ABSTRACT
BACKGROUND: In patients with craniosynostosis, imaging remains up to the discretion of the plastic surgeon or neurosurgeon. To inform best practice guidelines, we sought to obtain data surrounding the frequency at which craniofacial surgeons order computed tomography (CT), as well as indications. We hypothesized that we would identify considerable variation in both imaging and associated indications. METHODS: We surveyed members of the American Society of Maxillofacial Surgeons and the American Society of Craniofacial Surgeons to measure the frequency of preoperative and postoperative head CTs, as well as indications. Initial items were piloted with 2 craniofacial surgeons and 1 neurosurgeon, using interviews to ensure content validity. χ2 Tests were used to measure associations between operative volume, years in practice, and imaging. RESULTS: Eighty-five craniofacial surgeons responded (13.8% response rate), with the majority (63.5%) having performed a craniosynostosis operation in the last month. Only 9.4% of surgeons never order preoperative CTs. Of those who do, the most common indications included diagnosis confirmation (31.2%) and preoperative planning (27.3%). About 25% of surgeons always obtain postoperative head CTs, usually to evaluate surgical outcomes (46.7%). Only 13.3% of respondents order 2 or more postoperative scans. Higher operative volume was associated with a lower likelihood of ordering preoperative head CTs (P = 0.008). CONCLUSIONS: The majority of surgeons obtain preoperative head CTs, whereas only 25% obtain CTs postoperatively, often to evaluate outcomes. Because outcomes may be evaluated clinically, this is a poor use of resources and exposes children to radiation. Consensus guidelines are needed to create best practices and limit unnecessary studies.
Subject(s)
Craniosynostoses , Surgeons , Child , Craniosynostoses/diagnostic imaging , Craniosynostoses/surgery , Humans , Practice Patterns, Physicians' , Surveys and Questionnaires , Tomography, X-Ray Computed , United StatesABSTRACT
BACKGROUND: Repair of the soft tissue defect in myelomeningoceles remains challenging. The literature currently lacks a systematic approach, reporting high rates of complications. We present outcomes from the largest series to date and describe a simplified approach that minimizes morbidity and streamlines decision making. METHODS: Patients 1 year or younger who underwent myelomeningocele repair between 2008 and 2018 were reviewed. Flap types were categorized by tissue composition. Complications were dichotomized into early and late (<30 days and >30 days postoperative, respectively). Logistic regression was used to measure the impact of flap tissue composition and skin closure technique on odds of postoperative complications. RESULTS: Ninety-seven patients met inclusion criteria. Reoperation was required in only 3 (3.0%) patients-1 for wound dehiscence and 2 for surgical site infections. Zero cases of tethered cord or cerebrospinal fluid leak occurred. The most common minor complications were early wound complications (n = 18, 18.6%) and early infection (n = 5, 5.2%). Fascia-only flaps and muscle + other tissue flaps were not associated with higher odds of complications compared with muscle-only flaps (odds ratio [OR], 2.13; 95% confidence interval [CI], 0.53-8.50, P = 0.29; OR = 2.87, 95% CI 0.66-12.51, P = 0.16, respectively). Rhomboid flaps for skin closure were associated with higher odds of complications (OR, 4.47; 95% CI, 1.00-19.97; P = 0.05). CONCLUSIONS: Our approach to myelomeningocele repair demonstrated no cases of secondary tethered cord or cerebrospinal fluid leak, and reoperative rates were extremely low. Because complications were unrelated to flap type, we recommend a simplified approach using any tissue type for dural coverage and 2-layer primary closure of the skin.
