Case Report: Chemotherapy Indication in a Case of Neurofibromatosis Type 1 Presenting Optic Pathway Glioma: A One-Year Clinical Case Study Using Differential Tractography Approach

Abstract

Neurofibromatosis type 1 (NF1) is associated with peripheral and central nervous system tumors. It is noteworthy that the regions in which these tumors frequently arise are the optic pathways (OPs) and the brainstem. Thus, we decided to trace the procedure of diffusion Magnetic Resonance Imaging (dMRI) alterations along with Short-Wavelength Automated Perimetry (SWAP) examinations of the OPs after surgery and chemotherapy over 1 year, which enabled us to evaluate chemotherapy's efficacy in an NF1 patient with an OP tumor. In this study, a 25-year-old woman with NF1 and left optic radiation (OR) glioma underwent surgery to remove the glioma. Immunohistochemistry (IHC) revealed a Pilocytic Astrocytoma (PA) WHO grade I. Post-operation chemotherapy done using nine treatment cycles of administering Temozolomide (TMZ) for 5 days every 4 weeks. Applying the region of interest (ROI) differential tractography method and SWAP four times every 3 months allowed us to follow the patient's visual acuity alterations longitudinally. The differential deterministic tractography method and statistical analyses enabled us to discover the white matter (WM) tracts anisotropy alterations over time. Furthermore, statistical analyses on the SWAP results along time illustrated possible alterations in visual acuity. Then, we could compare and associate the findings with the SWAP examinations and patient symptoms longitudinally. Statistical analyses of SWAP tests revealed a significant improvement in visual fields, and longitudinal differential tractography showed myelination and dense axonal packing in the left OR after 1 year of treatment. In this study, we examined an old hypothesis suggesting that chemotherapy is more effective than radiotherapy for NF1 patients with OP gliomas (OPGs) because of the radiation side effects on the visual field, cognition, and cerebrovascular complications. Our longitudinal clinical case study involving dMRI and SWAP on a single NF1-OPG patient showed that chemotherapy did not suppress the OP myelination over time. However, it should be noted that this is a clinical case study, and, therefore, the generalization of results is limited. Future investigations might focus on genetic-based imaging, particularly in more cases. Further, meta-analyses are recommended for giving a proper Field Of View (FOV) to researchers as a subtle clue regarding precision medicine.

Keywords: diffusion tensor imaging; immunohistochemistry; low-grade glioma; neurofibromatosis type 1; optic pathway glioma; short-wavelength automated perimetry; temozolomide; visual field index.

Figure 1

Pre-Operation MRI and analyzed DTI scans displayed multiple tumors in our young adult NF1 patient. It is not uncommon for NF1 patients to have more than one CNS tumor. As the MRI presented, the NF1 brain showed a left OR glioma (A), Left thalamus cyst (B), and a right midbrain tumor (C). Deterministic tractography demonstrated the left OR involvement because of the left WM OR glioma with its massive edema (D,E). MRI, magnetic resonance imaging; DTI, diffusion tensor imaging; NF1, neurofibromatosis type 1; CNS, central nervous system; OR, optic radiation; WM, white matter.

Figure 2

Longitudinal SWAP examinations and statistical analyses were done. Perimetric tests revealed left visual field healing, but a homonymous hemianopsia defect occurred due to the left geniculate WM glioma (A). The polynomial regression method showed that both side vision acuity improved over time (B,C). SWAP, Short-Wavelength Automated Perimetry; WM, white matter.

Figure 3

Differential tractography approach and statistical analyses to discover the ORs connectivity and diffusion metric alterations. The analyses on pre-chemotherapy compared with pre-operation showed increased connectivity in the left and right OR. Furthermore, violin plots showed fiber maturation according to increased FA, decreased MD, and RD (A). This method used for post-chemotherapy vs. pre-chemotherapy revealed increased connectivity in the left and right OR, and statistical analyses on diffusion metrics showed no pathological indication (B). This method also revealed increased connectivity of both ORs after 1-year of post-operation compared to the pre-operation, and statistical analyses presented increased FA, decreased MD, and RD, which could be a picture of myelination and dense axonal packing in the left OR (C). Statistics performed on the diffusion metrics by two-tailed sample t-test, *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. OR, optic radiation; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity; AD, axial diffusivity; nFA, normal FA; nMD, normal MD; nRD, normal RD; nAD, normal AD.

Figure 4

Correlation test between the left OR diffusion metrics and perimetric parameters and diffusion metric alterations after 1 year. Analyses on the relationship between the left OR and VFI showed a significant correlation between left OR FA and the left VFI presented as a heatmap matrix (A). Statistical analyses on diffusion metrics of post-chemotherapy vs. normal control subjects as illustrated by violin plots revealed increased FA, decreased MD and RD, a picture of myelination, and dense axonal packing in the left OR (B). The relationship analyses done by the Pearson's correlation coefficient test and the statistics performed on the diffusion metrics by two-tailed sample t-test, *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.