帕金森病冻结步态的研究进展_West China Medical Journal

Authors：

 余文娟 ,  彭蓉

四川大学华西医院神经内科（成都，610041）;

Corresponding author：

彭蓉, Email: qrpeng@hotmail.com

Keywords：

冻结步态; 帕金森病; 病理生理机制; 评估; 治疗

DOI：

10.7507/1002-0179.20140048

Video：

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Abstract Full text Figures/Tables Video References Cited by

帕金森病是以静止性震颤、肌强直、运动徐缓及姿势步态异常为四大主要表现的神经变性疾病。冻结步态作为中晚期帕金森病常见且具有重要致残性的症状，近年来逐渐受到人们的重视，它主要表现为患者突发的短暂性迈步不能，增加了患者跌倒的几率，严重影响了患者的生存质量。目前冻结步态发生的病理生理机制尚不清楚，且治疗十分困难，现就帕金森病患者冻结步态的最新研究进展进行综述。

Citation： 余文娟, 彭蓉. 帕金森病冻结步态的研究进展. West China Medical Journal, 2014, 29(1): 155-159. doi: 10.7507/1002-0179.20140048 Copy

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2.	Tan DM, McGinley JL, Danoudis ME, et al. Freezing of gait and activity limitations in people with Parkinson's disease[J]. Arch Phys Med Rehabil, 2011, 92(7):1159-1165.
3.	Moore O, Peretz C, Giladi N, et al. Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait[J]. Mov Disord, 2007, 22(15):2192-2195.
4.	Okuma Y, Yanagisawa N, et al. The clinical spectrum of freezing of gait in Parkinson's disease[J]. Mov Disord, 2008, 23(Suppl 2):S426-S430.
5.	Lamberti P, Armenise S, Castaldo V, et al. Freezing gait in Parkinson's disease[J]. Eur Neurol, 1997, 38(4):297-301.
6.	Giladi N, McDermott MP, Fahn S, et al. Freezing of gait in PD:prospective assessment in the DATATOP cohort[J]. Neurology, 2001, 56(12):1712-1721.
7.	Giladi N, Treves TA, Simon ES, et al. Freezing of gait in patients with advanced Parkinson's disease[J]. Neural Transm, 2001, 108(1):53-61.
8.	Snijders AH, Nijkrake MJ, Bakker M, et al. Clinimetrics of freezing of gait[J]. Mov Disord, 2008, 23(Suppl 2):S468-S474.
9.	Alice N, Fabienne C, Anne-Marie W, et al. Does freezing in Parkinson's disease change limb coordination?[J]. Neurol, 2007, 254(9):1268-1277.
10.	Schaafsma, JD, Balash Y, Gurevich T, et al. Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson's disease[J]. Eur J Neurol, 2003, 10(4):391-398.
11.	Rahman S, Griffin HJ, Quinn NP, et al. The factors that induce or overcome freezing of gait in Parkinson's disease[J]. Behav Neurol, 2008, 19(3):127-136.
12.	Spildooren J, Vercruysse S, Desloovere K, et al. Freezing of gait in Parkinson's disease:the impact of dual-tasking and turning[J]. Mov Disord, 2010, 25(15):2563-2570.
13.	Giladi N, Hausdorff JM, et al. The role of mental function in the pathogenesis of freezing of gait in Parkinson's disease[J]. Neurol Sci, 2006, 248(1-2):173-176.
14.	Lieberman A. Are Freezing of Gait (FOG) and panic related?[J]. Neurol Sci, 2006, 248(1):219-222.
15.	Macht M, Kaussner Y, Moller JC, et al. Predictors of freezing in Parkinson's disease:a survey of 6,620 patients[J]. Mov Disord, 2007, 22(7):953-956.
16.	Garcia-Ruiz PJ. Gait disturbances in Parkinson disease. Did freezing of gait exist before levodopa? Historical review[J]. J Neurol Sci, 2011, 307(1-2):15-17.
17.	Snijders AH, Leunissen I, Bakker M, et al. Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait[J]. Brain, 2001, 134(1):59-72.
18.	Lewis SJG, Barker RA. A pathophysiological model of freezing of gait in Parkinson's disease[J]. Parkinsonism Relat Disord, 2009, 15(5):333-338.
19.	Youn J, Cho JW, Lee WY, et al. Diffusion tensor imaging of freezing of gait in patients with white matter changes[J]. Mov Disord, 2012, 27(6):760-764.