Subject(s)
Meningomyelocele , Plastic Surgery Procedures , Fascia , Humans , Meningomyelocele/surgery , Reoperation , Surgical FlapsABSTRACT
BACKGROUND: Cerebrospinal fluid (CSF) velocity at the craniovertebral junction (CVJ) is known to be altered in patients with Chiari I malformation (CMI), and normalization of CSF velocities is associated with symptom resolution. However, preoperative and intraoperative prediction methods have thus far failed to identify patients in whom CSF velocities can be normalized with posterior fossa decompression (PFD) without duraplasty. Phase contrast MRI (PC-MRI) may assist not only in diagnosis of CMI but also in guiding the intraoperative decision to perform duraplasty during PFD. PURPOSE: To use intraoperative MRI data to quantify changes in CSF hydrodynamics at the CVJ during each step of PFD with duraplasty (PFDD) in 12 consecutive patients. STUDY TYPE: Retrospective case series with all patients imaged before, during and after decompression, and all data analyzed postprocedure. POPULATION/SUBJECTS: Pediatric patients, mean age 14 years (range 4-18), undergoing PFD for CMI. FIELD STRENGTH/SEQUENCE: Intraoperative studies involved a dedicated 1.5T Siemens MRI imager. PC-MRI scans were in the axial plane at the CVJ. ASSESSMENT: Two observers assessed measurements. STATISTICAL TEST: The equality of matched pairs of observations was tested using the Wilcoxon matched-pairs signed-ranks test. RESULTS: Data analyses of the PC-MRI demonstrated a marked and immediate increase in CSF velocity at the posterior CVJ during PFDD. Mean cranially-directed velocities increased by a mean of 1.049cm/s (P = 0.028) from preincision to postoperative measurement. There was a mean 0.45 cm/s (P = 0.022) increase in mean cranial velocity from preincision to bone decompression scans, and a mean 0.48 cm/s (P = 0.018) increase in mean velocity from preincision to duraplasty. DATA CONCLUSION: In all subjects, significant increases in the mean and peak velocities of cranially- and caudally-directed velocities were observed from preincision to post-PFDD scans at the posterior CVJ. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;51:1463-1470.
Subject(s)
Arnold-Chiari Malformation , Decompression, Surgical , Adolescent , Arnold-Chiari Malformation/diagnostic imaging , Arnold-Chiari Malformation/surgery , Cerebrospinal Fluid/diagnostic imaging , Child , Child, Preschool , Humans , Magnetic Resonance Imaging , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: A lasting correction of trigonocephaly is difficult to achieve, as a durable correction requires significant expansion to overcome galeal restriction and soft tissue recoil of the scalp. High rates of relapse have been reported throughout the literature. The specific aim of this study was to determine if the senior author's method of "hypercorrection" decreases relapse and the need for subsequent revisional surgery. METHODS: Patients who underwent operative correction of metopic craniosynostosis between 1988 and 2011 were reviewed. All patients underwent the "hypercorrection" technique performed by the senior author. Hypercorrection consisted of a fronto-orbital advancement of 2.5 to 3.5âcm and a concomitant hyperexpansion of bitemporal projection. Split cranial bone grafting ensured adequate coverage of the significantly expanded cranial vault. Only patients who had at least 5 years of follow-up were included for review of outcomes. Relapse was defined as recurrence of bitemporal constriction or lateral orbital retrusion, requiring surgical correction. RESULTS: Fifty-eight patients met criteria. Mean age at the time of surgery was 11 months. Mean follow-up was 9.0 years. During this time, 2 patients exhibited relapse requiring camouflage procedures. Cranial bone defects were found in 4 patients (7%), 3 of whom underwent cranial bone grafting, while 1 underwent methylmethacrylate placement at an outside institution. One patient underwent fat grafting for areas of soft tissue irregularity. No patients exhibited persistent sequelae of hypercorrection significant enough to require repeat fronto-orbital advancement. CONCLUSION: Surgical hypercorrection of trigonocephaly seems to minimize relapse and the need for revision in long-term follow-up and is therefore an important technique to consider.
