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

Abstract

Objective:Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in TGF-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adult and children HHT patients.Methods:We conducted a case-control study among participants aged 1-64 years in the MarketScan® Commercial (2006-2019) and Multistate Medicaid Databases(2011-2019). We identified cases with HHT using International Classification of Diseases diagnosis codes (ICD-9-CM 448.0, ICD-10-CM I78.0). Control patients without HHT coding were frequency matched 10:1 to HHT patients by age, duration of insurance enrollment, sex, and Medicaid status. Outcomes of interest (brain abscess, stroke and intracranial/subarachnoid hemorrhage) were identified using the appropriate ICD-9/10 diagnosis codes. We calculated incidence and standardized rates of the various outcomes and compared rate ratios (RR) between HHT cases and controls.Results:5796 patients with HHT, of which 588 were children (age <16 years) were matched with 57,960 controls. There was increased incidence of brain abscesses in HHT cases compared with controls, with an RR of 35.6 (95% CI 15.4 – 82.5). No brain abscesses were recorded in children aged 15 years or less. Hemorrhagic strokes/subarachnoid hemorrhages were more common in HHT cases, with an RR of 4.01 (95% CI 2.8 to 5.7) in adults and 60.2 (95% CI 7.2 – 500.4) in children. Ischemic strokes were also more common in cases, with an RR of 3.7 (95% CI 3.0 – 4.5) in adults and 70.4 (95% CI 8.7– 572.3) in children.Conclusion:We observed much higher incidence of severe CNS vascular complications in HHT patients, particularly in children. Though higher incidence of brain abscesses was noted in adult HHT patients, no brain abscesses were recorded in children, a result that may be considered when surveillance recommendations for this population are revisited.

The Role of Hereditary Hemorrhagic Telangiectasia in Neurologic Practice

“…In this issue of Neurology ® , White et al 1 publish a study that identifies HHT as a causative disorder for brain abscess and stroke throughout the lifespan. The study draws on administrative data from 2 publicly available resources and uses International Classification of Disease diagnosis codes (ICD-9 and ICD-10) to identify HHT diagnosis and key neurologic complications.…”