Case Report: Mercury exposure and anti-LGI1/Caspr2 autoimmune encephalitis: a case series and literature review on the paradoxical worsening after chelation therapy.

BACKGROUND

Chronic mercury exposure may be a potential risk factor for anti-LGI1/Caspr2 autoimmune encephalitis (AE). The effect of chelation therapy on coexisting AE is unknown.

METHODS

We report three patients from West China Fourth Hospital, Sichuan University (September-November 2025) with confirmed chronic mercury exposure, anti-LGI1/Caspr2 antibody positivity, and DMPS chelation. Clinical course, antibody titers, and treatment response were analyzed.

RESULTS

Within 1-3 days of chelation initiation, all three patients developed acute neuropsychiatric deterioration, a phenomenon not previously documented. Each patient fully recovered with prompt immunotherapy, with favorable long-term outcomes (mRS 0-2). This observation appears to contrast with experimental animal models where chelators attenuate rather than exacerbate autoimmune neuroinflammation.

CONCLUSION

This series suggests that chelation therapy may be temporally associated with acute worsening in this specific population, highlighting a potential therapeutic dilemma: the standard treatment for mercury may, in some cases, be associated with exacerbation of the autoimmune process that may be related to its use. Screening for occult heavy metal exposure may be considered in unexplained AE, and immunotherapy should be initiated promptly if deterioration occurs.