Artificial Intelligence in Medical Imaging: Analyzing the Performance of ChatGPT and Microsoft Bing in Scoliosis Detection and Cobb Angle Assessment.

Open-source artificial intelligence models (OSAIM) find free applications in various industries, including information technology and medicine. Their clinical potential, especially in supporting diagnosis and therapy, is the subject of increasingly intensive research. Due to the growing interest in artificial intelligence (AI) for diagnostic purposes, we conducted a study evaluating the capabilities of AI models, including ChatGPT and Microsoft Bing, in the diagnosis of single-curve scoliosis based on posturographic radiological images. Two independent neurosurgeons assessed the degree of spinal deformation, selecting 23 cases of severe single-curve scoliosis. Each posturographic image was separately implemented onto each of the mentioned platforms using a set of formulated questions, starting from 'What do you see in the image?' and ending with a request to determine the Cobb angle. In the responses, we focused on how these AI models identify and interpret spinal deformations and how accurately they recognize the direction and type of scoliosis as well as vertebral rotation. The Intraclass Correlation Coefficient (ICC) with a 'two-way' model was used to assess the consistency of Cobb angle measurements, and its confidence intervals were determined using the F test. Differences in Cobb angle measurements between human assessments and the AI ChatGPT model were analyzed using metrics such as RMSEA, MSE, MPE, MAE, RMSLE, and MAPE, allowing for a comprehensive assessment of AI model performance from various statistical perspectives. The ChatGPT model achieved 100% effectiveness in detecting scoliosis in X-ray images, while the Bing model did not detect any scoliosis. However, ChatGPT had limited effectiveness (43.5%) in assessing Cobb angles, showing significant inaccuracy and discrepancy compared to human assessments. This model also had limited accuracy in determining the direction of spinal curvature, classifying the type of scoliosis, and detecting vertebral rotation. Overall, although ChatGPT demonstrated potential in detecting scoliosis, its abilities in assessing Cobb angles and other parameters were limited and inconsistent with expert assessments. These results underscore the need for comprehensive improvement of AI algorithms, including broader training with diverse X-ray images and advanced image processing techniques, before they can be considered as auxiliary in diagnosing scoliosis by specialists.

Domains in Action: Understanding Ddi1's Diverse Functions in the Ubiquitin-Proteasome System.

The ubiquitin-proteasome system (UPS) is a pivotal cellular mechanism responsible for the selective degradation of proteins, playing an essential role in proteostasis, protein quality control, and regulating various cellular processes, with ubiquitin marking proteins for degradation through a complex, multi-stage process. The shuttle proteins family is a very unique group of proteins that plays an important role in the ubiquitin-proteasome system. Ddi1, Dsk2, and Rad23 are shuttle factors that bind ubiquitinated substrates and deliver them to the 26S proteasome. Besides mediating the delivery of ubiquitinated proteins, they are also involved in many other biological processes. Ddi1, the least-studied shuttle protein, exhibits unique physicochemical properties that allow it to play non-canonical functions in the cells. It regulates cell cycle progression and response to proteasome inhibition and defines MAT type of yeast cells. The Ddi1 contains UBL and UBA domains, which are crucial for binding to proteasome receptors and ubiquitin respectively, but also an additional domain called RVP. Additionally, much evidence has been provided to question whether Ddi1 is a classical shuttle protein. For many years, the true nature of this protein remained unclear. Here, we highlight the recent discoveries, which shed new light on the structure and biological functions of the Ddi1 protein.

Artificial Intelligence in Scoliosis Classification: An Investigation of Language-Based Models.

