Conventional Epilepsy Treatments in Morocco and Recommendations for Future Research Directions: An Up-to-Date Review
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Abstract
Epilepsy affects around 70 million people globally, with a high prevalence in low- and middle-income countries like Morocco. Rural populations face difficulties accessing treatment due to economic challenges, poor healthcare infrastructure, and social stigma. Over 20 clinically approved medications are used for treatment. This review explores conventional approaches to epilepsy treatment in Morocco, emphasizing the need for improved healthcare access and culturally sensitive interventions. The study was conducted through a comprehensive literature search across various databases, including ScienceDirect, Springer, PubMed, MDPI, Frontiers, and Hindawi. Keywords, such as "epilepsy," "mental disorder and seizures," "brain disorder," and "epilepsy treatment" were used to perform the search. The literature review revealed a rising prevalence of epilepsy, affecting individuals of all ages and representing 0.6% of the global disease burden, particularly in low- and middle-income countries. Causes include stroke, infections, genetic factors, and environmental influences. Conventional treatments, such as antiepileptic drugs (AEDs) and surgical interventions, are vital for seizure control, but many patients experience medication resistance and side effects. Surgical options remain underutilized due to misconceptions and access issues. In rural areas, reliance on traditional healers and medicinal plants like Artemisia herba-alba and Mentha pulegium for alternative therapies highlights a gap in epilepsy awareness and diagnosis. The review emphasizes the need to integrate traditional knowledge with modern medical practices and calls for interdisciplinary research and equitable distribution of treatment centres. Future efforts should prioritize culturally sensitive, cost-effective strategies to improve early diagnosis, treatment access, healthcare services, and public awareness for better epilepsy outcomes in Morocco.
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References
1. Sperling MR. The consequences of uncontrolled epilepsy. CNS spectrums. 2004;9(2):98-109. Accessed April 30, 2024. https://www.cambridge.org/core/journals/cns-spectrums/article/consequences-of-uncontrolled-epilepsy/D24B49C12D1C602A9584E62F5C654DD5
2. Mac TL, Tran DS, Quet F, Odermatt P, Preux PM, Tan CT. Epidemiology, aetiology, and clinical management of epilepsy in Asia: a systematic review. Lancet Neurol. 2007;6(6):533-543. Accessed April 30, 2024. https://www.thelancet.com/journals/lancet/article/PIIS1474-4422(07)70127-8/abstract
3. Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and lifetime epilepsy: A meta‐analytic approach. Epilepsia. 2010;51(5):883-890. doi:10.1111/j.1528-1167.2009.02481.x
4. Organization WH. Atlas: Epilepsy Care in the World. World Health Organization; 2005. Accessed April 30, 2024. https://apps.who.int/iris/bitstream/handle/10665/43298/9241563036_eng.pdf?sequence=1
5. Kissani N, Cherkaoui Rhazouani O, Souirti Z, Khramaz, M, Meryem C, Mebrouk Y. and Ouazzani R. Epilepsy in Morocco: Realities, pitfalls and prospects. Epilepsia Open. 2021;6(1):13-21. doi:10.1002/epi4.12440
6. Boling W, Means M, Fletcher A. Quality of life and stigma in epilepsy, perspectives from selected regions of Asia and Sub-Saharan Africa. Brain sci. 2018;8(4):59. Accessed May 2, 2024. https://www.mdpi.com/2076-3425/8/4/59
