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Article ; Online: Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review.

Palermo, Giovanni / Giannoni, Sara / Bellini, Gabriele / Siciliano, Gabriele / Ceravolo, Roberto

International journal of molecular sciences

2021 Volume 22, Issue 20

Abstract: A major goal of current clinical research in Parkinson's disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical ... ...

Abstract	A major goal of current clinical research in Parkinson's disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Humans ; Molecular Imaging/methods ; Parkinson Disease/diagnosis ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/metabolism
Chemical Substances	Biomarkers ; Dopamine Plasma Membrane Transport Proteins
Language	English
Publishing date	2021-10-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222011234
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Article ; Online: Statins in Parkinson's Disease: Influence on Motor Progression.

Palermo, Giovanni / Giannoni, Sara / Giuntini, Martina / Belli, Elisabetta / Frosini, Daniela / Siciliano, Gabriele / Ceravolo, Roberto

Journal of Parkinson's disease

2021 Volume 11, Issue 4, Page(s) 1651–1662

Abstract: Background: It has been speculated that stains are neuroprotective and are associated with a reduced risk of Parkinson's disease (PD), but only a few studies have investigated the influence of statins on the progression of PD.: Objective: To evaluate ...

Abstract	Background: It has been speculated that stains are neuroprotective and are associated with a reduced risk of Parkinson's disease (PD), but only a few studies have investigated the influence of statins on the progression of PD. Objective: To evaluate whether long-term statin use may affect motor progression in a large cohort of de novo patients with PD. Methods: We conducted a 4-year retrospective observational cohort study to assess patients with PD. The patients were consecutively recruited from a single tertiary center between January 2015 and January 2017. Information on motor function was obtained using the MDS-Unified Parkinson Disease Rating Scale (UPDRS)-III and all subjects were extensively characterized, including information about lifestyle habits, cardiovascular risk factors and cholesterol blood levels. Results: Of the 181 participants included in the study, 104 patients were evaluated for eligibility (42 patients were exposed to statin therapies and 62 were not treated with statins). They presented similar scores in UPDRS III at baseline but the statin users had a lower motor impairment at 4 years compared to non-user PD patients. Additionally, statin treatment resulted in slower progression of the rigidity score of UPDRS over 4 years. No other significant differences were observed between PD patients with and without statins. Conclusion: Early PD patients with long-term statin usage showed lower motor deterioration after 4 years of disease duration compared with patients not taking statins at diagnosis, suggesting a possible influence of statins on disease progression in PD. Further investigation is warranted to understand the potential beneficial effects of statin treatment on clinical symptoms in PD.
MeSH term(s)	Cohort Studies ; Disease Progression ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Parkinson Disease/drug therapy ; Retrospective Studies
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2021-07-02
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-212655
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Article ; Online: Negative DAT-SPECT in Old Onset Parkinson's Disease: An Additional Pitfall?

Palermo, Giovanni / Giannoni, Sara / Depalo, Tommaso / Frosini, Daniela / Volterrani, Duccio / Siciliano, Gabriele / Bonuccelli, Ubaldo / Ceravolo, Roberto

Movement disorders clinical practice

2022 Volume 9, Issue 4, Page(s) 530–534

Abstract: Background: Scans without evidence of dopaminergic deficit (SWEDDs) refer to patients clinically diagnosed with Parkinson's disease (PD), but showing normal findings on dopamine transporter single-photon emission computed tomography (DAT-SPECT). This ... ...

