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Parkinson Disease: HELP
Articles by Gianni Pezzoli
Based on 122 articles published since 2010
(Why 122 articles?)
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Between 2010 and 2020, G. Pezzoli wrote the following 122 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Review Neuronal microtubules and proteins linked to Parkinson's disease: a relevant interaction? 2019

Calogero, Alessandra M / Mazzetti, Samanta / Pezzoli, Gianni / Cappelletti, Graziella. ·Department of Biosciences, Università degli Studi di Milano, via Celoria 26, I-20133 Milan, Italy. · Fondazione Grigioni per il Morbo di Parkinson, via Zuretti 35, I-20135 Milan, Italy. · Parkinson Institute, ASST "G.Pini-CTO", via Bignami 1, I-20133 Milan, Italy. · Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, via Balzaretti, I-20133 Milan, Italy. ·Biol Chem · Pubmed #31256059.

ABSTRACT: Neuronal microtubules are key determinants of cell morphology, differentiation, migration and polarity, and contribute to intracellular trafficking along axons and dendrites. Microtubules are strictly regulated and alterations in their dynamics can lead to catastrophic effects in the neuron. Indeed, the importance of the microtubule cytoskeleton in many human diseases is emerging. Remarkably, a growing body of evidence indicates that microtubule defects could be linked to Parkinson's disease pathogenesis. Only a few of the causes of the progressive neuronal loss underlying this disorder have been identified. They include gene mutations and toxin exposure, but the trigger leading to neurodegeneration is still unknown. In this scenario, the evidence showing that mutated proteins in Parkinson's disease are involved in the regulation of the microtubule cytoskeleton is intriguing. Here, we focus on α-Synuclein, Parkin and Leucine-rich repeat kinase 2 (LRRK2), the three main proteins linked to the familial forms of the disease. The aim is to dissect their interaction with tubulin and microtubules in both physiological and pathological conditions, in which these proteins are overexpressed, mutated or absent. We highlight the relevance of such an interaction and suggest that these proteins could trigger neurodegeneration via defective regulation of the microtubule cytoskeleton.

2 Review Glucocerebrosidase mutations and synucleinopathies: Toward a model of precision medicine. 2019

Blandini, Fabio / Cilia, Roberto / Cerri, Silvia / Pezzoli, Gianni / Schapira, Anthony H V / Mullin, Stephen / Lanciego, José L. ·Laboratory of Functional Neurochemistry, IRCCS Mondino Foundation, Pavia, Italy. · Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy. · Department of Clinical Neurosciences, Institute of Neurology, University College London, Hampstead, UK. · Institute of Translational and Stratified Medicine, Plymouth University Peninsula School of Medicine, Plymouth, UK. · Programa de Neurociencias, Fundación para la Investigación Médica Aplicada (FIMA), Universidad de Navarra, Pamplona, Spain. · Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CiberNed), Madrid, Spain. · Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. ·Mov Disord · Pubmed #30589955.

ABSTRACT: Glucocerebrosidase is a lysosomal enzyme. The characterization of a direct link between mutations in the gene coding for glucocerebrosidase (GBA1) with the development of Parkinson's disease and dementia with Lewy bodies has heightened interest in this enzyme. Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α-synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α-synuclein burden, thereby slowing down or even preventing neuronal death. Here we reviewed the current literature relating to the mechanisms underlying the cross talk between glucocerebrosidase and α-synuclein, the GBA1 mutation-associated clinical phenotypes, and ongoing therapeutic approaches targeting glucocerebrosidase. © 2018 International Parkinson and Movement Disorder Society.

3 Review The beneficial role of intensive exercise on Parkinson disease progression. 2013

Frazzitta, Giuseppe / Balbi, Pietro / Maestri, Roberto / Bertotti, Gabriella / Boveri, Natalia / Pezzoli, Gianni. ·Department of Parkinson Disease Rehabilitation, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Italy. ·Am J Phys Med Rehabil · Pubmed #23552330.

ABSTRACT: In the last decade, a considerable number of articles has shown that exercise is effective in improving motor performance in Parkinson disease. In particular, recent studies have focused on the efficacy of intensive exercise in achieving optimal results in the rehabilitation of patients with Parkinson disease. The effects of intensive exercise in promoting cell proliferation and neuronal differentiation in animal models are reported in a large cohort of studies, and these neuroplastic effects are probably related to increased expression of a variety of neurotrophic factors. The authors outline the relation between intensive exercises and neuroplastic activity on animal models of Parkinson disease and discuss the clinical results of different intensive strategies on motor performance and disease progression in patients with Parkinson disease.

4 Review Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. 2011

van Es, Michael A / Schelhaas, Helenius J / van Vught, Paul W J / Ticozzi, Nicola / Andersen, Peter M / Groen, Ewout J N / Schulte, Claudia / Blauw, Hylke M / Koppers, Max / Diekstra, Frank P / Fumoto, Katsumi / LeClerc, Ashley Lyn / Keagle, Pamela / Bloem, Bastiaan R / Scheffer, Hans / van Nuenen, Bart F L / van Blitterswijk, Marka / van Rheenen, Wouter / Wills, Anne-Marie / Lowe, Patrick P / Hu, Guo-fu / Yu, Wenhao / Kishikawa, Hiroko / Wu, David / Folkerth, Rebecca D / Mariani, Claudio / Goldwurm, Stefano / Pezzoli, Gianni / Van Damme, Philip / Lemmens, Robin / Dahlberg, Caroline / Birve, Anna / Fernández-Santiago, Rubén / Waibel, Stefan / Klein, Christine / Weber, Markus / van der Kooi, Anneke J / de Visser, Marianne / Verbaan, Dagmar / van Hilten, Jacobus J / Heutink, Peter / Hennekam, Eric A M / Cuppen, Edwin / Berg, Daniela / Brown, Robert H / Silani, Vincenzo / Gasser, Thomas / Ludolph, Albert C / Robberecht, Wim / Ophoff, Roel A / Veldink, Jan H / Pasterkamp, R Jeroen / de Bakker, Paul I W / Landers, John E / van de Warrenburg, Bart P / van den Berg, Leonard H. ·Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands. ·Ann Neurol · Pubmed #22190368.

