Novel Approaches for Treatment of Epilepsy

Treatment of Epilepsy


  • Muhammad Ahsan Waqar Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Mehak Saleem Children’s Hospital, Lahore, Pakistan
  • Tooba Mehboob Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Naila Tabassam Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Dawood Ilyas School of Applied Sciences, University of Huddersfield, West Yorkshire, United Kingdom
  • Muhammad Sajid Nawaz Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Mahnoor Foaad Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Maria Riaz Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Aimon Qureshi Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
  • Muhammad Waqas Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan



Epilepsy, Corpus Callostomy, Neurostimulation, Surgery


Epilepsy is a serious neurological disorder on the juncture of psychiatry and neurology. It is characterized by recurrent and episodic seizures which are due to excessive discharge by the brain neurons. The therapeutic response failure of more than one or two antiepileptic drugs (AEDs) is the benchmark of refractory or intractable epilepsy. The aim of the study was to determine new approaches which lead towards the treatment of epilepsy. In order to treat focal mesial temporal lobe epilepsy or neocortical epilepsy in adults and any malformation of cortical development such as focal dysplasia surgical resection remains the gold standard treatment. Disconnection procedures such as corpus callosotomy and multiple subpial transections are the best alternative treatment for that patient whose seizure origin is in eloquent cortex or having generalized epilepsy syndromes. Palliative neuromodulation procedures such as Vagus nerve stimulation (VNS), Responsive neurostimulation (RNS) and Deep brain stimulation (DBS) are best approach to treat intractable epileptic patients who are not suitable candidates of surgery.  As the search of better management of epilepsy continues gene therapy and optogenetics gain a momentum in neuroscience.


Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult Epilepsy. The Lancet. 2006 Feb; 367(9516): 1087-100. doi: 10.1016/S0140-6736(06)68477-8. DOI:

Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy. The Cochrane Database of Systematic Reviews. 2001 Jan; 1(3): CD001909-. doi: 10.1002/14651858.CD001909. DOI:

Dalic L and Cook MJ. Managing drug-resistant epilepsy: challenges and solutions. Neuropsychiatric Disease and Treatment. 2016 Oct; 12: 2605-16. doi: 10.2147/NDT.S84852. DOI:

Sisodiya SM, Lin WR, Harding BN, Squier MV, Thom M. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain. 2002 Jan; 125(1): 22-31. doi: 10.1093/brain/awf002. DOI:

Löscher W, Klitgaard H, Twyman RE, Schmidt D. New avenues for anti-epileptic drug discovery and development. Nature Reviews Drug Discovery. 2013 Oct; 12(10): 757-76. doi: 10.1038/nrd4126. DOI:

Tang F, Hartz AM, Bauer B. Drug-resistant epilepsy: multiple hypotheses, few answers. Frontiers in Neurology. 2017 Jul; 8: 301. doi: 10.3389/fneur.2017.00301. DOI:

Waqar MA, Riaz T, Munir M, Ashfaq A, Zulfiqar H, Sandhu M, et al. COVID-19 and Various Comorbidities: A Review: COVID-19 and Various Comorbidities. Pakistan Journal of Health Sciences. 2023 Jan; 4(1): 02-7. doi: 10.54393/pjhs.v4i01.485. DOI:

Brodie MJ and Kwan P. Staged approach to epilepsy management. Neurology. 2002 Apr; 58(8 suppl 5): S2-8. doi: 10.1212/WNL.58.8_suppl_5.S2. DOI:

Brodie MJ. Medical therapy of epilepsy: when to initiate treatment and when to combine? Journal of Neurology. 2005 Feb; 252: 125-30. doi: 10.1007/s00415-005-0735-x. DOI:

Shimizu H. Surgical treatment for intractable epilepsy. Rinsho Shinkeigaku= Clinical Neurology. 2001 Dec; 41(12): 1094-6.

Engel Jr J. Surgery for seizures. New England Journal of Medicine. 1996 Mar; 334(10): 647-53. doi: 10.1056/NEJM199603073341008. DOI:

Devlin AM, Cross JH, Harkness W, Chong WK, Harding B, Vargha‐Khadem F, et al. Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain. 2003 Mar; 126(3): 556-66. doi: 10.1093/brain/awg052. DOI:

González‐Martínez JA, Gupta A, Kotagal P, Lachhwani D, Wyllie E, Lüders HO, et al. Hemispherectomy for catastrophic epilepsy in infants. Epilepsia. 2005 Sep; 46(9): 1518-25. doi: 10.1111/j.1528-1167.2005.53704.x. DOI:

Shimizu H and Maehara T. Modification of peri-insular hemispherotomy and surgical results. Neurosurgery. 2000 Aug; 47(2): 367-73. doi: 10.1097/00006123-200008000-00018. DOI:

Shimizu H and Maehara T. Neuronal disconnection for the surgical treatment of pediatric epilepsy. Epilepsia. 2000 Sep; 41: 28-30. doi: 10.1111/j.1528-1157.2000.tb02216.x. DOI:

Schramm J, Behrens E, Entzian W. Hemispherical deafferentation: an alternative to functional hemispherectomy. Neurosurgery. 1995 Mar; 36(3): 509-16. doi: 10.1227/00006123-199503000-00010. DOI:

Maehara T and Shimizu H. Surgical outcome of corpus callosotomy in patients with drop attacks. Epilepsia. 2001 Jan; 42(1): 67-71. doi: 10.1046/j.1528-1157.2001.081422.x. DOI:

Jenssen S, Sperling MR, Tracy JI, Nei M, Joyce L, David G, et al. Corpus callosotomy in refractory idiopathic generalized epilepsy. Seizure. 2006 Dec; 15(8): 621-9. doi: 10.1016/j.seizure.2006.09.003. DOI:

Nei M, O'Connor M, Liporace J, Sperling MR. Refractory generalized seizures: response to corpus callosotomy and vagal nerve stimulation. Epilepsia. 2006 Jan; 47(1): 115-22. doi: 10.1111/j.1528-1167.2006.00377.x. DOI:

Asadi‐Pooya AA and Sperling MR. Strategies for surgical treatment of epilepsies in developing countries. Epilepsia. 2008 Mar; 49(3): 381-5. doi: 10.1111/j.1528-1167.2007.01383.x. DOI:

Chang EF, Rowland NC, Barbaro NM. Corpus callosotomy: indications and techniques. InSchmidek and Sweet Operative Neurosurgical Techniques. WB Saunders. 2012 Jan: 1295-1299. doi: 10.1016/B978-1-4160-6839-6.10112-1. DOI:

Ntsambi-Eba G, Vaz G, Docquier MA, van Rijckevorsel K, Raftopoulos C. Patients with refractory epilepsy treated using a modified multiple subpial transection technique. Neurosurgery. 2013 Jun; 72(6): 890-8. doi: 10.1227/NEU.0b013e31828ba750. DOI:

Devinsky O, Romanelli P, Orbach D, Pacia S, Doyle W. Surgical treatment of multifocal epilepsy involving eloquent cortex. Epilepsia. 2003 May; 44(5): 718-23. doi: 10.1046/j.1528-1157.2003.57102.x. DOI:

D’Giano CH, GARCıA MD, Pomata H, Rabinowicz AL. Treatment of refractory partial status epilepticus with multiple subpial transection: case report. Seizure. 2001 Jul; 10(5): 382-5. doi: 10.1053/seiz.2001.0521. DOI:

Chang EF, Englot DJ, Vadera S. Minimally invasive surgical approaches for temporal lobe epilepsy. Epilepsy & Behavior. 2015 Jun; 47: 24-33. doi: 10.1016/j.yebeh.2015.04.033. DOI:

Bailey P and Bremer F. A sensory cortical representation of the vagus nerve: with a note on the effects of low blood pressure on the cortical electrogram. Journal of Neurophysiology. 1938 Sep; 1(5): 405-12. doi: 10.1152/jn.1938.1.5.405. DOI:

Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR. A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy & Behavior. 2000 Apr; 1(2): 93-9. doi: 10.1006/ebeh.2000.0046. DOI:

Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, et al. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology. 2006 Jul; 31(7): 1345-55. doi: 10.1038/sj.npp.1301082. DOI:

Chakravarthy K, Chaudhry H, Williams K, Christo PJ. Review of the uses of vagal nerve stimulation in chronic pain management. Current Pain and Headache Reports. 2015 Dec; 19: 1-9. doi: 10.1007/s11916-015-0528-6. DOI:

Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. The Lancet Neurology. 2002 Dec; 1(8): 477-82. doi: 10.1016/S1474-4422(02)00220-X. DOI:

Velasco F, Velasco AL, Velasco M, Jimenez F, Carrillo-Ruiz JD, Castro G. Deep brain stimulation for treatment of the epilepsies: the centromedian thalamic target. Operative Neuromodulation: Volume 2: Neural Networks Surgery. 2007: 337-42. doi: 10.1007/978-3-211-33081-4_38. DOI:

Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW, Matthews K, McIntyre CC, Schlaepfer TE, Schulder M, Temel Y. Deep brain stimulation: current challenges and future directions. Nature Reviews Neurology. 2019 Mar; 15(3): 148-60. doi: 10.1038/s41582-018-0128-2. DOI:

Cooper IS, Upton AR, Amin I. Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man. Stereotactic and Functional Neurosurgery. 1980 May; 43(3-5): 244-58. doi: 10.1159/000102263. DOI:

Mirski MA and Fisher RS. Electrical stimulation of the mammillary nuclei increases seizure threshold to pentylenetetrazol in rats. Epilepsia. 1994 Nov; 35(6): 1309-16. doi: 10.1111/j.1528-1157.1994.tb01803.x. DOI:

Tyvaert L, Chassagnon S, Sadikot A, LeVan P, Dubeau F, Gotman J. Thalamic nuclei activity in idiopathic generalized epilepsy: an EEG-fMRI study. Neurology. 2009 Dec; 73(23): 2018-22. doi: 10.1212/WNL.0b013e3181c55d02. DOI:

Moeller F, Siebner HR, Wolff S, Muhle H, Boor R, Granert O, et al. Changes in activity of striato–thalamo–cortical network precede generalized spike wave discharges. Neuroimage. 2008 Feb; 39(4): 1839-49. doi: 10.1016/j.neuroimage.2007.10.058. DOI:

Dalkilic EB. Neurostimulation devices used in treatment of epilepsy. Current Treatment Options in Neurology. 2017 Feb; 19(2): 7. doi: 10.1007/s11940-017-0442-9. DOI:

Demarest ST and Brooks-Kayal A. From molecules to medicines: the dawn of targeted therapies for genetic epilepsies. Nature reviews Neurology. 2018 Dec; 14(12): 735-45. doi: 10.1038/s41582-018-0099-3. DOI:

McCown TJ. Adeno-associated virus (AAV) vectors in the CNS. Current gene therapy. 2005 Jun; 5(3): 333-8. doi: 10.2174/1566523054064995. DOI:

Waqar MA, Qureshi A, Ahsan A, Sadaqat S, Zulfiqar H, Razaq A, et al. Epidemiology, Clinical Manifestations, Treatment Approaches and Future Perspectives of Rift Valley Fever: Epidemiology of Rift Valley Fever. Pakistan Journal of Health Sciences. 2023 Apr; 4(4): 02-8. doi: 10.54393/pjhs.v4i04.603. DOI:

Morey N, Przybyla M, van der Hoven J, Ke YD, Delerue F, van Eersel J, et al. Treatment of epilepsy using a targeted p38γ kinase gene therapy. Science Advances. 2022 Dec; 8(48): eadd2577. doi: 10.1126/sciadv.add2577. DOI:

