IRCCS Hospital San Camillo

Venezia, Italy

IRCCS Hospital San Camillo

Venezia, Italy
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Vallelunga A.,IRCCS Hospital San Camillo | Ragusa M.,University of Catania | Di Mauro S.,University of Catania | Iannitti T.,University of Leeds | And 9 more authors.
Frontiers in Cellular Neuroscience | Year: 2014

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder which may be misdiagnosed with atypical conditions such as Multiple System Atrophy (MSA), due to overlapping clinical features. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in post-transcriptional gene regulation. We hypothesized that identification of a distinct set of circulating miRNAs (cmiRNAs) could distinguish patients affected by PD from MSA and healthy individuals. Results. Using TaqMan Low Density Array technology, we analyzed 754 miRNAs and found 9 cmiRNAs differentially expressed in PD and MSA patients compared to healthy controls. We also validated a set of 4 differentially expressed cmiRNAs in PD and MSA patients vs. controls. More specifically, miR-339-5p was downregulated, whereas miR-223*, miR-324-3p, and mir-24 were upregulated in both diseases. We found cmiRNAs specifically deregulated in PD (downregulation of miR-30c and miR-148b) and in MSA (upregulation of miR-148b). Finally, comparing MSA and PD, we identified 3 upregulated cmiRNAs in MSA serum (miR-24, miR-34b, miR-148b). Conclusions. Our results suggest that cmiRNA signatures discriminate PD from MSA patients and healthy controls and may be considered specific, non-invasive biomarkers for differential diagnosis. © Ragusa, Di Mauro, Iannitti, Pilleri, Biundo, Weis, Di Pietro, De Iuliis, Nicoletti, Zappia, Purrello and Antonini.


Braga M.,Science Neurologia | Pederzoli M.,Science Neurologia | Antonini A.,IRCCS Hospital San Camillo | Beretta F.,University of Milan | Crespi V.,Science Neurologia
Parkinsonism and Related Disorders | Year: 2014

Background: To characterize reasons for hospital admission, mortality and surgical procedures in patients with Parkinson's disease (PD) compared to controls. Methods: The clinical features of all consecutive patients from 2000 to 2007 were reviewed. We identified patients with PD (ICD 9 code 332.0) from a database of our General Hospital (Vimercate) with a catchment's population of 180,000. Data on admitting wards as well as reasons for admission, surgical procedures performed and clinical outcome were collected. Clinical data were compared to an age and sex matched control population admitted in the same period of time. Results: The total number of admissions was 367. Mean age was 76.7 years. The mean duration of stay was 9.2 days for controls and 9.7 for PD patients. A comorbid disorder was the cause of admission in 80% of cases and 79% of cases came from the Emergency Room. Infectious diseases, mainly respiratory infections, were more frequent in PD of both sexes, while trauma was significantly higher only in PD men. Percentage of patients treated surgically was similar in both cases and controls. Intrahospital mortality was 6% both in PD and controls. Infectious diseases were more frequent in PD patients while cardiovascular death was more frequent in controls. Conclusions: Comorbidity in PD is higher than reported in other reports. In our study PD patients had the same length of hospitalization and intrahospital mortality as controls. The presence of a control population allows to discriminate between general complications of the elderly and specific vulnerabilities of PD patients. © 2014 The Authors.


Antonini A.,IRCCS Hospital San Camillo | Bauer L.,UCB Pharma | Dohin E.,UCB Pharma | Oertel W.H.,University of Marburg | And 6 more authors.
European Journal of Neurology | Year: 2015

Background and purpose: Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. Methods: In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). Results: In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. Conclusions: Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings. © 2015 European Federation of Neurological Societies.


