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CLINICAL RESEARCH STUDY

Steroid-antiviral Treatment Improves the Recovery Rate

in Patients with Severe Bell’s PalsyHo 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 Bell’s 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 Bell’s palsy.

METHODS: This randomized, prospective study was performed in patients with severe to complete Bell’spalsy. 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 Bell’s palsy than steroid treatment alone.

© 2013 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2013) 126, 336-341

KEYWORDS: Bell’s Palsy; Electromyography; Electroneurography; Prognosis

Bell’s 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 Bell’s palsy.3 For treat-

ment of Bell’s 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 pred-

nisolone is an effective treatment, the use of antiviral agents

has led to some controversy. Researchers who are against

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

additional benefit.5,6 However, additional use of valacyclo-

vir has been shown to be more effective than steroid treat-

ment alone,7 and patients with severe Bell’s 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, andthat patients with paresis have an excellent prognosis, irre-

spective of treatment methods.4

Following a literature review, we hypothesized that the

additional effect of antiviral agents would be different ac-

cording 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

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: [email protected]

0002-9343/$ -see front matter © 2013 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1016/j.amjmed.2012.08.020

mailto:[email protected]



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conducted a prospective study to evaluate systematically the

effects of different treatment methods and related prognos-

tic factors in severe Bell’s palsy.

METHODSBetween September 2008 and Au-

gust 2011, we conducted a pro-spective, randomized study of pa-

tients who visited our tertiary

medical center due to acute uni-

lateral peripheral facial paralysis

without skin lesions or intraoral

lesions occurring within 7 days of

presentation. The House-Brack-

mann grading system was used

to evaluate the severity of facial

palsy, and only patients with se-

vere to complete Bell’s palsy

(House-Brackmann grade

5)were enrolled.9

All patients were hospitalized

for 1 week. Age, sex, duration

from onset to treatment, previous

history of facial palsy, and associ-

ated symptoms (such as pain

around the ear, taste disturbance,

and hyperacusis) were documented.

Patients were randomized using simple randomization

codes generated by Microsoft Excel 2007 (Microsoft Cor-

poration, Redmond, Wash) to treatment with a steroid (S

group) or a steroid-antiviral combination (SA group). Thedrug therapy protocol consisted of patients assigned to

the same group being treated on the same schedule. Both the

researchers and the enrolled patients were blinded to treat-

ment assignment. Steroid treatment consisted of methyl-

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

oral famciclovir (750 mg/d) for 7 days. Patients in the SA

group were administered steroid and famciclovir simultane-

ously. An otolaryngologist who did not participate in this

study was responsible for patient care during hospitalization

and assessed outcomes after 6 months.Bipolar needle EMG and ENoG were performed in all

patients. ENoG was conducted during the hospitalization

using bipolar cutaneous electrodes. A ground electrode was

attached to the arm and a recording electrode was placed in

the nasolabial fold. The compound muscle action potential

(CMAP) was obtained from the nasalis muscle measured at

the suprathreshold stimulation, and measurements were re-

ported as the percent maximal amplitude on the side of the

lesion/maximal amplitude on the healthy side. Poor ENoG

was defined as a loss of amplitude 90%.

The EMG was conducted after about 2 weeks from the

onset of the facial palsy. The following 6 muscles of ex-pression were examined separately: the frontalis, orbicularis

oculi, major zygomatic, orbicularis oris, levator labii supe-

rior, 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.Grades I and II at 6 months from

palsy onset were defined as com-

plete recovery, and grade III or

higher was defined as incomplete

recovery.

The criteria for exclusion were:

● Bell’s palsy that occurred more

than 7 days before presentation;

● Suspected Ramsay-Hunt syn-

drome, meningitis, myelitis, or

vasculopathy;● Patients who could not be ob-

served for at least 6 months;

● The initial use of several differ-

ent types of treatments;

● Age 16 years;

● Pregnancy or breast-feeding;

● Uncontrolled diabetes or hyper-

tension;

● Poor general medical conditions in which steroid or an-

tiviral therapy cannot be used;

● Suspicion of Borrelia infection;

● A tendency for neuropsychiatric disease; and● Refusal to participate in the study.

The Institutional Review Board of Kyung Hee Univer-

sity Hospital approved this study, and informed consent was

obtained from all patients.

