What We Know About Intracranial Hypertension in Children With Syndromic Craniosynostosis.

OBJECTIVE: A scoping review of literature about mechanisms leading to intracranial hypertension (ICH) in syndromic craniosynostosis (sCS) patients, followed by a narrative synopsis of whether cognitive and behavioral outcome in sCS is more related to genetic origins, rather than the result of ICH. METHODS: The scoping review comprised of a search of keywords in EMBASE, MEDLINE, Web of science, Cochrane Central Register of Trials, and Google scholar databases. Abstracts were read and clinical articles were selected for full-text review and data were extracted using a structured template. A priori, the authors planned to analyze mechanistic questions about ICH in sCS by focusing on 2 key aspects, including (1) the criteria for determining ICH and (2) the role of component factors in the Monro-Kellie hypothesis/doctrine leading to ICH, that is, cerebral blood volume, cerebrospinal fluid (CSF), and the intracranial volume. RESULTS: Of 1893 search results, 90 full-text articles met criteria for further analysis. (1) Invasive intracranial pressure measurements are the gold standard for determining ICH. Of noninvasive alternatives to determine ICH, ophthalmologic ones like fundoscopy and retinal thickness scans are the most researched. (2) The narrative review shows how the findings relate to ICH using the Monro-Kellie doctrine. CONCLUSIONS: Development of ICH is influenced by different aspects of sCS: deflection of skull growth, obstructive sleep apnea, venous hypertension, obstruction of CSF flow, and possibly reduced CSF absorption. Problems in cognition and behavior are more likely because of genetic origin. Cortical thinning and problems in visual function are likely the result of ICH.

The Course and Interaction of Ventriculomegaly and Cerebellar Tonsillar Herniation in Crouzon Syndrome over Time.

Children with Crouzon syndrome have a higher incidence of cerebellar tonsillar herniation (TH) and ventriculomegaly than the general population, or children with other craniosynostosis syndromes. OBJECTIVE: This retrospective cohort study aimed to determine how ventriculomegaly and TH develop and progress over time, and determine associations between ventriculomegaly and TH in Crouzon patients, treated according to our center's protocol. METHODS: Fronto-occipital horn ratio (FOHR) and TH were determined over time using brain-imaging. These data were used to fit a mixed-model to determine associations between them, and with clinical variables, head-circumference, and lambdoid suture synostosis. RESULTS: Sixty-three Crouzon patients were included in this study. Preoperatively, 28% had ventriculomegaly, and 11% had TH ≥ +5 mm. Postoperatively ventriculomegaly increased to 49%. Over time and with treatment, FOHR declined and stabilized around 5 years of age. TH ≥ +5 mm increased to 46% during follow-up. FOHR and TH were associated: expected FOHR with a TH of either 0 mm versus +8.6 mm at 0 years: 0.44 versus 0.49, and at 5 years: 0.34 versus 0.38; 10% increase of FOHR was associated with 1.6 mm increase in TH. Increased head-circumference was associated with increased FOHR. Lambdoid suture synostosis was associated with +6.9 mm TH increase. CONCLUSIONS: In Crouzon patients, FOHR was large at onset and decreased and stabilized with treatment and time. FOHR was associated with head-circumference and TH. TH was strongly associated with lambdoid suture synostosis and FOHR. Increased head-circumference was associated with an increased FOHR, and closed lambdoid sutures before 1 year of age were associated with a +6.92 mm increase in tonsil position.

Cerebral blood flow in children with syndromic craniosynostosis: cohort arterial spin labeling studies.

