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Review: Hippocampal sclerosis in epilepsy: a neuropathology review.

Thom M - Neuropathol. Appl. Neurobiol. (2014)

Bottom Line: The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed.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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neuropathology and Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK.

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Variability of hippocampal sclerosis (HS) in post-mortem and surgical samples. (A) Surgical hippocampectomy specimens, which on histological examination correlated to (i) end folium gliosis with no evidence of sclerosis; (ii) ILAE Type 3 HS (end-folium sclerosis); (iii) ILAE type 2 HS (CA1 predominant sclerosis); and (iv) ILAE type 1 HS (classical hippocampal sclerosis). In all of the images the arrow indicates the pyramidal cell layer of CA1. (B) A 9.4T MRI image of a post-mortem hippocampus from a patient with longstanding epilepsy and ILAE type 2 (CA1 predominant pattern) of HS at this level (shown in C in a luxol fast blue/cresyl violet preparation), although in other levels the pattern was type 1 (classical). The MRI has the ability to identify subfields and white matter tracts and, indistinctly (arrowed), the dentate gyrus. Improved high fields sequences in the future may be able to identify and define patterns of HS pre-operatively. The MRI image was provided with courtesy of Dr Sofia Eriksson at the Department of Clinical and Experimental Epilepsy, UCL, Institute of Neurology. (D to I) Paired sections of hippocampus from one hemisphere labelled with (D to F) GFAP/counterstained with cresyl violet and (G to I) calretinin: at the level of the subthalamic nucleus (STNc; D, G), lateral geniculate nucleus (LGNc; E, H) and hippocampal tail (F, I). Classical pattern (ILAE type 1) HS is seen in the anterior levels with sprouting of calretinin-positive fibres visible in the dentate gyrus (arrow) at this low magnification; in the tail gliosis and neuronal loss is visible in the CA4 region of the hippocampal tail. Bar is equivalent to approximately 3 mm (D to I).
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fig05: Variability of hippocampal sclerosis (HS) in post-mortem and surgical samples. (A) Surgical hippocampectomy specimens, which on histological examination correlated to (i) end folium gliosis with no evidence of sclerosis; (ii) ILAE Type 3 HS (end-folium sclerosis); (iii) ILAE type 2 HS (CA1 predominant sclerosis); and (iv) ILAE type 1 HS (classical hippocampal sclerosis). In all of the images the arrow indicates the pyramidal cell layer of CA1. (B) A 9.4T MRI image of a post-mortem hippocampus from a patient with longstanding epilepsy and ILAE type 2 (CA1 predominant pattern) of HS at this level (shown in C in a luxol fast blue/cresyl violet preparation), although in other levels the pattern was type 1 (classical). The MRI has the ability to identify subfields and white matter tracts and, indistinctly (arrowed), the dentate gyrus. Improved high fields sequences in the future may be able to identify and define patterns of HS pre-operatively. The MRI image was provided with courtesy of Dr Sofia Eriksson at the Department of Clinical and Experimental Epilepsy, UCL, Institute of Neurology. (D to I) Paired sections of hippocampus from one hemisphere labelled with (D to F) GFAP/counterstained with cresyl violet and (G to I) calretinin: at the level of the subthalamic nucleus (STNc; D, G), lateral geniculate nucleus (LGNc; E, H) and hippocampal tail (F, I). Classical pattern (ILAE type 1) HS is seen in the anterior levels with sprouting of calretinin-positive fibres visible in the dentate gyrus (arrow) at this low magnification; in the tail gliosis and neuronal loss is visible in the CA4 region of the hippocampal tail. Bar is equivalent to approximately 3 mm (D to I).

Mentions: Although the bulk of neuropathology research in the past decades has been carried out on surgical tissue with its obvious advantages optimally preserved tissues, homogeneous clinical cohorts and access to up-to-date electroencephalography (EEG) and neuroimaging studies we should not neglect the ongoing contribution that autopsy samples can provide in the study of HS in epilepsy. Primarily, PM tissues enable comparisons of HS occurring in epilepsy syndromes other than TLE (also known as secondary HS 7), the effects of a lifetime of seizures on the severity of hippocampal neuronal loss and its associated pathology 186, enable study of the bilaterality of HS 73, the extent of involvement along the entire length of the hippocampus 25 (Figure 5) and to address degeneration in wider networks that have been implied from quantitative MRI studies in TLE 20,187,188, in particular the amygdala, cortex 189, thalamus 190 and cerebellum 191. Neuropathology studies have, from the outset, recognized that more extensive pathology may accompany HS 15,21, the hippocampus being the epicentre of a wider process. Experimental data support widespread changes occurring following induced seizures 192 which could equally contribute to epileptogenesis. Involvement of wide networks has been shown in TLE 193,194 and functional and structural imaging of TLE indicates altered brain connections or connectome in TLE 195,196. As such, in recent years there has been a move away from a ‘hippocampocentric’ view of TLE 197,198 addressing contribution from other brain regions. The main studies have investigated (i) electrophysiological evidence to support origin of seizures from extrahippocampal structures 199,200; (ii) if wider disease offers the explanation for poor outcomes (in terms of seizure-freedom) following localized surgery; and (iii) if severity (or progression) of any extrahippocampal pathology correlates with comorbidities, such as cognitive decline.


