Supplemental Tables
Second International HHT Guidelines
Supplemental Table 1
Supplement Table 1. Curaçao Criteria for Clinical Diagnosis of HHT: Using these criteria, a diagnosis of HHT is considered ‘definite’ if three or more Curaçao criteria are present, ‘possible or suspected’ if two criteria are present, and ‘unlikely’ if 0 or 1 criterion is present.
| Criteria | Description |
| Epistaxis | Spontaneous and recurrent |
| Telangiectases | Multiple, at characteristic sites: lips, oral cavity, fingers, nose |
| Visceral lesions | Such as gastro-intestinal telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs |
| Family history | A first degree relative with HHT according to these criteria |
Supplemental Table 2
| Supplement Table 2: Randomized Controlled Trials for Treatment of Epistaxis in HHT. All trials were performed in adults (Age 18+) and included only patients with definite clinical diagnosis of HHT. | |||||
| Study, Year (Reference) | Participants | Intervention | Design and Methods | Primary Outcome Measures | Primary Outcome Results |
| Boyer H. et al. Int Forum Allergy Rhinol. 2015. (15) | N=17 | Sclerotherapy versus Control ("standard treatment", defined as continuation of any treatment that the patient had previously undergone) | RCT (crossover) Treatment= 6 weeks, each
Washout period: None. |
ESS | Improved ESS scores (0.95 difference, 1-sided p = 0.027),
The standard deviation of the difference scores was 1.82. Treatment order was not statistically significant. |
| Dupuis-Girod S. et al. JAMA 2016 (27) | N=80 | Bevacizumab nasal spray (25mg, 50mg, or 75mg) for 4 weeks vs placebo nasal spray | RCT Phase II-III (placebo controlled) Treatment: doses 14 days apart for a total treatment duration of 4 weeks, resulting in a total dose of 75mg, 150mg, and 225mg in each treatment group. | Mean monthly epistaxis duration for 3 months AFTER end of treatment compared with 3 months BEFORE beginning of treatment. | No statistical difference was observed in mean monthly epistaxis duration among treatment groups and placebo (p = .57), with higher standard deviation than expected in trial design. |
| Gaillard S. et al. J Thromb Haemost. 2014 (10) | N=135 | Oral tranexamic acid (3g per day) versus placebo | RCT (double-blind, placebo controlled crossover): Treatment: 3 months, each. | Mean monthly epistaxis duration for last 2 months of the treatment compared with the last 2months on placebo. | The mean duration of epistaxis per month was significantly shorter with tranexamic acid than placebo (0.19 on the log scale; SD = 0.07; p = 0.005). This difference corresponded to a decrease of 17.3% in the duration of epistaxis per month (95% CI, 5.5–27.6). |
| Geisthoff U.W. et al. Thromb Res.2014 (11) | N=22 | Oral tranexamic acid (3g per day) versus placebo | RCT (double-blind, placebo controlled crossover): Treatment: 3 months, each.
Washout period: None. |
Delta hemoglobin (final minus initial) for each treatment period. | No significant difference in delta hemoglobin between tranexamic acid and placebo was detected (p=0.33, Mann–Whitney-U test).
Post-hoc analysis: Mean hemoglobin concentrations were significantly greater for tranexamic acid versus placebo (p=0.013, Mann– Whitney-U test). |
| Riss D. et al. Head Neck. 2015 (28) | N=15 | Single dose of intranasal submucosal injection of bevacizumab | RCT (double-blind, placebo controlled, parallel group, stratified by age and epistaxis severity). Patients received a single intranasal submucosal injection of 100 mg of bevacizumab in 10 mL saline or placebo (10 mL saline). 5 mL were injected into each side of the nose. | Average daily post treatment epistaxis VAS score (range, 0–100) compared to average daily pretreatment score in the month before the intervention (R = VAS-post/VAS-pre), for days 11-84.Patients recorded in a diary their daily epistaxis VAS scores ranging from 0 (best situation) to 100 (worst case). | Average daily VAS scores dropped from 18.8 (±16.5 SD) pretreatment to 13.4 (±11.6 SD) post-treatment in the bevacizumab group and from 20.5 (±13.4 SD) to 19.7 (±12.6 SD) in the placebo group. No significant difference between average daily post-treatment VAS score compared to the average daily pretreatment score (p = 0.57). |
| Whitehead K. et al. JAMA 2016 (9) | N=121 | Topical therapy with bevacizumab 1% (4 mg/d) OR estriol 0.1% (0.4 mg/d) OR tranexamic acid 10% (40 mg/d) nasal sprays | RCT Phase II (double-blind, placebo controlled, stratified by epistaxis frequency) 4 treatment groups (bevacizumab 1% (4 mg/d), estriol 0.1% (0.4 mg/d), tranexamic acid 10% (40 mg/d), or placebo (0.9% saline) for 12 weeks. | Median weekly epistaxis frequency (weeks 5-12) for each patient. | Epistaxis frequency was not significantly different between any of the active drug groups and the placebo group or between any of the therapeutic agents. |
| Yaniv E. et al. Laryngoscope 2009 (64) | N=25 | Oral antiestrogen, Tamoxifen 20mg once daily | RCT (double-blind, placebo controlled) Treatment period=6 months. Washout period: None. | Frequency of epistaxis, duration of epistaxis, hemoglobin level. | Epistaxis frequency was significantly less in the treatment groups (p = 0.01), as was epistaxis severity (p = 0.049) at 6 months.
