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Abstract
Objective To 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.
Methods In 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.
Results GCL 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).
Conclusions No 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.
Glossary
- CV=
- cresyl violet;
- CVD=
- cerebrovascular disease;
- DG=
- dentate gyrus;
- EP-C=
- epilepsy disease controls;
- ERD=
- epilepsy-related deaths;
- GCL=
- granule cell layer;
- GCLE=
- granule cell layer thickness on the external blade (adjacent to CA2);
- GCLI=
- granule cell layer thickness on the internal blade (adjacent to subiculum);
- GCLM=
- the mean of GCLE and GCLI;
- HD=
- hippocampal dimension;
- HMAL=
- hippocampal malrotation;
- HS=
- hippocampal sclerosis;
- MCD=
- malformation of cortical development;
- NEC=
- nonepilepsy controls;
- PHG=
- parahippocampal gyrus;
- SIDS=
- sudden infant death syndrome;
- SUDC=
- sudden unexplained death in childhood;
- SUDEP=
- sudden unexpected death in epilepsy;
- TBI=
- traumatic brain injury;
- TLE=
- temporal lobe epilepsy
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received November 5, 2018.
- Accepted in final form April 1, 2019.
- © 2019 American Academy of Neurology
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