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BMC Endocrine Disorders Dec 2015Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with an extremely variable phenotype. In childhood NF1 can be associated with optic glioma... (Review)
Review
BACKGROUND
Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with an extremely variable phenotype. In childhood NF1 can be associated with optic glioma and central precocious puberty; the latter is more common when the optic chiasm is affected. The mutational spectrum of the NF1 gene is wide and complex; R681X is a rare severe mutation of the NF1 gene known to cause truncation of neurofibromin, with only ten reported cases in the literature so far.
CASE PRESENTATION
We describe a girl with NF1 associated with early central precocious puberty appearing at 2.5 years of age and optic glioma affecting the optic chiasm as seen on magnetic resonance imaging (MRI). Genetic analysis confirmed the presence of R681X. Therapy with a gonadotropin-releasing hormone agonist was instituted with good response to therapy. The lesions on MRI were stable and no significant vision impairment was present during the 6 years of follow-up.
CONCLUSION
Of the ten reported cases of NF1 due to R681X, one has presented with optic glioma and none with precocious puberty. Thus, to our knowledge, this is the first reported case of this mutation presenting with precocious puberty. We believe that this is a contribution to the few reports on the phenotype of this mutation and to the future elucidation of genotype-phenotype correlations of this disease.
Topics: Arginine; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Magnetic Resonance Imaging; Mutation; Neurofibromatosis 1; Neurofibromin 1; Optic Nerve Glioma; Puberty, Precocious; Treatment Outcome; Triptorelin Pamoate
PubMed: 26666878
DOI: 10.1186/s12902-015-0076-4 -
Brain Pathology (Zurich, Switzerland) Apr 1997Neurofibromatosis (NF) 1 and 2 are multisystem disorders associated with a variety of neoplastic and non-neoplastic manifestations that typically progress in severity... (Review)
Review
Neurofibromatosis (NF) 1 and 2 are multisystem disorders associated with a variety of neoplastic and non-neoplastic manifestations that typically progress in severity during the lifetime of the affected patient. The importance of appropriately diagnosing these disorders stems from the fact that the natural history of an associated neoplasm, such as a peripheral nerve tumor or an optic glioma, may be significantly different depending on whether or not the lesion arises in a person with NF. In addition, the indications for therapeutic intervention, hierarchy of treatment options and long-term management goals may differ substantially for patients with NF-related versus sporadic tumors. Finally, recognition of the diagnosis comprises an essential step for providing appropriate multidisciplinary evaluation and counseling to affected patients and their families. This article addresses the principal manifestations of these disorders and provides a contemporary review of the diagnostic and therapeutic issues that arise in children with NF1 and NF2.
Topics: Humans; Magnetic Resonance Imaging; Nervous System Diseases; Neurofibromatosis 1; Neurofibromatosis 2
PubMed: 9161732
DOI: 10.1111/j.1750-3639.1997.tb01067.x -
Neuro-oncology Advances 2020Optic pathway gliomas (OPGs) are low-grade tumors of the white matter of the visual system with a highly variable clinical course. The aim of the study was to generate a...
BACKGROUND
Optic pathway gliomas (OPGs) are low-grade tumors of the white matter of the visual system with a highly variable clinical course. The aim of the study was to generate a magnetic resonance imaging (MRI)-based predictive model of OPG tumor progression using advanced image analysis and machine learning techniques.
METHODS
We performed a retrospective case-control study of OPG patients managed between 2009 and 2015 at an academic children's hospital. Progression was defined as radiographic tumor growth or vision decline. To generate the model, optic nerves were manually highlighted and optic radiations (ORs) were segmented using diffusion tractography tools. For each patient, intensity distributions were obtained from within the segmented regions on all imaging sequences, including derivatives of diffusion tensor imaging (DTI). A machine learning algorithm determined the combination of features most predictive of progression.
RESULTS
Nineteen OPG patients with progression were matched to 19 OPG patients without progression. The mean time between most recent follow-up and most recently analyzed MRI was 3.5 ± 1.7 years. Eighty-three MRI studies and 532 extracted features were included. The predictive model achieved an accuracy of 86%, sensitivity of 89%, and specificity of 81%. Fractional anisotropy of the ORs was among the most predictive features (area under the curve 0.83, < 0.05).
