CLINICAL RESEARCH STUDY

Steroid-antiviral Treatment Improves the Recovery Rate

in Patients with Severe Bells Palsy
Ho Yun Lee, MD, Jae Yong Byun, MD, Moon Suh Park, MD, Seung Geun Yeo, MD, PhD
Department of Otorhinolaryngology, School of Medicine, Kyung Hee University, Seoul, Korea.

ABSTRACT
BACKGROUND: The extent of facial nerve damage is expected to be more severe in higher grades of facial
palsy, and the outcome after applying different treatment methods may reveal obvious differences between
severe Bells palsy and mild to moderate palsy. This study aimed to systematically evaluate the effects of
different treatment methods and related prognostic factors in severe to complete Bells palsy.
METHODS: This randomized, prospective study was performed in patients with severe to complete Bells
palsy. Patients were assigned randomly to treatment with a steroid or a combination of a steroid and an
antiviral agent. We collected data about recovery and other prognostic factors.
RESULTS: The steroid treatment group (S group) comprised 107 patients, and the combination treatment
group (SA group) comprised 99 patients. There were no significant intergroup differences in age, sex,
accompanying disease, period from onset to treatment, or results of an electrophysiology test (P .05).
There was a significant difference in complete recovery between the 2 groups. The recovery (grades I and
II) of the S group was 66.4% and that of the SA group was 82.8% (P .010). The SA group showed
a 2.6-times higher possibility of complete recovery than the S group, and patients with favorable
electromyography showed a 2.2-times higher possibility of complete recovery.
CONCLUSIONS: Combined treatment with a steroid and an antiviral agent is more effective in treating
severe to complete Bells palsy than steroid treatment alone.
2013 Elsevier Inc. All rights reserved. The American Journal of Medicine (2013) 126, 336-341
KEYWORDS: Bells Palsy; Electromyography; Electroneurography; Prognosis

Bells palsy is a common disease that occurs in 20-30

people of every 100,000 and is the most common cranial
neuropathy.1,2 The reactivation of herpes simplex virus is
known to be one of the causes of Bells palsy.3 For treatment of Bells palsy, the use of prednisolone is known to
result in high recovery rates and less synkinesis, and there is
no doubt that steroid treatment may prevent further nerve
damage and is beneficial in most cases.4
Although there is consensus that early use of prednisolone is an effective treatment, the use of antiviral agents
has led to some controversy. Researchers who are against
Funding: This research was supported by the Kyung Hee University
Research Fund in 2011(KHU-2011-1098).
Conflict of Interest: None.
Authorship: All authors had full access to the data and played a role
in writing this manuscript.
Requests for reprints should be addressed to Seung Geun Yeo, MD,
PhD, Department of Otorhinolaryngology, School of Medicine, Kyung Hee
University, #1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea.
E-mail address: yeo2park@gmail.com

0002-9343/$ -see front matter 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjmed.2012.08.020

the use of antiviral agents argue that there is no proof of

additional benefit.5,6 However, additional use of valacyclovir has been shown to be more effective than steroid treatment alone,7 and patients with severe Bells palsy show a
more favorable result with steroid-famciclovir combination
therapy.8 These findings have led some to advocate for the
use of antiviral agents.
Other researchers speculate that mixing patients with
different severities of palsy leads to inconsistent results, and
that patients with paresis have an excellent prognosis, irrespective of treatment methods.4
Following a literature review, we hypothesized that the
additional effect of antiviral agents would be different according to the severity of the palsy and that, in cases of
severe to complete palsy, there would be a difference in
recovery according to treatment methods. Increasing age;
onset of treatment; and results of electrophysiologic tests,
such as electromyography (EMG) and electroneurography
(ENoG), also may influence the prognosis. Therefore, we

Lee et al

Steroid-Antiviral Treatment in Severe Bells Palsy

337

conducted a prospective study to evaluate systematically the

effects of different treatment methods and related prognostic factors in severe Bells palsy.

