Update of Anticoagulation Use in Cardioembolic Stroke With a Special Reference to Endovascular Treatment.

Cardioembolic stroke is a major cause of morbidity, with a high risk of recurrence, and anticoagulation represents the mainstay of secondary stroke prevention in most patients. The implementation of endovascular treatment in routine clinical practice complicates the decision to initiate anticoagulation, especially in patients with early hemorrhagic transformation who are considered at higher risk of hematoma expansion. Late hemorrhagic transformation in the days and weeks following stroke remains a potentially serious complication for which we still do not have any established clinical or radiological prediction tools. The optimal time to initiate therapy is challenging to define since delaying effective secondary prevention treatment exposes patients to the risk of recurrent embolism. Consequently, there is clinical equipoise to define and individualize the optimal timepoint to initiate anticoagulation combining the lowest risk of hemorrhagic transformation and ischemic recurrence in cardioembolic stroke patients. In this narrative review, we will highlight and critically outline recent observational and randomized relevant evidence in different subtypes of cardioembolic stroke with a special focus on anticoagulation initiation following endovascular treatment. We will refer mainly to the commonest cause of cardioembolism, non-valvular atrial fibrillation, and examine the possible risk and benefit of anticoagulation before, during, and shortly after the acute phase of stroke. Other indications of anticoagulation after ischemic stroke will be briefly discussed. We provide a synthesis of available data to help clinicians individualize the timing of initiation of oral anticoagulation based on the presence and extent of hemorrhagic transformation as well as stroke severity.

Living with a Brain AVM: A Quality of Life Assessment.

BACKGROUND AND PURPOSE: Brain arteriovenous malformations (AVM) are uncommon vascular lesions with the risk of hemorrhage, epileptic seizures, neurological deficits, and headache. Comparing the risks of the natural history and that of preventive treatment, a recent study has found observation more beneficial than treatment for unruptured AVMs. This study, however, did not consider the long-term impact of carrying a brain AVM on everyday activities. In this study we analyzed the Quality Of Life (QOL) of patients with untreated AVMs, a measure increasingly used in clinical trials to asses this kind of impact. METHODS: We enrolled 36 patients with unruptured, untreated brain AVM from our hospital database and measured their QOL retrospectively using the EQ-5D-5L questionnaire. As a control group we used the results of the Research Report, a nationwide study based on the quality of life of 5534 healthy Hungarians in 2002. Due to the low number of cases, statistical analysis could not be made. RESULTS: Headache proved to be the most common AVM-related sign in our cohort (40%, n = 17), with a female predominance; neurological deficit was detected in 33% (n = 14), while epileptic seizures occurred in 26% (n = 11), more commonly affecting male subjects. Anxiety and discomfort seemed to be the most prevalent influencing factors on QOL, especially in the youngest age group (18-34 years). Female subjects showed a greater dependence than men in all age groups, though males had a more significant impairment in their usual activities. Older patients were affected more significantly in their self-care and usual activities compared with the younger population. CONCLUSIONS: Untreated AVMs have a significant negative impact on patients carrying unruptured brain AVMs, as proved by QOL assessment. Beside neurological deficits, this impact should also be considered in the therapeutic decision.

Coronary stent implantation for acute basilar artery occlusion with underlying stenosis.

AIMS: Our aim was to study the effectiveness of coronary stent implantation during the endovascular treatment (EVT) of acute basilar artery occlusion (BAO) with occlusion-underlying intracranial atherosclerotic stenosis (ICAS). METHODS AND RESULTS: We retrospectively analysed 91 consecutive BAO patients who underwent EVT between February 2014 and January 2019 in a single, high-volume neurointerventional centre. We studied the effect of immediate coronary stent implantation on the clinical outcome of BAO with occlusion-underlying stenosis. BAO patients with underlying ICAS (n=41) were characterised by longer symptom-onset-to-reperfusion times (231 min vs 173 min, p=0.0020), lower TICI 2b-3 reperfusion rates (65.85% vs 90.00%, p=0.0084), and higher overall mortality (HR 2.021, p=0.0417) compared to the BAO cases without ICAS (n=50). The patients undergoing stenting (n=18) had lower residual basilar artery (BA) stenosis (14.7% vs 81.0%, p<0.0001), higher chance for functional recovery (OR 7.6, p=0.0250) and higher chance of survival (HR 4.163, p=0.0026) compared to the BAO-ICAS cases treated without coronary stents (n=21). CONCLUSIONS: The immediate treatment of the occlusion-underlying stenosis with coronary stents and dual antiplatelet therapy (DAPT) in BAO was associated with improved overall survival and better functional outcomes.

