- Email: [email protected]
1.503 Genetics, plasticity and dyskinesia in PD
S84
Monday, 10 December 2007
development of dyskinesia. Only the patients on levodopa monotherapy or with ropinirole were analysed. Patients on ropinirole monotherapy were excluded. Results: Patients commenced on ropinirole as the initial therapy developed significantly less dyskinesia as compared to levodopa, 5% versus 34.6%, p < 0.001. Analysis of all 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% Confidence interval 1.023 to 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.
1.502 Body weight & Parkinson’s disease C. Bachmann1° , A. Zapf, E. Brunner, C. Trenkwalder 1 G¨ ottingen, Germany Objective: The aim of this study is to investigate whether PD patients in the advanced stages display body weight changes and to detect any correlations between medication and other putative determinants of body weight. Background: Several studies have suggested that Parkinson’s disease (PD) patients in the advanced stages show a lower body weight when compared with age-matched, healthy subjects, and that levodopa may play a role in body weight alterations of PD patients. Method: Charts of 210 PD patients, with fluctuations and dyskinesias, admitted within 6 months to a German movement disorders clinic, were investigated for body mass index (BMI), age at onset, disease duration, UPDRS motor score, eating coordination and medication such as levodopa, dopamine agonists, neuroleptics, amantadine, budipine, antidepressants, anticholinergics. Follow-up BMI was carried out again two years later. Control population data were taken from a survey of the German Federal Office for Statistics. Results: 4.2% of PD patients showed slight underweight (BMI < 18.5), 46.4% were normal (BMI 18.5−25); 33.7% overweight (BMI 25−30); 15.7% obese (BMI > 30). Dyskinesias, daily levodopa dosage per kg body weight and total levodopa dopaminergic dosage (levodopa/ entacapone/dopaminagonist) were negatively correlated with BMI. Overall, patients’ BMI had not significantly changed within 2 years of follow-up. Conclusion: PD patients with dyskinesias in a German movement disorders clinic showed a reduced BMI compared with the control population of similar age. Our findings demonstrate that patients with a lower BMI received a higher cumulative levodopa dosage and indicate that levodopa may be responsible for weight loss in PD.
1.503 Genetics, plasticity and dyskinesia in PD G. Linazasoro1° , N. van Blercom Sebastian, Spain
1 San
Objective: More than 50% of PD patients treated with levodopa develop levodopa-induced dyskinesia (LID) in the long-term. LID may be disabling, therefore, avoiding or delaying their appearance is one of the main objectives of the management of PD. Method: Physiopathology of LID is not fully known. Several features related to PD and to levodopa pulsatile treatment have been invoked as the most relevant risk factors. Severity of PD, high doses of levodopa and age of onset are the most commonly involved. However, a well known clinical observation is that whereas some patients exhibit severe dyskinesias soon after starting low doses of levodopa, others remain free
of this disabling complication in spite of being treated with high doses of levodopa. Thus, although pulsatile levodopa therapy and parkinsonism are necessary requirements, something else is needed. It is suggested that this could be the genetic influence on mechanisms involved on neural (synaptic) plasticity, which could also be related to age (LID are much more common in patients with young onset PD and plasticity is greater in young subjects than in old ones). Results: According to this idea, denervation and levodopa treatment would act as modulating and triggering factors of LID, respectively. One interesting question is whether these factors act independently or are closely related. Studies performed in animal models, as well as in patients with LID, suggest that synaptic proteins and certain polymorphisms of dopamine receptors and enzymes related to dopamine metabolism may play a role in the origin of this complication. Conclusion: The practical implications of these ideas and the role of pharmacogenetics in the near future, are emphasized. Treatment decisions will rely on this information, challenging the relevance of current hot debates about how to start treatment in PD. 1.504 Modifiable and non-modifiable, intrinsic and extrinsic risk factors for dyskenesia in Parkinson’s disease J. Sharma1° Notts., United Kingdom
1 Newark,
Objective: Approximately 40% of patients develop dyskinesia after 4 to 6 years of levodopa therapy. Thus 60% of patients remain free of this motor complication. Aim of this review is to identify and classify risk factors for dyskinesia. Method: Classifying the risk factors identified from literature search into groups – (a) intrinsic vs extrinsic and (b) modifiable vs non-modifiable. Results: Age and disease duration are the two major intrinsic nonmodifiable risk factors. Younger patients are at a higher risk of dyskinesia and increasing disease duration also increases this risk. It is not possible to modifiy these two factors. Younger patients have a four fold risk of dyskinesia, it is not possible to delay the onset of PD in any patient. Another intrinsic and non-modifiable risk factor is of gender, female patients seem to be at a higher risk of dyskinesia. Genetic changes and plasticity of the nigro-striatal pathways may determine pre-disposition to dyskinesia – these are currently non-modifiable factors, which seem to arise due to an interaction of intrinsic and extrinsic factors. Body weight seems to be a significant risk factor for dyskinesia. Patients with lower body weight are at a higher risk; female patients may thus be at a higher risk due to their lower body weight. More significantly a loss of weight during the course of disease increases risk of dyskinesia several fold as compared to nonweight losers. Higher absolute levodopa dose is known to be associated with dyskinesia; however it has been reported that levodopa dose per kilogram body weight is a more significant risk factor, higher levodopa dose per kg increases the risk of dyskinesia than absolute levodopa dose. Weight losers are thus at a risk of dyskinesia due to receiving higher levodopa dose per kg body weight and higher body weight might be protective against dyskinesia. Early use of non-levodopa medications i.e. dopamine agonists delays the onset of dyskinesia by its levodopa sparing effect. At ten years the levodopa first group patients have more dyskinesia than dopamine first group; the latter group receiving a lower dose of levodopa. Initial body weight might be a significant variable to consider when adjusting levodopa dose. Conclusion: A number of factors can be recognised in an individual patient that predict the risk of dyskinesia. Some of these are these are modifiable and may to delay or prevent the onset of dyskinesia in Parkinson’s disease. A body weight related approach to the dose of levodopa is one such modifiable factor.
Monday, 10 December 2007
development of dyskinesia. Only the patients on levodopa monotherapy or with ropinirole were analysed. Patients on ropinirole monotherapy were excluded. Results: Patients commenced on ropinirole as the initial therapy developed significantly less dyskinesia as compared to levodopa, 5% versus 34.6%, p < 0.001. Analysis of all 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% Confidence interval 1.023 to 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.
1.502 Body weight & Parkinson’s disease C. Bachmann1° , A. Zapf, E. Brunner, C. Trenkwalder 1 G¨ ottingen, Germany Objective: The aim of this study is to investigate whether PD patients in the advanced stages display body weight changes and to detect any correlations between medication and other putative determinants of body weight. Background: Several studies have suggested that Parkinson’s disease (PD) patients in the advanced stages show a lower body weight when compared with age-matched, healthy subjects, and that levodopa may play a role in body weight alterations of PD patients. Method: Charts of 210 PD patients, with fluctuations and dyskinesias, admitted within 6 months to a German movement disorders clinic, were investigated for body mass index (BMI), age at onset, disease duration, UPDRS motor score, eating coordination and medication such as levodopa, dopamine agonists, neuroleptics, amantadine, budipine, antidepressants, anticholinergics. Follow-up BMI was carried out again two years later. Control population data were taken from a survey of the German Federal Office for Statistics. Results: 4.2% of PD patients showed slight underweight (BMI < 18.5), 46.4% were normal (BMI 18.5−25); 33.7% overweight (BMI 25−30); 15.7% obese (BMI > 30). Dyskinesias, daily levodopa dosage per kg body weight and total levodopa dopaminergic dosage (levodopa/ entacapone/dopaminagonist) were negatively correlated with BMI. Overall, patients’ BMI had not significantly changed within 2 years of follow-up. Conclusion: PD patients with dyskinesias in a German movement disorders clinic showed a reduced BMI compared with the control population of similar age. Our findings demonstrate that patients with a lower BMI received a higher cumulative levodopa dosage and indicate that levodopa may be responsible for weight loss in PD.
1.503 Genetics, plasticity and dyskinesia in PD G. Linazasoro1° , N. van Blercom Sebastian, Spain
1 San
Objective: More than 50% of PD patients treated with levodopa develop levodopa-induced dyskinesia (LID) in the long-term. LID may be disabling, therefore, avoiding or delaying their appearance is one of the main objectives of the management of PD. Method: Physiopathology of LID is not fully known. Several features related to PD and to levodopa pulsatile treatment have been invoked as the most relevant risk factors. Severity of PD, high doses of levodopa and age of onset are the most commonly involved. However, a well known clinical observation is that whereas some patients exhibit severe dyskinesias soon after starting low doses of levodopa, others remain free
of this disabling complication in spite of being treated with high doses of levodopa. Thus, although pulsatile levodopa therapy and parkinsonism are necessary requirements, something else is needed. It is suggested that this could be the genetic influence on mechanisms involved on neural (synaptic) plasticity, which could also be related to age (LID are much more common in patients with young onset PD and plasticity is greater in young subjects than in old ones). Results: According to this idea, denervation and levodopa treatment would act as modulating and triggering factors of LID, respectively. One interesting question is whether these factors act independently or are closely related. Studies performed in animal models, as well as in patients with LID, suggest that synaptic proteins and certain polymorphisms of dopamine receptors and enzymes related to dopamine metabolism may play a role in the origin of this complication. Conclusion: The practical implications of these ideas and the role of pharmacogenetics in the near future, are emphasized. Treatment decisions will rely on this information, challenging the relevance of current hot debates about how to start treatment in PD. 1.504 Modifiable and non-modifiable, intrinsic and extrinsic risk factors for dyskenesia in Parkinson’s disease J. Sharma1° Notts., United Kingdom
1 Newark,
Objective: Approximately 40% of patients develop dyskinesia after 4 to 6 years of levodopa therapy. Thus 60% of patients remain free of this motor complication. Aim of this review is to identify and classify risk factors for dyskinesia. Method: Classifying the risk factors identified from literature search into groups – (a) intrinsic vs extrinsic and (b) modifiable vs non-modifiable. Results: Age and disease duration are the two major intrinsic nonmodifiable risk factors. Younger patients are at a higher risk of dyskinesia and increasing disease duration also increases this risk. It is not possible to modifiy these two factors. Younger patients have a four fold risk of dyskinesia, it is not possible to delay the onset of PD in any patient. Another intrinsic and non-modifiable risk factor is of gender, female patients seem to be at a higher risk of dyskinesia. Genetic changes and plasticity of the nigro-striatal pathways may determine pre-disposition to dyskinesia – these are currently non-modifiable factors, which seem to arise due to an interaction of intrinsic and extrinsic factors. Body weight seems to be a significant risk factor for dyskinesia. Patients with lower body weight are at a higher risk; female patients may thus be at a higher risk due to their lower body weight. More significantly a loss of weight during the course of disease increases risk of dyskinesia several fold as compared to nonweight losers. Higher absolute levodopa dose is known to be associated with dyskinesia; however it has been reported that levodopa dose per kilogram body weight is a more significant risk factor, higher levodopa dose per kg increases the risk of dyskinesia than absolute levodopa dose. Weight losers are thus at a risk of dyskinesia due to receiving higher levodopa dose per kg body weight and higher body weight might be protective against dyskinesia. Early use of non-levodopa medications i.e. dopamine agonists delays the onset of dyskinesia by its levodopa sparing effect. At ten years the levodopa first group patients have more dyskinesia than dopamine first group; the latter group receiving a lower dose of levodopa. Initial body weight might be a significant variable to consider when adjusting levodopa dose. Conclusion: A number of factors can be recognised in an individual patient that predict the risk of dyskinesia. Some of these are these are modifiable and may to delay or prevent the onset of dyskinesia in Parkinson’s disease. A body weight related approach to the dose of levodopa is one such modifiable factor.