Cell Proliferation and Granule Cell Dispersion in Human Hippocampal Sclerosis

ObjectiveTo determine hippocampal morphometric measures, including granule cell dispersion and features of malrotation, as potential biomarkers for sudden unexpected death in epilepsy (SUDEP) from an archival postmortem series.MethodsIn a retrospective study of 187 archival postmortems from 3 groups, SUDEP (68; 14 with hippocampal sclerosis [HS]), non-SUDEP epilepsy controls (EP-C = 66; 25 with HS), and nonepilepsy controls (NEC = 53), Nissl/hematoxylin & eosin–stained sections from left and right hippocampus from 5 coronal levels were digitized. Image analysis was carried out for granule cell layer (GCL) thickness and measurements of hippocampal dimensions (HD) for shape (width [HD1], height [HD2]) and medial hippocampal positioning in relation to the parahippocampal gyrus (PHG) length (HD3). A qualitative evaluation of hippocampal malrotational (HMAL) features, dentate gyrus invaginations (DGI), and subicular/CA1 folds (SCF) was also made.ResultsGCL thickness was increased in HS more than those without (p < 0.001). In non-HS cases, increased GCL thickness was noted in EP-C compared to NEC (p < 0.05) but not between SUDEP and NEC. There was no difference in the frequency of DGI, SCF, measurements of hippocampal shape (HD1, HD2, or ratio), or medial positioning among SUDEP, EP-C, and NEC groups, when factoring in HS, coronal level, and age at death. Comparison between left and right sides within cases showed greater PHG lengths (HD3) on the right side in the SUDEP group only (p = 0.018).ConclusionsNo hippocampal morphometric features were identified in support of either excessive granule cell dispersion or features of HMAL as definitive biomarkers for SUDEP. Asymmetries in PHG measurements in SUDEP warrant further investigation as they may indicate abnormal central autonomic networks.

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Balloon cells associated with granule cell dispersion in the dentate gyrus in hippocampal sclerosis

Acta Neuropathologica ◽

10.1007/s00401-008-0341-y ◽

2008 ◽

Vol 115 (6) ◽

pp. 697-700 ◽

Cited By ~ 14

Author(s):

M. Thom ◽

L. Martinian ◽

L. O. Caboclo ◽

A. W. McEvoy ◽

S. M. Sisodiya

Keyword(s):

Dentate Gyrus ◽

Granule Cell ◽

Hippocampal Sclerosis ◽

Balloon Cells ◽

Cell Dispersion

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Calbindin D28K expression in relation to granule cell dispersion, mossy fibre sprouting and memory impairment in hippocampal sclerosis: A surgical and post mortem series

Epilepsy Research ◽

10.1016/j.eplepsyres.2011.08.011 ◽

2012 ◽

Vol 98 (1) ◽

pp. 14-24 ◽

Cited By ~ 20

Author(s):

L. Martinian ◽

C.B. Catarino ◽

P. Thompson ◽

S.M. Sisodiya ◽

M. Thom

Keyword(s):

Granule Cell ◽

Memory Impairment ◽

Hippocampal Sclerosis ◽

Mossy Fibre ◽

Post Mortem ◽

Cell Dispersion ◽

Calbindin D28k

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Hippocampal morphometry in sudden and unexpected death in epilepsy (SUDEP)

10.1101/522300 ◽

2019 ◽

Author(s):

Alyma Somani ◽

Anita-Beatrix Zborovschi ◽

Yan Liu ◽

Smriti Patodia ◽

Zuzanna Michalak ◽

...

Keyword(s):