CONCLUSIONS
Our findings show that image analysis and machine learning can be applied to OPGs to generate a MRI-based predictive model with high accuracy. As OPGs grow along the visual pathway, the most predictive features relate to white matter changes as detected by DTI, especially within ORs.
PubMed: 32885166
DOI: 10.1093/noajnl/vdaa090 -
Frontiers in Surgery 2022Clinical and diagnostic evaluation in the follow-up of optic glioma patients with neurofibromatosis type 1 (NF-1) can be difficult. Determining whether and when to... (Review)
Review
PURPOSE
Clinical and diagnostic evaluation in the follow-up of optic glioma patients with neurofibromatosis type 1 (NF-1) can be difficult. Determining whether and when to provide treatment is a significant challenge in best managing these patients. Update on current information and future directions in management is included in this review.
CURRENT PRACTICE
NF-associated optic pathway gliomas (OPGs) present a significant management challenge with high stakes for visual outcomes. Monitoring vision and diagnostic tests are challenging in patients of a younger age. Regardless of whether few or many optic gliomas are encountered during clinical practice.
SUMMARY
This review of optic gliomas-NF1-associated gliomas includes the current approach and knowledge of OPG-NF1 and future directions in OPG-NF1 management. This includes the ongoing Multicenter Natural History Study and other clinical trials and outcomes in NF-1 patients with OPG.
PubMed: 36117804
DOI: 10.3389/fsurg.2022.908573 -
Neurologia Jun 2022Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological... (Review)
Review
INTRODUCTION
Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations.
METHODS
We reviewed medical histories of patients with NF1 followed up at our hospital's paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms.
RESULTS
A total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%).
CONCLUSIONS
The neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Epilepsy; Female; Headache; Humans; Infant; Magnetic Resonance Imaging; Male; Neurofibromatosis 1
PubMed: 35672119
DOI: 10.1016/j.nrleng.2019.05.008 -
Radiology Case Reports Feb 2019Malignant optic glioma presents a clinical and diagnostic challenge, as early imaging findings overlap with other more common causes of optic nerve enhancement and...
Malignant optic glioma presents a clinical and diagnostic challenge, as early imaging findings overlap with other more common causes of optic nerve enhancement and enlargement, potentially leading to delay in diagnosis. This rare diagnosis carries an extremely poor prognosis, with death usually occurring within 1 year. We present a case of malignant optic glioma that was initially diagnosed as optic neuritis and central retinal vein occlusion, and we emphasize the importance of serial imaging and definitive biopsy to promote early diagnosis and treatment of this entity.
PubMed: 30450148
DOI: 10.1016/j.radcr.2018.10.023 -
Frontiers in Surgery 2022Neurofibromatosis type 1 (NF1) has an incidence of 1 in 2,000 to 3,000 individuals and in 15% is associated with optic pathway glioma (OPG). Given the variability in...
Optic Pathway Glioma in Children with Neurofibromatosis Type 1: A Multidisciplinary Entity, Posing Dilemmas in Diagnosis and Management Multidisciplinary Management of Optic Pathway Glioma in Children with Neurofibromatosis Type 1.
INTRODUCTION
Neurofibromatosis type 1 (NF1) has an incidence of 1 in 2,000 to 3,000 individuals and in 15% is associated with optic pathway glioma (OPG). Given the variability in clinical presentation and related morbidity, a multidisciplinary approach for diagnosis and management of children with NF1 and OPG is required, but often lacks coordination and regular information exchange. Herein we summarize our experience and describe the care pathways/network provided by a multidisciplinary team. The role of the distinct team members is elucidated as well as the care amendments made over time.
METHODS
We performed a retrospective single-center observational study, including children treated at our institution between 1990 and 2021. Inclusion criteria were clinical diagnosis of NF1, radiographic and/or histopathological diagnosis of OPG and age below 18 years. Patients being treated elsewhere were excluded from the study. Data was abstracted from each child's health record using a standardized data collection form. Characteristics of children with NF1 and OPG were described using means (SD) and percentages. Outcomes were determined using Kaplan-Meier estimates.
