周征成+譚建萍+肖麗華+范華
[摘要] 目的 探討康復(fù)治療是否能延緩早期帕金森病運(yùn)動(dòng)癥狀的進(jìn)展。 方法 我院門診及住院新診斷帕金森病患者38例,隨機(jī)納入康復(fù)治療組及對(duì)照組,評(píng)估統(tǒng)一帕金森病評(píng)定量表(UPDRS)中UPDRS-Ⅱ、UPDRS-Ⅲ及左旋多巴服用劑量。 結(jié)果 經(jīng)過1年的觀察,康復(fù)治療組治療前后UPDRS-Ⅱ、UPDRS-Ⅲ有好轉(zhuǎn),而對(duì)照組治療前后無明顯變化,對(duì)照組左旋多巴服用劑量也明顯大于康復(fù)治療組。 結(jié)論 康復(fù)治療可以減少藥物需要量,延緩帕金森病運(yùn)動(dòng)癥狀進(jìn)展。
[關(guān)鍵詞] 康復(fù)治療;帕金森??;運(yùn)動(dòng)障礙
[中圖分類號(hào)] R742.5 [文獻(xiàn)標(biāo)識(shí)碼] B [文章編號(hào)] 1673-9701(2014)34-0022-03
帕金森病是常見的神經(jīng)變性疾病,疾病后期可嚴(yán)重影響患者生活質(zhì)量,目前仍無有效的根治方法,藥物的使用可以減輕患者的運(yùn)動(dòng)癥狀,但是藥物都會(huì)帶來各種各樣令人困擾的副作用。最近10年來,各種康復(fù)治療對(duì)帕金森病的運(yùn)動(dòng)癥狀都獲得了一些積極的效果。為了更好的明確康復(fù)治療對(duì)帕金森病運(yùn)動(dòng)癥狀的治療作用,由于新診斷患者均未使用抗帕金森藥物,可以排除藥物因素的作用,我們選用新診斷的帕金森病患者進(jìn)行研究,更有利于分析康復(fù)治療的作用。
1資料與方法
1.1 一般資料
納入標(biāo)準(zhǔn):2012年2月~2013年6月我院新診斷帕金森病患者38例,符合英國PD協(xié)會(huì)診斷標(biāo)準(zhǔn)[1],H-Y分級(jí):1~1.5。排除標(biāo)準(zhǔn):嚴(yán)重心、肺、肝、腎疾病、嚴(yán)重中樞系統(tǒng)疾病、精神疾病等不宜參加康復(fù)運(yùn)動(dòng)患者。其中男 25例,女 13例,年齡37~70歲,平均(59.2±7.1)歲。隨機(jī)納入康復(fù)治療組及對(duì)照組,每組19例?;颊呔鶠楸臼谐W∪丝冢炇鹋R床試驗(yàn)知情同意書。
1.2 藥物
多巴絲肼片(規(guī)格:0.25 g/40片,每片含左旋多巴200 mg與芐絲肼50 mg),生產(chǎn)企業(yè):上海羅氏制藥有限公司。
1.3 方法
康復(fù)治療組在研究開始時(shí)(T0)進(jìn)行時(shí)長21 d的綜合康復(fù)運(yùn)動(dòng)治療,在我科康復(fù)室康復(fù)師指導(dǎo)下進(jìn)行,每次訓(xùn)練45 min,每周3次。此后在社區(qū)家庭進(jìn)行維持訓(xùn)練(方法由康復(fù)師指導(dǎo)),每次訓(xùn)練45 min,每日1次。對(duì)照組不進(jìn)行康復(fù)運(yùn)動(dòng)治療。兩組患者均由臨床醫(yī)師根據(jù)病情需要服用多巴絲肼片。所有患者均于研究開始時(shí)(T0),3個(gè)月(T1)、6個(gè)月(T2)、12個(gè)月(T3)進(jìn)行UPDRS-Ⅱ、UPDRS-Ⅲ評(píng)分。所有患者評(píng)分均由同一位醫(yī)師完成。實(shí)驗(yàn)過程采用盲法。
1.3.1 康復(fù)治療 康復(fù)室采用綜合康復(fù)運(yùn)動(dòng)療法[2]:包含松弛訓(xùn)練、關(guān)節(jié)運(yùn)動(dòng)范圍訓(xùn)練、移動(dòng)訓(xùn)練、平衡活動(dòng)、日常生活功能訓(xùn)練、呼吸功能訓(xùn)練、步態(tài)訓(xùn)練。每次訓(xùn)練45 min,每周3次。研究開始時(shí)21 d在醫(yī)院康復(fù)室康復(fù)師指導(dǎo)下訓(xùn)練,此后在社區(qū)家庭進(jìn)行維持訓(xùn)練,包含面肌體操、頭頸部體操、肩部體操、軀干體操、上肢體操、手指體操、下肢體操、步伐體操、床上體操、呼吸體操。每次訓(xùn)練45 min,每日1次。
