C Pozzilli

Sapienza University of Rome, Roma, Latium, Italy

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Publications (356)1483.75 Total impact

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    ABSTRACT: Background: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. Objectives: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. Methods: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. Results: A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Conclusions: Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis.
    Multiple Sclerosis 10/2015; DOI:10.1177/1352458515611222 · 4.82 Impact Factor
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    ABSTRACT: Background: Multiple sclerosis (MS) is a debilitating disease that negatively impacts patients' lives. Objective: ENABLE assessed the effect of long-term prolonged-release (PR) fampridine (dalfampridine extended release in the United States) treatment on patient-perceived health impact in patients with MS with walking impairment. Methods: ENABLE was a 48-week, open-label, Phase 4 study of PR-fampridine 10 mg twice daily. Patients who showed any improvement in Timed 25-Foot Walk walking speed at weeks 2 and 4 and any improvement in 12-item MS Walking Scale score at week 4 remained on treatment. The primary endpoint was change from baseline in 36-Item Short-Form Health Survey (SF-36) physical component summary (PCS) score. Results: At week 4, 707/901 (78.5%) patients met the criteria to remain on treatment. Patients on treatment demonstrated significant and clinically meaningful improvements in SF-36 PCS scores from baseline (mean change (95% confidence interval)) to week 12 (4.30 (3.83, 4.78); p < 0.0001), week 24 (3.75 (3.23, 4.27); p < 0.0001), week 36 (3.46 (2.95, 3.97); p < 0.0001), and week 48 (3.24 (2.72, 3.77); p < 0.0001). Significant improvements from baseline were also demonstrated in secondary health measures in patients on treatment. Conclusion: PR-fampridine improved patient-perceived physical and psychological health impact of MS measured in a real-life setting.
    Multiple Sclerosis 10/2015; DOI:10.1177/1352458515606809 · 4.82 Impact Factor
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    31h Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Barcelona; 10/2015
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    ECTRIMS, Barcelona, Spain; 10/2015
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    ABSTRACT: Natalizumab is a promising option for pediatric multiple sclerosis (MS) patients with active evolution and a poor response to Interferon-beta or Glatiramer Acetate. However, no data are available in large cohorts of patients and after a long-term follow up. Our study was planned to shed lights on this topic. A registry was established in 2007 in Italy to collect MS cases treated with Natalizumab (NA) before 18 years of age. 101 patients were included (69 females), mean age of MS onset 12.9 ± 2.7 years, mean age at NA initiation 14.7 ± 2.4 years. Mean treatment duration was 34.2 ± 18.3 months. During NA treatment, a total of 15 relapses were recorded in 9 patients, annualized relapse rate was 2.3 ± 1.0 in the year prior to NA and decreased to 0.1 ± 0.3 (p < 0.001) at last NA infusion. Mean Expanded Disability Status Scale (EDSS) decreased from 2.6 ± 1.3 at initiation of NA to 1.8 ± 1.2 at the time of last visit (p < 0.001). At brain MRI, new T2 or Gd enhancing lesions were observed in 10/91 patients after 6 months, 6/87 after 12 months, 2/61 after 18 months, 2/68 after 24 months, 3/62 after 30 months, and 5/43 at longer follow up. At the time of last observation, 58 % of patients were free from clinical (relapses/increased EDSS) and/or MRI activity (new T2 or gadolinium-enhancing lesions). No relevant adverse events were recorded. NA was safe, well tolerated and very efficacious in the large majority of patients. Our data support the use of this medication in subjects with pediatric MS and an aggressive course. A relevant reduction of relapse rate and EDSS was observed during NA treatment, compared to pre-treatment period. No evidence of disease activity (NEDA) occurred in 58 % of cases.
    BMC Neurology 09/2015; 15(1):174. DOI:10.1186/s12883-015-0433-y · 2.04 Impact Factor

