Acquired bilateral facial palsy: a systematic review on aetiologies and management

Bilateral facial paralysis (BFP) is a rare entity, representing 0.3−2% of all facial palsies. It occurs in both paediatric and adult patients and can have a congenital or acquired cause among neurologic, idiopathic, infectious, neoplastic, traumatic, iatrogenic or metabolic disorders [1]. Simultaneous palsy is defined as the involvement of the opposite side within 30 days from the onset of the first side, whereas recurrent alternated palsy is referred to a contralateral facial palsy coming later than 30 days as the first involved hemi-face [2].

In contrast with unilateral facial palsy, in the majority of BFP cases it is possible to define the etiology and, given the severity of some diseases presenting with BFP and their potential benefit from specific treatment, it is mandatory to set up a correct differential diagnosis. BFP represents an extremely disabling condition for the patient, whose specific and timely treatment may significantly increase the chance of recovery.

Several case reports and case series of BFP have been reported in the literature, with extremely variable aetiologies. However, a comprehensive review regarding epidemiology, clinical presentation, diagnostic flowchart, treatment strategies and prognosis of this entity is lacking.

The aim of this study was to systematically review the published cases of BFP to gather evidence on the clinical assessment and management of this disabling pathology. An algorithm for the differential diagnosis and treatment of BFP is also provided to support healthcare practitioners from different fields in the management of these patients, with the aim of reducing misdiagnosis and increasing the chance of recovery through appropriate treatment.

This systematic review was conducted following the PRISMA statement recommendations [3]. The following search string was run on PubMed, Scopus, Medscape, Ovid databases: (infectious[All Fields] OR autoimmune[All Fields] OR acquired[All Fields] OR neoplastic[All Fields] OR traumatic[All Fields] OR metabolic[All Fields]) AND (bilateral[All Fields] OR (recurrent[All Fields] AND contralateral[All Fields])) AND ("facial paralysis"[MeSH Terms] OR ("facial"[All Fields] AND "paralysis"[All Fields]) OR "facial paralysis"[All Fields] OR ("facial"[All Fields] AND "palsy"[All Fields]) OR "facial palsy"[All Fields]).

After running the above search string in January 2023 and duplications removal, the 338 titles and abstracts obtained were screened independently by two of the authors (MG, LF), who subsequently met and discussed disagreements on citation inclusion. Inclusion criteria for citations were research articles of human patients affected by BFP, either central or peripheral; English, Italian, French, or Spanish language; availability of the abstract. Exclusion criteria were topics unrelated to facial palsy, and mention of unilateral or congenital facial palsy.

Afterwards, the full-text articles identified underwent a second screening by the same two authors. Full texts were considered regardless of their study design, in order not to miss any relevant data, and were included if BFP cases were confirmed. Types of BFP included in this review were: simultaneous bilateral palsy, defined as the development of facial palsy involving the initially spared side within four weeks after onset of first-side palsy (with the paralysis not necessarily being sudden or complete on both sides), and recurrent alternating palsy, consisting in recurrence of palsy involving the opposite side (at least one episode on one side and one episode on the opposite side, in the same patient) [2, 4].

Both treated and untreated patients were included for the data analysis. Articles reporting information on a previously published case series or whose full-text versions were not available were excluded. A further manual check of the references included in the articles was performed and the final number of articles included in the present review was defined. The flowchart of the selection process is described in Fig. 1.

The general results regarding information on patient's characteristics, clinical presentation and aetiology were extracted from the articles and recorded on an Excel database.

After the review of the included studies, only full-text articles reporting the diagnostic work-up, the management, and the prognosis (complete, partial or no recovery) of the facial paralysis for each patient were considered for further specific data analysis. Regarding the grade of facial palsy, the highest grade reached throughout the clinical course was reported as facial score at clinical presentation. There was no funding source for this study.

BFP is an extremely rare clinical finding for a physician. Incidence rate of Bell’s palsy has been estimated around 23–25 per 100.000 persons per year [6, 7] with the rate of simultaneous BFP being about 0.3–2.0% of the total [8]. This condition can often benefit from specific treatment if a proper diagnostic work-up is followed. An aetiological diagnosis was formulated in more than 80% of BFP cases, according to the present review. On the contrary, in unilateral facial palsy (UFP) the vast majority of causes remains unknown, defining this pathology as idiopathic or Bell’s palsy (60–75% or UFP cases [9]). Another difference is the sex prevalence, with males outnumbering females in BFP [10]. However, other characteristics such as age presentation are not different when compared to UFP, which also has a peak incidence between the second and fourth decades [10].

As far as aetiology is concerned, according to the analysed literature, the Authors suggest a modification of the classification by Price T et al. [11], including a total of 9 categories, namely in decreasing order of prevalence: autoimmune, infectious, traumatic, idiopathic, miscellaneous, neoplastic, iatrogenic, metabolic and vascular.

Autoimmune BFP constitutes the most frequent aetiology. This category includes different entities, such as vasculitis (i.e. Wegener granulomatosis), Sjogren’s syndrome, Guillain–Barré syndrome (GBS), Melkersson–Rosenthal syndrome, etc.…Other autoimmune pathologies have a less evident clinical presentation, and the diagnosis may require time, in these cases help comes from autoimmune laboratory tests. For example, particularly difficult is the diagnosis of Melkersson–Rosenthal syndrome, which requires a labial or cheek biopsy during granulomatous phase. Sarcoidosis is an immune-mediated pathology with formation of non-necrotizing granulomas that can affect every organ or tissue. Diagnosis is generally difficult given the variability of clinical presentations and symptoms [12].

