Pharmacological treatment in Parkinson's disease: Effects on gait

Gait impairments are a hallmark of Parkinson's disease (PD), both as early symptom and an important cause of disability later in the disease course. Although levodopa has been shown to improve gait speed and step length, the effect of dopamine replacement therapy on other aspects of gait is less well understood. In fact, falls are not reduced and some aspects of postural instability during gait are unresponsive to dopaminergic treatment. Moreover, many medications other than dopaminergic agents, can benefit or impair gait in people with PD. We review the effects of pharmacological interventions used in PD on gait, discriminating, whenever possible, among effects on four components of everyday mobility: straight walking, gait initiation, turning, gait adaptability. Additionally, we summarize the effects on freezing of gait. There is substantial evidence for improvement of spatial characteristics of simple, straight-ahead gait with levodopa and levodopa-enhancing drugs. Recent work suggests that drugs aiming to enhance the acetylcholine system might improve gait stability measures. There is a lack of well-designed studies to evaluate effects on more complex, but highly relevant walking abilities such as turning and making flexible adjustments to gait. Finally, paucity in the literature exists on detrimental effects of drugs used in PD that are known to worsen gait and postural stability in the elderly population.     

Falls in Parkinson's disease: evidence for altered stepping strategies on compliant surfaces

Background

Real-world environments comprise surfaces of different textures, densities and gradients, which can threaten postural stability and increase falls risk. However, there has been limited research that has examined how walking on compliant surfaces influences gait and postural stability in older people and PD patients.

Methods

PD patients (n = 49) and age-matched controls (n = 32) were assessed using three-dimensional motion analysis during self-paced walking on both firm and foam walkways. Falls were recorded prospectively over 12 months using daily falls calendars.

Results

Walking on a foam surface influenced the temporospatial characteristics for all groups, but PD fallers adopted very different joint kinematics compared with controls. PD fallers also demonstrated reduced toe clearance and had increased mediolateral head motion (relative to walking velocity) compared with control participants.

Conclusions

Postural control deficits in PD fallers may impair their capacity to attenuate surface-related perturbations and control head motion. The risk of falling for PD patients may be increased on less stable surfaces.     

Influence of pallidal stimulation and levodopa on gait and preparatory postural adjustments in Parkinson's disease.

In order to assess the influence of the bilateral internal globus pallidus (GPi) stimulation on gait and postural instability in Parkinson's disease (PD), we compared gait kinematic parameters and preparatory postural adjustments before and 3 months after stimulation in off- and on-drug conditions for seven patients. Gait kinematic parameters and displacements of centre of pressure (CP) and shoulder computed before a lateral raising task of the leg, were recorded using optoelectric Vicon system. Levodopa (L-dopa) induced a clear benefit for gait velocity (related to an increase of stride length) and also an increase of swing phase duration. GPi stimulation had a limited effect, since the increase of gait velocity was induced by a concomitant increase of stride length and cadence corresponding to a compensatory mechanism. The benefit on swing phase duration was also moderate. Displacements of CP were improved mainly by L-dopa. GPi stimulation and L-dopa had the same beneficial effect on the speed at which the CP was transferred back towards the support side, the ankle velocity, the onset time for ankle displacement, and the decrease of shoulder amplitude towards the support side, which reflects a better postural adjustment phase. This study, based on an objective method, revealed that chronic bilateral GPi stimulation may improve gait and preparatory postural adjustments in severe PD patients with a more limited effect than L-dopa.     

