Special Feature

Bell’s Palsy: New Trials for Better Smiles

By Michael W. Felz, MD

Introduction

Bell’s palsy (BP) is the most common affliction of the facial nerve and the most frequent cause of acute facial paralysis worldwide. Since its first clinical description in 1829 by Sir Charles Bell in England, BP has been surrounded by therapeutic controversy and its etiology has been shrouded in mystery.1 Recent literature, however, features evidence-based trials that enable emergency department (ED) clinicians to recommend more advanced treatment than ever before.

Clinical Features

BP affects all ages, attacks both genders equally, and occurs in all seasons, accounting for its frequent presentation in ED. The crooked smile, asymmetric face, and incompletely closed eye are telltale signs easily recognized by patient and physician. The motor insult to all five facial expression muscle groups is abrupt, tends to occur at night or on awakening, and attains maximal unilateral facial paralysis within 48 hours. Hyperacusis and distorted taste correlate with involvement of stapedius and chorda tympani branches of cranial nerve (CN) VII, respectively. Motor manifestations are expected to predominate, since CN VII is comprised of 70% motor axons and 30% sensory and autonomic fibers. Clinical compromise may be quantified by the House-Brackmann (HB) Facial Nerve Grading System, with stages ranging from 1 (no weakness) to 6 (total paralysis).2 Determination of HB grade allows for pretreatment assessment as well as progression/improvement over time.

Pathogenesis

For 60 years, BP was regarded as idiopathic. Historical associations with pregnancy, diabetes mellitus, multiple sclerosis, temporal bone surgery or masses, middle ear disease, sarcoidosis, Ramsay-Hunt syndrome (herpes zoster of external auditory canal with BP), Melkersson-Rosenthal syndrome (BP with facial edema and fissured tongue), and viral infections such as the human immunodeficiency virus have been proposed. Yet none of these associations generated a unified hypothesis of BP pathogenesis. BP occurs in association with Lyme disease—more frequently in children than in adults—but antibiotic therapy for Borrelia burgdorferi has no significant impact on clinical resolution.

In the last 10 years, however, more sophisticated clinical, immunologic, pathologic, and microbiologic investigations have clarified the biologic basis for acute CN VII dysfunction with some degree of certainty. The genome of herpes simplex virus (HSV) was demonstrated by polymerase chain reaction (PCR) of the geniculate ganglion of an elderly man who died six weeks after the onset of BP.3 Furthermore, in Japanese patients with BP undergoing surgical decompression of CN VII paralysis refractory to medical management, endoneural fluid and posterior auricular muscle tissue specimens of 11 of 14 patients (79%) had HSV-1 specific DNA fragments amplified by PCR, and 12 of 13 (92%) had high HSV-1 antibody titers by complement fixation testing.4 These authors concluded that, given the well-recognized neuropathogenicity of HSV-1, the presence of HSV-DNA at the lesion site of CN VII paralysis directly is related to the pathogenesis of BP. In addition, HSV DNA has been detected by PCR significantly more frequently (50% vs 19%, p < 0.05) in saliva samples of 42 BP patients in Japan compared to 16 healthy controls.5 Finally, a mouse model has demonstrated that subcutaneous inoculation of the ear or anterior tongue with HSV produces transient facial paralysis and inflammatory nerve swelling with vacuolar degeneration.6 HSV antigens were then detected by PCR of tissue specimens from CN VII, facial nerve nucleus, and geniculate ganglion in affected mice. Taken together, these investigations provide persuasive evidence supporting an etiologic role for HSV primary infection or reactivation in the pathogenesis of acute CN VII paralysis.

Therapy

Such experimental data not only confer plausibility to biologic causation of BP, but also set the stage for targeted therapy. Acute inflammation in CN VII biopsies, segmental demyelination and axonal degeneration on electromyographic testing, nerve edema and intraforaminal compression seen on magnetic resonance scanning, and active viral replication demonstrated by PCR are factors contributing to the rationale for therapy with steroids and antiviral agents. The good news is that 70% of BP patients regain some or all CN VII function within 3-6 months. Yet 30% have unfavorable outcomes, at least historically.

