A systematic review of Bell's Palsy as the only major neurological manifestation in COVID-19 patients.

BACKGROUND: Bell's palsy is an acute idiopathic paralysis of the facial nerve. The disease is caused by many viruses like Herpes simplex virus-1, Varicella zoster, Epstein-bar virus, Cytomegalovirus, Usutu virus, Human immunodeficiency virus, etc. Literature has reported few cases of COVID-19 patients with Bell's palsy as the only major neurological manifestation indicating the possible role of another virus in the etiopathogenesis of Bell's Palsy. This paper aims to evaluate the reported cases of COVID-19 positive patients, presented with Bell's palsy as the only major neurological manifestation from March 2020 to December 2020, and to investigate the association of SARS-CoV2 and Bell's palsy. MATERIALS AND METHODS: A systematic review of the published literature was performed using an electronic search in PubMed/Medline, Science Direct, Web of Science, Embase, J- STAGE, Google Scholar, China National Knowledge Infrastructure (CKNI) and Scopus databases, from March 2020 to Dec 2020 using keywords like 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Bell's palsy', 'Facial nerve', 'First', 'Only',' Neurological', 'Manifestation'. The studies reviewed were case series and case reports regarding the subject. RESULTS: Search strategy revealed thirteen articles from March 2020 to Dec 2020 with a total of 20 cases of COVID-19 with Bell's palsy as the only major neurological manifestation. CONCLUSION: Evidence of Bell's palsy as the only major neurological manifestation in COVID-19 patients signifies an important clinical finding but robust research is needed to investigate their association and the exact mechanisms by which SARS-CoV2 causes Bell's Palsy.

Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.

The complete features of the neurological complications of coronavirus disease 2019 (COVID-19) still need to be elucidated, including associated cranial nerve involvement. In the present study we describe cranial nerve lesions seen in magnetic resonance imaging (MRI) of six cases of confirmed COVID-19, involving the olfactory bulb, optic nerve, abducens nerve, and facial nerve. Cranial nerve involvement was associated with COVID-19, but whether by direct viral invasion or autoimmunity needs to be clarified. The development of neurological symptoms after initial respiratory symptoms and the absence of the virus in the cerebrospinal fluid (CSF) suggest the possibility of autoimmunity.

Metagenomic next-generation sequencing of viruses, bacteria, and fungi in the epineurium of the facial nerve with Bell's palsy patients.

Bell's palsy (BP) represents a major cause leading to facial paralysis in the world. The etiology of BP is still unknown, and virology is the prevailing theory. The purpose of this study is to explore the pathogenic microorganisms that may be related to BP, and it is of great significance to study the pathogenesis and treatment of BP. Metagenomic next-generation sequencing (mNGS) detection was performed in the epineurium of the facial nerve of 30 BP patients who underwent facial nerve epineurium decompression. A total of 84 pathogenic microorganisms were detected in 30 clinical samples, including 4 viruses, 10 fungi, and 70 bacteria. The species with the highest detection frequency in virus was human betaherpesvirus 7 (HHV-7). The species with the highest detection frequency in Fungi was Malassezia restricta. The species with the highest detection frequency in Bacteria was Pseudomonas aeruginosa. In this study, mNGS method was firstly used to detect the pathogenic microorganisms in the epineurium of the facial nerve with BP patients. We have for the first time identified HHV-7 and aspergillus in the epineurium of the facial nerve of BP patients. These results suggest that these two pathogenic microorganisms should be considered in the pathogenesis of BP.

The presence of herpes simplex-1 and varicella zoster viruses is not related with clinical outcome of Bell's Palsy.

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.

Failure of postexposure prophylaxis in a girl child attacked by rabid dog severing her facial nerve causing possible direct entry of rabies virus into the facial nerve.

On January 4, 2019 an eight-year-old girl child was bitten by a suspected rabid dog over the left parotid region. After a 17-h delay, the child was brought for rabies postexposure prophylaxis (PEP) at Civil Hospital Theog and was administered complete PEP. On January 29, 2019, the child was again brought to Theog Hospital with complaints of having fever, difficulty in walking, neck drop, and ptosis. On examination, pediatrician found photophobia, phonophobia, and hydrophobia and subsequently the patient died of cardiac arrest. On postmortem examination, the facial nerve was found dissected and injured at the inner end of the parotid gland. A severed end toward the brain was swollen and edematous. The entire brain was extracted and sent to Central Research Institute Kasauli for confirmation of rabies, where it tested positive for rabies by Fluorescent Antibodies Test and Biological Test. In situations where sensitive parts such as the face are involved, a thorough wound wash with soap and water and application of antiseptics along with immediate PEP may save some lives by not allowing the virus enough time to attach to and infect the nerve cells.

