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To compare 1D (linear) tumor volume calculations and classification systems with 3D-segmented volumetric analysis (SVA), focusing specifically on their effectiveness in the evaluation and management of NF2-associated vestibular schwannomas (VS). VS were clinically followed every 6 months with cranial, thin-sliced (< 3 mm) MRI. We retrospectively reviewed and used T1-weighted post-contrast enhanced (gadolinium) images for both SVA and linear measurements. 3D-SVA was performed manually or combined with semiautomated segmentation by using axial planes. The maximum linear dimensions (MLD) were determined in three dimensions (anteroposterior, transverse, and craniocaudal planes) using axial and coronal planes. The MLD was cubed (MLD 3 ), and orthogonal analysis (OA) was derived to establish comparability with the SVA. The Hannover and Koos classification was used to depict the size ratio in each MRI and tumor. A linear regression model was performed to compare 1D/classification systems to SVA, and the percentage deviation change of MLD 3 and OA to SVA was established using a one-way multivariate variance analysis. 2586 SVA and 10344 linear measurements were performed in a cohort of 149 NF2 patients and 292 associated VS. All measurement techniques (MLD 3 , OA, KOOS, and Hannover) significantly (and strongly, r 2  > 0.5) correlated with SVA (p < 0.001). The OA showed an even stronger positive correlation than the MLD 3 to SVA. Smaller classified tumors (T1/T2, K1/K2) exhibited a low-moderate positive correlation (r 2  = 0.23-0.44) compared to medium-sized (T3, K2/3) and large tumors (T4, K4; r 2  = 0.54-0.76). Pre- and postoperative MLD 3 and OA statistically significantly predict SVA (p < 0.001), but the postoperative correlation was weaker, particularly for MLD 3 to SVA values. All analyses showed a large scatter range. In the percentage deviation analysis of MLD 3 and OA from SVA, small tumors (K1/K2, T1/T2) were overestimated. Compared to the SVA, the MLD 3 and especially the OA are a time-saving alternative for monitoring the tumor volume of NF2-associated VS. However, the scatter range in small/surgically reduced tumors is enormous. For this reason, they are not recommended for monitoring off-label therapy with Bevacizumab or for treatment decisions depending on a precise assessment of tumor volume and growth. Developing deep learning-based volume determinations in the future is essential to reduce SVA's time intensity., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The ethics board of the Medical Faculty and the University Hospital of Tübingen approved this retrospective analysis (No 018/2019BO2, final approval date 17/01/2019). Consent to participate: Informed consent was obtained from all participants or their parents/legal guardians included in the study., (© 2025. The Author(s).)

NF2-related schwannomatosis (NF2) is a rare autosomal-dominant genetic disorder characterized by bilateral vestibular schwannomas and multiple meningiomas. This case report presents the extremely rare occurrence of an anaplastic meningioma in a 12-year-old male with previously undiagnosed NF2. The patient presented with a history of abdominal pain and episodic emesis, gait unsteadiness, right upper and lower extremity weakness, and facial weakness. He had sensorineural hearing loss and wore bilateral hearing aids. MR imaging revealed a sizable left frontoparietal, dural-based meningioma with heterogeneous enhancement with mass effect on the brain and midline shift. Multiple additional CNS lesions were noted including a homogenous lesion at the level of T5 indicative of compression of the spinal cord. The patient underwent a frontotemporoparietal craniotomy for the removal of his large dural-based meningioma, utilizing neuronavigation and transdural ultrasonography for precise en bloc resection of the mass. Histopathology revealed an anaplastic meningioma, WHO grade 3, characterized by brisk mitotic activity, small-cell changes, high Ki-67 proliferation rate, and significant loss of P16. We report an anaplastic meningioma associated with an underlying diagnosis of NF2 for which we describe clinical and histopathological features., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: NF2 -related schwannomatosis ( NF2 -SWN, formerly called neurofibromatosis type 2) is a tumor predisposition syndrome that is manifested by multiple vestibular schwannomas, nonvestibular schwannomas, meningiomas, and ependymomas. The condition is relentlessly progressive with no approved therapies. On the basis of preclinical activity of brigatinib (an inhibitor of multiple tyrosine kinases) in NF2 -driven nonvestibular schwannoma and meningioma, data were needed on the use of brigatinib in patients with multiple types of progressive NF2 -SWN tumors., Methods: In this phase 2 platform trial with a basket design, patients who were 12 years of age or older with NF2 -SWN and progressive tumors were treated with oral brigatinib at a dose of 180 mg daily. A central review committee evaluated one target tumor and up to five nontarget tumors in each patient. The primary outcome was radiographic response in target tumors. Key secondary outcomes were safety, response rate in all tumors, hearing response, and patient-reported outcomes., Results: A total of 40 patients (median age, 26 years) with progressive target tumors (10 vestibular schwannomas, 8 nonvestibular schwannomas, 20 meningiomas, and 2 ependymomas) received treatment with brigatinib. After a median follow-up of 10.4 months, the percentage of tumors with a radiographic response was 10% (95% confidence interval [CI], 3 to 24) for target tumors and 23% (95% CI, 16 to 30) for all tumors; meningiomas and nonvestibular schwannomas had the greatest benefit. Annualized growth rates decreased for all tumor types during treatment. Hearing improvement occurred in 35% (95% CI, 20 to 53) of eligible ears. Exploratory analyses suggested a decrease in self-reported pain severity during treatment (-0.013 units per month; 95% CI, -0.002 to -0.029) on a scale from 0 (no pain) to 3 (severe pain). No grade 4 or 5 treatment-related adverse events were reported., Conclusions: Brigatinib treatment resulted in radiographic responses in multiple tumor types and clinical benefit in a heavily pretreated cohort of patients with NF2 -SWN. (Funded by the Children's Tumor Foundation and others; INTUITT-NF2 ClinicalTrials.gov number, NCT04374305.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory., Methods: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL)., Results: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores., Conclusions: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011)., (© 2024. The Author(s).)

