CNS Drugs (2013) 27:97112
DOI 10.1007/s40263-012-0012-3
REVIEW ARTICLE
Postural Instability in Patients with Parkinsons Disease
Epidemiology, Pathophysiology and Management
Samuel D. Kim Natalie E. Allen Colleen G. Canning
Victor S. C. Fung
Published online: 18 October 2012
Springer International Publishing Switzerland 2012
Abstract Postural instability is one of the cardinal signs
in Parkinsons disease (PD). It can be present even at
diagnosis, but becomes more prevalent and worsens with
disease progression. It represents one of the most disabling
symptoms in the advanced stages of the disease, as it is
associated with increased falls and loss of independence.
Clinical and posturographic studies have contributed to
significant advances in unravelling the complex patho-
physiology of postural instability in patients with PD, but it
still remains yet to be fully clarified, partly due to the
difficulty in distinguishing between the disease process and
the compensatory mechanisms, but also due to the fact that
non-standardized techniques are used to measure balance
and postural instability. There is increasing evidence that
physical therapy, especially highly challenging balance
exercises, can improve postural stability and reduce the risk
of falls, although the long-term effects of physical therapy
interventions on postural stability need to be explored
given the progressive nature of PD. Pharmacotherapy with
dopaminergic medications can provide significant
improvements in postural instability in early- to mid-stage
PD but the effects tend to wane with time consistent with
spread of the disease process to non-dopaminergic
S. D. Kim
V. S. C. Fung (&)
Movement Disorders Unit, Department of Neurology, Westmead
Hospital, Darcy Rd, Westmead, NSW 2145, Australia
e-mail: vscfung@ozemail.com.au
S. D. Kim
V. S. C. Fung
Sydney Medical School-Western, The University of Sydney,
Sydney, NSW, Australia
N. E. Allen
C. G. Canning
Clinical and Rehabilitation Sciences Research Group,
Faculty of Health Sciences, The University of Sydney,
Sydney, NSW, Australia
pathways in advanced PD. Donepezil has been associated
with a reduced risk of falls and methylphenidate has shown
potential benefit against freezing of gait, but the results are
yet to be replicated in large randomized studies. Surgical
treatments, including lesioning and deep brain stimulation
surgery targeting the subthalamic nucleus and the globus
pallidus internus, tend to only provide modest benefit
for postural instability. New surgical targets such as the
pedunculopontine nucleus have emerged as a potential
specific therapy for postural instability and gait disorder
but remain experimental.
1 Introduction and Definition
Posture and balance are the foundation on which upright
stance and walking are executed. The term posture
describes the orientation of any body segment relative to
the gravitational vector and provides the mechanical sup-
port for performing movements, while balance is a gen-
eric term describing the dynamics of body posture that
prevents falling in quiet stance or during locomotion [1, 2].
Locomotion, on the other hand, describes the forward
progression associated with walking, and is critically
linked with the ability to initiate and maintain rhythmic
stepping [3]. Thus, postural and balance control can be
defined as stabilization or maintenance of equilibrium of
the body in relation to gravitational force under static and
dynamic conditions, and postural instability, is the
impairment in balance that compromises the ability to
maintain or change posture such as standing and walking.
Postural instability is considered to be one of the car-
dinal features of Parkinsons disease (PD) together with
rest tremor, rigidity and bradykinesia [4]. It is present in
some patients even at diagnosis and worsens with disease
98
progression, although when prominent early in the disease
course, it suggests the possibility of an atypical parkinso-
nian disorder such as progressive supranuclear palsy or
multiple system atrophy [5].
Postural instability is a major source of disability and
reduced quality of life in PD [6]. In the DATATOP
(Deprenyl And Tocopherol Antioxidative Therapy fOr
Parkinsons disease) cohort, greater disability and more
depression were observed in PD patients with predominant
postural instability and gait disorder than those who had
tremor-dominant PD [7]. Furthermore, it not only corre-
lates with falls [8] but also with fear of future falls, which
can be incapacitating in its own right [9].
Pathophysiology of postural instability is complex, with
contributions from the primary disease process and com-
pensatory strategies. The most significant abnormality in
postural control results from impaired postural reflexes
with as yet incompletely understood mechanisms [10].
This paper will review the epidemiology, pathophysiology
and, lastly, the management of postural instability in PD.
As posture and balance are intimately related to walking,
this paper will also briefly discuss the impact of postural
instability on gait and falls.
2 Epidemiology
2.1 Prevalence
Mild postural instability is reasonably common early in
untreated PD and seemingly inevitable in the later stages.
Information from the Sydney multi-centre longitudinal
study of PD shows that within 2 years of diagnosis, 34 %
of the sample already demonstrated postural instability on
the basis of abnormal reactive postural responses, i.e.
