REVIEWS

Therapeutic intervention in
oropharyngeal dysphagia
Rosemary Martino1,2* and Timothy McCulloch3*
Abstract | Oropharyngeal dysphagia is a frequent consequence of several medical aetiologies,
and even considered part of the normal ageing process. Early and accurate identification
provides the opportunity for early implementation of dysphagia treatments. This Review
describes the current state of the evidence related to dysphagia therapies — focusing on
treatments most clinically utilized and of current interest to researchers. Despite successes in
select studies, the level of evidence to support the efficacy of these treatments remains limited.
Heterogeneity exists across studies in both how interventions are administered and how their
therapeutic value is assessed, thereby making it difficult to establish external validation. Future
work needs to address these caveats. Also, to be most efficacious, dysphagia therapies need to
account for influences from pre-morbid patient characteristics as these factors have potential to
increase the risk of dysphagia and the resulting complications of aspiration, malnutrition and
psychological burden. Dysphagia therapies therefore need to incorporate the medical aetiology
that is at its root, the resulting swallow physiology captured from comprehensive clinical and/or
instrumental assessments, and the existing needs and supports of patients.

1
Departments of Speech
Language Pathology,
Rehabilitation Sciences
Institute, and Otolaryngology-
Head and Neck Surgery,
University of Toronto,
160–500 University Avenue,
Ontario M5G 1V7, Canada.
2
Krembil Research
Institute, University Health
Network, 399 Bathurst Street
(MP 11–331), Toronto,
Ontario M5T 2S8, Canada.
3
Division of Otolaryngology-
Head and Neck Surgery,
Department of Surgery,
School of Medicine and Public
Health, University of
Wisconsin, 600 Highland
Avenue, Madison,
Wisconsin 53792, USA.
*Both authors contributed
equally to this work.
Correspondence to R.M. 
rosemary.martino@
utoronto.ca
doi:10.1038/nrgastro.2016.127
Published online 14 Sep 2016;
corrected online 27 Sep 2016
This Review discusses the evidence for oropharyngeal
dysphagia treatments in adult patients regardless of aetio­
logy. By definition, high-level evidence includes only
properly conducted systematic reviews and/or original
randomized controlled trials (RCTs). However, other
study designs (including cohort or case–control studies
and occasional case reports) have been used to address
the merits of dysphagia management and thus, in our
opinion, have value in understanding the overall thera­
peutic benefit of dysphagia interventions. Furthermore,
defining a therapeutic benefit needs to go beyond simply
confirming improvement in swallow physiology or a pos­
itive shift along on a clinical rating scale. Benefit should
also include supporting a patient’s understanding of their
swallow limit­ations, providing counselling on risk accept­
ance within varying management choices and supporting
patients’ emotional barriers, psychological barriers and
rehabilitation expectations. Therapeutic value, we sub­
mit, needs to be proven both within a controlled clinical
­environment and within the context of everyday life.
Various treatments for oropharyngeal dysphagia have
been introduced and studied over the years. With few
exceptions, these available treatments can be categorized
into the following themes: compensatory; behavioural
exercise; neurostimulation; and surgical. We touch on
each of these approaches individually, but do not provide
a comprehensive systematic evaluation of the primary
sources related to unique therapies within each category.
Our primary sources herein are published systematic
reviews — some focused on select patient aetiologies and
others on particular therapy types. Limitations of avail­
able high-quality evidence and clinical experience might
preclude meaningful exchange about even commonly per­
formed clinical interventions. However, some therapies are
discussed in detail owing to their common use, available
high-quality published evidence and relative importance.
Evidence-based medicine
Early proponents of evidence-based medicine estab­
lished a hierarchy of best evidence that continues to be
supported1 (FIG. 1). Only a few dysphagia therapy trials
are RCTs, which is an unfortunate reality given that cause
and effect is most accurately shown in a hypothesis-driven
randomization study. A nonrandomized experimental
design — even a high-quality observational study — can
at best only show a strong correlation between treatment
and outcome. Fortunately, however, strong correlations
that are collectively reported from several independent
and properly run observational studies can in fact provide
convincing evidence for therapeutic value2. Whenever
possible, this Review highlights evidence from either
individ­ual RCTs or series of nonrandomized studies
with similar objectives to demonstrate the best available
­support for dysphagia therapies.

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 665

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

Key points Compensatory treatments


• Strong supportive evidence of effectiveness is not available for many dysphagia
treatments so clinicians need to use best available evidence to support therapy choice
• Unlike compensatory strategies, behavioural exercise therapies offer the opportunity
for long-term, and perhaps even permanent, improvements in the rehabilitation of
the oropharyngeal swallow
• The elements of feedback, education and patient compliance are critical in our design
of exercise therapies, and made even more so with exercises that patients
independently execute over time
• Evidence-based practice is only meritorious if it actually benefits both the patients’
swallow physiology and health
• Therapy must be tailored to an individual recognizing the person’s disease, limits,
attitudes, support systems and comorbidities
In addition to study design, this Review also
emphasizes the importance of study quality. Experts
in evidence-­based medicine have clearly demonstrated
that all levels of study design, from RCTs to observa­
tional studies, are equally vulnerable to flawed conduct 3.
If present, these flaws can seriously threaten a study’s
internal validity, resulting in an inaccurate estimate of
treatment benefit 4. Reporting guidelines are now avail­
able, such as the Consolidated Standards of Reporting
Trials (CONSORT)5, that offer easy to follow check­
lists for researchers to ensure these essential treatment
study design details are followed and reported in their
published papers. In this narrative review, we use the
CONSORT guidelines to present our critique of the dys­
phagia treatment literature. Accordingly, we define
strong evidence of treatment efficacy as that derived
from studies high in both design and quality.
Treatments
Finding high-level, high-quality evidence to support
clinical practices in dysphagia therapy is difficult.
The earliest systematic reviews of dysphagia treat­
ments were published between 2008–2009, targeting
dysphagia second­ary to neurological causes6,7, head
and neck ­cancer 8 and mixed aetiologies9. One such
review addressing the available evidence for com­
pensatory treatments noted that only two published
articles addressed these treatments under controlled
conditions, and all other studies were case series 7.
In that review, the evidence for dysphagia treatment
was declared to be in its infancy. A flurry of system­
atic reviews have also sought to update this evidence,
and sadly they too have reached this same conclusion.
Despite herculean efforts to find value, research on dys­
phagia therapy remains at an impasse. We draw from
these published reviews and select original papers to
discuss the best available evidence and suggest ways in
which we need to redirect our research efforts. Even
in the face of limited evidence, Speyer et al. concluded
that the literature supports the observation that most
interventions have a positive therapy outcome10. We
would agree that the collective intelligence and integ­
rity of clinicians who provide care for patients with
dysphagia is guided by many positive experiences
with their treatments.
Compensatory treatments aim to modify the swallow
action as it is being executed so as to effectively and
efficiently direct the bolus toward the oesophagus, thus
preventing airway entry or residue from remaining in
the oropharynx. Commonly used compensatory strat­
egies include postural modifications, such as the chin
tuck and/or head rotation. By design, these modifica­
tions are only effective if they accompany each swallow.
Considering that an average meal requires several hun­
dred swallows, patients who depend on such strategies
are at high risk of fatigue, diminished mealtime enjoy­
ment, and eventually even reduced nutritional intake.
Yet, in our experience, these treatments are prescribed
frequently and can be ingrained into a patient’s swallow
behaviour to ensure a safe swallow.
To date, only one high-level RCT has assessed com­
pensatory therapies (TABLE 1). Specifically, this multi-site
study compared the benefit of chin tuck versus thickened
liquid to reduce immediate aspiration of thin liquids
(as identified on videofluoroscopic examination)9, and
the long-term incidence of pneumonia during a cumula­
tive 3-month follow‑up period11. Three patient popu­
lations were included: patients with Parkinson disease,
patients with dementia, and patients with Parkinson
disease and dementia. The first of this two-part study 9
was initiated in 1989 and in its introduction described
the chin tuck strategy as already “commonly used”
— a statement demonstrating that clinicians are willing
to adopt treatment strategies even without established
strong evidence of effectiveness.
This study enrolled >700 patients over 7 years, clearly
showcasing the enormous efforts that this and other
RCTs require. This study rightly recognized that patients
with dementia have the greatest opportunity for success
with a relatively simple therapeutic technique to ensure
low cognitive burden, such as the chin tuck. The impor­
tance of aligning the therapy to the patient in this way
should not be underemphasized, as the value of any clin­
ical intervention only exists when it can easily integrate
into a patient’s life beyond the clinic setting. In the end,
the chin tuck posture was not identified in this study
as the best strategy for aspiration prevention. Instead,
the thickened liquid consistency (for example, honey
was better than nectar) proved a more effective therapy
for airway safety 9. Interestingly, patients themselves pre­
ferred the chin tuck posture to either of the thickened
liquids — an important finding as therapeutic benefit for
long-term outcomes such as pulmonary or nutritional
health can only be actualized if there is uptake by patients
in their everyday practice.
The use of the chin tuck has gained support from
basic research where it has been shown to change
­anatomic structural orientations around the larynx,
primar­ily narrowing the angle between the epiglottis and
the anterior tracheal wall and the width of the airway
entrance12. The posture does not seem to substantially
change pressure events during the swallow 13,14.
The second part of the RCT compared the long-
term benefit to pulmonary health after 3 months of
either the chin tuck posture or fluid intake restricted to

666 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

only thickened liquids11. Across all patients, the overall

incidence of pneumonia was ~10% regardless of thera­
peutic arm, which is lower than the anticipated 40% for
this patient cohort 15. By the 3‑month mark, no single
intervention could be identified as superior. However,
the secondary outcomes of dehydration and urinary
tract infections were more frequent in patients treated
with thickened liquids. These findings emphasize the
importance of careful surveillance of study partici­
pants, as well as patients in clinics, as interventions
designed to improve one outcome can unintentionally
worsen another.
This extensive multi-site longitudinal RCT empha­
sizes the difficultly in answering even the simple clin­
ical question of therapeutic value for one compensatory
technique. Understanding that at this time the chin tuck
is the only isolated compensatory strategy assessed over
time using rigorous high-level evidence, clinicians are
required to use judgments based on case series (level 4)
evidence to determine the potential value of other com­
pensatory techniques with little to no knowledge about
any possible collateral harmful effects.
Unlike the chin tuck posture, head rotation affects
pharyngeal swallowing pressures by raising pressure
toward the rotation and diminishing pressure opposite
the rotation14,16. The rotation also affects upper oesoph­
ageal sphincter (UES) function by diminishing resting
pressure and opening pressure, and producing a delay
in closure, with the effect of directing the bolus away
from the direction of rotation. A preliminary clinical
article evaluating head rotation in patients with lateral
medullary syndrome identified this population as a
potential patient subgroup who could benefit from this
­manoeuvre, especially those with unilateral pharyngeal
weakness and UES opening impairment 17.
In their practice, clinicians often use a combination
of simple interventions such as head postures (chin tuck
and head rotations) with thickened liquids to address
aspiration risk as assessed by contrast barium swallow.
In most cases, the recommendation is made after evalu­
ating the effect of single or combined interventions on
one or two viewed swallows. Even without a large body
of literature to support these individual recommenda­
tions, there is merit supporting the direct clinical obser­
vation of improvement. Maintaining an oral diet is
critical to the psychological well-being of most patients.
Behavioural exercise and retraining
Unlike postural therapies or modifications in diet,
behavioural exercise therapies might have other bene­
fits such as the opportunity for long-term change in
the central control of swallow via neuroplasticity. These
therapies specific­ally target motor rehabilitation of the
oropharyngeal swallow. The physiology of a normal
swallow is a complex series of rapid movements execu­
ted by >30 ­muscles18 and requires exact coordination
with respir­atory and phonatory systems19. Behavioural
therapies are designed to target these movements either
in isolation or in combination. Unlike compensa­
tory strategies that by definition are applied with food
intake, behavioural therapies can be executed with or
1 SR Highest
RCT
2
Cohort study
3
Case control
4
Case series
5 Opinion of experts Lowest
Mechanistic or physiological plausibility
Figure 1 | Level of evidence pyramid for evidence-based
Nature Reviews | Gastroenterology & Hepatology
medicine. At the top of this hierarchical pyramid are
systematic reviews (SR) of homogenous randomized
controlled trials (RCT). Next in line are individual
high-quality RCTs or nonrandomized experimental studies
with dramatic effects, followed by single nonrandomized
controlled cohort or longitudinal studies. Further down
this evidence hierarchy are case–control and case series
or historically controlled studies. Finally, at the bottom
are studies of mechanism or physiological plausibility.
without accompanying food. Clearly, current behavioural
­therapies align with the principles of neuroplasticity 20.
Behavioural exercises target different physiological
effects depending on the aetiology causing the dyspha­
gia. For example, in patients with stable or ameliorating
aetiologies, such as stroke or trauma, the therapeutic
goal is early and complete recovery of range, strength
and timing of physiological movements. However, for
patients with aetiologies that are progressive, such as
Parkinson disease, the goal is instead to maintain the
current swallow status for longer than would have
other­wise been possible. We suggest that these are crit­
ical aspects to consider when evaluating benefit from
behavioural therapies.
Therapies with food. The behavioural therapies that clin­
icians commonly administer with food include effortful
swallow and supraglottic swallow. Both are designed to
facilitate efficient propulsion of the bolus, with the added
benefit of a safe airway. In addition, the super-­supraglottic
and Mendelsohn strategies aim to maximize airway
protection during swallowing 6,12. Studies in this area
are sorely lacking and, of those available, no high-level
evidence exists for gains in swallow ability with thera­
pies that include food (TABLE 1). One randomized study
assessed the value of the Mendelsohn manoeuvre during
food intake, but was not sufficiently powered to identify
benefit (only 18 patients with stroke were included in
the study)21. The only other available evidence is limited
by case series design22,23, assessment in individuals with
unimpaired swallows24, or following complex therapeutic
programs tested only in observational studies that are not
easily reproduced25,26. Given the conceptual backing from
principles of neuroplasticity, we make a call for future
research to assess the value of exercise therapies executed
during food intake activities.