20.	Jenkinson N, Nandi D, Muthsamy K, et al. Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus[J]. Mov Disord, 2009, 24(3):319-328.
21.	Karachi C, Grabli D, Bernard FA, et al. Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson's disease[J]. J Clin Invest, 2010, 120(8):2745.
22.	Schweder PM, Hansen PC, Hansen PC, et al. Connectivity of the pedunculopontine nucleus in parkinsonian freezing of gait[J]. Neuroreport, 2010, 21(14):914-916.
23.	Kuo SH, Kenney C, Jankovic J, et al. Bilateral pedunculopontine nuclei strokes presenting as freezing of gait[J]. Mov Disord, 2008, 23(4):616-619.
24.	Knobl P, Kielstra L, Almeida Q, et al. The relationship between motor planning and freezing of gait in Parkinson's disease[J]. Neurol Neurosurg Psychiat, 2012, 83(1):98-101.
25.	Amboni M, Cozzolino A, Longo K, et al. Freezing of gait and executive functions in patients with Parkinson's disease[J]. Mov Disord, 2008, 23(3):395-400.
26.	Vandenbossche J, Deroost N, Soetens E, et al. Freezing of gait in Parkinson disease is associated with impaired conflict resolution[J]. Neurorehabil Neural Repair, 2011, 25(8):765-773.
27.	Amboni M, Barone P, Picillo M, et al. A two-year follow-up study of executive dysfunctions in parkinsonian patients with freezing of gait at on-state[J]. Mov Disord, 2010, 25(6):800-802.
28.	Nantel J, McDonald JC, Tan S, et al. Deficits in visuospatial processing contribute to quantitative measures of freezing of gait in Parkinson's disease[J]. Neuroscience, 2012, 221(9):151-156.
29.	Jovanov E, Wang E, Verhagen L, et al. defog-A real time system for detection and unfreezing of gait of Parkinson's patients[J]. Conf Proc IEEE Eng Med Biol Soc, 2009:5151-5154.
30.	Tan T, Almeida QJ, Rahimi F, et al. Proprioceptive deficits in Parkinson's disease patients with freezing of gait[J]. Neuroscience, 2011, 192(9):746-752.
31.	Vercruysse S, Spildooren J, Heremans E, et al. Freezing in Parkinson's disease:a spatiotemporal motor disorder beyond gait[J]. Mov Disord, 2012, 27(2):254-263.
32.	Chee R, Murphy A, Danoudis M, et al. Gait freezing in Parkinson's disease and the stride length sequence effect interaction[J]. Brain, 2009, 132(8):2151-2160.
33.	Moreau C, Defebvre L, Bleuse S, et al. Externally provoked freezing of gait in open runways in advanced Parkinson's disease results from motor and mental collapse[J]. Neural Transm, 2008, 115(10):1431-1436.
34.	Plotnik M, Giladi N, Hausdorff JM, et al. Bilateral coordination of walking and freezing of gait in Parkinson's disease[J]. Mov Disord, 2008, 27(8):1999-2006.
35.	Plotnik M, Hausdorff JM. The role of gait rhythmicity and bilateral coordination of stepping in the pathophysiology of freezing of gait in Parkinson's disease[J]. Mov Disord, 2008, 23(Suppl 2):S444-S450.
36.	Tessitore A, Amboni M, Cirillo G, et al. Regional gray matter atrophy in patients with Parkinson disease and freezing of gait[J]. AJNR Am J Neuroradiol, 2012, 33(9):1804-1809.
37.	Nieuwboer A, Rochester L, Herman T, et al. Reliability of the new freezing of gait questionnaire:agreement between patients with Parkinson's disease and their carers[J]. Gait Posture, 2009, 30(4):459-463.
38.	Giladi N, Tal J, Azulay T, et al. Validation of the freezing of gait questionnaire in patients with Parkinson's disease[J]. Mov Disord, 2009, 24(5):655-661.
39.	Shine JM, Moore ST, Bolitho SJ, et al. Assessing the utility of Freezing of Gait Questionnaires in Parkinson's disease[J]. Parkinsonism Relat Disord, 2012, 18(1):25-29.