Our pilot study aimed at exploratory radiogenomic data analysis in patients with NF2-associated schwannomatosis (formerly neurofibromatosis type II) to assume the potential of image biomarkers in this pathology. Fifty-three unrelated patients (37 (69.8%) women, avg. age 30.2 ± 11.2 y.o.) were enrolled in the study. First-order, gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), and geometry-based statistics were calculated (3718 features per region of interest). We demonstrated imaging patterns and statistically significant differences in radiomic features potentially related to the genotype and clinical phenotype of the disease. However, the clinical utility of these patterns should be further evaluated. The study was supported by the Russian Science Foundation grant 21-15-00262.

Background: Neurofibromatosis type 2 (NF2) is rare genetic disorder mainly characterized by the development of central nervous system lesions, but peripheral nerve pathology may also cause high morbidity including pain, motor, and sensory loss., Objective: To describe the tumor burden of patients with peripheral nerve pathology in NF2 including peripheral neuropathies and schwannomas and the results of surgery in the latter group., Methods: We conducted a retrospective chart review of all patients with NF2 followed up at our NF2 Reference Center to include all patients suffering from peripheral nerve pathology. Tumor detection relied on focal MRIs based on symptoms., Results: Thirty-four patients harboring 105 peripheral nerve schwannomas and 1 perineurioma were included. Schwannomas were mainly located in major nerves (n = 74, 71%) compared with subcutaneous (n = 23, 22%) and intramuscular (n = 8, 7%) cases. Most schwannomas (81/90-90%) were classical discrete tumors while multinodular cases represented only 9 cases (10%). During follow-up, 63 (60%) tumors were operated in 24 patients, including 39 schwannomas of major nerves. A complete resection was achieved in most of the cases (52/63, 83%) with a complete relief of preoperative pain in most patients (57/60, 95%). Persistent motor deficits (5/39, 13%) were mostly encountered in patients operated from multinodular schwannomas (4/5, 80%). Six patients had an associated peripheral neuropathy with 5 cases of pseudo-Charcot-Marie-Tooth-associated amyotrophy., Conclusion: Surgery remains a safe and effective method of treating peripheral nerve schwannoma-associated pain in NF2, with the exception of rare multinodular tumors. Special attention should be drawn to patients harboring severely debilitating neuropathies and perineuriomas., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Abstract: Neurofibromatosis type 2 (NF2) is an autosomal-dominant tumor predisposing syndrome that results from mutations in the NF2 tumor suppressor gene on chromosome 22. The development of bilateral vestibular schwannomas is the characteristic feature of the disease. However, other nervous system tumors, including meningiomas, ependymomas, and schwannomas, can be seen frequently. Herein, we present 68 Ga-DOTATATE PET/CT findings of 2 siblings with NF2., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: The goal of this study was to assess the utility of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to distinguish sporadic vestibular schwannomas (VSs) from those related to neurofibromatosis type 2 (NF2)., Methods: We retrospectively reviewed 265 patients pathologically diagnosed with VSs between January 2015 and October 2020 in a single institution. There were 28 patients (male: 19, female: 9; age 11-67 years) including 23 sporadic and five NF2-related VSs, who had pretreatment DWI and DCE-MRI. Normalized mean apparent diffusion coefficient (nADCmean) and DCE-MRI parameters along with tumor characteristics were compared between sporadic and NF2-related VSs as appropriate. The diagnostic performances were calculated based on the receiver operating characteristic curve analysis for the values that showed significant differences. To identify significant modalities, multivariate logistic regression analysis was performed using nADCmean and the combination of statistically significant DCE-MRI parameters., Results: NADCmean, fractional volume of extracellular space (Ve), and forward volume transfer constant (Ktrans) were significantly different between sporadic and NF2-related VSs (nADCmean: median 1.62 vs. 1.16, P = .002; Ve: median 0.40 vs. 0.66, P = .007; Ktrans: median 0.17 vs. 0.33, P = .007), whereas fractional plasma volume (Vp), reverse reflux rate constant (Kep), and tumor characteristics were not. The diagnostic performances of nADCmean, Ve, and Ktrans were 0.93, 0.90, and 0.90 area under the curves with cutoffs of 1.46, 0.51, and 0.29, respectively. nADCmean and the combination of Ve and Ktrans were both chosen as significant differentiators by multivariate logistic regression analysis (P = .027)., Conclusions: DWI and DCE-MRI are both promising modalities to distinguish sporadic and NF2-related VSs., (© 2022 American Society of Neuroimaging.)

Objective: The objective of this paper was to describe the volumetric natural history of meningiomas in patients with neurofibromatosis type 2 (NF2)., Methods: The authors performed a retrospective descriptive study by reviewing NF2 patients with meningiomas at their institution between 2000 and 2019. Demographic data were collected from the electronic medical records. Tumor volume was collected using volumetric segmentation software. Imaging characteristics including peritumoral brain edema (PTBE) and tumor calcification were collected for each patient from their first to most recent MRI at the authors' institution. An increase of 15% or more per year from original tumor size was used as the cutoff to define growth., Results: A total of 137 meningiomas from 48 patients were included in the analysis. The average number of tumors per person was 2.9. Ninety-nine (72.3%) tumors were in female patients. The median length of follow-up from first imaging to last imaging was 32 months (IQR 10.9, 68.3 months). Most tumors were located in the cerebral convexity (24.8%), followed by the falcine region (18.2%) and spine (10.2%). The median tumor growth was 0.12 cm3/yr (IQR 0.03, 0.52 cm3/yr). At the time of first imaging, 21.9% of tumors had calcifications, while 13.9% of meningiomas had PTBE. Of 137 tumors, 52 showed growth. Characteristics associated with tumor growth included PTBE (OR 9.12, 95% CI 1.48-56.4), tumor volume (per cm3) at first imaging (OR 0.91, 95% CI 0.83-0.99), and 10-year increased age at first imaging (OR 0.57, 95% CI 0.43-0.74). PTBE had the shortest median time to growth at 9.2 months., Conclusions: Although the majority of NF2-associated meningiomas do not grow in the short term, a wide range of growth patterns can be seen. Younger age at first imaging and presence of PTBE are associated with growth. Patients with these characteristics likely benefit from closer follow-up.