METHODS

oculi, major zygomatic, orbicularis oris, levator labii superior, and depressor anguli oris. The presence or absence of
the blink reflex was analyzed simultaneously and classified
as favorable or unfavorable by the physical medicine and
rehabilitation physician.
For follow-up, all patients were
instructed to visit the hospital 6
months after hospital discharge.
CLINICAL SIGNIFICANCE
Grades I and II at 6 months from
palsy onset were defined as com Although there is consensus that early
plete recovery, and grade III or
use of prednisolone is effective, prehigher was defined as incomplete
scription of antiviral agents remains
recovery.
controversial.
The criteria for exclusion were:

Between September 2008 and August 2011, we conducted a prospective, randomized study of patients who visited our tertiary
medical center due to acute unilateral peripheral facial paralysis
without skin lesions or intraoral
lesions occurring within 7 days of
presentation. The House-Brack A combination steroid/antiviral treat Bells palsy that occurred more
mann grading system was used
ment was more effective than steroid
than 7 days before presentation;
to evaluate the severity of facial
alone in patients with severe Bells
Suspected Ramsay-Hunt synpalsy, and only patients with sepalsy.
drome, meningitis, myelitis, or
vere to complete Bells palsy
vasculopathy;
(House-Brackmann grade 5)
Clinicians should consider initiating

Patients who could not be obwere enrolled.9

combination therapy with an inert steserved for at least 6 months;
All patients were hospitalized
roid and an antiviral of choice within 1
The initial use of several differfor 1 week. Age, sex, duration
week of the onset of high-grade Bells
ent types of treatments;
from onset to treatment, previous
palsy.
Age 16 years;
history of facial palsy, and associ Pregnancy or breast-feeding;
ated symptoms (such as pain
Uncontrolled diabetes or hyperaround the ear, taste disturbance,
tension;
and hyperacusis) were documented.
Poor general medical conditions in which steroid or anPatients were randomized using simple randomization
codes generated by Microsoft Excel 2007 (Microsoft Cortiviral therapy cannot be used;
poration, Redmond, Wash) to treatment with a steroid (S
Suspicion of Borrelia infection;
group) or a steroid-antiviral combination (SA group). The
A tendency for neuropsychiatric disease; and
drug therapy protocol consisted of patients assigned to
Refusal to participate in the study.
the same group being treated on the same schedule. Both the
The Institutional Review Board of Kyung Hee Univerresearchers and the enrolled patients were blinded to treatsity Hospital approved this study, and informed consent was
ment assignment. Steroid treatment consisted of methylobtained from all patients.
prednisolone for 10 days, 64 mg/d for the first 4 days,
followed by tapering to 48 mg/d for 2 days, 32 mg/d for 2
days, and 16 mg/d for 2 days. Antiviral therapy consisted of
RESULTS
oral famciclovir (750 mg/d) for 7 days. Patients in the SA
A total of 269 patients were enrolled in this study. After
group were administered steroid and famciclovir simultaneexcluding 32 patients who did not match the inclusion
ously. An otolaryngologist who did not participate in this
criteria and 31 patients who did not complete this study due
study was responsible for patient care during hospitalization
to adverse effects of treatment and did not present for
and assessed outcomes after 6 months.
follow-up, 206 patients completed the study (Figure 1).
Bipolar needle EMG and ENoG were performed in all
The steroid treatment group (S group) comprised 107
patients. ENoG was conducted during the hospitalization
patients,
and the combination treatment group (SA group)
using bipolar cutaneous electrodes. A ground electrode was
comprised
99 patients. There was no significant difference
attached to the arm and a recording electrode was placed in
in the distribution of facial grades between the 2 groups
the nasolabial fold. The compound muscle action potential
(P .498).
(CMAP) was obtained from the nasalis muscle measured at
There were no significant intergroup differences in age,
the suprathreshold stimulation, and measurements were resex, accompanying disease, period between onset and treatported as the percent maximal amplitude on the side of the
ment, or results of electrophysiology tests (P .05). There
lesion/maximal amplitude on the healthy side. Poor ENoG
was no significant difference between the treatment methwas defined as a loss of amplitude 90%.
ods with regard to the final grade and its trend. However,
The EMG was conducted after about 2 weeks from the
there was a significant difference in complete recovery
onset of the facial palsy. The following 6 muscles of exbetween the 2 groups. The recovery (grades I and II) of the
pression were examined separately: the frontalis, orbicularis

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The American Journal of Medicine, Vol 126, No 4, April 2013

Figure 1

Overview of patient enrollment.

SA group was 82.8% and that of the S group was 66.4%

(P .010) (Table 1).
Univariate analysis was performed using previously
known prognostic factors in addition to the treatment methods (Table 2). The prognostic factors predicting incomplete
recovery were steroid treatment and unfavorable EMG results, and the odds ratios for incomplete recovery were 2.0
and 1.6, respectively.
Multivariate analysis was performed on the identified
prognostic factors (Table 3). The probability of complete
recovery was 2.6 times higher in the SA group than in the
S group, and the odds ratio for complete recovery in patients
with favorable EMG results was 2.2.

