Lorena Lorefice - Academia.edu (original) (raw)

Papers by Lorena Lorefice

Journal of neurology, 2018

Few studies have evaluated the impact of physical activity (PA) on cognition and fatigue, and non... more Few studies have evaluated the impact of physical activity (PA) on cognition and fatigue, and none have considered the effects of PA on the relationship between cognition and fatigue. We evaluated the effect of PA in people with multiple sclerosis (pwMS) in a 6-month-long single-blind randomized controlled trial. We focused on the impact of exercise on cognition, fatigue, and the relationship between cognition and fatigue. We recruited pwMS, who were then randomly assigned 1:1 to either a PA protocol group or a control group (CG). All patients underwent assessments using the Brief International Cognitive Assessment for Multiple Sclerosis including symbol digit modality test (SDMT), Berg Balance Scale (BBS), gait analysis, 6-Minute Walk Test, Timed Up and Go (TUG) test, and the Modified Fatigue Impact Scale (MFIS) at the beginning of the study (T0), at the end of the study (EOS) 24 weeks after T0, and at 24 weeks following the EOS (FU). A Wilcoxon test revealed a significant effect o...

Multiple sclerosis (Houndmills, Basingstoke, England), 2015

Recent studies identified > 100 non-HLA (human leukocyte antigen) multiple sclerosis (MS) susc... more Recent studies identified > 100 non-HLA (human leukocyte antigen) multiple sclerosis (MS) susceptibility variants in Northern European populations, but their role in Southern Europeans is largely unexplored. We aimed to investigate the cumulative impact of those variants in two Mediterranean populations: Continental Italians and Sardinians. We calculated four weighted Genetic Risk Scores (wGRS), using up to 102 non-HLA MS risk variants and 5 HLA MS susceptibility markers in 1691 patients and 2194 controls from continental Italy; and 2861 patients and 3034 controls from Sardinia. We then assessed the differences between populations using Nagelkerke's R(2) and the area under the Receiver Operating Characteristic (ROC) curves. As expected, the genetic burden (mean wGRS value) was significantly higher in MS patients than in controls, in both populations. Of note, the burden was significantly higher in Sardinians. Conversely, the proportion of variability explained and the predict...

Multiple Sclerosis Journal, 2015

A 39-year-old woman was admitted to hospital because of a sensory hemisyndrome caused by a contra... more A 39-year-old woman was admitted to hospital because of a sensory hemisyndrome caused by a contrast-enhancing demyelinating lesion of the cervical cord. MRI, CSF examination and subsequent clinical and neuroradiological follow-up led to the diagnosis of multiple sclerosis. The patient had noticed an involuntary contraction of a small muscle fascicle on the right side of the chin for a year. Electromyographic and video recordings confirmed the synkinesis between the orbicularis oculi and lower facial muscles, a finding distinct from the myokymic discharges reported in multiple sclerosis and more similar to the synkinesis associated with hemifacial spasm.

Multiple Sclerosis Journal, 2014

Background and objective: A critical aspect of multiple sclerosis (MS) treatments is understandin... more Background and objective: A critical aspect of multiple sclerosis (MS) treatments is understanding the effect of disease-modifying drugs (DMDs) on the long-term risk of disability and whether the effect is related to disability at start of treatment.

Inflammation & Allergy-Drug Targets, 2014

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. It is char... more Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. It is characterized by a proinflammatory and neurodegenerative process that results in neuroaxonal damage. Over the last two decades, a wide range of immunomodulatory and immunosuppressive treatments have been used for the management of MS. Several treatments have been developed or are under evaluation for reducing relapses, disease progression and long-term MS-related disability. Recently, a growing interest has emerged for therapeutics with very selective actions, particularly monoclonal antibodies, to target several biological pathways involved in MS. To date, only Natalizumab (Tysabri(®)) has been approved for the treatment of active MS forms. Its therapeutic mechanism is the blockade of the a4-integrin molecule of many leukocytes, which leads to a decrease of immune cells migration, in particular of lymphocytes, across the blood-brain barrier. Furthermore, other promising molecules are under study in clinical trials. In this review, we summarize and discuss the history, pharmacodynamics and safety of monoclonal antibodies that have been approved or are under evaluation for the selective treatment of MS.

Journal of the Neurological Sciences, 2015

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recentl... more Background: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. Objectives: The objectives of this study were to confirm this association and evaluate its role in clinical features. Methods: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). Results: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10 −11 ), and 123 MS and 10 HCs (p = 2.59 × 10 −23 ), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). Conclusion: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.

