Lacosamide in Lennox-Gastaut Syndrome? Caution Is Still Needed

We read with interest the article by Miskin et al ¹ concerning the use of lacosamide in children with refractory epilepsy. This was a retrospective study attempting to evaluate the efficacy of lacosamide in patients with different forms of generalized epilepsies including Lennox-Gastaut syndrome. ¹ The authors observed a ≥50% seizure reduction in 7 of 8 Lennox-Gastaut syndrome patients. ¹

Lennox-Gastaut syndrome is characterized by different seizure types, including tonic seizures, cognitive impairment, interictal EEG pattern of diffuse, slow spike-wave complexes and fast (10-20 Hz) rhythms. ^{2 –4} However, in literature, Lennox-Gastaut syndrome has been often loosely used to denote severe seizure disorders of childhood featuring different types of generalized or focal seizures, and a substantial proportion of cases evade precise classification. ³ Miskin et al, surprisingly, do not specify inclusion criteria for Lennox-Gastaut syndrome patients and, hence, it is not possible to exclude that patients with different forms of generalized or focal epilepsy syndromes have been included in their series.

Some anecdotal reports ⁵ and one retrospective open-label study ⁶ reported the occurrence of seizure worsening (in particular tonic seizures) in Lennox-Gastaut syndrome patients starting treatment with lacosamide. It is well known that tonic seizures can have subtle clinical manifestations and might not be detected if specific strategies (close parents’ observation; video-polygraphic recording during wakefulness and sleep) are not adopted. ^3,4,7 Miskin et al also state that they had difficulty obtaining data regarding specific seizure type modified by lacosamide introduction; moreover, they do not specify how clinical evaluation was performed and if video-polygraphic recordings were obtained. Hence, there is a risk that authors missed the occurrence of tonic seizures aggravation. Finally, we disagree with Miskin et al’s conclusion that lacosamide is effective in patients with Lennox-Gastaut syndrome. We strongly suggest that lacosamide should be considered only after balance between risks and benefits in Lennox-Gastaut syndrome patients and that close parental monitoring and video-electroencephalographic (EEG) recording during wakefulness and sleep should be obtained after lacosamide introduction to promptly detect seizure worsening.