主诉为冻结步态的帕金森综合征诊治前瞻性研究
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摘要
目的观察以冻结步态为主诉的帕金森综合征(PDS)的诊疗过程,为延缓该症状进展提供线索。方法本研究为前瞻性研究。选择2010年11月至2016年1月在海军军医大学(第二军医大学)长征医院神经内科帕金森病专病门诊随访、以冻结步态为主诉的PDS患者,跟踪随访2～6年。所有患者均采用阶梯性诊治措施,即初始使用左旋多巴行基础治疗并观察疗效,如无效则先后选用其他抗帕金森病药物、抗抑郁药物、其他治疗方案(包括药物和手术治疗等)。患者初诊时,采用Hoehn-Yahr分级和统一帕金森病评分量表(UPDRS)的第二部分(Ⅱ)、第三部分(Ⅲ)评价运动功能,UPDRS的第一部分(Ⅰ)评价总体精神、行为和情绪情况,简易精神状态检查表(MMSE)评估认知功能,分别采用汉密尔顿抑郁量表(HAMD-17)和汉密尔顿焦虑量表(HAMA)评价抑郁、焦虑状态;初诊和每次随访时均采用起立-行走计时测试(TUGT)评价冻结步态的严重程度。结果 15例冻结步态患者中帕金森病6例,非帕金森病9例(包括2例进行性核上性麻痹、3例原发性进展型冻结步态、1例额颞叶痴呆、1例血管性PDS、1例药物性PDS、1例原因未明PDS)。两组患者年龄、性别,以及初诊时HoehnYahr分级、UPDRS-Ⅰ总分、UPDRS-Ⅱ总分、UPDRS-Ⅲ总分、MMSE总分、HAMD-17总分、HAMA总分和TUGT时间差异均无统计学意义(P均>0.05)。基线时帕金森病组冻结步态病程为(7.50±2.66)年,长于非帕金森病组[(2.56±0.88)年],差异有统计学意义(P<0.01)。帕金森病组左旋多巴治疗有效率高于非帕金森病组(4/6 vs0/9,P=0.01)。结论以冻结步态为主诉的PDS病因具有异质性,冻结步态病程长短有助于诊断原发性帕金森病,冻结步态严重程度对病因提示意义不大。增加左旋多巴剂量对帕金森病中晚期出现的冻结步态有效,对其他原因导致的冻结步态疗效不确定。
Objective To study the clinical diagnosis and treatment of parkinsonism(PDS) with freezing of gait(FoG),so as to provide clues to delay the progress of the symptom. Methods A prospective study was designed. The outpatients of PDS with the main complaint of FoG were included and followed up for 2-6 years in the Department of Neurology,Changzheng Hospital, Naval Medical University(Second Military Medical University) from Nov. 2010 to Jan. 2016. The patients were given L-dopa first, and then antidepressants and other therapies(including other medication and surgery) were given if the previous treatments were not effective. The motor function of patients was evaluated by Hoehn-Yahr staging scale and the second and third part of the unified Parkinson disease rating scale(UPDRS); the general mental, behavior and emotional state were evaluated by the first part of UPDRS; the cognition was evaluated by minimum mental state examination(MMSE); depression and anxiety were evaluated by 17-item Hamilton depression scale(HAMD-17) and Hamilton anxiety scale(HAMA); and the severity of FoG was evaluated by the timed up and go test(TUGT). Results Six of the 15 cases with FoG were diagnosed as Parkinson disease(PD), and 9 had other disorders(2 with progressive supranuclear palsy,3 with primary progressive FoG, 1 with frontotemporal dementia, 1 with vascular PDS, 1 with drug-induced PDS, and1 with unknown-cause PDS). There were no significant differences in age, gender, severity of symptom or mental state(Hoehn-Yahr stage, UPDRS-Ⅰ score, UPDRS-Ⅱ score, UPDRS-Ⅲ score, MMSE score, HAMD-17 score, HAMA score and TUGT time) between PD group and non-PD group(all P>0.05). At the baseline, the FoG duration of PD patients([7.50±2.66]years) was longer than that of non-PD patients([2.56±0.88] years, P<0.01). After treatment with increasing dose of L-dopa,4 PD patients were improved while non-PD patients had no responses(4/6 vs 0/9, P=0.01). Conclusion The causes of PDS with FoG are heterogeneous. The duration of FoG is helpful for diagnosis of idiopathic PD, while the severity of FoG has little value for etiological analysis. Increasing the dose of L-dopa is effective for FoG in advanced PD, while it has uncertain effect for FoG of other reasons.