Typical or Atypical Ramsay-Hunt Syndrome in Delayed Facial Palsy After Stapedectomy?

OBJECTIVES: The aim of this study was to define the typical pattern for varicella zoster virus (VZV) reactivation in delayed facial palsy (DFP) after stapedectomy for otosclerosis. MATERIALS AND METHODS: Review of the relevant literature, personal casistics, and case-report. RESULTS: In total, 48 cases of DFP after stapes surgery have been described so far, including the reported case with exclusive manifestation of atypical Ramsay Hunt syndrome (RH); in the personal series of 1253 stapedectomies, DFP occurred in only one case (0.08%). Complete DFP (House-Brackmann grade VI) rapidly developed 12 days after surgery; RH appeared 2 days later, confirming the role of VZV. The DFP started improving after 8 weeks and completely recovered 6 months later. CONCLUSION: Acute otalgia prior to DFP should raise the suspicion of VZV reactivation. Atypical RH is the most frequent pattern that occurs in DFP after stapedectomy.

Facial paralysis induced by ear inoculation of herpes simplex virus in rat.

OBJECTIVE: Bell's palsy is caused by the reactivation of herpes simplex virus type 1 (HSV-1). Using Balb/c mice inoculated with the KOS strain of HSV-1, we previously developed an animal disease model that simulated mild Bell's palsy. The current study developed an animal disease model of more severe facial palsy than that seen in the mouse model. METHODS: Three-week-old female Wister rats weighing 60-80g were inoculated on the auricle with HSV-1 and acyclovir was administered intraperitoneally to deactivate the infected HSV-1. Instead of HSV-1, phosphate-buffered saline was used for inoculation as a negative control. Quantitative polymerase chain reaction (PCR), behavior testing (blink reflex), electroneuronography, histopathology of the peripheral nerve, and immunohistochemistry of the facial nerve nucleus were evaluated. RESULTS: Facial palsy occurred 3-5 days after virus inoculation, and the severity of the facial palsy progressed for up to 7 days. Quantitative PCR showed an increase in HSV-1 DNA copies in the facial nerve from 24 to 72h, suggesting that HSV-1 infection occurred in the nerve. Electroneuronography values were 33.0±15.3% and 110.0±18.0% in HSV-1-inoculated and control rats, respectively. The histopathology of the peripheral nerve showed demyelination and loss of the facial nerve, and the facial nerve nucleus showed degeneration. CONCLUSION: Facial palsy developed in Wister rats following inoculation of the KOS strain of HSV-1 onto the auricles. The behavioral, histopathological, and electroneuronography data suggested that the severity of facial palsy was greater in our rats than in animals in the previous mouse disease model.

Reactivation and centripetal spread of herpes simplex virus complicating acoustic neuroma resection.

BACKGROUND: Herpes simplex is a common human pathogen that has rare but severe manifestations including encephalitis. CASE DESCRIPTION: A 44-year-old man underwent uneventful resection of an acoustic neuroma. Postoperatively, he developed swinging pyrexia, vomiting, and episodic confusion. Analysis of cerebrospinal fluid showed a lymphocytosis, and polymerase chain reaction revealed herpes simplex DNA. After treatment of herpes encephalitis with acyclovir, the patient made a good recovery. CONCLUSION: Herpes encephalitis is a rare complication of neurosurgical procedures, and the most likely etiology is reactivation of latent infection from manipulation of cranial nerves.

[Comparative study of several methods for producing experimental animal model of viral facial palsy].

