BJMB
Brazilian Journal of Motor Behavior
Special issue:
“Control of Gait and Posture: a tribute to Professor Lilian T. B.
Gobbi”
!
Oliveira, Teixeira,
Coelho
2023
VOL.17
N.4
93 of 102
Effect of antiparkinsonian medication on spatiotemporal gait parameters of individuals
with Parkinson’s disease: comparison between individuals with and without freezing of
gait
JÚLIA A. OLIVEIRA
1
| LUIS A. TEIXEIRA
1
| DANIEL B. COELHO
1,2
1
Human Motor Systems Laboratory, School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil
2
Biomedical Engineering, Federal University of ABC, São Bernardo do Campo, SP, Brazil
Correspondence to:!Daniel Boari Coelho - Centre for Engineering, Modeling and Applied Social Sciences (CECS), Federal University of ABC (UFABC), Alameda da
Universidade, s/no, Bairro Anchieta. São Bernardo do Campo, SP 09606-045 Brazil.
email: daniel.boari@ufabc.edu.br
https://doi.org/10.20338/bjmb.v17i4.351
HIGHLIGHTS
• The gait of pwPD tends to be slower, characterized by
narrow and short steps.
• Levodopa improves speed in gait in pwPD.
• Medication improved gait performance equivalently in
the freezers and non-freezers.
ABBREVIATIONS
FOG Freezing of gait
Freezers Individuals with FOG
H&Y Hoehn and Yahr
H1 Hypothesis 1
H2 Hypothesis 2
LEDD Levodopa-equivalent daily dose
Mini-BESTest Balance Assessment System Mini-Test
scale
MoCA Montreal Cognitive Scale Assessment
NFOG-Q New Freezing of Gait Questionnaire
Non-freezers Individuals without FOG
OFF ~12 h after the last medication ingestion
ON 1 h after medication ingestion
PD Parkinson’s disease
PIGD Postural instability and gait disturbances
TD Dominant tremor
UPDRS Unified Parkinson’s Disease Rating Scale
UPDRS_II Activities of daily living
UPDRS_III Motor symptoms
PUBLICATION DATA
Received 10 02 2023
Accepted 01 06 2023
Published 20 06 2023
BACKGROUND: The gait of individuals with Parkinson’s disease (PD) tends to be slower,
characterized by narrow and short steps. During the medication, the self-selected gait speed
of individuals with PD increases. However, when looking individually at the spatiotemporal
parameters of gait, the medication induces different and not always consistent effects.
However, the effects of medication and freezing of gait during walking in individuals with PD
are unknown.
AIM: The present study aims to analyze the effect of antiparkinsonian medication and freezing
of gait (FoG) on spatiotemporal gait parameters in individuals with PD.
METHOD: For this purpose, we compared gait parameters in individuals with FoG (freezers, n
= 11) and without FoG (non-freezers, n = 11). Spatiotemporal gait parameters (speed,
cadence, step length, step time, step width, stride length, stride time, swing phase, and double
support) and clinical scales (parts II and III of the Unified Parkinson’s Disease Rating Scale,
Hoehn and Yahr, Montreal Cognitive Assessment questionnaire and Mini-Test scale of
Balance Assessment System) were analyzed in two experimental sessions, counterbalanced
between individuals: one in the ON medication state (1 h after ingestion), and another in the
OFF medication state (~12 h after the last ingestion). Linear mixed effects models 2 (group:
freezers X non-freezers) X 2 (condition: ON X OFF) were used.
RESULTS: We found that gait speed, stride, and step length were significantly higher in the
ON than in the OFF condition for both freezers and non-freezers, and significantly lower in the
freezers than in the non-freezers, regardless of the medication state.
INTERPRETATION: These results indicate that medication improved gait performance
equivalently in both freezers and non-freezers.
KEYWORDS: Movement disorders | Levodopa | Motor control | Biomechanics
INTRODUCTION
The gait of individuals with Parkinson’s disease (PD) tends to be slower, characterized by narrow and short steps, flexed trunk,
little or no arm swing
1
, and slow and spasmodic turning
2
. When specifically analyzing the spatiotemporal parameters of gait in individuals
with PD compared to healthy individuals, studies have shown a decrease in speed
3,4,5,6
, an increase in the number of steps
5
, a decrease
in step length
4,5
and stride length
5
; shorter duration of swing phase and single-leg stance phase
5
; and longer duration of the double
support phase
5,7
. This change in gait pattern is considered one of the symptoms that most affect the quality of life of individuals with PD,
responsible for about 50% of the individual falls
8
, which can result in hospitalization and involvement of motor function.
