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Neuropediatrics 2017; 48(03): 143-151
DOI: 10.1055/s-0037-1601324
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Lennox–Gastaut Syndrome: A State of the Art Review

Mario Mastrangelo
1   Division of Pediatric Neurology, Department of Pediatrics, Child Neurology and Psychiatry, Sapienza-University of Rome, Rome, Italy
› Author Affiliations
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Publication History

17 January 2017

21 February 2017

Publication Date:
27 March 2017 (online)

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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
 

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