ABSTRACT: OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.

5 Review Diabetes and risk of Parkinson's disease: a systematic review and meta-analysis. 2011

Cereda, Emanuele / Barichella, Michela / Pedrolli, Carlo / Klersy, Catherine / Cassani, Erica / Caccialanza, Riccardo / Pezzoli, Gianni. ·Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. e.cereda@smatteo.pv.it ·Diabetes Care · Pubmed #22110170.

ABSTRACT: OBJECTIVE: Diabetes has been associated with chronic neurodegeneration. We performed a systematic review and meta-analysis to assess the relationship between pre-existing diabetes and Parkinson's disease (PD). RESEARCH DESIGN AND METHODS: Original articles in English published up to 10 May 2011 were searched for in electronic databases (PubMed, Embase, and Scopus) and by reviewing references of eligible articles. Prospective cohort and case-control studies providing risk and precision estimates relating to pre-existing diabetes and PD were considered eligible. RESULTS: Nine studies/1,947 citations (cohort, N = 4; case-control, N = 5) fulfilled inclusion criteria for meta-analysis. In prospective studies, the onset of diabetes before onset of PD was found to be a risk factor for future PD (relative risk [RR] = 1.37 [95%CI 1.21-1.55]; P < 0.0001). This association was confirmed by secondary analyses based on estimates derived after the exclusion of participants who had vascular disease at baseline and/or who developed vascular disease during follow-up (RR = 1.34 [1.14-1.58]; P < 0.001) and by sensitivity analyses addressing the association with diabetes at baseline or during follow-up. However, the association found for case-control studies was not significant (odds ratio [OR] 0.75 [95%CI 0.50-1.11]; P = 0.835). Sensitivity analysis based on estimates adjusted for BMI confirmed the lack of a relationship between PD and diabetes (OR 0.56 [0.28-1.15]; P = 0.089). CONCLUSIONS: Although data from cohort studies suggest that diabetes is a risk factor for PD, there is no conclusive evidence on this association. Further prospective studies focused on putative pathogenic pathways and taking a broad range of confounders into account is required to clarify this relationship.

6 Review Low-protein and protein-redistribution diets for Parkinson's disease patients with motor fluctuations: a systematic review. 2010

Cereda, Emanuele / Barichella, Michela / Pedrolli, Carlo / Pezzoli, Gianni. ·Department of Neuroscience, Parkinson Institute, Istituti Clinici di Perfezionamento, Milano, Italy. emanuele.cereda@virgilio.it ·Mov Disord · Pubmed #20669318.

ABSTRACT: The American Academy of Neurology suggests advising the redistribution of daily protein meal content to every Parkinson's disease (PD) patient with motor fluctuations during levodopa treatment. However, no comprehensive evaluation of this complementary therapy has been performed. A systematic review of intervention studies investigating the neurologic outcome of low-protein (<0.8 g/kg of ideal weight/day) and protein-redistribution diets in patients with PD experiencing motor fluctuations during levodopa treatment. All studies (uncontrolled or randomized) investigating a low-protein and/or a protein-redistribution diet (LPD and PRD) and involving patients with PD with motor fluctuations were included, provided that sufficient information on dietary protein content and neurologic outcome measures was available. We identified 16 eligible studies, but they were markedly heterogeneous. There was not enough evidence to support the use of LPD. Response to PRD seemed very good. Acceptability appeared high upon introduction, but it seemed to progressively decrease over time. On average, PRD resulted in improved motor function, but also complications occurred. At the beginning, drop-outs were due to levodopa side effects rather than unsatisfactory benefits. Long-term adherence was more affected by changes in dietary habits than by diet-related side effects. Efficacy and benefits appeared to be higher when the intervention was proposed to subjects in the early stages of PD. PRD can be safely advised to fluctuating patients with PD, but those in whom benefits override the possible inconveniences still need to be identified. The long-term effects of PRD on nutritional status should be evaluated and true effectiveness in clinical practice should be reassessed, given the changes in levodopa formulations and the introduction of several adjuvants (levodopa degradation inhibitors and/or dopamine agonists).

7 Review Levodopa in Parkinson's disease: from the past to the future. 2010

Pezzoli, Gianni / Zini, Michela. ·Director of Parkinson Institute, Istituti Clinici di Perfezionamento, Via Bignami 1, Milan, Italy. pezzoli@parkinson.it ·Expert Opin Pharmacother · Pubmed #20163273.

ABSTRACT: IMPORTANCE OF THE FIELD: Levodopa is the mainstay of symptomatic treatment for Parkinson's disease (PD). Although other treatments have been developed in the last 30 years, most patients use levodopa in view of its superior efficacy in controlling PD symptoms. Unfortunately, levodopa is associated with long-term motor complications (motor fluctuations and dyskinesias). The main causes of these undesirable effects are the narrowing of the therapeutic window with the natural progression of the disease, pulsatile dopaminergic stimulation due to the short half-life of the drug and erratic absorption. Several studies suggest that PD control could be enhanced by changing the mode of levodopa delivery so as to ensure continuous and stable supply of the drug to the brain. The objective of this text is to review the ascertained strengths and limitations of levodopa in PD, starting from its history, and propose novel modes of usage designed to cover currently unmet medical needs. AREAS COVERED IN THIS REVIEW: Medline literature search (from 1973 to date). WHAT THE READER WILL GAIN: A perspective on the evolution of PD pharmacological treatment. TAKE HOME MESSAGE: Levodopa still is the best treatment for PD. Truly stable and controlled formulations that ensure clinical response should be developed to reduce the undesirable effects that restrict its efficacy.

