Autoimmune Epilepsy Temporally Associated With Lyme Disease: A Report of Two Cases

The relationship between Lyme-associated illness and immune-mediated seizure disorders remains incompletely characterized. Infection-triggered neurologic immune syndromes are well described in some settings, but evidence linking Borrelia burgdorferi to autoimmune epilepsy remains limited and is based primarily on isolated reports. We describe two previously healthy patients, a 25-year-old male and a 14-year-old female, who developed new-onset seizures temporally associated with Lyme-associated illness and the initiation of antimicrobial therapy. Diagnostic evaluation included serologic testing for tick-borne disease performed through outside commercial laboratories and subsequent reference laboratory testing, cerebrospinal fluid (CSF) analysis, neuroimaging, electroencephalography, neural autoantibody testing, quantitative immunoglobulins, IgG subclass testing, and complement studies. In both cases, seizure activity persisted despite multiple antiseizure medications and worsened after initiation of antimicrobial therapy. Laboratory evaluation demonstrated hypogammaglobulinemia with IgG subclass deficiencies and complement abnormalities in both cases. Neural autoantibody testing revealed elevated anti-dopamine receptor D1 antibodies in both patients; the adult patient also had a low-titer serum N-methyl-D-aspartate receptor antibody detected by a cell-based assay. Immunomodulatory therapy with systemic corticosteroids, followed by intravenous immunoglobulin, administered while antimicrobial therapy was continued, was associated with marked seizure reduction and sustained clinical improvement. These cases demonstrate a temporal association between Lyme-associated illness, antimicrobial treatment, infection-associated immune activation, and treatment-refractory seizures. The clinical deterioration observed after initiation of antimicrobial therapy may reflect an inflammatory response associated with microbial die-off, similar to a Jarisch-Herxheimer-type reaction described in spirochetal infections. Although the findings do not establish a causal relationship between Lyme disease and autoimmune epilepsy, they raise the possibility that infection-associated immune dysregulation may contribute to seizure pathogenesis in selected patients. These observations are hypothesis-generating and support maintaining a broad differential diagnosis, including neuroimmune mechanisms, in patients presenting with new-onset seizures in the setting of suspected infectious illness.