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Maria Trojano

Publications and source records attributed to Maria Trojano.

At least 19 recordsLinked to original sources
PubMed2026

Big data in multiple sclerosis.

PURPOSE OF REVIEW: This review summarizes recent key advancements in multiple sclerosis (MS) achieved through the utilization of big data from diverse sources and advanced analytical techniques. RECENT FINDINGS: Real-world evidence (RWE) derived from MS big data has significantly enhanced treatment strategies, redefined the concept of disease progression, refined prognostic models, and facilitated personalized medicine. RWE has highlighted the long-term benefits of early intensive treatment compared to escalation strategies, the unfavorable risk profile associated with treatment de-escalation and the importance of managing treatments during pregnancy. Additionally, it has revealed similarities and differences in the effectiveness and safety of specific high-efficacy therapies, as well as key predictors for switching treatments. RWE has also emphasized the central role of progression independent of relapse activity as a significant driver of disability and predictor of unfavorable long-term outcomes in both adult and pediatric onset MS. A data-driven approach utilizing artificial intelligence and big data has established a comprehensive framework for understanding the disease's evolution. Multimodal big data frameworks - encompassing clinical data, MRI, genomics, biomarkers, and app-based metrics - have demonstrated their ability to enhance diagnostic performance and risk stratification in MS. SUMMARY: Big data approaches are transforming MS research and clinical practice by providing stronger RWE to guide therapeutic decision-making, refining models of disease progression, and developing more precise prognostic tools.

Humans↗
PubMed2007

Early prediction of the long term evolution of multiple sclerosis: the Bayesian Risk Estimate for Multiple Sclerosis (BREMS) score.

AIM: To propose a simple tool for early prediction of unfavourable long term evolution of multiple sclerosis (MS). METHODS: A Bayesian model allowed us to calculate, within the first year of disease and for each patient, the Bayesian Risk Estimate for MS (BREMS) score that represents the risk of reaching secondary progression (SP). RESULTS: The median BREMS scores were higher in 158 patients who reached SP within 10 years compared with 1087 progression free patients (0.69 vs 0.30; p<0.0001). The BREMS value was related to SP risk in the whole cohort (p<0.0001) and in the subgroup of 535 patients who had never been treated with immune therapies, thus reasonably representing the natural history of the disease (p<0.000001). CONCLUSIONS: The BREMS score may be useful both to identify patients who are candidates for early or for more aggressive therapies and to improve the design and analysis of clinical therapeutic trials and of observational studies.

Adult↗
PubMed2006

Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

Calcium-Binding Proteins↗
PubMed2006

Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort.

OBJECTIVES: A study of cognitive, psychological and social aspects in benign multiple sclerosis (MS). Methods One hundred and sixty three patients with benign MS (defined as disease duration > or = 15 years and Expanded Disability Status Scale (EDSS) score < or = 3.0 ) underwent neuropsychological testing on the Rao's Brief Repeatable Battery (BRB) and the Stroop test, evaluation of depression on the Montgomery and Asberg Depression Rating Scale (MADRS), of fatigue on the Fatigue Severity Scale (FSS) and of handicap on the Environmental Status Scale (ESS). Patients' cognitive performance was compared with that of 111 demographically matched healthy controls. Cognitive impairment was defined as the failure in at least 3 tests, using the fifth percentile of controls' performance as the cut-off point. Clinical correlates of cognitive impairment were determined by multiple logistic regression analysis. RESULTS: Cognitive assessment led to the identification of 74 subjects (45%) with cognitive impairment. Significant fatigue was found in 80 subjects (49%) and depression in 88 patients (54%). In comparison with cognitively preserved subjects, cognitively impaired patients exhibited higher handicap scores on the ESS (p = 0.005). In the regression analysis, only EDSS scores were significantly associated with cognitive impairment (OR 1.8, 95%CI 1.2-2.6). CONCLUSION: Current definitions of benign MS may overestimate this entity, since they are mainly weighted for the patients' motor abilities and fail to capture relevant disease-related cognitive, psychological and social problems.

