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Parkinson Disease: HELP
Articles by O. Rascol
Based on 25 articles published since 2008
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Between 2008 and 2019, O. Rascol wrote the following 25 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Guideline Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program. 2015

Odin, P / Ray Chaudhuri, K / Slevin, J T / Volkmann, J / Dietrichs, E / Martinez-Martin, P / Krauss, J K / Henriksen, T / Katzenschlager, R / Antonini, A / Rascol, O / Poewe, W / Anonymous2260838. ·Department of Neurology, Lund University Hospital, 221 85 Lund, Sweden; Klinikum-Bremerhaven, D-27574 Bremerhaven, Germany. Electronic address: per.odin@med.lu.se. · King's College London, and National Parkinson Foundation Centre of Excellence, Dept of Neurology, King's College Hospital, London, UK. · Department of Neurology, University of Kentucky College of Medicine, Kentucky Clinic L-445, 740 South Limestone Street, Lexington, KY 40536-0284, USA. · Department of Neurology, University Hospital of Würzburg, 97080 Würzburg, Germany. · Department of Neurology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway. · National Center for Epidemiology and CIBERNED, ISCIII, Avenida Monforte de Lemos 5, 28029 Madrid, Spain. · Department of Neurosurgery, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. · University Hospital of Bispebjerg, Bispebjerg Bakke 23, 2400 København, NV, Denmark. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Sozialmedizinisches Zentrum Ost - Donauspital, 1220 Wien Langobardenstraße 122, Austria. · Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy. · Clinical Investigation Center 1436 and Department of Clinical Pharmacology, INSERM and University Hospital of Toulouse, Toulouse University, 37 alées Jules Giesde, 31000 Toulouse, France; Clinical Investigation Center 1436 and Department of Neurosciences, INSERM and University Hospital of Toulouse, Toulouse University, 37 alées Jules Giesde, 31000 Toulouse, France. · Innsbruck Medical University/University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. ·Parkinsonism Relat Disord · Pubmed #26233582.

ABSTRACT: Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as 'critically important;' these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome 'off' periods (>1-2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS.

2 Editorial [UPDRS scale is dead. Long live MDS-UPDRS!]. 2010

Rascol, O. · ·Rev Neurol (Paris) · Pubmed #20074765.

ABSTRACT: -- No abstract --

3 Review Pain in Parkinson's disease: facts and uncertainties. 2018

Antonini, A / Tinazzi, M / Abbruzzese, G / Berardelli, A / Chaudhuri, K R / Defazio, G / Ferreira, J / Martinez-Martin, P / Trenkwalder, C / Rascol, O. ·University of Padua, Padua. · University of Verona, Verona. · University of Genoa, Genoa. · University of Rome, Rome. · IRCCS NEUROMED, Isernia, Italy. · Kings College London, London, UK. · University of Cagliari, Cagliari, Italy. · Hospital de Santa Maria, Lisbon, Portugal. · National Center of Epidemiology and CIBERNED, Madrid, Spain. · University Medical Center Goettingen, Goettingen, Germany. · Université de Toulouse, Toulouse, France. ·Eur J Neurol · Pubmed #29520899.

ABSTRACT: Pain is one of the most common and troublesome non-motor symptoms of Parkinson's disease (PD). It can appear at any time during the disease and is often present before diagnosis. However, there is little or no consensus on its definition. An expert group of clinicians with relevant research experience met to review the existing evidence and to identify gaps in our understanding leading towards AUTHOR: 'understanding towards' has been changed to 'understanding leading towards'. Please check and confirm that this is appropriate an optimized therapy of pain in PD. Key findings from epidemiologic, neurophysiologic, neuroimaging and clinical studies are reviewed. In each case, the evidence base is limited by wide variations in the definitions of pain applied, study methodologies and populations evaluated. Disease-related and medical conditions trigger spontaneous pain in patients with PD, which is then abnormally processed and results in painful manifestations in specific body parts. Dopaminergic medications, such as rotigotine, as well as opiate analgesics, such as oxycodone, have shown positive results but future studies with more detailed pain characterization at inclusion are warranted.

4 Review Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. 2013

Ferreira, J J / Katzenschlager, R / Bloem, B R / Bonuccelli, U / Burn, D / Deuschl, G / Dietrichs, E / Fabbrini, G / Friedman, A / Kanovsky, P / Kostic, V / Nieuwboer, A / Odin, P / Poewe, W / Rascol, O / Sampaio, C / Schüpbach, M / Tolosa, E / Trenkwalder, C / Schapira, A / Berardelli, A / Oertel, W H. ·Laboratory of Clinical Pharmacology and Therapeutics and Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. ·Eur J Neurol · Pubmed #23279439.

ABSTRACT: OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

5 Review Drugs and drug delivery in PD: optimizing control of symptoms with pramipexole prolonged-release. 2011

Rascol, O. ·Department of Clinical Pharmacology and Neurosciences, INSERM U825 and Clinical Investigation Center, University Hospital, Toulouse, France. rascol@cict.fr ·Eur J Neurol · Pubmed #21255197.

