The Intricacies of Developmental and Epileptic Encephalopathies: A Journey Towards Innovative Therapies

Dear Colleagues,

Developmental and epileptic encephalopathy (DEE) refers to a category of severe epilepsy syndromes accompanied by severe neurodevelopment impairments and subsequent cognitive and social deficits throughout life. DEE is characterized by frequent seizures that typically begin in infancy or early childhood and are typically refractory to anti-epileptic drugs (AEDs). There is debate around whether early life seizures are hindering the child's developmental progress or merely occurring alongside neurodevelopmental impairment. Currently, available antiepileptic medications, which primarily focus on targeting membrane ion channels or neural transmission pathways, serve as the front-line treatment for seizure control, but these AED therapies do not appear to effectively treat developmental impairments. Additionally, these existing AED therapies have shown limitations in effectively intervening in the process of early-onset epileptogenesis. Thus, there is a critical need to (1) develop more effective AEDs, (2) understand the mechanisms and develop therapies for neurodevelopment impairments, and (3) properly address whether early-onset seizures impact neurodevelopment progress.

In recent years, remarkable advancements in neuroscientific techniques—such as chemogenetics, optogenetics, neural circuitry tracing, neuroimaging, and high-throughput sequencing—have markedly enhanced our understanding of the abnormal neural circuits contributing to epileptogenesis. Continued research utilizing these innovations is crucial for discovering and developing new therapeutic strategies.

We propose to investigate novel mechanisms of epileptogenesis and develop potential therapeutic strategies inspired by these emerging targets. We invite submissions of original research articles and reviews that address, but are not limited to, the following themes:

- Investigations into the cellular and molecular mechanisms of early-onset epileptogenesis.

- Examine the link between early onset seizures and their contribution to developmental impairments.

- Exploration of innovative therapeutic approaches aimed at intervening in the process of infantile epileptogenesis.

- Explore novel therapies to ease the burden of cognitive and other behavioral deficits.

Dr. Muhammad Nauman Arshad
Dr. Paul Davies
Guest Editors

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• cognitive
• behavioral deficits