Infectious BFP represent the second most frequent etiological category, with the commonest infectious agent being Borrelia burgdorferi which causes Lyme’s disease, followed by HIV and HEV. Less common agents are viruses as HSV, JEV and enterovirus, bacteria as Clostridium botulinum, Ehrlichia chaffeensis, Leptospira interrogans, Micobatterium Tubercolosis or fungi as Cryptococcus and Toxoplasma genus.

Recently, few case reports described a BFP onset after COVID-19 infection or vaccination. Andreozzi et al. [13] described two cases of BFP with paresthesias, both occurring after the first dose of COVID-19 vaccine Vaxzevria^™, with favorable outcome. The Authors considered the bilateral palsy as a consequence of a GBS. Moreover, five case reports on BFP during COVID-19 infection, were described: two were considered as bilateral Bell’s palsy after COVID-19 [14, 15] in one a mixed infection with COVID-19 and EBV was detected [16] the last two were thought to be variants of GBS [17, 18].

Traumatic BFP is the easiest to evaluate, being the history of head trauma the main element that leads to diagnosis together with other cranial nerves palsy and neurological damages.

Neoplastic pathologies represent only 5% of all cases included by present review, the most common causing pathologies being leukaemia and lymphoma (65% of all neoplastic causes). Therefore, brain MRI for detection of solid neoplasm or meningeal involvement, a complete blood count and blood smear, and sometimes a CSF analysis, must be performed to rule out neoplastic aetiology.

Idiopathic aetiology represents only 16% of the analysed cases, even if the frequency of idiopathic BFP may be even lower.

The flow-chart (Fig. 2) on the work-up of BFP conveys the findings from this literature review, in an attempt to guide physician from any medical field to correctly frame the patient presenting with BFP and possibly increase the chance of recovery through the prompt delivery of the appropriate treatment. Several possibilities regarding the diagnosis can be speculated by careful collection of the medical history, particularly regarding other symptoms onset, which are frequent in BFP. First, the diagnosis of iatrogenic BFP is straightforward and an accurate patient history with previous medical data review is sufficient to lead to diagnosis. Second, the patient should be asked regarding recent head trauma. In this case, after head CT including temporal bone and temporo-mandibular joints, both ENT and neurologic evaluations must be performed. In doubtful cases or in case of additional neurological symptoms, attention should be paid to the intracranial compartment, by performing a brain MRI.

Patients without a history of head trauma or iatrogenic BFP, must be interviewed about recent travels, risky behaviours, tick bite, autoimmune, previous known autoimmune, metabolic and oncologic disorders. Afterwards, a complete physical exam, blood tests and autoimmune tests should be performed in all cases. If neurological signs and symptoms are present, neurology consultation is needed and CSF analysis required according to the specialist consultation. Serology for common infectious diseases that can cause BFP (see Table 1) should be ruled out in all patients and if infectious screening is positive, proper medical treatment must be administered. ENT consultation is recommended in all cases especially to investigate vestibulo-cochlear function.

Since some pathologies (such as neoplasm or temporal bone infections) may present with rapidly progressive symptoms and lead in short time to a poor prognosis, in our opinion it is necessary to perform all cited exams in all patients with no associated or nonspecific symptoms. When all the above-mentioned work up is inconclusive, before diagnosing a BFP as idiopathic, we suggest performing at least a contrast-enhanced brain MRI, which could exclude neoplastic or vascular disorders. A better understanding of the causes leads to a high rate of recovery from BFP (complete bilateral recovery in more than 60% of cases, with most patients improving within 3 months from the palsy onset).

BFP treatment strictly depends on correct diagnosis. Infectious causes may benefit from antibiotics or antivirals, Bell palsy or autoimmune causes may need steroids or Immunoglobulins. Additionally, regardless of specific aetiology, physical therapy by a speech therapist or a physiotherapist can be effective in helping patients to recover strength and relearn specific movements such as eye closure and smile, limiting long term impairment such as the development of synkinesis. When paralysis is congenital or results from physical disruption (i.e., traumatic or iatrogenic) of the facial nerve, or when conservative treatment fails, surgical intervention may be warranted. The dominant concern in upper facial paralysis is impaired eye closure, which can predispose the eye to corneal exposure and threaten vision. In the lower face, loss of oral competence and the ability to smile are primary concerns. Notably, the role of facial nerve decompression in acute stages for patients with complete idiopathic or posttraumatic paralysis (e.g., in Bell palsy and Melkersson–Rosenthal syndrome) is gaining increasing importance [19].

This review is not without limitations. First, literature is scarce of large cohorts of BFP patients, most published cases are case reports, with few retrospective case series usually limited to one specific aetiology. Moreover, studies frequently do not report the length of follow-up and the time between onset and best recovery grade of facial function. Also, there is a lack of data regarding the grading of BFP, both at the onset and at follow-up. Parallel to this, even when reported, the scoring systems used were not uniform. Considering the need for a common language between authors, to compare different studies and patients, the Authors suggest that facial function should always be graded through one, or better two, international grading systems, such as the House–Brackmann grading system and the Sunnybrook grading system [20].

BFP is a disturbing condition for the affected patient and contrary to UFP, it is generally attributable to a specific cause. Associated aetiologies are various and differential diagnosis is challenging. If a correct diagnosis is formulated, possibilities to recover are elevated and directly correlated to the initiation of appropriate treatment. Physicians should rule out all possible causes before claiming a BFP as idiopathic.