Antonini A.,IRCCS Hospital San Camillo | Yegin A.,Abbvie Inc. | Preda C.,Abbvie Inc. | Bergmann L.,Abbvie Inc. | Poewe W.,Innsbruck Medical University
Parkinsonism and Related Disorders | Year: 2015

Introduction: Intermittent oral delivery of levodopa is a major contributing factor for motor complications in Parkinson's disease (PD). Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) into the jejunum using a portable pump via percutaneous endoscopic gastrostomy (PEG) improves motor complications and quality of life (QoL). Objectives: To record long-term effectiveness of advanced PD patients undergoing LCIG infusion in routine care, by Unified Parkinson's Disease Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), PDQ-8 and EQ-5D questionnaires. Methods: Overall, 375 patients from 75 movement disorder centers in 18 countries were enrolled in this prospective non-interventional study. The 12-month interim outcomes of the first 172 included patients are presented here. Results: There were reductions of mean daily "Off" time from baseline (BL) (7.1±3.5h) and "On" time with dyskinesias (5.2±4.5h) at month 12 (M12) of -4.7±3.4 and -1.7±5.0h respectively (p<0.0001; p=0.0228). UPDRS II and III "On" scores decreased from BL to M12 (p=0.0107 and p=0.0128). Total NMSS and PDQ-8 scores improved at M12 (p=0.0014 and p=0.0100). Mean LCIG dose administered through PEG at first visit (day after implantation) was 1304±618mg/day and remained stable through M12. Continuous LCIG infusion tolerability and adverse drug reactions were consistent with the known safety profile of previous studies. Conclusions: This observational, routine-care study supports long-term safety and efficacy of LCIG infusion in advanced PD including motor, non-motor and QoL improvements. © 2015 AbbVie Inc. employs authors Yegin, Preda, and Bergmann.


Antonini A.,IRCCS Hospital San Camillo | Fung V.S.C.,Westmead Hospital and Sydney Medical School | Boyd J.T.,University of Vermont | Slevin J.T.,University of Kentucky | And 4 more authors.
Movement Disorders | Year: 2016

Objective: The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia. Methods: Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by ≥1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n=11 levodopa-carbidopa intestinal gel, n=12 oral levodopa-carbidopa; open label: n=144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed. Results: Although not significantly different from oral levodopa treatment (P > .05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline=3.1 [1.7], change from baseline to final=-1.8 [1.8], P=.014), increase in "on" time without troublesome dyskinesia (baseline=7.4 [2.2], change=4.4 [3.6], P=.004), and decrease in "off" time (baseline=5.5 [1.3], change=-2.7 [2.8], P=.015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r=-.073, P=.842; open label: r=-0.001, P=.992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure. Conclusion: Our exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society.


Olanow C.W.,Mount Sinai School of Medicine | Kieburtz K.,University of Rochester | Odin P.,Skåne University Hospital | Espay A.J.,University of Cincinnati | And 12 more authors.
The Lancet Neurology | Year: 2014

Background: Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. Methods: In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. Findings: From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4·04 h (SE 0·65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2·14 h (0·66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference -1·91 h [95% CI -3·05 to -0·76]; p=0·0015). Mean on-time without troublesome dyskinesia increased by 4·11 h (SE 0·75) in the intestinal gel group and 2·24 h (0·76) in the immediate-release oral group (difference 1·86 [95% CI 0·56 to 3·17]; p=0·0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Interpretation: Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. Funding: AbbVie. © 2014 Elsevier Ltd.


Vorovenci R.J.,Victor Babes University of Medicine and Pharmacy Timisoara | Vorovenci R.J.,IRCCS Hospital San Camillo | Antonini A.,IRCCS Hospital San Camillo
Expert Review of Neurotherapeutics | Year: 2015

The moderate and severe stages of Parkinson's disease (PD) are marked by motor and non-motor complications that still remain difficult to control with the currently available therapy. Adenosine A2A receptor antagonists target non-dopaminergic systems, and have emerged as promising add-on therapy in the management of PD, a little more than a decade ago. While the development of this new drug class was slower than initially expected, istradefylline was recently registered in Japan, because it provides reduction of the off-time, when given in association with levodopa. Effects on some non-motor features have also been suggested, and preliminary studies further suggest a potential neuroprotective effect. Associations of A2A receptor antagonists with dopaminergic agents, as well as enzyme blockers like catechol-O-methyltransferase (COMT) and monoamine oxidase-B (MAO-B) inhibitors, should provide even greater benefit in advanced PD patients, and, thus, a more individualized treatment approach would be at hand. © 2015 Taylor & Francis.


