Pediatric optic ner-glioma: A case study

PubMed, 2007

Aim: Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the prevalence and the outcome of OPG in 200 NF1 patients (122 males and 78 females, aged 1-25 years) followed up to 16 years (mean of 6 years). Methods: All children were evaluated by a detailed physical, neurological and ophthalmological examination. Fifteen out of 200 (7.5%) of these patients (7 males, 8 females) were identified with evidence of optic pathway tumours. Results: Nine children had symptoms such as endocranial hypertension, seizures, headache; 4 patients only showed anomalies at ophthalmological examination; 2 patients had no symptoms or signs. All children had evidence of optic pathway tumour on magnetic resonance imaging. Three had a prechiasmal tumour, 2 had a chiasmal tumour, 1 had prechiasmal/chiasmal tumour, 2 had a prechiasmal/chiasmal and postchiasmal tumour, 2 had a chiasmal and postchiasmal tumour, 4 had a massive involvement of the optic system, 1 child exhibited a bilateral involvement of the optic nerves with additional impairment of the chiasm. Four patients had partial and/or subtotal spontaneous regression. Conclusions: Because optic pathway tumours arise in children younger than 6 years of age, all NF1 children should undergo yearly ophtalmologic examination and growth assessment to monitor signs of precocious puberty.

American Journal of Ophthalmology, 2004

Archives of Disease in Childhood, 2002

Aims: To compare the natural history of sporadic optic glioma with those associated with neurofibromatosis type 1 (NF1). Methods: Optic glioma cases were identified using both the Manchester Children's Tumour Registry (CTR) and the North West Regional NF1 Database (NF1DB), with detailed information on natural history available from the former (in 34 of 36 cases identified). Results: A total of 52 cases over a period of 41 years were identified. From the 34 whose natural history was known, almost all (n = 31) were symptomatic, with mean ages of presentation of 4.5 and 5.1 years for NF1 and sporadic cases respectively. The majority (n = 22) presented with visual impairment, seven of whom were blind in at least one eye. Sporadic cases were over twice as likely as NF1 to have visual impairment. Recurrence occurred in 12 patients. Fewer NF1 patients died as a direct result of their optic glioma, but overall mortality and 5 and 10 year survival rates between the two groups were similar. All five primary (non-metastatic) second central nervous system (CNS) tumours occurred in NF1 cases, two of these following radiotherapy. Conclusions: Symptomatic sporadic optic gliomas presented with impaired vision more frequently and were more aggressive than NF1 optic gliomas. Only optic glioma cases with NF1 were at risk of developing a second CNS tumour. Aggressive treatment of sporadic optic gliomas and early surveillance of NF1 optic gliomas may be required.

European Journal of Cancer, 2006

A systematic literature review was carried out to evaluate best existing evidence on prognostic factors for progression of childhood optic pathway glioma. Databases were searched for relevant articles and articles selected independently by two authors. Information about study design, population, treatment, outcome and prognostic analysis were abstracted and the quality of each article was assessed. A total of 23 articles met the inclusion criteria. Many studies had important methodological limitations, regarding external and internal validity. Eleven studies evaluated possible prognostic factors in a multivariate analysis. Three high-quality studies indicated age < 1 year as an independent prognostic factor for a worse progression-free survival. Three studies with multivariate analysis, including one high-quality study, found that children with neurofibromatosis type 1 (NF-1) have a better progression-free survival than those without NF-1. Two studies with multivariate analysis found tumour site to be a prognostic factor, both with some methodological limitations. In conclusion, this systematic review demonstrates that only a few of the prognostic factors proposed have been proven to be clinically relevant. Age < 1 year is a clear and independent prognostic factor for progression-free survival. Other prognostic factors, such as NF-1, tumour site and others, are suggested, but are still without solid evidence and need further high-quality studies to be clearly proven.

Annals of Neurology, 2007

Optic pathway glioma (OPG), seen in 15% to 20% of individuals with neurofibromatosis type 1 (NF1), account for significant morbidity in young children with NF1. Overwhelmingly a tumor of children younger than 7 years, OPG may present in individuals with NF1 at any age. Although many OPG may remain indolent and never cause signs or symptoms, others lead to vision loss, proptosis, or precocious puberty. Because the natural history and treatment of NF1-associated OPG is different from that of sporadic OPG in individuals without NF1, a task force composed of basic scientists and clinical researchers was assembled in 1997 to propose a set of guidelines for the diagnosis and management of NF1-associated OPG. This new review highlights advances in our understanding of the pathophysiology and clinical behavior of these tumors made over the last 10 years. Controversies in both the diagnosis and management of these tumors are examined. Finally, specific evidence-based recommendations are proposed for clinicians caring for children with NF1.