7. Jost J, Millogo A, Preux PM. Antiepileptic treatments in developing countries. Curr Pharm Des. 2017;23(37):5740-5748. Accessed May 2, 2024. https://www.ingentaconnect.com/content/ben/cpd/2017/00000023/00000037/art00016
8. Beghi E, Giussani G. Aging and the epidemiology of epilepsy. Neuroepidemiol. 2018;51(3-4):216-223. Accessed May 2, 2024. https://karger.com/ned/article-abstract/51/3-4/216/226961
9. Aguiar CCT, Almeida AB, Araújo PVP, Abreu RN, Chaves EM, Vale OC, Macêdo DS, Woods DJ, Fonteles MM, Vasconcelos SM. Oxidative stress and epilepsy: literature review. Oxid. med. cell. long.. 2012;2012. Accessed May 2, 2024. https://www.hindawi.com/journals/oximed/2012/795259/abs/
10. Geronzi U, Lotti F, Grosso S. Oxidative stress in epilepsy. Expert Rev Neuroth. 2018;18(5):427-434. doi:10.1080/14737175.2018.1465410
11. De La Court A, Breteler MMB, Meinardi H, Hauser WA, Hofman A. Prevalence of Epilepsy in the Elderly: The Rotterdam Study. Epilepsia. 1996;37(2):141-147. doi:10.1111/j.1528-1157.1996.tb00005.x
12. Stefan H. Epilepsy in the elderly: facts and challenges: Epilepsy in the elderly. Acta Neurol Scand. 2011;124(4):223-237. doi:10.1111/j.1600-0404.2010.01464.x
13. Leppik IE, Birnbaum AK. Epilepsy in the elderly. Ann N Y Acad Sci. 2010;1184(1):208-224. doi:10.1111/j.1749-6632.2009.05113.x
14. Cantwell MF. Map of the spirit: Diagnosis and treatment of spiritual disease. Ad Mind Body Med. 2008;23(2):6-16. Accessed May 2, 2024. https://europepmc.org/article/med/20664140
15. Hesdorffer DC, Beck V, Begley CE, Bishop ML, Cushner‐Weinstein S, Holmes GL, Shafer PO, Sirven JI, Austin JK. Research implications of the Institute of Medicine Report, Epilepsy Across the Spectrum: Promoting Health and Understanding. Epilepsia. 2013;54(2):207-216. doi:10.1111/epi.12056
16. Kissani N, Moro M, Arib S. Knowledge, attitude and traditional practices towards epilepsy among relatives of PWE (patients with epilepsy) in Marrakesh, Morocco. E & B. 2020;111:107257. Accessed May 2, 2024. https://www.sciencedirect.com/science/article/pii/S1525505020304364
17. Bhalla D, Lotfalinezhad E, Timalsina U, Kapoor S, Kumar KS, Abdelrahman A, Giagante B, Tripathi M, Srivastava K, Irmansyah I. A comprehensive review of epilepsy in the Arab world. Seizure. 2016;34:54-59. Accessed May 2, 2024. https://www.sciencedirect.com/science/article/pii/S1059131115002836
18. Rajshekhar V, Raghava MV, Prabhakaran V, Oommen A, Muliyil J. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurol. 2006;67(12):2135-2139. doi:10.1212/01.wnl.0000249113.11824.64
19. Hickman LB, Stern JM, Silverman DH, Salamon N, Vossel K. Clinical, imaging, and biomarker evidence of amyloid-and tau-related neurodegeneration in late-onset epilepsy of unknown etiology. Front Neurol. 2023;14:1241638. Accessed May 3, 2024. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1241638/full
20. Brodie MJ, Elder AT, Kwan P. Epilepsy in later life. Lancet Neurol. 2009;8(11):1019-1030. Accessed May 3, 2024. https://www.thelancet.com/journals/lancet/article/PIIS1474-4422(09)70240-6/fulltext
21. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521. doi:10.1111/epi.13709
22. Engelborghs S, D’hooge R, De Deyn PP. Pathophysiology of epilepsy. Acta neurol Belg. 2000;100(4):201-213. Accessed May 7, 2024. http://www.actaneurologica.be/pdfs/2000-4/01-engelborghs-de%20deyn.pdf