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 667

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

In the past 5  years alone, studies from North
America27–29, the UK30–32, Europe33,34 and globally 35 have
systematically searched the literature for therapeutic
value of behavioural exercises. The focus has mainly
been on two aetiologies — head and neck cancer and
Parkinson disease. In the head and neck cancer popu­
lation, this interest is spurred by increasing awareness
of collateral damage to the swallow mechanism from
well-intentioned cancer treatments, including both sur­
gical ablation36 and organ-sparing treatments of radi­
ation and/or chemo­radiation therapy, affecting many
patients acutely 37 and even years later 38. In the Parkinson
disease population, there is even more urgency because
these patients often succumb, not to their disease, but
to aspir­ation pneumo­nia related to dysphagia15. Yet, the
overall conclusion from these comprehensive systematic
reviews is discouraging. Their collective findings iden­
tify no high-level or high-quality evidence to support
clinically relevant b
­ enefit to swallow physiology from
behavioural exercises.
Despite the current lack of evidence, some findings
give promise for the future. For example, although bene­
fits from device-guided jaw opening resistance exercises
have been inconsistent 39–41, findings from a better-­
powered randomized study identified patient compli­
ance as a potential confounder 41. In this study, patients

Table 1 | Compensatory, behavioural and neurostimulation therapies for oropharyngeal dysphagia

Intervention Level of evidence Intended therapeutic value Refs
Compensatory treatment
Bolus volume Case series Increase intraoral sensory awareness of the bolus to facilitate 137
bolus clearance
Chin tuck RCTs and case series Widens the valleculae and narrows the aditus laryngis, reducing 9,11,138,139
penetration depth into the larynx and trachea
Head rotation Case series Redirects the bolus to the contralateral unimpaired pyriform sinus 17
Supraglottic Case series Coordinates respiration with the swallow such that swallowing 23,140
occurs in the early expiratory phase
Combination of above Case series and Any or all of the above 6–8,10,12,31,
systematic reviews 141–145
Behavioural exercise and retraining
Tongue exercises RCTs and case series Increase lingual strength and/or range of movement 146,147
Effortful swallow Case series Increase lingual driving pressures 148
Masako (tongue-hold) Mechanism Strengthen the posterior pharyngeal wall 24
Jaw exercises RCTs and case series Increase mandibular range and/or strength during mastication 39–41,149–156
Super-supraglottic Case series Prolong and increase force of laryngeal adduction 23
Mendelsohn RCTs and systematic Strengthen supra-hyoid muscles via prolonged laryngeal 6,21,28
reviews elevation and laryngeal adduction
Shaker head lift RCTs Strengthen anterior neck muscles thereby increase opening of UES 46,157
Expiratory muscle strength training RCTs, case series and Strengthen expiratory and suprahyoid muscles 34,45,158
(EMST) systematic reviews
Lee Silverman voice treatment (LVST) Case series Strengthen laryngeal adduction via controlled increased vocal 159
intensity
McNeill Protocol (combination of Case–control and See effortful swallow above 25,26
effortful swallow, bolus modifications, case series
biofeedback, stimulation)
Biofeedback RCTs and case series Sensory motor re‑education 44,160–164
Combination of at least two of the RCTs, case series and Any or all of the above 8,10,12,22,23,27,
above (with or without compensatory systematic reviews 31–33,35,47–53,
and/or texture interventions) 141,165–168
Neurostimulation
Peripheral electrical RCTs, case series and Neural swallow pathway 27,28,34,58,61,
systematic reviews 62,169–178
Peripheral electrical combined with RCTs, case series and Neural swallow pathway 27,31,179–185
exercises systematic reviews
Peripheral nonelectrical RCTs, case series and Neural swallow pathway 7,34,174,170,
systematic reviews 186–191
Central RCTs and systematic Neural swallow pathway 60,192–198
reviews
RCT, randomized controlled trial; UES, upper oesophageal sphincter.

668 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

who reported more home practice were also those with
the greatest gain regardless of assistive device. Similarly,
other work focused on suprahyoid42 and respiratory 43
exercises report a benefit when patients are provided
with biofeedback to their exercise movements. Another
study has shown improved physiological gains in patients
who received education about their swallow 44. These
findings suggest that feedback and/or education might
have a potentiation effect to improve patient compliance
when combined with exercise therapies. At the very least,
patients who can track their efforts during exercise will
probably be more engaged. The elements of feedback,
education and compliance, we posit, are critical in the
design of exercise therapies. Their role is even more
important when the exercises are independently executed
over time and without clinical supervision.
Therapies without food. Having no reliance on food
eliminates the risk of aspiration, enabling more active
engagement of the muscles involved in respiration45 and
the supralaryngeal area46. This advantage is of course
tempered by the opinion of those who remain uncer­
tain, as previously mentioned, that gain following iso­
lated exercises will generalize to effective physiological
improvements during everyday consumption of food
and liquid. Collective evidence to date does not disprove
these naysayers.
Mixed protocols with or without food. In contrast to the
few high-level studies focused on individual behavioural
therapies, several high-level studies have used combin­
ations of behavioural therapies — some with food47,48
and others without 49–51.
The most notable early RCTs that assessed the bene­
fit of behavioural dysphagia therapy were those with the
stroke population — one in the rehabilitation setting 48
and the other in the acute setting 47 (TABLE 1). Both stud­
ies targeted a mixed therapeutic approach including a
combination of behavioural exercises, compensatory
strategies and texture modifications, all customized to
the individual physiological impairment of each study
participant. Thus, the experimental variable for these
RCTs was not the therapies themselves but instead the
number of patient visits that the treating clinician made
to monitor, adjust and reinforce the customized thera­
pies. Participants in the control arm received speech and
language pathology visits as needed (typical of standard
care) and those in the experimental arms received sched­
uled visits according to a pre-set time (for example, daily
versus weekly). The important health outcomes of mor­
tality and pneumonia were assessed in both studies and
provide opportunity for comparison.
The rehabilitation trial reported no deaths and few
pneumonia events with no difference across arms.
Unfortunately, this study was underpowered to detect
differences in health status from varying treatment
intensities. The acute trial, on the other hand, was larger
and more robust 47. It reported a statistically signifi­
cant increase in chest infections in patients receiving
the lowest intensity therapy (usual care) compared
with patients receiving either of the more intensive
therapies  (P <0.003). The evidence from this one
well-conducted RCT in patients with acute stroke sup­
ports the therapeutic value of individualized swallowing
protocols with intensive surveillance. The limitation of
this study is its generalization to the clinical setting as
the individualized protocol is challenging to replicate.
Furthermore, it is difficult to disambiguate the complex
protocol to identify the responsible therapeutic variable
that caused the positive outcome. Although mixed ther­
apy protocols are well intended and firmly grounded to
the impaired mechanism, establishing their therapeutic
value with external validation in the clinical setting is
near impossible.
Likewise, RCTs of mixed behavioural treatment
protocols in patients with head and neck cancer pres­
ent with the same limitation. Specifically, three studies
assessed the benefit of a series of oral and laryngeal exer­
cises administered during 49,50 or after 51 chemoradiation
therapy. Depending on the timing of these exercises,
their purpose was either to maintain muscle function or
restore it to premorbid levels. All three trials reported
benefit from behavioural exercises. Their protocols
included a mixed series of exercises and thus were not
designed to identify the most effective exercise. Similar
to the studies in stroke, the heterogeneity of these exercise
protocols makes them difficult to replicate.
Beyond being difficult to reproduce, the available
evidence for mixed exercise protocols is further limited
by poor outcome selection. This factor is well demon­
strated in two nonrandomized dysphagia studies52,53 that
assessed quality of life in patients with head and neck
cancer receiving mixed behavioural therapies versus no
therapy (as was standard in their facility). The authors
report a statistically significant improvement in quality
of life scores in the experimental arm versus the control
arm following even 2 weeks of therapy (P <0.0002 and
P <0.01). However, despite laudable efforts to select a
psycho­metrically sound tool (in both studies the MDADI
(MD Anderson Dysphagia Inventory) was used)54, qual­
ity of life alone is not an accurate measure of physiologi­
cal swallow improvement. Research in patients who have
dysphagia secondary to cancer 55, and even other aetiolo­
gies56, has shown that patients’ self-reporting of swallow
impairment is grossly under-reported. Furthermore,
gains in quality of life, unless properly controlled with a
sham group or equivalent, are vulnerable to response bias
(also known as the placebo effect), which if present will
overestimate any finding of treatment benefit5.
In summary, in this section we have highlighted sev­
eral limitations to the current evidence for behavioural
dysphagia therapies. The main weaknesses of this body
of work relate to the following: insufficient sample sizes;
combinations of therapies that cannot be easily replicated;
not accounting for patient compliance; and selection of
outcomes that do not comprehensively and meaning­
fully measure benefit. We urge researchers to consider
these points in their designs of future work to avoid these
same pitfalls.
Given that the evidence is not yet established, we
urge clinicians who continue to prescribe behavioural
exercises to do so responsibly. To maximize their benefit,

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 669

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

clinicians will need to maintain frequent contact, prov­
ide education, ensure adherence to treatment plans and
adjust those plans according to changing swallow status
and patient needs. Patients need to understand that due
to uncertainty with the evidence, these active therapies
are suggested based on physiological and mechanistic
logic and hence might or might not produce a benefit to
their swallow. Not explaining this factor to patients can
give them false hope or, even worse, a sense of failure if
despite their ardent commitment to these therapeutic
protocols they are left with no gains. Informed decision-­
making is a basic right for patients with dysphagia that
clinicians are obligated to provide.
Neurostimulation
Neurostimulation therapies administer sensory stimuli to
effect lasting changes in target neural networks. Specific
to swallowing, stimuli are delivered in one of three ways:
peripherally to various oral and pharyngeal structures,
centrally to the brain, or by pairing both peripheral and
central stimuli. To date, peripheral swallowing stimuli
have been one of the following: electrical — applied
directly on the anterior neck and suprahyoid area (known
as neuromuscular electrical stimulation or NMES) or on
the pharyngeal mucosa (known as pharyngeal electrical
stimulation or PES); tactile — cold touch or air-puffs
directed to the oropharynx; or gustatory — delivered
with boluses of varying tastes and temperatures. Central
stimuli targeting swallowing have included repetitive
transcranial magnetic stimulation (rTMS) or transcranial
direct current stimulation (tDCS).
Conceptually, these therapies are based on the same
principles of neuroplasticity that are the foundation for
behavioural therapies. However, unlike behavioural
therapies that require patients to actively execute a
motor response, these sensory stimuli are administered
passively 57. Considering that aetiologies that cause dys­
phagia often affect cognition, this feature gives neuro­
stimulation therapies an important advantage over
behavioural therapies.
Although based on sound theoretical backing, neuro­
stimulation therapies have not yet become part of main­
stream clinical practice. High-level evidence supporting
and guiding their uptake is currently lacking. As noted
in systematic reviews31,58–62, this line of research has sev­
eral small-scale trials conducted by independent inter­
national groups. However, even studies with similar
neurostimulation techniques do not apply them with
the same dosage, or measure their benefit with the same
targeted swallow­ing outcomes59. Despite these varying
study designs, meta-analyses have been conducted for the
three most studied neurostimulation therapies: NMES61,
PES62 and central brain stimulation60. These analyses,
although clearly breaching requirements to pool data,
offer i­ mportant considerations for future research.
Tan and colleagues61 identify that NMES seems to be
most effective when combined with behavioural thera­
pies, and overall is least effective in patients with stroke.
From this finding, the speculation is that NMES has the
potential to ‘boost’ gains from behavioural therapies in
select patients but not others. However, patient selection
for NMES therapy is still not well defined. In addition,
an RCT utilizing NMES therapy combined with a stand­
ard traditional therapy in patients with head and neck
cancer with post-treatment dysphagia failed to identify
any added value with the addition of NMES63. Future
research will need to identify which patient variables
show a positive response to NMES therapy so that it can
be ­appropriately utilized with the most suited patients64.
A meta-analysis by Scutt et al.62 showed that patients
with stroke receiving PES had marked gains in swal­
low function and safety compared to similar patients
with either sham or reduced stimulation intensity.
Although not statistically significant, patients in the PES
­experimental arm also had reduced length of hospital stay.
Pisegna and colleagues60 assessed the benefits from
central stimuli, namely rTMS and tDCS, in patients with
stroke. Their findings identified no clear difference in
efficacy between these central stimuli techniques, but
do suggest that excitatory stimulation is most effective
when applied to the unaffected hemisphere. They pro­
pose that, given the bilateral representation of swallow­
ing, the neuroplasticity of the unaffected hemisphere
has the greatest potential to facilitate swallow recovery.
Their findings also suggest, albeit with less convinc­
ing evidence, that inhibitory stimuli to the unaffected
hemi­sphere might improve the swallow. They suggest
this downregulation of the unaffected hemisphere might
decrease transcallosal inhibition to the affected hemi­
sphere and, therefore, enable neuroplastic recovery of
the affected hemisphere. Future research will need to
validate this differential hemispheric advantage and
determine whether it is excitatory or inhibitory stimuli
that produce the greatest benefit to swallow recovery.
Many clinicians consider neurostimulation to be
‘noninvasive’; however, because it targets the nervous
system we are in support of those who suggest a caution­
ary approach60. In our opinion, clinical implementation
needs to await findings from future trials showing that
the benefits of neurostimulation therapies outweigh any
possible adverse effects.
Surgical management
Evidence for the surgical management of dysphagia is
at best supported by case series reports, strengthened by
systematic reviews that combine their findings (TABLE 2).
To date, no studies have compared alternative forms of
surgical treatments, or surgery versus a behavioural treat­
ment and/or control group. Surgical interventions for the
most part target a single swallow-related problem. This
approach enables analysis of benefit to the swallow with
even pre or post case series designs. According to the
Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) guidelines65, bias can be sub­
stantially reduced in these observational studies provided
researchers declare confounding patient variables and
capture outcomes using psychometrically sound proto­
cols. Although limited by design, surgical case studies
targeting swallowing management provide a valuable
contribution to the body of evidence related to therapeu­
tic benefit. To date, surgical management of dysphagia in
adults has focused mainly on the UES and larynx.

