Publications by authors named "Lorena Lorefice"

53 Publications

MRI activity and extended interval of Natalizumab dosing regimen: a multicentre Italian study.

J Neurol Sci 2021 May 6;424:117385. Epub 2021 Mar 6.

Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy.

Background: To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID).

Methods: Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: <5 weeks, SID; ≥5 weeks, EID.

Results: One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84-7.70) vs 4.71% (95% CI:0.16-9.25%) [p = 0.89] and 8.50% (95% CI:4.05-12.95) vs 6.55% (95% CI:2.11-11.00%) [p = 0.56]. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up.

Conclusion: There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.
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http://dx.doi.org/10.1016/j.jns.2021.117385DOI Listing
May 2021

Does Multiple Sclerosis Differently Impact Physical Activity in Women and Man? A Quantitative Study Based on Wearable Accelerometers.

Int J Environ Res Public Health 2020 11 28;17(23). Epub 2020 Nov 28.

Department of Medical Sciences and Public Health, University of Cagliari, 09123 Cagliari, Italy.

In people with multiple sclerosis (pwMS), fatigue, weakness and spasticity may reduce mobility and promote sedentary behavior. However, little is known about the existence of possible differences in the way MS modifies the propensity to perform physical activity (PA) in men and women. The present study aimed to partly close this gap by means of quantitative analysis carried out using wearable sensors. Forty-five pwMS (23 F, 22 M, mean age 50.3) and 41 unaffected age- and sex-matched individuals wore a tri-axial accelerometer 24 h/day for 7 consecutive days. Raw data were processed to calculate average number of daily steps, vector magnitude (VM) counts, and percentage of time spent in sedentary behavior and in PA of different intensities (i.e., light and moderate-to-vigorous, MVPA). Women with MS spent more time in sedentary behavior and exhibited a reduced amount of light intensity activity with respect to men, while MVPA was similar across sexes. However, in comparison with unaffected individuals, the overall PA patterns appear significantly modified mostly in women who, in presence of the disease, present increased sedentary behavior, reduced MVPA, number of daily steps and VM counts. The findings of the present study highlight the urgency of including sex as variable in all studies on PA in pwMS.
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http://dx.doi.org/10.3390/ijerph17238848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729610PMC
November 2020

Risk attitude and personality in people with multiple sclerosis facing the choice of different disease-modifying therapy scenarios.

J Neurol Sci 2020 Oct 28;417:117064. Epub 2020 Jul 28.

Department of Neurology, San Raffaele Hospital Scientific Institute, Milan, Italy. Electronic address:

Background: As available disease-modifying therapies (DMTs) increase, evaluating benefit/risk presents greater difficulties, requiring people with MS (PwMS) to play crucial roles in choosing treatment. Although individual attitude toward risk may predict this evaluation, its relation to personality is little studied in MS literature.

Objective: To prospectively assess risk attitudes and personality traits of PwMS choosing a DMT.

Methods: In three Italian MS centers (2012-2015), 420 PwMS completed an ad hoc questionnaire on socio-demographic variables, personality, and standard-gamble questions, to evaluate MS- and DMT-related risks through two hypothetical drug scenarios. We assessed the influence of previously collected socio-demographic/clinical characteristics, and personality factors on risk attitude.

Results: Almost half of participants were mainly concerned about progressive multifocal leukoencephalopathy; <25% about relapses. Median acceptable risk of death for both hypothetical drug scenarios was 1:10,000; 19-20% would not take any risk related to DMT. Regression analysis revealed that being male, more educated, and with higher impulsivity/sensation-seeking propensity was significantly associated with a higher risk attitude.

Conclusions: Both socio-demographic and personality factors affect risk attitude of PwMS facing different DMT scenarios. These findings could affect the shared decision-making process in selecting best treatment option for PwMS.
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http://dx.doi.org/10.1016/j.jns.2020.117064DOI Listing
October 2020

Harmonization of real-world studies in multiple sclerosis: Retrospective analysis from the rirems group.

Mult Scler Relat Disord 2020 Oct 12;45:102394. Epub 2020 Jul 12.

Rehabilitation Department, Mons. L. Novarese, Moncrivello, Vercelli, Italy.

Background: Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies. In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group.

Methods: RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ).

Results: Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p = 0.02; τ=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p = 0.02; τ=1.00).

Discussion: We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.
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http://dx.doi.org/10.1016/j.msard.2020.102394DOI Listing
October 2020

Multi-Platform Characterization of Cerebrospinal Fluid and Serum Metabolome of Patients Affected by Relapsing-Remitting and Primary Progressive Multiple Sclerosis.

J Clin Med 2020 Mar 21;9(3). Epub 2020 Mar 21.

Department of Biomedical Sciences, Clinical Metabolomics Unit, University of Cagliari, 09121 Cagliari, Italy.

Background: Multiple sclerosis (MS) is a chronic immunemediated disease of the central nervous system with a highly variable clinical presentation and disease progression. In this study, we investigate the metabolomics profile of patients affected by relapsing-remitting MS (RRMS)and primary progressive MS (PPMS), in order to find potential biomarkers to distinguish between the two forms.

Methods: Cerebrospinal Fluid CSF and blood samples of 34 patients (RRMS = 22, PPMS = 12) were collected. Nuclear magnetic resonance (H-NMR) and mass spectrometry (coupled with a gas chromatography and liquid chromatography) were used as analytical techniques. Subsequently, a multivariate statistical analysis was performed; the resulting significant variables underwent U-Mann-Whitney test and correction for multiple comparisons. Receiver Operating Characteristic ROC curves were built and the pathways analysis was conducted.

