Mark Stewart, MD, PhD

Seizure activity in the limbic cortices and its spread through brain to impact systemic physiology

We use a number of approaches to address questions about how seizures can occur, how they spread through cortical and sub-cortical brain areas, and what the ultimate impact on the other body organs may be. The most serious consequence is sudden death.

Our main research focus has been the causes and consequences of seizure activity. One approach uses in vitro methods (brain slices, dissociated neurons) to study cellular and circuit mechanisms of seizure generation, and a second approach uses in vivo methods (animals, human subjects, human cases) to study seizure spread and systemic consequences of seizures.

We use multiple animal models, including a rat model that mirrors features of seizures and systemic pathology found in temporal lobe epilepsy patients. This model has permitted us to define many of the autonomic, cardiovascular, and respiratory consequences of acute and chronic seizures.  In particular, we have defined the mechanism for sudden death in epilepsy (SUDEP) as a consequence of seizure-induced laryngospasm sufficient to cause obstructive apnea, which lasts to the point of respiratory arrest.

Our work has enabled the development of tools and strategies to prevent death. In addition to biomarkers that can be used to signal the “death sequence” has started, we have derived other interventional devices from our work.  These devices are examples of practical therapeutic applications as one means for translating research from bench to bedside.

Personnel

Rena Orman, Ph.D., Research Assistant Professor

Service Functions

Co-director, Program in Nanomedicine (a joint program with the College of Nanoscale Science and Engineering, Albany, NY)

Co-director, Program in Developmental Neuroscience (a joint program with the Institute for Basic Research, Staten Island, NY)

• Nakase, K., Kollmar, R., Lazar, J., Arjomandi, H., Sundaram, K., Silverman, J., Orman, R., Weedon, J., Stefanov, D., Savoca, E., Tordjman, L., Stiles, K., Ihsan, M., Nunez, A., Guzman, L., and Stewart, M. (2016). Laryngospasm, central and obstructive apnea during seizures: defining pathophysiology for sudden death in a rat model. Epilepsy Res. 128, 126-139.
• Stewart, M., and Goodman, J. (2017). Monitoring cardiorespiratory and other physiological parameters during seizures in small animals. In: Models of Seizure and Epilepsy, Second Ed. A. Pitkänen, P. Buckmaster, A. S. Galanopoulou, and S. M. Moshe, eds. Elsevier, Chapter 12, pp. 161-179. 2017.
• Villiere, S., Nakase, K., Kollmar, R., Silverman, J., Sundaram, K., and Stewart, M. (2017). Seizure-associated central apnea in a rat model: evidence for resetting the respiratory rhythm and activation of the diving reflex. Neurobiol. Dis. 101, 8-15.
• Stewart, M., Kollmar, R., Nakase, K., Silverman, J., Sundaram, K., Orman, R., and Lazar, J. (2017). Obstructive apnea due to laryngospasm links ictal to postictal events in SUDEP cases and offers practical biomarkers for review of past cases and prevention of new ones. Epilepsia 58(6):e87-e90..
• Stewart, M. (2018). An explanation for sudden death in epilepsy (SUDEP). J Physiol. Sci. 68, 307-320.
• Villiere, S., Nakase, K., Kollmar, R., Arjomandi, H., Lazar, J., Sundaram, K., Silverman, J. B., Lucchesi, M., Wlody, D., and Stewart, M. A (2018) Resuscitation option for upper airway occlusion based on bolus transtracheal lung inflation. Laryngoscope Investig. Otolaryngol. 9, 296-303.
• Mooney, S., Chin, B., Villiere, S., Nakase, K., Kollma,r R., Kim, S., Sundaram, K., Silverman, J. B., Lazar, J., and Stewart, M (2019). Diving responses elicited by nasopharyngeal irrigation mimic seizure-associated central apneic episodes in a rat model. Neurobiol. Dis.124, 408-415.
• Mooney, S., Kollmar, R., Gurevich, R., Tromblee, J., Banerjee, A., Sundaram, K., Silverman, J. B., and Stewart, M. (2020) An oxygen-rich atmosphere or systemic fluoxetine extend the time to respiratory arrest in a rat model of obstructive apnea. Neurobiol. Dis. 134, 104682.
• Irizarry, R., Sukato, D., Kollmar, R., Schild, S., Silverman, J., Sundaram, K., Stephenson, S., and Stewart, M. (2020) Seizures induce obstructive apnea in DBA/2J audiogenic seizure-prone mice: Lifesaving impact of tracheal implants. Epilepsia doi: 10.1111/epi.16431. [Epub ahead of print]

List of Publications (Pub Med)