23. Katarina C, Pavlina D, Ondrej H, Klara SP, Senad KO, Hana OS, Stefania AU. Phenotypic spectrum of the SCN1A mutation (from febrile seizures to Dravet syndrome). Bratisl Med J/Bratisl Lek Listy. 2022;123(7). Accessed May 12, 2024. https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=00069248&AN=157785924&h=hfFJHgGH8khPlYcN1QqsMA451rdX0M4HlIyY6axGfIIl56G%2FUfNlPR6fyQTKqgPyxulSYOzoMvrxJL%2FdVtAerw%3D%3D&crl=c
24. Symonds JD, Zuberi SM, Johnson MR. Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment. Curr Opin Neurol. 2017;30(2):193-199. Accessed May 12, 2024. https://journals.lww.com/co-neurology/fulltext/2017/04000/advances_in_epilepsy_gene_discovery_and.13.aspx
25. McCormick DA, Contreras D. On The Cellular and Network Bases of Epileptic Seizures. Annu Rev Physiol. 2001;63(1):815-846. doi:10.1146/annurev.physiol.63.1.815
26. Kwan P, Brodie MJ. Early Identification of Refractory Epilepsy. N Engl J Med. 2000;342(5):314-319. doi:10.1056/NEJM200002033420503
27. Kissani, N., Belaidi, H., Othmani, M.B., Tahiri, S.M., Ouazzani, R., Chkili, T. Comparison of the profile of epileptic patients in Morocco over several years. Epilepsies. 2001; 13(4): 251–258. Accessed May 7, 2024. https://www.jle.com/en/revues/medecine/epi/e-docs/00/01/D4/D3/article.phtml
28. Janmohamed M, Lawn N, Spilsbury K, Chan J, Dunne J. Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute? Epilepsia. 2021;62(1):228-237. doi:10.1111/epi.16765
29. Walker LE, Frigerio F, Ravizza T, Ricci E, Tse K, Jenkins RE, Sills GJ, Jorgensen A, Porcu L, Thippeswamy T, Alapirtti T. Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy. J Clin Investig. 2017;127(6):2118-2132. Accessed May 7, 2024. https://www.jci.org/articles/view/92001
30. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521. doi:10.1111/epi.13709
31. Kobayashi K, Endoh F, Ohmori I, Akiyama T. Action of antiepileptic drugs on neurons. Brain Dev. 2020;42(1):2-5. Accessed May 8, 2024. https://www.sciencedirect.com/science/article/pii/S038776041930186X
32. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 2013;103(1):2-30. Accessed May 8, 2024. https://www.sciencedirect.com/science/article/pii/S0920121112002823
33. Rho JM, Donevan SD, Rogawski MA. Direct activation of GABAA receptors by barbiturates in cultured rat hippocampal neurons. J Physiol. 1996;497(2):509-522. doi:10.1113/jphysiol.1996.sp021784
34. Rogawski MA, Löscher W, Rho JM. Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harb Pers Med. 2016;6(5):a022780. Accessed May 8, 2024. https://perspectivesinmedicine.cshlp.org/content/6/5/a022780.short
35. Nardou R, Yamamoto S, Bhar A, Burnashev N, Ben-Ari Y, Khalilov I. Phenobarbital but not diazepam reduces AMPA/kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus. Front cell Neurosci. 2011;5:16. Accessed May 8, 2024. https://www.frontiersin.org/articles/10.3389/fncel.2011.00016/full
36. Lee C, Fu W, Chen C, Su M, Liou H. Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. Epilepsia. 2008;49(5):888-897. doi:10.1111/j.1528-1167.2007.01526.x
37. Hwang H, Kim KJ. New antiepileptic drugs in pediatric epilepsy. Brain Dev. 2008;30(9):549-555. Accessed May 8, 2024. https://www.sciencedirect.com/science/article/pii/S0387760408000260
38. Zeise ML, Kasparow S, Zieglgänsberger W. Valproate suppresses N-methyl-D-aspartate-evoked, transient depolarizations in the rat neocortex in vitro. Brain Res. 1991;544(2):345-348. Accessed May 8, 2024. https://www.sciencedirect.com/science/article/pii/000689939190078A
