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

Maurits W Sanders¹, Iskander Van der Wolf¹, Floor E Jansen¹, Eleonora Aronica¹, Christoph Helmstaedter¹, Attila Racz¹, Rainer Surges¹, Alexander Grote¹, Albert J Becker¹, Sylvain Rheims¹, Hélène Catenoix¹, John S Duncan¹, Jane De Tisi¹, Thomas S Jacques¹, J Helen Cross¹, Reetta Kalviainen¹, Tuomas Rauramaa¹, Francine Chassoux¹, Bertrand C Devaux¹, Giancarlo Di Gennaro¹, Vincenzo Esposito¹, Istvan Bodi¹, Mrinalini Honavar¹, Christian G Bien¹, Thomas Cloppenborg¹, Roland Coras¹, Hajo M Hamer¹, Petr Marusic¹, Adam Kalina¹, Tom Pieper¹, Manfred Kudernatsch¹, Till S Hartlieb¹, Tim J Von Oertzen¹, Martin Aichholzer¹, Georg Dorfmuller¹, Mathilde Chipaux¹, Soheyl Noachtar¹, Elisabeth Kaufmann¹, Andreas Schulze-Bonhage¹, Christian F Scheiwe¹, Cigdem Özkara¹, Thomas Grunwald¹, Kristina Koenig¹, Renzo Guerrini¹, Carmen Barba¹, Anna Maria Buccoliero¹, Flavio Giordano¹, Felix Rosenow¹, Katja Menzler¹, Rita Garbelli¹, Francesco Deleo¹, Pavel Krsek¹, Barbora Straka¹, Alexis A Arzimanoglou¹, Joseph Toulouse¹, Wim Van Paesschen¹, Tom Theys¹, José Pimentel¹, Isabel M Loução De Amorim¹, Nicola Specchio¹, Luca De Palma¹, Martha Feucht¹, Theresa Scholl¹, Karl Roessler¹, Rafael Toledano Delgado¹, Antonio Gil-Nagel¹, Savo Raicevic¹, Aleksandar J Ristic¹, Olaf Schijns¹, Jan Beckervordersandforth¹, Victoria San Antonio-Arce¹, Jordi Rumia¹, Ingmar Blumcke¹, Kees P Braun¹; as the European Epilepsy Brain Bank Consortium (EEBB)¹

