Sleep apnea after stroke: A novel target.

Sleep apnea is an independent risk factor for cerebrovascular diseases. Its prevalence in stroke survivors is high and the disorder negatively affects patients' outcomes. Despite the importance of sleep apnea assessment is highlighted also in the current guidelines, a high proportion of patients remain undiagnosed and lose the potential benefit of positive airway pressure treatment. The current paper describes links between sleep apnea and stroke. It focuses on the challenges of the diagnostic and therapeutical process and provides a brief insight into ongoing trials that could help to identify appropriate diagnostic and therapeutic approaches, their timing, and the patient population for whom treatment could be most beneficial.

The Interplay of Dyslipidemia, Oxidative Stress, and Clinical Outcomes in Acute Ischemic Stroke Patients with and without Coronary Artery Disease.

We assessed lipid and lipoprotein profiles, along with oxidative stress (OS) parameters, in patients within the crucial 24 h period following an acute ischemic stroke (AIS), comparing those with and without coronary artery disease (CAD). We aimed to correlate these measures with clinical condition scales (NIHSS, mRS) post-AIS. This study included 27 AIS patients without CAD (AIS group) and 37 AIS patients with CAD (CAD-AIS group). Using polyacrylamide gel electrophoresis (Lipoprint system), we determined plasma LDL and HDL subfractions. Spectrophotometric methods were used to assess plasma antioxidant capacity, lipoperoxides, homocysteine (HC) levels, paraoxonase1, and catalase activities. We also measured urine isoprostanes and the activities of antioxidant enzymes (SOD, GPx) with commercial kits. CAD-AIS patients had notably higher HC levels, while there were no significant differences in lipoprotein subfractions and OS parameters between both groups. In the AIS group, mRS scores showed negative correlations with catalase, GPx activities, and total cholesterol. In the CAD-AIS group, atherogenic lipoproteins (IDLC, LDL2, LDL3-7) exhibited a significant positive correlation with mRS. This study underscores the role of dyslipidemia and OS in the development of AIS and CAD. It emphasizes the complex connections between specific biomarkers and post-stroke clinical outcomes. Our results suggest a significant impact of CAD treatment on lipid profile but not on homocysteine levels. The traditional narrative associating high cholesterol as the ultimate risk factor for cardiovascular diseases needs to be challenged, at least with respect to neurological outcomes. These insights may guide more targeted therapeutic approaches.

Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

INTRODUCTION: Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. METHODS: MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. RESULTS: The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. CONCLUSION: Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

Association between cognitive impairment and the disability in people with multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) may be present in people with multiple sclerosis (PwMS) in different stages of the disease, as well as in PwMS with various degrees of disability. This study aimed to investigate cognitive decline over a period of 12 months and to examine an association between cognition and the disability in PwMS, also over a period of 12 months. METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used, containing the Symbol Digit Modalities Test (SDMT), the Categorical Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test-Revised (BVMT-R). The Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9-HPT) were used to assess the degree of disability. For the analysis of cognitive decline over the period of 12 months, Wilcoxon signed-rank test (paired sample t-test) was used. For the correlation between cognition and disability, Spearman's correlation test was used. RESULTS: We observed statistically meaningful difference only in one measure of cognition (CVLT), not the other two (SDMT and BVMT-R). SDMT significantly correlated with methods assessing the degree of disability in both time points. In the second examination, we observed a correlation between BICAMS and 9-HPT. Similarly, SDMT and BVMT-R also correlated with EDSS. CONCLUSION: To investigate the cognitive decline in PwMS, a longer period of time probably should have been chosen. EDSS is commonly used to monitor disease progression, but it does not include the evaluation of various parameters, such as cognition or upper limb function. Its use with the 9-HPT and cognitive tests may represent a more reliable and comprehensive assessment of a patient's clinical condition.

Lipoprotein Subfractions Associated with Endothelial Function in Previously Healthy Subjects with Newly Diagnosed Sleep Apnea-A Pilot Study.

BACKGROUND: Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects. MATERIAL AND METHODS: We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed. RESULTS: Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI. CONCLUSIONS: In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.