RESULTS
From 1990 to 2021, 1,337 children were followed in our institution. Of those, 195 were diagnosed with OPG (14.6%), including 94 (48.21%) females and 101 (51.79%) males. Comprehensive data were available in 150 patients. The mean (SD) age at diagnosis was 5.31(4.08) years (range: 0.8-17.04 years). Sixty-two (41.3%) patients remained stable and did not undergo treatment, whereas 88 (58.7%) patients required at least one treatment. The mean (SD) duration of follow up was 8.14 (5.46) years (range: 0.1-25.9 years; median 6.8 years). Overall survival was of 23.6 years (±1.08), comprising 5 deaths. A dedicated NF clinic, including pediatricians and a nurse, provides regular follow up and plays a central role in the management of children with NF1, identifying those at risk of OPG, coordinating referrals to Neuroradiology and other specialists as indicated. All children are assessed annually by Ophthalmology. Comprehensive care was provided by a multidisciplinary team consisting of Dermatology, Genetics, Neuro-oncology, Neuroradiology, Neurosurgery, Ophthalmology and Pediatrics.
CONCLUSIONS
The care of children with NF1 and OPG is optimized with a multidisciplinary team approach, coordinated by a central specialty clinic.
PubMed: 35592129
DOI: 10.3389/fsurg.2022.886697 -
Journal of Child Neurology Nov 2009Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by... (Review)
Review
Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by supratentorial diffuse fibrillary astrocytomas. Recent research has implicated activation of the RAS/RAF/MEK pathway in tumorigenesis of these tumors. Surgery is the mainstay of therapy. Overall survival rates for patients whose tumors are completely resected are 90% or greater, 10 years from diagnosis. Conversely, most optic pathway/hypothalamic, deep midline, and brain stem gliomas have minimal potential for resection; these tumors can be difficult to treat and deserve special attention. Combination chemotherapy is currently recommended as front-line adjuvant treatment for progressive or recurrent tumors. Second-line radiotherapy can also improve overall survival but is associated with more frequent and significant neurocognitive, endocrine, and other long-term toxicities.
Topics: Brain Neoplasms; Child; Glioma; Humans; Models, Neurological; Neoplasm Staging
PubMed: 19841428
DOI: 10.1177/0883073809342005 -
Cancers Dec 2022Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning...
BACKGROUNDS
Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking.
METHODS
We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009-2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated.
RESULTS
In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%).
CONCLUSION
Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ.
PubMed: 36551572
DOI: 10.3390/cancers14246087 -
American Journal of Ophthalmology Case... Mar 2020To present a case of glioblastoma multiforme which initially presented with only ophthalmic manifestations.
PURPOSE
To present a case of glioblastoma multiforme which initially presented with only ophthalmic manifestations.
OBSERVATIONS
A 48-year-old man presented with decreased vision and pain with eye movements of the right eye. MRI of the brain showed increased T2/FLAIR signal involving the right optic nerve with no other identified abnormalities. He was treated with intravenous steroids for presumed optic neuritis. His visual acuity then rapidly worsened to no light perception, with new orbital apex symptoms including central retinal artery and vein occlusions and inferior division third and fourth nerve palsies. Repeat MRI with contrast showed perineural enhancement surrounding the right optic nerve and markedly reduced diffusion along its entire course. After an unrevealing initial workup and then a 7 month period during which the patient refused follow up, he re-presented with left sided weakness, headache, and confusion. Repeat brain MRI revealed a large mass involving the right optic nerve, optic chiasm, basal ganglia, corpus callosum and brainstem. Biopsy led to a diagnosis of WHO grade IV glioblastoma multiforme. The disease was poorly responsive to temozolomide, bevacizumab and external beam radiation, and the patient passed away 5 months later.
CONCLUSIONS AND IMPORTANCE
Malignant optic glioma of adulthood is a challenging diagnosis with a poor prognosis. This rare case highlights the importance of maintaining neoplasm in the differential for optic neuritis masqueraders.
PubMed: 32395666
DOI: 10.1016/j.ajoc.2020.100594