Autoimmunity Reviews 12 (2012) 323–328

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Autoimmunity Reviews
journal homepage: www.elsevier.com/locate/autrev

Review

Bell's palsy and autoimmunity

A. Greco, A. Gallo, M. Fusconi, C. Marinelli, G.F. Macri ⁎, M. de Vincentiis
Head and Neck Department — ENT Department, Policlinico “Umberto I” University of Rome “Sapienza”, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: To review our current knowledge of the etiopathogenesis of Bell's palsy, including viral infection
Received 19 May 2012 or autoimmunity, and to discuss disease pathogenesis with respect to pharmacotherapy.
Accepted 30 May 2012 Systematic review methodology: Relevant publications on the etiopathogenesis, clinical presentation, diagno-
Available online 8 June 2012 sis and histopathology of Bell's palsy from 1975 to 2012 were analysed.
Results and conclusions: Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It ac-
Keywords:
counts for 60 to 75% of all cases of unilateral facial paralysis. The annual incidence of Bell's palsy is 15 to
Bell's palsy
Autoimmunity
30 per 100,000 people. The peak incidence occurs between the second and fourth decades (15 to 45 years).
Aetiology The aetiology of Bell's palsy is unknown but viral infection or autoimmune disease has been postulated as
Pathogenesis possible pathomechanisms. Bell's palsy may be caused when latent herpes viruses (herpes simplex, herpes
Therapy zoster) are reactivated from cranial nerve ganglia. A cell-mediated autoimmune mechanism against a myelin
basic protein has been suggested for the pathogenesis of Bell's palsy. Bell's palsy may be an autoimmune de-
myelinating cranial neuritis, and in most cases, it is a mononeuritic variant of Guillain–Barré syndrome, a
neurologic disorder with recognised cell-mediated immunity against peripheral nerve myelin antigens. In
Bell's palsy and GBS, a viral infection or the reactivation of a latent virus may provoke an autoimmune reac-
tion against peripheral nerve myelin components, leading to the demyelination of cranial nerves, especially
the facial nerve.
Given the safety profile of acyclovir, valacyclovir, and short-course oral corticosteroids, patients who present
within three days of the onset of symptoms should be offered combination therapy. However it seems logical
that in fact, steroids exert their beneficial effect via immunosuppressive action, as is the case in some other
autoimmune disorders. It is to be hoped that (monoclonal) antibodies and/or T-cell immunotherapy might
provide more specific treatment guidelines in the management of Bell's palsy.
© 2012 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2. Aetiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
2.1. Viral hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
2.2. Immunological hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
3. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327

1. Introduction nerve palsy may have a detectable cause (i.e. secondary facial nerve
palsy) or may be idiopathic (primary) without an obvious cause (i.e.
The most common causes of the abrupt onset of unilateral facial Bell's palsy) [2]. Secondary facial nerve palsy has a variety of causes
weakness are stroke and Bell's palsy [1]. Unilateral peripheral facial (Table a) and is generally less prevalent than Bell's palsy (25 vs.
75%) [3]. Bell's palsy was first described by NA Friedreich in 1797
⁎ Corresponding author at: Largo Valerio Bacigalupo 32 C, 00142 Rome, Italy. Tel.:
[4]. It is named after Sir Charles Bell (1774–1842), who described
+ 39 03478404236. the syndrome along with the anatomy and function of the facial
E-mail address: giano1979@hotmail.com (GF. Macri). nerve.

1568-9972/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.autrev.2012.05.008
324 A. Greco et al. / Autoimmunity Reviews 12 (2012) 323–328

Table a that carries taste sensation from the anterior two thirds of the tongue
Aetiologies of facial nerve palsy. through the chorda tympani nerve [10]. Parasympathetic fibres reach
From: Lorch M, Teach SJ. Facial nerve palsy: aetiology and approach to diagnosis and
treatment. Pediatric Emergency Care 2010; 26: 763–769.
the lacrimal glands via the greater superficial petrosal nerve, and they
reach the sublingual and submaxillary glands via the chorda tympani
Congential causes (Picture 1).
Birth trauma
Bell's palsy is diagnosed upon the abrupt onset of unilateral facial
Genetic syndromes
Melkerson–Rosenthal syndrome weakness or complete paralysis of all the muscles on one side of the
Albers–Schönberg disease (osteopetrosis) face, dry eye, pain around the ear, an altered sense of taste, hyperacusis
Möbiuossyndrome (hypersensitivity to sounds), or decreased tearing [11]. In patients with
Godenhar syndrome (oculoauriculovertebral dysplasia)
Bell's palsy, on attempted closure, the eye rolls upward (Bell's phenom-
Acquired causes
Infections
enon). The disease usually progresses from the onset of symptoms to
Lyme disease maximal weakness within three days.
Herpes simplex virus Various scoring systems are available to clinically assess the sever-
Otitis media ity of peripheral facial nerve palsy. The most widely applied is the
Other (human herpesvirus type 6, mumps, coxsackie virus, adenovirus)
House–Brackmann facial nerve grading system (HBS) (Table b).
Traumic
Malignancy associated Approximately 10% of patients with Bell's palsy experience one or
Hypertension associated more recurrences after a mean latency of 10 years [12].
