Apert syndrome: the Paris and Rotterdam philosophy

Introduction: Apert syndrome is a rare type of syndromic craniosynostosis. Patients have an explicit phenotype with craniofacial dysmorphologies and severe symmetrical syndactyly of the hands and feet. This review includes background information about the syndrome and several aspects of the treatment. Areas covered: The cause of Apert syndrome is found in unique mutations in the Fibroblast Growth Factors Receptor (FGFR) 2 gene in 99%. It results in cranial suture fusion, craniofacial dysmorphologies and severe symmetrical syndactyly of the hands and feet. Patients with Apert syndrome are at risk for mental retardation, mobility impairment and intracranial hypertension (ICHT). This is the result of a complex interaction between (1) abnormal skull growth, (2) ventriculomegaly, (3) venous outflow obstruction and (4) obstructive sleep apnea (OSA). Mental retardation is mainly determined by the FGFR2 mutation and treatment is directed at protecting the intrinsic potential of neurocognition. Expert Opinion: To prevent ICHT, we prefer an occipital expansion in the first year of life. Screening on ICHT and its underlying causes is necessary at least until the age of ten by means of skull circumference measurements, fundoscopy, optical coherence tomography, MRI and polysomnography. Multicentre studies on long-term outcome are required to validate the rationale of different clinical protocols

Does early resection of presumed low-grade glioma improve survival? A clinical perspective

Early resection is standard of care for presumed low-grade gliomas. This is based on studies including only tumors that were post-surgically confirmed as low-grade glioma. Unfortunately this does not represent the clinicians’ situation wherein he/she has to deal with a lesion on MRI that is suspect for low-grade glioma (i.e. without prior knowledge on the histological diagnosis). We therefore aimed to determine the optimal initial strategy for patients with a lesion suspect for low-grade glioma, but not histologically proven yet. We retrospectively identified 150 patients with a resectable presumed low-grade-glioma and who were otherwise in good clinical condition. In this cohort we compared overall survival between three types of initital treatment strategy: a wait-and-scan approach (n = 38), early resection (n = 83), or biopsy for histopathological verification (n = 29). In multivariate analysis, no difference was observed in overall survival for early resection compared to wait-and-scan: hazard ratio of 0.92 (95% CI 0.43–2.01; p = 0.85). However, biopsy strategy showed a shorter overall survival compared to wait-and-scan: hazard ratio

Intracranial hypertension and cortical thickness in syndromic craniosynostosis

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, 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

Cortical Thickness in Crouzon-Pfeiffer Syndrome: Findings in Relation to Primary Cranial Vault Expansion

Background: Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon–Pfeiffer syndrome patients to measure CT and evaluate associations with type of primary cranial vault expansion and synostosis pattern. Methods: Records from 34 Crouzon–Pfeiffer patients were reviewed along with MRI data on CT and intracranial volume to examine associations. Patients were grouped according to initial cranial vault expansion (frontal/occipital). Data were analyzed by multiple linear regression controlled for age and brain volume to determine an association between global/lobar CT and vault expansion type. Synostosis pattern

Saethre–Chotzen syndrome: long-term outcome of a syndrome-specific management protocol

Aim: To assess the long-term outcomes of our management protocol for Saethre–Chotzen syndrome, which includes one-stage fronto-orbital advancement. Method: All patients born with Saethre–Chotzen syndrome between January 1992 and March 2017 were included. Evaluated parameters included occipital frontal head circumference (OFC), fundoscopy, neuroimaging (ventricular size, tonsillar position, a

Improvement in Sleep Architecture is associated with the Indication of Surgery in Syndromic Craniosynostosis

Background: Children with syndromic craniosynostosis (sCS) often suffer from obstructive sleep apnea (OSA) and intracranial hypertension (ICH). Both OSA and ICH might disrupt sleep architecture. However, it is unclear how surgically treating OSA or ICH affects sleep architecture. The aim of this study was twofold: to explore the usefulness of sleep architecture analysis in detecting disturbed sleep and to determine whether surgical treatment can improve it. Methods: Eighty-three children with sCS and 35 control subjects, who had undergone a polysomnography (PSG), were included. Linear-mixed models showed the effects of OSA and ICH on sleep architecture parameters. In a subset of 19 patients, linear regression models illustrated the effects of OSA-indicated and ICHindicated surgery on pre-to-postoperative changes. Results: An increase in obstructive-apnea/hypopnea index (oAHI) was significantly associated with an increase in N2-sleep, arousal index, and respiratoryarousal index and a decrease in REM-sleep, N3-sleep, sleep efficiency, and sleep quality. ICH and having sCS were not related to any change in sleep architecture. OSA-indicated surgery significantly increased the total sleep time and sleep efficiency and decreased the arousal index and respiratory-arousal index. ICHindicated surgery significantly decreased REM-sleep, N1-sleep, sleep efficiency, and sleep quality. Conclusions: For routine detection of disturbed sleep in individual subjects, PSGassessed sleep architecture is currently not useful. OSA does disrupt sleep architecture, but ICH does not. OSA-indicated surgery improves sleep architecture, which stresses the importance of treating OSA to assure adequate sleep. ICH-indicated surgery affects sleep architecture, although it is not clear whether this is a positive or negative effect

Craniosynostosis affects the majority of mucopolysaccharidosis patients and can contribute to increased intracranial pressure

Background: The mucopolysaccharidoses are multisystem lysosomal storage diseases characterized by extensive skeletal deformities, including skull abnormalities. The objective of this study was to determine the incidence of craniosynostosis in the different mucopolysaccharidosis (MPS) types and its clinical consequences. Methods: In a prospective cohort study spanning 10 years, skull imaging and clinical evaluations were performed in 47 MPS patients (type I, II, VI,