Isolated Sixth Nerve Palsy and COVID-19: A Recurrent Case in a 7-Month-Old Child and Analysis of Reported Cases

Abstract

Background: With the SARS-CoV-2 pandemic (COVID-19), data on central and peripheral nervous system involvement, including those causing cranial nerve 6 (CN6) palsy, have been limited to case reports. To extract clinically relevant features of COVID-19–related CN6 palsy, we report on a recurrent pediatric case and analysis of reported cases associated with infection or immunization. Methods: A PubMed search revealed 18 cases of isolated CN6 palsy in addition to the index case (n = 19). Clinical characteristics, workup, and temporal associations between systemic symptoms onset or vaccination, symptoms onset, and resolution were compiled and analyzed. Results: The median age of CN6 onset was 43 years (interquartile range [IQR]: 28–52). Sixteen cases (84.2%) were associated with COVID-19 illness and 3 (15.8%) were associated with COVID-19 vaccination. Four cases (23.5%) had positive neuroimaging findings. The median latency from first COVID-19 symptoms or vaccination to onset of CN6 palsy was 6 days (IQR: 2.3–16), and the median time from onset to resolution was 30 days (IQR: 14–60). Latency to onset of CN6 palsy was significantly and directly associated with time to resolution (R2 = 0.401, P = 0.010). Patients who had a positive SARS-CoV-2 antibody test had significantly longer days from symptoms to onset (6.0 vs 24.5, P = 0.030), and patients with a positive SARS-CoV-2 polymerase chain reaction test had a significantly shorter time to resolution (17.50 vs 90, P = 0.042). Conclusions: Isolated CN6 palsy from COVID-19 is rare, can occur in infants as young as 7 months, and can be recurrent. Longer latency from systemic symptoms onset portends greater recovery times, and this relationship may reflect multiple mechanisms by which COVID-19 (and/or an immune response thereto) causes cranial neuropathies with direct clinical relevance.

Bilateral Sequential Abducens Nerve Palsy After Pfizer-BioNTech COVID-19 Vaccine (BNT162b2): A Case Report and Literature Review

“…However, none of the previous cases reported bilateral abducens nerve palsy. On the other hand, there are more reported cases of COVID-19 infection causing abducens palsy, including cases of isolated abducens palsy [4], one case with polyneuritis cranialis [16], two cases with Miller Fisher syndrome [16,17], one case with Wernicke's encephalopathy in a patient with bulimia [18], one case with mammillary body and hypothalamic involvement [18], and one case with reversible leukoencephalopathy [19].…”

“…In most of the previously published case reports, symptoms resolved within 5-12 weeks with only conservative treatment. Cranial nerve palsies were reported after several types of vaccines, and, recently, they were reported after the COVID-19 vaccination [3,4]. Except for facial palsy, abducens palsy was the most common isolated motor cranial nerve palsy and the most cranial nerve palsy reported to the US VAERS, followed by oculomotor and trochlear nerve palsies.…”

“…The pathophysiology of abducens palsy following vaccination can be elucidated from the more extensively studied Bell's palsy following COVID-19 vaccination, which is hypothesized to be via either mimicry of host molecules, bystander activation of dormant autoreactive T cells, or induction of innate immune activation and production of interferon proteins by a combined effect of mRNA and lipids [20]. According to previous research, there are three primary postulated processes underlying the development of CN6 palsy in connection to COVID-19 [4]. These mechanisms include inflammation or autoimmune injury caused by abnormal and excessive inflammation in COVID-19, potentially due to a cross-reaction between the SARS-CoV-2 spike protein and myelin basic protein.…”

“…Moreover, isolated abducens nerve injury was the most common injury reported to the US Vaccine Adverse Event Reporting System (VAERS) [3]. Furthermore, viral infections were associated with abducens nerve injury, including COVID-19 and other viral infections [4].…”