Evidence map›Paper›PMID 34054569›Full record

ArticleFrontiers in physiology2021

Cerebrovascular Reactivity Measures Are Associated With Post-traumatic Headache Severity in Chronic TBI; A Retrospective Analysis.

Franck Amyot, Cillian E Lynch, John Ollinger, J Kent Werner, E Silverman, Carol Moore, Cora Davis, L Christine Turtzo, Ramon Diaz-Arrastia, Kimbra Kenney

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Frontiers in physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01762475 (Sildenafil for the Treatment of Cerebrovascular Dysfunction During the Chronic Stage After Traumatic Brain Injury.), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01762475 phase2completednot on this map

Sildenafil for the Treatment of Cerebrovascular Dysfunction During the Chronic Stage After Traumatic Brain Injury.

TypeinterventionalSponsorUniformed Services University of the Health SciencesRan2013 to 2015Enrolled59ConditionsTraumatic Brain Injury, Post-concussive SyndromeArmsSildenafil
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. Alterations of cerebrovascular reactivity following pediatric mild traumatic brain injury are independent of neurodevelopmental changes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Franck AmyotNational Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States.
Cillian E LynchDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
John OllingerNational Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States.
J Kent WernerDepartment of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
E SilvermanDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Carol MooreDepartment of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Cora DavisNational Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States.
L Christine TurtzoNational Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Ramon Diaz-ArrastiaDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Kimbra KenneyNational Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States.
Uniformed Services University of the Health Sciences · USUniversity of Pennsylvania · USWalter Reed National Military Medical Center · USNational Institutes of Health · US

Funding

Transforming Research and Clinical Knowledge in Traumatic Brain InjuryU01NS086090 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DIAZ-ARRASTIA, RAMON, GIACINO, JOSEPH THOMAS · 2013 to 2017
$19.1M
NINDS NIH HHS U01 NS086090
6 · The paper itself

Abstract

objectiveTo characterize the relationship between persistent post-traumatic headache (pPTH) and traumatic cerebrovascular injury (TCVI) in chronic traumatic brain injury (TBI). Cerebrovascular reactivity (CVR), a measure of the cerebral microvasculature and endothelial cell function, is altered both in individuals with chronic TBI and migraine headache disorder (Amyot et al., 2017; Lee et al., 2019b). The pathophysiologies of pPTH and migraine are believed to be associated with chronic microvascular dysfunction. We therefore hypothesize that TCVI may contribute to the underlying migraine-like mechanism(s) of pPTH. MATERIALS AND

methods22 moderate/severe TBI participants in the chronic stage (>6 months) underwent anatomic and functional magnetic resonance imaging (fMRI) scanning with hypercapnia gas challenge to measure CVR as well as the change in CVR (ΔCVR) after single-dose treatment of a specific phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, which potentiates vasodilation in response to hypercapnia in impaired endothelium, as part of a Phase2a RCT of sildenafil in chronic TBI (NCT01762475). CVR and ΔCVR measures of each participant were compared with the individual's pPTH severity measured by the headache impact test-6 (HIT-6) survey.

resultsThere was a moderate correlation between HIT-6 and both CVR and ΔCVR scores [Spearman's correlation = -0.50 (

conclusionThere is a correlation between PTH and CVR in chronic moderate-severe TBI. This relationship suggests that chronic TCVI may underlie the pathobiology of pPTH. Further, our results suggest that novel treatment strategies that target endothelial function and vascular health may be beneficial in refractory pPTH.

Indexed as

cerebrovascular reactivitychronicmigrainepost-traumatic headachetraumatic brain injury

Identifiers

PMID34054569
PMCPMC8155500
OpenAlexW3162320819

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.