Appendicitis and Peritonitis in Children with a Ventriculo-Peritoneal Shunt.

The purpose of this study was to outline the management of patients with appendicitis and ventriculoperitoneal shunt (VPS) in the largest pediatric surgery department in Germany. Patients with VPS presenting with an acute abdomen between 2012 and 2022 at a tertiary-care pediatric facility were the subject of a retrospective descriptive analysis. Patients were divided into two groups based on their diagnoses: group A (appendicitis) and group B (primary peritonitis). Medical records were analyzed to look at the diagnostics, operative approach, complications, peritoneal and liquor culture, and antibiotic treatment. A total of seventeen patients were examined: seven patients in group A and ten individuals in group B. In the present study patients in group A typically presented younger, sicker, and with more neurological symptoms than those in group B. All patients with appendicitis had their VPS exteriorized, and a new shunt system into the peritoneum was reimplanted 20 days later. Surgery should be aggressively administered to patients who present with an acute abdomen and a VPS. Change of the whole shunt system is suggested. Shunt infection and dysfunction should be ruled out in patients with abdominal symptoms, and surgical care should be started with a low threshold.

External validation of the Chicago Chiari Outcome Scale in adults with Chiari malformation type I.

OBJECTIVE: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients. METHODS: The authors retrospectively analyzed the medical records of symptomatic patients with CM-I who underwent posterior fossa decompression between 2010 and 2018 in six neurosurgical departments. Each patient was clinically assessed at the latest available follow-up. Gestalt outcome was determined as improved, unchanged, or worsened compared with the preoperative clinical state. Additionally, the CCOS score was calculated for each patient based on the detailed clinical data. To verify the ability of the CCOS to determine clinical improvement, the area under the receiver operating characteristic (AUROC) curve was evaluated. A logistic regression analysis using all four components of the CCOS (pain symptoms, nonpain symptoms, functionality, and complications) was performed to establish predictors of the improved outcome. RESULTS: Seventy-five individuals with a mean age of 42 ± 15.32 years were included in the study. The mean follow-up duration was 52 ± 33.83 months. Considering gestalt outcome evaluation, 41 patients (54.7%) were classified as improved, 24 (32%) as unchanged, and 10 (13.3%) as worsened. All patients with a CCOS score of 14 or higher improved, while all those with a CCOS score of 8 or lower worsened. The AUROC was 0.986, suggesting almost perfect accuracy of the CCOS in delineating clinical improvement. A CCOS score of 13 showed high sensitivity (0.93) and specificity (0.97) for identifying patients with clinical improvement. Additionally, a meaningful correlation was found between higher CCOS scores in each component and better outcomes. Patient stratification by total CCOS score showed that those categorized as improved, unchanged, and worsened scored prevalently between 13 and 16 points, 10 and 12 points, and 4 and 9 points, respectively. CONCLUSIONS: In this adult cohort, the CCOS was found to be almost perfectly accurate in reflecting postoperative clinical improvement. Moreover, all four CCOS components (pain symptoms, nonpain symptoms, functionality, and complications) significantly correlated with patient clinical outcomes.

Development of the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement therapy (ERT) in CLN2 Disease" Based on 6 Years Treatment Experience in 48 Patients.

Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for neuronal ceroid lipofuscinosis (NCL) diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2-4 years followed by rapid loss of motor and language function, vision loss, and early death. Treatment with cerliponase alfa has shown to slow the rapid neurologic decline. However, the mode of administration by 4 hour-long intracerebroventricular infusions every 14 days represents a potentially greater risk of infection compared to intravenous enzyme replacement therapies. The Hamburg NCL Specialty Clinic was the first site worldwide to perform intracerebroventricular enzyme replacement therapy in children with CLN2 disease. In order to ensure maximum patient safety, we analysed data from our center from more than 3000 intracerebroventricular enzyme replacement therapies in 48 patients over 6 years with regard to the occurrence of device-related adverse events and device infections. Since starting intracerebroventricular enzyme replacement therapy, we have also developed and continuously improved the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement Therapy (ERT) in CLN2 Disease." Results from this study showed low rates for device-related adverse events and infections with 0.27% and 0.33%, respectively. Therefore, following our internal procedural guidelines has shown to improve standardization and patient safety of intracerebroventricular enzyme replacement therapy for CLN2 disease.

A Comparison between Pediatric and Adult Patients after Cranioplasty: Aseptic Bone Resorption Causes Earlier Revision in Children.

