# GENETICS OF EARLY NEUROLOGICAL INSTABILITY AFTER ISCHEMIC STROKE (GENISIS)

> **NIH NIH K23** · WASHINGTON UNIVERSITY · 2020 · $180,727

## Abstract

Stroke is the 2nd leading cause of death throughout the world, and the leading cause of long-term disability.
Ischemic stroke, the most common subtype, is caused by occlusion of an artery in the brain, resulting in the
abrupt development of neurological deficits. In the first hours after stroke onset, neurological deficits can
be highly unstable, with many patients improving while others deteriorate. These early changes have a
major impact on long-term outcome. In fact, changes in neurologic deficits during the first 24 hours account for
40% of the variance of the 90-day modified Rankin Scale (the most widely accepted stroke outcome measure)
in patients treated with tissue plasminogen activator (tPA). In my preliminary analyses, it was discovered that
baseline clinical factors account for very little of the variation seen in neurologic deficits during the first 24
hours while genetic factors appear to account for over 50%. Given the finding that genetics influence the
variance of early neurologic changes, it is my central hypothesis that genetics play a significant role in
determining the early outcomes experienced by patients suffering from acute ischemic stroke (AIS).
 As a fellowship-trained emergency physician subspecializing in neurologic emergencies, my long term
goal is to develop an independent research program to investigate genetic influences on acute
neurological emergencies to improve patient outcomes. In order to achieve this goal, I have developed
two short term goals that will be achieved during the award period: 1) to become technically proficient in
genetic/genomic analysis and research methodology and 2) to develop greater familiarity with cellular
and molecular mechanisms involved with brain and neurovascular injury following AIS. In order to
achieve these goals, I have crafted a multidisciplinary team of mentors, advisors and collaborators. Over the
past several years, I have been working closely with my primary mentor, Dr. Jin-Moo Lee (Director of the
Cerebrovascular Disease and Neurointensive Care Sections in Neurology) and my secondary mentor Dr.
Carlos Cruchaga (a human geneticist with expertise in complex genetic analyses), to examine possible genetic
influences on the early neurologic outcomes after acute ischemic stroke. They both have a strong track record
of mentoring junior investigators and bring complimentary backgrounds and expertise to my mentoring and
career development.
 Under the guidance of Drs. Jin-Moo Lee and Carlos Cruchaga, I will engage in structured coursework,
advanced training and independent study to become proficient in patient-oriented research, genetic analysis,
and research methodology. To capture early neurological change following AIS, we have developed a novel
quantitative endophenotype, termed ΔNIHSS24h, which is a measure of the change in NIH stroke scale
(NIHSS) score between baseline (<6 hours after onset) and 24 hours. Using a cohort of AIS patients treated
with IV tPA that will consist o...

## Key facts

- **NIH application ID:** 9840948
- **Project number:** 5K23NS099487-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Laura Heitsch
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $180,727
- **Award type:** 5
- **Project period:** 2017-01-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840948

## Citation

> US National Institutes of Health, RePORTER application 9840948, GENETICS OF EARLY NEUROLOGICAL INSTABILITY AFTER ISCHEMIC STROKE (GENISIS) (5K23NS099487-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9840948. Licensed CC0.

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