Immunomodulation With Azathioprine Therapy in Rasmussen Syndrome: A Multimodal Evaluation.

Area of Science:

• Neuroscience
• Pediatric Neurology
• Immunosuppressive Therapy

Background:

• Rasmussen syndrome (RS) is a rare, severe neurological disorder affecting one hemisphere of the brain.
• Corticosteroids are often used but have significant side effects, necessitating alternative treatments.
• Azathioprine (AZA) is an immunosuppressive drug with potential corticosteroid-sparing properties.

Purpose of the Study:

• To evaluate the safety and efficacy of azathioprine (AZA) as a corticosteroid-sparing agent in pediatric patients with Rasmussen syndrome (RS).
• To assess the impact of AZA on clinical progression, including seizures, epilepsia partialis continua (EPC), and hemiparesis.
• To correlate AZA therapy with neuroimaging markers of brain atrophy.

Main Methods:

• Retrospective analysis of a cohort of 30 pediatric RS patients treated with AZA and 23 untreated controls.
• Multimodal assessment of clinical features: seizures, EPC, hemiparesis.
• Neuroimaging analysis to evaluate progressive brain atrophy.

Main Results:

• Azathioprine (AZA) was well tolerated, with only one patient discontinuing due to pancytopenia.
• In corticosteroid-responding patients, AZA allowed for weaning or reduction of corticosteroids in 89% without seizure worsening.
• AZA treatment was associated with a lower prevalence of EPC (42% vs. 67%) and hemiparesis (64% vs. 92%) compared to controls.
• Cox regression indicated a delayed onset of EPC (approx. 2 years) and hemiparesis (approx. 1 year) in the AZA group.
• No significant differences were observed in cognitive decline or hemispheric gray matter atrophy between groups.

Conclusions:

• Azathioprine (AZA) is a well-tolerated and effective treatment for slowing the clinical progression of Rasmussen syndrome (RS) in patients who respond to corticosteroids.
• AZA offers significant benefits in delaying the onset of hemiparesis and epilepsia partialis continua (EPC), particularly in early disease stages.
• This treatment may provide valuable time for surgical decision-making in pediatric RS patients.