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Cell and Tissue Research Jun 2016Mutation of the Parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease. However, recently, it has been also linked to a wide variety of...
Mutation of the Parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease. However, recently, it has been also linked to a wide variety of malignancies, including glioblastoma multiforme (GBM). In this pathology, Parkin exhibits a tumor suppressor role by mitigating the proliferation rate in both in vitro and in vivo models. However, Parkin involvement in the hypoxic process has not as yet been investigated. GBM is the most common and aggressive primary brain tumor in adults and is characterized by hypoxic areas. The low oxygen supply causes the expression of hypoxia-inducible factors (HIFs) leading to an accumulation of pro-angiogenic factors and tumoral invasiveness. We assess the relationship between Parkin and two HIFs expressed during hypoxic conditions, namely HIF-1α and HIF-3α. Our data show that Parkin is downregulated under hypoxia and that it interferes with HIF expression based on cellular oxygen tension. These results suggest a role for the involvement of Parkin in GBM, although further studies will be needed to understand the mechanism by which it modulates HIF-1α and HIF-3α expression.
Topics: Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Cell Hypoxia; Cell Line, Tumor; Gene Knockdown Techniques; Gene Silencing; Glioblastoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Repressor Proteins; Ubiquitin-Protein Ligases
PubMed: 26742768
DOI: 10.1007/s00441-015-2340-3 -
Central sleep apnoea as an initial presentation of a posterior fossa juvenile pilocytic astrocytoma.BMJ Case Reports Dec 2022
Topics: Humans; Sleep Apnea, Central; Astrocytoma; Head; Brain Neoplasms
PubMed: 36524264
DOI: 10.1136/bcr-2022-253025 -
World Neurosurgery Jul 2018Clips implanted during intracranial neurosurgical procedures sometimes migrate intradurally with rare cases of spinal migration. The appearance of radicular symptoms of...
BACKGROUND
Clips implanted during intracranial neurosurgical procedures sometimes migrate intradurally with rare cases of spinal migration. The appearance of radicular symptoms of topography concordant with the position of the foreign body leads to discussion about the optimal therapeutic strategy.
CASE DESCRIPTION
We report the case of a 52-year-old woman suffering from L5 radicular pain resistant to medical treatment in the presence of L4L5 lumbar stenosis and a neurosurgical clip migrated to the L5S1 level. This clip had been implanted 19 years earlier during a surgical procedure in the posterior fossa, for resection of a juvenile astrocytoma. The imputability of this clip was deemed low given its location and history. A laminarthrectomy associated with circumferential arthrodesis of the L4L5 level was performed allowing complete improvement of radiculopathy. Surgical removal of the clip was not performed.
CONCLUSION
Craniospinal migrations of neurosurgical clips are rare. Their imputability in the appearance of root symptoms is random and is based on a bundle of clinical, radiologic, and neurophysiologic arguments. Surgical removal should not be the standard treatment, especially if there is another cause of root compression.
Topics: Dura Mater; Female; Foreign-Body Migration; Hemostasis, Surgical; Humans; Lumbar Vertebrae; Middle Aged; Neurosurgical Procedures; Pain; Radiculopathy; Sciatica; Surgical Instruments
PubMed: 29689402
DOI: 10.1016/j.wneu.2018.04.082 -
Journal of Neurosurgery Jun 2018Optic pathway gliomas (OPGs) are relatively common and benign lesions in children; however, in adults these lesions are nearly always malignant and hold a very poor...
Optic pathway gliomas (OPGs) are relatively common and benign lesions in children; however, in adults these lesions are nearly always malignant and hold a very poor prognosis. In this report the authors present the case of an adult patient with a benign OPG who underwent subtotal resection without adjuvant therapy and has had no tumor progression for more than 20 years. A 50-year-old woman presented with a 2-year history of personality changes, weight gain, and a few months of visual disturbances. Ophthalmological evaluation showed incomplete right homonymous hemianopsia. MRI demonstrated a 2.5 × 2.5 × 2.5-cm enhancing left-sided lesion involving the hypothalamus with extension into the suprasellar cistern, extending along the left optic tract and anterior to the level of the optic chiasm. A biopsy procedure revealed a juvenile pilocytic astrocytoma. A subtotal resection of approximately 80% of the tumor was performed. Postoperatively, the patient experienced complete resolution of her personality changes, and her weight decreased back to baseline. Ophthalmological examination showed increased right homonymous hemianopsia. In the years following her surgery, there was a spontaneous decrease in tumor size without adjuvant therapy. The patient continues to have an excellent quality of life despite a visual field defect, and no further tumor growth has been observed.
