Longitudinal Evolution and Plasma Biomarkers for Excessive Daytime Sleepiness in Parkinson's Disease.

BACKGROUND: Excessive daytime sleepiness (EDS) is one of the most frequent nonmotor symptoms in Parkinson's disease (PD); however, the pathogenesis of EDS is unclear, and there is a lack of information on plasma biomarkers for EDS in PD. We aimed to investigate the plasma biomarkers of EDS in a large PD cohort. METHODS: A total of 159 PD patients were included in the prospective cohort study and followed up annually for 3 years. Plasma biomarkers including glial fibrillary acidic protein, amyloid-beta, p-tau181, and neurofilament light chain (NfL), were measured using an ultrasensitive single-molecule array (Simoa) technology at each visit. EDS was evaluated using the Epworth Sleepiness Scale (ESS). RESULTS: The frequency of EDS in PD increased from 15.1% at baseline to 25.0% after 3 years. The mean ESS scores increased from 5.1 (standard deviation [SD]: 4.8) at baseline to 6.1 (SD: 5.5) at the third year of follow-up. At baseline, compared with patients with PD without EDS, those with EDS were more likely to be male, had poorer cognitive performance, and more severe motor and nonmotor symptoms. The adjusted generalized estimating equations models showed that higher plasma NfL levels (OR: 1.047 [1.002-1.094], p = .042) were associated with EDS during follow-ups. The adjusted linear mixed-effects model showed that higher plasma NfL levels (ß 0.097 [0.012-0.183], p = .026) were associated with ESS scores during follow-ups. CONCLUSIONS: Higher plasma NfL levels were associated with EDS in PD, indicating an association between neuro-axonal degeneration and EDS in PD.

Increasing systemic chronic inflammation mediated the association between poor sleep during pregnancy and gestational cardiovascular health.

OBJECTIVES: This study aimed to examine the association between sleep behaviors and cardiovascular health (CVH) during pregnancy and test whether high-sensitivity C-reactive protein (hs-CRP) mediates this association. METHODS: The study included 4204 pregnant women from the Maternal and Infant Health cohort study in Hefei (MIH-Hefei). Information on sleep (chronotype, sleep duration, snoring, daytime sleepiness, and insomnia) was collected through a touch-screen structured questionnaire at 16-23 weeks' gestation. CVH (body mass index, blood pressure, total cholesterol, glucose, and smoking) and hs-CRP were measured at 24-28 weeks' gestation. The role of hs-CRP in the association between sleep and CVH was explored in a mediation analysis, while adjusting for multiple confounding factors. RESULTS: Poor sleep score was significantly associated with poor gestational CVH metrics, including an RR of 0.872 (95% CI, 0.810, 0.938) for having all ideal (vs. any nonideal) CVH metrics; hs-CRP level was significantly associated with poor gestational CVH metrics, including an RR of 0.531 (95% CI, 0.432, 0.609) for having all ideal (vs. any nonideal) CVH metrics. Sleep scores were positively correlated with hs-CRP level (ß, 0.020, 95% CI, 0.006, 0.034). Mediation analysis revealed that the association between sleep and CVH mediated by hs-CRP was 12.31% (indirect effect, -0.0095, 95% CI, -0.0167, -0.0042). CONCLUSIONS: Poor sleep during pregnancy, particularly late chronotype and snoring, may worsen CVH by increasing systemic chronic inflammation.

Mediation effect of platelet indices on the association of daytime nap duration with 10-year ASCVD risk.

Daytime nap is associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the contribution of platelet to the association of daytime nap with ASCVD remains unclear. We analyzed the mediation effect of abnormal platelet indices on the association between daytime nap and 10-year ASCVD risk. The participants of this study were 2445 adults aged 30 to 74 years without ASCVD from the baseline Wuhan residents (n = 3053) of the Wuhan-Zhuhai (WHZH) Cohort Study. Participants completed the questionnaire and physical examination (including blood pressure, height, weight, and blood biochemical indicators). We assessed the association of daytime nap or nocturnal sleep duration with 10-year ASCVD risk and mediation effects of platelet indices on the associations using generalized linear models (GLM). Individuals with daytime nap duration of 30 or 60 min had a 1.37- (95%CI: 1.05, 1.78) or 1.44- (95%CI: 1.17, 1.78) fold increased risk of 10-year ASCVD compared with non-nappers. As compared with non-nappers, MPV values or MPV/PLT ratio mediated 15.29% or 6.18% of the association of daytime nap duration of 30 min with 10-year ADCVD risk as well as 19.21% or 7.61% of the association of daytime nap duration of 60 min with 10-year ADCVD risk (all p < .05). Platelet might partially contribute to increased 10-year ASCVD risk in individuals with daytime nap duration of 30 or 60 min.

