Quantitative detection and follow-up of intracranial hypertension in craniosynostosis:an optical coherence tomography study

BACKGROUND/PURPOSE: To evaluate in craniosynostosis: 1) the diagnostic accuracy of fundoscopy and optical coherence tomography (OCT) to detect intracranial hypertension (ICH); 2) the time course of retinal thickness after treatment of ICH; and 3) the relation between high hyperopia (HH) and fundoscopy/OCT scan findings.METHODS: Syndromic, multisuture, unicoronal, unilambdoid and sagittal synostosis patients visiting our national center were included in this longitudinal cohort study and formed a consecutive series. Retinal layers on OCT, OCT fundus image and fundoscopy were evaluated. ICH was scored according to presence of abnormal intracranial pressures, hydrocephalus, progressive cerebellar tonsillar herniation or fingerprinting and growth arrest. Diagnostic accuracy of OCT, fundoscopy and fundus image, the time course of retinal thickness after ICH and interference of HH were analyzed using linear mixed models.RESULTS: 577 OCT scans in 307 patients were included. ICH was found in 7.2%. Combining total retinal thickness (TRT), OCT fundus image and fundoscopy resulted in a sensitivity of 76% and 81% specificity to detect signs of ICH. TRT was increased in patients who have had signs of ICH versus patients who never had signs of ICH (β+44.9 µm in patients who have had ICH, 95%CI 9.0-80.8,P=0.01). TRT decreased to normal in the years after surgery (β -3.6 µm/year, 95%CI -7.2 - -0.05, P=0.047). There were greater odds of having increased TRT in patients with HH (OR 2.9, 95%CI 1.1-7.6,P=0.03).CONCLUSIONS: The correlation between TRT, OCT fundus image, fundoscopy and particularly for the combination of these parameters with ICP surrogate markers is fair. Increased TRT in the presence of a clinical suspicion of ICH warrants further screening.</p

Cerebral cortex maldevelopment in syndromic craniosynostosis

AIM: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis. METHOD: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo–24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log‐transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome. RESULTS: Mean ICV was greater in patients with FGFR (1519cm(3), SD 269cm(3), p=0.016) than in patients with TWIST1 (1304cm(3), SD 145cm(3)) or controls (1405cm(3), SD 158cm(3)). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61–0.76) in patients with FGFR compared to 0.81 (95% CI 0.50–1.12) in patients with TWIST1 and 0.77 (95% CI 0.61–0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42–0.59) and occipital (0.67, 95% CI 0.54–0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR. INTERPRETATION: Despite adequate ICV in FGFR‐mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR

Does the association between abnormal anatomy of the skull base and cerebellar tonsillar position also exist in syndromic craniosynostosis?

Purpose: Cerebellar tonsillar herniation (TH) occurs frequently in syndromic craniosynostosis; however, the exact pathogenesis is unknown. This study evaluates the association between skull base deformities and TH in syndromic craniosynostosis. Methods: Retrospective study MRI study comparing syndromic craniosynostosis to controls. Measured parameters included clivus length, skull base angle, Boogard's angle, foramen magnum area, and cerebellar tonsillar position (TP). The association between skull base parameters and TP was evaluated with linear mixed models, correcting for age and risk factors for TH in craniosynostosis (hydrocephalus, intracranial hypertension, craniocerebral disproportion, and lambdoid synostosis). Results: Two hundred and eighty-two scans in 145 patients were included, and 146 scans in 146 controls. The clivus was smaller at birth, and its growth was retarded in all syndromes. The skull base angle was smaller at birth in Apert and Crouzon syndromes, and the evolution through time was normal. Boogard's angle was smaller at birth in Apert syndrome, and its evolution was disturbed in Apert and Saethre-Chotzen syndromes. The foramen magnum was smaller at birth in Crouzon and Saethre-Chotzen syndromes, and its growth was disturbed in Apert, Crouzon, and Saethre-Chotzen syndromes. TP was higher at birth in Apert syndrome, but lowered faster. In Crouzon syndrome, TP was lower at birth and throughout life. A smaller clivus and larger foramen magnum were associated with a lower TP in controls (p<0.001, p=0.007), and in Crouzon syndrome, this applied to only foramen magnum size (p=0.004). Conclusion: The skull base and its growth are significantly different in syndromic craniosynostosis compared to controls. However, only foramen magnum area is associated with TP in Crouzon syndrome

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 [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

The use of OCT to detect signs of intracranial hypertension in patients with sagittal suture synostosis:Reference values and correlations

PURPOSE: To obtain pediatric normative reference values and determine whether optical coherence tomography (OCT) corresponds better with clinical signs of intracranial hypertension (ICH) compared to the traditional screening method fundoscopy in a large cohort of one type of single suture craniosynostosis. METHODS: Control subjects without optic nerve diseases and isolated sagittal synostosis patients aged 3–10 years who underwent fundoscopy and OCT were included in this prospective cohort study. Normative reference values were obtained through bootstrap analysis. Main outcome was the association between peripapillary total retinal thickness (TRT) and total retinal volume (TRV) and appearance on fundoscopy. Signs and symptoms suggestive of ICH, including skull growth arrest, fingerprinting, and headache, were scored. RESULTS: Sixty-four healthy controls and 93 isolated sagittal synostosis patients were included. Normative cut-off values for mean TRT are  504 μm and for mean TRV  0.39 mm(3). TRT was increased in 16 (17%) and TRV in 15 (16%) of 93 patients, compared to only 4 patients with papilledema on fundoscopy (4%). Both parameters were associated with papilledema on fundoscopy (OR = 16.7, p = 0.02, and OR = 18.2, p = 0.01). Skull growth arrest was significantly associated with abnormal OCT parameters (OR = 13.65, p < 0.01). CONCLUSIONS: The established cut-off points can be applied to screen for ICH in pediatrics. The present study detected abnormalities with OCT more frequent than with fundoscopy, which were associated with skull growth arrest. Therefore, a combination of OCT, fundoscopy, and skull growth arrest can improve clinical decision-making in craniosynostosis

Muenke syndrome : long-term outcome of a syndrome-specific treatment protocol

OBJECTIVE The authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure. METHODS This 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. RESULTS The 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. CONCLUSIONS Patients 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