No Difference in Sleep Desaturations Severity between Patients with Wake-Up and Non-Wake-Up Stroke: A PRESS Study Results.

BACKGROUND: Wake-up stroke (WUS) is a certain type of ischemic stroke in which a patient wakes up with a new neurological deficit due to cerebral ischemia. Sleep-disordered breathing is an independent risk factor for stroke, but the role of nocturnal oxygen desaturation in the pathophysiology of WUS is still insufficiently explored. According to several studies, patients with WUS have a significantly more severe sleep apnea syndrome and lower mean blood oxygen saturation. This study aimed to assess the severity of nocturnal desaturations in acute WUS and non-WUS patients using nocturnal pulse oximetry. MATERIAL AND METHODS: The cohort of 225 consecutive patients with neuroimaging-verified acute cerebral ischemia was prospectively enrolled. For further analyses, 213 subjects with known WUS/non-WUS status were selected (111 males and 102 females, average age 70.4 ±12.9, median baseline NIHSS = 5, median baseline mRS = 3). Patients were divided into the WUS group (n = 45) and the non-WUS group (n = 168). Overnight pulse oximetry was performed within 7 days of the stroke onset and data of both of the studied groups were compared. RESULTS: We found oxygen desaturation index (ODI) in the WUS group was 14.5 vs. 16.6 (p = 0.728) in the non-WUS group, basal O2 saturation was 92.2% vs. 92.5% (p = 0.475), average low O2 saturation was 90.3% vs. 89.6% (p = 0.375), minimal O2 saturation was 79.5% vs. 80.6% (p = 0.563), and time with O2 saturation <90% (T90) was 4.4% vs. 4.7% (p = 0.729). CONCLUSIONS: In the studied sample, monitored respiratory parameters including ODI, basal O2 saturation, average low O2 saturation, minimal O2 saturation, and T90 did not significantly differ between groups of WUS and non-WUS patients.

Adherence to positive airway pressure therapy initiated in the early subacute phase of ischemic stroke: a PRESS study follow-up.

BACKGROUND: Sleep-disordered breathing (SDB) is frequent in stroke patients and negatively affects stroke outcomes. Positive airway pressure (PAP) is the standard first-line treatment for patients with moderate-to-severe SDB. Despite a strong link between PAP adherence and therapeutic response, rates of post-stroke PAP adherence remain underexplored. Our study aimed to determine PAP adherence in patients undergoing comprehensive sleep apnea assessment and in-lab PAP titration in the early subacute phase of stroke. METHODS: In-hospital screening pulse oximetry was performed in consecutive patients with imaging-confirmed acute ischemic stroke. Subjects with desaturation index ≥ 15.3/h were selected as PAP candidates, and polysomnography was recommended. In a sleep laboratory setting, subjects underwent a diagnostic night followed by a titration night, and PAP therapy was initiated in subjects with apnea-hypopnea index ≥ 15/h. Adherence to PAP therapy was assessed at a 6-month follow-up visit. RESULTS: Of 225 consecutive patients with acute ischemic stroke, 116 were PAP candidates and 52 were able to undergo polysomnography. PAP therapy was initiated in 35 subjects. At a 6-month follow-up visit, out of 34 stroke survivors, PAP adherence (PAP use of > 4 h per night) was present in 47%. Except for the significantly lower minimal nocturnal O2 saturation determined from the polysomnography (74.6 ± 11.7% vs. 81.8 ± 5.2%, p = 0.025), no other significant difference in characteristics of the groups with PAP adherence and PAP non-adherence was found. CONCLUSIONS: Less than half of the stroke subjects remained adherent to PAP therapy at 6 months post-PAP initiation. Special attention to support adaptation and adherence to PAP treatment is needed in this group of patients.

Impairment of endothelial function in Parkinson's disease.

