Gait variability in Parkinson's disease: influence of walking speed and dopaminergic treatment.

Abstract

To study the effects of levodopa and walking speed on gait variability in individuals with Parkinson's disease (PD).
Thirty-three individuals with PD were studied. Their mean age was 70.61±9.23 year. The average time since diagnosis was 9.65±5.80 year. Gait variability was studied while 'OFF' and 'ON' dopaminergic medication when the subjects walked at their usual and fastest speeds.
Variability of step time, double support time, stride length and stride velocity decreased significantly (P=0.037; P=0.037; P=0.022; P=0.043, respectively) after dopaminergic treatment. When subjects increased walking speed, the variability of stride length and stride velocity decreased significantly (P=0.038 and P=0.004, respectively) both while 'OFF' and 'ON' levodopa. Increasing walking speed did not change the variability of step time and double support time regardless of medication status.
Levodopa decreased gait variability in persons with PD. Stride length and stride velocity variability appeared to be speed dependent parameters, whereas, the variability of step time and double support time appeared to be speed independent measures. Levodopa had positive effects on gait stability in PD.

Full text

Page 1

Published by Maney Publishing (c) W. S. Maney & Son Limited
Gait variability in Parkinson’s disease:
influence of walking speed and dopaminergic
treatment
Mon S Bryant1,2, Diana H Rintala2, Jyhgong G Hou3,4, Ann L Charness1, Angel L
Fernandez1, Robert L Collins3,4, Jeff Baker1, Eugene C Lai4,5, Elizabeth J Protas1
1School of Health Professions, University of Texas Medical Branch, Galveston, TX, USA,2Department of Physical
Medicine and Rehabilitation,3Department of Neurology, Baylor College of Medicine, Houston, TX, USA,
4Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA,5The Methodist Neurological Institutes,
Houston, TX, USA
Objectives: To study the effects of levodopa and walking speed on gait variability in individuals with
Parkinson’s disease (PD).
Methods: Thirty-three individuals with PD were studied. Their mean age was 70.61¡9.23 year. The average
time since diagnosis was 9.65¡5.80 year. Gait variability was studied while ‘OFF’ and ‘ON’ dopaminergic
medication when the subjects walked at their usual and fastest speeds.
Results: Variability of step time, double support time, stride length and stride velocity decreased
significantly (P50.037; P50.037; P50.022; P50.043, respectively) after dopaminergic treatment. When
subjects increased walking speed, the variability of stride length and stride velocity decreased significantly
(P50.038 and P50.004, respectively) both while ‘OFF’ and ‘ON’ levodopa. Increasing walking speed did
not change the variability of step time and double support time regardless of medication status.
Conclusions: Levodopa decreased gait variability in persons with PD. Stride length and stride velocity
variability appeared to be speed dependent parameters, whereas, the variability of step time and double
support time appeared to be speed independent measures. Levodopa had positive effects on gait stability
in PD.
Keywords: Parkinson’s disease, Gait variability, Levodopa, Walking speed
Introduction
Gait disturbance is one of the clinical hallmarks of
Parkinson’s disease (PD) and a frequent cause of
disability and impairment. The PD gait pattern is
characterized by reduced speed, short stride lengths,
shuffling steps and, occasionally, freezing episodes.1
Besides these visible clinical features, gait dysfunction
in PD includes gait instability and arrhythmicity, as
characterized by increased stride-to-stride variability,
a fluctuation in the value of a gait measure from one
stride to the next.2Increased variability reflects incon-
sistency in stepping patterns and reduced postural
control during walking.3Gait disturbances and in-
stability may predispose individuals with PD to fall.
Gait instability occurs in elderly persons, as well as
in persons with neurological conditions such as in PD
and Huntington’s disease.2,3Higher values of varia-
bility indicate greater instability and have been
associated with freezing of gait and falls in persons
with PD. Dopaminergic treatment has been shown to
decreased certain gait variability parameters, demon-
strating the role dopaminergic pathways play in the
impaired gait rhythmicity in PD.4
Although there have been previous reports on gait
variability in persons with PD, it is unclear whether
gait variability is speed dependent and how it is
modified by levodopa. Persons with PD walk with
a reduced speed, a potential confounder of the
observed changes in variability.5Several investigators
suggested that stride variability increases if gait speed
is lower than an optimal value.6,7Conversely, others
reported that walking speed and stride variability
may be independent.8,9No significant increase in
stride time variability was observed in healthy elderly
subjects even though they walked significantly slower
than young adults. Understanding the influences of
walking speed and levodopa may further clarify
mechanisms underlying gait variability in persons
with PD.
Correspondence to: Mon S Bryant, Rehabilitation Research (153), 2002
Holcombe Blvd, Houston, TX 77030, USA. Email: mon.bryant@
yahoo.com
? W. S. Maney & Son Ltd 2011
DOI 10.1179/1743132811Y.0000000044
Neurological Research
2011
VOL. 33
NO. 9
959

Page 2

Published by Maney Publishing (c) W. S. Maney & Son Limited
The main objective of this study was to demonstrate
how levodopa modulated gait variability in individuals
with PD when they walk at different speeds. It was
hypothesized that levodopa would influence gait
variability differently when walking at different speeds.
Materials and Methods
Subjects
Thirty-three individuals with idiopathic PD were
recruited from movement disorder outpatient clinics
in the Houston and Galveston, Texas areas. The
severity of PD in all subjects was assessed to be
between stage 2 and 3 on the Hoehn and Yahr
scale,10and subjects were able to stand and walk at
least 3 m without assistance. No subject had visual or
hearing deficits that would interfere with the walking
test. Subjects were excluded if they had clinically
significant musculoskeletal problems in their back,
hips, knees or ankles that currently interfered with
walking. All subjects reported no history of lower
extremity fracture.
All subjects had only medication treatment for PD.
None of them had had stereotactic brain surgery or
deep brain stimulation. All of them were receiving
dopamine treatment alone (carbidopa/levodopa or
carbidopa/levodopa/entacapone) or in combination
with other PD medications. The amount of levodopa
taken by the subjects ranged from 100 to 400 mg
(mean5162.90 mg). Additional medications included
dopamine agonist (pramipexole, requip) for 20 sub-
jects, monoamine oxidase type B (MAO-B) inhibitor
(rasagiline, selegiline) for six subjects, N-methyl-D-
aspartate antagonist (amantadine) for 13 subjects,
and catechol-O-methyltransferase (COMT) inhibitor
(entacapone) for five subjects.
Subjects were screened for significant cognitive im-
pairment with the Neurobehavioral Cognitive Status
Examination (Cognistat) and any subtest score in the
severely impaired range resulted in study exclusion
(Cognistat).11The Unified Parkinson Disease Rating
Scale (UPDRS)12and the Hoehn and Yahr Staging
Scale (HY) were used to assess disease severity of the
subjects.
Equipment and measures
The GAITRite system (GAITRite, CIR Systems Inc.,
Havertown, PA, USA), is a 5-m, instrumented walk-
way containing an array of six sensor pads encapsu-
lated in a roll-up carpet with an active area 61 cm wide
by 366 cm long and a sampling rate of 32.3–38.4 Hz.
While the subject walks, the system continuously scans
the sensors to detect pressures, and transfers the
information to the computer for calculating, record-
ing, and storing gait characteristics.
The parameters of interest were gait variability in
step time, double support time, stride length and stride
velocity. Variability of each parameter [coefficient of
variation (CV)] was calculated using the following
formula13
%CV~(standard deviation=mean)|100
Step time is the duration from the contact of one foot
to the contact of the opposite foot. Double support
time is the sum of the time elapsed between the first
contact of the current footfall and the last contact of
the previous footfall and the time elapsed between the
last contact of the current footfall and the first contact
of the next footfall. Stride length is the length of two
consecutive footfalls of the same extremity. Stride
velocity was calculated as stride length divided by
stride time.
Walking protocol
All subjects read andsigned an approved consent form
prior to participation. Usual speed and fastest walking
speed were tested while ‘ON’ and ‘OFF’ dopaminergic
medication on the same day. For off medication
testing, the subjects were tested in the morning after
abstaining from their dopaminergic medication over-
night.The wash-outperiod was at least 12 hours in the
‘OFF’ medication state. Subjects in the ‘OFF’
medication state were assessed with the UPDRS
Motor section III by a neurologist prior to performing
the walking test. After walking on the computerized
mat with theusual andfastest speeds, thesubjects took
their morning dose of their usual medications and
waited for the medications to take effect. Once the
subjects reported that they felt ‘ON’ their dopaminer-
gic medication, which was approximately 45 minutes
to one hour after taking the medication, the same
neurologist obtained the UPDRS motor scores again.
Then, the subjects followed the same walking protocol
as they did in the off-medication condition.
Subjects were instructed to walk at their self-
selected, usual speed and at their fastest speeds on the
computerized mat. Each walk was repeated twice,
and the combination of the two trials was used in
data analysis. This allowed us to analyze more strides
for each subject in each walking condition. All
subjects wore a gait belt during the walking experi-
ment and were closely guarded by a research assistant
for safety. Verbal instruction for each walk was given
before the subject started walking. No instruction
was given after the subject started walking in order to
prevent any influence of verbal cueing on gait
performance. The verbal instruction for the self-
selected speed walk was ‘Walk down the mat at your
usual,comfortablewalking
instruction for the fast speed walk was ‘Walk down
the mat as fast as you can’. Subjects were asked to
start walking a few steps before entering and after
leaving the walkway to allow some distance for
acceleration and deceleration.
speed’.Theverbal
Bryant et al.Gait variability in Parkinson’s disease
960
Neurological Research
2011
VOL. 33
NO. 9

