Branislav Kollár

Sleep disorders in patients with multiple sclerosis.

OBJECTIVE Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). The objective of the study was to assess the relationship between nocturnal polysomnographic (PSG) findings and quality of sleep, fatigue, and increased daytime sleepiness among patients with MS. METHODS Clinical characteristics were collected. Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and International Restless Legs Syndrome Rating Scale were used to assess quality of sleep, fatigue, excessive daytime sleepiness, and the presence of restless legs syndrome (RLS). All patients underwent nocturnal diagnostic PSG examination. RESULTS Fifty patients with MS were enrolled into the study. Age was the only independent variable significantly determining apnea-hypopnea index and desaturation index (DI) (beta = 0.369, p = 0.010, beta 0.301, p = 0.040). PSQI and ESS score were significantly higher in a population with RLS (p = 0.004, p = 0.011). FSS significantly correlated with DI (r = 0.400, p = 0.048). Presence of RLS was the only independent variable significantly determining PSQI and ESS (p = 0.005, p = 0.025). DI and presence of RLS were independent variables determining FSS (p = 0.015, p = 0.024). CONCLUSION Presence of RLS seems to be the main factor determining poor sleep, fatigue, and daytime somnolence. Sleep disordered breathing and its severity influences only fatigue in patients with MS.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients.

Oxidative Stress Markers and Their Dynamic Changes in Patients after Acute Ischemic Stroke

We have focused on determining the range of oxidative stress biomarkers and their dynamic changes in patients at different time points after the acute ischemic stroke (AIS). 82 patients with AIS were involved in our study and were tested: within 24 h from the onset of the attack (group A); at 7-day follow-up (group B); and at 3-month follow-up (group C). 81 gender and age matched volunteers were used as controls. Stroke patients in group A had significantly higher concentrations of plasma lipid peroxides and urine 8-isoprostanes when compared with controls. Protein carbonyls were not significantly different in any experimental group compared to controls. Antioxidant capacity of plasma was increased only in experimental group C. Activities of superoxide dismutase and catalase were elevated in all three experimental AIS groups compared to controls. Paraoxonase activity was reduced in groups A and B and unchanged in group C when compared to controls. Glutathione peroxide activity was elevated only in group A. Our results suggest that free radical damage is the highest within 24 h after the attack. During the next 3 months oxidative damage to lipids caused by free radicals is reduced due to activated antioxidant system.

Association of Sleep Disordered Breathing with Wake-Up Acute Ischemic Stroke: A Full Polysomnographic Study.

STUDY OBJECTIVES Sleep disordered breathing (SDB) is a frequent comorbidity in stroke patients. SDB is one of the independent risk factors for ischemic stroke. Conversely, stroke may contribute to SDB onset or aggravate premorbid SDB. Multiple mechanisms underlying SDB might be responsible for the development of stroke. The aim of this study was to compare polysomnographic, clinical, and laboratory characteristics of wake-up (WUS) and non-wake-up acute ischemic strokes (NWUS). METHODS We prospectively enrolled 88 patients with acute ischemic stroke. Clinical characteristics of the population were recorded on admission, and blood samples were obtained in the fasting condition following morning. SDB was assessed using standard overnight polysomnography in the acute phase of the stroke. RESULTS WUS were present in 16 patients (18.2%), and NWUS in 72 patients (81.8%). In WUS compared to NWUS, we observed significantly higher values of apnea-hypopnea index (24.8 vs. 7.6, p = 0.007), desaturation index ([DI] 26.9 vs. 8.8, p = 0.005), arousal index (22.6 vs. 13.1, p = 0.035), diastolic blood pressure (91.6 mm Hg vs. 85.2 mm Hg, p = 0.039), triglyceride levels ([TG] 1.9 mmol/L vs. 1.2 mmol/L, p = 0.049), and significantly lower levels of D-dimer (0.4 μg/L vs. 0.7 μg/L, p = 0.035). DI (CI: 1.003-1.054, p = 0.031) and TG (CI: 1.002-1.877, p = 0.049) were the only independent variables significantly associated with WUS in binary logistic regression model. CONCLUSIONS Although the design of our study does not prove the causal relationship between SDB and WUS, higher severity of SDB parameters in WUS supports this hypothesis. COMMENTARY A commentary on this article appears in this issue on page 467.

Genetic aspects of vitamin D receptor and metabolism in relation to the risk of multiple sclerosis.