三维运动解析系统测试脑卒中偏瘫步态的运动学定量评价*☆

背景：近年来兴起的三维运动解析技术,可获得多项行走过程中的生物力学参数,代表了目前步态生物力学研究的先进水平。目前该技术在国外开展较多,而国内则较少。国内有限的研究主要集中在对偏瘫患侧下肢矢状面上运动的分析。 目的：对偏瘫患者步行运动进行三维立体运动学分析,与正常步态对比,分析脑卒中偏瘫步态的运动学变化特征。 方法：运用三维运动解析系统,对10例首发缺血性脑卒中偏瘫患者进行步态分析,以10例健康者作为对照。检测健康对照组步行过程中的基本时空参数、步态周期参数与骨盆三维运动角度参数,并对其运动过程中的对称性进行分析。检测两组下肢髋、膝、踝关节的三维运动学角度参数,对比两组下肢关节运动在矢状面、横断面与冠状面上的变化特征。 结果与结论：偏瘫步态表现出下肢运动膝关节屈曲受限,膝关节活动度减小。髋关节内收、旋内不足,外展与旋外角度增大。提示三维运动解析系统测试可测定偏瘫患者步行功能,定量评价偏瘫患者下肢关节运动变化,从而进行相应针对性的稳定性与协调性训练。     

POSTURAL SWAY AND GAIT OF CHILDREN WITH CONVERGENT STRABISMUS

Postural sway and gait of 35 children with convergent strabismus were tested and compared with those of a control group. They were found to have a short stride-length and single-limb support time in walking, particularly at slow speeds. The girls had a large postural sway, but not the boys. The results suggest a common visuomotor disturbance of eye and limb motor-control.     

Is the dopaminergic loss associated with gait and postural impairments in subjects with Parkinson's disease at different motor stages?

Gait and postural control deficiencies in Parkinson's disease (PD) involve several specific motor aspects. The aim of this study was to identify and compare the main changes in gait kinematics and postural control with dopaminergic loss in the striatum region. This is a cross‐sectional study that included 42 individuals with PD at different motor stages, according to the Hoehn & Yahr scale (H&Y). Motor subsection of the Movement Disorder Society‐Unified Parkinson Disease Rating Scale—part III (MDS‐UPDRS III) was used to evaluate general motor aspects. Gait kinematics was assessed using a three‐dimensional motion capture system. Postural control was assessed by stabilometry using force platforms. Dopamine depletion was verified through 99mTc‐TRODAT‐1 (SPECT‐CT) examination. We included 12, 15 and 15 individuals classified as H&Y I, II and III, respectively. We identified worse values of dopamine transporter uptake, MDS‐UPDRS III, gait parameters (velocity, step length and stride length) and center of pressure displacement as the disease progressed. Our results indicate that higher dopaminergic loss and gait and postural control deficits occur between the H&Y levels II and III.     

Effect of bilateral subthalamic nucleus stimulation on balance and finger control in Parkinson's disease

We aimed to quantify the effects of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) on stance and gait ("axial"motor control), and related this to effects on finger movements ("appendicular" motor control). Fourteen PD patients and 20 matched controls participated. Subjects completed several balance and gait tasks (standing with eyes open or closed, on a normal or foam surface; retropulsion test; walking with eyes closed; walking up and down stairs; Get Up and Go test). Postural control was quantified using trunk sway measurements (angle and angular velocity) in the roll and pitch directions. Subjects further performed a pinch grip reaction time task, where we measured isometric grip forces, as well as movement and reaction times. Patients were examined with STN stimulators switched on or off (order randomised across patients), always after a supramaximal levodopa dosage. STN stimulation improved postural control, as reflected by a reduced trunk sway tremor during stance, a reduced duration for all gait tasks, an increased trunk pitch velocity while rising from a chair, and improved roll stability. STN stimulation also improved finger control, as reflected by a reduced time to reach maximum grip force, without altering reaction times and maximum force levels. Improvements in finger control timing did not correlate with reduced task durations during gait. We conclude that STN stimulation affords improvement of postural control in PD, over and above optimal drug treatment. STN stimulation also provides a simultaneous effect on distal and axial motor control. Because improvements in distal and axial motor control were not correlated, we assume that these effects are mediated by stimulation of different structures within the STN.     

