Yvonne Höller
Eugen Trinka
Julia Jacobs- 1Faculty of Psychology, School of Humanities and Social Sciences, University of Akureyri, Akureyri, Iceland
- 2Department of Neurology, Neurocritical Care and Neurorehabilitation, Member of European Reference Network EpiCARE, Centre for Cognitive Neuroscience, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
- 3Neuroscience Institute, Centre for Cognitive Neuroscience, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
- 4Karl Landsteiner Institute of Neurorehabilitation and Space Neurology, Salzburg, Austria
- 5Alberta Children's Research Institute & Hodgekiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
1 Introduction
The good and bad news regarding better health care for patients with epilepsy lie in the advances of research on the background of the negative impact of global challenges that are beyond the control of clinicians and researchers.
2 Epilepsy and climate change
Climate change as an important environmental variable in the generation and exacerbation of epilepsy can no longer be ignored (1). Consequences of climate change include more frequent and intense heatwaves and natural disasters and increased air pollution (2). Increased body temperature is well-known to lower seizure threshold and to increase the risk of seizure-related brain damage. Brain injury due to the exposure to natural disasters increases the risk for post-traumatic epilepsy (3). Poor air quality directly impacts epilepsy through neuroinflammation (4). Air pollution decreases sleep efficiency (5), rising temperatures decrease the duration and quality of sleep (6), and worries about climate change or natural disasters negatively impact sleep (7). Sleep deprivation increases the likelihood of seizures (8). Seasonal influences that interact with climate change, individual genetic variation and multiple other factors give rise to a complex interaction between epilepsy and climate change that calls for the scientific development of better health services for people with epilepsy living under the negative impacts of climate change (1).
3 Challenges in lower and middle income countries (LMIC) in the management of epilepsy
Climate change has its biggest impact in those countries being the least responsible for it. People in lower and middle income countries (LMICs), for example in the nations in Africa, Central and South America, and South East Asia, will experience additional 30 days of seasonal heat as a consequence of each additional increase of +1°C in global warming (9). The negative consequences for patients with epilepsy hit a situation where accurate diagnosis and appropriate treatment is for most patients impossible because there are no experts and no services available. The conditions differ certainly from region to region, but there are some common challenges that are noteworthy. For example, in sub-Saharan Africa there is only one neurologist available for 5 million people (10). The treatment gap in this region is also attributable to newer generation antiseizure medication being available only at larger clinical centers or private clinics (11) and even in these specialized centers, antiseizure medication is often out of stock (12). Additionally, patients in sub-Saharan Africa were found to prefer treatment with traditional healers, which are much more accessible than neurologists in numbers [one healer for 200 people (13)]) and also in terms of the distance between the patients in rural areas and health care centers, where high costs for traveling are often not affordable (14).
4 SUDEP
Especially in LMICs, sudden unexpected death in epilepsy (SUDEP) as a major cause of mortality in epilepsy remains largely unknown among patients and to some extent even among neurologists (15). Propensity to tell patients with epilepsy about SUDEP is more likely among neurologists in academic settings and with epilepsy fellowships (16). The length of the definition of SUDEP as “sudden, unexpected, witnessed or unwitnessed, non-traumatic and non-drowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (SE), in which post-mortem examination does not reveal other causes of death” (17) already suggests the complicated issue of diagnosing SUDEP (18). SUDEP can be registered in mouse models (19) which led to novel insights especially regarding the cardiac dysfunctions suspected to contribute to SUDEP (20), but leaves many questions open (21). There is need for clinical data to study the clinical risk factors and to guide the development of preventive devices (22) for people at risk and for the development of novel therapies including promising approaches based on vesicles (23).