Idiopathic (Bell's palsy) The first step in diagnosis is to determine whether facial weakness
is due to a problem in the central nervous system or one in the pe-
Bell's palsy is an idiopathic peripheral nerve palsy involving the ripheral nervous system. Central nervous system lesions (e.g. multi-
facial nerve. It accounts for 60 to 75% of all cases of unilateral facial ple sclerosis, stroke, and tumour) can also cause facial nerve palsy.
paralysis [5]. The annual incidence is 15 to 30 cases per 100,000 people However, some motor neurons to the forehead cross sides at the
[6]. level of the brainstem, so the facial nerve fibres going to the forehead
The peak incidence occurs between the second and fourth decades come from both cerebral hemispheres. Supranuclear (central) lesions
(15 to 45 years) [7]. The median age at onset is 40 years, but the dis- affecting the facial nerve will not paralyse the forehead on the affect-
ease may occur at any age [8]. Different studies have reported either a ed side, resulting in a unilateral facial paralysis with forehead sparing.
slight female preponderance [7] or that women and men are equally Brain magnetic resonance imaging (MRI) is not routinely indicat-
affected [9]. The prevalence is increased among pregnant women (43 ed, but when it is performed, the most common abnormality ob-
cases per 100,000) [9]. served is contrast enhancement of the distal intracanalicular and
The facial nerve consists of a major motor component, which sup- labyrinthine segments of the facial nerve. The geniculate ganglion
plies all the muscle of facial expression, and a small sensory branch may also be involved [13].

Picture 1. Anatomy of facial nerve.

From: Gilden DH. Clinical practice. Bell's palsy. N Engl J Med 2004; 351: 1323–31.
 A. Greco et al. / Autoimmunity Reviews 12 (2012) 323–328
Table b
House–Brackman scale grading.
From: Rath B, Linder T, Cornblath D, et al. All that palsies is not Bell's — the need to de-
fine Bell's palsy as an adverse event following immunization. Vaccine 2007; 26: 1–14.
Grade 1 — normal (100% function; measurementa: 8/8)
Normal facial function in all areas.
Grade 2 — mild dysfunction (76–99% function; measurementa 7/8)
Slight weakness noticeable only on close inspection. At rest: normal symmetry of
forehead, ability to close eye with minimal effort and slight asymmetry. No
synkinesis, contracture, or hemifacial spasm.
Grade 3 — moderate dysfunction (51–75% function; measurementa: 5/8–6/8)
Obvious but not disfiguring difference between two sides, no functional impairment;
noticeable but not severe synkinesis, contracture and/or hemifacial spasm. At rest:
normal symmetry and tone. Motion: slight to no movement of forehead, ability to
close eye with maximal effort and obvious asymmetry, ability to move corners of
mouth with maximal effort and obvious asymmetry. Patients who have obvious
but not disfiguring synkinesis, contracture, and/or hemifacial spasm are grade 3
regardless of degree of motor activity.
Grade 4 — moderately severe dysfunction (26–50% function; measurementa: 3/8–4/8)
Obvious weakness and/or disfiguring asymmetry. At rest: normal symmetry and
tone. Motion: no movement of forehead; inability to close eye completely with
maximal effort. Patients with synkinesis, mass action; and/or hamifacial spasm
severe enough to interfere with function are grade 4 regardless of motor activity.
Grade 5 — severe dysfunction (1–25% function; measurementa: 1/8–2/8)
Only barely perceptible motion. At rest: possible asymmetry with droop of corner
of mouth and decreased or absence of nasal labial fold. Motion: no movement of
forehead, incomplete closure of eye and only slight movement of lid with
maximal effort, slight movement of corner of mouth. Synkinesis, contracture,
and hemifacial spasm usually absent.
Grade 6 — total paralysis (0% function, measurementa: 0/8)
Loss of tone, asymmetry; no motion; no synkinesis, contracture, or hemifacial spasm.
a These features can be grouped under a unifying hypothesis that is
“Measurement” is determined by measuring the superior movement of the mid-
portion of the superior eyebrow and the lateral movement of the oral commissure. A
scale point of 1 is assigned for each 0.25 cm of motion up to 1 cm for both eyebrow
and commissure movement. The points are then added together. Thus, a total of
8 points can be obtained, if each structure moves 1 cm.
Liston and Kleid [14] found histologic changes in the facial nerve
that can be summarised as follows: 1) The nerve was infiltrated by
small, round inflammatory cells from the internal acoustic meatus
to the stylomastoid foramen. 2) There was a breakdown of the neuron
myelin sheaths that involved the macrophages. 3) There was an in-
crease in the spaces between the neurons, which was interpreted as
oedema. 4) The bony fallopian canal was normal, and there was no
sign of facial nerve compression by the bone of the fallopian canal.
The small round cells of lymphocytic nature and the breakdown of
myelin sheaths probably are the histologic expression of an autoim-
mune response.
The disparity of the histologic descriptions in previously reported
cases of Bell's palsy is not surprising. Bell's palsy is a clinical syn-
drome, and it is entirely possible that more than one disease entity
can produce an idiopathic facial palsy. In fact, some causes of facial
paralysis have only been recognised recently [14]. For example,
Lyme disease [15] was first recognised as a cause of facial paralysis
within the past few years.
