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Neuropathology of SUDEP (NS090415)

Specific Aims and Tasks

The Core will examine a large collection of SUDEP brains to explore the role of specific histopathological and biomolecular abnormalities in the brain, focusing on critical brainstem regions and the neurotransmitters serotonin and adenosine. The goal is to perform a large-scale study of SUDEP brains in hopes this will reveal microstructural abnormalities and alterations of interneurons as well as in purinergic and serotonergic systems in respiratory and autonomic regulating structures of the brain. The study will link phenotypic data to biopsy samples as well as to postmortem brains from SUDEP cases, control brains from patients with epilepsy who died from other causes and to patients without epilepsy who died suddenly. The central hypothesis is that neuropathological changes can be identified in cortical and brainstem regions that subserve regulation of autonomic regulatory function.

Principal Investigators

Publication Links

  1. Liu JY, Ellis M, Brooke-Ball H, de Tisi J, Eriksson SH, Brandner S, Sisodiya SM, Thom M. High-throughput, automated quantification of white matter neurons in mild malformation of cortical development in epilepsy. Acta Neuropathol Commun. 2014 Jun 13;2:72. doi: 10.1186/2051-5960-2-72. PubMed PMID: 24927775; PubMed Central PMCID: PMC4229809.
  2. Sinjab B, Martinian L, Sisodiya SM, Thom M. Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: a postmortem study. Epilepsia. 2013 Dec;54(12):2125-33. doi: 10.1111/epi.12403. Epub 2013 Oct 18. PubMed PMID: 24138281; PubMed Central PMCID: PMC3995016.
  3. Novy J, Belluzzo M, Caboclo LO, Catarino CB, Yogarajah M, Martinian L, Peacock JL, Bell GS, Koepp MJ, Thom M, Sander JW, Sisodiya SM. The lifelong course of chronic epilepsy: the Chalfont experience. Brain. 2013 Oct;136(Pt 10):3187-99. doi: 10.1093/brain/awt117. Epub 2013 Jul 3. PubMed PMID: 23824485.
  4. Feast A, Martinian L, Liu J, Catarino CB, Thom M, Sisodiya SM. Investigation of hypoxia-inducible factor-1α in hippocampal sclerosis: a postmortem study. Epilepsia. 2012 Aug;53(8):1349-59. doi: 10.1111/j.1528-1167.2012.03591.x. Epub 2012 Jul 19. PubMed PMID: 22812626.
  5. Liu JY, Thom M, Catarino CB, Martinian L, Figarella-Branger D, Bartolomei F, Koepp M, Sisodiya SM. Neuropathology of the blood-brain barrier and pharmaco-resistance in human epilepsy. Brain. 2012 Oct;135(Pt 10):3115-33. doi: 10.1093/brain/aws147. Epub 2012 Jun 28. PubMed PMID: 22750659.
  6. Catarino CB, Liu JY, Liagkouras I, Gibbons VS, Labrum RW, Ellis R, Woodward C, Davis MB, Smith SJ, Cross JH, Appleton RE, Yendle SC, McMahon JM, Bellows ST, Jacques TS, Zuberi SM, Koepp MJ, Martinian L, Scheffer IE, Thom M, Sisodiya SM. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology. Brain. 2011 Oct;134(Pt 10):2982-3010. doi: 10.1093/brain/awr129. Epub 2011 Jun 29. PubMed PMID: 21719429; PubMed Central PMCID: PMC3187538.
  7. Blanc F, Martinian L, Liagkouras I, Catarino C, Sisodiya SM, Thom M. Investigation of widespread neocortical pathology associated with hippocampal sclerosis in epilepsy: a postmortem study. Epilepsia. 2011 Jan;52(1):10-21. doi: 10.1111/j.1528-1167.2010.02773.x. Epub 2010 Dec 27. PubMed PMID: 21198557.
  8. Thom M, Seetah S, Sisodiya S, Koepp M, Scaravilli F. Sudden and unexpected death in epilepsy (SUDEP): evidence of acute neuronal injury using HSP-70 and c-Jun immunohistochemistry. Neuropathol Appl Neurobiol. 2003 Apr;29(2):132-43. PubMed PMID: 12662321.
  9. Thom M, Griffin B, Sander JW, Scaravilli F. Amygdala sclerosis in sudden and unexpected death in epilepsy. Epilepsy Res. 1999 Oct;37(1):53-62. PubMed PMID: 10515175.

9.4 TMRI of post-mortem brainstem

This patient had definite SUDEP and was neuropathology negative at post mortem. Image kindly provided by Professor Maria Thom, MD from University College, London.