Objective To study the clinical diagnosis and treatment of parkinsonism(PDS) with freezing of gait(FoG),so as to provide clues to delay the progress of the symptom. Methods A prospective study was designed. The outpatients of PDS with the main complaint of FoG were included and followed up for 2-6 years in the Department of Neurology,Changzheng Hospital, Naval Medical University(Second Military Medical University) from Nov. 2010 to Jan. 2016. The patients were given L-dopa first, and then antidepressants and other therapies(including other medication and surgery) were given if the previous treatments were not effective. The motor function of patients was evaluated by Hoehn-Yahr staging scale and the second and third part of the unified Parkinson disease rating scale(UPDRS); the general mental, behavior and emotional state were evaluated by the first part of UPDRS; the cognition was evaluated by minimum mental state examination(MMSE); depression and anxiety were evaluated by 17-item Hamilton depression scale(HAMD-17) and Hamilton anxiety scale(HAMA); and the severity of FoG was evaluated by the timed up and go test(TUGT). Results Six of the 15 cases with FoG were diagnosed as Parkinson disease(PD), and 9 had other disorders(2 with progressive supranuclear palsy,3 with primary progressive FoG, 1 with frontotemporal dementia, 1 with vascular PDS, 1 with drug-induced PDS, and1 with unknown-cause PDS). There were no significant differences in age, gender, severity of symptom or mental state(Hoehn-Yahr stage, UPDRS-Ⅰ score, UPDRS-Ⅱ score, UPDRS-Ⅲ score, MMSE score, HAMD-17 score, HAMA score and TUGT time) between PD group and non-PD group(all P>0.05). At the baseline, the FoG duration of PD patients([7.50±2.66]years) was longer than that of non-PD patients([2.56±0.88] years, P<0.01). After treatment with increasing dose of L-dopa,4 PD patients were improved while non-PD patients had no responses(4/6 vs 0/9, P=0.01). Conclusion The causes of PDS with FoG are heterogeneous. The duration of FoG is helpful for diagnosis of idiopathic PD, while the severity of FoG has little value for etiological analysis. Increasing the dose of L-dopa is effective for FoG in advanced PD, while it has uncertain effect for FoG of other reasons.
引文
[1]NUTT J G,BLOEM B R,GILADI N,HALLETT M,HORAK F B,NIEUWBOER A.Freezing of gait:moving forward on a mysterious clinical phenomenon[J].Lancet Neurol,2011,10:734-744.
[2]OKUMA Y.Freezing of gait and falls in Parkinson’s disease[J].J Parkinsons Dis,2014,4:255-260.
[3]HUGHES A J,DANIEL S E,KILFORD L,LEES A J.Accuracy of clinical diagnosis of idiopathic Parkinson’s disease:a clinico-pathological study of 100 cases[J].J Neurol Neurosurg Psychiatry,1992,55:181-184.
[4]LITVAN I,AGID Y,CALNE D,CAMPBELL G,DUBOIS B,DUVOISIN R C,et al.Clinical research criteria for the diagnosis of progressive supranuclear palsy(Steele-Richardson-Olszewski syndrome):report of the NINDS-SPSP international workshop[J].Neurology,1996,47:1-9.
[5]FACTOR S A,JENNINGS D L,MOLHO E S,MAREKK L.The natural history of the syndrome of primary progressive freezing gait[J].Arch Neurol,2002,59:1778-1783.
[6]MCKHANN G M,ALBERT M S,GROSSMAN M,MILLER B,DICKSON D,TROJANOWSKI J Q;Work Group on Frontotemporal Dementia and Pick’s Disease.Clinical and pathological diagnosis of frontotemporal dementia:report of the Work Group on Frontotemporal Dementia and Pick’s Disease[J].Arch Neurol,2001,58:1803-1809.
[7]ZIJLMANS J C,DANIEL S E,HUGHES A J,RéVéSZ T,LEES A J.Clinicopathological investigation of vascular parkinsonism,including clinical criteria for diagnosis[J].Mov Disord,2004,19:630-640.
[8]MARTINEZ-MARTIN P,SKORVANEK M,ROJO-ABUIN J M,GREGOVA Z,STEBBINS G T,GOETZ CG;members of the QUALPD Study Group.Validation study of the hoehn and yahr scale included in the MDS-UPDRS[J].Mov Disord,2018,33:651-652.
