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Jennifer Kosty and Timothy W. Vogel

For the past 2 decades, clinical and basic science researchers have gained significant insights into the molecular and genetic pathways associated with common forms of craniosynostosis. This has led to invaluable information for families and physicians in their attempts to understand the heterogeneity of craniosynostosis. Genetic mutations have been identified in the fibroblast growth factor receptors (FGFRs) as well as in other targets, including TWIST1, BMP, and RUNX2. Greater understanding of these and other pathways has led to the development of innovative approaches for applying medical therapies to the treatment of craniosynostosis, in particular by maintaining suture patency. In this article, the authors discuss the molecular pathophysiological mechanisms underlying various forms of craniosynostosis. They also highlight recent developments in the field of molecular craniosynostosis research with the hope of identifying targets for medical therapies that might augment the results of surgical intervention.

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Joseph C. Serrone, Ryan D. Tackla, Yair M. Gozal, Dennis J. Hanseman, Steven L. Gogela, Shawn M. Vuong, Jennifer A. Kosty, Calen A. Steiner, Bryan M. Krueger, Aaron W. Grossman and Andrew J. Ringer

OBJECTIVE

Many low-risk unruptured intracranial aneurysms (UIAs) are followed for growth with surveillance imaging. Growth of UIAs likely increases the risk of rupture. The incidence and risk factors of UIA growth or de novo aneurysm formation require further research. The authors retrospectively identify risk factors and annual risk for UIA growth or de novo aneurysm formation in an aneurysm surveillance protocol.

METHODS

Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 UIAs. The incidence of UIA growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for UIA growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed.

RESULTS

During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth and 4.3% of aneurysms had grown. Four de novo aneurysms formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth (UIA < 5 mm = 1.6% vs UIA ≥ 5 mm = 8.7%, p = 0.002). Patients with growing UIAs were more likely to also have de novo aneurysms (p = 0.01). Patient compliance with this protocol was 65%, with younger age predictive of better compliance (p = 0.01).

CONCLUSIONS

Observation of low-risk UIAs with surveillance imaging can be implemented safely with good adherence. Aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted.