Reduction in Seizure Generalization Associated With Long-Term Low-Dose Immunomodulatory Therapy Using Prednisolone...

Rett syndrome is a severe neurodevelopmental disorder most commonly associated with pathogenic variants of the MECP2 gene and frequently accompanied by epilepsy. Seizures occur in a substantial proportion of patients and may be resistant to conventional antiepileptic therapy. Emerging evidence suggests that neuroinflammatory processes may contribute to seizure propagation and represent a potential therapeutic target.

A girl born at term with initially normal early development is described. At approximately 2 years of age, she developed regression of speech and stereotypic hand movements, accompanied by seizures and other neurological features consistent with Rett syndrome. The patient received long-term therapy consisting of low-dose prednisolone and methotrexate in addition to anticonvulsant treatment. During follow-up, a reduction in seizure generalization and a shift in seizure pattern were observed, with generalized seizures becoming less frequent and replaced by brief focal seizures without secondary generalization.

In this single case, long-term low-dose prednisolone and methotrexate therapy was associated with a reduction in seizure generalization. Although a causal relationship cannot be established, this observation supports the hypothesis that immunomodulatory mechanisms may influence seizure propagation in pharmacoresistant epilepsy.