Open-source artificial intelligence models are finding free application in various industries, including computer science and medicine. Their clinical potential, especially in assisting diagnosis and therapy, is the subject of increasingly intensive research. Due to the growing interest in AI for diagnostics, we conducted a study evaluating the abilities of AI models, including ChatGPT, Microsoft Bing, and Scholar AI, in classifying single-curve scoliosis based on radiological descriptions. Fifty-six posturographic images depicting single-curve scoliosis were selected and assessed by two independent neurosurgery specialists, who classified them as mild, moderate, or severe based on Cobb angles. Subsequently, descriptions were developed that accurately characterized the degree of spinal deformation, based on the measured values of Cobb angles. These descriptions were then provided to AI language models to assess their proficiency in diagnosing spinal pathologies. The artificial intelligence models conducted classification using the provided data. Our study also focused on identifying specific sources of information and criteria applied in their decision-making algorithms, aiming for a deeper understanding of the determinants influencing AI decision processes in scoliosis classification. The classification quality of the predictions was evaluated using performance evaluation metrics such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and balanced accuracy. Our study strongly supported our hypothesis, showing that among four AI models, ChatGPT 4 and Scholar AI Premium excelled in classifying single-curve scoliosis with perfect sensitivity and specificity. These models demonstrated unmatched rater concordance and excellent performance metrics. In comparing real and AI-generated scoliosis classifications, they showed impeccable precision in all posturographic images, indicating total accuracy (1.0, MAE = 0.0) and remarkable inter-rater agreement, with a perfect Fleiss' Kappa score. This was consistent across scoliosis cases with a Cobb's angle range of 11-92 degrees. Despite high accuracy in classification, each model used an incorrect angular range for the mild stage of scoliosis. Our findings highlight the immense potential of AI in analyzing medical data sets. However, the diversity in competencies of AI models indicates the need for their further development to more effectively meet specific needs in clinical practice.

Assessment of the Functioning Profile of Patients with Lung Cancer Undergoing Lobectomy in Relation to the ICF Rehabilitation Core Set.

Lung cancer often presents with pain and breathlessness, frequently necessitating surgical procedures, such as lung lobectomy. A pivotal component of postoperative care is rehabilitation, aimed not only at improving the clinical condition but also at influencing the patient's functional profile. In a study conducted at the Clinic of Thoracic Surgery and Respiratory Rehabilitation in the Regional Multispecialist Center for Oncology and Traumatology of the Nicolaus Copernicus Memorial Hospital in Lodz, the effectiveness of rehabilitation intervention was assessed in 50 patients (n = 27 M, n = 23 F) postlobectomy due to early stage nonsmall cell lung cancer (NSCLC). The International Classification of Functioning, Disability, and Health-ICF Rehabilitation Core Set was used to evaluate the functional profile, the modified Laitinen scale for pain assessment, and the modified Borg scale for breathlessness evaluation. Additionally, lung-expansion time was monitored. The significance level of the statistical tests in this analysis was set at α = 0.05. The study employed an analysis of the normality of the distributions of the numerical variables, reporting of variable distributions, estimation of differences between groups, estimation of differences within groups, estimation of the independence of categorical variables, and regression analysis. The research confirmed that rehabilitation partially improves the functional profile of patients and reduces the sensation of breathlessness postsurgery. The study highlighted the need for future research with a larger number of participants and an extended observation period to gain a deeper understanding of the impact of rehabilitation on patients after lung lobectomy procedures.

Evaluating Scoliosis Severity Based on Posturographic X-ray Images Using a Contrastive Language-Image Pretraining Model.

Assessing severe scoliosis requires the analysis of posturographic X-ray images. One way to analyse these images may involve the use of open-source artificial intelligence models (OSAIMs), such as the contrastive language-image pretraining (CLIP) system, which was designed to combine images with text. This study aims to determine whether the CLIP model can recognise visible severe scoliosis in posturographic X-ray images. This study used 23 posturographic images of patients diagnosed with severe scoliosis that were evaluated by two independent neurosurgery specialists. Subsequently, the X-ray images were input into the CLIP system, where they were subjected to a series of questions with varying levels of difficulty and comprehension. The predictions obtained using the CLIP models in the form of probabilities ranging from 0 to 1 were compared with the actual data. To evaluate the quality of image recognition, true positives, false negatives, and sensitivity were determined. The results of this study show that the CLIP system can perform a basic assessment of X-ray images showing visible severe scoliosis with a high level of sensitivity. It can be assumed that, in the future, OSAIMs dedicated to image analysis may become commonly used to assess X-ray images, including those of scoliosis.

Congenital Anterior Dislocation of the Sacrococcygeal Bone in a Newborn.

We present a case of a child who was transported to the Neurosurgery Clinic from another hospital for the purpose of performing a surgical procedure of the spinal myelomeningocele. On the first day of the stay, a set of tests was performed, including an anterior-posterior (AP) projection X-ray, which clearly showed a developmental defect in the lumbar-sacral section of the spine. In the follow-up physical examination, there was a depression of the skin on the right side of the surgical scar after closing the open myelomeningocele. In the follow-up MRI of the lumbar-sacral section, an extremely rare congenital anterior dislocation of the sacrococcygeal bone was unexpectedly visualized. Despite recommendations for further diagnostics, the patient did not attend the required follow-up examinations. In the final section, we provide a general summary of the literature on rare developmental defects of the spine in children.

