Otology & Neurotology 32:141Y146 2010, Otology & Neurotology, Inc.

Prednisolone in Bell_s Palsy Related to Treatment Start and Age

*Sara Axelsson, Thomas Berg, Lars Jonsson, Mats Engstrom, Mervi Kanerva, Anne Pitkaranta, and *Anna Stjernquist-Desatnik
*Department of OtorhinolaryngologyYHead and Neck Surgery, Lund University Hospital, Lund; Departments of Plastic and Reconstructive Surgery, and OtorhinolaryngologyYHead and Neck Surgery, Uppsala University Hospital, Uppsala, Sweden; and Department of OtorhinolaryngologyYHead and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland

Objective: To evaluate if treatment start and age are related to the outcome in Bell_s palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebocontrolled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients: Data were collected from the Scandinavian Bell_s palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered.

Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone ( p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone. Key Words: Facial palsyVOutcomeVRecoveryVSunnybrook. Otol Neurotol 32:141Y146, 2011.

Acute idiopathic peripheral facial palsy, BBell_s palsy,[ is a diagnosis of exclusion. The ethiopathologic event in the disease remains unclear, but the most prevailing theory is reactivation of latent herpes viruses (1,2). Complete recovery in Bell_s palsy has been reported to be 57% to 70% without medical treatment (3,4). Conse-

Address correspondence and reprint requests to Sara Axelsson, M.D., Department of OtorhinolaryngologyYHead and Neck Surgery, Hospital of Helsingborg, SE-25187 Helsingborg, Sweden; E-mail: sara.axelsson@skane.se Funding: This study received grants from the County Council of Skne, the Acta Otolaryngologica Foundation, the Stig and Ragna Gorthon Foundation, the Torsten Birger Segerfalk Foundation, the Thelma Zoega_s Foundation, the Agnes Ljunggren_s Foundation, Margit Arstrup_s Foundation, Uppsala University, GlaxoSmithKline Sweden, Pfizer AB Sweden, Rosa and Emanuel Nachmansson_s Foundation, and the Helsinki University Central Hospital Research Funds.

quently, at least 30% of patients experience persistent weakness and/or sequelae (4). In most studies, recovery from Bell_s palsy has been reported to be related to age, with a poorer outcome in elderly patients (4Y8). In an uncontrolled study by Axelsson et al. (9), the combination of corticosteroids plus valacyclovir medication was more beneficial in older patients compared with young and middle-aged subjects. Two recent large, controlled trials demonstrated that treatment with prednisolone within 72 hours shortens time to complete recovery (3) and improves final outcome in Bell_s palsy (3,10). Antiviral treatment with acyclovir (10) or valacyclovir (3) was not proven to be effective and did not add effect to prednisolone. It can be assumed that early prednisolone administration may prevent progress of the nerve injury and thereby improve outcome of Bell_s palsy. To date, there are no large controlled reports on corticosteroid medication in relation to treatment start during the initial 72-hour 141

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S. AXELSSON ET AL.
system does not separately measure synkinesis and was therefore not used in the present study.

period. The effect of this medication in different age groups needs additional clarification. The present study explored the effect of prednisolone in relation to time of treatment start within the first 72 hours of Bell_s palsy and the effect of the drug in relation to the patient_s age. METHODS Patients
Data were extracted from the Scandinavian Bell_s palsy study, a randomized, double-blind, placebo-controlled, multicenter trial (3), with a prespecified analysis plan. Patients with acute, unilateral, peripheral facial palsy were screened by physicians at 16 public otorhinolaryngology centers in Sweden and 1 in Finland. The study period was from May 2001 to September 2007 (final follow-up). Patients aged 18 to 75 years with onset of palsy within 72 hours were screened for inclusion. The most common reasons for exclusion were more than 72 hours having elapsed since the onset of palsy, patients aged younger than 18 years or older than 75 years, unwillingness to participate, diabetes mellitus, previous facial palsy, signs of infection with Borrelia or herpes zoster, pregnancy or breastfeeding, other neurologic diseases, uncontrolled hypertension, and psychiatric disease (3). The study was approved by regional ethics review boards and performed in accordance with the Declaration of Helsinki and good clinical practice guidelines. Written informed consent was obtained from all patients. The study is registered in ClinicalTrials.gov (identifier: NCT00510263).

