帕金森病的早期症状与诊断方法研究进展
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摘要
帕金森病(PD)又称震颤麻痹,是第二大常见的神经系统退行性疾病,为黑质神经元丢失出现的纹状体多巴胺缺乏所致,黑质神经元胞内包涵体含有α-突触核苷聚集物,是PD的神经病理标志。PD包括一系列运动性与非运动性症状,但早期症状不典型,患者多不能自行发现,且会影响工作、生活等,故早期诊断显得尤为重要。以往多通过患者的运动性症状来进行诊断,但发现后多为中晚期,患者预后不良。未来,随着对PD认识的逐渐深入,其诊断将更加完善。
Parkinson's disease( PD),also known as tremor palsy,is the second most common degenerative disease of the nervous system,due to the striatal dopamine deficiency that appears in the loss of substantia nigra neurons. The inclusion bodies of the substantia nigra neurons contain α-synaptic nucleoside aggregation,which is a neuropathological sign of PD.PD includes a series of motor and non-motor symptoms,but the early symptoms are not typical,which mostly cannot be noticed by the patients themselves,and will affect the work and life of the patients,so early diagnosis is particularly important. In the past,most of the patients were diagnosed by motor symptoms,but most cases were already in the middle and late stage,and the prognosis was poor. In the future,with the gradual deepening of PD understanding,its diagnosis will be further improved.
Parkinson's disease( PD),also known as tremor palsy,is the second most common degenerative disease of the nervous system,due to the striatal dopamine deficiency that appears in the loss of substantia nigra neurons. The inclusion bodies of the substantia nigra neurons contain α-synaptic nucleoside aggregation,which is a neuropathological sign of PD.PD includes a series of motor and non-motor symptoms,but the early symptoms are not typical,which mostly cannot be noticed by the patients themselves,and will affect the work and life of the patients,so early diagnosis is particularly important. In the past,most of the patients were diagnosed by motor symptoms,but most cases were already in the middle and late stage,and the prognosis was poor. In the future,with the gradual deepening of PD understanding,its diagnosis will be further improved.
引文
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[8]Lin CH,Lin JW,Liu YC,et al.Risk of Parkinson's disease following anxiety disorders:A nationwide population-based cohort study[J].Eur J Neurol,2015,22(9):1280-1287.
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[10]Reijnders JS,Ehrt U,Weber WE,et al.A systematic review of prevalence studies of depression in Parkinson's disease[J].Mov Disord,2008,23(2):183-189.
[11]孟庆进,柴晓斌,胡国华.帕金森病后抑郁的最新研究进展[J].中国老年学杂志,2013,33(2):477-480.
[12]Santangelo G,Vitale C,Trojano L,et al.Subthreshold depression and subjective cognitive complaints in Parkinson's disease[J].Eur J Neurol,2014,21(3):541-544.
[13]Louter M,van der Marck MA,Pevernagie DA,et al.Sleep matters in Parkinson's disease:Use of a priority list to assess the presence of sleep disturbances[J].Eur J Neurol,2013,20(2):259-265.
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[17]梁战华,王琰,赵航,等.帕金森病早期运动症状的临床分析[J].临床荟萃,2011,26(19):1706-1708.
[18]Stamey W,Davidson A,Jankovic J.Shoulder pain:A presenting symptom of Parkinson disease[J].J Clin Rheumatol,2008,14(4):253-254.
[19]马玲玲,姚新苗,王健,等.帕金森病姿势控制的研究进展[J].中国康复医学杂志,2017,32(3):373-376.
[20]Arkadir D,Bergman H,Fahn S.Redundant dopaminergic activity may enable compensatory axonal sprouting in Parkinson disease[J].Neurology,2014,82(12):1093-1098.
[21]Chen H,Mosley TH,Alonso A,et al.Plasma urate and Parkinson's disease in the atherosclerosis risk in communities(ARIC)study[J].Am J Epidemiol,2009,169(9):1064-1069.
[22]Jesús S,Pérez I,Cáceres-Redondo MT,et al.Low serum uric acid concentration in Parkinson's disease in southern Spain[J].Eur J Neurol,2013,20(1):208-210.
