Leonardo Pantoni

Azienda Ospedaliero Universitaria Careggi, Firenzuola, Tuscany, Italy

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Publications (216)923.29 Total impact

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    ABSTRACT: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients.
    09/2014;
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    ABSTRACT: Background and Objective: Vascular cognitive impairment may have a selective neuropsychological profile. We developed a battery for assessing mild cognitive impairment (MCI) in patients with small vessel disease (SVD), its applicability, and psychometric properties. Methods: Among those proposed by the 2006 NINDS-CSN Consensus Conference, we selected tests for which norms based on healthy Italians and equivalent scores methodology were available. Confirmatory factor analysis was applied to ascertain the fit of the theoretically assumed dimensions to empirical data and to derive each cognitive dimension compound measures. Results: The entire battery was applied to 146 out of a cohort of 201 patients with MCI and SVD. Most tests showed good applicability. Fifty-five patients, who were older and cognitively more impaired, proved unable to complete the Trail Making Test part B, the Rey-Osterrieth Complex Figure, and the Stroop test, and were excluded from the analysis. Among the remaining patients, Mini-Mental State Examination proved largely normal, while Rey-Osterrieth Complex Figure, Symbol digit modalities test, and Trail Making Test part B resulted those most frequently abnormal. Confirmatory factor analysis showed a good fit of the 4-factor theoretical model to empirical data. Praxis domain resulted in the highest percentage of abnormal performance (65%), followed by Memory and Attention/EF domains (19% and 15%), and Language (8%). Conclusions: Our battery proved to be comprehensive, robust, and applicable. Attention-executive dysfunction and impaired memory and visuo-constructional abilities, were the prominent features. The assessment of the Consensus Conference, that included Trial Making Test, looks poorly applicable to older and cognitively impaired patients.
    Journal of Alzheimer's disease: JAD 08/2014; · 4.17 Impact Factor
  • Guido Chiti, Leonardo Pantoni
    08/2014;
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    ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3-negative patients with a phenotype closely resembling that of CADASIL.
    Acta Neurologica Scandinavica 08/2014; · 2.47 Impact Factor
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    ABSTRACT: Background and objective: Services dedicated to patients with cognitive and behavioral consequences of cerebrovascular diseases are not well established. In this paper, we report on the general organization of such a service (the Florence VAS-COG Clinic) after 9 years of activity, updating a previous work related to the first 5 years. Methods: The Florence VAS-COG clinic, started in 2006, is an outpatient service dedicated to the assessment and follow-up of patients with cerebrovascular diseases and related cognitive, psychiatric, and behavioral disturbances. The staff involved in the clinic is composed of certified neurologists, one neuropsychologist, and neurology residents. The diagnostic protocol includes detailed personal and family history, general and neurologic examinations, and functional, neuropsychological, and neuroimaging assessment. After this work-up, comprehensive diagnoses are made. Results: From January 2006 to March 2014, 600 patients (mean age 67.3 years ± 13.9; 52% females) have been evaluated in the clinic. Cognitive impairment, including mild cognitive impairment and dementia, mainly of vascular origin, was the most common (36.4%) diagnostic category, followed by suspected or confirmed familial micro-angiopathy (35.8%). Compared to the first years of activity, we are now facing the need of augmenting the number of visits due to increasing request and to better implement the multidisciplinarity of the team. Efforts are currently directed towards the definition of management protocols in pharmacological and non-pharmacological strategies. Conclusions: The establishment of a VAS-COG clinic represents an important step for the appreciation of the patient clinical needs and for the implementation of screening, diagnostic, and treatment options in the field of the neuropsychiatric consequences of cerebrovascular diseases.
    Journal of Alzheimer's disease: JAD 08/2014; · 4.17 Impact Factor
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    ABSTRACT: The frequency of Listeria monocytogenes (Lm) infection of the central nervous system is increasing. We report a patient recently treated with chemotherapeutic drugs for pulmonary adenocarcinoma who suddenly developed hemiparesis, was initially diagnosed with stroke, and was then found to be affected by Lm rhombencephalitis accompanied by a brain abscess. Lm meningoencephalitis mimicking ischemic stroke is rare but must be considered, especially in specific patients.
    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 06/2014;
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    ABSTRACT: Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2014; · 14.48 Impact Factor
