Abstracts

We describe experience of the use of azathioprine in the management of Rasmussen[apos]s Syndrome at two tertiary referral centres. Outcome (clinical, radiological and time to surgery) compared favourably with that of historical controls. Six children were commenced on azathioprine (1.5 mg/kg/day orally) for refractory seizures (n=2) and failure to wean from high dose steroids (n=4). Response was monitored, specifically; seizure control, motor dysfunction, cognitive dysfunction, neuro-imaging and time to epilepsy surgery. Outcome measures were compared to data available from a series of 13 children with Rasmussen[apos]s Syndrome, seen at our unit between 1987 and 2005, and not treated with azathioprine. Four children treated with azathioprine responded (all four had also shown previous response to steroids). Two patients did not respond to Azathioprine and indeed had also not shown clinical response to other medical treatments.
Compared to the non-azathioprine group, azathioprine-responders[apos] seizure frequencies decreased, steroids were weaned and anti-epileptic drugs reduced. A trial discontinuation of azathioprine resulted in deterioration of seizure control (n=1). Rate of progression of hemi-deficit slowed (4/4). Two of the 4 children had had previous surgery; one child is being considered for surgery (10 yrs from disease onset); one child does not yet require consideration (7 yrs from disease onset). Mean time from disease onset to surgery in the non-azathioprine group was 3.7 years. Mean duration of follow-up of azathioprine-responders is now 5 yrs from commencing azathioprine (8.9 yrs from disease onset). No or minimal evidence of radiological disease progression was seen in the azathioprine-responders, in contrast to definite progression in the non-azathioprine group. Although clinical impression was of cognitive stabilisation in azathioprine responders, neuropsychological testing did not demonstrate objective support of this observation. In this small series, azathioprine showed potential as an alternative medical therapy in the treatment of Rasmussen[apos]s Syndrome. Azathioprine may be acting as an immunosuppressive or as a steroid sparing agent. Further larger studies are needed better to examine azathioprine in Rasmussen[apos]s Syndrome. (Supported by Sophia Varadkar is supported by a Great Ormond Street Hospital/Institute of Child Health Springboard Clinical Research Training Fellowship. Catherine Riney is supported by Sport Aiding Medical Research for Kids (SPARKS). Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from Research and Development funding received from the NHS Executive.)