Overview
This case report and literature review describes three patients with confirmed chronic mercury exposure who developed anti-LGI1 and/or anti-Caspr2 antibody-positive autoimmune encephalitis (AE). All three patients showed acute neuropsychiatric deterioration within 1 to 3 days of initiating DMPS chelation therapy — a paradoxical worsening not previously documented systematically. Each patient recovered with prompt immunotherapy, with favorable long-term outcomes (modified Rankin Scale score 0 to 2). The paper proposes that chelation may transiently mobilize mercury, triggering acute immune activation in susceptible individuals with pre-existing voltage-gated potassium channel complex (VGKC) antibodies.
Key numbers
Measured blood and urine mercury at presentation (Table 1):
- Case 1 (female, 60s; mining area exposure, 8 years): blood mercury 24.2 microg/L (reference <7.8), urine mercury 113 micromol/mol creatinine (reference <2.25). Chelation exacerbation onset: day 1.
- Case 2 (female, 40s; suspected unregulated medication, 2 months): blood mercury 4.68 mg/L (reference 0-7.8), urine mercury 35.5 mmol/mol creatinine (reference 0-2.25). Chelation exacerbation onset: day 3.
- Case 3 (male, 50s; metallurgy, 2 years): blood mercury 14.7 microg/L, urine mercury 372 micromol/mol creatinine. Chelation exacerbation onset: day 1.
Post-treatment (following immunotherapy):
- Case 1: blood mercury 3.05 microg/L, urine mercury 1.73 mmol/mol chromium (Cr); mRS 1; anti-LGI1 antibodies negative.
- Case 2: blood mercury 3.62 microg/L, urine mercury 6.98 mmol/mol Cr; mRS 0; antibodies negative.
- Case 3: blood mercury 3.89 microg/L, urine mercury 9.23 mmol/mol Cr; mRS 2; anti-Caspr2 1:32.
Pre-chelation antibody titers:
- Case 1: anti-LGI1 IgG CSF/serum 1:3.2/1:10.
- Case 2: anti-Caspr2 IgG serum 1:10.
- Case 3: anti-Caspr2 IgG serum 1:1/1:320.
DMPS chelation regimen: 250 to 375 mg/day intravenously, 3 days on and 4 days off, 2 cycles.
Methods (brief)
Retrospective case series; n=3 patients identified at a single tertiary center over 3 months. Diagnosis confirmed by serum/CSF anti-LGI1 and anti-Caspr2 antibody testing using cell-based assay. Blood and urine mercury by toxicological screening (laboratory method not specified). Literature review: PubMed, EMBASE, CNKI, WanFang, and VIP China Science; search to December 2025 using terms for mercury, mercury (Hg), anti-LGI1, Caspr2, AE, chelation, immunotherapy. Final inclusion: 4 articles reporting 13 unique patients meeting criteria. EEG and MRI obtained in all cases; CSF analysis performed in all cases.
Limitations
Case series (n=3); no control group; cannot establish causal direction of chelation-to-worsening relationship. The small sample precludes epidemiological generalization. Cytokine profiling, HLA typing, and immune cell characterization were not performed. Authors cannot exclude that observed worsening reflected the natural history of untreated AE rather than a true chelation effect. Single-center; publication bias toward severe cases.
Implications
Certification: Establishes mercury as a potential trigger for anti-LGI1/Caspr2 autoimmune encephalitis. Screening for occult mercury exposure should be considered in unexplained AE, particularly in patients with occupational or environmental exposure history.
Courses: Illustrates the diagnostic complexity of metal-associated autoimmune neurological disease; relevant to the autoimmunity and neurotoxicology modules. The paradoxical chelation worsening is a clinical teaching point.
App: No food concentration data. Mercury autoimmunity endpoint contributes to health framing for total mercury (tHg) and methylmercury (MeHg).
Microbiome: Does not address gut microbiota.
Related evidence
Update history
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