Page 3

Published by Maney Publishing (c) W. S. Maney & Son Limited
Statistical analysis
Demographic data were descriptively summarized. All
analysis was performed using SPSS version 18.0. Two-
wayrepeated-measuresanalysis ofvariance (ANOVA)
was performed to demonstrate the main effects of
medication status (OFF vs ON) and walking speed
(usual vs fastest) on four gait variability parameters as
well as any interaction (medication status6walking
speed). The four dependent measures were step time
variability, double support time variability, stride
length variability, and stride velocity variability. The
independent measures were medication status and
walking speed. There were no between-subject factors.
Datacollectionwasperformedbythesamepersonnel
throughout the study and they were necessarily
unblinded to the medication status due to the design
of the study. The statistical analysis also was performed
in an unblinded condition with respect to medication
status. The significance level was set at P,0.05.
Results
Subject characteristics
Subject characteristics are displayed in Table 1. All
subjects were receiving dopaminergic treatment (carbi-
dopa/levodopa or carbidopa/levodopa/entacapone). The
amount of levodopa taken by the subjects ranged from
100 to 400 mg (mean5162.90 mg). Dyskinesias were
observedin12subjectswhiletheywere‘ON’medication.
All subjects were community-dwelling persons with PD.
All subjects were able to complete the walking test
without any assistive device. However, eight subjects
reported using a cane and seven subjects reported using
either awheeledor non-wheeledwalker for longdistance
ambulation.
Influence of levodopa on gait variability
There were significant main effects of levodopa on
step time variability [F (1, 32)54.74, P50.037],
double support time variability [F(1, 32)54.76,
P50.037], stride length variability [F (1, 32)55.80,
P50.022], and stride velocity variability [F (1,
32)54.44, P50.043) (Tables 2 and 3). Levodopa
reduced variability in all four of these gait variability
parameters.
Influence of walking speed on gait variability
There was no significant main effect of walking speed
on either step time variability [F (1, 32)51.023,
P50.319] or double support time variability [F (1,
32)50.05, P50.833]. However, there were significant
main effects of walking speed on stride length
variability [F (1, 32)54.67, P50.038] and stride velocity
variability [F (1, 32)59.62, P50.004] (Tables 2 and 3).
These findings indicated that an increase in gait speed
reduced variability in stride length and stride velocity
but did not affect variability in step time and double
support time.
Interaction of levodopa and walking speed on
gait variability
There was no significant interaction between walking
speed and levodopa on the variability of step time
(P50.365), double support time (P50.989), stride
length(P50.546)or stride
(Tables 2 and 3). Levodopa did not significantly
influence gait variability differently when walking at
different speeds (usual vs fastest). Gait speeds when
walking with usual and fastest speeds during ‘OFF’
and ‘ON’ medications are displayed in Table 4.
velocity(P50.843)
Discussion
The aim of the study was to assess whether the
influence of levodopa on gait variability differs
depending on walking speed (usual vs fastest) in
persons with PD. Our results demonstrated several
new findings. First, levodopa reduced variability in
step time, double support time, stride length, and
stride velocity regardless of walking speed. Second,
increased walking speed reduced variability in stride
length and stride velocity but not in step time and
Table 2 Effects of walking speed (usual vs fastest) and levodopa treatment (OFF vs ON) on the gait variability
Variability characteristicsOFF medication (N533) ON medication (N533)P value* (OFF vs ON)P value* (usual vs fast)
Usual walking speed
Step time (%)
Double support time (%)
Stride length (%)
Stride velocity (%)
Fastest walking speed
Step time (%)
Double support time (%)
Stride length (%)
Stride velocity (%)
5.38¡3.25
7.19¡2.88
5.24¡4.52
5.52¡3.27
4.32¡1.61
5.96¡2.36
4.01¡2.54
4.38¡2.00
0.037
0.037
0.022
0.043
0.319
0.833
0.038
0.004
4.83¡2.01
7.10¡4.02
4.49¡4.31
4.48¡4.12
4.23¡2.14
5.86¡3.31
2.92¡1.54
3.43¡1.82
Note: *Two-way repeated measures ANOVA; based on estimated marginal means.
Table 1Subject characteristics
PD (N533)
Gender
Age
Height (cm)
Weight (kg)
BMI (kg/m2)
Year of PD
HY Stage (‘ON’)
UPDRS ‘OFF’
UPDRS ‘ON’
Male 22; Female 11
70.61¡9.23
168.76¡11.37
75.70¡15.98
26.62¡5.30
9.65¡5.80
2.58¡0.42
29.12¡11.36
18.39¡8.55
Bryant et al.Gait variability in Parkinson’s disease
Neurological Research
2011
VOL. 33
NO. 9
961

Page 4

Published by Maney Publishing (c) W. S. Maney & Son Limited
double support time. Third, levodopa did not affect
gait variability differently when persons with PD
walked at different gait speeds. The results indicated
that stride length variability and stride velocity
variability were speed dependent, whereas step time
variability and double support time variability were
speed independent.
Our results are in agreement with a previous study
by Schaafsma et al.4that the levodopa reduced
stride time variability. In our study,
variability measures including step time, double
support time, stride length and stride velocity were
reduced after the administration of the levodopa.
Step time and stride time may have similar meanings
in terms of variability, a fluctuation across strides as
a person walks. Stride time is composed of one right
step time plus one left step time. An increase in
variability from one stride to the next, regardless of
whether the unit of measure is variability in step
time, variability in stride length, or variability in
stride velocity, reflects
regulate stride-to-stride variations in gait timing in
persons with PD.14
all gait
animpaired ability to
Almeida et al.15evaluated the influence of external
timing cues on gait variability and the impact of do-
paminergic treatment in persons with PD. In contrast to
our results, they found no significant difference between
medicated (‘ON’) and non-medicated (‘OFF’) subjects in
steptime anddouble support time variabilityduringself-
paced walking speed. Our results showed significant
reduction in step time variability and double support
time variability after the subjects with PD took their
usual medications.
The discrepancy between the two studies could be due
to a difference in study design. In the study by Almeida
et al.,15step time variability and double support time
variability of a group of medicated subjects were com-
pared to those of a group of non-medicated subjects.
Gait speed, cadence and step length were not different
between the two groups during a self-paced walk. We
used a repeated-measures design in this study to allow a
valid assessment of levodopa effects on gait. The same
subjectsperformedwalkingtestswhile‘OFF’medication
andthentooktheirusualmedicationsbeforebeingtested
while ‘ON’ medication. The ‘ON’ state was assured by
the subjects’ self-report and a neurologist.
Table 3 Effects of the walking speed and levodopa on gait variability
VariableSum of squaresdf Mean squareF Sig.
Medication
Step time variability
Double support time variability
Stride length variability
Stride velocity variability
Error
Step time variability
Double support time variability
Stride length variability
Stride velocity variability
Walking speed
Step time variability
Double support time variability
Stride length variability
Stride velocity variability
Error
Step time variability
Double support time variability
Stride length variability
Stride velocity variability
Walking speed6medication
Step time variability
Double support time variability
Stride length variability
Stride velocity variability
Error
Step time variability
Double support time variability
Stride length variability
Stride velocity variability
22.709
50.320
64.820
39.546
1
1
1
1
22.709
50.320
64.820
39.546
4.738
4.762
5.803
4.440
0.037
0.037
0.022
0.043
153.369
338.149
357.461
285.001
32
32
32
32
4.793
10.567
11.171
8.906
3.421
0.320
27.729
32.750
1
1
1
1
3.421
0.320
27.729
32.750
1.023
0.045
4.670
9.622
0.319
0.833
0.038
0.004
106.970
227.649
189.990
108.921
32
32
32
32
3.343
7.114
5.937
3.404
1.762
0.002
1.002
0.080
1
1
1
1
1.762
0.002
1.002
0.080
0.844
0.000
0.372
0.040
0.365
0.989
0.546
0.843
66.816
299.217
86.092
64.467
32
32
32
32
2.088
9.351
2.69
2.015
Table 4Comparison of gait speed of usual and fast walks during ‘ON’ and ‘OFF’ medication states
Gait speedPD-OFF (N533) PD-ON (N533) P value{ (usual vs fast) P value{ (ON vs OFF)
Usual speed (cm/second)
Fastest speed (cm/second)
82.70¡26.59
123.91¡35.62
98.94¡19.92
135.76¡27.59
,0.001*
,0.001*
Note: {Two-way repeated-measures ANOVA.
Bryant et al. Gait variability in Parkinson’s disease
962
Neurological Research
2011
VOL. 33
NO. 9