670 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

Table 2 | Surgical interventions for oropharyngeal dysphagia

Surgical intervention Level of evidence Intended therapeutic value Refs
Cricopharyngeal myotomy Case series, Improve bolus flow and eliminate UES outlet 67,74,76,
systematic reviews obstruction 77,79,81
Cricopharyngeal botulinum Case series, Improve bolus flow and eliminate UES outlet 83,85,
toxin injection systematic reviews obstruction 86,199
UES dilatation Case series, Improve bolus flow and eliminate UES outlet 88,89
systematic reviews obstruction
Vocal fold medialization Case series, Improve glottic closure during swallow 103,107,
systematic reviews 109–111
Endoscopic Zenker repair Case series, Improve bolus flow, eliminate UES outlet obstruction 90,95–99,
systematic reviews and bolus retention in diverticulum pouch 102
Transcervical Zenker repair Case series, Improve bolus flow, eliminate UES outlet obstruction 95,97
systematic reviews and bolus retention in diverticulum pouch
Laryngeal suspension Case series Protect the airway and decrease chronic aspiration 80,116–119
Tracheoesophageal diversion Case series Prevent aspiration 124,126
Laryngectomy Case series Prevent aspiration 125
UES, upper oesophageal sphincter.

Surgical management of the UES
Many patients with dysphagia begin their work‑up
with videofluoroscopy that reveals incomplete opening
of the UES segment, a cricopharyngeal bar, or residual
contrast in the pharynx after the swallow (FIG. 2). The
presence of a cricopharyngeal impression on swallow
study is not evidence of pharyngeal dysfunction, as the
relationship between UES activity, the pharynx and the
oesophagus are equally as important66–68. The finding of a
cricopharyngeal bar in a patient with dysphagia raises the
therapeutic question of whether an intervention directed
at this radiologic manifestation of dysphagia is w
­ arranted.
Factors that might be important when electing to inter­
vene with surgery at the level of the cricopharyngeus
include the extent of the apparent obstruction, the known
disease state most likely producing the failed relaxation,
and the state of the pharynx and oral cavity, as adequate
pharyngeal clearance pressure is a predictor of a successful
clinical outcome after myotomy 66,69.
The management of cricopharyngeal dysfunction
without Zenker’s diverticulum is controversial. Treatment
options include myotomy, dilatation and chemical
denerv­ation with botulinum toxin. Determining the
source of pathology is difficult, particularly when a prom­
inent ‘non-relaxing’ cricopharyngeal bar with associated
pharyn­geal residue is identified on videofluoroscopy. The
critical issue to address is whether there is inadequate
bolus propulsion due to tongue and pharyngeal weak­
ness, or increased resistance due to failed UES relaxation
in the face of normal tongue and pharyngeal muscular
activity. Complete opening of the UES is more compli­
cated than simple quiescence of baseline cricopharyngeal
muscle activity. Sufficient opening can depend on hyo­
laryngeal elevation, bolus propulsion forces, pharyngeal
clearance forces and low surface resistance70–72.
The diverse aetiologies leading to UES dysfunction
are usually coupled with pharyngeal or oesophageal
pathology that complicates management. Treating the
UES directly with dilatation, myotomy, or botulinum
toxin might only address a minor portion of the over­
all pathophysiology 73. These patients are numerous and
their clinical histories diverse; thus, the clinical care plan
requires a detailed analysis of the individual patient’s his­
tory, diagnostic studies, disease state and expected clin­
ical trajectory. Applying the same surgical management
approach to the entire patient group is not appropriate
and predicting the added value of a surgical intervention
is very difficult.
Evidence for the effectiveness of cricopharyngeal sur­
gical interventions in clinic populations was reviewed in
2016 by Kocdor et al.74 This systematic review included
32 articles, including articles on botulinum toxin injec­
tions without myotomy, and dilation procedures without
myotomy. Success rates were similar across treatments
(69% for botulinum toxin injection, 73% for dilation and
78% for myotomy)74. In general, complication rates were
low in all groups (<7%). The myotomy group did show
the highest rate of complications, but when comparing
an endoscopic myotomy to the standard open neck
approach, it seems that the complication rates can be
decreased to 2% without affecting treatment success, as
this subset of patients has a patient-weighted average of
success 84% of the time74.
UES dysfunction and cricopharyngeal myotomy.
Several diagnostic tools are available for swallow special­
ists to distinguish UES dysfunction from other causes of
dysphagia, including videofluoroscopic swallow studies,
standard pharyngeal manometry, and high-resolution
pharyngeal manometry. To date, most prior studies have
only used videofluoroscopy to compare pretreatment
and post-treatment swallow function and have also
focused primarily on changes following cricopharyngeal
myotomy. Conclusions gathered via videofluoroscopy
suggest that myotomy improves pharyngeal constriction
and pharyngoesophageal sphincter opening, but does
not substantially reduce stasis or aspiration68,75. These
findings were thought to be due to persistent pharyngeal

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 671

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

a b due to iatrogenic nerve injury 77,79. The manometric

Figure 2 | Barium contrast image of a cricopharyngeal bar. a | Before treatment.
Nature Reviews | Gastroenterology & Hepatology
b | After dilation and botulinum toxin injection.
weakness that is not addressed with a myo­tomy. St Guily
et al.76 reported that myotomy was success­ful when
standard manometry revealed normal and even dimin­
ished pressure, but failed in the aperistaltic pharynx.
However, some evidence suggests that patients might
find benefit even in the face of weak constrictor activ­
ity 77. Data from a case series with healthy controls using
standard pharyngeal manometry and videofluoroscopy
identified changes in intrabolus pressures after myo­
tomy, indicating improved bolus flow, at least in patients
with intact bolus driving forces67. The authors report that
the measurement of intrabolus pressures with mano­
metry should be able to identify patients who could
benefit from myotomy and/or dilatation67. However, the
data remain limited with regard to objective measure­
ments of pharyngeal and UES pressure abnormalities
that would warrant a UES intervention. In addition,
no manometric guidelines exist to quantify successful
surgical management of UES dysfunction. There are no
studies using pharyngeal high-resolution manometry
as a complement to videofluoroscopy in the analysis
of surgical interventions in general. In 2002, Bammer
et al. suggested that the use of a gradient pressure across
the UES would be the best single pressure measure to
identify patients who would benefit from myotomy 78.
However, no clinical data support this hypothesis.
No standard exists for measuring a surgically success­
ful outcome. Almost all studies rely on a patient symptom
report, augmented by diet choices and changes in aspir­
ation patterns on videofluoroscopy to create a composite
measure in order to stratify patient outcomes as successes
or failures75,78. Manometry does enable measurement of
UES baseline pressures, which after a successful myo­
tomy will drop to near zero indicating complete surgi­
cal disruption of the UES contractile force77. Identifying
the patient population that will or will not benefit from
myotomy remains unresolved. In the review by Kocdor
et al. looking at standard clinical practice, it seems that
most patients selected for surgery receive some benefit 74.
Certain groups seem to have an increased probability of
benefit, including patients with idiopathic cause, patients
with myogenic disease and patients with UES dysfunction
findings of impaired UES opening and the absence of
a discernible underlying cause appeared to best predict
success of myotomy in the Mason et al. study 79. However,
this study did exclude patients with severe pharyngeal
motility dysfunction on manometry. Myotomy is less
reliable in patients after stroke and with myopathic dis­
ease, which can not only impact UES relaxation but also
affect opening due to weakened hyolaryngeal elevation
and pharyngeal bolus propulsion. Myotomy might also
fail in patients treated with radiation therapy owing to
similar issues caused by fibrosis and muscle weakness77.
The choice of which patients should undergo myo­
tomy will always be a complex clinical decision, as there
are risks to the procedure and in many cases a pos­
itive outcome cannot be assured. This threat should be
weighed against the risk the patient is left with if ­swallow
does not improve. Many patients require substantial
diet modifications and have penetration and/or aspir­
ation on swallowing evaluation before under­going myo­
tomy 79 — a successful intervention markedly improves
this situation80. Myotomy might even improve swallow
function and quality of life during certain stages of
amyotrophic lateral sclerosis81,82. Regardless of the dis­
ease state, patients often endorse easier swallowing after
UES interventions even when objective data are lack­
ing. Notably, in almost all cases, patients have received
­combined surgical and nonsurgical therapy.
UES dysfunction and botulinum toxin injection. The
first use of botulinum toxin for UES dysfunction was
reported by Schneider et al. in 1994 (REF. 83). The use of
botulinum toxin is often described as chemical myotomy
and is effective at producing weakness in the targeted
muscle. Because the UES is a complex fibromuscular
system that can develop increased muscle tone, appro­
priately placed and dosed botulinum toxin will decrease
the symptoms of, and risks associated with, incomplete
UES opening 84. Most cases of dysphagia are multi­
factorial and the specific contribution of the UES is often
questionable. UES relaxation and opening rely on several
factors — botulinum toxin addresses only the abnormal
muscular activity within the UES; unlike with myotomy
and dilatation, inflammation and fibrosis within the
UES are not affected by this treatment. Documenting
the ­status of vocal fold motion and pharyngeal strength
is also important as poorly directed injections and dif­
fusion of botulinum toxin can lead to laryngeal paralysis
and pharyngeal weakness85.
The ideal patient for botulinum toxin injection is
similar to that described by Kelly 66 for cricopharyngeal
myotomy. The patient should have adequate hyolaryn­
geal elevation and tongue and/or pharyngeal propulsion.
The patient should also be medically and neurologically
stable, or improving. Additionally, the UES dysfunction
should be myogenic at its root cause with no or limited
fibrosis or connective tissue changes, such as fatty infil­
tration or inflammation. Including a dilation procedure
with the injection can be useful as many patients will
have a fibrotic component within the UES connective
tissue along with failure of muscle fibre relaxation.

