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Cureus Sep 2023The most common causes of vision loss in neurofibromatosis 1 (NF1) patients are sequelae from tumors such as optic pathway glioma, plexiform neurofibroma, or secondary...
The most common causes of vision loss in neurofibromatosis 1 (NF1) patients are sequelae from tumors such as optic pathway glioma, plexiform neurofibroma, or secondary glaucoma. Here we report the case of a six-year-old female with anisometropic amblyopia resulting from an isolated unilateral macro-ophthalmia with a known history of NF1. Our patient progressed to light perception vision in the left eye due to a non-neoplastic cause associated with NF1 with at least two years of documented unilateral macro-ophthalmia without any ophthalmology referral or evaluation. This case aims to highlight the importance of early and deliberate ophthalmologic examination in all patients with neurofibromatosis 1 to assess for appropriate visual development and early intervention.
PubMed: 37809258
DOI: 10.7759/cureus.44679 -
Pediatric Neurology Dec 2023Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are...
BACKGROUND
Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are pigmentary abnormalities such as café-au-lait spots and inguinal or axillary freckling, cutaneous and plexiform neurofibromas, hamartomas of the iris, optic gliomas, and bone lesions. The aim of this retrospective study was to define the clinical and molecular characteristics of a pediatric sample of NF1, as well as the mutational spectrum and genotype-phenotype correlation.
METHODS
The study included 40 children with clinically suspected NF1. The patients were screened for NF1 mutations by DNA-based sequencing. In addition, all the patients were studied by multiplex ligation-dependent probe amplification (MLPA) to identify any duplications or deletions in NF1. The demographic, clinical, and genetic features of the children were characterized.
RESULTS
A total of 40 children with NF1 were included. Of those, 28 were female and 12 were male. The mean age was 8.91 years. An NF1 variant was discovered in 28 of 40 patients (70%). Among these mutations, intronic mutations were the most frequently detected mutations; 15 of these variants had not been previously reported. Only one patient had a whole NF1 gene deletion.
CONCLUSIONS
This study expands the spectrum of mutations in the NF1 gene. This study also showed that genetic screening using both next-generation sequencing and MLPA had a positive effect on diagnosis and genetic counseling in patients with suspected NF1.
Topics: Child; Female; Humans; Male; Hamartoma; Neurofibroma, Plexiform; Neurofibromatosis 1; Optic Nerve Glioma; Retrospective Studies
PubMed: 37806041
DOI: 10.1016/j.pediatrneurol.2023.08.036 -
Journal of Neuro-oncology Sep 2023There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type...
The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.
PURPOSE
There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG).
METHODS
To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort.
RESULTS
Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size.
CONCLUSION
Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.
Topics: Humans; Child; Neurofibromatosis 1; Retrospective Studies; Gadolinium; Contrast Media; Follow-Up Studies; Optic Nerve Glioma; Disease Progression
PubMed: 37803102
DOI: 10.1007/s11060-023-04468-3 -
Pediatric Blood & Cancer Dec 2023In optic pathway glioma (OPG), bevacizumab-based therapy (BBT) has promising effects on radiographic tumor burden, but the impact on vision is less clear. This...
In optic pathway glioma (OPG), bevacizumab-based therapy (BBT) has promising effects on radiographic tumor burden, but the impact on vision is less clear. This single-institution study characterized visual acuity (VA) and visual field (VF) outcomes in 17 pediatric OPG patients treated with BBT. VA was stable or improved in 14 patients. Nine patients had evaluable VF data, six of whom experienced stability or improvement. Among six patients with vision deterioration as a treatment indication, stable or improved was observed for both VA and VF in five patients. In summary, BBT was associated with favorable visual outcomes in this cohort of patients with OPG.
PubMed: 37707323
DOI: 10.1002/pbc.30668 -
Journal of Pediatric Hematology/oncology Nov 2023Optic pathway gliomas (OPGs) are the most common pediatric optic nerve tumors. Their behavior ranges between rapid growth, stability, or spontaneous regression. Τhey...
Optic pathway gliomas (OPGs) are the most common pediatric optic nerve tumors. Their behavior ranges between rapid growth, stability, or spontaneous regression. Τhey are characterized by low mortality albeit with significant morbidity. We present the characteristics, management, and outcome of 23 OPG patients (16 females, median age: 4.8 y) managed in a Pediatric Oncology Department in Northern Greece over a 25-year period. Overall, 57% had a background of neurofibromatosis type 1. Diagnosis was based on imaging (10 patients) or biopsy (13 patients). Presenting symptoms were mostly visual impairment/squint (52%). Proptosis/exophthalmos, raised intracranial pressure, and headache were also noted. In 2 occasions, it was detected with surveillance magnetic resonance imaging in the context of neurofibromatosis type 1. Eight patients had unilateral and 2 bilateral optic nerve tumors (Modified Dodge Classification, stage 1a/1b), 3 had chiasmatic (stage 2a/b), and 10 had multiple tumors (stage 3/4). Predominant histology was pilocytic astrocytoma (77%). Management included: observation (4), chemotherapy only (9), surgery only (3), or various combinations (7). Chemotherapy regimens included vincristine and carboplatin, vinblastine, or bevacizumab with irinotecan. Most patients demonstrated a slow disease course with complete response/partial response to chemotherapy and/or surgery, whereas 39% presented ≥1 recurrences. After a median follow-up of 8.5 years (range to 19 y), 20 patients (87%) are still alive with stable disease, in partial/complete remission, or on treatment.
