Anna Paola Batocchi

Catholic University of the Sacred Heart , Milano, Lombardy, Italy

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Publications (122)559.43 Total impact

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    ABSTRACT: Background and purposeThe detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of ‘autoimmune epilepsy’. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy.Methods Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency.ResultsNeural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency.ConclusionsA significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.
    European Journal of Neurology 08/2014; · 4.16 Impact Factor
  • R. Iorio, F. Capone, D. Plantone, A.P. Batocchi
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    ABSTRACT: Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.
    Journal of Clinical Neuroscience. 01/2014; 21(1):174–175.
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    ABSTRACT: In this study we evaluated the percentages of CD3(-)CD56(bright), CD3(-)CD56(dim), CD3(-)CD56(bright)perforin(+) and CD3(-)CD56(dim)perforin(+) Natural Killer (NK) cells in peripheral blood from untreated secondary progressive (SP) and primary progressive (PP) multiple sclerosis (MS) patients and age and sex matched healthy subjects. Both PPMS patients and SPMS patients showed increased percentages of circulating CD3(-)CD56(dim)perforin(+) NK cells than healthy subjects. The increased percentage of CD3(-)CD56(dim) NK cells expressing perforin in patients affected by the progressive forms of MS suggests a possible role of this NK cell subpopulation in the pathogenesis of the disease.
    Journal of neuroimmunology 10/2013; · 2.84 Impact Factor
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    ABSTRACT: Objectives: Experimental evidences indicate that leptin is involved in the neuroinflammatory process sustaining multiple sclerosis (MS). However, the relationship between leptin and body fat, as assessed by body mass index (BMI), in MS was not previously evaluated. It was the aim of this study to compare serum leptin levels between patients with MS and healthy controls and to evaluate the possible relationship between circulating leptin levels and disease severity. Patients and Methods: Eighty-four MS patients and 57 sex-matched healthy volunteers were enrolled. Serum leptin levels were measured in all patients and controls. MS patients were stratified in 3 groups according to their degree of disability as assessed by the Expanded Disability Status Scale (EDSS). Patients were classified as having low (33 patients with an EDSS score <1.5), intermediate (28 patients with an EDSS score from 2 to 3) and high disability (23 patients with an EDSS score ≥3.5). Results: No significant differences in serum leptin levels and BMI were observed between patients and controls. In patients with MS, serum leptin levels were significantly correlated with BMI in those patients with low (R(2) = 0.363; p < 0.001) and intermediate disability (R(2) = 0.408; p < 0.001), but not in patients with a higher disability score (R(2) = 0.064; p = 0.256). Conclusion: BMI, the major determinant of leptin level in physiological conditions, has a minor role in determining the serum levels of leptin in MS patients with a high EDSS score. Future longitudinal studies will be required in order to provide further insights into the regulation of leptin secretion in patients with MS.
    NeuroImmunoModulation 08/2013; 20(6):341-347. · 1.84 Impact Factor
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    ABSTRACT: Longitudinally extensive transverse myelitis (LETM) is a characteristic feature of Neuromyelitis Optica (NMO), but it can also occur in several other inflammatory diseases of the central nervous system (CNS). An IgG autoantibody that binds to aquaporin-4 (AQP4), the predominant water channel of the CNS, is a reliable biomarker of the NMO spectrum disorders, and if detected predicts the recurrence of the myelitis. In this study, we compared the clinical and neuroimaging characteristics of AQP4-IgG+ and AQP4-IgG- LETM patients. Thirty-seven first-ever LETM patients were retrospectively evaluated and divided into two groups according to the presence of AQP4 autoantibodies. AQP4-IgG was detected in the serum and in the cerebrospinal fluid of sixteen patients. The female to male ratio was higher in AQP4-IgG+ patients. Intractable nausea and vomiting and paroxysmal tonic spasms often accompanied the LETM in AQP4-IgG+ patients. T2-weighted spinal cord MRI revealed that inflammatory lesions extending into the brainstem and involving the central grey matter occurred more frequently in AQP4-IgG+ LETM patients. Hypointense lesions on T1-weighted spinal cord MRI were detected more frequently in the seropositive group, and their presence correlated with attack severity. In conclusion, this study provides clinical and spinal cord neuroimaging clues that can help distinguishing AQP4-IgG+ LETM patients.