Statistical Analysis
Analyses were based on the ITT principle. All randomized patients receiving at least 1 dose of study drug were included in the analysis. Ten patients did not take any study medication and were excluded; the analysis should therefore be regarded as a modified ITT analysis. Data analyses were performed according to a prespecified analysis plan. For analysis of complete recovery, the lastobservation-carried-forward method was applied; missing data for facial grading were imputed for the postbaseline follow-up visits from the last observation available for each patient (n = 829). Synkinesis was assessed on the basis of the Sunnybrook score in those patients who attended the 12-month follow-up visit (n = 743), that is, complete-case analysis. In our previous study (3), valacyclovir was not shown to be effective as a single drug or add effect to prednisolone. Similarly, we found no interaction, positive or detrimental, between prednisolone and valacyclovir regarding complete recovery or synkinesis, in relation to age (p = 0.51 and p = 0.09, respectively) or start of treatment (p = 0.65 and p = 0.11, respectively). Results for continuous variables are given as median values with interquartile range (IQR; 25thY75th percentiles), and dichotomous data are given as proportions with 95% confidence interval using the normal approximation approach. The Kaplan-Meier method was used to create survival curves. Categorical variables were compared using Fisher_s exact test. Univariate Cox proportional hazards models were used to estimate the hazard ratio of recovery, including 95% confidence interval. All computations were performed using SAS, version 9.1 (SAS Institute, Cary, NC, USA), and R, version 2.7.0 (R Foundation for Statistical Computing, Vienna, Austria).

Trial Design
Patients were randomly assigned to 1 of 4 treatment groups within 72 hours of onset of palsy: placebo plus placebo, prednisolone plus placebo, valacyclovir plus placebo, or prednisolone plus valacyclovir. Prednisolone (or its placebo) 60 mg was given daily for 5 days, then reduced by 10 mg per day over the next 5 days, with a total treatment time of 10 days. Valacyclovir (or its placebo) was administered as two 500-mg tablets three times daily for 7 days. Time (in hours) from onset of palsy to treatment start was registered at the first visit within 72 hours. Follow-up visits were planned for Days 11 to 17, and at 1, 2, 3, 6, and 12 months. Patients with complete recovery (Sunnybrook score of 100) at 2 or 3 months had their next follow-up at 12 months. Of 839 randomized patients, 829 patients (341 women and 488 men) were included in the slightly modified, intention-totreat (ITT) analysis (see Statistical Analysis); 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valacyclovir plus placebo, and 206 prednisolone plus valacyclovir. Age, sex, and median Sunnybrook score at baseline were similar in the 4 treatment arms (3). The study design was factorial, with 4 analysis groups; 416 patients were treated with prednisolone, and 413 did not receive prednisolone. Valacyclovir was given to 413 patients, and 416 did not receive this drug. Of the 829 patients, 743 (90%) had a 12-month follow-up visit with assessment of facial function and synkinesis. The regionally weighted Sunnybrook scale was used as the main grading system of facial function (3). This sensitive and reliable system (11,12) includes evaluation of resting symmetry, degree of voluntary movements, and synkinesis to form a composite score from 0 to 100, where 0 is complete paralysis, and 100 is normal function (13). Complete recovery was defined as a Sunnybrook score of 100. Facial function also was assessed with the House-Brackmann grading system (14), but this scaling
Otology & Neurotology, Vol. 32, No. 1, 2011

RESULTS Data for one of the 829 patients in the no-prednisolone group was missing. The Effect of Prednisolone in Relation to Treatment Start In 308 (37%) of the 829 patients, treatment was started within 24 hours of onset of palsy. In the time interval 25 to 48 hours, 345 patients (42%) initiated therapy, and 175 patients (21%) started medication between 49 and 72 hours after palsy onset. The median Sunnybrook score at baseline for patients treated within 24 hours was 42 (IQR, 29Y58), compared with 37 (IQR, 22Y55) in patients treated between 25 and 48 hours, and 32 (IQR 19Y50) in patients receiving the treatment between 49 and 72 hours after onset. The patients_ age did not differ between the 3 time interval groups (Fig. 1). In subjects treated within 24 hours, complete recovery at 12 months was achieved in 103 (66%) of 156 patients receiving prednisolone, compared with 77 (51%) of 152 patients not treated with prednisolone (p = 0.008). The corresponding recovery rates for prednisolone treatment in the interval 25 to 48 hours were 128 (76%) of 168 in prednisolone-treated patients, compared with 102 (58%) of 177 patients not treated with prednisolone ( p = 0.0003), whereas in the interval 49 to 72 hours, 69