Results: The analysis of the serum and the CSF of the two classes, allowed the identification of several altered metabolites (lipids, biogenic amines, and amino acids). The pathways analysis indicated the following pathways were affected: Glutathione metabolism, nitrogen metabolism, glutamine-glutamate metabolism, arginine-ornithine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis etc. Conclusion: The analysis allowed the identification of a set of metabolites able to classify RRMS and PPMS patients, each of whom express different patterns of metabolites in the two biofluids.
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http://dx.doi.org/10.3390/jcm9030863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141510PMC
March 2020

The impact of modifiable risk factors on lesion burden in patients with early multiple sclerosis.

Mult Scler Relat Disord 2019 Dec 9;39:101886. Epub 2019 Dec 9.

MS Centre, Department of Medical Sciences and Public Health, University of Cagliari, Italy.

Introduction: Some studies have indicated the importance of considering smoking, vitamin D deficiency and obesity as negative prognostic factors for clinical and MRI outcomes in multiple sclerosis (MS). This study aimed to evaluate the possible effects of these modifiable risk factors on brain MRI lesion burden of patients with early MS, also exploring the influence on initial clinical features.

Methods: MS patients were enrolled at diagnosis time and examined for smoking, body mass index (BMI), serum level of lipids and 25(OH) vitamin D. Brain MRIs' were acquired and lesion volume assessed by Jim software. Clinical data (disease course, disease duration, and EDSS score) were also collected.

Results: 64 patients were enrolled, of these 4 (6.2%) had a primary progressive course. Mean age was 39.8 ± 11.1 years and mean EDSS 1.5 ± 1.1. Forty (62.5%) patients were smokers and 40 (62.5%) were overweight (BMI>25). Insufficient levels of vitamin D (<20 ng/mL) were reported in 36 (56.2%) patients, while 24 (37.5%) patients had an altered lipid profile with total cholesterol >200 mg/dl and LDL >100 mg/dl. No association between early clinical features and modifiable risk factors were reported. Multiple regression analysis showed an association between lesion burden and smoking status (p 0.003), while no association was reported with BMI, altered lipid profile and vitamin D insufficiency.

Conclusions: Several risk factors may play a role in evolution of MS. Our results show that smoking status, probably due to chronic vascular and neurotoxic effects of the cigarette components, can affect the brain damage from the early stages of MS. No association was observed with the other explored modifiable risk factors, although an effect due to the small sample size cannot be excluded.
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http://dx.doi.org/10.1016/j.msard.2019.101886DOI Listing
December 2019

Is There Any Relationship between Upper and Lower Limb Impairments in People with Multiple Sclerosis? A Kinematic Quantitative Analysis.

Mult Scler Int 2019 9;2019:9149201. Epub 2019 Oct 9.

Department of Mechanical, Chemical and Materials Engineering, University of Cagliari, Cagliari, Italy.

Background: In people with multiple sclerosis (pwMS), disability is generally assessed on the basis of ambulation abilities, whereas upper limb motor dysfunctions are less frequently considered. Nevertheless, they can severely affect the quality of life of pwMS. To date, it remains mostly unknown whether a relationship exists between upper and lower limb impairments.

Aim: To investigate the existence of a relationship between upper and lower limb impairments in pwMS based on two fundamental motor tasks, namely walking and hand-to-mouth (HTM) movement.

Methods: Twenty-eight pwMS with Expanded Disability Status Scale (EDSS) scores in the range of 1-6, and 21 healthy controls (HC) underwent a kinematic analysis of gait and HTM movement performed with a motion capture system. The spatiotemporal parameters for the two tasks were calculated and correlated using Spearman's rank correlation coefficients.

Results: The pwMS performed worse than HC on both tasks. Small to large correlations were found between the total HTM movement duration and most of the gait parameters (rho, 0.35-0.68; < 0.05).

Conclusions: Both upper and lower limb motor abilities in pwMS worsen as disability increases. Nevertheless, their relationship is only moderate. This finding emphasizes the need for specific tests to quantify disability considering the overall motor function in pwMS.
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http://dx.doi.org/10.1155/2019/9149201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803720PMC
October 2019

Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study.

Mult Scler Relat Disord 2020 Jan 19;37:101461. Epub 2019 Oct 19.

Rehabilitation Department, Mons. L. Novarese, Moncrivello, Vercelli, Italy.

Background: The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study.

Methods: Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data.

Results: Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier.

Conclusion: MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.
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http://dx.doi.org/10.1016/j.msard.2019.101461DOI Listing
January 2020

Treatment of multiple sclerosis with rituximab: A multicentric Italian-Swiss experience.

Mult Scler 2020 10 1;26(12):1519-1531. Epub 2019 Oct 1.

SCDO Neurologia e Centro di Riferimento Regionale Sclerosi Multipla, AOU San Luigi, Orbassano, Italy.

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS).

Objective: To investigate the effectiveness and safety of rituximab in relapsing-remitting (RR) and progressive MS.

Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed.

Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09,  < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06,  < .0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07,  = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose.

Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.
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http://dx.doi.org/10.1177/1352458519872889DOI Listing
October 2020

Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Neurotherapeutics 2020 01;17(1):200-207

Multiple Sclerosis Center, Spedali Civili of Brescia, Presidio di Montichiari, Brescia, Italy.

