Early Identification of Refractory Epilepsy
Open accessAbstract
BACKGROUND: More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. METHODS: We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. RESULTS: Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). CONCLUSIONS: Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.
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The remaining 30% of patients have drug-resistant epilepsy requiring consideration of surgical intervention, ketogenic dietary therapy, vagus nerve stimulation, or other neuromodulatory approaches.
“the remaining 30% have drug-resistant epilepsy requiring consideration of surgical intervention, ketogenic dietary therapy, vagus nerve stimulation, or other neuromodulatory approaches6,7”
Approximately 70% of patients with epilepsy can achieve seizure freedom with appropriate antiepileptic drug (AED) therapy.
“While approximately 70% of patients can achieve seizure freedom with appropriate antiepileptic drug (AED) therapy”
Cites
Guidelines for Epidemiologic Studies on Epilepsy
(1993) · Epilepsia · doi:10.1111/j.1528-1157.1993.tb00433.x · Cited by 1,360 · see citing works
Is the underlying cause of epilepsy a major prognostic factor for recurrence?
Semah, F., Picot, M., Adam, C., Broglin, D., Arzimanoglou, A. A., Bazin, B., Cavalcanti, D., & Baulac, M. (1998) · Neurology · doi:10.1212/wnl.51.5.1256 · Cited by 1,105 · see citing works
Engel, J. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603073341008 · Cited by 880 · see citing works
Long-Term Prognosis of Seizures with Onset in Childhood
Sillanpää, M. L., Jalava, M., Kaleva, O., & Shinnar, S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199806113382402 · Cited by 725 · see citing works
Remission of Seizures and Relapse in Patients with Epilepsy
Annegers, J. F., Hauser, W. A., & Elveback, L. R. (1979) · Epilepsia · doi:10.1111/j.1528-1157.1979.tb04857.x · Cited by 621 · see citing works
Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy
Brodie, M. J., UK Lamotrigine/Carbamazepine Monotherapy Trial Group, Richens, A., & Yuen, A. W. C. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90581-2 · Cited by 614 · see citing works
Self-citationMDR1 Gene Expression in Brain of Patients with Medically Intractable Epilepsy
Tishler, D. M., Weinberg, K. I., Hinton, D. R., Barbaro, N. M., Annett, G., & Raffel, C. (1995) · Epilepsia · doi:10.1111/j.1528-1157.1995.tb01657.x · Cited by 529 · see citing works
Multidrug resistance: molecular mechanisms and clinical relevance
Ling, V. W. T. (1997) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800051053 · Cited by 525 · see citing works
Brodie, M. J., Overstall, P. W., & Giorgi, L. (1999) · Epilepsy Research · doi:10.1016/s0920-1211(99)00039-x · Cited by 462 · see citing works
Self-citationBrodie, M. J., & Dichter, M. A. (1996) · New England Journal of Medicine · doi:10.1056/nejm199601183340308 · Cited by 438 · see citing works
Self-citationSome Aspects of Prognosis in the Epilepsies: A Review
Sander, J. W. A. S. (1993) · Epilepsia · doi:10.1111/j.1528-1157.1993.tb02126.x · Cited by 414 · see citing works
Remission of epilepsy: results from the National General Practice Study of Epilepsy
Cockerell, O. C., Sander, J. W. A. S., Hart, Y. M., Shorvon, S. D., & Johnson, A. L. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91208-8 · Cited by 383 · see citing works
Lamotrigine substitution study: evidence for synergism with sodium valproate?