2. Aetiology
The aetiology of Bell's palsy is unknown, but viral infection and auto-
immune disease have been postulated as possible pathomechanisms [16].
2.1. Viral hypothesis
Several features of Bell's palsy may be characteristic of a viral in-
fection [17]. These include 1) epidemicity [18], 2) a flu-like prodrome
[19], and 3) gadolinium enhancement of the facial nerve during the
acute phase of the disease on imaging of the geniculate ganglion [20].
325
Associations with several infectious pathogens, such as cytomega-
lovirus [21], Epstein–Barr virus [22], mumps [23], rubella [24] and
human immunodeficiency virus [25] have been documented. The an-
ecdotal reports do not unequivocally link these agents with the disor-
der [26]. However, for at least two infectious pathogens, the evidence
that they can and do indeed cause Bell's palsy is quite sound. These
include Borrelia burgdorferi in Lyme disease [27] and zoster virus in
Ramsay-Hunt syndrome [28,29]. There are many reports on the asso-
ciation between facial paralysis and viral infections, for example,
Varicella zoster [30–32] and herpes simplex [17].
The herpes viruses are DNA viruses with the unique ability to es-
tablish latent infections in their hosts and cause recurrent disease
by reactivation. Of the human herpes viruses, herpes simplex viruses
1 (HSV-1) and 2 (HSV-2) and Varicella zoster virus are neurotropic;
namely, they establish latent infections in the peripheral nervous sys-
tem, and the viral genome is maintained in the peripheral sensory
ganglia for the entire life of the host [33]. These peripheral sensory
ganglia are the reservoir from which the neurotropic herpes viruses
can reactivate and cause neurological and mucocutaneous disorders.
The three neurotropic herpes viruses vary in their clinical presen-
tation and differ in their molecular structure. However, they share
several features that govern the biology of their infection of the
human nervous system: 1) The primary infection involves the muco-
cutaneous surfaces, which serve as the portal of entry into the periph-
eral nervous system for the viral particles; 2) the primary and
infectious recurrent diseases caused by the same virus usually have
the same cutaneous distribution; 3) under normal (i.e., immune com-
petent) conditions, the reactivation infection usually does not spread
beyond the anatomic distribution and the vicinity of a single periph-
eral sensory ganglion.
now the dogma in herpes virology [34,35]. Following the primary in-
fection, the virus gains access to axon endings within the mucocuta-
neous surfaces and is transported to the peripheral sensory ganglia.
The viral genome is maintained within the peripheral sensory ganglia,
which serve as reservoirs for viral nucleic acids. Latent herpetic infec-
tion is a lifelong state. Under certain circumstances, the virus can
reactivate and travel to regions innervated by the respective periph-
eral sensory ganglia, causing recurrent disease there.
In Ramsey-Hunt syndrome, the acute facial paralysis is accompa-
nied with zostiform vesicles in the ear [36,37]. Varicella zoster virus
is most likely also the causative agent of Bell's palsy in a subgroup
of patients who have no cutaneous abnormality, but have serological
evidence of a Varicella zoster virus reactivation.
More convincing is recent molecular data demonstrating Varicella
zoster virus nucleic acids in the auricular skin exudates [38] and in
the peripheral mononuclear cells of patients with Bell's palsy [39].
The latter is in accordance with the identification of the Varicella zos-
ter virus genome in the peripheral mononuclear cells of patients with
zoster sine herpete [40]. Thus, Bell's palsy in a subgroup of patients
could eventually also be designated as ‘zoster sine herpete’.
In 1972, Mc Cormick hypothesised that the herpes simplex virus
(HSV) might be the causative agent of Bell's palsy [17]. The first sup-
port for this hypothesis arrived twenty years later, with studies that
identified herpes simplex virus nucleic acids in the geniculate gangli-
on [41,42].
Bell's palsy has been associated with serological evidence of an ac-
tive HSV-1 infection. HSV-1 DNA was detected during decompression
surgery in the endoneural fluids of the facial nerve in patients with id-
iopathic facial palsy [43].
When considering the possibility that HSV-1 is responsible for
Bell's palsy, several facts that do not favour this hypothesis should
be mentioned: 1) In humans, HSV-1 resides latent in the peripheral
sensory ganglia (PSG), although latency in the motor neurons has
been documented experimentally [44], and its mucocutaneous rea-
ctivations are not associated with motor impairment. 2) While
326 A. Greco et al. / Autoimmunity Reviews 12 (2012) 323–328
asymptomatic reactivations of HSV-1 and 2, namely viral shedding
without mucocutaneous disease, may take place [33], the opposite
situation (‘herpes sine herpetica’ with neurological abnormality) has
never been documented. 3) HSV-1 causes recurrent reactivations,
which raises the question of why Bell's palsy is an isolated episode
in the overwhelming majority of cases. 4) The HSV-1 genome seems
to be present in more trigeminal [45] than geniculate ganglia
[41,42], but by a factor less than the order of 1. This raises the ques-
tion of why Bell's palsy is such a rare condition when compared to
cold sores [46].