672 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

The temporary nature of botulinum toxin has value in
patients with high probability of spontaneous improve­
ment, and as an intervention when the role of UES dys­
function is questionable, as it has been shown to be an
effective treatment with no major adverse effects for
patients with isolated UES dysfunction and in patients
with complex dysphagia associated with bolus retention
and aspiration83,86.
Injection methods include electromyography-­
guided transcutaneous injection, transoral flexible
oesophagoscopy-­guided transmucosal injection, and
rigid oesophagoscopy-guided direct injection83. The
botulinum toxin dose in the literature also varies widely,
from 5 to 100 units75,82. The most common technique is
a transoral approach with a direct view of the abnor­
mal cricopharyngeal muscle bar. Direct visualization
enables precision with the injection and the opportu­
nity to perform either a balloon or semi-rigid serial
dilatation. This method is our preferred technique as it
enables precise injection into the muscle and an oppor­
tunity to evaluate the surrounding tissues for mucosal
scar bands and fibrosis within the muscle or soft tissues.
In the systematic review by Kocdor et al.74, twelve ­articles
containing 148 patients were reviewed noting a 69%
patient-weighted success rate, with a complication rate
of only 4%74. This success rate for botulinum toxin was
less than for myotomy (78%), but no study performed a
direct comparison. Botulinum toxin could be offered to
patients who might be concerned about risks of an open
procedure or as a test to determine if weakening the
UES would improve swallow before myotomy. Success
of botu­linum toxin often leads to myotomy in patients
seeking permanent benefit 82.
UES dysfunction and mechanical dilation. Mechanical
dilation seems to have a success rate (73%) somewhere
between that for myotomy and botulinum toxin 74.
Dilation of the UES might be most useful in patients
with known fibrosis within the region, which is most
commonly found after radiation therapy but would also
include patients with traumatic injury or peptic stric­
ture. Although this procedure often requires repetition,
it does reduce the risk associated with attempting an
open neck operation on a patient following radiation.
Stricture, in nearly all cases, is isolated to or extends
a b
E swallow function even if only subtle ­d isturbances
U Treatment in all cases should include a cricopharyn­
D
Figure 3 | Endoscopic view of Zenker diverticulum. a | Before treatment.
Nature Reviews
b | After CO2 laser myotomy, with diverticulum | Gastroenterology
opened into & Hepatology
oesophageal lumen.
D, posterior diverticulum; E, oesophageal lumen; U, upper oesophageal muscle.
to the mucosa, thus an external approach will fail to
address the primary issue unless the area is completely
opened and repaired. In a report by Agarwalla et al.87,
the mean number of dilations for a radiation-induced
stricture was three, although some required up to eight
with patency defined as a 14 mm lumen. Using this serial
dilatation technique the clinical success rate was 83%87.
Mechanical dilation can be completed under s­ edation
with balloon dilators, or with serial tapered bougie dila­
tors using a wire guide or direct visualization88. The use of
two balloon dilators at the level of the UES was reported
as an attempt to improve dilation outcomes and account
for the kidney shape of the UES89. However, e­ vidence that
this approach improved o ­ utcomes is limited.
Surgical management of Zenker diverticulum
Zenker diverticulum is a surgically managed dis­order, with
strong support in the literature that all cases be directed
to surgical care as the first line of treatment 90,91. Zenker
diverticulum is a pharyngeal outpouching ­superior and
posterior to the cricopharyngeus muscle, within a weak­
ness at the inferior border of the ­inferior pharyn­geal con­
strictor muscle in an area known as Killian’s ­triangle. The
cricopharyngeus ­muscle is the primary ­muscle implicated
in the formation of Zenker ­diverticulum and the key to
successful surgical intervention.
Abnormal cricopharyngeal relaxation coupled with
a natural weakness inferior to the pharyngeal constric­
tor muscles and secondarily elevated swallow pressures
is believed to produce this diverticulum and its symp­
toms. The diverticulum develops slowly over several
years as repeated swallows dilate the non-muscular sac
owing to the elevated bolus pressures above an incom­
pletely relaxed UES92. The average age of diagnosis is
~70 years and it is rarely seen <50 years93. Manometric
studies have shown that, with ageing, bolus transit time
increases, the normal UES pressure drop is delayed, and
the minimum UES opening pressure increases to a sub­
stantial positive value94. Increased fibro-adipose tissue
replacement and fibre degeneration in the cricopharyn­
geus of patients with Zenker diverticulum suggests that
structural changes in the muscle contribute to its failed
complete relaxation69.
Although many patients do not aspirate, lose weight,
or substantially modify their diet until the diverticulum
reaches a moderate size, the pathology is already present
and not reversible without surgical intervention. Early
intervention prevents the late effects of Zenker diverticu­
lum (such as aspiration pneumonia, complete obstruc­
tion and large, difficult-to‑treat diverticular pouches),
enables surgery on a healthier patient, and improves
are present.
geal myotomy using either an open or endoscopic
transmucosal approach, with or without removal of the
diverticulum itself (FIG. 3). The current trend is to treat
most patients transorally using a CO2 laser or stapling
techniques92. Results from either technique are reported
to be quite good, and the risks are similar 95–97. The data
for selecting a transoral laser approach when possible

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 673

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

are relatively compelling — with low-risk and high
success rates being reported repeatedly over multiple
decades98–101. Evidence suggests that the level of success
is best predicted by the ease and extent of exposure of
the diverticulum and the cricopharyngeal mucosal
impression, with better exposure predicting a better
long-term outcome102.
In a systematic review 95, 70 studies with almost 3,000
patients were identified to address the safety and effi­
cacy of the available surgical procedures. Both open and
endoscopic approaches seemed to have low complication
rates and comparatively high success rates. However,
endoscopic approaches were associated with frequent
difficulties with exposure, and there was a higher long-
term failure rate with endoscopic stapling compared to
open cricopharyngeal myotomy. Importantly, patients in
all treatment groups reported high satisfaction. Surgeons
should take an individualized approach, recognizing that
when an endoscopic approach is feasible, complication
rates are slightly lower than open approaches and laser
techniques have higher long-term success rates com­
pared to stapling. They also noted that all patients are
candidates for open approaches and a successful open
approach seems to have the lowest recurrence rate. Thus,
it would be favourable for young patients, patients with
a small diverticulum, and patients in whom endoscopic
exposure has failed.
Vocal fold paralysis and dysphagia
The majority of patients will have new onset of dys­phagia
symptoms with both solids and liquids when a vocal fold
paralysis occurs103. The role vocal fold paraly­sis has in
dysphagia is complicated but necessary to evaluate and
treat when encountered. The cause of the paralysis, the
patient’s medical condition at the time of the paralysis,
and the involvement of additional ­muscular dysfunc­
tion and sensory loss all come into play when prioritiz­
ing an intervention. High index of suspicion based on
medical and surgical history (for example, new-onset
brainstem stroke, recent cardiac surgery, known media­
stinal or skull base mass) combined with examination
findings showing voice change, weak cough, and cough
with liquid swallow, as well as aspir­ation on video­
fluoroscopy, should all lead to concern for a possible
vocal fold immobility.
This suspicion can be easily confirmed with endo­
scopic examination of swallow, flexible laryngoscopy,
or videostroboscopy. The flexible examination enables
some direct assessment of sensory problems by touch­
ing and air puff techniques on surrounding mucosal
surfaces104,105 and indirect assessment by watching the
patient’s laryngeal responses to mucus and salivary flow.
Many patients with vocal fold paralysis will have both a
sensory and motor deficit 106.
Confirming the presence of a glottic closure issue has
great value because of the ease and benefit of early inter­
vention; a minimally invasive vocal fold medialization
procedure can restore the physiologic benefit of active
glottic closure, including decreased aspiration risk with
thin liquids (although aspiration risk might not be totally
eliminated) and improved voice and effective cough107.
A large variety of safe injectable materials exist that
can last from weeks (hyaluronic acid gels) to months
(micronized particulate acellular human dermis) to
years (calcium hydroxyapatite paste)108. Radiologic,
clinical, and fluoroscopic studies support early inter­
vention86,87. Decreasing aspir­ation by improving glottic
closure enables clinicians to maintain swallowing during
therapy, thus broadening the options within the rehabil­
itation protocols109,110. Beyond the early interventions,
restoration of glottic function can include more invasive
procedures (medial­ization thyroplasty, arytenoid adduc­
tion and laryngeal re‑­innervation) with the intention
to extend the benefits of adequate closure beyond that
which is expected from injection techniques108,111. These
open procedures can be coupled with cricopharyn­
geal myotomy to improve swallow function in patients
with combined laryngeal and pharyngeal dysfunction
­secondary to cranial nerve or CNS pathology 112,113.
Pharyngeal muscle reduction procedures
The idea of pharyngeal muscle reduction to improve
swallowing in patients with pharyngeal weakness was
first put forward in 1995 (REF. 114). The concept is not
dissimilar to cardiac and pulmonary tissue reductions
— cardiac function is improved when nonfunctioning
tissues are removed, allowing for more effective cardiac
contractions, as a noncontractile segment dissipates
pressure generation115. Similarly, if a patient develops
a segment of noncontracting tissue in the pharynx
due to muscular paresis after cranial nerve injury or
stroke, eliminating that segment of muscle is theoret­
ically bene­ficial, enabling the intact muscle to create
a more effective contractile force. Limited literature
exists to support this concept and in almost all cases
it is performed in combination with a procedure to
address glottic insufficiency (type I thyroplasty) and a
cricopharyngeal myotomy 114.
Laryngohyoid suspension
Surgical suspension of the larynx and hyoid can augment
bolus passage into the oesophagus80. This procedure is
occasionally performed to treat patients with stroke-­
related or multifocal dysphagia; however, most of the
literature is related to the management of dys­phagia
associated with cancer surgery 116. The procedure is an
essential part of laryngeal cancer procedures in which
supraglottic and tongue base tissues are removed
(supraglottic laryngectomy and extended supraglottic
laryn­gectomy), and when anterior glottic structures
are removed (supracricoid laryngectomy)117–119. The
method of laryngeal suspension differs depending
on the retention of superior epiglottic tissue (crico­
hyoidoepiglottopexy or cricohyopexy). In all cases, the
retained laryngeal structures are suspended antero-­
inferior to the retained hyoid bone, the arytenoid cartil­
ages are sutured in a forward position, the trachea is
released from below, and in most cases a cricopharyn­
geal myotomy is completed. With this complex s­ urgery,
early aspiration risk is common but improves with
time and swallowing therapy 118,119. If the suspension
fails or is incomplete, aspiration is guaranteed and

674 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

only resolves by surgically correcting the suspension.
Laryngeal suspension is also useful after glossectomy
and pharyngeal resections120,121.
Aspiration prevention surgeries
Preventing aspiration can be accomplished with sur­
geries designed to separate the airway from the path of
the bolus. These approaches do not address the cause
of the dysphagia but once the aspiration risk is elimin­
ated the patient might have additional therapy options,
which could include swallowing food and liquids that
would not have been possible before the surgery. Some of
these techniques are reversible if the patient’s condition
improves enough to enable safe swallowing. All these
procedures require a tracheotomy or creation of tracheal
stoma. Some approaches close the supraglottic larynx at
the level of the arytenoids and epiglottis using valved
glottis stents, which prevent most aspirations and retain
some voice but still require a tracheotomy for airway
safety 122,123. Most of these techniques exclude the use of
the larynx for voicing.
Finally, two procedures can eliminate aspiration com­
pletely: tracheoesophageal diversion and narrow-field
laryngectomy 124–126. In both cases, swallowed material
cannot enter the airway even if a portion of the bolus
is retained in the pharynx as the connection between
the pharyngoesophageal tissues and the trachea and
lung is eliminated. These two procedures are used
almost exclusively in patients with severe chronic aspir­
ation, for example after cancer therapy, or in patients
with extensive neurologic dysfunction. Laryngectomy
is most commonly performed in patients who aspir­
ate substantially after organ-preserving treatments of
laryngeal cancer, which can include partial laryngec­
tomies and radiation therapy treatment protocols127.
Laryngectomy does have a role in other patients with
chronic aspiration and additional clinically significant
co‑morbid illness128. Clinicians might in fact be under­
using these techniques owing to an emphasis on retain­
ing vocal communication. It is important to weigh the
risks of chronic aspiration on long-term lung function,
repeated pneumonias and potential death against modi­
fied communication. Importantly, with these techniques
patients retain the ability to eat at least some foods and
might experience a true increase in length and quality
of life. Tracheoesophageal diversion was designed with
the potential for reversal once a patient’s dysphagia
improved, such as in stroke recovery. This procedure
is less common today, in an era of early percutaneous
gastro­stomy tube placement and patient transfer to
chronic care facilities.
Model to measure therapeutic benefit
Many of the dysphagia interventions described in this
Review arose from clinical observations and were envi­
sioned to address a single specific clinical problem.
Clearly, the clinician perspective motivated their design.
Broadly speaking, clinician perception is biased toward
biomedical issues129, and clinicians with expertise in
dysphagia are no exception130. Unsurprisingly then, the
speci­fic clinical problem targeted most often in dysphagia
treatment is swallow pathophysiology. The success of
these therapies is most frequently judged from changes
identified during videofluoroscopic contrast barium,
flexible direct endoscopic swallow studies, or high reso­
lution manometry. Given that any compromise in swal­
low physiology reduces swallow safety and efficiency,
we ­support the importance of physiological outcomes.
However, the patient perspective is also critical and
needs to be considered when judging the value of dys­
phagia treatments. Patients place importance on psycho­
logical issues related to dysphagia130. Acutely ill patients
report swallowing-related anxiety and fear of dying,
whereas patients with chronic dysphagia report feelings
of embarrassment, depression, isolation and abandon­
ment131. Thankfully, important aspects of the psychologi­
cal issues experienced by patients with chronic dysphagia
are alleviated by compensatory strategies taught to them
by clinicians. These strategies increase their ability to
control their swallow and thereby to return to eating
with family and friends. Furthermore, patients acknow­
ledge that these strategies serve to increase the safety of
their oral intake and reduce the risk of pneumonia and
mal­nutrition130 — biomedical outcomes important to
clin­icians. This work proves that, although patient per­
ception is related to that of the clinician, it is clearly dis­
tinct. A comprehensive evaluation of therapeutic value
needs to address both.
Another important consideration for both researchers
and clinicians is the degree to which patients adhere to
assigned therapeutic protocols, as poor compliance neg­
atively influences treatment benefit. This effect might be
less of a problem with comparative trials designed to have
equivalent patient burden across treatment study arms.
However, less rigorous study designs cannot adjust for
noncompliance. Furthermore, even with efforts to con­
trol for compliance, some patients might report more
than actual therapeutic adherence thereby nullifying
study findings132. Generally, com­pliance relates to adher­
ence to a therapeutic practice or maintenance of a plan,
and is greatest in people who prioritize their health133.
Pharmacological trials have identified other factors that
also have a positive influence on compliance in the clin­
ical setting, namely the following: tracking the therapeu­
tic activity; educating the patient about the therapy and its
purpose; and continued supervision by clinicians during
the treatment period134. Perhaps these factors generalize
to increase compliance with dysphagia treatments. If so,
clinicians will need to provide education that is meaning­
ful to patients and foster an understanding on how the
intervention will be helpful to them. Certainly, all patients
are unique and they will have varying levels of concern
about their swallowing problems, which might in turn
influence their motivation toward therapy. This factor
might explain why patients are especially non­compliant
with prophylactic dysphagia treatments prescribed before
there is any appreciation of the impending possible swal­
lowing problems42. Only by evaluating and monitoring
for poor compliance can clin­icians and researchers
mitigate to reduce it, and m ­ aximize benefit from those
swallow­ing interventions that are ­particularly dependent
on active patient participation.