In addition to the classic characteristics of parkinsonian gait, some individuals have freezing of gait (FoG), defined as “brief and
episodic absence or marked reduction in the forward progression of the feet, despite the intention to walk”
9
. Individuals with this symptom
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often report that their feet are stuck to the ground, making it impossible to perform the step for a few moments. These episodes affect
individuals’ gait, increasing the risk of falling and decreasing independence and quality of life. FoG is usually a transient and short-lived
episode. It can be triggered at different moments of gait, such as the beginning of the movement, turning, and passing obstacles, among
others. As the disease progresses, FoG may increase in both frequency and duration. Individuals with FoG (freezers), when compared to
individuals without FoG (non-freezers), have more severe motor and cognitive symptoms, longer duration of disease, use a higher
dosage of antiparkinsonian medication
10
, and have greater cortical activation during gait, indicating less automaticity
11
. Furthermore, a
longitudinal study by Glover et al.
12
showed that freezers had more pronounced gait changes with disease progression evaluated from
stride length and speed, duration of the swing phase, and single support compared to non-freezers. Landes et al.
13
showed that intra-
patient variability in spatiotemporal gait parameters in freezers is much higher compared to other groups.
One of the main drug treatments for PD aims at dopaminergic replacement based on the administration of levodopa, an
immediate precursor of dopamine, capable of overcoming the blood-brain barrier and entering the brain, unlike exogenous dopamine.
Once in the brain, levodopa rapidly converts to dopamine through simple enzymatic reactions. Dopaminergic replacement therapy is
made up of two main components. The first is characterized by short-term effects (about a few hours), related to the concentration of
circulating dopamine. The second is characterized by long-lasting effects (about days to weeks), related to neural plasticity induced by
dopaminergic signaling
14
. However, there is no evidence to demonstrate the decrease in disease progression with the conventionally
used drug treatment
15
. However, fluctuations in the motor response dependent on medication administration are observed, known as the
ON-OFF phenomenon, characterized by improvement of the motor pattern in the ON medication state and motor worsening with the
decrease in the blood concentration of the medication
14
. Specifically, regarding gait, during the ON medication, the self-selected gait
speed of individuals with PD increases
5,16
. However, when looking individually at the spatiotemporal parameters of gait, the drug induces
different and not always consistent effects. For example, Curtze et al.
16
showed that the ON state increased speed and stride length but
did not influence cadence, step initiation, double support time, and swing time.
On the other hand, Mondal et al.
5
showed a decrease in the double support time in the ON state, a decrease in the number of
steps, and an increase in step and stride lengths. Furthermore, in the same study, the medication did not affect cadence, unilateral
support time, step time, cycle time, swing time, and width of the support base. Thus, it is still unclear what the effect of dopaminergic
medication would be on the spatiotemporal parameters of the gait of the person with PD, causing different explanations to appear in the
literature. For example, Curtze et al.
16
argue that levodopa improves gait without changing the parameters related to its dynamic stability.
On the other hand, Mondal et al.
5
consider that parameters related to gait rhythm are resistant to levodopa and that parameters that
require caloric expenditure (i.e., stride length) are sensitive to medication.
Suppa et al.
17
analyze the effect of medication and FoG on spatiotemporal gait parameters. The authors found a non-
significant effect of the fact FoG, whereas the factor “dopaminergic therapy” was significant only for speed, but not for stride length, stride
time, and cadence. ANOVA also showed a significant interaction between factors FoG and “dopaminergic therapy” for speed, stride
length, and stride time. However, the authors measure gait during a modified 3-m Timed Up and Go, resulting in a limited number of
steps required for measurement
18
. In a turning task, McNeely and Earhart
19
compared the effect of medication on subjects with and
without FoG. Their results showed that in the OFF state, the group with FoG performed worse on this task. However, with medication,
both groups improved their performance on the task. Still, the group with FoG showed a more pronounced improvement and reached a
performance similar to that of the group without FoG in the ON medication state
19
. The authors concluded that this greater improvement
occurred because the group with FoG has a greater degree of disability in the OFF state and, therefore, a greater potential for
improvement. Therefore, it is possible to assume that the improvement in gait induced by the medication may follow this pattern, being
more evident in the group with FoG. However, the authors cite as a limitation the fact that the group with FoG took a higher drug dosage
than the group without FoG. Given this limitation, it is interesting to evaluate this hypothesis, controlling for it and other possible clinical
differences between these groups.