Hoehn and Yahr (H&Y) Stage 3 [11]. Ten years later,
71 % of the surviving participants demonstrated postural
instability, i.e. H&Y Stages 35 [12], while at the 15-year
follow-up, postural instability was reported in 92 % of
survivors [13]. At the 20-year follow-up, only one of the
surviving participants remained in H&Y Stage 2 [14]. In
addition to abnormal postural responses, there is mounting
evidence of abnormalities of anticipatory postural adjust-
ments early in the disease process. In individuals in H&Y
Stage 2, abnormal anticipatory postural adjustments during
turning have been reported [15], while abnormal sway in
standing has been reported in recently diagnosed and un-
medicated individuals [16]. Some postural instability in PD
could reasonably be attributed to the effects of ageing on
systems that contribute to postural stability. Nevertheless,
studies that have compared people with PD with an age-
matched control group consistently show people with PD
S. D. Kim et al.
have greater deficits in postural stability [1719] and
higher fall rates [2023]. In the largest prospective com-
parative study to date [23], even those people with PD who
did not fall in the 12-month follow-up period had signifi-
cantly poorer balance and gait scores than the healthy age-
matched control group.
In prospective studies, postural instability is consistently
identified as a risk factor for falls [24, 25]. Falls and
recurrent falls occur at an alarmingly high rate in people
with PD. In a recent systematic review, 21 prospective
studies reported the number of fallers and/or the number of
falls in a sample of people with PD [26]. Between 35 and
90 % of participants reported falling at least once during
monitoring periods ranging from 3 months to over 2 years,
while between 18 and 65 % of participants fell more than
once. Furthermore, a meta-analysis of six prospective
studies [27] shows that 21 % of people with PD who have
not fallen previously will fall within the next 3 months,
indicating that prior falls is inadequate for predicting all
falls.
In the USA (19992002), the direct annual healthcare
costs of PD was reported to be $US23,101 per person,
which is double that of controls [28]. Although the impact
of postural instability has not been specifically addressed
from an economic perspective, increasing levels of motor
disability have been reported to be associated with
increased healthcare and productivity costs [29].
2.2 Impact of Postural Instability and Falls on Activity
and Participation
Postural instability and falls are significant causes of dis-
ability, lost independence and reduced quality of life in
people with PD [3033]. The resulting pain [32], limitation
of activities [20, 34, 35], fear of falling [9, 36] and unac-
ceptably high levels of caregiver stress [37, 38] mean that
the consequences of postural instability and falling are
devastating and widespread. A recent longitudinal study
shows that progression to H&Y Stage 3 is specifically
associated with significant deterioration on quality of life
[34]. However, even newly diagnosed individuals with
postural and gait instability experience more significant
impact on everyday activities and quality of life than
patients with tremor-dominant symptoms [35]. As expec-
ted, fear of falling is consistently reported to be associated
with postural instability and falls [9, 39, 40]. However,
there does appear to be a small subset of people with PD,
who are highly unstable and fall frequently, while reporting
little fear of falling [41]. Recent work also shows that
people with PD with postural and gait instability are more
likely to experience anxiety than those with tremor-domi-
nant symptoms [42].
Postural Instability in Parkinsons Disease
2.3 Risk Factors and Predictors of Falls
Despite the high prevalence of postural instability and falls
in people with PD, the relationship between postural
instability and falls is not entirely straightforward, with
many other risk factors for falls likely to act as modulators.
A large number of risk factors for falls in people with PD
have been proposed in both prospective and retrospective
studies, but they have not been consistently identified
across studies [21, 24, 25, 27, 4346]. The two most
comprehensive prospective studies [24, 25] both identified
postural instability as an independent risk factor for falls.
Latt and colleagues [25] have published the best prospec-
tive explanatory model to date (sensitivity 77 %, specificity
82 %) identifying freezing of gait (FOG), flexed posture,
cognitive impairment, poor balance and leg weakness as
independent fall risk factors. Interestingly, although age
and co-morbidities such as postural hypotension and use of
multiple medications were associated with falls in univar-
iate models, these factors did not make a significant con-
tribution to the multivariate model [25]. In addition, a
meta-analysis of six prospective studies [27] indicates that
disease severity is not a good predictor of falls, possibly
because falls risk reduces with severe disease, which con-
fines patients to a wheelchair or bed [20].
The contribution of impaired cognition to falls has been
highlighted in a recent prospective study of 164 individuals
with PD [46]. Although specific measures of postural
instability were not taken, fall frequency was analysed with
respect to cognition, disease severity, age, medications,
orthostatic hypotension and visual impairment. In a
multivariate model, adjusted for disease severity, fall
frequency was associated with power of attention and
reaction time variability. Frontal cognitive impairment as
assessed using the Frontal Assessment Battery [47] was
also identified as an independent risk factor for falls [25],
more so than low scores on the Mini-Mental State Exam-
ination (MMSE) [48].
3 Pathophysiology
Postural and balance impairments are assessed either
through quantitative laboratory-based systems or through
clinical observational tests. These studies have yielded
limited and contradictory results, partly due to the fact that
the PD population is diverse, but also because of the dif-
ferences in study designs such as disease severity, defini-
tion of fallers versus non-fallers and medication states, as
well as methods used to measure balance and postural
instability [49]. The most significant insights have been
gained from posturographic studies, using static and
moveable force platforms that measure the foot centre of
99
pressure (COP) and other sway parameters under different
treatment states, i.e. dopaminergic medications and/or deep
brain stimulation (DBS) surgeries. However, these studies
are beset by the fact that the techniques have not been
standardized, making it difficult to interpret data obtained
across different studies. In particular, studies under static
conditions have shown increased, normal [50] or even
reduced [51] spontaneous body sway, perhaps reflecting
the fact that reliability of postural sway can be influenced
by disease and medication factors such as disabling dys-
kinesia [52]. It is noteworthy that performance in some of
these tests is only poorly related to clinical tests of balance
and history of falls [53]. In addition, the pull test, a com-
monly used clinical test, is difficult to standardize and does
not test anticipatory balance.