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 675

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

therefore one intervention will not generalize to all its

General category
of aetiology
History
Neurological
Education
Emotional
Mechanical
Diagnostics
support
Iatrogenic
Compliance
Systemic
Therapy
Psychological
Figure 4 | A comprehensive model depicting factors
Nature
that affect Reviewsbenefit
therapeutic | Gastroenterology & Hepatology
for oropharyngeal
dysphagia.
Despite critical gaps in the existing research for dys­
phagia treatments, we advocate that clinicians continue
to use best available information and clinical experi­
ence to treat patients. Provided that clinicians disclose
to patients the basis for their recommendations, we trust
that a therapeutic plan even without strong evidence is
better than no clinical intervention. At a minimum,
clin­icians should use the clinical opportunity to educate
patients and their families about the importance of safe
swallowing, and the potential risks of repeated aspiration,
malnutrition and dehydration. From the work described
herein, we know that even this conservative educational
approach will be of value to the patient and, in turn, will
facilitate improved c­ ompliance — a ­necessary basis for
any successful intervention.
Therapy planning for dysphagia needs to begin
with a good understanding of the swallow anatomy
and physiology. Swallowing disorders are now known
to be a sequelae of a variety of medical conditions and
perhaps even represent a condition associated with the
later phases of the normal ageing process. Thus, as our
understanding of swallow therapy could be described
as in its infancy, so too is our understanding of much
of the underlying pathophysiology of dysphagia. Very
few causes of dysphagia are fully understood. Future
work needs to address the neuropathological causes of
dysphagia according to medical aetiology, and delineate
the influence of important premorbid patient character­
istics that not only increase the risk of dysphagia but also
aspiration, malnutrition and psychological burden on
patients. To achieve this, dysphagia therapies need to
be planned according to the aetiology that is at its root,
modified to accommodate the resulting impairments in
swallow physiology captured from comprehensive clin­
ical and/or instrumental assessments, and customized
to support the needs of the individual patients and their
carers (FIG. 4).
Conclusions
More than two decades of research has yet to yield a
single therapeutic intervention with consistent value to
recovery of the swallow physiology. Part of the reason
might be that dysphagia is itself a sequelae of diverse
aetiologies influenced by several patient variables;
possible causes. Another reason might lie in the hetero­
geneity of the interventions assessed, of which few have
been tested in isolation. Despite the countless stud­
ies, these varied therapy protocols make it difficult to
determine which aspects are potentially most effective.
In addition, there is inconsistency with how therapeutic
value is measured — some studies measure physiological
benefit whereas others capture the patient perspective.
All of these factors limit comparison of findings across
studies, which is a necessary prerequisite to establish
external validation.
To get out of this standstill, some researchers and
clinicians have called for larger studies whereas others,
invoking the principles of evidence-based medicine,
have called for more RCTs. We support these changes
but argue that they are not enough. Additional changes
that are important include the following: establish suf­
ficiently powered samples sizes (not necessarily large);
detail an explicit study design that specifically minimizes
risk of bias and that can be replicated by others135; and
utilize outcomes that are validated, meaningful and
sensitive to clinically important change representing
what is considered important to both the clinician and
the patient.
Fortunately, dysphagia therapies continue to be
explored. In the case of behavioural therapies, the focus
is now on refining these exercises according to anatomi­
cal, neural and physiological findings from basic, animal
and human science. These discoveries hold promise that
soon they will unveil the true value of swallow rehabil­
itation. In the meantime, behavioural swallow thera­
pies can be part of clinician-guided sessions, at times
accompanied by devices that increase effort or provide
meaningful feedback. Alternatively, these therapies can
be executed as home exercise programs. It is important
to discover what elements make each of these scenarios
more effective to ultimately increase the likelihood of
success in swallow recovery.
We are optimistic that over time as the standard­
ized CONSORT reporting guidelines are increasingly
implemented by journals, improved critical appraisal
in the peer-review process will in turn motivate a shift
toward high-quality, innovative dysphagia treatment
research. Therapeutic innovations need proper scrutiny
at a peer-review level before they are introduced into
the clinical setting and certainly before entering the
market­place. Clinicians need an opportunity to critically
appraise these innovative therapies. To do so properly,
they need to evaluate its applicability to their practice
setting and make decisions about which patients are
most likely to benefit.
As Sackett et al.136 write, “Good [clinicians] use
both individual clinical expertise and the best available
external evidence, and neither alone is enough. Without
clinical expertise, practice risks becoming tyrannised
by evidence, for even excellent external evidence may
be inapplicable to or inappropriate for an individ­
ual patient. Without current best evidence, practice
risks becoming rapidly out of date, to the detriment
of patients”.