Cortical Hand Knob Stroke: Report of 25 Cases.

BACKGROUND: Although uncommon, cortical hand knob territory stroke is a well-defined stroke entity that mimics peripheral nerve damage. Atherosclerosis and hypertension are the most prevalent risk factors for the disease. Embolic origin, either artery-to-artery or cardioembolic, has been suggested as the most probable underlying mechanism. MATERIALS AND METHODS: Twenty-five patients with isolated hand palsy due to central origin were admitted to our department between 2006 and 2016. Cortical lesions were proven by either computed tomography or magnetic resonance imaging. RESULTS: The average age was 67 ± 12 years. Most of the cases were first-ever strokes (n = 23, 92%). Isolated infarct in the hand knob region was found in 18 of the 25 cases, whereas 7 had multiple acute infarctions. Supra-aortic atherosclerosis was found in 21 patients, 8 of them had 50% or greater ipsilateral stenosis of the internal carotid artery. Hypertension was the second most prevalent risk factor (n = 20, 80%). Quick improvement of symptoms was seen in almost every case (mean follow-up 17.5 months), 9 patients showed complete recovery, whereas 2 remained disabled and 1 died due to a malignant disease. Three patients suffered a recurrent stroke on follow-up. CONCLUSIONS: We conclude that distal arm paresis is a rare presentation of acute stroke with usually benign course.

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis.

AIM: To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODS: Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. RESULTS: A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA posvsneg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSION: Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

[The role of new oral anticoagulants in cerebrovascular diseases]. / Új típusú orális antikoagulánsok alkalmazása cerebrovaszkuláris betegségekben.

Cardioembolisation is responsible for 20 percent of ischaemic stroke cases, which most commonly derives from non-valvular atrial fibrillation. Although warfarin is highly effective in primary and secondary stroke prevention, its use is limited by the high risk of haemorrhagic complications and a narrow therapeutic range that needs regular monitoring of INR. These limitations explained the strong need for developing new oral anticoagulants. The so-called 'new oral anticoagulants' are trying to find new targets for modifying the coagulation cascade. Apixaban, edoxaban and rivaroxaban are direct factor Xa inhibitors, while dabigatran works as a direct thrombin inhibitor. Recent phase-III clinical trials proved their effectiveness in stroke prevention and risk reducing of haemorrhagic events as well, so they can already be found as recommended drugs in new guidelines of European and American societies of cardiology and stroke. The use of new oral anticoagulants instead of warfarin in patients with atrial fibrillation or as a secondary prevention after cardioembolic stroke has to be considered.

Can somatosensory evoked potentials predict disease course in early multiple sclerosis patients?

BACKGROUND: Multiple sclerosis (MS) is an autoimmune degenerating disease, where myelin degradation as well as axonal loss is present. PURPOSE: To asses whether recording the middle-latency components of the median nerve somatosensory evoked potentials (SEPs) increases the diagnostic sensitivity in patients with MS, and to investigate whether any of the abnormalities correlates with the severity of the clinical signs and predicts future outcome. METHODS: Twenty consecutive MS patients at early onset were included. Median and tibial nerve SEPs were recorded at the time of the referral. Extended Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) were assessed at the time of the referral and after 5-year followup. RESULTS: Recording the middle-latency components increased the sensitivity of the median nerve SEPs from 50% to 75%. The overall sensitivity of the SEPs (i.e. including also tibial nerve SEPs) modestly increased (from 80% to 90%). The amplitude of the cortical N20 potential of the median nerve was inversely correlated to the clinical severity. None of the parameters could predict the future outcome. CONCLUSIONS: Our results provide neurophysiological evidence for the role of axonal lesions in the clinical disability of the patients with MS.

Presence of anti-microbial antibodies in liver cirrhosis--a tell-tale sign of compromised immunity?

BACKGROUND: Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections. METHODOLOGY/PRINCIPAL FINDINGS: Sera of 676 patients with various chronic liver diseases (autoimmune diseases: 266, viral hepatitis C: 124, and liver cirrhosis of different etiology: 286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae (ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR: 1.62, 95%CI: 1.16-2.25), co-morbidities (OR: 2.22, 95%CI: 1.27-3.86), and ASCA positivity (OR: 1.59, 95%CI: 1.07-2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR: 1.85) and co-morbidities (p<0.001, OR: 2.02) by Cox-regression analysis. CONCLUSIONS/SIGNIFICANCE: The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.

Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis.

BACKGROUND & AIMS: Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosis due to the relative immuncompromised state. METHODS: Sera of 929 patients with various chronic liver diseases [autoimmune liver diseases (ALD), 406; viral hepatitis C (HCV), 185; and liver cirrhosis (LC) with various etiologies, 338] and 296 healthy controls (HC) were assayed for MBL concentration. Furthermore, a follow-up, observational study was conducted to assess MBL level as a risk factor for clinically significant bacterial infections in cirrhotic patients. RESULTS: MBL level and the prevalence of absolute MBL deficiency (<100 ng/ml) was not significantly different between patients and controls (ALD: 14.5%, HCV: 11.9%, LC: 10.7%, HC: 15.6%). In cirrhotic patients, the risk for infection was significantly higher among MBL deficient subjects as compared to non-deficient ones (50.0% vs. 31.8%, p=0.039). In a logistic regression analysis, MBL deficiency was an independent risk factor for infections (OR: 2.14 95% CI: 1.03-4.45, p=0.04) after adjusting for Child-Pugh score, co-morbidities, gender, and age. In a Kaplan-Meier analysis, MBL deficiency was associated with a shorter time to develop the first infectious complication (median days: 579 vs. 944, pBreslow=0.016, pLogRank=0.027) and was identified as an independent predictor in a multivariate Cox-regression analysis (p=0.003, OR: 2.33, 95% CI: 1.34-4.03). CONCLUSIONS: MBL deficiency is associated with a higher probability and shorter time of developing infections in liver cirrhosis, further supporting the impact of the MBL molecule on the host defense.

[Novel aspects in the pathogenesis of gastroesophageal reflux disease]. / A gastrooesophagealis refluxbetegség keletkezésének újabb szempontjai.

UNLABELLED: In addition to lower esophageal sphincter (LES) relaxations and decreased LES tone, increased intra-abdominal pressure can also play role in the pathogenesis of gastroesophageal reflux disease (GERD),. AIM: To analyze the correlation between occupation-related increased intra-abdominal pressure or straining (experienced for years) and the prevalence of GERD symptoms. METHODS: Reflux symptoms were analyzed through a questionnaire among professional singers, wind players and glassblowers in comparison with controls. RESULTS: Heartburn, regurgitation and hoarseness were significantly more frequent among professional singers than in controls (P<0.001). Among wind players heartburn (P<0.05) and regurgitation (P<0.01), among glassblowers regurgitation (P<0.01) were significantly more frequent in comparison with control subjects. Reflux symptoms correlated significantly with the duration of professional activity (P<0.05). CONCLUSIONS: Results suggest that reflux symptoms are more frequent among subjects with occupation-related increased intra-abdominal pressure. GERD seems to be a work-related disease in this aspect.

[Possible role of selected IGR and SLC22A4/SLC22A5 loci in development of inflammatory bowel diseases]. / Az 5q31 IBD5-régióban található IGR és SLC22A4/SLC22A5 variánsok lehetséges szerepe a gyulladásos bélbetegség kialakulásában.

UNLABELLED: The IBD5 locus (MIM#606348) on chromosome 5q31 has been demonstrated to confer increased risk for inflammatory bowel disease. Controversial reports have been published about the significance of individual loci located in this region. Here we investigated the possible genetic association of inflammatory bowel diseases with C1672T of SLC22A4 and G-207C SLC22A5 alleles, and with IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility variants of the IBD5 region located on chromosome 5q31. PATIENTS AND METHODS: Total of 440 patients, 206 with Crohn's disease, 234 with ulcerative colitis, and 279 controls were studied by PCR-RFLP methods. RESULTS: Neither the C1672T, and G-207C alleles, nor the TC haplotype were found to confer risk for Crohn's disease or ulcerative colitis. By contrast, both of the minor allele frequencies of IGR2096a_1 T (48.1%) and IGR2198a_1 C (46.1%) were increased in Crohn's disease subjects as compared with the controls (38.5% and 38.4%, respectively; p<0.05). Using regression analysis adjusted to age and gender these alleles were found to confer risk for Crohn's disease (OR=1.694, 95% CI: 1.137-2.522; p=0.010 for T allele, OR=1.644, 95% CI=1.103-2.449; p=0.015 for C allele of IGRs). In UC no such associations were found. CONCLUSIONS: Our results revealed the susceptibility nature of the examined IGR minor alleles in Hungarians, which nation differs historically from the surrounding Caucasian populations in origin of the founders of the state.

