Reply: Discussion Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study

Dear Editor,
We have read the letter to the editor from Long et al. with great interest. 1 The authors of this
letter stated two methodological concerns on which we will respond.
The first concern is that objective criteria are missing for true trigonocephaly or benign metopic
ridge. We only included moderate to severe trigonocephaly patients according to the definitions
of Birgfeld et al2. Birgfeld et al. provide both a phenotypical distinction between benign metopic
ridge and metopic synostosis in their article, as well as illustrative photographs with
corresponding CT-imaging in Figure 1.2 Cho et al. and Anolik et al. described CT measures to
assess severity of metopic synostosis. In both articles the cut-off point to determine surgical
indication remains subjective and poor consensus for the intermediate presentation of metopic
craniosynostosis is found.3, 4 In addition, Sisti et al. recently reviewed all literature in Pubmed
on trigonocephaly, relating to 15 anthropometric cranial measurements for surgical
indications.5 This study illustrates that most papers have a lack of diagnostic criteria for
trigonocephaly.5 At our center, the decision for surgery is made through shared decision
making with parents. In 2021 this resulted in surgery for 14 patients (moderate or severe
presentation) and a conservative treatment for 40 patients (18 mild, and 22 moderate or severe
presentation).
The second raised concern is the potential blunting effect of sevoflurane on CBF. If it does, a
similar effect on both the patients and controls is expected. In our previous ASL study in
patients with syndromic craniosynostosis using the same sedation protocol, we found a
difference between the groups.6 This suggests that the normal findings in patients with
trigonocephaly reflect normal CBF.
Very few studies have investigated the influence of anesthesia on ASL CBF in the pediatric
population. Carsin-Vu et al. included 84 subjects from 6 months to 15 years and showed no
significant CBF changes with sevoflurane in comparison with general anesthesia.7 Kaisti et al.
Without sedation, scanning of one sequence is possible, because of the limited timeframe.
However, more sequences, as in our protocol, requires a longer time period. Without sedation,
motion artifacts would make it impossible to analyze.
Finally, Long et al. mention that cerebral perfusion is a limited measure of neurodevelopment
and that fMRI studies in scaphocephaly patients have shown a difference in functional brain
connectivity compared to controls. However, there is still a lot unknown about the optimal way
of scanning, reproducibility, and interpretation of the fMRI results. Finding a difference in
connectivity in fMRI studies would be at the same level of evidence as the ASL brain MRI
study.
To conclude, our study further supports our hypothesis that surgery for trigonocephaly is rarely
indicated functionally. Parents should be informed about the unknown added value of surgery
regarding raised intracranial pressure and brain perfusion. Comparative research on outcome of
conservative versus surgical treatment of moderate to severe trigonocephaly is needed to establish clinical guidelines.