De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia

Abstract

Background: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening. We aimed to confirm whether brain VMs can form de novo in patients with HHT.

Methods: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review.

Results: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation.

Conclusions: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted.

Keywords: Brain arteriovenous malformation; Brain vascular malformation; Capillary malformation; De novo; Hereditary hemorrhagic telangiectasia.

Figure 1.

Conventional angiogram of woman with HHT at age 24 and again at age 37 years demonstrating a de novo brain VM. Coronal (A) and sagittal (B) views with no brain AVM visualized (circles) at age 24 years. Coronal (C) and sagittal (D) views demonstrating a de novo brain AVM in the left paramedian frontal lobe that was not present 13 years earlier (arrows).

Figure 2.

Brain MRI of a boy with ENG variant at 10 years (A -D) and again at 16 years (E and F) demonstrating a de novo brain capillary malformation. (A-C) Three slices on axial T2-weighted MRI at age 10 years with no evidence of brain capillary malformations. (D) Contrast-enhanced MRI without enhancement at age 10 years. (E) Contrast-enhanced MRI at age 16 years demonstrating enhancement (arrow) in a region that did not previously show enhancement at age 10 years (see D), consistent with a de novo capillary malformation. (F) Axial T2-weighted MRI at age 16 years at the same level as in (A) showing the capillary malformation (arrow) in the left frontal lobe.

Figure 3.

Brain MRI from an infant (A and B) with a large brain vein of Galen malformation with a de novo capillary malformation in the pons at age 10 years (C and D). (A) Axial time of flight MRI without contrast in infancy with no evidence of pontine capillary malformation. (B) Coronal T2-weighted MRI in infancy with no signal change in the pons. The large vein of Galen malformation is noted (circle). (C) Axial time of flight MRI with contrast at age 10 years with capillary malformation (arrow). (D) Coronal T2-weighted sequence at age 10 years with new signal change in the pons representing a capillary malformation (arrow).

Figure 4.

Brain MRIs at age 3 years (A and B) and at age 8 years (C and D) showing growth of a left occipital brain AVM with recruitment of new vessels. (A) Axial T2 FLAIR MRI with left mesial occipital brain AVM at age 3 years. (B) Axial time of flight on the same MRI as in (A) demonstrating the left occipital brain AVM. (C) Axial T2 FLAIR MRI at age 8 years in the same child demonstrating enlargement of the brain AVM. (D) Axial time of flight on the same MRI as in (C) showing multiple new vessels recruited to the brain AVM.