BACKGROUND AND STUDY AIMS/OBJECTIVE: Cranioplasty, a common neurosurgical intervention following decompressive craniectomy (DC), is associated with high complication rates. Bone flap resorption in particular leads to a considerable number of patients requiring further surgery. The aim of this study was to investigate the frequency and time of occurrence of complications following cranioplastic procedures in children and adults. MATERIAL AND METHODS: Data of children and adults who underwent cranioplasty between July 2010 and March 2018 were analyzed retrospectively. Clinical data, complications, and risk factors regarding aseptic bone resorption (ABR) were evaluated including patient age, occurrence of shunt-dependent hydrocephalus, and number of fragments in autologous bone flaps. RESULTS: Severe traumatic brain injury (TBI) was the leading cause for DC among children (66.7%), associated with a significantly higher number of fragments (p = 0.002). In the adult population, the most common cause was malignant infarction (55.9%) followed by TBI (24.6%). Pediatric patients in our institution received autologous bone flaps less frequently than adult patients (61.1% and 83.1%, respectively). Young age and a higher number of fragments in autologous bone flaps were associated with the occurrence of ABR. Children and adolescents showed significantly higher rates of aseptic bone necrosis (p = 0.007) and revision cranioplasty (p = 0.036). Kaplan-Meier estimates were used to further analyze bone flap resorption in children and adults, showing that revision surgery due to ABR was performed earlier in children (p = 0.001, log-rank test). CONCLUSION: Pediatric patients demand specific care when cranioplasty is performed following DC. We identified age as an independent risk factor. The higher number of fragments appears to be a correlation due to the higher number of TBIs in children. Our data indicate that young age is the most important risk factor for the development of ABR as a frequent and early complication with a shorter revision-free time interval in children. Consequently, the uncritical use of cryopreserved autologous bone flaps should be questioned in this population.

Predictive factors associated with ventriculoperitoneal shunting after posterior fossa tumor surgery in children.

PURPOSE: The aim of the study was to evaluate established risk factors and define new inflammation-associated factors associated with postoperative ventriculoperitoneal shunt placement. METHODS: The electronic medical records of children who underwent surgery for a tumor in the posterior fossa between January 2009 and January 2018 were retrospectively analyzed. Factors evaluated include age, clinical symptoms, tumor type, extent of surgical tumor resection, treatment with EVD and/or ETV, radiological findings, postoperative serum CRP, and leucocyte levels. Tumor tissue was stained immunohistochemically with antibodies against CD3, and leucocyte counts were performed. Patients with pre- or postoperative signs of infection or confirmation of a concurrent infection were excluded from some analyses. RESULTS: Seventy patients ages 0.4-20.8 years (median, 8.2) were included. Forty-five of 70 (65.3%) presented postoperative radiological signs of hydrocephalus. Fifteen of 70 (21.4%) patients required shunt placement postoperatively. Shunt placement was significantly associated with age < 3 years at diagnosis (p = 0.013), perioperative EVD placement (p < 0.001), signs of hydrocephalus in postoperative imaging (p = 0.047), a frontooccipital horn ratio (FOHR) > 0.46 within the first 72 h postoperatively (p < 0.001), and the presence of intraventricular blood postoperatively (p = 0.007). Six patients who underwent shunting had serum CRP levels > 40 mg/l (p = 0.030) within the first 48 h postoperatively. Tumor type or extent of resection did not correlate with shunt placement. CONCLUSIONS: Several established and new factors associated with shunt placement after posterior fossa tumor surgery could be identified. Additional studies are needed to explore the aseptic inflammation pathways involved with increased CRP levels and shunt placement.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

Unexplained loss of vision in a child: consider bilateral primary optic nerve sheath meningioma.

A 4-year-old girl gradually lost her vision to become practically blind at the age of 10 years. Examinations at several medical centers had been unable to establish an etiology. Traditional investigation using cerebral magnetic resonance imaging (MRI) initially showed normal results; however, later on it showed progressive atrophy of both optical nerves without recognizable cause. Subsequently, MRI including adequate orbital sequences, contrast-enhanced sequences, and fat suppression demonstrated bilateral primary optic nerve sheath meningioma, a rare but treatable tumor of childhood. The patient underwent neurosurgery and to date retains minimal vision. Adequate neuroradiological investigation of unexplained optic atrophy is advocated.

Nucleolar binding sequences of the ribosomal protein S6e family reside in evolutionary highly conserved peptide clusters.

Proteomic analyses of the nucleolus have revealed almost 700 functionally diverse proteins implicated in ribosome biogenesis, nucleolar assembly, and regulation of vital cellular processes. However, this nucleolar inventory has not unveiled a specific consensus motif necessary for nucleolar binding. The ribosomal protein family characterized by their basic nature should exhibit distinct binding sequences that enable interactions with the rRNA precursor molecules facilitating subunit assembly. We succeeded in delineating 2 minimal nucleolar binding sequences of human ribosomal protein S6 by fusing S6 cDNA fragments to the 5' end of the LacZ gene and subsequently detecting the intracellular localization of the beta-galactosidase fusion proteins. Nobis1 (nucleolar binding sequence 1), comprising of 4 highly conserved amino acid clusters separated by glycine or proline, functions independently of the 3 authentic nuclear localization signals (NLSs). Nobis2 consists of 2 conserved peptide clusters and requires the authentic NLS2 in its native context. Similarly, we deduced from previous publications that the single Nobis of ribosomal protein S25 is also highly conserved. The functional protein domain organization of the ribosomal protein S6e family consists of 3 modules: NLS, Nobis, and the C-terminal serine cluster of the phosphorylation sites. This modular structure is evolutionary conserved in vertebrates, invertebrates, and fungi. Remarkably, nucleolar binding sequences of small and large ribosomal proteins reside in peptide clusters conserved over millions of years.