ABSTRACT: Intermittent or pulsatile dopamine-receptor stimulation is postulated to induce plastic changes in motor systems that are responsible for the development of motor fluctuations and dyskinesia, complicating long-term levodopa therapy of Parkinson's disease (PD). Continuous dopamine stimulation (CDS) is a concept that refers to the hypothesis that more continuous dopamine-receptor stimulation will reduce the risk of motor complications, particularly dyskinesias, and may also treat established dyskinesias. In line with this hypothesis, the intermittent administration of dopaminergic agents with short half-lives induce motor complications in animal models, whilst the continuous administration of the same compounds via mini-pumps substantially reduces such symptoms. Continuous drug delivery (CDD) strategies are therefore explored in clinical trials to prevent or manage motor complications. The early use of a dopamine agonist reduces the risk of motor fluctuations compared with levodopa. Conversely, the early combination of the catechol-O-methyltransferase inhibitor entacapone with levodopa has failed to demonstrate a comparable advantage. Outcomes of uncontrolled long-term studies of PD patients with motor complications treated for several months with subcutaneous continuous infusion of apomorphine or intraduodenal levodopa are compatible with CDS. New once-daily prolonged-release formulations of dopamine agonists have demonstrated antiparkinsonian efficacy in randomized trials conducted in early as well as advanced patients with PD. Once-daily administration is convenient and may improve compliance. Other theoretical advantages in terms of efficacy or tolerability deserve further exploration.

6 Review Perspectives on recent advances in the understanding and treatment of Parkinson's disease. 2009

Schapira, A H / Agid, Y / Barone, P / Jenner, P / Lemke, M R / Poewe, W / Rascol, O / Reichmann, H / Tolosa, E. ·Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK. a.schapira@medsch.ucl.ac.uk ·Eur J Neurol · Pubmed #19723294.

ABSTRACT: There have been numerous important recent advances in our understanding of the causes of Parkinson's disease (PD), the treatments available and how these are best applied for the long-term management of patients. Novel genes causing familial PD have been discovered and mechanisms leading to cell dysfunction and death identified. The PD prodrome is now a subject of great interest and clinical markers are being defined that may in future, together with biochemical markers, support an early, pre-motor diagnosis of PD. This will become important as new therapies are developed to modify disease progression. In the interim, the optimization of existing therapies remains an important priority. The value of existing and novel continuous drug delivery systems in PD is seen as providing simplified regimens, maintenance of motor control, reduction in motor complications and improved patient adherence to drug use.

7 Review [Treatments in the early stage of Parkinson disease]. 2008

Rascol, O. ·Laboratoire de pharmacologie clinique, Centre d'Investigation clinique, INSERM U825, pôle neurosciences, Centre hospitalier universitaire, Toulouse. rascol@cict.fr ·Rev Neurol (Paris) · Pubmed #18680822.

ABSTRACT: -- No abstract --

8 Article Experience of care for Parkinson's disease in European countries: a survey by the European Parkinson's Disease Association. 2018

Schrag, A / Khan, K / Hotham, S / Merritt, R / Rascol, O / Graham, L. ·Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK. · Centre for Health Services Studies, University of Kent, Canterbury, UK. · University of Surrey, Guildford, UK. · Départements de Pharmacologie Clinique et de Neurosciences, Centre Hospitalo-Universitaire de Toulouse and INSERM, Centre d'Investigation Clinique CIC1436, Centre Expert Parkinson, NeuroToul COEN Centre of Excellence in Neurodegeneration, Université de Toulouse, Toulouse, France. · European Parkinson's Disease Association, Sevenoaks, UK. ·Eur J Neurol · Pubmed #29939446.

ABSTRACT: BACKGROUND: Few studies report on the experience of care for patients with Parkinson's disease (PD) from their own point of view. METHODS: An analysis was carried out of a survey in 11 European countries on self-reported access to services and satisfaction with different aspects of care. RESULTS: In all, 1775 people with PD (PwP) participated with disease duration ranging from <1 to 42 years. When referred to a specialist most were seen within 3 months but medication reviews occurred every 3 months in only 10%, every 6 months in 37%, once a year in 40% and every 2 years or less frequently in 13%. Waiting times to therapists were usually ≥4 months. Satisfaction with care was highest for involvement of PwP in decisions (63% of respondents satisfied) and involvement of family/carer (62%) followed by communication with PwP (57%), information received (54%), frequency of treatment reviews (52%) and suitability of treatment for the individual condition and circumstances (52%), but lowest for availability and accessibility of treatment when needed (48%) and collaborations between healthcare professionals in delivering care (41% satisfied). The main factors associated with overall satisfaction scores with care were the overall satisfaction with initial consultation (r = 0.26, P < 0.0001), the sensitivity with which the diagnosis was communicated, the quantity of information provided (both r = 0.24, P < 0.0001) and the frequency of medication review (r = 0.17, P < 0.0001). CONCLUSION: More coordinated and responsive care, tailored to the individual, with regular and timely medication reviews and information provision, is likely to improve satisfaction with care in current healthcare pathways.

