Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1.

BACKGROUND: Children with neurofibromatosis type 1 (NF1) are predisposed to both brain tumors and cognitive deficits. While changes in white matter integrity after multimodal therapy are associated with cognitive dysfunction, the effect of isolated chemotherapy in NF1 is unknown. To determine whether chemotherapy is associated with white matter microstructural changes, we examined diffusion tensor imaging (DTI) in NF1 subjects. PROCEDURE: We reviewed DTI measures in tracts associated with cognition but free from tumor in 24 children with NF1-associated optic pathway gliomas unexposed to surgery or radiation. Twelve age-matched pairs were identified based on exposure to chemotherapy. A paired t-test was used to compare fractional anisotropy (FA) in tracts of interest between subjects with and without chemotherapy exposure. RESULTS: On paired t-test, FA was significantly lower in the corpus callosum (P = 0.015) and cerebellothalamic (P = 0.038) tracts of subjects exposed to chemotherapy. There was no effect of age or time from chemotherapy on the difference between groups. In multivariable analysis, FA of these tracts was associated with chemotherapy exposure after adjusting for age, tumor location, and DTI acquisition. In longitudinal measures, FA decreased after chemotherapy exposure while FA increased with age in unexposed subjects. CONCLUSIONS: Exposure to low-intensity chemotherapy in NF1 is associated with changes in white matter microstructure in tracts associated with cognition. Future studies should determine whether these changes are associated with cognitive decline. While chemotherapy may spare cognition relative to radiation and surgery, children with NF1 exposed to chemotherapy may benefit from early cognitive testing to allow for earlier intervention.

Fractional anisotropy of the optic radiations is associated with visual acuity loss in optic pathway gliomas of neurofibromatosis type 1.

BACKGROUND: No more than half of patients with neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) develop vision loss. Prospectively identifying those who will require therapy remains challenging, because no reliable factors have yet been identified that predict future vision loss. To determine whether brain tissue microstructure is associated with visual acuity loss, we examined diffusion tensor imaging (DTI) and ophthalmologic evaluations in children with NF1-associated OPG. METHODS: We retrospectively reviewed ophthalmology records and concurrent DTI measurements of the optic nerves, tracts, and radiations from 50 children with NF1-associated OPGs. Multivariate linear regression measured the association between fiber trajectory quantity and white matter integrity on visual acuity measured by the logarithm of the minimal angle of resolution (logMAR). RESULTS: In multivariate analysis, fractional anisotropy (FA) of the optic radiations was associated with visual acuity loss (adjusted coefficient = -6.081 logMAR/FA; P = .006) after adjusting for age, extent of tumor, DTI acquisition type, prior chemotherapy, and fundus examination findings. The association remained after eliminating tumors involving the optic radiations. In an evaluation of 15 subjects with paired ophthalmologic examination and DTI a year apart, initial FA of the optic radiation was associated with a trend toward change in visual acuity a year later (coefficient = -2.652 logMAR/FA; P = .069). CONCLUSIONS: A decrease in FA of the optic radiations is associated with abnormal visual acuity in NF1-associated OPGs and may be predictive of visual acuity loss during the following year.