A unique presentation of Crouzon-like syndrome: Complex craniosynostosis in the absence of genetic mutations or familial predisposition - A case report.

Background: Crouzon syndrome is a rare genetic disorder characterized by premature fusion of skull sutures during skull development, resulting in various craniofacial abnormalities and complex craniosynostosis is a condition in which more than one such sutures of the skull fuse prematurely. Case Description: Herein, we present a case of a 5-year-old male diagnosed with Crouzon-like syndrome and complex craniosynostosis involving multiple cranial sutures, including metopic, sagittal, coronal (right and left), and lambdoid sutures, and without any identifiable mutations on karyotyping. The patient underwent successful surgical intervention with a satisfactory outcome, highlighting the importance of early diagnosis and intervention to prevent or minimize associated neurological manifestations and craniofacial abnormalities. Conclusion: Our case report underscores the involvement of multiple cranial sutures in complex craniosynostosis and the absence of identifiable mutations or family history of similar craniofacial abnormalities, providing important insights into the diagnosis and management of this condition.

Comparison of Machine Learning Approaches to Improve Diagnosis of Optic Neuropathy Using Photopic Negative Response Measured Using a Handheld Device.

The photopic negative response of the full-field electroretinogram (ERG) is reduced in optic neuropathies. However, technical requirements for measurement and poor classification performance have limited widespread clinical application. Recent advances in hardware facilitate efficient clinic-based recording of the full-field ERG. Time series classification, a machine learning approach, may improve classification by using the entire ERG waveform as the input. In this study, full-field ERGs were recorded in 217 eyes (109 optic neuropathy and 108 controls) of 155 subjects. User-defined ERG features including photopic negative response were reduced in optic neuropathy eyes (p < 0.0005, generalized estimating equation models accounting for age). However, classification of optic neuropathy based on user-defined features was only fair with receiver operating characteristic area under the curve ranging between 0.62 and 0.68 and F1 score at the optimal cutoff ranging between 0.30 and 0.33. In comparison, machine learning classifiers using a variety of time series analysis approaches had F1 scores of 0.58-0.76 on a test data set. Time series classifications are promising for improving optic neuropathy diagnosis using ERG waveforms. Larger sample sizes will be important to refine the models.

Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension.

Although pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy, diastolic dilation is prevented by subsequent resting myocardial stiffening.NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation.

Methods for Quantifying Optic Disc Volume and Peripapillary Deflection Volume Using Radial Optical Coherence Tomography Scans and Association With Intracranial Pressure.

Purpose: Papilledema and peripapillary deformation of Bruch's membrane (BM) are associated with elevated intracranial pressure (ICP). We have developed a novel methodology to measure these parameters using a radial optical coherence tomography (OCT) scan pattern and apply this to test the hypothesis that ICP is associated with volumetric features of ophthalmic structures. Methods: 6-radial OCT B-scans centered over the optic nerve head were acquired in 17 subjects (30 eyes) before lumbar puncture with measurement of ICP (range: 10-55 cm H2O). Internal limiting membrane (ILM) and BM were segmented. Three definitions of BM were studied to account for imaging artifact affecting peripapillary BM: connecting rater-identified BM margins(traditional), connecting rater-identified BM 1.6 mm on either side of the ONH(estimated), and excluding BM in the central 3.2 mm of the images(excluded). Optic nerve head volume (ONHV), BM displacement volume (BMDV) and cup volume (CV) were calculated by interpolating between B-scans. Ganglion cell complex volume (GCCV) was measured in the macula. Linear generalized estimating equations (GEE) modeled ONVH, BMDV, and CV as a function of ICP and GCCV. Results: Increased ONHV was associated with elevated ICP for traditional (p = 0.006), estimated (p = 0.003) and excluded (p = 0.05) BM definitions. Decreased BMDV was associated with elevated ICP for traditional (p < 0.0005), estimated (p < 0.0005) and excluded (p = 0.001) definitions. Decreased ONHV was independently associated with decreased GCCV (p = 0.001) and decreased ICP (p = 0.031) in multivariable models. CV was neither associated with ICP nor GCCV in univariate or multivariable models. Conclusions: Elevated ICP is associated with ONHV increase and BMDV decrease, calculated from OCT images accounting for image artifact. Ganglion cell atrophy affects the relationship between ICP and ONHV. OCT derived volumetric measures of the posterior eye may have application as biomarkers for elevated ICP.

