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The Autonomic and Imaging Biomarkers of SUDEP (NS090407)

Specific Aims and Tasks

Sudden Unexpected Death in Epilepsy (SUDEP) affects ~3000 individuals with epilepsy in the USA annually. Death results from profound breathing and/or cardiovascular dysfunction, but mechanisms underlying failure, and risk factors identifying those most at risk are unknown. Our goal is to identify patterns of physiological dysfunction surrounding seizure periods and the underlying neural injury contributing to those patterns. We aim to identify patterns of physiological dysfunction (changes in blood pressure, heart rate, arrhythmia, breathing and EEG patterns) surrounding seizure periods and the underlying neural injury (focal structural brain changes identified through brain imaging including MRI) contributing to those patterns.
  • This project will provide insight into mechanisms of failure in SUDEP, and suggest pre-mortem characteristics that lead to a fatal scenario that are suitable for targeted intervention.

Principal Investigators

Publication Links

  • Serum serotonin levels in patients with epileptic seizures. Murugesan A, Rani MRS, Hampson J, Zonjy B, Lacuey N, Faingold CL, Friedman D, Devinsky O, Sainju RK, Schuele S, Diehl B, Nei M, Harper RM, Bateman LM, Richerson G, Lhatoo SD. PMID:29771456.
  • Ictal laryngospasm monitored by video-EEG and polygraphy: a potential SUDEP mechanism. Lacuey N, Vilella L, Hampson JP, Sahadevan J, Lhatoo SD. PMID:29620011.
  • Automated Detection of Postictal Generalized EEG Suppression. Theeranaew W, McDonald J, Zonjy B, Kaffashi F, Moseley BD, Friedman D, So E, Tao J, Nei M, Ryvlin P, Surges R, Thijs R, Schuele S, Lhatoo S, Loparo KA.. PMID:29346105.
  • The incidence and significance of periictal apnea in epileptic seizures. Lacuey N, Zonjy B, Hampson JP, Rani MRS, Zaremba A, Sainju RK, Gehlbach BK, Schuele S, Friedman D, Devinsky O, Nei M, Harper RM, Allen L, Diehl B, Millichap JJ, Bateman L, Granner MA, Dragon DN, Richerson GB, Lhatoo SD. PMID:29336036.
  • Dysfunctional Brain Networking among Autonomic Regulatory Structures in Temporal Lobe Epilepsy Patients at High Risk of Sudden Unexpected Death in Epilepsy. Allen LA, Harper RM, Kumar R, Guye M, Ogren JA, Lhatoo SD, Lemieux L, Scott CA, Vos SB, Rani S, Diehl B. PMID:29085330.
  • ODaCCI: Ontology-guided Data Curation for Multisite Clinical Research Data Integration in the NINDS Center for SUDEP Research. Cui L, Huang Y, Tao S, Lhatoo SD, Zhang GQ PMID:28269839.
  • Amygdala and hippocampus are symptomatogenic zones for central apneic seizures. Lacuey N, Zonjy B, Londono L, Lhatoo SD. PMID:28087822.
  • Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Devinsky O, Hesdorffer DC, Thurman DJ, Lhatoo S, Richerson G . PMID:27571159.
  • NeuroPigPen: A Scalable Toolkit for Processing Electrophysiological Signal Data in Neuroscience Applications Using Apache Pig. Sahoo SS, Wei A, Valdez J, Wang L, Zonjy B, Tatsuoka C, Loparo KA, Lhatoo SD. PMID:27375472.
  • 2014 Epilepsy Benchmarks Area IV: Limit or Prevent Adverse Consequence of Seizures and Their Treatment Across The Lifespan. Goldman AM, LaFrance WC Jr, Benke T, Asato M, Drane D, Pack A, Syed T, Doss R, Lhatoo S, Fureman B, Dingledine R PMID:27330453.
  • Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures. Lhatoo SD, Nei M, Raghavan M, Sperling M, Zonjy B, Lacuey N, Devinsky PMID:27221596.
  • Left-insular damage, autonomic instability, and sudden unexpected death in epilepsy. Lacuey N, Zonjy B, Theerannaew W, Loparo KA, Tatsuoka C, Sahadevan J, Lhatoo SD PMID:26797084.
  • NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research. Zhang GQ, Tao S, Xing G, Mozes J, Zonjy B, Lhatoo SD, Cui L. PMID:26554419.
  • Wandschneider B, Koepp M, Scott C, Micallef C, Balestrini S, Sisodya S, Thom M, Harper R, Sander J, Vos S, Duncan J, Lhatoo S, Diehl B. Structural imaging biomarkers of sudden unexpected death in epilepsy (Accepted, Brain 2015).
  • Ryvlin P, Nashef L, Lhatoo SD, Bateman LM et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. PMID 24012372.
  • Bozorgi A, Chung S, Kaffashi F, Loparo KA, Sahoo SS, Zhang GQ, Kaiboriboon K, Lhatoo SD. Significant peri-ictal hypotension: Expanding the spectrum of seizure induced autonomic dysregulatory phenomena with polygraphy. PMID 23758665.
  • Lhatoo SD, Faulkner HJ, Dembny K, Trippick K, Johnson C, Bird JM (2010). An electroclinical case-control study of sudden unexpected death in epilepsy. PMID 20882604.
  • Lhatoo SD, Johnson AL, Goodridge DM, MacDonald BK, Sander JW, Shorvon SD. Mortality in epilepsy in the first 11 to 14 years after diagnosis: Multivariate analysis of a long-term, prospective, population-based cohort. PMID 11261508.

Regional grey matter volume differences between SUDEP, people at high risk and controls

Figure modified from: Structural imaging biomarkers of sudden unexpected death in epilepsy: Britta Wandschneider et al., Brain 2015, in press