Galna Brook, Lord Sue, Burn David J, Rochester Lynn
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK.
Mov Disord. 2015 Mar;30(3):359-67. doi: 10.1002/mds.26110. Epub 2014 Dec 27.
Gait impairment in Parkinson's disease (PD) persists despite the use of dopaminergic therapy. Motor phenotype associated with greater postural instability and gait difficulty is related to a greater risk of motor decline and may be influenced by non-dopaminergic pathology. This study documents the progression of gait impairment over 18 months in an incident cohort of PD with regard to phenotype and medication. Gait characteristics were measured in 121 PD and 184 controls, and 18 months later in 108 PD participants. Sixteen gait characteristics were examined with respect to five broad domains for PD and motor phenotype. Correlations between change in levodopa (l-dopa) equivalent daily dose and gait were used to identify dopa-responsive and nonresponsive characteristics. Pace and rhythm deteriorated over 18 months in people with PD, with other gait domains remaining stable. People with a postural instability and gait difficulty phenotype had more impaired gait at baseline compared with a tremor-dominant phenotype, which was most evident in temporal characteristics. In contrast, pace and variability deteriorated over the subsequent 18 months in the tremor-dominant phenotype only. Weak but statistically significant correlations were found between increased l-dopa medication and less deterioration in pace and asymmetry. Significant gait impairment is evident in very early disease despite optimal medication. Change over 18 months is subtle and discrete, and is more pronounced in the tremor-dominant phenotype. Some features of gait are refractory to dopaminergic therapy, implicating a non-dopaminergic contribution. This may explain more temporal gait disturbance in the postural instability and gait difficulty phenotype.
尽管使用了多巴胺能疗法，帕金森病（PD）患者的步态障碍仍然存在。与更大的姿势不稳和步态困难相关的运动表型与更大的运动功能衰退风险有关，并且可能受到非多巴胺能病理改变的影响。本研究记录了新发PD队列中18个月内步态障碍在表型和药物治疗方面的进展情况。对121例PD患者和184名对照者进行了步态特征测量，18个月后对108例PD参与者再次进行测量。针对PD和运动表型的五个广泛领域检查了16项步态特征。通过左旋多巴（l - 多巴）等效日剂量变化与步态之间的相关性来确定对多巴有反应和无反应的特征。PD患者在18个月内步速和节律变差，其他步态领域保持稳定。与震颤为主的表型相比，姿势不稳和步态困难表型的患者在基线时步态受损更严重，这在时间特征上最为明显。相比之下，仅震颤为主的表型在随后的18个月内步速和变异性变差。发现l - 多巴药物剂量增加与步速和不对称性恶化程度降低之间存在微弱但具有统计学意义的相关性。尽管进行了最佳药物治疗，但在疾病早期仍明显存在显著的步态障碍。18个月内的变化细微且离散，在震颤为主的表型中更为明显。步态的一些特征对多巴胺能疗法难治，这意味着存在非多巴胺能的作用。这可能解释了姿势不稳和步态困难表型中更多的时间性步态障碍。