9 Article Abnormal pain perception in patients with Multiple System Atrophy. 2018

Ory-Magne, F / Pellaprat, J / Harroch, E / Galitzsky, M / Rousseau, V / Pavy-Le Traon, A / Rascol, O / Gerdelat, A / Brefel-Courbon, C. ·Department of Neurology, University Hospital of Toulouse, Toulouse, France; INSERM, Imagerie Cérébrale et Handicaps Neurologiques, UMR 1214, Toulouse, France; Clinical Investigation Center 1436, Inserm and University of Hospital of Toulouse, Toulouse, France; French Reference Center for Multiple System Atrophy, France; Toulouse Parkinson Expert Center, Toulouse University Hospital, Toulouse, France; NeuroToul Centre of Excellence in Neurodegeneration (COEN), France. Electronic address: ory.f@chu-toulouse.fr. · INSERM, Imagerie Cérébrale et Handicaps Neurologiques, UMR 1214, Toulouse, France. · Department of Neurology, University Hospital of Toulouse, Toulouse, France; Clinical Investigation Center 1436, Inserm and University of Hospital of Toulouse, Toulouse, France; Toulouse Parkinson Expert Center, Toulouse University Hospital, Toulouse, France. · Clinical Investigation Center 1436, Inserm and University of Hospital of Toulouse, Toulouse, France; NeuroToul Centre of Excellence in Neurodegeneration (COEN), France. · Department of Clinical Pharmacology, University Hospital, Toulouse, France. · Department of Neurology, University Hospital of Toulouse, Toulouse, France; INSERM, Imagerie Cérébrale et Handicaps Neurologiques, UMR 1214, Toulouse, France; French Reference Center for Multiple System Atrophy, France; NeuroToul Centre of Excellence in Neurodegeneration (COEN), France. · Department of Neurology, University Hospital of Toulouse, Toulouse, France; INSERM, Imagerie Cérébrale et Handicaps Neurologiques, UMR 1214, Toulouse, France; Clinical Investigation Center 1436, Inserm and University of Hospital of Toulouse, Toulouse, France; Department of Clinical Pharmacology, University Hospital, Toulouse, France; French Reference Center for Multiple System Atrophy, France; Toulouse Parkinson Expert Center, Toulouse University Hospital, Toulouse, France; NeuroToul Centre of Excellence in Neurodegeneration (COEN), France. · Department of Neurology, University Hospital of Toulouse, Toulouse, France; INSERM, Imagerie Cérébrale et Handicaps Neurologiques, UMR 1214, Toulouse, France. ·Parkinsonism Relat Disord · Pubmed #29254664.

ABSTRACT: INTRODUCTION: Patients with Parkinson's disease or Multiple System Atrophy frequently experience painful sensations. The few studies investigating pain mechanisms in Multiple System Atrophy patients have reported contradictory results. In our study, we compared pain thresholds in Multiple System Atrophy and Parkinson's disease patients and healthy controls and evaluated the effect of l-DOPA on pain thresholds. METHODS: We assessed subjective and objective pain thresholds (using a thermotest and RIII reflex), and pain tolerance in OFF and ON conditions, clinical pain, motor and psychological evaluation. RESULTS: Pain was reported in 78.6% of Multiple System Atrophy patients and in 37.5% of Parkinson's disease patients. In the OFF condition, subjective and objective pain thresholds were significantly lower in Multiple System Atrophy patients than in healthy controls (43.8 °C ± 1.3 vs 45.7 °C ± 0.8; p = 0.0005 and 7.4 mA ± 3.8 vs 13.7 mA ± 2.8; p = 0.002, respectively). They were also significantly reduced in Multiple System Atrophy compared to Parkinson's disease patients. No significant difference was found in pain tolerance for the 3 groups and in the effect of l-DOPA on pain thresholds in Multiple System Atrophy and Parkinson's disease patients. In the ON condition, pain tolerance tended to be reduced in Multiple System Atrophy versus Parkinson's disease patients (p = 0.05). CONCLUSION: Multiple System Atrophy patients had an increase in pain perception compared to Parkinson's disease patients and healthy controls. The l-DOPA effect was similar for pain thresholds in Multiple System Atrophy and Parkinson's disease patients, but tended to worsen pain tolerance in Multiple System Atrophy.