Granule Cell ◽

Hippocampal Sclerosis ◽

Qualitative Evaluation ◽

Granule Cell Layer ◽

Parahippocampal Gyrus ◽

Unexpected Death ◽

Cell Dispersion ◽

Significant Difference ◽

Left And Right ◽

The Right

ABSTRACTObjectiveTo determine hippocampal morphometric parameters, including granule cell dispersion and features of malrotation, as potential biomarkers for SUDEP from an archival post-mortem series.MethodsIn a retrospective study of 187 archival post-mortems from three groups, SUDEP (68; 14 with hippocampal sclerosis (HS)), non-SUDEP epilepsy controls (EP-C =66; 25 with HS) and non-epilepsy controls (NEC= 53), Nissl/H&E stained sections from left and right hippocampus from five coronal levels were digitised. Image analysis was carried out for granule cell layer (GCL) thickness and measurements of hippocampal dimensions (HD) for shape [width (HD1), height (HD2)] and medial hippocampal positioning in relation to the parahippocampal gyrus (PHG) length (HD3). A qualitative evaluation of hippocampal malrotational (HMAL) features, dentate gyrus invaginations (DGI) and subicular/CA1 folds (SCF) was also made.ResultsGCL thickness was increased in HS more than those without (p<0.001). In non-HS cases increased GCL thickness was noted in EP-C compared to NEC (p<0.05) but not between SUDEP and NEC. There was no significant difference in the frequency of DGI, SCF, measurements of hippocampal shape (HD1, HD2 or ratio) or medial positioning between SUDEP, EP-C and NEC groups, when factoring in HS, coronal level and age at death. Comparison between left and right sides within cases showed significantly greater PHG lengths (HD3) on the right side in the SUDEP group only (p=0.018)ConclusionsNo hippocampal morphometric features were identified in support of either excessive granule cell dispersion or features of HMAL as biomarkers for SUDEP. Asymmetries in PHG measurements in SUDEP warrant further investigation as they may indicate abnormal central autonomic networks.

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Hippocampal Sclerosis, Granule Cell Dispersion, and Cortical Dysplasia

Developmental Neuropathology ◽

10.1002/9781119013112.ch10 ◽

2018 ◽

pp. 101-115

Author(s):

Maria Thom

Keyword(s):

Granule Cell ◽

Hippocampal Sclerosis ◽

Cortical Dysplasia ◽

Cell Dispersion

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Interictal psychosis following temporal lobe surgery: dentate gyrus pathology

Psychological Medicine ◽

10.1017/s0033291714000452 ◽

2014 ◽

Vol 44 (14) ◽

pp. 3037-3049 ◽

Cited By ~ 4

Author(s):

M. Thom ◽

M. Kensche ◽

J. Maynard ◽

J. Liu ◽

C. Reeves ◽

...

Keyword(s):

Dentate Gyrus ◽

Temporal Lobe ◽

Granule Cell ◽

Cellular Response ◽

Granule Cells ◽

De Novo ◽

Hippocampal Sclerosis ◽

Mossy Fibre ◽

Cannabinoid Type 1 Receptor ◽

Cell Dispersion

BackgroundDe novointerictal psychosis, albeit uncommon, can develop in patients following temporal lobe surgery for epilepsy. Pathological alterations of the dentate gyrus, including cytoarchitectural changes, immaturity and axonal reorganization that occur in epilepsy, may also underpin co-morbid psychiatric disorders. Our aim was to study candidate pathways that may be associated with the development of interictal psychosis post-operatively in patients with hippocampal sclerosis (HS).MethodA total of 11 patients with HS who developed interictal psychosis (HS-P) post-operatively were compared with a matched surgical HS group without psychosis (HS-NP). Resected tissues were investigated for the extent of granule cell dispersion, mossy fibre sprouting and calbindin expression in the granule cells. We quantified doublecortin, mini-chromosome maintenance protein 2 (MCM2) and reelin-expressing neuronal populations in the dentate gyrus as well as the distribution of cannabinoid type 1 receptor (CBR1).ResultsThe patterns of neuronal loss and gliosis were similar in both groups. HS-P patients demonstrated less mossy fibre sprouting and granule cell dispersion (p < 0.01) and more frequent reduction in calbindin expression in granule cells. There were no group differences in the densities of immature MCM2, doublecortin and reelin-positive cells. CBR1 labelling was significantly lower in Cornu ammonis area CA4 relative to other subfields (p < 0.01); although reduced staining in all hippocampal regions was noted in HS-P compared with HS-NP patients, the differences were not statistically significant.ConclusionsThe alterations in dentate gyrus pathology found in HS-P patients could indicate underlying differences in the cellular response to seizures. These mechanisms may predispose to the development of psychosis in epilepsy and warrant further investigation.

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