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Ophthalmic Plastic and Reconstructive... 2017Two children without neurofibromatosis type 1 presented with unilateral decreased vision and MRI revealing optic nerve tumors. In the first case, chemotherapy was...
Two children without neurofibromatosis type 1 presented with unilateral decreased vision and MRI revealing optic nerve tumors. In the first case, chemotherapy was initiated empirically for presumed optic pathway glioma, but the lesion increased in size with associated clinical worsening, raising concern for a possible alternate diagnosis. Biopsy of the involved optic nerve resulted in worsening of vision due to a branch retinal artery occlusion and showed a grade I pilocytic astrocytoma. In the second case, sudden symptom onset and rapid tumor growth prompted an optic nerve biopsy, resulting in vision loss due to a central retinal artery occlusion and revealing grade I pilocytic astrocytoma. In both cases, tissue diagnosis did not alter the course of management. Instead, biopsy was associated with additional vision loss, highlighting the risk of biopsy in children with isolated optic nerve tumors and imaging that is most consistent with an optic pathway glioma.
Topics: Adolescent; Biopsy; Blindness; Child; Female; Humans; Magnetic Resonance Imaging; Male; Optic Nerve; Optic Nerve Glioma
PubMed: 27046034
DOI: 10.1097/IOP.0000000000000687 -
Journal of Neuroradiology = Journal de... Nov 2022
Topics: Humans; Optic Nerve Glioma; Magnetic Resonance Imaging
PubMed: 35278584
DOI: 10.1016/j.neurad.2022.02.008 -
Journal of Child Neurology May 2018Isolated optic nerve glioma is a rare tumor with no consensus for the best therapeutic approach. Therefore, tumor control and preservation of visual function remain a...
Isolated optic nerve glioma is a rare tumor with no consensus for the best therapeutic approach. Therefore, tumor control and preservation of visual function remain a challenge. In this retrospective study, we describe our experience over 30 years in a single-institutional cohort of children with isolated optic nerve glioma, focusing on treatments and visual outcomes. Seventeen children were followed for a median period of 8 years (range, 2-22 years). Diagnosis was based on typical neuroradiologic findings, and 3 patients had histologic confirmation of their tumors. In our study, conservative management preserved the vision of most patients with neurofibromatosis type 1 (NF1). NF1-related optic nerve gliomas were less often treated but were associated with a lower probability of progression and with occasional spontaneous regression. Sporadic tumors more frequently exhibited aggressive clinical behavior with a higher propensity for posterior extension, often requiring surgical intervention.
Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Neurofibromatoses; Optic Nerve Glioma; Retrospective Studies; Treatment Outcome; Vision Disorders; Young Adult
PubMed: 29502465
DOI: 10.1177/0883073818758737 -
European Review For Medical and... Jun 2023Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder associated with an increased risk of developing a variety of benign and malignant tumors.... (Randomized Controlled Trial)
Randomized Controlled Trial
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder associated with an increased risk of developing a variety of benign and malignant tumors. Fifteen to 20% of children with NF1 are diagnosed with an optic pathway glioma (NF1-OPG) before 7 years of age, and more than half of them experience visual decline. At present, no effective therapy is available for prevention, restoration, or even stabilization of vision loss in subjects affected by NF1-OPG. This paper aims to review the main emerging pharmacological approaches that have been recently assessed in preclinical and clinical settings. We performed a search of the literature using Embase, PubMed, and Scopus databases to identify articles regarding NF1-OPGs and their treatment up to July 1st, 2022. The reference lists of the analyzed articles were also considered a source of literature information. To search and analyze all relevant English articles, the following keywords were used in various combinations: neurofibromatosis type 1, optic pathway glioma, chemotherapy, precision medicine, MEK inhibitors, VEGF, nerve growth factor. Over the past decade, basic research and the development of genetically engineered mice models of NF1-associated OPG have shed light on the cellular and molecular mechanisms underlying the disease and inspired animal and human testing of several compounds. A promising line of research is focusing on the inhibition of mTOR, a protein kinase controlling proliferation, protein synthesis rate and cell motility that is highly expressed in neoplastic cells. Several mTOR blockers have been tested in clinical trials, the most recent of which employed oral everolimus with encouraging results. A different strategy aims at restoring cAMP levels in neoplastic astrocytes and non-neoplastic neurons, since reduced intracellular cAMP levels contribute to OPG growth and, more importantly, are the major determinant of NF1-OPG-associated visual decline. So far, however, this approach has only been attempted in preclinical studies. Stroma-directed molecular therapies - seeking to target Nf1 heterozygous brain microglia and retinal ganglion cells (RGCs) - are another fascinating field. Microglia-inhibiting strategies have not yet reached clinical trials, but preclinical studies conducted over the last 15 years have provided convincing clues of their potential. The importance of NF1-mutant RGCs in the formation and progression of OPGs also holds promise for clinical translation. The evidence of Vascular Endothelial Growth Factor (VEGF)- Vascular Endothelial Growth Factor (VEGFR) signaling hyperactivity in pediatric low-grade gliomas prompted the use of bevacizumab, an anti-VEGF monoclonal antibody, which was tested in children with low-grade gliomas or OPGs with good clinical results. Neuroprotective agents have also been proposed to preserve and restore RGCs and topical eye administration of nerve growth factor (NGF) has demonstrated encouraging electrophysiological and clinical results in a double-blind, placebo-controlled study. Traditional chemotherapy in patients with NF1-OPGs does not significantly ameliorate visual function, and its effectiveness in halting tumor growth cannot be considered a satisfactory result. Newer lines of research should be pursued with the goal of stabilizing or improving the vision, rather than reducing tumor volume. The growing understanding of the unique cellular and molecular characteristics of NF1-OPG, coupled with the recent publication of promising clinical studies, raise hope for a shift towards precision medicine and targeted therapies as a first-line treatment.
