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

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.

Links Between Strokes and Hereditary Hemorrhagic Telangiectasia: A Population-Based Study.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a disease of abnormal vasculature where patients are predisposed to strokes of multiple etiologies. We assessed yearly stroke incidence among Albertans with HHT and compared with the general population. Given the tendency for stroke in HHT patients, we expected HHT patients to have higher stroke incidence, in particular at younger ages. METHODS: Population-based administrative health data on inpatient and ambulatory admissions were extracted over a 16-year period using International Classification of Diseases (ICD)-9 and ICD-10, Canada codes. We analyzed overall occurrence of strokes in Alberta by age, gender, stroke subtype, and diagnosis of HHT. RESULTS: The age-standardized incidence rate of stroke in HHT was 450 per 100,000 compared with 260 per 100,000 in the general population with a rate ratio of 1.73 (95% confidence interval (CI) [1.046-2.842]). This study found a higher HHT prevalence in Alberta (1 in 3800) compared to the world average of 1 in 5000. Women were also more likely to be diagnosed with HHT, with a 3.25:1 female gender preponderance in the yearly incidence.InterpretationThis study not only shows that HHT patients are at higher risk of having a stroke but also quantifies that risk using an age-adjusted metric in Alberta. This province has a higher than expected disease burden of HHT, with the majority of cases affecting women. Our study found that acute ischemic strokes and transient ischemic attacks are far more common than hemorrhage in HHT. As HHT is a rare, multi-system, chronic disease, these patients should be referred to an HHT Centre of Excellence.

CONTEXTE: La maladie de Rendu-Osler-Weber (MROW) est une maladie caractérisée par une anomalie du système vasculaire. Les patients qui en sont atteints deviennent prédisposés à être victimes d'AVC présentant de multiples étiologies. À cet égard, nous avons cherché à évaluer l'incidence annuelle d'AVC au sein de patients albertains atteints de la MROW comparativement à l'incidence annuelle d'AVC au sein de la population de cette province. Étant donné la prédisposition évoquée ci-haut, nous nous attendions à ce que l'incidence d'AVC chez des patients atteints de cette maladie soit plus élevée, particulièrement à un plus jeune âge. MÉTHODES: Des données administrative liées à la santé et basées sur une population déterminée ont été extraites au moyen des codes ICD-9 et ICD-10-CA. Elles concernaient des patients hospitalisés et ambulatoires au cours d'une période de 16 ans. Nous avons ensuite analysé l'incidence d'ensemble des AVC en Alberta en fonction de l'âge, du sexe, des sous-types d'AVC et de l'établissement préalable d'un diagnostic de MROW. RÉSULTATS: Le taux d'incidence normalisé selon l'âge des AVC chez les patients atteints de la MROW était de 450 pour 100 000 comparativement à 260 pour 100 000 au sein de la population générale. Le ratio des taux, lui, était de 1,73 (IC 95 % [1,046;2,842]). Notre étude a aussi constaté une prévalence plus élevée de la MROW en Alberta (1 sur 3 800) comparativement à la moyenne mondiale, qui est de 1 sur 5 000. Fait à souligner, les femmes étaient plus susceptibles de recevoir un diagnostic de MROW (prépondérance féminine de 3,25:1 sur une base annuelle). INTERPRÉTATION: Cette étude a montré que les patients atteints de la MROW étaient non seulement plus à risque d'être victimes d'un AVC mais a aussi quantifié ce risque au moyen d'un outil de mesure ajusté pour l'Alberta en fonction de l'âge. Cette province donne à voir une incidence plus élevée de MROW que ce à quoi on pouvait s'attendre, la majorité des patients étant de sexe féminin. Notre étude a en outre montré que les AVC ischémiques aigus et les accidents ischémiques transitoires (AIT) sont nettement plus courants que les hémorragies lorsqu'on est atteint de la MROW. Considérant qu'il s'agit d'une maladie chronique rare de nature multi-systémique, ceux et celles qui en sont atteints devraient être dirigés vers un centre d'excellence spécialisé dans son traitement.

Common bleeding disorders affecting individuals with Hereditary Hemorrhagic Telangiectasia.

PURPOSE: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder affecting vasculature in different organ systems; seen at a rate of approximately 1:5000 in North America. Complications, with significant increases in health service utilization, arise from bleeding and shunts, and are particularly problematic in the lung and liver. Although these patients tend to chronically bleed from the GI tract and nasal cavities, a single bleed from arterio-venous malformations in the lungs or brain can have serious health implications and may be fatal. Bleeding due to vascular wall fragility in HHT patients can be further complicated with a concomitant bleeding disorder. METHODS: The proportion of adult patients seen in the Edmonton HHT center with a concomitant bleeding disorder, as assessed by blood test results for Factor VIII and related factors (Ristocetin Cofactor), Factor IX and Factor XI, was determined in a retrospective, single centre study. RESULTS: Of 77 individuals with HHT, four had below normal values of von Willebrand Factor, Ristocetin Cofactor or Factor VIII. Two patients had laboratory parameters diagnostic of a bleeding disorder, accounting for 2.6% of confirmed HHT subjects. These results indicate that establishing screening for bleeding disorders in HHT centers is important in managing bleeding symptomatology. CONCLUSIONS: In individuals with HHT, the presence of a second bleeding disorder can have significant clinical implications on patient management and health care utilizations. This paper highlights areas that need to be reviewed with respect to best practice protocols for the management of HHT patients.