Immunomodulation With Azathioprine Therapy in Rasmussen Syndrome: A Multimodal Evaluation

To verify safety and efficacy of the corticosteroid-sparing drug azathioprine (AZA) in Rasmussen syndrome (RS), we retrospectively analyzed a cohort of patients with RS recruited in a single pediatric neuroscience center.

We compared outcomes in 30 patients with RS who received AZA with 23 patients who were not treated with this drug. We used a multimodal approach to correlate therapy with clinical features (seizures, epilepsia partialis continua [EPC], hemiparesis) and neuroimaging markers of progressive brain atrophy.

AZA was well tolerated; only 1 patient discontinued treatment due to pancytopenia. In 27 of 30 patients receiving AZA, all of whom were corticosteroid responders, corticosteroid therapy could be weaned or reduced without worsening of seizures in 89%. Patients receiving AZA had a lower prevalence of EPC (42% vs 67% in controls) and hemiparesis (64% vs 92%, respectively). Cox regression showed for the AZA group compared to controls a delayed time to (1) EPC (≈2 years, exp[B] = 0.295, 95% confidence interval [CI] 0.108-0.807; p = 0.017), (2) hemiparesis (≈1 year, exp[B] = 0.315, 95% CI 0.137-0.724; p = 0.007), and (3) surgery (≈2 years, exp[B] = 2.068, 95% CI 1.012-4.227; p = 0.046). However, there were no group differences in cognitive decline over time (IQ change per year) or in hemispheric gray matter atrophy on serial MRI scans.

AZA treatment appears to slow clinical progression of RS in steroid responders; this will give the greatest advantage in patients in the early stages of the disease in whom surgical decision-making may require further time.

This study provides Class III evidence that for pediatric patients with RS AZA is well tolerated and slows hemiparesis and appearance of EPC.