Telovelar versus transvermian approach to tumors of the fourth ventricle and their impact on postoperative neurological complications: A multicenter study.

Background: Tumors of the fourth ventricle are exceedingly rare; however, such lesions are formidable due to the severe postoperative neurological complications (pNCs) which often occur. The adoption of the telovelar approach over the transvermian was created to supposedly mitigate the pNCs; however, there is a lack of sufficient data supporting this theory. Methods: Records from six hospitals were reviewed for patients surgically treated for a single tumor within the 4th ventricle from 2016 to 2022. The pNCs which had 10 or more occurrences among the patients were individually assessed as the dependent variable in a binary logistic regression model against covariates which included the surgical approach. Results: This study of 67 patients confirms no significant differences in risk for pNCs between the transvermian and telovelar approach. Rather, multivariate analysis identified neurophysiological monitoring (IONM) as a protective factor for postoperative speech and swallowing defects (odds ratio [OR]: 0.076, 95% confidence interval [CI] 0.011-0.525). Furthermore, intraoperative external ventricular drainage (EVD) was a protective factor for postoperative gait and focal motor defects (OR: 0.075, 95% CI 0.009-0.648) and for postoperative hydrocephalus (OR: 0.020, 95% CI 0.002-0.233). A univariate meta-analysis pooling the present study's patients and an additional 304 patients from the three additional studies in the literature confirms no significant differences in risk between the transvermian and telovelar approach for pNCs. Conclusion: Intraoperative adjuncts including IONM and EVD may play a significant role in the postoperative outcome. Despite the present study's sample size being a major limitation, the findings may provide great value to neurosurgeons given the scarcity of the current literature.

Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.

BACKGROUND: Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease. METHODS: We undertook large-scale integrated characterization of the molecular features of rMB-molecular subgroup, novel subtypes, copy number variation (CNV), and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n = 107), alongside an independent reference cohort sampled at diagnosis (n = 282). rMB events were investigated for association with outcome post-relapse in clinically annotated patients (n = 54). RESULTS: Significant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. Non-infant MBSHH displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (eg, CDK amplifications) and novel (eg, USH2A mutations) events. Importantly, many hallmark features of MB were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (eg, SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (eg, DNA damage signaling) and specific events (eg, 3p loss) predicted survival post-relapse. CONCLUSIONS: rMB is characterised by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course.

mRNA and miRNA Expression Analyses of the MYC/E2F/miR-17-92 Network in the Most Common Pediatric Brain Tumors.

Numerous molecular factors disrupt the correctness of the cell cycle process leading to the development of cancer due to increased cell proliferation. Among known causative factors of such process is abnormal gene expression. Nowadays in the light of current knowledge such alterations are frequently considered in the context of mRNA-miRNA correlation. One of the molecular factors with potential value in tumorigenesis is the feedback loop between MYC and E2F genes in which miR-17-5p and miR-20a from the miR-17-92 cluster are involved. The current literature shows that overexpression of the members of the OncomiR-1 are involved in the development of many solid tumors. In the present work, we investigated the expression of components of the MYC/E2F/miR-17-92 network and their closely related elements including members of MYC and E2F families and miRNAs from two paralogs of miR-17-92: miR-106b-25 and miR-106a-363, in the most common brain tumors of childhood, pilocytic astrocytoma (PA), WHO grade 1; ependymoma (EP), WHO grade 2; and medulloblastoma (MB), WHO grade 4. We showed that the highest gene expression was observed in the MYC family for MYCN and in the E2F family for E2F2. Positive correlation was observed between the gene expression and tumor grade and type, with the highest expression being noted for medulloblastomas, followed by ependymomas, and the lowest for pilocytic astrocytomas. Most members of miR-17-92, miR-106a-363 and miR-106b-25 clusters were upregulated and the highest expression was noted for miR-18a and miR-18b. The rest of the miRNAs, including miR-19a, miR-92a, miR-106a, miR-93, or miR-25 also showed high values. miR-17-5p, miR-20a obtained a high level of expression in medulloblastomas and ependymomas, while close to the control in the pilocytic astrocytoma samples. miRNA expression also depended on tumor grade and histology.

Superior Hypophyseal Artery Ruptured Aneurysm in a 5-Month-Old Child Presenting as an Acute Subdural Hematoma: A Case Report.