39. Patel R, Dickenson AH. Mechanisms of the gabapentinoids and α2δ-1 calcium channel subunit in neuropathic pain. PR &P 2016;4(2):e00205. doi:10.1002/prp2.205
40. Guery D, Rheims S. Is the mechanism of action of antiseizure drugs a key element in the choice of treatment? Fundam Clin Pharma. 2021;35(3):552-563. doi:10.1111/fcp.12614
41. Sisodiya SM. Genetics of drug resistance in epilepsy. Curr Neurol Neurosci Rep. 2005;5(4):307-311. doi:10.1007/s11910-005-0076-2
42. MacDonald BK, Johnson AL, Goodridge DM, Cockerell OC, Sander JWAS, Shorvon SD. Factors predicting prognosis of epilepsy after presentation with seizures. Ann Neurol. 2000;48(6):833-841. doi:10.1002/1531-8249(200012)48:6<833::AID-ANA3>3.0.CO;2-U
43. Urzì Brancati V, Pinto Vraca T, Minutoli L, Pallio G. Polymorphisms Affecting the Response to Novel Antiepileptic Drugs. Inter J Mol Sci. 2023;24(3):2535. doi:10.3390/ijms24032535
44. Kumar P, Sheokand D, Grewal A, Saini V, Kumar A. Clinical side-effects based drug repositioning for anti-epileptic activity. J Biomol Struct Dyn. 2024;42(3):1443-1454. doi:10.1080/07391102.2023.2199874
45. Khotimah H, Rahmaniar FZ, Zahra FA, Anaqah R, Kurniawan SN, Rahayu M, Sulistomo HW. Unveiling the effects of nanoparticles-based antiepileptic drugs: Systematic review of in vivo studies. GSCBPS. 2024;26(3):140-158. Accessed May 11, 2024. http://gsconlinepress.com/journals/gscbps/content/unveiling-effects-nanoparticles-based-antiepileptic-drugs-systematic-review-vivo-studies
46. Wyono OP, Ernawati I, Yunitasari FD, Pradani EY, Islamiyah WR. Association of side effects to medication adherence of antiepileptic drug use in epileptic patients. IJPS. 2024; 22(1): 80-86. Published online 2024. Accessed May 11, 2024. http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/download/1269/696
47. Ekundayo BE, Obafemi TO, Adewale OB, Obafemi BA, Oyinloye BE, Ekundayo SK. Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer’s Disease. Cell Biochem Biophys. Published online March 12, 2024. doi:10.1007/s12013-024-01248-2
48. Lee HS, Arulsamy A, Shaikh MF. Epilepsy and Oxidative Stress. In: Mohamed E, ed. Handbook of Neurodegenerative Disorders. Springer Nature Singapore; 2024:1-10. doi:10.1007/978-981-19-3949-5_16-1
49. Wal P, Vig H, Alnaseer SM, Khan MMU, Mishra AK, Behl T. Role of inflammation, angiogenesis and oxidative stress in developing epilepsy. In: Targeting Angiogenesis, Inflammation, and Oxidative Stress in Chronic Diseases. Elsevier; 2024:293-322. Accessed May 10, 2024. https://www.sciencedirect.com/science/article/pii/B978044313587300014X
50. Zhou Z, Li K, Chu Y, Li C, Zhang T, Liu P, Sun T, Jiang C. ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy. Acta Pharm Sin B. 2023;13(3):1246-1261. doi:10.1016/j.apsb.2022.09.019
51. Lin L, Geng D, She D, Kuai X, Du C, Fu P, Zhu Y, Wang J, Pang Z, Zhang J. Targeted nanotheranostics for the treatment of epilepsy through in vivo hijacking of locally activated macrophages. Acta Biomater. 2024;174:314-330. Accessed May 11, 2024. https://www.sciencedirect.com/science/article/pii/S1742706123006839
52. Liu J, He Y, Zhang J, Li J, Yu X, Cao Z, Meng F, Zhao Y, Wu X, Shen T, Hong Z. Functionalized nanocarrier combined seizure-specific vector with P-glycoprotein modulation property for antiepileptic drug delivery. Biomaterials. 2016;74:64-76. Accessed May 11, 2024. https://www.sciencedirect.com/science/article/pii/S0142961215007929