PubMed: 29999469
DOI: 10.3171/2017.12.JNS172188 -
Journal of Neurosurgery. Pediatrics Apr 2016Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in...
Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration. As examples, we describe two cases of fatal hemorrhagic cerebellar PAs: one of a child with a slowly growing stereotypical WHO Grade I PA with a 1-year period of symptomatology that preceded a rapid clinical deterioration, and another of an asymptomatic child having a PA variant, presenting with progressive obtundation following a presumed Valsalva event. These two scenarios parallel previous reports in the literature of either a setting of progressive expression of cerebellar dysfunction and transient episodes of raised intracranial pressure (ICP), or abrupt onset of features of increased ICP in a previously well child. The literature is further reviewed for a current understanding of the factors that predispose, initiate and propagate bleeding, with specific reference to the role of vascular endothelial growth factor and other angiogenic agents in the genesis and stability of the vasculature in PAs. In this context, we propose that obliterative vascular mural hyalinization with associated altered flow dynamics and microaneurysm formation was the pathogenesis of the hemorrhage in our first case. In the second case, large tumor size, increased growth rate, looseness of the background myxoid matrix, and thinness of the tumor blood vessels with calcospherite deposition predisposed to vascular leakage and bleeding concurrent with sudden increases in intravascular hydrostatic pressure. In that cerebellar PAs are common, this report underscores the importance of considering in the differential diagnosis the possibility of a spontaneous hemorrhage in a posterior fossa PA in a child presenting with a sudden neurological ictus and raised ICP.
Topics: Astrocytoma; Cerebellar Neoplasms; Child; Child, Preschool; Fatal Outcome; Female; Humans; Intracranial Hemorrhages; Male
PubMed: 26684764
DOI: 10.3171/2015.10.PEDS1580 -
Cancer Genetics Sep 2014Pediatric brain tumors such as atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive and predominantly occur in young children. A characteristic feature of...
Pediatric brain tumors such as atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive and predominantly occur in young children. A characteristic feature of ATRT is aberrations of the SMARCB1 (hSNF5/INI1) gene. Developmental gene defects may play an important role in the biology of pediatric brain tumors. HOX genes are transcription factors that play a pivotal role in anterior-posterior body axis patterning and are misexpressed in tumors such as lung carcinoma, neuroblastoma, and glioma. HOX genes are also known to be associated with long noncoding RNAs (lncRNAs) such as HOTAIR, which induces transcriptional silencing of the HOXD locus by recruiting polycomb repressive complex 2 to the HOXD locus. In this study, transcriptome analysis using the nanoString platform was performed, and expression of the HOX and HOTAIR genes was studied in pediatric tumors: 20 ATRTs, 10 ependymomas, 10 medulloblastomas, six glioblastoma multiforme, and nine juvenile pilocytic astrocytomas (JPAs). Results indicate that in ATRTs, medulloblastomas, and JPAs, the HOTAIR and HOXC genes are highly expressed; however, HOXD8-10 genes are not silenced. In ependymomas, there is low expression of the HOXC, HOTAIR, and HOXD8-10 genes. These interesting results need to be elucidated further so that the functions of these genes in pediatric tumors is understood.
Topics: Astrocytoma; Brain Neoplasms; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Ependymoma; Gene Expression Profiling; Genes, Homeobox; Glioblastoma; Homeodomain Proteins; Humans; Medulloblastoma; RNA, Long Noncoding; Rhabdoid Tumor; SMARCB1 Protein; Teratoma; Transcription Factors
PubMed: 25085602
DOI: 10.1016/j.cancergen.2014.05.014 -
Neuropathology : Official Journal of... Dec 2020Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF...
Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAF mutation, the first case reported in a glioma. BRAF is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.
Topics: Adolescent; Brain Neoplasms; Epilepsy, Temporal Lobe; Glioma; Histones; Humans; Isocitrate Dehydrogenase; Male; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 32996219
DOI: 10.1111/neup.12693 -
Indian Journal of Pediatrics Jul 2016
Topics: Astrocytoma; Brain Neoplasms; Hallucinations; Humans; Magnetic Resonance Imaging
PubMed: 26548431
DOI: 10.1007/s12098-015-1935-8 -
Klinische Monatsblatter Fur... Mar 2018Neurofibromatosis type 2 (NF2) is a genetic condition with an autosomal dominant pattern of inheritance and incomplete penetrance. It is characterized by multiple benign... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neurofibromatosis type 2 (NF2) is a genetic condition with an autosomal dominant pattern of inheritance and incomplete penetrance. It is characterized by multiple benign tumors of the central and peripheral nervous system including astrocytomas, ependymomas, meningeomas, and schwannomas, among which bilateral vestibular schwannomas are the most frequent. Among ocular manifestations of NF2, juvenile subcapsular cataract is the most common followed by epiretinal membranes and combined hamartomas of the retina and retinal pigment epithelium.
