# Research 2-Carlson

> **NIH NIH P20** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2022 · $260,835

## Abstract

PROJECT SUMMARY/ ABSTRACT
Chronic Subdural Hematoma (cSDH) is an extremely common problem, particularly in the aging population,
where fluid like collections compress the brain, frequently requiring surgical drainage. After drainage, 25-50%
of patients experience post operative neurologic deficits such as weakness or confusion that are often not
explained by problems such as seizure, stroke, or mass effect from the fluid and blood. Recent subdural
recordings have demonstrated that some of these neurological deficits may be related to waves of spreading
depolarization (SD), which cause temporary neurological dysfunction. There is a fundamental gap in
knowledge as to how commonly such events are related to neurologic deficits and if they could be targeted
with pharmacotherapy to improve outcomes. This knowledge gap represents an important problem because
cSDH is expected to be the most common condition treated by neurosurgeons by 2030 and postoperative
neurological deficits in elderly patients can have a significant impact on outcomes and secondary risks such as
pneumonia and delayed mobilization. Our long-term goal is to develop effective treatments to improve recovery
in these patients by targeting SD. The overall objective of this application is to examine the relationship
between neurological deficits and SD and to assess feasibility of a pilot trial to determine if a strategy of
NMDA-R antagonism can effectively reduce SD and improve clinical recovery. We also plan to study detailed
neuropsychiatric outcomes and if these are worse in patients with SD. The central hypothesis is that SD plays
a causal role in some neurologic deficits after cSDH drainage. This hypothesis is based on our preliminary data
where SD was observed in 15% of such patients. In one case, repeated waves of SD were exactly time locked
to development of new language deficit. Guided by this promising preliminary data, we plan to rigorously
examine the relationship between SD and neurologic deficits after cSDH drainage in additional subjects (Aim
#1). We will then determine feasibility of performing a randomized trial to test if a strategy of NMDA-R
antagonism with a brief course of memantine effectively reduces SD and improves neurologic function (Aim
#2). Finally, we will determine the time course of neuropsychiatric recovery after cSDH evacuation at day 30,
90, and 180 and assess if this is worse in patients with SD (Aim#3). We expect that these studies will provide
exciting new therapeutic approaches for a previously unrecognized pathophysiology in a very common
problem. These data will provide the necessary groundwork for larger pivotal trials to test efficacy of such a
targeted, physiology based approach.

## Key facts

- **NIH application ID:** 10468697
- **Project number:** 5P20GM109089-08
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Andrew Phillip Carlson
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $260,835
- **Award type:** 5
- **Project period:** 2015-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468697

## Citation

> US National Institutes of Health, RePORTER application 10468697, Research 2-Carlson (5P20GM109089-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10468697. Licensed CC0.

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