INTRODUCTION
Acute motor deficit affecting the same-sided upper and lower face muscles occur in patients with Bell’s palsy, maximum within the first three days. Symptoms such as retro-auricular pain and ipsilateral face numbness are common (Prud’hon & Kubis 2018). Around 75% of patients can recover completely on their own; however, if oral corticotherapy is started within the first 72 hours, this rate can be increased. Adding an antiviral treatment has yet to be shown to be beneficial (Prud’hon & Kubis 2018).
Bell’s palsy has been classically described to result in solitary unilateral facial nerve palsy manifested as one-sided facial weakness or paralysis (Tiemstra & Khatkhate 2007). Since the facial nerves also carry parasympathetic innervation to salivary glands and the lacrimal, secretions of tear as well as saliva are impaired on the affected side, resulting in dry eyes and dry mouth (De Seta et al. 2014). Nevertheless, patients may experience excessive lacrimation and pooling of the saliva on the affected side, due to loss of eyelid control and weakness of buccinator muscle (Tiemstra & Khatkhate 2007). The incidence of dry mouth resulting from reduced salivation from submandibular and sublingual glands is prognostic for a severe grade of paralysis in Bell’s palsy (De Seta et al. 2014). Furthermore, because the chorda tympani branch of the facial nerve is involved in idiopathic Bell’s palsy, there is a significant frequency of changed taste (De Seta et al. 2014; Tiemstra & Khatkhate 2007). Patients with facial nerve palsy have also been seen to develop paralysis of the stapedius muscle, which is innervated by the facial nerve’s stapedial branch. Hypersensitivity to low-frequency sounds, also known as hyperacusis, may consequence as result from this (Heckmann et al. 2019).
At least 8% of the time, Bell’s palsy appears to be linked to cranial nerve polyneuritis (Benatar & Edlow 2004). It’s worth noting that a small but significant number of Bell’s palsy patients also have additional cranial nerve problems. All Bell’s palsy patients who presented to an emergency room over a two-year study period were evaluated. A total of 51 patients took part in the research (Benatar & Edlow 2004). Extracranial neuropathies were found in four of the individuals. Other cranial nerve involvement should never be assumed to be a symptom of Bell’s palsy; therefore, it should always be studied further.
MATERIALS AND METHODS
Study Objective
International Platform of Registered Systematic Review and Meta-analysis (INPLASY) (Registration Number: INPLASY202160111) was used to register this study. In addition to the facial nerve, this study seeked to explore other cranial nerve(s) co-involvement in Bell’s palsy in a clinical case setting.
Study Identification
Five electronic databases, namely CINAHL, Academic Search Complete, MEDLINE, SPORTDiscus, and Scopus, were used to conduct a full systematic search. The initial searches were performed on 13th February 2020 and updated on 10th May 2021. The development of keywords arose from a discussion among authors and a review of existing works of literature (Adour et al. 1978; Benatar & Edlow 2004). The following keywords were used in the research: “Bell palsy” OR “Bell’s palsy” OR “Facial Paralysis” OR “Cranial nerve palsy” OR “Facial nerve palsy” OR “Idiopathic nerve palsy” OR “Facial nerve paralysis” OR “Facial palsy” AND “Oculomotor nerve” OR “Trochlear nerve” OR “Abducens nerve” OR “Extraocular muscle” OR “Trigeminal nerve” OR “Mandibular nerve” OR “Olfactory nerve” OR “Optic nerve” OR “Vestibulocochlear nerve” OR “Glossopharyngeal nerve” OR “Vagus nerve” OR “Accessory nerve” OR “Hypoglossal nerve” AND “simultaneous” OR “concurrent” OR “coincid*” OR “concomitant” OR “involve*” OR “associat*” OR “connect*” OR “includ*” AND “human” OR “People” OR “homo sapiens” OR “patient*” OR “man” OR “men” OR “wom?n” AND NOT “animal*” OR “rabbit*” OR “mice” OR “mouse” OR “rat” OR “rabbit*” OR “monkey*” OR “pig*” OR “primate*” OR “dog*” OR “canine” OR “veterina*”. Boolean operator, and other commands such as truncation, wildcards, exact and parenthesis were used whenever appropriate.