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and sixty patients were enrolled. Median dose interval (MDI) following 24th infusion was 4.7 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Two hundred and sixteen patients were in the SID group (MDI = 4.3 weeks) and 144 in the EID group (MDI 6.2 weeks). Annualized relapse rate was 0.060 (95% CI = 0.033-0.087) in the SID group and 0.039 (95% CI = 0.017-0.063) in the EID group. The non-inferiority of EID versus SID was satisfied. In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID, supports the need of a randomized study to assess the need to change the standard of the natalizumab dosing schedule.
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http://dx.doi.org/10.1007/s13311-019-00776-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007494PMC
January 2020

Efficacy and safety of alemtuzumab in a real-life cohort of patients with multiple sclerosis.

J Neurol 2019 Jun 12;266(6):1405-1411. Epub 2019 Mar 12.

Multiple Sclerosis Center, University of Cagliari/ATS Sardegna, Via Is Guadazzonis, 2, 09126, Cagliari, Italy.

Background: No postmarketing randomised clinical trials are available about alemtuzumab, and real-world data are limited. We aimed to analyse the efficacy and safety of alemtuzumab in a single-centre cohort of patients with relapsing-remitting MS.

Methods: Patients who took alemtuzumab were enrolled. We collected the following data: age, sex, MS history, expanded disability status scale (EDSS), relapses, magnetic resonance imaging (MRI) parameters after alemtuzumab, and adverse events. EDSS scores before alemtuzumab and at the last follow-up were compared by Wilcoxon test. Time to first relapse was analysed after dividing the cohort on the basis of previous treatment.

Results: Ninety patients were enrolled [women 74.4%; naïve 7; mean follow-up 27 months (SD 23)]. The EDSS was reduced from a median of 2.5 (IQR 1.5-4) before alemtuzumab to 2.0 (IQR 1.5-3.5) after (p = 0.025). The time to first relapse was shorter in patients shifting from a second-line therapy (p = 0.011). Over 2 years, 43.7% had no evidence of disease activity. We observed infusion-related reactions in 95.5% patients, including 11.1% with pneumonitis, thyroiditis in 11%, and thrombocytopenia in 3.3%.

Conclusions: We confirmed the clinical and MRI efficacy of alemtuzumab in the clinical setting and the frequency of infusion-related reactions. Compared with that in clinical trials, higher number of patients developed pneumonitis during infusion.
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http://dx.doi.org/10.1007/s00415-019-09272-6DOI Listing
June 2019

Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by H-NMR Spectroscopy.

Neurotherapeutics 2019 07;16(3):797-807

Multiple Sclerosis Centre, Department of Medical Sciences and Public Health, Binaghi Hospital, University of Cagliari, via Is Guadazzonis 2, 09126, Cagliari, Italy.

Metabolomic research has emerged as a promising approach to identify potential biomarkers in multiple sclerosis (MS). The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response. Twenty-one MS patients starting IFN ß therapy (Rebif® 44 μg; s.c. 3 times per week) were enrolled. Blood samples were obtained at baseline and after 6, 12, and 24 months of IFN ß treatment and were analyzed by high-resolution nuclear magnetic resonance spectroscopy. Changes in metabolites were analyzed. After IFN ß exposure, patients  were divided into responders and nonresponders according to the "no evidence of disease activity" (NEDA-3) definition (absence of relapses, disability progression, and magnetic resonance imaging activity), and samples obtained at baseline were analyzed to evaluate the presence of metabolic differences predictive of IFN ß response. The results of the investigation demonstrated differential distribution of baseline samples compared to those obtained during IFN ß exposure, particularly after 24 months of treatment (RX = 0.812, RY = 0.797, Q = 0.613, p = 0.003). In addition, differences in the baseline metabolome between responder and nonresponder patients with respect to lactate, acetone, 3-OH-butyrate, tryptophan, citrate, lysine, and glucose levels were found (RX = 0.442, RY = 0.768, Q = 0.532, p = 0.01). In conclusion, a metabolomic approach appears to be a promising, noninvasive tool that could potentially contribute to predicting the efficacy of MS therapies.
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http://dx.doi.org/10.1007/s13311-019-00721-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694336PMC
July 2019

Quantifying gait impairment in individuals affected by Charcot-Marie-Tooth disease: the usefulness of gait profile score and gait variable score.

Disabil Rehabil 2020 03 18;42(5):737-742. Epub 2018 Oct 18.

Centro Sclerosi Multipla, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.

Gait analysis is a reliable tool to characterise ambulation in Charcot-Marie-Tooth, the obtained are complex data makes its use scarce in clinical practice. The use of synthetic measures may enable the clinician to easily interpret gait kinematics in Charcot-Marie-Tooth. To test the usefulness of Gait Profile Score as a method to quantify and monitor kinematic gait alterations in Charcot-Marie-Tooth. A group of patients with Charcot-Marie-Tooth and a control group underwent Gait Analysis. Neurological impairment was evaluated by means of the Charcot Marie Tooth neuropathy score in his original form and in the Rasch Analysis revised form. Differences in Kinematics scores induced by the pathology were assessed using the Mann-Whitney U test. The relationship between gait parameters and Charcot Marie Tooth neuropathy score was assessed by means of the Spearman correlation. Twenty patients were enrolled. Mann-Whitney U test revealed a significant effect of the pathology on Gait Profile Score (p < 0.001). Charcot Marie Tooth neuropathy score was positively correlated with Gait Profile Score (Rho = 0.708, p = 0.001). Gait profile score can differentiate Charcot Marie Tooth from unaffected people and to quantify ambulation impairment, also identifying the joints more affected by the disease.Implications for rehabilitationPhysiotherapy and orthotics constitute the sole possible clinical approach for Charcot Marie Tooth, but the clinical scales are scarcely effective for assessing the rehabilitative outcome.Synthetic measures are able to summarize Charcot Marie tooth kinematics in a single score, and Gait Profile Score is able to differentiate patients with Charcot Marie tooth from healthy controls.Gait Profile Score is related to clinical disability as measured by the Charcot Marie tooth neuropathy score.
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http://dx.doi.org/10.1080/09638288.2018.1506946DOI Listing
March 2020

Association between brain atrophy and cognitive motor interference in multiple sclerosis.