676 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

1. Guyatt, G. H. et al. Users’ guides to the medical
literature: XXV. Evidence-based medicine: principles
for applying the Users’ guides to patient care.
Evidence-Based Medicine Working Group. JAMA 284,
1290–1296 (2000).
2. Howick, J., Glasziou, P. & Aronson, J. K. The evolution
of evidence hierarchies: what can Bradford Hill’s
‘guidelines for causation’ contribute? J. R. Soc. Med.
102, 186–194 (2009).
3. Guyatt, G. H. et al. GRADE: an emerging consensus
on rating quality of evidence and strength of
recommendations. BMJ 336, 924–926 (2008).
4. Higgins, J. P. T. & Altman, D. G. in Cochrane
Handbook for Systematic Reviews of Interventions
(eds Higgins, J. P. T. & Green, S.) 187–241 (John
Wiley & Sons, 2008).
5. Boutron, I. et al. Methods and processes of the
CONSORT Group: example of an extension for trials
assessing nonpharmacologic treatments. Ann. Intern.
Med. 148, W60–W66 (2008).
6. Ashford, J. et al. Evidence-based systematic review:
oropharyngeal dysphagia behavioral treatments.
Part III — impact of dysphagia treatments on
populations with neurological disorders. J. Rehabil.
Res. Dev. 46, 195–204 (2009).
7. Foley, N., Teasell, R., Salter, K., Kruger, E.
& Martino, R. Dysphagia treatment post stroke:
a systematic review of randomised controlled trials.
Age Ageing 37, 258–264 (2008).
8. McCabe, D. et al. Evidence-based systematic review:
oropharyngeal dysphagia behavioral treatments.
Part IV — impact of dysphagia treatment on
individuals’ postcancer treatments. J. Rehabil. Res.
Dev. 46, 205–214 (2009).
9. Logemann, J. A. et al. A randomized study of three
interventions for aspiration of thin liquids in patients
with dementia or Parkinson’s disease. J. Speech Lang.
Hear. Res. 51, 173–183 (2008).
10. Speyer, R., Baijens, L., Heijnen, M. & Zwijnenberg, I.
Effects of therapy in oropharyngeal dysphagia by
speech and language therapists: a systematic review.
Dysphagia 25, 40–65 (2009).
11. Robbins, J. et al. Comparison of 2 interventions
for liquid aspiration on pneumonia incidence:
a randomized trial. Ann. Intern. Med. 148, 509–518
(2008).
12. Wheeler-Hegland, K. et al. Evidence-based systematic
review: oropharyngeal dysphagia behavioral
treatments. Part II — impact of dysphagia treatment
on normal swallow function. J. Rehabil. Res. Dev. 46,
185–194 (2009).
13. Castell, J. A., Castell, D. O., Schultz, A. R.
& Georgeson, S. Effect of head position on the
dynamics of the upper esophageal sphincter and
pharynx. Dysphagia 8, 1–6 (1993).
14. McCulloch, T. M., Hoffman, M. R. & Ciucci, M. R.
High-resolution manometry of pharyngeal swallow
pressure events associated with head turn and chin
tuck. Ann. Otol. Rhinol. Laryngol. 119, 369–376
(2010).
15. Guttman, M., Slaughter, P. M., Theriault, M. E.,
DeBoer, D. P. & Naylor, C. D. Parkinsonism in Ontario:
comorbidity associated with hospitalization in a large
cohort. Mov. Disord. 19, 49–53 (2004).
16. Ohmae, Y., Ogura, M., Kitahara, S., Karaho, T.
& Inouye, T. Effects of head rotation on pharyngeal
function during normal swallow. Ann. Otol. Rhinol.
Laryngol. 107, 344–348 (1998).
17. Logemann, J. A., Kahrilas, P. J., Kobara, M.
& Vakil, N. B. The benefit of head rotation on
pharyngoesophageal dysphagia. Arch. Phys. Med.
Rehabil. 70, 767–771 (1989).
18. Shaw, S. M. & Martino, R. The normal swallow:
muscular and neurophysiological control. Otolaryngol.
Clin. North Am. 46, 937–956 (2013).
19. Jean, A. Brain stem control of swallowing: neuronal
network and cellular mechanisms. Physiol. Rev. 81,
929–969 (2001).
20. Robbins, J. et al. Swallowing and dysphagia
rehabilitation: translating principles of neural plasticity
into clinically oriented evidence. J. Speech Lang. Hear.
Res. 51, S276–300 (2008).
21. McCullough, G. H. et al. Effects of Mendelsohn
maneuver on measures of swallowing duration post
stroke. Top. Stroke Rehabil. 19, 234–243 (2012).
22. Lazarus, C., Logemann, J. A., Song, C. W.,
Rademaker, A. W. & Kahrilas, P. J. Effects of voluntary
maneuvers on tongue base function for swallowing.
Folia Phoniatr. Logop. 54, 171–176 (2002).
23. Logemann, J. A., Pauloski, B. R., Rademaker, A. W.
& Colangelo, L. A. Super-supraglottic swallow in
irradiated head and neck cancer patients. Head Neck
19, 535–540 (1997).
24. Fujiu, M. & Logemann, J. A. Effect of a tongue-holding
maneuver on postural pharyngeal wall movement
during deglutition. Am. J. Speech Lang. Pathol. 5,
23–30 (1996).
25. Carnaby-Mann, G. D. & Crary, M. A. McNeill
dysphagia therapy program: a case–control study.
Arch. Phys. Med. Rehabil. 91, 743–749 (2010).
26. Crary, M. A., Carnaby, G. D., LaGorio, L. A.
& Carvajal, P. J. Functional and physiological
outcomes from an exercise-based dysphagia therapy:
a pilot investigation of the McNeill Dysphagia Therapy
Program. Arch. Phys. Med. Rehabil. 93, 1173–1178
(2012).
27. Carnaby, G. & Madhavan, A. A systematic review of
randomized controlled trials in the field of dysphagia
rehabilitation. Curr. Phys. Med. Rehabil. Rep. 1,
197–215 (2013).
28. Drulia, T. & Ludlow, C. Relative efficacy of swallowing
versus non-swallowing tasks in dysphagia
rehabilitation: current evidence and future directions.
Curr. Phys. Med. Rehabil. Rep. 1, 242–256 (2013).
29. Langmore, S. E. & Pisegna, J. M. Efficacy of exercises
to rehabilitate dysphagia: a critique of the literature.
Int. J. Speech Lang. Pathol. 17, 222–229 (2015).
30. Carnaby-Mann, G. & Lenius, K. The bedside
examination in dysphagia. Phys. Med. Rehabil. Clin.
N. Am. 19, 747–768 (2008).
31. Cousins, N., MacAulay, F., Lang, H., MacGillivray, S.
& Wells, M. A systematic review of interventions for
eating and drinking problems following treatment for
head and neck cancer suggests a need to look beyond
swallowing and trismus. Oral Oncol. 49, 387–400
(2013).
32. Roe, J. W. & Ashforth, K. M. Prophylactic swallowing
exercises for patients receiving radiotherapy for head
and neck cancer. Curr. Opin. Otolaryngol. Head Neck
Surg. 19, 144–149 (2011).
33. Kraaijenga, S. A., van der Molen, L.,
van den Brekel, M. W. & Hilgers, F. J. Current
assessment and treatment strategies of dysphagia in
head and neck cancer patients: a systematic review of
the 2012/13 literature. Curr. Opin. Support. Palliat.
Care 8, 152–163 (2014).
34. van Hooren, M. R. A., Baijens, L. W. J., Voskuilen, S.,
Oosterloo, M. & Kremer, B. Treatment effects for
dysphagia in Parkinson’s disease: a systematic
review. Parkinsonism Relat. Disord. 20, 800–807
(2014).
35. Paleri, V. et al. Strategies to reduce long-term
postchemoradiation dysphagia in patients with head
and neck cancer: an evidence-based review.
Head Neck 36, 431–443 (2014).
36. Chung, T. K., Rosenthal, E. L., Magnuson, J. S.
& Carroll, W. R. Transoral robotic surgery for
oropharyngeal and tongue cancer in the United States.
Laryngoscope 125, 140–145 (2014).
37. Wall, L. R., Ward, E. C., Cartmill, B. & Hill, A. J.
Physiological changes to the swallowing mechanism
following (chemo)radiotherapy for head and neck
cancer: a systematic review. Dysphagia 28, 481–493
(2013).
38. Hutcheson, K. A. Late radiation-associated dysphagia
(RAD) in head and neck cancer survivors. SIG 13
Perspectives on Swallowing and Swallowing Disorders
(Dysphagia) 22, 61–72 (2013).
39. Buchbinder, D., Currivan, R. B., Kaplan, A. J.
& Urken, M. L. Mobilization regimens for the
prevention of jaw hypomobility in the radiated patient:
a comparison of three techniques. J. Oral Maxillofac.
Surg. 51, 863–867 (1993).
40. van der Molen, L. et al. A randomized preventive
rehabilitation trial in advanced head and neck cancer
patients treated with chemoradiotherapy: feasibility,
compliance, and short-term effects. Dysphagia 26,
155–170 (2011).
41. van der Molen, L., van Rossum, M. A., Rasch, C. R.,
Smeele, L. E. & Hilgers, F. J. Two-year results of a
prospective preventive swallowing rehabilitation trial
in patients treated with chemoradiation for advanced
head and neck cancer. Eur. Arch. Otorhinolaryngol.
271, 1257–1270 (2014).
42. Wheeler-Hegland, K. M., Rosenbek, J. C.
& Sapienza, C. M. Submental sEMG and hyoid
movement during Mendelsohn maneuver, effortful
swallow, and expiratory muscle strength training.
J. Speech Lang. Hear. Res. 51, 1072–1087 (2008).
43. Martin-Harris, B. et al. Respiratory-swallow training in
patients with head and neck cancer. Arch. Phys. Med.
Rehabil. 96, 885–893 (2015).
44. Manor, Y., Mootanah, R., Freud, D., Giladi, N.
& Cohen, J. T. Video-assisted swallowing therapy for
patients with Parkinson’s disease. Parkinsonism Relat.
Disord. 19, 207–211 (2013).
45. Troche, M. S. et al. Aspiration and swallowing in
Parkinson disease and rehabilitation with EMST: a
randomized trial. Neurology 75, 1912–1919 (2010).
46. Shaker, R. et al. Rehabilitation of swallowing by
exercise in tube-fed patients with pharyngeal
dysphagia secondary to abnormal UES opening.
Gastroenterology 122, 1314–1321 (2002).
47. Carnaby, G., Hankey, G. J. & Pizzi, J. Behavioural
intervention for dysphagia in acute stroke:
a randomised controlled trial. Lancet Neurol. 5,
31–37 (2006).
48. DePippo, K. L., Holas, M. A., Reding, M. J.,
Mandel, F. S. & Lesser, M. L. Dysphagia therapy
following stroke: a controlled trial. Neurology 44,
1655–1660 (1994).
49. Carnaby-Mann, G., Crary, M. A., Schmalfuss, I.
& Amdur, R. “Pharyngocise”: randomized controlled
trial of preventative exercises to maintain muscle
structure and swallowing function during
head‑and‑neck chemoradiotherapy. Int. J. Radiat.
Oncol. Biol. Phys. 83, 210–219 (2012).
50. Kotz, T. et al. Prophylactic swallowing exercises
in patients with head and neck cancer
undergoing chemoradiation: a randomized trial.
Arch. Otolaryngol. Head Neck Surg. 138, 376–382
(2012).
51. Tang, Y. et al. A randomized prospective study of
rehabilitation therapy in the treatment of radiation-
induced dysphagia and trismus. Strahlenther. Onkol.
187, 39–44 (2011).
52. Kulbersh, B. D. et al. Pretreatment, preoperative
swallowing exercises may improve dysphagia quality
of life. Laryngoscope 116, 883–886 (2006).
53. Zhen, Y., Wang, J. G., Tao, D., Wang, H. J.
& Chen, W. L. Efficacy survey of swallowing function
and quality of life in response to therapeutic
intervention following rehabilitation treatment in
dysphagic tongue cancer patients. Eur. J. Oncol. Nurs.
16, 54–58 (2012).
54. Chen, A. Y. et al. The development and validation
of a dysphagia-specific quality-of‑life questionnaire
for patients with head and neck cancer: the M. D.
Anderson dysphagia inventory. Arch. Otolaryngol.
Head Neck Surg. 127, 870–876 (2001).
55. Hughes, P. J. et al. Dysphagia in treated
nasopharyngeal cancer. Head Neck 22, 393–397
(2000).
56. Kalf, J. G., de Swart, B. J., Bloem, B. R.
& Munneke, M. Prevalence of oropharyngeal
dysphagia in Parkinson’s disease: a meta-analysis.
Parkinsonism Relat. Disord. 18, 311–315 (2012).
57. Martin, R. E. Neuroplasticity and swallowing.
Dysphagia 24, 218–229 (2009).
58. Geeganage, C., Beavan, J., Ellender, S. & Bath, P. M.
Interventions for dysphagia and nutritional support in
acute and subacute stroke. Cochrane Database Syst.
Rev. 10, CD000323 (2012).
59. Michou, E. & Hamdy, S. Neurostimulation as an
approach to dysphagia rehabilitation: current
evidence. Curr. Phys. Med. Rehabil. Rep. 1, 257–266
(2013).
60. Pisegna, J. M. et al. Effects of non-invasive brain
stimulation on post-stroke dysphagia: a systematic
review and meta-analysis of randomized controlled
trials. Clin. Neurophysiol. 127, 956–968 (2016).
61. Tan, C., Liu, Y., Li, W., Liu, J. & Chen, L.
Transcutaneous neuromuscular electrical stimulation
can improve swallowing function in patients with
dysphagia caused by non-stroke diseases: a meta-
analysis. J. Oral Rehabil. 40, 472–480 (2013).
62. Scutt, P., Lee, H. S., Hamdy, S. & Bath, P. M.
Pharyngeal electrical stimulation for treatment of
poststroke dysphagia: individual patient data meta-
analysis of randomised controlled trials. Stroke Res.
Treat. 2015, 429053 (2015).
63. Langmore, S. E. et al. Efficacy of electrical stimulation
and exercise for dysphagia in patients with head and
neck cancer: a randomized clinical trial. Head Neck
38 (Suppl. 1), E1221–E1231 (2015).
64. National Institute for Health and Care Excellence.
Transcutaenous neuromuscular electrical stimulation
for oropharyngeal dysphagia. NICE https://
www.nice.org.uk/guidance/ipg490 (2013).
65. Von Elm, E. The Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE)
statement: guidelines for reporting observational
studies. Prev. Med. 45, 247–251 (2007).

