The most clearly defined viral cause of acute inflammatory paralysis of muscles innervated by the facial nerve is varicella-zoster virus infection; this condition is known as the Ramsay-Hunt syndrome. In this condition, acute facial paralysis is associated with vesicles in the ear from which varicella-zoster virus can be readily recovered. The stereotypy of this condition leaves little doubt that varicella-zoster virus causes an acute inflammatory involvement of the facial nerve with paralysis of the muscles innervated by the nerve. This is often associated with seroconversion, as shown by an increase in specific antibody titer to varicella-zoster virus [1].

However, although the known causes of acute inflammatory facial paralysis are many, the most common cause of acute idiopathic facial paralysis (Bell palsy) is unknown. Considerable attention has been paid to the possibility that herpes simplex virus (HSV) might be the causative agent; this hypothesis was first suggested in 1972 by McCormick [2]. The hypothesis was based on the analogy that HSV was the cause of recurrent cold sores, in all likelihood related to the latency of the virus in trigeminal ganglia. McCormick suggested that HSV might be present in the geniculate ganglia, where it could cause a seventh nerve neuropathy when the virus traveled down the nerve axon, perhaps infecting the Schwann cells. Later studies confirmed the latency of HSV in trigeminal ganglia [3] and thus established the basis for considering HSV to be the cause of recurrent oral or ocular lesions. Subsequent studies of autopsy material [4, 5] have shown latent HSV in the geniculate ganglia of humans.

Despite the tantalizing analogy between the biology of herpes simplex and herpes varicella-zoster virus, the cause of the ubiquitous Bell palsy remains obscure. A previous review [6] concluded that the reactivation of HSV from the geniculate ganglion was a potential cause of Bell palsy, although some clinical features were puzzling. The inflammatory nature of the process has been suggested strongly by several recent papers on magnetic resonance imaging that indicate the frequent phenomenon of gadolinium-induced enhancement of the facial nerve in acute cases of Bell palsy [7]. Cerebrospinal fluid taken from patients with Bell palsy tends to show mildly and inconsistently elevated cell counts and protein levels but has otherwise been unhelpful in identifying etiologic agents. Serologic titers have shown a slight preponderance of elevated titers against HSV in patients with Bell palsy compared with controls, but increased titers have been the exception rather than the rule [1, 8-10]. The pathology [11, 12] is that of an inflammatory process in the facial nerve composed largely of lymphocytes with associated demyelination or axonal destruction, or both.

A few clinical papers have associated acute HSV infections with facial paralysis. Recently, Santos and Adour [13] reported a single case of a young man who had developed severe bifacial paralysis after engaging in oral sex with a partner who had active genital herpes lesions.

Mulkens and colleagues [9] studied antibody responses to HSV and varicella-zoster virus in 120 patients with Bell palsy. Three of these patients showed increases in antibody titers to varicella-zoster virus; no increases in antibody titers to HSV were seen. Herpes simplex virus was isolated from the epineurium of 1 of 2 patients subjected to facial nerve decompression for Bell palsy. Burgess and coworkers [14] recently used the polymerase chain reaction (PCR) technique to identify HSV genomes in the geniculate ganglion of an 84-year-old man who died 6 weeks after developing idiopathic Bell palsy. Herpes simplex virus sequences could not be amplified from six control cases.

Against this background, Murakami and colleagues, in this issue [15], provide new information suggesting a strong association between Bell palsy and HSV infection. These authors used the powerful PCR technique to amplify viral genomic sequences from endoneurial fluid collected from the seventh nerve or tissue of the posterior auricular muscle innervated by the facial nerve in a series of 14 patients with Bell palsy and 9 patients with the Ramsay-Hunt syndrome. These specimens were obtained during decompressive surgery, and control specimens were obtained during similar surgery done in patients with temporal bone fractures or bacterial infections. Herpes simplex virus type 1 (HSV-1) genomes were amplified from the nerve or muscle tissue of 11 of the patients with Bell palsy; 1 of the 3 patients who did not have amplifiable sequences was a 3-year-old child with negative antibody titers to HSV-1, which suggests that the facial paralysis may have had another cause. Varicella-zoster virus sequences were not amplified in any of the Bell palsy cases. In contrast, varicella-zoster virus sequences were amplifiable in 8 of the persons with the Ramsay-Hunt syndrome, and HSV sequences were amplifiable in none of these patients. All of the controls, who were patients with temporal bone fractures, bacterial infections, parotid cancers, and chronic otitis media, tested negative for both HSV and varicella-zoster virus sequences.

The application of PCR to this problem has contributed useful new insights into the probable cause of Bell palsy. The PCR technique provides enormous amplification of viral genomes and thus is capable of detecting minute amounts of viral DNA in nervous system or other tissues. The disadvantage of PCR in applications such as this is that PCR does not distinguish between viral genomes that are present in a latent state and those that are present because of reactivated virus in the course of a productive infection. Additionally, the exquisite sensitivity of the technique is such that problems of laboratory contamination loom large in the analysis of results. Murakami and colleagues [15] wisely chose to look at patients with the Ramsay-Hunt syndrome as well as patients with Bell palsy; the absence of HSV genomes in the patients with the Ramsay-Hunt syndrome—another inflammatory disease of the facial nerve—constitutes an excellent control and weighs heavily against the possibility that the results in the Bell palsy cases were due to laboratory contamination or a nonspecific reactivation of HSV by an inflammatory process in the nerve. The detection of HSV sequences in peripheral nerve tissue probably would not reflect the presence of latent viral genomes. Previous work [3] on the detection of latent virus from trigeminal ganglia of unselected persons at the time of autopsy was successful in showing latent virus only in ganglionic tissue and not in peripheral nerve tissue belonging to the same patient. Thus, it is unlikely that latent HSV is usually present in the peripheral nerve outside of the sensory ganglia.

One could argue that some other (vascular, traumatic, infectious) process is responsible for the presence of HSV in the Bell palsy specimens. It is widely recognized that surgical trauma to the trigeminal root commonly provokes HSV to reactivate with excretion of virus and production of lesions in the oral mucosa. Herpes simplex virus in the trigeminal ganglion can produce dozens of episodes of labial herpes; thus, one might wonder why—if HSV causes Bell palsy—the episode is rarely repeated. Nevertheless, the results of Murakami and colleagues [15] suggest strongly that the reactivation of HSV genomes may cause idiopathic facial paralysis.

The implications of this finding for treatment would logically argue for the use of acyclovir as part of the management of Bell palsy. Studies currently in press [Adour KK. Personal communication] suggest a modest therapeutic advantage in terms of speed and completeness of recovery in patients with Bell palsy who receive acyclovir and prednisone compared with those who receive prednisone alone. The failure to achieve more dramatic results may result from several factors, including 1) that acyclovir is a suppressive rather than a virucidal agent and 2) that the initial sign of the condition is the paralyzed face, signifying completed damage to the facial nerve. Although the damage may be initiated by the virus, the anatomical disruption or immune reactions in the nerve, or both, would not be susceptible to repair by acyclovir. Murakami and colleagues [15] provide unique insights into the probable pathogenesis of Bell palsy. One might now question whether we should continue using the term "Bell palsy" to mean "idiopathic facial paralysis" or whether we should now recognize Bell palsy as "herpetic facial paralysis," confirming the hypothesis advanced initially in 1972 by McCormick [2].