Brodie, M. J., & Yuen, A. W. C. (1997) · Epilepsy Research · doi:10.1016/s0920-1211(96)01007-8 · Cited by 378 · see citing works
Self-citationThe Prognosis for Seizure Control in Newly Diagnosed Epilepsy
Elwes, R. D. C., Johnson, A. L., Shorvon, S. D., & Reynolds, E. H. (1984) · New England Journal of Medicine · doi:10.1056/nejm198410113111503 · Cited by 266 · see citing works
Treatment of first tonic-clonic seizure does not improve the prognosis of epilepsy
Musicco, M., Beghi, E., Solari, A., Viani, F., & First Seizure Trial Group (FIRST Group) (1997) · Neurology · doi:10.1212/wnl.49.4.991 · Cited by 262 · see citing works
Patients with Refractory Seizures
Devinsky, O. (1999) · New England Journal of Medicine · doi:10.1056/nejm199905203402008 · Cited by 257 · see citing works
Predictors of Intractable Epilepsy in Childhood: A Case‐Control Study
Berg, A. T., Levy, S. R., Novotny, E. J., & Shinnar, S. (1996) · Epilepsia · doi:10.1111/j.1528-1157.1996.tb00507.x · Cited by 226 · see citing works
Remission of Seizures and Predictors of Intractability in Long‐Term Follow‐Up
Sillanpää, M. (1993) · Epilepsia · doi:10.1111/j.1528-1157.1993.tb02114.x · Cited by 211 · see citing works
The Epidemiology of the Epilepsies: Future Directions
(1997) · Epilepsia · doi:10.1111/j.1528-1157.1997.tb01148.x · Cited by 188 · see citing works
The Epidemiology and Treatment of Chronic and Refractory Epilepsy
Shorvon, S. D. (1996) · Epilepsia · doi:10.1111/j.1528-1157.1996.tb06027.x · Cited by 185 · see citing works
Cockerell, O. C., Eckle, I., Goodridge, D. M., Sander, J. W. A. S., & Shorvon, S. D. (1995) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.58.5.570 · Cited by 156 · see citing works
Commission on European Affairs: Appropriate Standards of Epilepsy Care Across Europe
Brodie, M. J., Shorvon, S. D., Canger, R., Halász, P., Johannessen, S. I., Thompson, P. J., Wieser, H. G., & Wolf, P. (1997) · Epilepsia · doi:10.1111/j.1528-1157.1997.tb01224.x · Cited by 149 · see citing works
Self-citationCollaborative Group for the Study of Epilepsy (1992) · Epilepsia · doi:10.1111/j.1528-1157.1992.tb02281.x · Cited by 149 · see citing works
Do Seizures Beget Seizures? An Assessment of the Clinical Evidence in Humans
Berg, A. T., & Shinnar, S. (1997) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-199703000-00003 · Cited by 144 · see citing works
EEG and Other Early Predictors of Epilepsy Remission: A Community Study
Shafer, S. Q., Hauser, W. A., Annegers, J. F., & Klass, D. W. (1988) · Epilepsia · doi:10.1111/j.1528-1157.1988.tb03767.x · Cited by 115 · see citing works
Monotherapy versus Polytherapy in Epilepsy
Schmidt, D., & Gram, L. (1995) · CNS Drugs · doi:10.2165/00023210-199503030-00005 · Cited by 106 · see citing works
Pharmacoresistance in Epilepsy
Perucca, E. (1998) · CNS Drugs · doi:10.2165/00023210-199810030-00002 · Cited by 101 · see citing works
Camfield, C., CAMFIELD, P. R., Gordon, K., & Dooley, J. M. (1996) · Neurology · doi:10.1212/wnl.46.1.41 · Cited by 100 · see citing works
The Natural History of Untreated Epilepsy in a Rural Community in Africa
Watts, A. E. (1992) · Epilepsia · doi:10.1111/j.1528-1157.1992.tb01692.x · Cited by 82 · see citing works
Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant partial epilepsy
Brodie, M. J., & Mumford, J. P. (1999) · Epilepsy Research · doi:10.1016/s0920-1211(98)00110-7 · Cited by 74 · see citing works
Self-citationReynolds, E. H. (1995) · BMJ · doi:10.1136/bmj.310.6973.176 · Cited by 49 · see citing works
An outcome audit at the epilepsy clinic: results from 1000 consecutive referrals
Tobias, E. S., Brodie, A. F., & Brodie, M. J. (1994) · Seizure · doi:10.1016/s1059-1311(05)80161-x · Cited by 47 · see citing works
Self-citationRemission of seizures in untreated epilepsy.
