Summary The main target of SARS-CoV-2 is the respiratory tract; However, the virus can invade extrapulmonary organs such as the nervous system. Peripheral facial nerve palsy has been reported in COVID-19 cases as isolated, unilateral, or bilateral in the context of Guillain-Barré syndrome (GBS). In the present study, online databases including PubMed and Google Scholar were searched. Studies that did not focus on isolated peripheral facial nerve palsy and SARS-CoV-2 were excluded. Finally, 36 patients with facial nerve palsy were included in our study using reverse transcriptase polymerase chain reaction (RT-PCR) or positive SARS-CoV-2 antibody testing. Interestingly, 23 (63.8%) of these patients did not have a typical history of COVID-19, and facial nerve palsy was their first clinical manifestation . The present study concludes that there is sufficient evidence to suggest that SARS-CoV-2 infection may present with facial nerve paralysis as the initial clinical manifestation . |
The COVID-19 epidemic emerged in December 2019 in Wuhan, China, and has spread rapidly around the world. In addition to respiratory symptoms, COVID-19 can cause a variety of symptoms. Although lung inflammation and respiratory failure are of vital importance, in recent months various manifestations have been increasingly described, including asymptomatic kidney and heart abnormalities or involvement of the nervous system.
Neurological symptoms may be the first manifestation of COVID-19 or concomitant respiratory symptoms, including headaches, hyposmia, hypogeusia, dizziness, confusion, cerebrovascular diseases, Guillain-Barré syndrome (GBS), and encephalopathies. Neurological manifestations were observed in up to 36% of COVID-19 patients, especially in those suffering from severe respiratory tract infections.
According to previous studies, COVID-19 could cause peripheral facial nerve paralysis through angiotensin-converting enzyme 2 (ACE2) receptors, blood circulation, or invasion of olfactory nerves; however, the mechanism is unknown. Combined paralysis of the facial and trigeminal nerves can potentially occur after SARS-CoV-2 infection.
Numerous cases of facial nerve palsy associated with SARS-CoV-2 infection were reported as first presentation.
The COVID-19 pandemic has attracted the attention of doctors because cases of facial nerve paralysis increased after the COVID-19 pandemic compared to previous years.
Therefore, the present literature review aimed to summarize current studies and case series to suggest facial nerve palsy as the initial clinical presentation of COVID-19.
Mechanisms of neurological manifestations in patients with COVID-19
The SARS-CoV-2 genome sequence has a combined 89.1% similarity to SARS-like coronaviruses. SARS-CoV-1 has been detected in the CSF and brain tissue of patients, which is most similar to the human coronavirus, and detection of SARS-CoV-2 in CSF has also been reported.
So far, fragments of evidence have been provided for the neurotropism effect of SARS-CoV-2, for example involving the cranial nerves (hypogeusia, Bell’s palsy, hyposmia, and abducens nerve palsies) or neurological manifestations (head pain). headache, dizziness and altered consciousness). Many viruses, such as influenza, herpes, or human immunodeficiency virus (HIV), can cause neurological diseases by invading the nervous system. Since the neurotropic mechanisms of SARS-CoV-2 have not yet been established, SARS-CoV-1 and other viruses could play a role as a reference for SARS-CoV-2.
It has been unclear whether cranial neuropathies, as early neurological manifestations of COVID-19 infection, arise from direct viral infiltration of the nervous system or from an autoimmune response. Several hypotheses regarding the involvement of the nervous system in the environment of COVID-19 patients have been documented, which can be divided into 2 defensible underlying mechanisms. The first mechanism includes synaptic spread and entry of the virus from the ACE2 receptor. Based on previous studies, coronaviruses can invade the CNS through the ethmoid cribriform plate, and subsequent invasion of the olfactory neuroepithelium could cause neuronal death in mice.
The coronavirus can penetrate through synapses from the olfactory nerve neurons to the cardiorespiratory center, called the "synaptic spread theory." SARS-CoV-2 may involve respiratory failure according to this theory. SARS-CoV-2 could directly penetrate sensory nerve endings like other coronaviruses.
