[Introduction] A genetic abnormality in PCDH19 causes infantile-onset intractable epilepsy in females (i.e., PCDH19-related female-limited epilepsy, PCDH19-FLE). This condition is characterized by recurrent seizure clusters often involving limbic structures and frequently precipitated by febrile illness. Autoantibodies to N-methyl-D-aspartate receptor (NMDAR-Abs) cause limbic encephalitis, but also appear in some patients with epilepsy, suggesting a possible link between NMDAR-Ab-mediated inflammatory processes and the pathogenesis of the epilepsy.

[Methods] To examine whether such immune processes are involved in PCDH19-FLE, NMDAR-Abs in the serum and/or cerebrospinal fluid (CSF) were analyzed in 8 Japanese patients by using an enzyme-linked immunosorbent assay or immunoblotting assay. Glucocorticoid treatment efficacy was also evaluated in 4 patients.

[Results] Titers of NMDAR-Abs taken within 6 years of disease onset were significantly elevated in the serum of 7/8 patients (87.5%) and in the CSF of 4/6 patients (66.7%). However, in a follow-up evaluation of 3 patients, serum titers were reduced. Although seizures were refractory to anticonvulsants, glucocorticoids immediately suppressed ongoing seizure clusters in all 4 patients who received them; specifically, 10–30 mg/kg of intravenous methylprednisolone for 3 days was effective in 3 patients aged 3 years or younger, and 1 mg/kg oral prednisolone was effective in 1 patient aged 11 years.

[Discussion] The prevalence of NMDAR-Abs was extremely high in patients with PCDH19-FLE, particularly during the early disease stages. Although the clinical significance of NMDAR-Abs remains unclear, the immediate anticonvulsant efficacy of glucocorticoid treatment suggests that increased vulnerability of the blood–brain barrier to systemic inflammation might underlie PCDH19-FLE pathogenesis.