This application entitled Circadian Dysfunction, Encephalopathy, and Cognitive Outcomes after Critical Illness is being submitted by Dr. Matthew Maas for a Mentored Patient-Oriented Research Career Development Award. The circadian rhythm is a brain-controlled pattern of neurologic and hormonal signals that influence alertness, sleep, metabolism, body temperature, immune system activity, and other fundamental body functions that maintain homeostasis and health. Research over the last several years has shown that basic cellular health in the brain is negatively affected when the circadian rhythm is abnormal. Moreover, there is evidence that disruption of the circadian rhythm is common and severe in critically ill patients. Critically ill patients suffer inordinate risk of encephalopathy a condition of generalized brain dysfunction that can range in severity from mild to severe (coma), and those patients who develop encephalopathy are at increased risk of death or poor cognitive function for months or years after their illness. Neither the impact of circadian disruption during clinical illness nor the underlying causes of encephalopathy are well understood. This proposal will investigate whether disruption of the circadian rhythm is linked to the risk of encephalopathy and poor cognitive outcomes in critically ill patients. To accomplish this task, we will utilize methods that have been used to study circadian function in healthy patients, including non-invasive electrical recording of brain activity and blood samples to detect the level of the brain hormone melatonin, and combine them with critical care research methods for assessing encephalopathy and cognitive outcomes. Establishing whether a true association exists between these phenomena will allow us to develop strategies to prevent or treat circadian dysfunction with the goal of improving outcomes for severely ill patients. Dr. Maas is a neurologist and critical care specialist now appointed as an Assistant Professor of Neurology and Anesthesiology at Northwestern University. His overarching career goal is to improve the outcome of neurologic injuries in critically ill patients. His clinical training and prior experienes with patient-oriented research make him an ideal candidate to carry out this cross-disciplinary research. He will be supported by a team of experienced investigators with complementary expertise. Dr. Phyllis Zee, his primary mentor, is an expert in the field of circadian biology. Drs Andrew Naidech and Shyam Prabhakaran are accomplished researchers who study complications that affect outcomes for severely ill patients with neurologic injury. This award is mentored program designed to combine the experience of conducting this study with a career development plan for Dr. Maas. The training program will help him build his knowledge base around the science of circadian biology, methods used by neuroscientists to monitor brain function, study design, biostatistics, and other clinical research skills, with the goal the he wil become a productive independent clinical researcher.

Public Health Relevance

Critically ill patients often develop abnormal brain function, from slight confusion to coma, leading to an increased risk of death and worse cognitive outcomes for survivors. The circadian rhythm, a brain-controlled pattern of neurologic and hormonal signals that maintains healthy neural function, has also been found to be abnormal in very sick patients. This study seeks to determine whether abnormal circadian function is associated with altered mental status during critical illness and worse cognitive function after hospitalization by measuring a blood marker of the circadian rhythm, brain electrical activity measurements, and clinical mental status assessments.

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 #
1K23NS092975-01
Application #
8949498
Study Section
NST-2 Subcommittee (NST)
Program Officer
He, Janet
Project Start
2015-07-01
Project End
2020-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Naidech, Andrew M; Beaumont, Jennifer; Muldoon, Kathryn et al. (2018) Prophylactic Seizure Medication and Health-Related Quality of Life After Intracerebral Hemorrhage. Crit Care Med 46:1480-1485
Maas, Matthew B; Naidech, Andrew M; Kim, Minjee et al. (2018) Medication History versus Point-of-Care Platelet Activity Testing in Patients with Intracerebral Hemorrhage. J Stroke Cerebrovasc Dis 27:1167-1173
Maas, Matthew B (2018) Ecological Validity in the Critical Care Environment: Closing the Loop on Evidence Based Medicine. Respir Care 63:119-120
Liotta, Eric Michael; Romanova, Anna L; Lizza, Bryan D et al. (2018) Osmotic Shifts, Cerebral Edema, and Neurologic Deterioration in Severe Hepatic Encephalopathy. Crit Care Med 46:280-289
Rosenthal, Lisa J; Francis, Brandon A; Beaumont, Jennifer L et al. (2017) Agitation, Delirium, and Cognitive Outcomes in Intracerebral Hemorrhage. Psychosomatics 58:19-27
Maas, Matthew B; Francis, Brandon A; Sangha, Rajbeer S et al. (2017) Refining Prognosis for Intracerebral Hemorrhage by Early Reassessment. Cerebrovasc Dis 43:110-116
Ruff, Ilana M; Liberman, Ava L; Caprio, Fan Z et al. (2017) A resident boot camp for reducing door-to-needle times at academic medical centers. Neurol Clin Pract 7:237-245
Liotta, Eric M; Prabhakaran, Shyam; Sangha, Rajbeer S et al. (2017) Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage. Neurology 89:813-819
Fan, Emily P; Abbott, Sabra M; Reid, Kathryn J et al. (2017) Abnormal environmental light exposure in the intensive care environment. J Crit Care 40:11-14
Liotta, Eric M; Lizza, Bryan D; Romanova, Anna L et al. (2016) 23.4% Saline Decreases Brain Tissue Volume in Severe Hepatic Encephalopathy as Assessed by a Quantitative CT Marker. Crit Care Med 44:171-9