3.1 Postural Reflexes
Maintenance of an upright body posture in humans is an
automatic activity that requires minimal attention [17]. The
CNS provides coordination between posture, equilibrium
and movement by utilizing two main mechanisms. Auto-
matic postural reactions (APR) occur in response to sen-
sory information, which signal postural disturbances
caused by movement, received from the visual, vestibular
and somatosensory systems, while anticipatory postural
adjustments (APA) occur in association with voluntary
movements and dampen the effects of the forthcoming
disturbances by preceding the disturbance onset [54, 55].
Both anticipatory and reactive postural control mecha-
nisms are altered in PD. Variable changes in APA have
been reported, but this reflects the differences in the disease
severity of the study population. In early-stage PD patients,
there is an exaggerated movement preparation when per-
forming sit-to-stand tasks [56], while patients with more
advanced disease tend to have reduced APAs [57], being
more common in those with postural instability [58].
Additionally, there is a variable pattern of muscle activa-
tion [59] that does not correlate with bradykinesia, likely
reflecting deficits in the preparation and initiation of a
motor act in PD.
APR are also impaired in PD, with the early reactive
trunk movements being markedly reduced, and causing the
trunk to fall like a log in the direction of postural pertur-
bation [60]. The postural reflexes show an abnormal pattern
of activation. The destabilizing medium-latency stretch
reflexes are exaggerated, while the stabilizing long-latency
stretch reflexes have been reported as either normal or
diminished [18, 60, 61]. Furthermore, the innervation
sequence of long-latency reflexes is reversed in patients
with advanced disease [61]. Significantly, these reflexes
adapt poorly to changes in postural tasks, e.g. PD patients
have impaired ability in suppressing postural responses in
100
ankle muscles when the force platform perturbation sud-
denly changes from backward translation to toes up rota-
tion [62], and also display inadequate scaling of muscle
activation as well as impaired modification of the direction
of ground reactive forces in response to changes in stance
width [63, 64]. Moreover, PD patients have an impaired
ability to suppress medium- and long-latency reflexes when
changing from free stance to supported stance (holding
onto a stable structure) [50]. This impaired postural adap-
tation to changes in postural tasks has been referred to as
postural inflexibility [50, 51, 65].
There are variable reports of responsiveness of postural
instability to levodopa, likely reflecting the differences in
the PD population studied as involvement of non-dopa-
minergic systems becomes more important in advanced
stages of the disease, especially with respect to gait and
postural control. Some have reported that there is no
significant improvement or even worsening of postural
stability with levodopa, both clinically and as measured by
increased postural sway [7, 49], but others have contended
that postural sway amplitude is only loosely related to
postural stability [66], and there is good evidence that axial
impairments including postural instability and gait are
levodopa responsive, even in the advanced stages of the
disease, although these impairments are somewhat less
responsive than bradykinesia and rigidity [67].
A study [68] comparing the respective effects of levo-
dopa and subthalamic nucleus-DBS (STN-DBS) on pos-
tural stability in advanced PD patients (mean H&Y Stage 3
off therapy; mean disease duration 12.9 years) has dem-
onstrated that levodopa therapy provides a similar magni-
tude of benefit in clinical measures as measured by the
Unified Parkinsons Disease Rating Scale (UPDRS) [69]
compared with off states, although objective measures
(posturography) reveal a greater magnitude of benefit with
STN-DBS [68]. In this study, PD patients had abnormal
posterior displacement of foot COP and levodopa restored
a forward position in both static and dynamic conditions.
Similar posturographic results were reported by Bloem
et al. [70], although they only reported partial improvement
in COP displacement, and there was a failure of correction
of medium-latency reflex amplitudes.
3.1.1 What Underlies Impaired Postural Reflexes?
It has been hypothesized that disordered basal ganglia
physiology and dopaminergic deficit underlie the deranged
postural reflexes in PD. Specifically, increased medium-
latency reflex amplitude results from reduced inhibitory
output of the nigrostriatal circuit due to dopaminergic
deficit while reversed long-latency reflex innervation
sequence reflects failure of selection and initiation of
appropriate motor programmes in PD [18, 7173].
S. D. Kim et al.
Furthermore, dopaminergic deficit correlates with the
degree of impairment of stabilizing long-latency reflexes.
Patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-induced parkinsonism have greatest impairment in
stabilizing long-latency postural reflexes, followed in order
by young PD patients, those exposed to neuroleptic with or
without extrapyramidal symptoms, and normal controls,
suggesting that long-latency reflexes are under supraspinal
dopaminergic control [74].
In support of the role of basal ganglia in postural
instability, studies of ground reactive forces with moveable
force platforms have revealed that PD patients have larger
than normal passive reactive forces and smaller than nor-
mal reactive forces in the active period, consistent with
parkinsonian rigidity and bradykinesia, respectively [19].