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    ABSTRACT: Dural arteriovenous fistula (DAVF) may present with a variety of neurological symptoms, ranging from tinnitus to fatal hemorrhage. We report a case of rapidly progressive cognitive impairment due to cerebral venous engorgement that reversed after endovascular treatment in a patient with DAVF, cerebral sinus thrombosis and protein S deficiency. DAVF may be a cause of vascular cognitive impairment and should be considered particularly in cases with a rapidly progressive course because they are potentially treatable.
    Journal of Clinical Neuroscience 04/2014; · 1.25 Impact Factor
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    ABSTRACT: To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.
    Journal of Neurology 04/2014; · 3.58 Impact Factor
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    ABSTRACT: White matter hyperintensities (WMH) on MRI are a quantitative marker for sporadic cerebral small vessel disease and are highly heritable. To date, large-scale genetic studies have identified only a single locus influencing WMH burden. This might in part relate to biological heterogeneity of sporadic WMH. The current study searched for genetic modifiers of WMH volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease. We performed a genome-wide association study to identify quantitative trait loci for WMH volume by combining data from 517 CADASIL patients collected through 7 centers across Europe. WMH volumes were centrally analyzed and quantified on fluid attenuated inversion recovery images. Genotyping was performed using the Affymetrix 6.0 platform. Individuals were assigned to 2 distinct genetic clusters (cluster 1 and cluster 2) based on their genetic background. Four hundred sixty-six patients entered the final genome-wide association study analysis. The phenotypic variance of WMH burden in CADASIL explained by all single nucleotide polymorphisms in cluster 1 was 0.85 (SE=0.21), suggesting a substantial genetic contribution. Using cluster 1 as derivation and cluster 2 as a validation sample, a polygenic score was significantly associated with WMH burden (P=0.001) after correction for age, sex, and vascular risk factors. No single nucleotide polymorphism reached genome-wide significance. We found a polygenic score to be associated with WMH volume in CADASIL subjects. Our findings suggest that multiple variants with small effects influence WMH burden in CADASIL. The identification of these variants and the biological pathways involved will provide insights into the pathophysiology of white matter disease in CADASIL and possibly small vessel disease in general.
    Stroke 02/2014; · 6.16 Impact Factor
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    ABSTRACT: The frequency of Listeria monocytogenes (Lm) infection of the central nervous system is increasing. We report a patient recently treated with chemotherapeutic drugs for pulmonary adenocarcinoma who suddenly developed hemiparesis, was initially diagnosed with stroke, and was then found to be affected by Lm rhombencephalitis accompanied by a brain abscess. Lm meningoencephalitis mimicking ischemic stroke is rare but must be considered, especially in specific patients.
    Journal of Clinical Neuroscience. 01/2014;
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    ABSTRACT: Dural arteriovenous fistula (DAVF) may present with a variety of neurological symptoms, ranging from tinnitus to fatal hemorrhage. We report a case of rapidly progressive cognitive impairment due to cerebral venous engorgement that reversed after endovascular treatment in a patient with DAVF, cerebral sinus thrombosis and protein S deficiency. DAVF may be a cause of vascular cognitive impairment and should be considered particularly in cases with a rapidly progressive course because they are potentially treatable.
    Journal of Clinical Neuroscience. 01/2014;
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    ABSTRACT: Background Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear. Methods Population-based samples of 70- to 95-year-olds (n = 2462) in Gothenburg, Sweden, underwent neuropsychiatric examinations. Behavioral variant FTD (bvFTD) was diagnosed according to the International Behavioural Variant FTD Criteria Consortium (FTDC), the Frontotemporal Lobe Degeneration Consensus criteria, and the Lund-Manchester Research Criteria. A subset (n = 1074) underwent computerized tomography (CT) of the brain. Results The prevalence of bvFTD varied between 0.2% and 0.5% at age 70 to 79 years, between 2.5% and 3.6% at age 80 to 89 years, and between 1.7% and 2.2% at age 90 to 95 years. The agreement between different criteria was low to moderate (κ = 0.20–0.42). Among those with bvFTD according to FTDC, 93.3% had frontal and/or temporal lobar atrophy on CT, compared with 12.6% of those without bvFTD (P < .001). Conclusions The prevalence of bvFTD was higher than expected in this population. To a large extent, different criteria captured different individuals.
    Alzheimer's & Dementia. 01/2014;
  • Leonardo Pantoni, Fabio Fierini, Anna Poggesi
