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July 07, 2020; 95 (1) Article

Hemorrhage from cerebral cavernous malformations

The role of associated developmental venous anomalies

View ORCID ProfileBixia Chen, Annika Herten, Dino Saban, Steffen Rauscher, Alexander Radbruch, Boerge Schmidt, Yuan Zhu, Ramazan Jabbarli, Karsten H. Wrede, View ORCID ProfileChristoph Kleinschnitz, Ulrich Sure, Philipp Dammann
First published June 8, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009730
Bixia Chen
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Annika Herten
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Dino Saban
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Steffen Rauscher
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Alexander Radbruch
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Boerge Schmidt
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Yuan Zhu
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Ramazan Jabbarli
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Karsten H. Wrede
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Christoph Kleinschnitz
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Ulrich Sure
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Philipp Dammann
From the Department of Neurosurgery (B.C., A.H., D.S., S.R., Y.Z., R.J., K.H.W., U.S., P.D.), Institute of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), Institute for Medical Informatics, Biometry and Epidemiology (B.S.), and Department of Neurology (C.K.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Hemorrhage from cerebral cavernous malformations
The role of associated developmental venous anomalies
Bixia Chen, Annika Herten, Dino Saban, Steffen Rauscher, Alexander Radbruch, Boerge Schmidt, Yuan Zhu, Ramazan Jabbarli, Karsten H. Wrede, Christoph Kleinschnitz, Ulrich Sure, Philipp Dammann
Neurology Jul 2020, 95 (1) e89-e96; DOI: 10.1212/WNL.0000000000009730

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Abstract

Objective To determine the role of associated developmental venous anomalies (DVAs) in intracranial hemorrhage (ICH) caused by cerebral cavernous malformations (CCMs).

Methods We analyzed patient registry data of 1,219 patients with cavernous malformations treated in our institution between 2003 and 2018. Patients with spinal and familial CCM and patients without complete MRI data were excluded. The impact of various variables on ICH as a mode of presentation was assessed with multivariate binary logistic regression analysis. Kaplan Meier/Cox regression analysis was performed to analyze cumulative 5-year-risk for (re)hemorrhage and to identify baseline predictors of this outcome.

Results Seven hundred thirty-one patients with CCM were included. Multivariate logistic regression confirmed a statistically significant negative correlation with DVA (odds ratio [OR] 0.635 [95% confidence interval (CI) 0.459–0.878]) and positive correlation with brainstem localization (OR 6.277 [95% CI 4.287–9.191]) with ICH as the mode of presentation. Among 731 patients, 76 experienced (re)hemorrhage during 2,338 person-years of follow-up. Overall cumulative 5-year risk was 24.1% (95% CI 21.1%–27.5%). Cox regression analysis revealed initial presentation with ICH (hazard ratio [HR] 8.0 [95% CI 3.549–18.122]) and brainstem localization (HR 2.9 [95% CI 1.756–4.765]) as independent baseline predictors of (re)hemorrhage. Presence of DVA added no independent prognostic information (HR 1.1 [95% CI 0.717–1.885]).

Conclusion Patients with CCM with associated DVA are at lower risk to present with ICH. During untreated 5-year follow-up, they showed equal (re)hemorrhage risk compared to patients with CCM without DVA.

Glossary

CCM=
cerebral cavernous malformation;
CI=
confidence interval;
CRE=
cavernoma-related epilepsy;
DVA=
developmental venous anomaly;
ICH=
intracranial hemorrhage;
OR=
odds ratio

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 13

  • CME Course: NPub.org/cmelist

  • Received September 26, 2019.
  • Accepted in final form January 27, 2020.
  • © 2020 American Academy of Neurology
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