Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

Ingmar Blumcke, M.D., Roberto Spreafico, M.D., Ph.D., Gerrit Haaker, M.D., Roland Coras, M.D., Katja Kobow, Ph.D., Christian G. Bien, M.D., Margarete Pfäfflin, M.Sc., Christian Elger, M.D., Guido Widman, M.D., Johannes Schramm, M.D., Albert Becker, M.D., Kees P. Braun, M.D., Frans Leijten, M.D., Johannes C. Baayen, M.D., Eleonora Aronica, M.D., Ph.D., Francine Chassoux, M.D., Hajo Hamer, M.D., Hermann Stefan, M.D., Karl Rössler, M.D., Maria Thom, M.D., Matthew C. Walker, M.D., Sanjay M. Sisodiya, F.R.C.P., John S. Duncan, M.D., Andrew W. McEvoy, M.D., Tom Pieper, M.D., Hans Holthausen, M.D., Manfred Kudernatsch, M.D., H. Joachim Meencke, M.D., Philippe Kahane, M.D., Ph.D., Andreas Schulze-Bonhage, M.D., Josef Zentner, M.D., Dieter H. Heiland, M.D., Horst Urbach, M.D., Bernhard J. Steinhoff, M.D., Thomas Bast, M.D., Laura Tassi, M.D., Giorgio Lo Russo, M.D., Cigdem Özkara, M.D., Buge Oz, M.D., Pavel Krsek, M.D., Silke Vogelgesang, M.D., Uwe Runge, M.D., Holger Lerche, M.D., Yvonne Weber, M.D., Mrinalini Honavar, M.D., José Pimentel, M.D., Ph.D., Alexis Arzimanoglou, M.D., Adriana Ulate-Campos, M.D., Soheyl Noachtar, M.D., Elisabeth Hartl, M.D., Olaf Schijns, M.D., Renzo Guerrini, M.D., Carmen Barba, M.D., Thomas S. Jacques, F.R.C.Path., Ph.D., J. Helen Cross, F.R.C.P.C.H., Ph.D., Martha Feucht, M.D., Angelika Mühlebner, M.D., Thomas Grunwald, M.D., Ph.D., Eugen Trinka, M.D., Peter A. Winkler, M.D., Antonio Gil-Nagel, M.D., Ph.D., Rafael Toledano Delgado, M.D., Thomas Mayer, M.D., Martin Lutz, Ph.D., Basilios Zountsas, M.D., Kyriakos Garganis, M.D., Felix Rosenow, M.D., Anke Hermsen, M.Sc., Tim J. von Oertzen, M.D., Thomas L. Diepgen, M.D., Ph.D., and Giuliano Avanzini, M.D., for the EEBB Consortium*

N Engl J Med 2017; 377:1648-1656October 26, 2017DOI: 10.1056/NEJMoa1703784

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Background

Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy.

Methods

We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%).

Results

The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients.

Conclusions

In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.)

Supported by the European Union (FP7 DESIRE GA grant 602531, to Drs. Blumcke, Spreafico, Haaker, Tassi, Guerrini, and Barba; FP7 EPITARGET GA grant 602102, to Drs. Becker, Aronica, Walker, and Sisodiya; FP7 EPISTOP grant 602391, to Dr. Aronica; and FP7 EpimiRNA GA grant 602130, to Drs. Hamer and Rosenow); EpiGENet (DFG Bl 421/3-1, to Dr. Blumcke); the Johannes and Frieda Marohn Foundation of the Friedrich-Alexander University Erlangen-Nuremberg (support to Dr. Blumcke); the Austrian Science Fund (FWF grant J3499, to Dr. Mühlebner and grants P21636, P24367, DK W 1233-G17, KLI543-B27, and KLI12-B00, to Dr. Trinka); the Italian Ministry of Health (grant RF-2011-02350578, to Drs. Spreafico, Tassi, and Guerrini, and grant RF-2010-2309954, to Dr. Barba), the National Institute for Health Research University College London Hospitals Biomedical Research Centre (support to Drs. Thom, Walker, Sisodiya, Duncan, and McEvoy); Great Ormond Street Hospital Children’s Charity, the Brain Tumour Charity, Children with Cancer, Higher Education Funding Council for England, and the National Institute for Health Research (support to Dr. Jacques); the Anniversary Fund of the Central Bank of the Republic of Austria (grant ÖNB-12036, to Dr. Feucht); and Fundación Gmp (support to Dr. Gil-Nagel).

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