Stefano Zoccolella

Università degli Studi di Bari Aldo Moro, Bari, Apulia, Italy

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Publications (64)233.04 Total impact

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    ABSTRACT: Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies.
    Multiple sclerosis (Houndmills, Basingstoke, England). 08/2014;
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    Ann Neurol. 2014 . 05/2014;
  • American Academy of Neurology 2014; 04/2014
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    ABSTRACT: Objectives: To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). Methods: From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1166 population controls (matched for age, sex, and residency) were assessed. Upon direct interview, data were collected on occupation and history of sport and leisure activities, physical activity, and accidental injuries. Physical exercise was defined as having spent time doing activities which caused an individual to breath hard at least once a month and was coded as none, job-related and/or sport-related. Sport-related and work-related physical exercise were quantified using the metabolic equivalents (METs). Risks were calculated using conditional logistic regression models (adjusting for age, country, trauma and job-related physical activity) and expressed as odds ratios (OR) and adjusted OR (Adj OR) with 95% confidence intervals (CI). Results: Overall physical activity was associated with reduced odds of having ALS (Adj OR 0.65 [95% CI 0.48-0.89]) as were work-related physical activity (Adj OR 0.56 [95% CI 0.36-0.87]), and organized sports (Adj OR 0.49 [95% CI 0.32-0.75]). An inverse correlation was observed between ALS, the duration of physical activity (p=0.0041) and the cumulative MET scores, which became significant for the highest exposure (adj.OR 0.34 [0.21-0.54]).. An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events. Interpretation: Physical activity is not a risk factor for ALS and may eventually be protective against the disease. ANN NEUROL 2014. © 2014 American Neurological Association.
    Annals of Neurology 04/2014; · 11.19 Impact Factor
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    ABSTRACT: Background and purposeTo evaluate whether cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels could predict the time to generalization (TTG) in amyotrophic lateral sclerosis (ALS).Methods Cerebrospinal fluid NFL levels of 37 cases of sporadic ALS were measured and the time of symptom spreading from spinal or bulbar localization to both (TTG) was evaluated in all patients.ResultsKaplan−Meier analysis showed a short TTG in patients with high NFL levels (log-rank test chi-squared = 19.4, P < 0.0001). In a multivariate regression model patients with NFL levels above the median had an eight-fold higher risk of generalization (adjusted hazard ratio 7.9, 95% confidence interval 2.9–21.4, P < 0.0001) compared with those with NFL levels below the median.Conclusions This study shows that in sporadic ALS NFL, a marker of neurodegeneration, is correlated with TTG, a clinical intermediate parameter of survivorship.
    European Journal of Neurology 04/2014; · 4.16 Impact Factor
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    ABSTRACT: Investigations into prognostic factors in progressive supranuclear palsy have shown conflicting results. We performed a retrospective study in order to identify clinical predictors of survival in clinically diagnosed progressive supranuclear palsy patients referred to our centre. Data on medical history, survival and five clinical disability milestones (inability to walk unassisted, unintelligible speech, severe dysphagia, dementia and institutionalization) were collected from outpatients' medical records and by a telephone interview to caregivers. Patients were subdivided into Richardson's syndrome and PSP-Parkinsonism according to symptoms during the first 2 years of disease. Survival was analyzed by the Kaplan-Meier method and Cox regression analysis. Forty-three consecutive patients were enrolled (86% Richardson's syndrome). Motor disturbances were the most frequent symptoms of onset. During the follow-up, 60.5% of patients died after a median survival of 7.1 years (2.2-18). Older age at onset (>63) (HR 2.8; 95% CI: 1.3-5.7; p = 0.007), early dysphagia (HR 2.3; 95% CI: 1-5.3; p = 0.05) and early cognitive deficits (HR 3.6; 95% CI: 1.6-8.2; p = 0.002) were predictors of shorter survival. Compared to PSP-Parkinsonism patients, Richardson's syndrome patients had shorter survival and higher mortality risk although not statistically significant (HR 3 95% CI: 0.9-9.9; p = 0.07). Seventy-seven percent of patients developed severe disability during follow-up: shorter time to the first clinical disability milestone predicted shorter survival (HR 7.8; 95% CI: 2.3-26; p = 0.0008). Conclusions: early dysphagia, cognitive impairment, older age at onset, and time to disability were predictors of shorter survival; Richardson's syndrome had a less favorable course than PSP-Parkinsonism. Clinical milestones should be considered as possible endpoints in future clinical trials.
    Parkinsonism & Related Disorders 08/2013; · 3.27 Impact Factor
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    ABSTRACT: BACKGROUND: Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. OBJECTIVES: The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. METHODS: Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. RESULTS: CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. CONCLUSIONS: This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.
    Multiple Sclerosis 01/2013; · 4.47 Impact Factor
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease.
    PLoS ONE 01/2013; 8(11):e80748. · 3.53 Impact Factor