This study aims to analyze the effect of antiparkinsonian medication on gait spatiotemporal parameters, comparing freezers
versus non-freezers, in individuals with PD. The following hypotheses were formulated: (H1) The medication improves the gait both in
freezers and non-freezers; (H2) the medication induces a more pronounced improvement in gait in freezers.
METHODS
Participants
The study included 22 individuals (5 women; mean age = 64.1 years; disease duration = 10.5 years) with a clinical diagnosis of
idiopathic PD made by a neurologist. Eleven participants were freezers (based on the New Freezing questionnaire of Gait questionnaire,
NFOG-Q) and 11 were non-freezers. Participants were between stages 1 and 4 of PD, and classified by the criteria of the modified
Hoehn and Yahr (H&Y) scale (Median = 2; minimum = 1; maximum = 4), obtained a minimum score of 15 (Median = 24; minimum = 15;
maximum = 30) on the Montreal Cognitive Scale Assessment (MoCA), with self-declaration of no neurological impairment other than PD
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or musculoskeletal alterations that could impair task performance. Participants were informed about the objectives, benefits, and risks
associated with the study. All signed the informed consent form by the procedures approved by the local research ethics committee
(CAAE number 21948619.6.0000.5594).
Task and equipment
Participants walked barefoot at a self-selected comfortable speed over a 10-m long walkway for gait assessment. At ground
level, there was a pressure system (FDM, Zebris, sampling rate: 100Hz, accuracy 5%), composed of two coupled electronic walkways in
the middle of the walkway. The Zebris system is an electronic walkway with pressure-activated sensors embedded into a 60-cm wide x 6-
m long mat. With this equipment, it is possible to measure gait parameters in real time by detecting the change in pressure exerted by the
participant’s feet when walking on the footbridge. Data were automatically transferred to a computer connected to the system to be
further processed and analyzed off-line.
Procedures
The volunteers participated in two experimental sessions at the Laboratory of Biomechanics and Motor Control at the Federal
University of ABC, one of the sessions being in the ON medication state and the other in the OFF state. To be considered in the ON
state, participants had to have taken their dopaminergic medication one hour before starting the session to ensure dosage stabilization.
In the OFF state, participants had to have been at least 12 hours without using any PD medication at the experiment’s time. The order of
the sessions was counterbalanced among the participants, and they were held at an interval of one week. The total dose of these drugs
was converted into a levodopa-equivalent daily dose (LEDD), based on the formula developed by Tomlinson, Stowe
20
.
Initial assessments consisted of an anamnesis to collect clinical data, medication dosage, and time of diagnosis of the disease.
The following evaluation scales were also applied: parts II and III of the Unified Parkinson’s Disease Rating Scale (UPDRS, parts II-III) to
assess activities of daily living and motor symptoms, respectively, H&Y to assess disease severity, NFOG-Q to assess freezing of gait
21
,
MoCA questionnaire for cognitive assessment
22,
the Balance Assessment System Mini-Test scale (Mini-BESTest) for assessing global
body balance
23
. Classification of PD subtype into dominant tremor (TD) and postural instability and gait disturbances (PIGD) was
performed according to Stebbins, Goetz
24
, using the average of 8 scale items to calculate the TD score and five items for the PIGD
score. Individuals whose ratio between the average of the TD/PIGD scores ≥ 1.5 were classified as subtype TD, ≤ 1 classified as
subtype PIGD, and results between > 1 and < 1.5 were classified as undetermined. In addition, specific motor symptoms related to the
TD (UPDRS_TD) and PIGD (UPDRS_PIGD) subtypes were assessed using the average scores of the same items used for classification.
The same evaluator performed all clinical evaluations.
After the initial clinical evaluations and a 10-min rest period, the participants performed ten trials of the experimental task in
each condition (ON and OFF). Participants were instructed to walk at a comfortable speed for 10 m, passing over the electronic walkway.
The trials were made sequentially, with a short rest between them (<10 s). An evaluator was close by to ensure protection and prevent
the participants from falling during the entire experimental procedure.
Variables
The average result of all occurrences of a given variable in each trial was used and, subsequently, the average of the ten trials
per condition for each participant. The analyzed spatiotemporal gait parameters were the following:
a. Gait speed: average speed, computed as a function of the time spent to cover the 6-m distance to cross the walkway;
b. Cadence: given by the number of steps per minute;
c. Average step length: given by the distance between the heel of one foot and the heel of the other foot in each step during gait.
