Encephalitis is the inflammation of brain parenchyma, which usually occurs due to viral infections, autoimmune responses, or other infections [1]. Myelitis is a spinal cord inflammation that causes motor and sensory dysfunction [2]. Encephalomyelitis is the inflammation of both the spinal cord and brain. Mild symptoms may include headache and fever; moderate to severe manifestations can include seizures, paralysis, and even death [3]. Encephalitis is rare, and the global incidence is estimated to range from 3.5 to 12.3 cases per 100,000 individuals annually [4], [5].

Despite improved overall treatment outcomes, encephalitis remains a global concern due to its high morbidity and mortality [6], [7]. Large-scale studies indicate that more than 50 % of encephalitis cases typically lack an identified etiology, posing additional challenges in prognosis and treatment [8], [9], [10], [11]. This diagnostic uncertainty emphasizes the need for continued research and improved clinical strategies to address the burden of encephalitis and related neuroinflammatory conditions.

In the United States, encephalitis, myelitis, and encephalomyelitis continue to pose a significant disease burden with notable mortality rates [11], [12], [13]. West Nile Virus has become a key viral cause of encephalitis [14], [15]. The epidemiology of the HIV/AIDS epidemic has undergone substantial shifts [16], [17], and there has been growing attention among clinicians and researchers toward non-infectious etiologies [18], [19]. Furthermore, the broader U.S. healthcare landscape has evolved, with increasing emphasis on patient outcomes and quality of care [20].

Given the substantial incidence and significant economic burden associated with these conditions, analyzing mortality trends due to encephalitis, myelitis, and encephalomyelitis is crucial for understanding their broader impact. Therefore, we conducted a retrospective analysis using data from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database to examine mortality patterns across various demographics and regions within the United States. We aimed to investigate population-based mortality trends of encephalitis, myelitis, and encephalomyelitis in the United States over the past 20 years. Identifying and stratifying at-risk populations can help inform targeted monitoring strategies, aiding clinicians in assessing prognosis and optimizing treatment approaches. Such insights can enhance clinical decision-making, patient management, and overall outcomes for those affected by these neuroinflammatory conditions.