Excessive daytime sleepiness in sleep apnea: any role of testosterone or vitamin D?

Recent studies reported association of sleep-disordered breathing (SDB) with testosterone and vitamin D deficiency. Low testosterone and vitamin D levels have been linked to fatigue and excessive daytime sleepiness (EDS). However, the impact of testosterone and vitamin D deficiency on EDS in subjects with SDB remains unknown. The aim of this study was to explore the predictors of EDS in habitual snorers. Role of testosterone, and vitamin D was studied in detail. We also looked for associations between testosterone, vitamin D, and sleep-related indices. We prospectively enrolled 291 consecutive male patients with habitual snoring. Baseline clinical characteristics were recorded on admission. Standard overnight polysomnography was performed to detect SDB, and Epworth Sleepiness Scale (ESS) was used to assess EDS. Blood samples were obtained in a fasting condition in the morning after polysomnography to determine levels of testosterone and vitamin D. Respiratory disturbance index (RDI) (95 % CI: 1.004-1.024, p=0.005) and the use of antihistamines (95 % CI: 1.083-11.901, p=0.037) were the only independent variables significantly associated with EDS in binary logistic regression analysis. In linear multiple regression analysis, body mass index (BMI) (Beta=-0.282, p<0.001) and oxygen desaturation index (Beta=-0.150, p=0.043) were the only independent variables significantly associated with testosterone levels, and BMI (Beta=-0.142, p=0.016) was the only independent variable significantly associated with vitamin D. We failed to find any independent association of testosterone and vitamin D with subjectively rated EDS among habitual snorers. Our results suggest an independent association between the magnitude of nocturnal desaturation and testosterone levels.

Severity of Desaturations Reflects OSA-Related Daytime Sleepiness Better Than AHI.

STUDY OBJECTIVES: The aim was to investigate how the severity of apneas, hypopneas, and related desaturations is associated with obstructive sleep apnea (OSA)-related daytime sleepiness. METHODS: Multiple Sleep Latency Tests and polysomnographic recordings of 362 patients with OSA were retrospectively analyzed and novel diagnostic parameters (eg, obstruction severity and desaturation severity), incorporating severity of apneas, hypopneas, and desaturations, were computed. Conventional statistical analysis and multivariate analyses were utilized to investigate connection of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), conventional hypoxemia parameters, and novel diagnostic parameters with mean daytime sleep latency (MSL). RESULTS: In the whole population, 10% increase in values of desaturation severity (risk ratio = 2.01, P < .001), obstruction severity (risk ratio = 2.18, P < .001) and time below 90% saturation (t90%) (risk ratio = 2.05, P < .001) induced significantly higher risk of having mean daytime sleep latency ≤ 5 minutes compared to 10% increase in AHI (risk ratio = 1.63, P < .05). In severe OSA, desaturation severity had significantly (P < .02) stronger negative correlation (ρ = -.489, P < .001) with mean daytime sleep latency compared to AHI (ρ = -.402, P < 0.001) and ODI (ρ = -.393, P < .001). Based on general regression model, desaturation severity and male sex were the most significant factors predicting daytime sleep latency. CONCLUSIONS: Severity of sleep-related breathing cessations and desaturations is a stronger contributor to daytime sleepiness than AHI or ODI and therefore should be included in the diagnostics and severity assessment of OSA. CITATION: Kainulainen S, Töyräs J, Oksenberg A, Korkalainen H, Sefa S, Kulkas A, Leppänen T. Severity of desaturations reflects OSA-related daytime sleepiness better than AHI. J Clin Sleep Med. 2019;15(8):1135-1142.

Impact of autoimmune comorbidity on fatigue, sleepiness and mood in myasthenia gravis.