Gait abnormalities induced by acquired bilateral pallidal lesions

Background Bilateral pallidal lesions induce a range of cognitive and motor disorders, principally a parkinsonian syndrome in which severe disturbances of gait and gait initiation are frequently reported. However, the precise clinical features of these disorders (and the role of the pallidum therein) remain to be established. Objectives The goal of this study was to characterise gait and gait initiation disorders within the context of a parkinsonian syndrome in patients with acquired, bilateral, pallidal lesions (PAL patients), to compare these disorders to those seen in Parkinson’s disease (PD), and to assess the corresponding physiopathological implications. Patients and methods By using a video motion analysis system (VICON), we studied gait kinematic parameters in two patients presenting with bilateral, pallidal lesions. Kinematic and kinetic parameters were also determined during gait initiation. The two patients were compared with a group of 17 PD patients and to 20 healthy controls. Results In both PAL and PD patients, kinematic parameters (gait and gait initiation) and kinetic parameters (gait initiation) were similarly impaired, evidenced by akinesia (difficulty in initiating gait characterized by impairment of anticipatory postural adjustments). Hypokinesia and bradykinesia (respectively reduced stride length and reduced speed during gait) were also noted. Conclusion The gait and gait initiation disorders seen in cases of bilateral pallidal lesions (namely akinesia, hypokinesia and bradykinesia) are similar to those observed in PD. Subject to confirmation in more extensive studies, we hypothesize that bipallidal patients may present higher level gait disorders,with potential mediation by cognitive impairment.     

Postural sway and effect of levodopa in early Parkinson's disease

OBJECTIVE: To characterize postural stability control and levodopa responsiveness in early Parkinson's disease (PD). METHODS: Postural sway was studied during quiet stance in ten patients within six years of PD onset, both before (OFF) and after (ON) regular oral levodopa dosing. Postural sway was recorded using a force platform during 30 sec with eyes open, and six dependent variables were examined. RESULTS: Mild baseline subclinical changes in postural sway were recorded in our patients. Clear benefit was observed in five out of six characteristics (mean sway, transversal sway, sagittal sway, sway intensity, and sway area) in the ON condition. CONCLUSION: Postural control mechanisms are affected early in PD and modulated by dopamine.     

Gait disturbances related to dysfunction of the cerebral cortex and basal ganglia

This review aimed to characterize the gait disturbances in Parkinson disease (PD) and highlight how a rehabilitation program would affect the care of patients with PD. The typical PD gait is a type of hypokinetic gait characterized by reduced stride length and velocity; shortening of the swing phase; and increase in the stance phase, double-limb support duration, and cadence rate. In the advanced phase of PD, start hesitation, shuffling and festinating gait, propulsion, and freezing of gait (FOG) become remarkable. Notably, in PD, attention may influence gait control, and sensory cueing may improve the stride length. Our study on gait impairment in PD by using a three-dimensional motion analysis system revealed that the stride length and walking speed decreased, but there was no change in cadence. The decreased stride length was due to reduction in the range of movement at the leg and pelvic joints. A 4-week physical rehabilitation program for PD improved the stride length and walking speed;this was achieved by increasing the range of movement of at the leg and pelvic joints. We also assessed the effects of a rehabilitation program for patients with PD who experienced FOG. Although the lower limb function was more impaired in patients with PD and FOG than in those with PD without FOG, the rehabilitation program was effective even for patients with PD and FOG. FOG might be associated with functional impairment of the lower limb as well as dysfunction of the fronto-basal ganglia circuit. We also reported 3 cases of camptocormia (bent spine syndrome) with autonomic dysfunction and rapid eye movement (REM) sleep behavior disorders (RBD) and compared their symptoms with those reported elsewhere. We think that the pedunculopontine nuclear area may control the postural muscle tone and locomotion in PD. On the basis of the results of our rehabilitation programs, we speculate that physical modalities may modify synaptic plasticity by utilizing the cerebellar and/or afferent sensory system. These alternative systems are believed to be functionally intact in patients with PD.     