[23]Gao X,O'ReillyJ,Schwarzschild MA,et al.Prospective study of plasma urate and risk of Parkinson disease in men and women[J].Neurology,2016,86(6):520-526.
[24]Iwaki H,Ando R,Miyaue N,et al.One year safety and efficacy of inosine to increase the serum urate level for patients with Parkinson's disease in Japan[J].J Neurol Sci,2017,383:75-78.
[25]Gallegos S,Pacheco C,Peters C,et al.Features of alpha-synuclein that could explain the progression and irreversibility of Parkinson's disease[J].Front Neurosci,2015,9:59.
[26]Miller DB,O'Callaghan JP.Biomarkers of Parkinson's disease:Present and future[J].Metabolism,2015,64(1):40-46.
[27]El-Agnaf OM,Salem SA,Paleologou KE,et al.Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids,including human plasma[J].FASEB J,2003,17(13):1945-1947.
[28]Shi M,Zabetian CP,Hancock AM,et al.Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease[J].Neurosci Lett,2010,480(1):78-82.
[29]El-Agnaf OM,Salem SA,Paleologou KE,et al.Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease[J].FASEB J,2006,20(3):419-425.
[30]Frland MG,hrfelt A,Dalen I,et al.Evolution of cerebrospinal fluid total alpha-synuclein in Parkinson's disease[J].Parkinsonism Relat Disord,2018,49:4-8.
[31]Malec-Litwinowicz M,Plewka A,Plewka D,et al.The relation between plasmaα-synuclein level and clinical symptoms or signs of Parkinson's disease[J].Neurol Neurochir Pol,2018,52(2):243-251.
[32]Wang J,Hoekstra JG,Zuo C,et al.Biomarkers of Parkinson's disease:Current status and future[J].Drug Discov Today,2013,18(3/4):155-162.
[33]Lev N,Barhum Y,Pilosof NS,et al.DJ-1 protects against dopamine toxicity:Implications for Parkinson's disease and aging[J].J Gerontol A Biol Sci Med Sci,2013,68(3):215-225.
[34]Hong Z,Shi M,Chung KA,et al.DJ-1 andα-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease[J].Brain,2010,133(Pt 3):713-726.
[35]Xu S,Yang X,Qian Y,et al.Parkinson disease-related DJ-1 modulates the expression of uncoupling protein 4 against oxidative stress[J/OL].J Neurochem,2018[2018-04-27].https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14297.[published online ahead of print Jan 8,2018]
[36]郭舜源,张锦华,陈波,等.帕金森病患者脑部葡萄糖代谢特征分析[J].中国现代医生,2016,54(19):1-4,封3页.
[37]Van Laere K,Clerinx K,D'Hondt E,et al.Combined striatal binding and cerebral influx analysis of dynamic11C-raclopride PET improves early differentiation between multiple-system atrophy and Parkinson disease[J].J Nucl Med,2010,51(4):588-595.
[38]Bohlhalter S,Abela E,Hallett M.Hallett,Functional MRI of impaired finger dexterity in Parkinson's disease[J].Exp Neurol,2011,227(1):24-25.
[39]黄新明,孙斌,薛蕴菁,等.磁敏感加权成像检测帕金森病患者脑铁沉积[J].中华医学杂志,2010,90(43):3054-3058.
[40]储佺兵,胡中华,解渊,等.磁敏感加权成像在帕金森病及血管性帕金森综合征诊断、鉴别诊断中的临床研究[J].中国CT和MRI杂志,2015,13(8):8-9,13.
[41]van Vliet SA,Blezer EL,Jongsma MJ,et al.Exploring the neuroprotective effects of modafinil in a marmoset Parkinson model with immunohistochemistry,magnetic resonance imaging and spectroscopy[J].Brain Res,2008,1189:219-228.
[42]杨丽娟,张京芬,李月春,等.帕金森病的黑质超声表现[J].中华老年心脑血管病杂志,2012,14(4):390-393.
[43]Toomsoo T,Liepelt-Scarfone I,Kerner R,et al.Substantia nigra hyperechogenicity:Validation of transcranial sonography for Parkinson disease diagnosis in a large estonian cohort[J].J Ultrasound Med,2016,35(1):17-23.
