Developmental epileptic encephalopathies (DEEs) are a group of disorders characterized by early-onset seizures, abnormal electroencephalogram (EEG) patterns, and developmental delay or regression. They are characterized by complex etiology and are often refractory to treatment, severely impacting affected children, particularly infants and toddlers, and pose a challenge in pediatric neurology. In recent years, with the rise of precision medicine, an increasing number of pathogenic genes associated with DEEs have been discovered. However, the specific pathogenic mechanisms and signaling pathways of these genes in the body still require further investigation. This article primarily discusses the genetic patterns of DEEs and the selection of genetic testing, emphasizing the timing of genetic testing assisted by the epilepsy phenotype, especially in DEEs associated with single-gene mutations and new therapeutic drugs, to aid in clinical decision-making for DEEs. It also introduces the use of neurobiological models for DEE research to effectively advance epilepsy research, thereby enabling targeted gene therapy.
Severe psychomotor developmental delay resulting from early postnatal (within 3 months) seizures can be diagnosed as Early-Infantile Developmental and Epileptic encephalopathies (EIDEE). Its primary etiologies include structural, hereditary, metabolic and etc. The main pathogenesis may be related to the inhibition of normal physiological activity of the brain by abnormal electrical activity and the damage of the brain neural network. Ohtahara syndrome and Early Myoclonic Encephalopathy (EME) are typical types of EIDEE. The principle of treatment is to improve the cognitive and developmental function by controlling frequent seizures. When the seizure is difficult to control with drugs, surgical evaluation should be performed as soon as possible, and surgical treatment is the first choice for patients suitable for surgery. The types of surgery can be divided into excision surgery, dissociation surgery, neuromodulation surgery and etc. The current status of surgical treatment of EIDEE was described, and the curative effect of surgical treatment was explored, so as to help clinicians choose appropriate treatment methods.
Developmental and epileptic encephalopathy (DEE) is a group of diseases that severely affects the neurological development of children, characterized by frequent seizures and significant neurodevelopmental impairments. These diseases not only impact the quality of life of affected children but also impose a heavy burden on families and society. In recent years, the development of brain network theory has provided a new perspective on understanding the pathological mechanisms of DEE, especially the role of structural and functional brain networks in the process of epilepsy. This review systematically summarized the research progress of structural and functional brain networks in DEE, highlighted their importance in seizure activity, disease progression, and prognosis evaluation.
Developmental and epileptic encephalopathy (DEE) is a genetic neurological disease affecting 0.27–0.54 per 1000 newborns, with a strong genetic association. Currently, the majority of known pathogenic genes in genetic DEE can be classified into six functional categories: ion channels, organelles and cell membranes, growth and development, synaptic function, neurotransmitters and receptors, DNA and RNA regulation, and signal transduction pathways. Emerging evidence suggests that inflammatory regulation may play a critical role in genetic DEE pathogenesis. Specifically, astrocyte and microglial activation contributes to neuroinflammation in genetic DEE, while pro-inflammatory cytokines disrupt neuron-glia interactions, exacerbating epileptic seizures and neuronal damage. Targeting the source mechanism of neuroinflammation in genetic DEE, such as the activation of astrocytes and microglia, and intervening from the source, is expected to be a new target for the treatment of genetic DEE.