In line with this, PD patients when falling tend to fall like a
log, with smaller hip and knee displacements and excessive
co-contraction of antagonistic hip and trunk muscles,
consistent with the anticipated effects of truncal rigidity
[60]. However, the abnormal direction and inflexibility of
reactive forces (i.e. impaired postural reflexes) cannot be
explained solely on the basis of rigidity and bradykinesia,
suggesting additional deficits in APR [64]. Postural defi-
cits, at least in more severe disease, tend to be levodopa
resistant [19, 75], and the fact that levodopa has no sig-
nificant effect on axial tone, suggests that axial and
appendicular tone are controlled by different circuits [76].
Furthermore, nigral cell loss, as documented with fluo-
rodopa positron emission tomography (PET) scans, shows
an excellent correlation with bradykinesia, but much less so
with postural instability [77]. It is of potential relevance
that truncal rigidity can be a compensatory strategy in
response to fear of falls, as a stiffening strategy, which
reduces the degree of freedom of movement and simplifies
postural control. This strategy is seen in healthy controls
when made artificially fearful by standing on an elevated
platform [78, 79]. Disentangling pathological from
compensatory truncal stiffness in PD patients remains a
challenge.
3.2 Effects of Stooped Posture on Postural Control
In PD patients, there appears to be an excessive forward
shift in foot COP, which correlates with disease severity as
measured by the motor section of the UPDRS. However,
conflicting results have also been reported, including
reports of no significant change in foot COP [80], as well as
a variable change in foot COP depending on disease
severity, with a backward shift in the less affected and a
forward shift in more affected patients [50].
Although stooped posture has been identified as an
independent risk factor for falls in PD [25], this posture and
changes in foot COP may be compensatory [81, 82]. First,
Postural Instability in Parkinsons Disease
PD patients become more unstable when they voluntarily
adopt an upright posture, suggesting that stooping is
compensation for, and not a cause of, primary postural
deficits in PD [81]. Secondly, when asked to stand on a
movable platform, PD patients are predominantly unstable
when toppled backwards [60], and healthy subjects
adopting a stooped posture minimize backward centre of
mass displacements in response to toe-up rotations [70].
Finally, it has been shown that the postural changes in PD,
as noted by shifts in foot COP, do not fully account for
abnormal postural responses in PD despite the fact that it
has a destabilizing effect [83]. Therefore, PD subjects are
not unstable simply because they stoop, but because they
co-activate antagonistic muscle groups, stiffen their joints
and produce weak and abnormally directed ground reaction
forces.
Separately, another important but less common source
of postural instability is camptocormia or Pisa syndrome in
which there is abnormal forward and lateral flexion of the
trunk, respectively [10, 84]. The pathophysiology of
camptocormia and Pisa syndrome is likely to be predomi-
nantly due to axial dystonia, although some have argued
that camptocormia is due to paraspinal myopathy [8588].
The impairment of postural stability and gait likely arises
from the prominent displacement of the body centre of
mass superimposed on already impaired underlying pos-
tural reflexes in PD.
3.3 Postural Sway
Increased sway amplitude/area has been reported in PD
subjects compared with controls, and commonly reported
to increase further with medication, although a correlation
has not been shown between these and measures of pos-
tural instability [16, 49, 66, 75]. Recently, it has been
suggested that sway parameters increase with disease
severity (early vs. late) but unfortunately no direct corre-
lation was made with postural instability [89]. A study
comparing the effects of medication with STN-DBS has
shown increased sway velocity in the medio-lateral direc-
tion, as well as increased sway amplitude on medication,
while postural sway parameters tended to return to normal
control values on STN-DBS [89].
3.3.1 What Underlies Increased Sway?
It has been shown that PD patients sway significantly more
as a percentage of measures of leaning balance (maximal
balance range), suggesting that PD patients tend to
encroach upon their limits of stability to a much greater
extent [90]. This could be related to PD patients responding
with small joint angle displacements to externally gener-
ated, anticipated perturbations [83], consistent with the
101
findings that PD patients are unable to appropriately scale
their postural motor reactions [75, 91]. Levodopa increases
the force (but does not influence the degree of scaling) of
both voluntary and involuntary stabilizing motor responses
during rise-to-toes tasks [92].
3.4 Attention and Postural Instability
Dual task interference on postural control can be observed
in PD patients during performance of cognitive as well as
motor tasks [93], consistent with the hypothesis that PD
patients use attentional strategies to compensate for pos-
tural instability. However, switching from unitask (quiet
stance or external perturbation in upright stance) to con-
current verbal-cognitive dual task conditions in which
subjects attention is diverted showed similar rates of
change in standing balance in both controls and PD
patients, suggesting that there is no significant contribution
from attentional strategies in maintaining balance in PD
patients (although they have a higher risk of losing balance
due to their more severe initial deficit) [94].
3.5 Role of Sensory Information in Postural Control
The possibility of disordered sensory systems contributing
to postural instability in PD has been explored in a number
of studies. Proprioceptive deficit has been reported and it
has been proposed that this might be related to impaired
body orientation in PD [95, 96]. When trained foot dorsi-
flexion movements are preceded by vibration to the
Achilles tendon, the amplitude of the dorsiflexion move-
ments are significantly reduced in amplitude in both PD
patients and normal controls, but significantly less so in the
PD patients [96]. Furthermore, when postural control is
examined on a tilting support platform in the absence of
visual and vestibular information, unlike healthy subjects
who are able to maintain vertical body orientation, PD
patients are unable to maintain the vertical trunk orienta-
tion without vision and follow the oscillations of the sup-
porting platform [95, 97]. It is well established that PD
patients increasingly depend on visual cues for control of
locomotion and it might be that this visual dependence may
be an adaptive strategy to compensate for their proprio-
ceptive deficits [98]; while normal adults employ dynamic
visual information only when the conditions of equilibrium
are compromised, PD patients are highly dependent on
dynamic visual information for the control of their gait
velocity, even in unperturbed conditions of equilibrium
[99].