BACKGROUND: Disease burden in myasthenia gravis (MG) and in other autoimmune disorders is often determined by common accompanying symptoms such as fatigue, sleepiness and mood disturbances. Many MG patients have a second autoimmune disease, but it is unclear whether autoimmune comorbidities add to the severity of fatigue, sleepiness and mood disturbances. METHODS: We ascertained the presence of autoimmune comorbidities in 69 well-characterized MG patients. To assess fatigue, sleepiness and mood disturbances, we applied the Fatigue Severity Scale (FSS), the Fatigue Impact Scale (FIS), the Epworth Sleepiness Scale (ESS), as well as the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) to all patients. RESULTS: Thirteen MG patients had concomitant autoimmune thyroid disease (AITD), including 1 patient with rheumatoid arthritis as third autoimmune disease. Fatigue (68.1%), excessive daytime sleepiness (14.5%), moderate-severe depression (20.3%) and anxiety (26.1%) were common, but MG patients with and without autoimmune comorbidities had similar FSS, FIS, ESS, BDI and STAI scores. The presence of autoimmune comorbidities was not associated with altered clinical and immunological MG characteristics, but MG patients with autoimmune comorbidities have more often been treated with corticosteroids than patients without autoimmune comorbidities (92.3% vs. 60.7%; p = 0.03). CONCLUSIONS: While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the present study does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity.

Evaluating Transfer of Modafinil Into Human Milk During Lactation: A Case Report.

ABSTRACT: We present a case of a 27-year-old woman in whom idiopathic hypersomnolence was diagnosed in adolescence with adequate symptomatic control on daily dosage of 250 mg of modafinil. She maintained this dosage throughout her pregnancy and during the peripartum period, but did not breastfeed her newborn because of a lack of information on the transmission of modafinil in human breast milk. Samples of her breast milk were obtained at various times over a 24-hour period and analyzed using liquid chromatography mass spectrometry. The relative infant dose was calculated to be 5.3%, below the threshold of concern for drug passage via breast milk. This is the first reported case of modafinil transfer into human breast milk. Given the drug's use in a variety of sleep disorders, the results of this case can be used to advise breastfeeding mothers prescribed modafinil.

Dissociation of Objective and Subjective Daytime Sleepiness and Biomarkers of Systemic Inflammation in Sleep-Disordered Breathing and Systolic Heart Failure.

STUDY OBJECTIVES: Subjective versus objective sleepiness in heart failure (HF) remains understudied; therefore, we sought to examine the association of these measures and interrelationships with biochemical markers. METHODS: Participants with stable systolic HF recruited from a clinic-based program underwent attended polysomnography, Multiple Sleep Latency Testing, questionnaire data collection including Epworth Sleepiness Scale (ESS), and morning phlebotomy for biochemical markers. Linear regression was used to assess the association of mean sleep latency (MSL) and ESS (and other reported outcomes) with adjustment of age or body mass index or left ventricular ejection fraction (LVEF) (beta coefficients, 95% confidence interval) and also with biochemical markers (beta coefficients, 95% confidence interval). RESULTS: The final analytic sample comprised 26 participants: 52 ± 14 years with apnea-hypopnea index (AHI): 34 ± 27, LVEF: 34 ± 12%, MSL: 7 ± 5 minutes and ESS: 7 (5, 10). There was no significant association of MSL and ESS (-0.36, -0.81 to 0.09, P = .11), AHI, or other questionnaire-based outcomes in adjusted analyses. Although statistically significant associations of ESS and biomarkers were not observed, there were associations of MSL and cortisol (µg/dL) [-0.05: -0.08, -0.01, P = .012] and interleukin-6 (pg/mL) [-0.11: -0.18, -0.04, P = .006], which persisted in adjusted models. CONCLUSIONS: In systolic HF, although overall objective sleepiness was observed, this was not associated with subjective sleepiness (ie, a discordance was identified). Differential upregulation of systemic inflammation in objective sleepiness was observed, findings not observed with subjective sleepiness. These findings suggest that underlying mechanistic pathways of inflammation may provide the explanation for dissonance of objective and subjective sleepiness symptoms in HF, thus potentially informing targeted diagnostic and therapeutic approaches. COMMENTARY: A commentary on this article appears in this issue on page 1369.

[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism.

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men.

