|Year : 2019 | Volume
| Issue : 1 | Page : 21-27
Analysis of gait in Parkinson’s disease reflecting the effect of l-DOPA
Banashree Mondal, Supriyo Choudhury, Rebecca Banerjee, Koustav Chatterjee, Sayam Ghosal, Sidharth S Anand, Hrishikesh Kumar
Department of Neurology, RGCM Research Centre, Institute of Neurosciences, Kolkata, West Bengal, India
|Date of Web Publication||17-Apr-2019|
Dr. Hrishikesh Kumar
Department of Neurology and RGCM Research Centre, Institute of Neurosciences Kolkata, 185/1 AJC Bose Road, Kolkata 700017, West Bengal, India.
Source of Support: None, Conflict of Interest: None
BACKGROUND: Gait instability is one of the disabling clinical features of majority of patients suffering from Parkinson’s disease (PD). It is partially responsive to dopamine replacement therapy. Precise evaluation of distinct l-DOPA-sensitive and l-DOPA-resistant gait profiles might help in planning therapy of PD patients with gait disorder.METHOD: In this cross-sectional analytical study, we measured the gait parameters of 70 patients and 37 healthy participants using a 6.1-m long electronic walkway containing thousands of pressure sensors embedded in a carpet. The patients were evaluated in their OFF and ON phases of l-DOPA medication, and the data were compared with age- and gender-matched healthy controls.RESULTS: Except for the cadence, most gait parameters including velocity, stride length, and step length were deranged in PD patients. The mean velocity was significantly higher among healthy volunteers (99.19cm/s) compared to PD patients (73.90cm/s, P value 0.0001). However, the mean cadence was comparable between healthy and patient groups (103.29 vs. 103.39, P value 0.966). Certain temporal parameters (cadence, cycle time, and swing time) were nonresponsive to the dopaminergic therapy.CONCLUSION: On the basis of the findings, we propose that l-DOPA treatment improves most of the spatiotemporal gait parameters but cannot completely eliminate the risk of fall.
Keywords: Dopa responsiveness, gait, GAITRite®, Parkinson’s disease
|How to cite this article:|
Mondal B, Choudhury S, Banerjee R, Chatterjee K, Ghosal S, Anand SS, Kumar H. Analysis of gait in Parkinson’s disease reflecting the effect of l-DOPA. Ann Mov Disord 2019;2:21-7
|How to cite this URL:|
Mondal B, Choudhury S, Banerjee R, Chatterjee K, Ghosal S, Anand SS, Kumar H. Analysis of gait in Parkinson’s disease reflecting the effect of l-DOPA. Ann Mov Disord [serial online] 2019 [cited 2020 Aug 11];2:21-7. Available from: http://www.aomd.in/text.asp?2019/2/1/21/256494
| Introduction|| |
Parkinson’s disease (PD) is associated with a wide range of motor and non-motor symptoms including tremor, bradykinesia, rigidity, postural instability, gait difficulty, and cognitive impairment. Dopamine replacement by l-DOPA remains the mainstay of PD therapeutics to date. However, long-term l-DOPA treatment efficacy in PD is undermined with development of l-DOPA-induced motor fluctuations and involuntary dyskinetic movements. Gait difficulty is one the imposing clinical manifestations causing significant impairment of quality of life in majority of the PD patients.,
The gait patterns of PD patients have been studied for the last four decades., Despite this, contradictory findings are often noted in previous literature regarding changes in gait parameters., The temporal and spatial gait parameters denote function of time and geometric position of footprints in a two-dimensional (2D) plane, respectively. Recently developed tools can precisely measure temporal and spatial gait parameters including speed, step length, stride length, cadence, single support time, double support time, and other clinical gait parameters.,,,.
