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JCO Global Oncology Feb 2024Delayed diagnosis and poor awareness are significant barriers to the early intervention of pediatric brain tumors. This multicenter observational study aimed to evaluate... (Observational Study)
Observational Study
PURPOSE
Delayed diagnosis and poor awareness are significant barriers to the early intervention of pediatric brain tumors. This multicenter observational study aimed to evaluate the baseline routes and time to diagnosis for pediatric brain tumors in Tamil Nadu (TN), with the goal of promoting early diagnosis and timely referrals in the future.
METHODS
A standard proforma was used to retrospectively collect information on demographics, diagnosis, referral pathways, and symptoms of incident pediatric brain tumor cases between January 2018 and October 2020 across eight tertiary hospitals in TN. Dates of symptom onset, first presentation of health care, and diagnosis were used to calculate total diagnostic interval (TDI), patient interval (PI), and diagnostic interval (DI).
RESULTS
A total of 144 cases (mean age, 6.64 years; range, 0-15.1 years) were included in the analysis. Among those, 94% (135/144) were from city/district areas, 40% (55/144) were self-referred, and 90% (129/144) had one to three health care professional visits before diagnosis. Median TDI, PI, and DI were 3.5 (IQR, 1-9.3), 0.6 (IQR, 0.1-4.6), and 0.6 (IQR, 0-3.3) weeks, respectively. Low-grade gliomas had the longest median TDI (6.6 weeks), followed by medulloblastomas (4.6 weeks) and high-grade gliomas (3.3 weeks). Average number of symptoms recorded was 1.7 at symptom onset and 1.9 at diagnosis.
CONCLUSION
Although there are some similarities with data from the United Kingdom, many low-grade and optic pathway tumors were unaccounted for in our study. DIs were relatively short, which suggests that infrastructure may not be a problem in this cohort. Increased training and establishment of proper cancer registries, combined with proper referral pathways, could enhance early diagnosis for these children.
Topics: Child; Humans; Brain Neoplasms; Glioma; India; Referral and Consultation; Retrospective Studies; Infant, Newborn; Infant; Child, Preschool; Adolescent
PubMed: 38386953
DOI: 10.1200/GO.23.00214 -
Cureus Jan 2024Optic pathway gliomas (OPGs) are rare pediatric tumors that pose significant challenges in management due to their location and clinical manifestations. Traditional...
Optic pathway gliomas (OPGs) are rare pediatric tumors that pose significant challenges in management due to their location and clinical manifestations. Traditional transcranial approaches have been the mainstay for surgical intervention, but recent advancements in endoscopic endonasal transsphenoidal surgery offer a less invasive alternative. Here, we present a case of a 10-year-old female child with neurofibromatosis type-1 and an aggressive OPG who underwent endoscopic endonasal transsphenoidal debulking surgery. The pre-operative evaluation confirmed complete vision loss, and imaging revealed tumor progression. The surgery was successful, resulting in a subtotal resection and a diagnosis of pilocytic astrocytoma, WHO grade 1. Post-operative assessments showed no complications. This case highlights the feasibility of the endoscopic endonasal transsphenoidal approach for OPGs and emphasizes the importance of careful patient selection and multidisciplinary collaboration in achieving successful outcomes for these challenging tumors.
PubMed: 38380221
DOI: 10.7759/cureus.52649 -
Journal of AAPOS : the Official... Apr 2024Myelinated retinal nerve fiber layer (RNFL) is a rare structural anomaly that occurs from abnormal myelination extending anterior to the lamina cribrosa. Clinically,...
Myelinated retinal nerve fiber layer (RNFL) is a rare structural anomaly that occurs from abnormal myelination extending anterior to the lamina cribrosa. Clinically, myelinated RNFL is characterized as a gray-white lesion with feathered, well-demarcated borders obscuring the retinal vasculature. Myelinated RNFL is typically congenital, benign, and asymptomatic. It is most commonly noted as an incidental finding on ophthalmic examination. However, cases of acquired myelinated RNFL have been reported. We report the case of a patient with neurofibromatosis type 1 and optic pathway glioma with unilateral acquired myelinated RNFL.
