Abstracts

Rationale: Rett Syndrome (RTT) is a progressive neurological disorder characterized by a wide spectrum of phenotypes. Have been reported a classic form and an RTT variant caused by mutation respectively in the methyl-CpG binding protein 2 gene (MECP2) and in another X-linked gene, cyclin-dependent kinase-like 5 (CDKL5), responsible for the early-onset seizures variant. In the classic major clinical characteristics are developmental arrest, regression, stereotypic hand movements, ataxia, and epilepsy. In the early-onset form some variants have been described, displaying differences in disease onset and seizures severity such as infantile spasms. Epilepsy is reported to occur in 50 to 90% of patients with RTT. Seizures can be controlled with antiepileptic drugs (AEDs) in many patients, however, some develop medically refractory epilepsy. The aim of this study is to report the efficacy of Levetiracetam (LEV) in drug resistant patients with RTT.Methods: Patients with clinical and genetic diagnosis of RTT were recruited in an add-on, open-label treatment study. We selected 8 female patients with RTT with proved mutation of MECP2 gene (7 patients) and CDKL5 gene (1 patient). LEV was orally administrated as add-on therapy at the dose of 10 mg/kg/day each week up to the dose of 50-60 mg/kg/day in all cases. Seizures were classified according to the ILAE criteria. Efficacy parameters were reduction of seizure frequency and improvement of quality of life. Seizure frequency and type were recorded in an epilepsy diary.Results: The mean age at onset was 1.7+1.0 yrs. All patients but one presented mainly complex partial seizures, tonic seizures, myoclonic seizures and tonic-clonic generalized seizures which were unresponsive to several AEDs. One patient started to have infantile spasms, tonic seizures and myoclonic seizures at the age of 40 days associated with marked hypotonus. LEV has been administered at a mean dosage of 1700+800 mg/day. The patients have been followed-up for a mean period of 20+14 months. The mean monthly seizure frequency during the baseline period was 12.7 (range 3.5-35), and after LEV treatment was 2.2 (range 0-15). Two patients were seizure-free for more than 2 years, 2 patients were seizure-free for almost 1 year, 2 patients presented infrequent seizures and the last one had weekly seizures which were before almost daily. EEG evaluations showed multifocal and diffuse abnormalities in all patients, two patients had a marked activation of EEG abnormalities during sleep. Interictal EEG epileptiform abnormalities were reduced in 4 patients. One patient reported intermittent agitation which not required drug withdrawal.Conclusions: LEV seemed to be effective in our series of drug resistant RTT patients. All of them reported a reduction of seizures frequency and consequently a better quality of life also for caregivers. Although the limitation of this study is linked to the little number of patients we can confirm that LEV could be a valid chance in drug resistant RTT. More studies are needed to confirm our observational report with an higher number of RTT patients.