Stroke is one of the most frequent causes of epilepsy in the elderly, therefore post-stroke epilepsy studies are focusing on finding biomarkers to identify high-risk patients. This could allow not only to predict postinjury epilepsy outcomes, but also provide a greater understanding regarding the development of preventive therapeutic approaches.
Among the biomarkers discovered by the latest studies on epileptogenesis in post-stroke epilepsy
we find, for instance, cortical superficial siderosis and impaired function of the glymphatic system with subsequent enlargement or asymmetry of perivascular spaces. (1)
In recent years, studies have increasingly focused on the role of blood-brain barrier dysfunction.
In fact. it is well established that blood-brain barrier dysfunction (BBBD) causes an epileptogenic cascade that leads to pathological changes such as albumin extravasation and increased transforming growth factor β signaling, transcriptional changes in astrocytes, degradation of extracellular matrix, and growth of new excitatory synapses and reorganization of neural networks. (2)
Furthermore, BBB dysfunction sustains increasing neuroinflammation and extravasation of
excitatory compounds. (3) Therefore, the quantification of BBBD could be considered a useful biomarker in identifying patients at risk of post-stroke epilepsy. Furthermore, BBB-stabilising
treatments, through inhibition of TGFβR signaling or with anti-integrins, like natalizumab,, could be potential epilepsy-preventive therapeutic approaches. (4) (5)
Some possible preventive therapies (such as rapamycin, statins, losartan, semaglutide, and metformin) have shown efficacy or promise in animal stroke models (although one must take into account the limitations of animal studies). Another possible preventive therapy related to the repair of BBB dysfunction could be the modulation of pericyte migration.
Key Points:
- Post-stroke epilepsy is one of the major cause of epilepsy in adult patients, especially in the elderly
- Blood-brain barrier dysfunction is involved in epileptogenesis in post-stroke patients
- Therapeutic approaches aimed at reconstructing or stabilizing the blood-brain barrier may prevent epilepsy
References:
- Yang LT, Anthony G, Kaufer D. Inflammatory Astrocytic TGFβ Signaling Induced by Blood–Brain Barrier Dysfunction Drives Epileptogenesis. In: Noebels JL, Avoli M, Rogawski MA, Vezzani A, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 5th ed. New York: Oxford University Press; 2024. Chapter 28. PMID: 39637183.
- Meijer WC, Gorter JA. Role of blood-brain barrier dysfunction in the development of poststroke epilepsy. Epilepsia. 2024 Sep;65(9):2519-2536. doi: 10.1111/epi.18072. Epub 2024 Aug 5. PMID: 39101543.
- Hlauschek G, Nicolo JP, Sinclair B, Law M, Yasuda CL, Cendes F, Lossius MI, Kwan P, Vivash L. Role of the glymphatic system and perivascular spaces as a potential biomarker for post-stroke epilepsy. Epilepsia Open. 2024 Feb;9(1):60-76. doi: 10.1002/epi4.12877. Epub 2023 Dec 14. PMID: 38041607; PMCID: PMC10839409.
- Vezzani A, Balosso S, Varvel NH, Dingledine R. Anti-inflammatory strategies for disease modification: Focus on therapies close to translation. In: Noebels JL, Avoli M, Rogawski MA, Vezzani A, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 5th ed. New York: Oxford University Press; 2024. Chapter 74. PMID: 39637215.
- French JA, Cole AJ, Faught E, Theodore WH, Vezzani A, Liow K, Halford JJ, Armstrong R, Szaflarski JP, Hubbard S, Patel J, Chen K, Feng W, Rizzo M, Elkins J, Knafler G, Parkerson KA; OPUS Study Group. Safety and Efficacy of Natalizumab as Adjunctive Therapy for People With Drug-Resistant Epilepsy: A Phase 2 Study. Neurology. 2021 Nov 2;97(18):e1757-e1767. doi: 10.1212/WNL.0000000000012766. Epub 2021 Sep 14. PMID: 34521687; PMCID: PMC8610627.
Publish on behalf of the Scientific Panel Epilepsy