Cortical Neuronal Hypertrophy and mTOR Pathway Activation in Central Autonomic Brain Regions in SUDEP
Abstract number :
2.347
Submission category :
14. Neuropathology of Epilepsy
Year :
2021
Submission ID :
1826011
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:51 AM
Authors :
Maria Thom, FRCPath - UCL Queen Square Institute of Neurology; Freda Chung – Student, Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology; Hanaa El Hachami – Technician, Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology; Irene Stylianou – Student, Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology; Smriti Patodia – Post-doc, Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology
Rationale: Dysfunctional connectivity and pre-existing structural abnormalities of central autonomic network regions (CAN) have been shown on MRI in SUDEP and may be mechanistically relevant. In a previous post-mortem (PM) study we reported increased microglia in the superior temporal gyrus (STG) in SUDEP. Our aim was to quantify pS6 (a marker of MTOR pathway activation) and neuronal c-Fos (neuronal activation marker) in CAN regions in SUDEP compared to control groups.
Methods: In a series of 59 post-mortem cases (SUDEP (n=26), epilepsy controls (EPC) (n=14) and non-epilepsy controls (NEC) (n=19)) we quantified pS6-240/4, pS6-235/6 and c-Fos neuronal labelling (neuronal densities (ND) and percentage positive neurones (PP)) in the STG, anterior cingulate, insular, fronto-basal and pulvinar regions using quantitative immunohistochemistry with whole slide image analysis.
Results: Neuronal and glial pS6 and c-Fos labelling was variable between cases and brain regions. Cortical neuronal hypertrophy in the STG was observed in some SUDEP cases and pS6-240 highlighted hypertrophic neurones. pS6-235 highlighted neuronal intranuclear inclusions, mainly in SUDEP. Significantly more pS6 positive neurones were present in the STG in SUDEP cases but no differences noted for c-FOS in any region between cause of death groups. pS6 labelling in the STG also correlated with recent seizures prior to death.
Conclusions: Neuronal labelling for pS6 in the STG correlated with seizure activity in the period prior to death, it may represent a specific signature for SUDEP and further investigations required for its functional significance.
Funding: Please list any funding that was received in support of this abstract.: National Institute of Neurological Disorders And Stroke of the National Institutes of Health (Award Numbers neuropathology of SUDEP: 5U01NS090415).
Neuropathology of Epilepsy