Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue

Maurits W. Sanders; Iskander Van Der Wolf; Floor E. Jansen; Eleonora Aronica; Christoph Helmstaedter; Attila Racz; Rainer Surges; Alexander Grote; Albert J. Becker; Sylvain Rheims; Hélène Catenoix; John S. Duncan; Jane De Tisi; Thomas S. Jacques; J. Helen Cross; Reetta Kalviainen; Tuomas Rauramaa; Francine Chassoux; Bertrand C. Devaux; Giancarlo Di Gennaro; Vincenzo Esposito; Istvan Bodi; Mrinalini Honavar; Christian G. Bien; Thomas Cloppenborg; Roland Coras; Hajo M. Hamer; Petr Marusic; Adam Kalina; Tom Pieper; Manfred Kudernatsch; Till S. Hartlieb; Tim J. Von Oertzen; Martin Aichholzer; Georg Dorfmuller; Mathilde Chipaux; Soheyl Noachtar; Elisabeth Kaufmann; Andreas Schulze-Bonhage; Christian F. Scheiwe; Cigdem Özkara; Thomas Grunwald; Kristina Koenig; Renzo Guerrini; Carmen Barba; Anna Maria Buccoliero; Flavio Giordano; Felix Rosenow; Katja Menzler; Rita Garbelli; Francesco Deleo; Pavel Krsek; Barbora Straka; Alexis A. Arzimanoglou; Joseph Toulouse; Wim Van Paesschen; Tom Theys; José Pimentel; Isabel M. Loução De Amorim; Nicola Specchio; Luca De Palma; Martha Feucht; Theresa Scholl; Karl Roessler; Rafael Toledano Delgado; Antonio Gil-Nagel; Savo Raicevic; Aleksandar J. Ristic; Olaf Schijns; Jan Beckervordersandforth; Victoria San Antonio-Arce; Jordi Rumia; Ingmar Blumcke; Kees P. Braun

doi:10.1212/WNL.0000000000208007

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue

Maurits W. Sanders^*, Iskander Van Der Wolf, Floor E. Jansen, Eleonora Aronica, Christoph Helmstaedter, Attila Racz, Rainer Surges, Alexander Grote, Albert J. Becker, Sylvain Rheims, Hélène Catenoix, John S. Duncan, Jane De Tisi, Thomas S. Jacques, J. Helen Cross, Reetta Kalviainen, Tuomas Rauramaa, Francine Chassoux, Bertrand C. Devaux, Giancarlo Di GennaroVincenzo Esposito, Istvan Bodi, Mrinalini Honavar, Christian G. Bien, Thomas Cloppenborg, Roland Coras, Hajo M. Hamer, Petr Marusic, Adam Kalina, Tom Pieper, Manfred Kudernatsch, Till S. Hartlieb, Tim J. Von Oertzen, Martin Aichholzer, Georg Dorfmuller, Mathilde Chipaux, Soheyl Noachtar, Elisabeth Kaufmann, Andreas Schulze-Bonhage, Christian F. Scheiwe, Cigdem Özkara, Thomas Grunwald, Kristina Koenig, Renzo Guerrini, Carmen Barba, Anna Maria Buccoliero, Flavio Giordano, Felix Rosenow, Katja Menzler, Rita Garbelli, Francesco Deleo, Pavel Krsek, Barbora Straka, Alexis A. Arzimanoglou, Joseph Toulouse, Wim Van Paesschen, Tom Theys, José Pimentel, Isabel M. Loução De Amorim, Nicola Specchio, Luca De Palma, Martha Feucht, Theresa Scholl, Karl Roessler, Rafael Toledano Delgado, Antonio Gil-Nagel, Savo Raicevic, Aleksandar J. Ristic, Olaf Schijns, Jan Beckervordersandforth, Victoria San Antonio-Arce, Jordi Rumia, Ingmar Blumcke, Kees P. Braun

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background and Objective Patients with presumed nonlesional focal epilepsy - based on either MRI or histopathologic findings - have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. Methods We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. Results Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings - versus nonspecific reactive gliosis - (AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. Discussion This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery - even more if the hippocampus is resected - compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Original language	English
Article number	e208007
Journal	Neurology
Volume	102
Issue number	4
DOIs	https://doi.org/10.1212/WNL.0000000000208007
Publication status	Published - 27 Feb 2024
Externally published	Yes

Bibliographical note

Publisher Copyright:
© American Academy of Neurology.

