Serum IgG against Simian Virus 40 antigens are hampered by high levels of sHLA-G in patients affected by inflammatory neurological diseases, as multiple sclerosis

Background: Many investigators detected the simian polyomavirus SV40 footprints in human brain tumors and neurologic diseases and recently it has been indicated that SV40 seems to be associated with multiple sclerosis (MS) disease. Interestingly, SV40 interacts with human leukocyte antigen (HLA) class I molecules for cell entry. HLA class I antigens, in particular non-classical HLA-G molecules, characterized by an immune-regulatory function, are involved in MS disease, and the levels of these molecules are modified according with the disease status. Objective: We investigated in serum samples, from Italian patients affected by MS, other inflammatory diseases (OIND), non-inflammatory neurological diseases (NIND) and healthy subjects (HS), SV40-antibody and soluble sHLA-G and the association between SV40-prevalence and sHLA-G levels. Methods: ELISA tests were used for SV40-antibodies detection and sHLA-G quantitation in serum samples. Results: The presence of SV40 antibodies was observed in 6 % of patients affected by MS (N = 4/63), 10 % of OIND (N = 8/77) and 15 % of NIND (N = 9/59), which is suggestive of a lower prevalence in respect to HS (22 %, N = 18/83). MS patients are characterized by higher sHLA-G serum levels (13.9 \ub1 0.9 ng/ml; mean \ub1 St. Error) in comparison with OIND (6.7 \ub1 0.8 ng/ml), NIND (2.9 \ub1 0.4 ng/ml) and HS (2.6 \ub1 0.7 ng/ml) subjects. Interestingly, we observed an inverse correlation between SV40 antibody prevalence and sHLA-G serum levels in MS patients. Conclusion: The data obtained showed a low prevalence of SV40 antibodies in MS patients. These results seems to be due to a generalized status of inability to counteract SV40 infection via antibody production. In particular, we hypothesize that SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory HLA-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides

Multiple sclerosis and HERV-W/MSRV: A multicentric study

We designed a large multicentric study to analyse the presence of MSRV particles in blood and CSF of a large cohort of patients and controls from different European areas. 149 MS patients and 153 neurological and healthy controls were selected from Sardinia, Spain, Northern-Italy and Sweden. To avoid biological and inter-assay variability MSRV was detected within a single laboratory through nested and real-time PCR assays specific for pol and env genes. MSRV detection in blood and CSF of MS patients and controls in populations of different ethnicity gave significant differences (p<0.05 compared to neurological controls and <0.001 compared to healthy controls). The presence and viral load of MSRV are significantly associated with MS as compared to neurological and healthy controls in all ethnic groups

Added value of multiphase CTA imaging for thrombus perviousness assessment

Purpose: Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. Methods: Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). Results: TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04–1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01–1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919–1.19, AUC 0.53, p = 0.50)), and TiCTA (1.15(95%CI 1.02–1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein-Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing-remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis (p &lt; 0.0001) and NIND (p &lt; 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND (p &lt; 0.01) and in OIND than in NIND (p &lt; 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis (p &lt; 0.05) and in MRI inactive than in MRI active multiple sclerosis (p &lt; 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND (p &lt; 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively (p &lt; 0.05) and inversely (p &lt; 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis

Prevalence of anti-parkinson drugs use in Ferrara, Northern Italy, 1988

reserved7noINTRODUCTION: The period prevalence rate for anti-parkinson drugs (APD) use was reported in the Local Health Service of Ferrara (USL 31), Northern Italy, in 1988 (resident population: 177,000 inhabitants). MATERIAL AND METHODS: The study was performed through the analysis of the complete list of APD prescriptions in the USL 31 area provided by the computerized archives of USL 31 and the identification code of the patients which is unique for each resident of USL 31. The patients treated with neuroleptics known to be potential parkinsonism-inducing drugs were excluded. RESULTS: The period prevalence rate for APD users was 456.9 per 100,000 population. The prevalence rate for dopa derivatives users was 391.3 per 100,000. The prevalence did not varied between rural and urban zones of USL 31 both for APD and dopa derivatives users. A higher prevalence was obtained in a small rural commune of USL 31 both for APD users (758.5 per 100,000) and dopa derivatives users (718.6 per 100,000) than in the other 4 communes in which the study area is subdivided. CONCLUSION: The reported prevalence could provide information on the occurrence of most parkinsonisms in the study area and some suggestion on the role of possible environmental factors.mixedGOVONI V.; E. GRANIERI; TOLA MR.; CASETTA I.; MONETTI VC.; FAINARDI E.; PAOLINO E.Govoni, V.; Granieri, Enrico Gavino Giuseppe; Tola, M. R.; Casetta, I.; Monetti, V. C.; Fainardi, E.; Paolino, E