[9]MANCINI M,PRIEST K C,NUTT J G,HORAK F B.Quantifying freezing of gait in Parkinson’s disease during the instrumented timed up and go test[J].Conf Proc IEEEEng Med Biol Soc,2012,2012:1198-1201.
[10]HOOPS S,NAZEM S,SIDEROWF A D,DUDA J E,XIE S X,STERN M B,et al.Validity of the MoCAand MMSE in the detection of MCI and dementia in Parkinson disease[J].Neurology,2009,73:1738-1745.
[11]TORBEY E,PACHANA N A,DISSANAYAKA N N.Depression rating scales in Parkinson’s disease:a critical review updating recent literature[J].J Affect Disord,2015,184:216-224.
[12]KUMMER A,CARDOSO F,TEIXEIRA A L.Generalized anxiety disorder and the Hamilton Anxiety Rating Scale in Parkinson’s disease[J].Arq Neuropsiquiatr,2010,68:495-501.
[13]MACHT M,KAUSSNER Y,M?LLER J C,STIASNY-KOLSTER K,EGGERT K M,KRüGER H P,et al.Predictors of freezing in Parkinson’s disease:a survey of6,620 patients[J].Mov Disord,2007,22:953-956.
[14]AMBONI M,STOCCHI F,ABBRUZZESE G,MORGANTE L,ONOFRJ M,RUGGIERI S,et al;DEEP Study Group.Prevalence and associated features of self-reported freezing of gait in Parkinson disease:the DEEP FOG study[J].Parkinsonism Relat Disord,2015,21:644-649.
[15]BROWNER N,GILADI N.What can we learn from freezing of gait in Parkinson’s disease?[J].Curr Neurol Neurosci Rep,2010,10:345-351.
[16]FORSAA E B,LARSEN J P,WENTZEL-LARSEN T,ALVES G.A 12-year population-based study of freezing of gait in Parkinson’s disease[J].Parkinsonism Relat Disord,2015,21:254-258.
[17]OSAKI Y,MORITA Y,MIYAMOTO Y,FURUTA K,FURUYA H.Freezing of gait is an early clinical feature of progressive supranuclear palsy[J].Neurol Clin Neurosci,2017,5:86-90.
[18]SUPPA A,KITA A,LEODORI G,ZAMPOGNA A,NICOLINI E,LORENZI P,et al.l-DOPA and freezing of gait in Parkinson’s disease:objective assessment through a wearable wireless system[J/OL].Front Neurol,2017,8:406.doi:10.3389/fneur.2017.00406.
[19]GILAT M,EHGOETZ MARTENS K A,MIRANDA-DOMíNGUEZ O,ARPAN I,SHINE J M,MANCINI M,et al.Dysfunctional limbic circuitry underlying freezing of gait in Parkinson’s disease[J].Neuroscience,2018,374:119-132.
[20]MORGANTE F,FASANO A.Improvement with duloxetine in primary progressive freezing gait[J].Neurology,2010,75:2130-2132.
[21]YAO Z,SHAO Y,HAN X.Freezing of gait is associated with cognitive impairment in patients with Parkinson disease[J].Neurosci Lett,2017,656:126-130.
[22]FERRAYE M U,DEB?B,FRAIX V,XIE-BRUSTOLIN J,CHABARDèS S,KRACK P,et al.Effects of subthalamic nucleus stimulation and levodopa on freezing of gait in Parkinson disease[J].Neurology,2008,70(16 Pt 2):1431-1437.
[2]OKUMA Y.Freezing of gait and falls in Parkinson’s disease[J].J Parkinsons Dis,2014,4:255-260.
[3]HUGHES A J,DANIEL S E,KILFORD L,LEES A J.Accuracy of clinical diagnosis of idiopathic Parkinson’s disease:a clinico-pathological study of 100 cases[J].J Neurol Neurosurg Psychiatry,1992,55:181-184.
[4]LITVAN I,AGID Y,CALNE D,CAMPBELL G,DUBOIS B,DUVOISIN R C,et al.Clinical research criteria for the diagnosis of progressive supranuclear palsy(Steele-Richardson-Olszewski syndrome):report of the NINDS-SPSP international workshop[J].Neurology,1996,47:1-9.
[5]FACTOR S A,JENNINGS D L,MOLHO E S,MAREKK L.The natural history of the syndrome of primary progressive freezing gait[J].Arch Neurol,2002,59:1778-1783.
