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Why we urgently need improved seizure and epilepsy therapies for children and neonates
Ronit M Pressler1, Lieven Lagae2
1Neuroscience Unit, UCL Great Ormond Street Institute of Child Health, London, UK; Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Insights
Neonatal seizures and early-onset epilepsy present unique treatment challenges and can lead to developmental issues. New drug development and improved management guidelines are urgently needed for infants and neonates.
Area of Science:
- Pediatric Neurology
- Epileptology
- Neonatal Medicine
Background:
- Neonatal seizures and early-onset epilepsy pose distinct challenges compared to adult epilepsy.
- High seizure burden and epileptic encephalopathy are linked to adverse developmental, behavioral, and cognitive outcomes.
- Limited availability of licensed antiseizure medications for infants and neonates complicates treatment.
Purpose of the Study:
- To highlight the challenges in managing neonatal seizures and early-onset epilepsy.
- To emphasize the need for novel therapeutic strategies and improved drug development pathways for this population.
- To discuss the implications of molecular understanding for targeted therapies.
Main Methods:
- Review of current literature on neonatal seizures and early-onset epilepsy.
- Analysis of challenges in drug development and clinical trials for neonates.
- Discussion of emerging targeted therapies based on molecular understanding.
Main Results:
- Neonatal epilepsy requires specialized approaches due to unique clinical presentations and comorbidities.
- Drug trials in neonates are complex, requiring continuous EEG monitoring and addressing high co-morbidity.
- Advances in understanding molecular basis enable targeted therapies for specific epilepsy syndromes.
Conclusions:
- There is an urgent need for new antiepileptic drugs and rigorous evaluation of existing ones for neonates.
- Development of national policies and guidelines is crucial for effective management.
- Addressing the unique challenges of neonatal epilepsy is essential for improving long-term outcomes.
Abstract:
In contrast to epilepsy in adolescents and adults, neonatal seizures and early onset epilepsy poses unique challenges with significant repercussion for treatment choices. Most importantly, high seizure burden and epileptic encephalopathy are associated with developmental, behavioural and cognitive problems. The causes are multifactorial and include etiology, seizure burden, epileptic encephalopathy, but also antiseizure medication. In contrast to adults and older children only very few drugs have been licenced for infants and neonates, and after a long delay. Very recently, extrapolation of adult data has become possible as a path to speed up drug development for younger children but this is not necessarily possible for infants and neonates. With the advances in understanding the molecular basis of many epilepsies, targeted therapies become available, for example for KCNQ2 mutation related epilepsies, Dravet syndrome or tuberous sclerosis complex. Drug trials in neonates are particularly challenging because of their inconspicuous clinical presentation, the need for continuous EEG monitoring, high co-morbidity, and poor response to antiepileptic drugs. There is an urgent need for development of new drugs, evaluation of safety and efficacy of current antiseizure drugs, as well as for national policies and guidelines for the management of seizures and epilepsy in neonates and infants. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
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Seizures: Classification
Seizures are typically classified into two main categories: focal and generalized seizures.
Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types: