Patients with benign essential blepharospasm
or hemifacial spasm are known to use botulinum
toxin injections and alleviating maneuvers to
help control their symptoms. The clinical
correlates between the use of botulinum toxin
injections and the use of alleviating maneuvers
are not well established.
To determine whether the use of alleviating
maneuvers for benign essential blepharospasm or
hemifacial spasm correlates with disease
severity or botulinum toxin treatment.
A prospective cross-sectional observational
study (designed in September 2013) of 74
patients with benign essential blepharospasm and
56 patients with hemifacial spasm who were
consecutively recruited from adnexal clinics at
Moorfields Eye Hospital (January-June 2014) to
complete a questionnaire and undergo a clinical
review. Data analysis was performed in December
2015.
Prevalence and type of alleviating maneuvers
used for blepharospasm and hemifacial spasm,
dystonia severity, and dose and frequency of
botulinum toxin injections.
Of the 74 patients with blepharospasm, 39
(52.7%) used alleviating maneuvers (mean
[SD] age, 70.4 [9.1] years); of
the 56 patients with hemifacial spasm, 25
(44.6%) used alleviating maneuvers (mean
[SD] age, 66.5 [12.7] years).
The most commonly used maneuver was the touching
of facial areas (35 of 64 patients
91;54.7%]); other maneuvers included
covering the eyes (6 of 64 patients
[9.4%]), singing (5 of 64 patients
[7.8%]), and yawning (5 of 64
patients [7.8%]). Patients with
blepharospasm who used alleviating maneuvers
scored higher on the Jankovic Rating Scale
(median score, 5 vs 4; Hodges-Lehmann median
difference, 1 [95% CI, 0-2]; P_=_.01)
and the Blepharospasm Disability Index severity
score (median score, 11 vs 4; Hodges-Lehmann
median difference, 4 [95% CI, 1-7];
P_=_.01) than patients with blepharospasm who
did not use alleviating maneuvers. Patients with
hemifacial spasm who used alleviating maneuvers
scored higher on the 7-item Hemifacial Spasm
Quality of Life scale (median score, 7 vs 3;
Hodges-Lehmann median difference, 4 [95% CI,
1-7]; P_=_.01) and the SMC Severity Grading
Scale (median score, 2 vs 2; Hodges-Lehmann
median difference, 0 [95% CI, 0-1];
P_=_.03) than patients with hemifacial spasm who
did not use alleviating maneuver. The severity
of dystonia correlated with botulinum toxin
treatment for patients with blepharospasm
(r_=_0.23; P_=_.049) and patients with
hemifacial spasm (r_=_0.45; P_=_.001). There was
no difference found in botulinum toxin treatment
between patients who used alleviating maneuvers
and those who did not, in either the
blepharospasm group (150 vs 125 units;
Hodges-Lehmann median difference, 20 units
[95% CI, -10 to 70 units]; P_=_.15) or
the hemifacial spasm group (58 vs 60 units;
Hodges-Lehmann median difference, 0 units
[95% CI, -15 to 20 units];
P_=_.83).
Half of the patients with periocular facial
dystonias used alleviating maneuvers. Their use
was associated with more severe disease but not
with increased use of botulinum toxin. This may
help to guide future therapies, such as advice
on maneuver augmentation or tailored
devices.
Benign essential blepharospasm (BEB)
typically presents in the fifth and sixth
decades of life. Symptoms can be severe,
rendering some patients functionally blind. The
etiology of BEB is not fully understood,
although magnetic resonance imaging studies
indicate involvement of the basal ganglia,
thalamus, and cerebellum. Abnormalities in the
afferent arm of the blink reflex have also been
implicated. Hemifacial spasm (HFS) usually
appears in the fourth to sixth decade of life.
It is generally accepted thatHFS is caused by
vascular impingement of the facial nerve near
its origin from the brainstem.
Medical therapy for BEB and HFS includes
management of concurrentdry eye disease and
pharmacological treatment. A meaningful response
to medical therapy for HFS is reported in less
than 10% of patients. 7Anticholinergics,
antiepileptics, and presynaptic
monoamine-depleting agents can offer limited
symptomatic relief for some patientswith BEB,
but the adverse effects are often dose-limiting,
particularly in elderly patients. Surgery is
reserved for those who do not respond to medical
therapy or botulinum toxin (BTX) injections.
Surgical options for BEB and HFS include facial
nerve fiber disruption, percutaneous
thermolysis, and myectomy procedures. These
rarely offer long-term symptomatic relief and
carry the risk ofpermanent postoperative
complications.