8 Review Controlled-protein dietary regimens for Parkinson's disease. 2010

Cereda, Emanuele / Barichella, Michela / Pezzoli, Gianni. ·International Center for the Assessment of Nutritional Status (ICANS), Dipartimento di Scienze e Tecnologie Alimentari e Microbiologiche (DISTAM), Università degli Studi di Milano, via Botticelli 21, 20133 Milan, Italy. emanuele.cereda@virgilio.it ·Nutr Neurosci · Pubmed #20132652.

ABSTRACT: Continuous levodopa replacement still is the most efficacious treatment for patients with Parkinson's disease. Unfortunately, the neutral aromatic amino acids contained in dietary proteins may compete with this drug for intestinal absorption and transport across the blood-brain barrier, thus limiting its efficacy and being responsible for the occurrence of motor fluctuations. Current guidelines recommend low-protein dietary regimens with protein redistribution, as shifting protein intake to the evening has proved to ameliorate the response to levodopa. However, adherence to this dietary regimen does not seem to be satisfactory and response is variable. Recent studies have shown that low-protein products designed for chronic renal failure patients are safe, tasty, well-tolerated and useful in improving both adherence to low-protein dietary regimens and levodopa-related motor fluctuations. However, there still is the need to define the selection criteria for the patients who may benefit the most from adherence to this regimen.

9 Clinical Trial None 2017

Cilia, Roberto / Laguna, Janeth / Cassani, Erica / Cereda, Emanuele / Pozzi, Nicolò G / Isaias, Ioannis U / Contin, Manuela / Barichella, Michela / Pezzoli, Gianni. ·From the Parkinson Institute (R.C., E. Cassani, M.B., G.P.), ASST Gaetano Pini-CTO, Milan, Italy · Neurology Clinic (J.L.), Clinica Niño Jesus, Santa Cruz, Bolivia · Nutrition and Dietetics Service (E. Cereda), Fondazione IRCCS Policlinico San Matteo, Pavia · Department of Pathophysiology and Transplantation (N.G.P., I.U.I.), LAMB Pierfranco & Luisa Mariani, University of Milan, Italy · Department of Neurology (N.G.P., I.U.I.), University Hospital Würzburg and Julius-Maximilians-University, Würzburg, Germany · IRCCS-Institute of Neurological Sciences of Bologna (M.C.) · and Department of Biomedical and Neuromotor Sciences (M.C.), University of Bologna, Italy. ·Neurology · Pubmed #28679598.

ABSTRACT: OBJECTIVE: To investigate whether METHODS: We investigated efficacy and safety of single-dose intake of MP powder from roasted seeds obtained without any pharmacologic processing. Eighteen patients with advanced PD received the following treatments, whose sequence was randomized: (1) dispersible levodopa at 3.5 mg/kg combined with the dopa-decarboxylase inhibitor benserazide (LD+DDCI; the reference treatment); (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) pharmaceutical preparation of LD without DDCI (LD-DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP+DDCI; 3.5 mg/kg); (6) placebo. Efficacy outcomes were the change in motor response at 90 and 180 minutes and the duration of on state. Safety measures included any adverse event (AE), changes in blood pressure and heart rate, and the severity of dyskinesias. RESULTS: When compared to LD+DDCI, MP-Ld showed similar motor response with fewer dyskinesias and AEs, while MP-Hd induced greater motor improvement at 90 and 180 minutes, longer ON duration, and fewer dyskinesias. MP-Hd induced less AEs than LD+DDCI and LD-DDCI. No differences in cardiovascular response were recorded. CONCLUSION: Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile. CLINICALTRIALSGOV IDENTIFIER: NCT02680977.

10 Clinical Trial A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation. 2011

Antonini, Angelo / Isaias, Ioannis U / Rodolfi, Giorgia / Landi, Andrea / Natuzzi, Francesca / Siri, Chiara / Pezzoli, Gianni. ·Parkinson Institute, Istituti Clinici di Perfezionamento, Via Bignami, 1, 20126, Milan, Italy. ·J Neurol · Pubmed #20972684.

ABSTRACT: Prospective comparative long-term data on the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and continuous subcutaneous infusion of apomorphine (CSAI) in patients with advanced Parkinson disease (PD) are lacking. We report 5-year follow-up of 25 PD patients treated with either STN-DBS (n = 13) or CSAI (n = 12) who fulfilled CAPSIT-PD criteria. Cohorts were matched for disease duration and severity of motor complications. Baseline clinical and neuropsychological status did not differ among cohorts. Patients were assessed with the UPDRS, MMSE, HAMD-17 and Neuropsychiatric Inventory (NPI).Twelve subjects reached the 5-year follow-up with STN-DBS (one was lost at follow-up) versus two in the CSAI cohort. Drop-outs with CSAI were due to subcutaneous nodules (n = 2), insufficient control of motor fluctuations and dyskinesia (n = 4), death for unrelated reasons (n = 3) and one was lost at follow-up. Average apomorphine dose at last visit was 83.4 ± 19.2 mg/day and average treatment duration was 30 months. At 1-year as well as at last follow-up (intention-to-treat analysis), both therapies decreased daily off-time but only STN-DBS reduced dyskinesia duration and severity. Decrement of medications was greater with STN-DBS. There was a significant worsening of NPI after STN-DBS, primarily because four subjects developed apathy.

11 Article Resting energy expenditure in Parkinson's disease patients under dopaminergic treatment. 2020

Barichella, Michela / Cereda, Emanuele / Faierman, Samanta Andrea / Piuri, Gabriele / Bolliri, Carlotta / Ferri, Valentina / Cassani, Erica / Vaccarella, Eleonora / Donnarumma, Ornella Violetta / Pinelli, Giovanna / Caronni, Serena / Pusani, Chiara / Pezzoli, Gianni. ·Parkinson Institute, ASST G.Pini-CTO, Milan, Italy. · Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ·Nutr Neurosci · Pubmed #32264793.