Purpose: To examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology., Methods: In this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3-S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14-100 months. In one patient, imaging findings were further correlated to histology., Results: Follow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm 2 vs. 2.15 mm 2 , p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified., Conclusion: Peripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found., (© 2021. The Author(s).)

The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the safety of 3 Tesla (T) magnetic resonance imaging (MRI) in patients with auditory brainstem implants (ABI) with the magnet removed at implantation and report incidence of complications., Study Design: Retrospective chart review., Setting: Tertiary neurotology ambulatory practice., Patients: Patients with diagnosis of Neurofibromatosis, type 2 (NF2) with functional ABIs., Interventions: Observational recordings., Main Outcome Measures: Of the 89 patients meeting inclusion criteria, 7 patients underwent 3T MRI, with a total of 39 scans done. Three patients had 1 scan each, one patient had 4 scans, one patient had 5 scans, one patient had 6 scans, and one patient had 21 scans. The mean time between ABI placement and first 3 T scan was 118 ± 73 months. The most common indication for imaging was surveillance of NF2 lesions. The most frequent scans were MRI brain (25.6%), followed by MRI of cervical (15%), thoracic (15%) and lumbar (15%) spine, and MRI IAC (8%). There were no reported complications for any of the scans. No scans were interrupted due to patient discomfort. There were no device malfunctions., Conclusions: 3 T MRIs are safe in patients with ABIs as long as the magnet is removed. It is recommended that the magnet be removed at the time of implantation in all NF2 patients, who require frequent surveillance., Competing Interests: There are no relevant disclosures, no conflicts of interest, and no funding sources., (Copyright © 2021, Otology & Neurotology, Inc.)

Objectives: Factors contributing to auditory brainstem implant (ABI) outcomes are poorly understood. The aims of this study are to (1) characterize ABI electrode array position on postoperative imaging and (2) determine if variability in position is related to perceptual outcomes., Design: Retrospective cohort study. Subjects were selected from the adult ABI recipient population at Massachusetts Eye and Ear. Postoperative three-dimensional (3D) computed tomography (CT) reconstruction of the head was used to measure ABI array position in 20 adult ABI recipients (17 with Neurofibromatosis Type 2 (NF2) and three non-NF2 recipients). Three-dimensional electrode array position was determined based on angles from the horizontal using posterior and lateral views and on distances between the proximal array tip superiorly from the basion (D1), laterally (D2P) and posteriorly (D2L) from the midline. Array position was correlated with perceptual data (in 15 of the 20 recipients who used their ABI). Perceptual data included the number of electrodes that provided auditory sensation, location and type of side effects, level of speech perception (from no sound to open-set word recognition of monosyllables) and the amount of charge required for auditory perception., Results: Although the 3D orientation of the ABI array exhibited a variety of angles, all arrays were posteriorly tilted from the lateral view and most were medially tilted from the posterior view. ABI position relative to the basion from posterior showed mean distances of 1.71 ± 0.42 and 1.1 ± 0.29 cm for D1 and D2, respectively, and a mean D2 of 1.30 ± 0.45 cm from the lateral view. A strong linear negative correlation was found between the number of active electrodes and the distance of the proximal array tip laterally from the basion (D2P; rs = -0.73, p = 0.006) when measured in the posterior view. Although side effects were experienced in all recipients and varied in type and location across the array, electrodes in the middle part of the array tended to elicit auditory sensations while the proximal and distal tips of the array tended to elicit nonauditory side effects. Arrays with and without low charge thresholds appeared to generally overlap in position. However, the two recipients with the best (open-set) speech perception had low charge thresholds and had arrays that were tilted superiorly in the posterior view., Conclusion: ABI recipients with better speech perception appear to share a profile of arrays that are tilted superiorly as compared to recipients with lower speech perception levels. These ABI recipients have a high number of active electrodes (10 or more) and require less electrical charge on individual electrodes to achieve optimal stimulation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The anti-angiogenic agent bevacizumab is currently the only drug used clinically for neurofibromatosis type 2-related vestibular schwannomas (NF2-VS). Though benefits have been demonstrated in several cases, the standardized dosage remains unclear., Objective: Our meta-analysis was performed to systematically and comprehensively investigate the reliability and toxicity of bevacizumab in the treatment of NF2-VS, with particular emphasis on the impact of dosage., Methods: The literature search was conducted for studies providing data on patients treated with bevacizumab for NF2-VS across PubMed, Embase, and Cochrane Library until December 31, 2020. Two reviewers extracted the incidence rate of results independently. Then we calculated and pooled unadjusted incidence rate with 95% CIs for each study. The subgroups analyzed were conducted., Results: Fourteen citations (prospective or retrospective observational cohort studies) were eligible based on data from a total of 247 patients with NF2 and 332 related VSs. The pooled results showed that the radiographic response rate (RRR) was 30% [95% CI (20%-42%)], the hearing response rate (HRR) was 32% [95% CI (21%-45%)]. The incidence of major complications was: hypertension 29% [95% CI (23%-35%)], proteinuria 30% [95% CI (18%-44%)], menstrual disorders 44% [95% CI (16%-73%)], hemorrhage 14% [95% CI (4%-26%)], grade3/4 events 12% [95% CI (4%-22%)]., Conclusions: Nearly one-third of NF2-VS patients may benefit significantly from bevacizumab due to hearing improvement and tumor reduction. Menstrual disorders were the most common adverse events. The high-dose regimen didn't show better efficacy, but results varied considerably according to age., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Neurofibromatosis type 2 (NF2) is a genetic disorder that is associated with multiple tumors of the nervous system, and approximately one half of patients present with meningiomas. For patients with multifocal disease, somatostatin receptor-targeted peptide receptor radionuclide therapy (PRRT) might be a suitable systemic treatment option., Patients and Methods: Between March 2015 and August 2017, 11 NF2 patients (7 females and 4 males; mean age, 39 ± 12 years) with multifocal, progressive meningiomas underwent a median of 4 cycles of PRRT (range, 2-6 cycles). Acute and chronic adverse events were recorded according to National Institutes of Health's Common Toxicity Criteria (CTC) version 5.0. Follow-up MRIs (every 3 to 6 months), using the Response Assessment in Neuro-Oncology response criteria for meningiomas, were used to assess treatment responses., Results: Peptide receptor radionuclide therapy was well tolerated in all patients without any relevant acute adverse effects. Transient hematologic toxicity (CTC grade 3) was observed in 2 subjects. Somatostatin receptor-directed radiopeptide therapy resulted in radiological disease stabilization in 6 of 11 patients. Median progression-free survival was 12 months (range, 1-55 months), and overall survival was 37 months (range, 5-61 months)., Conclusions: Based on our retrospective pilot data, PRRT is feasible and well-tolerated in NF2 patients. It might offer a suitable treatment option in subjects with multiple, recurrent, or treatment-refractory meningiomas., Competing Interests: Conflicts of interest and sources of funding: This publication was funded by the Interdisciplinary Center of Clinical Research (IZKF) and the University of Würzburg in the funding program Open Access Publishing. None declared to all authors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Neurofibromatosis type 2 (NF2) is a rare, hereditary tumor syndrome, often requiring repeated surgeries for multiple lesions with significant cumulative morbidity. As such, non-operative management should be considered when possible for this patient population. The aim of this study is to provide a systematic review of the literature regarding this treatment strategy. A descriptive case of a patient in whom bevacizumab treatments enabled over 15 years of surgical postponement for a symptomatic spinal cord ependymoma is also provided. Evidence suggests that bevacizumab is a reasonable surgery-deferring option for cystic lesions, and it may be especially useful in NF2 patients to reduce cumulative morbidity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Ring chromosome 22 (r[22]) can lead to the development of intracranial tumors such as meningiomas, neurofibromas, and schwannomas similar to neurofibromatosis 2 (NF2)., Case Presentation: An 18-year-old female with r(22) and a history of global development delay and cognitive impairment presented with sudden hearing loss. MRI revealed bilateral vestibular schwannomas. Given documented audiologic decline in the patient's hearing, the larger tumor was treated with CyberKnife fractionated stereotactic radiosurgery, and the smaller tumor is being monitored., Conclusion: This case provides further evidence that patients with r(22) can develop clinical features of NF2, including the development of bilateral vestibular schwannomas, and should be monitored for hearing disturbances starting in puberty as a warning sign for these tumors., (© 2021 S. Karger AG, Basel.)

