Search

Background: We have reported casuistic observations that intracranial pressure (ICP) waveform analysis may be useful in the management of pediatric patients. Method: We here report our whole patient material of 65 children undergoing ICP monitoring with storage of their ICP raw data files during the years 2002–2005. We retrospectively explored the clinical symptoms/findings and radiological cerebral ventricular size before ICP monitoring. Mean ICP was the actively treated ICP parameter. Using an algorithm for identification of cardiac-beat-induced pressure waves we retrospectively determined the mean ICP wave amplitude and latency, in addition to mean ICP. Outcome with regard to change in symptoms/findings during a 1-year period was determined in 55 children. Results: The material includes children with hydrocephalus, craniosynostosis, shunt failure, benign intracranial hypertension and others. The ICP recordings gave wrong diagnostic information due to bad signal quality in 5 of 65 patients (7.7%). The mean ICP wave amplitude was increased in those with papilledema, lethargy and nausea. The main observations were that the mean ICP wave amplitude (not mean ICP) was increased in those that improved from clinical symptoms/findings after treatment and in those that were unchanged/worse after not being treated. Conclusions: Waveform analysis with computation of the mean ICP wave amplitude was more useful by providing information about the quality of the ICP recording, by comparing better with the symptoms/findings at the time of ICP monitoring and by best predicting outcome. Most significantly, 14 of 55 patients (25%) with high amplitudes and left untreated did not recover spontaneously. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017., Procedure: Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification., Results: We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review., Conclusion: Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Adolescent survivors of pediatric brain tumor (PBT) are a sparsely studied subset of childhood cancer survivors. Sustaining a PBT may complicate the development of executive functions (EFs), which play a vital role in long-term psychosocial adjustment. In this study, 48 adolescent survivors and their parents completed questionnaires assessing EF, psychological symptoms, fatigue, and adaptive functioning, and 26 survivors underwent neuropsychological assessment. Survivors reported significantly more problems with adaptive functioning than a healthy control group, and this was most strongly associated to executive dysfunction, compared to psychological symptoms and fatigue. The findings have important implications for long-term follow-ups.

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: We have previously characterized 19 ependymal tumors using Giemsa banding and high-resolution comparative genomic hybridization. The aim of this study was to analyze these tumors searching for fusion genes., Methods: RNA sequencing was performed in 12 samples. Potential fusion transcripts were assessed by seed count and structural chromosomal aberrations. Transcripts of interest were validated using fluorescence in situ hybridization and PCR followed by direct sequencing., Results: RNA sequencing identified rearrangements of the anaplastic lymphoma kinase gene (ALK) in 2 samples. Both tumors harbored structural aberrations involving the ALK locus 2p23. Tumor 1 had an unbalanced t(2;14)(p23;q22) translocation which led to the fusion gene KTN1-ALK. Tumor 2 had an interstitial del(2)(p16p23) deletion causing the fusion of CCDC88A and ALK. In both samples, the breakpoint of ALK was located between exons 19 and 20. Both patients were infants and both tumors were supratentorial. The tumors were well demarcated from surrounding tissue and had both ependymal and astrocytic features but were diagnosed and treated as ependymomas., Conclusions: By combining karyotyping and RNA sequencing, we identified the 2 first ever reported ALK rearrangements in CNS tumors. Such rearrangements may represent the hallmark of a new entity of pediatric glioma characterized by both ependymal and astrocytic features. Our findings are of particular importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients with lung cancer harboring ALK rearrangements. Thus, ALK emerges as an interesting therapeutic target in patients with ependymal tumors carrying ALK fusions., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading system remains controversial. Treatment is mainly surgical and by radiation. An improved knowledge of ependymoma biology is important to elucidate the pathogenesis, to improve classification schemes, and to identify novel potential treatment targets. Only 113 ependymoma karyotypes with chromosome aberrations are registered in the Mitelman database. We present the first study of ependymoma genomes combining karyotyping and high resolution comparative genomic hybridization (HR-CGH). Nineteen tumor samples were collected from three pediatric and 15 adult patients treated at Oslo University Hospital between 2005 and 2012. Histological diagnoses included subependymoma and myxopapillary ependymoma (WHO grade I), ependymoma (WHO grade II) and anaplastic ependymoma (WHO grade III). Four tumors were intraspinal and 15 were intracranial. Seventeen samples were successfully karyotyped, HR-CGH analysis was undertaken on 17 samples, and 15 of 19 tumors were analyzed using both methods. Twelve tumors had karyotypic abnormalities, mostly gains or losses of whole chromosomes. Structural rearrangements were found in four tumors, in two of which 2p23 was identified as a breakpoint region. Twelve tumors displayed genomic imbalances by HR-CGH analysis with loss of material at 6q as the most common. 6q loss, which was detected by one or both methods in seven of 12 (58%) abnormal tumors, and 5p gain (observed in five tumors; 42%) were the most common genomic aberrations in this series.