STUDYOBJECTIVES: Daytime sleep has been associated with increased risk of cardiovascular disease and heart failure (HF), but the mechanisms remain unclear. We have investigated the association between daytime and night-time sleep patterns and cardiovascular risk markers in older adults including cardiac markers and subclinical markers of atherosclerosis (arterial stiffness and carotid intima-media thickness (CIMT)). METHODS: Cross-sectional study of 1722 surviving men aged 71-92 examined in 2010-2012 across 24 British towns from a prospective study initiated in 1978-1980. Participants completed a questionnaire and were invited for a physical examination. Men with a history of heart attack or HF (n=251) were excluded from the analysis. RESULTS: Self-reported daytime sleep duration was associated with higher fasting glucose and insulin levels (p=0.02 and p=0.01, respectively) even after adjustment for age, body mass index, physical activity and social class. Compared with those with no daytime sleep, men with daytime sleep >1 hour, defined as excessive daytime sleepiness (EDS), had a higher risk of raised N-terminal pro-brain natriuretic peptide of ≥400 pg/mL, the diagnostic threshold for HF (OR (95% CI)=1.88 (1.15 to 3.1)), higher mean troponin, reduced lung function (forced expiratory volume in 1 s) and elevated von Willebrand factor, a marker of endothelial dysfunction. However, EDS was unrelated to CIMT and arterial stiffness. By contrast, night-time sleep was only associated with HbA1c (short or long sleep) and arterial stiffness (short sleep). CONCLUSIONS: Daytime sleep duration of >1 hour may be an early indicator of HF.

Objective, but Not Subjective, Sleepiness is Associated With Inflammation in Sleep Apnea.

Study objectives: Objective and subjective measures of excessive daytime sleepiness (EDS) are only weakly associated. No study, however, has examined whether these two measures of EDS differ in terms of underlying mechanisms and prognostic value. Pro-inflammatory cytokines, that is, interleukin-6 (IL-6) appear to promote sleepiness/fatigue, while the stress hormone cortisol promotes vigilance. We hypothesized that objective sleepiness is associated with increased levels of IL-6 and decreased levels of cortisol. Methods: We studied 58 obstructive sleep apnea (OSA) patients with clinical EDS and/or cardiovascular comorbidities who underwent 8-hour in-lab polysomnography for four consecutive nights. Objective and subjective daytime sleepiness were measured by Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS), respectively. Twenty-four-hour profiles of IL-6 and cortisol levels were assessed on the fourth day. Results: The agreement between objective and subjective EDS in OSA patients was fair (kappa = 0.22). Objective EDS (lower MSLT) in OSA patients was associated with significantly elevated 24-hour (ß = -0.34, p = .01), daytime (ß = -0.30, p = .02) and nighttime (ß = -0.38, p < .01) IL-6 levels, and significantly decreased daytime (ß = 0.35, p = .01) cortisol levels. In contrast, subjective EDS (higher ESS/SSS) was not associated with either elevated IL-6 levels or decreased cortisol levels. Conclusions: Our findings suggest that OSA with objective EDS is the more severe phenotype of the disorder associated with low-grade inflammation, a link to cardiometabolic morbidity and mortality. Compared to subjective EDS, objective EDS is a stronger predictor of OSA severity and may be useful in the clinical management of the disorder.

Changes at Mean Platelet Volume and Platelet Distribution Width Levels After Septoplasty and Its Correlation With Epworth Sleepness Scale.

OBJECTIVE: Nasal septum deviation may affect cardiopulmonary system. Those effects can be determined via blood tests and Epworth sleepness scale (ESS). In this study, it was aimed to measure mean platelet volume (MPV) and platelet distribution width (PDW) in patients with nasal septum deviation and to assess changes at their levels after septoplasty. Furthermore, it was purposed to document the correlation between ESS score and MPV, PDW levels. METHODS: Eighty-one patients who underwent septoplasty and 50 healthy controls composed the study group. Epworth sleepness scale was performed to all patients preoperatively and patients were divided into 2 groups in terms of ESS scores. Mean platelet volume and PDW levels were measured preoperatively and it was repeated postoperatively. RESULTS: In Group A (ESS <10), MPV reduced from 8.48 ±â€Š0.38 fl to 8.47 ±â€Š0.36 fl (P >0.05), PDW reduced from 14.56 ±â€Š1.27% to 14.43 ±â€Š1.03% after surgery (P >0.05). On the other hand, in Group B (ESS ≥10), MPV reduced from 9.54 ±â€Š0.68 fl to 8.87 ±â€Š0.44 fl (P <0.001), PDW reduced from 17.15 ±â€Š1.75% to 15.35 ±â€Š1.29% postoperatively (P <0.001). CONCLUSIONS: Statistically significant improvements at MPV and PDW levels after surgery were noticed only at patients with excessive daytime sleepness whose ESS score was 10 or above. According to this, it would be preferable to operate these patients earlier to protect them from systemic effects.

