Ausiliatrice Lucenti

Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.

Objective to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients. Methods We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed. Results HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1–2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09–1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB− (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10−7) outside the HLA region (65 Mb). Discussion genetic factors predispose to the development of OCB.

Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: A survey clinic-based study

The aim of this study was to determine if blood chitotriosidase (Chit) activity and lysosomal enzyme levels might represent markers of disease activity and progression in amyotrophic lateral sclerosis (ALS). It is a survey clinic-based study performed in a tertiary ALS centre. Blood samples were obtained from 76 patients with ALS in different stages of the disease and from 106 healthy individuals serving as controls. Chit activity and the levels of acid alpha-glucosidase, acid alpha-galattosidase A, beta-glucocerebrosidase, and alpha-l-iduronidase were detected using the dried blood spots (DBS) technique. The CHIT1 genotype for exon 10 duplication and for the p.G102S variant was also determined. Chit activity was significantly higher in ALS patients than in healthy individuals. This difference was independent of the genotypes at CHIT1 functional variants. Chit were significantly higher in 34 rapidly progressing patients as compared to 42 with slowly progressive disease. Acid alpha-glucosidase was higher than normal and significantly correlated with the severity of the disease. Glucocerebrosidase and alpha-l-iduronidase activity were significantly lower in patients than in the controls. Alpha-galactosidase A was higher than normal only in rapidly progressing patients. We have employed a very simple and affordable laboratory test to measure blood Chit and lysosomal enzymes activity which could be easily included in the screening of ALS patients recruited in clinical trials. Remarkably, high levels of chitinase and alpha-galactosidase A could help to distinguish patients with fast progression from those with slow progression of the disease and possibly to follow the effects of treatments on neuroinflammation and autophagy.

A reliability study of colour-Doppler sonography for the diagnosis of chronic cerebrospinal venous insufficiency shows low inter-rater agreement

Objective Chronic cerebrospinal venous insufficiency (CCSVI) has been extremely variable, associated with multiple sclerosis in colour-Doppler sonographic studies. We aimed to evaluate inter-rater agreement in a colour-Doppler sonography venous examination. Design Inter-rater agreement study. Setting First-referral multiple sclerosis centre. Participants 38 patients with multiple sclerosis and 55 age-matched (±5 years) controls. Intervention Sonography was carried out in accordance with Zamboni’s five criteria by eight sonographers with different expertise, blinded to the status of cases and controls. Each participant was evaluated by two operators. Primary and secondary outcome measures Inter-rater agreement was measured through the κ statistics and the intraclass correlation coefficient. Results The agreement was no higher than chance for criterion 2—reflux in the deep cerebral veins (κ=−0.02) and criterion 4—flow not Doppler detectable in one or both the internal jugular veins (IJVs) or vertebral veins (VVs; −0.09). It was substantially low for criterion 1—reflux in the IJVs and/or VVs (0.29), criterion 3—IJV stenosis or malformations (0.23) and criterion 5—absence of IJV diameter increase when passing from the sitting to the supine position (0.22). The κ value for CCSVI as a whole was 0.20 (95% confidence limit −0.01 to 0.42). Intraclass correlation coefficients for the measure of cross-sectional area ranged from 0.05 to 0.25. Inter-rater agreement was low for CCSVI experts (κ=0.24; −0.11 to 0.59) and non-experts (0.20; −0.33 to 0.73); neurologists (0.21; −0.06 to 0.47) and non-neurologists (0.18; −0.20 to 0.56); cases (0.19; −0.14 to 0.52) and controls (0.21; −0.08 to 0.49). Zamboni-trained neurosonographers ascertained CCSVI more frequently than the non-trained neurosonographers. Conclusions Agreement was unsatisfactory for the diagnosis of CCSVI as a whole, for each of its five criteria and according to the different subgroups. Standardisation of the method is urgently needed prior to its further application in studies of patients with multiple sclerosis or other neurological diseases.

The role of comprehensive geriatric assessment and functional status in evaluating the patterns of antithrombotic use among older people with atrial fibrillation

Aim of the study is to investigate the use of antithrombotic drugs in older patients with atrial fibrillation (AF) at the time of hospital discharge. We enrolled 399 ≥65 years old patients with AF consecutively admitted to our acute geriatric unit from September 2012 to February 2014. Utilization of antithrombotic drugs, comorbidities, functional, mental and nutritional status were evaluated through a comprehensive geriatric assessment (CGA). A Logistic regression model was used to assess variables associated with antithrombotic use. On admission, 198 patients (49.6%) used oral anticoagulants (OAC), 125 (21.3%) antiplatelets, 32 (8%) low weight molecular heparin (LMWH) and 44 (11%) none of them. At discharge the proportion of patients on OAC increased to 55.7%. Age>90years (OR=2.57, CI=1.28-5.16, p-value=0.008), severe functional impairment (OR=3.38, CI=1.63-7.01, p-value=0.001), polypharmacy (OR=2.07, CI=1.1-3.86, p-value=0.023), HAS-BLED score (OR=1.64, CI=1.09-2.47, p-value=0.019) and ≥1 OAC contraindication (OR=5.01, CI=2.68-9.34, p-value<0.001) were all associated with OAC underuse. In conclusion, OAC is underused in geriatric patients with AF, while antiplatelet, LMWH and no antithrombotic therapy are relatively overused. Factors associated with the decision to not prescribe OAC lie on a mix of clinical and geriatric variables, among which functional status is particularly relevant.

Multiple sclerosis progression is not associated with birth timing in Italy.

BACKGROUND Month of birth has been associated in some studies with the susceptibility to develop Multiple Sclerosis (MS). However, only few studies have evaluated whether birth timing also affects disease progression. OBJECTIVES To assess whether season and month of birth are associated with disease progression in a large cohort of Italian patients. METHODS Quantile regression was used to analyze the impact of each month and season of birth with all the others combined on the median Multiple Sclerosis Severity Score of 1866 MS patients. RESULTS No significant temporal trend was found after adjustment for multiple comparisons. CONCLUSIONS Birth timing showed no association with MS progression in Italian patients.