The trigeminal nerve is believed to serve as an entry point for viruses in several reported cases of conjunctivitis.
However, the view of the primary entry receptor ACE2 has been accepted in direct neuroinvasion contrasts. ACE2 is widely expressed in the human body, specifically in neurons and some non-neuronal cells, mainly astrocytes, oligodendrocytes and endothelial cells. SARS-CoV-2 enters host cells through binding to the ACE2 receptor with viral surface spike (S) proteins, similar to SARS-CoV-1 entry. Additionally, it can infect macrophages to migrate across the blood-brain barrier (BBB).30
The affinity of SARS-CoV-2 for the receptor is almost 20 times greater than that of SARS-CoV-1, which would explain many neurological manifestations such as headache, nausea and vomiting in patients with COVID-19.
The “cytokine storm” may be the second mechanism of affectation of endothelial cells. Intracranial cytokine storms could cause disruption of the BBB, which could be the main cause of encephalopathy or GBS. A large body of evidence in patients with COVID-19 has documented severe systemic manifestations, including cytokine storm and coagulopathy. This systemic inflammatory response could be attributed to several factors, particularly infections.
It is indisputable that our knowledge about SARS-CoV-2 is limited, especially regarding the neurological manifestations. In this sense, the exploration of neuronal tissue and detailed neurological examination can facilitate our understanding.
Management of facial nerve paralysis amid the COVID-19 pandemic
It is challenging to manage facial nerve palsy during the COVID-19 pandemic due to potential exposure, requirement for likelihood of isolation, and limited healthcare resources. Since the absence of common COVID-19 symptoms has been reported in patients with facial nerve palsy, it is recommended to take all protective measures until the COVID-19 status in these patients is clarified. Taking a patient’s detailed medical history and performing a neurological examination can ultimately lead to a diagnosis of Bell’s palsy after elimination of other differential diagnoses and conditions requiring immediate treatment.
COVID-19 patients with facial nerve palsy should undergo a full diagnostic workup.
In all patients who suddenly develop peripheral facial paralysis, lumbar puncture is considered a diagnostic procedure. Inflammatory responses from infectious pathogens can be rapidly detected in CSF. Detection of oligoclonal bands in CSF, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in CSF, anti-neuromyelitis optica (NMO) in CSF or ACE level should be considered. Plasma and CSF antibody levels could be measured due to viral infections (varicella-zoster, herpes simplex, cytomegalovirus, adenovirus, and Epstein-Barr) or Borrelia burgdorferi.
In some specific cases, human immunodeficiency virus serologic testing may be significantly elevated. Magnetic resonance imaging ( MRI) of the brain can particularly delineate the brainstem, posterior fossa, or petrosal bone.
Suggested therapeutic regimens are corticosteroids and antiviral agents and symptom therapy.
Steroid edema and swelling reduction can lead to facial nerve decompression, thus attracting more attention among other regimens. Early treatment immediately after the onset of symptoms (<72 hours) could improve patient outcomes and reduce auricular pain and nerve damage. The authors recommend a 1 mg/kg/day course of prednisolone and then gradually tapering over 5 to 10 days.
Pain with vesicles in the ear canal can be manifested by a zoster infection ; In this context, the combination of antivirals and steroids could be beneficial. The clinical trials that have been conducted to date to answer this question are relatively heterogeneous.
Available drugs are acyclovir (5 to 10 mg/kg BW IV three times a day or 800 mg PO 5 times a day), valacyclovir (1000 mg PO three times a day), brivudine (125 mg PO QD), and famciclovir (250 at 500 mg PO three times daily).
Patients’ eyes should receive special attention as they are unprotected and dry as a result of incomplete eyelid closure. Artificial tears and dexpanthenol ointment are prescribed, as well as a night eye protector to retain moisture.
Treatment is often complemented by exercises , either under the guidance of a physical therapist or with self-observation in a mirror.
