Clinical

Rehabilitation
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Randomized cross-over trial to investigate the efficacy of a two-week physiotherapy

programme with repetitive exercises of cueing to reduce the severity of freezing of gait in
patients with Parkinson's disease
Urban M Fietzek, Frauke E Schroeteler, Kerstin Ziegler, Jens Zwosta and Andres O Ceballos-Baumann
Clin Rehabil 2014 28: 902 originally published online 1 April 2014
DOI: 10.1177/0269215514527299
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research-article2014

CRE0010.1177/0269215514527299Clinical RehabilitationFietzek et al.

CLINICAL
REHABILITATION

Article

Randomized cross-over trial

to investigate the efficacy of a
two-week physiotherapy programme
with repetitive exercises of cueing
to reduce the severity of freezing
of gait in patients with
Parkinsons disease

Clinical Rehabilitation
2014, Vol. 28(9) 902911
The Author(s) 2014
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0269215514527299
cre.sagepub.com

Urban M Fietzek, Frauke E Schroeteler, Kerstin

Ziegler, Jens Zwosta and Andres O Ceballos-Baumann

Abstract
Objective: To investigate the efficacy of a two-week programme of repetitive exercise with cueing and
movement strategies upon freezing of gait in people with Parkinsons disease.
Design: Randomized cross-over trial.
Setting: Specialist clinic for Parkinsons disease.
Subjects: A total of 22 patients with Parkinsons disease and freezing while other symptoms had favorably
responded to dopaminergic treatment.
Intervention: Patients were randomized into a four-week cross-over trial, and received either treatment
(Group 1) or no treatment (Group 2) during Period 1, and switched during Period 2. Treatment consisted
of a two-week programme during which the patients exercised cueing, and movement strategies together
with a physiotherapist.
Main measure: The primary outcome measure was a freezing score assessed from blinded and
random ratings of video recordings. The secondary outcome measure was a patient-reported freezing
questionnaire. Mean differences between the treatment periods (treatment arms) were evaluated for
treatment (period) effects. Sums of treatment periods were evaluated for carry-over effects.
Results: The programme led to a significant treatment effect in the freezing score of 3.0 improvement (95%
confidence interval 0.95.0; p < 0.01). No carry-over or period effects were detected. The questionnaire
revealed a period effect, so groups were compared after Period 1, where a significant difference was
found (15.0 vs. 11.7; p < 0.05).
Schn Klinik Mnchen Schwabing, Munich, Germany
Corresponding author:
Andres O Ceballos-Baumann, Center for Parkinsons Disease
and Movement Disorders, Schn Klinik Mnchen Schwabing,
Parzivalplatz 4, Munich 80804, Germany.
Email: ACeballos-Baumann@schoen-kliniken.de

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Fietzek et al.

Conclusions: The two-week physiotherapy programme reduced the severity of freezing in patients with
Parkinsons disease.
Keywords
Randomized cross-over trial, Parkinsons disease, physiotherapy, freezing, gait
Received: 6 November 2013; accepted: 1 February 2014

Introduction
Freezing of gait is defined as an episodic inability
to generate effective stepping in the absence of any
known cause other than Parkinsonism or higherlevel gait disorders.1 Freezing is difficult to treat
because it is a heterogeneous and complex disorder
that varies in severity, time of occurrence, and triggering situations.2,3 Those patients who experience
freezing while other symptoms positively respond
to dopaminergic therapy pose a special therapeutic
challenge.4
Focused attention and external stimuli were
suggested to be helpful to overcome freezing episodes.5,6 Cueing was defined as the application of
spatial or temporal external stimuli to help initiate,
or facilitate gait,7 and can be presented as acoustic,
visual, or tactile stimuli.8
Although the efficacy of cueing to temporarily
improve gait parameters is well-established,9,10 the
evidence derived from controlled clinical studies is
scarce for the use of cueing to improve freezing.
The RESCUE trial investigated a three-week
home-based intervention using the patient-reported
freezing of gait questionnaire as a secondary endpoint, whereby a 5.5% improvement was demonstrated in the subgroup of patients with freezing.11
Later analyses of the RESCUE data showed that
the training of external rhythmical cueing had
improved turning12 and motor learning.13
Another research group used the freezing of gait
questionnaire in an open, parallel-group design
study to investigate the efficacy of cues with and
without additional treadmill training, thus showing
a beneficial effect.14 In a further study, 12 patients
were openly treated for six weeks, three times 45
min per week, with acoustic and visual cues. This
intervention led to a five point or 20.8% reduction
on the questionnaires range.15