2.2. Immunological hypothesis
A cell-mediated autoimmune mechanism has been suggested as
the pathogenesis of Bell's palsy [47–49]. Aviel et al. conducted a clin-
ical study of adults and found some alterations in the lymphocyte
subsets of the peripheral blood during the acute stage of the disease
[50].
Following the description by Abramsky et al. of immune-mediated
mechanisms against the basic myelin protein in the disease's pathogen-
esis, cellular and humoural immunologic alterations have been reported
in adult patients with Bell's palsy [51]. Decreased percentages of total T
cells (CD3) and T helper/inducer cells (CD4) have been documented in
the acute phase of disease compared with control patients [52].
Some evidence implicates the involvement of immune mechanisms
in Bell's palsy. Many reports have indicated the association between fa-
cial paralysis and Guillain–Barré syndrome (GBS) [53], a condition that
was recently shown to be a cell mediated, autoimmune neuritis [54].
Abramsky et al. [47] demonstrated a defined in vitro response to a
human basic protein (P1L) of peripheral nerve myelin in patients
with Bell's palsy. They suggested that cell-mediated autoimmune
mechanisms may be of importance in the pathogenesis of Bell's palsy.
Approximately the same in vitro transformation in the presence of
P1L protein was found in cases with GBS [55]. The specific in vitro
stimulation of lymphocytes from Bell's palsy and GBS patients using
peripheral P1L basic protein suggests that an in vivo sensitisation to
such self protein may occur in these two conditions, and that
cell­mediated autoimmune mechanisms may be an important factor
in the pathogenesis of the paralysis.
The similarities between GBS and Bell's palsy with regard to the
lymphocyte sensitisation to the same P1L protein suggest that Bell's
palsy may be a variant of GBS.
The percentage of T lymphocytes was reduced in Bell's palsy patients
[56], and a reduction in the percentage of total T lymphocytes has also
been found in patients with acute Guillain–Barré syndrome [57].
In Bell's palsy patients, the percentage of T suppressor cells was
significantly reduced, whereas the percentage of T helper cells was
normal [56]. This is in line with the findings in patients with acute
Guillain–Barré syndrome [58].
Aviel et al. found that Bell's palsy patients had a significant in-
crease in the percentage of B lymphocytes and a significant decrease
in the percentage of T lymphocytes [50]. Most suggestive is the fact
that similar changes in peripheral blood lymphocyte subpopulations
were also described in the course of several demyelinating diseases,
such as in acute exacerbations of multiple sclerosis and during the
acute stage of Guillain–Barré syndrome [49,57,59].
Bell's palsy, like Guillain–Barré syndrome, is an acute demyelinating
disease of the peripheral nervous system. In both diseases, an inflam-
matory demyelination neuritis has been found. The immunological sim-
ilarities between Bell's palsy and Guillain–Barré syndrome suggest that
the diseases may share a similar aetiology and pathogenesis [50]. In
most cases, Bell's palsy is a mononeuritic variant of Guillain–Barré syn-
drome [60].
It has also been proposed that Bell's palsy is in fact a polyneuropathy,
as the facial paralysis may be associated with involvement of other cra-
nial nerves [5]. Recent decades were rich with studies concerning the
role of viruses and immune responses in the etiopathogenesis of demy-
elinating diseases of both the central and peripheral nervous systems
[61,62]. Viruses and immune mechanisms involvement have also been
proposed in Bell's palsy, suggesting that it may be caused by an autoim-
mune postviral disease [47,63].
A viral infection may be the etiologic cause of Bell's palsy and GBS.
A viral infection may prompt an autoimmune reaction against a com-
ponent of the peripheral nerve myelin, leading to the demyelination
of cranial nerves, especially the facial nerve, in a way that is not yet
clear [50].
An examination of the serum samples of patients with Bell's palsy
shows elevated concentrations of the cytokines interleukin-1 (IL-1),
IL-6, and tumour necrosis factor-alpha (TNF-alpha) compared with
control populations [64], suggesting an activation of cell-mediated
effectors.
Some authors [65] have proposed that a breakdown of peripheral
tolerance occurred in patients with hepatitis C virus infection as a
consequence of interferon (IFN)-alpha therapy, which led to aug-
mented cell-mediated immune responses. Given that the majority of
cases of uncomplicated Bell's palsy recover fully, it may be that the
main lesion is not of the nerve itself, but of the myelin sheath and
its native cell, the Schwann cell. Further, the pharmacologic doses of
IFN-alpha used may cause a failure of peripheral tolerance by stimu-
lating a pool of lymphocytes already sensitised to native Schwann
cell membrane antigens, as described previously [47]. This failure of
tolerance occurs with induced autoimmune thyroid disease, which
is more common than Bell's palsy in IFN-alpha-treated patients [65].
The appearance of Bell's palsy in children after vaccination [66,67]
supports the immunological hypothesis. Intranasal administration of
influenza vaccines may reduce the transmission of influenza more ef-
ficiently than parenteral administration because it stimulates both
mucosal and systemic immune responses [68]. Over a seven-month
period, the Swiss Drugs Monitoring Centre received 46 case reports
of Bell's palsy among flu vaccine recipients. The risk of Bell's palsy
was highest during the second month after intranasal vaccination
suggesting an immunological mechanism [69].