There was no significant difference in hemoglobin between groups at 6 months. |
| Abbreviations: ESS= Epistaxis severity score, RCT=Randomized controlled trial, VAS=visual analogue scale | |||||
Supplemental Table 3
| Supplement Table 3: Lower Quality Uncontrolled Clinical Trials for Treatment of Epistaxis in HHT. All trials were performed in adults (Age 18+) and included only patients with HHT diagnosis. | ||||
| Study, Year (Reference) | Study Design | Intervention | Outcome of Interest | Outcome Results |
| Reh D.D. et al. Laryngoscope 2013 | Prospective study (N=20) | topical lubricant | ESS | Mean ESS improved (p<0.0001) at 3mo. |
| Fernandez-L A. et al. Thromb Haemost 2007 | Prospective study (N=14) | oral tranexamic acid | Epistaxis frequency&severity | 100% patients improved. |
| Zaffar N. et al.Ann Hematol. 2015 (12) | Retrospective study (N=29) | oral tranexamic acid | ESS | Mean ESS improved (p<0.001). |
| Jorgensen G. et al. Eur Arch Otorhinolaryngol 2011 | Prospective study (N=30) | laser | Epistaxis duration | Epistaxis duration reduced (p<0.05) at 1.5 mo.& 6 mo. |
| Kuan E.C. et al. Lasers Med Sci 2017 (13) | Retrospective study (N=20) | laser | SNOT-22 | Mean SNOT-22 improved at 1.5mo. |
| Fiorella M.L. et al. ACTA otorhinolaryngologica italica 2012 | Retrospective study (N=24) | laser (diode) | Epistaxis frequency&severity | Group improved. |
| Poje G. et al. ENT-Ear, Nose & Throat Journal 2017 | Retrospective study (N=17) | laser (diode) | Epistaxis frequency&severity | Group improved. |
| Papaspyrou G. et al. ORL 2016 | Retrospective study (N=38) | laser (Nd:YAG) | Need for recurrent intervention | Recurrent intervention in 18% at 3 years. |
| Papaspyrou G. et al.J Craniomaxillfac Surgery 2017 | Prospective study (N=45) | laser (Nd:YAG) +/- APC | Need for recurrent intervention | Recurrent intervention in 20-33%% at 3-10 years. |
| Abdelghany A.M. et al. 2013 | Prospective study (N=16) | radiofrequency coblation | Epistaxis frequency&intensity | 100% patients improved. |
| Luk L. et al. 2014 | Prospective study (N=11) | radiofrequency coblation vs laser (KTP) | ESS | No significant difference in mean ESS, at 12mo. |
| Mortuaire G. et al. 2013 | Prospective study (N=16) | radiofrequency coblation | Epistaxis frequency&duration | Reduced mean epistaxis frequency (p<0.05) at 6mo. |
| Rotenberg B. et al. 2015 (17) | Retrospective study (N=37) | radiofrequency coblation | ESS | Mean ESS improved (p=0.02) at 6 mo. |
| Boyer H. et al. 2011 (14) | Retrospective study (N=7) | sclerotherapy | Epistaxis frequency&severity | 100% patients improved. |
| Morais D.et al. 2012 | Retrospective study (N=45) | sclerotherapy | Epistaxis frequency&severity | 95% patients improved. |
| Pagella F.et al. 2013 | Retrospective study (N=26) | thermal coagulation (APC) | Epistaxis score | Mean score improved (p=0.005) at 12 mo. |
| Pagella F. et al.2006 | Prospective study (N=36) | thermal coagulation (APC) | Reported bleeding | 100% reported reduction in bleeding at 6mo. |
| Al-Samkari H. et al. 2018 (23) | Retrosepctive study (N=13) | IV bevacizumab | Epistaxis control | Epistaxis control (reduction in epistaxis grade to <2) was achieved in 85% of patients, from 0 patients at baseline (p < 0.001). |
| Dupuis-Girod S. et al. 2012 (18) | Prospective study (N=25) | IV bevacizumab | Reported bleeding duration | Mean duration of epistaxis, significantly decreased from 221 minutes per mo. at baseline to 43 minutes per mo. at 3 mo. (p= 0.008). |
| Epperla et al. 2016 (22) | Retrospective study (N=5) | IV bevacizumab | blood transfusions | blood transfusions were reduced from baseline in 5/5 patients. |