Background: There is no dedicated study on outcome after meningioma surgery in neurofibromatosis type 2 (NF2) patients., Methods: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningioma operated in NF2 patients between 2007 and 2017. Descriptive and survival analyses were performed., Results: This nationwide study found 184 patients who were operated on for 315 meningiomas over a 10-year period. 57.6 % were female, median age at first surgery was 40 years IQR[24.8-50.2] and 10.9 % were under 18 years. Cranial convexity (23.4 %) and posterior skull base (16.8 %) were the most common locations. 89.7 % of the tumours were benign and 3.3 % malignant. 16.3 % of the patient received radiotherapy and 13.6 % stereotactic radiosurgery. Median follow-up was 6.3 years, IQR[5.3-7]. At data collection, 28 patients were dead (15.2 %) and median age at death was 41.7 years, IQR [32.7-50.4]. 5 patients died within the year of meningioma surgery. OS rates at 5 and 10 years were: 87.8 %, 95 %CI[82.6-93.3] and 73.2 %, 95 %CI[63.7-84.1] respectively. In univariable Cox regression analysis, Mortality-Related Morbidity Index (MRMI) (HR = 1.57, 95 %CI[1.3-1.9], p < 0.001) Expenditure-Related Morbidity Index (HR1.16, 95 %CI[1.09-1.24], p < 0.001), a malignant meningioma (HR=8.15, 95 %CI[2.78-23.85], p < 0.001), and a diagnosis of deafness or vestibular schwannoma (HR=2.52, 95 %CI[1.02-6.23], p = 0.0447), were associated to the outcome. In multivariable analysis, solely the MRMI and a malignant meningioma remained significant predictors of reduce OS., Conclusion: Using this unique database, we found that outcome of NF2 patients after meningioma surgery is impaired, especially for those with significant co-morbidities and affected by a malignant meningioma., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by rearrangements on chromosome 22q13.3 or sequence variants in SHANK3. Individuals with PMS caused by a 22q terminal deletion and a ring chromosome are at increased risk for Neurofibromatosis type 2 (NF2). However, the prevalence of NF2 in individuals with PMS and a r (22) is unknown. Individuals with PMS and a r (22) chromosome evaluated at the Greenwood Genetic Center (GGC) or by international collaborators, or identified through the PMS International Registry (PMSIR) were contacted and participated in a clinical questionnaire. Forty-four families completed the questionnaire and consented for the study. Of the individuals with a r (22), 7 (16%) carried a diagnosis of NF2. The average age of diagnosis of r (22) was 18 years old in individuals with NF2 and three years old in individuals without NF2 (p-value <0.001). Clinical findings were similar among all individuals in our sample with the exception of hearing loss, present in 57% of individuals with NF2 and 8% of individuals without NF2 (p-value <0.01). This is the largest clinical report of individuals with PMS and a r (22) chromosome. We show a diagnosis of NF2 in individuals with r (22) is not uncommon and may be under ascertained. Moreover, the presentation of NF2 in this cohort is variable and lifelong routine screening for features of NF2 in this population should be considered., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Neurofibromatosis type 2 is a neurogenetic disorder with an incidence of about 1:33.000. Hallmarks are bilateral benign vestibular schwannomas, which can lead to deafness or brainstem compression. Volumetric tumor measurements are essential to assess the efficacy of new therapies. We present a statistical and methodical comparison of three volumetric image analysis tools. We performed volumetric measurements on phantoms with predefined volumes (0.1 to 8.0 ml) and tumors seen on 32 head MRI scans from eight NF2 patients with BrainLab, ITK-Snap, or OsiriX. The software was compared with regard to accuracy and reproducibility of the measurements and time required for analysis. The mean volume estimated by all three software programs differed significantly from the true volume of the phantoms, but OsiriX and BrainLab gave estimates that were not significantly different from each other. For the actual tumors, the estimated volumes with all three software tools showed a low coefficient of variability, but the mean volume estimates differed among the tools. OsiriX showed the shortest analysis time. Volumetric assessment of MRI images is associated to an intrinsic risk of miscalculation. For precise volumes it is mandatory to use the same volumetric tools for all measurements.

