Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia

• Published in: Orphanet journal of rare diseases Vol. 16; no. 1; p. 390
• Main Authors: Thompson, K P, Nelson, J, Kim, H, Weinsheimer, S M, Marchuk, D A, Lawton, M T, Krings, T, Faughnan, M E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19-09-2021; BioMed Central; BMC
• Subjects: Abnormalities; Activin Receptors, Type II; Anemia; Arteriovenous Fistula; Asymptomatic; Bleeding; Brain; Central Nervous System Vascular Malformations; Complications and side effects; Disability evaluation; Endoglin; Endoglin - genetics; Endoscopy; Enrollments; Genotypes; Heart; Hemorrhage; Hereditary hemorrhagic telangiectasia; Humans; Intracranial Arteriovenous Malformations; Liver; Medical research; Morbidity; Mutation; Patients; Prospective Studies; Rare diseases; Software; Stroke; Telangiectasia, Hereditary Hemorrhagic; Canada; United States; Netherlands
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-021-02012-y

Approximately 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.
1637 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.
Presence 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).
Most 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.