Coexistence of Trigonocephaly and Sylvian Arachnoid Cysts: A Coincidence?

Abstract Introduction: The association between trigonocephaly and Sylvian fissure arachnoid cysts (ACs) has been occasionally reported in the literature. However, the real incidence of this association and its clinical relevance remain unknown. Methods: The authors collected and retrospectively reviewed all clinical charts and CT scans of patients surgically treated for trigonocephaly at the Pediatric Neurosurgical Department of Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS from January 2014 to June 2023. Results: During the study period, 136 patients with trigonocephaly underwent surgery. Analysis of the clinical charts revealed that in 39.7% of the cases (54/136), preoperative CT scan depicted the presence of a Sylvian fissure AC. Of these, AC was bilateral in 23 cases and unilateral in the remaining 31. All unilateral ACs were on the left side. The ACs were classified as Galassi grade I in 52 cases (96.3%) and Galassi grade II in 2 cases (3.7%). Interestingly, in 1 case we reported a Galassi grade I AC enlargement during follow-up, thereby necessitating surgical fenestration. Conclusion: ACs and trigonocephaly are well-known conditions for pediatric neurosurgeons; however, their association is poorly defined. Despite the lack of reports on the incidence and clinical significance of this association, it is worth knowing that radiological follow-up is essential in monitoring AC evolution.

Conversely, the association between trigonocephaly and Sylvian ACs is sporadic, with male predominance being the only apparent common feature [7,8].Symptomatic Sylvian ACs exhibit relatively aspecific clinical manifestations, such as headache, epileptic seizures, and developmental delay [9], while trigonocephaly might lead to intracranial hypertension, as well as visual and cognitive disturbances.It is then easy to see how the coexistence of these two entities might have a synergistic pathogenetic mechanism.Nevertheless, there are scarce reports on this association throughout the literature, leading to a lack of evidence regarding its clinical impact.This study aimed to retrospectively analyze trigonocephalic patients at our institution.

Methods
The authors retrospectively collected clinical charts and CT scans of patients surgically treated for trigonocephaly at the Pediatric Neurosurgical Department of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS from January 2014 to June 2023.The authors then evaluated the CT scans to assess the presence of Sylvian ACs.In order to define trigonocephaly severity, we measured the interfrontal angle (IFA) as shown in Figure 1, with an IFA <100°considered severe and an IFA >100°considered moderate [10,11].

Results
During the study period, 136 patients with trigonocephaly underwent surgery.The authors then stratified them according to the IFA, removing 28 patients who only had MRI scans at diagnosis, thus rendering IFA incomparable.It is worth mentioning that outside the study group, there was a one-year-old boy diagnosed with borderline trigonocephaly who was deemed nonsurgical but later had to be operated on for Sylvian AC.Sylvian fissure ACs were identified in 54 cases (39.7%), with unilateral occurrence in 31 cases (57.4%) and bilateral occurrence in 23 cases (42.6%).All unilateral ACs were on the left side, and based on the Galassi classification, 52 cysts were grade I, while 2 cysts were grade II [12].
Subsequently, the authors coupled the previous results, highlighting how there was an AC in 46.7% of cases with severe trigonocephaly, whereas only 23.9% of the sample exhibited such an association in the moderate group (Table 1).Four patients plus the borderline case underwent late radiological follow-up due to clinical deterioration or other causes (head trauma, psychomotor delay).The follow-up in these 5 cases revealed an increase in AC volume in 2 cases, stability in 1 case, and the disappearance of cystic formations in the remaining 2.