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 677

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
REVIEWS

66. Kelly, J. H. Management of upper esophageal
sphincter disorders: indications and complications
of myotomy. Am. J. Med. 108 (Suppl. 4a), 43S–46S
(2000).
67. Ali, G. N. et al. Predictors of outcome following
cricopharyngeal disruption for pharyngeal dysphagia.
Dysphagia 12, 133–139 (1997).
68. Allen, J. E., White, C. J., Leonard, R. J. & Belafsky, P. C.
Posterior cricoid region fluoroscopic findings:
the posterior cricoid plication. Dysphagia 26,
272–276 (2011).
69. Cook, I. J., Blumbergs, P., Cash, K., Jamieson, G. G.
& Shearman, D. J. Structural abnormalities of the
cricopharyngeus muscle in patients with pharyngeal
(Zenker’s) diverticulum. J. Gastroenterol. Hepatol. 7,
556–562 (1992).
70. Rofes, L., Arreola, V., Martin, A. & Clave, P. Natural
capsaicinoids improve swallow response in older
patients with oropharyngeal dysphagia. Gut 62,
1280–1287 (2013).
71. Cook, I. J. et al. Opening mechanisms of the human
upper esophageal sphincter. Am. J. Physiol. 257,
G748–G759 (1989).
72. Omari, T. I. et al. Predicting the activation states
of the muscles governing upper esophageal sphincter
relaxation and opening. Am. J. Physiol. Gastrointest.
Liver Physiol. 310, G359–G366 (2016).
73. Cook, I. J. Diagnosis and management of
cricopharyngeal achalasia and other upper
esophageal sphincter opening disorders.
Curr. Gastroenterol. Rep. 2, 191–195 (2000).
74. Kocdor, P., Siegel, E. R. & Tulunay-Ugur, O. E.
Cricopharyngeal dysfunction: a systematic review
comparing outcomes of dilatation, botulinum toxin
injection, and myotomy. Laryngoscope 126, 135–141
(2016).
75. Munoz, A. A., Shapiro, J., Cuddy, L. D., Misono, S.
& Bhattacharyya, N. Videofluoroscopic findings in
dysphagic patients with cricopharyngeal dysfunction:
before and after open cricopharyngeal myotomy.
Ann. Otol. Rhinol. Laryngol. 116, 49–56 (2007).
76. St Guily, J. L. et al. Swallowing disorders in muscular
diseases: functional assessment and indications of
cricopharyngeal myotomy. Ear Nose Throat J. 73,
34–40 (1994).
77. Kos, M. P., David, E. F., Klinkenberg-Knol, E. C.
& Mahieu, H. F. Long-term results of external upper
esophageal sphincter myotomy for oropharyngeal
dysphagia. Dysphagia 25, 169–176 (2010).
78. Bammer, T., Salassa, J. R. & Klingler, P. J.
Comparison of methods for determining
cricopharyngeal intrabolus pressure in normal
patients as possible indicator for cricopharyngeal
myotomy. Otolaryngol. Head Neck Surg. 127,
299–308 (2002).
79. Mason, R. J. et al. Pharyngeal swallowing disorders:
selection for and outcome after myotomy. Ann. Surg.
228, 598–608 (1998).
80. Kos, M. P., David, E. F., Aalders, I. J., Smit, C. F.
& Mahieu, H. F. Long-term results of laryngeal
suspension and upper esophageal sphincter myotomy
as treatment for life-threatening aspiration. Ann. Otol.
Rhinol. Laryngol. 117, 574–580 (2008).
81. Lebo, C. P., Sangü, K. & Norris, F. H. Jr.
Cricopharyngeal myotomy in amyotrophic lateral
sclerosis. Laryngoscope 86, 862–868 (1976).
82. Takasaki, K., Umeki, H., Enatsu, K., Kumagami, H.
& Takahashi, H. Evaluation of swallowing pressure in
a patient with amyotrophic lateral sclerosis before and
after cricopharyngeal myotomy using high-resolution
manometry system. Auris Nasus Larynx 37,
644–647 (2010).
83. Schneider, I., Thumfart, W. F., Pototschnig, C.
& Eckel, H. E. Treatment of dysfunction of the
cricopharyngeal muscle with botulinum A toxin:
introduction of a new, noninvasive method. Ann. Otol.
Rhinol. Laryngol. 103, 31–35 (1994).
84. Moerman, M., Callier, Y., Dick, C. & Vermeersch, H.
Botulinum toxin for dysphagia due to cricopharyngeal
dysfunction. Eur. Arch. Otorhinolaryngol. 259, 1–3
(2002).
85. Moerman, M. B. Cricopharyngeal Botox injection:
indications and technique. Curr. Opin. Otolaryngol.
Head Neck Surg. 14, 431–436 (2006).
86. Haapaniemi, J. J., Laurikainen, E. A., Pulkkinen, J.
& Marttila, R. J. Botulinum toxin in the treatment of
cricopharyngeal dysphagia. Dysphagia 16, 171–175
(2001).
87. Agarwalla, A., Small, A. J., Mendelson, A. H.,
Scott, F. I. & Kochman, M. L. Risk of recurrent or
refractory strictures and outcome of endoscopic
dilation for radiation-induced esophageal strictures.
Surg. Endosc. 29, 1903–1912 (2015).
88. Dou, Z. et al. The effect of different catheter balloon
dilatation modes on cricopharyngeal dysfunction in
patients with dysphagia. Dysphagia 27, 514–520
(2012).
89. Belafsky, P. C. et al. The upper esophageal sphincter
is not round: a pilot study evaluating a novel,
physiology-based approach to upper esophageal
sphincter dilation. Ann. Otol. Rhinol. Laryngol. 122,
217–221 (2013).
90. Papaspyrou, G., Schick, B., Papaspyrou, S.,
Wiegand, S. & Al Kadah, B. Laser surgery for Zenker’s
diverticulum: European combined study. Eur. Arch.
Otorhinolaryngol. 273, 183–188 (2016).
91. van Overbeek, J. & Groote, A. Zenker’s diverticulum.
Curr. Opin. Otolaryngol. Head Neck Surg. 2, 55–58
(1994).
92. Veenker, E. & Cohen, J. I. Current trends in
management of Zenker diverticulum. Curr. Opin.
Otolaryngol. Head Neck Surg. 11, 160–165 (2003).
93. Achem, S. R. & Devault, K. R. Dysphagia in aging.
J. Clin. Gastroenterol. 39, 357–371 (2005).
94. Yokoyama, M., Mitomi, N., Tetsuka, K., Tayama, N.
& Niimi, S. Role of laryngeal movement and effect
of aging on swallowing pressure in the pharynx and
upper esophageal sphincter. Laryngoscope 110,
434–439 (2000).
95. Verdonck, J. & Morton, R. P. Systematic review
on treatment of Zenker’s diverticulum. Eur. Arch.
Otorhinolaryngol. 272, 3095–3107 (2015).
96. Narne, S., Cutrone, C., Bonavina, L., Chella, B.
& Peracchia, A. Endoscopic diverticulotomy for
the treatment of Zenker’s diverticulum: results
in 102 patients with staple-assisted endoscopy.
Ann. Otol. Rhinol. Laryngol. 108, 810–815 (1999).
97. Chang, C. W. et al. Carbon dioxide laser endoscopic
diverticulotomy versus open diverticulectomy for
Zenker’s diverticulum. Laryngoscope 114, 519–527
(2004).
98. van Overbeek, J. J. Meditation on the pathogenesis
of hypopharyngeal (Zenker’s) diverticulum and
a report of endoscopic treatment in 545 patients.
Ann. Otol. Rhinol. Laryngol. 103, 178–185 (1994).
99. Anagiotos, A. et al. Long-term symptom control after
endoscopic laser-assisted diverticulotomy of Zenker’s
diverticulum. Auris Nasus Larynx 41, 568–571
(2014).
100. Wouters, B. & van Overbeek, J. J. Endoscopic
treatment of the hypopharyngeal (Zenker’s)
diverticulum. Hepatogastroenterology 39, 105–108
(1992).
101. van Overbeek, J., Hoeksema, P. & Edens, E.
Microendoscopic surgery of the hypopharyngeal
diverticulum using electrocoagulation or carbon dioxide
laser. Ann. Otol. Rhinol. Laryngol. 93, 34–36 (1984).
102. Murer, K., Soyka, M. B., Broglie, M. A., Huber, G. F.
& Stoeckli, S. J. Zenker’s diverticulum: outcome of
endoscopic surgery is dependent on the intraoperative
exposure. Eur. Arch. Otorhinolaryngol. 272, 167–173
(2015).
103. Francis, D. O., McKiever, M. E., Garrett, C. G.,
Jacobson, B. & Penson, D. F. Assessment of patient
experience with unilateral vocal fold immobility:
a preliminary study. J. Voice 28, 636–643 (2014).
104. Hammer, M. J. Design of a new somatosensory
stimulus delivery device for measuring laryngeal
mechanosensory detection thresholds in humans.
IEEE Trans. Biomed. Eng. 56, 1154–1159 (2009).
105. Aviv, J. E. Clinical assessment of pharyngolaryngeal
sensitivity. Am. J. Med. 108 (Suppl. 4a), 68S–72S
(2000).
106. Tabaee, A., Murry, T., Zschommler, A. & Desloge, R. B.
Flexible endoscopic evaluation of swallowing with
sensory testing in patients with unilateral vocal fold
immobility: incidence and pathophysiology of
aspiration. Laryngoscope 115, 565–569 (2005).
107. Bhattacharyya, N., Kotz, T. & Shapiro, J. Dysphagia
and aspiration with unilateral vocal cord immobility:
incidence, characterization, and response to surgical
treatment. Ann. Otol. Rhinol. Laryngol. 111, 672–679
(2002).
108. Misono, S. & Merati, A. L. Evidence-based practice:
evaluation and management of unilateral vocal
fold paralysis. Otolaryngol. Clin. North Am. 45,
1083–1108 (2012).
109. Andrade Filho, P. A., Carrau, R. L. & Buckmire, R. A.
Safety and cost-effectiveness of intra-office flexible
videolaryngoscopy with transoral vocal fold injection
in dysphagic patients. Am. J. Otolaryngol. 27,
319–322 (2006).
110. Flint, P. W., Purcell, L. L. & Cummings, C. W.
Pathophysiology and indications for medialization
thyroplasty in patients with dysphagia and aspiration.
Otolaryngol. Head Neck Surg. 116, 349–354 (1997).
111. Siu, J., Tam, S. & Fung, K. A comparison of outcomes
in interventions for unilateral vocal fold paralysis:
a systematic review. Laryngoscope 126, 1616–1624
(2016).
112. Montgomery, W. W., Hillman, R. E. & Varvares, M. A.
Combined thyroplasty type I and inferior constrictor
myotomy. Ann. Otol. Rhinol. Laryngol. 103, 858–862
(1994).
113. Woodson, G. Cricopharyngeal myotomy and arytenoid
adduction in the management of combined laryngeal
and pharyngeal paralysis. Otolaryngol. Head Neck
Surg. 116, 339–343 (1997).
114. Mok, P., Woo, P. & Schaefer-Mojica, J. Hypopharyngeal
pharyngoplasty in the management of pharyngeal
paralysis: a new procedure. Ann. Otol. Rhinol.
Laryngol. 112, 844–852 (2003).
115. Griffith, B. P. Surgical treatment of congestive heart
failure: evolving options. Ann. Thorac Surg. 76,
S2254–S2259 (2003).
116. Calcaterra, T. C. Laryngeal suspension after
supraglottic laryngectomy. Arch. Otolaryngol. 94,
306–309 (1971).
117. Brasnu, D. F. Supracricoid partial laryngectomy with
cricohyoidopexy in the management of laryngeal
carcinoma. World J. Surg. 27, 817–823 (2003).
118. Laccourreye, H., Laccourreye, O., Weinstein, G.,
Menard, M. & Brasnu, D. Supracricoid laryngectomy
with cricohyoidopexy: a partial laryngeal procedure
for selected supraglottic and transglottic carcinomas.
Laryngoscope 100, 735–741 (1990).
119. Flores, T. C., Wood, B. G., Levine, H. L., Koegel, L. Jr
& Tucker, H. M. Factors in successful deglutition
following supraglottic laryngeal surgery. Ann. Otol.
Rhinol. Laryngol. 91, 579–583 (1982).
120. Weber, R. S., Ohlms, L., Bowman, J., Jacob, R.
& Goepfert, H. Functional results after total or near
total glossectomy with laryngeal preservation. Arch.
Otolaryngol. Head Neck Surg. 117, 512–515 (1991).
121. Goode, R. L. Laryngeal suspension in head and neck
surgery. Laryngoscope 86, 349–355 (1976).
122. Sato, K. & Nakashima, T. Surgical closure of the larynx
for intractable aspiration: surgical technique using
closure of the posterior glottis. Laryngoscope 113,
177–179 (2003).
123. Miller, F. R. & Eliachar, I. Managing the aspirating
patient. Am. J. Otolaryngol. 15, 1–17 (1994).
124. Tomita, T., Tanaka, K., Shinden, S. & Ogawa, K.
Tracheoesophageal diversion versus total
laryngectomy for intractable aspiration. J. Laryngol.
Otol. 118, 15–18 (2004).
125. Kawamoto, A. et al. Central-part laryngectomy
is a useful and less invasive surgical procedure
for resolution of intractable aspiration. Eur. Arch.
Otorhinolaryngol. 271, 1149–1155 (2014).
126. Lindeman, R. C. Diverting the paralyzed larynx:
a reversible procedure for intractable aspiration.
Laryngoscope 85, 157–180 (1975).
127. Hoffman, H. T., McCulloch, T., Gustin, D.
& Karnell, L. H. Organ preservation therapy
for advanced-stage laryngeal carcinoma.
Otolaryngol. Clin. North Am. 30, 113–130 (1997).
128. Cannon, C. R. & McLean, W. C. Laryngectomy for
chronic aspiration. Am. J. Otolaryngol. 3, 145–149
(1982).
129. Fair, B. S. Contrasts in patients’ and providers’
explanations of rheumatoid arthritis. J. Nurs.
Scholarsh. 35, 339–344 (2003).
130. Martino, R., Beaton, D. & Diamant, N. E. Using
different perspectives to generate items for a new
scale measuring medical outcomes of dysphagia
(MOD). J. Clin. Epidemiol. 62, 518–526 (2009).
131. Martino, R., Beaton, D. & Diamant, N. E. Perceptions
of psychological issues related to dysphagia differ in
acute and chronic patients. Dysphagia 25, 26–34
(2010).
132. Shinn, E. H. et al. Adherence to preventive exercises
and self-reported swallowing outcomes in post-
radiation head and neck cancer patients. Head Neck
35, 1707–1712 (2013).
133. Aronson, J. K. Compliance, concordance, adherence.
Br. J. Clin. Pharmacol. 63, 383–384 (2007).
134. Bergman-Evans, B. AIDES to improving medication
adherence in older adults. Geriatr. Nurs. 27,
174–182 (2006).
135. Collins, F. S. & Tabak, L. A. Policy: NIH plans to
enhance reproducibility. Nature 505, 612–613
(2014).