For analysis, an average was made between the length of the right and left steps;
d. Step time: given by the time interval obtained from two successive contacts of the feet with the ground;
e. Step width: transverse distance from the center of the heel of one foot to the center of the heel of the other;
f. Stride length: distance between two successive contacts of the same foot, measured from the heel;
g. Stride time: given by the time interval between two successive contacts of the same foot with the ground;
h. Relative time of the swing phase: given by the percentage of the stride time used in the swing phase, in which one of the feet is
not in contact with the ground, being projected forward to make the next contact;
i. Total double support: given by the percentage of stride time in the double support phase, in which both feet are in contact with
the ground simultaneously. This is the sum of two partial double supports.
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Data analysis
The Levene and Shapiro-Wilk tests were used to analyze the homogeneity of variances and normality in data distribution and
residuals. In addition, demographic data and clinical scales were analyzed using the Wilcoxon test for intragroup comparisons
(medication effect) and the Mann-Whitney U test for intergroup comparisons (FoG effect). To choose the data transformation method, the
Pearson P statistical function was divided by the degrees of freedom (P/df); this ratio can be compared between the different forms of
normalization and indicates which data follow the closest distribution normality (ratio close to 1). The arc-sine transformation was then
used to normalize the H&Y data, and the ordered quantile transformation to normalize the spatiotemporal gait parameters and data on
disease duration and medication dosage.
With the data normalized, linear mixed-effects models 2 (group: freezers X non-freezers) x 2 (medication: ON X OFF) were
fitted using restricted maximum likelihood estimation to investigate whether the results of the spatiotemporal gait parameters differed
between groups (freezers and non-freezers) and conditions (ON and OFF). Participants were considered random intercepts. The
significance level for all analyses was set at p < 0.05, and Bonferroni’s post hoc test was used to analyze interactions. Analyzes were
performed using Minitab (Minitab 19.2, 64-bit) and R (version 4.1.1). The means and standard deviations of the untransformed values will
be displayed.
RESULTS
Of the 11 individuals in the freezer group, eight were classified with the PIGD subtype, two with the TD subtype, and one
undetermined in the ON state; in the OFF state, there were 9, one, and one, respectively, for each subgroup. Of the 11 participants in the
non-freezers group, four were classified with the PIGD subtype, five with the TD subtype, and two undetermined in the ON state; in the
OFF state, there were two, six, and three, respectively, in each subgroup.
Table 1 presents the demographic and clinical characteristics of the participants, separated by groups. There were no
significant differences between groups in terms of age, weight, height, and disease duration, although the latter showed a tendency
towards statistical difference (p = 0.06). In addition, there were no significant differences between groups in MoCA, H&Y, UPDRS_TD,
and mini-BESTest scores in the ON medication condition. However, the freezers had greater motor severity symptoms (UPDRS- III) and
a higher mean score of the sub-items related to postural instability and gait disorders (UPDRS_PIGD) than the non-freezers in the ON
condition. In the OFF condition, there were no significant differences between groups in MoCA, H&Y, UPDRS -III_Total, UPDRS_TD, and
mini-BESTest scores. However, the freezers had a higher mean score for the sub-items related to postural instability and gait disorders
(UPDRS_PIGD) than the non-freezers in the OFF condition.
Effect of medication on clinical features
Table 2 shows the medication effect on each group’s clinical characteristics. For the freezers, there was no significant
differences between conditions in MoCA, H&Y, UPDRS - III_Total, UPDRS_TD, and Mini-BESTest scores. In the OFF state, the average
score of the sub-items related to postural instability and gait disturbances (UPDRS_PIGD) was higher than in the ON condition in the
freezers. The non-freezers did not show significant differences between conditions in MoCA, H&Y, UPDRS_PIGD, and mini-BESTest
scores. In the OFF condition, the non-freezers presented greater severity of symptoms (UPDRS-III_Total) and a higher mean score of the
sub-items related to dominant tremor (UPDRS_TD) when compared to the ON condition of the medication.
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Table 1. Means and standard deviations of demographic and clinical characteristics of participants
separately by the group.
