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Milano, Italy

Cilia R.,Parkinson Institute | Van Eimeren T.,NeuroImage Nord | Van Eimeren T.,Universitatsklinik Schleswig Holstein
Brain Structure and Function | Year: 2011

The development of an impulse control disorder (ICD) is now recognized as a potential nonmotor adverse effect of dopamine replacement therapy in Parkinson's disease (PD). Here, recent epidemiological, neurophysiological and genetic advances are summarized to outline potential mechanisms involved. It is safe to say that dopaminergic drugs, particularly dopamine agonists, are able to induce ICDs only in a minority of patients, while the majority are somehow protected from this adverse effect. While it seems clear that men with earlyonset PD are more vulnerable, other predisposing factors, such as various current or pre-PD personality traits, are a matter of debate. In terms of neurophysiological advances, one may find striking analogies to the addiction literature suggesting a causal chain beginning with certain predisposing conditions of striatal dopamine synapses, an "unnatural" increase of dopamine stimulation and a characteristic pattern of resulting functional changes in remote networks of appetitive drive and impulse control. Future prospects include potential add-on medications and the possible identification of genetic predispositions at a genome- wide scale. Functional imaging of pharmacogenetic interactions (imaging pharmacogenomics) may be an important tool on that road. © Springer-Verlag 2011. Source

Antonini A.,Parkinson Institute | Odin P.,Central Hospital | Odin P.,Lund University
Parkinsonism and Related Disorders | Year: 2010

Motor fluctuations and dyskinesia are common in advanced Parkinson's disease and can be poorly managed by current oral medications. Risk factors include the amount of l-dopa administered, gender and patient age. Continuous duodenal l-dopa or subcutaneous apomorphine infusions are helpful strategies because they can control motor complications by providing continuous dopaminergic drug delivery. Apomorphine subcutaneous infusion provides a motor benefit similar to that of dopamine and is relatively easy to use in advanced PD. However, it commonly requires concomitant administration of oral l-dopa and its long-term use is limited by compliance. Continuous administration of l-dopa/carbidopa by infusion in the duodenum/jejunum is a more complex procedure requiring a gastrostomy for the placement of the infusion tube, but it allows replacement of all oral medications and the achievement of a satisfactory therapeutic response paralleled by a reduction of motor complication severity. It should be noted that although these procedures are effective, most evidence relates to small case series and, particularly in the case of apomorphine, despite its long-term availability, there is a complete lack of randomized blinded studies. In addition, unlike deep brain stimulation, it is unclear which patients are the best candidates for these procedures, making any indirect comparison very complex, given the clinical heterogeneity of reported patients. This has consequences in resource allocation and in estimating cost-benefit ratios for these complex therapies in advanced PD. © 2009 Elsevier Ltd. All rights reserved. Source

Pezzoli G.,Parkinson Institute | Cereda E.,Fondazione IRCCS Policlinico San Matteo
Neurology | Year: 2013

Objective: To investigate the risk of Parkinson disease (PD) associated with exposure to pesticides and solvents using meta-analyses of data from cohort and case-control studies. Methods: Prospective cohort and case-control studies providing risk and precision estimates relating PD to exposure to pesticides or solvents or to proxies of exposure were considered eligible. The heterogeneity in risk estimates associated with objective study quality was also investigated. Results: A total of 104 studies/3,087 citations fulfilled inclusion criteria for meta-analysis. In prospective studies, study quality was not a source of heterogeneity. PD was associated with farming and the association with pesticides was highly significant in the studies in which PD diagnosis was self-reported. In case-control studies, study quality appeared to be a source of heterogeneity in risk estimates for some exposures. Higher study quality was frequently associated with a reduction in heterogeneity. In high-quality case-control studies, PD risk was increased by exposure to any-type pesticides, herbicides, and solvents. Exposure to paraquat or maneb/mancozeb was associated with about a 2-fold increase in risk. In high-quality case-control studies including an appreciable number of cases (>200), heterogeneity remained significantly high (>40%) only for insecticides, organochlorines, organophosphates, and farming; also, the risk associated with rural living was found to be significant. Conclusions: The literature supports the hypothesis that exposure to pesticides or solvents is a risk factor for PD. Further prospective and high-quality case-control studies are required to substantiate a cause-effect relationship. The studies should also focus on specific chemical agents. © 2013 American Academy of Neurology. Source

Frazzitta G.,Scientific Institute of Montescano | Pezzoli G.,Parkinson Institute | Bertotti G.,Scientific Institute of Montescano | Maestri R.,Scientific Institute of Montescano
Journal of Neurology | Year: 2013

It has been hypothesized that freezing of gait (FOG) in parkinsonian patients (PD) might be triggered by a breakdown in the normal symmetry of gait. In this study, we evaluated the relationship between asymmetry of gait and FOG and the effects of intensive treadmill treatment on asymmetry. We studied 30 patients with (FOG+) and 30 without (FOG-) freezing in "on" stage. Patients underwent a 4-week rehabilitation treatment using a treadmill with auditory and visual cues and were evaluated at enrolment and at the end of rehabilitation. Outcome measures were gait speed, stride length, asymmetry of gait, Six-minute walking test (6MWT), Unified Parkinson's Disease Rating Scale (UPDRS) II-III, Berg Balance Scale, Timed Up and Go Test, comfortable-fast gait speeds, freezing of gait questionnaire (FOGQ). At enrolment, no differences in gait parameters were observed between the two groups, which differed only in UPDRS-II and BBS. Both FOG+ and FOG- patients spent more time on the left foot (time on left/time on right foot 1.37, p = 0.002, 1.18, p = 0.016, respectively). Rehabilitation determined a homogeneous improvement in both groups of patients for all variables except UPDRS-II and balance, for which a better improvement was observed in FOG+ patients. The improvement in FOGQ in FOG+ patients was significantly correlated to the improvement in asymmetry of gait (Spearman R = 0.46, p = 0.013). Our data support a direct involvement of the asymmetry of gait in the development of FOG in PD. Treadmill training is effective in improving gait and balance in PD FOG+ patients and this might be related to a reduction of asymmetric gait. © 2012 Springer-Verlag. Source

Cereda E.,Parkinson Institute | Barichella M.,Parkinson Institute | Pedrolli C.,Dietetic and Clinical Nutrition Unit | Pezzoli G.,Parkinson Institute
Movement Disorders | Year: 2010

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. Longterm 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). © 2010 Movement Disorder Society. Source

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