5 AI for the management of epilepsy
Among the technological developments that are named the most these days—not only in epilepsy research –artificial intelligence (AI) stands out. It stands out because of the massive funding it receives, being on the one hand extremely promising, but on the other hand highly controversial and doubted and even perceived as dangerous. AI also stands out because it has infiltrated so many aspects of health care and life with epilepsy, including patient education (24), automated detection of epileptiform activity in the EEG (25), comparison of effectivity of antiseizure medication (26), automated delineation of the epileptic lesion (27), predicting seizure recurrence (28), and controlling neuromodulation (29), to name a few examples. The strength of AI is in the ability to extract information from extremely large databases where manual analysis to find systematic patterns is not possible. At the same time, the reliance on the availability of large databases is the biggest limitation of AI and the most common pitfall in its use, when AI models are trained with insufficient data, leading to unreliable results. Researchers and clinicians must be aware of these limitations when using AI and interpreting results generated with AI.
6 (Deep) brain stimulation in epilepsy and advances in invasive recordings
AI is also intensively used in neuromodulation and gives rise to recent advances in therapeutic brain stimulation. Following the general technical trend toward smaller devices, cortical electrodes based on novel nanomaterials including, for example, graphene (30) can improve solutions for brain mapping. Miniaturization of electrodes in pre-surgical and intra-surgical evaluation of eloquent vs. epileptogenic brain tissue holds the promise of a higher resolution and more accurate delineation of the to-be resected area. Miniaturization is especially relevant for novel concepts of DBS in epilepsy, such as promising approaches of multimodal thalamic DBS (31), with an overall promise that smaller scales of electrodes will also lead to more accurate targeting and fewer side effects (32). The further advances of chronically implanted devices for the control of seizures goes beyond a continuous stimulation toward closed-loop approaches. These are not restricted to implantable solutions. For example, recent advances in focused ultrasound stimulation (fUS) based on closed-loop technology have been demonstrated successfully in animal models (33). Low intensity fUS (LIFU) can be used for temporary modulation of brain activity and for opening the blood-brain barrier selectively for certain drugs while high intensity fUS can be employed to ablate epileptogenic tissue (34). Closed-loop developments are also a viable method to recover consciousness of patients during seizures using thalamic stimulation (35). The approach hits in the direction to treat the symptoms of seizures if their occurrence cannot be prevented.
7 Rare diseases and pediatric epilepsy syndromes
Poorly controlled seizures are the reality of many patients with underlying rare diseases, among them many pediatric epilepsy syndromes. Since genetic testing has become more widely available for the diagnostic assessment of childhood onset epilepsies, novel approaches including targeted next generation sequencing were applied to significantly sized samples including benign familial neonatal/infantile epilepsy, Dravet syndrome and epilepsy of infancy with migrating focal seizures (36). At the same time, therapeutic advances promise to reduce the occurrence of drug-resistant epilepsy for metabolic disorders if identified in-time (37). Therefore, experts call for neonatal screening for epileptic syndromes with actionable targeted therapies and emerging precision medicine approaches (37). However, the rare occurrence remains a challenge in the evaluation of new therapies, with a few exceptions including Dravet syndrome, Lennox–Gastaut syndrome, and West syndrome, for which considerable orphan drug development takes place (38). Nevertheless, recent examples such as the treatment of CDKL5 Deficiency Disorder with cannabidiol and tetrahydrocannabinol (39) and treatment of developmental and epileptic encephalopathy with spike wave activation in sleep with steroids (40) show that evidence consists often in anecdotal reports (39) and is generally limited by the absence of guidelines in formulations and dosages (40). Finally, more research is needed in the challenging transition from pediatric to adult care, especially among patients with comorbidities (41). Research of somatic mutations is an emerging field with promise to advance understanding of pediatric epilepsies (42). Pathogenic brain-limited somatic mutations can be detected in surgically resected cell tissue (43). Novel, minimally invasive methods through extraction of cell-free DNA from cerebrospinal fluid and microbulk tissue adherent to stereo-EEG electrodes allow the identification of these mutations that cause focal onset seizures (43).
8 Epilepsy comorbidities across the life span
Comorbidities are highly common in patients with developmental forms of epilepsy as the example of autism shows (44), but exist throughout the life span. The most striking insight is that for many of these comorbidities the relationship goes both ways. For example, psychiatric disorders including depression, anxiety, and psychosis are significantly more common among patients with epilepsy (44). However, patients with depression also have a higher risk of developing epilepsy (45). Also the relation between Alzheimer's disease and epilepsy is bidirectional (46). In this context the treatment options must be carefully assessed, especially for psychiatric comorbidities where antiseizure medication might successfully suppress seizures but exacerbate mental health symptoms.
9 Antiepileptogenesis
As the above-mentioned case of developmental epilepsies shows, under certain circumstances epilepsy can and should be prevented (37). Beyond the neonatal case, post-stroke epilepsy is a good candidate for the development and application of antiepileptogenic strategies, also because of its relatively high prevalence of about 10% among stroke survivors (47). While the identification of at-risk patients for post-stroke epilepsy is realistic, there is a lack of effective drugs that prevent the condition (47). For post-traumatic epilepsy and genetic, non-injury epilepsy, animal models showed promise e.g., using pregabalin (48). Further research is needed to clarify the translatability of promising therapeutic interventions from injury models to genetic models (48).
10 Advanced treatments in epilepsy
Treatment of epilepsy is still not satisfying as about 30% of patients suffer from uncontrolled seizures (49). Novel antiseizure drugs such as cenobamate give rise to hope for patients with drug-resistant focal epilepsy, especially when prescribed early (50). Research toward more effective ways of treating epilepsy has entered a new era with gene and cell therapy being among the most exciting developments (51). Gene therapies under examination include adeno-associated virus-mediated delivery of genes encoding neuromodulatory peptides, neurotrophic factors, enzymes, and potassium channels, where rat models showed promising decrease of seizure frequency (51). Cell therapy can be roughly grouped in nervous system cells that are intravenously infused (52) or transplanted (53), injected MSCs (54), exosomes, e.g., derived from MSCs (55), bone marrow mononuclear cells (50), and encapsulated cell biodelivery (56). In-vivo models testing viral vectors demonstrated beneficial effects but cell-based therapy has entered clinical trials providing evidence for the benefits and safety based on the neuroprotective, anti-inflammatory, and immunomodulatory properties of the transplanted cells (51). Extracellular vesicles were found to hold promise not only as biomarkers for epilepsy, but also as therapeutic means for restraining consequences of status epilepticus (23).
11 Wars
Today we are facing global threats to peace. Wars are fought without respecting human rights, at the costs of civilian's lives, including children. For example, the war unleashed by the Russian Federation on the Ukraine led to a mass migration of approximately 15 million people (57). Many of the people living under attack suffer from pre-existing diseases, including epilepsy. While violence is a general threat to health, from past wars we know that war negatively impacts patients with epilepsy, already because of the psychological distress and trauma (58). Loss of medical documentation and test results, loss of contact with the usual medical care provider, additional complexity associated with the psychological and physiological consequences of war are just a few of the difficulties patients with epilepsy and other chronic disorders suffer as a direct consequence of war and displacement (57). In Gaza and throughout occupied Palestine, healthcare has collapsed, due to the blockade of aid by Israel and the destruction of health infrastructure and detention of healthcare workers (59). A severe shortage of antiseizure medication led to admission of patients to the intensive care units because of uncontrolled seizures, where prolonged sedation is the only treatment until supply of anticonvulsants is secured. However, status epilepticus due to medication shortage and seizures as a consequence of brain injury are only the tip of the iceberg. International networking, joint research with experts in the occupied regions, and telemedicine are some of the methods that experts in epilepsy can leverage to support healthcare workers and their patients during man-made humanitarian crises.
Author contributions
YH: Writing – original draft, Writing – review & editing, Conceptualization. ET: Conceptualization, Writing – review & editing, Supervision. JJ: Writing – review & editing, Conceptualization.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Acknowledgments
Special thanks to Dr. Saber Alasmar for the insights provided into the challenges of providing medical treatment in the absence of medical supplies and the presence of epileptic seizures in injured and malnourished patients.