Gastroesophageal reflux disease: work-related disease?

BACKGROUND: An occupation-related susceptibility of professional singers to experience gastroesophageal reflux has been suggested. AIMS: To investigate the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers, wind players, glassblowers and water polo players in comparison with a sample of general population. SUBJECTS AND METHODS: A total of 202 professional opera choristers from well-known choirs in different Hungarian regions, 71 professional wind players, 43 glassblowers, 54 water polo players were identified and 115 control subjects were compared prospectively. Reflux symptoms together with selected individual characteristics and lifestyle habits were investigated in study groups through a reflux questionnaire. RESULTS: Professional opera choristers reported a statistically significantly higher prevalence of heartburn, regurgitation and hoarseness than control subjects (p < 0.001). Among professional wind players, heartburn and regurgitation were significantly more frequent compared with controls (p < 0.05 and p < 0.01, respectively). Glassblowers reported a significantly higher prevalence of acid regurgitation in comparison with controls (p < 0.01). The prevalence of reflux symptoms in water polo players was similar to that of controls. In opera choristers, wind players and glassblowers, reflux symptoms appeared to be significantly correlated with the cumulative lifetime duration of professional singing, playing and working activity, respectively (p < 0.05). CONCLUSIONS: Our results demonstrate that professional opera choristers, professional wind players and glassblowers have a higher prevalence of reflux symptoms compared with control subjects. Gastroesophageal reflux in these professions should be considered as a work-related disorder that may have an impact on quality of life and may negatively interfere with professional performance.

IGR2096a_1 T and IGR2198a_1 C alleles on IBD5 locus of chromosome 5q31 region confer risk for Crohn's disease in Hungarian patients.

BACKGROUND AND AIMS: We investigated the possible association of IBD with C1672T of SLC22A4 and G-207C of SLC22A5 alleles, and with the novel IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility loci, all located on IBD5 locus of chromosome 5q31. MATERIALS AND METHODS: DNA of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients were analyzed by polymerase chain reaction/restriction fragment length polymorphism methods. RESULTS: Neither the C1672T and G-207C alleles, nor the TC haplotype were found to be risk factors. By contrast, the minor allele frequencies of IGR2096a_1 T (47.2%) and IGR2198a_1 C (45.9%) were increased in Crohn's disease compared with the controls (38.2% and 37.7%, respectively; p < 0.05); multivariate regression analysis revealed a risk nature for Crohn's disease (OR = 1.748, 95% CI 1.186-2.574; p = 0.007 for T allele, OR = 1.646, 95% CI 1.119-2.423, p = 0.011 for C allele of IGRs). CONCLUSION: The data suggest a special haplotype arrangement of susceptibility genes at the IBD5 locus in Hungarians, which nation differs historically from the surrounding Caucasian ethnicities in its origin.

Galectin-2 3279TT variant protects against the lymphotoxin-alpha 252GG genotype associated ischaemic stroke.

OBJECTIVE: The galectin-2 protein is presumed to play a regulatory role in the intracellular trafficking of the lymphotoxin-alpha (LTA) cytokine. LTA is a pro-inflammatory factor, its 252GG homozygote variant is considered as a susceptibility factor for arteriosclerosis and cardiovascular diseases. By contrast, the galectin-2-encoding gene LGALS2 3279TT homozygote variant has been demonstrated to exert protection against myocardial infarction by reducing the transcriptional level of galectin-2, thereby leading to a reduced extracellular secretion of LTA. METHODS: In the present study, we examined whether the LGALS2 3279TT homozygote variant alone can influence the prevalence of ischaemic stroke, and whether it can interact somehow with the disadvantageous LTA 252GG homozygote variant. Genetic and clinical data of 385 ischemic stroke patients and 303 stroke and neuroimaging alteration-free controls were analysed. RESULTS: The combination of the LGALS2 3279TT and LTA 252GG homozygote was significantly less frequent in the ischemic stroke group (1.56%) than in the controls (5.94%, p<0.00187; overall stroke group: crude OR: 0.25, 95% CI: 0.1-0.64; adjusted OR: 0.03, 95% CI: 0.025-0.71). CONCLUSIONS: This finding suggests a gene-gene interaction.