[2]Alves G,Forsaa EB,Pedersen KF,et al.Epidemiology of Parkinson's disease[J].J Neurol,2008,255 Suppl 5:18-32.
[3]Kang JH,Mollenhauer B,Coffey CS,et al.CSF biomarkers associated with disease heterogeneity in early Parkinson's disease:The Parkinson's Progression Markers Initiative study[J].Acta Neuropathol,2016,131(6):935-949.
[4]Bohnen NI,Studenski SA,Constantine GM,et al.Diagnostic performance of clinical motor and non-motor tests of Parkinson disease:A matched case-control study[J].Eur J Neurol,2008,15(7):685-691.
[5]Braak H,Del Tredici K,Rüb U,et al.Staging of brain pathology related to sporadic Parkinson's disease[J].Neurobiol Aging,2003,24(2):197-211.
[6]Bohnen NI,Müller ML,Kotagal V,et al.Olfactory dysfunction,central cholinergic integrity and cognitive impairment in Parkinson's disease[J].Brain,2010,133(Pt 6):1747-1754.
[7]Wang J,You H,Liu JF,et al.Association of olfactory bulb volume and olfactory sulcus depth with olfactory function in patients with Parkinson disease[J].Ajnr Am J Neuroradiol,2011,32(4):677-681.
[8]Lin CH,Lin JW,Liu YC,et al.Risk of Parkinson's disease following anxiety disorders:A nationwide population-based cohort study[J].Eur J Neurol,2015,22(9):1280-1287.
[9]Clark AJ,Ritz B,Prescott E,et al.Psychosocial risk factors,premotor symptoms,and first-time hospitalization with Parkinson's Disease:A prospective cohort study[J].Eur J Neurol,2013,20(8):1113-1120.
[10]Reijnders JS,Ehrt U,Weber WE,et al.A systematic review of prevalence studies of depression in Parkinson's disease[J].Mov Disord,2008,23(2):183-189.
[11]孟庆进,柴晓斌,胡国华.帕金森病后抑郁的最新研究进展[J].中国老年学杂志,2013,33(2):477-480.
[12]Santangelo G,Vitale C,Trojano L,et al.Subthreshold depression and subjective cognitive complaints in Parkinson's disease[J].Eur J Neurol,2014,21(3):541-544.
[13]Louter M,van der Marck MA,Pevernagie DA,et al.Sleep matters in Parkinson's disease:Use of a priority list to assess the presence of sleep disturbances[J].Eur J Neurol,2013,20(2):259-265.
[14]Hyacinthe C,Barraud Q,Tison F,et al.D1 receptor agonist improves sleep-wake parameters in experimental parkinsonism[J].Neurobiol Dis,2014,63:20-24.
[15]曹辰杰,余舒扬,左丽君,等.帕金森病患者伴发自主神经功能障碍与运动症状和非运动症状相关性的研究[J/CD].中华临床医师杂志(电子版),2013,7(15):6898-6903.
[16]孔双艳,田成林.帕金森病自主神经功能障碍的回顾性分析[J].脑与神经疾病杂志,2009,17(4):288-290.
[17]梁战华,王琰,赵航,等.帕金森病早期运动症状的临床分析[J].临床荟萃,2011,26(19):1706-1708.
[18]Stamey W,Davidson A,Jankovic J.Shoulder pain:A presenting symptom of Parkinson disease[J].J Clin Rheumatol,2008,14(4):253-254.
[19]马玲玲,姚新苗,王健,等.帕金森病姿势控制的研究进展[J].中国康复医学杂志,2017,32(3):373-376.
[20]Arkadir D,Bergman H,Fahn S.Redundant dopaminergic activity may enable compensatory axonal sprouting in Parkinson disease[J].Neurology,2014,82(12):1093-1098.
[21]Chen H,Mosley TH,Alonso A,et al.Plasma urate and Parkinson's disease in the atherosclerosis risk in communities(ARIC)study[J].Am J Epidemiol,2009,169(9):1064-1069.
[22]Jesús S,Pérez I,Cáceres-Redondo MT,et al.Low serum uric acid concentration in Parkinson's disease in southern Spain[J].Eur J Neurol,2013,20(1):208-210.