Mult Scler Relat Disord 2018 Oct 31;25:208-211. Epub 2018 Jul 31.

Multiple Sclerosis Center, Department of Medical Science and Public Health, University of Cagliari, Via Is Guadazzonis 2, Cagliari 09126, Italy.

Introduction: Cognitive motor interference (CMI) is performance impairment due to simultaneuous task execution and is measured using the dual task cost (DTC). No pathological feature of MS has to date been associated with CMI.

Aim: To assess the relationship between brain volumes and CMI, as measured using the DTC, in a cross-sectional study.

Methods: A group of persons with MS (pwMS) and an age- and sex-matched healthy control (HC) group underwent 3D gait analysis during using the dual task paradigm. Brain volumes were measured on T1-weighted gradient echo scans using SIENAX software. The relationships between brain volumes and the DTCs of spatial temporal parameters were evaluated using Pearson correlation. A multiple regression model was used to evaluate the ability to predict the DTC of cadence based on brain volume and grey matter (GM) volume.

Results: Forty-four patients and 16 HCs underwent MRI and gait analysis. The mean expanded disability status scale (EDSS) was 2.4 ± 1.5. Significant relationships between brain volumes and DTC were found only in the pwMS group, with higher rho scores for the DTC of mean velocity, DTC of cadence, and DTC of stride time. A statistically significant regression equation with an R value of 0.684 was found using GM and Z-score on the Stroop test as predictors of the DTC of cadence (p < 0.001).

Conclusion: Brain atrophy, especially than in the GM, is a major determinant of DTC, although other pathological markers also contribute to CMI in patients with MS.
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http://dx.doi.org/10.1016/j.msard.2018.07.045DOI Listing
October 2018

Top-down proteomic profiling of human saliva in multiple sclerosis patients.

J Proteomics 2018 09 4;187:212-222. Epub 2018 Aug 4.

Department of Life and Environmental Sciences, Biomedical Section, University of Cagliari, Monserrato Campus, 09042 Monserrato, Cagliari, Italy.

Multiple sclerosis is a chronic disease of the central nervous system characterized by inflammation, demyelination and neurodegeneration which is of undetermined origin. To date a single diagnostic test of multiple sclerosis does not exists and novel biomarkers are demanded for a more accurate and early diagnosis. In this study, we performed the quantitative analysis of 119 salivary peptides/proteins from 49 multiple sclerosis patients and 54 healthy controls by a mass spectrometry-based top-down proteomic approach. Statistical analysis evidenced different levels on 23 proteins: 8 proteins showed lower levels in multiple sclerosis patients with respect to controls and they were mono- and di-oxidized cystatin SN, mono- and di-oxidized cystatin S1, mono-oxidized cystatin SA and mono-phosphorylated statherin. 15 proteins showed higher levels in multiple sclerosis patients with respect to controls and they were antileukoproteinase, two proteoforms of Prolactin-Inducible Protein, P-C peptide (Fr.1-14, Fr. 26-44, and Fr. 36-44), SV1 fragment of statherin, cystatin SN Des, cystatin SN P → L variant, and cystatin A T → M variant. The differences observed between the salivary proteomic profile of patients suffering from multiple sclerosis and healthy subjects is consistent with the inflammatory condition and altered immune response typical of the pathology. Data are available via ProteomeXchange with identifier PXD009440.

Significance: To date a single diagnostic test of multiple sclerosis does not exist, and diagnosis is based on multiple tests which mainly include the analysis of cerebrospinal fluid. However, the need for lumbar puncture makes the analysis of cerebrospinal fluid impractical for monitoring disease activity and response to treatment. The possible use of saliva as a diagnostic fluid for oral and systemic diseases has been largely investigated, but only marginally in multiple sclerosis compared to other body fluids. Our study demonstrates that the salivary proteome of multiple sclerosis patients differs considerably compared to that of sex and age matched healthy individuals and suggests that some differences might be associated with the different disease-modifying therapy used to treat multiple sclerosis patients.
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http://dx.doi.org/10.1016/j.jprot.2018.07.019DOI Listing
September 2018

Does focal inflammation have an impact on cognition in multiple sclerosis? An MRI study.

Mult Scler Relat Disord 2018 Jul 16;23:83-87. Epub 2018 May 16.

Multiple Sclerosis Centre, Binaghi Hospital, Department of medical sciences and public health, University of Cagliari, Cagliari, 09126, Italy.

Objective: Cognitive impairment concerns a significant percentage of patients with multiple sclerosis (MS). A transient impairment of cognition with a simultaneous presence of non-symptomatic gadolinium (Gd)-enhancing lesions in patients with MS was previously described. Our study aimed to evaluate modifications in cognitive function before and after the occurrence of asymptomatic MRI gadolinium (Gd)-enhancing lesions in relapsing MS patients.

