Infratentorial Developmental Venous Abnormalities and Inflammation Increase Odds of Sporadic Cavernous Malformation

J Stroke Cerebrovasc Dis. 2019 Jun;28(6):1662-1667. doi: 10.1016/j.jstrokecerebrovasdis.2019.02.025. Epub 2019 Mar 14.


Goal: Sporadic brain cavernous malformations commonly correlate with developmental venous anomalies; however, developmental venous anomalies may exist without cavernous malformations. Infratentorial location and specific angioarchitectural features of the developmental venous anomaly increase the odds of a concomitant malformation. Animal data also suggest chronic inflammatory disease, oxidative stress, and angiogenesis promote cavernous malformation development. We sought to determine potential clinical and radiologic factors promoting development of sporadic cavernous malformations.

Methods: One hundred and forty-five patients with sporadic, nonradiation-induced brain cavernous malformations (63 with radiologic-apparent and 82 with radiologic-occult developmental venous anomalies) were compared to developmental venous anomaly controls without associated malformation. Data collection included demographic information, comorbidities, medications at diagnosis, and location of the developmental venous anomaly and/or malformation. Logistic regression with likelihood ratios, odds ratios and 95% confidence intervals were calculated comparing malformation cases with controls. A similar analysis compared malformations with radiologic-apparent anomalies to controls.

Results: Compared to controls, cases were more likely to have had a major infectious illness (10.3% versus 2.3%; P = .0003 and/or chronic inflammatory disease (31.7% versus 21.3%; P = .0184) prior to diagnostic magnetic resonance imaging. Infratentorial location was more common in cavernous malformation cases (31.7% versus 15.7% controls; P ≤ .0001) with similar findings in cavernous malformation with radiologic-apparent developmental venous anomalies versus controls.

Conclusions: Infratentorial developmental venous anomalies location, major infectious illness, and chronic inflammatory disorders increase the odds of sporadic cavernous malformation formation. Inflammation may promote local thrombosis of developmental venous anomalies, trigger angiogenic response through increased vascular permeability, or promote cavernous malformation through Toll-like receptor 4.

Keywords: Cavernous malformation; case-control; cavernoma; chronic inflammation; developmental venous anomaly.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Central Nervous System Neoplasms / diagnostic imaging
  • Central Nervous System Neoplasms / etiology*
  • Cerebral Veins / abnormalities*
  • Cerebral Veins / diagnostic imaging
  • Child
  • Child, Preschool
  • Chronic Disease
  • Communicable Diseases / complications
  • Female
  • Hemangioma, Cavernous, Central Nervous System / diagnostic imaging
  • Hemangioma, Cavernous, Central Nervous System / etiology*
  • Humans
  • Inflammation / complications*
  • Inflammation / diagnosis
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Radiation Exposure / adverse effects
  • Registries
  • Risk Assessment
  • Risk Factors
  • Young Adult