Topics: Mice; Animals; Humans; Child; Neurofibromatosis 1; Vascular Endothelial Growth Factor A; Optic Nerve Glioma; TOR Serine-Threonine Kinases; Nerve Growth Factors
PubMed: 37401302
DOI: 10.26355/eurrev_202306_32804 -
Child's Nervous System : ChNS :... Sep 2023Congenital giant orbital tumors in infancy are relatively rare, especially when the tumors are associated with significant intracranial extension. We describe the use of...
Congenital giant orbital tumors in infancy are relatively rare, especially when the tumors are associated with significant intracranial extension. We describe the use of a transorbital neuroendoscopy-assisted resection of such a lesion. While this approach is increasingly gaining popularity for certain anterior and middle skullbase lesions in adults, this report represents the youngest patient reported on where this minimally invasive approach has been successfully used to resect the intracranial tumor. This surgical approach obviated the need for a separate craniotomy, with the additional benefit of minimizing blood loss.
Topics: Adult; Infant, Newborn; Humans; Neuroendoscopy; Craniotomy; Skull Base; Optic Nerve Glioma
PubMed: 37191728
DOI: 10.1007/s00381-023-05986-1 -
Journal of Child Neurology Mar 2014A patient with neurofibromatosis type 1 and the rare finding of concomitant meningioma and optic pathway glioma within the same optic nerve is presented. A 4-year-old...
A patient with neurofibromatosis type 1 and the rare finding of concomitant meningioma and optic pathway glioma within the same optic nerve is presented. A 4-year-old boy was admitted to our hospital with right-sided proptosis. He also had numerous café-au-lait macules and axillary freckling on physical exam. According to National Institutes of Health (NIH) criteria, he met the diagnostic criteria for neurofibromatosis type 1. On magnetic resonance imaging (MRI), a mass originating from the right optic nerve sheath with normal appearance of the optic nerve was observed, which was consistent with optic nerve sheath meningioma. Another mass lesion was observed in the prechiasmatic region of the same optic nerve, which was consistent with optic nerve glioma. Two different types of optic pathway tumors in the same optic nerve is an extraordinary case. It is important to recognize imaging findings of these tumors and make correct diagnosis.
Topics: Cafe-au-Lait Spots; Child, Preschool; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Meningioma; Neoplasms, Multiple Primary; Neurofibromatosis 1; Optic Nerve; Optic Nerve Glioma; Optic Nerve Neoplasms
PubMed: 23420652
DOI: 10.1177/0883073812475157 -
European Journal of Cancer (Oxford,... Aug 2010Overall prognosis for optic pathway glioma (OPG) in children is excellent. Little is known, however, about the effect of chemotherapy on visual outcome of these patients. (Review)
Review
INTRODUCTION
Overall prognosis for optic pathway glioma (OPG) in children is excellent. Little is known, however, about the effect of chemotherapy on visual outcome of these patients.
MATERIAL AND METHODS
A systematic review of the literature was carried out to identify all studies published in PubMed, EMBASE and Cochrane Library between 1990 and 2008 reporting visual outcome in children with OPG after chemotherapy. Studies were included when they included 10 or more children with OPG, main treatment was chemotherapy and visual outcome was described. Cochrane guidelines for meta-analysis of non-randomised clinical trials were followed and levels of quality were assigned.
RESULTS
Eighty-five potentially relevant publications were retrieved for detailed evaluation and only 8 were included. The review revealed 0 randomised controlled trials, 0 non-randomised controlled trials, 3 (37.5%) single-arm trials (1 multi-institutional and 2 single institution trials) and 5 (62.5%) retrospective series. All studies achieved a level of evidence of 4 according to CEBM classification (case-series and poor quality cohort and case-control studies). Only 25 of 174 children experienced improvement in vision after chemotherapy (14.4%), responses ranged from 0% to 45.5%. Vision was stable in 82 children (47.1%, range 27-100%). No study documented the duration of the visual response.