3. Treatment
Any evaluation must consider that 71% of untreated patients re-
cover completely, and 84% achieve near-normal function [70]. Thus,
the 20 to 30% who do not recover fully remain the focus of treatment.
In the past, the efficiency of prednisone in alleviating the disease
[71] has been attributed to its ability to reduce inflammation and oede-
ma. However, it seems logical that steroids in fact exert their beneficial
effect by means of immunosuppressive action, as in the case of some
other autoimmune disorders [72]. Therefore, it seems warranted to rec-
ommend the prednisone for patients with Bell's palsy based on findings
concerning the autoimmune aspects of this disease's pathogenesis.
Meta-analyses have compared glucocorticoids with placebo. One such
analysis showed significant improvement of facial weakness with glu-
cocorticoid therapy [73].
According to viral theory, one randomised trial with no placebo
group compared oral prednisone with acyclovir. This study indicated
that facial-muscle strength was better after treatment with predni-
sone than it was after treatment with acyclovir [74].
Although a 2004 Cochrane review found insufficient evidence to
support the use of these antivirals alone [75], two recent placebo-
controlled trials demonstrated full recovery in a higher percentage of
patients treated with an antiviral drug in combination with predniso-
lone than with prednisolone alone [76].
Prednisone is typically prescribed in a 10-day tapering course,
starting at 60 mg per day. Acyclovir 400 mg can be given five times
per day for seven days, and valacyclovir 1 g can be given three times
per day for seven days.
 A. Greco et al. / Autoimmunity Reviews 12 (2012) 323–328
Monoclonal antibodies represent the almost faster growing class
of therapeutics in autoimmunity. They offer the possibility to specifi-
cally target immunologically relevant molecules which appear critical
in the pathogenesis of peripheral nervous system autoimmune dis-
eases, like Bell's palsy. Based on theoretical grounds such approaches
appear very promising, however, the side effect profile of these drugs,
especially in long-term use, is not completely understood. As we
learned from the natalizumab trial in multiple sclerosis, severe com-
plications or worsening of symptoms, can occur after therapy has
been initiated [77,78].
Multiple sclerosis is an autoimmune disease characterized by
chronic demyelination affecting the central nervous system but usu-
ally not the peripheral nervous system, although subclinical peripher-
al nervous system involvement has occasionally been described [79].
In the past, surgical decompression within three weeks of onset
was recommended for patients with persistent loss of function. The
most common surgical complication is postoperative hearing loss.
Based on the significant potential for harms and the paucity of data
supporting benefit, the American Academy of Neurology does not
currently recommend surgical decompression for Bell's palsy [80].
Regarding indications for surgical decompression, it is unlikely that
the decompression will alter the course of viral infection or autoim-
mune reaction.
One of the greatest problems with Bell's palsy is the involvement
of the eye if the lid fissure remains open. In this case, eye care focuses
on protecting the cornea from dehydration, drying, or abrasions due
to insufficient lid closure or tearing [9]. Eye ointment is proposed dur-
ing day and night, supported by a watch glass bandage day and night.
Permanent eyelid weakness may require tarsorrhaphy or the implan-
tation of gold weights in the upper lid.
Facial asymmetry and muscular contractures may require cosmet-
ic surgical procedures or botulinum toxin (Botox) injections. In these
cases, consultation with an ophthalmologist or cosmetic surgeon is
needed [9,81].
4. Conclusions
In conclusion Bell's palsy is probably an autoimmune disease. A
viral infection may prompt an autoimmune reaction against a compo-
nent of the peripheral nerve myelin, leading to the demyelination of
the facial nerve.
Overall, the data suggest that glucocorticoids decrease the inci-
dence of permanent facial paralysis, although more studies are need-
ed to determine whether antiviral therapy confers additional benefits.
This therapeutic consideration “ex adiuvantibus” enhances the auto-
immune hypothesis. However, given the safety profile of acyclovir,
valacyclovir, and short-course oral corticosteroids, patients who pre-
sent within three days of the onset of symptoms should be offered
combination therapy.
It is to be hoped that (monoclonal) antibodies and/or T-cell immu-
notherapy might provide more specific treatment guidelines in the
management of Bell's palsy. Some cases of acute Bell's palsy result
from cell-mediated immunity against peripheral nerve antigens, but
the majority of these precise antigens have not been identified.
These results encourage further research in steroids and other immu-
notherapies for patients with Bell's palsy and related disorders [82].
Take-home messages
• Bell's palsy is an idiopathic peripheral nerve palsy involving the facial
nerve. Its etiopathogenesis includes viral infection caused by latent
herpes viruses (herpes simplex, herpes zoster) or an autoimmunity
cell-mediated reaction against a protein of the peripheral nerve mye-
lin. Bell's palsy may be a mononeuritic variant of Guillain–Barré
syndrome.
327
• Due to this disease's possible viral or autoimmune pathogenesis, a
combination therapy of antivirals and oral corticosteroids should be
administered. It is to be hoped that (monoclonal) antibodies and/or
T-cell immunotherapy might provide more specific treatment guide-
lines in the management of Bell's palsy. The role of surgical decom-
pression remains controversial, and it is not currently recommended
because of its potential for harm and the paucity of data supporting
its benefits.