53. Sagher O, Thawani JP, Etame AB, Gomez-Hassan DM. Seizure outcomes and mesial resection volumes following selective amygdalohippocampectomy and temporal lobectomy. Neurosurg Focus. 2012;32(3):E8. Accessed May 9, 2024. https://thejns.org/focus/view/journals/neurosurg-focus/32/3/2011.12.focus11342.xml
54. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy. N Engl J Med. 2001;345(5):311-318. doi:10.1056/NEJM200108023450501
55. Samanta D, Hoyt ML, Perry MS. Healthcare professionals’ knowledge, attitude, and perception of epilepsy surgery: A systematic review. E & B. 2021;122:108199. Accessed May 9, 2024. https://www.sciencedirect.com/science/article/pii/S1525505021004601
56. Souirti Z, Sghir A, Belfkih R, Messouak O. Focal drug-resistant epilepsy: Progress in care and barriers, a Morroccan perspective. J Clin Neurosci. 2016;34:276-280. Accessed May 9, 2024. https://www.sciencedirect.com/science/article/pii/S096758681630279X
57. Akhaddar A. Raphael Acquaviva: The Forgotten Pioneer of Modern Neurosurgery in Morocco. World Neurosurg. 2021;145:168-171. Accessed May 9, 2024. https://www.sciencedirect.com/science/article/pii/S187887502032074X
58. Ouazzani R. Epilepsy surgery in Morocco study and long-term follow-up in 51 cases. J Neurol Sci. 2013;333:e53-e54. Accessed May 9, 2024. https://www.jns-journal.com/article/S0022-510X(13)00502-9/abstract
59. McIntosh AM, Wilson SJ, Berkovic SF. Seizure Outcome after Temporal Lobectomy: Current Research Practice and Findings. Epilepsia. 2001;42(10):1288-1307. doi:10.1046/j.1528-1157.2001.02001.x
60. Williamson PD, French JA, Thadani VM, Kim JH, Novelly RA, Spencer SS, Spencer DD, Mattson RH. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol. 1993;34(6):781-787. doi:10.1002/ana.410340605
61. Mesraoua B, Kissani N, Deleu D, Elsheikh L, Ali M, Melikyan G, Al Hail H, Wiebe S, Asadi-Pooya AA. Complementary and alternative medicine (CAM) for epilepsy treatment in the Middle East and North Africa (MENA) region. Epilepsy Res. 2021;170:106538. doi:10.1016/j.eplepsyres.2020.106538
62. Chaachouay N, Benkhnigue O, Zidane L. Ethnobotanical study aimed at investigating the use of medicinal plants to treat nervous system diseases in the Rif of Morocco. J Chiropr Med. 2020;19(1):70-81. Accessed May 12, 2024. https://www.sciencedirect.com/science/article/pii/S1556370720300316
63. Es-Safi I, Mechchate H, Amaghnouje A, Elbouzidi A, Bouhrim M, Bencheikh N, Hano C, Bousta D. Assessment of antidepressant-like, anxiolytic effects and impact on memory of Pimpinella anisum L. total extract on swiss albino mice. Plants. 2021;10(8):1573. Accessed May 12, 2024. https://www.mdpi.com/2223-7747/10/8/1573
64. Rutebemberwa E, Ssemugabo C, Tweheyo R, Turyagaruka J, Pariyo GW. Biomedical drugs and traditional treatment in care seeking pathways for adults with epilepsy in Masindi district, Western Uganda: a household survey. BMC Health Serv Res. 2020;20(1):17. doi:10.1186/s12913-019-4879-2
65. Danesi MA, Adetunji JB. Use of Alternative Medicine by Patients with Epilepsy: A Survey of 265 Epileptic Patients in a Developing Country. Epilepsia. 1994;35(2):344-351. doi:10.1111/j.1528-1157.1994.tb02442.x
66. Audet CM, Ngobeni S, Graves E, Wagner RG. Mixed methods inquiry into traditional healers’ treatment of mental, neurological and substance abuse disorders in rural South Africa. PloS one. 2017;12(12):e0188433. Accessed May 12, 2024. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188433