The reference list of the included study was screened manually via manual searches. Each of the discovered cases were cross-check for the availability of the original report. The screening process for eligibility was then performed after relevant citations were chosen.
Eligibility Criteria
The following inclusion and exclusion requirements, as developed by discussion among the authors, were applied to each retrieved study to determine its eligibility. The inclusion criteria were as follows: (i) any study investigating Bell’s palsy; (ii) study in humans; and (iii) involvement of any cranial nerve(s). The final criterion was established by examining the other cranial nerve(s) that were discovered concurrently with Bell’s palsy. The exclusion criteria were as follows: (i) animal studies; (ii) investigate nerve(s) other than cranial; (iii) intervention analysis; (iv) full text not available in English; (vi) grey literature (thesis, conference, book), and (vii) no full text available.
Study Selection
Duplicates were eliminated before the screening process. The first author (RA) assessed each title for eligibility according to the predefined criteria, followed by an independent screening of the abstract and full text by all authors (RA, AA, MAK, WKH, SNHH, CKW, NFMN and MHR). The assigned authors double-checked all of the full texts. Any disagreements between the writers’ decisions were resolved through discourse until an agreement was reached.
Data Extraction and Analysis
A narrative review of the articles was used in the final analysis. The research objectives, study design, clinical case setting, findings, cranial nerve(s) involved, and limitations were extracted from each paper and tabulated into a table. Cranial nerves other than the 7th were then identified during its clinical setting, which was based on the presenting symptoms and signs.
Quality Appraisal of the Study
The quality of screened articles was evaluated using the Joanna Briggs Institute Manual for Evidence Synthesis (Moola et al. 2017). Only case studies/reports, case series and case-control were found; therefore, quality evaluation forms for the two designs were selected. The case report evaluation form consists of eight items, while the case series and case-control were evaluated using the same evaluation form, which consisted of 10 items. For both forms, each item was rated either ‘YES’, ‘NO’, or ‘UNSURE’. There was no total score calculated and each item was reported independently. At the end of the appraisal, overall evaluation was performed either to include, exclude or seek further info. RA and MHR administered quality assessments independently, which were then verified through discussion.
For the evidence of quality in this systematic review, Sackett’s hierarchy levels of evidence (Sackett 1989) was used. The evidence hierarchy has five levels: Level I (strong)-large randomized controlled trial with the clear cut result; Level II (moderate)-small RCT, other controlled trials; Level III (moderate)-cohort and case-control study; Level IV (weak)-case series or case-control study; and Level V (weak)-case report, studies with no control. Each study was classified into the hierarchy level based on the design. The use of evidence level is valid and useful to guide research application and indicates the trust and credibility of the evidence to be accepted in practice (Burns et al. 2011).
RESULTS
A total of 3883 articles were found, with 3860 found via electronic database searches and another 23 from the reference lists of the included studies, plus a list of related literature discovered using Google Scholar’s “cited by” feature. After identifying duplication, 2434 publications were rejected, and only 13 individual studies were chosen after the screening procedure, as shown in Figure 1. Table 1 contains a description of each included individual study, as well as its relation to the cranial nerve(s). All research was categorised using Sackett’s hierarchy levels of evidence, with each categorization following the year of publication in ascending order.
The Joanna Briggs Institute Manual for Evidence Synthesis was used to assess the quality of individual research, and the results are provided in Table 2. All articles that were chosen were grouped in the “included” section. Even though a few components had no ‘YES’ ratings, such as identifying adverse effects and reporting demographic information from the clinical presentation sites, most of the articles had clear clinical information, clear demographic characteristics, similar exposures to patients and controls, and acceptable statistical analysis, indicating high-quality literature.
Based on Sackett level of evidence, two case-control studies were categorized at Level III (Table 1) (McCandless & Schumacher 1979; Tawfik et al. 2015). The study demonstrated the enlargement of the vagus nerve in the symptomatic group compared to the healthy group by using neuromuscular ultrasound, even though this was insignificant. Nevertheless, the use of neuromuscular ultrasound as a tool for facial nerve assessment in this study was found to have low sensitivity. Moreover, evidence for the validity of the neuromuscular ultrasound -particularly the reliability and relations to other variables – were not established. Hence, further studies were required to provide the longitudinal measurements of the facial nerve parameters to confirm the findings. Furthermore, the involvement of the vestibulocochlear nerve was observed in standard audiologiy case-control studies of Bell’s palsy patients.