Page 5

Published by Maney Publishing (c) W. S. Maney & Son Limited
In addition, in the study by Almeida et al. the
subjects with PD walked at different walking speeds,
driven by various auditory cueing rates (60, 80,
100 steps/minute). The cueing rate of 100 steps per
minute was slower than the average self-paced
cadence of both the ‘ON’ (106.47 steps/minute) and
‘OFF’ (110.35 steps/minute) PD groups in their
study.15In other words, the cueing rates made the
subjects walk more slowly than their usual walking
speeds whereas in our study, they were asked to walk
at their usual and fastest speeds.
Based on our literature search, the study by Almeida
et al. is the only one that has investigated the effects of
both dopaminergic therapy and walking speed on gait
variability in persons with PD. Therefore, with our
within-subjects design, we demonstrated, for the first
time, that levodopa reduced gait variability in both
temporal (step time, double support time, and stride
velocity variability) and spatial gait parameters (stride
length variability), whereas internal modulation to
increase walking speed reduced variability in certain
temporal (stride velocity) and spatial (stride length) gait
parameters. These findings support the assertion by
Morrisetal.16thatincreasedtimingvariabilityinpersons
with PD may reflect disruption of the normal internal
cueing needed to string together sub-movements or a
diminished capacity to perform automatic, sequential
movements, and which can be improved by anti-PD
medications.Ourresultsalsoareconsistentwiththeview
that the basal ganglia may be involved in the neural
network for precise modulation of timing of repetitive
movement.17,18The medications work directly on this
neural network to alleviate these deficits, as indicated by
our results on variability in the temporal parameters.
Levodopa may improve hypokinesia or bradyki-
nesia and modulate temporal gait variability, where-
as, internal modulation or attentional strategies
influence only certain gait variability. Our results
indicated that levodopa had positive effects on gait
variability at the central control level, whereas, an
increase in walking speed using an attentional
strategy had positive effects on only biomechanical
control. These observations have been proposed to
be indicative of the role of the basal ganglia in
controlling spatial characteristics such as the scaling
of amplitude during gait.19
The results suggest that fluctuation in step time and
double support time depend on some aspect of the
central control system that is not merely related to
walking velocity. Double support time has been
considered an important indicator of abnormal
balance control in healthy, older adults and those
with cerebellar dysfunction, as well as those with
basal ganglia disease.2Variability of step time reflects
a disturbance of the gait patterning mechanism,
whereas variability of double limb support time has
been attributed to balance mechanisms.4,20A rela-
tionship between step time variability and falls has
been previously identified.4
measures in variability may be predominantly deter-
mined by balance-control mechanisms, whereas stride
length and stride velocity were predominantly deter-
mined by gait-patterning mechanisms through neu-
romuscular/biomechanical control.
Ourresults are consistent with a study by
Rochester and colleagues. Variability of step time
and double support time were not changed in people
with PD by an increase in walking speed, which was
driven by rhythmic auditory cues.13Our results also
showed that increased walking speed did not reduce
variability in step time and double support time. This
could suggest that gait speed alone is not the single
driver of variability, which is consistent with previous
reports that observed a dissociation between stride
length and variability.5,8,9
Callisaya et al.21studied the effect of gait speed on
gait variability in elderly persons and reported that a
faster gait speed was associated with less variability
including step time and double support time. From
our results, a faster gait speed did not change step
time and double support time in persons with PD.
This might indicate that persons with PD and the
elderly without PD use different controlling mechan-
isms to increase gait speed.
These two temporal
Limitations
There are some limitations of the study to be
addressed. Our sample consisted of individuals with
diagnosed idiopathic PD with mild to moderate
severity who reported either gait or balance impair-
ment or falls as a result of PD. Their gait patterns
might be different from persons with PD who do not
have gait and balance impairments or who never fall.
Thedesignof thestudynecessitatedthatwe measured
gait first when the subjects were ‘OFF’ medication and
second while ‘ON’ medication. We measured gait when
they had not had levodopa for approximately 12 hours
to assure the ‘OFF-state’ testing. We could not have
done the testing on the same day if we had measured
them while ‘ON’ medication first.
Fatigue might have occurred from travelling to the
laboratory in the morning without the medication
and having to endure impaired mobility and physical
discomfort from PD. However, no subject was too
fatigued to perform the walking tests. In addition, the
degree of gait improvement by levodopa may vary
depending on individual responses.
There were only33subjects withPD inthisstudy. The
sample size was not large enough to study the effects of
PD medications other than levodopa taken by the
subjects stratified by type of mechanisms (i.e. dopamine
receptor agonist, MAO-B inhibitor, anticholinergic
Bryant et al. Gait variability in Parkinson’s disease
Neurological Research
2011
VOL. 33
NO. 9
963

