Moore Steven T, MacDougall Hamish G, Gracies Jean-Michel, Ondo William G
Department of Neurology, Mount Sinai School of Medicine, Box 1135, 1 E 100th St., New York, NY 10029, USA.
Exp Brain Res. 2008 Feb;184(4):469-78. doi: 10.1007/s00221-007-1113-y. Epub 2007 Sep 8.
The aim of this study was to quantify the dynamic response of locomotion to the first oral levodopa administration of the day in patients with fluctuating Parkinson's disease (PD). Stride length, walking speed, cadence and gait variability were measured with an ambulatory gait monitor in 13 PD patients (8 males) with a clinical history of motor fluctuations. The Unified Parkinson's Disease Rating Scale (UPDRS) gait score (part 29) was also determined by a movement disorders specialist from video recordings. Subjects arrived in the morning in an 'off' state (no PD medication) and walked for a maximum length of 100 m. They then took their usual morning dose of oral levodopa and repeated the walking task at 13 min intervals (on average) over a 90 min period. Changes in stride length over time were fit with a Hill (Emax) function. Latency (time until stride length increased 15% of the difference between baseline and maximum response) and the Hill coefficient (shape of the 'off-on' transition) were determined from the fitted curve. Latency varied from 4.7 to 53.3 min post-administration [23.31 min (SD 14.9)], and was inversely correlated with age at onset of PD (R = -0.83; P = 0.0004). The Hill coefficient (H) ranged from a smooth hyperbolic curve (0.9) to an abrupt 'off-on' transition (16.9), with a mean of 8.1 (SD 4.9). H correlated with disease duration (R = 0.67; P = 0.01) and latency (R = 0.67; P = 0.01), and increased with Hoehn & Yahr stage in the 'off' state (P = 0.02) from 5.7 (SD 3.5) (H&Y III) to 11.9 (SD 4.7) (H&Y IV). Walking speed correlated with changes in mean stride length, whereas cadence and gait variability did not. UPDRS gait score also reflected improving gait in the majority of subjects (8), providing clinical confirmation of the objective measures of the locomotor response to levodopa. Increasing abruptness (H) of the 'off-on' transition with disease duration is consistent with results from finger-tapping studies, and may reflect reduced buffering capacity of pre-synaptic nigrostriatal dopaminergic neurons. Ambulatory monitoring of gait objectively measures the dynamic locomotor response to levodopa, and this information could be used to improve daily management of motor fluctuations.
本研究旨在量化帕金森病（PD）病情波动患者在每日首次口服左旋多巴后运动的动态反应。使用动态步态监测仪对13例有运动波动临床病史的PD患者（8例男性）的步长、步行速度、步频和步态变异性进行测量。运动障碍专家还根据视频记录确定统一帕金森病评定量表（UPDRS）步态评分（第29部分）。受试者于早晨处于“关”状态（未服用帕金森病药物）时前来，行走最长距离为100米。然后他们服用常规早晨剂量的口服左旋多巴，并在90分钟内平均每隔13分钟重复一次步行任务。步长随时间的变化采用希尔（Emax）函数拟合。从拟合曲线确定潜伏期（直到步长增加到基线与最大反应差值的15%所需的时间）和希尔系数（“关-开”转换的形状）。给药后潜伏期为4.7至53.3分钟[23.31分钟（标准差14.9）]，且与PD发病年龄呈负相关（R = -0.83；P = 0.0004）。希尔系数（H）范围从平滑的双曲线（0.9）到突然的“关-开”转换（16.9），平均值为8.1（标准差4.9）。H与疾病持续时间（R = 0.67；P = 0.01）和潜伏期（R = 0.67；P = 0.01）相关，并且在“关”状态下随霍恩和雅尔分期增加（P = 0.02），从5.7（标准差3.5）（H&Y III期）增加到11.9（标准差4.7）（H&Y IV期）。步行速度与平均步长的变化相关，而步频和步态变异性则不然。UPDRS步态评分在大多数受试者（8例）中也反映出步态改善，为左旋多巴运动反应的客观测量提供了临床证实。随着疾病持续时间的增加，“关-开”转换的突然性（H）增加，这与手指敲击研究的结果一致，可能反映了突触前黑质纹状体多巴胺能神经元缓冲能力的降低。动态步态监测客观地测量了对左旋多巴的动态运动反应，这些信息可用于改善运动波动的日常管理。
