(Stroke. 2001;32:2957.)
© 2001 American Heart Association, Inc.
Letters to the Editor |
Compelling Reasons to Screen Brain in HHT
Department of Medicine, Division of Neurology, Sunnybrook and Women’s HSC, University of Toronto
Department of Radiology, Yale University School of Medicine
Department of Respiratory Medicine, University of Toronto, HHT Program, St Michael’s Hospital, Toronto, Ontario, Canada
Department of Radiology, Yale University School of Medicine, Yale AVM Center, New Haven, Connecticut
To the Editor:
We read with great interest the article by Maher et al,1 in which the authors reviewed the medical records from hereditary hemorrhagic telangiectasia (HHT) patients seen at their institution over 20 years. However, we disagree with the authors’ final conclusion that HHT patients should not undergo routine screening for cerebrovascular malformations (CVMs) if asymptomatic. We advocate a single baseline MRI screen in all patients with HHT, as CVMs can cause devastating neurological complications.
The findings by Maher et al of a CVM prevalence rate of 12 of 321 (3.7%) in their patient group is rather low in comparison to those in other studies.2,3 The authors acknowledge this and attribute it to screening only symptomatic patients. We believe that neurological symptoms are not a good indicator of who should receive MRI screening, and, based on our experience, we have found that neurological symptoms are not necessarily present in individuals with CVMs.2–4 The consequences of a CVM-related hemorrhage could be devastating.
Other studies2–4 have described CVMs in HHT and have reported micro-arteriovenous malformations (AVMs), small AVMs, and macro-AVMs, as well as cerebral telangiectases and cavernomas. Fulbright et al,3 who used noncontrast and gadolinium-enhanced MRI, and Willemse et al,2 who used digital subtraction angiography (DSA), found a prevalence of CVMs of 22% and 12.2%, respectively. The difference in prevalence rates between these 2 studies may be due to increased detection of other CVMs, such as micro-AVMs and cerebral telangiectases found on contrast-enhanced MRI in the Fulbright et al study. However, in terms of AVMs (
10 mm in diameter), which are predisposed to symptoms, both studies found a prevalence rate of 11% to 12%, respectively, in consecutive patients with HHT imaged by these techniques. In the retrospective analysis by Maher et al,1 only 46 of 322 patients underwent MRI imaging. If Maher et al had performed MR imaging in all their patients, we would have predicted that at least 32 of 321 (10%) of their patients, rather than the 12 who were symptomatic, would have had a CVM, which could potentially cause symptoms.2–4
The study of Maher et al did not include the clinical characteristics of their patient population or a detailed pedigree analysis of the family members. Patients did fill out a questionnaire that included family history questions, but the findings were not reported in the article. The authors included only living patients and therefore likely failed to report deaths due to CVMs in family members, thus reducing the actual prevalence of CVMs in their group (survivor bias). A subset of HHT families may be more prone to harboring CVMs, and there is some evidence to suggest that families with a high prevalence of pulmonary AVMs (PAVMs) may have an increased likelihood of also having a CVM.5 The increased prevalence rate of CVMs in the other studies previously discussed2,3 may be related to this finding, as both centers have a strong referral bias for PAVMs. In the future, genotype-phenotype analyses will advance our understanding of the relationship of PAVMs and CAVMs.
There are still many unanswered questions with regard to CVMs and screening in HHT. The current gold standard for CVM screening is 4-vessel angiogram, but it remains too costly and invasive to be a standard screening technique. To better understand the relationship between CVMs and HHT, we need to combine data from multiple centers using our current available screening techniques, such as noncontrast and contrast-enhanced MRI, to determine the actual prevalence of CVMs in HHT and to characterize the morphology of HHT-related CVMs. Studies such as that by Matsubara et al4 have characterized CVMs in HHT in a small group of patients, but pooled center data will further expand this knowledge and also permit to characterize prospectively the risk of micro-, small, and macro-AVMs in a large, unselected group of HHT patients.