Conflict of interest
ET received personal fees from EVER Pharma, Marinus, Arvelle, Angelini, Argenx, Medtronic, Biocodex, Bial-Portela & Ca, Newbridge, GL Pharma, GlaxoSmithKline, Boehringer Ingelheim, LivaNova, Eisai, Epilog, UCB, Biogen, Sanofi, Jazz Pharmaceuticals and Actavis, and his institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union and FWF Österreichischer Fond zur Wissenschaftsforderung, Bundesministerium für Wissenschaft und Forschung and Jubiläumsfond der Österreichischen Nationalbank (none related to the presented work).
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
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References
1. Gulcebi MI, Bartolini E, Lee O, Lisgaras CP, Onat F, Mifsud J, et al. Climate change and epilepsy: Insights from clinical and basic science studies. Epilepsy Behav. (2021) 116:107791. doi: 10.1016/j.yebeh.2021.107791
2. Climate Change 2023: Synthesis report of the IPCC sixth Assessment Report (AR6) [Internet] (2023).
3. Agrawal A, Timothy J, Pandit L, Manju M. Post-traumatic epilepsy: an overview. Clin Neurol Neurosurg. (2006) 108:433–9. doi: 10.1016/j.clineuro.2005.09.001
4. item Aljafen BN, Shaikh N, AlKhalifah JM., Meo SA. Effect of environmental pollutants particulate matter (PM25, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ground level ozone (O3) on epilepsy BMC neurology. (2025) 25:133–10. doi: 10.1186/s12883-025-04228-y
5. Basner M, Smith MG, Jones CW, Ecker AJ, Howard K, Schneller V, et al. Associations of bedroom PM25, CO2, temperature, humidity, and noise with sleep: an observational actigraphy study. Sleep Health. (2023) 9:253–63. doi: 10.1016/j.sleh.2023.02.010
6. Minor K, Bjerre-Nielsen A, Jonasdottir SS, Lehmann S, Obradovich N. Rising temperatures erode human sleep globally. One Earth. (2022) 5:534–49. doi: 10.1016/j.oneear.2022.04.008
7. Rifkin DI, Long MW, Perry MJ. Climate change and sleep: a systematic review of the literature and conceptual framework. Sleep Med Rev. (2018) 42:3–9. doi: 10.1016/j.smrv.2018.07.007
8. Dell'Aquila JT, Soti V. Sleep deprivation: a risk for epileptic seizures. Sleep Sci. (2022) 15:245–9 doi: 10.5935/1984-0063.20220046
9. Perkins-Kirkpatrick SE, Gibson PB. Changes in regional heatwave characteristics as a function of increasing global temperature. Sci Rep. (2017) 7:265–12. doi: 10.1038/s41598-017-12520-2
10. Esterhuizen AI, Carvill GL, Ramesar RS, Kariuki SM, Newton CR, Poduri A, et al. Clinical application of epilepsy genetics in Africa: is now the time? Front Neurol. (2018) 9:276. doi: 10.3389/fneur.2018.00276
11. Wagner RG, Bertram MY, Gómez-Olivé FX, Tollman SM, Lindholm L, Newton CR, et al. Health care utilization and outpatient, out-of-pocket costs for active convulsive epilepsy in rural northeastern South Africa: a cross-sectional Survey. BMC Health Serv Res. (2016) 16:208. doi: 10.1186/s12913-016-1460-0
12. Preux P, Tiemagni F, Fodzo L, Kandem P, Ngouafong P, Ndonko F, et al. Antiepileptic therapies in the Mifi Province in Cameroon. Epilepsia. (2000) 41:432–9 doi: 10.1111/j.1528-1157.2000.tb00185.x
13. Wilmshurst JM, Kakooza-Mwesige A, Newton CR. The challenges of managing children with epilepsy in Africa. Semin Pediatr Neurol. (2014) 21:36–41 doi: 10.1016/j.spen.2014.01.005
14. Hjortsberg CA, Mwikisa CN. Cost of access to health services in Zambia. Health Policy Plan. (2002) 17:71–7. doi: 10.1093/heapol/17.1.71
15. Kozaa YA, Mohsen Y, Abuawwad MT, Rakab MS, Moustafa ARA, Shady MA, et al. Addressing the gap: SUDEP knowledge and communication among patients and neurologists. Epilepsy Res. (2025) 215:107584. doi: 10.1016/j.eplepsyres.2025.107584
16. Asadi-Pooya AA, Trinka E, Brigo F, Hingray C, Karakis I, Lattanzi S, et al. Counseling about sudden unexpected death in epilepsy (SUDEP): a global survey of neurologists' opinions. Epilepsy Behav. (2022) 128:108570. doi: 10.1016/j.yebeh.2022.108570
