The pharmacological management of Lennox-Gastaut syndrome and critical literature review. (December 2018)

• Record Type: Journal Article
• Authors: Verrotti, Alberto; Striano, Pasquale; Iapadre, Giulia; Zagaroli, Luca; Bonanni, Paolo; Coppola, Giangennaro; Elia, Maurizio; Mecarelli, Oriano; Franzoni, Emilio; Liso, Paola De; Vigevano, Federico; Curatolo, Paolo
• Is Part Of: Seizure. Volume 63(2018)
• Page Start: 17
• Page End: 25
• Publication Date: 2018-12
• Subjects: LGS Lennox-Gastaut syndrome -- AED antiepileptic drug -- ID intellectual disability -- CNS central nervous system -- MR magnetic resonance -- EEG electroencephalogram -- HV hyperventilation -- IPS intermittent photic stimulation -- SSW slow spike-waves -- PFA paroxysmal fast activity -- fMRI functional magnetic resonance imaging -- SE status epilepticus -- NCSE non-convulsive status epilepticus -- MAE myoclonic astatic epilepsy -- SMEI severe myoclonic epilepsy of infancy -- ABPE/PLS atypical benign partial epilepsy/pseudo-Lennox syndrome -- QoL quality of life -- VPA valproic acid -- NMDA N-metil-d-aspartate -- VGSCs voltage-gated sodium channels -- AEs adverse events -- FDA Food and Drug Administration -- EMA European Medicines Agency -- PBO placebo -- RCT randomized controlled trial -- LTG lamotrigine -- RCT randomized controlled trial -- TPM topiramate -- RUF rufinamide -- FBM felbamate -- CLB clobazam -- ZNS zonisamide -- LEV levetiracetam -- PER perampanel -- FFA fenfluramine -- CBD cannabidiol; Lennox-Gastaut syndrome -- Epileptic encephalopathy -- Cannabidiol -- Fenfluramine -- Antiepileptic therapy -- Drop attack; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2018.10.016
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: Lennox-Gastaut syndrome (LGS) is still burdened by highly drug-resistant seizures. The antiepileptic therapy must be individualized and based on seizure type. Despite many drugs available, valproate continues to have a role in the LGS treatment. Lamotrigine, rufinamide, topiramate, and clobazam are effective add-on therapies. Cannabidiol is effective against LGS seizures, mostly against drop attacks. Abstract: Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with a prevalence of 1–2% of all patients with epilepsy. It is characterized by multiple pharmaco-resistant seizure types, including tonic, atypical absences and tonic or atonic drop attacks, and the presence of electroencephalographic abnormalities, such as slow-spike waves and paroxysmal fast rhythms. Intellectual disability, behavioural and psychiatric disorders are common comorbidities; these disturbances have a multi-factorial pathogenesis. The selection of the most appropriate drug must be tailored to each patient and guided by the prevalent seizure type. In this paper available pharmacological options are discussed and for each pharmacological agent, current evidence of efficacy and tolerability is provided. Valproic acid represents one of the first-line options in the treatment of LGS. Anyway, other antiepileptic drugs (AEDs) may be considered and added: lamotrigine, rufinamide, topiramate, clobazam can be efficacious. The use of felbamate must be carefully evaluated because of its adverse events. Perampanel, zonisamide, levetiracetam and fenfluramine have shown to be useful in the treatment of selected patients; nevertheless, the lack of RCTs does not allow to recommend their use in a systematic way. Recently, cannabidiol has provided high evidence of efficacy against LGS seizures; however, these data must be confirmed by long-term extensive studies and by trials comparing different AEDs, one to each other.