Subject(s)
Craniosynostoses/surgery , Plastic Surgery Procedures/methods , Skull/surgery , Adipose Tissue/transplantation , Bone Transplantation , Child , Child, Preschool , Female , Follow-Up Studies , Frontal Bone/surgery , Humans , Infant , Male , Methylmethacrylate , Orbit/surgery , Recurrence , Reoperation , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: To assess the effects of cerebrospinal fluid (CSF) bidirectional motion in Chiari malformation type I (CMI), we monitored CSF velocity amplitudes on phase contrast MRI (PC-MRI) in patients before and after surgery; and in healthy volunteers. MATERIALS AND METHODS: 10 pediatric volunteers and 10 CMI patients participated in this study. CMI patients underwent PC-MRI scans before and approximately 14 months following surgery. Two parameters-amplitude of mean velocity (AMV) and amplitude of peak velocity (APV) of CSF-were derived from the data. Measurements were made at the mid-portion of the cerebral aqueduct, and anterior and posterior compartments of the spinal canal at the craniovertebral junction (CVJ). RESULTS: AMV and APV within the cerebral aqueduct were greater in preoperative assessments of the CMI patients compared to normal volunteers. Statistical significance was noted when comparing aqueductal AMV between the preoperative values and normal controls (P = 0.03), and before and after surgery in the CMI patients (P = 0.02). Lower values of AMV (P = 0.02) were noted in the anterior CVJ compartment in the patients before and after surgery when compared to the normal volunteers. There were no significant correlations (P = 0.06) noted for the APV at the CVJ between the normal control and patients, before or after surgery. CONCLUSION: In pediatric CMI patients, AMV for CSF within the cerebral aqueduct and anterior CVJ subarachnoid space are significantly elevated preoperatively and normalize following surgery. Given the biphasic CSF motion, measuring amplitude accounts for cranial and caudal flow. It may offer an alternative parameter to assess postsurgical outcome. J. Magn. Reson. Imaging 2016;44:463-470.
Subject(s)
Arnold-Chiari Malformation/diagnostic imaging , Arnold-Chiari Malformation/surgery , Cerebral Aqueduct/diagnostic imaging , Cerebrospinal Fluid/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Arnold-Chiari Malformation/cerebrospinal fluid , Cerebral Aqueduct/pathology , Cerebrospinal Fluid/cytology , Decompression, Surgical , Female , Humans , Male , Reproducibility of Results , Rheology/methods , Sensitivity and Specificity , Treatment OutcomeABSTRACT
Activation of a thrombin receptor, protease-activated receptor-1 (PAR-1), induces angiogenesis, cell proliferation, and invasion in tumors. The present study examined the effect of host PAR-1 gene deletion on glioma growth in a mouse model. F98 glioma cells were implanted into the right caudate of either wild type (WT) or PAR-1 knockout (KO) mice. Mice underwent magnetic resonance imaging (MRI) and the brains were used for measurements of brain water content and tumor mass. Levels of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were also measured by ELISA (enzyme-linked immunosorbent assay). We found brain water content in the ipsilateral hemisphere and the tumor mass were significantly lower in PAR-1 KO than WT mice at day 12 after implantation of F98 cells (p < 0.05). HIF-1α protein levels in the ipsilateral hemisphere were higher in the WT mice (373 ± 25 pg/g brain tissue vs 333 ± 35 pg/g brain tissue in PAR-1 KO mice, p < 0.05) 7 days after F98 cell implantation. VEGF protein levels were also higher in the ipsilateral hemisphere of WT mice (219 ± 21 vs 166 ± 22 pg/g brain tissue in PAR-1 KO mice, p < 0.01). In conclusion, PAR-1 has a role in glioma growth and could be a new therapeutic target for gliomas.
Subject(s)
Brain Neoplasms/genetics , Glioma/genetics , Receptor, PAR-1/genetics , Animals , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Disease Progression , Enzyme-Linked Immunosorbent Assay , Glioma/metabolism , Glioma/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Magnetic Resonance Imaging , Mice , Mice, Knockout , Neoplasm Transplantation , Rats , Tumor Burden , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Endoscopic strip craniectomy with postoperative helmet therapy has been introduced as a means to correct various forms of craniosynostosis. Although some authors have deemed the procedure safe and effective, many questions remain regarding this promising yet developing approach. The authors discuss 4 cases where patients were inadequately treated with endoscopic strip craniectomy resulting in a recommendation of complete secondary open cranial vault reconstruction. In addition, the authors present the findings from an informal survey of craniofacial colleagues to highlight an important discrepancy between published and anecdotal reports of complications. Finally, the authors highlight the need for further investigation into the proper indications and clinical outcomes of endoscopic strip craniectomy to better understand the role of this technique in the treatment of craniosynostosis.