Precise gait measurement could potentially estimate the risk factors of fall. Certain gait parameters were closely associated with gait stability and risk of fall., Bryant et al. evaluated the effects of l-DOPA on the forward and backward gait patterns and stability in 21 PD patients. Using various methods, the pattern of gait in PD, determinant of falls, and effects of l-DOPA on different gait parameters have also been evaluated by other investigators.,,,
Majority of the gait studies in PD have been conducted in Caucasian population with relatively small numbers of patients.,, Gait ought to be dependent on the body build of the subject should therefore vary with the race or ethnicity of the subjects.,, There is a paucity of published reports studying gait parameters among PD population in India. This study was undertaken to quantitatively evaluate and compare gait parameters in PD patients with healthy participants employing a validated electronic walkway GAITRite® system (GAITRite, CIR Systems Inc., Havertown, PA). The study also aimed to determine specific alterations in individual gait parameters in response to l-DOPA therapy.
| Methods|| |
In this cross-sectional analytical study, 70 idiopathic PD patients (as defined by UK Brain Bank criteria) were recruited from the Movement Disorders Clinic at Institute of Neurosciences Kolkata, a tertiary care referral hospital in West Bengal, India. The patients were between stage 1 and 3 on the Hoehn and Yahr (H and Y) scale with motor fluctuations. Thirty-seven age- and gender-matched healthy participants were recruited from the family members of the patients in the control group. The sample size and sampling were performed as per convenience without formal statistical approach. The participants were from both genders between 30 and 80 years of age. The patients and healthy volunteers with significant systemic (musculoskeletal, cardiovascular, respiratory, cerebrovascular) and other neurological diseases or uncorrected visual disturbances or local ailments that might modify the gait patterns were excluded from the study. The patients and healthy participants with dementia and cognitive impairment (Mini-Mental State Examination [MMSE] score <19) were also excluded. Patients with a history of brain surgery were excluded from the study. Patients who were capable of walking independently (at least 10 m at a stretch) without significant freezing episodes were included in our study. The patients were in a stable dose of l-DOPA for at least 1 month. Formal approval from the institutional ethics committee was obtained and all the study participants signed the informed consent document prior to the study participation.
The PD patients were asked to attend the RGCM Research Center at Institute of Neurosciences Kolkata in the morning without consuming their morning dose of l-DOPA, in the OFF state. The participants were screened based on their medical history and physical examinations. The patients were subjected to Unified Parkinson’s Disease Rating Scale (UPDRS), H and Y scale, and MMSE cognitive scale assessments. They were next instructed to walk at a comfortable pace on the GAITRite system, a 6.1-m long electronic walkway for 4 times (2 times in each direction) for objective measurement of gait parameters. However, the instruction was not reiterated during walking to avoid auditory cues. The average of the four walking trials was used in data analysis. The patients were then instructed to consume the morning dose of l-DOPA medication after the first cycle of assessment. When they returned to the ON phase, the gait assessment was repeated by the same investigator in an identical setting. The gait assessment (for a single cycle) was performed on the healthy participants in a similar way. Adequate care was taken to ensure protection of the patients from sudden fall during the walking trials.
Gait measurement and parameters
The GAITRite system is an electronic walkway containing thousands of pressure-activated sensors embedded in a roll-up carpet of 61-cm wide and 610-cm long. The instrument is designed to compute the gait parameters in real time, by detecting the changes in pressure exerted by the participant while walking. The data are transferred immediately to a connected computer for archival and further analysis.
Measurement of gait speed, cadence, stride length, and other parameters were recorded and stored on the computer for analysis.
Statistical analysis was performed using SPSS version 20.0 (IBM corporation). Demographic data were summarized with mean and standard deviation for numerical variables and frequency for categorical variables. The gait parameters of PD patients and healthy participants were compared using independent sample t test for parametric data and Mann–Whitney U test for nonparametric data. The gait parameters between the ON and OFF phases of the same individual were analyzed using paired sample t test for parametric data and Wilcoxon matched pair signed rank test for nonparametric data. Categorical data were compared by Fisher’s exact test. The significance level was considered as P < 0.05 in two-tailed tests of significance.
| Results|| |
The mean age of 70 PD patients and 37 healthy participants were 64.68±8.89 and 59.64±8.76 years, respectively (P value 0.103). Male subjects comprised of 75.7% of PD patients and 59.5% of healthy participants (P value 0.119). The mean height of the PD patients and healthy participants were 161.52±9.958 and 158.38±8.329cm, respectively. The amount of l-DOPA-equivalent dose consumed by the patients ranged from 200 to 1600mg/day (mean = 647.542mg). The mean UPDRS score in the OFF phase was 40.371±18.496 and in the ON phase was 20.57±12.63 with a P value 0.0001. The H and Y stage ranged from 1 to 3 and mean H and Y was 1.46 [Table 1].