Does postural asymmetry indicate directionality of rotation in rats: role of sex and handling

Postural asymmetry of male and female Wistar rats was assessed during 4 tests: (a) tail suspension, (b) tail holding, (c) tail pinch and (d) walking on a narrow path. The tests were conducted prior to and after (+)-amphetamine (1 mg/kg, i.p.) administration. Rotational directionality was assessed in a rotometer.Only in female rats did postural adjustment during the tail-pinch predict with borderline significance the direction of circling prior to and after amphetamine. In both surgically castrated and conjugated estrogen-treated male rats, and in sham-castrated and handled males, the tail-pinch test caused the same dominant directionality as rotation under amphetamine. The duplicity of postural tests suggests that there is a multitude of systems controlling and modulating postural response.     

Action observation improves sit-to-walk in patients with Parkinson's disease and freezing of gait. Biomechanical analysis of performance

IntroductionFreezing of gait (FoG) is one of the most disabling gait disorders in Parkinson's disease (PD), reflecting motor and cognitive impairments, mainly related to dopamine deficiency. Recent studies investigating kinematic and kinetic factors affecting gait in these patients showed a postural instability characterized by disturbed weight-shifting, inappropriate anticipatory postural adjustment, worse reactive postural control, and a difficulty executing complex motor tasks (i.e. sit-to-walk). These symptoms are difficult to alleviate and not very responsive to Levodopa. For this reason, additional therapeutic actions based on specific therapeutic protocols may help patients with their daily lives. We conducted a randomized control trial aimed to test if two clinical protocols for PD patients with FoG were effective to improve postural control.MethodsRehabilitation protocols, conceived to improve gait, were based on learning motor exercises with the Action Observation plus Sonification (AOS) technique, or by the use of external sensory cues. We collected biomechanical data (Center of Mass COM, Center of Pressure COP, and moving timings), using the sit-to-walk task as a measure of motor and gait performance.ResultsKinetic and kinematic data showed that when treatment effects consolidate, patients treated with AOS protocol are more efficient in merging subsequent motor tasks (sit-to-stand and gait initiation), and diminished the total moving time and the area of the COP positions.ConclusionWe demonstrated for the first time that PD patients with FoG treated with an AOS protocol aimed at relearning appropriate gait patterns increased balance control and re-acquired more efficient postural control.     

The unilateral 6-OHDA rat model of Parkinson's disease revisited: an electromyographic and behavioural analysis

The characteristic locomotor disturbances of Parkinson's disease (PD) include shuffling gait, short steps and low walking velocity. In this study we investigated features of walking and turning in a rat model of PD caused by unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed gait and electromyographic (EMG) patterns of the ankle flexor tibialis anterior and the knee extensor vastus lateralis of the hindlimb, and triceps brachii of the forelimb, during overground locomotion, spontaneous rotation (turning) and apomorphine-induced rotation. When compared with control rats, rats with unilateral dopamine depletion displayed a shuffling gait and short stride lengths. This locomotor pattern was accompanied by prolonged ankle flexor activity on the ipsilateral side, and prolonged activity of knee extensors on the contralateral side. The dopamine depletion also led to enhanced contraversive rotations after an apomorphine challenge. The EMG recordings during drug-induced rotation suggested that hindlimb stepping was a reflective response to an active drive produced by forelimbs. The EMG recordings of the contralateral side during rotation were marked by reduced ankle flexor activity and increased knee extensor activity. Furthermore, EMG recordings indicated that dopamine-agonists induce rotational bias by altering the coupling between ipsi- and contralateral hindlimbs, and between forelimbs. In straight walking, however, the gait of 6-OHDA lesion animals reflected normal, coupled hindlimb stepping as controlled by spinal pattern generators. The data suggest that the unilateral rat model of PD resembles key features of human parkinsonian gait, and that asymmetric descending input may underlie the observed changes in gait patterns.     