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    ABSTRACT: Background: Thrombolytic treatment is of proven benefit in acute ischemic stroke. The term cerebral small vessel disease (SVD) refers to a group of pathological processes affecting the small arteries, arterioles, venules and capillaries of the brain, and encompasses both ischemic and hemorrhagic lesions. Lacunar stroke, an expression of SVD, is associated with an unfavorable long-term prognosis for an increased risk of death, recurrent stroke and cognitive dysfunction. Nonetheless, the efficacy and safety of intravenous thrombolysis in patients with lacunar stroke has been debated for two main reasons. First, among all ischemic stroke subtypes, lacunar strokes have been considered the most benign. Second, the efficacy of a pharmacological reperfusion has been questioned given the absence of a clear demonstration of thrombosis. Intracerebral hemorrhage (ICH) remains the most devastating and unpredictable complication related to thrombolysis, and neuroimaging evidence of SVD is nowadays recognized as one of the risk factors for thrombolysis-related ICH. Summary: This review is structured in two parts dealing with the questions whether or not patients with lacunar stroke or SVD should be treated with thrombolysis. In the first part, we revised the literature concerning the efficacy of thrombolysis in patients with acute lacunar stroke. We included two types of studies: those in which patients with lacunar stroke receiving recombinant human tissue plasminogen activator (rt-PA) were compared with lacunar stroke patients receiving placebo, and those in which a comparison was made among different stroke subtype patients treated with rt-PA. In the second part, we reviewed the available evidence on the risk of ICH in patients treated with thrombolysis for ischemic stroke and presenting with neuroimaging evidence of SVD such as white matter lesions (WML) and cerebral microbleeds. We further questioned the extent to which WML and microbleeds could be used as reliable predictors of ICH and the feasibility of their detection in an acute setting. Key Messages: The studies herein reviewed show that thrombolysis is an effective treatment in acute lacunar stroke, and that the presence of cerebral SVD increases the risk of ICH during thrombolysis but does not represent an absolute exclusion criterion. In the future, it can be assumed that the use of MRI on a routine basis might lead to a better quantitative definition of SVD and its correlates, permitting a step forward in thrombolysis decision making. © 2013 S. Karger AG, Basel.
    Cerebrovascular Diseases 12/2013; 37(1):5-13. · 2.81 Impact Factor
  • Francesca Pescini, Anna Poggesi, Leonardo Pantoni
    Circulation 10/2013; 128(17):e362. · 15.20 Impact Factor
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    ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (β = -0.418, P < 0.003) in CADASIL patients and the executive function index (β = -0.321, P = 0.028) in ARL. This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.
    European Journal of Neurology 07/2013; · 4.16 Impact Factor
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    ABSTRACT: Background: Cross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care. Methods: 639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i.e. ARWMC) and outcome. Results: Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology. Conclusion: Only moderate and severe ARWMC is independently associated - on average - with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.
    Cerebrovascular Diseases 07/2013; 35(6):544-553. · 2.81 Impact Factor
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    ABSTRACT: Post-stroke cognitive impairment (PSCI) includes all forms of cognitive decline that develop after stroke, even if not severe enough to fit the criteria of dementia. Our aims were to investigate the predictive value of a brief bedside examination (Montreal Cognitive Assessment, MoCA) in the acute phase of stroke on the diagnosis of mid-term PSCI, taking into account other clinical, cognitive, functional, and neuroimaging predictors. Consecutive patients admitted to a stroke unit were evaluated with MoCA between 5 and 9 days after stroke. At baseline, clinical, functional, and neuroimaging data were collected. Patients were reassessed between 6 and 9 months after stroke by means of an extensive neuropsychological and functional evaluation. Out of 137 enrolled stroke patients, 80 (58.4 %) were followed up (mean age 68.2 ± 14.6 years, males 66 %, mean NIHSS score 3.6 ± 4.8). PSCI was diagnosed in 47 patients (59 %; 35 mild cognitive impairment, 12 dementia). Controlling for age, education, functional and cognitive pre-morbid status, stroke severity, and pre-existing lacunar infarcts, MoCA baseline score [OR (95 % CI) = 1.4(1.1-1.8)] for each point] and leukoaraiosis severity [OR (95 % CI) = 0.4(0.2-0.9)] for each point of the van Swieten scale] were independently associated with PSCI. Using a ROC analysis, a cut-off of 21 predicted the diagnosis of PSCI with 91.4 % sensitivity, 75.8 % specificity, 80 % positive predictive value, and 89.3 % negative predictive value. In a sample of mild stroke patients, MoCA seems to be a good predictor of mid-term PSCI, making it a possible candidate for a brief cognitive screening in the acute stroke setting.
    Journal of Neurology 05/2013; · 3.58 Impact Factor
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    ABSTRACT: BACKGROUND In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed. METHODS: We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months. RESULTS: A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. CONCLUSIONS: The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).
    New England Journal of Medicine 05/2013; 368(10):904-913. · 51.66 Impact Factor