MATERIALS AND METHODS
Multimodal imaging was performed in a female patient and her data were compared to an overview of published cases with retinal hamartoma in NF2.
RESULTS
We report on a case of a 14-year-old girl with genetically confirmed NF2 who presented with bilateral, asymptomatic hyperplasia of glia cells within the ganglion cell and the nerve fibre layer by spectral domain optical coherence tomography (SD-OCT). A metaanalysis of 25 published cases revealed combined hamartomas of the retina and retinal pigment epithelium (CHRRPE) as the most common (16 cases) retinal tumors followed by retinal astrocytic hamartomas (RAH, 7 cases). Retinal hamartomas were most often reported bilaterally and observed prior to the clinical diagnosis of NF2 in 11 of 25 cases. No correlation to sex was observed. Reduced visual acuity, cataracts and epiretinal membranes were the leading ocular manifestations.
CONCLUSION
There is a large spectrum of ocular-specific findings in NF2. These are seminal, especially at an early age, enabling an early diagnosis and timely therapy of further tumor manifestations. Retinal astrocytic hamartomas may be very discreet and easily missed on routine examination. Fundus infrared imaging is a useful tool allowing to detect even discreet changes rarely seen by ophthalmoscopy in young children. This allows for a more extensive evaluation by SD-OCT.
Topics: Adolescent; Angiography; Astrocytes; DNA Mutational Analysis; Diagnosis, Differential; Diagnostic Techniques, Ophthalmological; Female; Fluorescein Angiography; Fundus Oculi; Hamartoma; Humans; Meningeal Neoplasms; Meningioma; Neurofibromatosis 2; Neurofibromin 2; Retinal Diseases; Tomography, Optical Coherence
PubMed: 29534265
DOI: 10.1055/a-0583-0291 -
World Neurosurgery Nov 2014The aim of this study was to determine the utility of an intraoperative magnetic resonance imaging (i-MRI) system (Polestar N-10, 20, 30) in achieving maximal resection...
Intraoperative magnetic resonance imaging for resection of intra-axial brain lesions: a decade of experience using low-field magnetic resonance imaging, Polestar N-10, 20, 30 systems.
OBJECTIVE
The aim of this study was to determine the utility of an intraoperative magnetic resonance imaging (i-MRI) system (Polestar N-10, 20, 30) in achieving maximal resection of intra-axial brain lesions.
METHODS
The subjects comprised 163 patients with intra-axial brain lesions who underwent resection at Sheba Medical Center using the Polestar from February 2000 through February 2012. Demographic and imaging data were obtained and analyzed retrospectively. The patients included 83 men (50.9%) and had a mean age of 43 years. High-grade gliomas were diagnosed in 72 patients, low-grade gliomas in 35, metastases in 22, and various pathologies (e.g., cavernous angiomas, juvenile pilocytic astrocytoma, pleomorphic xanthoastrocytoma, etc.) were diagnosed in 34. The majority of the lesions (84, 51.5%) were located in or near eloquent areas. Fifty-one patients had nonenhancing lesions.
RESULTS
We intended to achieve complete resection in 110 of 163 cases, based on preoperative imaging. Complete resection was achieved in 90 of these 110 (81.8%) cases. Intraoperative MRI led to additional resection in 42.3% of the total cases and to complete resection in 43.3% of all the cases in which a complete resection was achieved. In 76.8% of these cases, 2 intraoperative scans were sufficient to achieve complete resection. Sex, age, intent of resection, recurrence, affected side, and radiologic characteristics did not differ significantly between cases in which intraoperative MRI led to further resection and cases in which it did not. Nonenhancing lesions of all types were 3 times more likely to require additional resection after obtaining intraoperative MRIs (P = .02).
CONCLUSIONS
The Polestar (N-10, 20, 30) proved useful for evaluating residual intra-axial brain lesions and achieving the maximal extent of resection in 42.3% of the total cases and in 43.3% of cases in which complete resection was achieved. Intraoperative MRI led to extended resection in 46.9% of patients for whom the initial intent was to perform an incomplete resection. Nonenhancement was the only independent variable predicting the usefulness of intraoperative MRI for additional lesion resection.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Female; Glioma; Hemangioma, Cavernous, Central Nervous System; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Monitoring, Intraoperative; Neoplasm Grading; Neurosurgical Procedures; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 24518885
DOI: 10.1016/j.wneu.2014.02.004