The effect of gait speed on three-dimensional analysis of hindlimb kinematics during treadmill locomotion in rats

The two-dimensional (2D) kinematic approach is by far the most popular technique in rat gait analysis. This is a simple inexpensive procedure, which requires only one camera to record the movement. However, maximal precision and accuracy of the kinematic values are expected when the experimental protocol includes a three-dimensional (3D) motion analysis methodology. Locomotor speed is a basic kinematic parameter that is often neglected in most studies of movement disorders and neurological diseases. Because locomotor speed can act as confounder for the interpretation of the obtained results we also focused our attention on the relation between speed and 3D hindlimb kinematics. Our experimental set-up consisted of a motion capture system with four CMOS cameras which allowed a non-invasive estimation of the instantaneous position of color markers in a 3D measurement volume. Data were recorded while rats walked at different treadmill speeds (30 vs 60 cm/s). For the first time we reported detailed kinematic data for the sagittal, coronal and transverse plane during treadmill locomotion in rats. Despite the overall time course patterns of the curves were identical, we found significant differences between values of joint angular motion at 30 and 60 cm/s at selected points of the step cycle. The adaptation to higher treadmill walking included greater joint angular excursions. The present report highlights the importance of walking speed when evaluating rat hindlimb kinematics during gait. Hopefully, this study will be useful in experimental data assessment when multiple gait abnormalities are expected to occur in all planes of motion.     

Managing Gait,Balance, and Posture in Parkinson’s Disease

Purpose of Review

Postural instability and gait difficulties inexorably worsen with Parkinson’s disease (PD) progression and become treatment resistant, with a severe impact on autonomy and quality of life. We review the main characteristics of balance instability, gait disabilities, and static postural alterations in advanced PD, and the available treatment strategies.

Recent Findings

It remains very difficult to satisfactorily alleviate gait and postural disturbances in advanced PD. Medical and surgical interventions often fail to provide satisfactory or durable alleviation of these axial symptoms, that may actually call for differential treatments. Exercise and adapted physical activity programs can contribute to improving the patients’ condition.

Summary

Gait, balance, and postural disabilities are often lumped together under the Postural Instability and Gait Difficulties umbrella term. This may lead to sub-optimal patients’ management as data suggest that postural, balance, and gait problems might depend on distinct underlying mechanisms. We advocate for a multidisciplinary approach from the day of diagnosis.

     

Footstep adjustments used to turn during walking in Parkinson's disease

Turning during walking is frequently problematic in Parkinson's disease (PD). The spatiotemporal characteristics of footstep adjustments used to turn 60 and 120 degrees were examined in 10 people with PD and 10 age, gender‐ and height‐matched control subjects, using three‐dimensional motion analysis. Control subjects used a recognizable pattern of spatial and temporal footstep modulations to turn. Participants with PD demonstrated significant differences in almost all variables. They (1) failed to turn as far as their peers; (2) showed a similar but scaled‐down pattern of spatial adjustments to turn; (3) used shorter strides when walking, with exaggerated reductions when turning; and (4) demonstrated small but significant temporal differences in step time adjustments. Group differences were more marked for the larger turn. Spatial results, interpreted in light of hypothesized basal ganglia dysfunction, are consistent with a normal motor command but impaired ability to maintain movement amplitude. Differences in adjustment of step time to turn may reflect impaired locomotor timing control in subjects with PD during challenging gait tasks. © 2008 Movement Disorder Society     

The assessment of gait disorders in patients with Parkinson's disease using the three-dimensional motion analysis system Vicon

