Abstract
Amaç: Lezyonel epilepsi, epilepsi olgularının önemli bir kısmını oluşturmakta olup tedavi yanıtı, lezyon tipi ve klinik özelliklere göre değişmektedir. Bu olgularda ilaç tedavisine dirence etki eden faktörlerin belirlenmesi, hasta yönetimi ve cerrahi operasyonların planlanmasında gereklidir. Bu çalışmanın amacı, erişkin lezyonel epilepsi hastalarında klinik, radyolojik ve elektroensefalografi (EEG) bulgularının ilaç tedavisinde elde edilen yanıt ile ilişkisini belirlemektir.
Gereç ve Yöntem: MRG (magnetik rezonans görüntüleme) ile doğrulanmış yapısal lezyonu bulunan, ≥18 yaşında ve en az bir yıl süreyle antiepileptik ilaç (AEİ) tedavisi almış hastalar geriye dönük olarak incelendi. Psikojenik non-epileptik nöbet, akut semptomatik nöbet, tedaviye uyumsuzluk ve önceki epilepsi cerrahisi öyküsü olan hastalar dışlandı. Demografik veriler, nöbet tipi, AEİ rejimi, MRG lezyon özellikleri ve interiktal EEG bulguları kaydedildi. İlaç direnci, iki uygun ve iyi tolere edilen AEİ rejiminin başarısızlığı olarak tanımlandı.
Bulgular: Toplam 96 hasta (41 erkek, 45 kadın; ortalama yaş: 42 yıl) dahil edildi. En sık görülen lezyon ensefalomalazi (%43) olup, bunu tümörler (%26), kortikal gelişim malformasyonları (KGM) (%8), kistik lezyonlar (%6), vasküler malformasyonlar (%6) ve mezial temporal skleroz (%5) izledi. İlaç direnci %26 oranında görüldü; KGM grubunda bu oran %62 ile anlamlı olarak daha yüksekti (p = 0,026). Cinsiyet, nöbet başlangıç yaşı, jeneralize motor nöbet varlığı, EEG anormallikleri ve lezyon lateralitesi ile ilaç direnci arasında anlamlı ilişki bulunmadı.
Sonuç: KGM, erişkin lezyonel epilepsi hastalarında ilaç direnci ile güçlü şekilde ilişkilidir. Bu hastaların erken dönemde tanınması, cerrahi değerlendirme sürecinin hızlandırılmasını ve nöbet kontrolünün iyileştirilmesini sağlayabilir.
Keywords
lezyonel epilepsi ilaç dirençli epilepsi epilepsi ilişkili serebral lezyonlar kortikal gelişim malformasyonları nöbet prognozu
References
- Brodie MJ, Dichter MA. Antiepileptic drugs. N Engl J Med. 1996;334(3):168-175. doi:10.1056/NEJM199601183340308.
- Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-319. doi:10.1056/NEJM200002033420503.
- French JA. Refractory epilepsy: clinical overview. Epilepsia 2007;48(Suppl.1):3–7.
- Camfield PR, Camfield CS. Antiepileptic drug therapy: when is epilepsy truly intractable? Epilepsia 1996;37(Suppl.1):S60–5.
- French JA. Response to Early AED Therapy and Its Prognostic Implications. Epilepsy Curr. 2002;2(3):69-71. doi:10.1111/j.1535-7597.2002.00025.x.
- Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 2007;75(2-3):192-196. doi:10.1016/j.eplepsyres.2007.06.003.
- Kwan P, Brodie MJ. Drug treatment of epilepsy: when does it fail and how to optimize its use?. CNS Spectr. 2004;9(2):110-119. doi:10.1017/s1092852900008476.
- Kwan P, Brodie MJ. Refractory epilepsy: a progressive, intractable but preventable condition?. Seizure. 2002;11(2):77-84. doi:10.1053/seiz.2002.0593.
- Cendes F. Neuroimaging predictors of AED resistance in new-onset epilepsies. Epilepsia. 2011;52 Suppl 4:7-9. doi:10.1111/j.1528-1167.2011.03143.x.
- Engel J Jr. Surgery for seizures. N Engl J Med. 1996;334(10):647-652. doi:10.1056/NEJM199603073341008.
- Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-482. doi:10.1111/epi.12550.
- Beniczky S, Trinka E, Wirrell E, Abdulla F, Al Baradie R, Alonso Vanegas M, et al. Updated classification of epileptic seizures: Position paper of the International League Against Epilepsy. Epilepsia. 2025;66(6):1804–1823. doi:10.1111/epi.18338.
- Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–1077. doi:10.1111/j.1528-1167.2009.02397.x
- Jones RM, Butler JA, Thomas VA, Peveler RC, Prevett M. Adherence to treatment in patients with epilepsy: associations with seizure control and illness beliefs. Seizure. 2006;15(7):504–8. doi:10.1016/j.seizure.2006.06.003.
- Aminoff MJ. Electrodiagnosis in clinical neurology. Electrodiagnosis in clinical neurology. 2005.
- Vattipally VR, Bronen RA. MR imaging of epilepsy: strategies for successful interpretation. Neuroimaging Clin N Am. 2004;14(3):349-372. doi:10.1016/j.nic.2004.04.002.
- Christensen J, Kjeldsen MJ, Andersen H, Friis ML, Sidenius P. Gender differences in epilepsy. Epilepsia. 2005;46(6):956-960. doi:10.1111/j.1528-1167.2005.51204.x
- Zaki MA, ElSherif LN & Shamloul RM. Assessment of the response to antiepileptic drugs in epileptic patients with structural lesion(s) on neuroimaging. Egypt J Neurol Psychiatry Neurosurg 2020;56:108. doi:10.1186/s41983-020-00243-7.
- Alare K, Ogungbemi B, Fagbenro A, Adetunji B, Owonikoko O, Omoniyo T, et al. Drug resistance predictive utility of age of onset and cortical imaging abnormalities in epilepsy: a systematic review and meta-analysis. Egypt J Neurol Psychiatry Neurosurg 2024;60:5. doi:10.1186/s41983-023-00753-w
- Doucet GE, Sharan A, Pustina D, Skidmore C, Sperling MR, Tracy JI. Early and late age of seizure onset have a differential impact on brain resting-state organization in temporal lobe epilepsy. Brain Topogr. 2015;28(1):113-126. doi:10.1007/s10548-014-0366-6.
- Angeleri F, Majkowski J, Cacchiò G, Sobieszek A, D'Acunto S, Gesuita R, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia. 1999;40(9):1222-1230. doi:10.1111/j.1528-1157.1999.tb00850.x.
- Uva L, Librizzi L, Wendling F, de Curtis M. Propagation dynamics of epileptiform activity acutely induced by bicuculline in the hippocampal-parahippocampal region of the isolated Guinea pig brain. Epilepsia. 2005;46(12):1914-1925. doi:10.1111/j.1528-1167.2005.00342.x.
- Dinner DS. Effect of sleep on epilepsy. J Clin Neurophysiol. 2002;19(6):504-513. doi:10.1097/00004691-200212000-00003.
- Sammaritano M, Gigli GL, Gotman J. Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy. Neurology. 1991;41(2 ( Pt 1)):290-297. doi:10.1212/wnl.41.2_part_1.290.
- Malow BA, Lin X, Kushwaha R, Aldrich MS. Interictal spiking increases with sleep depth in temporal lobe epilepsy. Epilepsia. 1998;39(12):1309-1316. doi:10.1111/j.1528-1157.1998.tb01329.x.
- Malow BA, Selwa LM, Ross D, Aldrich MS. Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy. Epilepsia.1999;40(11):1587-1592. doi:10.1111/j.1528-1157.1999.tb02044.x.
- Burkholder DB, Britton JW, Rajasekaran V, Fabris RR, Cherian PJ, Kelly-Williams KM, et al. Routine vs extended outpatient EEG for the detection of interictal epileptiform discharges. Neurology. 2016;86(16):1524-1530. doi:10.1212/WNL.0000000000002592.
- Basiri R, Shariatzadeh A, Wiebe S, Aghakhani Y. Focal epilepsy without interictal spikes on scalp EEG: A common finding of uncertain significance. Epilepsy Res. 2019;150:1-6. doi:10.1016/j.eplepsyres.2018.12.009.
