A new clinico-pathological classification system for mesial temporal sclerosis

Abstract

We propose a histopathological classiWcation system for hippocampal cell loss in patients suVering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subWelds CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The Wrst group comprised hippocampi with neuronal cell densities not signiWcantly diVerent from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subWelds excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subWelds (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury 123(IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the Wrst event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was signiWcantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%).Our classiWcation system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome

“…In our series of 66 patients, four distinct patterns of HS were recognized as suggested in a previous study 7 : no MTS (n=3, 4.5%, Fig 1A), MTS type 2 (n=4, 6.1%, Fig 1B), MTS type 1a (n=18, 27.3%, Fig 1C) and MTS type 1b (n=41, 62.1%, Fig 1D). Atypical end folium sclerosis (MTS type 3) was not found in this cohort of surgical specimens.…”

“…HE and NeuN staining method were carried out on the postmortem tissue. There was no difference accuracy between control's HE-and NeuN-stained sections as reported in previous studies 6,7 .…”

“…All epilepsy tissue and controls specimens were analyzed according to Blümcke et al 7 . Microscopically images were obtained utilizing an E600 microscope equipped to Moticam 2300 camera (Nikon, Japan).…”

“…Among other factors, it has been suggested that different patterns of neuronal cell loss within hippocampal subfields may be implicated in surgical results 6,7 .…”

The pathology of magnetic-resonance-imaging-negative epilepsy

“…Hippocampal sclerosis was defined by a characteristic loss of neurons and gliosis in the hippocampus, preferentially involving the dentate, CA4, CA3, and CA1 regions. 21 Hamartias were defined as collections of small neurons marked by scant cytoplasm and pericellular clearing. 22 Nodular heterotopia is marked by the presence of disordered gray matter tissue in the white matter.…”