481280

research-article2013
NNR27610.1177/1545968313481280Neurorehabilitation and Neural RepairNicastri et al

Clinical Research Article

Neurorehabilitation and

Efficacy of Early Physical Therapy in Severe

Neural Repair
27(6) 542­–551
© The Author(s) 2013
Bell’s Palsy: A Randomized Controlled Trial Reprints and permissions:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1545968313481280
nnr.sagepub.com

Maria Nicastri, MHS1, Patrizia Mancini, MD, PhD1, Daniele De Seta, MD1,
GianAntonio Bertoli, MD1, Luca Prosperini, MD, PhD2, Danilo Toni, MD2,
Maurizio Inghilleri, MD2, and Roberto Filipo, MD1

Abstract
Background. Bell’s palsy (BP) is the most frequent form of peripheral palsy of the facial nerve. Prognosis for recovery is good
for most patients; in the remaining cases, different grades of residual impairment persist. Physical therapy, in association
with drug administration, aims to improve outcomes. Objective. To assess the efficacy of early physical therapy in association
with standard drug administration versus pharmacological therapy only, in terms of time to maximum gains and grade of
recovery of function, and to examine who will most benefit from rehabilitation. Methods. From June 2008 to May 2010,
232 individuals were evaluated. The 87 patients meeting the eligibility criteria were randomly assigned to the experimental
group (prednisone and valacyclovir plus physical therapy, n = 39) or the control group (pharmacological therapy, n = 48)
within 10 days of onset. Intention-to-treat analyses were done. Results. The physical therapy had a significant effect on grade
(P = .038) and time (P = .044) to recovery only in patients presenting with severe facial palsy (House-Brackmann [HB] grade
V/VI). No significant differences were found between the study and control groups for outcome of synkinesis. Conclusion.
Physical therapy appears to be effective only in the more severe BP (baseline HB grade V/VI), whereas less severe BP
(baseline HB grade IV) results in complete spontaneous recovery, regardless of physical therapy.

Keywords
facial palsy, Bell’s palsy, rehabilitation, randomized controlled trial, physical therapy, intention-to-treat analysis