What evidence directs wise therapy? Prednisone 60 mg/d for five days and tapered for five days shortened time of resolution from 69.3 to 51.4 days among 76 BP patients seen in Los Angeles, and reduced the number of patients with poor HB grades at resolution.7 A meta-analysis of well-designed trials of steroids in BP estimates a 17% (99% CI: 0.01-0.32) improvement in likelihood of complete facial recovery for treatment groups over controls.8 In 99 BP patients randomized at the Cranial Nerve Research Center in Oakland, CA, acyclovir 2000 mg/d for 10 days plus prednisone 60 mg/d for five days and tapered for five days provided statistically better rates (92% vs 76%; p 0.02) of normalized CN VII volitional motion than did placebo plus prednisone treatment.9 Among 56 Swedish patients with BP, treatment with valacyclovir 1000 mg t.i.d. for seven days with prednisone 50 mg/d for five days and tapered for five days was superior to non-medical therapy, with 87.5% recovery to HB grade 1 in the treatment group vs. 68% in the controls (p < 0.05). Ten (18%) control patients had a final HB grade of 4 or worse, compared to one patient (1.8%) in the valacyclovir-prednisone group (p < 0.01).10

A meta-analysis of steroids plus antiviral agents (mainly acyclovir) in BP concluded that patients treated with combination therapy showed significantly better outcomes (RR for benefit: 1.22; 95% CI: 1.02-1.45) than those treated with prednisone alone.11

Conclusion

Current evidence seems cohesive that HSV and resultant inflammatory neuropathy accounts for much of the CN VII weakness evident in BP patients. Furthermore, 10 days of antiviral therapy against HSV, plus 10 days of steroids (five days at 1 mg/kg and tapered over five days) appears to confer modest benefit toward full CN VII recovery. It is prudent to follow the House-Brackmann grading score over time to document progressive improvement. Now that HSV is clearly known to be a major culprit in BP, it is time to fight back with new, proven weapons. Given these encouraging trials, perhaps BP patients can smile, and smile well, once again.

Dr. Felz, Associate Professor, Department of Family Medicine, Medical College of Georgia, Augusta, GA, is on the editorial board of Emergency Medicine Alert.

References

1. Goetz CG. Textbook of Clinical Neurology. Philadelphia: WB Saunders; 1999:171-183.

2. House JW, et al. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146-147.

3. Burgess RC, et al. Polymerase chain reaction amplification of Herpes simples viral DNA from the geniculate ganglion of a patient with Bell’s palsy. Ann Otol Rhinol Laryngol 1994;103:775-779.

4. Murakami S, et al. Bell palsy and herpes simplex virus: Identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med 1996;124:27-30.

5. Furuta Y, et al. Reactivation of herpes simplex virus type 1 in patients with Bell’s palsy. J Med Virol 1998; 54:162-166.

6. Sugita T, et al. Facial nerve paralysis induced by Herpes simplex virus in mice: An animal model of acute and transient facial paralysis. Ann Otol Rhinol Laryngol 1995;104:574-581.

7. Austin JR, et al. Idiopathic facial nerve paralysis: A randomized double blind controlled study of placebo versus prednisone. Laryngoscope 1993;103:1326-1333.

8. Ramsey MJ, et al. Corticosteroid treatment for idiopathic facial nerve paralysis: A meta-analysis. Laryngoscope 2000;110:335-341.

9. Adour KK, et al. Bell’s palsy treatment with acyclovir and prednisone compared with prednisone alone: A double blind, randomized, controlled trial. Ann Otol Rhinol Laryngol 1996;105:371-378.

10. Axelsson S, et al. Outcome of treatment with valcyclovir and prednisone in patients with Bell’s palsy. Ann Otol Rhinol Laryngol 2003;112:197-201.

11. Grogan PM, et al. Practice parameter: Steroids, acyclovir, and surgery for Bell’s palsy (an evidence-based review): Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001;56:830-836.