1.3.2 UPDRS-Ⅱ、UPDRS-Ⅲ評(píng)分 所有患者評(píng)分均由同一位醫(yī)師完成,且評(píng)分醫(yī)師對(duì)患者分組及服藥情況不知情。于研究開始時(shí)(T0),3個(gè)月(T1)、6個(gè)月(T2)、12個(gè)月(T3)進(jìn)行評(píng)分。
1.3.3 統(tǒng)計(jì)學(xué)方法 數(shù)據(jù)采用SPSS17.0統(tǒng)計(jì)軟件包進(jìn)行處理,計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示。采兩獨(dú)立樣本采用t檢驗(yàn),多組間比較采用單因素方差分析,檢驗(yàn)水準(zhǔn):α=0.05。
2 結(jié)果
康復(fù)治療組與對(duì)照組受試者年齡分別為(58.1±6.9)歲、(60.3±7.3)歲,兩獨(dú)立樣本t檢驗(yàn):P=0.343。H-Y分級(jí)分別為(1.2±0.2)級(jí),(1.1±0.2)級(jí),兩獨(dú)立樣本t檢驗(yàn):P=0.457,均無統(tǒng)計(jì)學(xué)差異。 見表1 。
在T0點(diǎn),康復(fù)治療組及對(duì)照組UPDRS-Ⅱ評(píng)分分別為7.9±0.5、8.0±0.5(P=0.747),UPDRS-Ⅲ評(píng)分分別為:15.1±1.4、14.8±1.8(P=0.611),均無統(tǒng)計(jì)學(xué)差異。在對(duì)照組,各觀察時(shí)間點(diǎn)UPDRS-Ⅲ評(píng)分分別為14.8±1.8(T0)、14.5±1.4(T1)、14.4±1.3(T2)、14.2±1.8(T3),均無明顯變化。而UPDRS-Ⅱ評(píng)分分別為:8.0±0.5(T0)、7.6±0.7(T1)、7.6±0.8(T2)、7.5±0.8(T3),僅T3與T0比較具有統(tǒng)計(jì)學(xué)差異;但在康復(fù)治療組,UPDRS-Ⅱ評(píng)分分別為:7.9±0.5(T0)、5.7±1.0(T1)、5.5±0.9(T2)、6.1±0.9(T3),UPDRS-Ⅲ評(píng)分分別為:15.1±1.4(T0)、9.3±2.3(T1)、8.9±2.0(T2)、9.1±1.9(T3)。治療后各時(shí)間點(diǎn)UPDRS-Ⅱ、UPDRS-Ⅲ均較T0有明顯提高。在T1、T2、T3三個(gè)觀察點(diǎn),康復(fù)治療組與對(duì)照組的左旋多巴服用劑量均存在顯著差異,康復(fù)治療組比對(duì)照組服用左旋多巴劑量明顯減少。見表2。
UPDRS-Ⅲ評(píng)分:方差分析F=0.436,P=0.728,無統(tǒng)計(jì)學(xué)差異(P>0.05)。
T1、T2、T3康復(fù)治療組與對(duì)照組左旋多巴用量比較:t值分別為:12.369,8.185,6.955;P均=0.000,存在統(tǒng)計(jì)學(xué)差異。
3討論
帕金森病是常見的神經(jīng)系統(tǒng)變性疾病,目前認(rèn)為其發(fā)病病理基礎(chǔ)是由于中樞神經(jīng)系統(tǒng)黑質(zhì)多巴胺能神經(jīng)元變性死亡,目前藥物治療也主要圍繞多巴胺遞質(zhì)展開。除了藥物治療,帕金森病的另一種治療方法是康復(fù)鍛煉,近年也開始被人注意。為進(jìn)一步了解康復(fù)鍛煉對(duì)帕金森病的進(jìn)展的影響我們進(jìn)行了本實(shí)驗(yàn)。