Neurofibromatosis type 2 (NF2) is a rare genetic disease involving multiple tumors of the central and peripheral nervous systems. Most patients with NF2 have bilateral vestibular schwannomas; nonvestibular schwannomas may also develop. While the majority of patients may present with hearing impairment, tinnitus, dizziness and balance disorders, some may present with cutaneous manifestations. We describe the case of a 20-year-old man who initially presented with a solitary subcutaneous painless nodule in the left preauricular area without any other symptoms. He received excisional biopsy for the preauricular mass and the pathologic diagnosis was schwannoma. Magnetic resonance imaging of brain and neck revealed multiple mass lesions over the bilateral cerebellopontine angle cisterns, extending to the bilateral internal auditory canals, bilateral cervical neuroforamens, cervical and upper thoracic spinal canals, and left posterior neck. The patient was diagnosed with NF2 according to the clinical criteria. He underwent gamma knife stereotactic radiosurgery for bilateral vestibular schwannomas and is now under regular monitoring. CONCLUSION: NF2 patients may present with an isolated solitary cutaneous schwannoma with no other associated clinical findings. Further assessment is thus warranted in young patients presenting with a peripheral schwannoma despite absence of other clinical findings.

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.

Objective: Closely paralleling previous radiologic studies, recent population-based prevalence data suggest sporadic vestibular schwannoma (VS) affects over one in 2,000 adults and up to one in 500 in those aged 70 years or older. Attributable to increased utilization of magnetic resonance imaging and screening protocols for asymmetrical sensorineural hearing loss, the increasing detection rate of sporadic VS fundamentally changes the perception of VS as a whole. The primary objective of the current study was to contextualize modern epidemiological trends in neurofibromatosis type 2 (NF2) in light of these recent advancements in the understanding of sporadic VS., Study Design: Population-based study., Setting: Olmsted County, Minnesota. Population size on January 1, 2017: 159,689 people., Patients: All patients with NF2 diagnosed between Jan 1, 1966 and Dec 31, 2016, identified using the Rochester Epidemiology Project., Main Outcome Measures: Incidence, prevalence., Results: Six incident cases were identified over the past 50 years. From 1966 to 2016, the age- and sex-adjusted incidence rate was 0.10 per 100,000 person-years. The incidence rate remained at 0.12 over the most recent decade. Five cases met disease prevalence criteria, and the age- and sex-adjusted prevalence of NF2 on Jan 1, 2017 was 3.1 per 100,000 persons. All prevalent cases were women, and the resultant prevalence among women only was 6.0 per 100,000 persons., Conclusions: The modern age- and sex-adjusted incidence rate and prevalence of NF2 is 0.10 per 100,000 person-years and 3.1 per 100,000 persons, respectively. In contrast to trends in incidence rates of sporadic VS over the last half-century, this study demonstrates that the incidence of NF2 has remained relatively stable since 1966. This divergence in epidemiological trends is likely attributed to the nature of NF2, with early clinical manifestations resulting in diagnosis regardless of modern advances, whereas the increased incidence of sporadic VS is heavily influenced by improved detection in a greater population of patients with minimally symptomatic or asymptomatic tumors.

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are three clinically distinct tumor predisposition syndromes with a shared tendency to develop peripheral and central nervous system neoplasms. Disease expression and complications of NF1, NF2, and SWN are highly variable, necessitating a multidisciplinary approach to care in order to optimize outcomes. This review will discuss the imaging appearance of NF1, NF2, and SWN and highlight the important role that imaging plays in informing management decisions in people with tumors associated with these syndromes. Recent technological advances, including the role of both whole-body and localized imaging strategies, routine anatomic and advanced magnetic resonance (MR) imaging sequences such as diffusion-weighted imaging (DWI) with quantitative apparent diffusion coefficient (ADC) mapping, and metabolic imaging techniques (MR spectroscopy and positron emission testing) are discussed in the context of the diagnosis and management of people with NF1, NF2, and SWN based on the most up-to-date clinical imaging studies.

