Published ahead of print on March 24, 2011
doi: 10.3174/ajnr.A2491

American Journal of Neuroradiology 32:E76-E77, April 2011
© 2011 American Society of Neuroradiology

M. Schumacher^a
aUniversity of Freiburg
Department of Neuroradiology
Freiburg, Germany

I read with interest the article entitled “Klippel-Trénaunay Syndrome and Spinal Arteriovenous Malformations: An Erroneous Association” by Alomari et al.¹ The classification of Klippel-Trénaunay syndrome (KTS) in the complex group of segmental angiomatous phakomatoses based on data from meta-analyses and the findings of 208 patients with the diagnosis KTS is commendable and important with respect to the diagnostic lack of clarity in the classification of overgrowth disorders.

It is, however, a difficult task to precisely define from the material described in 24 publications whether combinations of KTS and spinal arteriovenous malformation (AVM) exist or can be ruled out. The statement capability of a meta-analysis, which usually can confirm modifications or trends, thus appears overtaxed. Likewise, mention of the clinical or radiologic data of 208 patients at the Vascular Anomalies Center at Children’s Hospital Boston, when these data are not presented, is not suitable to support the central statement of the article that in principle, no combination of KTS and spinal AVMs exists. The Boston patient data leave unanswered the decisive question of which imagingdiagnostics were used to rule out spinal AVMs.

Our own case report² confirms, in my opinion, that KTS may be combined with spinal AVMs in the form of a Klippel-Trénaunay-Weber syndrome. Our patient presented all criteria of KTS, such as port-wine stain, congenital varices, lymphatic edema, and hypertrophy of soft tissue and of a lower extremity with additional extensive intraspinal and paraspinal AVMs (Fig 1 ). The observations of >16 years to date after embolization of 17 spinal (T7-L5) and paraspinal feeding arteries in this patient shows a largely normal physical development without exponential growth of the affected leg (Fig 2 after 5-year follow-up).

For the reasons cited above and based on my own experience, I consider combinations of KTS with spinal AVM to be possible, as described by Young et al (Table).³

References

1. Alomari AI, Orbach DB, Mulliken JB, et al. Klippel-Trenaunay syndrome and spinal arteriovenous malformations: an erroneous association. AJNR Am J Neuroradiol 2010;31:1608–12[Abstract/Free Full Text]
2. Orszagh M, Schulte DM, Korinthenberg R, et al. Analysis of hemodynamics by MR-angio and embolization of Klippel-Trenaunay-Weber syndrome: five year follow-up. Revista di Neuroradiologia 1999;12 (suppl 2):127–31
3. Young AE, Ackroyd J, Baskerville P. Combined vascular malformations. In: Mulliken JB, Young AE, eds. Hemangiomas and Malformations. Philadelphia:Saunders; 1988:246–74

Reply

Published ahead of print on March 24, 2011
doi: 10.3174/ajnr.A2513

American Journal of Neuroradiology 32:E78-E79, April 2011
© 2011 American Society of Neuroradiology

A.I. Alomari^a and D.B. Orbach^a
aDivision of Interventional Radiology

J.B. Mulliken^b
bDepartment of Plastic Surgery

S.J. Fishman^c
cDepartment of Surgery
Children’s Hospital Boston and Harvard Medical School
Boston, Massachusetts

A. Norbash^d
dDepartment of Radiology
Boston Medical Center and Boston University
Boston, Massachusetts

A. Bisdorff^e
eNeurointerventional Radiology
Hôpital Lariboisière
Paris, France

R. Alokaili^f
fDepartment of Medical Imaging
King Abdulazziz Medical City
Riyadh, Saudi Arabia

D.J. Lord^g
gDepartment of Radiology
Children’s Hospital Westmead
Sydney, Australia

P.E. Burrows^h
hDepartment of Diagnostic ImagingTexas Children’s Hospital
Houston, Texas

We thank Dr. Schumacher for his interest and comments on our article entitled “Klippel-Trenaunay Syndrome and Spinal Arteriovenous Malformations: An Erroneous Association.”¹ What is not surprising, and as we stated in the article, Klippel-Trenaunay syndrome (KTS) is still a field rife with controversy and disagreement. In his letter to the editor, Dr Schumacher made some valuable comments about KTS. However, we would like to take this opportunity to respond to some of the assertions with which we disagree.