40.	Moore ST, MacDougall HG, Ondo WG, et al. Ambulatory monitoring of freezing of gait in Parkinson's disease[J]. Neurosci Methods, 2008, 167(2):340-348.
41.	Popovic MB, Djuric-Jovicic M, Radovanovic S, et al. A simple method to assess freezing of gait in Parkinson's disease patients[J]. Braz J Med Biol Res, 2010, 43(9):883-889.
42.	Giladi N. Medical treatment of freezing of gait[J]. Mov Disord, 2008, 23(Suppl 2):S482-S488.
43.	Malkani R, Zadikoff C, Melen O, et al. Amantadine for freezing of gait in patients with Parkinson's disease[J]. Clin Neuropharmacol, 2012, 35(6):266-268.
44.	Moreau C, Delval A, Defebvre L, et al. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's disease undergoing subthalamic stimulation:a multicentre, parallel, randomised, placebo-controlled trial[J]. Lancet Neurol, 2012, 11(7):589-596.
45.	Fukada K, Endo T, Yokoe M, et al. L-threo-3,4-dihydroxypheny lserine (L-DOPS) co-administered with entacapone improves freezing of gait in Parkinson's disease[J]. Medical Hyoptheses, 2012, 80(2):209-212.
46.	Fasano A, Herzog J, Seifert E, et al. Modulation of gait coordination by subthalamic stimulation improves freezing of gait[J]. Mov Disord, 2011, 26(5):844-851.
47.	Ferraye MU, Debû B, Pollak P, et al. Deep brain stimulation and gait disorders in Parkinson disease[J]. Rev Neurol, 2012, 166(2):178-187.
48.	Ferraye M, Debu B, Fraix V, et al. Effects of subthalamic nucleus stimulation and levodopa on freezing of gait in Parkinson disease[J]. Neurology, 2008, 70(16 Part 2):1431-1437.
49.	Xie T, Kang UJ, Warnke P, et al. Effect of stimulation frequency on immediate freezing of gait in newly activated STN DBS in Parkinson's disease[J]. Neurol Neurosurg Psychiat, 2012, 83(10):1015-1017.
50.	Moreau C, Defebvre L, Destee A, et al. STN-DBS frequency effects on freezing of gait in advanced Parkinson disease[J]. Neurology, 2008, 71(2):80-84.
51.	Ferraye MU, Deba B, Fraix V,et al. Subthalamic nucleus versus pedunculopontine nucleus stimulation in Parkinson disease:synergy or antagonism?[J]. J Neural transm, 2011, 118(10):1469-1475.
52.	Ferraye MU, Debu B, Fraix V, et al. Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease[J]. Brain, 2010, 133(1):205-214.
53.	Thevathasan W, Cole MH, Graepel CL, et al. A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation[J]. Brain, 2012, 135(5):1446-1454.
54.	Litvinenko IV, Khalimov RR, Trufanov AG, et al. New approach to gait disorders therapy in late stages of Parkinson's disease[J]. Adv Gerontol, 2012, 25(2):267-74.
55.	Frazzitta G, Maestri R, Uccellini D, et al. Rehabilitation treatment of gait in patients with Parkinson's disease with freezing:a comparison between two physical therapy protocols using visual and auditory cues with or without treadmill training[J]. Mov Disord, 2009, 24(8):1139-1143.
56.	Lo AC, Chang VC, Gianfrancesco MA, et al. Reduction of freezing of gait in Parkinson's disease by repetitive robot-assisted treadmill training:a pilot study[J]. J Neuroeng Rehabil, 2010, 7:51.
57.	Bryant MS, Rintala DH, Lai EC, et al. A pilot study:influence of visual cue color on freezing of gait in persons with Parkinson's disease[J]. Disabil Rehabil Assist Technol, 2010, 5(6):456-461.
58.	Arias P, Cudeiro J. Effect of rhythmic auditory stimulation on gait in Parkinsonian patients with and without freezing of gait[J]. PloS One, 2010, 5(3):e9675.