678 | NOVEMBER 2016 | VOLUME 13 www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 REVIEWS

136. Sackett, D. L., Rosenberg, W. M., Gray, J. A.,
Haynes, R. B. & Richardson, W. S. Evidence based
medicine: what it is and what it isn’t. BMJ 312, 71–72
(1996).
137. Wintzen, A. R., Badrising, U. A., Roos, R. A. C.,
Vielvoye, J. & Liauw, L. Influence of bolus volume on
hyoid movements in normal individuals and patients
with Parkinson’s disease. 21, 57–59 (1994).
138. Shanahan, T. K., Logemann, J. A., Rademaker, A. W.,
Pauloski, B. R. & Kahrilas, P. J. Chin-down posture
effect on aspiration in dysphagic patients. Arch. Phys.
Med. Rehabil. 74, 736–739 (1993).
139. Lewin, J. S., Hebert, T. M., Putnam, J. B. Jr
& DuBrow, R. A. Experience with the chin tuck
maneuver in postesophagectomy aspirators.
Dysphagia 16, 216–219 (2001).
140. Nagaya, M., Kachi, T., Yamada, T. & Sumi, Y.
Videofluorographic observations on swallowing in
patients with dysphagia due to neurodegenerative
diseases. Nagoya J. Med. Sci. 67, 17–23 (2004).
141. Lazarus, C., Logemann, J. A. & Gibbons, P. Effects of
maneuvers on swallowing function in a dysphagic oral
cancer patient. Head Neck 15, 419–424 (1993).
142. Logemann, J. A., Rademaker, A. W., Pauloski, B. R.
& Kahrilas, P. J. Effects of postural change on
aspiration in head and neck surgical patients.
Otolaryngol. Head Neck Surg. 110, 222–227 (1994).
143. Zuydam, A. C., Rogers, S. N., Brown, J. S.,
Vaughan, E. D. & Magennis, P. Swallowing
rehabilitation after oro-pharyngeal resection for
squamous cell carcinoma. Br. J. Oral Maxillofac. Surg.
38, 513–518 (2000).
144. Bulow, M., Olsson, R. & Ekberg, O. Videomanometric
analysis of supraglottic swallow, effortful swallow,
and chin tuck in patients with pharyngeal dysfunction.
Dysphagia 16, 190–195 (2001).
145. Bogaert, E., Goeleven, A. & Dejaeger, E. Effectmeting
van therapeutische interventies tijdens radiologisch
slikonderzoek. Tijdschrift Voor Geneeskunde 59,
1410–1414 (2003).
146. Robbins, J. et al. The effects of lingual exercise in
stroke patients with dysphagia. Arch. Phys. Med.
Rehabil. 88, 150–158 (2007).
147. Lazarus, C. L. et al. Effects of exercise on swallowing
and tongue strength in patients with oral and
oropharyngeal cancer treated with primary
radiotherapy with or without chemotherapy.
Int. J. Oral Maxillofac. Surg. 43, 523–530 (2014).
148. Lazarus, C. et al. Does laryngectomy improve
swallowing after chemoradiotherapy?: A case study.
Arch. Otolaryngol. Head Neck Surg. 128, 54–57
(2002).
149. Brunello, D. L. & Mandikos, M. N. The use of a
dynamic opening device in the treatment of radiation
induced trismus. Aust. Prosthodont. J. 9, 45–48
(1995).
150. Cohen, E. G., Deschler, D. G., Walsh, K. &
Hayden, R. E. Early use of a mechanical stretching
device to improve mandibular mobility after composite
resection: a pilot study. Arch. Phys. Med. Rehabil. 86,
1416–1419 (2005).
151. Grandi, G., Silva, M. L., Streit, C. & Wagner, J. C.
A mobilization regimen to prevent mandibular
hypomobility in irradiated patients: an analysis and
comparison of two techniques. Med. Oral Patol. Oral
Cir. Bucal 12, E105–E109 (2007).
152. Dijkstra, P. U., Sterken, M. W., Pater, R.,
Spijkervet, F. K. & Roodenburg, J. L. Exercise therapy
for trismus in head and neck cancer. Oral Oncol. 43,
389–394 (2007).
153. Shulman, D. H., Shipman, B. & Willis, F. B. Treating
trismus with dynamic splinting: a cohort, case series.
Adv. Ther. 25, 9–16 (2008).
154. Rose, T., Leco, P. & Wilson, J. The development of
simple daily jaw exercises for patients receiving radical
head and neck radiotherapy. J. Med. Imaging Radiat.
Sci. 40, 32–37 (2009).
155. Stubblefield, M. D., Manfield, L. & Riedel, E. R. A.
Preliminary report on the efficacy of a dynamic jaw
opening device (Dynasplint Trismus System) as part
of the multimodal treatment of trismus in patients
with head and neck cancer. Arch. Phys. Med. Rehabil.
91, 1278–1282 (2010).
156. South, A. R., Somers, S. M. & Jog, M. S. Gum chewing
improves swallow frequency and latency in Parkinson
patients: a preliminary study. Neurology 74,
1198–1202 (2010).
157. Logemann, J. A. et al. A randomized study comparing
the Shaker exercise with traditional therapy:
a preliminary study. Dysphagia 24, 403–411 (2009).
158. Pitts, T. et al. Impact of expiratory muscle strength
training on voluntary cough and swallow function in
Parkinson disease. Chest 135, 1301–1308 (2009).
159. El Sharkawi, A. et al. Swallowing and voice effects of
Lee Silverman Voice Treatment (LSVT): a pilot study.
J. Neurol. Neurosurg. Psychiatry 72, 31–36 (2002).
160. Bryant, M. Biofeedback in the treatment of a selected
dysphagic patient. Dysphagia 6, 140–144 (1991).
161. Denk, D. M. & Kaider, A. Videoendoscopic
biofeedback: a simple method to improve the efficacy
of swallowing rehabilitation of patients after head and
neck surgery. ORL J. Otorhinolaryngol. Relat. Spec.
59, 100–105 (1997).
162. Crary, M. A., Carnaby Mann, G. D., Groher, M. E.
& Helseth, E. Functional benefits of dysphagia therapy
using adjunctive sEMG biofeedback. Dysphagia 19,
160–164 (2004).
163. Crary, M. A., Carnaby, G. D. & Groher, M. E.
Biomechanical correlates of surface electromyography
signals obtained during swallowing by healthy adults.
J. Speech Lang. Hear. Res. 49, 186–193 (2006).
164. Felix, V. N., Correa, S. M. & Soares, R. J. A therapeutic
maneuver for oropharyngeal dysphagia in patients
with Parkinson’s disease. Clinics (Sao Paulo) 63,
661–666 (2008).
165. Huckabee, M. L. & Cannito, M. P. Outcomes of
swallowing rehabilitation in chronic brainstem
dysphagia: a retrospective evaluation. Dysphagia 14,
93–109 (1999).
166. Carroll, W. R. et al. Pretreatment swallowing exercises
improve swallow function after chemoradiation.
Laryngoscope 118, 39–43 (2008).
167. Ahlberg, A. et al. Early self-care rehabilitation of head
and neck cancer patients. Acta Otolaryngol. 131,
552–561 (2011).
168. Argolo, N., Sampaio, M., Pinho, P., Melo, A.
& Nóbrega, A. C. Do swallowing exercises improve
swallowing dynamic and quality of life in Parkinson’s
disease? NeuroRehabilitation 32, 949–955 (2013).
169. Freed, M. L., Freed, L., Chatburn, R. L. & Christian, M.
Electrical stimulation for swallowing disorders caused
by stroke. Respir. Care 46, 466–474 (2001).
170. Power, M. L. et al. Evaluating oral stimulation as a
treatment for dysphagia after stroke. Dysphagia 21,
49–55 (2006).
171. Bulow, M., Speyer, R., Baijens, L., Woisard, V.
& Ekberg, O. Neuromuscular electrical stimulation
(NMES) in stroke patients with oral and pharyngeal
dysfunction. Dysphagia 23, 302–309 (2008).
172. Permsirivanich, W. et al. Comparing the effects of
rehabilitation swallowing therapy versus
neuromuscular electrical stimulation therapy among
stroke patients with persistent pharyngeal dysphagia:
a randomized controlled study. J. Med. Assoc. Thai
92, 259–265 (2009).
173. Ryu, J. S. et al. The effect of electrical stimulation
therapy on dysphagia following treatment for head
and neck cancer. Oral Oncol. 45, 665–668 (2009).
174. Regan, J., Walshe, M. & Tobin, W. O. Immediate
effects of thermal-tactile stimulation on timing of
swallow in idiopathic Parkinson’s disease. Dysphagia
25, 207–215 (2010).
175. Lin, P. H. et al. Effects of functional electrical
stimulation on dysphagia caused by radiation therapy
in patients with nasopharyngeal carcinoma.
Support. Care Cancer 19, 91–99 (2011).
176. Baijens, L. W. J. et al. The effect of surface electrical
stimulation on swallowing in dysphagic Parkinson
patients. Dysphagia 27, 528–537 (2012).
177. Rofes, L. et al. Effect of surface sensory and motor
electrical stimulation on chronic poststroke
oropharyngeal dysfunction. Neurogastroenterol.
Motil. 25, 888–e701 (2013).
178. Suntrup, S. et al. Electrical pharyngeal stimulation for
dysphagia treatment in tracheotomized stroke
patients: a randomized controlled trial. Intensive Care
Med. 41, 1629–1637 (2015).
179. Leelamanit, V., Limsakul, C. & Geater, A.
Synchronized electrical stimulation in treating
pharyngeal dysphagia. Laryngoscope 112,
2204–2210 (2002).
180. Blumenfeld, L., Hahn, Y., Lepage, A., Leonard, R.
& Belafsky, P. C. Transcutaneous electrical stimulation
versus traditional dysphagia therapy: a nonconcurrent
cohort study. Otolaryngol. Head Neck Surg. 135,
754–757 (2006).
181. Shaw, G. Y. et al. Transcutaneous neuromuscular
electrical stimulation (VitalStim) curative therapy for
severe dysphagia: myth or reality? Ann. Otol. Rhinol.
Laryngol. 116, 36–44 (2007).
182. Carnaby-Mann, G. D. & Crary, M. A. Adjunctive
neuromuscular electrical stimulation for treatment-
refractory dysphagia. Ann. Otol. Rhinol. Laryngol.
117, 279–287 (2008).
183. Xia, W. et al. Treatment of post-stroke dysphagia by
vitalstim therapy coupled with conventional swallowing
training. J. Huazhong Univ. Sci. Technolog. Med. Sci.
31, 73–76 (2011).
184. Heijnen, B. J., Speyer, R., Baijens, L. W. &
Bogaardt, H. C. Neuromuscular electrical stimulation
versus traditional therapy in patients with Parkinson’s
disease and oropharyngeal dysphagia: effects on
quality of life. Dysphagia 27, 336–345 (2012).
185. Baijens, L. S. et al. Surface electrical stimulation in
dysphagic Parkinson patients: a randomized clinical
trial. Laryngoscope 123, E38–E44 (2013).
186. Lazzara, G. L., Lazarus, C. & Logemann, J. A.
Impact of thermal stimulation on the triggering of
the swallowing reflex. Dysphagia 1, 73–77 (1986).
187. Logemann, J. A. et al. Effects of a sour bolus on
oropharyngeal swallowing measures in patients
with neurogenic dysphagia. J. Speech Hear. Res. 38,
556–563 (1995).
188. Rosenbek, J. C., Roecker, E. B., Wood, J. L.
& Robbins, J. Thermal application reduces the
duration of stage transition in dysphagia after stroke.
Dysphagia 11, 225–233 (1996).
189. Rosenbek, J. C. et al. Comparing treatment intensities
of tactile-thermal application. Dysphagia 13, 1–9
(1998).
190. Hamdy, S. et al. Modulation of human swallowing
behaviour by thermal and chemical stimulation in
health and after brain injury. Neurogastroenterol. Motil.
15, 69–77 (2003).
191. Theurer, J. A. et al. Proof‑of‑principle pilot study of
oropharyngeal air-pulse application in individuals with
dysphagia after hemispheric stroke. Arch. Phys. Med.
Rehabil. 94, 1088–1094 (2013).
192. Khedr, E. M., Abo-Elfetoh, N. & Rothwell, J. C.
Treatment of post-stroke dysphagia with repetitive
transcranial magnetic stimulation. Acta Neurol. Scand.
119, 155–161 (2009).
193. Kumar, S. et al. Noninvasive brain stimulation may
improve stroke-related dysphagia: a pilot study. Stroke
42, 1035–1040 (2011).
194. Kim, L., Chun, M. H., Kim, B. R. & Lee, S. J. Effect of
repetitive transcranial magnetic stimulation on
patients with brain injury and dysphagia. Ann. Rehabil.
Med. 35, 765–771 (2011).
195. Yang, E. J. et al. Effects of transcranial direct current
stimulation (tDCS) on post-stroke dysphagia.
Restor. Neurol. Neurosci. 30, 303–311 (2012).
196. Park, J. W., Oh, J. C., Lee, J. W., Yeo, J. S. & Ryu, K. H.
The effect of 5Hz high-frequency rTMS over
contralesional pharyngeal motor cortex in post-stroke
oropharyngeal dysphagia: a randomized controlled
study. Neurogastroenterol. Motil. 25, 324–e250
(2013).
197. Shigematsu, T., Fujishima, I. & Ohno, K. Transcranial
direct current stimulation improves swallowing
function in stroke patients. Neurorehabil. Neural
Repair 27, 363–369 (2013).
198. Michou, E., Mistry, S., Jefferson, S., Tyrrell, P.
& Hamdy, S. Characterizing the mechanisms of central
and peripheral forms of neurostimulation in chronic
dysphagic stroke patients. Brain Stimul. 7, 66–73
(2014).
199. Kelly, E. A. et al. Botulinum toxin injection for the
treatment of upper esophageal sphincter dysfunction.
Ann. Otol. Rhinol. Laryngol. 122, 100–108 (2013).
Acknowledgements
R.M. is supported through a Canada Research Chair (Tier II)
in Swallowing Disorders.
Author contributions
Both authors contributed equally to all aspects of the
manuscript.
Competing interests statement
The authors declare no competing interests.

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 13 | NOVEMBER 2016 | 679

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
 CORRECTION

ERRATUM

Therapeutic intervention in oropharyngeal dysphagia

Rosemary Martino & Timothy McCulloch
Nature Reviews Gastroenterology & Hepatology doi:10.1038/nrgastro.2016.127
In the version of this article orginally published online, there was an error in the title. The error has been corrected for the
HTML and PDF versions of the article.

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY www.nature.com/nrgastro

©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.