BACKGROUND: Rasmussen syndrome (RS) is a rare, immune-mediated, progressive epileptic encephalopathy. A comprehensive understanding of its heterogeneous clinical course, along with the identification of prognostic and early determinants, is crucial for timely intervention. To this end, we retrospectively analyzed 21 pediatric RS patients (2014-2024). Collected data encompassed epidemiology, clinical course, cognition, neuroimaging, immunology, histopathology, and treatment. Primary outcomes included the time from onset to the appearance of different clinical symptoms and cerebral atrophy. Cognitive decline was assessed through longitudinal Full-Scale IQ (FSIQ) measurements. RESULTS: Mean age at onset was 7.3 years; 52.4% were < 8 years. All patients presented with epilepsy as their initial manifestation and age at onset correlated with time to cognitive decline (r = 0.578, p = 0.049), motor symptoms (r = 0.568, p = 0.034) and epilepsia partialis continua (EPC) (r = 0.765, p = 0.004), identifying an age of 8 years as a cut-off to predict a different disease course. EPC occurred in 57.1% (median: 6.5 months) and its early onset was associated with a precocious appearance of motor deficit (r = 0.863, p < 0.001) and cerebral atrophy (r = 0.753, p = 0.007). The severity of cognitive decline was not related to age at disease onset, rapidity of development of cognitive impairment or baseline cognitive status. Four patients displayed atypical, slow-progressing forms with minimal deficits. Immunotherapy achieved partial or transient seizure control in most cases; rituximab was effective in 50%, particularly when started 2-5 years post-onset. Hemispherectomy yielded seizure freedom in 69.2%, with better postoperative FSIQ linked to higher preoperative FSIQ (r = 0.640, p = 0.025) and younger surgical age (r = -0.621, p = 0.003). CONCLUSIONS: Age at onset is a key prognostic factor in RS. The development of epilepsy and EPC, cognitive and motor impairment show a strong temporal association. The degree of cognitive decline does not parallel other clinical markers. Post-surgical cognitive outcomes are better in patients operated at a younger age and with greater cognitive preservation. We propose a clinical framework integrating immunotherapy selection and surgical planning to optimize outcomes and guide patient counseling.
Extremera et al. (Wed,) studied this question.