Topics: Child; Humans; Neurofibromatosis 1; Retinal Ganglion Cells; Nerve Fibers; Tomography, Optical Coherence; Optic Nerve Glioma
PubMed: 38360350
DOI: 10.1016/j.jaapos.2024.103850 -
Neuro-ophthalmology (Aeolus Press) 2024The purpose of this study was to evaluate the ophthalmologic findings in children with neurofibromatosis type 1 (NF1) and compare these findings in eyes with and without...
The purpose of this study was to evaluate the ophthalmologic findings in children with neurofibromatosis type 1 (NF1) and compare these findings in eyes with and without optic pathway gliomas (OPGs). We carried out a retrospective chart review of children with NF1. We recorded demographic characteristics, clinical manifestations of disease, and ophthalmologic findings including visual acuity, intraocular pressure, cup-to-disc ratio, visual field testing, and optical coherence tomography findings. Ophthalmologic findings were examined for the cohort for initial and final appointments. These findings were also compared between eyes with and without OPGs. The study included 119 participants with 238 total eyes. The most common clinical manifestations of NF1 in this cohort were café au lait macules (98%), axillary or inguinal freckling (91%), Lisch nodules (66%), and cutaneous neurofibromas (57%). Thirty-seven participants had imaging that allowed evaluation for choroidal abnormalities, and 28 (76%) had choroidal lesions. Twenty-seven participants (23%) had OPGs, and 44 eyes were affected. On initial assessment, eyes with OPGs had worse visual acuity. On final examination, eyes with OPGs were more likely to have a worse visual acuity and a thinner generalised retinal nerve fibre layer (RNFL) thickness, inferior RNFL thickness, and temporal RNFL thickness. This study provides longitudinal follow-up of children affected by NF1 with and without OPGs. Eyes with OPGs were found to be associated with worse visual acuity and thinner RNFLs overall on final testing.
PubMed: 38357619
DOI: 10.1080/01658107.2023.2276189 -
Frontiers in Oncology 2023Pediatric low-grade gliomas represent the most common childhood brain tumor class. While often curable, some tumors fail to respond and even successful treatments can... (Review)
Review
Pediatric low-grade gliomas represent the most common childhood brain tumor class. While often curable, some tumors fail to respond and even successful treatments can have life-long side effects. Many clinical trials are underway for pediatric low-grade gliomas. However, these trials are expensive and challenging to organize due to the heterogeneity of patients and subtypes. Advances in sequencing technologies are helping to mitigate this by revealing the molecular landscapes of mutations in pediatric low-grade glioma. Functionalizing these mutations in the form of preclinical models is the next step in both understanding the disease mechanisms as well as for testing therapeutics. However, such models are often more difficult to generate due to their less proliferative nature, and the heterogeneity of tumor microenvironments, cell(s)-of-origin, and genetic alterations. In this review, we discuss the molecular and genetic alterations and the various preclinical models generated for the different types of pediatric low-grade gliomas. We examined the different preclinical models for pediatric low-grade gliomas, summarizing the scientific advances made to the field and therapeutic implications. We also discuss the advantages and limitations of the various models. This review highlights the importance of preclinical models for pediatric low-grade gliomas while noting the challenges and future directions of these models to improve therapeutic outcomes of pediatric low-grade gliomas.
PubMed: 38318325
DOI: 10.3389/fonc.2023.1346949 -
Cureus Jan 2024We present a case of an adult patient experiencing progressive visual loss. An initial presentation was concerning for neuromyelitis optica with optic chiasm...
We present a case of an adult patient experiencing progressive visual loss. An initial presentation was concerning for neuromyelitis optica with optic chiasm involvement. However, persistent contrast enhancement observed in follow-up brain and orbit images raised suspicion for optic tract malignant neoplasm. Histopathological evolution of optic nerve biopsy confirmed the diagnosis of an optic chiasm glioma. The patient was then referred to oncology for chemotherapy.