| Iyer V. et al. 2018 (21) | Retrospective study (N=34) | IV bevacizumab | ESS | Significant reduction in ESS from baseline to 3mo (p<0.001). |
| Faughnan M.E. et al. 2019 (35) | Prospective study (N=7) | oral pazopanib | Epistaxis duration | 6/7 patients had >50% decrease, from baseline to during treatment. |
| Baysal M. et al. 2019 (34) | Retrospective study (N=6) | oral thalidomide | ESS | Mean ESS improved from pre-treatment (7.40+/-2.02) to post-treatment (3.10+/-1.79) (p=0.028). |
| Fang J. et al. 2017 (31) | Prospective study (N=7) | oral thalidomide | ESS | Mean ESS improved from pre-treatment (5.03 +/- 2.05), to end treatment (0.90 +/- 0.84, p= 0.003) and to 3 mo. after end treatment (1.98 +/- 1.33, p= 0.006), respectively. |
| Invernizzi R. et al. 2015 (32) | Prospective, Phase II (N=31) | oral thalidomide | frequency, intensity, or duration of epistaxis. | All patients responded to therapy with a significant decrease in all epistaxis parameters (p<0.0001 for frequency, intensity, and duration). |
| Lebrin F. et al. 2010 (30) | Prospective study (N=7) | oral thalidomide | Epistaxis severity | Self-reported severity of epistaxis improved in 5/7 (71%) of patients after treatment. |
| Peng H. et al. 2015 (29) | Prospective study (N=5) | oral thalidomide | ESS | Mean ESS improved from pre-treatment (6.966 +/- 3.093) to post-treatment (1.799 +/- 0.627) significantly (p = 0.009). |
| Ichimura K. et al. 2012 | Prospective study (N=7) | nasal closure | Epistaxis cessation | 57% had cessation of epistaxis. |
| Lund V. et al. 2017 (40) | Retrospective study (N=100) | nasal closure | Epistaxis cessation | 50% of patients responded. 94% had cessation of epistaxis. |
| Richer S. et al. 2012 (38) | Retrospective study (N=43) | nasal closure | Epistaxis cessation | 84% of patients responded. 83% had cessation of epistaxis. |
| Wirsching K.E.C. et al. 2017 | Prospective study (N=20) | temporary nasal occlusion with tape | ESS | ESS decreased from pre-treatment median of 3.59 to post-treatment (at 3 mo.) median of 2.43 (p = 0.01). |
| Harvey R. et al. 2008 | Retrospective study (N=33) | septodermoplasty | Frequency of KTP laser | Number of KTP laser treatments decreased from 1.83 (+/-1.99) pre-septodermoplasty to 0.78 (+/-0.85) post-septodermoplasty (p=0.012). |
| Ichimura K. et al. 2006 | Retrospective study (N=15) | septodermoplasty | Patient satisfaction | 100% of patients satisfied with procedure. |
| Lesnik G.T. et al. 2007 (37) | Retrospective study (N=9, severe) | septodermoplasty plus septectomy | Epistaxis frequency, QOL and blood transfusions | All patients had improved self-reported QOL. Blood transfusions were reduced from baseline 22.61/year to 9.57/year post-procedure (p < 0.05). |
| Levine C.G. et al. 2008 (36) | Retrospective study (N=106) | septodermoplasty | QOL | 62% of patients responded: 86% patients had improved QOL at mean 3.75 years. |
| Rimmer J. et al. 2014 (41) | Prospective study (N=7) | septodermoplasty | Epistaxis frequency&severity | 100% of patients reported reduction in epistaxis frequency and severity. |
| Abbreviations: ESS= Epistaxis severity score, mo.=month, QOL=quality of life, SNOT=sinonasal outcome test-22 | ||||
Supplemental Table 4
Supplement Table 4: Guidance for Prescribing and Safety Monitoring of Systemic Therapies for in HHT patients (as per recommendations A2, A4, B5, D5)
| Drug | Suggested Dosing | Safety Comments |
| Oral tranexamic acid | Start at 500mg BID, gradually increasing up to 1000mg QID or 1500mg TID. | Can be co-administered with systemic anti-angiogenic therapy.