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10.1212/WNL.0000000000208007

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Sanders, M. W., Van Der Wolf, I., Jansen, F. E., Aronica, E., Helmstaedter, C., Racz, A., Surges, R., Grote, A., Becker, A. J., Rheims, S., Catenoix, H., Duncan, J. S., De Tisi, J., Jacques, T. S., Cross, J. H., Kalviainen, R., Rauramaa, T., Chassoux, F., Devaux, B. C., ... Braun, K. P. (2024). Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue. Neurology, 102(4), Article e208007. https://doi.org/10.1212/WNL.0000000000208007

@article{98bbc454854e4268a8dbbad4396d0153,

title = "Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue",

abstract = "Background and Objective Patients with presumed nonlesional focal epilepsy - based on either MRI or histopathologic findings - have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. Methods We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. Results Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings - versus nonspecific reactive gliosis - (AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. Discussion This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery - even more if the hippocampus is resected - compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.",

author = "Sanders, {Maurits W.} and {Van Der Wolf}, Iskander and Jansen, {Floor E.} and Eleonora Aronica and Christoph Helmstaedter and Attila Racz and Rainer Surges and Alexander Grote and Becker, {Albert J.} and Sylvain Rheims and H{\'e}l{\`e}ne Catenoix and Duncan, {John S.} and {De Tisi}, Jane and Jacques, {Thomas S.} and Cross, {J. Helen} and Reetta Kalviainen and Tuomas Rauramaa and Francine Chassoux and Devaux, {Bertrand C.} and {Di Gennaro}, Giancarlo and Vincenzo Esposito and Istvan Bodi and Mrinalini Honavar and Bien, {Christian G.} and Thomas Cloppenborg and Roland Coras and Hamer, {Hajo M.} and Petr Marusic and Adam Kalina and Tom Pieper and Manfred Kudernatsch and Hartlieb, {Till S.} and {Von Oertzen}, {Tim J.} and Martin Aichholzer and Georg Dorfmuller and Mathilde Chipaux and Soheyl Noachtar and Elisabeth Kaufmann and Andreas Schulze-Bonhage and Scheiwe, {Christian F.} and Cigdem {\"O}zkara and Thomas Grunwald and Kristina Koenig and Renzo Guerrini and Carmen Barba and Buccoliero, {Anna Maria} and Flavio Giordano and Felix Rosenow and Katja Menzler and Rita Garbelli and Francesco Deleo and Pavel Krsek and Barbora Straka and Arzimanoglou, {Alexis A.} and Joseph Toulouse and {Van Paesschen}, Wim and Tom Theys and Jos{\'e} Pimentel and {Lou{\c c}{\~a}o De Amorim}, {Isabel M.} and Nicola Specchio and {De Palma}, Luca and Martha Feucht and Theresa Scholl and Karl Roessler and {Toledano Delgado}, Rafael and Antonio Gil-Nagel and Savo Raicevic and Ristic, {Aleksandar J.} and Olaf Schijns and Jan Beckervordersandforth and {San Antonio-Arce}, Victoria and Jordi Rumia and Ingmar Blumcke and Braun, {Kees P.}",

note = "Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2024",

month = feb,

day = "27",

doi = "10.1212/WNL.0000000000208007",

language = "English",

volume = "102",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "4",

}

Sanders, MW, Van Der Wolf, I, Jansen, FE, Aronica, E, Helmstaedter, C, Racz, A, Surges, R, Grote, A, Becker, AJ, Rheims, S, Catenoix, H, Duncan, JS, De Tisi, J, Jacques, TS, Cross, JH, Kalviainen, R, Rauramaa, T, Chassoux, F, Devaux, BC, Di Gennaro, G, Esposito, V, Bodi, I, Honavar, M, Bien, CG, Cloppenborg, T, Coras, R, Hamer, HM, Marusic, P, Kalina, A, Pieper, T, Kudernatsch, M, Hartlieb, TS, Von Oertzen, TJ, Aichholzer, M, Dorfmuller, G, Chipaux, M, Noachtar, S, Kaufmann, E, Schulze-Bonhage, A, Scheiwe, CF, Özkara, C, Grunwald, T, Koenig, K, Guerrini, R, Barba, C, Buccoliero, AM, Giordano, F, Rosenow, F, Menzler, K, Garbelli, R, Deleo, F, Krsek, P, Straka, B, Arzimanoglou, AA, Toulouse, J, Van Paesschen, W, Theys, T, Pimentel, J, Loução De Amorim, IM, Specchio, N, De Palma, L, Feucht, M, Scholl, T, Roessler, K, Toledano Delgado, R, Gil-Nagel, A, Raicevic, S, Ristic, AJ, Schijns, O, Beckervordersandforth, J, San Antonio-Arce, V, Rumia, J, Blumcke, I & Braun, KP 2024, 'Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue', Neurology, vol. 102, no. 4, e208007. https://doi.org/10.1212/WNL.0000000000208007