This study compares internal and external distraction devices in the treatment of midface retrusion. 20 patients were treated with midface distraction (12 Crouzon, 4 Apert, 4 others); 12 with internal distraction (MID device), 8 with external distraction (Red or Blue device). The two groups were compared regarding operation time, peroperative blood loss and complications. The groups were comparable regarding patient age, sex, weight and diagnosis. In the MID-group, 7 of 12 patients (58%) underwent Le Fort III, 5 underwent 12 monobloc (32%). In the Blue device group, three of eight patients underwent Le Fort II (38%), three of eight underwent Le Fort III (38%), and two of eight underwent monobloc (25%). Operation time was shorter in the Blue device (mean 298 min) than in the MID group (mean 354 min). Peroperative blood loss and complication rates were similar. The internal distraction device is the 'gold standard' for treating midface retrusion. The use of an external distraction device in midface distraction osteogenesis is associated with a shorter operation time; peroperative blood loss and complications were similar. An external device affords better 3-dimensional control during the distraction process, so external distraction is preferable in patients who will tolerate this treatment., (Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: A single-center, prospective, nonrandomized pilot study was performed to assess the Paedi-Gav gravity-assisted valve for the treatment of pediatric patients with hydrocephalus., Methods: Participants were pediatric patients (age <16 years) who were candidates for a hydrocephalus shunt system that required a valve insertion at the time of enrollment. The primary outcome event was shunt malfunction; subclassified into shunt obstruction, shunt overdrainage, loculated ventricles, or infection. The shunt obstructions were further subclassified according to site. A total of 32 patients were enrolled onto the study, with 2 undergoing first shunt insertion after failed ventriculostomy and 30 undergoing shunt revisions. On average, the patients had had 3.3 shunt procedures prior to insertion of a Paedi-Gav valve., Results: During a follow-up interval of minimum 52 weeks and a median of 24 months after the first implantation on-study, shunt revisions were required in 17 (53.1%) of the 32 patients. The 12-month shunt-survival rate without revision of any component was 53%, with a median shunt-survival time of 388 days. The most common reasons for shunt revision were shunt obstructions (12/17) and overdrainage (3/17). Shunt obstructions were caused by valve-related failures (9/12) and distal obstructions (3/12)., Conclusion: Although the small number of patients enrolled in this study warrants cautious conclusions, the overall results are comparable to those reported for primary shunt insertions with conventional valves in pediatric patients with hydrocephalus. Although this study provides a rationale for examining the Paedi-Gav gravity-assisted shunt valve in a larger prospective randomized controlled trial, the shunt failure pattern, with a rather high frequency of valve-related failures, may indicate potential for further improvements in the valve design and/or manufacturing., (Copyright 2005 S. Karger AG, Basel.)