Stathis P.,Mediterraneo Hospital | Konitsiotis S.,University of Ioannina | Antonini A.,IRCCS Hospital San Camillo
Expert Review of Neurotherapeutics | Year: 2014

Dyskinesias are common, often disabling motor complications emerging in Parkinson's disease following chronic levodopa treatment. Common views associate the development of dyskinesias both with progressive loss of striatal dopamine nerve terminals and with intermittent delivery of the short half-life levodopa. Thus, according to continuous dopaminergic stimulation theory, dopamine agonists having half-lifes longer than levodopa would minimize the risk of the development of dyskinesias. The article highlights some interesting aspects of the clinical trials testing dopamine agonists monotherapy as a strategy that can reduce the risk of motor complications, and raises some concerns in terms of their early use in Parkinson's disease treatment to prevent or delay dyskinesia. Finally, we emphasize the need for reconsideration of arguments against use of levodopa as a starting therapy for Parkinson's disease. © 2015 Informa UK Ltd.


Poewe W.,Innsbruck Medical University | Antonini A.,IRCCS Hospital San Camillo
Movement Disorders | Year: 2015

Ever since its early clinical use in the 1960s, levodopa has remained the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Motor response fluctuations and drug-induced dyskinesias seriously compromise the unparalleled symptomatic efficacy of l-dopa during long-term treatment. Discontinuous drug delivery resulting from the short half-life of l-dopa and erratic gastrointestinal absorption plays a major role in the pathophysiology of these motor complications. Several approaches to improve the pharmacokinetics and ways of administration of l-dopa are in different stages of clinical development and include novel formulations as well as nonoral routes of drug delivery. IPX066 is a novel extended-release l-dopa capsule that has successfully completed phase III clinical trials while the l-dopa prodrug XP21279 and a gastric retention formulation ("accordion pill") are in earlier phases of clinical development. Novel enzyme inhibitors enhancing l-dopa efficacy and half-life are also still being developed, including a novel catechol-O-methyltransferase inhibitor with once-daily pharmacokinetics, and there are studies testing the effects of increasing the dose of amino acid decarboxylase inhibitors given concomitantly with l-dopa. Intrajejunal infusion of a gel formulation of l-dopa/carbidopa is in clinical use in Europe, and its efficacy to smooth out motor fluctuations has recently been shown in a randomized, controlled trial. Subcutaneous and intrapulmonal delivery routes of l-dopa have reached phase III of clinical development. After more than 50 years of clinical use, l-dopa not only remains the gold standard of symptomatic efficacy, but it also remains a drug in active clinical development. © 2014 International Parkinson and Movement Disorder Society.


PubMed | University of Kentucky, IRCCS Hospital San Camillo, University of Illinois at Chicago, Westmead Hospital and Sydney Medical School and University of Vermont
Type: Journal Article | Journal: Movement disorders : official journal of the Movement Disorder Society | Year: 2016

The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinsons disease patients with troublesome dyskinesia.Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by 1 hour of on time with troublesome dyskinesia at baseline as recorded in Parkinsons disease symptom diaries (double blind: n=11 levodopa-carbidopa intestinal gel, n=12 oral levodopa-carbidopa; open label: n=144 levodopa-carbidopa intestinal gel). The changes in off time, on time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed.Although not significantly different from oral levodopa treatment (P>.05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in on time with troublesome dyskinesia (mean [standard deviation] hours: baseline=3.1 [1.7], change from baseline to final=-1.8 [1.8], P=.014), increase in on time without troublesome dyskinesia (baseline=7.4 [2.2], change=4.4 [3.6], P=.004), and decrease in off time (baseline=5.5 [1.3], change=-2.7 [2.8], P=.015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased on time with troublesome dyskinesia in either study (double blind: r=-.073, P=.842; open label: r=-0.001, P=.992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure.Our exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinsons disease.

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