Facial Nerve Palsy: An Early Sign of COVID-19

Abstract

Introduction Bell’s palsy is a peripheral lower motor neuron (LMN) facial nerve palsy, characterized by the acute onset (72 hours or less) of unilateral peripheral facial paresis without other neurologic signs. Bell’s palsy has been described at three clinical junctures of COVID-19 infection: as the unique initial signal of COVID-19, as an accompanying feature during the acute phase of COVID-19 when respiratory and systemic symptoms predominate, or during the recuperative phase beginning 2-3 weeks after resolution of respiratory and systemic covid symptoms. Case report We present a unique case of a COVID-19-related facial nerve palsy that occurred 3 weeks prior to the onset of pneumonia caused by COVID-19. Conclusions This case report suggests an association between early COVID-19 presenting as facial nerve palsy and alerts physicians about the ways in which COVID-19 may cause this phenomenon.

Introduction

Bell’s palsy is a common form of facial nerve paralysis. It is defined as peripheral lower motor neuron (LMN) facial nerve palsy [1]. This condition is characterized by the acute onset (72 hours or less) of unilateral peripheral facial paresis without other neurologic signs. The exact mechanism of pathogenesis causing facial nerve palsy is not fully understood. It has been speculated that inflammation of the facial nerve leads to compression of the nerve against the narrow bony canal resulting in facial nerve paralysis [2].

Bell’s palsy may be the initial signal of COVID-19 and may precede the onset of more common systemic symptoms of upper respiratory (URI) or lower respiratory (LRI) infection by several weeks [3]. Other presentations of facial nerve palsy occur during the acute phase of COVID-19 when respiratory symptoms of cough, fever, and malaise accompanied by pneumonia predominate [4,5]. COVID-19-related facial nerve palsy has also been described in the recuperative phase, beginning 2-3 weeks after resolution of respiratory or systemic COVID-19 symptoms [6].

We describe an interesting case of facial nerve palsy which occurred 3 weeks before the onset of systemic and respiratory symptoms of COVID-19.

Case report

A 47-year-old previously healthy male presented to Ascension St John Hospital Emergency Department on March 9, 2020 with the acute onset of right sided facial droop that had begun 24 hours prior to his arrival. Review of symptoms was notable for a loss of taste and smell which had begun three days before his presentation. He denied having symptoms of rash, headaches, cough, shortness of breath, fatigue, nausea, vomiting, or fever. He denied tobacco or any other recreational drug use and had no recent history of trauma. The patient was evaluated by our Neurology service. A full neurologic examination revealed right facial LMN weakness with intact sensation. Visual fields were normal. Eye closure was weak on the right side and was accompanied by weakness of the right frontalis muscle. His hearing was intact. There were no skin changes of rash, vesicles, or scabs on the face. The remaining motor examination was normal. Initial workup included CT imaging of the head with and without contrast, CT angiography of the head and neck, and MRI of the brain with and without contrast, which were all negative for findings. He was discharged the next day with a prescription for prednisone 50 mg daily for 10 days (which the patient completed). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nasal testing was not done. This patient had presented one week before the onset of the first COVID-19 wave in Michigan when there was a lack of clinical appreciation for this infection.

Three weeks later, our patient presented with a two-day history of dyspnea at rest and dry cough. He was noted to have consistent loss of taste and smell as described three weeks earlier. On admission, his blood pressure was 167/83 mmHg, heart rate 117 beats per minute, and temperature was 37.2 degrees Celsius. He had tachypnea with a respiratory rate of 18 per minute and he was hypoxic with pulse oximeter reading 88% on room air. He required 6 liters of supplemental oxygen. His BMI was 38 kg/M. His physical examination still revealed the residual but improving right sided facial droop. Lungs were clear to auscultation bilaterally. The remainder of the examination was normal. Laboratory examination showed leukocytosis (18930 cells/mm³) with a neutrophilic predominance (95%) and absolute lymphopenia (190 cells/mm³). Hemoglobin and platelet counts were normal (14.5 g/dL and 217000 cells/mm³, respectively). There was a slight increase of alanine aminotransferase (57 U/L) with normal aspartate aminotransferase (39 U/L) and normal serum creatinine (0.98 mg/dL). Several inflammatory markers were elevated, including C-reactive protein (231 mg/dL), ferritin (776 ng/mL), procalcitonin (0.3 ng/mL), lactate dehydrogenase (483 U/dL) – Table 1. A fourth generation HIV (human immunodeficiency virus) test and an enzyme immunoassay syphilis test were both negative. Polymerase chain reaction (PCR) from a nasopharyngeal swab for SARS-CoV-2 returned a positive result. The patient was febrile on several occasions during his hospital stay, with the highest recorded temperature of 39.3 degrees Celsius on day two of hospitalization. He required 15 liters of supplemental oxygen; this was tapered down as his condition improved. On day seven the patient was discharged home on room air with instructions to follow up in two weeks in the Infectious Disease clinic.