[23]Gao X,O'ReillyJ,Schwarzschild MA,et al.Prospective study of plasma urate and risk of Parkinson disease in men and women[J].Neurology,2016,86(6):520-526.
[24]Iwaki H,Ando R,Miyaue N,et al.One year safety and efficacy of inosine to increase the serum urate level for patients with Parkinson's disease in Japan[J].J Neurol Sci,2017,383:75-78.
[25]Gallegos S,Pacheco C,Peters C,et al.Features of alpha-synuclein that could explain the progression and irreversibility of Parkinson's disease[J].Front Neurosci,2015,9:59.
[26]Miller DB,O'Callaghan JP.Biomarkers of Parkinson's disease:Present and future[J].Metabolism,2015,64(1):40-46.
[27]El-Agnaf OM,Salem SA,Paleologou KE,et al.Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids,including human plasma[J].FASEB J,2003,17(13):1945-1947.
[28]Shi M,Zabetian CP,Hancock AM,et al.Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease[J].Neurosci Lett,2010,480(1):78-82.
[29]El-Agnaf OM,Salem SA,Paleologou KE,et al.Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease[J].FASEB J,2006,20(3):419-425.
[30]Frland MG,hrfelt A,Dalen I,et al.Evolution of cerebrospinal fluid total alpha-synuclein in Parkinson's disease[J].Parkinsonism Relat Disord,2018,49:4-8.
[31]Malec-Litwinowicz M,Plewka A,Plewka D,et al.The relation between plasmaα-synuclein level and clinical symptoms or signs of Parkinson's disease[J].Neurol Neurochir Pol,2018,52(2):243-251.
[32]Wang J,Hoekstra JG,Zuo C,et al.Biomarkers of Parkinson's disease:Current status and future[J].Drug Discov Today,2013,18(3/4):155-162.
[33]Lev N,Barhum Y,Pilosof NS,et al.DJ-1 protects against dopamine toxicity:Implications for Parkinson's disease and aging[J].J Gerontol A Biol Sci Med Sci,2013,68(3):215-225.
[34]Hong Z,Shi M,Chung KA,et al.DJ-1 andα-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease[J].Brain,2010,133(Pt 3):713-726.
[35]Xu S,Yang X,Qian Y,et al.Parkinson disease-related DJ-1 modulates the expression of uncoupling protein 4 against oxidative stress[J/OL].J Neurochem,2018[2018-04-27].https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14297.[published online ahead of print Jan 8,2018]
[36]郭舜源,张锦华,陈波,等.帕金森病患者脑部葡萄糖代谢特征分析[J].中国现代医生,2016,54(19):1-4,封3页.
[37]Van Laere K,Clerinx K,D'Hondt E,et al.Combined striatal binding and cerebral influx analysis of dynamic11C-raclopride PET improves early differentiation between multiple-system atrophy and Parkinson disease[J].J Nucl Med,2010,51(4):588-595.
[38]Bohlhalter S,Abela E,Hallett M.Hallett,Functional MRI of impaired finger dexterity in Parkinson's disease[J].Exp Neurol,2011,227(1):24-25.
[39]黄新明,孙斌,薛蕴菁,等.磁敏感加权成像检测帕金森病患者脑铁沉积[J].中华医学杂志,2010,90(43):3054-3058.
[40]储佺兵,胡中华,解渊,等.磁敏感加权成像在帕金森病及血管性帕金森综合征诊断、鉴别诊断中的临床研究[J].中国CT和MRI杂志,2015,13(8):8-9,13.
[41]van Vliet SA,Blezer EL,Jongsma MJ,et al.Exploring the neuroprotective effects of modafinil in a marmoset Parkinson model with immunohistochemistry,magnetic resonance imaging and spectroscopy[J].Brain Res,2008,1189:219-228.
[42]杨丽娟,张京芬,李月春,等.帕金森病的黑质超声表现[J].中华老年心脑血管病杂志,2012,14(4):390-393.
[43]Toomsoo T,Liepelt-Scarfone I,Kerner R,et al.Substantia nigra hyperechogenicity:Validation of transcranial sonography for Parkinson disease diagnosis in a large estonian cohort[J].J Ultrasound Med,2016,35(1):17-23.