Subject(s)
Craniosynostoses/surgery , Decompressive Craniectomy/methods , Endoscopy/methods , Cognition Disorders/diagnosis , Follow-Up Studies , Humans , Infant , Neuropsychological Tests , Postoperative Complications/diagnosis , Treatment OutcomeABSTRACT
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor, with dismal survival outcomes. Recently, cancer stem cells (CSCs) have been demonstrated to play a role in therapeutic resistance and are considered to be the most likely cause of cancer relapse. The identification of CSCs is an important step toward finding new and effective ways to treat GBM. Tenascin-C (TNC) protein has been identified as a potential marker for CSCs in gliomas based on previous work. Here, we have investigated the expression of TNC in tissue microarrays including 17 GBMs, 18 WHO grade III astrocytomas, 15 WHO grade II astrocytomas, 4 WHO grade I astrocytomas, and 7 normal brain tissue samples by immunohistochemical staining. TNC expression was found to be highly associated with the grade of astrocytoma. It has a high expression level in most of the grade III astrocytomas and GBMs analyzed and a very low expression in most grade II astrocytomas, whereas it is undetectable in grade I astrocytomas and normal brain tissues. Double-immunofluorescence staining for TNC and CD133 in GBM tissues revealed that there was a high overlap between theses two positive populations. The results were further confirmed by flow cytometry analysis of TNC and CD133 in GBM-derived stem-like neurospheres in vitro. A limiting dilution assay demonstrated that the sphere formation ability of CD133(+)/TNC(+) and CD133(-)/TNC(+) cell populations is much higher than that of the CD133(+)/TNC(-) and CD133(-)/TNC(-) populations. These results suggest that TNC is not only a potential prognostic marker for GBM but also a potential marker for glioma CSCs, where the TNC(+) population is identified as a CSC population overlapping with part of the CD133(-) cell population.
Subject(s)
Biomarkers, Tumor/analysis , Brain Neoplasms/metabolism , Glioblastoma/metabolism , Tenascin/analysis , Tissue Array Analysis/methods , Adolescent , Adult , Biomarkers, Tumor/metabolism , Brain Neoplasms/chemistry , Female , Glioblastoma/chemistry , Humans , Immunohistochemistry , Male , Middle Aged , Neoplastic Stem Cells , Tenascin/metabolism , Tumor Cells, Cultured , Young AdultABSTRACT
Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity.
Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/metabolism , MicroRNAs/genetics , Neuroectodermal Tumors, Primitive/genetics , Neuroectodermal Tumors, Primitive/metabolism , RNA-Binding Proteins/metabolism , Adolescent , Age of Onset , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Cell Line, Tumor , Child , Child, Preschool , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methylation , Diagnosis, Differential , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Male , Multigene Family , Neuroectodermal Tumors, Primitive/diagnosis , Neuroectodermal Tumors, Primitive/therapy , DNA Methyltransferase 3BABSTRACT
Although CD90 has been identified as a marker for various kinds of stem cells including liver cancer stem cells (CSCs) that are responsible for tumorigenesis, the potential role of CD90 as a marker for CSCs in gliomas has not been characterized. To address the issue, we investigated the expression of CD90 in tissue microarrays containing 15 glioblastoma multiformes (GBMs), 19 WHO grade III astrocytomas, 13 WHO grade II astrocytomas, 3 WHO grade I astrocytomas and 8 normal brain tissues. Immunohistochemical analysis showed that CD90 was expressed at a medium to high level in all tested high-grade gliomas (grade III and GBM) whereas it was barely detectable in low-grade gliomas (grade I and grade II) and normal brains. Double immunofluorescence staining for CD90 and CD133 in GBM tissues revealed that CD133(+) CSCs are a subpopulation of CD90(+) cells in GBMs in vivo. Flow cytometry analysis of the expression of CD90 and CD133 in GBM-derived stem-like neurospheres further confirmed the conclusion in vitro. The expression levels of both CD90 and CD133 were reduced along with the loss of stem cells after differentiation. Furthermore, the limiting dilution assay demonstrated that the sphere formation ability was comparable between the CD90(+)/CD133(+) and the CD90(+)/CD133(-) populations of GBM neurospheres, which is much higher than that of the CD90(-)/CD133(-) population. We also performed double staining for CD90 and a vascular endothelial cell marker CD31 in tissue microarrays which revealed that the CD90(+) cells were clustered around the tumor vasculatures in high-grade glioma tissues. These findings suggest that CD90 is not only a potential prognostic marker for high-grade gliomas but also a marker for CSCs within gliomas, and it resides within endothelial niche and may also play a critical role in the generation of tumor vasculatures via differentiation into endothelial cells.