DISCUSSION
Additional antiviral treatment in Bells palsy is based on the
hypothesis that herpes simplex virus infection may cause
inflammation of the facial nerve. Theoretically, the infectious agents are eradicated by antiviral treatment, and swelling of the facial nerve is reduced by corticosteroids.6 However, antiviral agents cannot actually destroy virus that has
already replicated, because these drugs prevent viral replication by interfering with viral DNA polymerase. In this

respect, Hato et al reported the importance of early administration of the valacyclovir and prednisolone.7,10
The 3 commonly used antivirals are acyclovir, famciclovir, and valacyclovir. Although acyclovir is one of the most
commonly used antiviral agents, it has some limitations.
Patients must take acyclovir 5 times daily because it has a
very low oral bioavailability (10%-20%), and correct administration is difficult to monitor because the drug is easily
compromised if taken with food.11,12 Famciclovir, a prodrug
of penciclovir, is known to have excellent oral bioavailability (60%-75%) and longer intracellular half-life than acyclovir and is not affected by concurrent food intake.8 Valacyclovir, a prodrug of acyclovir, is known to have greater
bioavailability compared with acyclovir and yields similar
plasma concentrations with only twice-daily dosing.13,14
In this study, we demonstrated that in severe to complete
palsy, that is equal to or higher than grade 5, famciclovir
treatment plus steroid treatment significantly increased the
chance of recovery. However, one important limitation of
this study was the potential risk of imbalance by simple
randomization, the fact that no significant differences were
shown in age, sex, and other influencing factors between 2
groups may imply that potential risks of bias were minimally increased by using simple randomization.

Lee et al
Table 1

Steroid-Antiviral Treatment in Severe Bells Palsy

Patient Characteristics
Combination
Steroid Only Therapy
P Value

Variable
Total n (%)
Age
Mean SD
Range
Sex, n (%)
Male
Female
EMG, n (%)
Favorable
Unfavorable
ENoG, n (%)
Poor
Good
Onset of treatment, n (%)
Within 3 days
3-7 days
Final facial grade, n (%)
Mean SD
I
II
III
IV
V
VI
Recovery rate (%)

107 (51.9)

99 (48.1)

48.6 15.1 46.7 16.2 .381

16-77
16-76
51 (47.7)
56 (52.3)

50 (50.5)
49 (49.5)

.780

85 (79.4)
22 (20.6)

75 (75.8)
24 (24.2)

.616

5 (4.7)
102 (95.3)

9 (9.1)
90 (90.9)

.271

84 (79.2)
22 (20.8)

67 (67.7)
32 (32.3)

.081

1.9 0.8
31 (31.3)
51 (51.5)
12 (12.1)
5 (5.1)
0 (0.0)
0 (0.0)
82.8

.216
.221

2.1 1.1
42 (39.3)
29 (27.1)
26 (24.3)
7 (6.5)
2 (1.9)
1 (0.9)
66.4

.010

EMG electromyography; ENoG electroneurography.

Different researchers have reported different conclusions

about whether combination treatment is effective in Bells
palsy, and it is often difficult to come to a firm conclusion
(Table 4, Figure 2).
One recent study reported that physicians discussed the
merits, drawbacks, and the cost of additional antiviral treatment with patients, and after this information was provided,
patients chose the combination therapy.18
Oral antivirals are known to be well tolerated if administered at standard doses, providing that patients are kept
well hydrated. Side effects of antiviral agents occur in 10%
to 20% of all cases, and the most common symptoms are
nausea, vomiting, and headache. The combination therapy

Table 2

Univariate Analysis for Incomplete Recovery

Condition
Steroid only treatment
Unfavorable EMG
Poor ENoG
Onset of treatment within
3 days
Age 60 years

Odds Ratios (95%

Confidence Interval)

P Value

2.0
1.6
0.9
0.9

(1.2-3.3)
(1.0-2.6)
(0.4-2.1)
(0.5-1.6)

.010
.048
.801
.728

1.4 (0.8-2.4)

.262

EMG electromyography; ENoG electroneurography.