OBJECTIVE: There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function in patients with PD and matched controls. In PD subjects, we searched for factors contributing to endothelial dysfunction as well. Traditional vascular risk factors, PD characteristics, and PD medication were considered. RESULTS: We prospectively enrolled 41 patients with PD and 41 controls matched for age, sex, body mass index, and vascular risk factors. Endothelial function (EF) was assessed using peripheral arterial tonometry (EndoPAT 2000 device) and expressed as reperfusion hyperemia index (RHI). Clinical characteristics including PD medication were recorded. RHI was non-significantly lower in the PD group than in controls (1.8 ± 0.5 vs. 1.9 ± 0.5, p = 0.478). In PD patients, in linear regression analysis, smoking (beta = -0.453, p = 0.008) and use of dopamine agonists (beta = -0.365, p = 0.030) were significant contributors in a model predicting RHI. Despite non-significant differences in endothelial dysfunction between PD patients and controls, our results suggest an association between smoking, dopamine agonists, and impaired EF in PD patients. The small sample size, as well as the absence of an extended search for traditional and non-traditional vascular risk factors, are the most important factors limiting the interpretation of the current results.

Cognition in Patients with Sleep-Disordered Breathing: Can Obstructive and Central Apneic Pauses Play a Different Role in Cognitive Impairment?

BACKGROUND: There are increasing data linking sleep apnea with cognitive impairment. We aimed to clarify the relationship between sleep-disordered breathing (SDB) and cognition. Detailed attention was assigned to the potential role of central versus obstructive apneic pauses in cognitive impairment. METHODS: Patients with suspected SDB were prospectively enrolled, and a complex sleep study was performed that included overnight polysomnography. A revised version of Addenbrooke's Cognitive Examination (ACE-R) was used to assess cognition, evaluating overall cognition and individual subdomains. RESULTS: A total number of 101 participants were included in the study. In multivariate binary logistic regression analysis, obstructive apnea index ([OAI], 95% CI: 1.009-1.057, p = 0.008) was the only significant contributor to the model predicting attention deficit. The proportion of N1 stage of NREM sleep was the only significant contributor to the model predicting impaired verbal fluency (95% CI: 1.004-1.081, p = 0.029). No significant differences in sleep-related indices were observed in the remaining ACE-R subdomains. CONCLUSION: Except for verbal fluency and attention, we failed to find any significant association of sleep-related indices with the impairment in different cognitive subdomains. Our data suggest that impairment observed in verbal fluency is associated with a higher proportion of shallow NREM sleep, and attention deficit is associated with higher OAI. Obstructive respiratory episodes seem to play a more important role in cognitive impairment when compared to central ones.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. METHODS: The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. RESULTS: OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3-7 and HDL8-10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. CONCLUSION: The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

Cerebral blood flow in stroke patients with sleep apnea: any role of single-night positive airway pressure therapy?

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) is more prevalent in patients with stroke than in the population without a history of stroke. SDB is an independent risk factor for stroke. SDB impairs cerebral circulation by several mechanisms, and therefore possibly contributes to wake-up stroke. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) is a novel technology able to detect cerebral blood flow noninvasively and in real-time, displaying cerebral flow as cerebral flow index (CFI). Positive airway pressure (PAP) is the most effective approach in the treatment of SDB. We aimed to assess if single-night PAP impacts cerebral blood flow in sleep apnea patients after stroke and without a history of stroke. MATERIALS AND METHODS: 11 stroke patients and six controls with sleep apnea were enrolled. Stroke patients underwent overnight pulse oximetry within seven days after stroke. Desaturation index ≥ 15/hour was considered a positive screening. Six weeks after stroke, patients with positive screening underwent overnight polysomnography together with cerebral blood flow monitoring using UT-NIRS (diagnostic night) and also with additional PAP therapy (therapeutic night). RESULTS: The number of respiratory events decreased significantly in the group of stroke patients (apnea-hypopnea index [AHI] from 22.6±9.0 to 9.9±9.9) and controls (AHI from 58.1±14.9 to 7.0±9.7). CFI showed no significant changes between a diagnostic and therapeutic night in both groups. CONCLUSION: Despite the significant reduction of respiratory events, single-night PAP therapy does not improve overall cerebral blood flow, as defined by CFI.

Mood disorders in patients with hypersomnia: comparison of sleep-related breathing disorders versus narcolepsy.

