A phenome-wide association study of rurality in the All of Us Research Program.

Mercury exposure is an established but frequently overlooked environmental risk factor for autoimmune phenomena. Its potential role in autoimmune encephalitis (AE)—particularly in anti-LGI1 and anti-Caspr2 antibody-associated syndromes—remains poorly defined, with only scattered case reports in the literature (–). Even less understood is the paradoxical effect of chelation therapy, which has been sporadically implicated in neurological deterioration rather than improvement (, ). Anti-LGI1 encephalitis typically presents with limbic dysfunction, hyponatremia, and faciobrachial dystonic seizures, while anti-Caspr2 antibodies are associated with central and peripheral hyperexcitability, including Morvan’s syndrome (, ). Although paraneoplastic and post-infectious triggers are well recognized, environmental toxicants such as mercury have not been systematically investigated in these specific serotypes. Here we report three patients with confirmed chronic mercury exposure and anti-LGI1/Caspr2 encephalitis—one positive for anti-LGI1, one for anti-Caspr2, and one dual-positive—all of whom exhibited acute neuropsychiatric worsening immediately following chelation therapy. Through detailed case analysis and literature review, we describe this association and document a consistent phenomenon of exacerbation temporally associated with chelation. These findings suggest that heavy metal screening may be considered in unexplained AE and highlight the need for further evaluation of chelation indications in antibody-positive patients.