Introduction The main problem concerning the efficacy of medica-

Bell’s palsy (BP) is the most frequent form of peripheral
palsy of the facial nerve and represents about 50% to 60%
of all etiologies, with a diversely reported annual inci-
dence of between 8 and 52.8 new cases per 100 000 indi-
viduals.1-7 From 69% to 85% have a complete spontaneous
recovery, whereas partial motor recovery, synkinesis,
hemifacial spasm, contractures, salivation, and lacrima-
tion alterations may persist in remaining cases.5,8,9 These
residual symptoms have a significant impact on the qual-
ity of life because they cause esthetic (asymmetry of the
face at rest, during movements, speech, and alterations in
smiling) and functional problems (difficulty in eating,
drinking, and speech).
The sequelae may trigger severe psychological prob-
lems10-13 because facial harmony and symmetry influence
the person’s own mental picture of themselves and how oth-
ers perceive them14 and are determinant factors of facial
attractiveness, markers of good health, and a vehicle of
expression of feelings.15,16 In an attempt to prevent or
reduce these residual deficits, continuous efforts have been
made to identify the most effective therapeutic approaches,
including medications,17 physical therapy,18 or a combina-
tion of both.19-21
tions such as steroids is the uncertain etiology of BP and the
timing of intervention. Pharmacological treatment starts
when the patient is assessed the first time: the time lapse
between paresis/paralysis and treatment may vary consider-
ably. Although therapy appears to reduce edema and sec-
ondary inflammation damage, it does not influence the
amount of damage already present when the patient pres-
ents for medical attention and starts steroid intake. At pres-
ent, efficacy has been shown for the use of corticosteroids
alone,17 with a better outcome if administered within 48
hours of onset of palsy.22
Physical therapy has been initially experimented with in an
attempt to avoid, or at least minimize, the sequelae associated
with drug administration. The first attempts were made using
electrostimulation, thermal methods, massage, and gross-
motor facial exercises, with and without biofeedback. Over
1
Department of Sense Organs
2
Department of Neurology and Psychiatry, University Sapienza of Rome,
Rome, Italy
Corresponding Author:
Patrizia Mancini, University Sapienza of Rome, Viale dell’Università 31,
Rome, 00161, Italy.
Email: p.mancini@uniroma1.it
Nicastri et al
the past few years, methods have changed in favor of tailored
and patient-centered approaches, based on exercises more
suitable for the particular physiology and function of facial
muscles and the management of psychological distress.
Efficacy of physical therapy, as the only alternative to no
treatment, has been shown in patients with stabilized
sequelae (long-standing paralysis) by several observational
studies.23-26 Beurskens and Heymans27 confirmed these
findings through a randomized trial, showing a significant
effect of mime therapy in an experimental group as opposed
to a control group who received no treatment while on a
waiting list. Benefits of physical therapy were stable 1 year
later.28 As shown by Pereira and colleagues29 in a recent
systematic review on the effect of facial exercise on facial
palsy, the above-mentioned trial presents sufficient data to
perform a meta-analysis and to provide evidence that physi-
cal therapy is effective in this typology of patients.
In contrast, the evaluation of physical therapy efficacy in
the acute clinical phase is more complex because of the
high rate of spontaneous recovery.5 In the literature, there
are only a few experimental or quasiexperimental studies,
most of which compare different physical techniques.30-33
Only 1 randomized trial has been designed to compare
patients who did and did not receive physical therapy dur-
ing the acute phase of BP.19 As shown by Teixeira and col-
leagues18 in a recent systematic review, this study is at high
risk of bias mainly because there is no description of ran-
dom allocation, an unclear definition of blinded status of
the assessors, and the short period of follow-up.
The present study was implemented to assess the effi-
cacy of early physical therapy compared with only drug
administration, in terms of time to improvement and grade
of recovery of function. We tested 2 main hypotheses: first,
that physical therapy procedures do not influence the rate of
recovery or improve the grade of recovery but can be of
help to the patient with a poor prognosis to better cope with
paralysis; second, not all patients need physical therapy
because it is possible to identify which of them have a
favorable prognoses.
Methods
Study Design
The study was designed as a 6-month, independent, single-
blinded, randomized controlled trial and implemented
according to the rules of the CONSORT statement.34 The
protocol was approved by the local ethics committee; each
patient gave written informed consent before commencing
any study-related procedure. The eligibility criteria were
age 15 to 70 years; unilateral “pure” BP diagnosed by clini-
cal and neurologicl assessment; facial palsy severity,
assessed by the House-Brackmann (HB) scale, ranging
from grade IV to VI on the 10th day after the onset of palsy;
onset of steroid treatment within 48 hours after the initial
543
symptoms of BP as oral administration of prednisone 1 mg/
kg for 10 days plus valacyclovir 500 mg 3 times a day for 6
days; not pregnant; no metabolic, neurologicl, infective,
neoplastic, toxic, or iatrogenic disease; and no traumatic
injury to the seventh nerve.
Study Groups and Randomization
Eligible patients were randomly assigned, in a 1:1.2 ratio, to
2 experimental groups: (1) a treatment group that received
the standardized pharmacological treatment plus the inter-
vention with physical therapy (group B) and (2) a control
group that received only the standardized pharmacological
treatment but not physical therapy (group A). This ratio was
set, assuming drop-out rates, during the 6-month follow-up
period, of 10% and 30%, respectively, for groups B and A.
According to previous studies,5,9 we also expected complete
recovery proportions of 0.85 in group B and of 0.58 in
group A (as estimated by the 1-sided Fisher’s exact test).
Consequently, we needed 45 individuals in group B and 54
in group A to achieve a power of 80% (type II error), with a
2-sided significance level of 5% (type I error).
Furthermore, to ensure a more reliable and accurate
comparison of the 2 groups, the randomization procedure
included stratification according to the HB grades at enrol-
ment, 10 days after palsy onset (IV, V, or VI). Therefore,
each stratum comprised 15 and 18 patients in groups B and
A, respectively. The randomization schedule, one for each
stratum, was arranged using the random number tables (ie,
aleatory or dependent on chance) created in 1959 by the
Institute of Statistics of “Sapienza” University in Rome.35
The random number tables were derived using the unit digit
of the first extract numbers of each national lottery wheel
from 1862 to March 1955. Therefore, these numbers were
uniformly distributed and truly random and not computer-
generated pseudorandom numbers.
Study Procedures
Assessment of patients was carried out using 2 of the routinely
used systems in clinical practice19,27,30,36,37: the HB facial grad-
ing system38 (see Supplementary Table 1 at http://nnr.sagepub
.com/content/by/supplemental-data) and the Sunnybrook
facial (SB) grading system39 (see Supplementary Figure 1 at
http://nnr.sagepub.com/content/by/supplemental-data).
The first system was selected to measure the global
degree of paresis/paralysis for its simplicity of administra-
tion, most frequent use, and its robustness, as assessed by
Smith et al,40 who estimated an internal consistency of 0.75,
and Evans et al,41 who found an interobserver reliability of
93%.
As HB lacks in delivering satisfactory information in
regional facial function,42 the SB was added to obtain
detailed data on symmetry—at rest and during motion—
and synkinesis. It was selected for its psychometric
544 Neurorehabilitation and Neural Repair 27(6)

Table 1. Baseline Characteristics of the Per-Protocol Population (n = 73), According to Treatment Groups.a

Group A, n = 48 Group B, n = 39 P Value

Sex, n (%) .39
Female 26 (54.2) 17 (43.6)
Male 22 (45.8) 22 (56.4)
Age, mean (SD), y 51.3 (16.1) 47.1 (16.2) .32
HB grade, n (%) .21
VI 7 (14.6) 8 (20.5)
V 18 (37.5) 8 (20.5)
IV 23 (47.9) 23 (59.0)
SB score, mean (SD) 29.3 (16.9) 24.3 (12.1) .22

Abbreviations: SD, standard deviation; HB, House-Brackmann facial grading scale; SB, Sunnybrook facial grading scale.
a
A, pharmacological treatment; B, pharmacological treatment plus physical therapy.