OBJECTIVE: To select the optimal method for developing experimental animal model of viral facial paralysis by comparing several inoculation methods. METHOD: One hundred and twenty Balb/c mice were divided into 4 groups, with each group having 30 mice. Group A, the posterior auricular branch of right facial nerve were incised and inoculated with 25 microl HSV-1; group B, 25 microl HSV-1 were inoculated into the posterior aspect of the right auricle by cutaneous scarification; group C, 25 microl HSV-1 were injected into subcutaneous tissue of the posterior aspect of the right auricle; group D, 100 microl HSV-1 were inoculated in the way similar to that of group C. The symmetry of mouse face was observed, and the incidence of paralysis and death were analyzed. The temporal bones of paralyzed mice were serially sectioned and stained with hematoxylin and eosin. RESULT: Thirteen (43.33%) mice developed the right facial paralysis and recovered from it 3-7 days later in group A. Six (20%) mice developed the paralysis and recovered from it 2-9 days later in group B. Group C had no signs of facial paralysis and group D had 1 paralyzed animal. Except for 12 mice in group D, there was no death in the other groups. Nerve swelling was observed in right temporal facial nerve of paralyzed mice. Facial nerve to facial canal cross-sectional area ratio (FN/FC) of the right side was much higher than that of the left side. CONCLUSION: Inoculating HSV-1 into the posterior auricular branch of facial nerve can produce an acute and transient facial paralysis in mice. With the advantage of higher morbidity of facial paralysis and lower mortality in comparison to the other methods, it is an optimal method.

Delayed facial nerve palsy following tympano-mastoid surgery: incidence, aetiology and prognosis.

OBJECTIVE: To establish the frequency of occurrence of delayed facial nerve paralysis following tympano-mastoid surgery in our department and to determine the aetiological factors and long term prognosis. SETTING: Tertiary care academic centre. MATERIALS AND METHODS: A retrospective review of all patients who had undergone tympano-mastoid surgery in our department over the previous five years was carried out. A total of 219 patients were included in the study. Only two patients were identified as having delayed onset facial nerve palsy over this period of time. The patients' medical records were reviewed and the patients clinically assessed. RESULTS: The frequency of delayed onset facial nerve palsy following tympano-mastoid surgery in our series was 0.91 per cent. Facial weakness set in on day eight and day 14 in the two patients. Serological investigations in both patients revealed raised titres of immunoglobulin (Ig) M and IgG to varicella-zoster virus, confirming the presence of varicella-zoster infection. In our experience, the combined use of prednisone and acyclovir was an effective form of treatment for both patients, whose facial nerve function fully recovered within six months of onset. CONCLUSION: The incidence of delayed facial nerve palsy following tympano-mastoid surgery is low. It can occur up to two weeks after the surgery. Our two cases confirm viral reactivation to be an important aetiological factor in the development of delayed onset facial nerve palsy. The overall prognosis for delayed facial nerve palsy following tympano-mastoid surgery appears to be good.

[Animal model of facial neuritis induced by herpes simplex virus].

OBJECTIVE: To study the role of herpes simplex virus type 1 ( HSV-1 ) in facial paralysis by developing an experimental animal model of viral facial paralysis. METHODS: Both sides of posterior auricular branch of facial nerve were anatomies and incised in 66 mice. The HSV-1 was inoculated into right ear branch and fetal bovine serum was inoculated into left ear branch as control. The symmetry of mouse face was observed and scored. The temporal bones were serially sectioned and stained with hematoxylin and eosin. The extratemporal facial nerves were stained with osmium tetroxide. HSV-1 DNA in bilateral facial nerve, brain stem, trigeminal ganglion and spinal cord was detected by the polymerase chain reaction. RESULTS: Twenty-eight (42. 42%) mice developed right facial paralysis between 2 and 5 days after inoculation. Continuing 3-6 days, the facial paralysis recovered spontaneously. Thirty-eight mice had no signs of facial paralysis. Compared with the left, nerve swelling, inflammatory cell infiltration were manifested in right temporal facial nerve of paralyzed mice. The ratio of the cross-sectional area of the facial nerve to the facial canal ( FN/FC ) was significantly higher than that on the control side (P < 0.01). Demyelinated nerve fibers were seen in the right extratemporal facial nerve. Not only in paralyzed mice, but also in non-paralyzed mice, HSV DNA was detected in some nerve tissues. CONCLUSIONS: Inoculating HSV-1 into posterior auricular branch of facial nerve can produce an acute and transient facial paralysis in mice. The possible pathophysiologic mechanism of the facial paralysis is viral invasion and transportation from distal branch to main trunk. Then the viral facial neuritis causes facial paralysis.

Bell's palsy with ipsilateral numbness.

Bell's palsy is an idiopathic facial palsy of the peripheral type. A herpes virus is the most likely mechanism. We report a patient with the often encountered combination of a facial palsy with ipsilateral sensory changes. Magnetic resonance imaging showed had contrast enhancement in the greater petrosal nerve. Viral spread through anatomical connections could be an explanation for the association of facial palsy with numbness.