INTRODUCTION: We present a very rare case of ruptured superior hypophyseal artery (SHA) aneurysm that presented as an acute subdural hematoma (SDH) discussing its initial presentation, diagnosis, and treatment modalities. To our knowledge it is one of very few if any cases of a ruptured aneurysm in infants regarding that specific vascular location. CASE REPORT: A 5-month-old boy was referred to our department due to acute SDH over the right cerebral hemisphere without significant mass effect nor hydrocephalus. Further evaluation revealed a right internal carotid artery (ICA) aneurysm arising from the SHA segment. Microsurgical clip ligation using a fenestrated, angled clip was performed with simultaneous subdural clot removal and proximal control of the ICA dissected in the neck. Our patient made an excellent recovery without any complicating features. CONCLUSION: Surgical management seems to be a better option in this subgroup of patients given the long life expectancy and durability of microsurgical clip ligation. We believe that our brief case report would add some insight into the management of this rare subgroup of patients, leading to better decision-making and outcome.

microRNA interaction with MAPK and AKT pathways in paediatric brain tumours - preliminary results and review of the literature.

Nowadays molecular investigations have a significant impact on the understanding of primary brain tumour biology,as well as on their classification and progress in the treatment modalities. Among novel type of biomarkers with potential therapeutic value, microRNAs (miRNAs) are considered in some cases. miRNAs are small molecules regu-lating gene expression, including genes encoding key proteins involved in signalling pathways responsible for growth and cell survival during tumour formation. Incorrectly hyperactivated pathways implicated in brain tumour development are inter alia the PI3K/AKT/mTOR and RAS/MAPK/ERK cascades associated with worse prognosis and decreased patient survival. This work presents relationships between changes in the expression of individual miRNAs and the genes involved in the regulation of PI3K/AKT/mTOR and RAS/MAPK/ERK signalling pathways in primary brain tumours. Herein we present the preliminary results of miR-17-5p and miR-20a (key representatives of the miR-17-92 oncogenic cluster) expression analysis and their connection with signalling pathway activation in two of the most frequent paediatric tumours: medulloblastoma and ependymoma. Our study was performed using the microarray and qPCR techniques and showed PI3K/AKT/mTOR and RAS/MAPK/ERK among the forefront of the list of pathways with the largest number of genes involved in their activation compared to the control. Predicted target analysis indicated the agents from miR-17-92 cluster within miRNAs regulating activity of PI3K/AKT/mTOR and RAS/MAPK/ERK deregulated genes. The expression level of key representatives of the oncogenic cluster, miR-17-5p, and miR-20a, increased with the WHO grade of the analysed cases; the highest levels were found in medulloblastomas.

Predicting conservative treatment failure in patients with lumbar disc herniation. Single center, case-control study.

OBJECTIVES: The aim of this study was to identify independent predictors of conservative treatment failure in patients presenting due to lumbar disc herniation-associated low back pain and sciatica. PATIENTS AND METHODS: This is a single institution, case-control study including 240 patients that were selected for microsurgical or conservative treatment due to lumbar disc herniation in a 2,5-year period. Bivariate and multivariate analyses were performed in order to identify independent predictors among demographic, clinical and radiographic factors. RESULTS: Statistically significant differences were observed between conservatively and surgically managed groups in bivariate analysis. Logistic regression models further revealed that leg paresthesia (p =  0,003; OR = 5,136) and percentage of spinal canal stenosis ratio (p < 0,001; OR = 1,055) had the strongest, independent correlation with conservative treatment failure in our cohort. Back-to-leg ratio did not reach statistical significance although it proved a strong correlation in bivariate analysis (p < 0,001, Cramér's V = 0,53). CONCLUSION: Increasing % canal compromise ratio (cut-off value 23%) and co-occurrence of leg paresthesia were the most important risk factors for surgery in our series of patients.

Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS).

PURPOSE: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. METHODS: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. RESULTS: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. CONCLUSION: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

Hedgehog signalling network gene status analysis in paediatric intracranial germ cell tumours.