Affiliations

Affiliation

¹ From the Department of Child Neurology (M.W.S, I.V.d.W., F.E.J, K.P.B.), Member of EpiCARE ERN, University Medical Center Utrecht, Utrecht; Department of (Neuro)Pathology (E.A.), Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam; Stichting Epilepsie Instellingen Nederland (SEIN) (E.A.), Heemstede, The Netherlands; Department of Epileptology (C.H., A.R., R.S.); Department of Neurosurgery (A.G.), University of Bonn Medical Center, Germany; Department of Neurosurgery (A.G.), Epilepsy Center Hessen, Philipps University, Marburgy; Department of Neuropathology (A.J.B.), University of Bonn Medical Center, Germany; Department of Functional Neurology and Epileptology (Sylvain Rheims, H.C.), Hospices Civils de Lyon and University of Lyon; Lyon's Neurosciences Research Center (INSERM U1028 / CNRS UMR5292) (Sylvain Rheims, Catenoix Hélène), France; UCL Queen Square Institute of Neurology, Department of Clinical and Experimental Epilepsy and National Hospital for Neurology and Neurosurgery (J.S.D., J.D.T.); Developmental Biology and Cancer Programme (T.S.J.), UCL Great Ormond Street Institute of Child Health and the Department of Histopathology, Great Ormond Street Hospital for Children, London; UCL- NIHR BRC Great Ormond Street Institute of Child Health (J.H.C.), Great Ormond Street Hospital for Children, Lingfield, United Kingdom; Kuopio Epilepsy Center (R.K., T.R.), Kuopio University Hospital and University of Eastern Finland; Department of Pathology (R.K., T.R.), Kuopio University Hospital and University of Eastern Finland, Member of EpiCARE ERN, Kuopio, Finland; Hospital Sainte-Anne (F.C., B.C.D.), GHU-Paris, France; IRCCS NEUROMED (G.D.G., V.E.), Pozzilli (IS), Italy; Department of Neurosurgery (V.E.), Sapienza University of Rome, Italy; Department of Clinical Neuropathology (Istvan Bodi, M.H.), King's College Hospital NHS Foundation Trust, Academic Neuroscience Center, Denmark Hill, King's College Hospital, London, United Kingdom; Department of Epileptology (Krankenhaus Mara) (C.G.B., T.C.), Medical School, Campus Bielefeld-Bethel, Bielefeld University; Department of Neuropathology (R.C.); Epilepsy Center (H.M.H.), University Hospital Erlangen, Germany; Department of Neurology (P.M., A.K.), Motol Epilepsy Center, Second Medical Faculty, Charles University, Motol University Hospital, Prague, Czech Republic; Center for Pediatric Neurology, Neurorehabilitation, and Epileptology (T.P., M.K.), Schoen-Clinic, Vogtareuth, Germany; Research Institute "Rehabilitation, Transition, Palliation" (M.K.), PMU Salzburg, Austria; Department of Neurology I (T.J.V.O.), Neuromed Campus, Kepler Universitätsklinikum; Faculty of Medicine (T.J.V.O., M.A.), Johannes Kepler University; Department of Neurosurgery (M.A.), Neuromed Campus, Kepler Universitätsklinikum, Linz, Austria; Pediatric Neurosurgery Department (M.C.), Foundation Rothschild Hospital, Paris, France; Epilepsy Center (S.N., E.K.), Department of Neurology, Ludwig-Maximilians University, Munich, Germany; Epilepsy Centre (A.S.-B.); Department of Neurosurgery (C.F.S.), University Hospital, Freiburg, Germany; Department of Neurology (C.O.), Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Turkey; Swiss Epilepsy Center and Department of Neurology (K.K.), University Hospital, Zurich, Switzerland; Neuroscience Department (Renzo Guerrini, C.B.), Pathology Unit (A.M.B.), and Neurosurgery Department (F.G.), Meyer Children's Hospital IRCCS, Florence, Italy; University of Florence (Renzo Guerrini, C.B., F.G.), Florence, Italy; Epilepsy Center Frankfurt Rhine-Main (F.R.), Department of Neurology, and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Frankfurt am Main; Department of Neurology (F.R., K.M.), Epilepsy Center Hessen, Philipps University, Marburg, Germany; Epilepsy Unit (Rita Garbelli, F.D.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; Department of Pediatric Neurology (P.K., B.S.), Motol Epilepsy Center, Second Medical Faculty, Charles University, Motol University Hospital, Prague, Czech Republic; Department of Pediatric Clinical Epileptology (A.A.A., J.T.), Sleep Disorders and Functional Neurology University Hospitals of Lyon (HCL), Lyon, France; Paediatric Epilepsy Unit (A.A.A., V.S.A.-A., J.R.), Child Neurology Department and Neurosurgery Department, Hospital Sant Joan de Déu, Barcelona, Spain; Department of Neurology (W.V.P.); Department of Neurosurgery (T.T.), University Hospital Leuven, Belgium; Laboratory of Neuropathology (J.P., I.M.L.D.A.), Department of Neurosciences and Mental Health, Department of Neurology, Hospital de Santa Maria (CHULN)Lisbon, Portugal; Clinical and Experimental Neurology (N.S., L.D.P.), Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy; Center for Rare and Complex Epilepsies (M.F., T.S.), Department of Pediatrics and Adolescent Medicine; Department of Neurosurgery (K.R.), Medical University of Vienna, Austria; Epilepsy Program (R.T.D., A.G.-N.), Hospital Ruber Internacional, Madrid, Spain; Laboratory for Neuropathology (Savo Raicevic), Department of Pathology; Department for Epilepsy (A.J.R.), Clinic of Neurology, Clinical Center of Serbia, Belgrade; Medical Faculty (A.J.R.), University of Belgrade, Serbia; Department of Neurosurgery (O.S.), Academic Center for Epileptology; Department of Pathology (J.B.), Maastricht University Medical Center, The Netherlands; and University Hospital Erlangen (Ingmar Blumcke), Neuropathology, Erlangen, Germany.

PMID: 38290094
PMCID: PMC10962914
DOI: 10.1212/WNL.0000000000208007

Observational Study

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

Maurits W Sanders et al. Neurology. 2024.

. 2024 Feb 27;102(4):e208007.

doi: 10.1212/WNL.0000000000208007. Epub 2024 Jan 30.

Authors

Affiliation

¹ From the Department of Child Neurology (M.W.S, I.V.d.W., F.E.J, K.P.B.), Member of EpiCARE ERN, University Medical Center Utrecht, Utrecht; Department of (Neuro)Pathology (E.A.), Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam; Stichting Epilepsie Instellingen Nederland (SEIN) (E.A.), Heemstede, The Netherlands; Department of Epileptology (C.H., A.R., R.S.); Department of Neurosurgery (A.G.), University of Bonn Medical Center, Germany; Department of Neurosurgery (A.G.), Epilepsy Center Hessen, Philipps University, Marburgy; Department of Neuropathology (A.J.B.), University of Bonn Medical Center, Germany; Department of Functional Neurology and Epileptology (Sylvain Rheims, H.C.), Hospices Civils de Lyon and University of Lyon; Lyon's Neurosciences Research Center (INSERM U1028 / CNRS UMR5292) (Sylvain Rheims, Catenoix Hélène), France; UCL Queen Square Institute of Neurology, Department of Clinical and Experimental Epilepsy and National Hospital for Neurology and Neurosurgery (J.S.D., J.D.T.); Developmental Biology and Cancer Programme (T.S.J.), UCL Great Ormond Street Institute of Child Health and the Department of Histopathology, Great Ormond Street Hospital for Children, London; UCL- NIHR BRC Great Ormond Street Institute of Child Health (J.H.C.), Great Ormond Street Hospital for Children, Lingfield, United Kingdom; Kuopio Epilepsy Center (R.K., T.R.), Kuopio University Hospital and University of Eastern Finland; Department of Pathology (R.K., T.R.), Kuopio University Hospital and University of Eastern Finland, Member of EpiCARE ERN, Kuopio, Finland; Hospital Sainte-Anne (F.C., B.C.D.), GHU-Paris, France; IRCCS NEUROMED (G.D.G., V.E.), Pozzilli (IS), Italy; Department of Neurosurgery (V.E.), Sapienza University of Rome, Italy; Department of Clinical Neuropathology (Istvan Bodi, M.H.), King's College Hospital NHS Foundation Trust, Academic Neuroscience Center, Denmark Hill, King's College Hospital, London, United Kingdom; Department of Epileptology (Krankenhaus Mara) (C.G.B., T.C.), Medical School, Campus Bielefeld-Bethel, Bielefeld University; Department of Neuropathology (R.C.); Epilepsy Center (H.M.H.), University Hospital Erlangen, Germany; Department of Neurology (P.M., A.K.), Motol Epilepsy Center, Second Medical Faculty, Charles University, Motol University Hospital, Prague, Czech Republic; Center for Pediatric Neurology, Neurorehabilitation, and Epileptology (T.P., M.K.), Schoen-Clinic, Vogtareuth, Germany; Research Institute "Rehabilitation, Transition, Palliation" (M.K.), PMU Salzburg, Austria; Department of Neurology I (T.J.V.O.), Neuromed Campus, Kepler Universitätsklinikum; Faculty of Medicine (T.J.V.O., M.A.), Johannes Kepler University; Department of Neurosurgery (M.A.), Neuromed Campus, Kepler Universitätsklinikum, Linz, Austria; Pediatric Neurosurgery Department (M.C.), Foundation Rothschild Hospital, Paris, France; Epilepsy Center (S.N., E.K.), Department of Neurology, Ludwig-Maximilians University, Munich, Germany; Epilepsy Centre (A.S.