1. Giladi N, Nieuwboer A, et al. Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stage[J]. Mov Disord, 2008, 23(Suppl 2):S423-S425.
2. Tan DM, McGinley JL, Danoudis ME, et al. Freezing of gait and activity limitations in people with Parkinson's disease[J]. Arch Phys Med Rehabil, 2011, 92(7):1159-1165.
3. Moore O, Peretz C, Giladi N, et al. Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait[J]. Mov Disord, 2007, 22(15):2192-2195.
4. Okuma Y, Yanagisawa N, et al. The clinical spectrum of freezing of gait in Parkinson's disease[J]. Mov Disord, 2008, 23(Suppl 2):S426-S430.
5. Lamberti P, Armenise S, Castaldo V, et al. Freezing gait in Parkinson's disease[J]. Eur Neurol, 1997, 38(4):297-301.
6. Giladi N, McDermott MP, Fahn S, et al. Freezing of gait in PD:prospective assessment in the DATATOP cohort[J]. Neurology, 2001, 56(12):1712-1721.
7. Giladi N, Treves TA, Simon ES, et al. Freezing of gait in patients with advanced Parkinson's disease[J]. Neural Transm, 2001, 108(1):53-61.
8. Snijders AH, Nijkrake MJ, Bakker M, et al. Clinimetrics of freezing of gait[J]. Mov Disord, 2008, 23(Suppl 2):S468-S474.
9. Alice N, Fabienne C, Anne-Marie W, et al. Does freezing in Parkinson's disease change limb coordination?[J]. Neurol, 2007, 254(9):1268-1277.
10. Schaafsma, JD, Balash Y, Gurevich T, et al. Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson's disease[J]. Eur J Neurol, 2003, 10(4):391-398.
11. Rahman S, Griffin HJ, Quinn NP, et al. The factors that induce or overcome freezing of gait in Parkinson's disease[J]. Behav Neurol, 2008, 19(3):127-136.
12. Spildooren J, Vercruysse S, Desloovere K, et al. Freezing of gait in Parkinson's disease:the impact of dual-tasking and turning[J]. Mov Disord, 2010, 25(15):2563-2570.
13. Giladi N, Hausdorff JM, et al. The role of mental function in the pathogenesis of freezing of gait in Parkinson's disease[J]. Neurol Sci, 2006, 248(1-2):173-176.
14. Lieberman A. Are Freezing of Gait (FOG) and panic related?[J]. Neurol Sci, 2006, 248(1):219-222.
15. Macht M, Kaussner Y, Moller JC, et al. Predictors of freezing in Parkinson's disease:a survey of 6,620 patients[J]. Mov Disord, 2007, 22(7):953-956.
16. Garcia-Ruiz PJ. Gait disturbances in Parkinson disease. Did freezing of gait exist before levodopa? Historical review[J]. J Neurol Sci, 2011, 307(1-2):15-17.
17. Snijders AH, Leunissen I, Bakker M, et al. Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait[J]. Brain, 2001, 134(1):59-72.
18. Lewis SJG, Barker RA. A pathophysiological model of freezing of gait in Parkinson's disease[J]. Parkinsonism Relat Disord, 2009, 15(5):333-338.
19. Youn J, Cho JW, Lee WY, et al. Diffusion tensor imaging of freezing of gait in patients with white matter changes[J]. Mov Disord, 2012, 27(6):760-764.
20. Jenkinson N, Nandi D, Muthsamy K, et al. Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus[J]. Mov Disord, 2009, 24(3):319-328.
21. Karachi C, Grabli D, Bernard FA, et al. Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson's disease[J]. J Clin Invest, 2010, 120(8):2745.
22. Schweder PM, Hansen PC, Hansen PC, et al. Connectivity of the pedunculopontine nucleus in parkinsonian freezing of gait[J]. Neuroreport, 2010, 21(14):914-916.