The findings of Maher et al1 support those of Willemse et al,2 who found that HHT-related CVMs have a lower risk of hemorrhage than sporadic CVMs, but these findings alone are not persuasive enough to suggest that routine screening in HHT patients should not be practiced. In light of this, we feel strongly that all HHT patients should undergo baseline MRI screening, as neurological complications can be devastating. The risk of neurological events in HHT patients outweighs the costs generated by prospective screening. Family members of families who have had a serious neurological event should be given priority for screening. Pooled center data will also permit setting up guidelines for treatment of specific aspects of HHT-related CVMs, such as their multiplicity and size. The goal of MRI screening in HHT is to prevent life-threatening complications from CVMs.
References
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Maher CO, Piepgras DG, Brown RD, Friedman JA, Pollock BE. Cerebrovascular manifestations in 321 cases of hereditary hemorrhagic telangiectasia. Stroke. 2001; 32: 877–882.
[Abstract/Free Full Text] - Willemse RB, Mager JJ, Westerman CJJ, Overtoom TTC, Mauser H, Wolberg JG. Bleeding risk of cerebrovascular malformations in hereditary hemorrhagic telangiectasia. J Neurosurg. 2000; 92: 779–784.[Medline] [Order article via Infotrieve]
- Fulbright RK, Chaloupka JC, Putman CM, Sze GK, Merriam M, M, Lee GK, Fayad PB, Awad IA, White RI. MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations. AJNR Am J Neuroradiol. 1998; 19: 477–484.[Abstract]
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Matsubara S, Mandzia J, L, ter Brugge K, Willinsky RA, Montanera W, Faughnan ME. Angiographic and clinical characteristics of patients with cerebral arteriovenous malformations associated with hereditary hemorrhagic telangiectasia. AJNR Am J Neuroradiol. 2000; 21: 1016–1020.
[Abstract/Free Full Text] - Cymerman U, Vera S, Pece-Barbara N, Bourdeau A, White RI, Dunn J, Letarte M. Identification of hereditary hemorrhagic telangiectasia type 1 in newborns by protein expression and mutation analysis of endoglin. Pediatr Res. 2000; 47: 24–35.[Medline] [Order article via Infotrieve]
Response
Departments of Neurosurgery and Neurology, Mayo Clinic, Rochester, Minnesota
We appreciate the interest of Mandzia et al in our study.1 We agree it is likely that the prevalence rate of CVMs in our report (3.7%) would be higher if we screened each patient with arteriography or MRI/MR angiography (MRA). It is not clear, however, that the increased yield would lead to better clinical outcomes. As Mandzia et al acknowledge, the natural history of CVMs in HHT is not well described. We reported a low occurrence of intracranial hemorrhage in this population (2.1%). This low risk of hemorrhage is supported by the data of Fulbright et al as well as that of Willemse et al.2,3 Furthermore, in our series, patients had generally good functional outcomes following hemorrhage.
Mandzia et al correctly state that a subset of HHT families may be more likely to harbor CVMs. As we stated in our discussion, we agree that there may be such a subset of patients at increased risk, and one should consider more aggressive screening in these families.
In conclusion, we agree with Mandzia et al that there are still many unanswered questions regarding screening for CVMs in HHT. Given the safety of performing a head MRI/MRA, a study evaluating the impact of these noninvasive techniques on clinical outcome is needed. We agree that pooled data analyses of HHT patients from multiple centers will provide useful information regarding the incidence, radiographic characteristics, and natural history of CVMs in HHT. Given the risk of arteriography, there is not a compelling reason to screen all patients with HHT with standard arteriography on the basis of available data.
References
- Maher CO, Piepgras DG, Brown RD, Friedman JA, Pollock BE. Cerebrovascular manifestations in 321 cases of hereditary hemorrhagic telangiectasia. Stroke. 2001; 32: 877–882.
- Fulbright RK, Chaloupka JC, Putman CM, Sze GK, Merriam MM, Lee GK, Fayad PB, Awad IA, White RI. MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations. AJNR Am J Neuroradiol. 1998; 19; 477–484.
- Willemse RB, Mager JJ, Westerman CJJ, Overtoom TTC, Mauser H, Wolberg JG. Bleeding risk of cerebrovascular malformations in hereditary hemorrhagic telangiectasia. J Neurosurg. 2000; 92: 779–784.
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