American Journal of Ophthalmology, 2001

2009

INTRODUCTION Neurofibromatosis type 1(NF I) is a common autosomal dominant condition that affects about 1 in 5000 people. Optic nerve glioma is one of the landmark lesions characterizing this disease. They usually occur in children during the first decade of life and are seen in 11–30% of patients with NF I. When associated with NF1, the tumors are more often benign, can be multifocal and bilateral, and are usually found within the optic nerves although they can occur anywhere along the optic pathway, all the way to the visual cortex. Although the unilateral occurrence is a finding quite common in this population (up to 30%) bilateral involvement of the optic nerves is rare. Further, the optic gliomas in NF1 are self-limiting lesions with a very slow growth (which stops in adolescence). As a result exophtalmus is a very rare finding and they require surgical intervention in a very small number of cases.

Cancers, 2019

Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15–20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG...

Cancers

The natural history of non-optic central nervous system (CNS) tumors in neurofibromatosis type 1 (NF1) is largely unknown. Here, we describe prevalence, clinical presentation, treatment, and outcome of 49 non-optic CNS tumors observed in 35 pediatric patients (0–18 years). Patient- and tumor-related data were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated. Eighteen patients (51%) harbored an optic pathway glioma (OPG) and eight (23%) had multiple non-optic CNS lesions. The majority of lesions (37/49) were managed with a wait-and-see strategy, with one regression and five reductions observed. Twenty-one lesions (42.9%) required surgical treatment. Five-year OS was 85.3%. Twenty-four patients progressed with a 5-year PFS of 41.4%. Patients with multiple low-grade gliomas progressed earlier and had a lower 5-year PFS than those with one lesion only (14.3% vs. 57.9%), irrespective of OPG co-presence. Non-optic CNS tumors are common in young patients w...

JAMA Ophthalmology, 2013

Importance: Optic pathway gliomas are an important neuro-ophthalmic cause of vision loss in children. Their management depends on whether they are considered neoplasms or hamartomas. Objective: To outline the evidence that optic pathway gliomas are slowly growing neoplasms and not hamartomas. Design: Review of relevant studies in the literature. Setting: The authors are from a pediatric tertiary referral center. Results: The growth patterns and histopathology of optic pathway gliomas are more consistent with those of neo-plasms. Spontaneous regression, thought to be a characteristic of hamartomas, can be seen in neoplasms of other types as well as in optic pathway gliomas. Chemotherapy used in low-grade gliomas has been shown to halt or improve vision loss in optic pathway gliomas in many cases. Conclusions and Relevance: Optic pathway gliomas are not hamartomas but truly are neoplasms. Thus, patients should be followed up closely, and chemotherapies should be used when clinical progression occurs. Other more directed therapies will certainly be used in the future.

Neuro-Oncology, 2007

We evaluated the visual outcome of a cohort of children with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) treated according to standardized therapeutic guidelines. The study population consisted of all consecutive patients with NF1 and OPG referred to a specialized pediatric neuro-oncology program between 1994 and 2004. Treatment was instituted only in cases of progressive disease or clinical deterioration. Treatment modalities were chemotherapy (based on vincristine/ carboplatin) for children younger than 5 years and radiotherapy for all others. Ten boys and 10 girls (seven with a positive family history) entered the trial (median age at diagnosis of OPG, 29 months). At a median follow-up time of 78 months, seven patients had been treated with chemotherapy only, four with radiotherapy, and four with chemotherapy plus radiotherapy. Five patients were observed only. Currently, 18 are alive and two have died. Eight patients were treated for progressive visual loss in the face of stable disease, five for tumor volume increase without visual deterioration, and two for symptomatic tumor volume increase. At referral, six ). children had a visual acuity (VA) of , 30% in both eyes; eight children had 100% VA bilaterally. At referral, the visual field (VF) could be assessed in three children: One had VF loss in both eyes, one had VF loss in one eye, and one had normal VF. At last follow-up, eight children had VA , 20% in both eyes; only two children had 100% VA in both eyes. Among 11 children who had some visual function, three had VF loss in one eye and three in both eyes, and five had an intact VF. Contrast and color sensitivity were abnormal in seven and six patients, respectively. Thirteen children fell into the WHO hypovision category. In summary, among the 15 children treated, one had a definitive and two a mild improvement in VA. In conclusion, the visual outcome of this selected cohort of NF1 patients with OPG is unsatisfactory. A critical reappraisal of the therapeutic strategy adopted is needed.