23. Kuo SH, Kenney C, Jankovic J, et al. Bilateral pedunculopontine nuclei strokes presenting as freezing of gait[J]. Mov Disord, 2008, 23(4):616-619.
24. Knobl P, Kielstra L, Almeida Q, et al. The relationship between motor planning and freezing of gait in Parkinson's disease[J]. Neurol Neurosurg Psychiat, 2012, 83(1):98-101.
25. Amboni M, Cozzolino A, Longo K, et al. Freezing of gait and executive functions in patients with Parkinson's disease[J]. Mov Disord, 2008, 23(3):395-400.
26. Vandenbossche J, Deroost N, Soetens E, et al. Freezing of gait in Parkinson disease is associated with impaired conflict resolution[J]. Neurorehabil Neural Repair, 2011, 25(8):765-773.
27. Amboni M, Barone P, Picillo M, et al. A two-year follow-up study of executive dysfunctions in parkinsonian patients with freezing of gait at on-state[J]. Mov Disord, 2010, 25(6):800-802.
28. Nantel J, McDonald JC, Tan S, et al. Deficits in visuospatial processing contribute to quantitative measures of freezing of gait in Parkinson's disease[J]. Neuroscience, 2012, 221(9):151-156.
29. Jovanov E, Wang E, Verhagen L, et al. defog-A real time system for detection and unfreezing of gait of Parkinson's patients[J]. Conf Proc IEEE Eng Med Biol Soc, 2009:5151-5154.
30. Tan T, Almeida QJ, Rahimi F, et al. Proprioceptive deficits in Parkinson's disease patients with freezing of gait[J]. Neuroscience, 2011, 192(9):746-752.
31. Vercruysse S, Spildooren J, Heremans E, et al. Freezing in Parkinson's disease:a spatiotemporal motor disorder beyond gait[J]. Mov Disord, 2012, 27(2):254-263.
32. Chee R, Murphy A, Danoudis M, et al. Gait freezing in Parkinson's disease and the stride length sequence effect interaction[J]. Brain, 2009, 132(8):2151-2160.
33. Moreau C, Defebvre L, Bleuse S, et al. Externally provoked freezing of gait in open runways in advanced Parkinson's disease results from motor and mental collapse[J]. Neural Transm, 2008, 115(10):1431-1436.
34. Plotnik M, Giladi N, Hausdorff JM, et al. Bilateral coordination of walking and freezing of gait in Parkinson's disease[J]. Mov Disord, 2008, 27(8):1999-2006.
35. Plotnik M, Hausdorff JM. The role of gait rhythmicity and bilateral coordination of stepping in the pathophysiology of freezing of gait in Parkinson's disease[J]. Mov Disord, 2008, 23(Suppl 2):S444-S450.
36. Tessitore A, Amboni M, Cirillo G, et al. Regional gray matter atrophy in patients with Parkinson disease and freezing of gait[J]. AJNR Am J Neuroradiol, 2012, 33(9):1804-1809.
37. Nieuwboer A, Rochester L, Herman T, et al. Reliability of the new freezing of gait questionnaire:agreement between patients with Parkinson's disease and their carers[J]. Gait Posture, 2009, 30(4):459-463.
38. Giladi N, Tal J, Azulay T, et al. Validation of the freezing of gait questionnaire in patients with Parkinson's disease[J]. Mov Disord, 2009, 24(5):655-661.
39. Shine JM, Moore ST, Bolitho SJ, et al. Assessing the utility of Freezing of Gait Questionnaires in Parkinson's disease[J]. Parkinsonism Relat Disord, 2012, 18(1):25-29.
40. Moore ST, MacDougall HG, Ondo WG, et al. Ambulatory monitoring of freezing of gait in Parkinson's disease[J]. Neurosci Methods, 2008, 167(2):340-348.