    Journal of Neurology 06/2013; · 3.58 Impact Factor
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    ABSTRACT: Objectives: In this prospective study, we used one diagnostic protocol to establish an early diagnosis in patients with ocular palsies in absence of other neurological findings. Materials and Methods: The study was performed on a consecutive series of 132 patients who visited our Neurological Department for ptosis and/or diplopia in absence of other neurological signs, using the same diagnostic protocol. Results: An etiological diagnosis was made in 74% of cases during a mean time of 17 ± 23 months from symptom onset. Myasthenia gravis was the most common diagnosis (n = 60, 45.5%). Thirty-four cases (26%) remained undiagnosed in spite of a follow-up lasting 32 ± 33 months on average. Conclusions: Identifying the cause of an isolated ocular palsy can be difficult, and an extended follow-up time does not aid in further establishment of the diagnosis.
    European Neurology 05/2013; 70(1):10-15. · 1.50 Impact Factor
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    ABSTRACT: OBJECTIVE: Sustained pattern stimulation in normal subjects induces adaptive changes in pattern electroretinogram (PERG), an effect that has been interpreted as a response of glial cells and retinal ganglion cells (RGC). The aim of this study was to compare the effect in normal subjects and in multiple sclerosis patients without previous optic neuritis. METHODS: PERGs were elicited by a 7.5Hz pattern stimulus, presented continuously over 152s. Response cycles were averaged in 20 packets of 60 events each and amplitude and phase of the 2nd harmonic response was measured. Adaptive changes are expressed as amplitude reduction over the full examination time. RESULTS: In normal subjects PERG amplitude declined progressively to a plateau (dA=-0.46μV, SE=0.09μV); in patients the effect size was severely reduced (dA=-0.20μV, SE=0.04μV). No significant difference was found in mean amplitude. CONCLUSIONS: The results show reduced RGC habituation in patients, suggesting an abnormal gain and sensitivity control in the inner retina, even in absence of clinical optic neuritis. Recent findings in astrocyte biology and indications drawn from a mathematical model point to a key role of glial cells in this process. SIGNIFICANCE: The proposed methodology may have implications in the assessment of MS patients and in understanding the pathophysiology of neurological and retinal disorders.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 04/2013; · 3.12 Impact Factor
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    ABSTRACT: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. An autoantibody (NMO-IgG) targeting the aquaporin-4 water channel distinguishes NMO from other inflammatory disorders of the CNS. Recent studies have demonstrated that the area postrema and other circumventricular organs (CVOs) can be targeted in NMO.We herein report the case of a 12-year-old girl who experienced anorexia six months before the onset of NMO. Anorexia caused by hypothalamic or CVO dysfunction may herald the onset of NMO.
    Internal Medicine 01/2013; 52(4):489-91. · 0.97 Impact Factor
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    ABSTRACT: The role of T lymphocytes in the pathogenesis of Celiac disease (CD) is well established. However, the mechanisms of T-cell involvement remain elusive. Little is known on the distribution of T subpopulations: T-regulatory (Treg), Th17, CD103, and CD62L cells at disease onset and after gluten-free diet (GFD). We investigated the involvement of several T subpopulations in the pathogenesis of CD. We studied T cells both in the peripheral blood (PB) and the tissue-infiltrating lymphocytes (TILs) from the mucosa of 14 CD patients at presentation and after a GFD, vs. 12 controls. Our results extend the involvement of Treg, Th1, and Th17 cells in active CD inflammation both in the PB and at the TILs. At baseline, Tregs, Th1, and Th17 cells are significantly higher in active CD patients in TILs and PB. They decreased after diet. Moreover, CD62L+ TILs were increased at diagnosis as compared with GFD patients. Our data show significant modifications of the above-mentioned subpopulations both in the PB and TILs. The increase of suppressive Tregs in active CD both in the PB and TILs is intriguing. T lymphocytes are known to have a crucial role in the pathogenesis of CD. We have shown that gluten trigger results in systemic recruitment of T lymphocytes, the unbalance between pro-inflammatory and anti-inflammatory populations and the increase of CD62L+ T cells in TILs. Our results delineate a more complete picture of T-cell subsets in active vs. GFD disease. Our data of T-cell subpopulations, combined with known data on cytokine production, support the concept that duodenal micro-environment acts as an immunological niche and this recognition may have an important role in the diagnosis, prognosis and therapeutical approach of CD.
