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Letter: High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study

Brinjikji, Waleed MD,; Sorenson, Thomas J BS; Lanzino, Giuseppe MD,

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doi: 10.1093/neuros/nyz445

To the Editor:

We read with interest the article by Roux et al1 entitled “High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study.” Their study of 162 pediatric patients with diffuse intrinsic pontine glioma (experimental set) and 142 pediatric patients with craniopharyngioma (control set) found a significantly higher prevalence of developmental venous anomaly (DVA) in the experimental set as compared to the control set of patients. This difference in prevalence was not significantly impacted by any other variables. The authors conclude that the increased DVA prevalence in pediatric diffuse pontine glioma patients suggests a potential underlying common predisposition or causal relationship.

The authors found that only one of the 39 DVAs was intralesional (ie, within the diffuse intrinsic pontine glioma [DIPG]), while the rest were in regions remote from the DVA. Aside from the one intralesional DVA, no other DVAs were located within the brainstem either. This suggests that the mechanism for DVA in this patient population is not from locoregional changes in the venous pressure and flow from the mass itself but rather from some other factor(s). Radiation-induced changes are also likely not to be blamed as a vast majority of cases were identified prior to any radiotherapy. The authors aptly point out that one potential pathophysiological link between DVAs and DIPG could be mutations in the PI3K catalytic subunit alpha (PI3KCA) gene as mutations in the PI3KCA gene are associated with high-grade gliomas in the pediatric population as well as the development of venous vascular malformations of the soft tissues, which are also associated with DVAs.2 As expected, a vast majority of the DIPGs were associated with H3-K27M mutations. Interestingly, a few studies have found that mutations in the PI3K pathway often accompany H3-K27M mutations among patients with neoplasms.3

We believe the Roux et al1 study is important for a couple of reasons. First, the study lends further support for the notion that a somatic mutation, perhaps in the PI3K pathway, could be responsible for the formation of developmental venous anomalies. Furthermore, this study may support a hypothesis of ours that many developmental venous anomalies are not necessarily congenital in nature but result from some insult—whether it be mechanical, genetic, or thrombotic, early in postnatal life. Of note, two-thirds of DVA patients were above 7 yr old in this study compared to half of patients without DVA. Furthermore, only one patient with a DVA was less than 4 yr old. In our recently published study on the age-related prevalence of DVAs, we found a sharp increase in the prevalence of DVAs from year 0 to 4 of birth, further suggesting that DVAs are not congenital but develop later in life.4


The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.


1. Roux A, Boddaert N, Grill J, et al. High prevalence of developmental venous anomaly in diffuse intrinsic pontine gliomas: a pediatric control study. Neurosurgery. published online: July 25, 2019 (doi:10.1093/neuros/nyz298).
2. Brinjikji W, Hilditch CA, Tsang AC, Nicholson PJ, Krings T, Agid R. Facial venous malformations are associated with cerebral developmental venous anomalies. AJNR Am J Neuroradiol. 2018;39(11):2103-2107.
3. Wan YCE, Liu J, Chan KM. Histone H3 mutations in cancer. Curr Pharmacol Rep. 2018;4(4):292-300.
4. Brinjikji W, El-Rida El-Masri A, Wald JT, Lanzino G. Prevalence of developmental venous anomalies increases with age. Stroke. 2017;48(7):1997-1999.
Copyright © 2019 by the Congress of Neurological Surgeons