Evidence map›Paper›PMID 32583883›Full record

ArticleAnnals of neurology2020

Anti-migraine Calcitonin Gene-Related Peptide Receptor Antagonists Worsen Cerebral Ischemic Outcome in Mice.

Inge A Mulder, Mei Li, Tessa de Vries, Tao Qin, Takeshi Yanagisawa, Kazutaka Sugimoto, Antoon van den Bogaerdt, A H Jan Danser, Marieke J H Wermer, Arn M J M van den Maagdenberg and 3 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05365880 (Sphenopalatine Ganglion Block for the Treatment of Post-Stroke Headache), which is not on this map. Cited by 65 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 3 pooled it
10.3field-weighted citation impact, top 1% 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.

NCT05365880 phase2withdrawnnot on this mapstarted 2022, after this paper: background citation

Sphenopalatine Ganglion Block for the Treatment of Post-Stroke Headache

TypeinterventionalSponsorUniversity of UtahRan2022 to 2025Enrolled0ConditionsHeadache, Stroke, Ischemic StrokeArmsLiquid Lidocaine, Placebo
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 3 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Pooled it
  4. Trial
  5. Article
  6. Headache Attributed to Genetic Vasculopathies.Current pain and headache reports · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Observational
  12. Article
  13. Article
  14. Article
  15. Review
  16. Headache After Stroke: An Update for the Clinician.Current neurology and neuroscience reports · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Article

5 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 3 countries.

Inge A MulderDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-6609-2206
Mei LiDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tessa de VriesDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Tao QinDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Takeshi YanagisawaDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kazutaka SugimotoDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-7666-2620
Antoon van den BogaerdtETB-BISLIFE, Heart Valve Bank, Beverwijk, the Netherlands.
A H Jan DanserDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Marieke J H WermerDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Arn M J M van den MaagdenbergDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Antoinette MaassenVanDenBrinkDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Michel D FerrariDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Cenk AyataDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USErasmus MC · NLLeiden University Medical Center · NLValve (United States) · US

Funding

Targeting ROCK for Neurogliovascular Plasticity & Remodeling After StrokeP01NS055104 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2007 to 2018
$13.3M
Non-invasive vagus nerve stimulation targeting cortical spreading depression in migrane prophylaxisR01NS102969 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI AYATA, CENK · 2017 to 2021
$1.9M
NINDS NIH HHS P01 NS055104NINDS NIH HHS R01 NS102969
6 · The paper itself

Abstract

objectiveCalcitonin gene-related peptide (CGRP) pathway inhibitors are emerging treatments for migraine. CGRP-mediated vasodilation is, however, a critical rescue mechanism in ischemia. We, therefore, investigated whether gepants, small molecule CGRP receptor antagonists, worsen cerebral ischemia.

methodsMiddle cerebral artery was occluded for 12 to 60 minutes in mice. We compared infarct risk and volumes, collateral flow, and neurological deficits after pretreatment with olcegepant (single or 10 daily doses of 0.1-1mg/kg) or rimegepant (single doses of 10-100mg/kg) versus vehicle. We also determined their potency on CGRP-induced relaxations in mouse and human vessels, in vitro.

resultsOlcegepant (1mg/kg, single dose) increased infarct risk after 12- to 20-minute occlusions mimicking transient ischemic attacks (14/19 vs 6/18 with vehicle, relative risk = 2.21, p < 0.022), and doubled infarct volumes (p < 0.001) and worsened neurological deficits (median score = 9 vs 5 with vehicle, p = 0.008) after 60-minute occlusion. Ten daily doses of 0.1 to 1mg/kg olcegepant yielded similar results. Rimegepant 10mg/kg increased infarct volumes by 60% after 20-minute ischemia (p = 0.03); 100mg/kg caused 75% mortality after 60-minute occlusion. In familial hemiplegic migraine type 1 mice, olcegepant 1mg/kg increased infarct size after 30-minute occlusion (1.6-fold, p = 0.017). Both gepants consistently diminished collateral flow and reduced reperfusion success. Olcegepant was 10-fold more potent than rimegepant on CGRP-induced relaxations in mouse aorta.

interpretationGepants worsened ischemic stroke in mice via collateral dysfunction. CGRP pathway blockers might thus aggravate coincidental cerebral ischemic events. The cerebrovascular safety of these agents must therefore be better delineated, especially in patients at increased risk of ischemic events or on prophylactic CGRP inhibition. ANN NEUROL 2020;88:771-784.

Indexed as

Brain IschemiaAnimalsArteriesCalcitonin Gene-Related PeptideCalcitonin Gene-Related Peptide Receptor AntagonistsDipeptidesHumansMicePiperazinesPiperidinesPyridinesQuinazolinesVasodilationCalcitonin Gene-Related PeptideCalcitonin Gene-Related Peptide Receptor AntagonistsDipeptidesolcegepantPiperazinesPiperidinesPyridinesQuinazolinesrimegepant sulfate

Identifiers

PMID32583883
PMCPMC7540520
OpenAlexW3037111965

What OpenQuestion holds

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LicenceCC BY-NC
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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.