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PREDNISOLONE IN BELL_S PALSY

15% (8%Y21%) G0.0001 15% (9%Y21%) G0.0001

143

n = 829

0Y72 h

n, % (95% CI)

Difference (95% CI)

Recovery and synkinesis in relation to treatment start in Bell_s palsy patients (n = 829)

j19% (j28% to j9%) 0.0003 69/92, 75% j5% (j19% to 8%) 0.50 300/416, 72% (66%Y84%) (68%Y76%) 58/83, 70% 237/413, 57% (60%Y80%) (53%Y62%)

3% (j8 to 15%)

Difference (95% CI)

0.66 51/370, 14% (10%Y17%) 107/373, 29% (24%Y33%)

103/156, 66% j15% (j26% to j4%) 0.008 128/168, 76% (58%Y73%) (70%Y83%) 77/152, 51% 102/177, 58% (43%Y59%) (50%Y65%)

TABLE 1.

The Effect of Prednisolone in Relation to Age Of all 829 randomized patients, 392 were aged 18 to 39 years; their median Sunnybrook score at baseline was 42 (IQR, 27Y58). The 317 patients aged 40 to 60 years had a median Sunnybrook score of 37 (IQR, 22Y53), and the 119 patients aged 61 to 75 years had a median Sunnybrook score of 33 (IQR, 17Y46). In the 18- to 39-year-old patient group, 137 (72%) of the 191 patients treated with prednisolone had complete recovery at 12 months, compared with 129 (64%) of 201 not receiving prednisolone ( p = 0.13). In subjects 40 to 60 years old, the corresponding values were 122 (77%) of 159 prednisolone-treated patients and 86 (54%) of 158 patients not treated with prednisolone ( p G 0.0001),

n, % (95% CI)

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Complete recovery Prednisolone (n = 416) versus No prednisolone (n = 413)a Synkinesis Prednisolone (n = 370) versus No prednisolone (n = 373)

24/139, 17% (11%Y24%) 44/141, 31% (23%Y39%)

14% (4%Y24%)

n = 308

0Y24 h

Difference (95% CI)

(75%) of 92 prednisolone-treated patients compared with 58 (70%) of 83 patients not treated with prednisolone achieved complete recovery (p = 0.5) (Table 1). Time to complete recovery was significantly shorter for patients who received prednisolone within 24 hours as well as for those treated within 48 hours compared with no prednisolone (p = 0.004 and p = 0.002) (hazard ratio, 1.51 and 1.49) (Fig. 2). Altogether, 743 patients with a 12-month follow-up were assessed for synkinesis. Table 1 shows that synkinesis at 12 months was significantly less common in patients treated with prednisolone within 24 hours than in those who did not receive prednisolone (17% versus 31%, p = 0.008). Likewise, it was significantly less common in patients treated with prednisolone between 25 and 48 hours compared with those who did not receive prednisolone (10% versus 32%, p G 0.0001). Prednisolone treatment started 49 to 72 hours after palsy onset was not shown to affect the occurrence of synkinesis, compared with no prednisolone (14% versus 18%, p = 0.66) (Table 1).

Treatment start

n, % (95% CI)

0.008 16/154, 10% (6%Y15%) 49/153, 32% (25%Y40%)

22% (13%Y31%)

25Y48 h

n = 345

Difference (95% CI)

G0.0001 11/77, 14% (6%Y22%) 14/79, 18% (9%Y26%)

FIG. 1. Median Sunnybrook score at baseline and median age in the patient groups with treatment start at 0 to 24, 25 to 48, and 49 to 72 hours after onset of palsy.

Last-observation-carried-forward method used for missing data points; synkinesis at 12 months in patients with a 12-month follow-up (n = 743). Data are given as number of patients, % (95% CI) and % difference (95% CI). Complete recovery defined as Sunnybrook score of 100. a Data missing for 1 patient. CI indicates confidence interval.