Discussion
ACs and trigonocephaly are well-known conditions for pediatric neurosurgeons.There are well-established management protocols for both of them whenever they are addressed as single entities.Nonetheless, our analysis suggests that the coexistence of ACs and trigonocephaly might be more frequent than occasionally reported.
In the literature, there are only two reports on the association between trigonocephaly and Sylvian ACs [7,8].In 2006, Börcek et al. [8] reported the case of an 11-month-old girl suffering from non-syndromic metopic suture synostosis and type II Sylvian AC.Bianchi/Agostini/Frassanito/Massimi/ Tamburrini Despite normal neurological examination and there being no seizure history, the authors decided to perform fronto-orbital advancement with forehead reconstruction for trigonocephaly and fenestration of the AC to the basal cisterns in a single procedure [8].On the other hand, in 2021, Baş et al. [7] reported in 2021 on 2 trigonocephaly patients who were both surgically treated with fronto-orbital advancement and calvarial remodeling without intervening on ACs.However, postoperative follow-ups showed radiological enlargement of the left temporal cyst in the first case and the right cyst in the second [7].This study is the first to attempt an evaluation of the real rate of association between ACs and trigonocephaly.Out of 136 children evaluated and treated at our institution for metopic craniosynostosis, 54 also had an AC, indicating an overall rate of 39.7%.Such a rate is much higher than the AC normal rate of presentation, suggesting something more than random evidence.A possible pathogenetic mechanism might reside in the combination of the dysmorphic anterior and middle cranial fossae with a focal increase in intracranial pressure that might hinder normal subarachnoid space development, leading to a focal lack of adequate opening and, thus, the formation of ACs.
The evidence in our sample, demonstrating a higher rate of AC presence in more severe trigonocephaly, seems to support such idea as almost half of the patients with an IFA ≤100°also had an AC, while only less than a third of the cases in the moderate group had such association.In addition, it is interesting to note the high rate of bilateral ACs in the presented cohort compared to the sporadic ones [13].Trigonocephaly, in fact, involves both the anterior and middle cranial fossa, necessitating bilateral correction, and almost half of our patients showed bilateral ACs.Though it is difficult to explain why none of our patients exhibited right-sided ACs only, the Trigonocephaly and Sylvian Arachnoid Cysts: A Coincidence? predominance of the left-sided ACs corresponds to what is well known for Sylvian fissure ACs [13].
Other data that might corroborate our suggestion relate to the majority of Galassi grade I cysts reported in both our sample and the literature.In fact, the cranial malformation might constrict the middle cranial fossa, thereby hindering the development of bigger cysts in addition to favoring an increase in local intracranial pressure.This idea could also explain why the reported ACs which increased in volume at followup were originally Galassi grade I. Somehow, the presence of a preoperative Galassi grade II AC might signify that the brain and subarachnoid space somewhat already found a different arrangement for the local condition favoring the development of ACs (Fig. 2).
The idea of a link between a dysmorphic bony anterior and middle fossa with AC presence might also be empowered by the evidence of the reported borderline trigonocephalic patient who also had an AC.Even though trigonocephaly was mild in the patient, it is arguable that the local condition was "not normal," increasing the likelihood of having a Sylvian fissure AC.Stretching the topic, it is possible to inquire whether borderline trigonocephaly could benefit from nonionizing radiological examination to exclude the presence of ACs.
Moving onto the reason for AC growth in this setting of patients, it is interesting to consider the potential contribution of surgery despite the known age-related risk of growth [14].In fact, fronto-orbital advancement and cranial remodeling lead to an abrupt increase of the aforementioned fossa, leaving extra space for the growing brain and subarachnoid space (Fig. 3).Taking into account the hypothesis of local intracranial hypertension and subarachnoid space isolation, the local cranial volume increase coupled with microsurgical trauma disallowed CSF redistribution, thus increasing the risk of AC enlargement.
As a limitation of the present study, it is worth noting that our data and those presented in the literature are biased by the actual lack of routine radiological follow-up for craniosynostosis patients.Patients, in fact, repeat neuroimaging only in cases of worsening of either clinical conditions or cranial contour.For the same reason, there were no further genetic evaluations in our series or in the literature.Nonetheless, despite only 5 patients in our cohort requiring a follow-up MRI, a noticeable growth of the cyst was highlighted in three of them, leading to surgical treatment in two.In those patients, cyst volume remained the same post-surgery, as expected after endoscopic procedures.

Conclusion
Coexistence of ACs and metopic craniosynostosis seems to be a much more common problem than previously thought.Thus, a scheduled radiological follow-up

Fig. 1 .
Fig. 1.CT scan, 3D reconstruction.IFA: Point A is defined as the absolute, anterior-most point of the cranium.The two lateral landmarks (B and C) are identified on the pterion, on the intersection of the coronal and squamosal sutures.

Fig. 2
Fig. 2. a Brain axial preoperative CT scan of a trigonocephaly patient showing the coexistence of metopic craniosynostosis and a bilateral Galassi grade I Sylvian AC. b Follow-up brain T2 axial scan showing AC enlargement after surgical decompression of the middle fossa.

Table 1 .
Coexistence of trigonocephaly and ACs