Objective: To examine the involvement of dorsal root ganglia and peripheral nerves in children with neurofibromatosis type 2 compared to healthy controls and symptomatic adults by in vivo high-resolution magnetic resonance neurography., Methods: In this prospective multicenter study, the lumbosacral dorsal root ganglia and sciatic, tibial, and peroneal nerves were examined in 9 polyneuropathy-negative children diagnosed with neurofibromatosis type 2 by a standardized magnetic resonance neurography protocol at 3T. Volumes of dorsal root ganglia L3 to S2 and peripheral nerve lesions were assessed and compared to those of 29 healthy children. Moreover, dorsal root ganglia volumes and peripheral nerve lesions were compared to those of 14 adults with neurofibromatosis type 2., Results: Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in children with neurofibromatosis type 2 (L3 +255%, L4 +289%, L5 +250%, S1 +257%, and S2 +218%, p < 0.001) with an excellent diagnostic accuracy. Moreover, peripheral nerve lesions occurred with a high frequency in those children compared to healthy controls (18.89 ± 11.11 vs 0.90 ± 1.08, p < 0.001). Children and adults with neurofibromatosis type 2 showed nonsignificant differences in relative dorsal root ganglia hypertrophy rates ( p = 0.85) and peripheral nerve lesions ( p = 0.28)., Conclusions: Alterations of peripheral nerve segments occur early in the course of neurofibromatosis type 2 and are evident even in children not clinically affected by peripheral polyneuropathy. While those early alterations show similar characteristics compared to adults with neurofibromatosis type 2, the findings of this study suggest that secondary processes might be responsible for the development and severity of associated polyneuropathy., (© 2019 American Academy of Neurology.)

Objective: To investigate whether [F]fluorothymidine (FLT) and/or [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate growth in neurofibromatosis 2 (NF2) related vestibular schwannomas (VS) and to evaluate the importance of PET scanner spatial resolution on measured tumor uptake., Methods: Six NF2 patients with 11 VS (4 rapidly growing, 7 indolent), were scanned with FLT and FDG using a high-resolution research tomograph (HRRT, Siemens) and a Siemens Biograph TrueV PET-CT, with and without resolution modeling image reconstruction. Mean, maximum, and peak standardised uptake values (SUV) for each tumor were derived and the intertumor correlation between FDG and FLT uptake was compared. The ability of FDG and FLT SUV values to discriminate between rapidly growing and slow growing (indolent) tumors was assessed using receiver operator characteristic (ROC) analysis., Results: Tumor uptake was seen with both tracers, using both scanners, with and without resolution modeling. FDG and FLT uptake was correlated (R = 0.67-0.86, p < 0.01) and rapidly growing tumors displayed significantly higher uptake (SUVmean and SUVpeak) of both tracers (p < 0.05, one tailed t test). All of the PET analyses performed demonstrated better discriminatory power (AUCROC range = 0.71-0.86) than tumor size alone (AUCROC = 0.61). The use of standard resolution scanner with standard reconstruction did not result in a notable deterioration of discrimination accuracy., Conclusion: NF2 related VS demonstrate uptake of both FLT and FDG, which is significantly increased in rapidly growing tumors. A short static FDG PET scan with standard clinical resolution and reconstruction can provide relevant information on tumor growth to aid clinical decision making.

Background: The vast majority of cerebellopontine angle tumors are benign with a favorable prognosis. Metastatic tumors occurring in the cerebellopontine angle are extremely rare. Herein, we report a case of colon carcinoma metastasis to the bilateral internal auditory canals., Case Description: A 59-year-old man presented with a 2-week history of binaural hearing loss. One year before admission, he was diagnosed with colon carcinoma and underwent surgical resection combined with chemotherapy. Physical examination showed complete hearing loss in bilateral ears and bilateral facial palsy. Magnetic resonance imaging of the brain revealed nodules in the bilateral internal auditory canals. Middle-ear computed tomography demonstrated soft-tissue masses extending into the bilateral internal auditory canals. A diagnosis of neurofibromatosis type II was suspected. A unilateral surgical resection of the cerebellopontine angle tumor was performed. Postoperatively, the hearing loss and facial palsy remained unchanged. Pathologic examination showed metastatic, poorly differentiated carcinoma. The patient was diagnosed with metastatic colon carcinoma in the bilateral internal auditory canals. The patient refused radiotherapy and chemotherapy. The tumor progressed rapidly, and the patient developed dysphagia and choking 1 month later. The patient died of respiratory and circulatory failure 2 months after the surgery., Conclusions: Clinicians should be aware of metastatic tumors in the internal auditory canals. Comprehensive clinicoradiologic evaluation should be highlighted. A history of malignancy and rapidly progressive hearing loss and facial palsy may suggest the diagnosis of metastasis to the internal auditory canal. The definitive diagnosis still depends on histopathologic examination., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Unlike adult neurofibromatosis type 2 (NF2), which presents with symptoms related to bilateral vestibular schwannomas, children with NF2 most frequently present with ocular, dermatological, and neurological symptoms. Arteriopathy, a well-established feature in neurofibromatosis type 1, is not a widely recognized feature of NF2. Here we report three children with NF2 with cerebral arteriopathy and/or arterial ischaemic stroke. Bevacizumab, a vascular endothethial growth factor inhibitor, is an established treatment for rapidly growing vestibular schwannomas; however, it carries a risk of both ischaemic and haemorrhagic stroke. Thus, the role of screening and risk to benefit ratio of bevacizumab in NF2 merit further consideration. WHAT THIS PAPER ADDS: Children with neurofibromatosis type 2 (NF2) may be at increased risk of cerebral vasculopathy and arterial ischaemic stroke. Targeted magnetic resonance angiography should be performed in children with NF2 who are being considered for bevacizumab therapy., (© 2018 Mac Keith Press.)

