Abstracts

Rationale: CDKL5 related disorder causes an early –onset epileptic encephalopathy that not only is highly refractory to anti-seizure treatment but it is also associated with loss of efficacy to medications over time (Muller et al. 2015). Use of steroids and IVIG in CDKL5 related epileptic encephalopathy has not been previously reported. This study describe the response of seizures and neurodevelopment in 3 children with CDKL5 treated with oral prednisone (OP) and IVIG over a course of a year. Methods: Candidates for treatment were selected from a population of CDKL5 children evaluated at the Cleveland Clinic CDKL5 center of excellence. All 3 children were experiencing brief and prolonged motor seizures (>5 minutes) every day and one had also epileptic spasms. Treatment with OP was started after the confirmation of the seizures on VEEG. Dose was 2mg/kg/day every morning for 4 weeks followed by a tapper of 0.5mg/kg/day every 4 weeks to final dose of 0 (length of treatment 5 months). Treatment with monthly IVIG infusion was added after 6 weeks of treatment with OP. Treatment response was evaluated in a monthly clinic appointment by reviewing the seizure log and evaluation the changes in the neurodevelopment. EEG/VEEG were done at the onset of treatment and repeated within the first month and between 2-3 months of treatment. Results: Demographic, genetic phenotype, clinical / EEG findings and anti-seizure treatment history are described in table 1. Table 2 shows treatment response (seizures, development, EEG and side effects) in each case. All children had reduction of frequency and duration of prolonged motor seizures but some short hypomotor seizures persisted during treatment with OP at doses above 1mg/kg/day. Seizure control and EEG findings deteriorated when the dose was reduced below 1 mg/kg/d Children received 3-8 serial doses of IVIG every month that overlapped with weaning phase of OP. IVIG did not provide added benefit to the seizure control in cases 2 and 3 but case 1 remained free of prolonged motor seizures during the 8 months of treatment. Follow up EEG in 2 children showed emergence of PDR and resolution of hypsarrhythmia. Case 1 developed hypertension. Case 2 and 3 had worsening dyskinesia during the treatment with OP. Severe dyskinesia led to premature weaning of OP in Case 3. Case 3 developed sleepiness and tiredness after the initial dose of IVIG. The other cases tolerated the IVIG infusion well. Conclusions: Oral prednisone is a reasonable treatment option for medically refractory seizures in selected children with CDKL5 related epileptic encephalopathy, in particular those experiencing frequent prolonged motor seizures. Serial IVIG doses (up to 8 doses) provided beneficial seizure control only in one child (Case 1). Improvement in alertness and gross motor skills were seen in all children during the course of with OP but it was not sustained overtime when seizure relapsed at doses of OP under 1mg/kg/day that coincided with the time when the IVIG was added. Funding: None