BACKGROUND: Anxiety and depression are common comorbidities of excessive daytime sleepiness (EDS). Sleep-related breathing disorders (SBD) and central disorders of hypersomnolence (like narcolepsy [NA]) are the most frequent causes of EDS. This study aimed to evaluate mood disorders in NA patients compared to the subjects with EDS due to SBD (SBD-EDS). METHODS: In a retrospective analysis, subjects with NA and SBD-EDS were compared. All subjects underwent overnight polysomnography. NA patients underwent also multiple sleep latency test. Epworth sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Becks questionnaire, and Zung depression scale were used to assess EDS, sleep quality, anxiety, and depression, respectively. RESULTS: We enrolled 24 NA and 41 SBD-EDS subjects. Values of PSQI and Zung scale were significantly worse in the SBD-EDS group than in NA patients (8.34±3.84 vs. 6.83±2.25, p=0.04; 46.86±12.69 vs. 40.81±11.27, p=0.03, respectively). Anxiety was significantly more frequent in SBD-EDS subjects compared to NA (63.4% vs. 37.5%, p=0.04). Out of all observed sleep-related indices, PSQI was the only factor, that significantly correlated with the measures of anxiety in both groups (NA: r=0.65, p=0.001; SBD-EDS: r=0.45, p=0.003) and with the measures of depression in NA subjects (r=0.51, p=0.01). In SBD-EDS group, measures of depression significantly correlated with PSQI (r=0.46, p=0.002), oxygen desaturation index (r=0.35, p=0.03), and ESS (r=0.5, p=0.001). CONCLUSION: Compared to NA, our results suggest significantly worse measures of depression and a significantly higher frequency of anxiety in the SBD-EDS population. Measures of anxiety and depression significantly correlated with quality of sleep in both groups.

Cardiac autonomic function in patients with early multiple sclerosis.

PURPOSE: Cardiac autonomic dysfunction has been reported in patients with long-standing multiple sclerosis (MS); however, data in early disease are limited. The present study was aimed at evaluating cardiac autonomic function in patients with early MS in the context of white matter metabolic status, which could potentially affect functions of the autonomic brain centers. METHODS: Cardiac sympathetic and baroreflex cardiovagal responses to the Valsalva maneuver, orthostatic test, and the Stroop test were evaluated in 16 early, treatment-naïve patients with relapsing-remitting MS, and in 14 healthy participants. Proton magnetic resonance spectroscopic imaging (MRSI) of the brain was performed in eight of these MS patients and in eight controls. RESULTS: Valsalva maneuver outcomes were comparable between patients and controls. At baseline, norepinephrine levels were lower (p = 0.027) in MS patients compared to controls. The patients had higher heart rate (p = 0.034) and lower stroke volume (p = 0.008), but similar blood pressure, cardiac output and norepinephrine increments from baseline to 2 min of the orthostatic test compared to controls. MS patients and controls did not differ in responses to the Stroop test. MRSI showed lower total N-acetylaspartate/total creatine (p = 0.038) and higher myo-inositol/total creatine (p = 0.013) in MS lesions compared to non-lesional white matter. CONCLUSION: Our results show normal cardiac sympathetic and baroreflex cardiovagal function in MS patients with relapsing-remitting MS with lesions at the post-acute/early resolving stage. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov under the Identifier: NCT03052595 and complies with the STROBE checklist for cohort, case-control, and cross-sectional studies.

Association of lipoprotein levels with sleep apnea: role of autonomic dysfunction.

