64 Chapter 4 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. showed in 8 healthy males (age range 20-26) that sevoflurane reduced regional CBF less than propofol.8 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
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