Keränen, T., & Riekkinen, P. J. (1993) · BMJ · doi:10.1136/bmj.307.6902.483 · Cited by 42 · see citing works
Antiepileptic drugs, clinical trials, and the marketplace
Brodie, M. J. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90863-6 · Cited by 34 · see citing works
Self-citationMonostars: An Aid to Choosing an Antiepileptic Drug as Monotherapy
Brodie, M. J. (1999) · Epilepsia · doi:10.1111/j.1528-1157.1999.tb00928.x · Cited by 33 · see citing works
Self-citationManaging seizures in the casualty department.
McKee, P. J., Wilson, E., Dawson, J., Larkin, J., & Brodie, M. J. (1990) · BMJ · doi:10.1136/bmj.300.6730.978 · Cited by 29 · see citing works
Self-citationEpilepsy surgery: past, present and future
Wieser, H. G. (1998) · Seizure · doi:10.1016/s1059-1311(98)80032-0 · Cited by 27 · see citing works
Five Years of Anticonvulsant Monitoring on Site at the Epilepsy Clinic
McKee, P. J. W., Larkin, J. G., Brodie, A. F., PERCY-ROBB, I. W., & Brodie, M. J. (1993) · Therapeutic Drug Monitoring · doi:10.1097/00007691-199304000-00003 · Cited by 19 · see citing works
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Sorted by citations
Kwan, P., Arzimanoglou, A. A., Berg, A. T., Brodie, M. J., Hauser, W. A., Mathern, G. W., Moshé, S. L., Perucca, E., Wiebe, S., & French, J. A. (2009) · Epilepsia · doi:10.1111/j.1528-1167.2009.02397.x · Cited by 4,918 · see citing works
Self-citationA Randomized Controlled Trial of Surgery for Temporal Lobe Epilepsy
Wiebe, S., Blume, W. T., Girvin, J. P., & Eliasziw, M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200108023450501 · Cited by 3,534 · see citing works
Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy
Fisher, R. S., Salanova, V., Witt, T. C., Worth, R. M., Henry, T. R., Gross, R. E., Oommen, K. J., Osorio, I., Nazzaro, J. M., Labar, D., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02536.x · Cited by 1,930 · see citing works
Chen, Z. Z., Brodie, M. J., Liew, D., & Kwan, P. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.3949 · Cited by 1,522 · see citing works
Self-citationResponsive cortical stimulation for the treatment of medically intractable partial epilepsy
Morrell, M. J. (2011) · Neurology · doi:10.1212/wnl.0b013e3182302056 · Cited by 1,282 · see citing works
Kwan, P., Schachter, S. C., & Brodie, M. J. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1004418 · Cited by 1,113 · see citing works
Self-citationThe Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018) · Cell · doi:10.1016/j.cell.2018.04.027 · Cited by 1,057 · see citing works
Devinsky, O., Vezzani, A., O'Brien, T. J., Jetté, N., Scheffer, I. E., de Curtis, M., & Perucca, P. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.24 · Cited by 967 · see citing works
Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery
Blümcke, I., Spreafico, R., Haaker, G., Coras, R., Kobow, K., Bien, C. G., Pfäfflin, M., Elger, C. E., Widman, G., Schramm, J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1703784 · Cited by 935 · see citing works
Patterns of treatment response in newly diagnosed epilepsy
Brodie, M. J., Barry, S., Bamagous, G. A., Norrie, J. D., & Kwan, P. (2012) · Neurology · doi:10.1212/wnl.0b013e3182563b19 · Cited by 931 · see citing works
Self-citationPractice parameter: Temporal lobe and localized neocortical resections for epilepsy
Engel, J., Wiebe, S., French, J. A., Sperling, M. R., Williamson, P. D., Spencer, D. D., Gumnit, R. J., Zahn, C. A., Westbrook, E. O., & Enos, B. (2003) · Neurology · doi:10.1212/01.wnl.0000055086.35806.2d · Cited by 909 · see citing works
Moshé, S. L., Perucca, E., Ryvlin, P., & Tomson, T. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60456-6 · Cited by 905 · see citing works
Drug resistance in brain diseases and the role of drug efflux transporters
Löscher, W., & Potschka, H. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1728 · Cited by 904 · see citing works
Cook, M. J., O'Brien, T. J., Berkovic, S. F., Murphy, M. A., Morokoff, A. P., Fabinyi, G., D'Souza, W. J., Yerra, R., Archer, J. S., Litewka, L., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70075-9 · Cited by 881 · see citing works
Blood-brain barrier active efflux transporters: ATP-binding cassette gene family
Löscher, W., & Potschka, H. (2004) · NeuroRx · doi:10.1602/neurorx.2.1.86 · Cited by 873 · see citing works
The epidemiology of epilepsy revisited
Sander, J. W. A. S. (2003) · Current Opinion in Neurology · doi:10.1097/01.wco.0000063766.15877.8e · Cited by 868 · see citing works
Guerrini, R. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68182-8 · Cited by 848 · see citing works
Epilepsy across the spectrum: Promoting health and understanding.
