In a recent review published in the journal Nature Reviews Neurology, researchers from the United Kingdom explored the links between vaccination and neurological diseases, examining examples of vaccine-related neurological risks. They emphasized that these risks are rare and discussed the potential mitigation strategies, especially considering the coronavirus disease 2019 (COVID-19) pandemic.

Review: Identifying and reducing risks of neurological complications associated with vaccination. Image Credit: sfam_photo / Shutterstock

Background

Vaccination has significantly reduced infectious diseases worldwide, saving millions of lives annually. While vaccines generally have a positive benefit-risk profile, they can occasionally cause neurological disorders, ranging from mild effects like headaches to rare severe complications such as Guillain–Barré syndrome (GBS) and cerebral venous sinus thrombosis (CVST). These rare neurological risks and low-quality safety data may raise public concern and jeopardize vaccination efforts. Research on vaccine-related neurological adverse events must be accurate, transparent, and capable of rapidly identifying and addressing safety concerns. In the present review, researchers explored the connection between vaccination and neurological diseases, emphasizing the role of neurologists in identifying safety signals, managing risks, and addressing common patient concerns regarding vaccination and neurological health.

Vaccine development and safety

Extensive preclinical and clinical testing is required to ensure robust vaccine safety and efficacy, especially for prophylaxis. Despite thorough testing, rare neurological adverse effects may not be detected until post-marketing surveillance, which relies on spontaneous reporting systems, case reports, and various study designs like cohort, case-control, and self-controlled case series (SCCS). Understanding the benefit-risk balance between vaccination and natural infection is crucial for public health and regulatory decisions.

Neurotropic complications of live vaccination

Live attenuated vaccines may cause neurotropic complications, especially in immunocompromised individuals. The yellow fever vaccine can lead to neurotropic disease (YEL-AND), manifesting as meningitis or encephalitis. Oral poliovirus vaccine (OPV) can revert to a more virulent form, causing vaccine-derived poliovirus (VDPV) and vaccine-associated paralytic poliomyelitis (VAPP). Measles vaccination, particularly in immunocompromised individuals, can lead to rare cases of measles inclusion body encephalitis (MIBE), though it significantly reduces overall morbidity and mortality.

Neuro-immunological sequelae of vaccination

Vaccination may rarely lead to neuro-immunological conditions like GBS, transverse myelitis, and narcolepsy. GBS has been associated with adenoviral COVID-19 vaccines, though the risk is higher with natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Certain vaccines have also caused inflammation of the central nervous system, including transverse myelitis and acute disseminated encephalomyelitis. Narcolepsy was notably linked to the 2009 swine influenza vaccine.

Neurovascular complications of vaccination

The neurovascular complications of vaccination include serious conditions such as CVST, which was notably linked to the ChAdOx1 nCoV-19 COVID-19 vaccine. This vaccine was associated with vaccine-induced immune thrombotic thrombocytopenia (VITT). The severity of VITT led to restrictions on adenoviral vector vaccines and a shift towards messenger ribonucleic acid (mRNA) vaccines. Although mRNA COVID-19 vaccines have been associated with rare cases of hemorrhagic stroke and myocarditis, these risks are significantly lower than those posed by natural SARS-CoV-2 infection.

Exacerbation of pre-existing neurological disease

For multiple sclerosis, recent data show no strong link between vaccination and disease relapses, and COVID-19 vaccines have been beneficial, especially for those with advanced disability. Concerns about vaccines worsening inflammatory neuropathies like GBS have been mostly alleviated, with evidence suggesting minimal risk. Myasthenia gravis patients showed a slight increase in hospitalization risk after the ChAdOx1 nCoV-19 vaccine, but the cause remains unclear. Overall, vaccinations are generally safe, with minimal impact on conditions like epilepsy.

Improving vaccine safety

Improving vaccine safety, especially during pandemics, requires rapid and coordinated global efforts. It calls for solid networks linking clinical, regulatory, and scientific fields. Effective safety monitoring involves spontaneous reporting, post-authorization studies, data linkage, and research funding. Identifying issues like VITT demonstrates the importance of swift research and response. Future efforts should focus on systematic biological studies, centralized data analysis, and greater transparency to enhance vaccine safety.

Vaccine-related questions in the neurology clinic

In neurology clinics, patients often question whether their neurological condition was caused by vaccination. Most neurological issues occurring shortly after vaccination are coincidental, though specific conditions like VITT and GBS have established links. For individuals with neurological diseases, the benefits of vaccination usually outweigh the risks, but precautions are necessary for live vaccines. If a patient has had a rare adverse event, a detailed risk assessment is needed before considering further vaccinations, with alternatives potentially being explored.

Conclusion

In conclusion, the study highlights the importance of vaccines in preventing serious infections and associated neurological diseases while acknowledging that rare neurological adverse events may occur. Early and accurate identification of these events throughout vaccine development is a significant public health challenge, with neurologists playing a crucial role. Advances during the COVID-19 pandemic have improved the timely detection of safety concerns. However, there remains a gap in understanding the mechanisms behind vaccine-associated neurological effects. In the future, coordinated, global research efforts linking epidemiological studies with clinical and laboratory analyses are required to address these challenges and maintain societal trust in vaccination.