由于既往診斷帕金森病患者可能已經(jīng)服用各種抗帕金森病藥物,而這些藥物可能影響帕金森病發(fā)展進(jìn)程,因此我們選擇對(duì)新診斷帕金森病患者的研究來明確康復(fù)治療對(duì)帕金森病發(fā)展的延緩作用,可以去除藥物因素對(duì)結(jié)果的干擾。通過本實(shí)驗(yàn)初步研究,觀察了康復(fù)運(yùn)動(dòng)對(duì)早期帕金森病運(yùn)動(dòng)障礙的近期(3個(gè)月)及中遠(yuǎn)期(6個(gè)月~1年)影響,我們發(fā)現(xiàn)在康復(fù)治療組,治療后3個(gè)月、6個(gè)月、1年三個(gè)時(shí)間點(diǎn)UPDRS-Ⅱ、UPDRS-Ⅲ均較康復(fù)治療前有明顯改善,而對(duì)照組,三個(gè)時(shí)間點(diǎn)UPDRS-Ⅲ均較入組時(shí)無明顯差異,僅1年時(shí)UPDRS-Ⅱ評(píng)分較入組時(shí)有改善,考慮可能與服用多巴絲肼藥物有關(guān)。提示康復(fù)運(yùn)動(dòng)治療可以減輕早期帕金森病運(yùn)動(dòng)癥狀,提高患者生活質(zhì)量,且患者在康復(fù)運(yùn)動(dòng)治療時(shí)均未出現(xiàn)不適癥狀,因此康復(fù)運(yùn)動(dòng)治療早期帕金森病運(yùn)動(dòng)癥狀安全、有效。曾有實(shí)驗(yàn)通過加強(qiáng)康復(fù)運(yùn)動(dòng)治療也得出與本實(shí)驗(yàn)類似結(jié)果[3]??祻?fù)鍛煉除改善帕金森病運(yùn)動(dòng)障礙,還可改善患者睡眠及步態(tài),從而改善患者生活質(zhì)量[4-6]??祻?fù)鍛煉對(duì)改善帕金森病患者生活質(zhì)量的作用可能是多方面的。
同時(shí)我們?cè)诔醪窖芯恐幸舶l(fā)現(xiàn),隨著時(shí)間發(fā)展,康復(fù)治療組左旋多巴劑量的增加比對(duì)照組明顯減少,提示康復(fù)治療可延緩帕金森病左旋多巴的劑量的增加。眾所周知,左旋多巴等抗帕金森病藥物是把雙刃劍,大劑量使用各種抗帕金森病藥物均可能出現(xiàn)各種令人煩擾的不良反應(yīng),甚至降低患者生活質(zhì)量。因此康復(fù)治療或許可以延緩帕金森病運(yùn)動(dòng)障礙的發(fā)展,可能具有神經(jīng)保護(hù)作用,可以安全有效地提高患者生活質(zhì)量。但康復(fù)治療影響帕金森病發(fā)展的作用機(jī)制尚不明確,近年來有研究表明中年后開始適當(dāng)?shù)倪\(yùn)動(dòng)鍛煉可以降低帕金森病發(fā)病風(fēng)險(xiǎn)[7]。既然運(yùn)動(dòng)鍛煉可阻止帕金森病發(fā)病,因此也可推測運(yùn)動(dòng)鍛煉可能延緩帕金森病的進(jìn)展。為了解運(yùn)動(dòng)鍛煉對(duì)帕金森病發(fā)展的作用機(jī)制,有研究者對(duì)帕金森病動(dòng)物模型進(jìn)行實(shí)驗(yàn),結(jié)果表明運(yùn)動(dòng)鍛煉可以促進(jìn)大腦神經(jīng)重塑[8-11],并可提高血漿多種神經(jīng)營養(yǎng)因子水平[12-13]。而在正常人體運(yùn)動(dòng)鍛煉后也發(fā)現(xiàn)血漿中多種生長因子水平升高[14],這些生長因子能通過血腦屏障作用于神經(jīng)細(xì)胞。因此,康復(fù)治療可能通過提高體內(nèi)多種生長因子水平,延緩腦細(xì)胞凋亡,增強(qiáng)神經(jīng)細(xì)胞可塑性,從而延緩帕金森病發(fā)生、進(jìn)展。最近的一項(xiàng)研究也提示社區(qū)有氧運(yùn)動(dòng)鍛煉有助于提高早期帕金森病生活質(zhì)量[15]。因此康復(fù)運(yùn)動(dòng)鍛煉是帕金森病的一種安全有效的治療方法,其機(jī)制需要進(jìn)一步研究。本研究為初步研究,樣本量較少,需要進(jìn)一步大樣本試驗(yàn)。
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[15] Uc EY,Doerschug KC,Magnotta V,et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease?in a community setting[J]. Neurology,2014,83(5):413-425.
