Evidence map›Paper›PMID 39910686›Full record

ArticleActa neuropathologica communications2025

Clinical, genomic, and histopathologic diversity in cerebral cavernous malformations.

Jian Ren, Daochao Wang, Leiming Wang, Chendan Jiang, An Tian, Ziwei Cui, Yeqing Ren, Lisong Bian, Gao Zeng, Guolu Meng and 20 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

30 authors.

Jian Ren *Department of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Daochao Wang *Department of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Leiming WangDepartment of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Chendan JiangDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
An TianDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Ziwei CuiDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Yeqing RenDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Lisong BianDepartment of Neurosurgery, Beijing Haidian Hospital, Beijing, China.
Gao ZengDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Guolu MengDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Yongzhi ShanDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Jiantao LiangDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Xinru XiaoDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Jie TangDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Yukui WeiDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Chuan HeDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Liyong SunDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Yongjie MaDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Jiaxing YuDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Guilin LiDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Ming YeDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Peng HuDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Jingwei LiDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Ye LiDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Lijian NiuDepartment of Neurosurgery, Beijing Fengtai YouAnMen Hospital, Beijing, China.
Qianwen LiDepartment of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Feng LingDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China.
Jan-Karl BurkhardtDepartment of Neurosurgery, Perelman School of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA.
Hongqi ZhangDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China. xwzhanghq@163.com.
Tao HongDepartment of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, No. 45 Changchun Street, Xicheng District, 100053, Beijing, China. hongtao.edu@gmail.com.

Funding

Beijing Municipal Science and Technology Commission Z201100005520024National Natural Science Foundation of China 82220108010National Natural Science Foundation of China 82425020, 82330038, 82122020, 81971104National Natural Science Foundation of China 82471325, 82201440
6 · The paper itself

Abstract

Cerebral cavernous malformations (CCMs) are hemorrhagic vascular disorders with varied clinical and radiological presentations, occurring sporadically due to MAP3K3 or PIK3CA mutations or through inherited germline mutations of CCM genes. This study aimed to clarify the clinical, genetic, and pathological features of CCMs using a multicenter cohort across three Chinese centers. We analyzed 290 surgical specimens from symptomatic CCM patients, utilizing whole-exome sequencing, droplet digital PCR, and targeted panel sequencing, alongside immunohistology to examine genotypic and phenotypic differences. Among 290 cases, 201 had somatic MAP3K3, PIK3CA, or germline CCM mutations, each associated with distinct clinical parameters: hemorrhage risk (P < 0.001), lesion size (P = 0.019), non-hemorrhagic epilepsy (P < 0.001), Zabramski classifications (P < 0.001), developmental venous anomaly presence (P < 0.001), and MRI-detected edema (P < 0.001). PIK3CA mutations showed a higher hemorrhage risk than MAP3K3 and combined MAP3K3 & PIK3CA mutations (P < 0.001). Within PIK3CA mutations, the p.H1047R variant correlated with higher bleeding risk than p.E545K (P = 0.007). For non-hemorrhagic epilepsy, patients with single MAP3K3 mutations or combined MAP3K3 & PIK3CA mutations were at greater risk than those with PIK3CA mutations alone. Histopathologically, lesions with PIK3CA mutations displayed cyst walls, pS6-positive dilated capillaries, and fresh blood cells, while MAP3K3 and double mutation lesions exhibited classic CCM pathology with SMA-positive and KLF4-positive vessels, collagen, and calcification. PIK3CA lesions had fewer KLF4-positive cells than double mutations lesions (P < 0.001), and EndMT (SMA-positive) cells compared to double mutation lesions (P < 0.05) and MAP3K3 mutations (P < 0.001), with more pS6 compared to MAP3K3 mutations (P < 0.05). This study underscores the diverse clinical, genomic, and histopathological characteristics in CCMs, suggesting potential predictive markers based on mutation subtypes and MRI features.

Indexed as

Class I Phosphatidylinositol 3-KinasesHemangioma, Cavernous, Central Nervous SystemMAP Kinase Kinase Kinase 3AdolescentAdultAgedChildChild, PreschoolCohort StudiesFemaleHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiddle AgedMutationClass I Phosphatidylinositol 3-KinasesKLF4 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription FactorsMAP3K3 protein, humanMAP Kinase Kinase Kinase 3PIK3CA protein, humanEpilepsyHemorrhageMAP3K3PIK3CAVascular malformations

Identifiers

PMID39910686
PMCPMC11795996

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.