Abstract
Lennox–Gastaut syndrome (LGS) is a severe age-dependent epileptic encephalopathy usually
with onset between 1 and 8 years of age. Functional neuroimaging studies recently
introduced the concept of Lennox–Gastaut as “secondary network epilepsy” resulting
from dysfunctions of a complex system involving both cortical and subcortical structures
(default-mode network, corticoreticular connections, and thalamus). These dysfunctions
are produced by different disorders including hypoxic–ischemic encephalopathies, meningoencephalitis,
cortical malformations, neurocutaneous disorders, or tumors. The list of etiologies
was expanded to pathogenic copy number variants at whole-genome array comparative
genomic hybridization associated with late-onset cases or pathogenic mutations involving
genes, such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2. Various clinical trials demonstrated the usefulness of different drugs (including
rufinamide, clobazam, lamotrigine, topiramate, or felbamate), ketogenic diet, resective
surgery, corpus callosotomy, and vagus nerve stimulation in the treatment of epileptic
manifestations. The outcome of LGS often remains disappointing regarding seizure control
or cognitive functioning. The realization of animal models, which are still lacking,
and the full comprehension of molecular mechanisms involved in epileptogenesis and
cognitive impairment would give a relevant support to further improvements in therapeutic
strategies for LGS patients.
Keywords
epileptic encephalopathies - intellectual disability - epilepsy