17. Langan Y. Sudden unexpected death in epilepsy (SUDEP): risk factors and case control studies. Seizure. (2000) 9:179–83. doi: 10.1053/seiz.2000.0388
18. Di Gennaro G, Tomasini A, Abeni D, Labate A, Bonaventura CD. SUDEP: the boundary between risk, care, and uncertainty in epilepsy. Epilepsy Behav. (2025) 110621. doi: 10.1016/j.yebeh.2025.110621
19. Samalens L, Beets C, Courivaud C, Kahane P, Depaulis A. Comorbidities in the mouse model of temporal lobe epilepsy induced by intrahippocampal kainate. Epilepsia. (2025) 13. doi: 10.1111/epi.18553
20. Chiang C-C, Kotamraju BP, Durand DM. Bradycardia is induced by hyperactivity of the vagus nerve and nucleus ambiguus during seizures propagating into the brainstem. Epilepsia Open. (2025) 11. doi: 10.1002/epi4.70060
21. Wenker IC. Dissecting the fatal seizure: the importance of forebrain neurons in SUDEP. Epilepsy Curr. (2025). doi: 10.1177/15357597251351466
22. Baumgartner C, Baumgartner J, Lang C, Lisy T, Koren JP. Seizure detection devices. J Clin Med. (2025) 14:863. doi: 10.3390/jcm14030863
23. Upadhya D, Shetty AK. Promise of extracellular vesicles for diagnosis and treatment of epilepsy. Epilepsy Behav. (2021) 121:106499. doi: 10.1016/j.yebeh.2019.106499
24. Singh A, Gupta N, Chien D, Singh R, Sachdeva A, Danasekaran K, et al. ChatGPT-4 in neurosurgery: improving patient education materials. Neurosurgery. (2025). doi: 10.1227/neu.0000000000003606
25. Li J, Goldenholz DM, Alkofer M, Sun C, Nascimento FA, Halford JJ, et al. Expert-level detection of epilepsy markers in EEG on short and long timescales. NEJM AI. (2025). doi: 10.1056/aioa2401221
26. Xie K, Korzun J, Zhou DJ, Chang E, Ghosn NJ, Lavelle S, et al. Comparative effectiveness of anti-seizure medications in emulated trials using medical informatics. Brain. (2025) awaf238. doi: 10.1093/brain/awaf238
27. Joshi S, Pant M, Malhotra A, Deep K, Snasel V. A nnU-Net-based automatic segmentation of FCD type II lesions in 3D FLAIR MRI images. Front Artif Intell. (2025) 8:1601815. doi: 10.3389/frai.2025.1601815
28. Pasini F, Quintana M, Rodrigo-Gisbert M, Campos-Fernández D, Abraira L, Fonseca E, et al. Predicting seizure recurrence after status epilepticus: a multicenter exploratory machine learning approach. Seizure. (2025) 131:163–71. doi: 10.1016/j.seizure.2025.06.019
29. Ervin B, Arya R. Artificial intelligence and machine learning in neuromodulation for epilepsy. J Clin Neurophysiol. (2025) 42:493–504. doi: 10.1097/WNP.0000000000001186
30. Yang S, Baeg E, Kim K, Kim D, Xu D, Ahn J, et al. Neurodiagnostic and neurotherapeutic potential of graphene nanomaterials. Biosens Bioelectron. (2024) 247:115906. doi: 10.1016/j.bios.2023.115906
31. Chang R, Reid B, McGeoch P, Lusk Z, Graber K, Fisher R, et al. Targeted multinodal thalamic deep brain stimulation for epilepsy: a retrospective case series. Epileptic Disord. (2025) 1–12. doi: 10.1002/epd2.70070
32. Ria N, Eladly A, Masvidal-Codina E, Illa X, Guimerà A, Hills K, et al. Flexible graphene-based neurotechnology for high-precision deep brain mapping and neuromodulation in Parkinsonian rats. Nat Commun. (2025) 16:2891. doi: 10.1101/2024.09.23.614449
33. Pang N, Sun J, Zhang H, Chen R, Yan J, Yuan Y. Closed-loop transcranial ultrasound stimulation based on deep learning effectively suppresses epileptic seizures in mice. IEEE Trans Neural Syst Rehabil Eng. (2025) 33:2764–9. doi: 10.1109/TNSRE.2025.3589089
34. Lescrauwaet E, Vonck K, Sprengers M, Raedt R, Klooster D, Carrette E, et al. Recent advances in the use of focused ultrasound as a treatment for epilepsy. Front Neurosci. (2022) 16:886584. doi: 10.3389/fnins.2022.886584
35. Blumenfeld H. Stimulation of the Thalamus for Arousal Restoral in Temporal Lobe Epilepsy: START Clinical Trial. (2023). p. 1225.