    Clinical and Translational Gastroenterology. 12/2012;
  • Rosaria Renna, Domenico Plantone, Anna Paola Batocchi
    Neurology 10/2012; 79(15):e134. · 8.25 Impact Factor
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    ABSTRACT: The aim of the study was to evaluate the type-1 immune response by analyzing T-bet expression in circulating T and B cells in Primary Progressive (PP) and Secondary Progressive (SP) Multiple Sclerosis (MS) patients. We found higher percentages of circulating CD4+T-bet+ and CD8+T-bet+ T cells in SPMS and PPMS than in remitting-relapsing MS patients and controls. Moreover, in SPMS, we observed a positive correlation between the percentages of circulating CD4+T-bet+ or CD8+T-bet+ T cells and disease severity. The increased percentages of Th1 and Tc1 cells suggest that MS progressive forms, unlike RRMS, are characterized by a permanent peripheral type-1 immune activation.
    Journal of neuroimmunology 05/2012; 249(1-2):112-6. · 2.84 Impact Factor
  • Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2012; 7(5):937-8. · 4.55 Impact Factor
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    ABSTRACT: Accurate diagnosis of depression in patients affected by MS is important, as it may be a cause of reduced quality of life and increased suicide risk. We present a new scale, the Multiple Sclerosis Depression Rating Scale (MSDRS), and assess its diagnostic accuracy in comparison to the Beck Depression Inventory (BDI). A total of 94 MS participants were classified as non-depressed (N = 44) or affected by mood disorder associated to MS with depressive manifestations (MSD-MDDM; N = 37) or with a major depression-like episode (MSD-MDL; N = 13). Each participant underwent a psychiatric interview, MSDRS, and BDI; diagnostic accuracy was evaluated using area under the ROC curve (AROC). The diagnostic accuracy of MSDRS and BDI was comparable when diagnosing both MSD-MDDM and MSD-MDL (AROC respectively 0.8998 and 0.8659); the MSDRS showed higher accuracy for the diagnosis of MSD-MDL (AROC respectively 0.9278 and 0.8314; p = .038). The MSDRS may be a reliable tool for the diagnosis of depression in MS.
    The Clinical Neuropsychologist 03/2012; 26(4):571-87. · 1.68 Impact Factor
  • Pain Medicine 03/2012; 13(4):610-2. · 2.46 Impact Factor
  • Journal of neurology, neurosurgery, and psychiatry 03/2012; 83(6):667-8. · 4.87 Impact Factor
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    ABSTRACT: Multiple Sclerosis (MS) is an inflammatory, chronic, degenerative and demyelinating disease of the Central Nervous System caused by activation of myelin-reactive T cells. Recently data provided for the first time, evidence that an expansion of peripheral T helper (Th) 17 cells are associated with disease activity in MS. Th17 cells, and Th1 cells, expanded in response to the self antigen Myelin Basic Protein, strongly supporting the hypothesis of an encephalitogenic role of Th17 in MS. To further characterize Th17 cells and to investigate the possible interplay between Th17 and Th1 cells in tissue damage, we used the so-called “Immunoscope” analysis (a TRBVTRBJ spectratyping) to investigate the TCR repertoire of T cells specific for the immunodominant epitope MBP85-99 in HLA-DR2+ (the human leukocyte antigen allele may linked to MS) patients: 8 untreated patients who fulfilled the McDonald diagnostic criteria for MS and 3 that presented an acute demyelinating event suggestive of MS (CIS). We identified 20 TRBV-TRBJ rearrangements belonging to cells that proliferate in a MBP85-99-dependent manner in the peripheral blood of HLA-DR2+ MS patients: 8 were shared between CIS and MS patients, one was shared only by three MS patients and one by all MS patients, suggesting that the repertoire of TCRs specific for MBP85-99 may be broader in CIS than in MS patients. Th17 and Th1 cells TCR repertoires were mutually exclusive: one TCR rearrangement was enriched among Th17 cells, while twenty-five % of the investigated TCR rearrangements were enriched among Th1cells. We evaluated the effect of IFN-beta therapy on Th17 and Th1 cells. Results indicate that IFN-beta therapy seems to result in a reduction of the total circulating MBP85-99 specific TCR repertoire. Out of twenty TCR rearrangements, only three were still expanded during IFN-beta therapy and all belonged to Th1 cells. This observation confirms recent data showing that Th17 cells are more sensitive than Th1 cells to the apoptotic effect of IFN-beta, suggesting that Th17 cells may be a selective target for IFN-beta.