Patients And Methods: All patients underwent a neuropsychological evaluation before (30-60 days) and after (30-60 days) brain MRI with Gd administration. Patients were classified as Gd positive (presence of enhancing-lesions) and Gd negative (absence of enhancing-lesions). We also recruited a healthy controls group underwent to the same neuropsychological assessment for two times with the same timing of MS patients.

Results: We included 84 relapsing-remitting patients and 40 healthy controls. Brain MRI results showed that 14/84 (16.7%) patients had asymptomatic Gd-enhancing-lesion. No significant variation in cognitive performance between baseline and follow-up was observed in patients with or without MRI-enhancing lesions. However, an increase between baseline and follow-up was observed in the mean scores of the Symbol Digit Modality Test (41.9 at baseline versus 46.7 at follow-up, p :< 0.001). This increase was significantly lower in Gd positive patients compared to Gd negative patients (mean increase 1.1 in Gd positive versus 4.9 in Gd negative, p: < 0.001) and to healthy controls groups (mean increase 7.2; p < 0.001) CONCLUSIONS: In our study, the absence of a practice effect in Gd positive compared to Gd negative patients and to healthy controls suggests a possible role of focal inflammation on cognitive function of MS patients.
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http://dx.doi.org/10.1016/j.msard.2018.05.012DOI Listing
July 2018

A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls.

BMC Neurol 2018 May 11;18(1):67. Epub 2018 May 11.

Multiple Sclerosis Center Binaghi Hospital, Department of Medical Sciences and Public Health, University of Cagliari, via Is Guadazzonis 2, 09126, Cagliari, Italy.

Background: The principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume.

Methods: At baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months.

Results: Cognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p < 0.001), average-RNFL (p = 0.001), temporal-RNFL (p = 0.006), and papillo-macular bundle-RNFL (p = 0.009). No association was found between OCT, MRI, and cognitive changes.

Conclusions: Brain volume, cognitive functions, and RNFL are continuous measures of different neurodegenerative aspects. BICAMS and OCT have low costs and can be easily used in clinical practice to monitor neurodegeneration.
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http://dx.doi.org/10.1186/s12883-018-1065-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946463PMC
May 2018

New horizons for multiple sclerosis therapeutics: milestones in the development of ocrelizumab.

Neuropsychiatr Dis Treat 2018 23;14:1093-1099. Epub 2018 Apr 23.

Multiple Sclerosis Center Binaghi Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system, and both T and B cells are involved in its pathogenesis. The vast majority of disease-modifying drugs used for MS act on the inflammatory component of the disease and are approved for use in relapsing-remitting (RR) patients. Ocrelizumab (OCR) is the only MS drug that has been approved by the US Food and Drug Administration (FDA) not only for patients with RRMS but also for patients with primary progressive (PP) MS. OCR is a humanized anti-CD20 monoclonal antibody that can deplete the targeted B cells through antibody-dependent cellular cytotoxicity. Treatment involves administration by intravenous infusion every 6 months. OCR can cause long-lasting B-cell depletion and change the pool of reconstituted B cells. Phase III clinical trials have confirmed the results of previous Phase II studies. In particular, OPERA I and II trials, which were performed in patients with RRMS, showed a reduction in the annualized relapse rate, the risk of disability progression, and the number of new/enlarging T2 lesions and enhancing lesions measured using brain magnetic resonance. The ORATORIO trial, performed in PP subjects, showed that OCR can reduce disability progression, improve performance on the timed 25-foot walk, and decrease the total volume of T2 lesions and the mean number of new or enlarging T2 lesions. The most frequent adverse events were the infusion-related reactions and infections. Infections were mostly nasopharyngitis, as well as upper respiratory and urinary tract infections. OCR gives no indication for severe or opportunistic infections. There is not a clear increased risk of malignancies. Nevertheless, it could not be excluded. Real-life registries will provide more information about the long-term safety, the risk of exposure during pregnancy, and the risk of rare adverse events. In this review, we analyze the evidence regarding the efficacy and the safety of OCR.
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http://dx.doi.org/10.2147/NDT.S147874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922247PMC
April 2018

Fatigue, as measured using the Modified Fatigue Impact Scale, is a predictor of processing speed improvement induced by exercise in patients with multiple sclerosis: data from a randomized controlled trial.

J Neurol 2018 Jun 24;265(6):1328-1333. Epub 2018 Mar 24.

Department of Medical Sciences and Public Health, Multiple Sclerosis Center, University of Cagliari, Cagliari, Italy.

Background: 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.

Objectives: 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.

Methods: 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).

Results: A Wilcoxon test revealed a significant effect of exercise in the PA group, but not in the CG. Significant differences between T0 and EOS were found in the spatiotemporal parameters of gait, and performance on the SDMT, TUG, BBS, and MFIS. These differences were also present during the FU period. A regression model revealed that the baseline MFIS score predicted processing speed improvement (R = 0.65, p < 0.01), as the SDMT T score increased by 0.3 for each one-unit increase in the MFIS score at T0.

Conclusion: PA affects multiple aspects of the pathology in pwMS. Patients with greater fatigue must not be discouraged from exercise, as they may greatly benefit from PA. Specifically, PA was shown to improve information processing speed.
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http://dx.doi.org/10.1007/s00415-018-8836-5DOI Listing
June 2018

Autoimmune comorbidities in multiple sclerosis: what is the influence on brain volumes? A case-control MRI study.

J Neurol 2018 May 5;265(5):1096-1101. Epub 2018 Mar 5.

Department of Medical Sciences and Public Health, Multiple Sclerosis Center, Binaghi Hospital, ATS Sardegna, University of Cagliari, via Is Guadazzonis 2, 09126, Cagliari, Italy.

