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

We have read with great interest the letter from Long et al. regarding our article.1 Their letter stated two methodological concerns to which we will respond. The first concern is that objective criteria are missing for true trigonocephaly or benign metopic ridge. We only included patients with moderate to severe trigonocephaly according to the definitions of Birgfeld et al.2 In their article, Birgfeld et al. provide a phenotypical distinction between benign metopic ridge and metopic synostosis, as well as illustrative photographs with corresponding computed tomographic imaging.2 Cho et al.3 and Anolik et al.4 described computed tomographic measures to assess severity of metopic synostosis. In both studies, the cut-off point to determine surgical indication remained subjective, and poor consensus for the intermediate presentation of metopic craniosynostosis was found. In addition, Sisti et al.5 recently reviewed all literature in PubMed on trigonocephaly, relating to 15 anthropometric cranial measurements for surgical indications. They found that most articles have a lack of diagnostic criteria for trigonocephaly. 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 with mild presentation and 22 with moderate or severe presentation). The second concern Long et al. raise is the potential blunting effect of sevoflurane on cerebral blood flow (CBF). If there is a blunting effect, a similar effect on both patients and controls is expected. In our previous arterial spin labeling 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 arterial spin labeling CBF in the pediatric population. Carsin-Vu et al.7 included 84 subjects ranging in age from 6 months to 15 years and showed no significant CBF changes with sevoflurane in comparison to general anesthesia. Kaisti et al.8 showed in eight healthy male patients (age range, 20 to 26 years) that sevoflurane reduced regional CBF less than propofol did. 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 functional magnetic resonance imaging (MRI) studies in patients with scaphocephaly have shown a difference in functional brain connectivity compared with controls. However, there is still a lot unknown about the optimal method of scanning, reproducibility, and interpretation of functional MRI results. Finding a difference in connectivity in functional MRI studies would be at the same level of evidence as the arterial spin labeling brain MRI study.9 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. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. Catherine A. de Planque, MDDepartment of Plastic, Reconstructive Surgery, and Hand SurgeryErasmus MC-Sophia Children’s HospitalUniversity Medical Center RotterdamRotterdam, The Netherlands Jan Petr, PhDHelmholtz-Zentrum Dresden-RossendorfInstitute of Radiopharmaceutical Cancer ResearchDresden, Germany Linda Gaillard, MDDepartment of Plastic, Reconstructive Surgery, and Hand SurgeryErasmus MC-Sophia Children’s HospitalUniversity Medical Center RotterdamRotterdam, The Netherlands Henk J. M. M. Mutsaerts, MD, PhDVrije Universiteit AmsterdamAmsterdam NeuroscienceAmsterdam, The Netherlands Marie-Lise C. van Veelen, MD, PhDDepartment of Neurosurgery Sarah L. Versnel, MD, PhDDepartment of Plastic, Reconstructive Surgery, and Hand Surgery Marjolein H. G. Dremmen, MDDepartment of Radiology and Nuclear Medicine Irene M. J. Mathijssen, MD, PhD, MBA-HDepartment of Plastic, Reconstructive Surgery, and Hand SurgeryErasmus MC-Sophia Children’s HospitalUniversity Medical Center RotterdamRotterdam, The Netherlands