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Prednisolone or Acyclovir in Bells Palsy

To the Editor: Sullivan et al. (Oct. 18 issue)1 report that early treatment with prednisolone significantly improves the chances of complete recovery in patients with Bells palsy, whereas no evidence of a benefit of acyclovir could be found. Idiopathic peripheral-facial-nerve paralysis of sudden onset is difficult to diagnose because other causes that are associated with a significantly higher risk of defective healing2 must be ruled out. Since zoster sine herpete which can mimic the signs and symptoms of Bells palsy caused by varicellazoster virus has an incidence rate of up to 34% among patients with Bells palsy,3 information about the virologic backgrounds of all participating patients, obtained by means of serologic and polymerase-chain-reaction examinations, is needed. However, the authors have not provided virologic data to ensure the exclusion of patients with zoster sine herpete from this study. Dirk Beutner, M.D.
University of Cologne 50924 Cologne, Germany dirk.beutner@uni-koeln.de
1. Sullivan FM, Swan IRC, Donnan PT, et al. Early treatment 2. Kawaguchi K, Inamura H, Abe Y, et al. Reactivation of her-

pes simplex virus type 1 and varicella-zoster virus and therapeutic effects of combination therapy with prednisolone and valacyclovir in patients with Bells palsy. Laryngoscope 2007;117: 147-56. 3. Grosheva M, Guntinas-Lichius O. Significance of electromyography to predict and evaluate facial function outcome after acute peripheral facial palsy. Eur Arch Otorhinolaryngol 2007; 264:1491-5.

To the Editor: Sullivan and colleagues found no benefit of acyclovir (at a dose of 400 mg five times per day for 10 days) for the treatment of Bells palsy, either alone or in combination with prednisolone. They excluded patients with herpes zoster. However, occult varicellazoster virus reactivation (zoster sine herpete) may cause up to 29% of cases of Bells palsy.1 The optimal dose of acyclovir for the treatment of varicellazoster virus infection (according to the package insert) is 800 mg five times per day. Thus, a significant subgroup of patients with Bells palsy might still benefit from higher-dose antiviral treatment than that used in the study by Sullivan et al. Steven Leiner, N.P.
Mission Neighborhood Health Center San Francisco, CA 94110 stevenleiner@hotmail.com
1. Furuta Y, Ohtani F, Kawabata H, Fukuda S, Bergstrm T.

with prednisolone or acyclovir in Bells palsy. N Engl J Med 2007; 357:1598-607.

this weeks letters 306 Prednisolone or Acyclovir in Bells Palsy 308 CTGF Polymorphism Associated with Systemic Sclerosis 310 Hypertriglyceridemia 311 Taenia in the Gastrointestinal Tract 312 A Man with Abdominal Pain and Elevated Creatinine 313 Leishmania donovani in Indian Mucosal Leishmaniasis

High prevalence of varicella-zoster virus reactivation in herpes simplex virus-seronegative patients with acute peripheral facial palsy. Clin Infect Dis 2000;30:529-33.

To the Editor: The methodologic superiority of the Scottish pivotal trial of early treatment of Bells palsy, reported by Sullivan et al., as compared with the Japanese trial recently reported by Hato et al.,1 is obvious and clearly highlighted in Gilden and Tylers editorial accompanying the article by Sullivan et al.2 However, one clinically relevant difference between the two trials that favors the Japanese study seems to have been dis-

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correspondence

regarded. Hato et al. classified their patients according to the baseline severity of the facial palsy and presented their efficacy data for the different subgroups. Sullivan et al. mention adjustment of the analysis for baseline characteristics, including the score on the HouseBrackmann scale, without clearly presenting results for this. It would be helpful for daily practice and would strengthen their findings if Sullivan and colleagues could confirm that their efficacy findings hold for subgroups of patients with lower and higher baseline HouseBrackmann scores. If not, we agree with Gilden and Tyler that the early use of (val)acyclovir (in combination with glucocorticoids) could still be considered in patients with severe or complete facial palsy. Esther S. Korf, M.D., Ph.D. Joep Killestein, M.D., Ph.D.
VU Medical Center 1081 HV Amsterdam, the Netherlands j.killestein@vumc.nl
1. Hato N, Yamada H, Kohno H, et al. Valacyclovir and prednis-

olone treatment for Bells palsy: a multicenter, randomized, placebo-controlled study. Otol Neurotol 2007;28:408-13. 2. Gilden DH, Tyler KL. Bells palsy is glucocorticoid treatment enough? N Engl J Med 2007;357:1653-5.

The authors reply: We agree with Beutner and Leiner that a definitive diagnosis of idiopathic facial paralysis within the 48-to-72-hour window for early intervention is difficult. Baseline virologic studies would potentially have been valuable in determining whether the subgroup University of Dundee of patients with zoster sine herpete had a recov- Dundee DD1 4HN, United Kingdom f.m.sullivan@chs.dundee.ac.uk ery rate that was different from the rate for Swan, M.D. those who did not have zoster sine herpete. Iain University of Glasgow However, we estimate that 800 patients would Glasgow G12 8QQ, United Kingdom have been needed to complete follow-up, in or- Fergus Daly, Ph.D. der to provide equivalent power for our study. University of Dundee The dose of acyclovir that we used (2 g daily) Dundee DD1 4HN, United Kingdom rather than the higher dose suggested by Leiner 1. Sipe J, Dunn L. Acyclovir for Bells palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 2001;2:CD001869. was chosen because that was the dose used in 2. Altman DG, Bland JM. Absence of evidence is not evidence two of the three studies included in the Cochrane of absence. BMJ 1995;311:485.
Table 1. Rate of Recovery According to the Assigned Treatment and the Severity of Bells Palsy at Onset. Severity at Onset Prednisolone Moderate (HouseBrackmann score, 24) Severe (HouseBrackmann score, 56) All patients 169/176 (96.0) 42/49 (85.7) 211/225 (93.8) No Prednisolone 122/145 (84.1) 59/80 (73.8) 181/225 (80.4) Rate of Recovery Acyclovir 149/166 (89.8) 44/62 (71.0) 193/228 (84.6) No Acyclovir 142/155 (91.6) 57/67 (85.1) 199/222 (89.6) Total 291/321 (90.7) 101/129 (78.3) 392/450 (87.1) number/total number (percent)

review that was available at that time (one study used 2.4 g daily).1 In response to Korf and Killesteins point, we present here the subgroup analysis of response according to initial disease severity. For 450 of 496 patients who completed the study and for whom we had relevant data, we characterized those with a grade of 2 to 4 at onset as having moderate Bells palsy and those with a grade of 5 to 6 as having severe Bells palsy. The recovery rates at 9 months for patients treated with prednisolone and with acyclovir are shown in Table 1. Overall, the recovery rate in the prednisolone group was 93.8%, as compared with 80.4% in the no-prednisolone group (odds ratio, 3.66; 95% confidence interval [CI], 1.92 to 7.28; P<0.001; interaction between prednisolone and baseline severity was nonsignificant, P=0.18). The recovery rate in the acyclovir group was 84.6%, as compared with 89.6% in the no-acyclovir group (odds ratio, 0.64; 95% CI, 0.36 to 1.12; P=0.12; interaction was nonsignificant, P=0.35). The combined recovery rate in the moderately affected group was 90.7%, as compared with 78.3% in the severely affected group (odds ratio, 2.69; 95% CI, 1.49 to 4.82; P<0.001). As with the point about the dose of acyclovir, we cannot say whether valacyclovir may be effective because it was not an intervention in our study. Absence of evidence is not evidence of absence.2 Frank Sullivan, Ph.D.

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