Unlabelled: Traditionally, the cerebral hemispheres have been regarded as the region of the brain responsible for cognitive functions, while the cerebellum has been considered to be primarily involved in motor functions. Recent studies focus also on the possible involvement of the cerebellum in neurocognitive functions. The aim of this study was to determine the neuropsychological profile of young adults treated for a posterior fossa tumor in childhood and look for possible support for the presence of the so-called 'cerebellar cognitive affective syndrome' in these patients. Two groups of young adults were studied. The astrocytoma group (n = 12) had been treated for a low-grade cerebellar astrocytoma with surgery alone (mean age at surgery was 8.6 years and mean age at neuropsychological testing was 23.5 years). The medulloblastoma group (n = 11) had been treated with surgery followed by radiotherapy and chemotherapy (mean age at surgery was 6.1 years and mean age at neuropsychological testing was 23.1 years). The neuropsychological test battery comprised measures of intelligence, motor function, attention, psychomotor speed, verbal memory and visual memory. The medulloblastoma group performed poorer than the astocytoma group on all neuropsychological measures except one. Nonetheless, the astrocytoma group also had impaired scores compared with standard norms on measures of motor speed, attention and executive function. No significant correlation between age at time of treatment and grade of neuropsychological impairment was found in the astrocytoma group, though there was a tendency that young age at time of treatment correlated with better outcome on IQ measures. In the medulloblastoma group, age was significantly correlated with outcome, for both IQ and degree of neuropsychological impairment. For this group, young age at time of treatment indicated a worse outcome., Conclusions: Persistent cognitive dysfunction was detected in patients treated for posterior fossa medulloblastoma and cerebellar astrocytoma. The astrocytoma group was treated with surgery alone, indicating that a cerebellar lesion can result in cognitive dysfunction. Thus, this study gives support to the existence of the cerebellar cognitive affective syndrome. Follow-up of all patients treated for posterior fossa tumor in childhood should include an extensive neuropsychological testing at regular intervals. This may be of benefit for school planning and later work planning., (Copyright 2005 S. Karger AG, Basel.)

In this study, we explored two strategies of assessing continuous intracranial pressure (ICP) recordings in children with craniosynostosis, namely either by computation of the mean ICP or by computation of the accurate numbers of ICP elevations of different durations. The ICP recordings of 121 consecutive patients with a tentative diagnosis of craniosynostosis who underwent continuous ICP monitoring were examined. The relationship between mean ICP and numbers of ICP elevations was defined. The distribution of numbers of ICP elevations between patients either undergoing surgery or conservative treatment was also compared, since the choice of treatment was heavily dependent on the results of ICP monitoring. At the time of ICP monitoring, calculation of mean ICP was the main parameter for assessment of ICP curves. After a median observation period of 16 months, the ICP curves were reexamined by means of the software Sensometrics Pressure Analyser, which presents the ICP curve as a matrix of numbers of ICP elevations of different levels (20-40 mm Hg) and durations (0.5- 20 min). Since the recording period differed between the cases, the numbers were standardized to a given recording time of 10 h, to allow for comparisons between patients. Cases with a borderline mean ICP during sleep (mean ICP 10-15 mm Hg) constituted 40.5% of the 121 patients. In this group, a rather weak relationship between mean ICP and the number of ICP elevations above 20 mm Hg was found, as well as a relatively high number of ICP elevations above 20 mm Hg of various durations. As compared to the patients undergoing surgery, a rather high number of ICP elevations above 20 mm Hg of various durations was found in patients undergoing conservative treatment. The study confirmed our hypothesis that in children with craniosynostosis, calculation of mean ICP does not describe the ICP curve in a reliable way. Decision-making should also include the computation of the distribution of numbers of ICP elevations, since this procedure represents a more sensitive strategy of detecting intracranial hypertension., (Copyright 2002 S. Karger AG, Basel)

This study reports the results of quantitative analysis of continuous intracranial pressure (ICP) recordings in 33 hydrocephalic children. The aim of the study was to compare the exact numbers of increases in ICP during sleep or the awake state in hydrocephalic children who were treated either surgically or conservatively. At the time of ICP monitoring, the ICP curves were assessed by the calculation of mean ICP and visual inspection for the detection of plateau waves. Quantitative analysis was performed with the software Sensometrics Pressure Analyser, which presented the ICP curve as a matrix of numbers of ICP elevations of different levels (20-40 mm Hg) and durations (0.5-20 min). In each case, the numbers of ICP elevations were standardized to 10 h of recording time, providing the opportunity for comparisons of ICP curves between individuals. Compared to the surgery group, there was a rather high number of ICP elevations of 20 mm Hg of various durations in the nonsurgery group, e.g. ICP elevations of 20 mm Hg lasting 10 min occurred in 13 of 19 children (68%) in the nonsurgery group. There was no apparent relationship between ICP and age or between the size of the cerebral ventricles and ICP. In children with hydrocephalus, the presentation of the ICP data as a matrix of ICP elevations of different levels and durations may enhance the informative value of continuous ICP monitoring, as compared to the calculation of mean ICP and visual detection of plateau waves., (Copyright 2002 S. Karger AG, Basel)