67. Bifftu BB, Dachew BA, Tiruneh BT, Alemu WG. First choice of treatment place in the pathways to epileptic care at the outpatient department of University of Gondar Hospital, Northwest Ethiopia: Cross-sectional institutional based study. PloS one. 2017;12(8):e0181310. Accessed May 12, 2024. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181310
68. Kpobi L, Swartz L. Implications of healing power and positioning for collaboration between formal mental health services and traditional/alternative medicine: the case of Ghana. Glob Health Action. 2018;11(1):1445333. doi:10.1080/16549716.2018.1445333
69. Qiu J. Traditional medicine: a culture in the balance. Nature. 2007;448(7150):126-129. Accessed May 12, 2024. https://go.gale.com/ps/i.do?id=GALE%7CA185560763&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=00280836&p=AONE&sw=w
70. Jamshidi-Kia F, Lorigooini Z, Amini-Khoei H. Medicinal plants: Past history and future perspective. J Herbmed Pharmacol. 2017;7(1):1-7. Accessed May 12, 2024. https://herbmedpharmacol.com/PDF/jhp-7-1.pdf
71. Schippmann UWE, Leaman D, Cunningham AB. A comparison of cultivation and wild collection of medicinal and aromatic plants under sustainability aspects. Frontis. Published online 2006:75-95. Accessed May 12, 2024. https://library.wur.nl/ojs/index.php/frontis/article/view/1225
72. Muceniece R, Saleniece K, Krigere L, Rumaks J, Dzirkale Z, Mezhapuke R, Kviesis J, Mekss P, Klusa V, Schiöth HB, Dambrova M. Potato (Solanum tuberosum) Juice Exerts an Anticonvulsant Effect in Mice through Binding to GABA Receptors. Planta Med. 2008;74:491-496. doi:10.1055/s-2008-1074495
73. Amtaghri S, Slaoui M, Eddouks M. Mentha pulegium: A Plant with Several Medicinal Properties. Endocrine, Metabolic & Immune Disorders-Drug Targets. EMIDDT. 2024;24(3):302-320. Accessed October 12, 2024. https://www.ingentaconnect.com/content/ben/emiddt/2024/00000024/00000003/art00004
74. Qneibi M, Bdir S, Maayeh C, Bdair M, Sandouka D, Basit D, Hallak M. A Comprehensive Review of Essential Oils and Their Pharmacological Activities in Neurological Disorders: Exploring Neuroprotective Potential. Neurochem Res. 2024;49(2):258-289. doi:10.1007/s11064-023-04032-5
75. Kolawole OT, Adeyeba OA, Awodele O, Wakeel OK, Ayankunle AA. Protective effects of crude extract and fractions of Newbouldia laevis leaves in chemoconvulsant-induced seizures. TJNPR. 2021. 5(1); 217-224. Published online 2021. Accessed October 12, 2024. https://www.cabidigitallibrary.org/doi/full/10.5555/20210314432
76. Nazifi AB, Ahmed A, Hassan FI, Mohammed N, Danbala AA, Odoma S. Comparative Anticonvulsant Activity of Leaf, Stem Bark and Root Bark Extracts of Bombax costatum Pellegr. and Vuillet in Acute Models of Epilepsy. TJNPR. 2020; 4(10); 844-849. doi. org/10.26538/tjnpr/v4i10. 30. TJNPR. 2020;4(10):844-849. Accessed October 12, 2024. https://www.researchgate.net/profile/Saidi-Odoma/publication/345262272_Comparative_Anticonvulsant_Activity_of_Leaf_Stem_Bark_and_Root_Bark_Extracts_of_Bombax_costatum_Pellegr_and_Vuillet_in_Acute_Models_of_Epilepsy/links/5fa22111299bf1b53e60fb65/Comparative-Anticonvulsant-Activity-of-Leaf-Stem-Bark-and-Root-Bark-Extracts-of-Bombax-costatum-Pellegr-and-Vuillet-in-Acute-Models-of-Epilepsy.pdf
77. Bolanle OI, Oviasogie OD, Owolabi OJ, Akhigbemen AM, Obarisiagbon PA, Osaigbovo CA. Evaluation of the Anti-Convulsant Activity of Aqueous Leaf Extract of Jatropha curcas (Euphorbiaceae) in Mice: doi. org/10.26538/tjnpr/v2i11. 5. TJNPR. 2018;2(11):489-493.