ABSTRACT:

12 Article Gait Initiation in Parkinson's Disease: Impact of Dopamine Depletion and Initial Stance Condition. 2020

Palmisano, Chiara / Brandt, Gregor / Vissani, Matteo / Pozzi, Nicoló G / Canessa, Andrea / Brumberg, Joachim / Marotta, Giorgio / Volkmann, Jens / Mazzoni, Alberto / Pezzoli, Gianni / Frigo, Carlo A / Isaias, Ioannis U. ·Department of Neurology, University Hospital Würzburg and The Julius Maximilian University of Würzburg, Würzburg, Germany. · MBMC Lab, Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy. · Translational Neural Engineering Area, The Biorobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Italy. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), Cernusco s/N (Milan), Italy. · Department of Nuclear Medicine, University Hospital Würzburg and The Julius Maximilian University of Würzburg, Würzburg, Germany. · Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. · Centro Parkinson, ASST G. Pini-CTO, Milan, Italy. ·Front Bioeng Biotechnol · Pubmed #32211390.

ABSTRACT: Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson's disease (PD). Still, the contribution of the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI [imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment.

13 Article Could Mucuna pruriens be the answer to Parkinson's disease management in sub-Saharan Africa and other low-income countries worldwide? 2020

Fothergill-Misbah, Natasha / Maroo, Harshvadan / Cham, Momodou / Pezzoli, Gianni / Walker, Richard / Cilia, Roberto. ·Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom. Electronic address: n.fothergill-misbah@newcastle.ac.uk. · Parkinson's Support Group, P.O. Box, 14542-00800, Nairobi, Kenya. Electronic address: harsh.maroo@gmail.com. · Richard Novati Catholic Hospital, Sogakope, Ghana. Electronic address: modoufa@gmail.com. · Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy; Parkinson Institute, ASST "Gaetano Pini-CTO, Milan, Italy. Electronic address: gianni.pezzoli@gmail.com. · Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom. Electronic address: Richard.walker@nhct.nhs.uk. · Fondazione IRCCS Istituto Neurologico Carlo Besta, Movement Disorders Unit, Milan, Italy. Electronic address: roberto.cilia@istituto-besta.it. ·Parkinsonism Relat Disord · Pubmed #32179240.

ABSTRACT: Parkinson's disease (PD) is a progressive, disabling, neurodegenerative disease that requires long term care and pharmaceutical treatment. Levodopa remains the gold standard treatment for PD globally, although it is largely unavailable and unaffordable for the majority of patients in many sub-Saharan African and other low-income countries (LICs). We suggest the potential for Mucuna pruriens (MP), a leguminous plant, to replace or supplement levodopa-based medicines in countries where levodopa is unaffordable and inaccessible due to its low costs of preparation and high natural availability. MP has been shown to induce a great improvement of motor symptoms with few adverse events in recent studies. However, caution is important until more robust data on the long-term safety of MP are available. We believe that MP could potentially be part of the answer to affordable, symptomatic treatment of PD in LICs worldwide.

14 Article α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson's disease. 2020

Mazzetti, Samanta / Basellini, Milo J / Ferri, Valentina / Cassani, Erica / Cereda, Emanuele / Paolini, Matilde / Calogero, Alessandra M / Bolliri, Carlotta / De Leonardis, Mara / Sacilotto, Giorgio / Cilia, Roberto / Cappelletti, Graziella / Pezzoli, Gianni. ·Department of Biosciences, Università degli Studi di Milano, Milan, Italy. · Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy. · Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy. · Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milan, Italy. ·Brain · Pubmed #32025699.

ABSTRACT: A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson's disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson's disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson's disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson's disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson's disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson's disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.

15 Article The imbalance between dynamic and stable microtubules underlies neurodegeneration induced by 2,5-hexanedione. 2020

Casagrande, Francesca V M / Amadeo, Alida / Cartelli, Daniele / Calogero, Alessandra M / Modena, Debora / Costa, Ilaria / Cantele, Francesca / Onelli, Elisabetta / Moscatelli, Alessandra / Ascagni, Miriam / Pezzoli, Gianni / Cappelletti, Graziella. ·Department of Biosciences, University of Milan, Milan, Italy. Electronic address: francesca.casagrande@ifom.eu. · Department of Biosciences, University of Milan, Milan, Italy; Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy. · Department of Biosciences, University of Milan, Milan, Italy. · Unitech NOLIMITS, University of Milan, Milan, Italy. · Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy. · Department of Biosciences, University of Milan, Milan, Italy; Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy. Electronic address: graziella.cappelletti@unimi.it. ·Biochim Biophys Acta Mol Basis Dis · Pubmed #31672549.

ABSTRACT: Exposure to environmental toxins, including hydrocarbon solvents, increases the risk of developing Parkinson's disease. An emergent hypothesis considers microtubule dysfunction as one of the crucial events in triggering neuronal degeneration in Parkinson's disease. Here, we used 2,5-hexanedione (2,5-HD), the toxic metabolite of n-hexane, to analyse the early effects of toxin-induced neurodegeneration on the cytoskeleton in multiple model systems. In PC12 cells differentiated with nerve growth factor for 5 days, we found that 2,5-HD treatment affected all the cytoskeletal components. Moreover, we observed alterations in microtubule distribution and stability, in addition to the imbalance of post-translational modifications of α-tubulin. Similar defects were also found in vivo in 2,5-HD-intoxicated mice. Interestingly, we also found that 2,5-HD exposure induced significant changes in microtubule stability in human skin fibroblasts obtained from Parkinson's disease patients harbouring mutations in PRKN gene, whereas it was ineffective in healthy donor fibroblasts, suggesting that the genetic background may really make the difference in microtubule susceptibility to this environmental Parkinson's disease-related toxin. In conclusion, by showing the imbalance between dynamic and stable microtubules in hydrocarbon-induced parkinsonism, our data support the crucial role of microtubule defects in triggering neurodegeneration.

