Childhood-onset Epileptic Encephalopathy Research Articles

Rational approach to treatment options for Lennox‐Gastaut syndrome

Lennox-Gastaut syndrome (LGS) is an intractable childhood-onset epileptic encephalopathy. Seizure freedom is rare in LGS. One of the hallmarks of LGS is medical intractability, with generally poor response to antiepileptic drugs (AEDs). Nevertheless, several treatment options are available that can mitigate the severity of seizures and curtail their frequency. New AEDs have been validated in randomized, controlled trials for the treatment of seizures in LGS. In some cases, nonpharmacologic options may be effective, although more data are needed to confirm efficacy outcomes. Comprehensive patient assessments are critical to achieve an optimal AED treatment regimen and minimize the potential for adverse effects.

Rufinamide in refractory childhood epileptic encephalopathies other than Lennox–Gastaut syndrome

To report on the first multicenter Italian experience with rufinamide as adjunctive drug in children, adolescents and young adults with refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. Thirty-eight patients (19 males, 19 females), aged between 4 and 34 (mean 13.7 ± 8.3, median 12.5), all affected by different types of childhood-onset refractory epileptic encephalopathies other than Lennox-Gastaut syndrome, were treated with rufinamide as adjunctive drug for a mean period of 11.4 months (range 3-26 months). Fifteen of 38 patients (39.5%) had a ≥ 50% seizure reduction in countable seizures. Complete seizure freedom was achieved in one of these patients (2.6%). Three patients (7.9%) had a 25-49% seizure reduction, whilst seizure frequency remained unchanged in 15 (39.5%) and increased in five patients (13.1%). Eleven patients (28.9%) reported adverse side effects. Vomiting was reported in five patients (13.1%); drowsiness, decreased appetite and irritability with migraine manifested in other four patients. They were transient and mild in all cases. Rufinamide may be an effective and well-tolerated adjunctive drug for the treatment of refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. Rufinamide was most effective in patients with drop-attacks and (bi)frontal spike-wave discharges.

Update on rufinamide in childhood epilepsy

Rufinamide is an orally active, structurally novel compound (1-[(2,6-difluorophenil1) methyl1]-1 hydro 1,2,3-triazole-4 carboxamide), which is structurally distinct from other anticonvulsant drugs. It was granted orphan drug status for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in the United States in 2004, and released for use in Europe in 2007. In January 2009, rufinamide was approved by the United States Food and Drug Administration for treatment of LGS in children 4 years of age and older. It is also approved for adjunctive treatment for partial seizures in adults and adolescents. Rufinamide’s efficacy mainly against atonic/tonic seizures in patients with LGS seems nowadays indubitable and has been confirmed both in randomized controlled trial and in open label extension studies. More recently, rufinamide was evaluated for the adjunctive treatment of childhood-onset epileptic encephalopathies and epileptic syndromes other than LGS, including epileptic spasms, multifocal epileptic encephalopathy with spasm/tonic seizures, myoclonic-astatic epilepsy, Dravet syndrome and malignant migrating partial seizures in infancy. This review updates the existing literature data on the efficacy and safety/tolerability of rufinamide in childhood-onset epilepsy syndromes.

Landau–Kleffner syndrome, electrical status epilepticus in slow wave sleep, and language regression in children

The Landau-Kleffner syndrome (LKS) and electrical status epilepticus in slow wave sleep (ESES) are rare childhood-onset epileptic encephalopathies in which loss of language skills occurs in the context of an epileptiform EEG activated in sleep. Although in LKS the loss of function is limited to language, in ESES there is a wider spectrum of cognitive impairment. The two syndromes are distinct but have some overlap. The relationship between the epileptiform EEG abnormalities and the loss of cognitive function remains controversial, even in LKS which is the most widely accepted as an acquired epileptic aphasia. Language regression also occurs in younger children, frequently in the context of a more global autistic regression. Many of these children have epileptiform EEGs. The term autistic regression with epileptiform EEG has been proposed for these children. Whether these children are part of an extended LKS spectrum is very controversial, because there are differences in age of onset, clinical phenotype, and EEG findings. An understanding of the available data on clinical characteristics, EEG findings, pathology, prognosis, and treatment of these syndromes is essential for further progress in this area.