Developmental and epileptic encephalopathies: recognition and approaches to care

Abstract

The term "developmental and epileptic encephalopathy'' (DEE) refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. Many DEEs are related to gene variants and the onset is typically during early childhood. In this setting, neurocognition, whilst not improved by seizure control, may benefit from some precision therapies. In patients with non-progressive diseases with cognitive impairment and co-existing epilepsy, in whom the epileptiform activity does not affect or has minimal effect on function, the term "developmental encephalopathy'' (DE) can be used. In contrast, for those patients with direct impact on cognition due to epileptic or epileptiform activity, the term "epileptic encephalopathy'' (EE) is preferred, as most can revert to their normal or near normal baseline cognitive state with appropriate intervention. These children need aggressive treatment. Clinicians must tailor care towards individual needs and realistic expectations for each affected person; those with DE are unlikely to gain from aggressive antiseizure medication whilst those with EE will gain. Patients with DEE might benefit from a precision medicine approach in order to reduce the overall burden of epilepsy.

Detection of Deregulated miRNAs in Childhood Epileptic Encephalopathies

“…In particular, many biological pathways may play a role in the pathogenesis of DEEs. DNA repair, transcriptional regulation, axon myelination, metabolite and ion transport, and paroxysmal function may all be involved in DEE (Hamdan 2017;Raga 2021).…”

Difficulties of Prenatal Genetic Counseling for a Subsequent Child in a Family With Multiple Genetic Variations

“…DEE is a group of severe epilepsy disorders characterized by both intractable neonatal-onset seizures and profound global developmental delay. Developmental impairment and epileptic activity impact the cognitive and behavioral states of the affected person ( Raga et al, 2021 ). Most DEE patients have a genetic etiology responsible for both cognitive impairment and severe epilepsy, and the control of seizures does not prevent cognitive impairment from worsening ( Raga et al, 2021 ).…”

“…Developmental impairment and epileptic activity impact the cognitive and behavioral states of the affected person ( Raga et al, 2021 ). Most DEE patients have a genetic etiology responsible for both cognitive impairment and severe epilepsy, and the control of seizures does not prevent cognitive impairment from worsening ( Raga et al, 2021 ). A number of genes have been associated with DEE ( Hamdan et al, 2017 ).…”

De novo SCN8A and inherited rare CACNA1H variants associated with severe developmental and epileptic encephalopathy

“…Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that are characterized by seizures often drug-resistant, and developmental delay leading to varying degrees of intellectual, psychiatric, behavioral, and motor disabilities [ 1 ]. DEEs are primarily attributed to genetic causes and while recessive and X-linked variants have been found, the majority of patients show de novo pathogenic variants [ 2 ].…”