Brain dysfunction in tubular and tubulointerstitial kidney diseases.

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research.

Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges.

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system.

Association between stroke occurrence and changes in atmospheric circulation.

BACKGROUND: The impact of weather on morbidity from stroke has been analysed in previous studies. As the risk of stroke was mostly associated with changing weather, the changes in the daily stroke occurrence may be associated with changes in atmospheric circulation. The aim of our study was to detect and evaluate the association between daily numbers of ischaemic strokes (ISs) and haemorrhagic strokes (HSs) and the teleconnection pattern. METHODS: The study was performed in Kaunas, Lithuania, from 2000 to 2010. The daily numbers of ISs, subarachnoid haemorrhages (SAHs), and intracerebral haemorrhages (ICHs) were obtained from the Kaunas Stroke Register. We evaluated the association between these types of stroke and the teleconnection pattern by applying Poisson regression and adjusting for the linear trend, month, and other weather variables. RESULTS: During the study period, we analysed 4038 cases (2226 men and 1812 women) of stroke. Of these, 3245 (80.4%) cases were ISs, 533 (13.2%) cases were ICHs, and 260 (6.4%) cases were SAHs. An increased risk of SAH was associated with a change in mean daily atmospheric pressure over 3.9 hPa (RR = 1.49, 95% CI 1.14-1.96), and a stronger El Niño event had a protective effect against SAHs (RR = 0.34, 95% CI 0.16-0.69). The risk of HS was positively associated with East Atlantic/West Russia indices (RR = 1.13, 95% CI 1.04-1.23). The risk of IS was negatively associated with the Arctic Oscillation index on the same day and on the previous day (RR = 0.97, p < 0.033). During November-March, the risk of HS was associated with a positive North Atlantic Oscillation (NAO) (RR = 1.29, 95% CI 1.03-1.62), and the risk of IS was negatively associated with the NAO index (RR = 0.92, 95% CI 0.85-0.99). CONCLUSIONS: The results of our study provide new evidence that the North Atlantic Oscillation, Arctic Oscillation, East Atlantic/West Russia, and El Niño-Southern Oscillation pattern may affect the risk of stroke. The impact of these teleconnections is not identical for various types of stroke. Emergency services should be aware that specific weather conditions are more likely to prompt calls for more severe strokes.

Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke.

BACKGROUND: Emotional disturbances, such as anxiety and depression are common after acute ischemic stroke (AIS). Individual variation in emotional outcome is strongly influenced by genetic factors. One of pituitary axis, is the hypothalamic-pituitary-thyroid axis, a critical regulator of post-stroke recovery, suggesting that allelic variants in thyroid hormone (TH) signaling regulation can influence stroke outcome. AIM: To determine associations between AIS emotional outcome and allelic variants of the TH metabolizing enzymes 1-3 type deiodinase (DIO1-3) and the membrane transporting organic anion polypeptide 1C1 (OATP1C1). METHODS: Eligible AIS patients from Lithuania (n=168) were genotyped for ten DIO1-3 and OATP1C1 single nucleotide polymorphisms (SNP): DIO1 rs12095080-A/G, rs11206244-C/T, and rs2235544-A/C; DIO2 rs225014-T/C and rs225015-G/A; DIO3 rs945006-T/G; OATP1C1 rs974453-G/A, rs10444412-T/C, rs10770704-C/T, and rs1515777-A/G. Emotional outcome was evaluated using the Hospital Anxiety and Depression Scale at discharge from the neurology department after experienced index AIS. RESULTS: After adjustment for potential confounders, the major allelic (wild-type) DIO1-rs12095080 genotype (AA) was associated with higher odds ratio of anxiety symptoms (OR = 5.16; 95% CI: 1.04-25.58; p = 0.045), conversely, DIO1-rs11206244 wild-type genotype (CC) and wild-type OATP1C1-rs1515777 allele containing the genotypes (AA + AG) were associated with lower odds ratio of symptoms of anxiety (OR = 0.37; 95% CI: 0.14-0.96; p = 0.041 and OR = 0.30; 95% CI: 0.12-0.76; p = 0.011, respectively). Wild-type OATP1C1-rs974453 genotype (GG) was associated with higher odds ratio of symptoms of depression (OR = 2.73; 95% CI: 1.04-7.12; p = 0.041). CONCLUSION: Allelic variants in thyroid axis genes may predict emotional outcomes of AIS.

Cerebrospinal fluids from Alzheimer's disease patients exhibit neurotoxic effects on neuronal cell cultures.

A growing number of studies suggest amyloid-ß and tau present in cerebrospinal fluid (CSF) and blood as putative biomarkers for Alzheimer's disease (AD). However, there is a question whether these compounds present in patients' bodily fluids can directly cause neurotoxic effects. We investigated effects of AD and other dementia (OD) patients' blood serum and CSF on viability of cells in primary cerebellar granule cell cultures. Overall, 59 individuals participated in the study from whom 55 samples of biological fluids were taken. Participants were classified into early (E-AD) and middle (M-AD) stages of AD, cognitively healthy control (HC) and OD groups. We found that concentrations of total and phosphorylated tau were higher in CSF from AD patients, while amyloid-ß42 and amyloid-ß40 in the serum was lower compared to HC. The most cytotoxic effects were induced by CSFs from M-AD patients which caused neuronal necrosis and suppressed microglial proliferation, whereas CSFs from the groups of other patients did not kill neurons. Serum and CSF from the E-AD group caused a reduction of neuronal numbers in cultures. There were no significant differences in levels of CSF biomarkers between the AD groups although both tau species in CSFs from M-AD patients were found to be significantly elevated compared to HC. Our data suggest that biological fluids from E-AD induce neuronal loss, whereas effects of CSF on the reduction in neuronal viability can serve as an indicator of M-AD and may be associated with extracellular tau.

Transcranial Ultrasonographic Image Analysis System for Decision Support in Parkinson Disease.

OBJECTIVES: Transcranial ultrasonography (US) is a relatively new neuroimaging modality proposed for early diagnostics of Parkinson disease (PD). The main limitation of transcranial US image-based diagnostics is a high degree of subjectivity caused by low quality of the transcranial images. The article presents a developed image analysis system and evaluates the potential of automated image analysis on transcranial US. METHODS: The system consists of algorithms for the segmentation and assessment of informative brain regions (midbrain and substantia nigra) and a decision support subsystem, which is equipped with 64 classification algorithms. Transcranial US images of 191 participants (118 patients with a clinical PD diagnosis and 73 healthy control participants) were analyzed. RESULTS: The diagnostic sensitivity and specificity achieved by the proposed system were 85% and 75%, respectively. CONCLUSIONS: Digital transcranial US image analysis is challenging, and the application of a such system as the sole instrument for decisions in clinical practice remains inconclusive. However, the proposed system could be used as a supplementary tool for automated assessment of US parameters for decision support in PD diagnostics and to reduce observer variability.

Development of the Lithuanian Version of Sniffin' Sticks 12 Odor Identification Test.

Background: Evaluation of smell function is essential especially in cases of gradual deterioration, e.g., in neurodegenerative diseases, where rates of unawareness of the disorder are high and the importance of screening for olfactory dysfunction is increasing. To date, none of the tests for evaluation of olfactory dysfunction has been validated in Lithuania. The aim of the study was to develop a Lithuanian version of Sniffin' Sticks 12 (SS12) odor identification test. Materials and Methods: The study was performed in 4 stages. The first stage included translation and back-translation from German, pilot group testing and language adaptation of the original SS12 test. In the second stage a survey group of 99 subjects was questioned for familiarity with the descriptors, used in the original version of the test. In the third stage after replacement of the least familiar distracters, a modified version of SS12 was created. Original and modified versions of SS12 were tested on 112 and 119 healthy subjects accordingly. The fourth stage of the study proved necessary as neither of the two SS12 versions turned out to be valid. After another round of replacement of the misleading distracters the second modified version of SS12 was created and it was tested on 115 healthy subjects. Results: Unsatisfactory correct identification rates of less than 75 percent in the same one item (lemon) were observed using both original and modified SS12 versions. With the second modification of distracters of SS12, identification of lemon increased significantly and overcame 75 percent. The decrease of SS12 scores in relation to age was ascertained in the study sample. Gender and smoking status did not prove to be independent predictors of SS12 scores in multiple linear regression analysis. Conclusion: The study presents an olfactory testing tool, which is adapted and modified culturally for use in the Lithuanian population.

