# Redefining Chiari Type I Malformation and its Impact on Brain Development

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2024 · $1,508,020

## Abstract

PROJECT SUMMARY
Overall: Abstract
Since its original description by Hans Chiari in the 1890s, Chiari type I malformation (CM) has been defined as
caudal displacement (ectopia) of the cerebellar tonsils below the foramen magnum. This definition oversimplifies
the complex range of craniovertebral junction pathology affecting more than 1% of the population and has little
relevance to the neurological effects of CM. However, current clinical practice continues to rely heavily on this
oversimplified and outdated definition of CM, with most management decisions based on a single, static 2D
sagittal MRI image, failing to consider the dynamic pathophysiology at the interface of the cerebellum, brainstem,
and spinal cord. Investigations from our group and others implicate a hyperdynamic pathophysiological state in
CM, with turbulent CSF flow patterns, exaggerated pulsatile motion of the tonsils and brainstem, and dysfunction
or injury to the cerebellum, brainstem, or spinal cord. The relationship of these changes at the CVJ to patient
experience (pain and/or neurological deficits), cognitive or behavioral outcome, and CM-associated
syringomyelia (SM, spinal cord cavitation), remains unclear and under-investigated.
The Park-Reeves Chiari & Syringomyelia Center (PRCSC) at Washington University was established in 2011
and has become the international leader and vibrant focal point for research into CM. The Overarching Theme
of this PRCSC Program Project Proposal is “Redefining Chiari Type I Malformation and its Impact on
Neurological Outcome.” This proposal will leverage key strengths and scientific advances at Washington
University to investigate the largest and most refined cohort of CM patients in the world. Four Cores
[Administrative (AC), Clinical (CC), Genetic (GC), and Radiology (RC) Cores] will support 4 Projects: Genetic
Underpinnings of CM and Effect on Brain Development [Haller, Project Lead (PL); Solnica-Krezel, Co-Lead (CL)];
Functional Connectivity, Brain Development, and Outcomes in CM [Dosenbach, PL; Roland and Marek, CL];
CSF-Mediated Pathophysiology and Microstructural Injury Determines Outcomes in CM [Strahle, PL; Song, CL];
and Redefining CM Using Genotype-Phenotype Relationships and Impact on Outcome [Limbrick, PL; Greenberg
and Lu, CL]. Although these Cores and Projects each address unique Specific Aims, they will generate a wealth
of multidimensional data from PRCSC participants to permit a cohesive, synergistic, and comprehensive
examination of the overarching Aims of this application. Indeed, PRCSC as a whole is much greater than the
sum of its Cores and Projects.
 Overall Specific Aim 1. Determine the genetic factors contributing to CM, brain development, and
 neurological function.
 Overall Specific Aim 2. Determine the pathophysiological basis for CM-related neurological effects.
 Overall Specific Aim 3: Create a novel CM framework to enhance treatment response and outcomes.

## Key facts

- **NIH application ID:** 10876257
- **Project number:** 5P01NS131131-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** David Delmar Limbrick
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,508,020
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876257

## Citation

> US National Institutes of Health, RePORTER application 10876257, Redefining Chiari Type I Malformation and its Impact on Brain Development (5P01NS131131-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10876257. Licensed CC0.

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