Furthermore, eight studies were identified as Level IV. An ocular electromyographic evaluation was conducted to substantiate the clinical results of an aberration in the Bell’s manifestation in amyotrophic lateral sclerosis revealing the involvement of the oculomotor nerve (Esteban et al. 1978). In addition, a disruption in voluntary oculopalpebral motions was discovered in a few patients.
With occurrences ranging from 5% to 20% of cases, auditory disorders with indications of idiopathic facial paralysis were common (Edstrom et al. 1984). In some cases, hearing function disturbance resulting from the impairment of the stapedius muscle and due to central origin causes, vestibulocochlear nerve palsy (Welkoborsky et al. 1991). Another study reported pathological auditory-evoked brain-stem responses (ABRs) in 20% of Bell’s palsy patients (Rosenhall et al. 1983). In addition, five articles showed involvement of six cranial nerves: optic, trigeminal, vestibulocochlear, glosopharyngeal, vagus and hypoglossal nerve (Adour et al. 1978; Benatar & Edlow 2004; Hanner et al. 1987a; Lee et al. 2011; Maller et al. 2018).
Finally, three studies were categorized under Level V. Of these, two case reports (Lagman et al. 2016; Shaikh et al. 2000) showed involvement of trigeminal and vestibulocochlear nerve during the incidence of Bell’s phenomenon. Interestingly, both studies were using MRI to delineate the cranial nerve(s) involvement. The other case report study exhibited single cranial nerve involvement (trigeminal nerve) in a patient with painful tic convulsion following ipsilateral Bell’s palsy (Jiao et al. 2013).
DISCUSSION
This review shows that in Bell’s palsy, lower motor neuron palsy of the facial nerve coexists with other cranial neuropathies (Holland & Weiner 2004). Although Bell’s palsy is classified as a mononeuropathy condition, clinical and epidemiologic reviews suggested that this condition is often presented with a myriad of clinical features that reflect mononeuritis multiplex or cranial polyneuritis (Holland & Weiner 2004; Adour et al. 1978). Distinguishing between polyneuropathy and facial nerve mononeuropathy in Bell’s palsy is crucial, as these have implications for identifying the aetiology, developing a management plan, and determining the prognosis of the disease (Zhang et al. 2019; Lee & Lew 2019). It is important to generate an accurate diagnosis of unilateral facial paralysis as Bell’s palsy, because this condition is benign, and may not require active intervention to resume the function of facial muscles (Brach & Vanswearingen 1999). On the other hand, other differential diagnoses such as cranial base and parotid gland tumours, which can also produce unilateral facial paralysis, require early detection and intervention, as these conditions may jeopardize the functions of facial and other cranial nerves permanently (Brach & Vanswearingen 1999).
Nonetheless, other cranial nerves were shown to be involved in this study, namely optic, oculomotor, trigeminal, vestibulocochlear, glossopharyngeal, vagus, and accessory nerves, in Bell’s palsy cases. The patient diagnosed with acute myeloid leukaemia (AML) showed unilateral facial palsy with involvement of bilateral optic nerve in Lee et al. (2018). Furthermore, oculomotor function was affected by the alteration of Bell’s phenomenon affected in patients with ALS (Esteban et al. 1978). Patients presented with either unstained upward displacement of the eyeballs upon closing the eyelids, absence of upward displacement of the eyeball or downward displacement of the eyes, a phenomenon of three degrees of altered Bell’s. Hence, to rule out the 3rd cranial nerve involvement, an electromyographic assessment of oculomotor function may be required.