Prevalence and burden of headache disorders in Lithuania and their public-health and policy implications: a population-based study within the Eurolight Project.

BACKGROUND: The Eurolight project assessed the impact of headache disorders in ten EU countries, using the same structured questionnaire but varying sampling methods. In Lithuania, sample selection employed methods in line with consensus recommendations for population-based burden-of-headache studies. METHODS: The survey was cross-sectional. We identified, from the Residents' Register Service, a sample of inhabitants of Kaunas city and surrounding Kaunas region reflecting age (in the range 18-65 years), gender and rural/urban distributions of Lithuania. Medical students called unannounced at their homes and conducted face-to-face interviews employing a structured questionnaire. RESULTS: Of 1137 people in the pre-identified sample, 573 (male 237 [41.4%], female 336 [58.6%]; mean age 40.9 ± 13.8 years) completed interviews (participation proportion: 50.4%). Gender-adjusted 1-year prevalences were: any headache 74.7%; migraine 18.8%; tension-type headache (TTH) 42.2%; all headache on ≥15 days/month 8.6%; probable medication-overuse headache (pMOH) 3.2%. Migraine (OR: 3.6) and pMOH (OR: 2.9) were associated with female gender. All headache types except TTH were associated with significantly diminished quality of life. Migraine caused a mean 4.5% loss in paid worktime per affected male and 3.5% per affected female. Lost per-person times due to TTH were much less, but to pMOH and other headache on ≥15 days/month much higher. Among the entire workforce, lost productivity to migraine was estimated at 0.7%, to TTH 0.3% and to pMOH or other headache on ≥15 days/month 0.5%. The total of 1.5% may translate directly into lost GDP. Alternative calculations based on headache yesterday (with little recall error) produced, for all headache, a corroborating 1.7%. Similar losses from household work would also drain the nation's economy. Our findings were comparable to those from earlier studies using similar methods in Russia and Georgia. CONCLUSIONS: The multiple burdens from headache in Lithuania indicate substantial ill-health and unmet need for health care. The heavy burdens on individuals are matched by heavy economic burden. Of particular concern is the high prevalence of headache on ≥15 days/month, seen also in Russia and Georgia. Health policy in Lithuania must heed WHO's advice that effective treatment of headache, clearly desirable for its health benefits, is also expected to be cost-saving.

Evaluation of clinical teaching quality in competency-based residency training in Lithuania.

BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into the competency-based medical education curriculum (CBME). In 2015, we implemented the validated EFFECT questionnaire together with the EFFECT-System for quality assessment of clinical teaching in residency training. The aim of this study was to investigate the influence of characteristics of the resident (year of training) and clinical teacher (gender, age, and type of academic position) on teaching quality, as well as to assess areas for teaching quality improvement. MATERIALS AND METHODS: Residents from 7 different residency study programs filled out 333 EFFECT questionnaires evaluating 146 clinical teachers. We received 143 self-evaluations of clinical teachers using the same questionnaire. Items were scored on a 6-point Likert scale. Main outcome measures were residents' mean overall (MOS), mean subdomain (MSS) and clinical teachers' self-evaluation scores. The overall comparisons of MOS and MSS across study groups and subgroups were done using Student's t test and ANOVA for trend. The intraclass correlation coefficient (ICC) was calculated in order to see how residents' evaluations match with self-evaluations for every particular teacher. To indicate areas for quality improvement items were analyzed subtracting their mean score from the respective (sub)domain score. RESULTS: MOS for domains of "role modeling", "task allocation", "feedback", "teaching methodology" and "assessment" valued by residents were significantly higher than those valued by teachers (P<0.01). Teachers who filled out self-evaluation questionnaires were rated significantly higher by residents in role modeling subdomains (P<0.05). Male teachers in (sub)domains "role modeling: CanMEDS roles and reflection", "task allocation", "planning" and "personal support" were rated significantly higher than the female teachers (P<0.05). Teachers aged 40 years or younger were rated higher (P<0.01). Residents ratings by type of teachers' academic position almost in all (sub)domains differed significantly (P<0.05). No correlation observed between MOS of a particular teacher and MOS as rated by residents (ICC=0.055, P=0.399). The main areas for improvement were "feedback" and "assessment". CONCLUSIONS: Resident evaluations of clinical teachers are influenced by teachers' age, gender, year of residency training, type of teachers' academic position and whether or not a clinical teacher performed self-evaluation. Development of CBME should be focused on the continuous evaluation of quality, clinical teachers educational support and the implementation of e-portfolio.