Bell's palsy and Herpes simplex virus: fact or mystery?

HYPOTHESIS AND BACKGROUND: In recent years, progress has been made in the understanding of Bell's palsy, the most common form of acute facial weakness. Herpes simplex virus (HSV) reactivation within the geniculate ganglion with subsequent inflammation and entrapment of the nerve at the meatal foramen has been proposed to be the pathogenetic mechanism. We challenged its accuracy by analyzing our own data on the presence of viral genomic DNA of HSV-1 and 2, human herpes virus (HHV)-6A/B, as well as varizella zoster virus (VZV) in patients with Bell's palsy and in control patients without the disease. METHODS: Polymerase chain reaction was performed with primer sets specific for viral genomic DNA of HSV-1, HSV-2, and VZV in facial muscle biopsy specimens from patients with Bell's palsy. As control specimens, the Scarpa's ganglion of patients with Meniere's disease and the geniculate ganglion harvested at autopsy from patients without history of facial palsy. In a second study, we used polymerase chain reaction with primers specific for HSV-1, -2, and HHV-6A, -6B to analyze for the presence of these viruses in tear fluid samples from control patients and patients with acute Bell's palsy. RESULTS: HSV-1 and VZV genomic DNA were detected in 86 and 43%, respectively, of geniculate ganglion preparations from control specimen. We were not able to detect the presence of HSV-1, HSV-2, or VZV genomic DNA in ganglion scarpae or muscle biopsy results in control and Bell's palsy patients. HHV-6A could be detected in tear fluid samples in 40% of control patients and 30% of Bell's palsy patients. CONCLUSIONS: The sole presence of HSV genomic DNA within the sensory ganglion along the facial nerve does not explain the direct association with Bell's palsy. The missing link would be the identification of an active replicating virus, an investigation that has not yet been carried out.

Varicella-zoster virus DNA level and facial paralysis in Ramsay Hunt syndrome.

We have investigated whether the copy number of varicella-zoster virus (VZV) in saliva correlates with the clinical symptoms in patients with Ramsay Hunt syndrome. A real-time quantitative polymerase chain reaction assay was used to examine the VZV DNA copy number in saliva samples from 37 patients. We detected VZV DNA in 6 of the 7 patients with oropharyngeal zoster lesions (86%) and in 17 of the 30 patients who had zoster lesions only on the skin (57%). Patients with oropharyngeal zoster lesions had a high VZV load in their saliva, and the difference between the copy number in patients with oropharyngeal zoster lesions and those without was around 10,000 copies per 50 microL. In addition, patients with oropharyngeal zoster lesions showed worse recovery of facial function than those without. It seems that the VZV DNA level in saliva reflects the kinetics of viral reactivation in the facial nerve, as well as in the oropharyngeal epithelium, in patients with Ramsay Hunt syndrome.

Prevalence and distribution of HSV-1, VZV, and HHV-6 in human cranial nerve nuclei III, IV, VI, VII, and XII.

The etiology of idiopathic cranial nerve palsies often remains unresolved. It has been hypothesised that viral reactivation of herpesviruses in the corresponding nuclei in the brainstem is the cause. We investigated the distribution of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) in nuclei that are associated with peripheral sensory ganglia [oculomotor (nIII), facial (nVII) nuclei] and in nuclei that are not associated with peripheral sensory ganglia [trochlear (nIV), abducens (nVI), and hypoglossal (nXII) nuclei] of five human brainstems. Samples of the cranial nerve nuclei and adjacent control tissue were taken from histological sections after precise identification of every single nucleus and control tissue. DNA and RNA amplification methods were used to determine the prevalence and distribution of HSV-1 and VZV. The distribution of human herpes virus type 6 (HHV-6) was also determined and served as a control, since HHV-6 infection has never been associated with idiopathic cranial nerve palsies. HSV-1 was distributed at random in all cranial nerve nuclei and control tissue, whereas VZV DNA was not detected in any of the samples examined. Surprisingly, HHV-6 was present in almost all samples where HSV-1 was also present, however, the latency associated transcript (LAT) of HSV-1 was not found in any of the samples positive for HSV-1 DNA. The absence of LAT in the samples positive for HSV-1 and the distribution of HSV-1 and HHV-6 do not support the hypothesis that idiopathic cranial nerve palsies result from viral reactivation in the brainstem nuclei.