PLoS ONE, 2013

We performed a case-control study in 2,555 multiple sclerosis (MS) Sardinian patients and 1,365 h... more We performed a case-control study in 2,555 multiple sclerosis (MS) Sardinian patients and 1,365 healthy ethnically matched controls, analyzing the interactions between HLA-DRB1-DQB1 haplotypes and defining a rank of genotypes conferring a variable degree of risk to the disease. Four haplotypes were found to confer susceptibility (*13:03-*03:01 OR = 3.3, Pc 5.1610 25 , *04:05-*03:01 OR = 2.1, Pc 9.7610 28 , *15:01-*06:02 OR = 2.0, Pc = 9.1610 23 , *03:01-*02:01 OR = 1.7 Pc = 7.9610 222 ) and protection (*11, OR = 0.8, Pc = 2.7610 22 , *16:01-*05:02 OR = 0.6, Pc = 4.8610 216 , *14:01-4-*05:031 = OR = 0.5, Pc = 9.8610 24 and *15:02-*06:01 OR = 0.4, Pc = 5.1610 24 ). The relative predispositional effect method confirms all the positively associated haplotypes and showed that also *08 and *04 haplotypes confers susceptibility, while the *11 was excluded as protective haplotype. Genotypic ORs highlighted two typologies of interaction between haplotypes: i) a neutral interaction, in which the global risk is coherent with the sum of the single haplotype risks; ii) a negative interaction, in which the genotypic OR observed is lower than the sum of the OR of the two haplotypes. The phylogenic tree of the MS-associated DRB1 alleles found in Sardinian patients revealed a cluster represented by *14:01, *04:05, *13:03, *08:01 and *03:01 alleles. Sequence alignment analysis showed that amino acids near pocket P4 and pocket P9 differentiated protective from predisposing alleles under investigation. Furthermore, molecular dynamics simulation performed on alleles revealed that position 70 is crucial in binding of MBP 85-99 peptide. All together, these data suggest that propensity to MS observed in Sardinian population carried by the various HLA-DRB1-DQB1 molecules can be due to functional peculiarity in the antigen presentation mechanisms.

PLoS ONE, 2012

Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated a... more Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.

Neurological Sciences, 2014

There is an urgent need to identify the best strategies to prevent the loss of natalizumab (N) be... more There is an urgent need to identify the best strategies to prevent the loss of natalizumab (N) beneficial effects after its suspension. The objective is to evaluate the clinical and radiological disease activity and to test the efficacy of immunomodulatory/immunosuppressive drugs (IT) after N suspension. Clinical and radiological data from 54 patients 2 years before treatment (pre-N), during treatment (on-N) and after interruption, during 1-year follow-up (post-N) were retrospectively collected. Annualized relapse rate (ARR), expanded disability status scale (EDSS), presence of new T2 lesions and Gd+ (gadolinium enhancing) T1 lesions were evaluated. Pre-N ARR at 1 year was 1.74 while post-N ARR was 0.94 (p = 0.0053). We observed that post-N disease activity never raised over pre-N levels, neither post-N ARR nor post-N EDSS. In patients retreated with N after suspension, post-N ARR was significantly lower than pre-N ARR (p = 0.017), but not in patients treated with other IT or in patients not treated with any disease modifying drugs (DMD). The mean time of freedom from new T2 lesions and new Gd+ lesions was lower in post-N period compared to on-N (T2 lesions p = 0.0000, Gd+ lesions p = 0.0000). In conclusion, a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;rebound&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; pattern was not identified in our cohort, though the disease activity rapidly returned after N, regardless of the treatment used.

Multiple Sclerosis Journal, 2011

Background: Sardinia is a known high-risk area for multiple sclerosis (MS), but no data for south... more Background: Sardinia is a known high-risk area for multiple sclerosis (MS), but no data for south-western Sardinia (SWS) are available. SWS has a genetically homogeneous population, apart from St Peter Island, and represents a peculiar environment related to the industrial, mineralogical and military economy. Objective: To estimate prevalence and incidence and to evaluate temporal trends and geographical distribution of MS in SWS. Methods: MS prevalence was evaluated on 31 December 2007 and crude mean annual incidence rate was defined between 2003 and 2007. Temporal trend in MS incidence was assessed using the Armitage test. To identify MS clusters, Standard Morbidity Ratio (SMR) was calculated for each village and geographical distribution prevalence by means of a Bayesian hierarchical model. Results: Total crude prevalence rate was 210.4 (95% CI 186.3-234.5): 280.3 (95% CI 241.4-319.3) for females, 138 (95% CI 110.1-165.8) for males. The crude mean annual incidence rate was 9.7/100,000 (95% CI 3.4-13.2): 4.7/100,000 (95% CI 2.4-17.0) and 14.6/100,000 (95% CI 11.8-34.8) for males and females respectively. MS incidence has increased over the last 50 years. Cluster analysis showed an SMR of 0.2 (95% CI 0.05-0.68, p ¼ 0.002) on the island of San Pietro, and 2.0 (95% CI 1.35-2.95, p ¼ 0.001) in Domusnovas. Spatial distribution of MS was confirmed by Bayesian geographical analysis. Conclusions: Our data confirm Sardinia as a high-risk area for MS and support the relevance of genetic factors in MS, as evidenced in St Peter Island. However, we found an unexpectedly high MS prevalence in one village, in particular in males, suggesting an environmental influence on MS occurrence.

BMC Neurology, 2013

Background: Multiple sclerosis (MS) has a major impact on the physical, psychological and social ... more Background: Multiple sclerosis (MS) has a major impact on the physical, psychological and social life of patients and their families. The aim of this study was to evaluate the different perceptions of patients and caregivers about management of MS, particularly about the same items, to gather information to ameliorate the care of patients.