  • 28° Congresso Nazionale AINR, Napoli; 09/2015
  • C Pozzilli · M Pugliatti ·
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    ABSTRACT: Although pregnancy in women with multiple sclerosis (MS) is not generally considered high risk, there are some associated therapeutic challenges. The pregnancy-associated reduction in the relapse rate, especially in the third trimester, is followed by a sharp increase in the first few months postpartum. Nevertheless, retrospective evidence for pregnant women with and without MS followed for up to 10 years indicates that pregnancy has no perceptible effect on long-term disease course or disability progression. Likewise, MS has no apparent effects on the pregnancy course or fetal outcomes. All disease-modifying therapies (DMTs) have potential adverse effects on fertility and pregnancy outcomes, but the level of risk varies amongst agents. There is some support for continued use of interferon-β and glatiramer acetate throughout pregnancy to reduce the risk of relapse. Use of DMTs during breastfeeding is best avoided if possible. Close evaluation of drug safety information is imperative when managing women with MS who are pregnant or wish to become pregnant. Decision-making should be a shared experience between patient and physician, and the approach must be individualized for each patient.
    European Journal of Neurology 09/2015; 22 Suppl 2(S2):34-9. DOI:10.1111/ene.12797 · 4.06 Impact Factor
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    ABSTRACT: The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.
    Brain 09/2015; DOI:10.1093/brain/awv260 · 9.20 Impact Factor
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    ABSTRACT: To test the effect of oral contraceptives (OCs) in combination with interferon β (IFN-β) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFN-β-1a subcutaneously (SC) only (group 1), IFN-β-1a SC plus ethinylstradiol 20 μg and desogestrel 150 μg (group 2), or IFN-β-1a SC plus ethinylestradiol 40 μg and desogestrel 125 μg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81-1.14) in group 1, 0.84 (95% CI 0.66-1.02) in group 2, and 0.72 (95% CI 0.53-0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-β or OC discontinuations were equally distributed across groups. Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research. This study provides Class II evidence that in women with RRMS, IFN-β plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-β alone.
    08/2015; 2(4):e120. DOI:10.1212/NXI.0000000000000120
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    ABSTRACT: . The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). Methods . We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. Results . We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, p = 0.014 ) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, p = 0.034 ). Conclusions . Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS.
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    ABSTRACT: Background. The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). Methods. We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. Results. We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, í µí± = 0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, í µí± = 0.034). Conclusions. Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS.
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    ABSTRACT: To define the pathological substrate underlying disability in multiple sclerosis by evaluating the relationship of resting-state functional connectivity with microstructural brain damage, as assessed by diffusion tensor imaging, and clinical impairments. Thirty relapsing-remitting patients and 24 controls underwent 3T-MRI; motor abilities were evaluated by using measures of walking speed, hand dexterity and balance capability, while information processing speed was evaluated by a paced auditory serial addiction task. Independent component analysis and tract-based spatial statistics were applied to RS-fMRI and diffusion tensor imaging data using FSL software. Group differences, after dual regression, and clinical correlations were modelled with General-Linear-Model and corrected for multiple comparisons. Patients showed decreased functional connectivity in 5 of 11 resting-state-networks (cerebellar, executive-control, medial-visual, basal ganglia and sensorimotor), changes in inter-network correlations and widespread white matter microstructural damage. In multiple sclerosis, corpus callosum microstructural damage positively correlated with functional connectivity in cerebellar and auditory networks. Moreover, functional connectivity within the medial-visual network inversely correlated with information processing speed. White matter widespread microstructural damage inversely correlated with both the paced auditory serial addiction task and hand dexterity. Despite the within-network functional connectivity decrease and the widespread microstructural damage, the inter-network functional connectivity changes suggest a global brain functional rearrangement in multiple sclerosis. The correlation between functional connectivity alterations and callosal damage uncovers a link between functional and structural connectivity. Finally, functional connectivity abnormalities affect information processing speed rather than motor abilities. © The Author(s), 2015.
