Neurologic Complications in Hereditary Hemorrhagic Telangiectasia with Pulmonary Arteriovenous Malformations: A Systematic Review

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multi-organ condition occurring with a 1 in 3800 prevalence in Alberta. This genetic disorder leads to vascular malformations in different organs including the lungs and brain, commonly affecting pulmonary vasculature leading to pulmonary arteriovenous malformations (PAVMs). PAVMs lead to right-to-left shunts, which may be associated with neurologic complications. We aimed to evaluate and summarize the reported neurologic manifestations of individuals with HHT with pre-existing PAVMs. Methods: We performed a qualitative systematic review to determine available literature on neurological complications among patients with PAVMs and HHT. Published studies included observational studies, case studies, prospective studies, and cohort studies including search terms HHT, PAVMs, and various neurologic complications using MEDLINE and EMBASE. Results: A total of 449 manuscripts were extracted including some duplicates of titles, abstracts, and text which were screened. Following this, 23 publications were identified for inclusion in the analysis. Most were case reports (n = 15). PAVMs were addressed in all these articles in association with various neurological conditions ranging from cerebral abscess, ischemic stroke, hemorrhagic stroke, embolic stroke, and migraines. Conclusion: Although HHT patients with PAVMs are at risk for a variety of neurological complications compared to those without PAVMs, the quality and volume of evidence characterizing this association is low. Individuals with PAVMs have a high prevalence of neurological manifestations such as cerebral abscess, transient ischemic attack, cerebral embolism, hemorrhage, and stroke. Mitigating stroke risk by implementing proper standardized screening techniques for PAVMs is invaluable in preventing increased mortality.

High risk of ischaemic stroke amongst patients with hereditary haemorrhagic telangiectasia

“…An incidence of 9.52/1000 patient-years of ischaemic cerebral stroke or TIA is an approximately 3.5 times higher incidence compared to the Danish background population (2.6/1000 patient-years). Whilst comparing rates of incidence from a small group to the Danish background population has several problems, it does show a surprisingly high incidence, and does confirm the previously reported high incidence of ischaemic stroke in HHT [4] as being limited to HHT patients with macroscopic PAVM.…”

“…Several studies have tried to investigate the effect of the severity of PAVMs on the risk of cerebral ischaemic events, with mixed results [4]. Until now, there has not been a threshold to determine with certainty when a PAVM is clinically relevant regarding the risk of cerebral ischaemic events.…”

Brain Abscess and Stroke in Children and Adults With Hereditary Hemorrhagic Telangiectasia

“…Arteriovenous malformations (AVMs) may result in intracranial hemorrhage when present in the brain, pulmonary hemorrhage when present in the lung, and high output heart failure when present in the liver. Brain abscess or ischemic stroke may also occur, due to right to left shunting through pulmonary AVMs 7 .…”

“…Brain abscess or ischemic stroke may also occur because of right to left shunting through pulmonary AVMs. 7…”

“…Brain abscess or ischemic stroke may also occur because of right to left shunting through pulmonary AVMs. 7 Although the overall prevalence of HHT is estimated to be between 1:5,000 and 1:8,000 in various populations, 8 precise estimates of the risk of complications from HHT have been difficult to ascertain because of both the rarity of HHT and the observation that most people with HHT have not yet been diagnosed. This has been particularly true for children with HHT.…”