16 Article Resting state oscillations suggest a motor component of Parkinson's Impulse Control Disorders. 2019

Spay, Charlotte / Meyer, Garance / Lio, Guillaume / Pezzoli, Gianni / Ballanger, Bénédicte / Cilia, Roberto / Boulinguez, Philippe. ·Université de Lyon, 92 rue Pasteur, 69007 Lyon, France; Université Lyon 1, 43 boulevard du 11 novembre 1918, 69622 Villeurbanne, France; INSERM, U 1028, Lyon Neuroscience Research Center, 95 boulevard Pinel, 69500 Bron, France; CNRS, UMR 5292, Lyon Neuroscience Research Center, 95 boulevard Pinel, 69500 Bron, France. · Centre de Neuroscience Cognitive, UMR 5229, 67 boulevard Pinel, 69675 Bron, France. · Parkinson Institute, ASST Gaetano Pini-CTO, Via bignami 1, 20126 Milan, Italy. · Université de Lyon, 92 rue Pasteur, 69007 Lyon, France; Université Lyon 1, 43 boulevard du 11 novembre 1918, 69622 Villeurbanne, France; INSERM, U 1028, Lyon Neuroscience Research Center, 95 boulevard Pinel, 69500 Bron, France; CNRS, UMR 5292, Lyon Neuroscience Research Center, 95 boulevard Pinel, 69500 Bron, France. Electronic address: philippe.boulinguez@univ-lyon1.fr. ·Clin Neurophysiol · Pubmed #31541984.

ABSTRACT: OBJECTIVES: Impulse control disorders (ICDs) in Parkinson's disease (PD) have been associated with cognitive impulsivity and dopaminergic dysfunction and treatment. The present study tests the neglected hypothesis that the neurofunctional networks involved in motor impulsivity might also be dysfunctional in PD-ICDs. METHODS: We performed blind spectral analyses of resting state electroencephalographic (EEG) data in PD patients with and without ICDs to probe the functional integrity of all cortical networks. Analyses were performed directly at the source level after blind source separation. Discrete differences between groups were tested by comparing patients with and without ICDs. Gradual dysfunctions were assessed by means of correlations between power changes and clinical scores reflecting ICD severity (QUIP score). RESULTS: Spectral signatures of ICDs were found in the medial prefrontal cortex, the dorsal anterior cingulate and the supplementary motor area, in the beta and gamma bands. Beta power changes in the supplementary motor area were found to predict ICDs severity. CONCLUSION: ICDs are associated with abnormal activity within frequency bands and cortical circuits supporting the control of motor response inhibition. SIGNIFICANCE: These results bring to the forefront the need to consider, in addition to the classical interpretation based on aberrant mesocorticolimbic reward processing, the issue of motor impulsivity in PD-ICDs and its potential implications for PD therapy.

17 Article Freezing of gait in Parkinson's disease reflects a sudden derangement of locomotor network dynamics. 2019

Pozzi, Nicoló G / Canessa, Andrea / Palmisano, Chiara / Brumberg, Joachim / Steigerwald, Frank / Reich, Martin M / Minafra, Brigida / Pacchetti, Claudio / Pezzoli, Gianni / Volkmann, Jens / Isaias, Ioannis U. ·Department of Neurology, University Hospital and Julius Maximilian University, Würzburg, Germany. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), Cernusco s/N (Milan), Italy. · Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genoa, Genoa, Italy. · Department of Electronics, Information and Bioengineering, MBMC Lab, Politecnico di Milano, Milan, Italy. · Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. · Parkinson and Movement Disorder Unit, IRCCS Mondino Foundation, Pavia, Italy. · Centro Parkinson ASST G. Pini-CTO, Milan, Italy. ·Brain · Pubmed #31505548.

ABSTRACT: Freezing of gait is a disabling symptom of Parkinson's disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication between the cortex and the subthalamic nucleus, two main nodes of the locomotor network, in seven freely-moving subjects with Parkinson's disease with a novel deep brain stimulation device, which allows on-demand recording of subthalamic neural activity from the chronically-implanted electrodes months after the surgical procedure. Multisite neurophysiological recordings during (effective) walking and ongoing gait freezing were combined with kinematic measurements and individual molecular brain imaging studies. Patients walked in a supervised environment closely resembling everyday life challenges. We found that during (effective) walking, the cortex and subthalamic nucleus were synchronized in a low frequency band (4-13 Hz). In contrast, gait freezing was characterized in every patient by low frequency cortical-subthalamic decoupling in the hemisphere with less striatal dopaminergic innervation. Of relevance, this decoupling was already evident at the transition from normal (effective) walking into gait freezing, was maintained during the freezing episode, and resolved with recovery of the effective walking pattern. This is the first evidence for a decoding of the networked processing of locomotion in Parkinson's disease and suggests that freezing of gait is a 'circuitopathy' related to a dysfunctional cortical-subcortical communication. A successful therapeutic approach for gait freezing in Parkinson's disease should aim at directly targeting derangements of neural network dynamics.

18 Article Muscle-targeted nutritional support for rehabilitation in patients with parkinsonian syndrome. 2019

Barichella, Michela / Cereda, Emanuele / Pinelli, Giovanna / Iorio, Laura / Caroli, Diana / Masiero, Irene / Ferri, Valentina / Cassani, Erica / Bolliri, Carlotta / Caronni, Serena / Maggio, Marcello / Ortelli, Paola / Ferrazzoli, Davide / Maras, Antonios / Riboldazzi, Giulio / Frazzitta, Giuseppe / Pezzoli, Gianni. ·From the Parkinson Institute (M.B., D.C., I.M., V.F., E.C., C.B., S.C., G. Pezzoli), ASST G.Pini-CTO, ex ICP, Milan · Clinical Nutrition and Dietetics Unit (E.C.), Fondazione IRCCS Policlinico San Matteo, Pavia · Dipartimento Riabilitazione Malattia di Parkinson e Disturbi del Movimento (G. Pinelli, P.O., D.F., G.F.), Ospedale Classificato Moriggia Pelascini di Gravedona · U.S. Riabilitazione Parkinson (L.I., A.M., G.R.), Fondazione Gaetano e Piera Borghi di Brebbia · and UOC Clinica Geriatrica (M.M.), Dipartimento Medico-Geriatrico-Riabilitativo, Università-Azienda Ospedaliero-Universitaria di Parma, Italy. ·Neurology · Pubmed #31278117.