Contraindications: Recent VTE or arterial thrombosis. Relative contra-indications: Atrial fibrillation, thrombophilia or other procoagulant tendencies (e.g. elevated Factor VIII). |
| Intravenous bevacizumab (induction) | 5 mg/kg every 2 weeks for 6 doses. | Monitor for:
Contraindicated in pregnancy. |
| Intravenous bevacizumab (maintenance) | Variable, from none to 5mg/kg every 1-3 months for 1 year, followed by gradually longer intervals. | As above.
Additional risks of long-term maintenance therapy not known. |
Abbreviations: VTE=venous thromboembolism
Supplemental Table 5
| Supplement Table 5: Diagnostic yield of gastrointestinal diagnostic procedures in adults with definite HHT. All studies were in adults (18 years+). |
|||
| Study, Year (Reference) | Population | Tests | Diagnostic Yields |
| Canzonieri C. et al. 2014 (45) | Definite HHT, consecutive adults, 22 (13 male), mean age 59 years (+/-9) | Esophagogastroduodenoscopy
Capsule endoscopy Colonoscopy |
82%
91% 10% |
| Chamberlain S.M. et al. 2007 (49) | Definite HHT, consecutive adults with suspected GI bleeding, 32/38 complete (18 male), mean age 54 years (+/-13) | Capsule endoscopy | Any GI telangiectasia=81%
Gastric=28% Proximal small bowel=56% Mid small bowel=59% Distal small bowel=63% |
| Chetcuti Zammit S. et al. 2018 (60) | Definite HHT, consecutive adults with suspected GI bleeding, 10 patients (6 male), mean age 63 years (+/-14) | Capsule endoscopy (N=7) | Proximal small bowel=86%
Mid small bowel=11% Distal small bowel=33% |
| Greve E. et al. 2010 (44) | Definite HHT, consecutive adults with anemia and suspected GI bleeding, 30 patients (10 male), mean age 58 years (+/-11) | Capsule endoscopy | Gastric=47%
Small bowel=87% |
| van Tuyl S.A. et al. 2007 (43) | Definite HHT, consecutive adults with anemia, 25 patients (13 male), mean age 49 years (+/-15) | Esophagogastroduodenoscopy
Capsule endoscopy Colonoscopy |
67%
76% 32% |
Supplemental Table 6
| Supplement Table 6: Lower Quality Uncontrolled Clinical Trials for Treatment of GI Bleeding in HHT. All trials were performed in adults (Age 18+) and included only patients with HHT diagnosis. | ||||
| Study, Year (Reference) | Study Design | Intervention | Outcome of Interest | Outcome Results |
| Zaffar N. et al. 2015 (12) | Retrospective study (N=29, of whom 10 had GI bleeding) | oral tranexamic acid | Requirement for any GI-endoscopic intervention | Reduced from 80% pre-treatment to 40% on treatment (trend, p=0.07). |
| Al-Samkari H. et al. 2019 (23) | Retrospective study (N=13, of whom 10 had GI bleeding) | IV bevacizumab | Change in hemoglobin. Reduction in pRBCs | Mean hemoglobin improved by 4g/dL or by 45% from the pre-treatment period to the maintenance period (P<0.001).