Page 6

Published by Maney Publishing (c) W. S. Maney & Son Limited
medication, COMT inhibitor). However, most PD
patients usually receive a combination of PD medica-
tions to effectively control their PD symptoms, enhance
qualityoflifeandextendsurvival.22Afuturelargerstudy
might include other medications as a factor of interest.
Variability measures of either walking at the usual
speed or while ‘OFF’ medication might be more
representative of gait variability than either walking at
a faster speed or while ‘ON’ medication because more
strides were produced and examined. However,
Hausdorff et al.23reported that gait variability over
a small number of strides is statistically similar to
variationsthat occur overthousands of strides because
gait variability takes on a fractal organization in
persons. We, therefore, have confidence that our data
on variability in each walking condition are valid.
Conclusions
Insummary,levodopareducedgaitvariabilityinpersons
with PD by decreasing variability in step time, double
support time, stride length and stride velocity. This may
imply that levodopa induced more normal gait patterns
in persons with PD. Intentional modulation of speed
reduced variability in certain spatial gait parameters
includingstride length and stride velocityin persons with
PD, thus intentional modulation might be a useful
strategy in gait rehabilitation aimed at improving
stability.
Acknowledgements
This work was supported partially by the National
Institute of Health, grant no. R01 HD051844, and
no. K12 HD055929. The authors thank Steven P
Rivas for his assistance with data collection and the
subjects for their time and effort.
References
1 Pedersen SW, Oberg B, Larsson LE, Lindval B. Gait analysis,
isokinetic muscle strength measurement in patients with
Parkinson’s disease. Scand J Rehabil Med 1997;29(2):67–74.
2 Hausdorff JM, Cudkowicz ME, Firtion R, Wei JY, Goldberger
AL. Gait variability and basal ganglia disorders: stride-to-stride
variations of gait cycle timing in Parkinson’s disease and
Huntington’s disease. Mov Disord 1998;13(3):428–37.
3 Hollman JH, Kovash FM, Kubik JJ, Linbo RA. Age-related
differences in spatiotemporal markers of gait stability during
dual task walking. Gait Posture 2007;26(1):113–9.
4 Schaafsma JD, Giladi N, Balash Y, Bartels AL, Gurevich T,
HausdorffJM.GaitdynamicsinParkinson’sdisease:relationship
to Parkinsonian features, falls and response to levodopa.
J Neurol Sci 2003;212(1–2):47–53.
5 Frenkel-Toledo S, Giladi N, Peretz C, Herman T, Gruendlinger
L, Hausdorff JM. Effect of gait speed on gait rhythmicity in
Parkinson’s disease: variability of stride time and swing time
respond differently. J Neuroeng Rehabil 2005;31(2):23.
6 Yamasaki M, Sasaki T, Torii M. Sex difference in the pattern of
lower limb movement during treadmill walking. Eur J Appl
Physiol Occup Physiol 1991;62(2):99–103.
