C Pozzilli

Sapienza University of Rome, Roma, Latium, Italy

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Publications (346)1464.45 Total impact

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    ABSTRACT: Background: 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. Methods: A registry was established in 2007 in Italy to collect MS cases treated with Natalizumab (NA) before 18 years of age. Results: 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. Discussion: 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. Conclusions: 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
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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; 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; DOI:10.1177/1352458515570768 · 4.82 Impact Factor
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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
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    ABSTRACT: Multiple sclerosis (MS) frequently affects women of childbearing age. While short-term effects of pregnancy on MS course are well-known, whether pregnancy may influence long-term disability progression is debated. A two-centre retrospective study to investigate long-term effect of pregnancy on disability was performed in a population of MS women. Survival analyses and multivariate Cox proportional regression models (including early predictors of MS severity and exposure to disease-modifying treatments) were performed to compare time to reach well-established disability milestones in nulliparous women and in those with pregnancies after MS onset ('parous'). Women with pregnancies before MS onset were excluded from analyses as they represent a heterogeneous group. Data about 445 women (261 nulliparous, 184 'parous') were analysed. A longer time to reach Expanded Disability Status Scale (EDSS) 4.0 and 6.0 was observed in parous women; Cox regression models revealed a lower risk for 'parous' than nulliparous women in reaching EDSS 4.0 and 6.0 (HR = 0.552, p = 0.008 and HR = 0.422, p = 0.012 respectively). Our findings suggest that pregnancy after MS onset is associated with a slower long-term disability progression. Whether this represents a biological/immunological effect, or reflects a higher propensity toward childbearing in women with milder disease, it remains uncertain deserving further investigations. © The Author(s), 2014.
    Multiple Sclerosis 12/2014; 21(10). DOI:10.1177/1352458514561907 · 4.82 Impact Factor
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    ABSTRACT: Objective: To evaluate the effectiveness of a home-based cognitive rehabilitation (CR) program based on the video game Dr Kawashima's Brain Training (DKBT; Nintendo, Japan), in improving attention, processing speed, and working memory of patients with multiple sclerosis (MS). Methods: This was a randomized, wait-list control study. Patients with MS and failure in at least one between Stroop Test (ST), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test (SDMT) were submitted to an 8-week home-based CR program playing DKBT. Patients were evaluated at baseline and after DKBT by the aforementioned tests, by the Modified Fatigue Impact Scale (MFIS) and by the MS Quality of Life-54 questionnaire (MSQoL-54). Results: Fifty-two 52 patients were screened for eligibility; 35 (mean [standard deviation] age of 43.9 [8.4] years, median Expanded Disability Status Scale score of 2.0 (range = 2.0-6.0) were randomly assigned to the intervention group (n = 18) or wait-list control group (n = 17). ANCOVA analysis showed a significant effect of DKBT on ST (F = 5.027; P = .034; F(2) = 0.210), SDMT (F = 4.240; P = .049; F(2) = 0.177), and on some subscales of MSQoL-54. The PASAT and cognitive subscale of MFIS also showed an improvement, but this was just not significant (F = 4.104, P = .054, F(2) = 0.171, and F = 4.226, P = .054, F(2) = 0.237, respectively). Conclusion: We suggest that a home-based DKBT program may improve cognitive functions, some aspects of QoL, and cognitive fatigue in patients with MS.
    Neurorehabilitation and neural repair 11/2014; 29(5). DOI:10.1177/1545968314554623 · 3.98 Impact Factor
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    11/2014; 1(2):1-13. DOI:10.17653/2374-9091.SS0005
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    ABSTRACT: Background. Resting brain activity can be modulated by motor tasks to adapt to function. In multiple sclerosis (MS) patients, altered resting-state functional connectivity (RS-FC) has been reported and associated with impaired function and disability; little is known on how RS-FC is modulated by a simple repetitive motor task. Objective. To assess changes in RS-FC in early relapsing-remitting MS (RRMS) patients associated with repetitive thumb flexions (RTFs). Methods. A total of 20 right-handed patients with early RRMS and 14 healthy controls underwent a resting functional magnetic resonance imaging (fMRI) scan, before and after 25 minutes of alternate 30-s blocks of right RTF and rest. Dual-regression analysis of resting fMRI data followed the independent component analysis. Individual spatial maps of coherence between brain areas for 2 networks of interest, sensorimotor and cerebellar, were compared at the group level and correlated with measures of both clinical impairment and brain damage. Results. Significant RTF-induced differences in RS-FC were observed between groups in the cerebellar network because of increased RS-FC in patients but not in controls. In the sensorimotor network, the RS-FC after RTF increased in both groups, with no significant between-group differences. The sensorimotor and the cerebellar RS-FC were intercorrelated only in patients and only after the RTF. The sensorimotor RS-FC increase in patients correlated with structural MRI alterations. Conclusions. Our study unmasked RS-FC changes of motor-related networks occurring after a simple repetitive motor task in early RRMS patients only. Evaluation of altered RSN dynamics might prove useful for anticipating neuroplasticity and for MRI-informed neurorehabilitation.
    Neurorehabilitation and neural repair 11/2014; 29(6). DOI:10.1177/1545968314558600 · 3.98 Impact Factor
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    ABSTRACT: Objective: The aim of the study was to perform a third cognitive assessment in our pediatric-onset multiple sclerosis (MS) patient cohort and determine predictors of the individual cognitive outcome. Methods: After 4.7 ± 0.7 years from baseline evaluation, 48 of 63 patients in the original cohort were reassessed on an extensive neuropsychological battery and compared with 46 healthy controls. Two alternate versions of the tests were used at different assessment points. Cognitive impairment was defined as the failure of ≥3 tests; individual change in the cognitive impairment index was measured. Results: At year 5, 38% of the subjects with MS fulfilled our criterion for impairment. Between years 2 and 5, regarding individual cognitive impairment index change, 66.7% of the patients improved. However, comparing baseline and 5-year testing (when the same versions of the tests were used), cognitive impairment index deterioration was observed in 56% of the patients, improvement in 25%, and stability in 18.8%. A deteriorating performance was related to male sex, younger age and age at MS onset, and lower education. None of these variables, however, was retained in the multivariate analysis. Conclusions: Cognitive outcome in pediatric-onset MS can be heterogeneous. Progression of cognitive problems in a few subjects and potential for compensation and improvement in others call for systematic cognitive screening in this population and development of effective treatment strategies.
    Neurology 09/2014; DOI:10.1212/WNL.0000000000000885 · 8.29 Impact Factor

Publication Stats

8k Citations
1,464.45 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
    • University of Milan
      • Department of Neurological Sciences
      Milano, Lombardy, Italy
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 1998
    • Università Degli Studi Roma Tre
      Roma, Latium, Italy
  • 1988
    • National Institute of Radiological Sciences
      Tiba, Chiba, Japan
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1981
    • Medical Research Council (UK)
      Londinium, England, United Kingdom