10 Article L-DOPA-induced dyskinesias, motor fluctuations and health-related quality of life: the COPARK survey. 2017

Perez-Lloret, S / Negre-Pages, L / Damier, P / Delval, A / Derkinderen, P / Destée, A / Meissner, W G / Tison, F / Rascol, O / Anonymous5830920. ·INSERM, Services de Pharmacologie Clinique et Neurosciences, Centre d'Investigation Clinique CIC 1436, NS-Park/FCRIN Network, NeuroToul COEN Center, Université de Toulouse UPS, CHU de Toulouse, Toulouse, France. · Institute of Cardiology Research, University of Buenos Aires, National Research Council (CONICET-ININCA), Buenos Aires, Argentina. · LN Pharma, Toulouse. · Département d'Information Médicale, Unité de Recherche Clinique et Epidémiologie, Hôpital la Colombière, Montpellier. · Department of Neurology, INSERM, NS-Park/FCRIN Network, Université de Nantes, CHU de Nantes, Nantes. · Department of Neurology, INSERM, NS-Park/FCRIN Network, Université de Lille, CHU de Lille, U 837 Eq6, Lille. · CNRS, CHU de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Service de Neurologie, NS-Park/FCRIN Network, Université de Bordeaux, Bordeaux, France. ·Eur J Neurol · Pubmed #28940893.

ABSTRACT: BACKGROUND AND PURPOSE: Studies assessing the correlations between L-DOPA-induced dyskinesias (LIDs) and motor fluctuations with health-related quality of life (HRQoL) in Parkinson's disease (PD) have yielded conflicting results. This study aimed to assess the relationship between LIDs and motor fluctuations with HRQoL in patients with PD, and to assess the relative contribution of their severity and duration in a large sample of patients with PD. METHODS: A total of 683 patients with PD from the COPARK survey were evaluated. HRQoL was assessed using the 39-Item Parkinson's Disease Questionnaire (PDQ-39) (primary outcome) and 36-Item Short Form Survey (SF-36). The daily duration and severity of LIDs were obtained from Unified Parkinson's Disease Rating Scale (UPDRS) IV items 32 and 33, respectively. The daily duration of motor fluctuations was obtained from UPDRS IV item 36 and severity was estimated as the difference between the UPDRS 2 (Activities of Daily Living) score in 'OFF' versus 'ON' condition. RESULTS: A total of 235 patients with PD (35%) experienced motor fluctuations and 182 (27%) experienced LIDs. The PDQ-39 total and SF-36 physical scores were significantly worse in patients with LIDs, after adjusting for the presence of motor fluctuations. The PDQ-39 total score and SF-36 physical and mental score were significantly worse in patients with motor fluctuations, after adjusting for the presence of LIDs. The severity of LIDs and the duration of motor fluctuations significantly and independently affected PDQ-39 scores. The SF-36 physical score was affected only by the severity of motor fluctuations, whereas the mental score was not affected by any of the aforementioned variables. CONCLUSION: Our findings suggest that LIDs (mainly their severity) and motor fluctuations (mainly their duration) correlate independently with HRQoL in patients with PD.

11 Article French consensus procedure for assessing cognitive function in Parkinson's disease. 2016

Dujardin, K / Auzou, N / Lhommée, E / Czernecki, V / Dubois, B / Fradet, A / Maltete, D / Meyer, M / Pineau, F / Schmitt, E / Sellal, F / Tison, F / Vidal, T / Azulay, J-P / Welter, M-L / Corvol, J-C / Durif, F / Rascol, O / Anonymous13020871. ·Université de Lille, Inserm U1171, Degenerative & Vascular Cognitive Disorders, 59000 Lille, France; CHU de Lille, Neurology and Movement Disorders, 59000 Lille, France. Electronic address: kathy.dujardin@univ-lille2.fr. · Institute of Neurodegenerative Disorders, CHU de Bordeaux, 33000 Bordeaux, France; Université de Bordeaux, Psychology Laboratory, EA4139, 33000 Bordeaux, France. · CHU de Grenoble Alpes, Inserm U1216, 38000 Grenoble, France; Université Grenoble Alpes, Grenoble Institut des Neurosciences (GIN), 38000 Grenoble, France. · CRICM UMRS 975, Neurology Department, AP-HP, Salpetrière Hospital, 75013 Paris, France. · Université Pierre-et-Marie-Curie, Paris VI, ICM, Inserm UMR_S975, Dementia Research Center (IM2A), Salpêtrière Hospital, 75013 Paris, France. · CHU de Poitiers, Neurology & Neuropsychology, Expert Referent Center of Parkinson Disease, CMRR, 86000 Poitiers, France. · Department of Neurology, Rouen University Hospital, 76031 Rouen, France; Inserm U1073, Rouen Faculty of Medicine, 76031 Rouen, France. · CHU de Nancy, Department of Neurology, 54000 Nancy, France. · Département de Neurologie, Hôpitaux Civils de Colmar, 68000 Colmar, France. · Université Pierre-et-Marie-Curie, Paris VI, ICM, Inserm UMR_S975, Dementia Research Center (IM2A), Salpêtrière Hospital, 75013 Paris, France; CHU de Poitiers, Neurology & Neuropsychology, Expert Referent Center of Parkinson Disease, CMRR, 86000 Poitiers, France. · Département de Neurologie, Hôpitaux Civils de Colmar, 68000 Colmar, France; Inserm U1118, Université de Strasbourg, 67085 Strasbourg, France. · Institute of Neurodegenerative Disorders, CHU de Bordeaux, 33000 Bordeaux, France. · CHU de Clermont-Ferrand, Movement Disorders Centre, 63000 Clermont-Ferrand, France; CHU de Clermont-Ferrand, Resource and Research Memory Centre, 63000 Clermont-Ferrand, France. · Neurology and Movement Disorders, Hôpital de la Timone, AP-HM, Institut des Neurosciences de la Timone, Université Aix-Marseille, 13385 Marseille, France. · Inserm UMRS-1127, 75013 Paris, France. · Sorbonne Universités, UPMC Université Paris 06, Inserm UMRS-1127, CIC-1422, CNRS UMR-7225, AP-HP, ICM, Hôpital Pitié-Salpêtrière, Département des Maladies du Système Nerveux, 75013 Paris, France. · CHU de Clermont-Ferrand, Movement Disorders Centre, 63000 Clermont-Ferrand, France. · Clinical Investigation Center (CIC) 1436, Department of Clinical Pharmacolgy and Neurosciences, Inserm, Toulouse University Hospital, University of Toulouse, 31059 Toulouse, France. ·Rev Neurol (Paris) · Pubmed #27318613.

ABSTRACT: INTRODUCTION: One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. METHODS: A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. RESULTS: Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. DISCUSSION AND CONCLUSION: A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease.

12 Article King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation. 2015

Chaudhuri, K Ray / Rizos, A / Trenkwalder, C / Rascol, O / Pal, S / Martino, D / Carroll, C / Paviour, D / Falup-Pecurariu, C / Kessel, B / Silverdale, M / Todorova, A / Sauerbier, A / Odin, P / Antonini, A / Martinez-Martin, P / Anonymous40834. ·King's College Hospital, London, UK. · King's College London, London, UK. · University Hospital Lewisham, London, UK. · Paracelsus-Elena Hospital, Kassel, Germany. · Clinical Investigation Center 1436 and Departments of Clinical Pharmacology and Neurosciences, INSERM and University Hospital of Toulouse, Toulouse, France. · Forth Valley Royal Hospital, Scotland, UK. · Lewisham & Greenwich NHS Trust, London, UK. · Plymouth University and Plymouth Hospitals NHS Trust, Plymouth, UK. · St Georges Hospital, London, UK. · Transilvania University, Brasov, Romania. · Princess Royal University Hospital site, King's College Hospital, Orpington, UK. · Greater Manchester Neuroscience Centre, Manchester, UK. · University of Lund, Lund, Sweden. · Klinikum Bremerhaven Reinkenheide, Bremerhaven, Germany. · Parkinson and Movement Disorders Unit; IRCCS Hospital San Camillo, Venice, Italy. · National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Mov Disord · Pubmed #26096067.

ABSTRACT: Pain is a key unmet need and a major aspect of non-motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross-sectional, open, multicenter, one-point-in-time evaluation with retest study of the first PD-specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy-eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29-85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non-PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser-Mayer-Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item-total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD-Motor, Non-Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD.

13 Article Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial. 2015

Antonini, A / Bauer, L / Dohin, E / Oertel, W H / Rascol, O / Reichmann, H / Schmid, M / Singh, P / Tolosa, E / Chaudhuri, K Ray. ·Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy. · UCB Pharma, Monheim am Rhein, Germany. · UCB Pharma, Paris, France. · Department of Neurology, Philipps University, Marburg, Germany. · Clinical Investigation Centre CIC1436, and Departments of Clinical Pharmacology and Neurosciences, INSERM and Toulouse University Hospital, Toulouse, France. · Department of Neurology, University of Dresden, Dresden, Germany. · Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona Catalonia, Spain. · National Parkinson Foundation International Centre of Excellence, King's College Hospital, Kings College and Kings Health Partners, London, UK. ·Eur J Neurol · Pubmed #26095948.

ABSTRACT: 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.

14 Article Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease. 2014

Hauser, R A / Schapira, A H V / Barone, P / Mizuno, Y / Rascol, O / Busse, M / Debieuvre, C / Fraessdorf, M / Poewe, W / Anonymous3120794. · ·Eur J Neurol · Pubmed #24834511.

ABSTRACT: BACKGROUND AND PURPOSE: To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). METHODS: In two double-blind (DB) studies of early PD and one of advanced PD,active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375-4.5 mg q.d.). RESULTS: Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0%were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) PartsII + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at -6.6 and -6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and -11.5 and -9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. CONCLUSIONS: These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

15 Article Success rate, efficacy, and safety/tolerability of overnight switching from immediate- to extended-release pramipexole in advanced Parkinson's disease. 2013

Schapira, A H V / Barone, P / Hauser, R A / Mizuno, Y / Rascol, O / Busse, M / Debieuvre, C / Fraessdorf, M / Poewe, W. ·Department of Clinical Neurosciences, University College London Institute of Neurology, London, UK. a.schapira@medsch.ucl.ac.uk ·Eur J Neurol · Pubmed #22845710.

ABSTRACT: BACKGROUND AND PURPOSE: For Parkinson's disease (PD), an extended-release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate-release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER. METHODS: Levodopa users experiencing motor fluctuations were randomized to adjunctive double-blind (DB) placebo, IR, or ER. Amongst completers of ≥18 weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5 weeks, all patients underwent ER titration to optimal open-label maintenance dosage. RESULTS: One week post-switch, 86.2% of 123 IR-to-ER and 83.8% of 105 ER-to-ER patients had ≤15% (or ≤3-point, for pre-switch scores ≤20) increase on UPDRS Parts II + III, and 77.9% (of 122) and 70.2% (of 104) had ≤1-h increase in daily OFF-time. At 32 weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II + III, adjusted mean (SE) changes of -14.8 (1.5) for IR-to-ER and -13.3 (1.6) for ER-to-ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR-to-ER and 4.9% for ER-to-ER. CONCLUSIONS: By OFF-time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial.

16 Article Effect of levodopa on both verbal and motor representations of action in Parkinson's disease: a fMRI study. 2013

Péran, P / Nemmi, F / Méligne, D / Cardebat, D / Peppe, A / Rascol, O / Caltagirone, C / Demonet, J F / Sabatini, U. ·Inserm, Imagerie Cérébrale et Handicaps Neurologiques, UMR 825, 31059 Toulouse, France. patrice.peran@inserm.fr ·Brain Lang · Pubmed #22841350.

ABSTRACT: Previous studies have demonstrated that non-demented Parkinson's disease (PD) patients have a specific impairment of verb production compared with noun generation. One interpretation of this deficit suggested the influence of striato-frontal dysfunction on action-related verb processing. The aim of our study was to investigate cerebral changes after motor improvement due to dopaminergic medication on the neural circuitry supporting action representation in the brain as mediated by verb generation and motor imagery in PD patients. Functional magnetic resonance imaging on 8 PD patients in "ON" dopaminergic treatment state (DTS) and in "OFF" DTS was used to explore the brain activity during three different tasks: Object Naming (ObjN), Generation of Action Verbs (GenA) in which patients were asked to overtly say an action associated with a picture and mental simulation of action (MSoA) was investigated by asking subjects to mentally simulate an action related to a depicted object. The distribution of brain activities associated with these tasks whatever DTS was very similar to results of previous studies. The results showed that brain activity related to semantics of action is modified by dopaminergic treatment in PD patients. This cerebral reorganisation concerns mainly motor and premotor cortex suggesting an involvement of the putaminal motor loop according to the "motor" theory of verb processing.

17 Article Patient-reported convenience of once-daily versus three-times-daily dosing during long-term studies of pramipexole in early and advanced Parkinson's disease. 2013

Schapira, A H V / Barone, P / Hauser, R A / Mizuno, Y / Rascol, O / Busse, M / Debieuvre, C / Fraessdorf, M / Poewe, W / Anonymous3700724. ·Department of Clinical Neurosciences, University College London Institute of Neurology, London, UK Università di Napoli Federico II-IDC Hermitage Capodimonte, Napoli, Italy. a.schapira@ucl.ac.uk ·Eur J Neurol · Pubmed #22537207.

ABSTRACT: BACKGROUND AND PURPOSE:   In chronic diseases including Parkinson's disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less-effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical-trial designs preclude direct comparisons of adherence to various schedules. METHODS:   In two double-blind (DB) studies of early PD and one of advanced PD, subjects received three-times-daily (t.i.d.) pramipexole or placebo. In open-label (OL) extensions, subjects took extended-release, once-daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. RESULTS:   Of 590 DB-trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it 'very much more convenient' and 27.8%'more convenient'), 2.7% preferred t.i.d., and 2.9% chose 'no difference'. Of 465 DB-trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it 'very much more convenient' and 40.1%'more convenient'), 5.7% preferred t.i.d., and 5.4% chose 'no difference'. Results excluding DB-placebo recipients were highly similar. CONCLUSIONS:   In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine-agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced-PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.

18 Article Pardoprunox as adjunct therapy to levodopa in patients with Parkinson's disease experiencing motor fluctuations: results of a double-blind, randomized, placebo-controlled, trial. 2012

Rascol, O / Bronzova, J / Hauser, R A / Lang, A E / Sampaio, C / Theeuwes, A / van de Witte, S V. ·Department of Clinical Pharmacology and Neurosciences, INSERM CIC9302 and UMR835, University Hospital and University of Toulouse, 37 Allées Jules Guesde, 31000 Toulouse, France. rascol@cict.fr ·Parkinsonism Relat Disord · Pubmed #22316635.