49Y72 h

n = 175

n, % (95% CI)

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S. AXELSSON ET AL. whereas in patients aged 61 to 75 years, the values were 41 (62%) of 66 and 21 (40%) of 53, respectively ( p = 0.02) (Table 2). In patients aged 18 to 39 years, synkinesis at 12 months was present in 18 (11%) of the 160 patients in the prednisolone group, compared with 44 (25%) of 178 in the same age group not treated with prednisolone (p = 0.002). In the group aged 40 to 60 years, synkinesis occurred in 20 (13%) of 150 patients treated with prednisolone and in 44 (31%) of 144 patients not receiving prednisolone ( p = 0.0004). Finally, the corresponding values for patients 61 to 75 years old were 22% (13/60) for prednisolone and 37% (19/51) for no prednisolone (p = 0.09) (Table 2). DISCUSSION We assessed the effect of prednisolone in Bell_s palsy in relation to treatment start and age. Prednisolone administered within 48 hours of onset resulted in significantly higher recovery rates and less synkinesis compared with no treatment. In the patients aged 40 years or older, treatment with prednisolone gave significantly higher recovery rates compared with no treatment with this medication. In a controlled study by Sullivan et al. (10), it was shown that prednisolone given within 72 hours significantly improves the outcome of Bell_s palsy at 3 and 9 months, when compared with no prednisolone. In our previous study (3), prednisolone administered within 72 hours shortened time to complete recovery and improved final outcome at 12 months. To our knowledge, the present controlled trial is the largest, thus far, to study the effect of prednisolone given in the very early stages of Bell_s palsy. We found that the outcome of palsy significantly improved in patients given prednisolone within 48 hours but not in those with treatment start after 48 hours. Consequently, our results indicated that prednisolone should be given in the early stage of palsy. This is in accordance with findings in a controlled study by Yeo et al. (15), where treatment with prednisolone within 3 days was associated with higher recovery rates than later treatment. Furthermore, Shafshak et al. (16) also reported better outcome with early treatment within 24 hours, but their study was not double-blinded and only included 160 patients, all with complete or nearcomplete paralysis. The results of uncontrolled studies diverge concerning the relation between time for treatment start with corticosteroids and outcome of palsy. In a retrospective study by Sittel et al. (17), patients treated with intravenous highdose prednisolone, dextran, and pentoxifylline within 3 days had a better outcome compared with those with treatment start between 4 and 12 days. Sathirapanya and Sathirapanya (18) reported that steroid treatment within 7 days of palsy onset gave a significantly better outcome than therapy initiated after this period. In another uncontrolled study, Adour et al. (19) found no significant difference in facial outcome scores between patients starting treatment within 3 days and those starting treatment 4 to 7 days after onset of paralysis.

FIG. 2. Kaplan-Meier estimates of patients with complete recovery, defined as a Sunnybrook score of 100, in relation to treatment start at 0 to 24, 25 to 48, and 49 to 72 hours after onset of palsy. Estimates are based on the actual number of days from onset of palsy to the first follow-up visit when the patient had completely recovered. Follow-up visits not occurring on the exact day or at the exact time interval scheduled in the protocol are the cause of the zigzag shape of the lines. Otology & Neurotology, Vol. 32, No. 1, 2011

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PREDNISOLONE IN BELL_S PALSY

0.09 51/370, 14% j15% G0.0001 (10%Y17%) (j21% to j9%) 107/373, 29% (24%Y33%) G0.0001