Meningioangiomatosis (MA) is a rare, complex and heterogeneous disease of meningovascular proliferation that is found primarily in the leptomeninges and cerebral cortex but can involve subcortical white matter and other brain regions such as the cerebellum and deep gray matter. MA may be found in pediatric or adult populations and may be sporadic or neurofibromatosis-associated. The presentation of MA is highly variable: it may be associated with other neurological diseases; clinically presents on a spectrum from asymptomatic to seizures or focal deficits; radiologically presents with multifocal, tumor-like, or cystic lesions, or may appear normal; and pathologically may have cellular or vascular predominance. In this article, we review the various manifestations of MA including neurofibromatosis-associated MA, multifocal MA, cystic MA, and MA associated with meningioma, other brain tumors, focal cortical dysplasia, neurodegenerative changes, and post-radiation changes. The treatment of MA is also reviewed. While the pathogenesis of MA remains elusive, we discuss the proposed theories such as developmental, dysplastic, hamartomatous or reactive ethology in given variants. It is important for physicians to be aware of MA as more research on this complex entity is needed and timely diagnosis may benefit outcomes in patients with MA., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: Resection of a vestibular schwannoma may result in facial paralysis and hearing loss on the side of the tumor. We evaluated clinical, audiologic, and intraoperative events and radiologic parameters in a case of contralateral side sensorineural hearing loss. We also performed a literature search using PubMed., Case Description: A 25-year-old woman with neurofibromatosis 2 developed contralateral side sensorineural hearing loss immediately after resection of vestibular schwannoma. The patient regained partial hearing with a short course (2 months) of steroid therapy over 6 months., Conclusions: Literature search yielded 20 cases. We evaluated possible etiology, pattern, extent, recovery, and final outcome in these patients with management options. Several etiologies have been proposed, including development of endolymphatic hydrops, vascular phenomenon, mechanical injury, barotrauma, and autoimmune cochleolabyrinthitis. Sudden release of cerebrospinal fluid seemed to be the most likely explanation in the present case. There is no way to predict this complication beforehand. Operating in supine position, slow release of cerebrospinal fluid, irrigation of the operating field, maintenance of normotension, and judicious use of the drill may help in prevention. A short course of corticosteroids and vasodilators helped in spontaneous recovery in most of the cases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Epidermal growth factor receptors EGFR and ErbB2 are overexpressed in schwannomas and meningiomas. Preclinical and clinical data indicate that lapatinib, an EGFR/ErbB2 inhibitor, has antitumor activity against vestibular schwannomas in neurofibromatosis type 2 (NF2) patients. Its antitumor activity against meningiomas, however, is unknown., Methods: We conducted a retrospective review of patients with NF2 and progressive vestibular schwannomas treated on a phase 2 clinical trial with lapatinib (NCT00973739). We included patients with at least one volumetrically measurable meningioma (> 0.5 cm 3 ) who received at least five 28-day courses of treatment. Patients received lapatinib 1500 mg daily. Meningioma response was assessed using 3-dimensional MRI volumetrics. Progressive meningioma growth and response were defined as + 20 and - 20% change in tumor volume from baseline, respectively. Off-treatment was defined as any period > 5 months without lapatinib., Results: Eight patients (ages: 20-58 years) who met criteria had 17 evaluable meningiomas with a combined volume of 61.35 cc at baseline, 61.17 cc during treatment, and 108.86 cc (+ 77.44% change) off-treatment, p = 0.0033. Median time on-treatment and off-treatment was 15.5 and 16.7 months, respectively. On-treatment mean and median annualized growth rates were 10.67 and 1.32%, respectively. Off-treatment mean and median annualized growth rates were 20.05 and 10.42%, respectively. The best volumetric response was - 26.1% after 23 months on lapatinib. Two tumors increased > 20% volumetrically on-treatment, compared to eight tumors off-treatment., Conclusions: These data suggest that lapatinib may have growth-inhibitory effects on meningiomas in NF2 patients, and support prospective studies of lapatinib for NF2 patients with progressive meningiomas.

