Elsevier

Pediatric Neurology

Volume 110, September 2020, Pages 49-54
Pediatric Neurology

Original Article
Cerebrovascular Malformations in a Pediatric Hereditary Hemorrhagic Telangiectasia Cohort

https://doi.org/10.1016/j.pediatrneurol.2020.05.008Get rights and content

Abstract

Background

We determined the frequency of cerebrovascular malformations in a pediatric cohort with hereditary hemorrhagic telangiectasia.

Methods

Retrospective cohort study of 54 children diagnosed with hereditary hemorrhagic telangiectasia at a tertiary care center. All neuroimaging was reviewed to assess for number and types of cerebrovascular malformations and for intracerebral hemorrhage and arterial ischemic stroke. Clinical charts were reviewed for clinical manifestations, genetic mutation, and clinically evident intracerebral hemorrhages and arterial ischemic strokes.

Results

Among 54 children with hereditary hemorrhagic telangiectasia with a median age of 3.5 years (interquartile range 0.4 to 7.9 years) at diagnosis, neuroimaging was performed in 52 (96.3%) at a median age of 5.2 years (interquartile range 1.8 to 9 years). Fourteen of 52 imaged children (26.9%) had cerebrovascular malformations. Cerebrovascular malformations included arteriovenous malformations, arteriovenous fistulas, vein of Galen malformations, and developmental venous anomalies. Six of the 14 children with cerebrovascular malformations (42.9%) had multiple malformations. Three children developed new cerebral arteriovenous malformations over time. Six children (11.1%) had clinically evident intracerebral hemorrhage, arterial ischemic stroke, or transient ischemic attack. The three children with intracerebral hemorrhage presented at young ages (4.3 to 7.7 years).

Conclusions

More than a quarter of children with hereditary hemorrhagic telangiectasia who were imaged had cerebrovascular malformations, and overt stroke occurred in more than 10%. Intracerebral hemorrhages can occur in pediatric hereditary hemorrhagic telangiectasia patients at young ages, and new cerebral arteriovenous malformations may develop over time. Early screening with neuroimaging including neurovascular imaging as well as repeat neuroimaging may be warranted in children with hereditary hemorrhagic telangiectasia.

Introduction

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia affecting about one in 10,000 in North America.1 Several genes have been implicated in this disease,1 and manifestations include telangiectasias and arteriovenous malformations (AVMs), which can affect the skin, mucosa, and organs like the lungs, gastrointestinal tract, and brain.2 A systematic review and meta-analysis examining literature from 1990 to 2016 found a prevalence of cerebral AVMs of 10.4% in people with HHT.3 Reports demonstrate that patients with HHT are also at risk for other cerebrovascular malformations like arteriovenous fistulas and capillary vascular malformations.4,5 The risk of cerebral hemorrhage in men and women with HHT who are younger than 45 years is 20 times and six times than that in the general population, respectively.6 Most studies about cerebral AVMs in HHT have been conducted in adults or in mixed cohorts of adults and children4,7, 8, 9; few studies have been devoted exclusively to pediatric patients with HHT.10,11 A pediatric series exists that describes nine children who presented with intracerebral hemorrhage and were found to have HHT, including one infant,10 and several of these children died. In another series of 115 children with HHT, 11 (9.6%) had brain AVMs, four of whom presented with intracerebral hemorrhage.11

In HHT, blood vessels do not develop normally, leading to an increased propensity for AVM formation, which could be congenital or develop de novo. AVMs in HHT are often thought of as having a low risk of hemorrhage during childhood. However, given the lack of early imaging and serial imaging in most patients with HHT, it is not known whether children with HHT who have AVMs are born with the malformations or whether the malformations develop later in childhood or adulthood. Therefore the optimal timing and imaging modality for screening for cerebrovascular malformations in this population are not firmly established. Because of the frequency of cerebrovascular malformations in patients with HHT and the potential for intracerebral hemorrhage, which can cause permanent neurological deficits or even death, a greater understanding of the pathophysiology and characteristics of cerebrovascular malformations in the disease is important. The purpose of this study was to describe the frequency and types of cerebrovascular malformations in pediatric patients with HHT, with the hope that our description will lead to improved recommendations for screening for cerebrovascular malformations in these children.

