Evidence map›Paper›PMID 38552890›Full record

ArticleJournal of stroke and cerebrovascular diseases : the official journal of National Stroke Association2024

Pathologic features of brain hemorrhage after radiation treatment: case series with somatic mutation analysis.

Roberto J Alcazar-Felix, Abhinav Srinath, Stephanie Hage, Akash Bindal, Andrew Ressler, Peter Pytel, Sammy Allaw, Romuald Girard, Douglas A Marchuk, Issam A Awad and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 23% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. The Role of the Microbiome and the Neurovascular Unit.The Surgical clinics of North America · 2025
    Review
  3. 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

11 authors at 2 institutions in 1 country.

Roberto J Alcazar-FelixDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Abhinav SrinathDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Stephanie HageDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Akash BindalDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Andrew ResslerMolecular Genetics and Microbiology Department, Duke University Medical Center, USA.
Peter PytelDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Sammy AllawDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Romuald GirardDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Douglas A MarchukMolecular Genetics and Microbiology Department, Duke University Medical Center, USA.
Issam A AwadDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA.
Sean P PolsterDepartment of Neurosurgery, Biological Sciences Division, University of Chicago, USA. Electronic address: spolster@uchicago.edu.
University of Chicago · USDuke University · US

Funding

Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)T32HD007009 · NICHD · UNIVERSITY OF CHICAGO · PI NANCY B SCHWARTZ · 1985 to 2026
$13.0M
Neurosurgeon Research Career Development Program (NRCDP)K12NS129164 · NINDS · WASHINGTON UNIVERSITY · PI Sepideh Amin-Hanjani, Emad N Eskandar · 2023 to 2026
$6.7M
NICHD NIH HHS T32 HD007009NINDS NIH HHS K12 NS129164
6 · The paper itself

Abstract

backgroundRadiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations.

methodsWe retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies.

resultsOne lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes.

conclusionsDespite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

Indexed as

MutationRadiation InjuriesAdultBiopsyCerebral HemorrhageClass I Phosphatidylinositol 3-KinasesCranial IrradiationDatabases, FactualDNA Mutational AnalysisFemaleGenetic Predisposition to DiseaseHigh-Throughput Nucleotide SequencingHumansIntracranial Arteriovenous MalformationsIntracranial HemorrhagesMaleClass I Phosphatidylinositol 3-KinasesPIK3CA protein, humanPTEN PhosphohydrolasePTEN protein, humanAdverse radiation effectsCase seriesHemorrhageMutationStereotactic radiosurgery

Identifiers

PMID38552890
PMCPMC11299161
OpenAlexW4393238330

What OpenQuestion holds

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Registered trials

None linked

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.