Etiologies of Multidrug-Resistant Epilepsy in Latin America: A Comprehensive Review of Structural, Genetic, Metabolic, Inflammatory, and Infectious Origins: A Systematic Review

Epilepsy is a prevalent neurological disorder that affects millions worldwide, with a significant portion of individuals experiencing drug-resistant forms of the condition. In Latin America, the challenge of identifying the underlying causes of multidrug-resistant epilepsy (MDRE) is particularly pressing. (1) Background: This systematic review aims to highlight the critical importance of understanding the etiology of MDRE in Latin America. (2) Methods: A systematic review of Medline (PubMed), Scopus, and Web of Science was conducted following the PRISMA methodology; articles were selected if they included information on the etiology of MDRE in Latin-American participants, and the NHLBI tool was used to assess bias. (3) Results: A total of 37 published articles were finally included in the review. The most frequently documented cause of drug-resistant epilepsy was structural, affecting 725 patients, with hippocampal atrophy and sclerosis predominantly involving both the right and left lobes. The second most common cause was genetic, identified in 362 individuals who exhibited polymorphisms in genes such as <i>ABCB1</i>, <i>CYP2C9</i>, <i>SCN1A</i>, <i>SLC6A4</i>, and <i>MDR-1</i>, among others. The third most frequent cause was metabolic, and the fourth was inflammatory, affecting 258 individuals, which was associated with various inflammatory markers, including IL-1β, IL-6, CD8+, CD-25, and HLA-DR. Finally, infectious causes were also reported. (4) Conclusions: Structural causes are the leading etiology of MDRE in Latin America, followed by genetic, metabolic, inflammatory, and infectious origins. The regional pattern contrasts with findings from Europe and Asia, highlighting the influence of socioeconomic, environmental, and population-specific genetic factors. Our findings underscore the urgent need for regionally tailored research and interventions, particularly in understudied areas such as infectious causes and neuroinflammation.