Section snippets

Study design and patient identification

The present study is a retrospective single-center cohort of children aged 0 to 18 years presenting to a tertiary care center between 2008 and 2018 from a two-practitioner neurology clinic for patients with HHT. Patients were identified from the HHT clinic database. At our institution, all pediatric patients with known HHT or suspected HHT are referred to one of two neurologists. Referrals are made directly from our university’s adult HHT center (when patients have children) or from cardiology

Results

Fifty-four children with HHT were identified, 50 (92.6%) with definite HHT and four (7.4%) with possible HHT. Thirty-two children (59.3%) were male, and median age at HHT diagnosis was 3.5 years (interquartile range 0.4 to 7.9 years). Racial distribution was as follows: 40 (74%) white, five (9.3%) black or African American, and nine (16.7%) other or unknown race. Two children (3.7%) were of Hispanic ethnicity. Genetic mutations and clinical manifestations are presented in Table 1. Most had a

Discussion

In this single-center cohort of children with HHT, over 95% had neuroimaging. Of those imaged, more than a quarter had cerebral or spinal vascular malformations, of whom seven (13.5%) had cerebral AVMs, a figure that may be slightly higher than the reported 9.6% with AVMs in the pediatric series by Saleh et al.11 The prior series included patients from an earlier time period, so it is possible that differences in imaging technique and resolution may be responsible for any differences in AVM

References (17)

  • J. McDonald et al.

    Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis

    Genet Med

    (2011)
  • M. Saleh et al.

    Brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia: clinical presentation and anatomical distribution

    Pediatr Neurol

    (2013)
  • C.O. Maher et al.

    Cerebrovascular manifestations in 321 cases of hereditary hemorrhagic telangiectasia

    Stroke

    (2001)
  • W. Brinjikji et al.

    Prevalence and characteristics of brain arteriovenous malformations in hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis

    J Neurosurg

    (2017)
  • T. Krings et al.

    Neurovascular phenotypes in hereditary haemorrhagic telangiectasia patients according to age. Review of 50 consecutive patients aged 1 day-60 years

    Neuroradiology

    (2005)
  • T. Krings et al.

    Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations

    AJNR Am J Neuroradiol

    (2015)
  • A.J. Easey et al.

    Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22,061 years of HHT patient life

    J Neurol Neurosurg Psychiatry

    (2003)
  • R.K. Fulbright et al.

    MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations

    AJNR Am J Neuroradiol

    (1998)
There are more references available in the full text version of this article.

Cited by (4)

  • Hereditary hemorrhagic telangiectasia

    2023, Revue des Maladies Respiratoires
  • Neurovascular Manifestations in Pediatric Patients With Hereditary Haemorrhagic Telangiectasia

    2022, Pediatric Neurology
    Citation Excerpt :

    The prevalence of neurovascular lesions and specifically of intracranial AVM in this investigation of 221 children with HHT was found to be 28.9% and 9.0%, respectively. In a recent report on 54 children,17 28.8% had vascular malformations, including 13.5% AVM, whereas the largest adult series suggests a prevalence of 12.8%,18 and a 7.7% incidence was reported in a non–age-restricted study in patients with HHT.6 We found that intracranial AVMs in HHT were more common supratentorially and were mainly located superficially, which is corroborative of data from prior studies on HHT.4,8,18

  • Systemic and CNS manifestations of inherited cerebrovascular malformations

    2021, Clinical Imaging
    Citation Excerpt :

    They tend to be supratentorial and superficial, usually <3 cm, Spetzler-Martin grade 1 or 2, although serious hemorrhage or larger AVMs can occur. In HHT new AVMs may develop in childhood76; de novo appearance in adulthood has not been described. Rarely, a pial AVF shunting lesion with direct arterial-venous shunting and no nidus may occur (Fig. 8).

Conflict of interest and source of funding statement: The authors declare no conflicts of interest or financial disclosures concerning the materials or methods used in this study or the findings specified in this article.

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