Adult↗
PubMed2006

The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Adjuvants, Immunologic↗
PubMed2005

Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis.

There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of brain magnetic resonance imaging (MRI) lesions in MS patients. Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients. Seventy-three patients (36.5%) showed at least one enhancing lesion. Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004). The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age. Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p<0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions. This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.

Adult↗
PubMed2005

Osteopontin gene haplotypes correlate with multiple sclerosis development and progression.

Osteopontin (OPN) is an inflammatory cytokine highly expressed in multiple sclerosis (MS) plaques. In a previous work, we showed that four OPN polymorphisms form three haplotypes (A, B, and C) and that homozygotes for haplotype-A display lower OPN levels than non-AA subjects. In this work, we evaluated the distribution of these OPN haplotypes in 425 MS patients and 688 controls. Haplotype-A homozygotes had about 1.5 lower risk of developing MS than non-AA subjects. Clinical analysis of 288 patients showed that AA patients displayed slower switching from a relapsing remitting to a secondary progressive form and milder disease with slower evolution of disability. MS patients displayed increased OPN serum levels, which were partly due to the increased frequency of non-AA subjects. Moreover in AA patients, OPN levels were higher than in AA controls and similar to those found in both non-AA patients and controls, which suggests a role of the activated immune response. These data suggest that OPN genotypes may influence MS development and progression due to their influence on OPN levels.

Adult↗
PubMed2005

Dopamine fails to regulate activation of peripheral blood lymphocytes from multiple sclerosis patients: effects of IFN-beta.

The neurotransmitter dopamine counteracts T cell functions through its specific receptor subtype D5R but favors T cell proliferation and adhesion when acting on D3R. We found diminished mRNA and protein levels of D5R, but not of D3R, in peripheral blood mononuclear cells (PBMCs) from untreated multiple sclerosis (MS) patients. Dopamine reduced T cell proliferation, secretion of interferon-gamma (IFN-gamma), and production of matrix metalloproteinase-9 (MMP-9) mRNA in PBMCs from controls but not from MS patients. By contrast, reduced levels of D3R and renewed dopamine-associated regulatory functions were found in PBMCs from IFN-beta treated MS patients. Failure of the dopaminergic system of lymphocytes may lessen the threshold of T cell activation and sustain the pathogenic cascade of MS.

Adult↗
PubMed2005

Subclinical visual involvement in multiple sclerosis: a study by MRI, VEPs, frequency-doubling perimetry, standard perimetry, and contrast sensitivity.

PURPOSE: To evaluate the effectiveness of visual evoked potentials (VEPs), frequency-doubling perimetry (FDP), standard achromatic perimetry (SAP), contrast sensitivity (CS) test, and magnetic resonance imaging (MRI), isolated or in combination, in detecting subclinical impairment of visual function in multiple sclerosis (MS). METHODS: Twenty-two eyes of 11 patients affected by clinically definite MS, without a history of optic neuritis and asymptomatic for visual disturbances, underwent full ophthalmic examination and, in addition, VEPs, FDP, SAP, CS, and MRI. Abnormal results were taken to be as follows: for VEPs, a P100 latency >115 ms; for FDP, abnormal mean deviation (MD) or pattern SD (PSD); for SAP, abnormal MD or PSD; for CS, abnormal CS at one spatial frequency, at least; and for MRI, evidence of at least one demyelinating plaque along the visual pathway. RESULTS: VEPs showed abnormal results in 12 eyes (54.4%), FDP in 11 (50%), SAP in 14 (63.6%), CS in 17 (77.1%), and MRI in 16 (72.7%). In only two (9.1%) eyes of the same patient was no abnormality found. No single test detected all the abnormal eyes. Four (18.2%) eyes had pure optic nerve involvement and the remaining 16 (72.7%) had both pre- and postchiasmal involvement. CONCLUSIONS: In patients affected by clinically definite MS without history of optic neuritis and no visual symptoms, there is a large prevalence of visual pathway involvement that can be diagnosed only by performing multiple tests. The comparison of the tests is also useful to detect the presence of multiple lesions in the same patient.