|Table 1: Demographic and clinical characteristics of patients with Parkinson’s disease and healthy participants|
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A comparative assessment of gait parameters between PD patients and healthy participants is presented in [Table 2]. Various gait parameters were significantly different between these two groups including step count, ambulation time, velocity, step length, stride length, and swing time. However, mean cadence, step time, cycle time, and stance time were not statistically different in PD patients as compared to the healthy participants. The mean velocities were slower in PD patients (73.90cm/s) than healthy participants (99.19cm/s, P value 0.0001). However, the mean cadence was comparable between PD patients and healthy participants (103.39 vs. 103.29, P value 0.966).
|Table 2: Comparative assessment of gait parameters between PD patients and healthy participants|
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The Spearman’s correlation coefficient between total UPDRS score (OFF phase) and velocity was −0.508 (P value 0.001). The same between total UPDRS score (OFF phase) and stride length (left, right) were −0.521 (P value 0.001) and −0.513 (P value 0.001), respectively.
[Table 3] represents the differences of gait parameters in the OFF and ON phases. There was a significant increase in the mean velocity from the OFF (73.90cm/s) to the ON phase (83.51cm/s, P value 0.0001) in response to l-DOPA. Most of the temporal and spatial gait parameters showed a significant improvement with administration of l-DOPA, except cadence and single support time.
[Table 4] represents the historical data of selected gait parameters from previous studies conducted in the United States and European Union and a comparison of those with the current study findings.
|Table 4: Comparative review of historical data of selected gait parameters|
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| Discussion|| |
This study evaluates spatiotemporal gait parameters in PD patients using a validated electronic walkway, GAITRite system. The demographic variables (age and gender) were comparable between the cohorts of PD patients and healthy participants. Most of the gait parameters of PD patients (recorded during OFF phase) were significantly different from those of healthy participants. Certain parameters were bilaterally asymmetrical such as step length, stride length, single support time, and double support time. Velocity, ambulation time, step length, stride length, stride velocity, single support time (percentage of cycle time), and double support time (percentage of cycle time) were significantly affected in the PD patients. The number of cycles per minute (cadence), step length differential, cycle time differential, cycle time, base width, stance time, and heel off-on time (percentage of cycle time), however, did not show any significant difference compared to healthy participants. The reduction of velocity in PD patients compared to controls is shown through reductions in both the stride length and stride velocity. Putting it differently, observed variation of gait parameters validates the known clinical characteristics of short, shuffling, and slow gait among PD patients. It was noted that single support time of one foot which corresponds to swing time of opposite foot was reduced significantly in PD patients. Shorter swing time/single support time was possibly due to smaller stride length in PD patients compared to healthy controls.
In the current study, the double support time was found to be higher among PD patients compared to healthy participants but it was not affected in study carried out by Stolze et al. This difference may be reflection of different cohort of patients studied.
As expected, patients with more severe symptoms tend to have a higher degree of gait derangement among PD patients. We appreciated a negative association between the PD severity index (UPDRS) and gait velocity/stride length.
Interestingly, we noticed that certain extent of asymmetry during locomotion existed in healthy participants. The asymmetry indices were measured through cycle time differential, step time differential, and step length differential. In patients with PD, the gait asymmetry is higher compared to healthy participants. We found a significantly higher step time asymmetry (differential) among PD patients compared to healthy participants. This confirmed the finding of an earlier study, which proposed that gait asymmetry (expressed through swing time variability) is increased in PD patients compared to healthy participants and this gait asymmetry is independent of the lateralization of the disease. This gait asymmetry was also found to be heavily dependent on mental attention and cognition among PD patients.
We found that the base width was slightly wider but was not significantly different as compared to the healthy subjects. This is consistent with the expected clinical finding of gait in PD patients where base width remains relatively normal in contrast to patients with normal pressure hydrocephalus (NPH) or ataxia. In a previous clinical study, the gait of NPH patients when compared with that of PD patients revealed that the base width among PD patients was significantly less compared to NPH patients, whereas it was comparable to healthy volunteers. Similar observations on gait speed, cadence, double support time, and stride length were made by previous investigators., However, increased cycle time in PD patients when compared to historical control has been reported. This was contrary to no observed difference in cycle time between PD patients and healthy participants in our study. The reduced swing time and increased stance time balanced the cycle time in our sample of PD patients with that of healthy participants. Consistent with our own observations, Stolze et al. also showed that cycle time was comparable between PD patients and healthy volunteer’s group.