On the other hand, the involvement of vestibular dys-
function as one of the main causes of parkinsonian insta-
bility has been previously excluded [100]. A recent study,
however, by Vitale et al. [101] has raised the possibility of
102
unilateral peripheral vestibular hypofunction in PD patients
affected by lateral trunk flexion, but the number was small
and the results need to be validated in a larger study.
4 Management
4.1 Physical Therapy
There is an increasing body of evidence that physical
therapy interventions can improve postural stability and
balance-related activity performance, i.e. gait and mobility,
of people with PD. There are four systematic reviews that
have specifically addressed the effect of physical therapy
interventions on balance in people with PD [102105].
Dibble et al. [103] concluded that there is moderate evi-
dence that physical activity and exercise can improve
performance on measures of postural stability and balance-
related activities in people with mild to moderate PD.
However, the authors commented that the small number
and limited quality of the included trials indicated that
more research is required to further clarify the impact of
exercise interventions on balance. More recently, three
systematic reviews with meta-analyses examined the effect
of physical therapy-based interventions on balance [102,
104, 105]. Results showed that physical therapy had a
small but favourable effect on the Berg Balance Scale [104,
105], functional reach [104], the Timed Up and Go [104,
105] and overall performance of balance-related activities
[106]. However, both of the reviews that considered falls
found that there was insufficient evidence to determine if
this improvement in balance translated to a reduction in
falls [104, 106].
Many different modes of physical therapy intervention
have been shown to have some impact on balance and
balance-related activity performance. These include
exercise programmes with balance training components
[107111], external cueing training [112, 113], supervised
treadmill training [114116], training of responding to
external perturbations [109, 111, 116119], movement
strategy training [120], Tai Chi classes [121, 122] and
partnered dance classes [123125]. However, there is
currently no evidence of different treatment effects with
different types of physical therapy intervention [104].
Therefore, while physical therapy can improve the postural
stability of people with PD, the optimal design and delivery
of programmes remains unclear.
There have been seven moderate- to large-sized (n C 30
per group), high-quality (Physiotherapy Evidence Database
quality rating 6/10 or higher) [126], randomized controlled
trials of physical-therapy based interventions for people
with PD that reported outcome measures related to postural
stability (Table 1). Overall, all of these studies report some
S. D. Kim et al.
favourable results. However, most improvements are small
to moderate in size and there are variable results between
trials for any given outcome measure.
The most recent large, randomized controlled trial has
provided the largest improvements in postural stability. Li
et al. [121] compared Tai Chi, resistance training and
stretching programmes conducted by people with PD in
group settings, twice per week for 6 months. Results
showed that after training, the Tai Chi group made clini-
cally significant improvements and performed consistently
better than the other two groups on measures of postural
stability and stride length. Furthermore, this is the only trial
in which these improvements translated to a reduction in
falls, with the Tai Chi group experiencing 67 % fewer falls
during the intervention period than the stretching group.
Treadmill walking has become a relatively common
feature of many training programmes for people with PD.
There is evidence that treadmill walking is beneficial in
improving gait speed and stride length [127], with a small
amount of evidence that it may improve postural stability
[114, 115, 117]. It must be noted that these treadmill training
interventions were closely supervised [114, 115, 117], often
requiring participants to wear a harness for safety [115, 117].
Several trials have utilized external perturbations as part
of a balance training programme, often in the form of
shoulder pushes from the therapist [109, 116, 118, 119] and/
or standing on a compliant surface or moveable platform
[119, 128, 129]. Several of these trials report improvements
in balance outcomes and/or the performance of balance-
related activities [109, 111, 119, 128]. However, all of these
trials used external perturbations as one aspect of a balance
training programme, which also included training of antic-
ipatory and ongoing postural adjustments. It is therefore not
possible to ascertain the contributions of the different forms
of balance training to the overall improvement.
Despite the evidence of the benefits of physical therapy
on postural stability in people with PD, the optimal mode,
dose and delivery of balance training remains uncertain.
