Background: Neuroinflammatory conditions involving the central nervous system (CNS) are on the rise and while the etiology is currently unknown the parallel rise in cases to mass COVID-19 vaccination is of particular interest. This study explores the association between the CNS infection rate and vaccination. Methods: This is a retrospective study. Retrospective data were utilized from the U. S. centers for disease control and prevention (CDC) and the U.S. food and drug administration (FDA) vaccine adverse event reporting system (VAERS). Adverse events (AEs) encompassing CNS conditions following all vaccines were queried from January 1, 1990, through November 30, 2024. The timeframe for all vaccines except COVID-19 vaccines was 419 months and the timeframe for COVID-19 vaccines was 47 months (January 1, 2021, to November 30, 2024). Observed AEs are presented as odds ratios (ORs) by time which compare these events occurring after COVID-19 vaccination to those after influenza vaccination and to those after all other vaccines. Results: Comparing COVID-19 vaccination to annual influenza vaccinations and all vaccines combined, the CDC/FDA’s safety signal thresholds were breached for the multiple outcomes. Data are expressed as OR, 95% confidence interval (CI), p value, Z score. All CNS categories reviewed produced a safety signal when comparing events after COVID-19 vaccination to influenza vaccination (referent). Thirty-nine events were categorized as CNS infection (29.4, 21.6-40.1, <000.1, 21.4); 11 events grouped as herpetic CNS Infection (171, 93.9-312, <000.1, 16.8); and 4 categorized as CNS abscess (107, 40.9-280, <000.1, 9.53). Similarly, CNS Infections, herpetic CNS infection, and CNS abscess categories also produced a safety signal when comparing events after COVID-19 vaccination to all vaccines combined (referent) (except COVID-19): 39 events categorized as CNS Infections (4.11, 3.03-5.57, <000.1, 9.09); 11 events grouped as herpetic CNS Infection (22.3, 15.4-32.4, <000.1, 16.4) and; 4 events noted as CNS abscess (17.8, 10.5-30.4, <000.1, 10.6). When comparing COVID-19 vaccination to influenza vaccination as well as all vaccines combined, 7 of 9 events in the uncommon neurological disease grouping exceeded safety thresholds for both comparisons. Conclusions: All safety signals reported are concerning and support an immediate global ban on the COVID-19 vaccination program.