Topics: Female; Child; Humans; Child, Preschool; Neurofibromatosis 1; Greece; Optic Nerve Glioma; Optic Nerve Neoplasms; Astrocytoma; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 37696004
DOI: 10.1097/MPH.0000000000002753 -
Ophthalmic Genetics Apr 2024Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily affects the skin and peripheral nervous system and is caused by chromosomal abnormalities and...
BACKGROUND
Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily affects the skin and peripheral nervous system and is caused by chromosomal abnormalities and mostly truncating variants in the gene. Ocular complications such as Lisch nodules and optic pathway gliomas (OPGs) can occur in NF1 patients. Herein, we report a novel variant in an NF1 patient with bilateral optic atrophy.
METHODS
Ophthalmological examinations and genetic analyses were performed using targeted next-generation sequencing (NGS).
RESULTS
A 14-year-old girl diagnosed with NF1 visited our hospital with decreased visual acuity (VA). The patient had no family history of NF1 or visual impairment. Brain and orbital magnetic resonance imaging revealed no remarkable findings. Ophthalmoscopy revealed temporal pallor of the optic discs, which was confirmed by optical coherence tomography findings of significant thinning of the circumpapillary retinal nerve fiber layer in both eyes. At 23 years of age, the decimal-corrected VA had deteriorated to 0.2 in the right eye and 0.1 in the left eye. Additionally, the targeted NGS panel revealed a novel heterozygous stop-gain variant (p.Tyr628Ter) in the gene; however, no pathogenic variants in or the mitochondrial DNA were identified.
CONCLUSIONS
A patient with NF1 without OPGs developed bilateral optic atrophy and carried a novel stop-gain variant of . Although the relationship between variants and bilateral optic atrophy remains unclear, further investigations are required.
Topics: Female; Humans; Adolescent; Optic Nerve Glioma; Neurofibromatosis 1; Optic Disk; Vision, Low; Optic Atrophy
PubMed: 37599594
DOI: 10.1080/13816810.2023.2245464 -
Geometric evaluations of CT and MRI based deep learning segmentation for brain OARs in radiotherapy.Physics in Medicine and Biology Aug 2023Deep-learning auto-contouring (DL-AC) promises standardisation of organ-at-risk (OAR) contouring, enhancing quality and improving efficiency in radiotherapy. No...
Deep-learning auto-contouring (DL-AC) promises standardisation of organ-at-risk (OAR) contouring, enhancing quality and improving efficiency in radiotherapy. No commercial models exist for OAR contouring based on brain magnetic resonance imaging (MRI). We trained and evaluated computed tomography (CT) and MRI OAR autosegmentation models in RayStation. To ascertain clinical usability, we investigated the geometric impact of contour editing before training on model quality.Retrospective glioma cases were randomly selected for training (= 32, 47) and validation (= 9, 10) for MRI and CT, respectively. Clinical contours were edited using international consensus (gold standard) based on MRI and CT. MRI models were trained (i) using the original clinical contours based on planning CT and rigidly registered T1-weighted gadolinium-enhanced MRI (MRIu), (ii) as (i), further edited based on CT anatomy, to meet international consensus guidelines (MRIeCT), and (iii) as (i), further edited based on MRI anatomy (MRIeMRI). CT models were trained using: (iv) original clinical contours (CTu) and (v) clinical contours edited based on CT anatomy (CTeCT). Auto-contours were geometrically compared to gold standard validation contours (CTeCT or MRIeMRI) using Dice Similarity Coefficient, sensitivity, and mean distance to agreement. Models' performances were compared using paired Student's t-testing.The edited autosegmentation models successfully generated more segmentations than the unedited models. Paired t-testing showed editing pituitary, orbits, optic nerves, lenses, and optic chiasm on MRI before training significantly improved at least one geometry metric. MRI-based DL-AC performed worse than CT-based in delineating the lacrimal gland, whereas the CT-based performed worse in delineating the optic chiasm. No significant differences were found between the CTeCT and CTu except for optic chiasm.T1w-MRI DL-AC could segment all brain OARs except the lacrimal glands, which cannot be easily visualized on T1w-MRI. Editing contours on MRI before model training improved geometric performance. MRI DL-AC in RT may improve consistency, quality and efficiency but requires careful editing of training contours.
Topics: Humans; Deep Learning; Head and Neck Neoplasms; Retrospective Studies; Radiotherapy Planning, Computer-Assisted; Organs at Risk; Brain; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Image Processing, Computer-Assisted
PubMed: 37579753
DOI: 10.1088/1361-6560/acf023 -
Cancers Aug 2023Brain tumour surgery in visual eloquent areas poses significant challenges to neurosurgeons and has reported inconsistent results. This is a single-centre prospective...
