OBJECT Patients with syndromic and complex craniosynostosis are characterized by the premature fusion of one or more cranial sutures. These patients are at risk for developing elevated intracranial pressure (ICP). There are several factors known to contribute to elevated ICP in these patients, including craniocerebral disproportion, hydrocephalus, venous hypertension, and obstructive sleep apnea. However, the causal mechanism is unknown, and patients develop elevated ICP even after skull surgery. In clinical practice, the occipitofrontal circumference (OFC) is used as an indirect measure for intracranial volume (ICV), to evaluate skull growth. However, it remains unknown whether OFC is a reliable predictor of ICV in patients with a severe skull deformity. Therefore, in this study the authors evaluated the relation between ICV and OFC. METHODS Eighty-four CT scans obtained in 69 patients with syndromic and complex craniosynostosis treated at the Erasmus University Medical Center-Sophia Children’s Hospital were included. The ICV was calculated based on CT scans by using autosegmentation with an HU threshold < 150. The OFC was collected from electronic patient files. The CT scans and OFC measurements were matched based on a maximum amount of the time that was allowed between these examinations, which was dependent on age. A Pearson correlation coefficient was calculated to evaluate the correlations between OFC and ICV. The predictive value of OFC, age, and sex on ICV was then further evaluated using a univariate linear mixed model. The significant factors in the univariate analysis were subsequently entered in a multivariate mixed model. RESULTS The correlations found between OFC and ICV were r = 0.908 for the total group (p < 0.001), r = 0.981 for Apert (p < 0.001), r = 0.867 for Crouzon-Pfeiffer (p < 0.001), r = 0.989 for Muenke (p < 0.001), r = 0.858 for Saethre- Chotzen syndrome (p = 0.001), and r = 0.917 for complex craniosynostosis (p < 0.001). Age and OFC were significant predictors of ICV in the univariate linear mixed model (p < 0.001 for both factors). The OFC was the only predictor that remained significant in the multivariate analysis (p < 0.001). CONCLUSIONS The OFC is a significant predictor of ICV in patients with syndromic and complex craniosynostosis. Therefore, measuring the OFC during clinical practice is very useful in determining which patients are at risk for impaired skull growth.

OBJECTIVEThe authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure.METHODSThis was a prospective observational cohort study of Muenke syndrome patients who underwent surgery for craniosynostosis within the first year of life. Symptoms and determinants of intracranial hypertension were evaluated by longitudinal monitoring of the presence of papilledema (fundoscopy), obstructive sleep apnea (OSA; with polysomnography), cerebellar tonsillar herniation (MRI studies), ventricular size (MRI and CT studies), and skull growth (occipital frontal head circumference [OFC]). Other evaluated factors included hearing, speech, and ophthalmological outcomes.RESULTSThe study included 38 patients; 36 patients underwent fronto-supraorbital advancement. The median age at last follow-up was 13.2 years (range 1.3–24.4 years). Three patients had papilledema, which was related to ophthalmological disorders in 2 patients. Three patients had mild OSA. Three patients had a Chiari I malformation, and tonsillar descent < 5 mm was present in 6 patients. Tonsillar position was unrelated to papilledema, ventricular size, or restricted skull growth. Ten patients had ventriculomegaly, and the OFC growth curve deflected in 3 patients. Twenty-two patients had hearing loss. Refraction anomalies were diagnosed in 14/15 patients measured at ≥ 8 years of age.CONCLUSIONSPatients with Muenke syndrome treated with a single fronto-supraorbital advancement in their first year of life rarely develop signs of intracranial hypertension, in accordance with the very low prevalence of its causative factors (OSA, hydrocephalus, and restricted skull growth). This illustrates that there is no need for a routine second craniofacial procedure. Patient follow-up should focus on visual assessment and speech and hearing outcomes.

Aim To evaluate the impact of risk factors for intracranial hypertension (ICH) on cerebral cortex thickness in syndromic craniosynostosis. Method ICH risk factors including papilloedema, hydrocephalus, obstructive sleep apnea (OSA), cerebellar tonsillar position, occipitofrontal circumference (OFC) curve deflection, age, and sex were collected from the records of patients with syndromic craniosynostosis (Apert, Crouzon, Pfeiffer, Muenke, Saethre‐Chotzen syndromes) and imaging. Magnetic resonance images were analysed and exported for statistical analysis. A linear mixed model was developed to determine correlations with cerebral cortex thickness changes. Results In total, 171 scans from 107 patients (83 males, 88 females [including repeated scans], mean age 8y 10mo, range 1y 1mo–34y, SD 5y 9mo) were evaluated. Mean cortical thickness in this cohort was 2.78mm (SD 0.17). Previous findings of papilloedema (p=0.036) and of hydrocephalus (p=0.007) were independently associated with cortical thinning. Cortical thickness did not vary significantly by sex (p=0.534), syndrome (p=0.896), OSA (p=0.464), OFC (p=0.375), or tonsillar position (p=0.682). Interpretation Detection of papilloedema or hydrocephalus in syndromic craniosynostosis is associated with significant changes in cortical thickness, supporting the need for preventative rather than reactive treatment strategies. What this paper adds Papilloedema is associated with thinning of the cerebral cortex in syndromic craniosynostosis, independently of hydrocephalus.

Therapeutic, III.

OBJECTIVEIntracranial hypertension is a major concern in children with syndromic craniosynostosis (sCS). Cerebral venous hypertension caused by cerebral venous outflow obstruction is believed to contribute to intracranial hypertension. The authors therefore hypothesized that cerebral venous volume would be increased in those children with sCS and intracranial hypertension.METHODSIn a case series of 105 children with sCS, of whom 32 had intracranial hypertension, cerebral MRI techniques were used to quantify the volume of the superior sagittal sinus, straight sinus (StrS), and both transverse sinuses.RESULTSLinear regression showed that total cerebral venous volume increased by 580.8 mm3 per cm increase in occipitofrontal head circumference (p < 0.001). No significant difference was found between the intracranial hypertension group and the nonintracranial hypertension group (p = 0.470). Multivariate ANOVA showed increased StrS volume (as a proportion of total volume) in the intracranial hypertension group (8.5% vs 5.1% in the nonintracranial hypertension group, p < 0.001). Multivariate logistic regression showed that a 100-mm3 increase in StrS volume is associated with increased odds of having intracranial hypertension by 60% (OR 1.60, 95% CI 1.24–2.08).CONCLUSIONSAlthough intracranial hypertension was not associated with total cerebral venous volume increase, it was associated with an isolated increase in StrS volume. Hence, it is unlikely that general cerebral venous outflow obstruction is the mechanism of intracranial hypertension in sCS. Rather, these findings indicate either a central cerebral vulnerability to intracranial hypertension or a mechanism involving venous blood redistribution.