帕金森病运动并发症的影响因素分析
摘要
目的:对影响帕金森病(Parkinson’s disease, PD)运动并发症产生的因素进行探索,以期明确运动并发症发生的主要影响因素,寻找到预防或延缓运动并发症发生的方法应用于临床。
方法:收集临床已确诊的98例PD患者的相关资料,包括性别、年龄、发病年龄、吸烟史、病程、首发症状、左旋多巴(Levodopa,LD)平均日剂量、LD疗程、有无使用其他抗PD药物及药物种类、有无运动并发症的产生及并发症种类等,并分别对每例患者进行Hoehn-Yah(rH-Y)分级和Webster评分。将上述各因素经单因素Logistic回归分析后,选取P<0.1的因素进行多因素非条件Logistic回归分析,寻找与PD运动并发症发生相关的因素。
结果:对各因素进行单因素Logistic回归分析的结果提示,发病年龄、吸烟史、病程、H-Y分级、Webster评分、LD平均日剂量、LD疗程与运动并发症的产生有关(P<0.1)。进一步对上述因素进行多因素非条件Logistic回归分析,得出发病年龄、病程、H-Y分级、LD平均日剂量、LD疗程与PD运动并发症的发生有关(P<0.05),其中发病年龄为保护性因素(β<0),病程、H-Y分级、LD平均日剂量、LD疗程为危险因素(β>0)。按其危险程度大小依次为LD疗程、病程、LD平均日剂量、H-Y分级。单独抽取男性患者的数据进行单因素Logistic回归分析,证实吸烟史与男性PD患者运动并发症的发生有关(P<0.05),且为保护性因素(β<0)。
结论:PD运动并发症的产生受发病年龄、病程、H-Y分级、LD平均日剂量、LD疗程的影响,其中发病年龄为保护性因素,病程、H-Y分级、LD平均日剂量、LD疗程为危险因素。按其危险程度大小依次为LD疗程、病程、LD平均日剂量、H-Y分级。因此,在临床治疗过程中需因人而异,结合相关因素,选取最佳治疗方案,以达到控制症状,延缓疾病进展,避免和减少药物并发症的目的。
Objective : Explorling the factors for motor complications of Parkinson's disease,in order to search out the main factors affecting the appearance of complications, and find method to prevent or delay the motor complications in clinical use.
Methods: We collected the information of 98 cases of confirmed PD,including gender,age,onset age,smoking history,course of disease,first symptoms,average daily dose of LD,treatment time of LD,whether use of any other anti-PD drugs and the type of drug, whether had a motor complication and the type.Then had H-Y classification and Webster score for them. Using univariate logistic regression to analyse the above factors,and selecting the factors with the P<0.1 for the non-conditional logistic regression analysis , to look for the factors associated with motor complications of Parkinson's disease.
Results: The result of univariate logistic regression shows that onset age,smoking history,course of disease,H-Y classification,Webster score,average daily dose of LD,treatment time of LD are associated with the appearance of motor complications (P<0.1). Used non-conditional logistic regression to analyse the above factors and found that the onset age,course of disease,H-Y classification, average daily dose of LD,treatment time of LD are related in the motor complications(P<0.05),in which age of onset is protective factor (β<0) and course of disease,H-Y classification,average daily dose of LD,treatment time of LD are risk factors(β>0).The order according to their degree of risk is treatment time of LD,course of disease,average daily dose of LD,H-Y classification. Picking out the data of male patients for univariate logistic regression shows that smoking is associated with the occurrence of motor complications in male patients (P<0.05),and is the protective factor(β<0).
Conclusion: Motor complications of PD is affected by onset age,course of disease,H-Y classification,average daily dose of LD,treatment time of LD,including onset age is a protective factor,course of disease,H-Y classification, average daily dose of LD,treatment time of LD,are risk factors. The order according to their degree of risk is treatment time of LD,course of disease,average daily dose of LD,H-Y classification. Thus,In the clinical course of treatment we should consider the different condition of each patient with related factors and select the best treatment,on the purpose of controling symptoms,slowing down the development of disease,prevening and reducing the complications caused by drug.
方法:收集临床已确诊的98例PD患者的相关资料,包括性别、年龄、发病年龄、吸烟史、病程、首发症状、左旋多巴(Levodopa,LD)平均日剂量、LD疗程、有无使用其他抗PD药物及药物种类、有无运动并发症的产生及并发症种类等,并分别对每例患者进行Hoehn-Yah(rH-Y)分级和Webster评分。将上述各因素经单因素Logistic回归分析后,选取P<0.1的因素进行多因素非条件Logistic回归分析,寻找与PD运动并发症发生相关的因素。
结果:对各因素进行单因素Logistic回归分析的结果提示,发病年龄、吸烟史、病程、H-Y分级、Webster评分、LD平均日剂量、LD疗程与运动并发症的产生有关(P<0.1)。进一步对上述因素进行多因素非条件Logistic回归分析,得出发病年龄、病程、H-Y分级、LD平均日剂量、LD疗程与PD运动并发症的发生有关(P<0.05),其中发病年龄为保护性因素(β<0),病程、H-Y分级、LD平均日剂量、LD疗程为危险因素(β>0)。按其危险程度大小依次为LD疗程、病程、LD平均日剂量、H-Y分级。单独抽取男性患者的数据进行单因素Logistic回归分析,证实吸烟史与男性PD患者运动并发症的发生有关(P<0.05),且为保护性因素(β<0)。
结论:PD运动并发症的产生受发病年龄、病程、H-Y分级、LD平均日剂量、LD疗程的影响,其中发病年龄为保护性因素,病程、H-Y分级、LD平均日剂量、LD疗程为危险因素。按其危险程度大小依次为LD疗程、病程、LD平均日剂量、H-Y分级。因此,在临床治疗过程中需因人而异,结合相关因素,选取最佳治疗方案,以达到控制症状,延缓疾病进展,避免和减少药物并发症的目的。
Objective : Explorling the factors for motor complications of Parkinson's disease,in order to search out the main factors affecting the appearance of complications, and find method to prevent or delay the motor complications in clinical use.
Methods: We collected the information of 98 cases of confirmed PD,including gender,age,onset age,smoking history,course of disease,first symptoms,average daily dose of LD,treatment time of LD,whether use of any other anti-PD drugs and the type of drug, whether had a motor complication and the type.Then had H-Y classification and Webster score for them. Using univariate logistic regression to analyse the above factors,and selecting the factors with the P<0.1 for the non-conditional logistic regression analysis , to look for the factors associated with motor complications of Parkinson's disease.
Results: The result of univariate logistic regression shows that onset age,smoking history,course of disease,H-Y classification,Webster score,average daily dose of LD,treatment time of LD are associated with the appearance of motor complications (P<0.1). Used non-conditional logistic regression to analyse the above factors and found that the onset age,course of disease,H-Y classification, average daily dose of LD,treatment time of LD are related in the motor complications(P<0.05),in which age of onset is protective factor (β<0) and course of disease,H-Y classification,average daily dose of LD,treatment time of LD are risk factors(β>0).The order according to their degree of risk is treatment time of LD,course of disease,average daily dose of LD,H-Y classification. Picking out the data of male patients for univariate logistic regression shows that smoking is associated with the occurrence of motor complications in male patients (P<0.05),and is the protective factor(β<0).
Conclusion: Motor complications of PD is affected by onset age,course of disease,H-Y classification,average daily dose of LD,treatment time of LD,including onset age is a protective factor,course of disease,H-Y classification, average daily dose of LD,treatment time of LD,are risk factors. The order according to their degree of risk is treatment time of LD,course of disease,average daily dose of LD,H-Y classification. Thus,In the clinical course of treatment we should consider the different condition of each patient with related factors and select the best treatment,on the purpose of controling symptoms,slowing down the development of disease,prevening and reducing the complications caused by drug.
引文
[1] Driver J A, Logroscino G, Gaziano J M, et al. Incidence and remaining lifetime risk of Parkinson disease in advanced age[J]. Neurology, 2009, 72(5)::432-438
[2] Zhang ZX,Roman GC,Hong Z,et al. Parkinson’s disease in China:Prevalence in Beijing,Xi’an,and Shanghai. Lancet,2005,365:595-597
[3] Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson Disease[J]. Arch Neurol,2006,63:1756-1760
[4] Thanvi BR,Lo TC. Long term motor complications of levodopa:clinical features,mechanisms and management strategies[J]. Postgrad Med J,2004,80:452-458
[5] Aubert I,Guigoni C,Hakansson K,el a1.Increased D1 dopamine receptor signaling in levodopa induced dyskinesia[J].Ann Neurol,2005.57(1):l7 26
[6] Encarnacion EV, Hauser RA. Levodopa-Induced Dyskinesias in Parkinson’s Disease: Etiology, Impact on Quality of Life, and Treatments[J]. Eur Neurol,2008,60:57–66
[7]巴茂文,刘振国.左旋多巴诱发异动症的病理生理机制研究进展[J].中华神经科杂志,2005,38(6):403-404
[8]中华医学会神经病学分会运动障碍及帕金森病学组.帕金森病的诊断[J].中华神经科杂志,2006;6(39):408-409
[9] de la Fuente-Fernandez R, Sossi V, Huang Z,et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias[J]. Brain,2004,127: 2747-2754
[10] Sossi V,De La Fuente-Fernáindez R,Schulzer M,et al. Age-related differences in levodopa dynamics in Parkinson’s : Implications for motor complications[J]. Clinical Neurology,2006,2(9):41-42
[11] Vaamonde J,Ibanez R,Gudin M,et a1. Fluctuations and dyskinesias as early L-dopa-induced motor complications in severe Parkinsonian’s patients[J]. Neurologia,2003,18:162-165
[12] Pearce RK,Heikkila M,Linden IB,et a1.L—dopa induces dyskinesia in normal monkeys:behavioural and pharmacokinetic observations[J].Psychopharmacology (Berl),2001,156:402-409
[13] Kieburtz K. Therapeutic strategies to prevent motor complications in Parkinson’s disease[J].J Neurol, 2008,255 (Suppl 4):42–45
[14] Boyce S, Rupniak NM, Steventon MJ, et al. Nigrostriatal damage is required for induction of dyskinesia by L-dopa in squirrel monkeys[J]. Clin Neuropharmacol 1990;13:448–58
[15] Thanvi BR,Lo TC. Long term motor complications of levodopa:clinical features,mechanisms and management strategies[J]. Postgrad Med J,2004,80:452-458.
[16] Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management[J].J Neurol,2008,255(4):32–41
[17] Quik M, Cox H, Parameswaran N,et al. Nicotine reduces levodopa-induced dyskinesias in leision monkeys[J]. Ann Neurol,2007, 62:588-596
[1] Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson Disease[J]. Arch Neurol,2006,63:1756-1760
[2] Aubert I,Guigoni C,Hakansson K,el a1.Increased D1 dopamine receptor signaling in levodopa induced dyskinesia[J].Ann Neurol,2005.57(1):l7 26
[3] Encarnacion EV, Hauser RA. Levodopa-Induced Dyskinesias in Parkinson’s Disease: Etiology, Impact on Quality of Life, and Treatments[J]. Eur Neurol,2008,60:57–66
[4] de la Fuente-Fernandez R, Sossi V, Huang Z,et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias[J]. Brain,2004,127: 2747-2754
[5] Sossi V,De La Fuente-Fernáindez R,Schulzer M,et al. Age-related differences in levodopa dynamics in Parkinson’s : Implications for motor complications[J]. Clinical Neurology,2006,2(9):41-42
[6] Schoenfeld MA, Pantelie CM, Schwartz B.Clinical criteria for the switch of treatment strategies in Parkinson's disease[J]. Clin Neurol Neurosurg,2003,05(4): 241-244
[7] Vaamonde J,Ibanez R,Gudin M,et a1. Fluctuations and dyskinesias as early L-dopa-induced motor complications in severe Parkinsonian’s patients[J]. Neurologia,2003,18:162-165
[8] Thanvi BR,Lo TC. Long term motor complications of levodopa:clinical features,mechanisms and management strategies[J]. Postgrad Med J,2004,80:452-458.