Nonetheless, there is evidence to suggest that highly
challenging balance exercises may be more beneficial than
other forms of exercise. These highly challenging balance
exercises are performed standing and involve narrowing of
the base of support and minimization of upper limb support
combined with controlled movements of the centre of mass
[130]. One of the aforementioned systematic reviews with
meta-analyses [102] found that those trials that contained
highly challenging balance training tended to have a
greater pooled effect on balance-related activity perfor-
mance than those without. However, the difference
between these two groups of trials did not reach statistical
significance, indicating that more randomized controlled
trials of highly challenging balance interventions are
required to be sure of their greater effect. Highly
Table 1 Randomized controlled trials of physical therapy-based interventions to improve postural instability in Parkinsons disease
First author, H&Y stage, Initial Intervention description Intervention duration and frequency Results (between-group comparisons related
year tested group sizes to postural stability outcomes)
ON/OFF

Ashburn, H&Y 24, 70 Exercise and strategy training: leg muscle 6 weeks, 1 home visit per week, 1 h per Fallsa
2007 tested ON strengthening, range of movement, balance and visit, daily independent exercise Fall eventsa
walking exercises. Strategies for falls prevention,
movement initiation and compensation Injurious falls

72 Control: usual care Near fallsb

Berg Balance Scale
Functional Reachb (significant only at 6-month follow-
up)
Sit to stand time
Postural Instability in Parkinsons Disease

Timed Up and Go
Duncan, H&Y 14, 32 Argentine Tango dancing: community-based classes 12 months, 2 sessions per week, 1 h per Gait velocity (preferred paceb, fast pace, dual task at
2012 tested OFF where participants danced in both leader and follower session preferred paceb, backwards)
roles MiniBESTestb
30 Control: usual care PIGDb
Ellis, 2005 H&Y 23, 35 Physiotherapy: small classes (n = 4) with 6 weeks, 2 sessions per week, 1.5 h per Gait velocity (preferred pace on treadmill without hand
tested ON cardiovascular warm-up, stretching exercises, session support)b
functional strengthening exercises, overground and
treadmill walking with auditory cueing, balance
training, recreational games and relaxation exercises
35 Control: usual care
Goodwin, H&Y 14, 64 Exercise: community-based exercise classes consisting 10 weeks, 1 exercise class per week, 1 h Fallsa
2011 tested ON of a warm-up (cardiovascular exercise, range of per class, 2 home exercise sessions per Fall eventsa
motion exercise and stretches), strength and balance week
exercises and a cool-down (stretches) Injurious falls

66 Control: Usual care Berg Balance Scaleb

Falls Efficacy Scale-Internationalb
Timed Up and Go
Li, 2012 H&Y 14, 65 Tai Chi: Tai Chi protocol specifically designed to 24 weeks, 2 sessions per week, Maximum excursiona,b
tested ON challenge balance and gait 1 h per session Directional controla,b
65 Resistance training: progressive lower limb Fallsb
strengthening using weighted vests and ankle weights
Functional Reachb
65 Stretching: control condition with seated and standing
stretches Gait velocity (preferred pace)b
Stride length (preferred pace)b
Timed Up and Gob
(Tai Chi better than resistance training and stretching
groups for maximum excursion, directional control,
stride length and functional reach. Tai Chi group had
fewer falls, faster gait velocity and faster Timed Up
and Go than the stretching group, but not the
resistance training group.)
103
Table 1 continued
104

First author, H&Y stage, Initial Intervention description Intervention duration and frequency Results (between-group comparisons related
year tested group sizes to postural stability outcomes)
ON/OFF

Nieuwboer, H&Y 24, 76 Cueing training: home-based cueing training practiced 3 weeks, 3 sessions per week, 30 min PG scorea,b
2007 tested ON in a variety of tasks and environmental situations per session Cadence (preferred pace)
77 Control: usual care Falls
Functional Reach
Gait velocity (preferred pace)b
Step length (preferred pace)b
Single leg stand timeb
Timed Up and Go
Smania, H&Y 34, 33 Balance training: balance exercises focussed on 7 weeks, 3 sessions per week, 50 min ABC scalea,b
2010 tested ON responding to self-initiated movements and external per session Berg Balance scalea,b
perturbations as well as walking over obstacles
Sit to stand timea,b
31 General exercises: control condition with exercises not
aimed at improving postural reactions CFP during self-destabilizationa,b
Fallsa,b,c

ABC Activities specific balance confidence, BESTest Balance Evaluation Systems Test, CFP centre of foot pressure, H&Y Hoehn and Yahr, PG score posture and gait score derived from summing items
1315 and 2930 of the Unified Parkinsons Disease Rating Scale (UPDRS), PIGD postural instability/gait disorder measure derived from summing items 3.93.13 in the Movement Disorder Society
(MDS)-UPDRS
a
Primary outcome measures
b
Statistically significant improvement in the intervention group compared with the control group
c
MannWhitney test used to compare falls between groups, rather than the accepted negative binominal regression method with adjustment for baseline falls
S. D. Kim et al.
Postural Instability in Parkinsons Disease
challenging balance exercises have been found to improve
the effectiveness of fall prevention programmes designed
for the general older population [130]. Additionally, Tai
Chi meets the criteria for highly challenging balance
exercises and is the only intervention to date with evidence
that it can reduce falls in people with PD [121]. Taken
together, these results suggest that the inclusion of highly
challenging balance exercises in physical therapy pro-
grammes for people with PD should be recommended.
There is a wide range in the disease severity, dominant
impairments and cognitive status of individuals with PD,
and optimum physical therapy for postural instability may
differ for people with different disease severities and pre-
sentations. However, most randomized controlled trials
have wide inclusion criteria and therefore a wide range of
disease severity is represented (see Table 1). Additionally,
few studies have the statistical power to undertake sub-
group analysis, and those that have done such analyses
have not assessed the effect of disease severity on postural
stability outcomes. Further large-scale trials powered to
detect effects in sub-groups are required in order to develop
more specific recommendations.
