Page 24 - ILAE_Lectures_2015

HIPPOCAMPAL SCLEROSIS

Hippocampal sclerosis (also referred to as mesial temporal sclerosis, MTS, or Ammon’s horn
sclerosis, AHS) describes atrophy of the hippocampus with a stereotypical pattern of neuronal
loss and gliosis. This manifests as a reduction in the volume of this structure as seen on
neuroimaging or macroscopic examination. Hippocampal sclerosis is strongly associated with
the clinical syndrome of mesial temporal lobe epilepsy (MTLE) but can be seen in other epilepsy
syndromes as well as in ageing without epilepsy32. The neuropathological features have been
recognised for over a century (for historical review see Thom 200933) but its cause, and in turn
how it causes epilepsy, is still the focus of ongoing research, utilising both human tissue and
experimental models.

Patterns of sclerosis: The pathological diagnosis of hippocampal sclerosis is based on the
identification of pyramidal neuronal loss and gliosis involving mainly CA1, CA4 and CA3
subfields of the hippocampal formation (see Figure below). This distinctive pattern of neuronal
loss is apparent on qualitative histological examination and may even be evident on visual
examination of the surgically resected tissue and previously referred to as ‘classical’ hippocampal
sclerosis. CA2 sector is more resistant to neuronal loss and often the pyramidal cells in this region
appear better preserved, as do those of the subiculum. The granule cell layer may appear
preserved, although in 4050% of cases shows dispersion or looser packing of the neurones. ‘End
folium sclerosis’ describes a pattern of neuronal damage confined to the hilar and CA4 pyramidal
cells in a small number of patients. In other cases neuronal loss may appear restricted to CA1
region.

There is no single explanation for the regional selectivity of pyramidal cell loss between
subfields; excitatory pathways and networks, altered inhibitory input, and the effectiveness and
variability of endogenous neuroprotective mechanisms are likely to be involved.

Several schemes have been previously used for the sub-classification and quantitation of neuronal
loss in hippocampal sclerosis as the Wyler system and many quantitative evaluations carried out
(see review34). The ILAE system, based on the semi-quantitative analysis of subfields, was
introduced in 2013, is reproducible between centres and integrates previous schemes (see Table
below) and has been shown to provide prognostic information in terms of outcome35.