Elsevier

The Lancet Neurology

Volume 7, Issue 11, November 2008, Pages 993-1000
The Lancet Neurology

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Prednisolone and valaciclovir in Bell's palsy: a randomised, double-blind, placebo-controlled, multicentre trial

https://doi.org/10.1016/S1474-4422(08)70221-7Get rights and content

Summary

Background

Previous trials of corticosteroid or antiviral treatments for Bell's palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients.

Methods

In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263.

Findings

Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1·40, 95% CI 1·18 to 1·64; p<0·0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1·01, 0·85 to 1·19; p=0·90). The number of patients with adverse events was similar in all treatment arms.

Interpretation

Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery.

Funding

Uppsala University; GlaxoSmithKline (Sweden); Pfizer AB (Sweden); Acta Otolaryngologica Foundation; Rosa and Emanuel Nachmanssons Foundation; Stig and Ragna Gorthon Foundation; Torsten Birger Segerfalk Foundation; Margit Arstrups Foundation; County Council of Skåne; Helsinki University Central Hospital Research Funds.

Introduction

Bell's palsy presents as unilateral weakness or paralysis of the face due to acute dysfunction of the peripheral facial nerve with no readily identifiable cause.1 Bell's palsy accounts for 70% of peripheral facial palsies and the yearly incidence is about 30 per 100 000.2, 3 About 70% of patients with Bell's palsy recover completely within 6 months without treatment. The remainder have sequelae that include residual paresis, contracture, and synkinesis.2 To minimise the time to recovery and sequelae from Bell's palsy, the most effective medical therapy has to be established.

A possible cause of Bell's palsy is inflammation of the facial nerve,4, 5, 6 which might be related to the herpes virus;7, 8, 9, 10 this has led many investigators to study the efficacy of corticosteroids and antivirals to treat Bell's palsy. The Cochrane database report11 on corticosteroid therapy concluded that trials12, 13, 14, 15 that met the inclusion criteria were too small (179 patients in total) to detect the benefits of corticosteroids. Another Cochrane report assessed the efficacy of aciclovir or similar antiviral drugs.16 Three studies (246 patients) were reviewed,17, 18, 19 and a need for adequately powered clinical trials of aciclovir and valaciclovir with a follow-up of 1 year was identified.16

Our aim was to study the short-term and long-term effects of treatment with prednisolone and/or valaciclovir on the recovery of the facial nerve in a large number of patients with Bell's palsy. We also studied the side-effects of the drugs and their effects on synkinesis. Valaciclovir was chosen because it has higher bioavailability than aciclovir. To improve reliability when assessing potential treatment effects, the regional Sunnybrook20 and the gross House-Brackmann21 scales were used to grade facial function.

Section snippets

Patients

Patients with acute, unilateral, peripheral facial palsy, who were referred from general practitioners or emergency departments, or who sought care directly, were screened by physicians at 16 public otorhinolaryngological centres in Sweden and one centre in Finland. Each study centre had at least one experienced ear, nose, and throat physician with a special interest in facial palsy who was responsible for implementing the study. Patients aged 18 to 75 years with onset of palsy within 72 h were

Results

From May, 2001, to September, 2006, 1953 patients (910 women and 1043 men) with acute peripheral facial palsy were screened and registered. At the initial examination, 1114 of the 1953 patients did not meet the inclusion criteria and were registered with separate forms. Patients who were screened but not included were not registered at the Helsinki centre; thus, the number of patients who were screened was greater than 1953. Reasons for ineligibility were: more than 72 h had elapsed since the

Discussion

This large, double-blind, placebo-controlled trial assessed corticosteroid and antiviral treatment for Bell's palsy. The patients who received prednisolone had a shorter time to complete recovery, and outcomes at 12 months were more favourable in these patients than in those who did not receive prednisolone. Valaciclovir was not proven to be effective and did not affect prednisolone treatment.

In 2001, the American Academy of Neurology concluded in their practice guideline meta-analysis that

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