Most trials to date have been short term, highly super-
vised and facility based, conducted in either a hospital or
university setting [131]. However, some trials have been
semi-supervised with participants completing all or most of
the intervention at home [107, 108, 110, 112]. It is easier to
deliver effective, highly challenging, balance training in
fully supervised, facility-based settings. However, most
healthcare systems would not be able to support such
resource-intensive programmes in the long term. Given the
progressive nature of PD, the effects of physical therapy
interventions on postural stability over the long term need
to be explored. To this end, protocols for providing
effective, highly-challenging, engaging and safe pro-
grammes that are sustainable and cost effective warrant
further exploration. Recent advances in technology have
opened up many possibilities, which could be utilized in
the provision of such programmes. In particular, the use of
interactive exercise video games [128, 132], Internet video
conferencing [133135] and wearable monitoring tech-
nology [136] are emerging as potentially effective,
engaging and cost-effective rehabilitation tools whose use
in the provision of physical therapy programmes for people
with PD remains largely unexplored.
4.2 Pharmacological and Surgical Treatment
4.2.1 Management of Early- to Mid-Stage Parkinsons
Disease
In early- to mid-stage PD, clinical observations show that
problems of postural instability and gait disorder can be
105
successfully treated with dopaminergic therapy. Both
impaired postural reflexes and FOG, when present, are
typically seen in the off state and usually improve with
dopaminergic therapy.
However, it should be noted that, not only are postural
instability and gait disorder significantly less responsive to
levodopa than all other cardinal features of PD [137], these
also become increasingly refractory to treatment over time,
e.g. failure of stabilizing long-latency reflexes [70, 75, 80,
138, 139], although some postural abnormalities can at least
be partially levodopa responsive, e.g. delayed execution of
anticipatory postural adjustments for self-generated step
initiation and defective voluntary postural corrections [74,
75, 140, 141]. This early benefit with later failure of
response to dopaminergic medications suggests spread of the
pathological process to non-dopaminergic systems involved
in postural control in the advanced stages.
4.2.1.1 Donepezil Recently, the cholinesterase inhibitor,
donepezil has been studied for its anti-falling effect in PD
patients with frequent falls based on the premises that [1]
anticholinergic medications increase falls in the elderly, [2]
evidence for cholinergic cell loss in the nucleus in the
pedunculopontine nucleus and [3] the cholinergic system is
important in the maintenance of cognition, and dementia is
associated with a risk of falls. One such study has reported
a significant reduction in the rate of falls, but the results
have yet to be replicated in a large randomized trial [142].
4.2.1.2 Methylphenidate Reduction in noradrenaline
(norepinephrine) due to locus coeruleus degeneration has
been suggested as a possible underlying mechanism of gait
disorders and FOG in the late stages of PD [143, 144]. This
has drawn some attention to methylphenidate, which
inhibits presynaptic dopamine and noradrenaline trans-
porters, and thereby blocks dopamine and noradrenaline
reuptake in the striatum and prefrontal cortex. However,
although benefits were reported from three earlier open-
label studies [145147], methylphenidate failed to show
significant improvements in gait parameters and FOG in a
6-month, double-blind, placebo-controlled, crossover trial
in patients with moderate gait impairment (n = 23) [148].
Notwithstanding this, a 90-day, multi-centre, randomized,
placebo-controlled trial of methylphenidate 1 mg/kg/day in
patients who had received STN-DBS, demonstrated sig-
nificant improvements in FOG in both off and on
levodopa conditions, as well as gait in the off levodopa
condition, suggesting that it might be a therapeutic option
for gait disorder in the advanced stages of PD [149].
4.2.1.3 Monoamine Oxidase Type B (MAO-B) Inhibi-
tors In the DATATOP study, selegiline was effective in
decreasing the number of patients with FOG, but this was
106
in a cohort of drug-nave PD patients who only had mild
and non-significant FOG, and the benefit was related to the
symptomatic benefit [150]. However, among the DATA-
TOP cohort, those who went on to have levodopa but also
continued with selegiline, were less likely to develop FOG
as measured by the UPDRS 5-point scale, in a 2-year
prospective study [151]. Significantly, this benefit was
unrelated to the symptomatic benefit, suggesting that
selegiline might have a specific symptomatic or protective
effect on gait and FOG.
Rasagiline, when used as an adjunctive therapy to
levodopa in a 10-week, double-blind, placebo-controlled
trial in a subgroup (n = 150) of PD patients who partici-
pated in the LARGO (Lasting effect in Adjunct therapy
with Rasagiline Given Once daily) study [152], was asso-
ciated with a statistically significant decrease in the FOG
Questionnaire score compared with placebo, but the mag-
nitude of benefit was not clinically significant, with only a
one-point difference in the FOG Questionnaire (maximal
score = 24) [153, 154].
Thus, current evidence suggests that use of monoamine
oxidase type B (MAO-B) inhibitors is associated with
reduced FOG, but it remains unanswered whether this is
accompanied by clinically significant benefit.