Objectives. Although multiple mechanisms, including autonomic dysfunction, seem to link sleep-disordered breathing (SDB) with dyslipidemia in animal studies, the data in clinical studies are limited. The aim of this study was to explore the association of lipoprotein levels with SDB measures in healthy habitual snorers. We supposed that autonomic dysfunction is the linking mechanism.Methods. We enrolled 110 previously healthy subjects with complaints of habitual snoring. To assess SDB, polysomnography was performed. Blood samples for the analysis of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were obtained in a fasting condition after the polysomnography. Baroreflex sensitivity (BRS) was used to assess the autonomic dysfunction.Results. In stepwise multiple linear regression analysis, minimal nocturnal blood oxygen saturation (beta=-0.240, p=0.020) and neck circumference (beta=0.224, p=0.03) were the only significant contributors in model predicting TG. SDB measures were not identified as significant contributors in models predicting TC, LDL, and HDL. We failed to find any significant difference in BRS in SDB subjects when compared according to the presence or absence of hypercholesterolemia/ hypertriglyceridemia. In SDB subjects, the area under the curve in a receiver operating curve to predict hypercholesterolemia and hypertriglyceridemia by BRS was 0.468 (95% CI: 0.328-0.608) and 0.425 (95% CI: 0.304-0.546), respectively.Conclusions. Our results suggest that minimal nocturnal blood oxygen saturation is significant contributor in model predicting TG. No significant decrease in BRS was found in SDB subjects with hypercholesterolemia and hypertriglyceridemia. In SDB subjects, the role of autonomic dys-function in the development of dyslipidemia remains controversial.

Sleep apnea prediction in acute ischemic stroke (SLAPS score): a derivation study.

BACKGROUND: Despite its high prevalence and negative impact, sleep-disordered breathing (SDB) remain commonly underdiagnosed and undertreated in stroke subjects. Multiple stroke comorbidities and risk factors, including obesity, hypertension, diabetes mellitus, ischemic heart disease, atrial fibrillation, and heart failure (H.F.) have been associated with SDB. This study aimed to examine associations of clinical and demographic characteristics with moderate-to-severe SDB (msSDB) in stroke patients and to develop a predictive score. METHODS: Consecutive patients with ischemic stroke were enrolled in an open, prospective study. SDB was assessed using standard polysomnography. Clinical and demographic characteristics, as well as findings from echocardiography, entered the analysis. Multivariate logistic regression models were used to examine the associations with msSDB. Based on the results, an original score to predict msSDB was proposed and tested. RESULTS: 120 patients with acute ischemic stroke (mean age: 64.0 ± 12.2 years, median NIHSS: 4) were included. Body-mass index (BMI), wake-up stroke onset (WUS), and diastolic dysfunction were independently associated with msSDB. A score allocating 1 point for BMI≥25 kg/m2 and <30 kg/m2, 2 points for BMI≥30 kg/m2, 1 point for WUS and 1 point for diastolic dysfunction resulted in an area under the curve of 0.81 (95% CI 0.71-0.90, p<0.001), sensitivity 82.9%, specificity 71.9% to identify stroke patients with msSDB. CONCLUSIONS: BMI, WUS, and diastolic dysfunction were associated with msSDB. A simple score might help to identify acute stroke patients with msSDB, who are usual candidates for positive airway pressure therapy.

Obstructive sleep apnea and hypertension: the role of gut microbiome.

Obstructive sleep apnea is common disorder affecting approximately one quarter of the common population. Prevalence is even higher in a population with increased vascular risk. Obstructive sleep apnea is a significant risk factor for hypertension, with approximately 50% of obstructive sleep apnea patients suffering hypertension. While the relationship between sleep apnea and hypertension has been firmly established, mechanisms linking these disorders are still poorly understood. Importance of sympathetic nervous system and renin-angiotensin-aldosterone system hyperactivity as well as endothelial dysfunction is suspected. There is increasing evidence supporting gut dysbiosis as one of the underlying mechanisms. Current article describes possible mechanisms linking obstructive sleep apnea with the development of hypertension. The role of gut microbiota in this process is discussed more closely.

Heart rate entropy is associated with mortality after intracereberal hemorrhage.

BACKGROUND: Autonomic nervous system changes have been associated with outcome after intracerebral hemorrhage (ICH) previously. We aimed to investigate the association of heart rate entropy (HRE) with mortality after ICH. METHODS: Sample HRE, heart rate variability and baroreflex sensitivity were examined in consecutive ICH patients. Hematoma volume, intraventricular hemorrhage, infratentorial origin, consciousness impairment and age were combined into standard ICH score. RESULTS: In 47 patients suffering ICH (mean age 61 years, median hemorrhage volume 38 mL) the areas under the curve (AUC) for mortality were 0.86, 0.83, 0.76, 0.74, 0.72 and 0.7 for HRE, ICH-score, normalized low frequency powers, low frequency/high frequency powers ratio, normalized high frequency powers and BRS, respectively. HRE and ICH score were associated with mortality independently (adjusted odd ratio (aOR) 0.09, 95% confidence interval (CI) 0.1-0.8, p = .03 and aOR 2.6, CI 1.03-6.6, p = .04). Combining ICH score with HRE into a novel score resulted in an AUC of 0.94, CI 0.88-0.99, p < .001. CONCLUSION: Compared to several autonomic markers HRE seems to bear the largest amount of information on death probability after ICH. Moreover, HRE may predict mortality comparable to ICH score. Combining HRE with ICH score may increase the predictive performance for mortality after ICH.