Characteristics
PD freezers
PD non-freezers
p-value
Demographics and anthropometrics
Man/Woman (n)
8/3
9/2
Age (years)
61.5±10.98
64.42±8.65
0.15
Weight (kg)
72.06±13.52
70.84±12.70
0.73
Height (cm)
166.25±7.39
166.17±7.03
0.94
Clinics
NFOG – Q (score)
18.83±5.25
0±0
<0.01
Disease duration (years)
12.5±5.66
8.08±5.07
0.07
Levodopa-equivalent daily dose (mg/day)
1085.13±527.48
610.55±385.69
0.01
ON condition clinics
MoCA (score)
23.55±2.91
22.18±5.53
0.72
H&Y (I / II / III / IV)
1/5/4/1
1/8/2/0
0.25
UPDRS- II (score)
6.36±3.53
2.90±3.27
0.03
UPDRS- III (score)
29.91±14.95
17.64±7.86
0.04
UPDRS_ PIGD (score)
1.00±0.56
0.36±0.38
0.01
UPDRS_TD (score)
0.74±0.63
0.43±0.30
0.28
Mini-BESTest (score)
24.45±6.31
26.36±3.96
0.57
OFF condition clinics
MoCA (score)
24.09±3.02
22.64±5.10
0.60
H&Y (I / II / III / IV)
0 / 5 / 5 / 1
1/8/2/0
0.06
UPDRS- II (score)
9.54±2.73
3.82±2.32
0.01
UPDRS- III (score)
30.09±14.81
22.82±7.48
0.19
UPDRS_ PIGD (score)
1.45±0.61
0.40±0.24
<0.01
UPDRS_TD (score)
0.93±0.86
0.85±0.50
0.74
Mini-BESTest (score)
23.00±687
25.36±3.98
0.51
NFOG - Q = New Freezing of Gait Questionnaire; MoCA = Montreal Cognitive Assessment scale;
UPDRS-III = Unified Parkinson’s Disease Rating Scale, motor part (total score and separate score for
PIGD and TD subtypes); Mini-BESTest = Balance Assessment System Mini-Test.
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Table 2. Mean and standard deviation of the clinical characteristics of the
participants separated by comparisons (ON vs. OFF for the same group).
Freezers
ON
OFF
p-value
MoCA (score)
23.55±2.91
24.09±3.02
0.65
H&Y (I / II / III / IV)
1/5/4/1
0/5/5/1
0.17
UPDRS- III (score)
29.91±14.95
30.09±14.81
0.89
UPDRS-III_ PIGD (score)
1.00±0.56
1.45±0.61
0.01
UPDRS-III_TD (score)
0.74±0.63
0.93±0.86
0.22
Mini-BESTest (score)
24.45±6.31
23.00±6.87
0.17
Non-freezers
ON
OFF
p-value
MoCA (score)
22.18±5.53
22.64±5.10
0.59
H&Y (I / II / III / IV)
1/8/2/0
1/8/2/0
UPDRS- III (score)
17.64±7.86
22.82±7.48
0.02
UPDRS-III_ PIGD (score)
0.36±0.38
0.40±0.24
0.80
UPDRS-III_TD (score)
0.43±0.30
0.85±0.50
0.02
Mini-BESTest (score)
26.36±3.96
25.36±3.98
0.26
MoCA = Montreal Cognitive Assessment scale; UPDRS-III = Unified Parkinson’s
Disease Rating Scale, motor part (total score and separate score for PIGD and TD
subtypes); Mini-BESTest = Balance Assessment System Mini-Test.
Gait spatiotemporal parameters
During the experimental task, no freezing of gait episodes occurred; therefore, all trials were used for gait analysis. Table 4
shows results for the gait analysis. Analysis showed group and medication main effects for speed, and the spatial parameters step length
and stride length. The freezers showed significantly lower values for speed, stride length, and step length when compared to the non-
freezers. Analysis of the medication effect showed that in the ON state, speed, stride length, and step were greater than in the OFF state.
Regarding the gait phases, our results showed the main effect of medication for the swing phase being greater in the ON condition when
compared to the OFF condition.
Table 3. Mean and standard deviation of spatiotemporal gait variables separated by group (freezers and non-freezers) and medication
condition (ON and OFF)
Variables
Freezers
ON
Freezers
OFF
Non-freezers
ON
Non-freezers
OFF
Stride length (cm)
97.31±27.15
76.03±35.06
116.85±16.59
108.76±12.58
Step length (cm)
48.63±13.59
38.01±17.53
58.95±7.71
54.37±6.28
Step width (cm)
11.01±5.85
11.52±4.48
10.60±2.23
10.67±2.10
Stride time (s)
1.15±0.18
1.24±0.48
1.07±0.09
1.11±0.10
Step time (s)
0.57±0.09
0.62±0.24
0.54±0.04
0.55±0.05
Cadence (stride/min)
53.30±7.22
52.39±11.65
56.32±4.75
54.66±4.76
Speed (m/s)
3.17±1.10
2.44±1.23
3.96±0.80
3.56±0.50
Swing time (%)
33.07±5.20
29.49±8.81
36.16±1.69
35.40±2.43
Total double support (%)
33.83±10.43
42.02±20.12
28.30±2.85
29.21±4.86
Table 4. Results of the statistical model applied for analysis of gait parameters.