4.2.1.4 Freezing in On Versus Off Conditions The
issue of FOG is an important consideration in patients with
postural instability as the frequency of falls can be signif-
icantly increased. FOG had been long considered to be a
dopamine-resistant symptom in PD patients [155], but
studies have demonstrated that FOG usually responds to
levodopa and is more common in the off state [43]. In the
ELLDOPA (Earlier versus Later Levodopa Therapy in
Parkinsons Disease) study, drug-nave PD patients, who
were prospectively treated with levodopa, had significantly
decreased rates of FOG, although there was no correlation
with dose [156]. However, FOG becomes more resistant to
treatment out of proportion to bradykinesia and rigidity
with disease progression [157].
FOG can sometimes occur in the on state, but most of
these cases occur as patients are under-dosed for allevi-
ating FOG although they have good control of brady-
kinesia, rigidity and tremor, with FOG improving on a
higher dopaminergic treatment [158]. A relatively small
group of patients walk normally in the off state and start
freezing when turning on, particularly after the morning
dose, and such patients improve with medication reduc-
tion [158].
Dopamine agonists have been shown to be associated
with a higher incidence of FOG when compared with
levodopa in prospective randomized trials [159, 160], and
this has been postulated to be due to the effects on dopa-
mine D2 receptors, as a selective and potent D2 receptor
S. D. Kim et al.
agonist, MK-458, but not pergolide, a D2 and D1 receptor
agonist, is associated with this complication [161, 162].
4.2.2 Management of Advanced PD
The mainstays of treatment against motor fluctuations and
dyskinesias in advanced PD are surgery including lesioning
and DBS, and dopaminergic therapy in the form of apo-
morphine and levodopa/carbidopa intestinal gel (LCIG)
[163]. All of these treatments have proven benefit against
motor fluctuations and dyskinesias but their effects on
postural instability and gait disorder, the source of major
disability in advanced PD, have yet to be fully elucidated.
There has been a lack of studies examining the effects of
LCIG and apomorphine on postural instability and gait
disorder, likely due to the fact that oral dopaminergic
therapies are often ineffective in the advanced stages
of PD.
4.2.2.1 Apomorphine A retrospective analysis of 82
patients on continuous subcutaneous apomorphine infusion
reported significant improvement in gait imbalance [164].
However, an audit of 71 PD patients treated with contin-
uous subcutaneous apomorphine infusion showed that
although patients remained responsive to apomorphine
over a 1- to 5-year period, overall benefit deteriorated due
to increasing postural instability, falls and cognitive
impairment [165].
4.2.2.2 Levodopa/Carbidopa Intestinal Gel Devos [166]
reported improvement in approximately two-thirds of
patients (n = 91) with advanced disease who experienced
postural instability and freezing when treated with LCIG,
although the proportion of subjects reporting benefit was
less than those with motor fluctuations, dyskinesia and
dystonia.
4.2.2.3 Deep Brain Stimulation Although surgical treat-
ments are highly effective against motor fluctuations,
dyskinesias, tremor and rigidity, improvements in gait and
postural stability are more variable and less durable [167].
In recent times, there has been renewed interest in DBS,
with the emergence of pedunculopontine nucleus (PPN) as
a potential target for postural instability and gait disorder.
STN-DBS gives initial benefit in posture, postural
instability, freezing and gait in the best on condition but
this benefit wanes with time, eventually leading to pro-
gression of postural instability and gait disturbances in the
best on condition, likely reflecting disease progression
and extension of the pathological process beyond the
dopaminergic system [168172]. A careful study shows
that STN-DBS increases the gait velocity and improves the
variability of stride length and cadence, consistent with an
Postural Instability in Parkinsons Disease
increase in stability of walking pattern [173]. However, it
should also be noted that DBS, particularly STN-DBS may
worsen postural instability and gait disorder, as compared
with the best medical therapy [170, 174]. In contrast, pal-
lidotomy or chronic stimulation of globus pallidus internus
(GPi) seems to improve axial symptoms, although the
effect seems to be short-lived, lasting only 36 months
[175, 176].
There have been numerous reports of partial improve-
ment in gait dysfunction and postural instability with PPN
stimulation [177180], but the numbers studied have been
small. Significantly, a recent double-blind, crossover study
in six patients has shown variable results in FOG and a lack
of effect on axial symptoms [181]. There is ongoing con-
troversy whether the optimal site for stimulation is situated
in the PPN or adjacent areas. A clinical study has shown
the best effects on gait with active contacts located slightly
posterior to the PPN, in the cuneiform and subcuneiform
nuclei [181]. Additionally, the combination of PPN stim-
ulation with either STN or GPi may have superior effects
than stimulation of either region alone [178]. For the
moment, this treatment should be considered as experi-
mental and further evaluation in larger controlled trials is
needed in order to determine its efficacy.
5 Conclusions
Postural instability can occur at all stages of PD, but
becomes increasingly common with disease progression.
Significant insights have been gained in the understanding
of its pathophysiology, but further work using standardized
measures in carefully selected patients is required to fully
unravel the underlying mechanism. There is increasing
evidence for the efficacy of physical therapies and new
targets for DBS, but this needs to be clarified in large-scale
trials. Further research into physical, medical and surgical
therapies is required in the advanced stages of PD when
postural instability and gait disorder become increasingly
refractory to treatment.
Acknowledgments No funding was provided for the preparation of
the paper. There were no conflicts of interest for all authors. No other
persons other than those listed as authors contributed to the work.
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