Evidence map›Paper›PMID 40638881›Full record

ArticleNeurology2025

Lifetime Risk of First Symptomatic ICH or Seizure in Familial Cerebral Cavernous Malformations: A Multicenter Patient Data Analysis.

Philipp Dammann, Alejandro N Santos, Laven Mavarani, Stéphanie Guey, Hugues Chabriat, Dominique Herve, Jacob Croft, Mellisa Renteria, David Jang, Jun Zhang and 48 more

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

Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

58 authors.

Philipp DammannDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.
Alejandro N SantosDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.ORCID 0000-0002-6616-5313
Laven MavaraniInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Germany.
Stéphanie GueyTranslational Neurovascular Centre (CNVT) and Reference Center for Rare Vascular Diseases of the Central Nervous System and the Retina (CERVCO), Department of Neurology, FHU NeuroVasc, Hôpital Lariboisière AP-HP, Université Paris Cité, France.ORCID 0000-0001-6096-3595
Hugues ChabriatTranslational Neurovascular Centre (CNVT) and Reference Center for Rare Vascular Diseases of the Central Nervous System and the Retina (CERVCO), Department of Neurology, FHU NeuroVasc, Hôpital Lariboisière AP-HP, Université Paris Cité, France.ORCID 0000-0001-8436-6074
Dominique HerveTranslational Neurovascular Centre (CNVT) and Reference Center for Rare Vascular Diseases of the Central Nervous System and the Retina (CERVCO), Department of Neurology, FHU NeuroVasc, Hôpital Lariboisière AP-HP, Université Paris Cité, France.ORCID 0000-0001-6197-6275
Jacob CroftDepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso.
Mellisa RenteriaDepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso.
David JangDepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso.
Jun ZhangDepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso.ORCID 0000-0002-4379-3616
Da LiDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China.
Zhen WuDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China.
Jian-Cong WengDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China.ORCID 0000-0001-8337-4670
Antonio PetraccaDivision of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, Foggia, Italy.
Carmela FuscoDivision of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, Foggia, Italy.
Leonardo D'AgrumaDivision of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, Foggia, Italy.
Marco CastoriDivision of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Cappuccini snc, San Giovanni Rotondo, Foggia, Italy.
Matthias RathDepartment of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Germany.ORCID 0000-0002-7834-4650
Robin A PilzDepartment of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Germany.
Ute FelborDepartment of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Germany.
Gary K SteinbergDepartment of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine, CA.ORCID 0000-0001-6374-1058
Jeanne GuDepartment of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine, CA.
David BerviniDepartment of Neurosurgery, Bern University Hospital and University of Bern, Switzerland.ORCID 0000-0003-4873-4452
Johannes GoldbergDepartment of Neurosurgery, Bern University Hospital and University of Bern, Switzerland.
Andreas RaabeDepartment of Neurosurgery, Bern University Hospital and University of Bern, Switzerland.
Andrés CervioDepartment of Neurosurgery, Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia, Buenos Aires, Argentina.
Facundo VillamilDepartment of Neurosurgery, Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia, Buenos Aires, Argentina.
Julieta RosalesVascular Neurology Division, Department of Neurology, Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia, Buenos Aires, Argentina.
Laurèl RauschenbachDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.ORCID 0000-0001-8348-4298
Christoph RiessDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.
Marvin Darkwah OppongDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.
Hannah KaradachiDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.
Yahya AhmadipourDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.
Karsten H WredeDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.
Ramazan JabbarliDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.ORCID 0000-0002-8356-6629
Cornelius DeuschlInstitute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Germany.
Yan LiInstitute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Germany.
Guilherme Santos PiedadeDepartment of Neurosurgery, University of Miami, FL.
Martin KöhrmannDepartment of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Germany.
Benedikt FrankDepartment of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Germany.
Thomas WälchliDepartment of Neurosurgery, University of Toronto, ON, Canada.
Börge SchmidtInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Germany.
Manou OverstijnsDepartment of Neurosurgery, Medical Center, University of Freiburg, Germany.
Jürgen BeckDepartment of Neurosurgery, Medical Center, University of Freiburg, Germany.ORCID 0000-0002-7687-6098
Christian FungDepartment of Neurosurgery, Medical Center, University of Freiburg, Germany.ORCID 0000-0002-8709-5932
Rustam Al-Shahi SalmanCentre for Clinical Brain Sciences, The University of Edinburgh, United Kingdom.ORCID 0000-0002-2108-9222
Kelly D FlemmingDepartment of Neurology, Mayo Clinic Rochester, MN.ORCID 0000-0001-6021-1190
Giuseppe LanzinoDepartment of Neurosurgery, Mayo Clinic Rochester, MN.ORCID 0000-0003-1479-465X
Atif ZafarHealth Sciences, University of New Mexico, Albuquerque.
Shantel WeinsheimerCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California-San Francisco; and.
Jeffrey NelsonCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California-San Francisco; and.
Joseph M Zabramskithe Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group.
Amy Akersthe Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group.
Leslie Morrisonthe Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group.ORCID 0000-0002-0092-193X
Charles E McCullochthe Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group.
Helen KimCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California-San Francisco; and.ORCID 0000-0002-1937-354X
Ulrich SureDepartment of Neurosurgery and Spine Surgery, University Hospital Essen, Germany.ORCID 0000-0002-9073-1821
Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group

Funding

VCRC Administration UnitU54NS065705 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KIM, HELEN · 2009 to 2023
$20.8M
NINDS NIH HHS U54 NS065705
6 · The paper itself

Abstract

BACKGROUND AND

objectivesFamilial cavernous malformations (FCMs) are vascular lesions that pose a lifelong risk of symptomatic hemorrhage (SH) and seizures, yet their natural history remains unclear. This study aims to determine the cumulative lifetime risk of a first SH and/or seizure and assess whether genetic variations influence these risks.

methodsThis international, multicenter retrospective cohort study included data from 16 tertiary referral centers and 1 patient advocacy group. Eligible patients had confirmed or suspected FCM, available magnetic resonance imaging (MRI) data, documented baseline clinical features, and longitudinal follow-up (FU). Functional outcomes were assessed using the modified Rankin Scale (mRS) at last FU. Direct adjusted survival curves and mixed-effects Cox regression analyses were performed to estimate cumulative lifetime risk. The association between genetic variations and SH/seizure rates was evaluated, and mixed-effects logistic regression assessed the effect of SH/seizures on mRS outcomes.

resultsA total of 1,592 patients with FCM were included, with a mean age of 37.6 years (SD 17.1) and 55.7% female. The median FU was 42 years (IQR: 27-55), totaling 64,146 person-years. Of these, 869 (54.6%) had confirmed FCM, 775 (48.7%) experienced at least 1 hemorrhage, and 447 (28.1%) had at least 1 seizure. Genetic testing was performed in 47.7%, identifying DISCUSSION: The event rate of SH and seizures remained stable over time, leading to high cumulative lifetime risks. Patients with

Indexed as

Cerebral HemorrhageHemangioma, Cavernous, Central Nervous SystemSeizuresAdultCarrier ProteinsCohort StudiesFemaleHumansKRIT1 ProteinMagnetic Resonance ImagingMaleMiddle AgedRetrospective StudiesRisk FactorsYoung AdultCarrier ProteinsCCM2 protein, humanKRIT1 ProteinKRIT1 protein, human

Identifiers

PMID40638881
PMCPMC12428507

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.