ABSTRACT: AIMS: To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson's disease (PD) experiencing motor fluctuations. METHODS: Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale). RESULTS: Pardoprunox significantly reduced OFF time versus placebo (-1.62 h/day versus -0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid. CONCLUSIONS: Pardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa-treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non-motor symptoms deserves further investigation.

19 Article Oro-buccal symptoms (dysphagia, dysarthria, and sialorrhea) in patients with Parkinson's disease: preliminary analysis from the French COPARK cohort. 2012

Perez-Lloret, S / Nègre-Pagès, L / Ojero-Senard, A / Damier, P / Destée, A / Tison, F / Merello, M / Rascol, O / Anonymous5730690. ·Department of Clinical Pharmacology, University Hospital and University of Toulouse, Toulouse, France. ·Eur J Neurol · Pubmed #21453441.

ABSTRACT: INTRODUCTION: Abnormal oro-buccal functions including dysarthria, sialorrhea and dysphagia commonly affect patients with Parkinson's disease (PD). OBJECTIVES: To estimate the prevalence of such oro-buccal symptoms at baseline in the first 419 patients with PD included in the COPARK cohort and to analyze their correlations with patients' demographics, clinical characteristics, and drugs consumption. METHODS: Patients were assessed using the Unified PD Rating Scale, the Hospital Anxiety and Depression Scale, and the PDQ-39. Dysarthria, sialorrhea, and dysphagia were defined as UPDRS items 5, 6, or 7 ≥ 1. RESULTS: Dysarthria, sialorrhea, or dysphagia were present in 51%, 37%, or 18% out of the 419 patients, respectively. At least one of these symptom was present in 267/419 patients (65%), whilst a combination of symptoms was present in 136/419 (33%). Logistic regression showed that the presence of each of the three oro-buccal symptoms was significantly correlated with that of the two others. Other correlations included male gender, hallucinations, disease severity, levodopa use and lack of opiates consumption for dysarthria; disease severity, orthostatic hypotension and absence of antidepressants consumption for sialorrhea; female gender, motor fluctuations, and depressive symptoms for dysphagia. None of the three oro-buccal symptoms were associated with a reduced PDQ-39 score. CONCLUSION: Oro-buccal symptoms were present in two of three patients with moderate PD, the presence of each symptoms being significantly correlated with that of the two others.

20 Article Extended-release pramipexole in early Parkinson disease: a 33-week randomized controlled trial. 2011

Poewe, W / Rascol, O / Barone, P / Hauser, R A / Mizuno, Y / Haaksma, M / Salin, L / Juhel, N / Schapira, A H V / Anonymous4710702. ·Innsbruck Medical University, Innsbruck, Austria. werner.poewe@i-med.ac.at ·Neurology · Pubmed #21832218.

ABSTRACT: OBJECTIVE: To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) pramipexole. METHODS: This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to pramipexole IR, pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test pramipexole ER noninferiority to pramipexole IR based on a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed -3 points. RESULTS: Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was -8.2 for ER and -8.7 for IR, a difference of -0.5 with a 95% CI of -2.3 to 1.3. Compared with placebo (n = 103), pramipexole ER and pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated. CONCLUSIONS: As monotherapy for early PD, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that pramipexole ER is not inferior to pramipexole IR in patients with early PD.

21 Article Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial. 2011

Schapira, Anthony H V / Barone, P / Hauser, R A / Mizuno, Y / Rascol, O / Busse, M / Salin, L / Juhel, N / Poewe, W / Anonymous4700702. ·Institute of Neurology, University College London, London, UK. a.schapira@ucl.ac.uk ·Neurology · Pubmed #21832216.

ABSTRACT: BACKGROUND: In advanced Parkinson disease (PD), immediate-release pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy. METHODS: For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375-4.5 mg/day). The primary endpoint was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout. RESULTS: Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0-41.7) by an adjusted mean of -11.0 for extended-release pramipexole and -12.8 for immediate-release pramipexole vs -6.1 for placebo (p = 0.0001 and p < 0.0001) and off-time decreased (from baseline means of 5.8-6.0 hours/day) by an adjusted mean of -2.1 and -2.5 vs -1.4 hours/day (p = 0.0199 and p < 0.0001). Other outcomes were largely corroborative, including a significant improvement in early morning off symptoms. Among 249 pramipexole patients completing 33 weeks, UPDRS II+III and off-time findings showed ≤10.1% change from 18-week values. Both formulations were well-tolerated. CONCLUSIONS: Extended-release pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release pramipexole compared with placebo. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the extended-release form of pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD.

22 Article Motor activation in multiple system atrophy and Parkinson disease: a PET study. 2010

Payoux, P / Brefel-Courbon, C / Ory-Magne, F / Regragui, W / Thalamas, C / Balduyck, S / Durif, F / Azulay, J P / Tison, F / Blin, O / Esquerre, J P / Rascol, O. ·Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825, Toulouse, France. payoux.p@chu-toulouse.fr ·Neurology · Pubmed #20876470.