TY - JOUR

T1 - Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue

AU - Sanders, Maurits W.

AU - Van Der Wolf, Iskander

AU - Jansen, Floor E.

AU - Aronica, Eleonora

AU - Helmstaedter, Christoph

AU - Racz, Attila

AU - Surges, Rainer

AU - Grote, Alexander

AU - Becker, Albert J.

AU - Rheims, Sylvain

AU - Catenoix, Hélène

AU - Duncan, John S.

AU - De Tisi, Jane

AU - Jacques, Thomas S.

AU - Cross, J. Helen

AU - Kalviainen, Reetta

AU - Rauramaa, Tuomas

AU - Chassoux, Francine

AU - Devaux, Bertrand C.

AU - Di Gennaro, Giancarlo

AU - Esposito, Vincenzo

AU - Bodi, Istvan

AU - Honavar, Mrinalini

AU - Bien, Christian G.

AU - Cloppenborg, Thomas

AU - Coras, Roland

AU - Hamer, Hajo M.

AU - Marusic, Petr

AU - Kalina, Adam

AU - Pieper, Tom

AU - Kudernatsch, Manfred

AU - Hartlieb, Till S.

AU - Von Oertzen, Tim J.

AU - Aichholzer, Martin

AU - Dorfmuller, Georg

AU - Chipaux, Mathilde

AU - Noachtar, Soheyl

AU - Kaufmann, Elisabeth

AU - Schulze-Bonhage, Andreas

AU - Scheiwe, Christian F.

AU - Özkara, Cigdem

AU - Grunwald, Thomas

AU - Koenig, Kristina

AU - Guerrini, Renzo

AU - Barba, Carmen

AU - Buccoliero, Anna Maria

AU - Giordano, Flavio

AU - Rosenow, Felix

AU - Menzler, Katja

AU - Garbelli, Rita

AU - Deleo, Francesco

AU - Krsek, Pavel

AU - Straka, Barbora

AU - Arzimanoglou, Alexis A.

AU - Toulouse, Joseph

AU - Van Paesschen, Wim

AU - Theys, Tom

AU - Pimentel, José

AU - Loução De Amorim, Isabel M.

AU - Specchio, Nicola

AU - De Palma, Luca

AU - Feucht, Martha

AU - Scholl, Theresa

AU - Roessler, Karl

AU - Toledano Delgado, Rafael

AU - Gil-Nagel, Antonio

AU - Raicevic, Savo

AU - Ristic, Aleksandar J.

AU - Schijns, Olaf

AU - Beckervordersandforth, Jan

AU - San Antonio-Arce, Victoria

AU - Rumia, Jordi

AU - Blumcke, Ingmar

AU - Braun, Kees P.

PY - 2024/2/27

Y1 - 2024/2/27

N2 - Background and Objective Patients with presumed nonlesional focal epilepsy - based on either MRI or histopathologic findings - have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. Methods We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. Results Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings - versus nonspecific reactive gliosis - (AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. Discussion This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery - even more if the hippocampus is resected - compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

AB - Background and Objective Patients with presumed nonlesional focal epilepsy - based on either MRI or histopathologic findings - have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. Methods We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. Results Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings - versus nonspecific reactive gliosis - (AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. Discussion This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery - even more if the hippocampus is resected - compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

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U2 - 10.1212/WNL.0000000000208007

DO - 10.1212/WNL.0000000000208007

M3 - Article

AN - SCOPUS:85193717979

SN - 0028-3878

VL - 102

JO - Neurology

JF - Neurology

IS - 4

M1 - e208007

ER -

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue

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