England, M. J., Liverman, C. T., Schultz, A. M., & Strawbridge, L. M. (2012) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2012.06.016 · Cited by 733 · see citing works
Duncan, J. S., Sander, J. W. A. S., Sisodiya, S. M., & Walker, M. C. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68477-8 · Cited by 726 · see citing works
Chronic epilepsy and cognition: A longitudinal study in temporal lobe epilepsy
Helmstaedter, C., Kurthen, M., Lux, S., Reuber, M., & Elger, C. E. (2003) · Annals of Neurology · doi:10.1002/ana.10692 · Cited by 718 · see citing works
Adverse effects of antiepileptic drugs
Perucca, P., & Gilliam, F. G. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70153-9 · Cited by 703 · see citing works
The consequences of refractory epilepsy and its treatment
Laxer, K. D., Trinka, E., Hirsch, L. J., Cendes, F., Langfitt, J. T., Delanty, N., Resnick, T., & Benbadis, S. R. (2014) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2014.05.031 · Cited by 681 · see citing works
Clinical Proton MR Spectroscopy in Central Nervous System Disorders
Öz, G., Alger, J. R., Barker, P. B., Bartha, R., Bizzi, A., Boesch, C., Bolan, P. J., Brindle, K. M., Cudalbu, C., Di̇nçer, A., et al. (2014) · Radiology · doi:10.1148/radiol.13130531 · Cited by 663 · see citing works
French, J. A., Kanner, A. M., Bautista, J. F., Abou‐Khalil, B., Browne, T. R., Harden, C. L., Theodore, W. H., Bazil, C. W., Stern, J. M., Schachter, S. C., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000123693.82339.fc · Cited by 654 · see citing works
Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases
Löscher, W., & Potschka, H. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.04.006 · Cited by 617 · see citing works
Cannabidiol: State of the art and new challenges for therapeutic applications
Pisanti, S., Malfitano, A. M., Ciaglia, E., Lamberti, A., Ranieri, R., Cuomo, G., Abate, M., Faggiana, G., Proto, M., Fiore, D., et al. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.041 · Cited by 625 · see citing works
Modern antiepileptic drug development has failed to deliver: Ways out of the current dilemma
Löscher, W., & Schmidt, D. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03024.x · Cited by 593 · see citing works
The epidemiology of drug‐resistant epilepsy: A systematic review and meta‐analysis
Kalilani, L., Sun, X., Pelgrims, B., Noack‐Rink, M., & Villanueva, V. (2018) · Epilepsia · doi:10.1111/epi.14596 · Cited by 589 · see citing works
Paz, J. T., Davidson, T. J., Frechette, E. S., Delord, B., Parada, I., Peng, K. K., Deisseroth, K. A., & Huguenard, J. R. (2012) · Nature Neuroscience · doi:10.1038/nn.3269 · Cited by 567 · see citing works
Pregabalin Pharmacology and Its Relevance to Clinical Practice
Ben‐Menachem, E. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.455003.x · Cited by 543 · see citing works
Predictors of pharmacoresistant epilepsy
Hitiris, N., Mohanraj, R., Norrie, J. D., Sills, G. J., & Brodie, M. J. (2007) · Epilepsy Research · doi:10.1016/j.eplepsyres.2007.06.003 · Cited by 530 · see citing works
Self-citationDrug Resistance in Epilepsy: Putative Neurobiologic and Clinical Mechanisms
Schmidt, D., & Löscher, W. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.54904.x · Cited by 483 · see citing works
Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers
Tang, F., Hartz, A. M. S., & Bauer, B. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00301 · Cited by 483 · see citing works
Symonds, J. D., Zuberi, S. M., Stewart, K., McLellan, A., O‘Regan, M., MacLeod, S., Jollands, A., Joss, S., Kirkpatrick, M., Brunklaus, A., et al. (2019) · Brain · doi:10.1093/brain/awz195 · Cited by 459 · see citing works
Molecular Targets for Antiepileptic Drug Development
Meldrum, B. S., & Rogawski, M. A. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2006.11.010 · Cited by 473 · see citing works
Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy
Ramgopal, S., Thome-Souza, S., Jackson, M., Kadish, N. E., Sánchez Fernández, I., Klehm, J., Bosl, W., Reinsberger, C., Schachter, S., & Loddenkemper, T. (2014) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2014.06.023 · Cited by 469 · see citing works
Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy
Brodie, M. J., Perucca, E., Ryvlin, P., Ben-Menachem, E., & Meencke, H.-J. (2007) · Neurology · doi:10.1212/01.wnl.0000252941.50833.4a · Cited by 467 · see citing works
Self-citationAntiseizure Medications for Adults With Epilepsy
Kanner, A. M., & Bicchi, M. M. (2022) · JAMA · doi:10.1001/jama.2022.3880 · Cited by 480 · see citing works
MR-guided stereotactic laser ablation of epileptogenic foci in children
Curry, D. J., Gowda, A., McNichols, R. J., & Wilfong, A. A. (2012) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2012.04.135 · Cited by 446 · see citing works
High-frequency oscillations (HFOs) in clinical epilepsy
Jacobs, J., Staba, R. J., Asano, E., Otsubo, H., Wu, J., Zijlmans, M., Mohamed, I., Kahane, P., Dubeau, F., Navarro, V., et al. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.03.001 · Cited by 444 · see citing works
Incidence and Prevalence of Drug-Resistant Epilepsy
Sultana, B., Panzini, M.-A., Carpentier, A. V., Comtois, J., Rioux, B., Gore, G. C., Bauer, P. R., Kwon, C., Jetté, N., Josephson, C. B., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000011839 · Cited by 442 · see citing works
The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions
Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A., & Walker, S. (2000) · Epilepsy Research · doi:10.1016/s0920-1211(00)00126-1 · Cited by 438 · see citing works
Yap, J. Y. Y., Keatch, C., Lambert, É., Woods, W., Stoddart, P. R., & Kameneva, T. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00284 · Cited by 442 · see citing works
Neuropsychological effects of epilepsy and antiepileptic drugs
Kwan, P., & Brodie, M. J. (2001) · The Lancet · doi:10.1016/s0140-6736(00)03600-x · Cited by 434 · see citing works
Self-citationEffectiveness of First Antiepileptic Drug
Kwan, P., & Brodie, M. J. (2001) · Epilepsia · doi:10.1046/j.1528-1157.2001.04501.x · Cited by 432 · see citing works
Self-citationRefractory Epilepsy: Clinical Overview
French, J. A. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.00992.x · Cited by 431 · see citing works
Role of oxidative stress in epileptic seizures
Shin, E., Jeong, J. H., Chung, Y. H., Kim, W.-K., Ko, K.-H., Bach, J., Hong, J., Yoneda, Y., & Kim, H. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.03.025 · Cited by 424 · see citing works
Epilepsy in low‐grade gliomas: The impact on cognitive function and quality of life
Klein, M., Engelberts, N. H. J., van der Ploeg, H. M., Trenité, D. G. A. K.-N., Aaronson, N. K., TAPHOORN, M. J. B., Baaijen, H., Vandertop, W. P., Muller, M. J., Postma, T. J., et al. (2003) · Annals of Neurology · doi:10.1002/ana.10712 · Cited by 422 · see citing works