Negative studies were published also. A total of

12 patients, who had freezing while their other
Parkinson symptoms were responding to medication, received acoustic cueing with a metronome
recording on an audiocassette. After one week no
significant changes in frequency and duration of
freezing episodes were observed.16
The adoption of movement strategies where
patients learn to focus attention on gait, or divide a
complex movement into several easier-to-perform
components might enhance the gait in Parkinson
patients.1719Confirmatory clinical trials that primarily investigated freezing are missing for such
interventions.
The lack of a clinical assessment tool to evaluate freezing could have contributed to the observed
paucity of clinical reporting. Therefore, prior to the
conduction of this trial, we designed a novel score
to assess the severity of freezing.20,21 With this
instrument, we aimed to investigate the efficacy of
a two-week physiotherapy programme that included
the exercise of cues, and that taught the patients to
adopt specific movement strategies.

Methods
The trial protocol was approved by the Ethics
Committee of the Technical University Munich, and
was performed in accordance with the ethical standards laid down in the Declaration of Helsinki and its
later amendments. It was registered at the German
clinical trial registration at the University Freiburg
(GCTR, clinical trial number 00000070). Written
informed consent was obtained from all patients
involved in the study prior to any procedures.
The inclusion criteria were a diagnosis of
Parkinsons disease according to UK Brain Bank

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Clinical Rehabilitation 28(9)

criteria,22 a gait disorder with freezing, while other

motor symptoms, e.g. bradykinesia, rigidity,
tremor, convincingly responded to dopaminergic
medication, a Hoehn & Yahr score of less than
four,23 and the ability to walk independently outside the house.
Diagnosis of freezing was established clinically
by four criteria: (1) history taking (with positive
history), (2) neurological examination by a
movement disorder specialist (direct observation),
(3) self-evaluation with the freezing of gaitquestionnaire (score of question 3 1),24 and (4) by
rating the patient in a standardized setting (freezing
score >0). Patients medication were recorded and
kept stable throughout the study. All measurements
were taken during maximal mobility of the patient
at the same time of the day.
As neither standard nor sham physiotherapy for
freezing is available, for this study we chose a
cross-over design with treatment and no treatment
to constitute the two interventions. Hereby, the
subjects serve as their own controls, as the intergroup comparison of the mean intraindividual differences between treatment periods is taken for
efficacy evaluation.25 The trial included three study
visits (week 0, (end of) week 2, (end of) week 4)
and a follow-up contact by letter at week 8 (see
also Figure 1). Participants received baseline
assessments at week 0, and were allocated to either
treatment during Period 1 (week 1 and 2) (Group
1), or during Period 2 (week 3 and 4) (Group 2).
After two weeks patients switched treatment.
The individual therapy programme was conducted by two experienced and certified physiotherapists on site. The programme lasted two weeks
with three training sessions per week of 30 minutes
duration each, or three hours in total. Before the
first training visit, all patients individually were
shown video recordings of their own gait performance for educational purposes. They were then
offered a choice of cueing modalities, i.e. rhythmic
auditory cueing (e.g. metronome), visual one-off
cueing (e.g. modified inverted stick or laser pointer),
auditory-tactile-visual cueing (e.g. long walking
stick), or mental cueing (e.g. counting, imagined
music) that also could be used in combination. After
a try-out session they were trained individually on