Background: Endoscopic third ventriculocisternostomy has gained widespread use in the treatment of hydrocephalus., Materials and Methods: In 1999 and 2000 endoscopic third ventriculostomy was performed in 120 patients (60 males) at Rikshospitalet, Oslo, Norway. Median age was 3.3 years (range 0.0 to 71.7). 69 procedures were done as primary treatment of hydrocephalus and 51 procedures for shunt failure., Results: After one year, 62% of the patients older than 6 months at time of treatment and 8% of the patients younger than 6 months were successfully treated for their hydrocephalus with ventriculostomy only. The success rate for patients with hydrocephalus secondary to aqueductal stenosis or a space-occupying lesion in the posterior fossa was 72% and 31% for patients with other causes of hydrocephalus. The success rate of endoscopic third ventriculostomy as primary treatment of hydrocephalus was 55%; for the procedure at time of shunt failure 45%. The overall likelihood of success was significantly correlated to age, cause of hydrocephalus, and whether the procedure was done as primary treatment of hydrocephalus or at time of shunt failure., Interpretation: Endoscopic third ventriculostomy seems to be effective in treating hydrocephalus caused by aqueductal stenosis or a space-occupying lesion in the posterior fossa in patients older than 6 months. The procedure should not be routinely attempted on patients younger than 6 months.

The effect of calvarial expansion on symptom relief and intracranial pressure (ICP) in three children with slit ventricle syndrome (SVS) and intracranial hypertension despite a functioning ventricular shunt is reported. These children presented with a clinical picture of SVS, accompanied by slit-like ventricles on cranial computer tomography scan and intracranial hypertension. Calvarial expansion was performed by mans of an anterior approach in one case and a posterior approach (modified tiara plastic) in the other two cases. After calvarial expansion, symptoms of intracranial hypertension were abolished in one case and markedly reduced in two cases (observation period 25-36 months). Comparison of ICP before and after surgery was performed by means of new software (Sensometrics Pressure Analyser, version 1.2) that revealed a significant reduction in the number of abnormal ICP elevations after surgery. The results were not accompanied by changes in the size of the cerebral ventricles. This study demonstrates that in children with SVS and intracranial hypertension despite a functioning shunt, calvarial expansion may reduce ICP and produce long-lasting symptom relief. In these cases, we suggest that intracranial hypertension was caused by compromised intracranial volume., (Copyright 2001 S. Karger AG, Basel)

Object: This study was undertaken to compare the results of two tests that are widely used to assess intracranial pressure-volume relationships in children: the lumbar steady state infusion test providing information about the resistance to cerebrospinal fluid (CSF) outflow (Rout), and continuous intracranial pressure (ICP) monitoring., Methods: The study included 28 children aged 5-91 months, on whom both tests were performed. The median duration between the tests was 1 month. With the child in general narcosis, the lumbar CSF pressure was recorded before and during infusion of artificial CSF, and the Rout was calculated on the basis of the opening (Po) and plateau (Pp) pressures (Rout=Pp-Po/infusion rate). ICP was recorded every 5 s using a computer-based system., Conclusions: We found no significant correlation between Rout and mean ICP asleep. There were no significant relationships between abnormal mean ICPs during sleep (defined as either 10 or 15 mmHg) and abnormally high Rout values (defined as either 10 or 12 mmHg/ml/min), and no significant relationships between abnormally high Rout values (10 or 12 mmHg ml(-1) min(-1)) and the presence of abnormal ICP elevations (defined as either 20 or 25 mmHg and lasting 5 min). Therefore the calculation of Rout by the infusion test performed on children under general anesthesia gave no reliable prediction of abnormal ICP.

Choroid plexus tumors are rare intraventricular tumors, and they represent 2-4% of brain tumors in children. This single-institution retrospective study involves 16 consecutive choroid plexus tumors: 13 papillomas and 3 carcinomas. Tumor locations were the lateral ventricles in 13 cases, the third ventricle in 2 cases and the fourth ventricle in 1 case. The mean age at presentation was 3.1 years. Two patients died of perioperative blood loss. Five-year survival was 85% with papillomas and 33% with carcinomas. None of the papillomas recurred after total tumor resection, and the functional outcome in long-term survivors after papilloma surgery was excellent in 92% of the cases. Two of the carcinoma patients had disseminated disease. Fifty percent of the patients had persistent hydrocephalus after tumor resection, and these required cerebrospinal fluid diversion.