Inflammation of the geniculate ganglion of the facial nerve is one of the recent postulations of Bell’s palsy, which results in ischemia and demyelination of the nerve (Tiemstra & Khatkhate 2007). However, studies have shown that Bell’s palsy patients with trigeminal dysfunction displayed evidence of brainstem involvement indicating central nervous system affection (Hanner et al. 1986). Likewise, central nervous system involvement was also reported in a patient with Bell’s palsy with concurrent bilateral visual loss, which was due to the optic nerve infiltration by malignant cells (Lee et al. 2018). It was also noted that Bell’s palsy patients with ophthalmic clinical conditions such as paralytic strabismus, diplopia, nystagmus, and limited extraocular muscles, had involvement of oculomotor, trigeminal, and trochlear nerve (Lee & Lew 2019). This polyneuropathic condition worsened the prognosis of the ophthalmic sign, and thus required special attention and management by the ophthalmologist (Lee & Lew 2019). Furthermore, the incidence of hyperacusis in Bell’s palsy is commonly related to the involvement of the vestibulocochlear nerve, as some of the auditory fibres that are in proximity with the facial nerve are susceptible to changes in tone frequency (Lee & Lew 2019). This condition was in agreement with a finding of a previous study that reported smaller diameters and cross-sectional areas of the internal acoustic meatus – which was traversed by both facial and vestibulocochlear nerves – of the affected compared to the unaffected sides in Bell’s palsy patients (Yilmaz et al. 2015). Acoustic reflexes are absent or abnormal in the majority of auditory nerve injuries.
Bell’s palsy may occur as a result of reactivation of the herpes simplex virus (HSV) in acute benign cranial polyneuritis. In the cross-sectional study by Adour et al. (1978), the incidence of motor cranial nerve dysfunction (V and IX) was found to be attributable to inflammation and demyelination rather than ischemic compression. According to the findings of spinal fluid research, the condition appears to be a central nervous system phenomenon with secondary peripheral neural symptoms. The HSV may migrate to the chorda tympani in the geniculate ganglion via sensory neuron axon.
Furthermore, the majority of individuals with facial palsy complained of face skin irritation in the acute stage. Several patients’ facial feelings had returned to normal when they were evaluated a few days later (Hanner et al. 1987b). The presence of sensory nerve fibres within the face of the skin may be an early component of the formation of facial nerve paresis could explain the temporary symptoms. However, as we discovered in our literature search, the most plausible explanation was caused by trigeminal nerve engagement. Clinical and neurophysiologic evidence backs this up. The facial discomfort, on the other hand, diminished as the facial nerve disease progressed (Hanner et al. 1987b). Other tests to elicit other cranial nerve involvement include corneal reflex, vibration sense test, skin pin-prick test, and fundoscopic examination.
Besides, in patient with acute unilateral peripheral facial palsy, trigeminal dysfunction occurred as evidenced by the trigeminus-evoked potential test (TEP) and blink reflex test (BR), which are suggestive of trigeminal pathology with brainstem involvement and multifocal lesions (Hanner et al. 1986). The blink reflex test gives information on trigeminal and facial nerve functions in addition to electroneuronography (ENoG) results (Lee et al. 2011). This research suggests that in Bell’s palsy, facial nerve dysfunction may be accompanied by subclinical trigeminal nerve involvement. Furthermore, the authors determined the severity and the extent of nerve involvement in Bell’s palsy (Hanner et al. 1987b). Five individuals had an abnormal audiometry brainstem response (ABR), indicating that they had neuropathy in both the central auditory system and the facial tracts. This is in line with the findings of McCandless & Schumacher (1979). Patients with idiopathic facial paralysis due to a facial nerve injury proximal to the stapedius branch experienced the following clinical manifestations: (i) a decrease in loudness tolerance; (ii) a reduction in speech discrimination at high intensities; and (ii) an excessive increase in loudness as sound intensity increases.