Variables
p-value
Group effect
Medication effect
Group*Medication
Stride length
0.02
<0.01
0.25
Step length
0.01
<0.01
0.40
Step width
0.80
0.18
0.23
Step time
0.70
1.00
0.68
Cadence
0.62
0.73
0.32
Speed
0.04
<0.01
0.13
Swing phase
0.05
0.02
0.48
Total double support
0.08
0.17
0.16
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Table 5 shows the size of clinical and spatiotemporal gait variables separated by group, medication and group-medication
interaction.
Table 5. Effect size and confidence interval (95% CI) of the parameters separated by group, medication and interaction between group and medication. In
bold are statistically significant effect sizes.
Group effect
Medication Effect
Group*Medication
Freezers On
vs
Non-freezers On
Freezers Off
vs
Non-freezers Off
Freezers On
vs
Freezers Off
Non-freezers On
vs
Non-freezers Off
Freezers On
vs
Non-freezers Off
Freezers Off
vs
Non-freezers On
Effect size (95% CI)
Effect size (95% CI)
Effect size (95% CI)
Stride length
0.72**
(0.08, 1.36)
0.93***
(0.22, 1.65)
-0.78**
(-1.02, -0.54)
-0.49*
(-0.83, -0.15)
0.42 #
(-0.29, 1.13)
1.16***
(0.55, 1.78)
Step Length
0.76**
(0.12, 1.40)
0.93***
(0.22, 1.65)
-0.78**
(-1.02, -0.54)
-0.59**
(-0.99, -0.20)
0.42 #
(-0.29, 1.14)
0.93***
(0.22, 1.65)
Step width
-0.07
(-0.77, 0.63)
-0.19
(-0.82,0.44)
0.09
(-0.07, 0.24)
0.03
(-0.23, 0.29)
-0.06
(-0.74, 0.62)
-0.21
(-0.88, 0.47)
Stride time
-0.41
(-1.05, 0.22)
-0.28
(-0.87,0.30)
0.51**
(0.11, 0.91)
0.38*
(0.13, 0.63)
-0.23
(-0.86, 0.40)
-0.35
(-0.86, 0.16)
Step time
-0.34
(-1.02, 0.33)
-0.28
(-0.87,0.30)
-0.50**
(0.11, 0.90)
0.25
(-0.09, 0.58)
-0.23
(-0.86, 0.40)
-0.33
(-0.87, 0.21)
Cadence
0.42
(-0.22, 1.05)
0.19
(-0.38,0.77)
-0.13
(-0.48, 0.23)
-0.35*
(-0.59, -0.11)
0.19
(-0.44, 0.81)
0.34
(-0.20, 0.88)
Speed
0.71**
(0.08, 1.35)
0.91***
(0.24, 1.59)
-0.67**
(-0.88, -0.46)
-0.49*
(-0.82, -0.16)
0.35 #
(-0.36, 1.06)
1.24***
(0.62, 1.85)
Speed variability
-0.16
(-0.63, 0.32)
-0.70
(-1.44,0.05)
0.54**
(0.09, 0.99)
-0.12
(-0.49, 0.26)
-0.26
(-0.89, 0.37)
-0.61
(-1.33, 0.11)
Swing Phase
0.59
(-0.02, 1.21)
0.67
(-0.03, 1.37)
-0.69**
(-0.85, -0.53)
-0.45*
(-0.73, -0.17)
0.45
(-1.14, 0.24)
0.76**
(0.15, 1.37)
Total Double Support
-0.53
(-1.16, 0.10)
-0.64
(-1.33,0.06)
0.78**
(0.65, 0.92)
0.32*
(0.03, 0.62)
-0.44
(-1.13, 0.25)
-0.68
(-1.32, 0.04)
UPDRS III
-0.82***
(-1.53, -0.11)
-0.34
(-0.93,0.25)
-0.07
(-0.39, 0.26)
0.77**
(0.31, 1.22)
-0.41#
(-1.05, 0.23)
-0.74**
(-1.48, -0.01)
H&Y
-0.33
(-1.03, 0.37)
-0.53
(-1.21,0.15)
0.11
(-0.04, 0.26)
0
(0.0, 0.0)
-0.33
(-1.03, 0.37)
0.53
(-1.21, 0.15)
MiniBest
0.14
(-0.53, 0.81)
0.22
(-0.41,0.84)
-0.18
(-0.39, 0.04)
-0.14
(-0.42, 0.13)
0.05
(-0.55, 0.66)
0.29
(-0.40, 0.98)
MoCA
-0.62**
(-1.10, -0.14)
-0.13
(-0.73,0.46)
-0.03
(-0.52, 0.46)
0.26
(-0.05, 0.58)
-0.15
(-0.53, 0.24)
-0.67**
(-1.20, -0.14)
* represents small effect size (<0.50), ** represents moderate effect size (< 0.80) and *** represents large effect size (≥0.80).!