There is no doubt that the diagnosis of overgrowth syndrome can be challenging, particularly when vascular anomalies arealso present. Several factors (including the rarity of these diseases, the complexity of the clinical features, and some overlap between these conditions) lead to the diagnostic inaccuracy commonly noted in the published literature.²

The assertion by Dr Schumacher that “the statement capability of a meta-analysis … appears overtaxed” does not apply toour article. The analysis of the published cases of presumed KTS and spinal arteriovenous malformation (AVM) was a criticalsystematic review, not a meta-analysis. Meta-analysis, as defined by the Cochrane Collaboration, refers to statistical techniques in a systematic review to integrate the results of included studies; it should not be misused as a synonym for systematic reviews.³

Regarding the lack of clinical and radiologic evidence of KTS and spinal AVM in the cohort of the Vascular Anomalies Centerat Children’s Hospital Boston, we unreservedly agree with Dr Schumacher that including these data to support the theory ofour article leaves unanswered questions. Nevertheless, the objective of the article was neither to prove a negative through inductive reasoning (ie, lack of this association in nature) nor to present incontrovertible evidence. We rather opted specifically to disprove the presence of positive evidence of such an association. We were cognizant not to claim infallibility in this work. The onus lies with the authors who report such an association to prove that their patients do have KTS and not any other vascular condition.

Regardless of whether one adopts a “lumper” or “splitter” approach to these disorders, it is imperative not to disregard the advances in knowledge in vascular anomalies. Defining KTS as a combination of slow-flow vascular malformations (capillary, lymphatic, and venous) in an overgrown limb⁴ allows for better understanding of the disease, for distinction from other disorders and for the emergence of newly described syndromes. The result of such careful diagnosis is that many patients who initially had the diagnosis of KTS turned out to have other conditions such as CLOVES syndrome, capillary malformation-AVM, isolated phlebectasia, extensive venous malformation, capillary malformation with overgrowth, combined vascular anomalies, Parkes-Weber syndrome (PWS), and so forth. These disorders have distinct clinical and imagingfeatures, though unfortunately, the published literature still commonly lumps many of them under KTS. As an example, thetable provided by Dr Schumacher compared the diagnostic features of KTS with those of PWS. Some of the information in this table seems to be based on older data that have been revised, updated, and changed in the light of the progress in understanding of these diseases (Table).

On the basis of the limited information provided regarding the patient presented by Dr Schumacher, it is difficult to draw a solid conclusion. The child has a pink port-wine stain on 1 leg and pelvic wall with enlarged vessels on the MR images.Because the child failed to meet the criteria of either KTS or PWS, Dr Schumacher, without a clear justification, picked some of the KTS features and others from PWS and called the disorder “Klippel-Trenaunay-Weber” syndrome. The type and distribution of the stain, the MR imaging findings, and the interval improvement between 1 and 5 years of age are not classic features of KTS, in addition to the arbitrary nature of the diagnosis. PWS is not “KTS with arteriovenous shunts.” KTS and PWS are 2 distinct disorders with different vascular components and natural histories. The use of nonspecific terms such as “angiomatous phakomatosis” and the triple eponym “Klippel-Trenaunay-Weber” syndrome is confusing and creates further nosologic uncertainty. Improper terminology can lead to the wrong diagnosis, mistreatment, and misdirected research efforts.⁵

In conclusion, we appreciate Schumacher’s comments on our article, but we strongly disagree with the assertion that an association between KTS and spinal AVM has been unquestionably proved. The historical temptation to diagnose any large extremity with a vascular lesion as KTS is a common fundamental diagnostic fallacy and should be curtailed.

References

1. Alomari AI, Orbach DB, Mulliken JB, et al. Klippel-Trenaunay syndrome and spinal arteriovenous malformations: an erroneous association. AJNR Am J Neuroradiol2010;31:1608–12[Abstract/Free Full Text]
2. Turner JT, Cohen MM, Jr, Biesecker LG. Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. Am J Med Genet A 2004;130A:111–22
3. Higgins JP, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.2. The Cochrane Collaboration, 2009. www.cochrane-handbook.org. Accessed January 11, 2011.
4. Mulliken JB. Cutaneous vascular anomalies. Semin Vasc Surg 1993;6:204–18[Medline]
5. Cohen MM, Jr. Klippel-Trenaunay syndrome. Am J Med Genet 2000;93:171–75[CrossRef][Medline]