36. Barcia G, Chemaly N, Gobin-Limballe S, Losito E, Aubart M, Sarda E, et al. Genetic etiologies with a large NGS panel in a monocentric cohort of 1000 patients with pediatric onset epilepsies. Epilepsia Open. (2025) 10:1065–73. doi: 10.1002/epi4.70057
37. Nabbout R, Kuchenbuch M. Embracing the future: neonatal screening for epileptic syndromes. Epilepsia. (2025) 66:1843–53. doi: 10.1111/epi.18285
38. Auvin S, Avbersek A, Bast T, Chiron C, Guerrini R, Kaminski RM, et al. Drug development for rare paediatric epilepsies: current state and future directions. Drugs. (2019) 79:1917–35. doi: 10.1007/s40265-019-01223-9
39. Massey S, Quigley A, Rochfort S, Christodoulou J, Van Bergen NJ. Cannabinoids and genetic epilepsy models: a review with focus on CDKL5 deficiency disorder. Int J Mol Sci. (2024) 25:10768. doi: 10.3390/ijms251910768
40. Canbay D, Jansen FE, Schönberger J, San Antonio-Arce V, Jacobs J, Klotz KA. European experience of steroid therapy in children with developmental and epileptic encephalopathy with spike wave activation in sleep ((D)EE-SWAS). Orphanet J Rare Dis. (2025) 20:204–8. doi: 10.1186/s13023-025-03725-0
41. Aihara T, Abe Y, Hayakawa I. Transition to adult care in childhood-onset epilepsy: a retrospective cohort study at a Japanese Children's Hospital. Epilepsia Open. (2025) 1–8. doi: 10.1002/epi4.70092
42. Poduri A, Evrony GD, Cai X, Walsh CA. Somatic mutation, genomic variation, and neurological disease. Science. (2013) 341:1–43. doi: 10.1126/science.1237758
43. Fariyike OA, Narayan N, Liu HY, Sanchez DR, Phillips HW. Advancing precision diagnostics: minimally invasive approaches for understanding the role of brain-limited somatic mutations in pediatric drug-resistant epilepsy. Front Surg. (2025) 12:1568939. doi: 10.3389/fsurg.2025.1568939
44. Zhu F, Zhong R, Li F, Li C, Din N, Sweidan H, et al. Development and validation of a deep transfer learning-based multivariable survival model to predict overall survival in lung cancer. Transl Lung Cancer Res. (2023) 12:471–82. doi: 10.21037/tlcr-23-84
45. Sampogna G, Brugnoli R, Didato G, Elia M, Ferlazzo E, Serafini G, et al. Clinical characterization and management of persons with comorbid epilepsy and depression: an expert opinion paper. Front Pharmacol. (2025) 16:1592650. doi: 10.3389/fphar.2025.1592650
46. Dupont S. Epilepsy and Alzheimer disease: new insights and perspectives. Rev Neurol. (2025) 181:382–90. doi: 10.1016/j.neurol.2025.03.005
47. Tanaka T, Ihara M, Fukuma K, Mishra NK, Koepp MJ, Guekht A, et al. Pathophysiology, diagnosis, prognosis, and prevention of poststroke epilepsy. Neurology. (2024) 102:e209450. doi: 10.1212/WNL.0000000000209450
48. Prince DA, Gu F. Chapter 68: Prophylaxis of epileptogenesis in injury and genetic epilepsy models. In: Noebels JL, Avoli M, Rogawski MA, Vezzani A, Delgado-Escueta AV, , editors. Jasper's Basic Mechanisms of the Epilepsies. 5th ed. New York, NY: Oxford University Press (2024).
49. Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia. (2018) 59:2179–93. doi: 10.1111/epi.14596
50. DaCosta JC, Portuguez MW, Marinowic DR, Schilling LP, Torres CM, DaCosta DI, et al. Safety and seizure control in patients with mesial temporal lobe epilepsy treated with regional superselective intra-arterial injection of autologous bone marrow mononuclear cells. J Tissue Eng Regen Med. (2018) 12:e648–56. doi: 10.1002/term.2334
51. Shaimardanova AA, Chulpanova DS, Mullagulova AI, Afawi Z, Gamirova RG, Solovyeva VV, et al. Gene and cell therapy for epilepsy: a mini review. Front Mol Neurosci. (2022) 15:868531. doi: 10.3389/fnmol.2022.868531
52. de Gois da Silva ML, da Silva Oliveira GL, de Oliveira Bezerra D, da Rocha Neto HJ, Feitosa MLT, Argôlo Neto NM, et al. Neurochemical properties of neurospheres infusion in experimental-induced seizures. Tissue Cell. (2018) 54:47–54. doi: 10.1016/j.tice.2018.08.002
53. Waldau B, Hattiangady B, Kuruba R, Shetty AK. Medial ganglionic eminence-derived neural stem cell grafts ease spontaneous seizures and restore GDNF expression in a rat model of chronic temporal lobe epilepsy. Stem Cells. (2010) 28:1153–64. doi: 10.1002/stem.446
54. Hlebokazov F, Dakukina T, Potapnev M, Kosmacheva S, Moroz L, Misiuk N, et al. Clinical benefits of single vs repeated courses of mesenchymal stem cell therapy in epilepsy patients. Clin Neurol Neurosurg. (2021) 207:106736. doi: 10.1016/j.clineuro.2021.106736
55. Xian P, Hei Y, Wang R, Wang T, Yang J, Li J, et al. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice. Theranostics. (2019) 9:5956–75. doi: 10.7150/thno.33872
56. Paolone G, Falcicchia C, Lovisari F, Kokaia M, Bell WJ, Fradet T, et al. Long-term, targeted delivery of GDNF from encapsulated cells is neuroprotective and reduces seizures in the pilocarpine model of epilepsy. J Neurosci. (2019) 39:2144–56. doi: 10.1523/JNEUROSCI.0435-18.2018
57. Dubenko A, Litovchenko T. Helping patients with epilepsy during a full-scale war in the country: some aspects of Ukrainian experience. Seizure. (2023) 110:153–6. doi: 10.1016/j.seizure.2023.06.015
58. Bosnjak J, Vukovic-Bobic M, Mejaski-Bosnjak V. Effect of war on the occurrence of epileptic seizures in children. Epilepsy Behav. (2002) 3:502–9. doi: 10.1016/S1525-5050(02)00602-9
Keywords: epilepsy, climate change, LMIC, SUDEP, deep brain stimulation, AI, orphan diseases
Citation: Höller Y, Trinka E and Jacobs J (2025) Epilepsy grand challenge 2025. Front. Neurol. 16:1693132. doi: 10.3389/fneur.2025.1693132
Received: 26 August 2025; Accepted: 29 August 2025;
Published: 15 September 2025.
Approved by:
Frontiers Editorial Office, Frontiers Media SA, SwitzerlandCopyright © 2025 Höller, Trinka and Jacobs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yvonne Höller, eXZvbm5lQHVuYWsuaXM=