Validation of the EFFECT questionnaire for competence-based clinical teaching in residency training in Lithuania.

BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into a competency-based medical education curriculum. To assess the quality of clinical teaching in residency training, we chose the EFFECT (evaluation and feedback for effective clinical teaching) questionnaire designed and validated at the Radboud University Medical Centre in the Netherlands. The aim of this study was to validate the EFFECT questionnaire for quality assessment of clinical teaching in residency training. MATERIALS AND METHODS: The research was conducted as an online survey using the questionnaire containing 58 items in 7 domains. The questionnaire was double-translated into Lithuanian. It was sent to 182 residents of 7 residency programs (anesthesiology reanimathology, cardiology, dermatovenerology, emergency medicine, neurology, obstetrics and gynecology, physical medicine and rehabilitation). Overall, 333 questionnaires about 146 clinical teachers were filled in. To determine the item characteristics and internal consistency (Cronbach's α), the item and reliability analyses were performed. Furthermore, confirmatory factor analysis (CFI) was performed using a model for maximum-likelihood estimation. RESULTS: Cronbach's α within different domains ranged between 0.91 and 0.97 and was comparable with the original version of the questionnaire. Confirmatory factor analysis demonstrated satisfactory model-fit with CFI of 0.841 and absolute model-fit RMSEA of 0.098. CONCLUSIONS: The results suggest that the Lithuanian version of the EFFECT maintains its original validity and may serve as a valid instrument for quality assessment of clinical teaching in competency-based residency training in Lithuania.

Accuracy, Precision, Sensitivity, and Specificity of Noninvasive ICP Absolute Value Measurements.

An innovative absolute intracranial pressure (ICP) value measurement method has been validated by multicenter comparative clinical studies. The method is based on two-depth transcranial Doppler (TCD) technology and uses intracranial and extracranial segments of the ophthalmic artery as pressure sensors. The ophthalmic artery is used as a natural pair of "scales" that compares ICP with controlled pressure Pe, which is externally applied to the orbit. To balance the scales, ICP = Pe a special two-depth TCD device was used as a pressure balance indicator. The proposed method is the only noninvasive ICP measurement method that does not need patient-specific calibration.

Interictal burden attributable to episodic headache: findings from the Eurolight project.

BACKGROUND: Most primary headaches are episodic, and most estimates of the heavy disability burden attributed to headache derive from epidemiological data focused on the episodic subtypes of migraine and tension-type headache (TTH). These disorders give rise directly but intermittently to symptom burden. Nevertheless, people with these disorders may not be symptom-free between attacks. We analysed the Eurolight dataset for interictal burden. METHODS: Eurolight was a cross-sectional survey using modified cluster sampling from the adult population (18-65 years) in 10 countries of the European Union. We used data from nine. The questionnaire included headache-diagnostic questions based on ICHD-II and several question sets addressing impact, including interictal and cumulative burdens. RESULTS: There were 6455 participants with headache (male 2444 [37.9 %]). Interictal symptoms were reported by 26.0 % of those with migraine and 18.9 % with TTH: interictal anxiety by 10.6 % with migraine and avoidance (lifestyle compromise) by 14.8 %, both much more common than in TTH (3.1 % [OR 3.8] and 4.7 % [OR 3.5] respectively). Mean time spent in the interictal state was 317 days/year for migraine, 331 days/year for TTH. Those who were "rarely" or "never" in control of their headaches (migraine 15.2 %, TTH 9.6 %) had significantly raised odds of interictal anxiety, avoidance and other interictal symptoms. Among those with migraine, interictal anxiety increased markedly with headache intensity and frequency, avoidance less so but still significantly. Lost productive time was associated with high ORs (up to 5.3) of anxiety and avoidance. A third (32.9 %) with migraine and a quarter (26.7 %) with TTH (difference: p < 0.0001) were reluctant to tell others of their headaches. About 10 % with each disorder felt families and friends did not understand their headaches. Nearly 12 % with migraine reported their employers and colleagues did not. Regarding cumulative burden, 11.8 % reported they had done less well in education because of headache, 5.9 % reported reduced earnings and 7.4 % that their careers had suffered. CONCLUSIONS: Interictal burden in those with episodic headache is common, more so in migraine than TTH. Some elements have the potential to be profoundly consequential. New methodology is needed to measure interictal burden if descriptions of headache burden are to be complete.