Subject(s)
Astrocytoma/metabolism , Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Thy-1 Antigens/metabolism , AC133 Antigen , Adult , Antigens, CD/metabolism , Astrocytoma/blood supply , Astrocytoma/pathology , Brain Neoplasms/blood supply , Brain Neoplasms/pathology , Case-Control Studies , Female , Glycoproteins/metabolism , Humans , Male , Middle Aged , Peptides/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Spheroids, Cellular/metabolism , Tissue Array Analysis , Young AdultABSTRACT
BACKGROUND: Cranial vault remodeling (CVR) for craniosynostosis is a procedure with the potential for significant blood loss. Aminocaproic acid (ACA) has been used at our institution during CVR for its antifibrinolytic effects. The purpose of this study was to investigate the effect of ACA on blood loss and transfusion rates during primary CVR. METHODS: Three hundred eighty-three patients with craniosynostosis underwent primary CVR at a single institution by a single surgeon over 15 years. Patients were included if they received either ACA or no antifibrinolytic. The estimated blood loss (EBL) and volume of blood transfused was recorded. Thrombotic-related complications were identified. Comparisons were made between subgroups using independent Student t test and Fisher exact test. RESULTS: Among the study population, 148 patients met inclusion criteria. ACA was given to 30 patients, while 118 patients received no antifibrinolytic. There was no difference in the average intraoperative EBL between the ACA (322 mL) and control groups (327 mL, P > 0.05). Additionally, the incidence of transfusion was not significantly different between subgroups (97% vs. 86%, respectively, P > 0.05). Patients treated with ACA, however, received lower average perioperative transfusion volumes (25.5 mL/kg) compared to control patients (53.3 mL/kg, P < 0.0001). Furthermore, patients in the ACA subgroup were less likely to require a second unit of blood (21% vs. 43%, P < 0.0001) and therefore had fewer exposures to donor blood antigens (ARR = 22%, NNT = 4.6). CONCLUSIONS: The use of intraoperative ACA minimizes blood transfusion volumes and donor exposures in children who undergo primary CVR for craniosynostosis. Antifibrinolytics should be considered for routine use in pediatric craniofacial surgery.
Subject(s)
Aminocaproic Acid/therapeutic use , Antifibrinolytic Agents/therapeutic use , Blood Loss, Surgical/prevention & control , Blood Transfusion , Craniosynostoses/surgery , Arterial Pressure/physiology , Cohort Studies , Erythrocyte Transfusion , Hematocrit , Humans , Plastic Surgery Procedures/methods , Retrospective Studies , Skull/surgery , Thrombosis/etiologyABSTRACT
OBJECTIVE: Given the lack of a definitive treatment and the poor prognosis of patients with diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG), socioeconomic status (SES) may affect treatment access and therefore survival. Therefore, this study aimed to examine the relationship between SES and treatment modalities, progression-free survival (PFS), and overall survival (OS) in children with DMG/DIPG. METHODS: A retrospective, single-institution review was conducted of medical records of patients ≤ 18 years of age who had DMG or DIPG that was diagnosed between 2000 and 2022. Patient demographics, surgical interventions, chemotherapy, radiation therapy, clinical trial enrollment, and medical care-related travel were extracted. SES variables (education and mean income) for associated patient census tracts were collected and stratified. Statistical analysis using unpaired t-tests, chi-square analysis, and log-rank tests was conducted. RESULTS: Of the 96 patients who met the inclusion criteria, the majority were female (59%) and non-Hispanic White (57%). The median PFS, median OS, and time from diagnosis to treatment did not differ between races/ethnicities or sex. Ninety-one of 96 patients had census tract data available. Patients from higher-income census tracts (> 50% of families with annual household income greater than $50,000) had a longer median OS (480 vs 235 days, p < 0.001) and traveled significantly longer distances for medical care (1550 vs 1114 miles, p = 0.048) than families from lower-income census tracts. Patients from the highest education quartile traveled significantly farther for treatment than the lowest education quartile (mean 2964 vs 478 miles, p = 0.047). Patients who received both oral and intravenous chemotherapy were more likely to be from higher-income census tracts than those who received intravenous or no chemotherapy. Duration of PFS, rates of clinical trial enrollment, biopsy rates, H3K27 mutation status, ventriculoperitoneal shunt placement rates, and radiotherapy rates were not associated with SES variables. CONCLUSIONS: Patients from families from higher-income census tracts experienced longer OS and traveled farther for treatment. Patients from families from higher-education-level census tracts traveled more often for treatment. The authors' findings suggest that SES influences DMG and DIPG OS. More studies should be done to understand the role of SES in the outcomes of children with DMG/DIPG.
