Abstract
To accelerate the process of licensing antiseizure medication (ASM) in children, extrapolation of efficacy data for focal-onset seizures from adults to children ≥2 or ≥4 years of age is now accepted. We summarized the efficacy evidence from randomized, controlled trials that was used to grant approval for the pediatric indication of focal-onset seizures for the different ASMs available in Europe. Data from high-quality randomized, controlled trials in young children are limited, especially on the use of ASMs in monotherapy. Licensure trials are typically focused on seizure type irrespective of etiology or epilepsy syndrome. We elaborate on the importance of etiology- or syndrome-driven research and treatment, illustrating this with examples of childhood epilepsy syndromes characterized by predominantly focal-onset seizures. Some of these syndromes respond well to standard ASMs used for focal-onset seizures, but others would benefit from a more etiology- or syndrome-driven approach. Advances in molecular genetics and neuroimaging have made it possible to reveal the underlying cause of a child's epilepsy and tailor research and treatment. More high-quality randomized, controlled trials based on etiology or syndrome type are needed, including those assessing effects on cognition and behavior. In addition, study designs such as “N-of-1 trials” could elucidate possible new treatment options in rare epilepsies. Broadening incentives currently in place to stimulate the development and marketing of drugs for rare diseases (applicable to some epilepsy syndromes) to more common pediatric epilepsy types and syndromes might be a means to enable high-quality trials, and ultimately allow more evidence-based treatment in children.
Highlights
Epilepsy, a chronic neurological disorder characterized by the recurrence of unprovoked seizures, affects nearly 50 million people worldwide [1]
The sparsity of highquality randomized, controlled trials in children, in the very young, and the lack of etiology- or syndrome-specific data in such trials complicates the selection of the optimal antiseizure medication (ASM)
While some childhood epilepsy syndromes respond well to most or several ASMs used for focal-onset seizures, a more etiology- or syndrome-driven approach is needed for others
Summary
A chronic neurological disorder characterized by the recurrence of unprovoked seizures, affects nearly 50 million people worldwide [1]. The epilepsy prevalence is highest in young children and older adults [1–3] and was estimated to be 6.2/1,000 people globally in 2016 [1]. Epileptic seizures can initiate in one region of one hemisphere of the brain—focal-onset seizures—or in both hemispheres—generalized-onset seizures [4]. Epilepsy types and syndromes can be characterized by either exclusively focal or generalized seizures or by a combination of both [5]. Causes of epilepsy include genetic mutations, infections, metabolic disorders, immune disorders and structural abnormalities [5]. Determining the etiology of epilepsy may allow optimizing treatment; for instance, certain focal brain malformations can be amenable to curative surgery, and the identification of a genetic mutation may enable effective targeted treatment [3, 6]
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