Targeting LDH enzymes with a stiripentol analog to treat epilepsy
Sada, N., Lee, S., Katsu, T., Otsuki, T., & Inoue, T. (2015) · Science · doi:10.1126/science.aaa1299 · Cited by 413 · see citing works
Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study
Sillanpää, M. L., & Schmidt, D. (2006) · Brain · doi:10.1093/brain/awh726 · Cited by 414 · see citing works
The natural history of epilepsy: an epidemiological view
Kwan, P. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.045690 · Cited by 408 · see citing works
Self-citationMolecular and cellular mechanisms of pharmacoresistance in epilepsy
Remy, S., & Beck, H. (2005) · Brain · doi:10.1093/brain/awh682 · Cited by 408 · see citing works
Practice Parameter: Temporal Lobe and Localized Neocortical Resections for Epilepsy
Engel, J., Wiebe, S., French, J. A., Sperling, M. R., Williamson, P. D., Spencer, D. D., Gumnit, R. J., Zahn, C. A., Westbrook, E. L., & Enos, B. (2003) · Epilepsia · doi:10.1046/j.1528-1157.2003.48202.x · Cited by 401 · see citing works
Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy
Chen, B., Choi, H., Hirsch, L. J., Katz, A. D., Legge, A. W., Buchsbaum, R., & Detyniecki, K. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.08.039 · Cited by 400 · see citing works
Halász, P., Kälviäinen, R. K., Mazurkiewicz‐Bełdzińska, M., Rosenow, F., Doty, P., Hebert, D., Sullivan, T., & on behalf of the SP755 Study Group (2009) · Epilepsia · doi:10.1111/j.1528-1167.2008.01951.x · Cited by 392 · see citing works
The Role of Magnesium in Neurological Disorders
Kirkland, A. E., Sarlo, G. L., & Holton, K. F. (2018) · Nutrients · doi:10.3390/nu10060730 · Cited by 382 · see citing works
Beenhakker, M. P., & Huguenard, J. R. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.015 · Cited by 374 · see citing works
Lamberink, H. J., Otte, W. M., Blümcke, I., Braun, K. P. J., Aichholzer, M., Amorim, I., Aparicio, J., Aronica, E., Arzimanoglou, A. A., Barba, C., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30220-9 · Cited by 371 · see citing works
Löscher, W., & Klein, P. (2021) · CNS Drugs · doi:10.1007/s40263-021-00827-8 · Cited by 381 · see citing works
Deep Brain Stimulation in Patients with Refractory Temporal Lobe Epilepsy
Boon, P., Vonck, K. E. J., Herdt, V. D., Dycke, A. V., Goethals, M., Goossens, L., Zandijcke, M. V., Smedt, T. D., Dewaele, I., Achten, R., et al. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01005.x · Cited by 368 · see citing works
Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy
von Oertzen, T. J. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.6.643 · Cited by 365 · see citing works
Predictors of epilepsy surgery outcome: a meta-analysis
Tonini, C., Beghi, E., Berg, A. T., Bogliun, G., Giordano, L., Newton, R. W., Tetto, A., Vitelli, E., Vitezić, D., & Wiebe, S. (2004) · Epilepsy Research · doi:10.1016/j.eplepsyres.2004.08.006 · Cited by 364 · see citing works
Elliott, R. E., Morsi, A., Kalhorn, S. P., Marcus, J., Sellin, J. N., Kang, M. M., Silverberg, A., Rivera, E., Geller, E. B., Carlson, C., et al. (2010) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2010.10.017 · Cited by 361 · see citing works
Quek, A. M. L. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.2985 · Cited by 360 · see citing works
