The Pathology of Magnetic-Resonance-Imaging-Negative Epilepsy

Z Irene Wang; Andreas V Alexopoulos; Stephen E Jones; Zeenat Jaisani; Imad M Najm; Richard A Prayson


Mod Pathol. 2013;26(8):1051-1058. 

In This Article

Abstract and Introduction


Patients with magnetic-resonance-imaging (MRI)-negative (or 'nonlesional') pharmacoresistant focal epilepsy are the most challenging group undergoing presurgical evaluation. Few large-scale studies have systematically reviewed the pathological substrates underlying MRI-negative epilepsies. In the current study, histopathological specimens were retrospectively reviewed from MRI-negative epilepsy patients (n=95, mean age=30 years, 50% female subjects). Focal cortical dysplasia cases were classified according to the International League Against Epilepsy (ILAE) and Palmini et al classifications. The most common pathologies found in this MRI-negative cohort included: focal cortical dysplasia (n=43, 45%), gliosis (n=21, 22%), hamartia+gliosis (n=12, 13%), and hippocampal sclerosis (n=9, 9%). The majority of focal cortical dysplasia were ILAE type I (n=37) or Palmini type I (n=39). Seven patients had no identifiable pathological abnormalities. The existence of positive pathology was not significantly associated with age or temporal/extratemporal resection. Follow-up data post surgery was available in 90 patients; 63 (70%) and 57 (63%) attained seizure freedom at 6 and 12 months, respectively. The finding of positive pathology was significantly associated with seizure-free outcome at 6 months (P=0.035), but not at 12 months. In subgroup analysis, the focal cortical dysplasia group was not significantly correlated with seizure-free outcome, as compared with the negative-pathology groups at either 6 or 12 months. Of note, the finding of hippocampal sclerosis had a significant positive correlation with seizure-free outcome when compared with the negative-pathology group (P=0.009 and 0.004 for 6- and 12-month outcome, respectively). Absence of a significant histopathology in the resected surgical specimen did not preclude seizure freedom. In conclusion, our study highlights the heterogeneity of epileptic pathologies in MRI-negative epilepsies, with focal cortical dysplasia being the most common finding. The existence of positive pathology in surgical specimen may be a good indication for short-term good seizure outcome. There is a small subset of cases in which no pathological abnormalities are identified.


Patients with magnetic-resonance-imaging (MRI)-negative (or 'nonlesional') pharmacoresistant focal epilepsy constitute the most challenging group undergoing presurgical evaluation.[1–3] The overall prevalence of nonlesional epilepsy in all surgical studies is ~26%.[4] At present, surgical management of MRI-negative pharmacoresistant focal epilepsy patients relies heavily on invasive intracranial electroencephalography, which is based on complimentary review of other noninvasive modalities including positron emission tomography, ictal single-photon emission computed tomography, and magnetoencephalography when available.[5–8] Despite substantial efforts, the lack of a lesion on MRI has consistently been shown to be one of the predictors for surgical failure.[9,10] Therefore, MRI-negative patients are usually considered unfavorable surgical candidates[4] and are often denied epilepsy surgery. Yet, surgical resection can be effective in well-selected patients with no visible MRI abnormality. In order to improve surgical outcome of MRI-negative patients, it is important to understand the pathologies that these patients may demonstrate on examining their surgically resected tissues.

The pathologic substrates underlying pharmacoresistant focal epilepsy are well established and most commonly include hippocampal sclerosis, focal cortical dysplasia, tumors, and remote ischemic events/infarcts.[11,12] Studies specifically on the surgical pathology of MRI-negative patients, however, are limited to small-scale experiences of individual centers,[13–16] or cases buried in larger series containing both MRI-positive and -negative patients.[17,18] Moreover, with the advance in MRI technology over the last decade and the establishment of more uniform epilepsy MRI protocols, the definition of 'MRI-negative' cases in recent studies may not be equivalent to earlier ones. The purpose of this study is to systematically review one institution's recent experience with the pathological substrates underlying strictly defined MRI-negative epilepsies.