INTRODUCTION: Germ cell tumours (GCTs) in the children comprise a group of tumours that originate from primordial germ cells but their pathogenesis is not clear. Intracranial GCTs represent a special subset of these paediatric neoplasms. Hedgehog (Hh) pathway gene status in GCTs is generally unexplored, while Hh signalling is involved in germ cell biology. MATERIAL AND METHODS: Comparative genomic profiling analysis with a microarray-comparative genomic hybridization (CGH) + single nucleotide polymorphism (SNP) technique in a group of intracranial paediatric GCTs was performed. The analysis included evaluation of genes being ligands, receptors, regulators, effectors, and targets of Hh signalling. RESULTS: Chromosomal aberrations were found in 62% of examined tumours, showing their heterogeneity. A number of private genomic imbalances were observed, but only a few recurrent ones. The most common numerical changes were trisomies 19, 21 and monosomies 13, 18 while the most frequent structural aberration was gain/amplification of the chromosome 12p. The analysis of the gene status of Hh network elements showed imbalances in a proportion of tumours. PTCH1, GLI2, IHH and ZIC2 gene aberrations occurred most frequently. Moreover, six tumours had various copy gains or losses of several other genes involved in the pathway, including HHIP, GLI1, GLI3, DHH, SHH, SMO, PTCH2, and several genes from the WNT group. Interestingly, four cases showed losses of pathway repressors, with parallel gains of activators in two of them. Correlations with patho-clinical tumour features were not found, most probably due to the heterogeneity of the examined limited group. CONCLUSIONS: Our results show few genomic alterations related to the Hh signalling pathway genes in paediatric intracranial GCTs. Further analysis of Hedgehog pathway alterations can potentially disclose its biological significance and define new prognostic factors and/or therapeutic targets for high-risk patients.

Expression-based decision tree model reveals distinct microRNA expression pattern in pediatric neuronal and mixed neuronal-glial tumors.

BACKGROUND: The understanding of the molecular biology of pediatric neuronal and mixed neuronal-glial brain tumors is still insufficient due to low frequency and heterogeneity of those lesions which comprise several subtypes presenting neuronal and/or neuronal-glial differentiation. Important is that the most frequent ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) showed limited number of detectable molecular alterations. In such cases analyses of additional genomic mechanisms seem to be the most promising. The aim of the study was to evaluate microRNA (miRNA) profiles in GGs, DNETs and pilocytic asytrocytomas (PA) and test the hypothesis of plausible miRNA connection with histopathological subtypes of particular pediatric glial and mixed glioneronal tumors. METHODS: The study was designed as the two-stage analysis. Microarray testing was performed with the use of the miRCURY LNA microRNA Array technology in 51 cases. Validation set comprised 107 samples used during confirmation of the profiling results by qPCR bioinformatic analysis. RESULTS: Microarray data was compared between the groups using an analysis of variance with the Benjamini-Hochberg procedure used to estimate false discovery rates. After filtration 782 miRNAs were eligible for further analysis. Based on the results of 10 × 10-fold cross-validation J48 algorithm was identified as the most resilient to overfitting. Pairwise comparison showed the DNETs to be the most divergent with the largest number of miRNAs differing from either of the two comparative groups. Validation of array analysis was performed for miRNAs used in the classification model: miR-155-5p, miR-4754, miR-4530, miR-628-3p, let-7b-3p, miR-4758-3p, miRPlus-A1086 and miR-891a-5p. Model developed on their expression measured by qPCR showed weighted AUC of 0.97 (95% CI for all classes ranging from 0.91 to 1.00). A computational analysis was used to identify mRNA targets for final set of selected miRNAs using miRWalk database. Among genomic targets of selected molecules ZBTB20, LCOR, PFKFB2, SYNJ2BP and TPD52 genes were noted. CONCLUSIONS: Our data showed the existence of miRNAs which expression is specific for different histological types of tumors. miRNA expression analysis may be useful in in-depth molecular diagnostic process of the tumors and could elucidate their origins and molecular background.

Sensitive detection of FGFR1 N546K mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder, with only about 100 cases reported worldwide. It is characterized by congenital lesions of the eye, skin, and central nervous system. Only recently, potential causative FGFR1 point mutations have been identified in brain tumors and cultured skin biopsies from patients with this condition. Here, we analyzed the molecular status of a patient with ECCL and a coexisting pilocytic astrocytoma with detected FGFR1 N546K mutation. The presence of the alteration in both affected and unaffected tissues has been evaluated using Sanger sequencing and droplet digital polymerase chain reaction (ddPCR) technique. The ddPCR analysis showed differential distribution of the alteration in all specimens, including unaffected and untreated samples. Therefore, we confirm that FGFR1 N546K is a plausible causative mutation of ECCL patients and could be associated with a risk of brain tumor development. We also show the usefulness of sensitive ddPCR method for detection of low levels of autosomal mosaic mutation in blood or swabs. We suggest that utilization of this method may improve the diagnostic process, especially when targeted therapies are considered.

