Does Vaccination Increase Risk for NMOSD Attacks Among Patients?

In patients with neuromyelitis optica spectrum disorder (NMOSD), the frequency of vaccine-associated attacks is low, thus reinforcing the safety of vaccination in this population, according to findings from a systematic review and meta-analysis published in the journal Multiple Sclerosis and Related Disorders.

Among individuals with NMOSD, infections are a major cause of death and may be linked to an increased risk for attacks. Strategies aimed at the prevention of infections, including vaccines, thus, are considered important in this patient population. Among those with NMOSD, however, vaccination presents challenges, with several case reports documenting NMOSD attacks following the administration of a variety of vaccines. Scant data are available on the risk for and characteristics of attacks that occur following vaccination in patients with NMOSD.

For the study, researchers in Brazil performed a systematic review and meta-analysis to assess the frequency vaccination-associated attacks and to describe the clinical features of these attacks. Attacks were defined as “typical NMOSD attacks that occurred up to 30 days after vaccine administration.”

The meta-analysis included a total of 5 studies in 377 participants, in which the frequency of NMOSD attacks following vaccination were reported. Only 1.9% (7 of 377) of the participants presented with attacks that occurred after vaccination, with 3 of these attacks a first attack and 4 of them relapses. This yielded a vaccine-associated attack frequency of 2% (95% CI, 1%-4%; I² = 0%).

Further, a clinical description of the attacks was provided in 17 studies that included 24 patients. There were 13 different vaccines, including those protecting against COVID-19, tetanus, influenza, and hepatitis, associated with NMOSD attacks. Overall, 70.8% (17 of 24) of the patients presented with an initial event of NMOSD following a vaccination. A female-to-male ratio of 1.1:1 was observed in these individuals. Participants’ ages ranged between 15 and 87 years.

Acute myelitis was the most commonly reported clinical manifestation, which was reported in 70.8% of patients, followed by optic neuritis in 40.0% of patients, and area postrema syndrome in 12.5% of patients. Among 29.2% of the participants, simultaneous multiregional attacks were reported — in particular, the combination of optic neuritis and myelitis, which was observed in 20.8% of patients. In all, 66.7% (16 of 24) of the participants tested positive for the aquaporin-4 (AQP4) antibody.

A subgroup analysis of patients who were anti-AQP4 positive or anti-AQP4 negative was conducted. Anti-AQP4-negative individuals had a higher frequency of optic neuritis (66.7%) and multiregional attacks (50%), compared with a 31.3% frequency of optic neuritis and 25% frequency of multiregional relapses among anti-AQP4-positive patients.

Study limitations include its small sample size and the significant rates of missing data, which may compromise the assessment of predictors of NMOSD attacks that were observed following vaccination. An additional limitation is the fact that the study with the most patients was conducted with use of an anonymous online questionnaire, with no medical confirmation of the NMOSD attacks.

“[C]urrent evidence not only suggest vaccines are generally safe in patients with NMOSD, but also points that vaccines may reduce annualized relapse rate, possibly [through] the decrease of infection-associated relapses,” the researchers noted.