[6]MCKHANN G M,ALBERT M S,GROSSMAN M,MILLER B,DICKSON D,TROJANOWSKI J Q;Work Group on Frontotemporal Dementia and Pick’s Disease.Clinical and pathological diagnosis of frontotemporal dementia:report of the Work Group on Frontotemporal Dementia and Pick’s Disease[J].Arch Neurol,2001,58:1803-1809.
[7]ZIJLMANS J C,DANIEL S E,HUGHES A J,RéVéSZ T,LEES A J.Clinicopathological investigation of vascular parkinsonism,including clinical criteria for diagnosis[J].Mov Disord,2004,19:630-640.
[8]MARTINEZ-MARTIN P,SKORVANEK M,ROJO-ABUIN J M,GREGOVA Z,STEBBINS G T,GOETZ CG;members of the QUALPD Study Group.Validation study of the hoehn and yahr scale included in the MDS-UPDRS[J].Mov Disord,2018,33:651-652.
[9]MANCINI M,PRIEST K C,NUTT J G,HORAK F B.Quantifying freezing of gait in Parkinson’s disease during the instrumented timed up and go test[J].Conf Proc IEEEEng Med Biol Soc,2012,2012:1198-1201.
[10]HOOPS S,NAZEM S,SIDEROWF A D,DUDA J E,XIE S X,STERN M B,et al.Validity of the MoCAand MMSE in the detection of MCI and dementia in Parkinson disease[J].Neurology,2009,73:1738-1745.
[11]TORBEY E,PACHANA N A,DISSANAYAKA N N.Depression rating scales in Parkinson’s disease:a critical review updating recent literature[J].J Affect Disord,2015,184:216-224.
[12]KUMMER A,CARDOSO F,TEIXEIRA A L.Generalized anxiety disorder and the Hamilton Anxiety Rating Scale in Parkinson’s disease[J].Arq Neuropsiquiatr,2010,68:495-501.
[13]MACHT M,KAUSSNER Y,M?LLER J C,STIASNY-KOLSTER K,EGGERT K M,KRüGER H P,et al.Predictors of freezing in Parkinson’s disease:a survey of6,620 patients[J].Mov Disord,2007,22:953-956.
[14]AMBONI M,STOCCHI F,ABBRUZZESE G,MORGANTE L,ONOFRJ M,RUGGIERI S,et al;DEEP Study Group.Prevalence and associated features of self-reported freezing of gait in Parkinson disease:the DEEP FOG study[J].Parkinsonism Relat Disord,2015,21:644-649.
[15]BROWNER N,GILADI N.What can we learn from freezing of gait in Parkinson’s disease?[J].Curr Neurol Neurosci Rep,2010,10:345-351.
[16]FORSAA E B,LARSEN J P,WENTZEL-LARSEN T,ALVES G.A 12-year population-based study of freezing of gait in Parkinson’s disease[J].Parkinsonism Relat Disord,2015,21:254-258.
[17]OSAKI Y,MORITA Y,MIYAMOTO Y,FURUTA K,FURUYA H.Freezing of gait is an early clinical feature of progressive supranuclear palsy[J].Neurol Clin Neurosci,2017,5:86-90.
[18]SUPPA A,KITA A,LEODORI G,ZAMPOGNA A,NICOLINI E,LORENZI P,et al.l-DOPA and freezing of gait in Parkinson’s disease:objective assessment through a wearable wireless system[J/OL].Front Neurol,2017,8:406.doi:10.3389/fneur.2017.00406.
[19]GILAT M,EHGOETZ MARTENS K A,MIRANDA-DOMíNGUEZ O,ARPAN I,SHINE J M,MANCINI M,et al.Dysfunctional limbic circuitry underlying freezing of gait in Parkinson’s disease[J].Neuroscience,2018,374:119-132.
[20]MORGANTE F,FASANO A.Improvement with duloxetine in primary progressive freezing gait[J].Neurology,2010,75:2130-2132.
[21]YAO Z,SHAO Y,HAN X.Freezing of gait is associated with cognitive impairment in patients with Parkinson disease[J].Neurosci Lett,2017,656:126-130.
[22]FERRAYE M U,DEB?B,FRAIX V,XIE-BRUSTOLIN J,CHABARDèS S,KRACK P,et al.Effects of subthalamic nucleus stimulation and levodopa on freezing of gait in Parkinson disease[J].Neurology,2008,70(16 Pt 2):1431-1437.