Epilepsies associated with hippocampal sclerosis

Abstract

Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of "gliosis only, no-HS". Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca(2+) influx into neurons, the imbalance of Ca(2+)-binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion.

Phosphorus magnetic resonance spectroscopy in the investigation of temporal lobe epilepsy: ‘reading between the lines’ of metabolic abnormalities

“…In fact, these data support the underlying basis of the metabolic disturbance found in 1 H-MRS and FDG-PET studies 8,9,10 . …”

“…Evidences from MRS and other imaging modalities give support for the more widespread functional impairment extending beyond the mesial temporal structures in patients with MTLE 6,8 . More detailed high-resolution quantitative MRI analyses reveals a network of gray matter atrophy and dysfunction that involves mesial temporal and other structures interconnected with the limbic system, including thalamus and striatum 9 ; a finding that was expanded further by the study of Park et al…”

MicroRNAs as biomarkers in molecular diagnosis of refractory epilepsy

“…Moreover, temporal lobe epilepsy (TLE) represents the most common syndrome in adults and often develops pharmacoresistence [7]. TLE frequently develops into DRE as a result of hippocampal sclerosis (HS) [8][9][10], inflammation [11], neurocysticercosis [12], brain insult [13], or malformations of cortical development [14,15]. However, a consensus definition and prognosis for DRE remained elusive [16,17].…”

Neuroimaging in Focal Epilepsies: An Update

“…[15] The MRI findings often show volumetric reduction of hippocampal formation (atrophy), increased signal intensity in T2-weighted sequences, loss of normal hippocampal architecture with loss of hippocampal head digitation ( Figure 5) better identified in thin coronal MRI slices, perpendicular to the axis of the hippocampus. [16] Secondary MRI findings of HS include: atrophy of structures of the limbic system, such as amygdala, ipsilateral mammillary body, entorhinal cortex, ipsilateral fornix, posterior thalamus, cingulate gyrus and contralateral cerebellum. [17,18] Atrophy-signal alterations of the contralateral hippo- Sagittal images parallel to the long axis of hippocampus 1) T2WI 3D: no gap, FOV = 230x230, voxel size = 1,5x1,5x1,5 mm, TR = 1800 ms, TE shortest.…”