the cueing modality that had shown the most promising effects to overcome the freezing episodes.
During the programme, patients were either
trained with permanent acoustic cueing by metronome (n = 13), a combination of metronome plus a
long walking stick that was rhythmically tapped on
the floor (n = 4), a long walking stick as one-off
cue (n = 1), one-off cueing using a laser pointer, a
modified inverted walking stick (n = 1), or mental
cueing (n = 2). For patients with acoustic cueing,
the frequency was adopted to the individual
cadence according to the algorithm proposed by
Willems et al.26
At each session, patients trained in freezingprovoking situations with up to 50 repetitions per
situation. For each patient, two situations were
chosen from five standard provoking situations:
(1) 180 degree turns, performed with three to six
steps, (2) 360 degree turns with four to eight steps,
(3) walking and passage through a door, (4) starting
to walk, (5) starts and stops during walking with
turns. To avoid the habituation of the cue, and to use
the cue for the patients daily life activities, the
training was adopted to the patients individual
performance. This was done by introducing dual-task
situations to simulate real life situations.27

In addition, patients were taught up to five behavioral strategies to overcome or avoid any freezing
episodes. The strategies were: (1) to slow down or
increase their gait velocity, (2) to perform turns in
a wider curve, (3) to pause before initiating the
next step, (4) to initiate movements after breathing
out, and (5) to shift weight from one leg to the
other.
For blinded rating of the freezing score, the leg
movements of the patients were videotaped for
each of the three task levels of the score at each
visit, and the video clips were given 6-digit computer generated random codes (e.g. HY3Z1G).
Following completion of the last patients last visit,
the 207 video clips (23 patients 3 tasking levels
3 visits) were presented in alphabetical order, and
thus, random order, and rated by two experienced
raters with high inter-rater reliability (Spearmans
Rho 0.90, p < 0.0001) who were both blinded to
randomization and treatment allocation. The results

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Fietzek et al.

Figure 1. CONSORT flow diagram.

of the initial rating of rater one were used for further analyses.
A secondary outcome measure was the freezing
questionnaire that records the patients last weeks
experience of his freezing disorder with six
questions.24

We further explored the freezing item of the

Movement Disorder Society Unified Parkinsons
Disease Rating Scale, pt. III (MDS-UPDRS) (question 11)28 at the end of the four-week programme,
and the mobility section of the Parkinsons Disease
Quality of Life Questionnaire 39 (PDQ-39) at

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Clinical Rehabilitation 28(9)

follow-up.29 For safety assessment, patients

recorded any falls in a diary during the four weeks
therapy. This allowed to calculate the mean number
of falls per week, in order to demonstrate that the
programme would not lead to an increase rate of
falling.
A sample size of 40 patients (alpha 5%; power
80%; two-sided test) was considered sufficient for
the detection of a 10% reduction of the freezing
score (range 0 to 36), based on the assumption of a
within-patient standard deviation of 5 in this crossover trial.
The randomization was performed by a study
coordinator who was not involved in other study
procedures, using a computer-generated random
list (Runs test on randomness, pmin 0.057, pmax
0.395, block size of 30), which was concealed from
personnel involved in the recruitment of patients.
Random numbers 1 and 6 were inadvertently disclosed to the first two screen failure patients, and
therefore discarded.
The sums and the intraindividual differences for
the two treatment periods (cross-over differences)
of the primary and secondary outcome measure
were tested for normality distribution, and then for
carry-over, treatment, and period effects with the
two-sided t-test.25 Levels of 5% and 10% were considered statistically significant for treatment and
carry-over/period effects, respectively. Levels of
10% were chosen to increase the chance to detect
the latter effects. Baseline comparisons were calculated using chi-square test for qualitative data,
t-tests for normally, and MannWhitney U-test for
not normally distributed data. Movement Disorder
Society-Unified Parkinsons Disease Rating Scale
(MDS-UPDRS) item 11, and Parkinsons Disease
Quality of Life Questionnaire (PDQ-39) (mobility
domain) were analyzed between baseline and week
four (item 11) and follow-up (PDQ-39) with paired
tests (Wilcoxon signed rank analysis for MDSUPDRS, t-test for PDQ-39). A 5% level was considered significant. The inter-rater reliability of
the freezing score rating was estimated using
Spearmans rank correlation coefficient. Normality
was ascertained with the ShapiroWilk test.
Normal data are presented as mean standard
deviation (SD), other data as median (interquartile