145

The nerve damage in Bell_s palsy is consistent with edema and inflammation of the nerve within the Fallopian canal (20Y22). Early administration of anti-inflammatory corticosteroids may reduce edema and subsequent spreading of a conduction block or axonothmesis (23). The effect of early prednisolone treatment in Bell_s palsy accords with the reported effect of corticosteroids in vestibular neuritis (24), a disease which may have the same pathogenesis as Bell_s palsy (24,25). Patients not treated with prednisolone and included 49 to 72 hours after onset had a higher recovery rate (70%) and less synkinesis (18%) compared with those included within 24 hours (recovery, 51%; synkinesis, 31%) and 25 to 48 hours (recovery, 58%; synkinesis, 32%) of palsy onset. The median Sunnybrook score at baseline was 32 in the 49- to 72-hour group compared with the milder palsy scores of Sunnybrook 42 and 37 in the 0- to 24-hour and 25- to 48-hour groups. The better outcome in the patients not treated with prednisolone and included in the late group (49Y72 h) therefore cannot be explained by differences in severity at baseline. It may be speculated that patients with a mild progression of disease, and consequently more beneficial outcome, seek medical care later than those with more progressive palsy. In our study, subjects aged 40 to 60 and 61 to 75 years had significantly higher recovery rates with prednisolone treatment compared with those who did not receive prednisolone. In the high-dose prednisolone study by Sittel et al. (17), old age was not found to influence the functional outcome of palsy. Cha et al. (26) retrospectively found no significant differences in recovery rates between 301 adults and 102 children with Bell_s palsy, treated with corticosteroids. Yeo et al. (27) recently reported that prednisolone-treated patients older than 60 years showed a tendency to have a higher degree of recovery and a similar final status compared with younger age groups. Our findings support the statement by Yeo et al. (27) that otolaryngologists should encourage older patients to participate in more active and intensive treatment. In the age group younger than 40 years, the recovery rate for patients treated with prednisolone was 72% compared with 64% for those not given prednisolone, the difference being statistically insignificant. It can be speculated whether the number of patients in the present study was too small to achieve significance. In this group of patients aged younger than 40 years, however, synkinesis at 12 months was less common with prednisolone treatment. Altogether, our results showed that in regard to recovery rates and/or synkinesis, prednisolone was effective in all age groups. In patients not treated with prednisolone and aged 18 to 39 years, the recovery rate was 64% compared with 54% in the 40- to 60-year group and 40% in patients older than 60 years. The finding that higher age is a negative prognostic factor for outcome accords with the results of previous reports (4,6,7,28). A limitation of this study was that subgroup analyses reduced the number of patients and thereby made statistical comparisons more hazardous.
Otology & Neurotology, Vol. 32, No. 1, 2011

p 18Y75 yr n = 829 p n, % (95% CI) Difference (95% CI)

j23% (j40% to 5%)

0.02 300/416, 72% 15% (8%Y21%) (68%Y76%) 236/413, 57% (53%Y62%)

16% (j1% to 33%)

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Complete recovery Prednisolone (n = 416) versus No prednisolone (n = 413)a Synkinesis Prednisolone (n = 370) versus No prednisolone (n = 373)

Last-observation-carried-forward method used for missing data points; synkinesis at 12 months in patients with a 12-month follow-up (n = 743). Data are given as number of patients, % (95% CI) and % difference (95% CI). Complete recovery defined as Sunnybrook score of 100. a Data missing for 1 patient. CI indicates confidence interval.

Recovery and synkinesis by age in Bell_s palsy patients (n = 829)

61Y75 yr

n = 119

n, % (95% CI)

Difference (95% CI)

j22% G0.0001 41/66, 62% (j33% to j12%) (50%Y74%) 21/53, 40% (26%Y53%) j8% (j17% to 2%) 0.13 122/159, 77% (70Y83%) 86/158, 54% (47%Y62%) 137/191, 72% (65%Y78%) 129/201, 64% (57%Y71%)

Difference (95% CI)

n, % (95% CI)

TABLE 2.

18Y39 yr

n = 392

n, % (95% CI)

18/160, 11% (6%Y16%) 44/178, 25% (18%Y31%)

14% (5%Y22%)

Difference (95% CI)

0.002 20/150, 13% (8%Y19%) 44/144, 31% (23%Y38%)

17% (8%Y27%)

40Y60 yr

n = 317

0.0004 13/60, 22% (11%Y32%) 19/51, 37% (24%Y52%)