(收稿日期:2014-09-30)
同時(shí)我們?cè)诔醪窖芯恐幸舶l(fā)現(xiàn),隨著時(shí)間發(fā)展,康復(fù)治療組左旋多巴劑量的增加比對(duì)照組明顯減少,提示康復(fù)治療可延緩帕金森病左旋多巴的劑量的增加。眾所周知,左旋多巴等抗帕金森病藥物是把雙刃劍,大劑量使用各種抗帕金森病藥物均可能出現(xiàn)各種令人煩擾的不良反應(yīng),甚至降低患者生活質(zhì)量。因此康復(fù)治療或許可以延緩帕金森病運(yùn)動(dòng)障礙的發(fā)展,可能具有神經(jīng)保護(hù)作用,可以安全有效地提高患者生活質(zhì)量。但康復(fù)治療影響帕金森病發(fā)展的作用機(jī)制尚不明確,近年來有研究表明中年后開始適當(dāng)?shù)倪\(yùn)動(dòng)鍛煉可以降低帕金森病發(fā)病風(fēng)險(xiǎn)[7]。既然運(yùn)動(dòng)鍛煉可阻止帕金森病發(fā)病,因此也可推測運(yùn)動(dòng)鍛煉可能延緩帕金森病的進(jìn)展。為了解運(yùn)動(dòng)鍛煉對(duì)帕金森病發(fā)展的作用機(jī)制,有研究者對(duì)帕金森病動(dòng)物模型進(jìn)行實(shí)驗(yàn),結(jié)果表明運(yùn)動(dòng)鍛煉可以促進(jìn)大腦神經(jīng)重塑[8-11],并可提高血漿多種神經(jīng)營養(yǎng)因子水平[12-13]。而在正常人體運(yùn)動(dòng)鍛煉后也發(fā)現(xiàn)血漿中多種生長因子水平升高[14],這些生長因子能通過血腦屏障作用于神經(jīng)細(xì)胞。因此,康復(fù)治療可能通過提高體內(nèi)多種生長因子水平,延緩腦細(xì)胞凋亡,增強(qiáng)神經(jīng)細(xì)胞可塑性,從而延緩帕金森病發(fā)生、進(jìn)展。最近的一項(xiàng)研究也提示社區(qū)有氧運(yùn)動(dòng)鍛煉有助于提高早期帕金森病生活質(zhì)量[15]。因此康復(fù)運(yùn)動(dòng)鍛煉是帕金森病的一種安全有效的治療方法,其機(jī)制需要進(jìn)一步研究。本研究為初步研究,樣本量較少,需要進(jìn)一步大樣本試驗(yàn)。
[參考文獻(xiàn)]
[1] Meara J,Bhowmick BK,Hobson P. Accuracy of diagnosis in patients with presumed Parkinsons disease[J]. Age Ageing,1999; 28(2): 99-102.
[2] 朱鏞連. 神經(jīng)康復(fù)學(xué)[M]. 北京:人民軍醫(yī)出版社,2001;358-363.
[3] Frazzitta G,Bertotti G,Riboldazzi G,et al. Effectiveness of intensive inpatient rehabilitation treatment on disease progression in Parkinsonian patients:a randomized controlled trial with 1-year follow-up[J]. Neurorehabil Neural Repair. 2012;26(2):144-150.