OBJECTIVE: In comparison with the general population, children with syndromic craniosynostosis (sCS) have abnormal cerebral venous anatomy and are more likely to develop intracranial hypertension. To date, little is known about the postnatal development change in cerebral blood flow (CBF) in sCS. The aim of this study was to determine CBF in patients with sCS, and compare findings with control subjects. METHODS: A prospective cohort study of patients with sCS using MRI and arterial spin labeling (ASL) determined regional CBF patterns in comparison with a convenience sample of control subjects with identical MRI/ASL assessments in whom the imaging showed no cerebral/neurological pathology. Patients with SCS and control subjects were stratified into four age categories and compared using CBF measurements from four brain lobes, the cerebellum, supratentorial cortex, and white matter. In a subgroup of patients with sCS the authors also compared longitudinal pre- to postoperative CBF changes. RESULTS: Seventy-six patients with sCS (35 female [46.1%] and 41 male [53.9%]), with a mean age of 4.5 years (range 0.2-19.2 years), were compared with 86 control subjects (38 female [44.2%] and 48 male [55.8%]), with a mean age of 6.4 years (range 0.1-17.8 years). Untreated sCS patients < 1 year old had lower CBF than control subjects. In older age categories, CBF normalized to values observed in controls. Graphical analyses of CBF by age showed that the normally expected peak in CBF during childhood, noted at 4 years of age in control subjects, occurred at 5-6 years of age in patients with sCS. Patients with longitudinal pre- to postoperative CBF measurements showed significant increases in CBF after surgery. CONCLUSIONS: Untreated patients with sCS < 1 year old have lower CBF than control subjects. Following vault expansion, and with age, CBF in these patients normalizes to that of control subjects, but the usual physiological peak in CBF in childhood occurs later than expected.

The effect of early fusion of the spheno-occipital synchondrosis on midface hypoplasia and obstructive sleep apnea in patients with Crouzon syndrome.

INTRODUCTION: The investigators hypothesized that patients with Crouzon syndrome and premature fusion of the spheno-occipital synchondrosis (SOS) more often have, or have more severe midface hypoplasia and obstructive sleep apnea (OSA). METHODS: A prospective cohort study was performed among patients with Crouzon syndrome to analyze SOS closure, midface hypoplasia represented by the sella-nasion angle (SNA) and OSA. RESULTS: Forty patients were included in whom the OSA-prevalence was 65%. Kaplan Meier analyses suggest a trend towards earlier closure of synchondrosis in patients with OSA (p = 0.066). The mean SNA was 74.7°. There was a positive effect of age on the SNA (p = 0.020). There was no difference in SNA for patients with an open SOS as compared to patients with a closed SOS after correction for age. CONCLUSIONS: The longitudinal data are suggestive of a trend towards earlier fusion of the SOS in patients with Crouzon syndrome and OSA as compared to patients with Crouzon syndrome without OSA. Although the SNA increases with age, our results suggest that this increase in independent closure of the SOS.

Upper airway endoscopy to optimize obstructive sleep apnea treatment in Apert and Crouzon syndromes.

INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent in children with Apert and Crouzon syndromes. Although often related to midface hypoplasia, it is a multi-level problem for which routine midface advancement might be a suboptimal treatment choice. We therefore wished to: 1.) use upper airway endoscopy to examine the level of obstruction in children with OSA; 2.) determine the relationship between endoscopic assessment and OSA severity; and 3.) evaluate the effect of surgery on endoscopic assessment and OSA severity. METHODS: Prospective observational cohort study of patients considered for midface advancement, underwent upper airway endoscopy. Endoscopy findings were scored according to the system of Bachar, based on level (nose, uvulopalatine plane, tongue base, hypopharynx and larynx); and severity (no, partial or complete obstruction). Polysomnography was used to diagnose OSA. RESULTS: We included 22 children (Apert N = 10, Crouzon N = 12), 17 had OSA, 14 of whom had multilevel obstruction and 3 single-level obstruction. The endoscopy findings were correlated with OSA severity: R = 0.56, P = 0.01. Midface advancement (N = 8) reduced Bachar's severity index in 7 of 8 patients, and OSA in all patients. CONCLUSIONS: OSA in children with Apert or Crouzon syndrome is often a multi-level problem. Upper airway endoscopy is essential to optimizing OSA treatment.