Cranial repair after traumatic brain injury in children is still burdened by unsolved problems and controversial issues, mainly due to the high rate of resorption of autologous bone as well as the ...absence of valid alternative material to replace the autologous bone. Indeed, inert biomaterials are associated to satisfactory results in the short period but bear the continuous risk of complications related to the lack of osteointegration capacity. Biomimetic materials claiming osteoconductive properties that could balance their mechanical limits seem to allow good cranial bone reconstruction. However, these results should be confirmed in the long term and in larger series. Further complicating factors that may affect cranial reconstruction after head injury should be identified in the possible associated alterations of CSF dynamics and in difficulties to manage the traumatic skin lesion and the surgical wound, which also might impact on the cranioplasty outcome. All the abovementioned considerations should be taken into account when dealing with the cranial reconstruction after decompressive craniectomy in children.
The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and ...glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water−acetonitrile solutions containing proteases inhibitors and analyzed by LC−high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3−22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.
Purpose
Susceptibility-weighted imaging (SWI) is useful for glioma grading and discriminating between brain tumor categories in adults, but its diagnostic value for pediatric brain tumors is unclear. ...Here we evaluated the usefulness of SWI for pediatric tumor grading and differentiation by assessing intratumoral susceptibility signal intensity (ITSS).
Methods
We retrospectively enrolled 96 children with histopathologically diagnosed brain tumors, who underwent routine brain MRI exam with SWI (1.5 T scanner). Each tumor was assigned an ITSS score by a radiology resident and an experienced neuroradiologist, and subsequently by consensus. Statistical analyses were performed to differentiate between low-grade (LG) and high-grade (HG) tumors, histological categories, and tumor locations. Inter-reader agreement was assessed using Cohen’s kappa (κ).
Results
The interobserver agreement was 0.844 (0.953 between first reader and consensus, and 0.890 between second reader and consensus). Among all tumors, we found a statistically significant difference between LG and HG for ITSS scores of 0 and 2 (
p
= 0.002). This correlation was weaker among astrocytomas alone, and became significant when considering only off-midline astrocytomas (
p
= 0.05). Scores of 0 and 2 were a strong discriminating factor (
p
= 0.001) for astrocytomas (score 0) and for embryonal, choroid plexus, germ-cell, pineal, and ependymoma tumors (score 2). No medulloblastoma showed a score of 0.
Conclusions
Our preliminary ITTS results in pediatric brain tumors somewhat differed from those obtained in adult populations. These findings highlight the potential valuable role of ITSS for tumor grading and discriminating between some tumor categories in the pediatric population.
The basis for molecular and cellular heterogeneity in ependymomas of the central nervous system is not understood. This study suggests a basis for this phenomenon in the selection for ...mitogen-independent (MI) stem-like cells with impaired proliferation but increased intracranial tumorigenicity. MI ependymoma cell lines created by selection for EGF/FGF2-independent proliferation exhibited constitutive activation of EGFR, AKT, and STAT3 and sensitization to the antiproliferative effects of EGFR tyrosine kinase inhibitors (TKI). One highly tumorigenic MI line harbored membrane-bound, constitutively active, truncated EGFR. Two EGFR mutants (ΔN566 and ΔN599) were identified as products of intrachromosomal rearrangements fusing the 3' coding portion of the
gene to the 5'-UTR of the
, yielding products lacking the entire extracellular ligand-binding domain of the receptor while retaining the transmembrane and tyrosine kinase domains. EGFR TKI efficiently targeted ΔN566/ΔN599-mutant-mediated signaling and prolonged the survival of mice bearing intracranial xenografts of MI cells harboring these mutations. RT-PCR sequencing of 16 childhood ependymoma samples identified
chimeric mRNAs in one infratentorial ependymoma WHO III, arguing that this fusion occurs in a small proportion of these tumors. Our findings demonstrate how
culture selections applied to genetically heterogeneous tumors can help identify focal mutations that are potentially pharmaceutically actionable in rare cancers.
.
Abstract
We present the first case of clival cystic chordoma with extradural location, transdural transgression, and moderate bone involvement in a 10-year-old girl. Chordoma showed unconventional ...appearances on computed tomography (CT) and magnetic resonance imaging (MRI), due to cystic components, extradural space location with extensive intradural extension, moderate superficial bone involvement. Surgery confirmed the extradural location and histopathological examination revealed cystic chordoma. MRI and CT findings were not characteristic for a single lesion; differential diagnoses included cystic lesions such as epidermoid and dermoid cyst, ecchordosis physaliphora, and benign notochordal cell tumors.
Introduction
Cranioplasty aims at restoring the physiological integrity and volume of the skull. Any disproportion between the intracranial content and the volume of the container may favor the ...occurrence of complications. A classification of volume mismatches is proposed. A negative mismatch, consisting of intracranial content minor to skull volume, is well represented by the sinking flap. On the other side, a positive mismatch, consisting of intracranial content higher than skull volume, usually depends on CSF collection or hydrocephalus once the brain edema is regressed. Though, in children, this condition may result from physiological brain growth after decompressive craniectomy. Treatment algorithm based on this classification is presented.
