Abstract
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a complex neuroinflammatory condition often triggered by underlying factors such as viral infections or malignancies, although idiopathic cases are not uncommon. Here, we present a unique case of a 27-year-old female patient diagnosed with anti-NMDAR encephalitis, where Lyme disease emerges as a plausible yet underrecognized trigger. The patient initially presented to the emergency department (ED) with acute psychosis and was later found to have positive Borrelia burgdorferi immunoglobulin G (IgG) titers, antibodies against the NR1 subunit of NMDA, and subacute thyroiditis. A detailed investigation ruled out other paraneoplastic or infectious causes, pointing to Lyme disease as the most likely precipitant. Notably, her exposure to B. burgdorferi preceded the onset of encephalitis by two years. Treatment with immunotherapy and antibiotics resulted in significant clinical improvement. This case highlights the importance of a thorough evaluation of potential triggers of anti-NMDAR encephalitis, emphasizing that it should not be presumed idiopathic without exhaustive investigation. Awareness of Lyme disease as a possible etiological factor may facilitate more targeted management, reduce prolonged hospital stays, and mitigate the burden of extensive diagnostic workups. By addressing the root cause, clinicians can improve patient outcomes and prevent disease recurrence or complications associated with empiric treatment alone.