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Understanding and management of Parkinson's Disease - new insights, #EFNS, #ENFS2011 by Mind Map: Understanding and management of
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Understanding and management of Parkinson's Disease - new insights, #EFNS, #ENFS2011

Chairman: Olivier Rascol



Günther Deuschl


Publications by speaker on Pubmed


Hoehn Yahr staging, Slide image, Slide image, slide image

Preclinical phase of PD, Hilker et al Arch of NEurol 2005, RBD, Constipation, Hyposmia, Atipcal tremors, Autonomic symptoms

Disease modification - preclinical definitions, Neuroprotection, interventions to prevent cell death to slow disease progression, neurorescue, dying neurones are rescued by reversol of established metabolic abnormalities, neurorestoration, compensatory mechanisms

Disease modification - clinical standpoint, clinical outcome/defined endpoint, surrogate markers may support the determination of disease modifying effects

Untangling drugs with different effects, Natural disease progression, symptomatic, disease modifying, symptomatic + disease modifying, How to bring the above into studies, L-dopa - DATATOP study, placebo, Withdrawal study, short term medication effect, long term effects of medication, storing effects, plasticity of the motor system, you never know how long it takes to withdraw, Surrogate markers?, DAT scanning, would dopamin terminals be saved?, ELLDOPA study, Delayed start design, Placebo group, rasagiline starts later, Rasagiline treatment, Disease modifying effet after 36 weeks..., ADAGIO study, link, link, link, We are waiting for ADAGIO follow up study, in 2-3 years, PROUD study, delayed start trial w the DA agonist pramipexole, Schapira et al 2009, Author Schapira pubmed, TEMPO study - signal of potential disease-modifying effect of rsagiline, TEMPO long-term extension, How do we progress towards improved treatment strategies?, missed, Summary - slide

Oliver Rascol


Author on Pubmed



slide, full image of slide, close up

Why is it important to understand the progression of PD in its early stage?, to have a better progrnosis of PD, to try to stop or slow down disease progression, keeping the patient in the pre-symptomatic phase for as l ong as possible, to provide more appropriate counselling to patients, to help choose between the different early treatment options, to design better disease modification trials

Disease progress in beginning faster than later in disease course seems to happen, Post-mortem studies suggest a faster rate of cell death in early PD than in late PD, Fearnley, brain 1991, Neuro-imaging observations suggest a faster rate of degeneration in early PD than in late PD, Pirker 2003, Previous clinical trials in mild, untreated PD report placebo progression rates of 8-12 UPDRS units/year

slide, detail on references

ADAGIO, Main adagio objective: to prospectively examine rasagiline as a disease modifying therapy in PD, objective of placebo progression analysis: to describe the natural progression of clinical symptoms in a large cohort of early patients w PD, Rate of progression in placeboa arm of ADAGIO was slower than anticipated from previous clinical trials in mild, untreated PD, slide, ADAGIO placebo progression analysis - patient disposition, of the 595 patients initially randomised to placebo, 588 were included in analysis, sungroups analysis to baseline score, separated by UPDRS score, UPDRS progression was baseline, lower quartile of progress, lower progress, lower age, higher quartile of progress, higher score at baseline = faster progress, higher age: faster progress, ADAGIO included an early PD population raising the possibility of potential misdiagnoses, lower quartile: SWEDDs?, previous trials in early PD have reported a SWEDDS rate of 10%, Scans without evidence for Dopaminergic Depletion = SWEDDS, What does 1.7 UPDRS units less disease progression mean for clinical practice?, Is the UPDRS-ADL subscore a more appropriate measure of disease progression?, Section II: UPDRS-ADL, speech, salivation, swallowing, handwriting, etc., Should we focus more on patient centered outcome?, Harrison et al 2008: hypothesis, UPDRS activity of Daily living, Schrag et al 2009: objective and methods, Goetz et al, 2002: commentary, Relative contribution of UPDRS-mental, ADL, and motor-sub scores to UPDRS, Conclusion: ADL is important

Fabrizio Stocchi


Publications by speaker on Pubmed


Disease progression over time, Non-motor symptoms, slide

Objectives of treatment, modify natural disease progression, improve symptoms and quality of life, induce a physiological DA stimulation, Delay complications and dyskinesia, obtain patient's compliance, minimise side effects

Factors unfluencing drug choice, patient characteristics, consideration of other factors (e.g. age, cognition, comorbidities, efficacy, tolerability, convenience

Therapeutic options in early patients, MAO-B, Dopamine agonist, Levodopa

Some research data, no notes taken, Pramixpexole, rasagiline, etc...

Levodopa is still the most effective drug in the treatment of PD

Today, there are no drugs that are able to maintain mobility in patients with advanced disease without the "help" of levodopa

Challenge balance between side effects vs effects, rasagiline was well tolerated and safe in PD, Dopamine agonist, list of adverse effects, Impulse control disorders w dopamine agonist, DOMINION study - evaluation of ICDs in PD, ACTOR study, rasagiline vs pramipexole safety profile, Concerns, Melanoma, Serotonin syndrome, Cheese effects, Ref: olanow 2009, New England Journal of medicine

Summary slide, Pharmacological fluctuations, Slide, Ropinirol, rotigotine, pramipexole, PRESTO study, reduction of OFF time in different study segments - radagiline PRESTO study