Age

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9. Axelsson S, Lindberg S, Stjernquist-Desatnik A. Outcome of treatment with valacyclovir and prednisone in patients with Bells palsy. Ann Otol Rhinol Laryngol 2003;112:197Y201. 10. Sullivan FM, Swan IR, Donnan PT, et al. Early treatment with prednisolone or acyclovir in Bells palsy. N Engl J Med 2007; 357:1598Y607. 11. Hu WL, Ross B, Nedzelski J. Reliability of the Sunnybrook Facial Grading System by novice users. J Otolaryngol 2001;30:208Y11. 12. Kanerva M, Poussa T, Pitkaranta A. Sunnybrook and House Brackmann Facial Grading Systems: intrarater repeatability and interrater agreement. Otolaryngol Head Neck Surg 2006;135: 865Y71. 13. Ross BG, Fradet G, Nedzelski JM. Development of a sensitive clinical facial grading system. Otolaryngol Head Neck Surg 1996; 114:380Y6. 14. House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146Y7. 15. Yeo SG, Lee YC, Park DC, Cha CI. Acyclovir plus steroid vs steroid alone in the treatment of Bells palsy. Am J Otolaryngol 2008;29:163Y6. 16. Shafshak TS, Essa AY, Bakey FA. The possible contributing factors for the success of steroid therapy in Bells palsy: a clinical and electrophysiological study. J Laryngol Otol 1994;108:940Y3. 17. Sittel C, Sittel A, Guntinas-Lichius O, Eckel HE, Stennert E. Bells palsy: a 10-year experience with antiphlogistic-rheologic infusion therapy. Am J Otol 2000;21:425Y32. 18. Sathirapanya P, Sathirapanya C. Clinical prognostic factors for treatment outcome in Bells palsy: a prospective study. J Med Assoc Thai 2008;91:1182Y8. 19. Adour KK, Wingerd J, Bell DN, Manning JJ, Hurley JP. Prednisone treatment for idiopathic facial paralysis (Bells palsy). N Engl J Med 1972;287:1268Y72. 20. Engstrom M, Abdsaleh S, Ahlstrom H, et al. Serial gadolinium enhanced magnetic resonance imaging and assessment of facial nerve function in Bells palsy. Otolaryngol Head Neck Surg 1997;117:559Y66. 21. Fisch U, Esslen E. Total intratemporal exposure of the facial nerve. Pathologic findings in Bells palsy. Arch Otolaryngol 1972;95: 335Y41. 22. Song MH, Kim J, Jeon JH, et al. Clinical significance of quantitative analysis of facial nerve enhancement on MRI in Bells palsy. Acta Otolaryngol 2008;128:1259Y65. 23. Liston SL, Kleid MS. Histopathology of Bells palsy. Laryngoscope 1989;99:23Y6. 24. Strupp M, Zingler VC, Arbusow V, et al. Methylprednisolone, valacyclovir, or the combination for vestibular neuritis. N Engl J Med 2004;351:354Y61. 25. Gianoli G, Goebel J, Mowry S, Poomipannit P. Anatomic differences in the lateral vestibular nerve channels and their implications in vestibular neuritis. Otol Neurotol 2005;26:489Y94. 26. Cha CI, Hong CK, Park MS, Yeo SG. Comparison of facial nerve paralysis in adults and children. Yonsei Med J 2008;49:725Y34. 27. Yeo SW, Lee DH, Jun BC, Chang KH, Park YS. Analysis of prognostic factors in Bells palsy and Ramsay Hunt syndrome. Auris Nasus Larynx 2007;34:159Y64. 28. Ikeda M, Abiko Y, Kukimoto N, et al. Clinical factors that influence the prognosis of facial nerve paralysis and the magnitudes of influence. Laryngoscope 2005;115:855Y60.

In conclusion, treatment start with prednisolone within 48 hours of onset of palsy resulted in significantly higher recovery rates and less synkinesis compared with no prednisolone treatment. In the patients aged 40 years or older, prednisolone gave significantly higher recovery rates than in those not treated with this drug. In subjects aged younger than 40 years, prednisolone was not shown to improve the recovery rate, but it reduced synkinesis significantly.
Acknowledgments: The authors thank Malou Hultcrantz and Per Hanner in the steering committee of the Scandinavian Bell_s palsy study. The authors also thank Nermin Hadziosmanovic and Lars Berglund (Biostatisticians, Uppsala Clinical Research Center) for valuable help with the statistics, Par Lundqvist (Systems Developer, Uppsala Clinical Research Center) for developing the database, Adam Taube (Department of Information Science/Statistics, Uppsala University) for help with planning and with the final analysis of the Scandinavian Bell_s palsy study, and Charlotte Cervin-Hoberg (Biomedical analyst, Lund University Hospital) for help with the study. The authors also thank all doctors, nurses, and staff at the otorhinolaryngology centers for participating in this multicenter trial.

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