Search Results

You are looking at 1 - 6 of 6 items for

  • Author or Editor: D. Gareth Evans x
Clear All Modify Search
Restricted access

Graham Dow, Nigel Biggs, Gareth Evans, Jimmie Gillespie, Richard Ramsden and Andrew King

Object. The authors conducted a study to examine the incidence, classification, and progression of spinal tumors in patients with neurofibromatosis Type 2 (NF2) treated at a single center, and to examine relationships with the known mutational subtypes of NF2.

Methods. They performed a retrospective review of clinical records, neuroimaging studies, and genetic data obtained in 61 patients with NF2.

Forty-one (67%) of 61 patients harbored one or more spinal tumors. Thirty-four patients had undergone serial spinal magnetic resonance imaging during a mean follow-up period of 52 months (range 10–103 months; median 53 months). In 16 patients there were multiple extramedullary tumors smaller than 5 mm, which did not progress. Fourteen patients harbored at least one extramedullary tumor that was greater than 5 mm; of these, radiological progression was demonstrated or spinal tumor excision was performed during the follow-up period in eight cases (57%). Eleven patients harbored intramedullary cord tumors in addition to small and large extramedullary tumors, three (27%) of which exhibited radiological progression. In cases in which genotypes were known, protein-truncating mutations were significantly more likely to be associated with the presence of spinal tumors than in other types (p = 0.03, Fisher exact test). No associations between clinical behavior of spinal tumors and genotype, however, could be demonstrated.

Conclusions. Spinal tumors in cases involving NF2 are heterogeneous in type, distribution, and behavior but larger-size tumors are more likely to progress significantly. Intramedullary tumors usually accompany multiple extramedullary tumors. In the authors' experience subtyping of the NF2 mutation has not yet influenced management. Protein-truncating mutations are associated with an increased prevalence of spinal tumors.

Full access

Mueez Waqar, Susan Huson, D. Gareth Evans, John Ealing, Konstantina Karabatsou, K. Joshi George and Calvin Soh

OBJECTIVE

C2 nerve root neurofibromas have been reported frequently in patients with neurofibromatosis type 1 (NF1), although their genetic and imaging characteristics are unexplored. The aim of this study was to characterize genetic and spinal imaging findings in a large cohort of NF1 patients with C2 neurofibromas.

METHODS

The authors performed a review of national NF1 referrals between 2009 and 2016. Inclusion criteria were at least 1 C2 root neurofibroma and cervical-spine or whole-spine MRI scans available for analysis. Blinded imaging review was performed by a neuroradiologist with an interest in NF1.

RESULTS

Fifty-four patients with 106 C2 neurofibromas were included. The median age was 32.5 years (range 15–61 years), and there were slightly more male patients (33 vs 21 female patients). Splice-site (30%) and missense (20%) variants were frequent. Spinal neurofibromas were distributed in all spine regions (65%) or in the cervical spine alone (22%). Most (93%) C2 neurofibromas were visible on MRI scans of the head. Intradural invasion and cord compression in the cervical spine included the C2 level in 95% and 80% of patients, respectively. Compared with all other cervical spine neurofibromas in these patients, C2 neurofibromas had higher rates of intraspinal extension (75% vs 32%; OR 6.20, 95% CI 3.85–9.97; p < 0.001), intradural invasion (53% vs 26%; OR 3.20, 95% CI 2.08–4.92; p < 0.001), and cord compression (25% vs 13%; OR 2.26, 95% CI 1.35–3.79; p = 0.002). However, C2 neurofibromas had lower rates of extraforaminal growth beyond the transverse process (12% vs 62%; OR 0.09, 95% CI 0.05–0.16; p < 0.001).

CONCLUSIONS

C2 neurofibromas are associated with an aggressive intraspinal phenotype, limited growth outside the spinal canal, and an uncommon genetic profile. These observations require future study.

Full access

Linton T. Evans, Jack Van Hoff, William F. Hickey, Miriam J. Smith, D. Gareth Evans, William G. Newman and David F. Bauer

Clear cell meningioma (CCM) is an uncommon variant of meningioma. The authors describe a case of a pediatric CCM localized to the lumbar spine. After resection, sequencing revealed an inactivating mutation in the SWI/SNF chromatin remodeling complex subunit SMARCE1, with loss of the second allele in the tumor. The authors present a literature review of this mutation that is associated with CCM and a family history of spine tumors.

Restricted access

D. Gareth R. Evans, Richard T. Ramsden, Andrew Shenton, Carolyn Gokhale, Naomi Bowers, Susan M. Huson and Andrew J. Wallace

Object

Individuals who develop a unilateral vestibular schwannoma (VS) and other neurogenic tumors are at high risk of having the inherited condition neurofibromatosis Type 2 (NF2). The risk of bilateral disease and transmission risk to offspring are important in surgical planning and counseling. The authors have attempted to resolve these risks.

Methods

A large NF2 dataset was interrogated for individuals who had initially presented with a unilateral VS and other tumors before developing bilateral disease, to assess the contralateral and offspring risks.

Results

Ninety-six patients with a unilateral VS and additional neurogenic tumors had a bilaterality rate of 48% at 20 years in those initially diagnosed when > 18 years of age and 82% if presenting earlier. Constitutional NF2 mutations were found in blood in 25 (27%) of 92, but 13 (76%) of 17 patients presenting with unilateral VS at ≤ 18 years of age. Tumor analysis suggests that the vast majority of the remainder are mosaic for an NF2 mutation.

Conclusions

Patients with unilateral VS and other NF2-related tumors who fulfill Manchester criteria have a high risk of developing a contralateral tumor, especially if presenting in childhood. Transmission risks are reduced for offspring, particularly in the older patients who are likely to be mosaic.

Full access

Katrina A. Morris, Shazia K. Afridi, D. Gareth Evans, Anke E. Hensiek, Martin G. McCabe, Mark Kellett, Dorothy Halliday, Pieter M. Pretorius and Allyson Parry

OBJECTIVE

People with neurofibromatosis Type 2 (NF2) have a genetic predisposition to nervous system tumors. NF2-associated schwannomas stabilize or decrease in size in over half of the patients while they are receiving bevacizumab. NF2 patients treated with bevacizumab for rapidly growing schwannoma were retrospectively reviewed with regard to ependymoma prevalence and response to treatment.

METHODS

The records of 95 NF2 patients receiving bevacizumab were retrospectively reviewed with regard to spinal ependymoma prevalence and behavior. The maximum longitudinal extent (MLE) of the ependymoma and associated intratumoral or juxtatumoral cysts were measured on serial images. Neurological changes and patient function were reviewed and correlated with radiological changes.

RESULTS

Forty-one of 95 patients were found to have ependymomas (median age 26 years; range 11–53 years). Thirty-two patients with a total of 71 ependymomas had scans appropriate for serial assessment with a mean follow-up of 24 months (range 3–57 months). Ependymomas without cystic components showed minimal change in MLE. Twelve patients had ependymomas with cystic components or syringes. In these patients, reductions in MLE were observed, particularly due to decreases in the cystic components of the ependymoma. Clinical improvement was seen in 7 patients, who all had cystic ependymomas.

CONCLUSIONS

Bevacizumab treatment in NF2 patients with spinal cord ependymomas results in a decrease in the size of intratumoral and juxtatumoral cysts as well as adjacent-cord syringes and a decrease in cord edema. This may provide clinical benefit in some patients, although the changes do not meet the current criteria for radiological tumor response.

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.