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

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

Bray, David P MD; Buster, Bryan E MD, MPH; Boucher, Andrew B MD; Wrubel, David M MD

doi: 10.1093/neuros/nyaa285

To the Editor:

It is with great interest that we read the manuscript by Roux et al1 entitled “High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study” published in April 2020.

The authors1 compared 162 pediatric patients with diffuse intrinsic pontine glioma (DIPG) to 142 pediatric patients with craniopharyngioma. They found a significantly higher prevalence of developmental venous anomaly (DVA) in the pediatric patients with DIPG vis-à-vis pediatric patients with craniopharyngioma. The association of presence of DVA with DIPG was not influenced nor predicted by other patient demographic, radiographic, or histopathological factors. The authors surmise that their observation of association between DIPG and extralesional DVAs may be secondary to a shared genetic mutation that has been noted in the development of soft tissue venous anomalies and high-grade pediatric glioma.2,3

The authors1 should be commended on their work, especially in their considerable experience in investigating DIPG tissue with histopathological analysis. It is clear that continued, safe acquisition of DIPG tissue is necessary to develop new treatment modalities for patients that harbor this grim diagnosis.4-8

Our institutional experience is that there is no significant association of extralesional DVA with DIPG.9 This is different than the data the authors presented in Roux et al.1

We queried the cohort of patients with a new diagnosis of DIPG treated at Children's Hospital of Atlanta (CHOA) from 2004 to 2019. We included all patients with a new diagnosis of DIPG who had imaging reviewable on our pictures archiving and communicating system. Images were reviewed by an attending neuroradiologist and confirmed by the lead author and senior author neurosurgeons (DPB and DMW). Characteristics of the patients (Table 1), tumor appearance on magnetic resonance imaging (MRI; Table 2), and pathology data were collected in a retrospective fashion. Descriptive statistics as well as categorical and univariate regression analyses were performed using statistical analysis system.

TABLE 1. - Demographic Information of Patient Population (n = 101)
 Male 44.5%
 Female 55.5%
Age 7 or younger 61.4%
Cavernous malformation present? 0%
Presenting symptoms
 Headache 28%
 CN Neuropathy 32%
 Emesis 5%
 Ataxia 23%
 Lethargy 2%
 Motor weakness 10%

TABLE 2. - Radiographic Features of Presenting MRI Brain With and Without Contrast (n = 101)
Midbrain involvement
 Yes N = 64
 No N = 37
Pons involvement
 Yes N = 100
 No N = 1
Medulla involvement
 Yes N = 41
 No N = 60
Hydrocephalus at diagnosis
 Yes N = 27
 No N = 74
Contrast enhancement
 Yes N = 56
 No N = 45
Biopsy performed
 Yes N = 19
 No N = 82
DVA present
 Yes N = 5
 No N = 96

A total of 101 patients met our inclusion criteria. Our observed frequency of extralesional DVA in patients with a new diagnosis of DIPG was much lower than what has been presented by Roux et al.1 Only 5 patients, or 4.95% of our cohort, were found to have an extralesional DVA at the time of diagnosis (Table 2). On univariate analysis, location/extension of tumor, symptoms leading to diagnosis of DIPG, and pathology data (when applicable) did not predict occurrence of DVA with DIPG (Table 3). The presence of contrast enhancement predicted the observation of DVA upon new diagnosis of DIPG. Younger age upon diagnosis of DIPG (less than 7 yr of age) and likelihood of observing a DVA trended toward significance.

TABLE 3. - Analysis of Predictors of DVA Presence on Presenting MRI Brain With and Without Contrast (n = 101)
DVA present (n) No DVA present (n) P value
Age .06
 7 or younger 3 59
 Older than 7 2 37
Presenting symptoms .31
 Headache 3 25
 CN Neuropathy 0 32
 Emesis 0 5
 Ataxia 2 21
 Lethargy 0 2
 Weakness 0 10
Radiographic features
 Midbrain 2 62 .28
 Pons 5 95 .75
 Medulla 3 38 .37
 Hydrocephalus 2 25 .51
 Contrast enhancement 3 53 .044

We present our data as a way of externally validating the research published by Roux et al. Our finding that less than 5% of patients presenting with a DIPG have a DVA is fitting with the observed “normal” occurrence rate of incidental DVAs.8 There are multiple reasons why our findings may be different than Roux et al. Our study population is younger than the population in Roux et al. Others have suggested the prevalence of DVAs increases with age, suggesting that DVAs develop secondary to an insult, rather than being congenital in nature.10 Second, the Roux et al population DIPGs had more intralesional contrast-enhancement observed. These findings may suggest our DIPG populations are genetically divergent.

In sum, our data regarding the association of DVA and DIPG differ from those reported by Roux et al.1 More studies, pathological/genetic DIPG analysis, and multi-institutional experience are needed to further our understanding of the complex association of DVA and DIPG.


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. 2020;86(4):517-523.
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