Anti-NMDA autoimmune encephalitis associated with renal adenocarcinoma and drug-induced Brugada syndrome: a systematic review

Abstract

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis is a prevalent autoimmune condition marked by diverse neuropsychiatric symptoms, primarily impacting young females (Alzghoul et al., 2024). Approximately 38-40% of cases exhibit a paraneoplastic relationship, with ovarian teratomas being the most commonly associated malignancy (94% of tumor cases) (Vervloet Sollero et al., 2024; Alzghoul et al., 2024). The association between anti-NMDAr encephalitis and renal carcinoma is extremely rare, with isolated cases reported in the literature (Yang et al., 2020; Vervloet Sollero et al., 2024). Brugada syndrome is a cardiac channelopathy that predisposes to malignant ventricular arrhythmias and can be triggered by drugs, including those used in the management of encephalitis (Brugada et al., 2002). Objective: To synthesize the available evidence on anti-NMDA autoimmune encephalitis associated with renal adenocarcinoma and drug-induced Brugada syndrome. Methodology: Systematic review following PRISMA 2020 guidelines (Page et al., 2021). A systematic search was conducted in PubMed, LILACS, SciELO and Cochrane for studies published between 2000 and 2026 on anti-NMDA encephalitis, renal carcinoma and drug-induced Brugada syndrome. Results: Seven relevant studies documenting the association between anti-NMDA encephalitis and renal carcinoma were identified. Cases of young patients (20-54 years) with anti-NMDA encephalitis presenting clear cell renal carcinoma as underlying tumor were reported (Yang et al., 2020; Vervloet Sollero et al., 2024). Diagnosis was made through detection of anti-NMDAr antibodies in serum and CSF, and imaging studies revealing renal masses (Yang et al., 2020). Management included tumor resection, immunotherapy (corticosteroids, rituximab, cyclophosphamide) and plasmapheresis, with variable improvement of symptoms (Vervloet Sollero et al., 2024). The association with drug-induced Brugada syndrome has not been documented in the reviewed literature, but represents a potentially fatal complication requiring close electrocardiographic monitoring during immunosuppressive treatment (Brugada et al., 2002). Conclusion: Anti-NMDA encephalitis associated with renal carcinoma is an exceptional entity that requires a high index of suspicion and multidisciplinary management. Early diagnosis with imaging studies and antibody detection is essential to initiate timely immunosuppressive therapy and tumor resection. Electrocardiographic monitoring during treatment is essential to detect and manage drug-induced Brugada syndrome.