78. Salaria P, Subrahmanyeswara Rao NN, Dhameliya TM, Amarendar Reddy M. In silico investigation of potential phytoconstituents against ligand- and voltage-gated ion channels as antiepileptic agents. 3 Biotech. 2024;14(4):99. doi:10.1007/s13205-024-03948-1
79. Ahmad N, Hui-Yin Y, Makmor-Bakry M. Mechanisms of natural products as potential antiepileptic drugs. PJPS 2022;35(4). Accessed May 13, 2024. https://www.researchgate.net/profile/Hui-Yin-Yow/publication/363024895_Mechanisms_of_natural_products_as_potential_antiepileptic_drugs/links/634d775f12cbac6a3ed4b651/Mechanisms-of-natural-products-as-potential-antiepileptic-drugs.pdf
80. He LY, Hu MB, Li RL, Zhao R, Fan LH, He L, Lu F, Ye X, Huang YL, Wu CJ. Natural Medicines for the Treatment of Epilepsy: Bioactive Components, Pharmacology and Mechanism. Front Pharmacol. 2021;12. doi:10.3389/fphar.2021.604040
81. Kaur J, Famta P, Famta M, Mehta M, Satija S, Sharma N, Vyas M, Khatik GL, Chellappan DK, Dua K, Khurana N. Potential anti-epileptic phytoconstituents: An updated review. J Ethnopharmacol. 2021;268:113565. doi:10.1016/j.jep.2020.113565
82. Gull A, Lone AA, Wani NUI. Biotic and abiotic stresses in plants. Abiotic and biotic stress in plants. Published online 2019:1-19. Accessed May 13, 2024. https://books.google.com/books?hl=en&lr=&id=sHH8DwAAQBAJ&oi=fnd&pg=PA3&dq=These+compounds+are+produced+by+plants+to+counteract+the+deleterious+effects+of+abiotic+and+biotic+agents+&ots=AOOFCLtKQj&sig=Q_MM8CbQsgYB7AkYL1CcihqV2J8
83. Nilsson J, Sterner O. Modulation of GABAA receptors by natural products and the development of novel synthetic ligands for the benzodiazepine binding site. Curr Drug Targ. 2011;12(11):1674-1688. Accessed May 13, 2024. https://www.ingentaconnect.com/content/ben/cdt/2011/00000012/00000011/art00010
84. Zhu HL, Wan JB, Wang YT, Li BC, Xiang C, He J, Li P. Medicinal compounds with antiepileptic/anticonvulsant activities. Epilepsia. 2014;55(1):3-16. doi:10.1111/epi.12463
85. Medina JH, Paladini AC, Wolfman C, de Stein ML, Calvo D, Diaz LE, Peña C. Chrysin (5, 7-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties. Biochem Pharmacol. 1990;40(10):2227-2231. Accessed May 14, 2024. https://www.sciencedirect.com/science/article/pii/000629529090716X
86. Hakami T. Neuropharmacology of Antiseizure Drugs. Neuropsychopharm Rep. 2021;41(3):336-351. doi:10.1002/npr2.12196
87. Gauthier AC, Mattson RH. Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy. CNS Neurosci Ther. 2015;21(7):543-548. doi:10.1111/cns.12399
88. He QC, Chen W, Liu T. Clinical Observation on Chaihu Shugan Decoction (柴胡疏肝汤) Combined with Zhebeimu (Fritillaria Thun bergii Miq.) and Western Medicine Treating 60 Patients with Intractable Epilepsy. J Tradit Chin Med. 2016;57:1662-1665.