Publication Stats

6k Citations
923.29 Total Impact Points

Institutions

  • 2013–2014
    • Azienda Ospedaliero Universitaria Careggi
      • Stroke and Neurology Unit
      Firenzuola, Tuscany, Italy
    • ISCTE-Instituto Universitário de Lisboa
      Lisboa, Lisbon, Portugal
  • 1991–2014
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florens, Tuscany, Italy
  • 2007–2012
    • University of Helsinki
      • • Department of Neurology
      • • Department of Psychology
      Helsinki, Southern Finland Province, Finland
    • Copenhagen University Hospital Hvidovre
      • Danish Research Centre for Magnetic Resonance
      Hvidovre, Capital Region, Denmark
  • 2006–2012
    • Hospital de Santa Maria
      Lisboa, Lisbon, Portugal
  • 1998–2012
    • Helsinki University Central Hospital
      • Department of Neurology
      Helsinki, Province of Southern Finland, Finland
  • 2008–2011
    • Rigshospitalet
      • Department of Neurology
      Copenhagen, Capital Region, Denmark
    • Hirakata General Hospital For Developmental Disorders
      Ōsaka, Ōsaka, Japan
    • Technical University of Denmark
      • Department of Informatics and Mathematical Modelling
      Copenhagen, Capital Region, Denmark
  • 2009–2010
    • Medical University of Graz
      Gratz, Styria, Austria
  • 2006–2010
    • University of Gothenburg
      • Institute of Neuroscience and Physiology
      Göteborg, Vaestra Goetaland, Sweden
  • 2008–2009
    • Universität Heidelberg
      • Neurological Clinic
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2005–2008
    • VU University Amsterdam
      • Department of Neurology
      Amsterdam, North Holland, Netherlands
  • 2006–2007
    • VU University Medical Center
      • Department of Neurology
      Amsterdam, North Holland, Netherlands
  • 2005–2007
    • Newcastle University
      • Institute for Ageing and Health
      Newcastle upon Tyne, ENG, United Kingdom
  • 2003
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 2001
    • National Research Council
      Roma, Latium, Italy
    • Karolinska Institutet
      • Institutionen för klinisk neurovetenskap
      Solna, Stockholm, Sweden
  • 1995–1997
    • Henry Ford Hospital
      • Department of Neurology
      Detroit, MI, United States