Figure 1. Study flowchart.

Nicastri et al
characteristics; as described by Ross et al,39 it has a good
sensitivity to clinical changes (P = .0000), and as assessed
by Pavese et al,43 it has a high internal consistency (Cronbach
α of .91) and an elevated repeatability (interrater reliability
= 0.96; intrarater reliability = 0.98). The overall agreement
between the SB and HB facial grading systems showed a
weighted k value ranging from 0.56 (for days 1 to 14) to
0.71 (for days 61 to 180).44
Each patient was videotaped on his or her first visit to the
clinic, 10 days thereafter, and then monthly until the end of
follow-up (sixth month), for a total of 8 evaluation sessions.
Video recordings were evaluated by an experienced and
trained ear, nose, and throat physician blinded to the group
assignment.
Interventions in the experimental group were conducted
by a physiotherapist and speech therapist, trained according
to the neuromuscular retraining principles.14,23,31,45,46 Each
patient was treated in the outpatient clinic by means of indi-
vidual sessions lasting 45 minutes each, twice a week for
the first 3 months and once a week thereafter, until the
follow-up was completed. Patients were instructed to fol-
low a daily program of exercise implemented during the
individual sessions, which are detailed below.
•• They were educated on facial muscle physiology and
functions and changes induced by paralysis.
•• Education was imparted regarding face massages to
improve circulation, 10 minutes twice a day.
•• Active motion exercises with and without mirror
feedback were used to promote motor control and to
avoid altered patterns of movements and overactivity
of the unaffected side. The aim was to train patients
to produce symmetric, isolated, small movements
with a slow execution; to avoid the activation of
abnormal motor patterns; and to reinforce a normal
physiological response and offer better control and
the opportunity to learn new patterns of movements.
Patients were instructed to practice at home daily, 4
times/d, for no more than 10 minutes.
•• Daily management of drinking, eating, and smiling
problems were addressed with strategies identified
during the individual sessions.
•• Daily management of speech was addressed, training
the patient with modified patterns of motion to pro-
duce vowels, and bilabial, labial-dental, and affricate
consonants to allow more symmetric movements.
•• Stretching of face muscles and relaxation activities
were implemented when signs of spasm or synkine-
sis were present.
In the case of complete recovery, rehabilitation was no
longer performed, although assessment continued until the
sixth month.
545
Outcomes Definition
The primary outcome was the proportion of patients to
reach a HB grade of II or less at the end of the 6-month
follow-up period.
The secondary outcomes were the time to reach a HB
grade of II or less, the differences over time in the mean SB
total score, and the proportion of patients having a synkine-
sis subscore of 0 (ie, no synkinesis) at the end of the 6-month
follow-up period.
Statistical Analysis
Analyses were carried-out according to the intention-to-
treat (ITT) principle.47,48 All randomized patients were ana-
lyzed for primary and secondary outcomes, regardless of
whether they dropped out of the study. Missing values were
replaced according to the last observation carried forward
approach; therefore, final values of the outcome variables
are replaced by the last known value before the participant
was lost to follow-up.
Values are expressed as means (±standard deviation) for
continuous variables and proportion for categorical vari-
ables, as appropriate. Demographic and clinical data con-
sidered at baseline included the following: sex (female or
male), age, HB grade, and SB score. Differences between
the 2 treatment arms (ie, A and B groups) in baseline char-
acteristics were tested using Fisher exact test, the χ2 test, or
the Mann-Whitney U test, as appropriate. The differences in
proportions of patients between groups (A vs B) who expe-
rienced recovery of function and disappearance of synkine-
sis were investigated by logistic regression analyses
adjusted for age and sex, with the prespecified outcome
measure as the dependent variable and group assignment as
the independent variable.
The time taken to reach the recovery of function (as
defined above) was investigated using a Cox proportional
hazard regression model, adjusted for age and sex. We con-
sidered the length of follow-up (in months) between base-
line and the last 6-month visit or outcome reach as the main
time variable, whichever came first. Survival curves, show-
ing the time-to-event unadjusted analysis, were also pro-
vided and the differences between the 2 groups analyzed by
the log-rank test.
Changes over time in SB scores were investigated by
means of an analysis of variance (ANOVA), with time
(T0, T1, T2, T3, T4, T5 and T6 monthly visits) and treat-
ment group (A vs B) as the between-subjects factors. A
time-treatment interaction analysis was run to evaluate the
