METHODS: Assessments of sleep duration and sleep quality were performed on 57 newly diagnosed study subjects with OSA (46 men; median age, 63 yr; apnea-hypopnea index, >20 h-1) at baseline and 3 months after initiation of CPAP therapy. Measurements included in-laboratory sleep tests (polysomnography), assessments of habitual sleep (actigraphy with sleep diary for 7 d), and questionnaires on subjective symptoms (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale). RESULTS: Actigraphic night sleep time did not change after CPAP (from 354.0 ± 64.5 min to 353.0 ± 57.0 min; P = 0.87) in the entire group, despite improvements in sleep efficiency and sleep fragmentation. Changes in habitual night sleep duration varied among the participants; habitual night sleep duration increased by 33 minutes (interquartile range, 14-45 min) in 28 participants (sleep time restorers) and decreased by 23 minutes (interquartile range, -48 to -11 min) in 29 participants (sleep time nonrestorers). Subgroup analyses revealed that sleep time restorers were characterized at baseline as having shorter and more fragmented sleep with frequent daytime napping. Nonrestorers were characterized by frequent use of hypnotic drugs and comorbid insomnia, despite longer habitual sleep duration. Actigraphic sleep fragmentation, sleep efficiency, daytime sleepiness, and the frequency of daytime napping were improved after CPAP only in the sleep time restorers, whereas subjective sleep quality was improved in the nonrestorers. Multivariate linear regression showed that shorter baseline night sleep time, baseline daytime napping, and percentage of sleep time under CPAP were positive predictors of the restoration of actigraphic night sleep time, whereas hypnotic use was a negative predictor. CONCLUSIONS: Short-term CPAP did not affect habitual night sleep duration in the group as a whole but induced intraindividual changes in relation to phenotypic features of OSA. Clinical trial registered with www.umin.ac.jp (UMIN000012639).

Relationship between obstructive sleep apnea and endogenous carbon monoxide.

Endogenous carbon monoxide (CO) levels are recognized as a surrogate marker for activity of heme oxygenase-1, which is induced by various factors, including hypoxia and oxidative stress. Few reports have evaluated endogenous CO in patients with obstructive sleep apnea (OSA). Whether OSA more greatly affects exhaled or blood CO is not known. Sixty-nine patients with suspected OSA were prospectively included in this study. Exhaled and blood CO were evaluated at night and morning. Blood and exhaled CO levels were well correlated both at night and morning (r = 0.52, P < 0.0001 and r = 0.61, P < 0.0001, respectively). Although exhaled CO levels both at night and morning significantly correlated with total sleep time with arterial oxygen saturation < 90% (ρ = 0.41, P = 0.0005 and ρ = 0.27, P = 0.024, respectively), blood CO levels did not correlate with any sleep parameter. Seventeen patients with an apnea and hypopnea index (AHI) < 15 (control group) were compared with 52 patients with AHI ≥ 15 (OSA group). Exhaled CO levels at night in the OSA group were significantly higher than in the control group (3.64 ± 1.2 vs. 2.99 ± 0.70 ppm, P < 0.05). Exhaled CO levels at night decreased after 3 mo of continuous positive airway pressure (CPAP) therapy in OSA patients (n = 36; P = 0.016) to become nearly the same level as in the control group (P = 0.21). Blood CO levels did not significantly change after CPAP therapy. Exhaled CO was positively related to hypoxia during sleep in OSA patients, but blood CO was not. Exhaled CO might better correlate with oxidative stress associated with OSA than blood CO. NEW & NOTEWORTHY: Endogenous carbon monoxide (CO) levels are recognized to be a surrogate marker of oxidative stress. No study has evaluated both exhaled and blood CO at the same time in obstructive sleep apnea (OSA) patients. Here we provide evidence that exhaled CO levels positively correlated with hypoxia during sleep in OSA patients, but blood CO levels did not, and that continuous positive airway pressure therapy significantly decreased exhaled CO levels in the OSA group, but did not significantly affect blood CO.

Epileptic network of hypothalamic hamartoma: An EEG-fMRI study.

OBJECTIVE: To investigate the brain networks involved in epileptogenesis/encephalopathy associated with hypothalamic hamartoma (HH) by EEG with functional MRI (EEG-fMRI), and evaluate its efficacy in locating the HH interface in comparison with subtraction ictal SPECT coregistered to MRI (SISCOM). METHODS: Eight HH patients underwent EEG-fMRI. All had gelastic seizures (GS) and 7 developed other seizure types. Using a general linear model, spike-related activation/deactivation was analyzed individually by applying a hemodynamic response function before, at, and after spike onset (time-shift model=-8-+4s). Group analysis was also performed. The sensitivity of EEG-fMRI in identifying the HH interface was compared with SISCOM in HH patients having unilateral hypothalamic attachment. RESULTS: EEG-fMRI revealed activation and/or deactivation in subcortical structures and neocortices in all patients. 6/8 patients showed activation in or around the hypothalamus with the HH interface with time-shift model before spike onset. Group analysis showed common activation in the ipsilateral hypothalamus, brainstem tegmentum, and contralateral cerebellum. Deactivation occurred in the default mode network (DMN) and bilateral hippocampi. Among 5 patients with unilateral hypothalamic attachment, activation in or around the ipsilateral hypothalamus was seen in 3 using EEG-fMRI, whereas hyperperfusion was seen in 1 by SISCOM. SIGNIFICANCE: Group analysis of this preliminary study may suggest that the commonly activated subcortical network is related to generation of GS and that frequent spikes lead to deactivation of the DMN and hippocampi, and eventually to a form of epileptic encephalopathy. Inter-individual variance in neocortex activation explains various seizure types among patients. EEG-fMRI enhances sensitivity in detecting the HH interface compared with SISCOM.