References
[1] Gilden DH. Clinical practice. Bell's palsy. N Engl J Med 2004;351:1323–31.
[2] Kawiak W, Dudkowska A, Adach B. Diagnostic difficulties in etiology of the lesion
of peripheral neuron of the facial nerve during the growth from of sialoma. Ann
Univ Mariae Curie Sklodowska Med 1993;8:125–8.
[3] Peitersen E. Bell's palsy: the spontaneous course of 2,500 peripheral facial nerve
palsies of different etiologies. Acta Otolaryngol Suppl 2002;549:4–30.
[4] Wolf SR. Idiopathic facial paralysis. HNO 1998;46:786–98.
[5] Adour KK, Byl FM, Hilsinger Jr RL, Kahn ZM, Sheldon MI. The true nature of Bell's
palsy: analysis of 1,000 consecutive patients. Laryngoscope 1978;88:787–801.
[6] Morris AM, Deeks SL, Hill MD, Midroni G, Goldstein WC, Mazzulli T, et al. Annual-
ized incidence and spectrum of illness an outbreak investigation of Bell's palsy.
Neuroepidemiology 2002;21:255–61.
[7] Prescott CA. Idiopathic facial nerve palsy (the effect of treatment with steroids).
J Laryngol Otol 1988;102:403–7.
[8] Katusic SK, Beard CM, Wiederholt WC, Bergstralh EJ, Kurland LT. Incidence, clini-
cal features, and prognosis in Bell's palsy. Rochester, the Minnesota 1968–1982.
Ann Neurol 1986;20:622–7.
[9] Holland NJ, Weiner GM. Recent developments in Bell's palsy. Br Med J 2004;329:
553–7.
[10] Karens WE. Diseases of seventh cranial nerve. In: Dyck PJ, Thomas PK, Griffin JW,
Low PA, Podulso JF, editors. Pheripheral neuropathy. 3rd ed. Philadelphia:
Saunders; 1993. p. 818–36.
[11] Ahmed A. When is facial paralysis Bell palsy? Current diagnosis and treatment.
Cleve Clin J Med 2005;72:398–401.
[12] Pitts DB, Adour KK, Hilsinger Jr RL. Recurrent Bell's palsy: analysis of 140 patients.
Laryngoscope 1988;98:535–40.
[13] Sartoretti-Schefer S, Wichmann W, Valavanis A. Idiopathic, herpetic, and
HIV-associated facial nerve palsies: abnormal MR enhancement patterns. Am J
Neuroradiol 1994;15:479–85.
[14] Liston SL, Kleid MS. Histopathology of Bell's palsy. Laryngoscope 1989;99:23–6.
[15] Clark JR, Carlson RD, Sasaki CT. Facial paralysis in Lyme disease. Laryngoscope
1985;95:1341–5.
[16] Atzema C, Goldman RD. Should we use steroids to treat children with Bell's palsy?
Can Fam Physician 2006;52:313–4.
[17] Mc Cormick DP. Herpes simplex virus as a cause of Bell's palsy. Lancet 1972;1:937.
[18] Leibowitz U. Epidemic incidence of Bell's palsy. Brain 1969;92:109–14.
[19] Kynvett AF. Viral infection of the nervous system. Med J Aust 1959;2:118–21.
[20] Schwaber MK, Larson TC, Zealer DL, Creasy J. Gadolinium-enhanced magnetic reso-
nance imaging in Bell's palsy. Laryngoscope 1990;100:1264–9.
[21] Traavik T, Storvold G, Sundsfjord A, Lund S, Mair IW. Peripheral facial palsy and
coincidental cytomegalovirus infection or reactivation. Scand J Infect Dis
1983;15:233–8.
[22] Grose C, Feorino PM, Dye LA, Rand J. Bell's palsy and infectious mononucleosis.
Lancet 1973;2:231–2.
[23] Njoo FL, Werthheim-van Dillen P, Devriese PP. Serology in facial paralysis caused
by clinically presumed herpes zoster infection. Arch Otolaryngol 1988;245:230–7.
[24] Jamal GA, Al Husaini A. Bell's palsy and infection with rubella virus. J Neurol Neu-
rosurg Psychiatry 1983;46:678–80.
[25] Brown MM, Thompson A, Goh BT, Forster GE, Swash M. Bell's palsy and HIV infec-
tion. J Neurol Neurosurg Psychiatry 1988;51:425–6.
[26] Morgan M, Nathwani D. Facial palsy and infection. The unfolding story. Clin Infect
Dis 1992;14:263–71.
[27] Smouha EE, Coyle PK, Skukri S. Facial nerve palsy in Lyme disease: evaluation of
clinical diagnostic criteria. Am J Otol 1997;18:257–61.
[28] Hunt JR. On herpetic inflammation of the geniculate ganglion. A new syndrome
and its complications. J Nerv Ment Dis 1907;34:73–96.
[29] Aitkin RS, Brain RT. Facial palsy and infectious zoster virus. Lancet 1933;1:19–22.
[30] Ravin LC. Facial paralysis as a complication of chicken-pox. Am J Ophthalmol
1961;52:723–4.
