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Updated: Mar 3, 2026
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Published on: June 23, 2022
Inflammation in Epileptic Encephalopathies
Oleksii Shandra1, Solomon L Moshé2, Aristea S Galanopoulou2
1Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, NY, United States.
Insights
West syndrome (WS) involves infantile spasms and developmental issues. This review explores inflammation
Area of Science:
- Neuroscience
- Pediatric Neurology
- Immunology
Background:
- West syndrome (WS) is a severe infantile epileptic encephalopathy characterized by infantile spasms (IS), hypsarrhythmia, and poor neurodevelopmental outcomes.
- Etiologies include structural-metabolic (60%), genetic (12-15%), and unknown causes, with current treatments like hormonal therapy and vigabatrin having limitations.
- There is a critical need for novel therapeutic targets and more effective treatments for WS, prompting investigation into emerging pathways.
Purpose of the Study:
- To critically review the evidence for and against the role of inflammatory pathways in the pathogenesis, comorbidities, and progression of West syndrome.
- To investigate potential interactions between inflammation and the neuroendocrine system in WS.
- To explore whether inflammation contributes to the transition from WS to Lennox-Gastaut syndrome and identify potential anti-inflammatory therapeutic targets.
Main Methods:
- This is a targeted review of existing clinical and preclinical data, including animal models of WS.
- The review analyzes evidence related to the activation of brain inflammatory signaling pathways in WS.
- It examines genetic findings implicating inflammation and interactions with other signaling pathways like the neuroendocrine system.
Main Results:
- Emerging evidence from clinical and preclinical data supports the involvement of inflammatory pathways in WS pathogenesis.
- Seizures themselves can activate proinflammatory pathways, suggesting a bidirectional relationship.
- Genetic studies reveal numerous genes linked to WS that are involved in inflammatory processes.
Conclusions:
- Inflammatory pathways are increasingly implicated in the cause and progression of West syndrome and its comorbidities.
- Understanding the interplay between inflammation, neuroendocrine factors, and epileptogenesis is crucial for developing new therapies.
- Targeting specific inflammatory pathways presents a promising avenue for future therapeutic development in WS.
Abstract:
West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation?
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