    Multiple Sclerosis 06/2015; 21(13). DOI:10.1177/1352458514568826 · 4.82 Impact Factor
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    ABSTRACT: Two simultaneously performed tasks may compete for common brain network resources in patients with multiple sclerosis (MS), suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for walking and gait, data on static balance are scarce. In this cross-sectional study, 92 patients and 46 sex/age-matched healthy controls (HCs) were tested by means of static posturography under eyes opened (single-task condition) and while performing the Stroop word-colour task (dual-task condition), to estimate the dual-task cost (DTC) of standing balance. The patient group also underwent the Expanded Disability Status Scale, 25-foot walking test, 12-item MS walking scale, Modified Fatigue Impact Scale, and Symbol Digit Modalities Test. Patients had larger postural sway under both single-task and dual-task conditions (p<0.001), as well as greater DTC of standing balance (p=0.021) than HCs. Although secondary progressive (SP) patients had larger sway in both conditions than relapsing-remitting (RR) patients (p<0.05), these latter ones exhibited a greater DTC of postural balance (p=0.045). Deficits in sustained attention and information processing speed, as assessed by the SDMT, were also independently associated with the magnitude of DTC of standing balance (p=0.005). The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography and was associated with impaired sustained attention and information processing speed, especially in RR patients. The smaller DTC of standing balance observed in SP patients may be due to the ceiling effect of postural sway, or alternatively to the lack of postural reserve which constrained the more disabled patients to prioritize the balance over the cognitive task. Copyright © 2015 Elsevier B.V. All rights reserved.
    Gait & Posture 02/2015; 41(3). DOI:10.1016/j.gaitpost.2015.02.002 · 2.75 Impact Factor
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    ABSTRACT: The objective of this paper is to estimate the risk of reaching well-established disability milestones after withdrawal of natalizumab (NTZ) due to concern about the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS). Data from 415 patients with MS followed-up for six years after starting NTZ were collected from seven tertiary MS centers. The risk of disability worsening, i.e. reaching Expanded Disability Status Scale (EDSS) scores of 4.0 or 6.0, and the likelihood of experiencing a disability reduction of one EDSS point (or more), were assessed by propensity score-adjusted analyses in patients who discontinued and in those still on treatment at the end of follow-up. A total of 318 patients who received standard NTZ treatment without experiencing evidence of disability worsening in the first two years were included in the six-year follow-up analysis, with 196 (61.6%) still on treatment and 122 (38.4%) discontinuing after a median time of 3.5 years. Patients in the discontinuing group had a more than two-fold increased risk of disability worsening (p = 0.007), and a 68% decreased likelihood of experiencing disability reduction (p = 0.009) compared with the continuing group. While discussing the overall risk/benefit profile of NTZ, patients should be advised that, in case of treatment discontinuation, the risk of disability worsening is one in three, and increases to one in two if the EDSS score at NTZ start is above 3.0. © The Author(s), 2015.
    Multiple Sclerosis 02/2015; 21(13). DOI:10.1177/1352458515570768 · 4.82 Impact Factor
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  • L De Giglio · C Gasperini · C Tortorella · M Trojano · C Pozzilli ·
