# Prospective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study

**Authors:** Richard Robert Riker, Haley R Torr, Sara Penrod, Stephanie C Chan, Angela Leclerc, Teresa L May, David B Seder, David J Gagnon

PMC · DOI: 10.21203/rs.3.rs-8744330/v1 · Research Square · 2026-02-10

## TL;DR

This study evaluates the use of amantadine for nontraumatic brain injuries in ICU patients, showing it is feasible and potentially effective.

## Contribution

The study introduces a pragmatic observational approach to assess amantadine's effectiveness in nontraumatic acute brain injury patients.

## Key findings

- Amantadine treatment showed a 90% response rate in patients with adequate treatment trials.
- Responders had a significant increase in CRS-R scores after treatment.
- Most treated patients were discharged to rehabilitation or skilled nursing facilities.

## Abstract

Amantadine, an effective neurostimulant for traumatic brain injury, has limited data supporting its use for other acute brain injuries (ABI). This pragmatic study evaluated amantadine for nontraumatic ABI monitored in the ICU with the Coma Recovery Scale-Revised (CRS-R).

This prospective open-label cohort study developed a protocol to treat impaired consciousness after ABI with amantadine, assessing participants with CRS-R as 0–100 Rasch units, monitoring feasibility, safety, and effectiveness.

40 patients (age 64 [52–73] years, 25 [62%] female) were included during this protocol development phase: 13 ischemic stroke, 10 intracerebral hemorrhage, 7 subarachnoid hemorrhage, 4 hypoxic-ischemic encephalopathy, 3 other ABI. The median baseline CRS-R was 11 (IQR 7–16), including 16 meeting criteria for Disorder of Consciousness. Among 30 participants with an adequate amantadine treatment trial, 27 (90%) responded, with disposition to home (1,4%), skilled nursing facility (6,22%), acute inpatient rehabilitation (15,56%), or withdrawal of life support (5,18%). Pre- versus post-treatment CRS-R increased for responders by 8 (6–11), equivalent to 26 (15–45) Rasch units. Among 10 untreated or inadequate trial patients, 3 (30%) were discharged to rehab, 7 (70%) had support withdrawn.

It is feasible to measure responsiveness to amantadine using the CRS-R for ICU patients with ABI.

## Linked entities

- **Chemicals:** amantadine (PubChem CID 2130)
- **Diseases:** traumatic brain injury (MONDO:0858950), ischemic stroke (MONDO:1060198), intracerebral hemorrhage (MONDO:0013792), subarachnoid hemorrhage (MONDO:0005099), hypoxic-ischemic encephalopathy (MONDO:0006663)

## Full-text entities

- **Diseases:** paroxysmal sympathetic hyperactivity (MESH:D006948), AIS (MESH:D000083242), Seizures (MESH:D012640), intraventricular hemorrhage (MESH:D000074042), hypoxic (MESH:D002534), unresponsive wakefulness syndrome (MESH:C567934), ICH (MESH:D020300), Stroke (MESH:D020521), hyperactive delirium (MESH:D003693), ischemic encephalopathy (MESH:D002545), West Nile (MESH:D014901), sleeplessness (MESH:D007319), infectious encephalitis (MESH:D000069544), cardiac arrest (MESH:D006323), traumatic brain injury (MESH:D000070642), Parkinson's disease (MESH:D010300), hypoxic-ischemic encephalopathy (MESH:D020925), Powassan virus encephalitis (MESH:D004675), brain tumor (MESH:D001932), sepsis (MESH:D018805), HIE (MESH:D007589), cognitive linguistic disorder (MESH:D003072), CRS-R (MESH:D003128), renal dysfunction (MESH:D007674), Eastern (MESH:D020242), valproic acid (MESH:C536525), post (MESH:D000094025), ischemic stroke (MESH:D002544), Agitation (MESH:D011595), Encephalitis (MESH:D004660), aphasia (MESH:D001037), toxicity (MESH:D064420), SAH (MESH:D013345), intracerebral hemorrhage (MESH:D002543), Disorder of Consciousness (MESH:D003244), ABI (MESH:D001930), encephalopathy (MESH:D001927), death (MESH:D003643), myoclonus (MESH:D009207)
- **Chemicals:** Amantadine (MESH:D000547), Creatinine (MESH:D003404), CRS-R (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12919211/full.md

## References

18 references — full list in the complete paper: https://tomesphere.com/paper/PMC12919211/full.md

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Source: https://tomesphere.com/paper/PMC12919211