Abstract	Background: Scans without evidence of dopaminergic deficit (SWEDDs) refer to patients clinically diagnosed with Parkinson's disease (PD), but showing normal findings on dopamine transporter single-photon emission computed tomography (DAT-SPECT). This entity remains highly debated, but recent findings suggesting that DAT-SPECT does not reflect either nigral cell bodies or striatal fibers of dopaminergic nigrostriatal neurons could improve our understanding of SWEDDs. Notably, compensatory downregulation of DAT in the early stages of PD seems to be less efficient in older-onset than in young-onset patients. Cases: We report eight patients with old-onset clinical parkinsonism and a positive response to levodopa in which DAT-SPECT was normal both visually and semiquantitatively. Two subjects demonstrated an abnormal scan when repeated later. Conclusions: We suggest that old-onset patients may truly have dopaminergic degeneration despite normal imaging results, presumably because they are diagnosed in the early stages confirming less efficient striatal compensatory strategies in old-age onset PD.
Language	English
Publishing date	2022-04-15
Publishing country	United States
Document type	Case Reports
ISSN	2330-1619
ISSN (online)	2330-1619
DOI	10.1002/mdc3.13441
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Article: Distinct limbic connectivity in left and right benign mesial temporal lobe epilepsy: Evidence from a resting state functional MRI study.

Pizzanelli, Chiara / Pesaresi, Ilaria / Milano, Chiara / Cecchi, Paolo / Fontanelli, Lorenzo / Giannoni, Sara / Giorgi, Filippo Sean / Cosottini, Mirco / Bonanni, Enrica

Frontiers in neurology

2022 Volume 13, Page(s) 943660

Abstract: Background: Functional connectivity (FC) studies showed that pharmaco-resistant mesial temporal lobe epilepsy (MTLE) affects not only the limbic system, but also several extra-limbic regions, including areas belonging to resting state networks. Less is ... ...

Abstract	Background: Functional connectivity (FC) studies showed that pharmaco-resistant mesial temporal lobe epilepsy (MTLE) affects not only the limbic system, but also several extra-limbic regions, including areas belonging to resting state networks. Less is known about FC in subjects with benign MTLE (i.e., sensitive to antiseizure medication, bMTLE). Aim and methods: We evaluated FC of hippocampus and amygdala in subjects with bMTLE, distinguished based on the epileptic focus lateralization. We enrolled 19 patients (10 with left and 9 with right bMTLE) and 10 age-matched healthy subjects. Connectivity was investigated at rest by using a seed-based regression analyses approach with four regions of interest (left and right hippocampus, left and right amygdala). Patients were also tested with a neuropsychological battery and their scores were correlated with fMRI data. Results and conclusions: Our study documented an asymmetrical disruption of FC in bMTLE, in relation to the side of the focus. Right subjects only exhibited limited altered connections, while left subjects-who performed worse in verbal memory tests-showed a wide bilateral hypoconnectivity of hippocampus and amygdala with areas belonging to language and memory network. The strength of FC between left limbic areas and language and memory network correlated with better performances in verbal memory tests. Moreover, we observed an increased FC with areas of default mode network, more pronounced in left subjects, a possible attempt to compensate cognitive deficit but without effectiveness.We believe that these findings could help to better characterize bMTLE, in which a dysfunction of limbic connectivity is detectable despite well-controlled epilepsy.
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.943660
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Article ; Online: Post-Stroke Detection of Subclinical Paroxysmal Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source in the Real World Practice: The Empoli ESUS Atrial Fibrillation (E 2 AF) Study.

Grifoni, Elisa / Baldini, Giulia / Baldini, Mariella / Pinto, Gabriele / Micheletti, Irene / Madonia, Elisa M / Cosentino, Eleonora / Bartolozzi, Maria L / Bertini, Elisabetta / Dei, Alessandro / Signorini, Ira / Giannoni, Sara / Del Rosso, Attilio / Prisco, Domenico / Guidi, Leonello / Masotti, Luca

The neurologist

2023 Volume 28, Issue 1, Page(s) 25–31

Abstract: Background: Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the ... ...