Background: Several studies indicated that multiple sclerosis (MS) is frequently associated with other autoimmune diseases. However, it is little known if the coexistence of these conditions may influence the radiologic features of MS, and in particular the brain volumes.

Objectives: To evaluate the effect of autoimmune comorbidities on brain atrophy in a large case-control MS population.

Methods: A group of MS patients affected by a second autoimmune disorder, and a control MS group without any comorbidity, were recruited. Patients underwent a brain MRI and volumes of whole brain (WB), white matter (WM), and gray matter (GM) with cortical GM were estimated by SIENAX.

Results: The sample included 286 MS patients, of which 30 (10.5%) subjects with type 1 diabetes (T1D), 53 (18.5%) with autoimmune thyroiditis (AT) and 4 (0.1%) with celiac disease. Multiple regression analysis found an association between T1D and lower GM (p = 0.038) and cortical GM (p = 0.036) volumes, independent from MS clinical features and related to T1D duration (p < 0.01), while no association was observed with AT and celiac disease.

Conclusions: Our data support the importance of considering T1D as possible factors influencing the brain atrophy in MS. Further studies are needed to confirm our data and to clarify the underlying mechanisms.
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http://dx.doi.org/10.1007/s00415-018-8811-1DOI Listing
May 2018

Exploring cognitive motor interference in multiple sclerosis by the visual Stroop test.

Mult Scler Relat Disord 2018 May 24;22:8-11. Epub 2018 Feb 24.

Department of Mechanical, Chemical and Materials Engineering, University of Cagliari, Cagliari, Italy. Electronic address:

Background: The dual task paradigm (the simultaneous performance of motor and cognitive task) is used in a laboratory setting to evaluate walking impairments that affect patients' daily lives. Although promising, it is poorly standardized and neither the cognitive task nor the motor task have been validated in a matched healthy control group (HC) for multiple sclerosis (MS).

Objective: Our aim was to set up a standardized instrument to evaluate cognitive motor interference in MS using the interference test par excellence: the stroop colour word test (SCWT).

Methods: Patients with MS and HC underwent 3D gait analysis with a dual task protocol, using the SCWT as a cognitive task. Gait performance impairment during the dual task was evaluated by dual task cost (DTC). A MANOVA was used to verify the effect of status (MS, HC) on DTC, calculated for the spatiotemporal parameter of the gait.

Results: In MS, the DTC was higher for the following gait parameters: speed (p = .013), cadence (p = .004), stride time (p = .005) stance phase (p < .001), and swing phase duration (p = .032).

Conclusion: DTC is present in MS and HC, but the motor cost in MS is higher. The present work provides a useful and validated basis for future studies about cognitive motor interference in MS.
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http://dx.doi.org/10.1016/j.msard.2018.02.026DOI Listing
May 2018

The impact of visible and invisible symptoms on employment status, work and social functioning in Multiple Sclerosis.

Work 2018 ;60(2):263-270

Department of Medical Sciences and Public Health, Multiple Sclerosis Centre, University of Cagliari, Sardinia, Italy.

Background: Frequently diagnosed in young adulthood, multiple sclerosis (MS) and several MS-related factors can influence patients' unemployment status and negatively affect work productivity and daily functioning.

Objective: We examined MS patients' employment status and evaluated clinical features influencing it. Furthermore, we investigated patients' burdens due to visible and invisible MS symptoms through their worsening daily functioning.

Methods: The study included outpatients affected by MS according to the 2010 McDonald criteria. The co-occurrence of invisible symptoms (fatigue, depression and apathy) was stated using validated, self-administered tools: Fatigue Severity Scale (FSS); Beck Depression Inventory-Second Edition (BDI-II); Apathy Evaluation Scale (AES). Impairment in daily functioning due to MS was assessed using the Work and Social Adjustment Scale (WSAS). Descriptive statistics, hierarchical regression analyses, Pearson's correlation, and the t-test were conducted.

Results: Of the 123 participants, 52 (42.3%) were unemployed. Results showed employment to be positively associated with higher education levels (p 0.01); female gender (p 0.03) and higher disability (p 0.02) showed negative associations with employment. No associations were found between employment and fatigue or clinically relevant depressive and apathetic symptoms. High correlations were found between WSAS score and Expanded Disability Status Scale score (r = 565, p < 0.001), BDI-II score (r = 588, p < 0.001), and FSS score (r = 545, p < 0.001).

Conclusion: Our study revealed physical disability's significance in determining MS patients' unemployment. Alternatively, invisible MS symptoms negatively affected principally patients' social lives. Therefore, programs should be designed to improve MS patients' work integration and daily activities.
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http://dx.doi.org/10.3233/WOR-182682DOI Listing
January 2019

Long-term follow-up of pediatric MS patients starting treatment with injectable first-line agents: A multicentre, Italian, retrospective, observational study.

Mult Scler 2019 03 24;25(3):399-407. Epub 2018 Jan 24.

Multiple Sclerosis Study Center, Gallarate Hospital, ASST Valle Olona, Via Eusebio Pastori 4, 21013 Gallarate, Italy.

Background: Few data are available on very long-term follow-up of pediatric multiple sclerosis (MS) patients treated with disease modifying treatments (DMTs).

Objectives: To present a long-term follow-up of a cohort of Pediatric-MS patients starting injectable first-line agents.

Methods: Data regarding treatments, annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and serious adverse event were collected. Baseline characteristics were tested in multivariate analysis to identify predictors of disease evolution.

