Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Abstract

Background and Purpose-Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for developing cerebral vascular malformations and pulmonary arteriovenous fistulae. We assessed the risk of neurological dysfunction from these malformations and fistulae. Methods-Three hundred twenty-one consecutive patients with HHT seen at a single institution over a 20-year period were studied. Any evidence of prior neurological symptoms or presence of an intracranial vascular malformation was recorded. All cases of possible cerebral arteriovenous malformation were confirmed by conventional arteriography. Results-Twelve patients (3.7%) had a history of cerebral vascular malformations. Ten patients had arteriovenous malformations, 1 had a dural arteriovenous fistula, and 1 had a cavernous malformation. Seven patients (2.1%) presented with intracranial hemorrhage, 2 presented with seizures alone, and 3 were discovered incidentally. The average age at the time of symptomatic intracranial hemorrhage was 25.4 years. All patients with a history of intracranial hemorrhage were classified as Rankin grade I or II at a mean follow-up interval of 6.0 years. A history of cerebral infarction or transient ischemic attack was found in 29.6% of patients with HHT and a pulmonary arteriovenous fistula. Conclusions-The risk of intracranial hemorrhage is low among people with HHT. Furthermore, a majority of these patients have a good functional outcome after hemorrhage. The data do not suggest a compelling indication for routine screening of patients with HHT for asymptomatic cerebral vascular malformations. 1 The estimated prevalence is 1 or 2 cases per 100 000. 1,2 Chromosomes 9q and 12q have been implicated in the inheritance of this disease. 3-7 A family history of HHT, although not required to make the diagnosis, is almost universally present. The vascular malformations of HHT may occur in multiple organs, including the lung, liver, kidney, and brain. 8,9 Epistaxis is the most common presentation, followed by gastrointestinal bleeding. 10,11 Pulmonary arteriovenous fistulae (AVFs) are often accompanied by dyspnea or hemoptysis and, less frequently, ischemic neurological symptoms. [12][13][14] Telangiectasias are frequently noted on the skin and mucous membranes, often not appearing until the second or third decade. 8,9 Brown et al 15,16 have reported that the detection rate of intracranial vascular malformations in a population-based study in the most recent time period was 2.75 per 100 000 person-years. The prevalence of intracranial hemorrhage from a vascular malformation was 7.50 per 100 000 people in the population at large. 15,16 Patients with HHT are thought to be at increased risk for harboring cerebral vascular malformations compared with the entire population. Arteriovenous malformations (AVMs), cavernous malformations, dural arteriovenous fistulae, and aneurysms have all been reported in these patients ( Figure 1). 14,17-24 Vascular malformations are found throughout the central nervous system, including the spinal cor...

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

“…115 In these series, there was no evidence for an increase in mortality in patients presenting later in life, 4 but an excess mortality in patients who had presented with HHT at a younger age, (<60 years) 4 or in young adults (in a series precluding childhood deaths). 115 These findings are in keeping with multiple other series that indicate early mortality due to AVMs, particularly cerebral AVM bleeds in childhood and young adults 68,88,116 , and pregnancy related maternal deaths 55,109 , although the article by Kjeldsen AD et al 4 , the strongest predictor of early mortality appeared to be the severity of nasal or gastrointestinal haemorrhage. More recent life expectancy data of 300 parents of HHT patients 117 , and 562 HHT-patients 118 suggest potentially better survival rates, although formal peer reviewed publication is awaited.…”

“…Recommendations for intensive screening programmes derived in such a healthcare culture may be neither appropriate, nor affordable, for other healthcare systems. Wide-scale screening programmes will raise these issues for high proportions of screened individuals, since cerebral vascular malformations may be present in up 22.8% of patients 212,213 , with high flow AVMs in 3.7-11% 88,212,213 . We find that even where an asymptomatic individual is in a higher risk group (having a family history of cerebral haemorrhage) for whom our group suggest MRI scans based on the advice from the late Prof Pierre Lasjaunias, 55,208 the decision to undergo this study is not straightforward.…”

“…34,87,88 Modification of local stroke management protocols 226 may be required, including consideration of early MR imaging to assist the diagnosis of brain abscess. In the case of ischaemic stroke, while in our experience anti-platelets are tolerated surprisingly well by many patients, the likely presence of AVMs would be considered an absolute contraindication to thrombolysis were HHT to be recognised 227 .…”

Term neonate with intracranial hemorrhage and hereditary hemorrhagic telangiectasia: a case report and review of the literature

“…Although children and adult patients with HHT who have ICH typically have good functional outcomes with minimal residual deficits, the contrary has been observed in the neonatal population. [4][5][6][7][8][9] There are seven reports in the literature of neonates and young infants with known or suspected HHT with symptomatic cerebral AVMs. Their outcomes are presented in Table 1 of the Supplementary Information.…”

Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations

“…[61] A loss of local microvascular flow regulation may in and of itself lead to the development of arteriovenous shunts, as predicted by computational modeling studies. [46] As a class, the inherited AVMs in HHT have some distinguishing morphological features, but are generally similar to the sporadic lesions and cannot be distinguished individually on the basis of their angioarchitecture [37,40]. Brain AVMs are approximately ten times more common in HHT1/ENG (~20%) than HHT2/ALK-1 (~2%) patients [6,36,50].…”