[4] Wassom DJ1,Lyons KE,Pahwa R,et al. Qigong exercise may improve sleep quality and gait performance in Parkinson's disease: a pilot study[J]. Int J Neurosci,2014,18:1-29.
[5] Ayán C,Cancela JM,Gutiérrez-Santiago A,et al. Effects of two different exercise programs on gait parameters in individuals with Parkinson's disease: a pilot study[J]. Gait Posture,2014,39(1):648-651.
[6] Janssens J,Malfroid K,Nyffeler T,et al. Application of LSVT BIG intervention to address gait,balance,bed mobility,and dexterity in people with Parkinson disease:a case series[J]. Phys Ther,2014,94(7):1014-1023.
[7] Xu Q,Park Y,Huang X,et al. Physical activities and future risk of Parkinson disease[J]. Neurology. 2010,75(4):341-348.
[8] Petzinger G,F(xiàn)isher B,McEwen S,et al. Exercise-enhanced europlasticity targeting motor and cognitive circuitry in Parkinsons disease[J]. Lancet Neurol,2013,12(7):716-726.
[9] Petzinger G,F(xiàn)isher B,Van Leeuwen JE,et al. Enhancing neuroplasticity in the basal ganglia: the role of exercise in Parkinsons disease[J]. Mov Disord,2010,25(Suppl 1):s141-s145.
[10] Vuckovic MG,Li Q,F(xiàn)isher B,et al. Exercise elevates dopamine D2 receptor in a mouse model of Parkinsons disease: in vivo imaging with [18F]fallypride[J]. Mov Disord,2010,25(16):2777-2784.
[11] Fisher BE,Petzinger GM,Nixon K,et al. Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia[J]. J Neurosci Res,2004,77(3):378-390.
[12] Tajiri N,Yasuhara T,Shingo T,et al. Exercise exerts neuroprotective effects on Parkinsons disease model of rats[J]. Brain Res,2010,1310:200-207.
[13] Frazzitta G1,Maestri R,Ghilardi MF,et al. Intensive rehabilitation increases BDNF serum levels in parkinsonian patients: a randomized study[J]. Neurorehabil Neural Repair,2014,28(2):163-168.
[14] Coelho FG,Gobbi S,Andreatto CA,et al. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor(BDNF):a systematic review of experimental studies in the elderly[J]. Arch Gerontol Geriatr,2013, 56(1):10-15.
[15] Uc EY,Doerschug KC,Magnotta V,et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease?in a community setting[J]. Neurology,2014,83(5):413-425.
(收稿日期:2014-09-30)
同時(shí)我們?cè)诔醪窖芯恐幸舶l(fā)現(xiàn),隨著時(shí)間發(fā)展,康復(fù)治療組左旋多巴劑量的增加比對(duì)照組明顯減少,提示康復(fù)治療可延緩帕金森病左旋多巴的劑量的增加。眾所周知,左旋多巴等抗帕金森病藥物是把雙刃劍,大劑量使用各種抗帕金森病藥物均可能出現(xiàn)各種令人煩擾的不良反應(yīng),甚至降低患者生活質(zhì)量。因此康復(fù)治療或許可以延緩帕金森病運(yùn)動(dòng)障礙的發(fā)展,可能具有神經(jīng)保護(hù)作用,可以安全有效地提高患者生活質(zhì)量。但康復(fù)治療影響帕金森病發(fā)展的作用機(jī)制尚不明確,近年來有研究表明中年后開始適當(dāng)?shù)倪\(yùn)動(dòng)鍛煉可以降低帕金森病發(fā)病風(fēng)險(xiǎn)[7]。既然運(yùn)動(dòng)鍛煉可阻止帕金森病發(fā)病,因此也可推測運(yùn)動(dòng)鍛煉可能延緩帕金森病的進(jìn)展。為了解運(yùn)動(dòng)鍛煉對(duì)帕金森病發(fā)展的作用機(jī)制,有研究者對(duì)帕金森病動(dòng)物模型進(jìn)行實(shí)驗(yàn),結(jié)果表明運(yùn)動(dòng)鍛煉可以促進(jìn)大腦神經(jīng)重塑[8-11],并可提高血漿多種神經(jīng)營養(yǎng)因子水平[12-13]。而在正常人體運(yùn)動(dòng)鍛煉后也發(fā)現(xiàn)血漿中多種生長因子水平升高[14],這些生長因子能通過血腦屏障作用于神經(jīng)細(xì)胞。因此,康復(fù)治療可能通過提高體內(nèi)多種生長因子水平,延緩腦細(xì)胞凋亡,增強(qiáng)神經(jīng)細(xì)胞可塑性,從而延緩帕金森病發(fā)生、進(jìn)展。最近的一項(xiàng)研究也提示社區(qū)有氧運(yùn)動(dòng)鍛煉有助于提高早期帕金森病生活質(zhì)量[15]。因此康復(fù)運(yùn)動(dòng)鍛煉是帕金森病的一種安全有效的治療方法,其機(jī)制需要進(jìn)一步研究。本研究為初步研究,樣本量較少,需要進(jìn)一步大樣本試驗(yàn)。
[參考文獻(xiàn)]
[1] Meara J,Bhowmick BK,Hobson P. Accuracy of diagnosis in patients with presumed Parkinsons disease[J]. Age Ageing,1999; 28(2): 99-102.
