Pearls & Oy-sters: Facial nerve palsy in COVID-19 infection

Discussion

We are in the exponential phase of learning about COVID-19, an emerging infectious disease, which has caused an ongoing global pandemic. In a cohort of 214 Chinese patients, COVID-19 presents most commonly with fever in 88.7% and cough in 67.8% of patients, 5% of whom required intensive care monitoring.¹ Neurologic manifestations of COVID-19 have been reported in up to 36.4%.² Thus far, impairment of taste and smell, dizziness, and headache have been reported as common symptoms in COVID-19.²

Recently, reports of significant neurologic associations have emerged, including increased incidences of Guillain-Barré syndrome, encephalopathy, and strokes.^2,–,5 In an Italian cohort, Guillain-Barré syndrome has been reported in approximately 0.5% of patients with COVID-19, with the first symptoms of flaccid paralysis and facial diplegia occurring at 5–10 days after onset of acute respiratory symptoms.⁵ In Strasbourg, France, encephalopathic features were commonly seen in patients with severe COVID-19 who had acute respiratory distress syndrome, some of whom had MRI abnormalities including leptomeningeal enhancement, perfusion abnormalities, and ischemic stroke.⁴ A case of acute hemorrhagic necrotizing encephalopathy associated with COVID-19 infection has also been reported in Detroit, Michigan, and postulated to be due to intracranial cytokine storm, with MRI showing T2 fluid-attenuated inversion recovery hyperintensities within the thalami and bilateral medial temporal lobes with rim enhancement post contrast.³ The incidence of stroke was 5.7% in patients with COVID-19 with more severe respiratory symptoms in Wuhan, China.² A case series from Spain described cranial nerve manifestations associated with COVID-19 in 2 patients, 1 of whom had Miller Fisher syndrome and the other presenting with polyneuritis cranialis.⁶ To our knowledge, isolated cranial neuropathies have yet to be described.

Facial nerve palsy can be associated with infections, most commonly HSV, as well as VZV and HIV, Lyme disease, and Mycobacterium tuberculosis. Noninfectious causes include sarcoidosis and neoplasms. The exact pathogenesis of acute facial nerve palsy remains unclear, but in association with neurotropic herpesviruses (HSV and VZV), it is thought to be related to axonal spread and viral replication leading to inflammation and demyelination.⁷

Coronaviruses are known to have a neuroinvasive propensity. Animal models show that severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus could potentially have a transcribial route to the brain, causing CNS manifestations.⁸ The mechanism underlying neurologic symptoms in COVID-19 has yet to be clearly elucidated. Similar to the patients with Miller Fisher syndrome and perineuritis cranialis described in Spain and those with Guillain-Barré syndrome described in Italy, our patient developed an isolated facial nerve palsy during the early phase of his illness, on day 6.^5,6 This may suggest a parainfectious phenomenon. Serum GD1b immunoglobulin G antibodies were also detected in the patient with Miller Fisher syndrome. In all of these cases with Guillain-Barré syndrome and Miller Fisher syndrome, SARS-CoV-2 was not detected in the CSF. As such, cranial neuropathies may be related to immune-mediated injury from proinflammatory cytokines rather than direct viral neutrophism.⁶

Studies of viral dynamics show that viral loads are highest 1–2 days prior to symptom onset, and decrease in a monotonic pattern with prolonged viral shedding hovering near the level of detection, resulting in RT-PCR results that vacillate between positive and negative.⁹ Lopinavir/ritonavir is a protease inhibitor combination approved for use in HIV-1 and has demonstrated in vitro activity against SARS-CoV-2. A recent randomized trial conducted in China on patients with COVID-19 with severe respiratory symptoms compared lopinavir/ritonavir, in addition to standard care, to standard care alone, and found no significant decrease in viral load or clinical benefit with lopinavir/ritonavir.¹⁰ However, in this study, the frequency of RT-PCR testing was only every 4–7 days, and it has been proposed that daily sampling following antiviral treatment may have provided more detailed characterization of the viral load kinetics. More studies are needed to determine if there is a direct effect of lopinavir/ritonavir on viral load, an indirect effect on the immune response, or no effect on the natural course of the disease process. In our patient, we observed a declining trend in SARS-CoV-2 viral load (which is inversely related to the cycle threshold or Ct value) determined by daily nasopharyngeal swab samples after lopinavir/ritonavir was initiated.

This case report only suggests a possible association between isolated cranial neuropathies and COVID-19. More cases are required to support causality. We are reporting this case to inform and alert physicians of the possibility of cranial nerve involvement in the presentation of patients with COVID-19.