[31] Peitersen E, Caunt AE. The incidence of herpes zoster antibodies in patients with
peripheral facial palsy. J Laryngol 1970;84:65–70.
[32] Tomita H, Hayakawa W, Hondo R. Varicella-zoster virus in idiopathic facial palsy.
Arch Otolaryngol 1972;95:364–8.
[33] Steiner I. Human herpes viruses latent infection in the nervous system. Immunol
Rev 1996;152:157–73.
[34] Goodpasture EW. Herpetic infections with special reference to involvement of the
nervous system. Medicine 1929;8:223–43.
[35] Hope-Simpson RE. The nature of herpes zoster: a long term study and a new hy-
pothesis. Proc R Soc Med 1965;58:9–20.
[36] Tomita H, Tanaka M, Kukimoto N, Ikeda M. An ELISA study on Varicella-zoster virus
infection in acute peripheral facial palsy. Acta Otolaryngol 1988;446:S6–S10.
328 A. Greco et al. / Autoimmunity Reviews 12 (2012) 323–328
[37] Morgan M, Moffat M, Ritchie L, Collacott I, Braun T. Is Bell's palsy a reactivation of
Varicella zoster virus ? J Infect 1995;30:29–36.
[38] Murakami S, Honda N, Mizobuchi M, Nakashiro Y, Hato N, Gyo K. Rapid diagnosis
of varicella zoster virus infection in acute facial palsy. Neurology 1998;51:1202–5.
[39] Terada K, Niizuma T, Kawano S, Kataoka N, Akisada T, Orita Y. Detection of
Varicella-zoster virus DNA in peripheral mononuclear cells from patients with
Ramsey Hunt syndrome or zoster sine herpete. J Med Virol 1998;56:359–63.
[40] Gilden DH, Dueland AN, Devlin ME, Mahalingam R, Cohrs R. Varicella-zoster virus
reactivation without rash. J Infect Dis 1992;166(Suppl. 1):S30–4.
[41] Takasu T, Furuta Y, Sato KC, Fukuda S, Inuyama Y, Nagashima K. Detection of la-
tent herpes simplex virus DNA and RNA in human geniculate ganglia by the poly-
merase chain reaction. Acta Otolaryngol 1992;112:1004–11.
[42] Schulz P, Arbusow V, Strupp M, Dieterich M, Rauch E, Brandt T. Highly variable
distribution of HSV-1 specific DNA in human geniculate, vestibular and spiral
ganglia. Neurosci Lett 1998;252:139–42.
[43] Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell's palsy
and herpes simplex: identification of viral DNA in endoneural fluids and muscle.
Ann Intern Med 1996;127:27–30.
[44] Dobson AT, Margolis TP, Sedarati F, Stevebs JG, Feldman LT. A latent, nonpatho-
genic HSV-1 derived vector stably expresses beta galactosidase in mouse neurons.
Neuron 1990;5:353–60.
[45] Steiner I, Spivack JG, O'Boyle DR, Lavi E, Fraser NW. Latent herpes simplex virus
type 1 transcription in human trigeminal ganglia. J Virol 1988;62:3493–6.
[46] Whitley RI. Epidemiology of herpes simplex viruses. In: Roizman B, editor. The
herpes viruses, vol. 3. New York: Plenum Publishing; 1985. p. 1–44.
[47] Abramsky O, Webb C, Teitelbaum D, Arnon R. Cellular immune response to pe-
ripheral nerve basic protein in idiopathic facial paralysis (Bell's palsy). J Neurol
Sci 1975;26:13–20.
[48] Mc Govern FH, Estevez J, Jackson R. Immunological concept for Bell's palsy: fur-
ther experimental study. Ann Otol Rhinol Laryngol 1977;86:300–5.
[49] Mulkens PS, Bleeker JD, Schroeder FP. Acute facial paralysis: a virological study.
Clin Otolaryngol 1980;5:303–9.
[50] Aviel A, Ostfeld E, Burstein R, Marshak G, Bentwich Z. Peripheral blood T and B lym-
phocyte subpopulations in Bell's palsy. Ann Otol Rhinol Laryngol 1983;92:187–91.
[51] Mañós-Pujol M, Buendia E, Mestre M, Jimenéz R, Gil E, Menén JP, et al. Cellular im-
munity abnormalities in patients with recurrent Bell's palsy. Clin Otolaryngol
1987;12:283–7.
[52] Gorodezky C, Carranza JM, Bustamante A, et al. The HLA system and T-cell subsets
in Bell's palsy. Acta Otolaryngol 1991;111:1070–4.
[53] Charous DI, Saxe BI. The Landry Guillain Barré syndrome. Report of an unusual
case, with a comment on Bell's palsy. N Engl J Med 1962;267:1334–8.
[54] Abramsky O, Webb C, Teitelbaum D, Arnon R. Cell-mediated immunity to neural
antigens in idiopathic polyneuritis and myeloradiculitis. Clinical–immunological
classification of the nervous system autoimmune demyelinating disorders. Neu-
rology 1975;25:1154–9.
[55] Vedeler C, Nyland H, Matre R. Antibodies to peripheral nerve tissue in sera from
patients with acute Guillain Barré syndrome demonstrated by a mixed
haemagglutination technique. J Neuroimmunol 1982;2:209–14.
