Neurovascular Manifestations in Hereditary Hemorrhagic Telangiectasia: Imaging Features and Genotype-Phenotype Correlations

Abstract

BACKGROUND AND PURPOSE Hereditary hemorrhagic telangiectasia is an autosomal dominant disease that presents in 10%–20% of patients with various brain vascular malformations. We aimed to report the radiologic features (phenotype) and the genotype-phenotype correlations of brain vascular malformations in hereditary hemorrhagic telangiectasia. MATERIALS AND METHODS Demographic, clinical, genotypic and imaging information of 75 HHT patients with hereditary hemorrhagic telangiectasia with brain arteriovenous malformations enrolled in the Brain Vascular Malformation Consortium from 2010 to 2012 were reviewed. RESULTS Non-shunting, small, superficially located conglomerates of enhancing vessels without enlarged feeding arteries or draining veins called “capillary vascular malformations” were the most commonly observed lesion (46 of 75 patients; 61%), followed by shunting “nidus-type” brain AVMs that were typically located superficially with a low Spetzler-Martin Grade and a small size (32 of 75 patients; 43%). Direct high-flow fistulous arteriovenous shunts were present in 9 patients (12%). Other types of vascular malformations (dural AVF and developmental venous anomalies) were present in 1 patient each. Multiplicity of vascular malformations was seen in 33 cases (44%). No statistically significant correlation was observed between hereditary hemorrhagic telangiectasia gene mutation and lesion type or lesion multiplicity. CONCLUSIONS Depending on their imaging features, brain vascular malformations in hereditary hemorrhagic telangiectasia can be subdivided into brain AVF, nidus-type AVM, and capillary vascular malformations, with the latter being the most common phenotype in hereditary hemorrhagic telangiectasia. No genotype-phenotype correlation was observed among patients with this condition.

Cerebrovascular Manifestations of Hereditary Hemorrhagic Telangiectasia

“…These lesions have many other features that portend a poorer natural history, including arterial stenoses, feeding artery aneurysms, multiple draining veins, venous ectasia, and a pseudophlebitic pattern. 48 The angioarchitecture of pial AVFs is also thought to differ by age. One series of 41 patients with supratentorial pial AVFs, Hetts et al 49 noted that patients ≤2 years of age were more likely to have large, complex, multihole AVFs, whereas patients >2 years of age were more likely to harbor single-hole pial AVFs.…”

“…These lesions are usually superficially located with only a tiny minority located in the deep portions of the brain. 48 Over 90% of these lesions have a supratentorial location. Pial AVFs generally have high shunt volumes, which result in marked feeding artery enlargement and local hypoxemia.…”

“…The large AVMs/AVFs typically but not exclusively become clinically manifest in young children, whereas small AVMs are typically discovered in older age groups. 48 Micro-AVMs are typically found in older children and young adolescents. AVFs represent ≈10% of CAVMs, whereas nidus type AVMs represent ≈50% of CAVMs.…”

“…47 CAVMs seen in patients with HHT can be classified into three types (1) large single-hole pial arteriovenous fistulae (AVF; Figure 1), (2) AVMs with a nidus (Figures 2 and 3), and (3) microAVMs or capillary vascular malformation 48 ( Figure 4). The large AVMs/AVFs typically but not exclusively become clinically manifest in young children, whereas small AVMs are typically discovered in older age groups.…”

“…AVFs represent ≈10% of CAVMs, whereas nidus type AVMs represent ≈50% of CAVMs. 48 Approximately 60% of patients with CAVMs have micro-AVMs/capillary vascular malformations.…”