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Thomas E. Merchant, Heather Lee, Junhong Zhu, Xiaoping Xiong, Gregory Wheeler, Sean Phipps, Frederick A. Boop and Robert A. Sanford

Object. The goal of this study was to determine the influence of hydrocephalus on intelligence quotient (IQ) in children with infratentorial ependymoma before and after the administration of focal radiation.

Methods. Measurements of ventricular size, including Evans index (EI), cella media index (CMI), frontal horn diameter (FHD), and ventricular angle, were performed using magnetic resonance imaging at the time of diagnosis and again at 3, 6, 9, and 12 months after the initiation of radiation therapy. Of the 59 patients (median age at time of radiation treatment, 4.1 years), the clinical diagnosis established in 50 (85%) was hydrocephalus and 23 (39%) required placement of a cerebrospinal fluid (CSF) shunt. Extent of resection was gross or near total in 50 (85%). Before and after radiation treatment, IQ was measured using age-appropriate testing. The correlation between multiple ventricular measurements and IQ was investigated using standard regression techniques and a generalized linear model. Patients with a higher EI (p = 0.04), CMI (p = 0.001), and FHD (p = 0.0002) at the time of diagnosis were more likely to have lower IQ scores before radiation treatment. Patients with higher CMI (p = 0.04) and FHD (p = 0.01) at the time of diagnosis were more likely to exhibit an increase in IQ score after radiotherapy. The rate of change in IQ after radiation treatment was positively correlated with the CMI intercept (p = 0.015) and negatively correlated with the rate of FHD change (p = 0.006).

Conclusions. Changes in IQ score before and after radiation treatment are significantly influenced by the extent and treatment of hydrocephalus at the time of diagnosis. Hydrocephalus is an important factor to include when analyzing the effects of treatment. Patients who undergo a second surgery for ependymoma are more likely to require the placement of a CSF shunt (p = 0.0001).

Open access

Daniel Lewis, Carmine A. Donofrio, Claire O’Leary, Ka-loh Li, Xiaoping Zhu, Ricky Williams, Ibrahim Djoukhadar, Erjon Agushi, Cathal J. Hannan, Emma Stapleton, Simon K. Lloyd, Simon R. Freeman, Andrea Wadeson, Scott A. Rutherford, Charlotte Hammerbeck-Ward, D. Gareth Evans, Alan Jackson, Omar N. Pathmanaban, Federico Roncaroli, Andrew T. King and David J. Coope

OBJECTIVE

Inflammation and angiogenesis may play a role in the growth of sporadic and neurofibromatosis type 2 (NF2)–related vestibular schwannoma (VS). The similarities in microvascular and inflammatory microenvironment have not been investigated. The authors sought to compare the tumor microenvironment (TME) in sporadic and NF2-related VSs using a combined imaging and tissue analysis approach.

METHODS

Diffusion MRI and high-temporal-resolution dynamic contrast-enhanced (DCE) MRI data sets were prospectively acquired in 20 NF2-related and 24 size-matched sporadic VSs. Diffusion metrics (mean diffusivity, fractional anisotropy) and DCE-MRI–derived microvascular biomarkers (transfer constant [Ktrans], fractional plasma volume, tissue extravascular-extracellular space [ve], longitudinal relaxation rate, tumoral blood flow) were compared across both VS groups, and regression analysis was used to evaluate the effect of tumor size, pretreatment tumor growth rate, and tumor NF2 status (sporadic vs NF2-related) on each imaging parameter. Tissues from 17 imaged sporadic VSs and a separate cohort of 12 NF2-related VSs were examined with immunohistochemistry markers for vessels (CD31), vessel permeability (fibrinogen), and macrophage density (Iba1). The expression of vascular endothelial growth factor (VEGF) and VEGF receptor 1 was evaluated using immunohistochemistry, Western blotting, and double immunofluorescence.

RESULTS

Imaging data demonstrated that DCE-MRI–derived microvascular characteristics were similar in sporadic and NF2-related VSs. Ktrans (p < 0.001), ve (p ≤ 0.004), and tumoral free water content (p ≤ 0.003) increased with increasing tumor size and pretreatment tumor growth rate. Regression analysis demonstrated that with the exception of mean diffusivity (p < 0.001), NF2 status had no statistically significant effect on any of the imaging parameters or the observed relationship between the imaging parameters and tumor size (p > 0.05). Tissue analysis confirmed the imaging metrics among resected sporadic VSs and demonstrated that across all VSs studied, there was a close association between vascularity and Iba1+ macrophage density (r = 0.55, p = 0.002). VEGF was expressed by Iba1+ macrophages.

CONCLUSIONS

The authors present the first in vivo comparative study of microvascular and inflammatory characteristics in sporadic and NF2-related VSs. The imaging and tissue analysis results indicate that inflammation is a key contributor to TME and should be viewed as a therapeutic target in both VS groups.