treatment effect on the SB score over time, after adjusting
for age and sex. Simple contrasts were conducted for each
significant time main effect to determine the source of the
significant difference, where necessary.
546
Table 2. Differences in Proportion of Patients Reaching HB Grade II at the End of the 6-Month Follow-up Between the 2 Treatment
Groups A and B, as Calculated by Propensity Score Inverse-Weighting-Adjusted Multivariate Logistic Regression Analyses.a
Group A
Whole study sample 36/48 (75%)
HB grade V/VI 11/23 (48%)
HB grade IV 25/25 (100%)
Abbreviation: HB, House-Brackmann Facial Grading Scale.
a
A, pharmacological treatment; B, pharmacological treatment plus physical therapy. P values significant at a level of significance α = .05 (2-sided) are in
bold.
All 3 outcomes were investigated in the entire study pop-
ulation as well as after stratifying patients according to their
baseline HB grades (IV and V/VI). P values less than .05
(2-sided) were considered as significant. Analyses were
carried out using the Statistical Package for Social Sciences,
version 16.0 (SPSS Inc, Chicago, Illinois).
Results
Participants
A total of 232 individuals affected by BP from June 2008 to
May 2010 were invited to take part in the study. All patients
were recruited at the University Hospital “Umberto I” of
Rome, referred by the neurologists of the emergency depart-
ment, where they arrived soon after onset of symptoms and
having started pharmacological treatment as outlined above.
According to the randomization tables described above, 87
patients who met all the eligibility criteria were assigned to
the 2 arms (48 in group A and 39 in group B). Their baseline
characteristics are summarized in Table 1. The 2 groups
were comparable in terms of baseline demographics and
clinical characteristics.
Figure 1 shows the flowchart of the study. The number
of dropouts after randomization in group A was high (n =
11), especially among those patients presenting with higher
HB grades because of the desire to get rehabilitation.
Therefore, a total of 76 patients (37 in group A, 39 in group
B) concluded the follow-up according to the study protocol
before reaching the preplanned sample size.
Primary Outcome
No significant effect of physical therapy treatment on the
primary outcome was found when the entire study sample
was taken into consideration. As shown in Table 2, at the
end of the 6-month follow-up period, 36 (75%) patients in
group A and 33 (86%) in group B experienced recovery of
function (P = .27), as defined in the outcome definition sec-
tion. In contrast, when stratification was considered, the
physical therapy treatment had a significant effect (P =
.038) on patients with HB grade V/VI (see also Table 3). All
the patients with HB grade IV reached the primary outcome
Neurorehabilitation and Neural Repair 27(6)
Group B Adjusted P Value
33/39 (86%) .27
17/23 (74%) .038
16/16 (100%) 1.00
(final HB grade I or II), regardless of the treatment group
assignment.
Secondary Outcomes
There were no differences in the time taken to reach the
primary outcome between the 2 groups (hazard ratio [HR] =
1.20, 95% confidence interval [CI] = 0.78-1.96; P = .52). In
the entire study sample, the only variable able to predict a
shorter time to reach the outcome was the baseline HB
grade (HR = 5.05, 95% CI = 3.02-8.45; P < .001). The
Kaplan-Meier curve shows that 50% of the study sample
reached the outcome within the second month of follow-
up when the HB grade at baseline was IV and within the
fourth month when the HB grade at baseline was V or VI
(Figure 2).
In contrast, when taking into consideration only the sub-
group of patients with a baseline HB grade V/VI, it was
found that group B reached the primary outcome faster than
group A (HR = 2.24, 95% CI = 1.02-4.93; P = .044), as also
shown in the Kaplan-Meier curve (P = .048 by the log-rank
test; Figure 3). This finding was not replicated in the sub-
group of patients with a baseline HB grade IV (HR = 0.78,
95% CI = 0.41-1.50; P = .46).
At the end of the 6-month follow-up period, SB scores
were 80 (28) and 86 (23) for the A and B groups, respec-
tively (P = .67 by the Mann-Whitney U test). A significant
effect of time was observed, indicating that SB scores
increased over time in both groups (F = 8.29; P < .001).
Moreover, there was also a significant Time × Treatment
effect (F = 2.58; P = .025), suggesting that the rehabilitation
treatment could have led to a greater increase in the SB
scores at specific time points. This was demonstrated by a
simple contrast analysis that revealed significant differ-
ences between the 2 groups at T4 (F = 5.09; P = .018), T5
(F = 7.86; P = .006), and T6 (F = 7.39; P = .008) examina-
tions (when compared with the previous examination;
Figure 4).
When only those patients presenting with a HB grade of
V or VI were taken into consideration, a significant differ-
ence was observed between the 2 groups for final SB scores:
60 (29) and 79 (27), for the A and B groups, respectively
(P = .021 by the Mann-Whitney U test). In contrast, when
Nicastri et al 547