Adolescent↗
PubMed2004

Clinical characteristics, course and prognosis of relapsing Devic's Neuromyelitis Optica.

OBJECTIVES: To evaluate the clinical characteristics, course and prognosis of Devic's neuromyelitis optica (DNO), to evaluate the prognostic role of demographic and clinical features, to evaluate the current DNO diagnostic criteria. METHODS: Demographic, clinical, CSF and MRI data of patients affected by DNO were collected from fifteen Italian MS centres. Inclusion criteria were: 1) two or more acute episodes of neurological dysfunction indicating involvement of the optic nerve and spinal cord, in a simultaneous or subsequent temporal relationship; 2) no evidence of lesions beyond the optic nerve or the spinal cord; 3) brain MRI at onset negative or non-specific for multiple sclerosis (MS) (white matter lesions < or = 2). Disability was scored by means of Kurtzke's Expanded Disability Status Scale (EDSS). RESULTS: 46 patients with relapsing DNO were included, 37 females and 9 males, with mean age at onset of 40.1 +/- 16.3 years (range 12-77 years). The follow up duration was 8.8 +/- 3.5 years, the mean annualised relapse rate was 1.3 +/- 1.2. After 5, 10 and 15 years EDSS 3.0 was reached respectively by 65%, 82 % and 86% of cases, EDSS 6.0 respectively by 42%, 53 % and 69% of cases, EDSS 10 respectively by 8%, 12% and 23% of cases. The probability of reaching EDSS 3 was statistically correlated with age at onset, interval between the first and 2(nd) attack, and relapse rate. The probability of reaching EDSS 6.0 was correlated with the residual EDSS at onset and to relapse rate. During the follow up, brain white matter lesions appeared in 8 subjects. Spinal cord MRI showed lesions extending across 3 or more segments in 39 subjects, only 1 lesion involving 1 segment in 4 subjects, and was normal in 3 subjects. One or more CSF abnormalities were found at least once in 29/44 patients (65.9 %), the most frequent findings being pleocytosis (38.6 %), oligoclonal bands (34.1 %), high protein level (25 %), and high albumin ratio (20.5 %). CONCLUSIONS: DNO has a poor prognosis in most cases. Compared with MS, DNO patients have a higher age at onset, females are more frequently affected, the course is more severe. Brain and spinal cord MRI permit the differentiation of DNO from MS. CSF supports the probability of DNO if it shows increased cells and proteins.

Adolescent↗
PubMed2004

Association between Synapsin III gene promoter polymorphisms and multiple sclerosis.

Although multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease, increasing evidence indicates that it is also an axonal pathology; indeed, studies of experimental allergic encephalitis showed that several neuronal proteins such as synapsins take part in the pathogenesis of the axonal dysfunction. Synapsins are a family of abundant neuron-specific phosphoproteins with crucial roles in synaptogenesis and neuronal plasticity. Distinct genes encode the three different isolated proteins (I, II and III); of interest, the gene of synapsin III (SYN3) is located in the chromosome 22q12-q13, a locus close to one of the candidate susceptibility regions (22q13.1) for MS. In the present study we selected two polymorphisms (g.-631C > G and g.-196A > G) within the SYN3 5'-promoter region because of the protein's role and genetic location; we analysed the allele and genotype distributions of these polymorphisms in a selected MS population of southern Italy. An inverse association between MS and the g-631C > G polymorphism was found; indeed, the two polymorphisms were in almost complete linkage disequilibrium and the haplotype analysis showed that the C631/A196 haplotype seemed to confer a significant protection against MS.

Adolescent↗
PubMed2004

Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-epsilon4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons. OBJECTIVE: To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS. METHODS: Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms. RESULTS: Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the epsilon4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable. CONCLUSION: The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.

Adult↗
PubMed2004

European validation of a standardized clinical description of multiple sclerosis.