    VIII SIICA conference, Riccione, RN, Italy; 09/2011
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    ABSTRACT: Objective: Multiple Sclerosis (MS) is an inflammatory, chronic, degenerative and demyelinating disease of the Central Nervous System (CNS). The heterogeneous, progressive clinical course of this dynamic disease leads frequently to physical disability. An increased incidence among certain families and high frequency of human leukocyte antigen (HLA) DR2 among patients suggest genetic susceptibility. MS is supposed to involve an immunologic mechanism: demyelination in MS is possibly caused by the activation of myelin-reactive T cells in the periphery, inducing the expression of adhesion molecules that then allow their entry in the CNS through the Blood-Brain Barrier (BBB). Primed T cells are activated through antigen presentation by antigen-presenting cells (APC) such as macrophages and microglia, or B cells. We investigated the TR-β repertoire of T cells specific for epitope MBP85-99 that is immunodominant in HLA-DR2+ patients, following the protocol published previously in our study about the T cells response specific for type II collagen, in rheumatoid arthritis (Ria et al. Arthr. Res. Ther. 10 (6) 2008 ). Methods: We studied 8 untreated, DR2+ patients who fulfilled the diagnostic criteria for MS (McDonald et al. Ann Neurol 2001; 50: 121–27), Other three patients presented an acute demyelinating event suggestive of MS, Clinically Isolated Syndrome (CIS). In addition we enrolled three healthy DR2+ subjects as a control. PBMC were cultured in vitro either in presence or in absence of MBP85-99 and also as a negative control in presence of MBP111-129. We used the so-called “Immunoscope” technique (a TRBV-TRBJ spectratyping) to investigate the TR-β repertoire of T cells. We also performed the magnetic separation (MACS®) of the IL17+ and the IFN+ populations of the enrolled subjects, and successively we analyze the TR-β repertoire of the TH17 and the TH1 cells. Moreover we performed the sequencing analysis of the more interesting TRBV-TRBJ rearrangements, to find shared CDR3-β between different subjects. Results: We identified 20 MBP85-99 specific TRBV-TRBJ recombinations shared among MS DR2+ patients: 8 were shared by CIS and MS patients; one was shared only by three MS patients; and one TRBV-TRBJ was detected in all MS patients. To confirm these data we investigated also the MBP 111-129 specific rearrangements founding other different expansions not shared with the immunodominant epitope. We also found that one of these 20 TCR rearrangements was exclusively expanded by Th17 cells and was downregulated by IFNβ therapy that seemed to reduce overall circulating MBP specific TCR repertoire especially that one belonging to Th17 phenotipe..On the other side the Th1 sorted cells presented interesting expansion in 25% of the total investigated TCR rearrangements. We performed the sequencing of the shared TRBV-TRBJ rearrangement to confirm the similar response to MBP85-99 in the MS patients, not detectable in the CIS and healthy subjects. Conclusions: Although these data are preliminary and need to be confirmed in a larger cohort of patients, they hint that the repertoire of TCR specific for MBP85-99 may be broader in CIS than in MS patients. If these data were confirmed we could be able to monitor the identified specific TCRs in the peripheral blood of the MS patients during the various relapsing-remitting phases of the disease and during therapy.
    XXI AINI congress, Pollenzo, CN, Italy; 09/2011
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    ABSTRACT: Multiple Sclerosis (MS) is an inflammatory, chronic, degenerative and demyelinating disease of the Central Nervous System (CNS). The heterogeneous, progressive clinical course of this dynamic disease leads frequently to physical disability. An increased incidence among certain families and high frequency of human leukocyte antigen (HLA) DR2 among patients suggest genetic susceptibility. MS is supposed to involve an immunologic mechanism: demyelination in MS is possibly caused by the activation of myelin-reactive T cells in the periphery, inducing the expression of adhesion molecules that then allow their entry in the CNS through the Blood-Brain Barrier (BBB). Primed T cells are activated through antigen presentation by antigen-presenting cells (APC) such as macrophages and microglia, or B cells. We used the so-called “Immunoscope” analysis (a TRBV-TRBJ spectratyping) to investigate the TR-β repertoire of T cells specific for epitope MBP85-99 that is immunodominant in HLA-DR2+ patients, following the protocol published previously in our study about the T cells response specific for type II collagen, in rheumatoid arthritis (Ria et al. Arthr. Res. Ther. 10 (6) 2008 ). We studied 8 untreated, DR2+ patients who fulfilled the diagnostic criteria for MS (McDonald et al. Ann Neurol 2001; 50: 121–27), Other three patients presented an acute demyelinating event suggestive of MS, Clinically Isolated Syndrome (CIS). In addition we enrolled three healthy DR2+ subjects as a control. PBMC were cultured in vitro either in presence or in absence of MBP85-99 and also as a negative control in presence of MBP111-129. We identified 20 MBP85-99 specific TRBV-TRBJ recombinations shared among MS DR2+ patients: 8 were shared by CIS and MS patients; one was shared only by three MS patients; and one TRBV-TRBJ was detected in all MS patients. To confirm these data we investigated also the MBP 111-129 specific rearrangements founding other different expansions not shared with the immunodominant epitope. We also found that one of these 20 TCR rearrangements was exclusively expanded by Th17 cells and was downregulated by IFNβ therapy that seemed to reduce overall circulating MBP specific TCR repertoire especially that one belonging to Th17 phenotipe..On the other side the Th1 sorted cells presented interesting expansion in 25% of the total investigated TCR rearrangements. We performed the sequencing of the shared TRBV-TRBJ rearrangement to confirm the similar response to MBP85-99 in the MS patients, not detectable in the CIS and healthy subjects. Although these data are preliminary and need to be confirmed in a larger cohort of patients, they hint that the repertoire of TCR specific for MBP85-99 may be broader in CIS than in MS patients.