Mazarati AM and Wasterlain CG. Anticonvulsant effects of four neuropeptides in the rat hippocampus during self-sustaining status epilepticus. Neuroscience Letters. 2002 Oct; 331(2): 123-7. doi: 10.1016/S0304-3940(02)00847-9. DOI:

Mazarati AM. Galanin and galanin receptors in epilepsy. Neuropeptides. 2004 Dec; 38(6): 331-43. doi: 10.1016/j.npep.2004.07.006. DOI:

Erickson JC, Clegg KE, Palmiter RD. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature. 1996 May; 381(6581): 415-8. doi: 10.1038/381415a0. DOI:

Sørensen AT and Kokaia M. Novel approaches to epilepsy treatment. Epilepsia. 2013 Jan; 54(1): 1-0. doi: 10.1111/epi.12000. DOI:

Song C and Knöpfel T. Optogenetics enlightens neuroscience drug discovery. Nature Reviews Drug Discovery. 2016 Feb; 15(2): 97-109. doi: 10.1038/nrd.2015.15. DOI:

Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, De Lecea L, et al. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nature Protocols. 2010 Mar; 5(3): 439-56. doi: 10.1038/nprot.2009.226. DOI:

Yizhar O, Fenno LE, Davidson TJ, Mogri M, Deisseroth K. Optogenetics in neural systems. Neuron. 2011 Jul; 71(1): 9-34. doi: 10.1016/j.neuron.2011.06.004. DOI:

Deisseroth K. Optogenetics. Nature Methods. 2011 Jan; 8(1): 26-9. doi: 10.1038/nmeth.f.324. DOI:

Ventola CL. Epilepsy management: newer agents, unmet needs, and future treatment strategies. Pharmacy and Therapeutics. 2014 Nov; 39(11): 776.

Schmidt D and Schachter SC. Drug treatment of epilepsy in adults. Bmj. 2014 Feb; 348. doi: 10.1136/bmj.g254. DOI:

Ramaratnam S, Baker GA, Goldstein LH. Psychological treatments for epilepsy. Cochrane Database of Systematic Reviews. 2008 Jul; 3: 1-33. doi: 10.1002/14651858.CD002029.pub3. DOI:

Haut SR, Gursky JM, Privitera M. Behavioral interventions in epilepsy. Current Opinion in Neurology. 2019 Apr; 32(2): 227-36. doi: 10.1097/WCO.0000000000000661. DOI:

Panebianco M, Sridharan K, Ramaratnam S. Yoga for epilepsy. Cochrane Database of Systematic Reviews. 2017 Oct; 10: 1-37. doi: 10.1002/14651858.CD001524.pub3. DOI:

Longo R, Peri C, Cricrì D, Coppi L, Caruso D, Mitro N, et al. Ketogenic diet: a new light shining on old but gold biochemistry. Nutrients. 2019 Oct; 11(10): 2497. doi: 10.3390/nu11102497. DOI:

Liu W, Ge T, Pan Z, Leng Y, Lv J, Li B. The effects of herbal medicine on epilepsy. Oncotarget. 2017 Jul; 8(29): 48385. doi: 10.18632/oncotarget.16801. DOI:

Holló A, Clemens Z, Kamondi A, Lakatos P, Szűcs A. Correction of vitamin D deficiency improves seizure control in epilepsy: a pilot study. Epilepsy & Behavior. 2012 May; 24(1): 131-3. doi: 10.1016/j.yebeh.2012.03.011. DOI:



DOI: 10.54393/pjhs.v4i08.971
Published: 2023-08-31

How to Cite

Waqar, M. A. ., Saleem, M. ., Mehboob, T. ., Tabassam, N. ., Ilyas, D., Nawaz, M. S. ., Foaad, M. ., Riaz, M. ., Qureshi, A. ., & Waqas, M. . (2023). Novel Approaches for Treatment of Epilepsy: Treatment of Epilepsy. Pakistan Journal of Health Sciences, 4(08), 02–08.



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