ABSTRACT: OBJECTIVE: We evaluated the efficacy of muscle-targeted nutritional support on the functional outcomes of multidisciplinary intensive rehabilitation treatment (MIRT) in patients with Parkinson disease (PD) or parkinsonism. METHODS: We conducted a pragmatic, bicentric, randomized (1:1), assessor-blind controlled trial (Protein, Leucine and Vitamin D Enhancing Rehabilitation [PRO-LEADER]; April 2017 to January 2018) in cognitively intact patients with PD or parkinsonism and undergoing a 30-day MIRT. Patients (n = 150) received a standard hospital diet with or without a whey protein-based nutritional supplement enriched with leucine and vitamin D twice daily. The primary efficacy endpoint was the increase in the distance walked during a 6-minute walking test (6MWT). Secondary endpoints were changes in 4-meter walking speed, Timed Up and Go test (TUG), Berg balance scale, handgrip strength, Self-assessment Parkinson's Disease Disability Scale, body weight, and skeletal muscle mass (SMM). RESULTS: Nutritional support resulted in greater increase in the distance walked during 6MWT (mean 69.6 meters [95% confidence interval (CI) 60.7-78.6]) than no support (51.8 meters [95% CI 37.0-66.7]): center-adjusted mean difference, 18.1 meters (95% CI 0.9-35.3) ( CONCLUSION: The consumption of a whey protein-based nutritional formula enriched with leucine and vitamin D with MIRT improved lower extremity function and preserved muscle mass in patients with PD or parkinsonism.Clinicaltrials.gov IDENTIFIER: NCT03124277. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with parkinsonism undergoing intensive rehabilitation, a whey protein-based nutritional formula enriched with leucine and vitamin D increased distance walked on the 6MWT.

19 Article Sit-to-walk performance in Parkinson's disease: A comparison between faller and non-faller patients. 2019

Palmisano, Chiara / Brandt, Gregor / Pozzi, Nicoló Gabriele / Leporini, Alice / Maltese, Virginia / Canessa, Andrea / Volkmann, Jens / Pezzoli, Gianni / Frigo, Carlo Albino / Isaias, Ioannis Ugo. ·Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080 Würzburg, Germany; Department of Electronic, Information and Bioengineering, MBMC Lab, Politecnico di Milano, via Colombo 40, 20133 Milan, Italy. · Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. · Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genoa, via all'Opera Pia 13a, 16145 Genoa, Italy; Fondazione Europea di Ricerca Biomedica (FERB Onlus), Via Uboldo 18, 20063 Cernusco s/N, Milan, Italy. · Centro Parkinson ASST G. Pini-CTO, via Bignami 1, 20126 Milan, Italy. · Department of Electronic, Information and Bioengineering, MBMC Lab, Politecnico di Milano, via Colombo 40, 20133 Milan, Italy. · Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080 Würzburg, Germany; Centro Parkinson ASST G. Pini-CTO, via Bignami 1, 20126 Milan, Italy. Electronic address: Isaias_I@ukw.de. ·Clin Biomech (Bristol, Avon) · Pubmed #30889433.

ABSTRACT: BACKGROUND: Falls are one of the main concerns in people with Parkinson's disease, leading to poor quality of life and increased mortality. The sit-to-walk movement is the most frequent postural transition task during daily life and is highly demanding in terms of balance maintenance and muscular strength. METHODS: With the aim of identifying biomechanical variables of high risk of falling, we investigated the sit-to-walk task performed by 9 Parkinson's disease patients with at least one fall episode in the six months preceding this study, 15 Parkinson's disease patients without previous falls, and 20 healthy controls. Motor performance was evaluated with an optoelectronic system and two dynamometric force plates after overnight suspension of all dopaminergic drugs and one hour after consumption of a standard dose of levodopa/benserazide. FINDINGS: Poor trunk movements critically influenced the execution of the sit-to-walk movement in patients with a history of falling. The peak velocity of the trunk in the anterior-posterior direction discriminated faller from non-faller patients, with high specificity and sensitivity in both the medication-off and -on state. INTERPRETATION: Our results confirm the difficulties in merging consecutive motor tasks in patients with Parkinson's disease. Trunk movements during the sit-to-walk can provide valuable measurements to monitor and possibly predict the risk of falling.

20 Article Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism. 2019

Barichella, Michela / Severgnini, Marco / Cilia, Roberto / Cassani, Erica / Bolliri, Carlotta / Caronni, Serena / Ferri, Valentina / Cancello, Raffaella / Ceccarani, Camilla / Faierman, Samanta / Pinelli, Giovanna / De Bellis, Gianluca / Zecca, Luigi / Cereda, Emanuele / Consolandi, Clarissa / Pezzoli, Gianni. ·Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini-CTO, Milan, Italy. · Institute of Biomedical Technologies (IBT), Italian National Research Council (CNR), Milan, Italy. · IRCCS Istituto Auxologico Italiano, Obesity Research Laboratory, Milan, Italy. · Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, Milan, Italy. · Department of Parkinson Disease Rehabilitation, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Fondazione Europea Ricerca Biomedica (FERB), Gravedona, Italy. · Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY USA. · Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ·Mov Disord · Pubmed #30576008.