range (IQR)). Statistical tests were calculated with

the XL-Stat software for Microsoft Excel.

Results
Outpatients from the Schn Klinik Mnchen
Schwabing, a specialist Parkinson clinic and
Movement Disorders center were recruited
between February 2009 and January 2010. The
hospital treats about 1200 cases with the diagnosis
of Parkinsons disease every year. A total of 53
patients with freezing were interested in participating. After an initial phone or direct interview to
ascertain the qualification for the programme, 37
patients were invited for screening. We excluded
14 patients who had freezing episodes only when
dopaminergic efficacy had worn off (n = 7),
Parkinsonism of other etiology, e.g. vascular parkinsonism (n = 3), severe orthopedic disabilities (n
= 1), or internal disease (n = 1), clinically obvious
dementia (n = 1), or receiving deep brain stimulation (n = 1). A total of 23 patients were included
into the trial, and 22 patients completed the study
(see also Figure 1). One patient did not comply
with the protocol by starting exercising on his own,
and was excluded after week two. According to
protocol we had aimed to include 40 patients, but
we had to stop recruitment owing to funding
restrictions after 23 patients were randomized.
A total of 22 datasets were eligible for statistical
evaluation. More male patients (N = 16) were
included than female patients (N = 8). Patients in
Group 2 were younger than patients from Group 1
by 5.9 years. With respect to disease stage, duration of disease, levodopa dose, and efficacy variables, similarly no significant differences were seen.
An overview of baseline characteristics is presented in Table 1. Detailed patient and group characteristics data, including medication, are available
online as electronic Supplement 1.
During the physiotherapy programme, the patients
freezing scores decreased by mean 7.2 points during Period 1 in Group 1, and by mean 4.9 points
during Period 2 in Group 2. During no treatment,
the scores increased by mean 2.2 points during
Period 2 in Group 1, but decreased during Period 1
in Group 2 by mean 2.4 points.

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Fietzek et al.
Table 1. Baseline characteristics of Group 1 and 2.
Variable

Group 1

Group 2

Group 1 vs. Group 2

N = 14

N=8

7 M:1 F
3 (23)
64.2 5.88
13.3 3.58
556 195.4

0.24
0.50
0.06
0.66
0.30

11.6 4.75
15.6 2.39
13.5 9.30
1.5 (0.75;2)
0.6 1.2

0.97
0.17
0.96
0.79
0.85

6 of 8
3 of 8

0.85
0.42

Clinical data
Gender
9 M:5 F
Hoehn & Yahr stage
3 (23)
Age (years)
69.8 6.52
Disease duration (years)
12.1 6.40
Levodopa daily dose (mg)
664 242.9
Efficacy variables/safety
Freezing score
11.5 7.30
Freezing questionnaire
13.5 3.74
PDQ-39 (mobility domain)
13.7 8.04
MDS-UPDRS question 11
1 (0;2)
Falls during period 1
0.8 1.8
Therapy modality chosen (only for N>2)
Metronome
11 of 14
Walking stick
3 of 14

Shown are mean standard deviation, and median (interquartile range).

PDQ-39: Parkinsons Disease Quality of Life Questionnaire; MDS-UPDRS: Movement Disorder Society-Unified Parkinsons Disease Rating Scale.