Intractable epilepsy: management and therapeutic alternatives
Schuele, S., & Lüders, H. O. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70108-x · Cited by 346 · see citing works
Astrocytes: Role and Functions in Brain Pathologies
Siracusa, R., Fusco, R., & Cuzzocrea, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01114 · Cited by 342 · see citing works
Diagnosing refractory epilepsy: response to sequential treatment schedules
Mohanraj, R., & Brodie, M. J. (2006) · European Journal of Neurology · doi:10.1111/j.1468-1331.2006.01215.x · Cited by 340 · see citing works
Self-citationRyvlin, P., Cucherat, M., & Rheims, S. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70193-4 · Cited by 339 · see citing works
Optimizing health outcomes in active epilepsy
Gilliam, F. G. (2002) · Neurology · doi:10.1212/wnl.58.8_suppl_5.s9 · Cited by 334 · see citing works
The pharmacological treatment of epilepsy in adults
Perucca, E., & Tomson, T. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70047-3 · Cited by 334 · see citing works
Drug treatment of epilepsy in adults
Schmidt, D., & Schachter, S. C. (2014) · BMJ · doi:10.1136/bmj.g254 · Cited by 327 · see citing works
Results of treatment changes in patients with apparently drug‐resistant chronic epilepsy
Luciano, A. L., & Shorvon, S. D. (2007) · Annals of Neurology · doi:10.1002/ana.21064 · Cited by 323 · see citing works
The ketogenic diet: metabolic influences on brain excitability and epilepsy
Lutas, A., & Yellen, G. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.11.005 · Cited by 321 · see citing works
Gunthorpe, M. J., Large, C. H., & Sankar, R. (2012) · Epilepsia · doi:10.1111/j.1528-1167.2011.03365.x · Cited by 319 · see citing works
Wolking, S., Schaeffeler, E., Lerche, H., Schwab, M. G., & Nies, A. T. (2015) · Clinical Pharmacokinetics · doi:10.1007/s40262-015-0267-1 · Cited by 312 · see citing works
Several major antiepileptic drugs are substrates for human P-glycoprotein
Luna‐Tortós, C., Fedrowitz, M., & Löscher, W. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.08.032 · Cited by 310 · see citing works
Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy
Englot, D. J., Rolston, J. D., Wright, C. W., Hassnain, K. H., & Chang, E. F. (2015) · Neurosurgery · doi:10.1227/neu.0000000000001165 · Cited by 310 · see citing works
Likelihood of seizure remission in an adult population with refractory epilepsy
Callaghan, B. C., Anand, K., Hesdorffer, D. C., Hauser, W. A., & French, J. A. (2007) · Annals of Neurology · doi:10.1002/ana.21166 · Cited by 309 · see citing works
The anterior thalamus provides a subcortical circuit supporting memory and spatial navigation
Jankowski, M. M., Rönnqvist, K. C., Tsanov, M., Vann, S. D., Wright, N. F., Erichsen, J. T., Aggleton, J. P., & O’Mara, S. M. (2013) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2013.00045 · Cited by 309 · see citing works
Epilepsy after the first drug fails: substitution or add-on?
Kwan, P., & Brodie, M. J. (2000) · Seizure · doi:10.1053/seiz.2000.0442 · Cited by 306 · see citing works
Self-citationDeep brain stimulation in epilepsy with particular reference to the subthalamic nucleus
Chabardès, S., Kahane, P., Minotti, L., Koudsié, A., Hirsch, É., & Benabid, A. (2002) · Epileptic Disorders · doi:10.1684/j.1950-6945.2002.tb00549.x · Cited by 306 · see citing works
How long does it take for partial epilepsy to become intractable?