The objective of this retrospective study was to evaluate the relative effect of surgery and radiotherapy (RT) on the survival of 25 consecutive children and young adults treated for ependymoma [18 in the posterior fossa (PF), 2 in supratentorial locations (ST) and 5 in intraspinal locations (IS)]. Five-year survival rates for patients with PF, ST and IS tumors were 28%, 0% and 100%, respectively. Total tumor resection was a positive prognostic factor in the case of PF tumors. No patients with subtotal removal of a PF tumor survived for longer than 5 years. The effect of RT on survival of patients with PF ependymomas in this series was uncertain. No patients with PF ependymoma had disseminated disease at diagnosis, and all tumor recurrences were local. Based on these observations, we see no indications for craniospinal RT of PF ependymomas, except in rare cases of disseminated disease. If RT is given, it should only be targeted to the tumor site. The two patients with ST ependymoma died within 3.8 years after primary treatment. Our series of ST ependymomas does not allow any specific treatment recommendations. One patient with IS ependymoma was cured by surgery alone. Four patients with IS ependymoma had documented residual tumor after surgery. RT induced remission in these patients. For IS ependymomas we recommend no RT if total tumor removal can be documented. In patients with subtotal removal of IS ependymomas local RT is effective and should be given.

Background: Premature closure of the metopic suture leads to inhibited growth of the frontal bones, producing a keel-shaped forehead (trigonocephaly). Simple metopic synostosis is usually sporadic. Trigonocephalic patients account for 8-16% of the referrals to craniofacial centers, with a marked male predominance. Intracranial pressure (ICP) may be increased, whereas shunt-dependent hydrocephalus is infrequent. Infrequently, patients have intra- or extracerebral anomalies; one third have varying degrees of neuropsychological problems. The treatment is primarily surgical., Material and Methods: We present two patients who during infancy developed increasingly keel-shaped foreheads, retruded orbital rims, increased biparietal diameter and close-set eyes (hypothelorism). Both had raised ICP, but normal psychomotoric development. They were operated using radical fronto-orbital surgical remodelling., Results: Recovery was uneventful. Three months post-operatively, they had pleasing cosmetic results with no symptoms of increased ICP., Interpretation: Where metopic craniosynostosis is suspected, the infant should be examined clinically with palpation of fontanelles and sutures, evaluated with respect to the shape and development of the facial skeleton, as well as by X-ray of the skull sutures. Radical fronto-orbital surgical remodelling gives a stable correction of the craniofacial deformity and generally a satisfactory cosmetic result.

Background: Surgical treatment of syndromal craniofacial synostosis consists of combined neurosurgical and maxillofacial reconstructions of the neurocranium and midface. Patients often need several operations if they are to achieve a functionally and cosmetically good result. This is, in part, due to limitations in the amount of "acute" correction possible peroperatively with conventional surgical technique., Material and Methods: In recent years, a new method called distraction osteogenesis has been developed, by which the skeletal elements are gradually advanced. The method is based upon a process whereby the reparative callus formed between the surfaces of two bone segments is subjected to traction. This leads to new bone formation parallel to the vector of distraction., Results: Distraction osteogenesis allows for greater mobilizations, hence the promise of fewer reoperations., Interpretation: The method seems to be a valuable treatment modality in syndromal craniofacial synostosis, where major fronto-orbital, midface or maxillary reconstructions are often called for.

Frontoethmoidal meningoencephalocele is a rare congenital disease where intracranial masses protrudes through a midline defect at foramen coecum from the anterior cranial fossa into the facial skeleton. The patient presents at birth with a soft-tissue swelling at the nasal bridge. In the majority of cases, the cele is completely covered by skin. The face is elongated, the nasal bridge is broad, the upper part of the nose is long, and the patients have telecanthus. Frequently, the patients have a normal psychomotor development, but may have intracerebral malformations and a shunt dependent hydrocephalus. Spinal fluid leakage may result in meningitis. Anosmia is infrequent. The patients may have a wide range of ophthalmological problems. Newborns with meningoencephalocele should be examined by a neurosurgeon. The investigation and work-up commences with a multidisciplinary approach. We present two patients with meningoencephaloceles.