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. 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. 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. 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.

Summary: Purpose: The orbitofrontal (OF) region is one of the least explored regions of the cerebral cortex. There are few studies on patients with electrophysiologically and surgically confirmedOFepilepsy and a negative magnetic resonance imaging (MRI) study. We aimed to examine the neuroimaging characteristics ofMRI‐negativeOFepilepsy with the focus on a voxel‐based morphometricMRIpostprocessing technique.Methods: We included six patients withOFepilepsy, who met the following criteria: surgical resection of theOFlobe with/without adjacent cortex, seizure‐free for ≥12 months, invasive video–electroencephalography (EEG) monitoring showing ictal onset from theOFarea, and preoperativeMRIregarded as negative. Patients were investigated in terms of their image postprocessing and functional neuroimaging characteristics, electroclinical characteristics obtained from noninvasive and invasive evaluations, and surgical pathology.MRIpostprocessing on T₁‐weighted high‐resolution scans was implemented with a morphometric analysis program (MAP) inMATLAB.Key Findings: SingleMAP+ abnormalities were found in four patients; three were in theOFregion and one in the ipsilateral mesial frontal area. These abnormalities were included in the resection. One patient had bilateralMAP+ abnormalities in theOFregion, with the ipsilateral one completely removed. TheMAP+ foci were concordant with invasive electrophysiologic data in the majority ofMAP+ patients (four of five). The localization value of 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) and ictal single‐photon emission computed tomography (SPECT) is low in this cohort. Surgical pathology included focal cortical dysplasia, remote infarct, Rosenthal fiber formation and gliosis.Significance: Our study highlights the importance ofMRIpostprocessing in the process of presurgical evaluation of patients with suspected orbitofrontal epilepsy and “normal”MRI. UsingMAP, we were able to positively identify subtle focal abnormalities in the majority of the patients.MAPresults need to be interpreted in the context of their electroclinical findings and can provide valuable targets in the process of planning invasive evaluation.

The diagnosis of epilepsy primarily depends on description of the observed seizure. The aim of this study was to determine the reliability of witness' description among groups with different medical education. A group of 44 respondents (15 laymen, 15 medical students, and 14 doctors at neurology residency program) were shown video footages of focal epileptic seizure (ES) with secondary generalization and psychogenic non-epileptic seizure (PNES) of the same patient. The ability to describe ES and PNES characteristics, to estimate duration of seizures, and to detect of accurate seizure type was evaluated using a questionnaire. For the analysis of primary data obtained from questionnaires, we used descriptive statistical methods and methods for testing statistical hypotheses. The sensitivity (Sn) and specificity (Sp) for accurate recognition of ES are different in the examined groups (laymen Sn = 53.3%, Sp = 33.3%; medical students Sn = 100%, Sp = 13.3%; neurology residents Sn = 100%, Sp = 71.4%). Evaluated duration of PNES and ES do not differ between examined groups. The impression that ES and PNES are distinct events is reciprocal for medical students and neurology residents, but not in laymen group. Neurology residents notice the essential characteristics of ES in high percentage. Accurate classification of the attacks is associated with the observers' level of medical knowledge. Witnesses with specific, neurological knowledge with higher probability, compared to the laity and medical students, differentiate ES from PNES.