Sleep duration and quality, and risk of gestational diabetes mellitus in pregnant Chinese women.

AIMS: To examine the association between sleep disturbances during pregnancy and risk of gestational diabetes mellitus. METHODS: From 2010 to 2012, 12 506 women in Tianjin, China, were screened using a 50-g 1-h glucose challenge test at 24-28 weeks' gestation. Those with glucose challenge test values of ≥ 7.8 mmol/l were invited to further undergo a 75-g 2-h oral glucose tolerance test. Gestational diabetes was determined according to the International Association of Diabetes and Pregnancy Study Group's definition. Self-reported sleep duration and sleep quality during pregnancy was documented using a modified questionnaire. Logistic regression was used to obtain odds ratios and 95% CIs. RESULTS: A total of 919 women (7.3%) had gestational diabetes. Sleep duration was found to have an approximate J-shaped association with gestational diabetes risk after adjusting for covariates. Compared with a sleep duration of 7-9 h/day (43% of 12 506 women), the adjusted odds ratios for sleep duration of ≥ 9 h/day (55%) and < 7 h/day (2%) for gestational diabetes were 1.21 (95% CI 1.03-1.42) and 1.36 (95% CI 0.87-2.14), respectively. Compared with good sleep quality (37.9% of 12 506 women), the adjusted odds ratios of moderate (59.9%) and poor sleep quality (2.2%) for gestational diabetes were 1.19 (95% CI 1.01-1.41) and 1.61 (95% CI 1.04-2.50), respectively. CONCLUSION: In pregnant Chinese women, poor sleep quality, and shorter and longer duration of sleep during pregnancy were independently associated with an increased risk of gestational diabetes.

Daytime sleepiness is associated with hyperhomocysteinemia in rural area of China: A cross-sectional study.

OBJECTIVE: To ascertain whether sleep abnormalities including daytime sleepiness, snoring, apnea, sleep disruption and sleep duration abnormity are significantly associated with hyperhomocysteinemia (Hhcy). METHODS: A total of 5992 participants were involved in the cross-sectional study. Sleep abnormalities were evaluated by a structured questionnaire. Hhcy was defined as plasma levels of homocysteine ≥15µm/L. RESULTS: After adjustment for age, gender, education, current smoking status and current drinking status, daytime sleepiness (OR, 1.597; 95%CI, 1.210-2.110, P=0.001), sleep duration <6h (OR, 1.273; 95%CI, 1.063-1.524, P=0.009) and sleep duration >8h (OR, 1.205; 95%CI, 1.065-1.364, P=0.003) were significantly associated with Hhcy. While snoring (OR, 1.065; 95%CI, 0.950-1.195, P=0.279), apnea (OR, 1.170; 95%CI, 0.924-1.482, P=0.193), and sleep disruption (OR, 1.065; 95%CI, 0.852-1.331, P=0.580) were not. After further adjustment for body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol, physical activity, diabetes, coronary heart disease, stroke, depression, glomerular filtration rate, hypertension and hyperuricemia, still the increased OR could be found in the daytime sleepiness group (OR, 1.569; 95%CI, 1.145-2.150, P=0.005). However, sleep duration <6h (OR, 1.067; 95%CI, 0.788-1.445, P=0.676) and sleep duration >8h groups (OR, 1.080; 95%CI, 0.883-1.320, P=0.453) were no longer significantly associated with Hhcy. CONCLUSIONS: Daytime sleepiness, but not sleep duration abnormity, snoring, apnea and sleep disruption was an independent risk factor for Hhcy.

Anti-GQ1b antibody syndrome: anti-ganglioside complex reactivity determines clinical spectrum.