-B.); Department of Neurosurgery (C.F.S.), University Hospital, Freiburg, Germany; Department of Neurology (C.O.), Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Turkey; Swiss Epilepsy Center and Department of Neurology (K.K.), University Hospital, Zurich, Switzerland; Neuroscience Department (Renzo Guerrini, C.B.), Pathology Unit (A.M.B.), and Neurosurgery Department (F.G.), Meyer Children's Hospital IRCCS, Florence, Italy; University of Florence (Renzo Guerrini, C.B., F.G.), Florence, Italy; Epilepsy Center Frankfurt Rhine-Main (F.R.), Department of Neurology, and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Frankfurt am Main; Department of Neurology (F.R., K.M.), Epilepsy Center Hessen, Philipps University, Marburg, Germany; Epilepsy Unit (Rita Garbelli, F.D.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; Department of Pediatric Neurology (P.K., B.S.), Motol Epilepsy Center, Second Medical Faculty, Charles University, Motol University Hospital, Prague, Czech Republic; Department of Pediatric Clinical Epileptology (A.A.A., J.T.), Sleep Disorders and Functional Neurology University Hospitals of Lyon (HCL), Lyon, France; Paediatric Epilepsy Unit (A.A.A., V.S.A.-A., J.R.), Child Neurology Department and Neurosurgery Department, Hospital Sant Joan de Déu, Barcelona, Spain; Department of Neurology (W.V.P.); Department of Neurosurgery (T.T.), University Hospital Leuven, Belgium; Laboratory of Neuropathology (J.P., I.M.L.D.A.), Department of Neurosciences and Mental Health, Department of Neurology, Hospital de Santa Maria (CHULN)Lisbon, Portugal; Clinical and Experimental Neurology (N.S., L.D.P.), Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy; Center for Rare and Complex Epilepsies (M.F., T.S.), Department of Pediatrics and Adolescent Medicine; Department of Neurosurgery (K.R.), Medical University of Vienna, Austria; Epilepsy Program (R.T.D., A.G.-N.), Hospital Ruber Internacional, Madrid, Spain; Laboratory for Neuropathology (Savo Raicevic), Department of Pathology; Department for Epilepsy (A.J.R.), Clinic of Neurology, Clinical Center of Serbia, Belgrade; Medical Faculty (A.J.R.), University of Belgrade, Serbia; Department of Neurosurgery (O.S.), Academic Center for Epileptology; Department of Pathology (J.B.), Maastricht University Medical Center, The Netherlands; and University Hospital Erlangen (Ingmar Blumcke), Neuropathology, Erlangen, Germany.

PMID: 38290094
PMCID: PMC10962914
DOI: 10.1212/WNL.0000000000208007

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.

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Conflict of interest statement

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Comment in

Out of Sight, Not Yet Out of Reach: Surgical Outcomes in MRI-Negative and Pathology-Negative Epilepsy Patients.
Li Y. Li Y. Epilepsy Curr. 2024 May 14;24(4):251-253. doi: 10.1177/15357597241253413. eCollection 2024 Jul-Aug. Epilepsy Curr. 2024. PMID: 39309064 Free PMC article. No abstract available.

References

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

Affiliation

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

Authors

Affiliation

Abstract

Conflict of interest statement

Comment in

References

Publication types

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LinkOut - more resources

Full Text Sources

Medical