Anti-NMDAR antibodies are not prevalent in Lyme neuroborreliosis: a retrospective cohort study

BACKGROUND: Four published case reports have proposed Lyme neuroborreliosis (LNB) as a trigger for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. In this study, we examined the prevalence of anti-NMDAR antibodies in a well-characterized cohort of patients with LNB.

METHODS: In this retrospective cohort study, archived cerebrospinal fluid (CSF) samples from patients diagnosed with LNB between 2001 and 2012 were analyzed for anti-NMDAR IgG using a standard commercial cell-based assay. LNB diagnosis followed the European Federation of Neurological Societies guidelines. To identify potential later development of anti-NMDAR encephalitis, an infectious disease specialist systematically reviewed medical records in 2021, and the national reference center for neural autoantibody testing verified testing history in 2025.

RESULTS: We included 82 patients with a median age of 52 years (interquartile range [IQR]: 34-63); 55% were male. Median symptom duration before diagnosis was 21 days (IQR: 7-45). The most frequent symptoms were cranial nerve palsy (51%) and radiating pain (50%). Among 70 patients with available CSF data, limited by access to laboratory records, the median CSF leukocyte count was 124 × 106 cells/L (IQR: 61-236). None of the 82 CSF samples tested positive for anti-NMDAR antibodies, resulting in an estimated prevalence of 0% (95% CI: 0.0-4.4). No patients were clinically suspected of autoimmune encephalitis or tested for it.

CONCLUSION: Anti-NMDAR antibodies were not detected in the CSF of LNB patients, suggesting their presence is rare in this population at diagnosis. Although the sample size may limit statistical power, the absence of later clinical suspicion or testing supports the hypothesis that LNB is an uncommon trigger for anti-NMDAR encephalitis.