RESULTSA total of 269 patients were enrolled in this study. After

excluding 32 patients who did not match the inclusion

criteria and 31 patients who did not complete this study due

to adverse effects of treatment and did not present forfollow-up, 206 patients completed the study (Figure 1).

The steroid treatment group (S group) comprised 107

patients, and the combination treatment group (SA group)

comprised 99 patients. There was no significant difference

in the distribution of facial grades between the 2 groups

(P .498).

There were no significant intergroup differences in age,

sex, accompanying disease, period between onset and treat-

ment, or results of electrophysiology tests (P .05). There

was no significant difference between the treatment meth-

ods with regard to the final grade and its trend. However,

there was a significant difference in complete recoverybetween the 2 groups. The recovery (grades I and II) of the

CLINICAL SIGNIFICANCE

● Although there is consensus that earlyuse of prednisolone is effective, pre-scription of antiviral agents remainscontroversial.

● A combination steroid/antiviral treat-ment was more effective than steroidalone in patients with severe Bell’spalsy.

● Clinicians should consider initiatingcombination therapy with an inert ste-roid and an antiviral of choice within 1week of the onset of high-grade Bell’spalsy.

337Lee et al Steroid-Antiviral Treatment in Severe Bell’s Palsy

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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 meth-

ods (Table 2). The prognostic factors predicting incomplete

recovery were steroid treatment and unfavorable EMG re-

sults, 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.

DISCUSSIONAdditional antiviral treatment in Bell’s palsy is based on the

hypothesis that herpes simplex virus infection may cause

inflammation of the facial nerve. Theoretically, the infec-

tious agents are eradicated by antiviral treatment, and swell-

ing of the facial nerve is reduced by corticosteroids.6 How-

ever, antiviral agents cannot actually destroy virus that has

already replicated, because these drugs prevent viral repli-cation by interfering with viral DNA polymerase. In this

respect, Hato et al reported the importance of early admin-

istration of the valacyclovir and prednisolone.7,10

The 3 commonly used antivirals are acyclovir, famciclo-

vir, 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 ad-

ministration 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 bioavailabil-

ity (60%-75%) and longer intracellular half-life than acy-clovir and is not affected by concurrent food intake.8 Vala-

cyclovir, 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 mini-mally increased by using simple randomization.

Figure 1 Overview of patient enrollment.

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Different researchers have reported different conclusionsabout whether combination treatment is effective in Bell’s

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 treat-

ment with patients, and after this information was provided,

patients chose the combination therapy.18

Oral antivirals are known to be well tolerated if admin-

istered 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

for Ramsay-Hunt syndrome is justified and essential given

the possibility of a lifelong paralysis.19,20

This applies equally to Bell’s palsy as one of the other

acute peripheral facial palsies. The relatively low chance of

life-threatening major side effects makes combination treat-

ment appropriate for severe Bell’s palsy, in which nerve

damage is expected to be severe.

However, we do not endorse indiscriminate use of anti-

viral agents. One previous study speculated that the initial

grade is not a significant predictor of prognosis,21 whereasothers reported that a higher initial House-Brackmann grade

reduces the probability of satisfactory recovery.22 Our find-

ings 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

Bell’s 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 poorprognostic factors in recurrent facial palsy.25 Taken to-

gether, 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 periph-

eral vascular degeneration.26 In contrast, another study re-

ported that age above 50 years did not significantly influ-

ence the long-term prognosis of Bell’s palsy.22 Consistentwith that study, a trend test showed no significant differ-

ences between age and recovery.27 We assumed that these

different studies had different results because gerontological

problems might act as a confounding factor, and sophisti-

cated 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 Bell’s 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 differ-ence in effect according to the onset of treatment and

Table 1 Patient Characteristics

Variable Steroid Only

Combination

Therapy P Value

Total n (%) 107 (51.9) 99 (48.1)

Age

Mean SD 48.6 15.1 46.7 16.2 .381

Range 16-77 16-76Sex, n (%)

Male 51 (47.7) 50 (50.5) .780

Female 56 (52.3) 49 (49.5)

EMG, n (%)

Favorable 85 (79.4) 75 (75.8) .616

Unfavorable 22 (20.6) 24 (24.2)

ENoG, n (%)

