The pharmacological management of Lennox-Gastaut syndrome and critical literature review

Abstract

A B S T R A C TLennox-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.

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies

“…Given the complex nature of the syndrome, with its highly drug-resistant seizures, the treatment of LGS is challenging [1,5,[22][23][24][25], necessitating novel effective and tolerable treatments that reduce seizures and improve QoL. This review summarises the current and future options for the treatment of seizures associated with LGS (Fig.…”

Biological bases for a possible effect of cannabidiol in Parkinson’s disease

“…72 The concentration of CBD in cannabis is highly variable, depending on plant phenotype, cultivation conditions, and which part of the plant is used to obtain the extract. 73 CBD exerts a variety of effects in laboratory animals and humans, including sedative/hypnotic, 74,75 anticonvulsant, 76,77 neuroprotective, 78,79 cardiovascular, 80,81 and anti-inflammatory. 78,82 These actions do not seem to be dependent on cannabinoid receptors.…”

Antiepileptic Drug Selection According to Seizure Type in Adult Patients with Epilepsy

“…Lamotrigine, 49 topiramate, 50 and rufinamide 51 are also used as adjunctive treatment for atonic seizure. However, rufinamide has recently been reported to aggravate atonic seizure.…”