BACKGROUND AND PURPOSE: Gait disorders are a common symptom of Parkinson's disease (PD) and can occur in the early stage of the disease. The most characteristic gait disorders in that disease affect pace and cadence. This study was designed to assess spatiotemporal and kinematic gait parameters of patients with PD using the three-dimensional motion analysis system Vicon. MATERIAL AND METHODS: 32 patients (14 women and 18 men; age range: 50-75) treated for PD in the Department of Neurology were studied. The control group consisted of 32 healthy persons (13 women and 19 men, age range: 52-77). Gait analysis using the Vicon 3D system took place in the Biokinetics Laboratory in the Academy of Physical Education in Kraków. The Vicon 3D system enables computerized registration and analysis of motion in three-dimensional space. RESULTS: The analysis of basic spatiotemporal parameters of gait revealed that PD patients had considerably lower walking speed, stride length and cadence and longer time of double support than controls. The assessment of kinematic gait parameters showed that PD patients had decreased motion range in the joints of the lower limbs and began the double support phase earlier and delayed the swing phase when compared to healthy controls. CONCLUSION: Our study shows a difference between PD patients and healthy controls at similar age both in angle changes and in spatiotemporal parameters of gait.     

Falls in Parkinson's disease: Kinematic evidence for impaired head and trunk control

Changes in stride characteristics and gait rhythmicity characterize gait in Parkinson's disease and are widely believed to contribute to falls in this population. However, few studies have examined gait in PD patients who fall. This study reports on the complexities of walking in PD patients who reported falling during a 12‐month follow‐up. Forty‐nine patients clinically diagnosed with idiopathic PD and 34 controls had their gait assessed using three‐dimensional motion analysis. Of the PD patients, 32 (65%) reported at least one fall during the follow‐up compared with 17 (50%) controls. The results showed that PD patients had increased stride timing variability, reduced arm swing and walked with a more stooped posture than controls. Additionally, PD fallers took shorter strides, walked slower, spent more time in double‐support, had poorer gait stability ratios and did not project their center of mass as far forward of their base of support when compared with controls. These stride changes were accompanied by a reduced range of angular motion for the hip and knee joints. Relative to walking velocity, PD fallers had increased mediolateral head motion compared with PD nonfallers and controls. Therefore, head motion could exceed “normal” limits, if patients increased their walking speed to match healthy individuals. This could be a limiting factor for improving gait in PD and emphasizes the importance of clinically assessing gait to facilitate the early identification of PD patients with a higher risk of falling. © 2010 Movement Disorder Society     

Progression of postural control and gait deficits in Parkinson's disease and freezing of gait: A longitudinal study

Background and aimsThe relationship between impaired postural control and freezing of gait (FOG) in Parkinson's disease (PD) is still unclear. Our aim was to identify if postural control deficits and gait dysfunction progress differently in freezers compared to non-freezers and whether this relates to FOG development.Methods76 PD patients, classified as freezer (n = 17) or non-freezer (n = 59), and 24 controls underwent a gait and postural control assessments at baseline and after 12 months follow-up. Non-freezers who developed FOG during the study period were categorized as FOG converters (n = 5). Gait was analyzed during walking at self-preferred pace. Postural control was assessed using the Mini-BESTest and its sub-categories: sensory orientation, anticipatory, reactive and dynamic postural control.ResultsMini-BESTest scores were lower in PD compared to controls (p < 0.001), and in freezers compared to non-freezers (p = 0.02). PD has worse anticipatory (p = 0.01), reactive (p = 0.02) and dynamic postural control (p = 0.003) compared to controls. Freezers scored lower on dynamic postural control compared to non-freezers (p = 0.02). There were no baseline differences between converters and non-converters. Decline in postural control was worse in PD compared to controls (p = 0.02) as shown by a greater decrease in the total Mini-BESTest score. Similar patterns were found in freezers (p = 0.006), who also showed more decline in anticipatory (p < 0.001) and dynamic postural control (p = 0.02) compared to non-freezers. FOG converters had a greater decline in the total Mini-BESTest (p = 0.005) and dynamic postural control scores (p = 0.04) compared to non-converters. Gait outcomes showed no significant differences in any of the analyses.ConclusionFOG is associated with more severe decline in postural control, which can be detected by the clinical Mini-BESTest.