DISCUSSION
The present study aimed to compare the effect of antiparkinsonian medication on the spatiotemporal gait parameters between
freezers and non-freezers. It was observed that the freezers used a higher dose of medication, tended to be in a more advanced stage of
the disease, and had the disease for a longer time than the non-freezers. In addition, the freezers showed greater severity of motor
symptoms in the ON state and higher scores on items that indicate the PIGD subtype of the disease, both in the ON and OFF states,
showing greater severity of motor symptoms related to gait and postural instability. The freezers showed lower gait speed, step length,
and stride length when compared to the non-freezers, indicating greater gait impairment in individuals with FoG regardless of medication
status. Corroborating the hypothesis that the medication improves gait in both the freezers and non-freezers (H1), our results showed
increased gait speed, stride length, and step length in both groups. However, contrary to H2, the results indicated that the improvement in
gait parameters was similar between the two groups.
During the experimental task, the freezers showed no FoG episodes across all trials. However, even without FoG, gait speed,
stride, and step length were lower in the freezers when compared to the non-freezers, regardless of the assessed drug condition,
indicating greater gait impairment in the freezers. Glover, Pillai
12
showed that freezers have greater gait decline with disease progression
as measured by the most marked reduction in stride length, duration of the swing phase and single support, and the greatest increase in
stride time variability than non-freezers. Furthermore, they found that this greater decline of gait parameters in freezers was unrelated to
initial medication dosage, duration of drug therapy, or drug dose changes during the study.
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Unlike our results, Vitorio, Stuart
11
found no difference in gait speed and stride length between freezers and non-freezers, in
evaluation only in the OFF medication. We suggest that while the individuals in the study by Vitorio, Stuart
11
seem to have maintained
this compensatory mechanism, our participants may have been unable to make such a compensation, resulting in the change found in
the gait of the freezers even when controlling for clinical differences. Furthermore, our results showed that while the freezers are mostly
classified with the PIGD subtype of PD, showing greater postural instability and gait disorders, the non-freezers had both subtypes in
similar proportions. Although there was an improvement in the mean score of the items related to the PIGD subtype of the freezers, this
improvement was not enough for this score to approach the score of the non-freezers, with maintenance of the clinical difference,
reflecting the difference found in the objective gait parameters.
Regarding the effect of the medication, our results corroborate the findings of previous studies showing that the medication
induces an increase in gait speed, stride and step length without altering the temporal parameters cadence, step duration, and stride
duration
5,16
. Furthermore, these changes were consistent between the groups of freezers and non-freezers, indicating that the
medication induced a similar improvement in gait in individuals with PD regardless of having FoG. It is known that gait speed is
associated with changes in spatiotemporal parameters of gait, which vary according to the self-selected speed
25
. By analyzing gait
parameters in individuals with PD, Frenkel-Toledo, Giladi
26
showed that a reduction in gait speed was associated with a decrease in the
length of the stride, the duration of the swing phase, and an increase in the duration of the stride. Furthermore, Turcato, Godi
27
showed
that, while walking in a straight line, spatiotemporal parameters such as cadence or stride length were not different between individuals
with PD and healthy individuals when compared at the same self-selected speed. Finally, Avila de Oliveira, Bazan
28
showed through a
Bayesian mediation analysis that changes in gait speed have greater explanatory power of changes in spatiotemporal parameters, thus
mediating the effect of dopaminergic medication on these parameters in individuals with PD. Therefore, these results indicate that
changes in spatiotemporal gait parameters are strongly related to changes in gait speed induced by the ON condition of the medication.