Statistical analyses showed that the freezing

scores were more reduced during treatment compared with no treatment (p < 0.01). The treatment
effect could be estimated with 3.0 (95% confidence
interval 0.95.0). Neither carry-over (p = 0.34) nor
period effects (p = 0.45) were detected (see also
Table 2).
Supporting results were detected with the freezing questionnaire. During treatment the questionnaire scores from Group 1 improved by mean 1.8
points, and by mean 3.1 points in Group 2. Patients
from Group 2 reported stable questionnaire scores
after two weeks of no treatment. After four weeks
patients in Group 1 had further improved by mean
0.7, despite receiving no treatment. While waiting
for treatment in Period 1, patients in Group 2
improved by mean 0.6.
Statistical analyses revealed no interaction, i.e.
carry-over effect, as the observed difference of
periods mean sums was 4.2 (p = 0.13). A period
effect was detected and could be estimated at 1.9
(90% confidence interval 0.93.9; p < 0.01).
Therefore, we compared the questionnaire scores
after Period 1 at week 2, treating the data as in a

parallel-group designed trial. This comparison

revealed a significant subjective treatment response
(p < 0.05) (see also Table 2).
Question 11 of the MDS-UPDRS specifically
asks for freezing and was assessed before the start
and after completion of both periods at week 4, and
was improved (p < 0.05).
Patients from both groups reported a similar frequency of falls at baseline. For the patients of
Group 1 we found neither increases nor reductions
of falls in Period 2 after patients had completed
treatment (p = 0.15).
A total of 21 patients filled out and sent back the
PDQ-39. No clinically relevant signals were
detected in the mobility section of this quality of
life questionnaire one month after completion of
the programme (p = 0.50).

Discussion
In this cross-over trial, we combined cueing
and the adoption of movement strategies, and
had the patients repetitively exercise in freezingprovoking situations to achieve effective treatment.

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Clinical Rehabilitation 28(9)

Table 2. Results of Group 1 and 2.

Primary outcome measure freezing score
Period 1

Period 2

Tested effect
Group 1
Group 2
P

4.3 4.9
9.3 7.1

6.5 5.6
5.5 3.3

Period 1
Period 2

Treatment
no treatment

Period 1 +
Period 2

Treatment

Period

Carryover

2.2 2.8
3.8 6.7
p = 0.008

2.2 2.8
3.8 6.7
p = 0.455

10.8 10.1
14.8 8.7
p = 0.365

Period 1
Period 2

Treatment
No Treatment

Period 1 +
Period 2

Treatment

Period

Carryover

0.7 3.1
3.1 1.8
p = 0.005

22.7 6.7
26.9 3.8
p = 0.125

Secondary outcome measure freezing questionnaire

Period 1

Period 2

Tested effect
Group 1
Group 2
P

11.7 3.6
15.0 2.3
p = 0.032

11.0 3.8
11.9 1.9

0.7 3.1
3.1 1.8
p = 0.059

Week 0

Week 4

Week 8

MDSUPDRS
question 11
PDQ39 mobility

1 (0;2)

0 (0;1)

Exploratory variables

13.6 8.3

p
p = 0.028

14.4 8.9

p = 0.504

Safety variable

Falls
Within Group 1

In Period 1

In Period 2

0.8 1.8

0.5 1.1

p = 0.149

Shown are mean standard deviation, and median (interquartile range).

PDQ-39: Parkinsons Disease Quality of Life Questionnaire; MDS-UPDRS: Movement Disorder Society-Unified Parkinsons Disease Rating Scale.

