Abstracts

Rationale: Mutations of or deletions in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) cause an epileptic encephalopathy with early-onset severe neurological impairment and intractable seizures. So far there is no concept how to treat these rare patients. In this retrospective study we evaluated the efficacy of antiepileptic drugs in patients with CDKL5 mutations. Methods: 29 patients (25 female; 4 male; age: 1.6-22.4 years; mean 7.5) with CDKL5 mutations were included. All of them showed a severe global retardation. We retrospectively analyzed the efficacy of AED after 3 and 6 months. Responder rate was defined as a 50% seizure reduction. Results: The patients were treated with 4 to 21 (mean: 9) different AED: The five most frequently used drugs were LEV (100%), VPA (93%), TPM (79%), PB (69%) and steroids (69%). 26 patients (90%) showed initial response to at least one AED for several weeks. In most of them, loss of efficacy occurred in the following weeks. One patient became (and still remains) seizure free with CBZ for 9 years. In the other patients seizures recurred after weeks to months. The responder rate to at least one AED after 3 months was 69% (20/29) and 24% (7/29) after 6 months. The highest rate of seizure reduction after 3 months was reported during treatment with FBM (2/3), CLB (5/13), steroids (6/20), VPA (6/27) and LEV (6/29). 12 patients (41%) experienced a seizure aggravation to at least one AED. LEV (5/29), CBZ (4/12) and LTG (3/16) were described most frequently as aggravating, which lead to discontinuation. One patient (1/1) responded to intravenous immunoglobulines and 2/11 to ketogenic diet. Conclusions: Most patients showed some but only initial response to various AEDs with different modes of actions. Seizure aggravation was frequently reported. Because of age-related and spontaneous fluctuation in seizure frequency and types, overall benefit of different antiepileptic drugs remains unclear. Collaborated clinical long-term observations might help clinicians to define treatment stretegies in patients with this rare and refractory epileptic encephalopathy.