PubMed: 38313959
DOI: 10.7759/cureus.51614 -
Journal Francais D'ophtalmologie Feb 2024
Topics: Child; Humans; Optic Nerve Glioma; Neurofibromatosis 1; Remission, Spontaneous; Magnetic Resonance Imaging
PubMed: 38311491
DOI: 10.1016/j.jfo.2023.104028 -
Acta Neuropathologica Communications Feb 2024Tissue injury and tumorigenesis share many cellular and molecular features, including immune cell (T cells, monocytes) infiltration and inflammatory factor (cytokines,...
Tissue injury and tumorigenesis share many cellular and molecular features, including immune cell (T cells, monocytes) infiltration and inflammatory factor (cytokines, chemokines) elaboration. Their common pathobiology raises the intriguing possibility that brain injury could create a tissue microenvironment permissive for tumor formation. Leveraging several murine models of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome and two experimental methods of brain injury, we demonstrate that both optic nerve crush and diffuse traumatic brain injury induce optic glioma (OPG) formation in mice harboring Nf1-deficient preneoplastic progenitors. We further elucidate the underlying molecular and cellular mechanisms, whereby glutamate released from damaged neurons stimulates IL-1β release by oligodendrocytes to induce microglia expression of Ccl5, a growth factor critical for Nf1-OPG formation. Interruption of this cellular circuit using glutamate receptor, IL-1β or Ccl5 inhibitors abrogates injury-induced glioma progression, thus establishing a causative relationship between injury and tumorigenesis.
Topics: Mice; Animals; Optic Nerve Glioma; Neurofibromatosis 1; Microglia; Brain Injuries; Neurons; Carcinogenesis; Tumor Microenvironment
PubMed: 38308315
DOI: 10.1186/s40478-024-01735-w -
Molecular Biology Reports Jan 2024Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder typified by various combination of numerous Café-au-lait macules, cutaneous and plexiform... (Review)
Review
BACKGROUND
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder typified by various combination of numerous Café-au-lait macules, cutaneous and plexiform neurofibromas, freckling of inguinal or axillary region, optic glioma, Lisch nodules and osseous lesions. Cherubism is a rare genetic syndrome described by progressive swelling of the lower and/or upper jaw due to replacement of bone by fibrous connective tissue. Patients are reported in the literature with NF1 and cherubism-like phenotype due to the NF1 osseous lesions in the jaws. The purpose of this case report is the description of a young male genetically diagnosed with both NF1 and cherubism.
METHODS AND RESULTS
A 9 years and six month old patient with clinical findings of NF1 and cherubism in whom both diseases were genetically confirmed, is presented. The patient was evaluated by a pediatrician, a pediatric endocrinologist, an ophthalmologist, and an oral and maxillofacial surgeon. A laboratory and hormonal screening, a histological examination, a chest X-ray, a magnetic resonance imaging (MRI) of the orbit and a digital panoramic radiography were performed. Genetic testing applying Whole Exome Sequencing was conducted.
CONCLUSIONS
A novel and an already reported pathogenic variants were detected in NF1 and SH3BP2 genes, respectively. This is the first described patient with coexistence of NF1 and cherubism. The contribution of Next Generation Sequencing (NGS) in gene variant identification as well as the importance of close collaboration between laboratory scientists and clinicians, is highlighted. Both are essential for optimizing the diagnostic approach of patients with a complex phenotype.
Topics: Child; Humans; Male; Cafe-au-Lait Spots; Cherubism; Genetic Testing; Neurofibromatosis 1; Phenotype
PubMed: 38281202
DOI: 10.1007/s11033-024-09214-0 -
Journal of Neuro-ophthalmology : the... Mar 2024Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the...
BACKGROUND
Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs).
METHODS
Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations.
RESULTS
Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05).
CONCLUSIONS
CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.
Topics: Child; Humans; Female; Adolescent; Male; Neurofibromatosis 1; Prospective Studies; Cross-Sectional Studies; Longitudinal Studies; Nerve Fibers; Retinal Ganglion Cells; Optic Nerve Glioma; Tomography, Optical Coherence
PubMed: 38252486
DOI: 10.1097/WNO.0000000000002075