No 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.

Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5–1% and a lifetime incidence of 1–3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on society and global health. In recent decades, dietary regimens have been used effectively in the treatment of drug-resistant epilepsy, following the path of a non-pharmacological approach. The ketogenic diet and its variants (e.g., the modified Atkins diet) have an established role in contrasting epileptogenesis through the production of a series of cascading events induced by physiological ketosis. Other dietary regimens, such as caloric restriction and a gluten free diet, can also exert beneficial effects on neuroprotection and, therefore, on refractory epilepsy. The purpose of this review was to analyze the evidence from the literature about the possible efficacy of different dietary regimens on epilepsy, focusing on the underlying pathophysiological mechanisms, safety, and tolerability both in pediatric and adult population. We believe that a better knowledge of the cellular and molecular biochemical processes behind the anticonvulsant effects of alimentary therapies may lead to the development of personalized dietary intervention protocols.