Poor 5 (4.7) 9 (9.1) .271

Good 102 (95.3) 90 (90.9)

Onset of treatment, n (%)

Within 3 days 84 (79.2) 67 (67.7) .081

3-7 days 22 (20.8) 32 (32.3)

Final facial grade, n (%)Mean SD 2.1 1.1 1.9 0.8 .216

I 42 (39.3) 31 (31.3) .221

II 29 (27.1) 51 (51.5)

III 26 (24.3) 12 (12.1)

IV 7 (6.5) 5 (5.1)

V 2 (1.9) 0 (0.0)

VI 1 (0.9) 0 (0.0)

Recovery rate (%) 66.4 82.8 .010

EMG electromyography; ENoG electroneurography.

Table 2 Univariate Analysis for Incomplete Recovery

Condition

Odds Ratios (95%

Confidence Interval) P Value

Steroid only treatment 2.0 (1.2-3.3) .010

Unfavorable EMG 1.6 (1.0-2.6) .048

Poor ENoG 0.9 (0.4-2.1) .801

Onset of treatment within

3 days

0.9 (0.5-1.6) .728

Age 60 years 1.4 (0.8-2.4) .262

EMG electromyography; ENoG electroneurography.

Table 3 Results of Multiple Logistic Regression Analysis for

Complete Recovery

Variable

Odds Ratios (95%

Confidence Interval) P Value

Favorable EMG 2.2 (1.1-4.5) .034

Steroid-antiviral treatment 2.6 (1.3-5.1) .006

EMG electromyography.

339Lee et al Steroid-Antiviral Treatment in Severe Bell’s Palsy

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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 retrospec-

tive study.28 Consistent with our study, others have as-sumed 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 treat-

ment increases the possibility of recovery in severe to com-

plete Bell’s palsy irrespective of onset, at least within 7

days.

Clinicians should consider combination therapy with

inert steroid and antiviral of choice in individuals withhigh-grade Bell’s palsy within 1 week of onset. In con-

clusion, steroid plus antiviral treatment is more effective

in treating severe to complete Bell’s palsy than steroid

treatment alone.

References1. 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.

2. Yanagihara N. Incidence of Bell’s palsy. Ann Otol Rhinol Laryngol

Suppl. 1988;137:3-4.

3. Murakami S, Mizobuchi M, Nakashiro Y, et al. Bell palsy and herpes

simplex virus: identification of viral DNA in endoneural fluid and

muscle. Ann Intern Med . 1996;124:27-30.

4. Linder TE, Abdelkafy W, Cavero-Vanek S. The management of

peripheral facial nerve palsy: “paresis” versus “paralysis” and

sources of ambiguity in study designs. Otol Neurotol. 2010;31:319-

327.

5. Sullivan FM, Swan IR, Donnan PT, et al. Early treatment with pred-

nisolone or acyclovir in Bell’s palsy. N Engl J Med . 2007;357:1598-

1607.

Figure 2 A Forest plot of data from recent studies.

Table 4 Summary of the Findings of Recent Studies in Which Antiviral Agents Were Used to Treat Bell’s Palsy

Authors

Steroid

(Initial Dose)

Antiviral

(Initial Dose) Summary of Results

Follow-up

Period

Axelsson et al, 201215 Prednisolone (60 mg/d) Valacyclovir (1000 mg/d) Prednisolone enhanced the complete

recovery rate. Valacyclovir had no

additional significant effect.

12 months

Minnerop et al, 20088

Prednisolone (1 mg/kg/d) Famciclovir (750 mg/d) Combination treatment should beconsidered for patients with

severe Bell’s palsy.

3 months

Engström et al, 200817 Prednisolone (60 mg/d) Valacyclovir (1000 mg/d) Prednisolone hastened complete

recovery. Valacyclovir was

ineffective, and combined steroid/

antiviral therapy was no better

than the steroid alone.

12 months

Yeo et al, 200816 Prednisolone (1 mg/kg per

day, maximally 80 mg/d)

Acyclovir (2400 mg/d) No benefit of acyclovir was

definitely established.

6 months

Hato et al, 20077 Prednisolone (60 mg/d) Valacyclovir (1000 mg/d) Early combined use of valacyclovir

and prednisone was effective,

especially in those with severe to

complete palsy.

6 months

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