Review: Hippocampal sclerosis in epilepsy: a neuropathology review.

Thom M - Neuropathol. Appl. Neurobiol. (2014)

Variability of hippocampal sclerosis (HS) in post-mortem and surgical samples. (A) Surgical hippocampectomy specimens, which on histological examination correlated to (i) end folium gliosis with no evidence of sclerosis; (ii) ILAE Type 3 HS (end-folium sclerosis); (iii) ILAE type 2 HS (CA1 predominant sclerosis); and (iv) ILAE type 1 HS (classical hippocampal sclerosis). In all of the images the arrow indicates the pyramidal cell layer of CA1. (B) A 9.4T MRI image of a post-mortem hippocampus from a patient with longstanding epilepsy and ILAE type 2 (CA1 predominant pattern) of HS at this level (shown in C in a luxol fast blue/cresyl violet preparation), although in other levels the pattern was type 1 (classical). The MRI has the ability to identify subfields and white matter tracts and, indistinctly (arrowed), the dentate gyrus. Improved high fields sequences in the future may be able to identify and define patterns of HS pre-operatively. The MRI image was provided with courtesy of Dr Sofia Eriksson at the Department of Clinical and Experimental Epilepsy, UCL, Institute of Neurology. (D to I) Paired sections of hippocampus from one hemisphere labelled with (D to F) GFAP/counterstained with cresyl violet and (G to I) calretinin: at the level of the subthalamic nucleus (STNc; D, G), lateral geniculate nucleus (LGNc; E, H) and hippocampal tail (F, I). Classical pattern (ILAE type 1) HS is seen in the anterior levels with sprouting of calretinin-positive fibres visible in the dentate gyrus (arrow) at this low magnification; in the tail gliosis and neuronal loss is visible in the CA4 region of the hippocampal tail. Bar is equivalent to approximately 3 mm (D to I).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4265206&req=5

fig05: Variability of hippocampal sclerosis (HS) in post-mortem and surgical samples. (A) Surgical hippocampectomy specimens, which on histological examination correlated to (i) end folium gliosis with no evidence of sclerosis; (ii) ILAE Type 3 HS (end-folium sclerosis); (iii) ILAE type 2 HS (CA1 predominant sclerosis); and (iv) ILAE type 1 HS (classical hippocampal sclerosis). In all of the images the arrow indicates the pyramidal cell layer of CA1. (B) A 9.4T MRI image of a post-mortem hippocampus from a patient with longstanding epilepsy and ILAE type 2 (CA1 predominant pattern) of HS at this level (shown in C in a luxol fast blue/cresyl violet preparation), although in other levels the pattern was type 1 (classical). The MRI has the ability to identify subfields and white matter tracts and, indistinctly (arrowed), the dentate gyrus. Improved high fields sequences in the future may be able to identify and define patterns of HS pre-operatively. The MRI image was provided with courtesy of Dr Sofia Eriksson at the Department of Clinical and Experimental Epilepsy, UCL, Institute of Neurology. (D to I) Paired sections of hippocampus from one hemisphere labelled with (D to F) GFAP/counterstained with cresyl violet and (G to I) calretinin: at the level of the subthalamic nucleus (STNc; D, G), lateral geniculate nucleus (LGNc; E, H) and hippocampal tail (F, I). Classical pattern (ILAE type 1) HS is seen in the anterior levels with sprouting of calretinin-positive fibres visible in the dentate gyrus (arrow) at this low magnification; in the tail gliosis and neuronal loss is visible in the CA4 region of the hippocampal tail. Bar is equivalent to approximately 3 mm (D to I).
Mentions: Although the bulk of neuropathology research in the past decades has been carried out on surgical tissue with its obvious advantages optimally preserved tissues, homogeneous clinical cohorts and access to up-to-date electroencephalography (EEG) and neuroimaging studies we should not neglect the ongoing contribution that autopsy samples can provide in the study of HS in epilepsy. Primarily, PM tissues enable comparisons of HS occurring in epilepsy syndromes other than TLE (also known as secondary HS 7), the effects of a lifetime of seizures on the severity of hippocampal neuronal loss and its associated pathology 186, enable study of the bilaterality of HS 73, the extent of involvement along the entire length of the hippocampus 25 (Figure 5) and to address degeneration in wider networks that have been implied from quantitative MRI studies in TLE 20,187,188, in particular the amygdala, cortex 189, thalamus 190 and cerebellum 191. Neuropathology studies have, from the outset, recognized that more extensive pathology may accompany HS 15,21, the hippocampus being the epicentre of a wider process. Experimental data support widespread changes occurring following induced seizures 192 which could equally contribute to epileptogenesis. Involvement of wide networks has been shown in TLE 193,194 and functional and structural imaging of TLE indicates altered brain connections or connectome in TLE 195,196. As such, in recent years there has been a move away from a ‘hippocampocentric’ view of TLE 197,198 addressing contribution from other brain regions. The main studies have investigated (i) electrophysiological evidence to support origin of seizures from extrahippocampal structures 199,200; (ii) if wider disease offers the explanation for poor outcomes (in terms of seizure-freedom) following localized surgery; and (iii) if severity (or progression) of any extrahippocampal pathology correlates with comorbidities, such as cognitive decline.

Bottom Line: The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed.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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neuropathology and Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK.

Show MeSH
Related in: MedlinePlus