Table 3. Sex-and Age-Adjusted Cox Regression Models to Reach HB Grade II or I at the End of the 6-Month Follow-up.a

95% Confidence Interval

HR Lower Bound Upper Bound Adjusted P value

Whole study sample 1.20 0.78 1.96 .52
HB grade V/VI 2.24 1.02 4.93 .044
HB grade IV 0.78 0.41 1.50 .46

Abbreviations: HB, House-Brackmann Facial Grading Scale; HR, hazard ratio.

a
HR > 1 favors group B (pharmacological treatment plus physical therapy). P values significant at a level of significance α = .05 (2 sided) are in bold.

Figure 2. Kaplan-Meier curves showing time taken to reach primary outcome (ie, House-Brackmann [HB] grade II) according to HB
grade at baseline. Black line, HB grade IV; gray line, HB grades V/VI. *P value by log-rank test.

we considered only patients presenting with a HB grade of
IV, the final SB scores did not significantly differ for the A
and B groups: 98 (7) versus 97 (7); P = .71 by the Mann-
Whitney U test.
Nevertheless, considering the rate of recovery, SB scores
increased over time, regardless of the physical therapy
treatment, even after dividing the entire study population
according to baseline HB grades (IV and V/VI; Table 4).
Synkinesis was found in 25 (29%) patients, and in the
majority of cases, it started after the fourth month of follow-
up and persisted even at the end of the study. Only one
61-year-old woman had the synkinesis started at the second
month of follow-up; at the end of the study, this patient also
had the highest synkinesis subscore, equal to 7. As far as the
proportion of patients with a synkinesis subscore of 0 at the
end of the study period was concerned, no differences were
found between the 2 treatment groups (Table 5). Finally, a
logistic regression analysis showed that the only baseline
clinical variable useful in predicting which patients might
develop synkinesis during follow-up was the presence of a
HB grade of V (odds ratio [OR] = 4.32, 95% CI = 1.33-
14.03; P = .015) or VI (OR = 9.60, 95% CI = 2.34-39.42;
P = .002), irrespective of age and sex.
Discussion
Physical therapy has played an important role in the treat-
ment of BP. Over the years, approaches have focused more
548
Figure 3. Subgroup of patients with House-Brackmann (HB) grade V or VI at study entry (n = 38): Kaplan-Meier curves showing time
to reach primary outcome (ie, HB grade II) according to treatment group. Group A, pharmacological treatment; group B, pharmacological
treatment plus physical therapy. *P value by log-rank test.
Figure 4. Changes (expressed as mean ± standard error [SE])
in Sunnybrook (SB) scores over the 6-month study period,
according to treatment group. Group A, pharmacological treatment;
group B, pharmacological treatment plus physical therapy. *P < .05.
and more on the specificity and peculiarity of facial nerve
physiology and on permanent sequelae related to the recov-
ery processes during nerve regeneration. These procedures
and strategies, implemented for long-standing facial palsy,
Neurorehabilitation and Neural Repair 27(6)
have been developed to help the patient control the sym-
metry of the face, through slow movements and voluntary
control of synkinesis. The patient is encouraged to experi-
ment with different modes of movement and to practice and
automatize them in daily activities and expression of emo-
tions.10,26 Treatment often includes botulinum toxin, mas-
sage, and stretching to reduce synkinesis and hypertonus.20,21
Specific exercises and compensation strategies are imple-
mented also for the correct management of problems occur-
ring when drinking, speaking (eg. slowing speech), eating,
and smiling.24,26,49 These approaches may improve health
status and quality of life,14 as supported by the experimental
results of Beurskens and colleagues.27,28 Two randomized
clinical studies designed to assess the efficacy of mime
therapy have shown how significant improvements can be
obtained both rapidly27 and 1 year after rehabilitation.28
Rehabilitation seemed to be effective in regaining facial
symmetry, in reducing the severity of paresis by 0.6 grades
on the HB scale, and in controlling synkinesis. Functional
improvements were reflected in the patient’s perception of
disability, measured using the Facial Disability Index50:
patients in the experimental group continued to show an
improvement even 1 year after the end of rehabilitation.28
Diels and Combs14 and Coulson et al26 have shown simi-
lar results on facial palsy sequelae using neuromuscular
retraining and video self-modeling. Unfortunately, these
outcomes are characterized by low levels of evidence,18
mainly related to lack of experimental protocol design or to
Nicastri et al 549

Table 4. Summary of Sunnybrook Facial Grading Scores Over Time, According to HB Grade at Baseline.a

Visit Group HB V/VI HB IV

Baseline A 19.9 (11.8) 42.1 (11.0)
B 15.4 (8.3) 37.6 (13.7)
T1 A 36.8 (23.9) 75.8 (17.6)
B 41.0 (24.7) 74.5 (27.8)
T2 A 46.3 (29.2) 92.4 (15.0)
B 54.0 (26.2) 85.4 (26.0)
T3 A 51.2 (30.9) 97.0 (10.3)
B 59.9 (27.1) 89.5 (21.9)
T4 A 53.4 (31.3) 97.0 (10.3)
B 69.7 (27.1) 96.4 (8.8)
T5 A 55.8 (31.1) 97.0 (10.3)
B 75.9 (27.7) 97.2 (7.1)
T6 A 59.7 (29.9) 98.1 (7.1)
B 78.7 (27.7) 97.2 (7.1)

Abbreviation: HB, House-Brackmann Facial Grading Scale.

a
Values are reported as mean (±standard deviation).

Table 5. Differences in Proportion of Patients Having No Synkinesis (ie, a Score of 0 in the Corresponding Scale) at the End of
the 6-Month Follow-up Period Between the 2 Treatment Groupsa as Calculated by a Propensity Score Inverse-Weighting Logistic
Regression Analysis.