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    ABSTRACT: The humanized monoclonal alpha4-integrin antibody Natalizumab (NTZ) (Tysabri(©) , Biogen Idec, Cambridge, MA, USA) has shown to be effective in multiple sclerosis (MS) therapy; however, the interruption of the drug has been related to a disease restart. This risk has to be carefully considered in case of accidental or desired pregnancies. To report the risk of disease restart in patients who interrupted NTZ because of pregnancy and discuss the implication of NTZ choice in female childbearing patients with MS. Clinical histories and MRI images of four pregnant women with MS who interrupted NTZ. Despite pregnancy is usually related with disease stability, the cases presented here showed an abrupt increase of disability with high number of MRI lesions, some of them with a mass effect. We recommend that female patients on childbearing age must be informed before starting NTZ treatment of the risk of a return of disease activity when the drug is discontinued. The risk occurs even during pregnancy a condition that is considered as protective for women with MS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Acta Neurologica Scandinavica 01/2015; 131(5). DOI:10.1111/ane.12364 · 2.40 Impact Factor
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    ABSTRACT: Dear Sirs,The so-called “far transfer effect” or “transfer of training” refers to the occurrence of transferring improved performance in a specific function to different untrained functional domains. This implies little overlap between situations, being the original and transfer settings dissimilar [1].Commercial video games may provide integrated and adaptable training paradigms in which a transfer effect to executive functions (e.g.: problem solving, planning, reasoning, working memory or multitasking) can be achievable [2-4].Task-specific training using video games is emerging as a feasible approach for enhancing multitasking skills in older adults, and even for recovering motor and cognitive functions in patients affected by neurological diseases, such as multiple sclerosis (MS). Emerging evidence supports the use of computer-assisted and video game-based cognitive rehabilitation to enhance working memory, complex attention function, visuo-constructive performance and even cognitiv ...
    Journal of Neurology 01/2015; 262(3). DOI:10.1007/s00415-015-7640-8 · 3.38 Impact Factor
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    ABSTRACT: OBJECTIVES: to evaluate the effect of age, sex and onset symptoms on the risk of the second clinical attack in a cohort of pediatric patients with a clinically isolated syndrome suggestive of MS (pCIS). BACKGROUND: Pediatric onset occurs in 5-10[percnt] of Multiple Sclerosis (MS) patients. Due to its rare incidence limited epidemiological data are available. METHODS: Demographic and clinical data of a cohort of patients with pCIS and onset <= 15 years were extracted from the Italian iMedWeb registry and from the MSBase platform. A Cox-model adjusted for age at onset, sex and onset symptom(s) was performed to evaluate the time to a second clinical attack during the follow-up. Proportions of patients with different onset symptom(s) (optic, spinal, supratentorial, brainstem/cerebellum and multifocal) were calculated and compared between children (age at onset < 12 years) and adolescents (age at onset > 12) (chi-square test). RESULTS: a total of 1357 of pCIS patients with onset before 15 years was extracted. A shorter time to a second clinical attack was found in female pCIS (male vs female: HR= 0.82; p< 0.02) and in pCIS with an age at onset > 12 years (HR = 1.32; 95[percnt] CI: 1.13-1.54; p=0.0006). Brainstem onset was found to be more frequent in pCIS with an age at onset < 12 years in comparison to pCIS with an age at onset > 12 years (35.93 vs 26.43[percnt]; p=0.0019). CONCLUSIONS: the results indicate that the most significant factors influencing the time to reach a clinically definite MS diagnosis in pCIS are the female sex and an age at onset > 12 years. Moreover the results confirm that brainstem symptoms at onset are more frequent in children than in adolescents.
    Neurology 01/2015; 84(14 Supl.):P4. 024. · 8.29 Impact Factor

Publication Stats

9k Citations
1,483.75 Total Impact Points


  • 1987-2015
    • Sapienza University of Rome
      • • Department of Neurology and Psychiatry
      • • Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science
      Roma, Latium, Italy
    • Second University of Naples
      Caserta, Campania, Italy
  • 2012
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florens, Tuscany, Italy
  • 2011
    • Sant´Andrea Hospital
      Roma, Latium, Italy
  • 1985-2011
    • The American University of Rome
      Roma, Latium, Italy
  • 2007-2009
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 2003
    • VU University Medical Center
      • Department of Neurology
      Amsterdam, North Holland, Netherlands
  • 1999
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 1988-1999
    • University of Milan
      • Department of Neurological Sciences
      Milano, Lombardy, Italy
    • National Institute of Radiological Sciences
      Tiba, Chiba, Japan
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1998
    • Università Degli Studi Roma Tre
      Roma, Latium, Italy
  • 1981
    • Medical Research Council (UK)
      Londinium, England, United Kingdom