Abstract	Background: Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the probability of AF detection in ESUS. Methods: We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores. Results: Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores. Conclusions: In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.
MeSH term(s)	Aged ; Female ; Humans ; Atrial Fibrillation/complications ; Atrial Fibrillation/diagnosis ; Embolic Stroke/complications ; Hypertension/complications ; Hypertension/diagnosis ; Retrospective Studies ; Risk Factors ; Stroke/complications ; Stroke/diagnosis ; Male
Language	English
Publishing date	2023-01-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1361380-7
ISSN	2331-2637 ; 1074-7931
ISSN (online)	2331-2637
ISSN	1074-7931
DOI	10.1097/NRL.0000000000000440
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Article ; Online: Validation of Empoli Embolic Stroke of Undetermined Source Atrial Fibrillation (E 2 AF) Score for Detecting Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source.

Masotti, Luca / Grifoni, Elisa / Baglini, Alessia / Sivieri, Irene / Mannini, Marianna / Iandoli, Gina / Madonia, Elisa Maria / Cosentino, Eleonora / Micheletti, Irene / Signorini, Ira / Cioni, Elisa / Sansone, Teresa / Pelagalli, Giulia / Baldini, Mariella / Giannoni, Sara / Bertini, Elisabetta / Di Donato, Ilaria

The neurologist

2023 Volume 28, Issue 6, Page(s) 426–428

MeSH term(s)	Humans ; Atrial Fibrillation/complications ; Atrial Fibrillation/diagnosis ; Embolic Stroke ; Heart Atria ; Stroke/complications ; Stroke/diagnosis ; Risk Factors
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1361380-7
ISSN	2331-2637 ; 1074-7931
ISSN (online)	2331-2637
ISSN	1074-7931
DOI	10.1097/NRL.0000000000000497
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Article: Fluid Biomarkers in Alzheimer's Disease and Other Neurodegenerative Disorders: Toward Integrative Diagnostic Frameworks and Tailored Treatments.

Giampietri, Linda / Belli, Elisabetta / Beatino, Maria Francesca / Giannoni, Sara / Palermo, Giovanni / Campese, Nicole / Tognoni, Gloria / Siciliano, Gabriele / Ceravolo, Roberto / De Luca, Ciro / Baldacci, Filippo

Diagnostics (Basel, Switzerland)

2022 Volume 12, Issue 4

Abstract: The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer's Disease (AD) so far highlighted the need for a ... ...

Abstract	The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer's Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.
Language	English
Publishing date	2022-03-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12040796
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Article ; Online: Dopamine Transporter, Age, and Motor Complications in Parkinson's Disease: A Clinical and Single-Photon Emission Computed Tomography Study.

Palermo, Giovanni / Giannoni, Sara / Frosini, Daniela / Morganti, Riccardo / Volterrani, Duccio / Bonuccelli, Ubaldo / Pavese, Nicola / Ceravolo, Roberto

Movement disorders : official journal of the Movement Disorder Society

2020 Volume 35, Issue 6, Page(s) 1028–1036

Abstract: Background: Previous molecular imaging studies comparing dopamine function in vivo between early-onset PD and late-onset PD patients have shown contradictory results, presumably attributable to the aging-related decline in nigrostriatal function.: ... ...

Abstract	Background: Previous molecular imaging studies comparing dopamine function in vivo between early-onset PD and late-onset PD patients have shown contradictory results, presumably attributable to the aging-related decline in nigrostriatal function. Objectives: (1) To investigate baseline dopamine transporter availability in early-onset PD (<55 years) and late-onset PD (>70 years) patients, z-scores values of putamen and caudate [ Methods: In this retrospective study, 105 de novo PD patients who underwent [ Results: Despite a less-severe motor phenotype, early-onset PD patients exhibited more reduced [ Conclusions: Our findings indicate that a lower dopamine transporter binding in early-onset PD predicts the later development of motor complications, but it is not related to severity of motor symptoms, suggesting age-related differences in striatal compensatory mechanisms in PD. © 2020 International Parkinson and Movement Disorder Society.
MeSH term(s)	Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Humans ; Parkinson Disease/complications ; Parkinson Disease/diagnostic imaging ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon
Chemical Substances	Dopamine Plasma Membrane Transport Proteins ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2020-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.28008
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Article ; Online: Predictive Factors for Hemorrhagic Transformation in Acute Ischemic Stroke in the REAL-World Clinical Practice.