Periocular BTX injections currently form the
most common treatment modality for both patients
with BEB and patients with HFS. Botulinum toxin
inhibits the release of acetylcholine at the
neuromuscular junction by preventing the fusion
of neurotransmitter axonal vesicles, causing
flaccid paralysis. Treatment with BTX has a
transient effect and offers 90% of patients
clinically significant symptomatic relief for 8
to 16 weeks. However, the response to BTX can
vary widely, with some patients perceiving no
benefit.
A distinct phenomenon in dystonia is the
sensory trick or geste antagoniste. Sensory
tricks are purposefulmaneuvers that temporarily
reduce the severity of dystonic posturing and/or
movements. Previous studies suggest that 55% to
72% of patients with BEB and 38.5% of patients
with HFS use trick maneuvers to alleviate their
symptoms.
Many different maneuvers have been described
as sensory tricks; the most common is touching
specific areas of the face (mostly the upper
eyelid), but humming, whistling, yawning,
coughing, adjustingglasses, andcovering1 eye,
amongothers, have alsobeen reported.
Because thesemaneuvers caninvolve not only
sensory but also motor stimulation, they have
recently been
referredtomoreaccuratelyasalleviatingmaneuvers.
17Themechanism underlying this phenomenon is
unclear, but alleviating maneuvers seem to
reduce cortical activity in the supplementary
motor cortex, perhaps by altering central
processing.
We aimed to assess the prevalence of the
alleviating maneuvers used among patients with
BEB or HFS and whether the use of these
maneuvers is related to both disease severity
and treatment with BTX injections. One might
expect that as disease severity increases, the
patient would develop alleviating maneuvers for
disease control. As such, it may act as a proxy
for disease severity. If alleviating maneuvers
are associatedwith more severe disease, thismay
help to guide future therapies and tailor
patient management. To our knowledge, this is
the first study to investigate the relationship
between BEB or HFS severity and the use of
alleviating maneuvers.
Discussion
To our knowledge, this study is the largest
observational study of the use of alleviating
maneuvers for patients with BEB or HFS to date,
and it is the first to investigate the
relationship between these maneuvers and both
disease severity and BTX treatment.
Our study found that 39 of 74 patients with
BEB (52.7%) and 25 of 56 patients with HFS
(44.6%) used alleviating maneuvers. Of the
patients that use alleviatingmaneuvers, 64.9% of
the patients with BEB and45.8% of the patients
with HFS reported that their maneuver either
abolished or reduced the symptoms of dystonia by
at least 50%. Martino et al15 found that 42 of
59 patients with BEB (71.2%) used alleviating
maneuvers, and Loyola et al14 reported that
55%of patients with BEB and 38.5%of patients
with HFS used alleviating maneuvers. For these
patients, the maneuvers abolished or reduced the
symptoms of dystonia by at least 50% in 63.6% of
patientswith BEB and50%of patients with HFS.
This is in keeping with our findings and further
strengthens the observation that patients with
HFS benefit from alleviating maneuvers, which
had only previously been reported by Loyola et
al.
This study reports novel findings that the
use of alleviating maneuvers correlated strongly
with disease severity, in both patients with BEB
and patients with HFS. Although the underlying
mechanism for this phenomenon is not clear, it
may support the input-output mismatch hypothesis
for the development of dystonia. There is a
growing body of evidence that proprioceptive
dysfunction and abnormal sensorimotor
integration exist in focal dystonias, with loss
of mechanisms such as cortical surround
inhibition.
Proprioceptive dysfunction in BEB is
supported by a recent study that found a
reduction in both corneal sensitivity and the
number of subbasal corneal nerves inpatientswith
BEB. Dystonia and BEB may therefore result from
a mismatch between sensory input and motor
output, with a resultant increase in the
facilitation to inhibition ratio.
Indeed, alleviating maneuvers have
previously been shown to reduce this abnormal
increase in intracortical facilitation.
Therefore, it is possible that as disease
severity increases, with an increase in the
facilitation to inhibition ratio, patients
develop alleviating maneuvers as a corrective
inhibitory afferent input. As such, alleviating
maneuvers may be a proxy for worsening disease.
A previous study by Patel et al that looked at
cervical dystonia found no correlation between
disease severity and the use of alleviating
maneuvers. However, their study17 had a large
discrepancy in group size (154 people who used
alleviating maneuvers vs 16 peoplewhodid not),
and, as the authors acknowledge, this may well
have hidden any potential correlation. We found
no difference in BTX treatment between patients
who use alleviating maneuvers and those who do
not, in both the BEB and HFS groups. This is
perhaps surprising given that we found that
overall disease severity correlated with
increased use of BTX. Interestingly, a recent
study found that patients with cervical dystonia
who use alleviating maneuvers derive more
subjective benefit from BTX treatment than
patients with cervical dystonia who do not use
alleviating maneuvers. This is supported by a
functional magnetic resonance imaging study,
which found that the administration of BTX led
to reduced activity in the supplementary motor
area, an area that also shows reduced activation
during the performance of alleviating
maneuvers.
