Sunday, August 2, 2015

Magnetic resonance imaging screening for optic pathway gliomas in children with neurofibromatosis type 1

Carlos E. Prada,  Robert B. Hufnagel , Trent R. Hummel,  Anne M. Lovell, Robert J. Hopkin, Howard M. Saal, Elizabeth K. Schorry.  The Use of Magnetic Resonance Imaging Screening for Optic Pathway Gliomas in Children with Neurofibromatosis Type 1.  Journal of Pediatrics.  Published Online: July 29, 2015.



To evaluate the utility of screening brain/orbital magnetic resonance imaging (MRI) in a large population of children with neurofibromatosis type 1 (NF1) over a 20-year period.

Study design

A retrospective analysis of clinical and imaging data from children with NF1 seen at a single center between 1990 and 2010 was performed.


During the 20-year study period, 826 individuals with NF1 (402 females, 424 males) ages 1-9 years were screened for optic pathway gliomas (OPGs) using brain/orbital MRI; 18% were identified with OPGs with a median age at detection of 3 years. Fifteen percent of patients with OPGs had radiologic or clinical progression requiring therapy. Children with chiasmatic and postchiasmatic tumors were more likely to require therapy compared with patients with prechiasmatic OPGs ( P < .0001). Patients with visual deficits at the time of diagnosis were more likely to experience visual decline despite therapy when compared with patients treated based on radiologic progression ( P < .012).


Our findings confirm that chiasmatic and postchiasmatic OPG in children with NF1 have the highest risk for progression and vision loss. Early identification of OPG by screening MRI prior to the development of vision loss may lead to improved visual outcomes. Children with negative brain and orbital MRI screening at age 15 months or later did not develop symptomatic OPGs.

From the article:

Prior to therapy, 12 children had vision abnormalities and 10 children had normal ophthalmologic evaluations. Patients with postchiasmatic tumors (3/4) and chiasmatic tumors (8/15) were more likely to develop vision abnormalities compared with patients with isolated prechiasmatic OPGs (1/3) ( P < .01). The most common ophthalmologic findings were decreased visual acuity (11/22), abnormal/atrophic optic disc (8/22), visual field defects (6/22), and unilateral abnormal pupillary response (1/22). The majority of children with OPGs received chemotherapy before 6 years of age (median 5 years; range 1.5-12 years). All patients initially received a regimen of vincristine and carboplatin, with the exception of 1 patient who subsequently received vincristine and dactinomycin after experiencing an allergic reaction to carboplatin. Seven patients relapsed after therapy (median 3 years; range 1-8 years). Surgical resections were performed in 2 patients who had progressive tumors despite chemotherapy, with severe vision abnormalities. Indications for OPG surgery were hydrocephalus (n = 1) and mass effect (n = 1)…

Children with OPGs with visual findings prior to therapy were more likely to experience visual decline (10/12) when compared with children treated based on radiologic progression of OPGs (2/10) ( P < .012). Fifty percent (50%) of patients with visual findings at diagnosis (6/12) progressed to vision loss (final vision of 20/200 or worse) in 1 or both eyes (5 unilateral, 1 bilateral). None of the patients treated based on radiologic progression had visual acuities of 20/200 or worse…

In prior decades, many children with NF1 and asymptomatic optic gliomas received unnecessary treatment for what is often a very indolent lesion.  Listernick et al were among the first to assert that OPGs in asymptomatic children with NF1 infrequently progress. In 1997, the OPG Task Force concluded early detection of tumors would not reduce the rate of loss of vision, and there was no compelling evidence to support OPG screening with neuroimaging.  Blazo et al reported their results of brain MRI screening of 84 children with NF1, where 13 children were found to have OPG. They reported that 3 asymptomatic children with enlarging chiasmal lesions were treated with chemotherapy and had preservation of vision, whereas 5 children ascertained outside of screening guidelines had substantial vision loss, and suggested that routine surveillance for OPG could improve outcomes. Listernik and Charrow  responded to the Blazo article, noting that 4 of the 5 tumors in the symptomatic patients were associated with proptosis and represented a biologically different group of tumors; they upheld their principle of screening only with ophthalmologic examinations in young asymptomatic children.

Our study suggests that MRI screening has the potential to improve and maintain visual outcome in young children with OPG. Supporting this assertion is that none of the children who were identified only with MRI (no visual symptoms) with progressive OPG, progressed to vision loss. However, 50% of children who presented with visual symptoms at the time of diagnosis of a progressive OPG demonstrated eventual vision loss in 1 or both eyes. This suggests that screening MRIs in patients with NF1 may identify aggressive lesions sooner and that this will lead to early treatment and, subsequently, better visual outcomes…

A potentially negative consequence of brain/orbital MRI screening is detection of lesions that would never progress or could resolve spontaneously. This could lead to unnecessary parental anxiety and high costs associated with frequent imaging. Our study suggests that the location of the OPGs is an important marker for tumor progression and need for therapy given that isolated prechiasmatic tumors are more likely to regress (25%) and to be indolent than chiasmatic and postchiasmatic OPGs (10%). It is also important to consider that chiasmatic and postchiasmatic OPGs are most likely to lead to visual symptoms, supporting consideration of therapy for this group if tumor growth is documented. Future studies will help to validate if frequency of neuroimaging surveillance could be modified based on glioma location…

Our study also found an increased risk for need for therapy in females with NF1 and OPG, confirming recent studies suggesting that sex plays a role in the development of gliomas and neuronal dysfunction in patients with NF1.
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