Quantification of CSF and serum levels and intrathecal synthesis of anti-EBV antibodies in patients with multiple sclerosis and with other neurological disorders.

none9Purpose: Epidemiological studies suggest that Multiple Sclerosis (MS) pathogenesis could be related to an infection superimposed on a predisposing genetic background. Epstein-Barr virus (EBV) is currently considered to be the most plausible candidate for MS autoimmunity since seroepidemiological studies have demonstrated that EBV seropositivity is more frequent in MS than in controls whereas the risk of developing MS is increased by the presence of elevated serum levels of EBV-specific antibodies and a history of EBV-induced mononucleosis. In addition, high concentrations of anti-EBV antibodies have been found in CSF and blood of MS patients. Considering these observations, the aim of our study was to investigate CSF and serum levels and the presence of an intrathecal synthesis of anti-EBV IgG in MS and controls. Materials and methods: We measured by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-EBV IgG in 80 relapsing-remitting (RR) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Eighty-six patients with other inflammatory neurological disorders (OIND) and 67 with non-inflammatory neurological disorders (NIND) served as neurological controls. Anti-EBV nuclear antigen-1 (EBNA-1) and anti viral capsid antigen (VCA) IgG levels were expressed as arbitrary units and quantitative intrathecal synthesis of anti-EBNA and anti-VCA IgG was determined by Antibody Specific Index (ASI). After checking data for normality, statistical analysis was performed by Kruskal-Wallis test, followed by Mann-Whitney U test, to compare mean values among the various groups of patients. Chi-square test (χ2) was used to compare the patient group percentages. Bonferroni correction was utilized for multiple comparisons. Results: Detectable levels of CSF and serum anti-EBNA-1 IgG and serum anti-VCA IgG were equally represented in MS, OIND and NIND, whereas measurable CSF concentrations anti-VCA IgG were more frequent in OIND than in MS (p < 0.0001) and NIND (p < 0.001) and equivalent in MS and NIND. CSF and serum mean levels of anti-EBNA-1 IgG were different among the groups of patients examined (p < 0.02 and p < 0.001, respectively). While CSF mean values were higher in MS than in NIND (p < 0.02), serum mean concentrations were greater in MS than in OIND and NIND (p < 0.001 and p < 0.02, respectively). CSF and serum mean levels of anti-VCA IgG were also different among the patient groups analyzed (p < 0.0001 and p < 0.05, respectively). CSF mean values were more elevated in OIND than in MS (p < 0.0001) and NIND (p < 0.02), whereas serum mean titers were increased in OIND than in MS (p < 0.05). In addition, serum mean levels of anti-VCA IgG were more prominent in MRI inactive than in MRI active MS (p < 0.0001). ASI values suggestive of an intrathecal synthesis of anti-EBNA-1 and of anti-VCA IgG were present in a small proportion of MS (6.3% and 2.5%, respectively), OIND (3.5% in both cases) and NIND (1.5 and 0%, respectively), without any significant differences among the various group explored. Conclusions: These findings do not seem to support a crucial role of an intrathecal humoral immune response to EBV in MS pathogenesis. However, the altered anti-EBV antibody production detected in MS for CSF anti-EBNA-1 IgG and serum anti-VCA IgG remains to be clarified. On the other hand, elevated CSF levels of anti-VCA IgG found in OIND are probably blood-derived because they are related to the more frequent occurrence of blood-brain barrier dysfunction. Work supported by FISM (2008-R-12) and by Programma di ricerca Regione-Università 2007-2009.noneCastellazzi M; Tamborino C; Cani A; Negri E; Baldi E; Seraceni S; Contini C; Granieri E; Fainardi E.Castellazzi, Massimiliano; Tamborino, Carmine; Cani, Alice; Negri, E; Baldi, Eleonora; Seraceni, Silva; Contini, Carlo; Granieri, Enrico Gavino Giuseppe; Fainardi, Enric