Subject(s)
Brain Stem Neoplasms , Diffuse Intrinsic Pontine Glioma , Glioma , Social Class , Humans , Female , Male , Brain Stem Neoplasms/therapy , Brain Stem Neoplasms/pathology , Child , Retrospective Studies , Diffuse Intrinsic Pontine Glioma/therapy , Child, Preschool , Glioma/therapy , Glioma/pathology , Glioma/mortality , Adolescent , Treatment Outcome , Infant , Progression-Free SurvivalABSTRACT
An important problem involves isolating subpopulations of cells defined by protein markers in clinical tissue samples for proteomic studies. We describe a method termed Immunohistochemical staining, laser capture microdissection (LCM) and filter-aided sample preparation (FASP)-Assisted Proteomic analysis of Target cell populations within tissue samples (ILFAPT). The principle of ILFAPT is that a target cell population expressing a protein of interest can be lit up by immunohistochemical staining and isolated from tissue sections using LCM for FASP and proteomic analysis. Using this method, we isolated a small population of CD90(+) stem-like cells from glioblastoma multiforme tissue sections and identified 674 high-confidence (false discovery rate < 0.01) proteins from 32 nL of CD90(+) cells by LC-MS/MS using an Orbitrap Elite mass spectrometer. We further quantified the relative abundance of proteins identified from equal volumes of LCM-captured CD90(+) and CD90(-) cells, where 109 differentially expressed proteins were identified. The major group of these differentially expressed proteins was relevant to cell adhesion and cellular movement. This ILFAPT method has demonstrated the ability to provide in-depth proteome analysis of a very small specific cell population within tissues. It can be broadly applied to the study of target cell populations within clinical specimens.
Subject(s)
Brain Neoplasms/pathology , Brain/pathology , Glioblastoma/pathology , Laser Capture Microdissection/methods , Proteome/analysis , Proteomics/methods , Brain/metabolism , Brain Neoplasms/metabolism , Fibronectins/analysis , Fibronectins/metabolism , Glioblastoma/metabolism , Humans , Immunohistochemistry/methods , Protein Interaction Maps , Proteome/metabolism , Staining and Labeling/methods , Thy-1 Antigens/analysis , Thy-1 Antigens/metabolismABSTRACT
Our aim with this study was to develop a user-friendly method for pediatric sonographically guided lumbar punctures so that we can visualize intrathecal anatomy, confirm intrathecal injection at the time of injection, and, most importantly, avoid ionizing radiation to a child's already radiosensitive pelvis. Sonographically guided lumbar puncture was prospectively performed in children aged 7 weeks to 16 years. All attempts (n = 9) were successful. We were able to identify relevant anatomy (including the conus in children 10 years and younger), confirm intrathecal injection, visualize intrathecal hematoma, and avoid radiation. Sonography is a promising modality for image-guided lumbar punctures without radiation in children.