Illustrative case
A 1-year-old boy with a severe traumatic brain injury underwent right decompressive craniectomy, evacuation of subdural hematoma, and dural expansion at another institution. After failure of autologous bone-assisted cranioplasty for infection, a helmet was recommended in order to postpone the cranial repair. Patient was admitted to our institution 3 years later. CT scan showed brain herniation through the cranial defect, associated to a condition of acquired craniocerebral disproportion, due to the condition of “open skull”. Augmented hydroxyapatite cranioplasty (CustomBone, Finceramica, Faenza, Italy) was performed in order to manage this rare condition of positive volume mismatch. Subsequent course was uneventful and no complication was recorded at 30-month follow-up.
Conclusions
This illustrative case highlights the possible occurrence of a positive structural mismatch between the skull and the intracranial content after decompressive craniectomy, thus configuring a condition of acquired craniocerebral disproportion, aside of other brain or CSF complications. We firstly recognize this condition in the literature and propose it as a possible factor affecting the outcome of cranioplasty in infants and young children.
Lumbosacral lipomas (LLs) may remain asymptomatic or lead to progressive neurological deterioration. However, sudden neurological deterioration is a rare and severe event. Herein, we report rare ...occurrences of sudden clinical deterioration in two previously asymptomatic children harbouring intradural LLs without dermal sinus tracts or signs of occult dysraphism. A review of the pertinent literature is also included.
One child exhibited acute deterioration because of an epidural abscess associated with a filar lipoma without a sinus tract (probably caused by haematogenous spreading from a respiratory tract multiple infection), and the other child exhibited acute deterioration because of a very large, holocord syringomyelia-like cyst associated with a small conus lipoma. Both patients were 4 years old. In case #2, a previously undetected, severe tethered cord (conus at the S3-S4 level) was also present. A complete recovery was attained after an urgent surgical operation in both cases (in addition to targeted antibiotic therapy in case #1). All cases of deterioration in the literature were caused by abscess formation in dermal sinus tracts.
Prophylactic surgery may be indicated even in asymptomatic children that have tethered cord and surgically favourable LLs (small dorsal and filar LLs), especially if the conditions are associated with progressive syringomyelia. Similarly, intradural dermal sinus tracts should be regarded as surgery-indicated, even if the conus is in its normal position and the patient is asymptomatic because there is a consistent risk of severe, infection-related complications. Finally, asymptomatic patients with filar LLs and a normally located conus can be candidates for surgery or an accurate clinical and radiological follow-up.
Sagittal craniosynostosis (SC) remains the most common type of synostosis, accounting for about a half of all forms. It would result from a mesenchymal disorder involving the intramembranous ...ossification of the sagittal suture and leading to its early fusion. No specific data on the etiologic factors are currently available. The premature ossification of the sagittal suture can result in three main types of SC, according to the different segment prevalently involved: anterior, posterior, and complete SC. The diagnosis is easily obtained by clinical examination. However, a radiological work up (3D CT scan) may be necessary to rule out hidden venous or cranial anomalies possibly associated with most severe cases, or for the surgical planning. The most common indication for surgery is the improvement of the cosmetic appearance of the skull, since a cranial deformation may have a significant psychological impact on affected subjects. To relieve from raised intracranial pressure is a further indication to surgery. Although an increased intracranial pressure can be demonstrated in a minority of affected children at diagnosis, indeed, it can present later (usually after the second/third year of life) with chronic symptoms. The role of surgery in the preservation of cognitive functions in scaphocephalic patients does not seem to be relevant, since minor anomalies of the cerebral development associated with SC would occur independently from the cranial shape. On the other hand, the surgical correction may show a protective effect on some visual skills, like the ability to fix and follow, and the fixation shift.
Summary
Background
Decompressive craniectomy is an effective treatment option in case of refractory intracranial hypertension after severe head injury. The incidence of complications following ...cranial repair after decompressive craniectomy for traumatic brain injury is not negligible, particularly in infants and young toddlers. However, only a few dedicated papers can be found in the literature.
Method
We describe the complications observed in two boys and one girl under 1 year of age that were treated in the last decade by hemicranial decompressive craniotomy and enlarging hemispheric duraplasty, and subsequent cranial repair by means of autologous bone-flap replacement.
Findings
Despite good clinical and neurological outcome, the postoperative clinical course was complicated in all cases by early or late evidence of subdural fluid collections associated to the occurrence of hydrocephalus and causing recurrent dislocation and progressive resorption of the autologous bone flap.
Conclusions
Infants less than 1 year old, undergoing decompressive craniectomy after traumatic brain injury, experience a high rate of complications following subsequent cranial repair. Subdural collections and resorption of the autologous bone flap are to be considered as extremely common complications.
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