Results: In total, 97 patients were followed for 12.5 ± 3.3 years. They started therapy at 13.9 ± 2.1 years, 88 with interferons and 9 with copaxone. During the whole follow-up, 82 patients changed therapy, switching to immunosuppressors/second-line treatment in 58% of cases. Compared to pre-treatment phase, the ARR was significantly reduced during the first treatment (from 3.2 ± 2.6 to 0.7 ± 1.5, p < 0.001), and it remained low during the whole follow-up (0.3 ± 0.2, p < 0.001). At last observation, 40% had disability worsening, but EDSS score remained <4 in 89%. One patient died at age of 23 years due to MS. One case of natalizumab-related progressive multifocal encephalopathy (PML) was recorded. Starting therapy before 12 years of age resulted in a better course of disease in multivariate analysis.

Conclusion: Pediatric-MS patients benefited from interferons/copaxone, but the majority had to switch to more powerful drugs. Starting therapy before 12 years of age could lead to a more favorable outcome.
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http://dx.doi.org/10.1177/1352458518754364DOI Listing
March 2019

Pulse steroid therapy in multiple sclerosis and mood changes: An exploratory prospective study.

Mult Scler Relat Disord 2018 Feb 31;20:104-108. Epub 2018 Jan 31.

Multiple Sclerosis Center, Binaghi Hospital, ATS Sardegna, Department of Medical Sciences and Public Health, University of Cagliari, via Is Guadazzonis, 2, 09126 Cagliari, Italy.

Background: Several reports suggest a higher risk of psychiatric disorders after high-dose corticosteroids (HDC), routinely used to treat clinical relapses in multiple sclerosis (MS). The present study aimed to examine the possible effect of HDC on mood in patients with MS and to determine the specific factors that influence mood changes.

Methods: The study included MS patients prior to receive HDC. The presence of depressive and bipolar symptoms was determined with the Beck Depression Inventory-Second Edition (BDI-II) and the Mood Disorder Questionnaire (MDQ). These assessments were made at three time points: prior to HDC initiation, after HDC completion, and 1 month after HDC.

Results: The study included 101 MS patients. At baseline, 32 (31.7%) patients had depressive symptoms (BDI-II scores ≥ 14) and 20 (19.8%) patients had bipolar symptoms (MDQ scores ≥ 7). While it was observed a reduction of BDI-II scores after HDC, an increase in MDQ score was found in patients with MDQ positivity at baseline, resulting associated with a higher number of HDC infusions (p 0.018).

Conclusions: Our results emphasize the importance of accurate screening for mood disorders in patients with MS prior to HDC initiation, and indicate that HDC should be used with caution in patients with MDQ positivity.
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http://dx.doi.org/10.1016/j.msard.2018.01.012DOI Listing
February 2018

Intrathecal oligoclonal bands synthesis in multiple sclerosis: is it always a prognostic factor?

J Neurol 2018 Feb 22;265(2):424-430. Epub 2017 Dec 22.

Multiple Sclerosis Center, Department of Medical Sciences and Public Health, University of Cagliari, Via Is Guadazzonis 2, 09126, Cagliari, Italy.

Background: Oligoclonal IgM (OCMB) and IgG (OCGB) bands were found to be associated with poor multiple sclerosis (MS) prognosis.

Objective: We aimed to evaluate the prognostic value of OCMB/OCGB in a cohort of Sardinian MS patients.

Materials And Methods: We recruited patients from the University of Cagliari. They underwent lumbar puncture for diagnostic purposes. Demographic and the following clinical data were recorded: clinical course; time to reach EDSS 3 and 6; EDSS at last follow-up; and MS treatments. The influence of gender, clinical course, age at onset, treatments, and OCGB/OCMB on reaching EDSS 3 was analysed using Cox regression. Kaplan-Meier curves were used to study the time to reach EDSS 3 considering OCMB/OCGB and therapies.

Results: The enrolled number of subjects was 503. The variables influencing the achievement of EDSS 3.0 were: male gender (p = 0.005); progressive course (p = 0.001); age at onset (p < 0.001); and disease-modifying drugs (p < 0.001). The OCGB/OCMB status was not significant. Kaplan-Meier analysis showed no difference in time to reach EDSS 3 for patients with and without OCGB or OCMB in both treated and non-treated groups.

Conclusion: Our study did not confirm the poor prognostic value of OCMB/OCGB. These results may be influenced by the peculiar genetic background associated with the risk of MS in Sardinians.
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http://dx.doi.org/10.1007/s00415-017-8716-4DOI Listing
February 2018

Long-term follow-up more than 10 years after HSCT: a monocentric experience.

J Neurol 2018 Feb 21;265(2):410-416. Epub 2017 Dec 21.

Department of Medical Sciences and Public Health, Multiple Sclerosis Center, ATS Sardegna, Ospedale Binaghi, University of Cagliari, Via Is Guadazzonis 2, 09126, Cagliari, Italy.

Background: Autologous hematopoietic stem cell transplantation (aHSCT) is used in aggressive relapsing and progressive multiple sclerosis (MS). The multicentre studies and case series reported have relatively short follow-up.

Aim: To evaluate long-term effect and safety of HSCT in MS.

Materials And Methods: Patients referred to the MS centre of Cagliari and undergoing HSCT were included. Variations in relapses and EDSS before and after HSCT were evaluated by Wilcoxon test. A descriptive analysis was made for other clinical data.