ABSTRACT: BACKGROUND: Although several studies have suggested that abnormalities in gut microbiota may play a critical role in the pathogenesis of PD, data are still extremely heterogeneous. METHODS: 16S gene ribosomal RNA sequencing was performed on fecal samples of 350 individuals, subdivided into idiopathic PD (n = 193, of whom 39 were drug naïve) stratified by disease duration, PSP (n = 22), MSA (n = 22), and healthy controls (HC; n = 113). Several confounders were taken into account, including dietary habits. RESULTS: Despite the fact that unadjusted comparison of PD and HC showed several differences in relative taxa abundances, the significant results were greatly reduced after adjusting for confounders. Although most of these differences were associated with disease duration, lower abundance in Lachnospiraceae was the only difference between de novo PD and HC (remaining lower across almost all PD duration strata). Decreased Lachnospiraceae and increased Lactobacillaceae and Christensenellaceae were associated with a worse clinical profile, including higher frequencies of cognitive impairment, gait disturbances, and postural instability. When compared with HC, MSA and PSP patients shared the changes in PD, with a few exceptions: in MSA, Lachnospiraceae were not lower, and Prevotellaceae were reduced; in PSP, Lactobacillaceae were similar, and Streptococcaceae were reduced. CONCLUSIONS: Gut microbiota may be an environmental modulator of the pathogenesis of PD and contribute to the interindividual variability of clinical features. Data are influenced by PD duration and several confounders that need to be taken into account in future studies. Prospective studies in de novo PD patients are needed to elucidate the net effect of dysbiosis on the progression of the disease. © 2018 International Parkinson and Movement Disorder Society.

21 Article Excitability of the supplementary motor area in Parkinson's disease depends on subcortical damage. 2019

Casarotto, Silvia / Turco, Francesco / Comanducci, Angela / Perretti, Alessio / Marotta, Giorgio / Pezzoli, Gianni / Rosanova, Mario / Isaias, Ioannis U. ·Department of Biomedical and Clinical Sciences "L. Sacco", LASEB Laboratory, University of Milan, via GB Grassi 74, 20157, Milan, Italy. Electronic address: silvia.casarotto@unimi.it. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy; Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. Electronic address: francesco.turco1989@gmail.com. · Department of Biomedical and Clinical Sciences "L. Sacco", LASEB Laboratory, University of Milan, via GB Grassi 74, 20157, Milan, Italy. Electronic address: angela.comanducci@unimi.it. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy. Electronic address: paramiauxparkinson@gmail.com. · Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122, Milan, Italy. Electronic address: marottag@policlinico.mi.it. · Parkinson Institute ASST G. Pini-CTO, via Bignami 1, 20126, Milan, Italy. Electronic address: gianni.pezzoli@gmail.com. · Department of Biomedical and Clinical Sciences "L. Sacco", LASEB Laboratory, University of Milan, via GB Grassi 74, 20157, Milan, Italy; Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy. Electronic address: mario.rosanova@unimi.it. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy; Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080, Würzburg, Germany; Parkinson Institute ASST G. Pini-CTO, via Bignami 1, 20126, Milan, Italy. Electronic address: Isaias_I@ukw.de. ·Brain Stimul · Pubmed #30416036.

ABSTRACT: BACKGROUND: Cortical dysfunctioning significantly contributes to the pathogenesis of motor symptoms in Parkinson's disease (PD). OBJECTIVE: We aimed at testing whether an acute levodopa administration has measurable and specific cortical effects possibly related to striatal dopaminergic deficit. METHODS: In thirteen PD patients, we measured the electroencephalographic responses to transcranial magnetic stimulation (TMS/EEG) of the supplementary motor area and superior parietal lobule (n = 8) before and after an acute intake of levodopa. We also performed a single-photon emission computed tomography and [ RESULTS: We found that levodopa intake induces a significant increase (P < 0.01) of cortical excitability nearby the supplementary motor area in the more affected brain side, greater (P < 0.025) than in the less affected brain side. Notably, cortical excitability changes nearby the superior parietal lobule were not statistically significant. CONCLUSIONS: These results strengthen the idea that dysfunction of specific cortico-subcortical circuits may contribute to pathophysiology of PD symptoms. Most important, they support the use of navigated TMS/EEG as a non-invasive tool to better understand the pathophysiology of PD.

22 Article Pathological Gambling in Parkinson's disease: Autonomic measures supporting impaired decision-making. 2019

Angioletti, Laura / Siri, Chiara / Meucci, Nicoletta / Pezzoli, Gianni / Balconi, Michela. ·Department of Psychology, Catholic University of the Sacred Heart, Milan, Italy. · Research Unit in Affective and Social Neuroscience, Catholic University of the Sacred Heart, Milan, Italy. · Parkinson Institute, ASST G. Pini-CTO, ex ICP, Milan, Italy. ·Eur J Neurosci · Pubmed #29888425.

ABSTRACT: According to the somatic marker hypothesis, autonomic measures and arousal modulation can reveal a difference in subgroups of patients developing impaired decision-making because of addictions. Previously, pathological gambling (PG) and Parkinson's disease (PD) have been associated with differential arousal levels during gambling behavior. However, no research considered the specific autonomic responses of Parkinson's disease patients with pathological gambling and with a previous history of gambling. Thus, this study investigated skin conductance responses (SCRs), skin conductance level (SCL) and heart rate (HR) during the Iowa Gambling Task (IGT) in two groups of PD patients with gambling disorder, active (PD Gamblers; n = 14) or remitted (PD Non-Gamblers; n = 13) and a control group of patients with Parkinson's disease only (n = 13). Anticipatory autonomic responses to disadvantageous decks and advantageous decks during the Iowa Gambling Task were measured for each participant. The PD Gamblers group performed worse than the PD Non-Gamblers and the control groups at the IGT task and exhibited lower SCRs, SCL, and HR during the decision-making processing of cards belonging to disadvantageous decks. The role of autonomic and behavioral measures was considered.