BACKGROUND AND PURPOSE: Anti-GQ1b antibodies have been found in patients with Miller Fisher syndrome as well as its related conditions. Our aim was to identify the mechanism by which autoantibodies produce various clinical presentations in 'anti-GQ1b antibody syndrome'. METHODS: Immunoglobulin G antibodies to ganglioside complex (GSC) of GQ1b or GT1a with GM1, GD1a, GD1b or GT1b were tested in sera from patients with anti-GQ1b (n = 708) or anti-GT1a (n = 696) IgG antibodies. Optical densities of the single anti-GQ1b or anti-GT1a antibodies were used as reference (100%), and those of anti-GSC antibodies were expressed in percentages to reference. The relationships between anti-GSC antibody reactivity and the corresponding clinical features were assessed by multivariate logistic regression analysis. RESULTS: Ophthalmoplegia and hypersomnolence were significantly associated with complex-attenuated anti-GQ1b and anti-GT1a antibodies. Ataxia was associated with GD1b- and GT1b-enhanced anti-GQ1b antibodies or GM1-enhanced anti-GT1a antibodies. Bulbar palsy was associated with GT1b-enhanced anti-GQ1b antibodies. Neck weakness was associated with GD1a-enhanced anti-GQ1b antibodies. Arm weakness was associated with GD1b-enhanced anti-GQ1b and GD1a-enhanced anti-GT1a antibodies. Leg weakness was associated with GD1a-enhanced anti-GQ1b and anti-GT1a antibodies. CONCLUSIONS: Differences in fine specificity of anti-GQ1b antibodies are associated with clinical features, possibly due to the different expression of gangliosides in different parts of the nervous system.

IL-1ß and BDNF are associated with improvement in hypersomnia but not insomnia following exercise in major depressive disorder.

Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1ß (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1ß were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.

Sleepiness, inflammation and oxidative stress markers in middle-aged males with obstructive sleep apnea without metabolic syndrome: a cross-sectional study.

BACKGROUND: The simultaneous occurrence of metabolic syndrome and excessive daytime sleepiness are very common in obstructive sleep apnea (OSA) patients. Both conditions, if present in OSA, have been reported to be associated with inflammation and disruption of oxidative stress balance that impair the cardiovascular system. To verify the impact of daytime sleepiness on inflammatory and oxidative stress markers, we evaluated OSA patients without significant metabolic disturbance. METHODS: Thirty-five male subjects without diagnostic criteria for metabolic syndrome (Adult Treatment Panel III) were distributed into a control group (n = 10) (43 ± 10.56 years, apnea-hypopnea index - AHI 2.71 ± 1.48/hour), a non-sleepy OSA group (n = 11) (42.36 ± 9.48 years, AHI 29.48 ± 22.83/hour) and a sleepy OSA group (n = 14) (45.43 ± 10.06 years, AHI 38.20 ± 25.54/hour). Excessive daytime sleepiness was considered when Epworth sleepiness scale score was ≥ 10. Levels of high-sensitivity C-reactive protein, homocysteine and cysteine, and paraoxonase-1 activity and arylesterase activity of paraoxonase-1 were evaluated. RESULTS: Patients with OSA and excessive daytime sleepiness presented increased high-sensitivity C-reactive protein levels even after controlling for confounders. No significant differences were found among the groups in paraoxonase-1 activity nor arylesterase activity of paraoxonase-1. AHI was independently associated and excessive daytime sleepiness tended to have an association with high-sensitivity C-reactive protein. CONCLUSIONS: In the absence of metabolic syndrome, increased inflammatory response was associated with AHI and daytime sleepiness, while OSA was not associated with abnormalities in oxidative stress markers.

Methylphenidate intoxication: somnolence as an uncommon clinical symptom and proof of overdosing by increased serum levels of ritalinic acid.

There is considerable evidence for an increase of methylphenidate (MPH) abuse; thus, physicians might be confronted more frequently with MPH intoxications. Possible symptoms of intoxications with MPH are orofacial, stereotypic movements and tics as well as tachycardia, cardiac arrhythmias, arterial hypertension, hyperthermia, hallucinations and epileptic seizures. Here we report a patient who demonstrated somnolence as an uncommon clinical feature of MPH intoxication. The patient exhibited subnormal MPH serum levels (3 µg/l), however markedly increased serum levels of ritalinic acid (821 µg/l; inactive metabolite of MPH), that finally confirmed the initially suspected MPH intoxication. Due to the short half-life of orally administered MPH (t1/2~3 h) the sole measurement of MPH serum levels might be misleading concerning the proof of MPH overdosing in some cases. Parallel measurement of MPH and ritalinic acid is recommended in cases with suspected MPH intoxication and insufficient anamnestic data.