Headache, depression and anxiety: associations in the Eurolight project.

BACKGROUND: Headache disorders and psychiatric disorders are both common, while evidence, mostly pertaining to migraine, suggests they are comorbid more often than might be expected by chance. There are good reasons for establishing whether they are: symptoms of comorbid illnesses may summate synergistically; comorbidities hinder management, negatively influencing outcomes; high-level comorbidity indicates that, where one disease occurs, the other should be looked for. The Eurolight project gathered population-based data on these disorders from 6624 participants. METHODS: Eurolight was a cross-sectional survey sampling from the adult populations (18-65 years) of 10 EU countries. We used data from six. The questionnaire included headache-diagnostic questions based on ICHD-II, the Headache-Attributed Lost Time (HALT) questionnaire, and HADS for depression and anxiety. We estimated odds ratios (ORs) to show associations between migraine, tension-type headache (TTH) or probable medication-overuse headache (pMOH) and depression or anxiety. RESULTS: pMOH was most strongly associated with both psychiatric disorders: for depression, ORs (vs no headache) were 5.5 [2.2-13.5] (p < 0.0001) in males, 5.5 [2.9-10.5] (p < 0.0001) in females; for anxiety, ORs were 10.4 [4.9-21.8] (p < 0.0001) and 7.1 [4.5-11.2] (p < 0.0001). Migraine was also associated with both: for depression, ORs were 2.1 [1.3-3.4] (p = 0.002) and 1.8 [1.1-3.1] (p = 0.030); for anxiety 4.2 [2.8-6.3] (p < 0.0001) and 2.4 [1.7-3.4] (p < 0.0001). TTH showed associations only with anxiety: ORs 2.5 [1.7-3.7] (p < 0.0001) for males, 1.5 [1.1-2.1] (p = 0.021) for females. Participants with migraine carried 19.1 % probability of comorbid anxiety, 6.9 % of depression and 5.1 % of both, higher than the representative general-population sample (14.3, 5.6 and 3.8 %). Probabilities in those with MOH were 38.8, 16.9 and 14.4 %; in TTH, they did not exceed those of the whole sample. Comorbid psychiatric disorder did not add to headache-attributed productive time losses, but weak associations existed (R (2) = 0.020-0.082) for all headache types between lost productive time and probabilities of depression and, less so, anxiety. CONCLUSION: In this large study we confirmed that depression and especially anxiety are comorbid more than by chance with migraine, and showed the same is true, but more strongly, with MOH. Arguably, migraine patients and, more certainly, MOH patients should be screened with HADS in pursuit of best outcomes.

Trends and regional inequalities in mortality from stroke in the context of health care reform in Lithuania.

BACKGROUND AND OBJECTIVE: The objective of the study was to analyze mortality from stroke in Lithuania the context of health care reform with particular interest in urban/rural and regional inequalities. Based on the analysis of trends in mortality, and to detection of break-points over two decades of socioeconomic transition, it focused on the challenges in stroke care provision. MATERIALS AND METHODS: The analysis covered the entire country. Information on deaths from 1991 to 2012 was gathered from death certificates held by the Lithuanian Department of Statistics. The joinpoint analysis was used to identify the best-fitting points, wherever a statistically significant change in mortality occurred. Age-standardized mortality rates were calculated for 60 municipalities of Lithuania. RESULTS: The positive break-points in mortality from stroke were registered in 2007 for females and 2008 for males, when the increasing trends reversed to the declining. More positive changes occurred in urban areas, where stroke mortality is lower compare to rural since 1996. Considerable inequalities were disclosed among administrative regions of Lithuania: ratio between the highest and the lowest rates in different municipalities reached 4.88 for males and 3.35 for females. CONCLUSIONS: There are good reasons to expect the favorable stroke mortality trends observed will follow the same direction in the future. Stroke centers are growing up in their competence while networking is also under the development. The new strategies in stroke care should result not only in the declining mortality rates and numbers of severely handicapped stroke patients, but also in diminishing regional and urban/rural inequalities.

