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Multiple sclerosis (MS) is the autoimmune, neurodegenerative disease of the central nervous system (CNS). Typically, it affects the young adult population, however, up to 10% of the cases, it can develop in childhood. Atypical manifestations, such as the tumefactive variant (tMS) or acute disseminated encephalomyelitis (ADEM), especially coupled with fulminant disease course, are even more rare and pose a considerable differential diagnostic and therapeutic challenge. Recently, the therapeutic strategy on the use of disease modifying therapies (DMTs) in MS has shifted to the direction of a more individualized approach, that takes the personal differences heavily into account, in particular regard to the activity and prognosis of the disease. Despite this change has only been applied to adults yet, it is plausible to predict, that it will soon be applied to pediatric patients as well, particularly, as several randomized studies are under way concerning DMTs in pediatric populations. To our best knowledge, we are the first to report a successful natalizumab treatment of pediatric fulminant tMS, in case of a 13.5 years old girl. We feel that this report demonstrates the need of early and adequate treatment in such an aggressive case, because it can reverse the course of a possibly fatal disease. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating, autoimmune diseases affecting the central nervous system. Typically, recurrent optic neuritis and longitudinal extensive transverse myelitis dominates the clinical picture. In most cases NMOSD are associated with autoantibodies targeting the water channel aquaporin-4 (AQP-4). NMOSD usually present in young adults. Clinical findings suggestive of NMOSD in elderly patients should raise the suspicion of a paraneoplastic etiology. To our knowledge, we report the first case of a 66 year-old female patient with paraneoplastic NMOSD that is associated with squamous cell lung carcinoma. Anti-AQP-4 was present in both the serum and cerebrospinal fluid of the patient. However, immunhistological staining of the malignant tissue did not show presence of AQP-4 on the surface of tumour cells. [ABSTRACT FROM AUTHOR]

Background Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS); its prevalence is reported to be 43–70%. It is one of the most important determinants of MS patients’ quality of life, as it is one of the main factors for MS patients becoming unemployed. Aim We aimed to determine the prevalence of CI among the relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS) patients in Hungary, to evaluate the predicting factors of CI and to assess the differences between sexes and patients with different educational levels. Patients and methods Five-hundred and fifty-three CIS and RRMS patients were enrolled to our study from three Hungarian MS centers. Age at screening, age at disease onset, disease duration, EDSS score, sex and educational levels were analyzed as socio-demographic factors. The BICAMS battery was used to assess their cognitive state, the BDI-II battery to assess depression. For statistical analysis, we utilized logistical regression, and used Fisher exact tests, chi-square tests and one-way ANOVA. Results The mean age of our patients was 44.93 ± 11.69 years, mean age at disease onset was 31.95 ± 10.01 years, the mean disease duration was 13.05 ± 8.05 years and the median EDSS score 2.0 (Range: 6.5, IQR:2.0) points. Three-hundred and sixteen (57.1%) patients had CI. Sex, educational level and EDSS score proved to be significant predictors of CI (OR: 2.71, p < 0.001; OR: 1.94, p = 0.023; OR: 0.47, p = 0.003 respectively). CI was significantly (p < 0.001) more frequent among men (70.1%) than women (52.0%). We found, that educational level and EDSS score were only a significant predicting factor among women. Thus, the prevalence of CI among women with college or university degree was significantly (p < 0.001) less common (39.4%) than women with 12–15 years of education (57.4%) and women without a high school degree (66.7%). Also, we found that among women with higher EDSS score than 2 points, the prevalence of CI is 69.9% as compared to women with EDSS score between 0 and 2 points, where the prevalence is 42.8% (p < 0.001). No such differences were observed among man. Discussion Our prevalence data is similar to those reported in the literature (43–70%), and almost identical to the one assessment using the BICAMS battery. We found that men are more vulnerable to CI than women in MS, as was reported recently. We are the first to report however, that higher educational level and lower EDSS scores are only associated with better cognitive performance in women. [ABSTRACT FROM AUTHOR]