pRBC requirements decreased by 92% from the pretreatment period to the maintenance period. |
| Iyer V. et al. 2018 (21) | Retrospective study (N=34, of whom 19 had GI bleeding) | IV bevacizumab | Requirement for any GI-endoscopic intervention | Significant reduction in RBC transfusions (p=0.007) in the entire group (GI bleeders not reported separately). |
| Faughnan M.E. et al. 2019 (35) | Prospective study (N=7) | oral pazopanib | Epistaxis duration | 6/7 patients had >50% decrease, from baseline to during treatment. |
| Abbreviations: GI=gastrointestinal, pRBC=packed red-blood cells | ||||
Supplemental Table 7
| Supplement Table 7: Diagnostic Accuracy of Testing for Liver VMs in Adults with Definite HHT. All studies were in adults (18 years+) and reported measures of diagnostic accuracy or agreement. | |||
| Study, Year (Reference) | Population | Tests | Operating Characteristics |
| Buonamico P. et al. 2008 (124) | Definite HHT (N=153) | Ultrasound Doppler "color spots".
Multiphase CT as reference standard |
Sensitivity=95%
Specificity=68% Diagnostic accuracy=92% |
| Buscarini E. et al. 2008 (125) | Definite HHT (N=110) | Ultrasound Doppler | Sensitivity=97-99%
Specificity=97-99% Moderate inter-observer agreement (Kendall's coefficient of concordance=0.26) for severity. |
| Cavel A. et al. 2016 (126) | Confirmed or suspected HHT (N=62) | Ultrasound Doppler versus Multiphase CT | Significant disagreement with kappa=0.376 and a Bhapkar critical probability of p=0.0053. Staging of liver involvement was significantly more severe with CT in cases of disagreement. |
| Milot L. et al. 2008 (128) | Definite HHT (N=23) versus Controls (N=23) | MRI liver | Hepatic artery diameter: greater in HHT patients than in controls: 8.69+/-1.63 mm versus 5.17+/-0.44 mm (p<0.05).
Vascular abnormalities: 91% HHT vs 0% controls Ischemic cholangitis: 39% HHT vs 0% controls Good interobserver agreement for vascular abnormalities (0.62) Moderate interobserver agreement (0.42) with biliary ischemia. |
| Scardapane A. et al.2012 (129) | Definite HHT (N=52) | Multiphase CT versus 4D-MRA | CT Diagnostic Yield=69%
MRA Diagnostic Yield=69% No significant difference accuracy Kappa=0.9 (good) for type of shunt. |
| Wu J.S.et al. 2006 (127) | Definite HHT and symptomatic liver VMs (N=24) | Multiphase CT | Diffuse telangiectasias: 100%.
Dilated hepatic artery: 100% Cardiomegaly: 48% Hepatic arteriovenous shunt: 54% Arterioportal shunt: 25% Agreement between CT and clinical type: 54% |
| Abbreviations: CT=computed tomography, VM=vascular malformation | |||
Supplemental Table 8
| Supplement Table 8: Lower Quality Uncontrolled Clinical Trials for Treatment of Liver VMs in HHT. All trials were performed in adults (Age 18+) and included only patients with HHT diagnosis. | ||||
| Study, Year (Reference) | Study Design | Intervention | Outcome of Interest | Outcome Results |
| Dupuis-Girod A. et al. 2012 (18) | Uncontrolled series (N=25, HHT with HOCF from liver VMs) | IV bevacizumab | Decrease in cardiac output (from high-output state) | Cardiac output improved or normalized in 83% |
| Azzopardi N. et al.2015. | Uncontrolled series (N=25, HHT with HOCF from liver VMs) | IV bevacizumab (maintenance dosing) | Maintenance of improved cardiac output with different length bevacizumab intervals, after induction | Every 3 mo.: Maintained in 41%
Every 2 mo.: Maintained in 45% Every 1 mo.: Maintained in 50% (All at 24 mo.) |
| Chavan A. et al. 2017 (20) | Uncontrolled series (N=21, HHT with symptomatic liver VMs) | IV bevacizumab | Clinical symptom improvement | Abdominal pain grade improved from 3·0 ± 2·2 (95% CI 1·99–3·91) pretherapy to 0·9 ± 1·0 post‐therapy (95% CI 0·48–1·33) (p <0 .001).