The effect amounted to three points or about 10%

improvement on the freezing scores range. Its
duration was not assessed in the follow-up, and,
thus, remains uncertain. As no carry-over effect
was found in the scores data, a significant duration over the period of two weeks is unlikely.
Therefore, the question towards its clinical relevance cannot finally be answered by the data of
this study. Other research with levodopa or deep
brain stimulation using the same freezing assessment had shown larger improvements of 12 points,
or 814 points on the scores range, respectively.21,30 Furthermore, the treatment did not
change the patients self-evaluation of their

mobility-associated quality of life four weeks after

the end of the programme.
For the information from previous research
on cueing, the magnitude of the effect is not
surprising.11,15 While the trials data will not discern the active component of the intervention, we
have learned that short-term effective treatment of
freezing is feasible, and should be explored further.
The cueing modality most frequently chosen by
about 75% of the patients was external rhythmical
cueing with a metronome. Because both positive
and negative results for the use of acoustic cueing
on Parkinsonian gait were described in earlier
trials,9,16 this trials positive finding might be

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Fietzek et al.
explained by the choice of an adapted frequency as
described by other researchers.26 Meanwhile,
acoustic rhythmical cueing has also been shown to
have positive effects on turning, and motor learning.12,13 Therefore, this well researched cueing
modality could be chosen for a more focused treatment approach in future studies.
The result of the freezing assessment was confirmed by further observations in the open patientreported outcome measure. Results by the freezing
questionnaire revealed a significant period effect,
i.e. both groups improved over the time irrespective of treatment. Such an observation may have
resulted from unspecific positive responses in both
groups, such as an increased motivation or attention for gait, or simply from habituation to the
environment. It also may have resulted from the
relatively long evaluation period of one week,
which supports the tendency to detect longer lasting effects.31
It is known that cueing and movement strategies
affect the gait disorder immediately, although
patients have to familiarize themselves with their
new tool. The new motor behavior is best learned
in the context-specific high-demanding situations.32 Therefore, in our trial, patients repetitively
exercised during freezing-provoking situations,
such as starts and turns, which are part of many
activities of daily living. We trained patients in the
hospital, and observed improvements despite the
designed practice setting and the relatively short
duration of the programme. However, patients
experienced a loss of positive effects after the end
of intensive training, and such results are in agreement with data reported from other physiotherapy
studies and clinical experience.33,34 Thus, it is likely
that to increase the magnitude of effect or to sustain
effectiveness, patients may need to receive refreshment therapy, or may need to practice continuously
by themselves. Providing the programme at home
in daily life situations for longer time periods might
further increase transfers of learned motor behavior, and increase the duration of the treatment
effect.
We enrolled patients with Parkinsons disease
whose bradykinetic motor symptoms were clearly
responsive to dopaminergic treatment, but who

nonetheless experienced therapy resistant and often

disabling freezing while responding favorably to
dopaminergic treatment. All of the included patients
also experienced freezing when their pharmacological treatment had worn off. By treating this type of
patients, we aimed to minimize any pharmacological therapy bias, as positive dopaminergic effects
might else have interfered with the interpretation of
the causality of the physiotherapy effect. Limiting
the trial to this population, however, substantially
reduced the number of eligible patients, and we
failed to meet our optimistic enrolment target. The
trials cross-over design, which evaluates intraindividual changes, still allowed the detection of a
therapy response, which might have been missed in
a similarly sized parallel group study.
This cross-over trial provides class III evidence35 of beneficial short-term effects of a twoweek physiotherapy programme for Parkinson
patients who experienced freezing while their other
Parkinson symptoms responded to dopaminergic
medication. Therefore, we consider it an important
adjunction for this group of patients. Sufficiently
powered randomized multi-center trials are needed
to further increase the level of evidence for physiotherapeutic treatment of freezing.

Clinical message

 two-week programme of exercising cueA

ing and movement strategies was effective to reduce the severity of freezing of
gait in patients with Parkinsons disease.

Acknowledgement
We thank Kathy Thomas-Urban, Inga Krte and Klaus
Starrost for reading the manuscript and providing valuable suggestions.

Conflict of interest
The authors declare that there is no conflict of interest.

Funding
This work was supported by the Deutsche Parkinson
Vereinigung (German Parkinson Asscociation); and the

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Clinical Rehabilitation 28(9)

Deutsche Stiftung Neurologie (German Foundation

Neurologie).

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