Dr. Catherine Chu is a practicing pediatric epileptologist and clinical neurophysiologist at Massachusetts General Hospital (MGH), whose goal is to develop an independent research program utilizing non-invasive human imaging and neurophysiological recordings to improve our understanding of the mechanisms, disease process, and indicators of seizure risk in the developing brain. Dr. Chu proposes to study the most common pediatric epilepsy syndrome, benign epilepsy with Centro temporal spikes (BECTS) using novel methods to integrate advanced neuroimaging, electrophysiology, and signal processing techniques to identify key cortical biomarkers of seizure risk. Despite extensive clinical experience with this disease, it remains a challenge to determine who will benefit from antiepileptic drug (AED) treatment and when it is safe to discontinue. One- third of these children will have only a single seizure, while two-thirds may have recurrent seizures over several years. Although non-treatment or premature taper may result in seizures, chronic AED exposure introduces cognitive side effects in 30-70% of exposed children. A biomarker to isolate which children are at risk for ongoing seizures is needed to prevent the unnecessary consequences of over- or under-medication during critical years of cognitive, psychosocial and behavioral maturation in this large cohort of children. As seizures are thought to result from abnormal cortical excitability and connectivity, Dr. Chu hypothesizes those principled measures of these properties using available non-invasive techniques will identify clinically relevant biomarkers of seizure risk. Dr. Chu has developed preliminary results supporting the feasibility of her proposed approach. Under the joint mentorship of leading translational researchers Drs. Kevin Staley, Sydney Cash and Steven Stufflebeam at MGH, Dr. Chu proposes to first evaluate children with BECTS with active epilepsy and in remission in a cross-sectional study to identify candidate cortical biomarkers for seizure risk using advanced EEG and MRI techniques. She will then assess the utility of adding longitudinal data to the predictive models by re-studying th subjects in the cross sectional dataset one year after initial evaluation. The knowledge gained by these studies will lead to: 1) quantification of the physiological and anatomical processes associated with increased seizure risk in childhood epilepsy; 2) identification of candidate biomarkers of seizure risk which may have broader relevance to other epilepsies; 3) the development of novel tools and advanced expertise to identify and quantify these processes; and 4) preliminary data for an R01-funded clinical trial to test non- invasive biomarkers of seizure risk in childhood epilepsy. The career development program outlined in this proposal provides the candidate with advanced training in multimodal imaging techniques, prospective clinical research, and biostatistics in an outstanding training environment. The expertise that she will develop will position her for a productive independent career in patient-oriented research in which she can focus advanced imaging technologies to address pressing and clinically relevant questions in pediatric epilepsy.

Public Health Relevance

Benign epilepsy with Centro temporal spikes (BECTS) is the most common childhood epilepsy syndrome, accounting for 20% of all childhood epilepsy and characterized by a period of seizure susceptibility of uncertain duration in school-age children. Despite extensive clinical experience, it remains a challenge to determine which children will benefit from antiepileptic drug treatment and for how long. This project aims to identify cortical biomarkers that will aid in predicting and monitoring ongoing seizure risk in children with BECTS in order to avoid the unnecessary consequences of over- or under-medication during critical years of cognitive, psychosocial and behavioral maturation in this large cohort of children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS092923-02
Application #
9133481
Study Section
NST-2 Subcommittee (NST)
Program Officer
Whittemore, Vicky R
Project Start
2015-09-01
Project End
2020-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
Berg, Anne T; Chakravorty, Samya; Koh, Sookyong et al. (2018) Why West? Comparisons of clinical, genetic and molecular features of infants with and without spasms. PLoS One 13:e0193599
Grinspan, Zachary M; Shellhaas, Renée A; Coryell, Jason et al. (2018) Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy. JAMA Pediatr 172:352-360
Shellhaas, Renée A; Wusthoff, Courtney J; Tsuchida, Tammy N et al. (2017) Profile of neonatal epilepsies: Characteristics of a prospective US cohort. Neurology 89:893-899
Shellhaas, Renée A; Berg, Anne T; Grinspan, Zachary M et al. (2017) Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus. Pediatr Neurol 75:73-79
Sidorov, Michael S; Deck, Gina M; Dolatshahi, Marjan et al. (2017) Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis. J Neurodev Disord 9:17
Herlopian, Aline; Rosenthal, Eric S; Chu, Catherine J et al. (2017) Extreme delta brush evolving into status epilepticus in a patient with anti-NMDA encephalitis. Epilepsy Behav Case Rep 7:69-71
Edlow, Brian L; Chatelle, Camille; Spencer, Camille A et al. (2017) Early detection of consciousness in patients with acute severe traumatic brain injury. Brain 140:2399-2414
Demarest, Scott T; Shellhaas, Renée A; Gaillard, William D et al. (2017) The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia 58:2098-2103
Glass, Hannah C; Shellhaas, Renée A; Tsuchida, Tammy N et al. (2017) Seizures in Preterm Neonates: A Multicenter Observational Cohort Study. Pediatr Neurol 72:19-24
Chu, Catherine J; Chan, Arthur; Song, Dan et al. (2017) A semi-automated method for rapid detection of ripple events on interictal voltage discharges in the scalp electroencephalogram. J Neurosci Methods 277:46-55

Showing the most recent 10 out of 19 publications