Associations of HLA DRB1 alleles with IgG oligoclonal bands and their influence on multiple sclerosis course and disability status.

BACKGROUND AND AIM: Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients. MATERIALS AND METHODS: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immunofixation to test for the presence of intrathecal specific OCB. RESULTS: HLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present. CONCLUSIONS: OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS.

Crucial role of carotid ultrasound for the rapid diagnosis of hyperacute aortic dissection complicated by cerebral infarction: A case report and literature review.

Aortic dissection is a life-threatening rare condition that may virtually present by any organ system dysfunction, the nervous system included. Acute cerebral infarction among multiple other neurological and non-neurological presentations is part of this acute aortic syndrome. Rapid and correct diagnosis is of extreme importance keeping in mind the possibility of thrombolytic treatment if a patient with a suspected ischemic stroke arrives to the Emergency Department within a 4.5-h window after symptom onset. Systemic intravenous thrombolysis in the case of an acute brain infarction due to aortic dissection may lead to fatal outcomes. In this neurological emergency it is important to rule out underlying aortic dissection by choosing appropriately quick and accurate diagnostic tool. We aimed to present a prospective follow-up case, where carotid ultrasound examination was the primary key method that led to a correct diagnosis in hyperacute (<24h) Stanford type A aortic dissection presenting as an acute ischemic stroke, and thereafter with a repeated contrast-enhanced computed tomography and transthoracic echocardiography, helped to monitor topography of intravascular processes and hemodynamic properties during the clinical course of a disease, which influenced treatment decisions. Thus, we reviewed the literature mainly focusing on the various neurological aspects associated with aortic dissection.

Ultrasonographic (TCS) and clinical findings in overlapping phenotype of essential tremor and Parkinson's disease (ET-PD).

BACKGROUND: Essential tremor (ET) and Parkinson's disease (PD) are considered distinct disorders. The aim of the study was to look for a link or any distinguishing features by transcranial sonography (TCS), together with the clinical examination findings in a group of patients with overlapping phenotype of ET and PD (ET-PD). METHODS: A prospective observational case-control study was carried out from the 3rd January 2011 until 30th January 2013 at the Hospital of Lithuanian University of Health Sciences. The final study group consisted of 15 patients with ET-PD, 116 patients with ET-only and 141 patients with PD-only. The control group included 101 subjects. Clinical diagnosis was of a diagnostic standard. RESULTS: The main ultrasonographic findings in the ET-PD group were similar to those of the PD-only: hyperechogenicity of the substantia nigra (66.7%, p < 0.001) and nuclei raphe interruptions/absence (38.5%, p < 0.001). The single distinguishing TCS finding in ET-PD group was a lentiform nucleus hyperechogenicity (26.7%), however this was only significant when compared to controls (p = 0.006). An asymmetrical onset of symptoms (73.3%) in ET-PD group was characteristic to PD-only. The ET-PD patients had the longest disease duration (median 6 years, p < 0.001), the most frequent rate of positive family history (53.3%, p = 0.005), rather low prevalence of cogwheel rigidity (26.7%, p < 0.001), and higher mean Hoehn & Yahr scores compared to PD-only (2.6 ± 0.8 vs. 1.8 ± 0.8, p = 0.012). CONCLUSIONS: The main TCS findings of the present study in patients with overlapping ET-PD phenotype were similar to the PD-only group. The highest positive family history rate among ET-PD patients indicates a strong hereditary predisposition and needs genetic underpinnings. Some ET patients, who look like they may be developing co-morbid PD clinically, may have an alternative diagnosis for Parkinsonism, which could be delineated by TCS examination.

Headache yesterday in Europe.