Therefore, alleviating maneuvers may act as
a substitute for BTX treatment. This may explain
why our patients who used alleviating maneuvers
did not require higher BTX doses, despite having
more severe symptoms of the disease. The
majority of both the patients with BEB and the
patients with HFS touched specific areas of
their face to alleviate their dystonia, in
keeping with previous series. Other alleviating
maneuvers included motor activity, such as
singing, yawning, and opening or closing
the eyes, aswell as sensory stimulation, such as
covering the eyes. These have previously been
described, but their frequency of use has not
previously been reported. Classically, sensory
tricks have described maneuvers that involve
predominantly sensory stimulation, but our
findings, and those of others, support the
notion that motor stimulation is an important
part o falleviating maneuvers. Therefore,
strictly sensory tricks form a subset of the
alleviating maneuvers used to reduce the
symptoms of dystonia.
The physiology underlying both sensory and
nonsensory alleviating maneuvers used by
patients with dystonia is not fully understood
and seemingly complex. Studies investigating the
"sensory trick" phenomenon using
electromyography and neuroimaging suggest that
proprioceptive or sensory stimulation can
influence sensorimotor integration, with a
resultant reduction in abnormal motor output.
Indeed, the nonsensory or motor component of
sensory tricks also seems to be of particular
importance. One study found that one-third of
patients experience a trick's benefit prior to
contact with their sensory target and that the
majority of patients seemed to get no benefit if
another individual performs the sensory trick on
their behalf. Indeed, one study even found that
15% of patients benefited from purely imagining
performing their sensory trick. This suggests
that the initiation of movement is also
important in influencing sensorimotor
integration and helps explainwhy maneuvers such
as singing and yawning were effective in
reducing the symptoms of dystonia. The
observation that intricate, combined
motor/sensory activities such as dancing and
playing the piano are also effective certainly
suggests that the mechanism underlying
alleviating maneuvers is indeed complex. It is
interesting that an action such as covering the
eyes was noted to reduce the symptoms of BEB.
This is in keeping with a recent randomized
case-control study that found a reduction in BEB
severity if patients wore FL-41&endash;tinted
spectacles.
A positron emission tomographic study found
activation of the visual cortices during
alleviating maneuvers, even when the
participants' eyeswere closed. This prompted the
authors to suggest that this cortical area is
part of the complex neuronal network activated
by alleviating maneuvers. It is possible that by
covering their eyes, the patients are able to
augment this network, thus reducing their
symptomsof dystonia. It is less clear why
patients with HFS, which is classed as a
myoclonic rather than a dystonic condition,
benefit from alleviating maneuvers. This is an
observation that has only recently been
reported. It is generally thought that HFS is
caused by vascular impingement at the root of
the facial nerve by the posterior circulation.
Evidence, however, suggests that increased
excitability of the facial nucleus may also
contribute to the pathophysiology. It is
therefore conceivable that sensory/motor
stimulation may also centrally inhibitmotor
activity from the facial nucleus, in a similar
way to what has been proposed for BEB. Further
studies are needed to investigate these
potential mechanisms. This study shows that
despite treatment with BTX, patients still
experience symptoms of severe disease. Treatment
with BTX is also not without its risks. Patients
and clinicians have to strike the balance
between symptom control and the adverse effects
of the treatment. We found an association in
this study between those patients who report
more severe symptoms and the use of alleviating
maneuvers. Furthermore, both the patientswith
BEB and the patients with HFS reported a benefit
from their alleviating maneuvers, and half
reported a more than 50% decrease in the
movement after using their maneuver. These
patients may therefore be good candidates for a
multimodal approach to their care, including
advice on augmenting their alleviating maneuvers
or tailoring devices to mimic the maneuver to
help maximize the effect.
Pressure devices, in particular, may
potentially be useful in mimicking the effect of
touching specific parts of the face to stop the
spasms. There were several limitations to this
study. Patients were recruited from a specialist
clinic at a single center. So we may have
selected patients with a more severe disease
profile, although the average age of the
patients and the prevalence of the alleviating
maneuvers used were similar to a previous study.
Patients reported their alleviating maneuvers
via a questionnaire, rather than through direct
observation. This may have led to a degree of
recall bias. Not all parameters in the severity
scales were relevant to all the patients (eg,
driving). This may have affected the results,
although the number of patients affected was
similar in both groups.
In conclusion, approximately half of all
patients with periocular facial dystonia use
alleviating maneuvers. The use of alleviating
maneuvers was associated with greater disease
severity but not with increased use of BTX.