  • Journal of Neurology 12/2012; 19(12):1509-17. · 3.58 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Published reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case-control study done in a large population. METHODS: A case-control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population-based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non-degenerative) disease and one with a non-neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee. RESULTS: The study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non-neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25-2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86-5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36-4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events that occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant. CONCLUSION: Antecedent trauma, repeated trauma, and severe trauma may be risk factors for ALS.
    European Journal of Neurology 12/2012; 19(12):1509-17. · 4.16 Impact Factor
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    ABSTRACT: Our objective was to assess the role of defects of mitochondrial function as contributing factors in the pathogenesis and/or progression of amyotrophic lateral sclerosis (ALS); mitochondrial genome structural alterations were investigated. DNA lesions, point alterations and gross rearrangements were screened by specific applications of real-time PCR including an optimized rapid gene-specific method for the accurate quantification of mitochondrial DNA (mtDNA) lesions as well as sequencing on skeletal muscle biopsies of three patients presenting with motor neuron disease. We found a higher frequency of mtDNA lesions, including multiple deletions, particularly in the only SOD1 mutated patient as well as in a patient negative for mutations in SOD1 but presenting a severe form of the disease. The occurrence and the extent of mtDNA lesions of the cases here presented were consistent in all the examined clinical phenotypes of ALS (SOD1 related ALS, bulbar onset, spinal onset) and correlated with the severity of clinical course of the illness and with the presence of SOD1 mutation as well. In conclusion, the strong association with mtDNA damages supports the hypothesis that mitochondrial dysfunction in skeletal muscle may contribute to the pathogenesis and progression of ALS.
    Amyotrophic Lateral Sclerosis 10/2012; · 3.40 Impact Factor
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    European Journal of Neurology 10/2012; 19(10):e117-8. · 4.16 Impact Factor
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    European Journal of Neurology 07/2012; 19(7):e63-4. · 4.16 Impact Factor
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    ABSTRACT: BACKGROUND: To date there are no biomarkers with proven reliability as measure of disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to assess the neurofilament light chain (NFL) in cerebrospinal fluid (CSF) samples as a measure of disease activity and progression in ALS. METHODS: Thirty-seven consecutive patients with ALS, 25 with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and 21 with other neurodegenerative diseases (OND) were evaluated. CSF NFL levels were assayed by two-site solid-phase sandwich ELISA. In patients with ALS, neurological status was assessed by revised ALS Functional Rating Scale (ALSFRS-r) and Medical Research Council (MRC), and the progression of the disease was evaluated using the 'diagnostic delay' and the 'progression rate'. RESULTS: Cerebrospinal fluid NFL levels were higher in ALS cases than in controls (P < 0.0001). Using the Receiver Operating Curve (ROC) analysis, an optimal NFL cut-off of 1981 ng/l discriminated between patients with ALS and neurological controls, with a sensitivity of 78.4% and specificity of 72.5%. Multivariate logistic regression confirmed the association between CSF NFL levels and the presence of ALS (age and sex adjusted odds ratio for ALS 8.9; 95% CI 3.1-25.8; P < 0.0001). In ALS, CSF NFL negatively correlated with the diagnostic delay (P < 0.0001) and the ALSFRS-r (P = 0.014) and positively with the progression rate (P < 0.0001). CONCLUSIONS: High CSF NFL levels were found in patients with ALS, reflecting the burden of neurodegeneration. The significant relation between CSF NFL levels and disease progression suggests that NFL may be a useful marker of disease activity and progression in ALS.
    European Journal of Neurology 06/2012; · 4.16 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Published reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case-control study done in a large population. METHODS: A case-control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population-based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non-degenerative) disease and one with a non-neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee. RESULTS: The study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non-neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25-2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86-5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36-4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant. CONCLUSION: Antecedent trauma, repeated trauma, and severe trauma may be risk factors for ALS.
    European Journal of Neurology 04/2012; · 4.16 Impact Factor