[56] Vedeler CA, Matre R, Nyland H, Moller P. Immunoglobulins, complement compo-
nents and lymphocyte subpopulations in Bell's palsy. Eur Neurol 1986;25:177–82.
[57] Nyland H, Naess A. Lymphocytes subpopulations in blood and cerebrospinal fluid
from patients with acute Guillain–Barré syndrome. Eur Neurol 1978;17:247–52.
[58] Hughes R, Aslan S, Gray I. Lymphocytes subpopulations and suppressor cell activ-
ity in acute polyradiculoneuritis (Guillain–Barré syndrome). Clin Exp Immunol
1983;51:448–54.
[59] Lisak RP, levinson AI, Zweiman B, Abdou NI. T and B lymphocytes in multiple scle-
rosis. Clin Exp Immunol 1975;22:30–4.
[60] Chaco J. Subclinical pheripheral nerve involvement in unilateral Bell's palsy. Am J
Phys Med 1973;52:195–7.
[61] Weiner LP, Johnson RT, Herndon RM. Viral infections and demyelinating diseases.
N Engl J Med 1973;288:1103–9.
[62] Lampert PW. Autoimmune and virus induced demyelinating diseases. Am J Pathol
1978;91:176–208.
[63] Mc Govern FH, Estevez J. The concept of Bell's palsy as an immunologically medi-
ated disease. In: Shambaugh GE, Shea JJ, editors. Proceedings of the Shambaugh
Fifth International Workshop on Middle Ear Microsurgery and Fluctuant Hearing
Loss. Huntsville, Ala: The Strode Publishers; 1976. p. 229–32.
[64] Yilmaz M, Tarakcioglu M, Bayazit N, Bayazit YA, Namiduru M, Kanlikama M.
Serum cytokine levels in Bell's palsy. J Neurol Sci 2002;197:69–72.
[65] Hoare M, Woodall T, Alexander GJ. Bell's palsy associated with IFN-alpha and riba-
virin therapy for hepatitis C virus infection. J Interferon Cytokine Res 2005;25:
174–6.
[66] Maning JJ, Adour KK. Facial paralysis in children. Pediatrics 1972;49:102–9.
[67] Martin GI, Weintraub MI. Brachial neuritis and seventh nerve palsy. A rare hazard
of DPT vaccination. Clin Pediatr 1973;12:506–7.
[68] Mc Neela EA, Mills KHG. Manipulating the immune system: humoral versus
cell-mediated immunity. Adv Drug Deliv Rev 2001;51:43–54.
[69] Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, et al. Use of the
inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland.
N Engl J Med 2004;350:896–903.
[70] Adour KK, Wingerd J. Idiopathic facial paralysis (Bell's palsy): factors affecting se-
verity and outcome in 446 patients. Neurology 1974;24:1112–6.
[71] Adour KK, Wingerd J, Bell DN, Maning JJ, Hurley JP. Prednisone treatment for idi-
opathic facial paralysis (Bell's palsy). N Engl J Med 1972;287:1268–72.
[72] Gabrielsen AE, Good RA. Chemical suppression of adaptive immunity. Adv
Immunol 1967;6:91–229.
[73] Williamson IG, Whelan TR. The clinical problem of Bell's palsy: is treatment with
steroids effective? Br J Gen Pract 1996;46:743–7.
[74] De Diego JI, Prim MP, De Sarria MJ, Madero R, Gavilan J. Idiopathic facial paralysis:
a randomized, prospective, and controlled study using single dose prednisone
versus acyclovir three times daily. Laryngoscope 1998;108:573–5.
[75] Allen D, Dunn L. Aciclovir or valaciclovir for Bell's palsy (idiopathic facial paraly-
sis). Cochrane Database Syst Rev 2004(3):CD001869.
[76] Hato N, Yamada H, Kohno H, Matsumoto S, Honda N, Gyo K, et al. Valacyclovir and
prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-
controlled study. Otol Neurotol 2007;28:408–13.
[77] Kieseier BC, Lehmann HC, Horste GM. Autoimmune diseases of the peripheral ner-
vous system. Autoimmun Rev 2012;11:191–5.
[78] Selmi C, Mix E, Zettl UK. A clear look at the neuroimmunology of multiple sclerosis
and beyond. Autoimmun Rev 2012;11:159–62.
[79] Kamm C, Zettl UK. Autoimmune disorders affecting both the central and periph-
eral nervous system. Autoimmun Rev 2012;11:196–202.
[80] Grogan PM, Gronseth GS. Practice parameter: steroids, acyclovir, and surgery for
Bell's palsy (an evidence-based review): report of the Quality Standards Subcom-
mittee of the American Academy of Neurology. Neurology 2001;56:830–6.
[81] Bulstrode NW, Harrison DH. The phenomenon of the late recovered Bell's palsy:
treatment options to improve facial symmetry. Plast Reconstr Surg 2005;115:
1466–71.
[82] Hughes GB, Barna BP, Kinney SE, Goren H, Sweeney PJ, Valenzuela R, et al. Im-
mune reactivity in Bell's palsy. Otolaryngol Head Neck Surg 1986;95:586–8.