Berg, A. T., Langfitt, J. T., Shinnar, S., Vickrey, B. G., Sperling, M. R., Walczak, T. S., Bazil, C. W., Pacia, S. V., & Spencer, S. S. (2003) · Neurology · doi:10.1212/01.wnl.0000031792.89992.ec · Cited by 304 · see citing works
Lundgren, T., Dahl, J., Yardi, N., & Melin, L. (2008) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2008.02.009 · Cited by 301 · see citing works
Manford, M. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8394-2 · Cited by 302 · see citing works
Antiepileptic drug therapy the story so far
Brodie, M. J. (2010) · Seizure · doi:10.1016/j.seizure.2010.10.027 · Cited by 298 · see citing works
Self-citationTreatment of pediatric epilepsy: European expert opinion, 2007
Wheless, J. W., Clarke, D., Arzimanoglou, A. A., & Carpenter, D. P. (2007) · Epileptic Disorders · doi:10.1684/epd.2007.0144 · Cited by 294 · see citing works
Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy
Bernhardt, B. C., Bonilha, L., & Gross, D. W. (2015) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2015.06.005 · Cited by 290 · see citing works
Outcome of Prolonged Video‐EEG Monitoring at a Typical Referral Epilepsy Center
Benbadis, S. R., O’Neill, E. B., Tatum, W. O., & Heriaud, L. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.14504.x · Cited by 290 · see citing works
The mechanisms of action of commonly used antiepileptic drugs
Kwan, P., Sills, G. J., & Brodie, M. J. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(01)00122-x · Cited by 289 · see citing works
Self-citationPotential Role of Drug Transporters in the Pathogenesis of Medically Intractable Epilepsy
Kwan, P., & Brodie, M. J. (2005) · Epilepsia · doi:10.1111/j.0013-9580.2005.31904.x · Cited by 281 · see citing works
Self-citationPhenobarbital for the Treatment of Epilepsy in the 21st Century: A Critical Review
Kwan, P., & Brodie, M. J. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.12704.x · Cited by 279 · see citing works
Self-citationRosenberg, E. C., Tsien, R. W., Whalley, B. J., & Devinsky, O. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0375-5 · Cited by 282 · see citing works
LaRoche, S. M., & Helmers, S. L. (2004) · JAMA · doi:10.1001/jama.291.5.605 · Cited by 277 · see citing works
Bauer, S., Baier, H., Baumgärtner, C., Bohlmann, K., Fauser, S., Graf, W. D., Hillenbrand, B., Hirsch, M., Last, C., Lerche, H., et al. (2016) · Brain stimulation · doi:10.1016/j.brs.2015.11.003 · Cited by 273 · see citing works
Tatum, W. O. (2012) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0b013e31826b3ab7 · Cited by 273 · see citing works
Patsalos, P. N. (2014) · Epilepsia · doi:10.1111/epi.12865 · Cited by 272 · see citing works
Epilepsy surgery trends in the United States, 1990–2008
Englot, D. J., Ouyang, D., Garcia, P. A., Barbaro, N. M., & Chang, E. F. (2012) · Neurology · doi:10.1212/wnl.0b013e318250d7ea · Cited by 273 · see citing works
Wilby, J., Kainth, A., Hawkins, N., Epstein, D. M., McIntosh, H., McDaid, C., Mason, A., Golder, S., O’Meara, S., Sculpher, M. J., et al. (2005) · Health Technology Assessment · doi:10.3310/hta9150 · Cited by 271 · see citing works
The Pharmacoresistant Epilepsy: An Overview on Existent and New Emerging Therapies
Fattorusso, A., Matricardi, S., Mencaroni, E., Dell’Isola, G. B., Cara, G. D., Striano, P., & Verrottı, A. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.674483 · Cited by 276 · see citing works
Stefan, H., Kreiselmeyer, G., Kerling, F., Kurzbuch, K., Rauch, C., Heers, M., Kasper, B. S., Hammen, T., Rzonsa, M., Pauli, E., et al. (2012) · Epilepsia · doi:10.1111/j.1528-1167.2012.03492.x · Cited by 270 · see citing works
- Authors
- Kwan, P., & Brodie, M. J.
- Affiliations
- Western Infirmary (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-02-03
- Volume
- 342
- Issue
- 5
- Pages
- 314-319
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1974809694
- Cited by
- 5,204
- References
- 39
- Citations by year
- 2026: 225 · 2025: 241 · 2024: 259 · 2023: 275 · 2022: 269 · 2021: 328 · 2020: 348 · 2019: 253 · 2018: 270 · 2017: 228 · 2016: 249 · 2015: 230 · 2014: 205 · 2013: 233 · 2012: 248
- FWCI
- 55.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- CRC Press eBooks (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- drug-resistant epilepsy, antiepileptic drugs, seizure control, newly diagnosed epilepsy, idiopathic epilepsy, symptomatic epilepsy, cryptogenic epilepsy, seizure frequency, predictors of treatment failure, adverse drug reactions, polypharmacy
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Anticonvulsants, Child, Epilepsy, Female, Humans, Male, Middle Aged, Prospective Studies, Remission Induction, Treatment Failure
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