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    ABSTRACT: Elevated homocysteine (Hcy) levels exert several neurotoxic actions and vascular dysfunctions that may be involved in pathogenesis and progression of multiple sclerosis (MS). The effective role of Hcy in MS however remains to be determined. The aim of this work was to compare plasma Hcy levels in MS patients and neurological disease controls (NDC) and to evaluate their relationships with clinical and demographic variables. In this cross-sectional study, we examined plasma Hcy levels in 217 patients with MS [53 clinically isolated syndromes (CIS) suggestive of MS, 134 relapsing remitting (RR), 23 secondary progressive (SP) and seven primary progressive (PP) MS], recruited among patients attending a tertiary clinical center in southern Italy and in 219 age/sex-matched controls. Median Hcy levels were slightly higher in MS patients compared to NDC (9.1 μmol/l; range, 3.4-35.9 vs. 8.6, range 3.5-27.4; p = 0.02). Median Hcy concentrations were increased in males more than in females in the MS population (10.4 vs. 8.4; p < 0.0001), whereas no differences across genders were found in NDC (9.1 vs. 8.5). Hcy levels were higher in male MS patients compared to the male NDC patients (p = 0.001). Patients with CIS had lower Hcy (7.5 μmol/l; p = 0.004) compared to patients with RR (9.5 μmol/l), SP (10.1 μmol/l) and PP (9.9 μmol/l). Median Hcy concentration was higher in patients with disease duration longer than 22 months (9.7 vs. 8.6 μmol/l; p = 0.02). Plasma Hcy levels are increased in patients with definite MS. Higher Hcy levels are associated with male sex, suggesting a role of Hcy in neurodegenerative processes of MS, which are prominent in male patients.
    Journal of Neurology 03/2012; 259(10):2105-10. · 3.58 Impact Factor
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    ABSTRACT: Natalizumab reduces the relapse rate and magnetic resonance imaging activity in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). So far the influence of natalizumab on cognitive functions and fatigue in MS remains uncertain. The aim of this prospective, open-label, observational study was to evaluate the possible effects of natalizumab on cognition and fatigue measures in RRMS patients treated for up to two years. Cognitive performances were examined by the Rao's Brief Repeatable Battery (BRB), the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months. Patients who failed in at least 3 tests of the BRB and the ST were classified as cognitively impaired (CI). Fatigue Severity Scale (FSS) was administered every 12 months to assess patient's self-reported fatigue. One hundred and 53 patients completed 1 and 2 year-natalizumab treatment, respectively. After 1 year of treatment the percentage of CI patients decreased from 29% (29/100) at baseline to 19% (19/100) (p = 0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p = 0.008). These significant effects were confirmed in the subgroup of patients treated up to two years. These results demonstrate that a short-term NTZ treatment may significantly improve cognitive performances and fatigue in RRMS patients.
    PLoS ONE 01/2012; 7(4):e35843. · 3.53 Impact Factor
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    ABSTRACT: Urate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain. To evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables. Levels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC). Median serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: -0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis. Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.
    PLoS ONE 01/2012; 7(7):e40608. · 3.53 Impact Factor
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    ABSTRACT: N -acetylaspartate (NAA) level is a biomarker of functional integrity and vitality in neurons. In vivo multisection proton ((1)H)-magnetic resonance spectroscopy studies indicate that NAA level decreases in specific cortical brain areas of patients with amyotrophic lateral sclerosis (ALS). To study NAA level in serum samples as a possible biomarker of ALS. Serum NAA assay by liquid chromatography-mass spectrometry in a case-control series. Department of Neurological and Psychiatric Sciences, Policlinico, University of Bari, Bari, Italy. One hundred twelve consecutive patients with ALS and 51 age- and sex-matched healthy control subjects. General estimating equations tested associations between serum NAA level and clinical variables in patients with ALS. Serum NAA level was significantly higher in ALS cases than in controls. Multivariate logistic regression analysis showed a direct association between serum NAA level and the presence of ALS. After stratifying serum NAA level based on the median value (0.171 mmol/L), the age- and sex-adjusted odds ratio for ALS was 19.97 (95% confidence interval, 7.18-55.55) (P < .001). N -acetylaspartate level did not differ across ALS clinical phenotypes. Riluzole treatment did not affect NAA level. A significant correlation was found between serum NAA level and ALS progression rate. High serum NAA level was found in patients with ALS, which may relate to greater excretion of NAA into the blood circulation following increased release of this metabolite from damaged neurons. The correlation between serum NAA level and disease progression rate suggests that it may be a useful biomarker of ALS.
    Archives of neurology 10/2011; 68(10):1308-12. · 7.58 Impact Factor
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    ABSTRACT: The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007-2010). For each patient, 2 age- and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for ≥6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was ≥30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk.
    American journal of epidemiology 09/2011; 174(9):1002-8. · 5.59 Impact Factor

Publication Stats

603 Citations
233.04 Total Impact Points

Institutions

  • 2002–2014
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy
  • 2010–2011
    • Università degli studi di Foggia
      • Department of Medical and Surgical Sciences
      Foggia, Apulia, Italy
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      Giovanni Rotondo, Apulia, Italy
  • 2009–2011
    • Azienda Ospedaliero - Universitaria "Ospedali Riuniti" Trieste
      Trst, Friuli Venezia Giulia, Italy
    • Mario Negri Institute for Pharmacological Research
      • Laboratory of Neurological Disorders
      Milano, Lombardy, Italy
  • 2009–2010
    • Ospedali Riuniti di Bergamo
      Bérgamo, Lombardy, Italy
  • 2008–2010
    • Ospedale Generale Regionale "F. Miulli"
      Acquaviva delle Fonti, Apulia, Italy