Cigarette smoke-triggered inflammatory cascades and consequent tissue damage are the main causes of chronic obstructive pulmonary disease (COPD). There is no effective therapy and the key mediators of COPD are not identified due to the lack of translational animal models with complex characterization. This integrative chronic study investigated cardiopulmonary pathophysiological alterations and mechanisms with functional, morphological and biochemical techniques in a 6-month-long cigarette smoke exposure mouse model. Some respiratory alterations characteristic of emphysema (decreased airway resistance: Rl; end-expiratory work and pause: EEW, EEP; expiration time: Te; increased tidal mid-expiratory flow: EF50) were detected in anaesthetized C57BL/6 mice, unrestrained plethysmography did not show changes. Typical histopathological signs were peribronchial/perivascular (PB/PV) edema at month 1, neutrophil/macrophage infiltration at month 2, interstitial leukocyte accumulation at months 3–4, and emphysema/atelectasis at months 5–6 quantified by mean linear intercept measurement. Emphysema was proven by micro-CT quantification. Leukocyte number in the bronchoalveolar lavage at month 2 and lung matrix metalloproteinases-2 and 9 (MMP-2/MMP-9) activities in months 5–6 significantly increased. Smoking triggered complex cytokine profile change in the lung with one characteristic inflammatory peak of C5a, interleukin-1α and its receptor antagonist (IL-1α, IL-1ra), monokine induced by gamma interferon (MIG), macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) at months 2–3, and another peak of interferon-γ (IFN-γ), IL-4, 7, 13, 17, 27 related to tissue destruction. Transient systolic and diastolic ventricular dysfunction developed after 1–2 months shown by significantly decreased ejection fraction (EF%) and deceleration time, respectively. These parameters together with the tricuspid annular plane systolic excursion (TAPSE) decreased again after 5–6 months. Soluble intercellular adhesion molecule-1 (sICAM-1) significantly increased in the heart homogenates at month 6, while other inflammatory cytokines were undetectable. This is the first study demonstrating smoking duration-dependent, complex cardiopulmonary alterations characteristic to COPD, in which inflammatory cytokine cascades and MMP-2/9 might be responsible for pulmonary destruction and sICAM-1 for heart dysfunction. [ABSTRACT FROM AUTHOR]

Transgene-mediated programming is a preeminent strategy to direct cellular identity. To facilitate cell fate switching, lineage regulating genes must be efficiently and uniformly induced. However, gene expression is often heterogeneous in transgenic systems. Consistent with this notion, a non-uniform reporter gene expression was detected in our doxycycline (DOX)-regulated, murine embryonic stem (ES) cell clones. Interestingly, a significant fraction of cells within each clone failed to produce any reporter signals upon DOX treatment. We found that the majority of these non-responsive cells neither carry reporter transgene nor geneticin/G418 resistance. This observation suggested that our ES cell clones contained non-recombined cells that survived the G418 selection which was carried out during the establishment of these clones. We successfully eliminated most of these corrupted cells with repeated chemical (G418) selection, however, even after prolonged G418 treatments, a few cells remained non-responsive due to epigenetic silencing. We found that cell sorting has been the most efficient approach to select those cells which can uniformly and stably induce the integrated transgene in this ES cell based platform. Together, our data revealed that post-cloning chemical re-selection or cell sorting strongly facilitate the production of ES cell lines with a uniform transgene induction capacity. [ABSTRACT FROM AUTHOR]