- Mattson RH, Cramer JA, Collins JF. Prognosis for total control of complex partial and secondarily generalized tonic–clonic seizures: Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group. Neurology. 1996;47(1):68-76. doi:10.1212/WNL.47.1.68.
- Palmini A, Andermann F, Olivier A, Tampieri D, Robitaille Y, Andermann E, et al. Focal neuronal migration disorders and intractable partial epilepsy: a study of 30 patients. Ann Neurol. 1991;30(6):741-749. doi:10.1002/ana.410300602.
- Semah F, Picot MC, Adam C, Broglin D, Arzimanoglou A, Bazin B, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51(5):1256-1262. doi:10.1212/wnl.51.5.1256.
- Park KM, Shin KJ, Ha SY, Park J, Kim SE, Kim SE. Response to antiepileptic drugs in partial epilepsy with structural lesions on MRI. Clin Neurol Neurosurg. 2014;123:64–68. doi:10.1016/j.clineuro.2014.04.029.
- Arroyo S, Santamaria J. What is the relationship between arachnoid cysts and seizure foci? Epilepsia.1997;38(10):1098–1102. doi:10.1111/j.1528-1157.1997.tb01199.x.
- Aydin S, Darko K, Detchou D, Barrie U. Arachnoid cysts and epilepsy: seizures and epileptogenesis. Neurosurg Rev. 2024;47(1):544. doi:10.1007/s10143-024-02826-x.
- Volpe JJ. Neurology of the Newborn. Saunders; 2001.
- Ho SS, Kuzniecky RI, Gilliam F, Faught E, Bebin M, Morawetz R. Congenital porencephaly: MR features and relationship to hippocampal sclerosis. AJNR Am J Neuroradiol. 1998;19(1):135–141.
- Galovic M, Döhler N, Erdélyi-Canavese B, Felbecker A, Siebel P, Conrad J, et al. Prediction of late seizures after ischaemic stroke with a novel prognostic model [the SeLECT score]: a multivariable prediction model development and validation study. Lancet Neurol. 2018;17(2):143–152. doi:10.1016/S1474-4422(17)30404-0.
- Lee JW, Wen PY, Hurwitz S, Black P, Kesari S, Drappatz J, et al. Morphological characteristics of brain tumors causing seizures. Arch Neurol. 2010;67(3):336–342. doi:10.1001/archneurol.2010.2.
Predictive factors for drug resistance in adult lesional epilepsy: Evidence from a cross-sectional study
Abstract
Aim: Lesional epilepsy accounts for a substantial proportion of epilepsy cases, with treatment outcomes varying according to lesion type. Identifying predictors of drug resistance is essential to guide management and surgical planning. This study evaluated clinical, radiological, and electroencephalographic (EEG) predictors of treatment response in adults with lesional epilepsy.
Materials and Methods: Medical records of patients ≥18 years with MRI (magnetic resonance imaging)-confirmed structural lesions and ≥1 year of antiepileptic drug (AED) therapy were retrospectively reviewed. Patients with psychogenic non-epileptic seizures, acute symptomatic seizures, non-adherence, or prior epilepsy surgery were excluded. Data included demographics, seizure type, AED regimen, MRI lesion features, and interictal EEG findings. Drug resistance was defined as failure of two appropriately chosen, well-tolerated AED regimens.
Results: Ninety-six patients (41 males, 45 females; mean age 42 years) were included. Encephalomalacia was the most frequent lesion (43%), followed by tumors (26%), malformations of cortical development (MCD) (8%), cystic lesions (6%), vascular malformations (6%), and mesial temporal sclerosis (5%). Drug resistance occurred in 26% of cases, with MCD showing the highest rate (62%, p = 0.026). Gender, age at onset, generalized motor seizures, EEG abnormalities, and lesion laterality were not significantly associated with drug resistance.
Conclusion: MCD is strongly associated with AED resistance in adults with lesional epilepsy, while other lesion types tend to respond more favorably. Early recognition of high-risk patients may facilitate timely surgical evaluation and improve seizure control outcomes.
Keywords
lesional epilepsy drug resistant epilepsy epilepsy related cerebral lesions malformations of cortical development seizure prognosis
References
- Brodie MJ, Dichter MA. Antiepileptic drugs. N Engl J Med. 1996;334(3):168-175. doi:10.1056/NEJM199601183340308.
- Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-319. doi:10.1056/NEJM200002033420503.
- French JA. Refractory epilepsy: clinical overview. Epilepsia 2007;48(Suppl.1):3–7.
- Camfield PR, Camfield CS. Antiepileptic drug therapy: when is epilepsy truly intractable? Epilepsia 1996;37(Suppl.1):S60–5.
- French JA. Response to Early AED Therapy and Its Prognostic Implications. Epilepsy Curr. 2002;2(3):69-71. doi:10.1111/j.1535-7597.2002.00025.x.
- Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 2007;75(2-3):192-196. doi:10.1016/j.eplepsyres.2007.06.003.
- Kwan P, Brodie MJ. Drug treatment of epilepsy: when does it fail and how to optimize its use?. CNS Spectr. 2004;9(2):110-119. doi:10.1017/s1092852900008476.
- Kwan P, Brodie MJ. Refractory epilepsy: a progressive, intractable but preventable condition?. Seizure. 2002;11(2):77-84. doi:10.1053/seiz.2002.0593.
- Cendes F. Neuroimaging predictors of AED resistance in new-onset epilepsies. Epilepsia. 2011;52 Suppl 4:7-9. doi:10.1111/j.1528-1167.2011.03143.x.
- Engel J Jr. Surgery for seizures. N Engl J Med. 1996;334(10):647-652. doi:10.1056/NEJM199603073341008.
- Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-482. doi:10.1111/epi.12550.
- Beniczky S, Trinka E, Wirrell E, Abdulla F, Al Baradie R, Alonso Vanegas M, et al. Updated classification of epileptic seizures: Position paper of the International League Against Epilepsy. Epilepsia. 2025;66(6):1804–1823. doi:10.1111/epi.18338.
- Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–1077. doi:10.1111/j.1528-1167.2009.02397.x
- Jones RM, Butler JA, Thomas VA, Peveler RC, Prevett M. Adherence to treatment in patients with epilepsy: associations with seizure control and illness beliefs. Seizure. 2006;15(7):504–8. doi:10.1016/j.seizure.2006.06.003.
- Aminoff MJ. Electrodiagnosis in clinical neurology. Electrodiagnosis in clinical neurology. 2005.
- Vattipally VR, Bronen RA. MR imaging of epilepsy: strategies for successful interpretation. Neuroimaging Clin N Am. 2004;14(3):349-372. doi:10.1016/j.nic.2004.04.002.
- Christensen J, Kjeldsen MJ, Andersen H, Friis ML, Sidenius P. Gender differences in epilepsy. Epilepsia. 2005;46(6):956-960. doi:10.1111/j.1528-1167.2005.51204.x
- Zaki MA, ElSherif LN & Shamloul RM. Assessment of the response to antiepileptic drugs in epileptic patients with structural lesion(s) on neuroimaging. Egypt J Neurol Psychiatry Neurosurg 2020;56:108. doi:10.1186/s41983-020-00243-7.
- Alare K, Ogungbemi B, Fagbenro A, Adetunji B, Owonikoko O, Omoniyo T, et al. Drug resistance predictive utility of age of onset and cortical imaging abnormalities in epilepsy: a systematic review and meta-analysis. Egypt J Neurol Psychiatry Neurosurg 2024;60:5. doi:10.1186/s41983-023-00753-w
- Doucet GE, Sharan A, Pustina D, Skidmore C, Sperling MR, Tracy JI. Early and late age of seizure onset have a differential impact on brain resting-state organization in temporal lobe epilepsy. Brain Topogr. 2015;28(1):113-126. doi:10.1007/s10548-014-0366-6.
- Angeleri F, Majkowski J, Cacchiò G, Sobieszek A, D'Acunto S, Gesuita R, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia. 1999;40(9):1222-1230. doi:10.1111/j.1528-1157.1999.tb00850.x.
- Uva L, Librizzi L, Wendling F, de Curtis M. Propagation dynamics of epileptiform activity acutely induced by bicuculline in the hippocampal-parahippocampal region of the isolated Guinea pig brain. Epilepsia. 2005;46(12):1914-1925. doi:10.1111/j.1528-1167.2005.00342.x.