[9] Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management[J].J Neurol,2008,255(4):32–41
[10] Pearce RK,Heikkila M,Linden IB,et a1.L—dopa induces dyskinesia in normal monkeys:behavioural and pharmacokinetic observations[J].Psychopharmacology (Berl),2001,156:402-409
[11] Kostic VS,Marinkovic J,Svetel M,et a1. The efect of stage of Parkinson’s disease at the onset of levodopa therapy on development of motor complications[J]. Eur J Neurol,2002,9:9-14
[12]刘春风,尹伟华,罗蔚峰.帕金森病患者运动障碍和症状波动的影响因素[J].中华神经科杂志,2003,36(6):411-413
[13] Kieburtz K. Therapeutic strategies to prevent motor complications in Parkinson’s disease[J].J Neurol, 2008,255 (Suppl 4):42–45
[14] Hitzeman N, Rafii F. Dopamine agonists for early Parkinson disease[J].Am FamPhysician.,2009,Jul 1;80(1):28-30
[15] Albrecht S, Buerger E. Potential neuroprotection mechanisms in PD: focus on dopamine agonist pramipexole[J]. Curr Med Res Opin.,2009,25(12):2977-87
[16] Naoi M, Maruyama W. Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease[J].Expert Rev Neurother,2009,Aug; 9(8):1233-50
[17] Ahn TB, Im JH, Lee MC, et al. One-year open-label study of entacapone in patients with advanced Parkinson disease[J].Clin Neurol, 2007,3(2):82-85
[18] Quik M, Cox H, Parameswaran N,et al. Nicotine reduces levodopa-induced dyskinesias in leision monkeys[J]. Ann Neurol,2007, 62:588-596
[19] Samadi P,Gregoire L,Rouillard C. Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys[J]. Ann Neurol,2006,59:282-288
[2] Zhang ZX,Roman GC,Hong Z,et al. Parkinson’s disease in China:Prevalence in Beijing,Xi’an,and Shanghai. Lancet,2005,365:595-597
[3] Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson Disease[J]. Arch Neurol,2006,63:1756-1760
[4] Thanvi BR,Lo TC. Long term motor complications of levodopa:clinical features,mechanisms and management strategies[J]. Postgrad Med J,2004,80:452-458
[5] Aubert I,Guigoni C,Hakansson K,el a1.Increased D1 dopamine receptor signaling in levodopa induced dyskinesia[J].Ann Neurol,2005.57(1):l7 26
[6] Encarnacion EV, Hauser RA. Levodopa-Induced Dyskinesias in Parkinson’s Disease: Etiology, Impact on Quality of Life, and Treatments[J]. Eur Neurol,2008,60:57–66
[7]巴茂文,刘振国.左旋多巴诱发异动症的病理生理机制研究进展[J].中华神经科杂志,2005,38(6):403-404
[8]中华医学会神经病学分会运动障碍及帕金森病学组.帕金森病的诊断[J].中华神经科杂志,2006;6(39):408-409
[9] de la Fuente-Fernandez R, Sossi V, Huang Z,et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias[J]. Brain,2004,127: 2747-2754
[10] Sossi V,De La Fuente-Fernáindez R,Schulzer M,et al. Age-related differences in levodopa dynamics in Parkinson’s : Implications for motor complications[J]. Clinical Neurology,2006,2(9):41-42
[11] Vaamonde J,Ibanez R,Gudin M,et a1. Fluctuations and dyskinesias as early L-dopa-induced motor complications in severe Parkinsonian’s patients[J]. Neurologia,2003,18:162-165
[12] Pearce RK,Heikkila M,Linden IB,et a1.L—dopa induces dyskinesia in normal monkeys:behavioural and pharmacokinetic observations[J].Psychopharmacology (Berl),2001,156:402-409
[13] Kieburtz K. Therapeutic strategies to prevent motor complications in Parkinson’s disease[J].J Neurol, 2008,255 (Suppl 4):42–45
[14] Boyce S, Rupniak NM, Steventon MJ, et al. Nigrostriatal damage is required for induction of dyskinesia by L-dopa in squirrel monkeys[J]. Clin Neuropharmacol 1990;13:448–58
[15] Thanvi BR,Lo TC. Long term motor complications of levodopa:clinical features,mechanisms and management strategies[J]. Postgrad Med J,2004,80:452-458.