DISCUSSION
Published studies on childhood low grade gliomas have not shown satisfactorily whether chemotherapy improves outcome of vision in children with OPG. Based on our systematic review it appears that treatment with chemotherapy does not improve resulting vision in the majority of children with OPG. The data available does not allow us to assess whether vision is stabilised sufficiently prior to treatment with radiotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Humans; Infant; Optic Nerve Glioma; Treatment Outcome; Vision Disorders; Visual Acuity
PubMed: 20400294
DOI: 10.1016/j.ejca.2010.03.028 -
Journal of Pediatric Ophthalmology and... Jan 2019To evaluate the prevalence of strabismus in neurofibromatosis type 1 (NF-1) by comparing children with normal neuroimaging to those with optic pathway glioma.
PURPOSE
To evaluate the prevalence of strabismus in neurofibromatosis type 1 (NF-1) by comparing children with normal neuroimaging to those with optic pathway glioma.
METHODS
A retrospective data collection of all children with NF-1 with neuroimaging studies examined at a single medical center between 2000 and 2016.
RESULTS
Of the 198 children with NF-1 reviewed, 109 (55%) were male, 121 (61%) had normal neuroimaging, and 77 (39%) had an optic pathway glioma. Mean age at presentation was 6.3 ± 4.7 years and mean follow-up was 4.8 ± 3.1 years. Strabismus was present in 29 (15%) children and was significantly more prevalent in children with NF-1 with optic pathway glioma (21 of 77 [27%]) than in those with normal neuroimaging (8 of 121 [7%], P < .001). Sensory strabismus was only found in children with optic pathway glioma, accounting for most cases (12 of 21 [57%]). A strong association between strabismus and optic pathway glioma is demonstrated by an odds ratio of 5.29 (P < .001). Children with NF-1 with optic pathway glioma have a 4.13 times higher relative risk of developing strabismus than children with NF-1 without it (P = .001). The direction of ocular misalignment in children with NF-1 with optic pathway glioma was not significantly different than that observed in children without optic pathway glioma (P = .197, Fisher's exact test). Only 5 (17%) children with NF-1 with strabismus (3 with optic pathway glioma) underwent corrective surgery to align their eyes.
CONCLUSIONS
Optic pathway glioma in children with NF-1 is associated with an increased risk of strabismus that is often sensory. Although exotropia is the most common ocular misalignment associated with optic pathway glioma, the direction of strabismus cannot be used as an accurate predictor for its presence. [J Pediatr Ophthalmol Strabismus. 2019;56(1):19-22.].
Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Forecasting; Humans; Infant; Israel; Magnetic Resonance Imaging; Male; Neurofibromatosis 1; Optic Nerve Glioma; Optic Nerve Neoplasms; Prevalence; Retrospective Studies; Strabismus
PubMed: 30371910
DOI: 10.3928/01913913-20180925-02 -
Brain Tumor Pathology Jan 2021Optic nerve glioma (ONG) is a rare, typically slow-growing WHO I grade tumor that affects the visual pathways. ONG is most commonly seen in the pediatric population, in...
Optic nerve glioma (ONG) is a rare, typically slow-growing WHO I grade tumor that affects the visual pathways. ONG is most commonly seen in the pediatric population, in association with neurofibromatosis type 1 syndrome. However, sporadic adult cases may also occur and may clinically behave more aggressively, despite benign histopathology. Genetic characterization of these tumors, particularly in the adult population, is lacking. A 39-year-old female presented with 1 month of progressive left-sided visual loss secondary to a enhancing mass along the left optic nerve sheath. Initial empiric management with focal radiotherapy failed to prevent tumor progression, prompting open biopsy which revealed a WHO I pilocytic astrocytoma of the optic nerve. Whole-exome sequencing of the biopsy specimen revealed somatic mutations in NF1,FGFR1 and PTPN11 that may provide actionable targets for molecularly guided therapies. Genetic characterization of ONG is lacking but is needed to guide the management of these rare but complex tumors. The genomic alterations reported in this case contributes to understanding the pathophysiology of adult sporadic ONG and may help guide future clinical prognostication and development of targeted therapies.
Topics: Adult; Astrocytoma; Disease Progression; Female; Humans; Mutation; Neurofibromin 1; Optic Nerve Glioma; Optic Nerve Neoplasms; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Receptor, Fibroblast Growth Factor, Type 1; Exome Sequencing
PubMed: 33098465
DOI: 10.1007/s10014-020-00383-x -
Pediatric Hematology and Oncology 2023Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic...
Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic disorders due to intrinsic nerve aberrations in Crouzon Syndrome have not been described. Optic pathway gliomas (OPGs) are low grade gliomas that are intrinsic to the visual pathway, frequently associated with Neurofibromatosis type 1 (NF-1). OPGs involving both optic nerves without affecting the optic chiasm are rarely seen outside of NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month-old male patient with Crouzon Syndrome without any clinical or genetic findings of NF-1. This case suggests that close ophthalmologic follow up and orbital MRIs may benefit patients with Crouzon Syndrome.
Topics: Humans; Male; Infant; Optic Nerve Glioma; Neurofibromatosis 1; Visual Pathways; Optic Nerve Neoplasms; Craniofacial Dysostosis
PubMed: 37334681
DOI: 10.1080/08880018.2023.2201264