Pulse oximetric routine examination of sleep apnea in acute stroke (PRESS).

BACKGROUND: Sleep-disordered breathing (SDB) is present in more than 70% of stroke patients. Despite its association with increased morbidity, mortality, and reduced functional outcomes, targeted assessment of SDB in stroke patients, remain controversial. Polysomnography ("gold standard" examination) is a technically demanding and costly test with limited availability. The use of screening questionnaires is limited due to low specificity and sensitivity. Pulse oximetry seems to be a sensible alternative. Our study aimed to assess the feasibility and predictive value of routine pulse oximetric screening for assessment of SDB in patients with acute stroke. METHODS: Patients with acute stroke were enrolled in an open, prospective study. A single-night pulse oximetric assessment was used for SDB screening. Subsequently, polysomnography was performed to confirm SDB. Moderate-to-severe SDB was defined as apnea-hypopnea index ≥15. RESULTS: Out of 420 enrolled patients, refusal to undergo examination was reported in 4 and non-cooperation during the investigation in 21 subjects. The area under the curve in a receiver operating curve to predict moderate-to-severe SDB by desaturation index (DI) was 0.86 (95% CI: 0.76-0.97), and optimal DI cut-off by Youden index was 15.3. Positive pulse oximetric screening (DI ≥ 15.3) had 90.5% sensitivity and 75% specificity to predict moderate-to-severe SDB. CONCLUSIONS: Our results suggest a good adherence of acute stroke patients to the pulse oximetric screening. Pulse oximetry represents a simple, cost-effective, and sensitive examination that might be used in stroke patients as an appropriate tool for further selection for targeted diagnostic and therapeutic processes of SDB in the sleep laboratory.

Neurofilament light chain and MRI volume parameters as markers of neurodegeneration in multiple sclerosis.

BACKGROUND: Neurofilament light chain (NfL) is considered a major marker of neurodegeneration and disease activity. Higher levels of NfL are associated with worse clinical outcomes and increased brain atrophy. In treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS), we aimed to determine the level of NfL, an association between NfL and demographic, clinical and magnetic resonance imaging (MRI) characteristics as well as brain volume parameters. We wanted to confirm that level of NfL is clinically useful as biomarker of neurodegeneration and disease activity. METHODS: 56 treated RRMS patients were enrolled. Plasmatic levels of NfL (pNfL) were measured by SIMOA® technique. Clinical severity of MS was expressed by Expanded Disability Status Scale (EDSS), and volumetric analysis of MRI data was performed using Icobrain software. RESULTS: The mean pNfL level was significantly higher in MS patients than in healthy controls (14.73 ± 6.38 versus 6.67 ± 3.9, p<0.001). In patients, we did not find association between pNfL and MRI activity, number of new T2 lesions, and number of enhancing lesions. Levels of pNfL correlated significantly with atrophy of whole brain volume (Wbv), atrophy of grey matter volume (Gmv), and negatively with Wbv. We found significantly positive correlation between pNfL levels and EDSS. CONCLUSION: Study shows association of pNfL with Wbv, presence of brain atrophy and EDSS, and strong correlation of EDSS with multiple MRI volume parameters. We did not confirm association pNfL with disease activity. Our data suggest that pNfL and MRI volume parameters could be considered as biomarkers of neurodegeneration in MS.

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

BACKGROUND: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis. METHODS: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. RESULTS: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. CONCLUSION: Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03052595 Registered on Feb 14, 2017.