Abstract
BackgroundApproximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up.Methods1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit.ResultsPresence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0–2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26–0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27–0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09–0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype (Endoglin vs ACVRL1). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21–1.08, p = 0.004).ConclusionMost HHT-brain VM patients had good functional capacity (mRS scores 0–2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group.
Highlights
Brain vascular malformations (VMs) remain a therapeutic and prevention challenge in hereditary hemorrhagic telangiectasia (HHT), present in approximately 10% of HHT patients, across all ages and all HHT genotypes [1,2,3]
1687 HHT patients were enrolled by the Brain Vascular Malformation Consortium (BVMC, https://www.rarediseasesnetwork.org/cms/bvmc/) at multiple recruiting centers in the US, Canada and the Netherlands between 2010 and 2020
Patients were screened for organ VMs and other clinical features as part of their routine clinical care according to standard clinical practice [23] and International HHT Guidelines [24, 25], including: comprehensive history, physical, routine blood tests, screening for pulmonary arteriovenous malformations (AVMs) by contrast echocardiography, brain VM screening by magnetic resonance imaging, clinical screening for liver VM and clinical screening for recurrent spontaneous epistaxis (> 1 episode per month for > 1 year), and HHT-related GI-bleeding
Summary
Brain vascular malformations (VMs) remain a therapeutic and prevention challenge in hereditary hemorrhagic telangiectasia (HHT), present in approximately 10% of HHT patients, across all ages and all HHT genotypes [1,2,3]. Intracranial hemorrhage (ICH) from brain VMs can Thompson et al Orphanet J Rare Dis (2021) 16:390 be fatal and can occur in children and adults with HHT [4], leading to death or morbidity and disability. Though the overall annual rate of ICH from brain VMs in HHT is relatively low, the distribution is wide, with a large range of risk [6]. One high-risk subgroup consisting of HHT-brain VM patients with previous ICH has been previously identified [6]. 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up
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