Background The common symptoms of multiple sclerosis are fatigue, depression, cognitive dysfunction, pain and sexual dysfunction, which influence the health-related quality of life of the patients. Objective We aimed to determine the correlations between the health-related quality of life, the level of disability, fatigue and depression in glatiramer acetate-treated patients with multiple sclerosis in Hungary. Methods The Hungarian versions of the Multiple Sclerosis Quality of Life-54, Fatigue Impact Scale and Beck Depression Inventory questionnaires were completed by 428 relapsing-remitting multiple sclerosis patients treated with glatiramer acetate from 19 Hungarian centers. Results The prevalence of fatigue was found to be 62.4%. The prevalence of depression was lower (13.4%) than that described in previous studies (36–54%) among patients with multiple sclerosis. Significant differences in the health-related quality of life were found between fatigued and non-fatigued patients. The level of disability, fatigue, depression and the duration of the disease correlated significantly with the quality of life. However, linear regression analysis indicated that the quality of life was predicted by the level of disability, depression, social and cognitive fatigue, but not by physical fatigue. Conclusions Decreasing the disease activity in multiple sclerosis with immunomodulatory therapy, together with improvements of the diagnostics and treatment of the accompanying depression and fatigue are of high priority to improve the health-related quality of life of patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background Multiple Sclerosis (MS) causes not only somatic, but also cognitive impairment regardless of the patients׳ age or the course of the disease. The Brief International Cognitive Assessment for MS (BICAMS) test, published in 2011, is a short cognitive questionnaire: a fast, reliable, sensitive and specific tool for the evaluation of the patients׳ cognitive state. Objectives Our primary objective was to assess the validity of the Hungarian version of the BICAMS test. Our secondary objective was to evaluate the impact of the cognitive impairment on the patient׳s quality of life and fatigue׳s impact on the patients׳ cognitive state. Methods 65 RR-MS patients and 65 age, sex and education matched healthy control (HC) subjects completed the test and were retested after 3 weeks. The patients also completed the MS Quality of Life 54 (MSQoL54) and the Fatigue Impact Scale (FIS) assessments. Group differences were calculated by paired sample T-tests. The test-retest reliability was measured by intraclass correlation coefficients. To analyze the difference between the test-retest performances of the two groups we used two-way repeated measures ANOVA where the BICAMS battery was the single composite outcome and one-way repeated measures ANOVA. To assess the impact of the cognitive decline on the patients׳ quality of life and fatigue׳s impact on the cognitive state, we examined the correlations between results in the BICAMS and the MSQoL54 and FIS. Results We found significant difference ( p ≤0.001, p =0.017 in the first CVLT-II assessment) between MS patients and members of the HC group in all four evaluated parameters of BICAMS test in both sessions. The correlation coefficients were very strong between the tests and retests ( r >0.8; p <0.001; r =0.678, p <0.001 between the CVLT-II assessments). We found that the HC group performed significantly ( p =0.020) better in the retest sessions as compared to their original performance than the patients did and this difference is solely due to the difference between the CVLT-II performances. We have found significant negative correlation between the patients׳ cognitive function and the fatigue score ( r <−0.3, p <0.05). Seven of the MSQoL-54 subscales correlated with the BICAMS performance ( r >0.3; p <0.05). Conclusions The Hungarian version of the BICAMS test is a valid and reliable method for the evaluation of MS patients׳ cognitive function. It seems that because of the short retest period, the members of the HC group remembered the CVLT-II words thus performed better than the patients did. Also apparently fatigue can have a negative impact on the patients׳ cognitive state, and cognitive impairment could worsen the patients׳ quality of life. [ABSTRACT FROM AUTHOR]

Background: Atrioesophageal fistula is an uncommon but life-threatening complication of atrial fibrillation (AF) ablation. Esophageal ulcerations (ESUL) have been proposed to be potential precursor lesions. Objective: The purpose of our study was to prospectively investigate the incidence of ESUL in a large patient population undergoing radiofrequency catheter ablation (RFA). Additionally, we aimed to link demographic data and lesion sets with anatomical information given by multislice computed tomography imaging and to correlate these data with the development of ESUL. Methods: This study included 267 patients and consecutively screened all individuals for evidence of ESUL 24 h after RFA of AF by endoscopy of the esophagus. A standardized ablation approach using a 25-W energy maximum at the posterior left atrial (LA) wall without esophagus visualization, temperature monitoring, or intracardiac ultrasound was performed. Results: In total, we found 2.2% of patients (6 of 267) presenting with ESUL. Parameters exposing a specific patient to risk of developing ESUL in univariate analysis were persistent AF (5 of 95, P = .023), additional lines performed (roofline: 6 of 114, P = .006; LA isthmus: 4 of 49, P = .011; coronary sinus: 5 of 66, P = .004), and LA enlargement (P = .001) leading to sandwiching of the esophagus between the LA and thoracic spine. Multivariate analysis revealed LA-to-esophagus distance as the only significant risk factor. Conclusion: This study is the first to link anatomical information and procedural considerations to the development of ESUL in radiofrequency ablation for AF. Furthermore, it reveals the correlation and individual impact of these factors. Not a single patient with pulmonary vein isolation alone developed ESUL. [ABSTRACT FROM AUTHOR]

