This case illustrates AQP4 antibody-positive NMOSD after a second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine. NMOSD is an antibody-mediated disease of the central nervous system . Typical presentations of NMOSD include attacks of severe unilateral, bilateral, or rapidly sequential optic neuritis and transverse myelitis, which generally involve three or more vertebral segments on MRI (termed longitudinally extensive transverse myelitis or LETM). In addition, other areas of the central nervous system (CNS) can also be affected, resulting in area postrema, other brainstem, diencephalic, or cerebral presentations in some patients .
Factors responsible for triggering CNS inflammatory diseases, including NMOSD, are not well understood, but evidence suggests immunizations may be implicated in some cases. In a study by Karussis & Petrou, vaccinations were estimated to carry an overall risk of 0.1% in triggering central nervous system (CNS) inflammatory diseases. The most common post-vaccination CNS syndromes in this study were acute optic neuritis and transverse myelitis. NMOSD, acute disseminated encephalomyelitis (ADEM), and encephalitis with white matter involvement were also reported . Vaccinations that have been associated with NMOSD onset and/or relapses include influenza, tetanus and diphtheria (Td), tetanus, diphtheria, and pertussis (Tdap), human papillomavirus, pneumococcal, hepatitis A, hepatitis B, typhoid, yellow fever, and Japanese encephalitis vaccines . Interestingly, the risk of an NMOSD relapse after vaccination seems to be most clearly observed in patients who are not on preventative immunotherapy .
The pathophysiology of vaccine-triggered CNS disease remains incompletely understood, but some studies suggest post-vaccination demyelination is most likely triggering clinical disease expression in individuals who already have an underlying disease process . Evidence suggests that AQP4 antibodies may be detected long before clinical NMOSD onset, suggesting AQP4 antibody carriers can be asymptomatic for extended periods of time . Theoretically, these individuals may be particularly susceptible to developing clinical symptoms when faced with a possible trigger.
In the era of the COVID-19 pandemic with increasing vaccination rates worldwide, vaccine safety remains at the forefront of discussion. Neurological symptoms which have been reported in the Centers for Disease Control Vaccine Adverse Event Reporting System include dizziness, headache, pain, muscle spasms, myalgia, and paresthesias as well as rare cases of tremor, diplopia, tinnitus, dysphonia, seizures, and reactivation of herpes zoster. There are also rare cases of stroke, Guillan Barre Syndrome, facial palsy, transverse myelitis, and acute disseminated encephalomyelitis. With regards to NMOSD, there is very limited data linking COVID-19 vaccinations with disease onset. A case report from Fujikawa and colleagues describe a 46-year-old woman presenting with LETM involving C6-T2 without enhancement diagnosed 10 days following the SARS-CoV-2 mRNA-1273 (Moderna) vaccine . In contrast to our case, serum AQP4 antibodies were negative. Another case report described a middle-aged woman who developed mild fever, diarrhea, and area postrema syndrome three days after her first dose of an “inactivated virus vaccine.” MRI brain demonstrated area postrema and bilateral hypothalamus lesions without gadolinium enhancement. Serum testing was positive for AQP4, antinuclear, SSA, SSB, Ro-52, and p-ANCA antibodies. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity .
Overall, the risk of CNS disease post-vaccination remains lower than rates following infections against which the vaccines are aimed to protect. Additionally, current epidemiological data suggests the benefits of vaccinations both at an individual and population level prevail over potential risks of CNS complications [3,8]. Our case of a man with no previous history of neurological or inflammatory disease presenting with LETM, is, to our knowledge, the first case of de novo AQP4 positive NMOSD following BNT162b SARS-CoV-2 vaccination. Although we cannot prove causality, it is plausible that vaccination may have triggered disease activity in an individual with underlying susceptibility. Thus, we believe that people with presumed post-vaccine myelitis should be tested for AQP4 antibodies and, if the diagnostic criteria are met , managed like other patients with NMOSD.