Mean NYHA stage improving from 2·8 ± 0·7 (95% CI 2·49–3·13) pretherapy to 1·6 ± 0·9 (95% CI 1·25–1·99) (p <0 .0001) following therapy. Mean epistaxis grade fell from 2·4 ± 0·8 (95% CI 2·04–2·73) to 0·9 ± 0·4 (95% CI 0·70–1·01) (p<0 .0001). |
| Lerut J. et al. 2006 (119) | Uncontrolled case series (N=40) | Liver transplant | Survival post-transplant | 1-, 5- and 10-year survival rates= 82.5%. |
| Dupuis-Girod S. et al.2010 (134) | Uncontrolled case series (N=13) | Liver transplant | Survival post-transplant | Mean follow-up 109mo., Survival 92.3% |
| Liu Z.C. et al. 2016 | Uncontrolled series (N=13, HHT with symptomatic liver VMs) | Double banding/ligation of hepatic arteries | Clinical effectiveness measures | Cardiac function improved: NYHA III-IV vs. NYHA I-II
Pulmonary arterial pressure decreased in all patients (48 +/- 8 mmHg vs. 24 +/- 4 mmHg; p <0 .001). Gamma-glutamyl transpeptidase and alkaline phosphatase decreased in 11 patients (144 +/- 94 U/L vs. 71 +/- 34 U/L; p=0 .003) and 10 patients (207 +/- 71 U/L vs. 105 +/- 32 U/L; p =0 .001), respectively. |
| Abbreviations: HOCF=high-output cardiac failure, mo.=month, IV=intravenous, NYHA=New York Heart Association, VMs=vascular malformations | ||||
Supplemental Table 9
| Supplement Table 9: Diagnostic Accuracy of Testing for Pulmonary AVMs in Children with Definite HHT. All studies were in children (<18 years) with reported measures of diagnostic accuracy or agreement for pulmonary AVMs. | |||
| Study, Year (Reference) | Population | Tests | Operating Characteristics |
| Soysal N. et al. 2017 | Definite HHT ( N=59) | High-resolution CT chest | Yield: pulmonary AVMs 25% |
| Al-Saleh S. et al. 2012 (148) | Definite HHT (N=75) | TTCE screening
CT chest (reference standard) |
Intraobserver and interobserver agreement for interpreting TTCE results were excellent (kappa = 0.97 and 0.92, respectively)
Sensitivity=100% , Specificity=82% PPV=39% , NPV=100% |
| Karam C. et al. 2015 (149) | Definite HHT (N=93) | TTCE screening CT chest (reference standard) | Yield: Pulmonary AVMs 52%.
Sensitivity=100%, Specificity= 95% PPV=96%, NPV=100% |
| Fernandopulle N. et al. 2018 (150) | Possible HHT (N=293) | TTCE screening CT chest (reference standard) | TTCE positive: 26%.
Bubble timing was associated with need for treatment (p=0.008). Shunt intensity was associated with presence of CT-detectable pulmonary AVMs (p<0.001) and need for intervention (p=0.005). |
| Westermann C.J.J. et al. 2003 (171) | Definite HHT (N=112) | Screening with pulse oximetry and chest x-ray | Yield: Pulmonary AVMs 22%, of whom 48% had had serious complication. |
| Hosman A.E. et al. 2017 (147) | Definite HHT (N=175) | Screening with pulse oximetry and chest x-ray | Yield: Pulmonary AVMs 22%, of whom 85% required embolization. |
| Abbreviations: AVM=arteriovenous malformation, CT=computed tomography, TTCE= transthoracic contrast echocardiography | |||
Supplemental Table 10
| Supplement Table 10: Lower Quality Uncontrolled Clinical Trials for Treatment of Pulmonary AVMs and Brain VMs in HHT. All trials were performed in children (<18 years) and included only patients with HHT diagnosis. | ||||
| Study, Year (Reference) | Study Design | Intervention | Outcome of Interest | Outcome Results |
| Faughnan M.E. et al. 2004 (146) | Definite HHT and pulmonary AVMs (N=42) | Transcatheter embolization of pulmonary AVMs | Reperfusion rate and safety | Reperfusion in 15% of embolized pulmonary AVMs . No serious or long-term procedural complications. |
| Meybodi A.T. et al. 2018 (166) | Definite HHT and brain VMs (N=6 children treated) | Surgical management of brain VMs | Neurological outcomes | 5/6 children: improved or stable mRS post-op and 1/6 had temporarily worsened mRS post-op. |
| Krings T. et al. 2005 (172) | Definite HHT and brain VMs (N=25 children treated, including 14 with brain AVFs) | Embolization | Clinical outcomes | 87% patients had stabilization of the disease, ameliorating the symptoms or even complete resolution. |
| Abbreviations: AVM=arteriovenous malformation, VM=vascular malformations, mRS=modified Rankin score | ||||