- Dinner DS. Effect of sleep on epilepsy. J Clin Neurophysiol. 2002;19(6):504-513. doi:10.1097/00004691-200212000-00003.
- Sammaritano M, Gigli GL, Gotman J. Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy. Neurology. 1991;41(2 ( Pt 1)):290-297. doi:10.1212/wnl.41.2_part_1.290.
- Malow BA, Lin X, Kushwaha R, Aldrich MS. Interictal spiking increases with sleep depth in temporal lobe epilepsy. Epilepsia. 1998;39(12):1309-1316. doi:10.1111/j.1528-1157.1998.tb01329.x.
- Malow BA, Selwa LM, Ross D, Aldrich MS. Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy. Epilepsia.1999;40(11):1587-1592. doi:10.1111/j.1528-1157.1999.tb02044.x.
- Burkholder DB, Britton JW, Rajasekaran V, Fabris RR, Cherian PJ, Kelly-Williams KM, et al. Routine vs extended outpatient EEG for the detection of interictal epileptiform discharges. Neurology. 2016;86(16):1524-1530. doi:10.1212/WNL.0000000000002592.
- Basiri R, Shariatzadeh A, Wiebe S, Aghakhani Y. Focal epilepsy without interictal spikes on scalp EEG: A common finding of uncertain significance. Epilepsy Res. 2019;150:1-6. doi:10.1016/j.eplepsyres.2018.12.009.
- Mattson RH, Cramer JA, Collins JF. Prognosis for total control of complex partial and secondarily generalized tonic–clonic seizures: Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group. Neurology. 1996;47(1):68-76. doi:10.1212/WNL.47.1.68.
- Palmini A, Andermann F, Olivier A, Tampieri D, Robitaille Y, Andermann E, et al. Focal neuronal migration disorders and intractable partial epilepsy: a study of 30 patients. Ann Neurol. 1991;30(6):741-749. doi:10.1002/ana.410300602.
- Semah F, Picot MC, Adam C, Broglin D, Arzimanoglou A, Bazin B, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51(5):1256-1262. doi:10.1212/wnl.51.5.1256.
- Park KM, Shin KJ, Ha SY, Park J, Kim SE, Kim SE. Response to antiepileptic drugs in partial epilepsy with structural lesions on MRI. Clin Neurol Neurosurg. 2014;123:64–68. doi:10.1016/j.clineuro.2014.04.029.
- Arroyo S, Santamaria J. What is the relationship between arachnoid cysts and seizure foci? Epilepsia.1997;38(10):1098–1102. doi:10.1111/j.1528-1157.1997.tb01199.x.
- Aydin S, Darko K, Detchou D, Barrie U. Arachnoid cysts and epilepsy: seizures and epileptogenesis. Neurosurg Rev. 2024;47(1):544. doi:10.1007/s10143-024-02826-x.
- Volpe JJ. Neurology of the Newborn. Saunders; 2001.
- Ho SS, Kuzniecky RI, Gilliam F, Faught E, Bebin M, Morawetz R. Congenital porencephaly: MR features and relationship to hippocampal sclerosis. AJNR Am J Neuroradiol. 1998;19(1):135–141.
- Galovic M, Döhler N, Erdélyi-Canavese B, Felbecker A, Siebel P, Conrad J, et al. Prediction of late seizures after ischaemic stroke with a novel prognostic model [the SeLECT score]: a multivariable prediction model development and validation study. Lancet Neurol. 2018;17(2):143–152. doi:10.1016/S1474-4422(17)30404-0.
- Lee JW, Wen PY, Hurwitz S, Black P, Kesari S, Drappatz J, et al. Morphological characteristics of brain tumors causing seizures. Arch Neurol. 2010;67(3):336–342. doi:10.1001/archneurol.2010.2.
Details
| Primary Language | English |
|---|---|
| Subjects | Central Nervous System, Neurology and Neuromuscular Diseases |
| Journal Section | Research Article |
| Authors | |
| Publication Date | December 8, 2025 |
| Submission Date | August 29, 2025 |
| Acceptance Date | September 9, 2025 |
| Published in Issue | Year 2025 Volume: 64 Issue: 4 |
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