BACKGROUND: Surveys enquiring about burden of headache over a prior period of time (e.g., 3 months) are subject to recall bias. To eliminate this as far as possible, we focused on presence and impact of headache on the preceding day ("headache yesterday"). METHODS: Adults (18-65 years) were surveyed from the general populations of Germany, Italy, Lithuania, Luxembourg and the Netherlands, from a work-force population in Spain and from mostly non-headache patient populations of Austria, France and U.K. A study of non-responders in some countries allowed detection of potential participation bias where initial participation rates were low. RESULTS: Participation rates varied between 11% and 59% (mean 27%). Non-responder studies suggested that, because of participation bias, headache prevalence might be overestimated in initial responders by up to 2% (absolute). Across all countries, 1,422 of 8,271 participants (15-17%, depending on correction for participation bias) had headache yesterday lasting on average for 6 hours. It was bad or very bad in 56% of cases and caused absence from work or school in 6%. Among those who worked despite headache, 20% reported productivity reduced by >50%. Social activities were lost by 24%. Women (21%) were more likely than men (12%) to have headache yesterday, but impact was similar in the two genders. CONCLUSIONS: With recall biases avoided, our findings indicate that headache costs at least 0.7% of working capacity in Europe. This calculation takes into account that most of those who missed work could make up for this later, which, however, means that leisure and social activities are even more influenced by headache.

The impact of headache in Europe: principal results of the Eurolight project.

BACKGROUND: European data, at least from Western Europe, are relatively good on migraine prevalence but less sound for tension-type headache (TTH) and medication-overuse headache (MOH). Evidence on impact of headache disorders is very limited. Eurolight was a data-gathering exercise primarily to inform health policy in the European Union (EU). This manuscript reports personal impact. METHODS: The study was cross-sectional with modified cluster sampling. Surveys were conducted by structured questionnaire, including diagnostic questions based on ICHD-II and various measures of impact, and are reported from Austria, France, Germany, Italy, Lithuania, Luxembourg, Netherlands, Spain and United Kingdom. Different methods of sampling were used in each. The full methodology is described elsewhere. RESULTS: Questionnaires were analysed from 8,271 participants (58% female, mean age 43.4 y). Participation-rates, where calculable, varied from 10.6% to 58.8%. Moderate interest-bias was detected. Unadjusted lifetime prevalence of any headache was 91.3%. Gender-adjusted 1-year prevalences were: any headache 78.6%; migraine 35.3%; TTH 38.2%, headache on ≥15 d/mo 7.2%; probable MOH 3.1%. Personal impact was high, and included ictal symptom burden, interictal burden, cumulative burden and impact on others (partners and children). There was a general gradient of probable MOH > migraine > TTH, and most measures indicated higher impact among females. Lost useful time was substantial: 17.7% of males and 28.0% of females with migraine lost >10% of days; 44.7% of males and 53.7% of females with probable MOH lost >20%. CONCLUSIONS: The common headache disorders have very high personal impact in the EU, with important implications for health policy.

Variations in acute stroke care and the impact of organised care on survival from a European perspective: the European Registers of Stroke (EROS) investigators.

BACKGROUND: The need for stroke care is escalating with an ageing population, yet methods to estimate the delivery of effective care across countries are not standardised or robust. Associations between quality and intensity of care and stroke outcomes are often assumed but have not been clearly demonstrated. OBJECTIVE: To examine variations in acute care processes across six European populations and investigate associations between the delivery of care and survival. METHODS: Data were obtained from population-based stroke registers of six centres in France, Lithuania, UK, Spain, Poland and Italy between 2004 and 2006 with follow-up for 1 year. Variations in the delivery of care (stroke unit, multidisciplinary team and acute drug treatments) were analysed adjusting for case mix and sociodemographic factors using logistic regression methods. Unadjusted and adjusted survival probabilities were estimated and stratified by levels of Organised Care Index. RESULTS: Of 1918 patients with a first-ever stroke registered, 30.7% spent more than 50% of their hospital stay in a stroke unit (13.9-65.4%) among centres with a stroke unit available. The percentage of patients assessed by a stroke physician varied between 7.1% and 96.6%. There were significant variations after adjustment for confounders, in the organisation of care across populations. Significantly higher probabilities of survival (p<0.01) were associated with increased organisational care. CONCLUSIONS: This European study demonstrated associations between delivery of care and stroke outcomes. The implementation of evidence-based interventions is suboptimal and understanding better ways to implement these interventions in different healthcare settings should be a priority for health systems.