Plasma Incretin Levels and Dipeptidyl Peptidase-4 Activity in Patients with Obstructive Sleep Apnea.

RATIONALE: Incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) activity are important factors in glucose metabolism and have not been investigated in patients with obstructive sleep apnea (OSA). OBJECTIVES: The objective of this study was to investigate the association between OSA and incretin and DPP-4 activity. METHODS: This study included 96 consecutive patients without diabetes who were suspected of having OSA. We investigated the fasting and post-prandial incremental area under the curve (IAUC) of GLP-1, GIP serum levels, and serum DPP-4 activity levels, as well as their association with OSA. Changes in clinical variables were evaluated in the 43 patients who continued continuous positive airway pressure therapy for 3 months. MEASUREMENTS AND MAIN RESULTS: Apnea-hypopnea index was an independent determining factor for fasting GLP-1 (ß = 0.31; P = 0.0019) and IAUC GIP (ß = -0.21; P = 0.037) after adjusting for known confounding factors. In those with very severe OSA (apnea-hypopnea index ≥50), the IAUCs for GLP-1 and GIP were significantly decreased, while fasting GLP-1 and fasting GIP were significantly increased. DPP-4 activity had no relation to OSA parameters or severity, while body mass index was significantly higher in those with severe OSA. Although significant changes in incretin secretion were not seen for 3 months after onset of continuous positive airway pressure therapy, the fasting GLP-1 level in the treated patients with severe OSA decreased to the same level as in untreated patients with normal to moderately severe OSA. CONCLUSIONS: OSA is associated with elevated serum levels of the incretin hormones GLP-1 (fasting) and GIP (post-prandial) in patients without diabetes. A significant association between body mass index and DPP-4, which is said to exist in healthy persons, was not found in the patients with OSA. Fasting GLP-1 in patients without diabetes with OSA may influence fasting glucose levels.

Role of mitochondrial hydrogen peroxide induced by intermittent hypoxia in airway epithelial wound repair in vitro.

The airway epithelium acts as a frontline barrier against various environmental insults and its repair process after airway injury is critical for the lung homeostasis restoration. Recently, the role of intracellular reactive oxygen species (ROS) as transcription-independent damage signaling has been highlighted in the wound repair process. Both conditions of continuous hypoxia and intermittent hypoxia (IH) induce ROS. Although IH is important in clinical settings, the roles of IH-induced ROS in the airway repair process have not been investigated. In this study, we firstly showed that IH induced mitochondrial hydrogen peroxide (H2O2) production and significantly decreased bronchial epithelial cell migration, prevented by catalase treatment in a wound scratch assay. RhoA activity was higher during repair process in the IH condition compared to in the normoxic condition, resulting in the cellular morphological changes shown by immunofluorescence staining: round cells, reduced central stress fiber numbers, pronounced cortical actin filament distributions, and punctate focal adhesions. These phenotypes were replicated by exogenous H2O2 treatment under the normoxic condition. Our findings confirmed the transcription-independent role of IH-induced intracellular ROS in the bronchial epithelial cell repair process and might have significant implications for impaired bronchial epithelial cell regeneration.

Microalbuminuria in Patients with Obstructive Sleep Apnea-Chronic Obstructive Pulmonary Disease Overlap Syndrome.

RATIONALE: Microalbuminuria is said to reflect systemic vascular damage and endothelial dysfunction and is an established indicator of cardiovascular morbidity and mortality. Patients with obstructive sleep apnea (OSA)-chronic obstructive pulmonary disease (COPD) overlap syndrome have worse survival than those with OSA or COPD alone. OBJECTIVES: This study evaluated the association between overlap syndrome and microalbuminuria. METHODS: Data on patients in whom OSA was suspected and who underwent polysomnography between January 2010 and December 2012 were reviewed. Microalbuminuria was defined as an albumin-creatinine ratio between 20 and 299 mg/g in men and between 30 and 299 mg/g in women. MEASUREMENTS AND MAIN RESULTS: Of 740 consecutive patients, 344 were analyzed. Sixty-four were control participants, 248 had OSA only, 4 had COPD only, and 28 had OSA-COPD overlap syndrome. Prevalence of microalbuminuria significantly increased in the order of control, OSA, and overlap syndrome groups (3.1, 12.9, and 32.1%, respectively; P = 0.0006). After adjusting for age and sex, multivariate logistic regression analysis demonstrated a significant association of overlap syndrome with microalbuminuria compared with OSA (odds ratio, 2.61; 95% confidence interval, 1.02-6.38; P = 0.047), but after adjusting for other confounding factors, the difference in the association did not reach significance (odds ratio, 2.54; 95% confidence interval, 0.93-6.72; P = 0.070). Of 63 patients reevaluated after 3 months of continuous positive airway pressure therapy, the logarithm of the albumin-creatinine ratio in 36 patients with good compliance significantly decreased, but there was no difference in patients with poor compliance. CONCLUSIONS: OSA-COPD overlap syndrome was more prevalent than OSA alone in patients with microalbuminuria, but the difference might be mediated by conventional risk factors rather than the addition of COPD itself.

Changes in Energy Metabolism after Continuous Positive Airway Pressure for Obstructive Sleep Apnea.

RATIONALE: Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear. OBJECTIVES: To explore the underlying mechanism by which patients with OSA gain weight after CPAP. METHODS: A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity. MEASUREMENTS AND MAIN RESULTS: BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain. CONCLUSIONS: Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).