339
Table 3 Results of Multiple Logistic Regression Analysis for
Complete Recovery
Variable

Odds Ratios (95%

Confidence Interval)

P Value

Favorable EMG
Steroid-antiviral treatment

2.2 (1.1-4.5)
2.6 (1.3-5.1)

.034
.006

EMG electromyography.

for Ramsay-Hunt syndrome is justified and essential given

the possibility of a lifelong paralysis.19,20
This applies equally to Bells palsy as one of the other
acute peripheral facial palsies. The relatively low chance of
life-threatening major side effects makes combination treatment appropriate for severe Bells palsy, in which nerve
damage is expected to be severe.
However, we do not endorse indiscriminate use of antiviral agents. One previous study speculated that the initial
grade is not a significant predictor of prognosis,21 whereas
others reported that a higher initial House-Brackmann grade
reduces the probability of satisfactory recovery.22 Our findings were consistent with those previously reported, and
indicated that combination therapy was effective in patients
with severe to complete facial palsy. Further validation,
however, is required in patients with mild to moderate
Bells palsy. Larger prospective clinical trials are required
to validate our results, because it may have a ripple effect in
clinical practice.
The detection of spontaneous fibrillation on needle EMG
is known as a sign predicting unfavorable outcome.23,24 An
unfavorable EMG result was reported as one of the poor
prognostic factors in recurrent facial palsy.25 Taken together, EMG is a reliable diagnostic tool that physicians can
use to predict prognosis.
In addition, we found that age and onset of treatment did
not significantly influence recovery. There is controversy
about the effect of age on prognosis. Previously, age was
reported as a parameter that significantly influenced the final
recovery.1 Others have assumed that increasing age reduces
the probability of a satisfactory recovery because of peripheral vascular degeneration.26 In contrast, another study reported that age above 50 years did not significantly influence the long-term prognosis of Bells palsy.22 Consistent
with that study, a trend test showed no significant differences between age and recovery.27 We assumed that these
different studies had different results because gerontological
problems might act as a confounding factor, and sophisticated history-taking and statistical analysis is required in
order to compensate.
In this study, we found that the onset of treatment also
was a nonsignificant factor in the prognosis of Bells palsy.
Based on treatment within 3 days, early treatment did not
affect recovery significantly (Table 2). Although Hato et al
provided the theoretical background for the use of early
combination treatment, they did not clearly show a difference in effect according to the onset of treatment and

340
Table 4

The American Journal of Medicine, Vol 126, No 4, April 2013

Summary of the Findings of Recent Studies in Which Antiviral Agents Were Used to Treat Bells Palsy

Authors

Steroid
(Initial Dose)

Antiviral
(Initial Dose)

Axelsson et al, 201215

Prednisolone (60 mg/d)

Valacyclovir (1000 mg/d)

Minnerop et al, 20088

Prednisolone (1 mg/kg/d)

Famciclovir (750 mg/d)

Engstrm et al, 200817

Prednisolone (60 mg/d)

Valacyclovir (1000 mg/d)

Yeo et al, 200816

Prednisolone (1 mg/kg per

day, maximally 80 mg/d)
Prednisolone (60 mg/d)

Acyclovir (2400 mg/d)

Hato et al, 20077

Figure 2

Summary of Results

Valacyclovir (1000 mg/d)

Prednisolone enhanced the complete

recovery rate. Valacyclovir had no
additional significant effect.
Combination treatment should be
considered for patients with
severe Bells palsy.
Prednisolone hastened complete
recovery. Valacyclovir was
ineffective, and combined steroid/
antiviral therapy was no better
than the steroid alone.
No benefit of acyclovir was
definitely established.
Early combined use of valacyclovir
and prednisone was effective,
especially in those with severe to
complete palsy.

Follow-up
Period
12 months

3 months

12 months

6 months
6 months

A Forest plot of data from recent studies.

only highlighted the merits of combination treatment.7 In

fact, in their earlier study, they reported that all patients
who were treated with acyclovir and prednisolone within
3 days of onset recovered completely; however, that
study had limited significance because it was a retrospective study.28 Consistent with our study, others have assumed that the onset of treatment is not a significant
prognostic factor.18
With 7 days classified as a delayed start of treatment,
another report demonstrated that there was no statistically
significant difference in recovery.22 Therefore, physicians
should take into consideration that delayed treatment does
not always lead to poor recovery, and combination treatment increases the possibility of recovery in severe to complete Bells palsy irrespective of onset, at least within 7
days.
Clinicians should consider combination therapy with
inert steroid and antiviral of choice in individuals with
high-grade Bells palsy within 1 week of onset. In con-

clusion, steroid plus antiviral treatment is more effective

in treating severe to complete Bells palsy than steroid
treatment alone.

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