ABSTRACT: BACKGROUND: Multiple system atrophy (MSA) is an atypical parkinsonian syndrome including cerebellar impairment and poor response to levodopa. We assessed right hand motor activation in patients with MSA before and after an acute levodopa challenge in comparison with patients with PD and healthy volunteers (HVs). METHODS: Eighteen patients with MSA, 8 patients with PD, and 10 age-matched HVs were included. Regional cerebral blood flow measurements with H(2)(15)O PET were performed at rest and during a right hand movement. Statistical parametric mapping was used to analyze motor vs rest in OFF and ON conditions and the effect of levodopa on motor activation. RESULTS: Before levodopa, patients with MSA activated most known cerebral motor areas. Compared with HVs, patients with MSA exhibited less bilateral cerebellar activation and greater left superior parietal activation. They also had less bilateral cerebellar and greater supplementary motor and left superior parietal activation than patients with PD. Conversely, patients with PD had greater activation than HVs in the right cerebellum and less in the supplementary motor cortex. After levodopa, patients with MSA exhibited reduced activation in anterior cingulate, whereas patients with PD had greater activation in the right cerebellum. CONCLUSION: Patients with MSA and patients with PD recruited different motor networks. Patients with PD preferentially activated cerebellar pathways, possibly to compensate for basal ganglia dysfunction. This was not observed in patients with MSA, probably because of cerebellar dysfunction; other frontoparietal cortical areas were recruited.

23 Article Safety and tolerability of pardoprunox, a new partial dopamine agonist, in a randomized, controlled study of patients with advanced Parkinson's disease. 2009

Hauser, R A / Bronzova, J / Sampaio, C / Lang, A E / Rascol, O / Theeuwes, A / van de Witte, S V / Anonymous6430627. ·University of South Florida, Tampa, FL 33606, USA. rhauser@hsc.usf.edu ·Eur Neurol · Pubmed #19407454.

ABSTRACT: AIMS: To investigate the safety and tolerability of pardoprunox (SLV308), a novel partial dopamine agonist, as an adjunct to levodopa in patients with advanced Parkinson's disease, using two titration schedules. METHODS: Patients were randomized to pardoprunox (n = 51) or placebo (n = 11). Pardoprunox was titrated to the highest tolerated dose (range, 0.3-42 mg/day) over 7 weeks, using a gradual dose escalation without intermediate steps (group 1) or with intermediate steps (group 2). RESULTS: The cumulative drop-out rate was greater in group 1 (without intermediate steps, 56.0%) than in group 2 (with intermediate steps, 34.6%), or with placebo (9.1%). In group 2, doses up to 18 mg/day were well tolerated with a cumulative drop-out rate of 7.7% (2/26) and a drop-out rate due to adverse events of 4.0% (1/26). The most common adverse events reported were nausea, vomiting, headache, and dizziness. There was a trend for reduced OFF time (p = 0.054) in the combined pardoprunox group compared to placebo. CONCLUSIONS: The pardoprunox safety and tolerability profile as an adjunct to levodopa was improved using a gradual titration schedule that included intermediate dose steps. Using this titration, doses up to 18 mg/day were well tolerated.

24 Article Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight. 2008

Sharma, J C / Ross, I N / Rascol, O / Brooks, D. ·Newark Hospital, Newark, UK. jagdish.sharma@sfh-tr.nhs.uk ·Eur J Neurol · Pubmed #18355302.

ABSTRACT: PURPOSE: Levodopa dose per kilogram body weight is reported to be a significant factor for dyskinesia in Parkinson's disease. We have investigated this hypothesis in data from the studies comparing ropinirole versus levodopa as the initial therapy. METHODS: Data from the ropinirole versus levodopa studies 056 and REAL-PET in early Parkinson's disease were pooled and manipulated to calculate levodopa dose per kilogram body weight. Logistic regression analysis was performed to investigate significant variables for the development of dyskinesia. Only the patients on levodopa monotherapy or with ropinirole were analyzed. RESULTS: Analysis of levodopa therapy patients revealed that dyskinetic patients had received significantly higher absolute levodopa dose and levodopa dose per kilogram body weight. Logistic regression revealed that the most significant factor was the higher levodopa dose per kilogram body weight, P = 0.005, odds ratio 1.078, 95% CI 1.023-1.135; younger age was the second factor -P = 0.026. Variables of gender, absolute levodopa dose, weight, disease duration and initial motor Unified Parkinson's disease rating score were not significant. CONCLUSION: Higher levodopa dose per kilogram body weight is an independently significant factor for developing dyskinesia. This relationship should be considered in treatment of Parkinson's disease patients aiming to prevent and manage dyskinesia.

25 Minor The delayed-start study in Parkinson disease: can't satisfy everyone. 2010

Olanow, C Warren / Rascol, O. ·Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. Warren.olanow@mssm.edu ·Neurology · Pubmed #20368635.

ABSTRACT: -- No abstract --