89. Tao F, Cai Y, Deng C, Chen Z, Shen Y, Sun H. A narrative review on traditional Chinese medicine prescriptions and bioactive components in epilepsy treatment. Ann Translat Med. 2023;11(2). Accessed May 12, 2024. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929833/
90. Xu XX, Shi RX, Fu Y, Wang JL, Tong X, Zhang SQ, Wang N, Li MX, Tong Y, Wang W, He M. Neuronal nitric oxide synthase/reactive oxygen species pathway is involved in apoptosis and pyroptosis in epilepsy. Neural Regen Res. 2023;18(6):1277-1285. Accessed May 12, 2024. https://journals.lww.com/nrronline/fulltext/2023/06000/Neuronal_nitric_oxide_synthase_reactive_oxygen.23.aspx
91. Yunhong Y, Wei X, Changjun W. Chaihushugan decoction exerts antiepileptic effects by increasing hippocampal glutamate metabolism in pentylenetetrazole-kindled rats. J Trad Chin Med. 2015;35(6):659-665. Accessed May 12, 2024. https://www.sciencedirect.com/science/article/pii/S0254627215301564
92. Zhang Y, Tong L, Chen G, Deng J, Zhang L, Li H, Chang P. Analysis of medication rule of primary epilepsy based on xiaocheng yan’s clinical experience collection of epilepsy. eCAM 2022;2022. Accessed May 12, 2024. https://www.hindawi.com/journals/ecam/2022/9539944/
93. Wang ZH, Chen BH, Lin YY, Xing J, Wei ZL, Ren L. Herbal decoction of Gastrodia, Uncaria, and Curcuma confers neuroprotection against cerebral ischemia in vitro and in vivo. J Integr Neurosci. 2020;19(3):513. doi:10.31083/j.jin.2020.03.002
94. Ping X, Qin SK, Liu SN, Lu Y, Zhao YN, Cao YF, Zhang YH, Zhang SD, Chu L, Pei L. Effects of Huazhuo Jiedu Shugan Decoction on Cognitive and Emotional Disorders in a Rat Model of Epilepsy: Possible Involvement of AC-cAMP-CREB Signaling and NPY Expression. eCAM 2019;2019:e4352879. doi:10.1155/2019/4352879
95. Heidari MR, Ayeli M. Effects of methyl alcoholic extract of Pimpinella anisum L. on picrotoxin induced seizure in mice and its probable mechanism. SJKU 2005; 10 (3) :1-8. Published online 2005. Accessed May 12, 2024. https://www.sid.ir/paper/76567/en
96. Debnath J, Sharma UR, Kumar B, Chauhan NS. Anticonvulsant activity of ethanolic extract of fruits of Terminalia chebula on experimental animals. Inter J Drug Dev Res. 2010;2(4):764-768.
97. Deshmane DN, Gadgoli CH, Halade GV. Anticonvulsant effect of Origanum majorana L. Pharmacologyonline. 2007;2007(1):64. Accessed May 12, 2024. https://digitalcommons.usf.edu/intmed_facpub/80/
98. Pahuja M, Mehla J, Reeta KH, Joshi S, Gupta YK. Root extract of Anacyclus pyrethrum ameliorates seizures, seizure-induced oxidative stress and cognitive impairment in experimental animals. Epilepsy Res. 2012;98(2-3):157-165. Accessed May 12, 2024. https://www.sciencedirect.com/science/article/pii/S0920121111002701
99. Sayyah M, Valizadeh J, Kamalinejad M. Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole-and maximal electroshock-induced seizures. Phytomed. 2002;9(3):212-216. Accessed May 12, 2024. https://www.sciencedirect.com/science/article/pii/S094471130470104X
100.Economou NT, Lascaratos J. The Byzantine Physicians on Epilepsy. J His Neurosci. 2005;14(4):346-352. doi:10.1080/096470490889385