41. Popovic MB, Djuric-Jovicic M, Radovanovic S, et al. A simple method to assess freezing of gait in Parkinson's disease patients[J]. Braz J Med Biol Res, 2010, 43(9):883-889.
42. Giladi N. Medical treatment of freezing of gait[J]. Mov Disord, 2008, 23(Suppl 2):S482-S488.
43. Malkani R, Zadikoff C, Melen O, et al. Amantadine for freezing of gait in patients with Parkinson's disease[J]. Clin Neuropharmacol, 2012, 35(6):266-268.
44. Moreau C, Delval A, Defebvre L, et al. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's disease undergoing subthalamic stimulation:a multicentre, parallel, randomised, placebo-controlled trial[J]. Lancet Neurol, 2012, 11(7):589-596.
45. Fukada K, Endo T, Yokoe M, et al. L-threo-3,4-dihydroxypheny lserine (L-DOPS) co-administered with entacapone improves freezing of gait in Parkinson's disease[J]. Medical Hyoptheses, 2012, 80(2):209-212.
46. Fasano A, Herzog J, Seifert E, et al. Modulation of gait coordination by subthalamic stimulation improves freezing of gait[J]. Mov Disord, 2011, 26(5):844-851.
47. Ferraye MU, Debû B, Pollak P, et al. Deep brain stimulation and gait disorders in Parkinson disease[J]. Rev Neurol, 2012, 166(2):178-187.
48. Ferraye M, Debu B, Fraix V, et al. Effects of subthalamic nucleus stimulation and levodopa on freezing of gait in Parkinson disease[J]. Neurology, 2008, 70(16 Part 2):1431-1437.
49. Xie T, Kang UJ, Warnke P, et al. Effect of stimulation frequency on immediate freezing of gait in newly activated STN DBS in Parkinson's disease[J]. Neurol Neurosurg Psychiat, 2012, 83(10):1015-1017.
50. Moreau C, Defebvre L, Destee A, et al. STN-DBS frequency effects on freezing of gait in advanced Parkinson disease[J]. Neurology, 2008, 71(2):80-84.
51. Ferraye MU, Deba B, Fraix V,et al. Subthalamic nucleus versus pedunculopontine nucleus stimulation in Parkinson disease:synergy or antagonism?[J]. J Neural transm, 2011, 118(10):1469-1475.
52. Ferraye MU, Debu B, Fraix V, et al. Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease[J]. Brain, 2010, 133(1):205-214.
53. Thevathasan W, Cole MH, Graepel CL, et al. A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation[J]. Brain, 2012, 135(5):1446-1454.
54. Litvinenko IV, Khalimov RR, Trufanov AG, et al. New approach to gait disorders therapy in late stages of Parkinson's disease[J]. Adv Gerontol, 2012, 25(2):267-74.
55. Frazzitta G, Maestri R, Uccellini D, et al. Rehabilitation treatment of gait in patients with Parkinson's disease with freezing:a comparison between two physical therapy protocols using visual and auditory cues with or without treadmill training[J]. Mov Disord, 2009, 24(8):1139-1143.
56. Lo AC, Chang VC, Gianfrancesco MA, et al. Reduction of freezing of gait in Parkinson's disease by repetitive robot-assisted treadmill training:a pilot study[J]. J Neuroeng Rehabil, 2010, 7:51.
57. Bryant MS, Rintala DH, Lai EC, et al. A pilot study:influence of visual cue color on freezing of gait in persons with Parkinson's disease[J]. Disabil Rehabil Assist Technol, 2010, 5(6):456-461.
58. Arias P, Cudeiro J. Effect of rhythmic auditory stimulation on gait in Parkinsonian patients with and without freezing of gait[J]. PloS One, 2010, 5(3):e9675.

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