Background: Induction of gastroesophageal reflux after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) may have an impact on the progression of esophageal injury. Objective: The purpose of this study was to assess the acute effect of RFCA on distal esophageal acidity using leadless pH-metry capsules. Methods: A total of 31 patients (27 male and 4 female; 25 with paroxysmal AF) who underwent RFCA and esophagoscopy 24 hours before and after ablation were assessed for reflux and esophageal lesions. A leadless pH-metry capsule was inserted into the lower esophagus to screen for pH changes, number and duration of refluxes, and the DeMeester score (a standardized measure of acidity and reflux). No patient had a history of reflux or was taking proton pump inhibitors within 4 weeks before and 24 hours after ablation. Results: Five patients (16.1%) who presented with asymptomatic reflux prior to ablation were excluded from further examination. Of the remaining 26 patients, 5 (19.2%) demonstrated a significant pathologic increase in DeMeester score after ablation. No statistical differences in baseline parameters, method of sedation, ablation approach, and total energy delivered on the posterior wall were observed between patients with and those without a pathologic DeMeester score. One patient with asymptomatic reflux prior to ablation developed esophageal ulceration. Conclusion: A significant number of patients undergoing RFCA of AF develop pathologic acid reflux after ablation. In addition, a subgroup of patients has a preexisting condition of asymptomatic reflux prior to ablation. This finding may explain a potential mechanism for progression of esophageal injury to atrio-esophageal fistulas in patients undergoing RFCA. [Copyright &y& Elsevier]

• Diffusion parameters predicting performance on SDMT and BVMT tests could be well separated from those related to CVLT. • Patterns of diffusion parameters representing demyelination and axonal damage in certain spatial arrangements corresponds to cognitive dysfunctions. • About one quarter of the cognitive impairment's variance may be explained by putative axonal damage in MS, which has presumably little potential for regeneration. Cognitive decline is a prominent symptom of MS. Clear connection between cognitive status and white matter microstructural changes has not been unequivocally observed to date. To characterise the relationship between white matter microstructure and cognitive performance a partial least squares (PLS) approach was used. 53 RR MS patients' T1 and DTI images and BICAMS subtests were used in our analysis. Standard FSL pipeline was used to obtain diffusion parameters. A PLS approach was applied to reveal the diffusion parameter patterns responsible for the cognitive dysfunction. The first latent variable (LV) was mainly associated with demyelination, while the second and third explained axonal damage. While the first two LV represented mainly Brief Visuospatial Memory Test (BVMT) and Single Digit Modality Test (SDMT), the third LV depicted diffusion alterations mainly the verbal subtest. The first LVs spatial map showed demyelination in the corpus callosum. The second LVs spatial map showed the diffusion alterations in the thalamus. The third LV depicted diffusion alterations in the putative left superior longitudinal fascicle. Visual memory demanding tasks versus language functions depend on distinct patterns of diffusion parameters and the spatial organisation. Axial diffusivity alterations, a putative marker of irreversible axonal loss explained around 20% of variability in the cognitive functions. [ABSTRACT FROM AUTHOR]

Purpose To investigate irradiation techniques for simultaneous integrated boost (SIB) treatment of nasopharyngeal cancer (NPC) case in terms of organs at risk (OAR) toxicity and patient specific quality control (QC). This study is a part of an end-to-end audit programme for dose delivery using intensity modulated radiation therapy (IMRT). Methods CIRS SHANE Phantom was used to create four different treatment plans for a NPC patient. SIB schedule prescribes 54 Gy, 60 Gy and 70 Gy in 30 fractions for elective nodes (both sides), involved nodes (right side) and primary nasopharynx respectively, using 1, 2 or 3 arcs RapidArc (RA) or 7 field Sliding Window (SW) techniques. Patient specific quality control measurements were performed using EPID. Varian Portal Dosimetry was used with local gamma analysis using 2%/2 mm and 3%/3 mm criteria with 10% threshold. Results All plans met the criteria of dose to OARs: D 2% of the spinal cord and the brainstem on average were 35 Gy and 35.5 Gy; mean dose of the left parotid on average was 22.9 Gy. Patient specific QC was performed without any interruption. MUs for 1, 2, 3 arcs and 7 field SW were 602, 706, 696 and 2447, respectively. Gamma analysis on EPID images gave 96.2%, 96.2%, 96.7%, 82.6% and 98,8%, 98.9%, 99.3%, 92,1% passing rate on average for 2%/ 2 mm and 3%/ 3 mm criteria, respectively. Conclusions All treatment techniques are suitable for NPC irradiation with SIB in terms of OAR toxicity although RA with 2 or 3 arcs are more preferable in terms of number of MUs. [ABSTRACT FROM AUTHOR]