Journal of neurosurgery. Pediatrics, 2017

OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway gliomas (OPGs). Due to the rarity of this condition and the difficulty in differentiating IONGs from other types of OPGs in most clinical series, little is known about these tumors. Currently, due to lack of evidence, they are managed the same as any other OPG. METHODS The authors conducted a multicenter retrospective cohort study aimed at determining the natural history of IONGs. Included were patients with clear-cut glioma of the optic nerve without posterior (chiasmatic/hypothalamic) involvement. At least 1 year of follow-up, 2 MRI studies, and 2 neuro-ophthalmological examinations were required for inclusion. RESULTS Thirty-six patients with 39 tumors were included in this study. Age at diagnosis ranged between 6 months and 16 years (average 6 years). The mean follow-up time was 5.6 years. Twenty-five patients had neurofibromatosis Type 1. During the follow-up period, 59% of the tumors pro...

Journal of Pediatrics, 1994

To assess the natural history of optic pathway tumors (OPT) in children with neurofibromatosis type 4 (NF-I), from January 1985 through May 1993 we performed a prospective, longitudinal study of OPT in an unselected population of children with NF-I. Of 227 children with NF-1 seen in a specialty clinic, 176 (77%) underwent neuroimaging. Children in whom tumors were identified were followed closely by both repeated neuroimaging and ophthalmologic examinations to detect tumor growth or visual deterioration. Thirty-three children (19%) were found to have OPT at a median age of 4.2 years. The median age of children who had ophthalmologic complaints was significantly lower than that of children who had no such complaints (1.9 vs 5.3 years; p < 0.001). Although eight tumors were discovered because of ophthalmologic complaints or evidence of precocious puberty, 25 children (76%) were free of symptoms at the time of diagnosis. Twenty-one children (64%) had normal ophthalmologic findings at diagnosis; six children, all with chiasmal tumors, had previously unrecognized decreased visual acuity. Only three children (9%) had evidence of either tumor growth or deteriorating vision after diagnosis; the median duration of neuroimaging follow-up was 2.4 years (range, 0.2 to 7.2 years) and of ophthalmologic examinations 3.4 years (range, 0.2 to 8.1 years). All symptomatic OPT were diagnosed before 6 years of age. We conclude that OPT rarely progress during the next few years in children with NF-1 once the OPT have been discovered. The utility of screening neuroimaging for OPT in symptom-free children with NF-I appears very limited. (J PEDIATR 1994;125:63-6) Although optic pathway tumors account for only 2% to 5% of all brain tumors in childhood, as many as 70% of the cases are associated with neurofibromatosis type 1.1 Estimates of the incidence of OPT in individuals with NF-1 range from 1.5% in a population-based survey 2 to 15% in a NF-1 referral clinic with a mean age of 20 years. 3 In a previous study, we identified OPT by computed tomography in 15% of an

American Journal of Medical Genetics, 2003

Children with neurofibromatosis type 1 (NF1) may present with optic pathway gliomas (OPG) that can progress to visual loss or other neurologic symptoms. These tumors may become evident either as a result of patient signs or symptoms or as an incidental finding on ''baseline'' neuroimaging studies. In an attempt to determine if there were differences between symptomatic and asymptomatic children with OPG, a retrospective cohort study of ninety children with NF1 and OPG was performed using data from two large NF1 referral centers. Age at diagnosis, presenting symptoms, tumor location, associated features, and clinical response were assessed for children who were initially symptomatic from their OPG (n ¼ 51) and compared to similar data of asymptomatic children whose tumors were incidentally discovered by MRI (n ¼ 39). There were no differences in age at presentation, tumor location, NF1-associated symptoms, or clinical response between the groups. Initially symptomatic children were much more likely to require treatment (OR: 14.8, 95% CI [1.9-116.7]) than those with incidentally discovered, asymptomatic OPG. Although 36% of OPG were diagnosed in children over the age of 6 years, none received prior neuroimaging and only two children had previously normal eye examinations, suggesting that the vast majority of OPG in this group were longstanding, undiagnosed tumors. Based on these findings, we do not advocate ''baseline'' MRI in children with NF1, but strongly recommend that all children of the age 10 years and younger with NF1 have complete annual ophthalmologic evaluations.

Neuro-Oncology, 2012