Recent findings suggest that polymorphisms in vitamin D pathway genes are candidates for association with multiple sclerosis susceptibility. It has been now well demonstrated that vitamin D has immunomodulatory functions that may be favorable for reduction of multiple sclerosis risk. Current research has been focused on identification of new variants of genes involved in vitamin D pathway, namely in vitamin D receptor and enzymes of vitamin D metabolism. These variants have been intensively studied as possible genetic predictors of both vitamin D levels and the risk of multiple sclerosis. Considering the findings available up-to-date, we may recognize two groups of genetic variants. The first group of genes was found to predict vitamin D levels but not the risk of multiple sclerosis. The second group of genetic variants is represented by promising genes predicting vitamin D levels as well as the risk of multiple sclerosis. A strong association with increased risk of the disease has been observed for a rare variant in the CYP27B1 gene encoding a vitamin D-activating enzyme. Observed interaction between genetic and epidemiological findings brings the rationale for supplementation trials of vitamin D. Although promising effects of vitamin D supplementation have emerged, the results obtained so far are inconclusive and the real therapeutic significance of vitamin D supplementation remains to be elucidated.

Characteristics of Sleep-Disordered Breathing in Etiologic Subtypes of Minor-to-Moderate Acute Ischemic Stroke

BACKGROUND Sleep-disordered breathing (SDB) is frequent in stroke patients. A strong association has been suggested between SDB and atrial fibrillation (AF). In this study, we evaluated the characteristics of SDB in etiologic subtypes of acute ischemic stroke. We also investigated the relationship between SDB and AF in acute ischemic stroke. METHODS We prospectively enrolled 72 patients with minor-to-moderate acute ischemic stroke. Clinical and laboratory characteristics of population were recorded on admission. SDB was assessed using standard polysomnography within 7 days after stroke onset. RESULTS Apnea-hypopnea index (AHI) in small-vessel strokes was significantly lower than that in large-artery atherosclerosis strokes (P = .031), cardioembolic strokes (P = .011), and strokes of other or unknown etiology (.008). Desaturation index (DI) in small-vessel strokes was significantly lower than that in cardioembolic strokes and in large-artery strokes (P = .008, P = .035). Arousal index (AI) in large-artery strokes was significantly higher than that in small-vessel strokes (P = .013), cardioembolic strokes (P = .007), and strokes of other or unknown etiology (.027). In a multivariate regression model were age (odds ratio [OR], 1.083; 95% confidence interval [CI], 1.022-1.148; P = .007) and DI (OR, 1.037; 95% CI, 1.004-1.071; P = .026) the only significant variables independently associated with AF. CONCLUSIONS We observed higher AHI, DI, and AI in large-artery strokes that may relate to more severe neurologic deficit in this subgroup. Age and DI were the only independent variables significantly associated with AF in acute ischemic stroke. Higher AHI and DI in cardioembolic strokes may thus mirror more frequent premorbid presence of SDB in patients with AF.

Causes of Excessive Daytime Sleepiness in Patients with Acute Stroke—A Polysomnographic Study

BACKGROUND Sleep disorders are common in stroke patients. Sleep-disordered breathing (SDB), which is present in up to 72% of stroke patients, is the most frequent cause of excessive daytime sleepiness (EDS) in common population. The aim of this study was to assess the frequency of EDS in stroke patients and to analyze the impact of SDB, stroke severity, and location of stroke on EDS in the acute phase of stroke. METHODS We enrolled 102 patients with the clinical diagnosis of acute stroke. Baseline clinical characteristics were recorded on admission. An Epworth sleepiness scale score higher than 9 was considered as EDS. To detect SDB, we performed standard overnight polysomnography within 4 ± 2 days after the stroke onset. RESULTS EDS was present in 21 patients (20.6%). In a population with EDS, we found a significantly higher number of obstructive apneic pauses, central apneic pauses, as well as significantly higher values of respiratory disturbance index (RDI), RDI during nonrapid eye movement sleep, desaturation index, and significant decrease of REM sleep duration. RDI (odds ratio [OR], 1.031; 95% confidence interval [CI], 1.007-1.056; P = .01) and duration of REM sleep (OR, .922; 95% CI, .853-.997; P = .042) were the only independent variables significantly associated with EDS in a binary multivariate regression model. CONCLUSION SDB is a common, significant, and treatable cause of EDS in acute stroke patients. We suppose that examination in sleep laboratories is reasonable in all stroke patients with EDS, although the impact of SDB therapy on EDS and overall outcome in acute stroke remains unknown.

Clinical accuracy of the distinction between Alzheimer's disease and frontotemporal lobar degeneration