Group A Group B Adjusted P Value

Whole study sample 38/48 (79%) 24/39 (62%) .46
HB grades V/VI 16/23 (70%) 10/23 (44%) .10
HB grade IV 22/25 (88%) 14/16 (88%) .96

Abbreviation: HB, House-Brackmann Facial Grading Scale.

a
A, pharmacological treatment; B, pharmacological treatment plus physical therapy.

an excess of potential bias because of small sample size,
short follow-up period, or absence of randomization of
treatment. The lack of significant data is more evident when
intervention is considered in the early phase of palsy, when
the high rate of spontaneous recovery complicates the
assessment of the effect of any intervention.
The present study was originally planned to control and
reduce bias (selection, allocation, and attrition) through
accurate sample size count, randomization of treatment, and
blind assessment. Therefore, its main limit is the failure to
achieve the calculated sample size. In our study, a signifi-
cant number of V and VI HB grade patients dropped out
after being assigned to the control group when they did not
observe any spontaneous improvement because they wanted
to get physical therapy. To overcome these limitations, an
ITT analysis was carried out, and missing values were
replaced according to the last-observation-carried-forward
approach.48 Although it has been reported that this method
may introduce bias,47 this approach is simple and does not
require statistical sophistication.51 Moreover, it is likely that
in our study patients enrolled in the control group were
those who did not spontaneously recover from BP.
Therefore, replacing missing final outcome values by the
last known values should not have strongly affected the
analyses.
Despite the limits discussed above, to our knowledge,
the present study is the largest clinical trial, with the longest
follow-up, focusing on the effect of physical therapy in the
early phase of BP compared with only drug administration.
Moreover, the present study is the first in which patients
have been stratified according to the severity of paresis and
where the patients’ assessment was initiated at the same
point of time, 10 days after the onset of palsy, considered as
the most effective time to evaluate the degree of damage.52
As expected, almost all patients showed spontaneous
recovery. The differences between treated and control
patients did not reach statistical significance, although
results showed a positive trend for treated patients in terms
of grade and time of recovery.
A different result was found on analysis of participants
presenting with IV and V/VI HB grades at the time of enrol-
ment. The rehabilitation treatment had a significant effect
550
on grade (P = .039) and time (P = .04) of recovery. Results
on efficacy of physical therapy are in agreement with those
of Barbara et al.19 However, comparison with this study is
limited by differences in the characteristics of the patients
enrolled (HB grade III-VI vs IV-VI), physical therapy pro-
cedures (Kabat vs NMR), and length of follow-up (15 days
vs 6 months).
When only those patients with HB grade IV were taken
into consideration, we found that all reached the primary
outcome (final HB grade of I-II), regardless of the treat-
ment. This finding can be compared with those reported by
Peitersen,5 who, in his study on the spontaneous course of
2500 peripheral facial nerve palsies, reported a complete
recovery of 94% in those patients with an initial incomplete
palsy; 6% of the differences between our findings and
Peitersen’s can be related to the different grading systems
used (House-Brackman vs Peitersen Grading System):
Peitersen grade III (severe but incomplete) includes HB
grades IV and V, whereas we considered grade V separately.
Complete spontaneous recovery in the HB IV group could
be explained by the presence of neuropraxis in these
patients,53 although we do not have electromyography and
electroneurography data to support this hypothesis.
Less severe paresis (II-IV) would appear to have a posi-
tive spontaneous prognosis and not benefit from physical
therapy. This is an important aspect from the viewpoints of
clinical practice and cost-effectiveness. The speed of recov-
ery experienced by these patients is such that improvements
can become evident within the first weeks: this in turn has a
positive impact on self-perception and allows them to trust
the clinicians in a “wait and scan” condition.
In our trial, 23 (31%) patients developed persistent syn-
kinesis, as assessed at the end of the study, regardless of the
group assignment. Hence early rehabilitation does not
appear to prevent or reduce synkinesis, although the num-
ber of patients with this finding may have been too low or