Comparison of cross sectional optical coherence tomography images of elevated optic nerve heads across acquisition devices and scan protocols.

BACKGROUND: Optic nerve head measurements extracted from optical coherence tomography (OCT) show promise for monitoring clinical conditions with elevated optic nerve heads. The aim of this study is to compare reliability within and between raters and between image acquisition devices of optic nerve measurements derived from OCT scans in eyes with varying degrees of optic nerve elevation. METHODS: Wide angle line scans and narrow angle radial scans through optic nerve heads were obtained using three spectral domain(SD) OCT devices on 5 subjects (6 swollen optic nerves, 4 normal optic nerves). Three raters independently semi-manually segmented the internal limiting membrane(ILM) and Bruch's membrane(BM) on each scan using customized software. One rater segmented each scan twice. Segmentations were qualitatively and quantitatively compared. Inter-rater, intra-rater and inter-device reliability was assessed for the optic nerve cross sectional area calculated from the ILM and BM segmentations using intraclass correlation coefficients and graphical comparison. RESULTS: Line scans from all devices were qualitatively similar. Radial scans for which frame rate could not be adjusted were of lower quality. Intra-rater reliability for segmentation and optic nerve cross sectional area was better than inter-rater reliability, which was better than inter-device reliability, though all ICC exceeded 0.95. Reliability was not impacted by the degree of optic nerve elevation. CONCLUSIONS: SD-OCT devices acquired similar quality scans of the optic nerve head, with choice of scan protocol affecting the quality. For image derived markers, variability between devices was greater than that attributable to inter and intra-rater differences.

Association Between Peripapillary Bruch's Membrane Shape and Intracranial Pressure: Effect of Image Acquisition Pattern and Image Analysis Method, a Preliminary Study.

Background/Aims: High intracranial pressure (ICP) is associated with changes in peripapillary Bruch's membrane (pBM) shape on optical coherence tomography (OCT) images of the optic nerve head. It is not known if image acquisition pattern and analysis method impact this association. Materials and Methods: Cross sectional OCT scans of the optic nerve head were obtained at six angles using a radial scan pattern in 21 subjects immediately prior to ICP measurement via lumbar puncture. On each image, Bruch's membrane was manually segmented and defined by either 14 or 16 semi-landmarks and either rater identified, or distance identified boundaries. For each of these four image analysis strategies, geometric morphometric analysis identified the first principal component of Bruch's membrane shape for all images and for the set of images taken at each angle. Repeated measures ANOVA of the first principal component magnitude (PC1) for all images assessed for shape difference between image angles. Linear generalized estimating equation models assessed association between angle specific first principal component magnitudes (PC1) and ICP for each angle. Receiver operating characteristic analysis assessed angle specific PC1s' ability to differentiate elevated from normal ICP. Results: The first principal component represented deflection into the vitreous for all scan angles, but quantitatively differed across scan angles (p < 0.005, repeated measures ANOVA). Angle specific first principal components were positively correlated with ICP (p < 0.005 for all angles, generalized estimating equation models). All angle specific first principal components showed excellent ability to classify ICP (area under curve ≥ 0.8 for all). These results were independent from image analysis strategy. Discussion: Though qualitative changes in Bruch's membrane shape are similar regardless of cross-sectional angle of the 2-D OCT scan, they differ quantitatively between OCT scan angles, meaning that pBM is not axially symmetric and therefore PC1 extracted from different 2-D scan angles can't be compared between individuals. However, we do not identify an optimal scan angle for classification of ICP since there is a similarly strong linear relationship between the first principal component of shape and ICP and angle specific first principal components of Bruch's membrane shape showed similarly excellent ability to differentiate elevated from normal ICP. The results support development of Bruch's membrane shape extracted from 2-D cross sectional optic nerve head OCT scans as a biomarker of ICP and emphasize the importance of consistency of scan angle. This is relevant for developing diagnostic protocols that use OCT to detect high ICP states.