International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from theILAECommission on Diagnostic Methods

Abstract

Summary Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug‐resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well‐preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no‐HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes

“…Semiquantitative HIA ratings have been shown to be a significant predictor of the laterality of seizure onset in TLE17, 33 and were integrated into image analysis in order to determine if HIA correlates with gross hippocampal and subfield volumes as estimated by Freesurfer version 6. Each T2STIR image slice that depicted the hippocampus was graded with a score of “1” when no internal architecture was perceptible to “4” where excellent internal architecture differentiation could be appreciated 33.…”

“…Importantly, these patterns of HS appear to be related to various clinical aspects of TLE and may have significance for postoperative prognosis. ILAE HS type 1 is more frequently associated with a history of initial precipitating injuries in early childhood, an early seizure onset and improved seizure outcome after temporal lobe surgery 17, 18, 19, 20. ILAE HS type 2 and 3 appear to be associated with a later age of onset and a less favorable postoperative outcome,17, 18, 19, 20 although there are some inconsistencies in these relationships 21.…”

“…The International League Against Epilepsy (ILAE) Commission on Diagnostic Methods have reported three principle patterns of HS based on histopathological analysis 17. The most common pattern of cell loss, ILAE HS type 1, is manifest as predominant loss of neurons and gliosis in CA1 and CA4 subfields 17, 18.…”

“…The most common pattern of cell loss, ILAE HS type 1, is manifest as predominant loss of neurons and gliosis in CA1 and CA4 subfields 17, 18. ILAE HS type 2 and 3 are less common patterns of HS, manifest as pathological changes predominantly in CA1 or CA4, respectively 17, 18.…”

“…ILAE HS type 1 is more frequently associated with a history of initial precipitating injuries in early childhood, an early seizure onset and improved seizure outcome after temporal lobe surgery 17, 18, 19, 20. ILAE HS type 2 and 3 appear to be associated with a later age of onset and a less favorable postoperative outcome,17, 18, 19, 20 although there are some inconsistencies in these relationships 21. Given the clinical relevance of regional hippocampal subfield pathology in TLE, it is important to develop and apply MRI approaches that permit assessment of hippocampal subfield structure and volume in this patient group, particularly if such non‐invasive imaging measures can be used to predict treatment outcome.…”