[16] Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management[J].J Neurol,2008,255(4):32–41
[17] Quik M, Cox H, Parameswaran N,et al. Nicotine reduces levodopa-induced dyskinesias in leision monkeys[J]. Ann Neurol,2007, 62:588-596
[1] Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson Disease[J]. Arch Neurol,2006,63:1756-1760
[2] Aubert I,Guigoni C,Hakansson K,el a1.Increased D1 dopamine receptor signaling in levodopa induced dyskinesia[J].Ann Neurol,2005.57(1):l7 26
[3] Encarnacion EV, Hauser RA. Levodopa-Induced Dyskinesias in Parkinson’s Disease: Etiology, Impact on Quality of Life, and Treatments[J]. Eur Neurol,2008,60:57–66
[4] de la Fuente-Fernandez R, Sossi V, Huang Z,et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias[J]. Brain,2004,127: 2747-2754
[5] Sossi V,De La Fuente-Fernáindez R,Schulzer M,et al. Age-related differences in levodopa dynamics in Parkinson’s : Implications for motor complications[J]. Clinical Neurology,2006,2(9):41-42
[6] Schoenfeld MA, Pantelie CM, Schwartz B.Clinical criteria for the switch of treatment strategies in Parkinson's disease[J]. Clin Neurol Neurosurg,2003,05(4): 241-244
[7] Vaamonde J,Ibanez R,Gudin M,et a1. Fluctuations and dyskinesias as early L-dopa-induced motor complications in severe Parkinsonian’s patients[J]. Neurologia,2003,18:162-165
[8] Thanvi BR,Lo TC. Long term motor complications of levodopa:clinical features,mechanisms and management strategies[J]. Postgrad Med J,2004,80:452-458.
[9] Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management[J].J Neurol,2008,255(4):32–41
[10] Pearce RK,Heikkila M,Linden IB,et a1.L—dopa induces dyskinesia in normal monkeys:behavioural and pharmacokinetic observations[J].Psychopharmacology (Berl),2001,156:402-409
[11] Kostic VS,Marinkovic J,Svetel M,et a1. The efect of stage of Parkinson’s disease at the onset of levodopa therapy on development of motor complications[J]. Eur J Neurol,2002,9:9-14
[12]刘春风,尹伟华,罗蔚峰.帕金森病患者运动障碍和症状波动的影响因素[J].中华神经科杂志,2003,36(6):411-413
[13] Kieburtz K. Therapeutic strategies to prevent motor complications in Parkinson’s disease[J].J Neurol, 2008,255 (Suppl 4):42–45
[14] Hitzeman N, Rafii F. Dopamine agonists for early Parkinson disease[J].Am FamPhysician.,2009,Jul 1;80(1):28-30
[15] Albrecht S, Buerger E. Potential neuroprotection mechanisms in PD: focus on dopamine agonist pramipexole[J]. Curr Med Res Opin.,2009,25(12):2977-87
[16] Naoi M, Maruyama W. Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease[J].Expert Rev Neurother,2009,Aug; 9(8):1233-50
[17] Ahn TB, Im JH, Lee MC, et al. One-year open-label study of entacapone in patients with advanced Parkinson disease[J].Clin Neurol, 2007,3(2):82-85
[18] Quik M, Cox H, Parameswaran N,et al. Nicotine reduces levodopa-induced dyskinesias in leision monkeys[J]. Ann Neurol,2007, 62:588-596
[19] Samadi P,Gregoire L,Rouillard C. Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys[J]. Ann Neurol,2006,59:282-288