Alzheimers disease (AD) is the most common cause of dementia. Frontotemporal lobar degeneration (FTLD), although less prevalent overall, is almost as common as AD in patients under the age of 65. AD and FTLD are histopathologically distinct, with AD being characterised by extracellular amyloid plaques and intraneuronal neurofibrillary tangles, and FTLD by the presence of non-AD histological pathology, most commonly either tau-positive inclusions or ubiquitin-positive or TDP 43 positive inclusions. Clinically, AD and FTLD may occur with overlapping symptoms, especially in the early stages of the disease. In the case of Alzheimers disease, it is represented by isolated decline of recent episodic memory; later on, by the impairment of time and space orientation, whereby the alteration of social behaviour and amnesic aphasia occur predominantly in the advanced phases of the disease. Frontotemporal lobar degeneration is demonstrated in three clinical subunits: 1) The behavioural-dysexecutive variant of FTLD (frontotemporal dementia, the frontal variant of FTLD, {fvFTLD}), 2) Progressive non-fluent aphasia, 3) Semantic dementia (SD) with the profound impairment of social conduct (fvFTLD) or with severe speech impairment (PNFA, SD). Considering the different clinical symptomatology with FTLD diagnostics, it is necessary to use different psychometric tests than in the case of Alzheimers disease. Therapy and the degree of dependence of the affected person are also different. All three diseases within the FTLD category, mainly the behavioural-dysexecutive variant, require a higher level of nursing care on the part of other persons or institutions in comparison with Alzheimers disease. The goal of our publication is to point to the differences in clinical manifestation and the findings of auxiliary examinations that are helpful in the clinical accuracy of the distinction between these two types of dementia (Tab. 1, Fig. 3, Ref. 18).

Carotid intima-media thickness is not associated with homocysteine and vitamin D levels in obstructive sleep apnea

Abstract Obstructive sleep apnea syndrome (OSA) is associated with increased vascular morbidity. Accelerated atherosclerosis might be one of the most important mechanisms linking OSA with the development of vascular disorders. Homocysteine (HCY) and vitamin D has been associated with atherogenesis. The aim of this study was to assess a possible association between the levels of HCY and vitamin D and the carotid intima-media thickness (cIMT), which is a known marker for subclinical atherosclerosis in patients with OSA. We prospectively enrolled 110 patients with the history of snoring, who underwent standard overnight polysomnography. Clinical characteristics of the population were recorded on admission and blood samples were obtained in the fasting condition following morning. Extracranial cIMT measurements were performed according to the standardized scanning protocol. A significant correlation was found between cIMT and apnea-hypopnea index (r = .276, p = .006), age (r = .486, p < .001), diabetes mellitus (r = .377, p < .001), coronary artery disease (r = .274, p = .006) and history of stroke (r = .251, p = .012). We failed to find any significant correlation between cIMT and the levels of HCY (r = .036, p = .724) or vitamin D (r = .027, p = .800). In conclusion, our data suggest that the association of cIMT with the severity of OSA can be influenced by multiple metabolic consequences of OSA including traditional and non-traditional risk factors. HCY and vitamin D do not seem to play a superior role in this process.

Solitary Epileptic Seizures in the Clinical Practice

An epileptic seizure may be conceptualized as a paroxysmal pathological process in the brain of a heterogeneous etiology with heteromorphic clinical and electrophysiological manifestation.The cases of epileptic seizures are classified according to The International Classification of Epileptic Seizures (ICES) published for the first time by The International League Against Epilepsy (ILAE) in 1970 and revised in 1981 (Commission on Classification and Terminology of the International League Against Epilepsy, 1981). This classification is a clinical one related to semiology of the seizures not to their etiology. Therefore it is necessary to exclude an acutely occurring cause responsible for occurrence of the seizure. In such cases we talk about the so-called acute symptomatic seizures. The underlying cause may be structural (e.g. head trauma), metabolic, toxic (e.g. alcohol), or an acute CNS infection, etc.. The most frequent acute symptomatic seizures are the febrile seizures. In fact, the acute symptomatic seizures occur more frequently than epilepsy (“unprovoked” seizures). The risk of occurrence during one’s life is very high approximately 5% in males and 2.5% in females. If the acutely occurring cause has been withdrawn or cured without a residuum in the form of a brain lesion, the seizures do not recur (Dasheiff, 1987; Fromm, 1987). The antiepileptic medication is necessary for suppressing the seizures in the acute stage but usually there is no need for treatment continuation after the complete cure of the underlying disease. If the acutely occurring cause was not responsible for epileptic seizure we talk about a so-called unprovoked seizure. If the unprovoked epileptic seizure occurs in relation to a preceding neurological insult, the disorders is regarded as secondary to this insult; we call it the late symptomatic epileptic seizure or late symptomatic epilepsy in case of seizure recurrence. A general principle of treatment for the symptomatic (secondary) epileptic seizures has been a primary effort for resolution of the underlying disease that is the etiological factor responsible for the seizures. Given that it is impossible, the antiepileptic treatment in accordance with the treatment guidelines for individual seizure types (together with adherence to right living, behavioural precautions and concomitant solutions of the social and psychological issues) is indicated (Hovorka et al. 2004a; Hovorka et al. 2004b; Oslejskova, 2007). Approximately 5% of the population experiences one unprovoked epileptic seizure in the lifetime (Forsgren et al., 1996; Hauser et al. 1993). The febrile seizure before the age of 5 occurs in approximately 5% of population (Hauser et al. 1996). Only about 25% of people experiencing the first unprovoked seizure see the doctor and nearly always the seizure is a generalized tonic-clonic one. Most of the people have no