The oscillatory flow of the cerebrospinal fluid in the Sylvian aqueduct and the prepontine cistern measured with phase contrast MRI in children with hydrocephalus-a preliminary report.

INTRODUCTION: Recognizing patients with ventriculomegaly who are at risk of developing acute hydrocephalus presents a challenge for the clinician. The association between disturbed cerebrospinal fluid flow (CSF) and impaired brain compliance may play a role in the pathogenesis of hydrocephalus. Phase contrast MRI is a noninvasive technique which can be used to assess CSF parameters. The aim of the work is to evaluate the effectiveness of phase contrast MRI in recognizing patients at risk of acute hydrocephalus, based on measuring the pulsatile CSF flow parameters in the Sylvian aqueduct and prepontine cistern in children with ventriculomegaly. AIM: The aim of the work is to characterize the parameters of cerebrospinal fluid (CSF) flow in the Sylvian aqueduct and prepontine cistern in children with ventriculomegaly with regard to patient age and symptoms. We hypothesize that the relationship between CSF flow parameters in these two regions will vary according to analyzed factors and it will allow to recognize children at risk of hydrocephalus. MATERIALS AND METHODS: A group of 26 children with ventriculomegaly (five girls and 21 boys) underwent phase contrast MRI examinations (Philips 3T Achieva with Q-flow integral application). Amplitudes of average and peak velocities of the CSF flow through the Sylvian aqueduct and prepontine cistern were used to calculate ratios of oscillation and peak velocities, respectively. The relationship between the oscillation coefficient, the peak velocity coefficient, and stroke volume was then assessed in accordance with age and clinical symptoms. RESULTS: The peak velocity coefficient was significantly higher in patients with hyper-oscillating flow through the Sylvian aqueduct (3.04 ± 3.37 vs. 0.54 ± 0.28; p = 0.0094). Moreover, these patients tended to develop symptoms more often (p = 0.0612). No significant age-related changes were observed in CSF flow parameters. CONCLUSION: Phase contrast MRI is a useful tool for noninvasive assessment of CSF flow parameters. The application of coefficients instead of direct values seems to better represent hemodynamic conditions in the ventricular system. However, further studies are required to evaluate their clinical significance and normal limits.

Expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma.

The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness. METHODS: Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB. RESULTS: There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p<0.001), while TTF-1 correlated negatively with the age of patients (p=0.039). PAX5 expression correlated with ISL-1 (p=0.039) and showed a trend toward higher expression in the desmoplastic subtype (p=0.069). CONCLUSIONS: SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients.

Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma.

BACKGROUND: Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors. METHODS: The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR. RESULTS: Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses. CONCLUSIONS: Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome.

Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor associated with intractable drug-resistant epilepsy. In order to identify underlying genetic alterations and molecular mechanisms, we examined three family members affected by multinodular DNETs as well as 100 sporadic tumors from 96 patients, which had been referred to us as DNETs. We performed whole-exome sequencing on 46 tumors and targeted sequencing for hotspot FGFR1 mutations and BRAF p.V600E was used on the remaining samples. FISH, copy number variation assays and Sanger sequencing were used to validate the findings. By whole-exome sequencing of the familial cases, we identified a novel germline FGFR1 mutation, p.R661P. Somatic activating FGFR1 mutations (p.N546K or p.K656E) were observed in the tumor samples and further evidence for functional relevance was obtained by in silico modeling. The FGFR1 p.K656E mutation was confirmed to be in cis with the germline p.R661P variant. In 43 sporadic cases, in which the diagnosis of DNET could be confirmed on central blinded neuropathology review, FGFR1 alterations were also frequent and mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple mutants in cis (25/43; 58.1 %) while BRAF p.V600E alterations were absent (0/43). In contrast, in 53 cases, in which the diagnosis of DNET was not confirmed, FGFR1 alterations were less common (10/53; 19 %; p < 0.0001) and hotspot BRAF p.V600E (12/53; 22.6 %) (p < 0.001) prevailed. We observed overexpression of phospho-ERK in FGFR1 p.R661P and p.N546K mutant expressing HEK293 cells as well as FGFR1 mutated tumor samples, supporting enhanced MAP kinase pathway activation under these conditions. In conclusion, constitutional and somatic FGFR1 alterations and MAP kinase pathway activation are key events in the pathogenesis of DNET. These findings point the way towards existing targeted therapies.