Source: Gagyor I, Madhok VB, Daly F, et al. Antiviral treatment for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 2015;(11):CD001869.
Study Population: 1,315 adults (age ≥18 years) with unilateral facial paralysis of unknown cause from eight trials
Efficacy Endpoints: Incomplete recovery of facial function, motor synkinesis, or crocodile tears syndrome
Harm Endpoints: Not clearly defined; listed only as ‘adverse events’
Narrative: Idiopathic facial paralysis (a.k.a. Bell’s Palsy) is the most common cause of unilateral facial paralysis.1 Maximal disability occurs within 48 to 72 hours, with symptoms involving both the upper and the lower face.1 Patients may exhibit flattening of the forehead and nasolabial fold on the affected side, with the forehead remaining flat on the affected side when the patient raises his/her eyebrows. Additional symptoms may include poor eyelid closure, eye pain, blurred vision, posterior auricular pain, otalgia, hyperacusis, and taste disturbances. The propensity for cranial nerve (CN) VII to form connections with adjacent CNs may explain occasional features including altered facial sensation (CN V), vestibular dysfunction (CN VIII), or pharyngeal symptoms (CN IX and X).2 Reduced lacrimation and salivation may occur secondary to parasympathetic effects.2 Although bilateral simultaneous Bell’s palsy can develop, it is rare with an occurrence rate 0.3% to 2% of that for unilateral palsy.
The annual incidence is 23 to 37 cases per 100,000 people,3, 4, 5 and recurrence rates of 7% to 11% have been reported.6, 7 It may occur at any age, but peaks between ages 30 to 45 years and age > 70.3, 4 There is no sex predominance.1, 4 The incidence is higher in pregnancy, following viral upper respiratory infection, and in the immunocompromised setting. The risk of disease and incomplete recovery is increased in diabetic patients (30% each).1 Possible etiologies include infections (e.g., herpes zoster and Epstein-Barr viruses, cytomegalovirus, human immunodeficiency virus, Lyme disease, syphilis, and mycoplasma), inflammation or autoimmune reactions, microvascular disease, and hereditary causes.8, 9, 10
Clinically important improvement occurs within 3 weeks (85%).11 Patients failing to show improvement by 3 weeks may have suffered severe facial nerve degeneration.11 Overall, 71% of patients will experience complete recovery in facial muscle function.11 The remainder may have incomplete recovery defined as either permanent residual weakness (29%), contracture (17%; together termed incomplete recovery), or hemifacial spasm (synkinesis; 16%).11 In some cases, damaged nerve fibers destined for a salivary gland mistakenly regrow into a tear glad resulting in excessive tearing during mastication (a.k.a. gustolacrimal reflex; crocodile tears syndrome).
The Cochrane meta-analysis cited here assesses the effectiveness of antiviral treatment alone or in combination with corticosteroids to decrease the risk of incomplete recovery from Bell’s palsy.4 It includes 10 clinical trials (2,280 participants).4 The analysis (eight trials, 1,365 participants) suggests that antivirals plus corticosteroids reduces the incidence of incomplete recovery when compared either to corticosteroids alone (RR = 0.61, 95% confidence interval [CI] = 0.39 to 0.97, absolute risk difference [ARD] = 6.5%, number needed to treat [NNT] = 15; quality of evidence = low) or to placebo or no treatment (RR = 0.56, 95% CI = 0.41 to 0.76, ARD = 12%, NNT = 8, quality of evidence = low).4 Antivirals alone did not improve the risk of incomplete recovery rates when compared to placebo/no treatment (RR = 1.10, 95% CI = 0.87 to 1.40; quality of evidence = low) and increased rates of incomplete recovery when compared to corticosteroids alone (RR = 1.52, 95% CI = 1.08 to 2.12, quality of evidence = low).4, 12
The risk of long-term aftereffects including motor synkinesis (abnormal involuntary facial movement) or crocodile tears syndrome (unilateral tearing when eating) was decreased when antivirals plus corticosteroids were compared to corticosteroids alone (RR = 0.56, 95% CI = 0.36 to 0.87, ARD = 8.5%, NNT = 12; quality of evidence = moderate), whereas corticosteroids alone decreased long-term aftereffects greater than antivirals alone (RR 1.52, 95% CI = 1.08 to 2.12, quality of evidence = moderate).4 No published data were available comparing either antivirals plus corticosteroids or antivirals alone with placebo or no treatment for this specific outcome.
The referenced meta-analysis contained an overall lack of details regarding adverse reactions. That being said, aggregate adverse events was significantly less with antivirals alone when compared to corticosteroids alone (RR = 0.85, 95% CI = 0.57 to 1.28, ARD = 2.04%, NNT = 49; quality of evidence = low) or placebo or no treatment (RR = 0.83, 95% CI = 0.56 to 1.24, ARD = 2.8%, NNT = 36, n = 651, quality of evidence = low).4 Adverse events were not significantly different when comparing antivirals plus corticosteroids to either corticosteroids alone (RR = 1.18, 95% CI = 0.83 to 1.69) or placebo or no treatment (RR = 1.14, 95% CI = 0.79 to 1.65).
Caveats: This systematic review and meta-analysis assesses the safety and efficacy of antivirals for decreasing the risk of incomplete recovery and long-term aftereffects in patients with Bell’s palsy. Unfortunately, the analysis does not control for antiviral type or administration route. Our search identified two clinical trials not reported in the Cochrane analysis that compared either antivirals alone13 or with corticosteroids12 to corticosteroids alone. The study by Khedr et al.12 supports the Cochrane analysis findings that the combination of antiviral plus corticosteroid decreases incomplete recovery in patients with moderately severe to complete acute Bell’s palsy. The study by Ghorbani and Kazemi13 also showed that antivirals alone does not outperform corticosteroids alone.
A green color recommendation is based on the evidence of low-quality evidence supporting the benefits that antiviral with corticosteroid therapy decreases rates of incomplete recovery from Bell’s palsy. Antiviral plus corticosteroid combination therapy also reduces longterm sequala including motor synkinesis or crocodile tears syndrome. Although this is supported by moderate-quality evidence, only two trials reported this outcome. Antivirals alone earned a red color recommendation as monotherapy failed to show benefit for prevention of incomplete recovery over placebo/no treatment. Antivirals do not appear to have serious adverse effects (low-quality evidence).
Conclusion: When taken with corticosteroids for Bell’s palsy, antivirals decrease incomplete recovery (NNT = 8) and longterm aftereffects including motor synkinesis and crocodile tears syndrome (NNT = 12) when compared to placebo or no treatment. Antivirals in combination with corticosteroids should be considered in the management of patients with Bell’s palsy in the ED.
Author: Roberto C. Portela, MD; Andrew C. Miller, MD
Published/Updated: November 16, 2018
The title bar is color-coded with our overall recommendation.