23 Article Multiparametric MR imaging of Parkinsonisms at 3 tesla: Its role in the differentiation of idiopathic Parkinson's disease versus atypical Parkinsonian disorders. 2018

Calloni, S F / Conte, G / Sbaraini, S / Cilia, R / Contarino, V E / Avignone, S / Sacilotto, G / Pezzoli, G / Triulzi, F M / Scola, E. ·Post-graduation School in Radiodiagnostics, University of Milan, Milan, Italy. Electronic address: calloni.sonia@gmail.com. · Neuroradiology Unit, Ospedale Maggiore Policlinico IRCCS Ca' Granda, Milan, Italy. · Post-graduation School in Radiodiagnostics, University of Milan, Milan, Italy. · Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy. ·Eur J Radiol · Pubmed #30527319.

ABSTRACT: OBJECTIVES: The Nigrosome-1 and putaminal hypointensity depicted on susceptibility-weighted imaging (SWI), and midbrain atrophy assessed on T1-weighted are some of the most common radiological parameters to diagnose Parkinsonism at Magnetic Resonance (MR) imaging. Our aim is to assess the feasibility of these signs in the differentiation of Idiopathic Parkinson's disease (IPD) patients versus disease (DC) and healthy controls (HC) and in the assessment of the Atypical Progressive Parkinsonisms (APPs). METHODS: Presence or loss of the Nigrosome-1 was assessed retrospectively on multiple-echo SWI obtained on a 3 T scan by two neuroradiologists. Results were compared with the 123I-FP-CIT SPECT images. Morphologic diagnostic features suggestive of APPs such as midbrain atrophy and putaminal hypointensity were evaluated by qualitative scores. The midbrain and putaminal scores were summed (combined score) and then added to the Nigrosome-1 score (global score). RESULTS: The study included 126 patients with IPD (n = 56), APPs patients (n = 30; 18 PSP, 3 MSA-C, 9 MSA-P), 16 DC and 24 HC. Sensitivity and specificity of the Nigrosome-1 in discriminating IPD from controls were 96,43% and 85.00%, APPs from controls were 100% and 85%, IPD from APPs were 96,43% and 0% respectively. Combined score for midbrain atrophy and putaminal hypointensity resulted in the most accurate for distinguishing APPs from IPD with a value of ≥ 2 (AUC = 0.98). CONCLUSION: Nigrosome-1 is a valid tool to differentiate IPD-APPs from controls. The combined score of midbrain atrophy and putaminal hypointensity represents a valid diagnostic pointer in the differential diagnosis of APPs from IPD.

24 Article Cortical response to levodopa in Parkinson's disease patients with dyskinesias. 2018

Turco, Francesco / Canessa, Andrea / Olivieri, Chiara / Pozzi, Nicoló G / Palmisano, Chiara / Arnulfo, Gabriele / Marotta, Giorgio / Volkmann, Jens / Pezzoli, Gianni / Isaias, Ioannis U. ·Fondazione Europea di Ricerca Biomedica (FERB Onlus), Milan, Italy. · Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genoa, Genoa, Italy. · Department of Neurology, University Hospital Wuerzburg and Julius-Maximillian-University, Wuerzburg, Germany. · Department of Electronics, Information and Bioengineering, MBMC Lab, Politecnico di Milano, Milan, Italy. · Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. · Parkinson Institute ASST G. Pini-CTO, Milan, Italy. ·Eur J Neurosci · Pubmed #30117212.

ABSTRACT: Levodopa-induced dyskinesias are a common and disabling side effect of dopaminergic therapy in Parkinson's disease, but their neural mechanisms in vivo are still poorly understood. Besides striatal pathology, the importance of cortical dysfunction has been increasingly recognized. The supplementary motor area in particular, may have a relevant role in dyskinesias onset given its involvement in endogenously generated actions. The aim of the present study was to investigate the levodopa-related cortical excitability changes along with the emergence of levodopa-induced peak-of-dose dyskinesias in subjects with Parkinson's disease. Thirteen patients without dyskinesias and ten with dyskinesias received 200/50 mg fast-acting oral levodopa/benserazide following overnight withdrawal (12 hr) from their dopaminergic medication. We targeted transcranial magnetic stimulation to the supplementary motor area, ipsilateral to the most dopamine-depleted striatum defined with single-photon emission computed tomography with [

25 Article Phase matters: A role for the subthalamic network during gait. 2018

Arnulfo, Gabriele / Pozzi, Nicolò Gabriele / Palmisano, Chiara / Leporini, Alice / Canessa, Andrea / Brumberg, Joachim / Pezzoli, Gianni / Matthies, Cordula / Volkmann, Jens / Isaias, Ioannis Ugo. ·Department of Neurology, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany. · Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genoa, Genoa, Italy. · Department of Electronics, Information and Bioengineering, MBMC Lab, Politecnico di Milano, Milan, Italy. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), Cernusco s/N (Milan), Italy. · Department of Nuclear Medicine, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany. · Centro Parkinson ASST G. Pini-CTO, Milan, Italy. · Department of Neurosurgery, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany. ·PLoS One · Pubmed #29874298.

ABSTRACT: The role of the subthalamic nucleus in human locomotion is unclear although relevant, given the troublesome management of gait disturbances with subthalamic deep brain stimulation in patients with Parkinson's disease. We investigated the subthalamic activity and inter-hemispheric connectivity during walking in eight freely-moving subjects with Parkinson's disease and bilateral deep brain stimulation. In particular, we compared the subthalamic power spectral densities and coherence, amplitude cross-correlation and phase locking value between resting state, upright standing, and steady forward walking. We observed a phase locking value drop in the β-frequency band (≈13-35Hz) during walking with respect to resting and standing. This modulation was not accompanied by specific changes in subthalamic power spectral densities, which was not related to gait phases or to striatal dopamine loss measured with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane and single-photon computed tomography. We speculate that the subthalamic inter-hemispheric desynchronization in the β-frequency band reflects the information processing of each body side separately, which may support linear walking. This study also suggests that in some cases (i.e. gait) the brain signal, which could allow feedback-controlled stimulation, might derive from network activity.

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