We designed this study with the objective to differentiate and analyze l-DOPA sensitive and l-DOPA resistant gait parameters. We observed that velocity, ambulation time, step length, stride length, double support time, stance time, and base support responded to l-DOPA. However, cadence, step time differential, step length differential, cycle time differential, step time, cycle time, swing time, and single support time did not respond to l-DOPA.
Various mechanisms of l-DOPA-induced changes in gait parameters have been proposed. The temporal parameters related to rhythm were l-DOPA resistant, and parameters requiring expenditure of energy (stride length) were l-DOPA sensitive. The l-DOPA-resistant gait variables are possibly regulated through non-dopaminergic neuronal circuit.
Another aspect of this study was to identify specific gait parameters associated with the risk of fall, which are nonresponsive to l-DOPA. A prospective study by Verghese et al. identified specific markers for fall risk among elderly subjects. They suggested that velocity, swing time, double support time, swing time variability, and stride length variability had significant associations with fall risk. Of these specific markers of fall risk, swing time was found to be l-DOPA resistant in our study. Possibly this finding indicates that l-DOPA might not be able to completely eliminate the risk of fall among PD patients.
In contrast to the hypothesis by Yogev et al., our findings reveal that the gait asymmetry parameters are nonresponsive to l-DOPA. Clinically this observation demands attention, as the asymmetry in gait might lead to increased chances of fall. Hence, inadequate correction of step time differential, step length differential, and cycle time differential by l-DOPA might suggest that l-DOPA may not prevent fall completely. While comparing the gait parameters among diverse studies conducted across countries, it was noted that speed, cadence, and stride length were higher among Caucasians compared to Indian participants, possibly due to differences in height and body build between these two cohorts. Previously, it has been reported that cadence of normal speed walking in healthy elderly men and women were 114 and 121 step/min, respectively, which is at least 10cm/s more than the cadence assessed in our current. Swing time variability was found to be higher in PD patients when compared to the healthy volunteers as reported by Verghese et al. The 2D spatiotemporal parameters in our study were congruent to the three-dimensional (3D) data reported by Rioz et al. The gait parameters of PD patients with the parameters of historical control were compared in earlier studies., The study showed that the mean speed and stride length in PD patients were markedly reduced when compared to the control and the mean cycle time was increased due to the irregularity in swing time. In contrast, our study did not find any significant difference in the mean cycle time or cycle time differential.
Our study has its share of limitations. We did not follow a formal statistical approach in calculating sample size in this study. The gait parameters were measured in a 2D plane due to unavailability of appropriate 3D gait measuring tool in our set up. A future multicentric study with a larger sample size might be planned to reinforce our study findings. The comparison of gait parameters between PD patients with and without gait instability might be another interesting area of work in the future. In this study, we have taken a detailed snapshot of the gait parameters in PD patients but we did not follow-up the patients prospectively. Prospective studies in future might be designed to validate the GAITRite instrument as a tool for estimation of therapeutic responses.
To conclude, our study is the first to report the gait parameters in PD patients compared to healthy control and identify l-DOPA-sensitive and l-DOPA-resistant parameters in India. We found that most of the gait parameters were deranged in PD patients including velocity, stride length, and step length. However, cadence and HH-base support remained unaffected in PD. Several temporal parameters (cadence, step time, cycle time, and swing time) were identified as l-DOPA-resistant gait parameters. It is proposed that l-DOPA cannot completely eliminate the risk of fall as several important gait parameters, which could be marker of falls, were inadequately corrected by l-DOPA. The comparative assessment of gait parameters also revealed sufficient differences across races and ethnicity possibly based on body build and height of the population under review.
| Acknowledgement|| |
We acknowledge our institution for providing support to carry this research project and are thankful to our patients.
| Financial support and sponsorship|| |
Institutional research fund; no extramural funding.
| Conflicts of interest|| |
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]