7 Danion F, Varraine E, Bonnard M, Pailhous J. Stride variability
in human gait: the effect of stride frequency and stride length.
Gait Posture 2003;18(1):69–77.
8 Grabiner PC, Biswas ST, Grabiner MD. Age-related changes in
spatial and temporal gait variables. Arch Phys Med Rehabil
2001;82(1):31–5.
9 Hausdorff JM. Stride variability: beyond length and frequency.
Gait Posture 2004;20(3):304.
10 Hoehn M, Yahr MD. Parkinsonism: onset, progression, and
mortality. Neurology 1967;17:427–42.
11 Oehlert ME, Hass SD, Freeman MR, Williams MD, Ryan JJ,
Sumerall SW. The Neurobehavioral cognitive status examina-
tion: accuracy of the ‘Screen-Metric’ approach in a clinical
sample. J Clin Psychol 1997;53:733–7.
12 Fahn S, Elton RL. Members of the UPDRS Development
Committee. Unified Parkinson’s Disease Rating Scale. In: Fahn
S, Marsden CD, Calne DB, Goldstein M, editors. Recent
developments in Parkinson’s disease. Vol. 2. Florham Park:
Macmillan Health Care Information; 1987.
13 Rochester L, Burn DJ, Woods G, Godwin J, Nieuwboer A.
Does auditory rhythmical cueing improve gait in people with
Parkinson’s disease and cognitive impairment? A feasibility
study. Mov Disord 2009;24(6):839–45.
14 Hollman JH, Salamon KB, Priest AW. Aged-related differences
in stride-to-stride variability during dual task walking: a pilot
study. J Geriatric Phys Ther 2004;27(3):83–7.
15 AlmeidaQJ,FrankJS,RoyEA,PatlaAE,JogMS.Dopaminergic
modulation of timing control and variability in the gait of
Parkinson’s disease. Mov Disord 2007;22(12):1735–42.
16 Morris ME, Iansek R, Matyas TA, Summers JJ. The patho-
genesis of gait hypokinesia in Parkinson’s disease. Brain 1994;
117(Pt 5):1169–81.
17 Rao SM, Harrington DL, Haaland KY, Bobholz JA, Cox RW,
Binder JR. Distributed neural systems underlying the timing of
movements. J Neurosci 1997;17(14):5528–35.
18 Harrington DL, Haaland KY, Knight RT. Cortical networks
underlying mechanisms of time perception. J Neurosci 1998;
18(3):1085–95.
19 Morris ME, Iansek R, Matyas TA, Summers JJ. Stride length
regulation in Parkinson’s disease. Normalization strategies and
underlying mechanisms. Brain1996;119(Pt 2):551–68.
20 Yogev G, Giladi N, Peretz C, Springer S, Simon ES, Hausdorff
JM. Dual tasking, gait rhythmicity, and Parkinson’s disease:
which aspects of gait are attention demanding? Eur J Neurosci
2005;22(5):1248–56.
21 Callisaya ML, Blizzard L, Schmidt MD, McGinley JL,
Srikanth VK. Ageing and gait variability–a population-based
study of older people. Age Ageing 2010;39(2):191–7.
22 Rezak M. Current pharmacotherapeutic treatment options in
Parkinson’s disease. Dis Mon 2007;53(4):214–22.
23 HausdorffJM,PurdonPL,PengCK,LadinZ,WeiJY,Goldberger
AL. Fractal dynamics of human gait: stability of long-range
correlations in stride interval fluctuations. J Appl Physiol 1996;
80(5):1448–57.
Bryant et al. Gait variability in Parkinson’s disease
964
Neurological Research
2011
VOL. 33
NO. 9