    A/ECTRIMS, Amsterdam, NL; 08/2011
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    ABSTRACT: Swine-origin H1N1 influenza virus (S-OIV) appeared in 2009 with a higher incidence rate among children. Although fever was the most common symptom, some complicated cases occurred. We evaluated the percentages of effector T cells, B cells, and regulatory T cells in peripheral blood from 5 children infected by S-OIV (1 with acute necrotizing encephalitis, 2 with pneumonia, and 2 without complications), 5 children with seasonal influenza, and 5 healthy children. We found higher percentages of T-bet(+) CD4(+)CD8(+) T cells, monocytes, and B cells, granzyme B(+) and perforin(+) CD4(+), and CD8(+) T cells in affected children with both seasonal and H1N1 influenza than in controls, whereas both groups demonstrated similar percentages of CD4(+)CD25(+)Foxp3(+) regulatory T cells. In infected children with complications we observed high percentages of perforin(+) and interferon-γ(+) CD4(+) and CD8(+) T cells associated with low percentages of T regulatory cells. Our data suggest a dysregulation of antipathogen type I immune responses in complicated S-OIV infections.
    Human immunology 05/2011; 72(8):632-5. · 2.55 Impact Factor
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    ABSTRACT: The spinal cord can be affected by multiple heterogeneous disorders often difficult to diagnose. We describe ten patients affected by a progressive ascending myelopathy with a poor prognosis. The patients, during the follow-up period, underwent neurological examinations, cerebrospinal fluid analysis, hematological, microbiological, auto-antibodies screening, brain and spinal cord magnetic resonance imaging (MRI) and electroneurophysiological study. At disease onset spinal cord MRI showed ≥1 myelopathic lesions extended for <2 segments and then evidenced a progressive spinal cord atrophy without any new lesion. All patients showed an increase of the visual evoked potential P100 latency. All of them showed two or more clinical recurrences of myelitis and then, after a period ranging from 3 to 5 years from the disease onset, a progressive course. Five patients became unresponsive to intravenous high-dose steroid treatments and/or intravenous immunoglobulins and to any other therapeutic attempts, developed a progressive ascending myelopathy to tetraplegia and died from respiratory failure. The other five patients are in progressive phase of the disease with an initial involvement of the upper limbs and show mild cervical spinal cord atrophy at MRI, configuring the early stage of an ascending progressive myelopathy. In our opinion, the more suitable diagnosis is an atypical form of MS although is not possible to exclude a new nosological entity that could be included in the expanding range of spinal cord diseases.
    Journal of Neurology 04/2011; 258(11):1965-70. · 3.58 Impact Factor

Publication Stats

1k Citations
559.43 Total Impact Points

Institutions

  • 1992–2014
    • Catholic University of the Sacred Heart
      • • School of Geriatrics
      • • Institute of Neurology
      Milano, Lombardy, Italy
  • 1988–2014
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2011
    • Ospedale Pediatrico Bambino Gesù
      Roma, Latium, Italy
  • 2009
    • Policlinico Universitario Agostino Gemelli
      Roma, Latium, Italy
  • 2000–2006
    • Università Degli Studi Roma Tre
      Roma, Latium, Italy