Review: Hippocampal sclerosis in epilepsy: a neuropathology review

Abstract

Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post-mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post-mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long-term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho-aetiological subtypes of HS.

Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

“…This supports the idea that these neocortical areas have a shared vulnerability to pathological changes. As FLAIR signal intensity in TLE has been correlated with glial cell count11, 12, 13 and mesiotemporal and neocortical gliosis has been documented in postmortem studies,2, 7, 35 FLAIR changes in the temporal neocortex may indeed reflect gliotic changes. However, T2/FLAIR signal could also reflect alterations in intra‐cortical myelin content,36, 37 particularly given that a similar distribution of neocortical regions demonstrated quantitative T1 changes in an adult TLE cohort 38…”

Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn‐1 gene

“…Recordings from intracerebral implanted electrodes demonstrate that the first electrographic abnormalities in TLE without mesial temporal sclerosis (MTS) often appear within hippocampus (Van Roost, Solymosi, Schramm, van Oosterwyck, & Elger, 1998). This suggests that network changes in the hippocampal formation are important in epileptogenesis, but that morphological changes such as MTS while perhaps augmenting the process are not essential (Thom, 2014; Wang, Smith, Murphy, & Cook, 2010). A major drawback to all post‐SE chemical kindling models is that the epileptogenesis associated with most TLE is not initiated by an episode of status epilepticus, raising the question: what changes are primary to epileptogenesis and what are epiphenomena to the model?…”

Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis

“…Possibly, this discrepancy results from a slight difference in severity of HS together with the fact that, we have used total hippocampus. Although the so-called classical and severe cell loss patterns in HS [32], are now internationally classified as HS ILAE type1 [3], the hippocampal sclerotic tissue used by Wyler et al was, at that time, diagnosed and classified as the most severe form, Wyler grade 4 [37]. A significant decrease of VGLUT1 protein was described in subfields with neuronal loss and a significant increase in the DG, marked by mossy fiber sprouting [33].…”

“…In 60-80% of all TLE-HS cases, HS International League Against Epilepsy (ILAE) type1 is observed. This type of HS is marked by significant neuronal cell loss and gliosis predominantly pronounced in CA1 and CA4, with more variable damage to CA3 and DG subregions and sparing of CA2 [3,32].…”

“…TLE is characterized by spontaneous, recurrent seizures (SRS), caused by abnormal synchronized, high frequency neuronal discharges with hippocampal sclerosis (HS), being the most common neuropathological co-morbidity in patients undergoing surgery for intractable TLE [32]. In 60-80% of all TLE-HS cases, HS International League Against Epilepsy (ILAE) type1 is observed.…”