the follow-up time too short; the usual onset is at the fourth
to sixth month and continues to evolve throughout the
twelfth month after the onset of palsy.
Conclusions
This study is the largest randomized clinical trial to focus
on the effect of physical therapy in patients in the early
phase of BP. Overall results and ITT statistical analysis
strongly indicate that physical therapy in BP is effective in
the more severe (V-VI) grades only, whereas HB grades II
to IV result in complete spontaneous recovery. Also, at the
6-month follow-up, early physical therapy did not appear to
prevent or reduce the occurrence of synkinesis. These find-
ings might help in clinical practice for counseling of patients
and facilitate decision making regarding who may most
benefit from physical therapy, to optimize the use of health
care resources.
Neurorehabilitation and Neural Repair 27(6)
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, author-
ship, and/or publication of this article.
References
1. Kazemi BA. Survey of idiopathic facial palsy (Bell’s palsy) in
southern Iran. Pahlavi Med. 1977;7:436-440.
2. Katusic SK, Beard CM, Wiederholt WC, et al. Incidence,
clinical features, and prognosis in Bell’s palsy, Rochester,
Minnesota, 1968-1982. Ann Neurol. 1986;20:622-627.
3. Yanagihara N. Incidence of Bell’s palsy. Ann Otol Rhinol
Laryngol Suppl. 1988;137:1373-1374.
4. De Diego JI, Prim MP, Madero R, et al. Seasonal patterns of
idiopathic facial paralysis: a 16-year study. Otolaryngol Head
Neck Surg. 1999;120:269-271.
5. Peitersen E. Bell’s palsy: the spontaneous course of 2,500
peripheral facial nerve palsies of different etiologies. Acta
Otolaryngol Suppl. 2002;(549):4-30.
6. Campbell KE, Brundage JF. Effects of climate, latitude, and
season on the incidence of Bell’s palsy in the US Armed
Forces, October 1997 to September 1999. Am J Epidemiol.
2002;156:32-39.
7. Savettieri G, Salemi G, Rocca WA, et al. Incidence and life-
time prevalence of Bell’s palsy in two Sicilian municipalities.
Acta Neurol Scand. 1996;94:71-75.
8. Shafshak TS, Essa AY, Bakey FA. The possible contribut-
ing factors for the success of steroid therapy in Bell’s palsy:
a clinical and electrophysiological study. J Laryngol Otol.
1994;108:940-943.
9. Holland NJ, Weiner GM. Recent developments in Bell’s
palsy. BMJ. 2004;329:553-557.
10. Devriese PP. Treatment of sequelae after facial paralysis: a
global approach. J Laryngol Otol. 1998;112:429-431.
11. Ishii L, Godoy A, Encarnacion CO, et al. Not just another
face in the crowd: society’s perceptions of facial paralysis.
Laryngoscope. 2012;122:533-538.
12. VanSwearingen JM, Cohn JF, Bajaj-Luthra A. Specific
impairment of smiling increases the severity of depressive
symptoms in patients with facial neuromuscular disorders.
Aesthetic Plast Surg. 1999;23:416-423.
13. Fu L, Bundy C, Sadiq SA. Psychological distress in peo-
ple with disfigurement from facial palsy. Eye (Lond).
2011;25:1322-1326.
14. Diels HJ, Combs D. Neuromuscular retraining for facial
paralysis. Otolaryngol Clin North Am. 1997;30:727-743.
15. Heymans PG. The impact of facial paresis: psychological
mechanism. In: Beurskens CHG, van Gelder RS, Heymans
PG, et al, eds. The Facial Palsies. Utrecht, Netherlands:
Lemma; 2005:335-356.
16. Godoy A, Ishii M, Byrne PJ, et al. How facial lesions impact
attractiveness and perception: differential effects of size and
location. Laryngoscope. 2011;121:2542-2547.
Nicastri et al
17. Numthavaj P, Thakkinstian A, Dejthevaporn C, et al.
Corticosteroid and antiviral therapy for Bell’s palsy: a net-
work meta-analysis. BMC Neurol. January 2011;11:1-10.
18. Teixeira LJ, Valbuza JS, Prado GF. Physical therapy for
Bell’s palsy (idiopathic facial paralysis). Cochrane Database
Syst Rev. 2011;(12):CD006283.
19. Barbara M, Antonini G, Vestri A, et al. Role of Kabat physi-
cal rehabilitation in Bell’s palsy: a randomized trial. Acta
Otolaryngol. 2010;130:167-172.
20. Monini S, De Carlo A, Biagini M, et al. Combined protocol
for treatment of secondary effects from facial nerve palsy.
Acta Otolaryngol. 2011;131:882-886.
21. Azuma T, Nakamura K, Takahashi M, et al. Mirror biofeed-
back rehabilitation after administration of single-dose botu-
linum toxin for treatment of facial synkinesis. Otolaryngol
Head Neck Surg. 2012;146:40-45.
22. Axelsson S, Berg T, Jonsson L, et al. Prednisolone in Bell’s
palsy related to treatment start and age. Otol Neurotol.
2011;32:141-146.
23. Brach JS, VanSwearingen JM, Lenert J, et al. Facial neuro-
muscular retraining for oral synkinesis. Plast Reconstr Surg.
1997;99:1922-1931.
24. Beurskens CH, Heymans PG. Positive effects of mime ther-
apy on sequelae of facial paralysis: stiffness, lip mobility, and