Self-selected gait speed is considered mechanically more efficient, as it induces less variability in stride length, optimization of
muscle activation, and range of hip joint rotation, thus allowing less energy expenditure
26,29,30
. Furthermore, dopaminergic replacement
from levodopa ingestion induces a reduction in bradykinesia and joint stiffness, improvement in automaticity, increased movement vigor
and task engagement
14,31,32
, which together can explain the increase in self-selected gait speed in the ON condition. Based on this, it is
possible that antiparkinsonian medication induces improvement of gait in individuals with PD through the increase in self-selected speed,
which, in turn, is associated with changes in some of the spatiotemporal gait parameters that are adjusted to this new speed. Therefore,
there are not necessarily spatiotemporal parameters responsive or resistant to levodopa. Instead, they vary according to the variation in
gait speed induced by dopaminergic replacement.
Finally, contrary to our expectations, the medication failed to exert a more marked improvement in gait in freezers (H2), even
with the gait of this group being more debilitated than that of non-freezers in the OFF state. Therefore, unlike the more pronounced
improvement of freezers found in the turning test
19
, the effect of medication on gait seem to not be proportional to the degree of
impairment assessed in the OFF state. McNeely and Earhart
19
proposed the hypothesis that the more pronounced improvement in
freezers could be related to the higher medication dosage of these individuals; therefore, the effect could be proportional to the dosage.
It was observed in our results that the medication did not induce global improvement in motor symptoms assessed by the
UPDRS-III score in the freezers. At the same time, only the non-freezers showed this improvement in the ON state score. This result
leads to the assumption that some freezers have reduced responsiveness to levodopa being resistant to the medication. Alternatively,
they could have an inadequate medication dosage, which could be considered a limitation of the conclusions raised about the effect of
the medication between the groups. Nevertheless, when analyzing the specific score of symptoms related to the PIGD subtype, the
medication significantly improved the freezers’ gait, with almost all individuals showing good responsiveness to the medication to the
UPDRS_PIGD score. This indicates that this supposed resistance does not apply to specific results regarding gait characteristics;
therefore, this limitation probably does not interfere with our results on the effect of medication on spatiotemporal parameters of gait.
The main limitation to be considered in this study is the low responsiveness to medication observed from the UPDRS-III scores
of the freezers. This indicates that the drug dosage used by some individuals in the group did not induce a relevant improvement in motor
symptoms in the ON state, which could interfere with the findings related to spatiotemporal gait parameters. As a result, the improvement
caused by the medication in the ON of the freezers may be underestimated. Thus, caution is needed when generalizing these results to
individuals with greater responsiveness to the medication. As multiple comparisons corrections were not performed, our results need to
be taken with care and can be considered as an exploratory analysis. Another limitation is that we do not know the habits regarding
physical exercise and other behaviors that interact with the disease.
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CONCLUSION
The results of the present study indicated that the intake of antiparkinsonian medication by individuals with PD led to an
increase in self-selected gait speed, step length, and stride length. Contrary to our expectations, this improvement occurred equally
between freezers and non-freezers, so that in the medicated state the difference between groups was not attenuated regarding that
observed in the non-medicated state.
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Citation: Oliveira JA, Teixeira LA, Coelho DB. (2023).!The Effect of antiparkinsonian medication on spatiotemporal gait parameters of individuals with Parkinson’s disease:
comparison between individuals with and without freezing of gait. Brazilian Journal of Motor Behavior, 17(4):93-102.
Editor-in-chief: Dr Fabio Augusto Barbieri - São Paulo State University (UNESP), Bauru, SP, Brazil. !
Associate editors: Dr José Angelo Barela - São Paulo State University (UNESP), Rio Claro, SP, Brazil; Dr Natalia Madalena Rinaldi - Federal University of Espírito Santo
(UFES), Vitória, ES, Brazil; Dr Renato de Moraes – University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
Guest editors: Dr Fabio Augusto Barbieri - São Paulo State University (UNESP), Bauru, SP, Brazil; Dr Lucas Simieli; Dr Victor Spiandor Beretta - São Paulo State
University (UNESP), Presidente Prudente, SP, Brazil.
Copyright:© 2023 Oliveira, Teixeira and Coelho and BJMB. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non
Commercial-No Derivatives 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source
are credited.
Funding: Nothing to report.
Competing interests: The authors have declared that no competing interests exist.
DOI:!https://doi.org/10.20338/bjmb.v17i4.351