Brain tumour surgery in visual eloquent areas poses significant challenges to neurosurgeons and has reported inconsistent results. This is a single-centre prospective cohort study of patients admitted for asleep surgery of intra-axial lesions in visual eloquent areas. Demographic and clinical information, data from tractography and visual evoked potentials (VEPs) monitoring were recorded and correlated with visual outcomes. Thirty-nine patients were included (20 females, 19 males; mean age 52.51 ± 14.08 years). Diffuse intrinsic glioma was noted in 61.54% of patients. There was even distribution between the temporal, occipital and parietal lobes, while 55.26% were right hemispheric lesions. Postoperatively, 74.4% remained stable in terms of visual function, 23.1% deteriorated and 2.6% improved. The tumour infiltration of the optic radiation on tractography was significantly related to the visual field deficit after surgery ( = 0.016). Higher N75 ( = 0.036) and P100 ( = 0.023) amplitudes at closure on direct cortical VEP recordings were associated with no new postoperative visual deficit. A threshold of 40% deterioration of the N75 ( = 0.035) and P100 ( = 0.020) amplitudes correlated with a risk of visual field deterioration. To conclude, direct cortical VEP recordings demonstrated a strong correlation with visual outcomes, contrary to transcranial recordings. Invasion of the optic radiation is related to worse visual field outcomes.
PubMed: 37568762
DOI: 10.3390/cancers15153943 -
The Canadian Veterinary Journal = La... Aug 2023A 4-year-old mixed-breed dog was presented for hyphema and glaucoma of the right eye. Enucleation of the right globe was carried out, and histopathology examination...
A 4-year-old mixed-breed dog was presented for hyphema and glaucoma of the right eye. Enucleation of the right globe was carried out, and histopathology examination revealed an optic nerve glioma with incomplete surgical margins. At 8 wk after surgery, the dog had depressed mentation and a diminished pupillary light reflex of the left eye. Magnetic resonance imaging revealed an irregular, heterogeneously T2 hyperintense/T1 isointense mass in the region of the optic chiasm. Compression of the rostral thalamus was present, with effacement of the pituitary gland and involvement of the right orbit. The dog was euthanized 4.5 mo after initial presentation. An undefined glioma of the right optic nerve with extension to the diencephalon was diagnosed on necropsy. Key clinical message: Although rare, intraocular glioma is a differential diagnosis for hyphema, glaucoma, and retinal detachment. Magnetic resonance imaging should be considered in cases of intraocular neoplasia, notably in those with incomplete surgical margins of the optic nerve.
Topics: Animals; Dogs; Optic Nerve Glioma; Hyphema; Margins of Excision; Optic Nerve; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Glaucoma; Dog Diseases
PubMed: 37529389
DOI: No ID Found -
Frontiers in Oncology 2023Optic pathway gliomas (OPGs) are associated with significant risk of visual and endocrine morbidity, but data on long-term outcomes in symptomatic patients is sparse....
INTRODUCTION
Optic pathway gliomas (OPGs) are associated with significant risk of visual and endocrine morbidity, but data on long-term outcomes in symptomatic patients is sparse. This study reviews the clinical course, disease progression, survival outcomes and long-term sequelae in pediatric patients with symptomatic OPGs in our institution over three decades.
METHODS
Retrospective review of patients with symptomatic OPG treated in a single tertiary pediatric oncology center from 1984 to 2016.
RESULTS
A total of 37 patients were diagnosed with symptomatic OPG. Decreased visual acuity was the commonest presenting symptom (75.7%). Surgical intervention was performed in 62.2%; 56.5% underwent biopsy, 26.1% surgical debulking and 17.4% had orbital decompression with cystic fenestration and cosmetic optic nerve excision at different treatment intervals. CSF diversion was performed in 47.8% patients. Histopathologic examination confirmed 86% to be pilocytic astrocytoma and 1 ganglioglioma. 46% received chemotherapy and 48% had radiotherapy, at different intervals. Median follow-up was 13.74 years. In NF1 patients, overall survival (OS) was 100% at 5 years and 55.6 ± 24.8% at 25 years while progression-free-survival (PFS) was 50 ± 15.8% at 5 and 20 years. In non-NF1 patients, OS was 96.2 ± 3.8% at 5 years and 87.4 ± 9% at 25-years. 5-year PFS was 53.8 ± 9.8% and 25-year PFS was 49.0 ± 10%. Cumulative PFS was 53 ± 8.3% at 5 years and 49.7 ± 8.4% at 20 years while cumulative OS was 97.2 ± 2.7% at 5 years and 77.5 ± 10.8% at 25 years. 59.5% patients developed post-operative endocrinopathy. Long-term vision was normal in 8.1%, improved in 13.5%, stabilized in 40.5% but worsened in 37.8% patients. Three patients treated with radiotherapy developed second brain tumors.
CONCLUSION
25-year OS in this cohort was 77.5% but survivorship carried significant long-term morbidities including radiation-induced second malignant brain tumors.
PubMed: 37519788
DOI: 10.3389/fonc.2023.1157909