social and physical aspects of facial disability. Otol Neurotol.
2003;24:677-681.
25. VanSwearingen JM, Brach JS. Changes in facial movement
and synkinesis with facial neuromuscular reeducation. Plast
Reconstr Surg. 2003;111:2370-2375.
26. Coulson SE, Adams RD, O’Dwyer NJ, et al. Physiotherapy
rehabilitation of the smile after long-term facial nerve palsy
using video self-modeling and implementation intentions.
Otolaryngol Head Neck Surg. 2006;134:48-55.
27. Beurskens CH, Heymans PG. Mime therapy improves facial
symmetry in people with long-term facial nerve paresis: a ran-
domised controlled trial. Aust J Physiother. 2006;52:177-183.
28. Beurskens CH, Heymans PG, Oostendorp RA. Stability of
benefits of mime therapy in sequelae of facial nerve paresis
during a 1-year period. Otol Neurotol. 2006;27:1037-1042.
29. Pereira LM, Obara K, Dias JM, Menacho MO, Lavado EL,
Cardoso JR. Facial exercise therapy for facial palsy: system-
atic review and meta-analysis. Clin Rehabil. 2011;25:649-
658.
30. Dalla Toffola E, Bossi D, Buonocore M, et al. Usefulness
of BFB/EMG in facial palsy rehabilitation. Disabil Rehabil.
2005;27:809-815.
31. Manikandan N. Effect of facial neuromuscular re-education
on facial symmetry in patients with Bell’s palsy: a random-
ized controlled trial. Clin Rehabil. 2007;21:338-343.
32. Alakram P, Puckree T. Effects of electrical stimulation on
House-Brackmann scores in early Bell’s palsy. Physiother
Theory Pract. 2010;26:160-166.
33. Barbara M, Monini S, Buffoni A, et al. Early rehabilitation
of facial nerve deficit after acoustic neuroma surgery. Acta
Otolaryngol. 2003;123:932-935.
34. Schulz KF, Altman DG, Moher D; CONSORT Group.
CONSORT 2010 Statement: updated guidelines for reporting
parallel group randomised trials. Int J Surg. 2011;9:672-677.
551
35. Castellano V. Tavole di numeri aleatori. Editore Istituto di
Statistica dell’ Università di Roma—Sezione di Statistica
Metodologica. Rome, Italy: Tipografia Failli Roma; 1959.
36. Mantsopoulos K, Psillas G, Psychogios G, Brase C, Iro H,
Costantinidis J. Predicting the long term outcome after idio-
pathic facial nerve paralysis. Otol Neurotol. 2011;32:848-
851.
37. Grosheva M, Wittekindt C, Guntinas-Lichius O. Prognostic
value of electroneurography and electromyography in facial
palsy. Laryngoscope. 2008;118:394-397.
38. House JW, Brackmann DE. Facial nerve grading system.
Otolaryngol Head Neck Surg. 1985;93:146-147.
39. Ross BR, Fradet G, Nedzelski JM. Development of a sensitive
clinical facial grading system. Otolaryngol Head Neck Surg.
1996;114:380-386.
40. Smith IM, Murray JAM, Cull RE, Slattery J. A comparison of
facial grading systems. Clin Otolaryngol. 1992;17:303-307.
41. Evans RA, Harries ML, Baguley DM, Moffat DA. Reliability
of the House and Brackmann grading system for facial palsy.
J Laryngol Otol. 1989;103:1045-1046
42. Reitzen SD, Babb JS, Lalwani AK. Significance and reliabil-
ity of the House-Brackmann grading system for regional facial
nerve function. Otolaryngol Head Neck Surg. 2009;140:154-
158.
43. Pavese C, Tinelli C, Furini F, et al. Validation of the Italian
version of the Sunnybrook Facial Grading System [published
online April 10, 2012]. Neurol Sci. doi:10.1007/s10072-012-
1025-x.
44. Berg T, Jonsson L, Engstrom M. Agreement between the
Sunnybrook, House-Brackmann, and Yanagihara facial nerve
grading systems in Bell’s palsy. Otol Neurotol. 2004;25:1020-
1026.
45. Balliet R, Shinn JB, Bach-y-Rita P. Facial paralysis rehabili-
tation: retraining selective muscle control. Int Rehabil Med.
1982;4:67-74.
46. DeSouza CM, Legedza AT, Sankoh AJ. An overview of prac-
tical approaches for handling missing data in clinical trials. J
Biopharm Stat. 2009;19:1055-1073.
47. Streiner D, Geddes J. Intention to treat analysis in clinical
trials when there are missing data. Evid Based Ment Health.
2001;4:70-71.
48. Streiner DL. Missing data and the trouble with LOCF. Evid
Based Ment Health. 2008;11:3-5.
49. Van Gelder L. Speech problems in facial palsies. In:
Beurskens CHG, van Gelder RS, Heymans PG, et al, eds. The
Facial Palsies. Utrecht, Netherlands: Lemma; 2005:335-356.
50. VanSwearingen JM, Brach JS. The Facial Disability Index:
reliability and validity of a disability assessment instrument
for disorders of the facial neuromuscular system. Phys Ther.
1996;76:1288-1298.
51. Berg T, Marsk E, Engström M, et al. The effect of study
design and analysis methods on recovery rates in Bell’s palsy.
Laryngoscope. 2009;119:2046-2050.
52. Valls-Solé J, Montero J. Movement disorders in patients with
peripheral facial palsy. Mov Disord. 2003;18:1424-1435.
53. Dalla Toffola E, Tinelli C, Lozza A, et al. Choosing the best
rehabilitation treatment for Bell’s palsy. Eur J Phys Rehabil
Med. 2012;48:1-8.