In addition, 19 patients had aberrant ABR patterns due to high-frequency hearing loss alone (20.4%). Nevertheless, cochlear lesions have various clinical signs which are relatively non-specific. Audiometry brainstem response audiometry should be conducted on both ears within 6 weeks of the onset of the condition. Pure-tone and speech audiometry, as well as impedance audiometry, are all required (Yilmaz et al. 2015). A previous study postulated that a delay in the ABR and facial palsy share common pathophysiology in which neuropathy could occur in the central auditory and facial nerve pathways (Welkoborsky et al. 1991). To establish the evidence of CN VIII involvement, stapedial reflex recordings, pure-tone and speech audiometry, and temporal bone radiography were used. In addition, the amplitude of four ABR peaks was observed to be reduced in 14 patients with normal ABR readings (II, III, IV, V). All of the participants’ audiometric thresholds were within normal ranges. Idiopathic facial palsy can occur in several stages, starting with inflammation and progressing to oedema and swelling of the facial nerve, extending proximally to the geniculate ganglion and internal auditory canal. This points to a cranial nerve VIII compression. A pioneered study that led to the understanding of bilateral idiopathic facial palsy through magnetic resonance (MR) images showed abnormal enhancement of proximal intracanalicular segments of cranial nerve VII/VIII complexes bilaterally, particularly in the leptomeningeal regions (Shaikh et al. 2000).
The term “interventional neuromuscular ultrasonography” refers to a variety of treatments used to diagnose and treat peripheral nervous system disorders. Recent advances in ultrasound resolution, as well as obstacles in electrophysiological cranial neuropathology evaluation, have advocated the use of neuromuscular ultrasound. The imaging of extracranial regions of cranial nerves VII and X using high-resolution ultrasonography revealed ultrasonographic characteristics in Bell’s palsy. Serial sonographic scanning of the nerve from the commencement of the disease until recovery, as well as an evaluation of inter- and intrarater reliability, would all help this promising technique advance (Tawfik et al. 2015). Interestingly, this study also revealed unusual anatomical locations of the vagus nerve. In one cadaver, the nerve was discovered in the front section of the carotid sheath, while in another, a cervical lymph node was discovered near to the nerve, implying that facial palsy is linked to a more widespread polyneuropathy.
Thus, patients with Bell’s palsy require detailed neurological examination of other cranial nerves as this information would lead to detection of cause and site of the lesion (Wormald et al. 1995). Even though the aetiology of Bell’s palsy is classically documented as idiopathic, this diagnosis is by exclusion, and so elimination of other potential etiologies of Bell’s palsy is pertinent (Zhang et al. 2019).
During the screening procedure, a few information gaps were discovered. Laterality manifestations of the cranial nerves lesion, whether ipsilateral or contralateral, were less well described. Furthermore, the findings of each study did not specify whether the nervous system was sensory, motor, somatic or autonomic. On the other hand, the majority of the less-experienced neurologists who initially recognized and followed up on their Bell’s palsy patients may miss the identification of other cranial polyneuropathy involvement. Some investigations also had a small number of respondents and a lack of proof of the tools’ validity. Furthermore, several investigations found no link between the severity of cranial neuropathy involvement and neurologic prognosis, hence limiting the findings. The occurrence of Bell’s palsy was likewise limited when the brainstem lesion was less evaluated with the frequency of several cranial neuropathies. Finally, the effects of the COVID-19 pandemic may have influenced the attendance of follow-up patients in the clinic, resulting in a reduction in undetected cranial polyneuropathy cases.
CONCLUSION
According to our results, various cranial nerve co-involvement might occasionally occur in conjunction with an otherwise usual idiopathic facial neuropathy (Bell’s palsy) (Figure 2). Following the screening process, thirteen studies were chosen. Among the seven potential cranial nerves associated with Bell’s palsy are the optic, oculomotor, trigeminal, vestibulocochlear, glossopharyngeal, vagus, and hypoglossal nerves. The trigeminal and vestibulocochlear nerves were found to be the most involved cranial nerves. Notably, evidence of other cranial nerve involvement was discovered in a small but considerable number of Bell’s palsy patients. We do not want to imply that polyneuritis cranialis is always linked to Bell’s palsy, but we do think that such cases should be extensively investigated. As a result, Bell’s palsy patient needs a comprehensive neurological examination of extracranial nerves to ascertain the cause and location of the lesion.
ACKNOWLEDGEMENT
This systematic review’s protocol was registered on INPLASY (INPLASY202160111) and is available in full at http://inplasy.com/INPLASY202160111. Because no human volunteers were engaged, there was no need for an ethical evaluation of this study.