Subject(s)
Cerebrospinal Fluid/cytology , Cerebrospinal Fluid/diagnostic imaging , Image-Guided Biopsy/methods , Spinal Puncture/methods , Ultrasonography, Interventional/methods , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Intracranial bleeding is a common and serious consequence of traumatic brain injury (TBI). In the present study, we investigated cerebral hematoma occurrence, brain edema formation, blood-brain barrier (BBB) disruption, and heme oxygenase-1 (HO-1) expression after TBI. Moderate severity (1.8-2.2 atmospheres [ATM]) TBI was induced by lateral fluid percussion in male adult Sprague-Dawley rats. Sham rats underwent only a craniotomy. Rats were euthanized 24 h later for brain histology and immunoblotting analysis. We found TBI-induced cerebral hematomas and iron deposition in the ipsilateral hemisphere in all rats. TBI also caused marked BBB disruption (p < 0.05) and brain swelling (p < 0.05). HO-1, a key enzyme for heme degradation, was upregulated significantly after TBI (419 ± 89 vs 194 ± 59 pixels in the sham, p < 0.05). These results suggest that cerebral hematomas might play a role in brain injury after TBI. Future studies should determine the role of iron released from the cerebral hematoma in TBI.
Subject(s)
Brain Edema/etiology , Brain Injuries/complications , Brain Injuries/enzymology , Cerebral Hemorrhage/etiology , Gene Expression Regulation, Enzymologic/physiology , Heme Oxygenase-1/metabolism , Animals , Disease Models, Animal , Functional Laterality , Male , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Previous studies have demonstrated the benefit of releasing symptomatic tethered cords; however, complications such as seroma, cerebrospinal fluid leak, and infection continue to plague these patients. We propose that composite tissue closure of tethered cord repairs yields superior outcomes and that a collaborative effort between neurosurgery and plastic surgery may result in enhanced structural and functional results. METHODS: This is a retrospective study comprised of consecutive patients with tethered cord syndrome by 2 neurosurgeons and 2 plastic surgeons between 1994 and 2008 at a single institution. All consecutive patients who underwent tethered cord release by neurosurgery and subsequent composite tissue closure with fascial and musculofascial flaps by plastic surgery were included. Data were collected by retrospective chart review and analyzed using parametric methods. RESULTS: A total of 86 consecutive patients were included in this study, with follow-up ranged from 12 to 144 months (average follow-up, 29 months). There were no statistical differences in follow-up time, comorbidities, or surgeon when comparing hospital readmission or reoperation. There was no statistical difference in complications when comparing the different flap closures. We had a 1.2% infection rate, a 4.7% readmission rate, and a 3.5% reoperation rate. CONCLUSION: We believe that local soft tissue rearrangement improves the closure by providing an additional layer of vascularized tissue between the skin and the spinal cord. We believe our series represents a significant sample size compared with those previously reported for an experience that achieves multilayered soft tissue closure after tethered cord repair. Our results support the idea that neurosurgeons should consider consultation of plastic surgeons when treating patients with tethered cord syndrome surgically.