Results: Nine patients (female 6, males 3; 5 relapsing-remitting, 2 secondary progressive, 1 primary progressive, and 1 progressive relapsing) performed HSCT (1999-2006). The median follow-up was 11 years (11-18). Eight patients underwent aHSCT, seven using a low intensity conditioning regimen, and one an intermediate intensity. The primary progressive underwent allogeneic HSCT, due to onco hematological disease. The relapses number decreased in the 2 years following the procedure compared to the two preceding years (p = 0.041). New relapses or disease progressions were observed after a range of 7 (low intensity regimen)-118 (intermediate intensity) months. At last follow-up, the EDSS was stable in two patients, improved in two, and worse in five (maximum 2 EDSS in one patient). Six patients showed new lesions, and seven gadolinium-enhancing on brain MRI after a mean of 23.3 and 19.8 months, respectively. Two serious adverse events were reported: melanoma, and progressive multifocal leukoencephalopathy.

Conclusions And Discussion: Our results confirm in a long follow-up the efficacy of HSCT in reducing relapses and disability progression. The risk/benefit profile is better for intermediate intensity regimens.
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http://dx.doi.org/10.1007/s00415-017-8718-2DOI Listing
February 2018

PML in a person with multiple sclerosis: Is teriflunomide the felon?

Neurology 2018 01 6;90(2):83-85. Epub 2017 Dec 6.

From University of Cagliari (L.L., G.F., J.F., G.C., M.G.M., E.C.); IRCCS San Raffaele Hospital (S.G.), Milan; and Binaghi Hospital (M.A.B., F.C.), ATS Sardegna, Italy.

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http://dx.doi.org/10.1212/WNL.0000000000004804DOI Listing
January 2018

Multiple sclerosis and HLA genotypes: A possible influence on brain atrophy.

Mult Scler 2019 01 7;25(1):23-30. Epub 2017 Nov 7.

Multiple Sclerosis Center, Binaghi Hospital, ATS Sardegna, Cagliari, Italy/Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.

Background: The strongest genetic determinant for multiple sclerosis (MS) is located at the human leukocyte antigen (HLA) class II DRB1 and DQB1 loci.

Objectives: To investigate the possible role of predisposing HLA genotypes in determining brain atrophy.

Methods: HLA genotypes were categorized as high risk (two predisposing haplotypes) or medium/low risk (one or no predisposing haplotypes). Patients underwent a brain magnetic resonance imaging (MRI) study and volumes of white matter (WM), gray matter (GM), and whole brain (WB) were estimated with SIENAX. Longitudinal atrophy was also assessed with SIENA.

Results: The study included 240 MS patients. In 51/240 (21%) subjects, a high-risk HLA genotype was observed, while medium- and low-risk HLA genotypes were 109/240 (45%) and 80/240 (34%), respectively. Multiple regression analysis found that the high-risk HLA genotype was associated with significant reduction in WB ( p = 0.02) and GM ( p = 0.03) volumes compared with the medium-/low-risk HLA genotypes, independently from MS clinical features. The longitudinal study included 60 patients and showed a brain volume loss of -0.79% in high-risk HLA genotype group versus -0.56% in low-risk HLA genotype.

Conclusion: Our results suggest an influence of HLA genotype on WB and GM atrophy. Further investigations are necessary to confirm these findings.
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http://dx.doi.org/10.1177/1352458517739989DOI Listing
January 2019

Rescue therapy with alemtuzumab in multiple sclerosis post-natalizumab puerperium reactivation.

Neurol Sci 2018 02 7;39(2):389-390. Epub 2017 Oct 7.

Department of Medical Sciences and Public Health, University of Cagliari, Multiple Sclerosis Centre, Ospedale Binaghi, Via Is Guadazzonis, 2, 09126, Cagliari, Italy.

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http://dx.doi.org/10.1007/s10072-017-3135-yDOI Listing
February 2018

'Timed up and go' and brain atrophy: a preliminary MRI study to assess functional mobility performance in multiple sclerosis.

J Neurol 2017 Nov 11;264(11):2201-2204. Epub 2017 Sep 11.

Multiple Sclerosis Center, Department of Medical Sciences and Public Health, Binaghi Hospital, University of Cagliari, Via Is Guadazzonis 2, 09126, Cagliari, Italy.

Motor and cognitive disabilities are related to brain atrophy in multiple sclerosis (MS). 'Timed up and go' (TUG) has been recently tested in MS as functional mobility test, as it is able to evaluate ambulation/coordination-related tasks, as well as cognitive function related to mobility. The objective of this study is to evaluate the relationship between brain volumes and TUG performances. Inclusion criteria were a diagnosis of MS and the ability to walk at least 20 m. TUG was performed using a wearable inertial sensor. Times and velocities of TUG sub-phases were calculated by processing trunk acceleration data. Patients underwent to a brain MRI, and volumes of whole brain, white matter (WM), grey matter (GM), and cortical GM (C) were estimated with SIENAX. Sixty patients were enrolled. Mean age was 41.5 ± 11.6 years and mean EDSS 2.3 ± 1.2. Total TUG duration was correlated to lower WM (ρ = 0.358, p = 0.005) and GM (ρ = 0.309, p = 0.017) volumes. A stronger association with lower GM volume was observed for intermediate (ρ = 0.427, p = 0.001) and final turning (ρ = 0.390, p = 0.002). TUG is a useful tool in a clinical setting as it can not only evaluate patients' disability in terms of impaired functional mobility, but also estimate pathological features, such as grey atrophy.
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http://dx.doi.org/10.1007/s00415-017-8612-yDOI Listing
November 2017