On his follow up visit at 3 weeks after hospital discharge, the patient reported that he continued to slowly improve. His nonproductive cough had largely resolved. There were no reported symptoms of coryza or pharyngeal discomfort. His loss of taste and smell had subjectively improved. There was continued notable improvement in the right sided facial droop as compared to his original presentation on March 9, 2020. He has begun returning to normal levels of activity.

Discussion

Previously known etiologies of facial palsy include herpes simplex virus 1 (HSV) and varicella zoster virus (VZV) [7,8]. Less common viral etiologies include Epstein-Barr virus (EBV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Zika virus, and Usutu virus (an African mosquito-borne flavivirus) [3,9,10]. Bacterial etiologies include Borrelia burgdorferi (Lyme disease), Mycobacterium tuberculosis, and Treponema pallidum (syphilis) [4,11,12,13].

Noninfectious causes include autoimmune diseases (granulomatosis with polyangiitis), metabolic abnormalities (diabetes), tumors, and trauma [9]. COVID-19 has recently been discovered as an etiology of facial nerve palsy. COVID-19 can cause nervous tissue injuries through three proposed mechanisms: neuroinvasion (direct access to nervous system), damage secondary to COVID-19 induced proinflammatory cytokines along with or without microthrombosis, or autoimmune related facial nerve injury [3,4,6,14,15].

Coronaviruses have been described as neurotropic with neuroinvasive potential. There are various species of previously identified human coronaviruses (HCoVs) which have been implicated as causing demyelinating diseases. The mechanism is postulated as an effect of inflammation secondary to cytokine release vs. a post infectious autoimmune phenomenon [16,17,18]. This includes the well-known SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV), which caused earlier epidemics preceding COVID-19. The lack of facial nerve palsy by these earlier coronaviruses likely reflects underreporting secondary to low incidence. Thus, prior to COVID-19, no facial nerve palsy attributed to another coronavirus has been described. Previous studies from Wuhan and elsewhere described neurological manifestations of severe COVID-19 initially presenting with only neurological symptoms of facial nerve palsy, as in our case [14,15,19]. Before the onset of overt clinical symptoms, the virus enters the brain via the olfactory bulb and spreads quickly by a transneuronal route. COVID-19 has a high affinity of binding to ACE2 receptors, which are expressed throughout the nervous system (including the facial nerve).

During the acute phase of COVID-19, the virus causes activation of central nervous system (CNS) microglial cells producing neuropathologically-relevant proinflammatory mediators such as cytokines, chemokines, nitric oxide, and reactive oxygen intermediates (Figure 1). This causes an inflammatory response affecting facial nerve function. Local antigen presentation to infiltrating T lymphocytes further contributes to this neuroinflammatory state. A reduction in blood flow to the facial nerve secondary to microthrombosis in the perineural arteriovenous plexus is another mechanism of nerve injury that was proposed after an FDG-PET/CT assessment of the facial nerve was done on a patient with COVID-19-induced facial nerve palsy [20] . Other considerations during the acute phase of COVID-19 include nerve damage as a result of axonal transport of human coronavirus OC43 protein into the nervous system resulting in direct injury or inflammatory demyelination [16].

Finally, in addition to infectious and ischemic mechanisms, COVID-19 related facial nerve palsy may be related to an immune response to the infection. This phenomenon has been previously described following use of a HIV glycoprotein 140 subunit vaccine given intranasally in combination with a potent mucosal antigen known as LTK63 [21]. An immunogenic response resulting in transient interference of facial peripheral nerve function was observed. Facial nerve secretomotor fibers richly supply nasal mucosa and can transport molecules to the geniculate ganglion. The immune response to COVID-19 infection (or COVID-19 vaccination) may follow the same mechanism. This has yet to be proven.

A standard of treatment of facial nerve palsy includes use of oral steroids. A large review by Peiterson et al. shows that 85% of a patient’s facial nerve function was returned within three weeks and the remaining 15% after three to five months [22]. Previously published guidelines for treatment of facial nerve palsy of other etiologies indicate that oral steroids should be started within 72 hours of symptom onset and continued in tapering doses for 10 days [2,9]. Our patient continued to report loss of smell and taste during the 3-week time period from his initial presentation of Bell’s palsy until the development of shortness of breath and cough, pointing towards the lower respiratory tract involvement. We hypothesized that SARS-CoV-2 entered through the nasal cavity and involved the olfactory bulb, causing the symptoms of loss of smell and taste. A course of steroids prescribed at the patient’s initial presentation on March 9, 2020, might have prolonged the shredding of virus and lead to spread of the virus into the lower respiratory tract.

Conclusions

This case report suggests an association between early COVID-19 and the development of facial nerve palsy. We are reporting this case to further inform and alert physicians about the ways in which COVID-19 may cause this phenomenon.