Grifoni, Elisa / Bini, Chiara / Signorini, Ira / Cosentino, Eleonora / Micheletti, Irene / Dei, Alessandro / Pinto, Gabriele / Madonia, Elisa Maria / Sivieri, Irene / Mannini, Marianna / Baldini, Mariella / Bertini, Elisabetta / Giannoni, Sara / Bartolozzi, Maria Letizia / Guidi, Leonello / Bartalucci, Paola / Vanni, Simone / Segneri, Antonio / Pratesi, Alessandra /

Giordano, Antonio / Dainelli, Francesca / Maggi, Francesca / Romagnoli, Mario / Cioni, Elisa / Cioffi, Elisa / Pelagalli, Giulia / Mattaliano, Chiara / Schipani, Elena / Murgida, Giuseppe Salvatore / Di Martino, Stefania / Sisti, Eleonora / Cozzi, Andrea / Francolini, Valentina / Masotti, Luca

The neurologist

2023 Volume 28, Issue 3, Page(s) 150–156

Abstract: Background: Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to develop a score for predicting HT.: ... ...

Abstract	Background: Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to develop a score for predicting HT. Methods: We retrospectively analyzed the clinical, radiographic, and laboratory data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit along two years. Patients with HT were compared with those without HT. A multivariate logistic regression analysis was performed to identify independent predictors of HT on CT scan at 24 hours to develop a practical score. Results: The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT at 24 hours (4.9% symptomatic). NIHSS score ≥8 at Stroke Unit admission (3 points), cardioembolic etiology (2 points), acute revascularization by systemic thrombolysis and/or mechanical thrombectomy (1 point), history of previous TIA/stroke (1 point), and major vessel occlusion (1 point) were found independent risk factors of HT and were included in the score (Hemorrhagic Transformation Empoli score (HTE)). The predictive power of HTE score was good with an AUC of 0.785 (95% CI: 0.749-0.818). Compared with 5 HT predictive scores proposed in the literature (THRIVE, SPAN-100, MSS, GRASPS, SITS-SIC), the HTE score significantly better predicted HT. Conclusions: NIHSS score ≥8 at Stroke Unit admission, cardioembolism, urgent revascularization, previous TIA/stroke, and major vessel occlusion were independent predictors of HT. The HTE score has a good predictive power for HT. Prospective studies are warranted.
MeSH term(s)	Humans ; Aged ; Aged, 80 and over ; Brain Ischemia/complications ; Brain Ischemia/diagnostic imaging ; Ischemic Stroke/complications ; Ischemic Stroke/diagnostic imaging ; Retrospective Studies ; Ischemic Attack, Transient ; Stroke/complications ; Stroke/diagnostic imaging ; Risk Factors
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1361380-7
ISSN	2331-2637 ; 1074-7931
ISSN (online)	2331-2637
ISSN	1074-7931
DOI	10.1097/NRL.0000000000000462
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Article: Does the Degree of Trunk Bending Predict Patient Disability, Motor Impairment, Falls, and Back Pain in Parkinson's Disease?

Geroin, Christian / Artusi, Carlo Alberto / Gandolfi, Marialuisa / Zanolin, Elisabetta / Ceravolo, Roberto / Capecci, Marianna / Andrenelli, Elisa / Ceravolo, Maria Gabriella / Bonanni, Laura / Onofrj, Marco / Telese, Roberta / Bellavita, Giulia / Catalan, Mauro / Manganotti, Paolo / Mazzucchi, Sonia / Giannoni, Sara / Vacca, Laura / Stocchi, Fabrizio / Casali, Miriam /

Falup-Pecurariu, Cristian / Zibetti, Maurizio / Fasano, Alfonso / Lopiano, Leonardo / Tinazzi, Michele

Frontiers in neurology

2020 Volume 11, Page(s) 207

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2020-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2020.00207
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