OBJECTIVES: The EDMUS system is a clinical database specifically tailored to the description of multiple sclerosis (MS). The EVALUED (Evaluation of the EDMUS system) study is an European project with two objectives: 1) to assess the inter-examiner reliability of the whole EDMUS system; 2) to validate the EDMUS-Grading Scale (EGS),which is a simplified version of the Kurtzke Disability Status Scale (DSS). METHODS: The protocol included 12 neurologists working in pairs within six European centres (Bari, Basel, Florence, London, Lyon, Würzburg). They assessed independently 30 MS patients in their centre, filling in the EDMUS forms. The reliability of the system was assessed on selected key items in the history of the MS onset, the clinical course and the disease course classification. The clinical examination of the patients permitted an assessment of the Kurtzke Expanded Disability Status Scale (EDSS) and the EGS. Level of agreement was measured in terms of kappa and weighted kappa indexes whenever appropriate. RESULTS: The study included 180 patients with definite or probable MS of whom 37% were males. Age was 35.8+/-9.6 years (mean +/- SD), disease duration 7.8+/-5.7 years, and mean EDSS score 4.1+/-2.2. The disease course was relapsing-remitting in 67%, secondary progressive in 22%, and progressive from disease onset in 11%. For key items of the history, the inter-examiner reliability level ranged from moderate to excellent. Concerning the disability scales, perfect agreement was reached in 59 % for EDSS and 78% for EGS. The close correlation and linear association (r=0.94, p<0.0001) between both scales demonstrated EGS's construct validity. CONCLUSION: The EDMUS system allows a consistent clinical description of MS using a common language. This standardized follow-up of MS patients is valuable especially in studies requiring a critical mass of informative patients.

Adult↗
PubMed2004

Can databasing optimise patient care?

Long-term, prospective databasing of multiple sclerosis (MS) information provides a useful resource for natural history studies. Furthermore, it is the only way to address the question of whether early treatment eliminates or delays the inevitable and irreversible clinical worsening that is the hallmark of the late phase of the illness. Due to the variable nature of MS, it is useful to monitor large numbers of individuals over time. The limitations of single databases may be overcome by regional, national or international pooling of data. In this paper, the Italian Multiple Sclerosis Database Network (MSDN) and the international web-based MSBase registry are described.

Adult↗
PubMed2004

Post-receptorial mechanisms underlie functional disregulation of beta2-adrenergic receptors in lymphocytes from Multiple Sclerosis patients.

Increased density of beta2-adrenergic receptors has been demonstrated on peripheral blood mononuclear cells (PBMCs) from Multiple Sclerosis (MS) patients. In this study we found that isoproterenol reduces T-cell proliferation and IFNgamma secretion in PBMCs cultures from healthy controls and IFNbeta-treated but not untreated MS patients. Reduced expression levels of G protein coupled receptor kinase (GRK)2/3 (p < 0.05) and increased isoproterenol-induced cAMP accumulation (p < 0.0001) were found in PBMCs from all MS patients. Dibutyryl cAMP reduced the proliferation of PBMCs from all subgroups but in a slighter manner in untreated MS patients. We conclude that signalling through beta2-adrenergic receptors is chronically up-regulated but functionally uncoupled to immunoregulatory functions of lymphocytes from MS patients. Disregulation downstream the cAMP-associated signalling may underlie such a phenomenon.

Adrenergic beta-Agonists↗
PubMed2003

Genetic interaction of CTLA-4 with HLA-DR15 in multiple sclerosis patients.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family-based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119-122

Abatacept↗
PubMed2003

Apolipoprotein E genotype does not influence the progression of multiple sclerosis.

OBJECTIVE: To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS. METHODS: We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the -491 A/T polymorphism of the APOE promoter were determined. RESULTS: No association was observed between the APOE epsilon4 allele and clinical characteristics of our study population. We also investigated the -491 A/T APOE promoter polymorphism in 236 MS subjects and did not find any association between the -491 A/T polymorphism and the selected clinical variables. CONCLUSIONS: In our population the APOE epsilon4 allele and the -491 A/T APOE promoter polymorphism are not associated with a more rapid course of MS.

Adolescent↗