[2] 朱鏞連. 神經(jīng)康復(fù)學(xué)[M]. 北京:人民軍醫(yī)出版社,2001;358-363.
[3] Frazzitta G,Bertotti G,Riboldazzi G,et al. Effectiveness of intensive inpatient rehabilitation treatment on disease progression in Parkinsonian patients:a randomized controlled trial with 1-year follow-up[J]. Neurorehabil Neural Repair. 2012;26(2):144-150.
[4] Wassom DJ1,Lyons KE,Pahwa R,et al. Qigong exercise may improve sleep quality and gait performance in Parkinson's disease: a pilot study[J]. Int J Neurosci,2014,18:1-29.
[5] Ayán C,Cancela JM,Gutiérrez-Santiago A,et al. Effects of two different exercise programs on gait parameters in individuals with Parkinson's disease: a pilot study[J]. Gait Posture,2014,39(1):648-651.
[6] Janssens J,Malfroid K,Nyffeler T,et al. Application of LSVT BIG intervention to address gait,balance,bed mobility,and dexterity in people with Parkinson disease:a case series[J]. Phys Ther,2014,94(7):1014-1023.
[7] Xu Q,Park Y,Huang X,et al. Physical activities and future risk of Parkinson disease[J]. Neurology. 2010,75(4):341-348.
[8] Petzinger G,F(xiàn)isher B,McEwen S,et al. Exercise-enhanced europlasticity targeting motor and cognitive circuitry in Parkinsons disease[J]. Lancet Neurol,2013,12(7):716-726.
[9] Petzinger G,F(xiàn)isher B,Van Leeuwen JE,et al. Enhancing neuroplasticity in the basal ganglia: the role of exercise in Parkinsons disease[J]. Mov Disord,2010,25(Suppl 1):s141-s145.
[10] Vuckovic MG,Li Q,F(xiàn)isher B,et al. Exercise elevates dopamine D2 receptor in a mouse model of Parkinsons disease: in vivo imaging with [18F]fallypride[J]. Mov Disord,2010,25(16):2777-2784.
[11] Fisher BE,Petzinger GM,Nixon K,et al. Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia[J]. J Neurosci Res,2004,77(3):378-390.
[12] Tajiri N,Yasuhara T,Shingo T,et al. Exercise exerts neuroprotective effects on Parkinsons disease model of rats[J]. Brain Res,2010,1310:200-207.
[13] Frazzitta G1,Maestri R,Ghilardi MF,et al. Intensive rehabilitation increases BDNF serum levels in parkinsonian patients: a randomized study[J]. Neurorehabil Neural Repair,2014,28(2):163-168.
[14] Coelho FG,Gobbi S,Andreatto CA,et al. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor(BDNF):a systematic review of experimental studies in the elderly[J]. Arch Gerontol Geriatr,2013, 56(1):10-15.
[15] Uc EY,Doerschug KC,Magnotta V,et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease?in a community setting[J]. Neurology,2014,83(5):413-425.
(收稿日期:2014-09-30)