Subject(s)
Neural Tube Defects/surgery , Neurosurgical Procedures/methods , Plastic Surgery Procedures/methods , Surgical Flaps , Wound Closure Techniques , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Recovery of Function , Reoperation/statistics & numerical data , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Childhood CNS primitive neuro-ectodermal brain tumours (PNETs) are very aggressive brain tumours for which the molecular features and best treatment approaches are unknown. We assessed a large cohort of these rare tumours to identify molecular markers to enhance clinical management of this disease. METHODS: We obtained 142 primary hemispheric CNS PNET samples from 20 institutions in nine countries and examined transcriptional profiles for a subset of 51 samples and copy number profiles for a subset of 77 samples. We used clustering, gene, and pathway enrichment analyses to identify tumour subgroups and group-specific molecular markers, and applied immunohistochemical and gene-expression analyses to validate and assess the clinical significance of the subgroup markers. FINDINGS: We identified three molecular subgroups of CNS PNETs that were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Patients with group 1 tumours were most often female (male:female ratio 0·61 for group 1 vs 1·25 for group 2 and 1·63 for group 3; p=0·043 [group 1 vs groups 2 and 3]), youngest (median age at diagnosis 2·9 years [95% CI 2·4-5·2] for group 1 vs 7·9 years [6·0-9·7] for group 2 and 5·9 years [4·9-7·8] for group 3; p=0·005), and had poorest survival (median survival 0·8 years [95% CI 0·5-1·2] in group 1, 1·8 years [1·4-2·3] in group 2 and 4·3 years [0·8-7·8] in group 3; p=0·019). Patients with group 3 tumours had the highest incidence of metastases at diagnosis (no distant metastasis:metastasis ratio 0·90 for group 3 vs 2·80 for group 1 and 5·67 for group 2; p=0·037). INTERPRETATION: LIN28 and OLIG2 are promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials. FUNDING: Canadian Institute of Health Research, Brainchild/SickKids Foundation, and the Samantha Dickson Brain Tumour Trust.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Genomics , Nerve Tissue Proteins/genetics , Neuroectodermal Tumors, Primitive/genetics , RNA-Binding Proteins/genetics , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Cell Lineage/genetics , Chi-Square Distribution , Child , Child, Preschool , Cluster Analysis , Europe , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genomics/methods , Humans , Immunohistochemistry , Japan , Kaplan-Meier Estimate , Male , Neuroectodermal Tumors, Primitive/mortality , Neuroectodermal Tumors, Primitive/secondary , North America , Oligodendrocyte Transcription Factor 2 , Principal Component Analysis , Prognosis , Reproducibility of Results , Republic of Korea , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
Chiari I malformation is a common condition seen by adult and pediatric neurosurgeons. With increased utilization of MRI over time, incidental findings of Chiari I malformation are occurring more frequently. The prevalence of symptomatic Chiari I malformation is much smaller than that of asymptomatic Chiari I malformation. The prevalence of Chiari I malformation-associated syringomyelia is likely overestimated in the literature. The epidemiology of Chiari I malformation and associated syringomyelia differs based on age, sex, ethnicity, race, and socioeconomic status. The natural history of Chiari I malformation and associated syringomyelia appears to be quite benign as few patients who are managed nonsurgically later require surgical intervention.
Subject(s)
Arnold-Chiari Malformation , Syringomyelia , Adult , Humans , Child , Syringomyelia/complications , Syringomyelia/epidemiology , Syringomyelia/surgery , Arnold-Chiari Malformation/complications , Arnold-Chiari Malformation/epidemiology , Arnold-Chiari Malformation/surgery , Magnetic Resonance ImagingABSTRACT
BACKGROUND: Currently, there is no consensus recommendation regarding the safety of sports participation for pediatric patients with Chiari I malformation (CM-I). OBJECTIVE: To prospectively survey the treated and untreated patients with CM-I to define the risk of sports-associated neurological injury. METHODS: A prospective survey was administered to 744 pediatric patients at one neurosurgery clinic between 2010 and 2021. Data were recorded on demographic information, imaging characteristics, treatment, sports participation, and presence of sports-related neurological injury. Patients with incomplete data were called. Two hundred seven patients completed at least 1 subsequent survey and were prospectively followed (mean 1.6 years). RESULTS: Of 744 patients with completed surveys, 462 participated in sports. Sports participants were more likely to be older at presentation ( P < .001) and have rounded cerebellar tonsil morphology ( P < .001). Seasons of sports played before and after CM-I decompression (CMD) totaled 5918.7 and 936, respectively. There were 84 sports-related concussions among 55 patients; 79 in untreated patients and 5 after CMD. For all sports participants, the concussion rate was 12.3/1000 seasons of all sports, 9.2/1000 seasons of limited-contact sports, and 13.8/1000 of contact sports. The concussion rate after CMD was 5.3/1000 seasons of all sports, 9.2/1000 seasons of limited-contact sports, and 7.1/1000 seasons of contact sports. There were no reports of long-lasting neurological issues postconcussion or of permanent spinal cord injury. CONCLUSION: No permanent or catastrophic sports-associated neurological injuries were reported. The concussion rates in treated and untreated patients with CM-I were low. Therefore, sports participation in this population should be permitted in most cases.