Brain Arteriovenous Malformation Multiplicity Predicts the Diagnosis of Hereditary Hemorrhagic Telangiectasia Quantitative Assessment
ABSTRACT The purpose of this study was to quantitatively estimate the relationship between multiplicity of brain arteriovenous malformations (bAVMs) and the diagnosis of hereditary hemorrhagic telangiectasia (HHT).
We combined databases from 2 large North American bAVM referral centers, including demographics, clinical presentation, and angiographic characteristics, and compared patients with HHT with non-HHT patients. Logistic regression analysis was performed to quantify the association between bAVM multiplicity and odds of HHT diagnosis. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated to determine accuracy of bAVM multiplicity for screening HHT.
Prevalence of HHT was 2.8% in the combined group. bAVM multiplicity was present in 39% of patients with HHT and was highly associated with diagnosis of HHT in univariate (OR, 83; 95% CI, 40-173; P<0.0001) and multivariable (OR, 86; 95% CI, 38-195; P<0.001) models adjusting for age at presentation (P=0.013), symptomatic presentation (P=0.029), and cohort site (P=0.021). bAVM multiplicity alone was associated with high specificity (99.2%; 95% CI, 98.7%-99.6%) and negative predictive value (98.3%; 95% CI, 97.6%-98.8%) and low sensitivity (39.3%; 95% CI, 26.5%-53.2%) and positive predictive value (59.5%; 95% CI, 42.1%-75.2%). Positive and negative likelihood ratio was 51 and 0.61, respectively, for diagnosis of HHT. HHT bAVMs were also more often smaller in size (<3 cm), noneloquent in location, and associated with superficial venous drainage compared with non-HHT bAVMs.
Multiplicity of bAVMs is highly predictive of the diagnosis of HHT. The presence of multiple bAVMs should alert the clinician to the high probability of HHT and lead to comprehensive investigation for this diagnosis.
- Developmental Medicine & Child Neurology 09/2012; DOI:10.1111/j.1469-8749.2012.04425.x · 3.29 Impact Factor
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ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26 ± 18 range, (0-68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26 ± 16 (range, 2-50) and 18 ± 21 (0-48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT. © 2012 Wiley Periodicals, Inc.American Journal of Medical Genetics Part A 11/2012; 158A(11):2829-34. DOI:10.1002/ajmg.a.35622 · 2.05 Impact Factor
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ABSTRACT: Brain vascular malformations are resource-intensive to manage effectively, are associated with serious neurological morbidity, lack specific medical therapies, and have no validated biomarkers for disease severity and progression. Investigators have tended to work in "research silos" with suboptimal cross-communication. We present here a paradigm for interdisciplinary collaboration to facilitate rare disease research. The Brain Vascular Malformation Consortium (BVMC) is a multidisciplinary, inter-institutional group of investigators, one of 17 consortia in the Office of Rare Disease Research Rare Disease Clinical Research Network (RDCRN). The diseases under study are: familial Cerebral Cavernous Malformations type 1, common Hispanic mutation (CCM1-CHM); Sturge-Weber Syndrome (SWS); and brain arteriovenous malformation in hereditary hemorrhagic telangiectasia (HHT). Each project is developing biomarkers for disease progression and severity, and has established scalable, relational databases for observational and longitudinal studies that are stored centrally by the RDCRN Data Management and Coordinating Center. Patient Support Organizations (PSOs) are a key RDCRN component in the recruitment and support of participants. The BVMC PSOs include Angioma Alliance, Sturge Weber Foundation, and HHT Foundation International. Our networks of clinical centers of excellence in SWS and HHT, as well as our PSOs, have enhanced BVMC patient recruitment. The BVMC provides unique and valuable resources to the clinical neurovascular community, and recently reported findings are reviewed. Future planned studies will apply successful approaches and insights across the three projects to leverage the combined resources of the BVMC and RDCRN in advancing new biomarkers and treatment strategies for patients with vascular malformations.