Purpose: To study the natural history, clinical and radiological characteristics of primary paediatric optic nerve sheath meningioma (PPONSM)., Methods: Retrospective study of eight paediatric patients who were treated between 1994 and 2016 at the University Hospital Zurich, Switzerland and the Royal Adelaide Hospital, Australia. Clinical records and imaging studies were reviewed., Results: The mean age at presentation was 11 years (range: 6-17 years). There were six female patients and two male patients. 2/8 patients had associated neurofibromatosis type 2. Patients were followed up for 71-297 months (mean 156±70 months). 6/8 patients were observed through the course of their disease and 2/8 patients were treated with radiotherapy. 2/8 patients who were observed had minimal change in vision and did not experience tumour growth after long-term follow-up., Conclusions: This is the largest PPONSM case series with long-term data on patients treated conservatively. We highlight that a small subset of these tumours are indolent and can be managed using observation alone., Competing Interests: Competing interests: GT is supported by ‘Filling the Gap’ of the University of Zurich, Zurich, Switzerland., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Previous studies have measured cerebral blood flow (CBF) with DSC-MRI using an "early time points" (ET) method based on microsphere theory., Purpose: To develop and assess a new ET method for absolute CBF estimation using low-dose high-temporal (LDHT) T1W-DCE-MRI., Study Type: Retrospective cohort study., Subjects: Seven patients with sporadic vestibular schwannoma (VS) who underwent test-retest imaging; one patient with glioblastoma multiforme (GBM) imaged pretreatment; and 12 neurofibromatosis type 2 (NF2) patients undergoing bevacizumab treatment, imaged pre- and 90 days posttreatment., Field Strength/sequence: LDHT-DCE-MRI was performed at 1.5 and 3.0T, using 3D spoiled gradient echo with phase cycling. DSC-MRI performed in one patient, using 3D echo-shifted multi-shot echo-planar imaging (PRESTO) at 3T., Assessment: Through Monte Carlo simulations, CBF estimation using three newly developed average contrast agent concentration (AC) -based methods (ACrPK, ACrMG, ACcomb), was compared against conventional maximum gradient (MG) approaches, at varying Rician noise levels. Reproducibility and applicability of the ACcomb method was assessed in our sporadic-VS/GBM/NF2 patient cohort, respectively., Statistical Tests: Reproducibility was measured using test-retest coefficient of variation (CoV). Pre- and posttreatment CBF values were compared using paired t-test with Bonferroni correction., Results: Monte Carlo stimulations demonstrated that AC-based methods, particularly ACcomb, offered superior accuracy to conventional MG approaches. Overall test-retest CoV using the ACcomb method was 5.76 in normal-appearing white matter (NAWM). The new ACcomb method produced gray matter/white matter CBF estimates in the NF2 patient cohort of 55.9 ± 13.9/25.8 ± 3.5 on day 0; compared with 155.6 ± 17.2/128.4 ± 29.1 for the classical MG method. There was a moderate (10% using ACcomb and ACrPK) increase in CBF of NAWM 90 days post therapy (P = 0.03 and 0.005)., Data Conclusion: Our new AC-based method of CBF estimation offers excellent reproducibility, and displays more accuracy in both Monte Carlo analysis and clinical data application, than conventional MG-based approaches., Level of Evidence: 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2018;48:543-557., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: Patients with neurofibromatosis type 2 and bilateral vestibular schwannoma (VS) are frequently treated surgically for any tumor progression, and often repeated surgery or radiation treatment is even considered. Some VS progression occurs without the development of new clinical symptoms, or it does not progress in size over many years, even in the absence of any specific treatment., Case Description: A 61-year-old male patient with neurofibromatosis type 2 presented with bilateral VS. In a long-term follow-up, both had increased in size but also showed bilateral spontaneous regression during an 11-year follow-up period with a "watch-and-wait" strategy., Conclusions: We emphasize conservative treatment ("watch and wait") in older patients even with long-term tumor progression without significant compression-related clinical symptoms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The wait and scan policy is being increasingly used as the first measure after the diagnosis of a vestibular schwannoma (VS) using magnetic resonance imaging (MRI). As part of the European Academy of Otology and Neuro-Otology (EAONO) position statement on VS, the frequency of imaging has been studied in the literature. Among 163 studies, 29 fulfilled the inclusion criteria and were scored using the Grading of Recommendations, Assessment, Development, and Evaluation system. Because tumor growth rate during the first 5 years of follow-up is predictive of further growth during the upcoming years, a protocol for wait and scan is useful for centers dealing with this condition. The EAONO proposal is that after the initial diagnosis by MRI, a first new MRI would take place after 6 months, annually for 5 years, and then every other year for 4 years, followed by a lifelong MRI follow-up every 5 years. The first early MRI is to screen for fast-growing tumors, and the lifelong follow-up with tapered intervals is to detect late repeated growth.

Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and peripheral neuropathy has been reported in both. We prospectively applied in vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4, + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni-adjusted p < 0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. Ann Neurol 2018;83:854-857., (© 2018 American Neurological Association.)

Most patients diagnosed with neurofibromatosis type 2 (NF2) have bilateral vestibular schwannomas (VS). Through reviewing surgical method and clinical outcomes, we tried to find out a strategy for treatments in NF2 patients with VS.We retrospectively reviewed patients diagnosed pathological NF2 and have had microsurgery (MS) for VS in the PLA Army General Hospital. Seventeen patients were included from January 2000 to December 2016. Fifteen patients had progressive hearing impairment, and 7 ears were totally deaf. Computed tomography and magnetic resonance imaging were used for preoperative and postoperative evaluation. House-Brackmann (H-B) classification was used to evaluate facial function, and the hearing outcome was classified according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification system. The outcomes included functional hearing, facial function, and complications.In the 17 patients, 9 were men, and the mean age was 27.2 years old. The mean duration of disease was 38.4 months. Twenty-six VS were excised. Nine patients with bilateral VS and unilateral surgery had repeated surgery for the contralateral tumor after 3 to 12 months. The hearing preservation rate was 41.6%. In the 26 excisions for VS, 24 had intact facial nerve. In the other 2 tumor excision, damaged facial nerves had head-to-head adhesion using biological fibrin glue. The rate of facial nerve function preservation was 60%. No mortality or major complication was reported. The follow-up time ranged from 11 to 78 months with a mean value of 39 months.MS is an effective treatment for NF2 patients with VS. The operation for bilateral VS should be staged according to tumor size and bilateral hearing function. However, methods on how to preserve functional hearing and facial function remain the issue. Further randomized controlled studies are needed to find out a better treatment for NF2 patients with VS according to the overall condition.

Introduction: Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce., Methods: We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS)., Results: A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings., Discussion: HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018., (© 2017 Wiley Periodicals, Inc.)

OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm 3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients experienced worsening of trigeminal nerve function. Facial nerve function worsened in 1 patient (2.5%). No significant differences in tumor control, hearing preservation, or complications were found in comparing the results of GKRS for NF2-related VS versus GKRS for sporadic VS. CONCLUSIONS With modern GKRS, the use of low margin doses for treating growing VSs in patients with NF2 demonstrates good long-term tumor control rates. Feiling-Gardner phenotype and tumor volume smaller than 6 cm 3 seem to be independently associated with prolonged progression-free survival, highlighting the clinical importance of phenotype assessment before GKRS treatment. In addition, no significant differences in tumor control rates or complications were found in the matched-control cohort analysis comparing GKRS for VS in patients with NF2 and GKRS for sporadic VS. These results show that GKRS is a valid treatment option for NF2-related VS, in addition to being a good option for sporadic VS, particularly in patients with the Feiling-Gardner phenotype and/or tumors that are small to medium in size. Larger tumors in patients with the Wishart phenotype appear to respond poorly to radiosurgery, and other treatment modalities should therefore be considered in such cases.

Background: For treating a patient with multiple falcine and parasagittal lesions, we believe that it is beneficial to resect the maximum possible number of lesions during one operation, even if some lesions are asymptomatic. This practice can potentially reduce the total number of operations during a patient's lifetime., Methods: We provide an introduction of a concurrent endoscopic approach via the interhemispheric fissure., Conclusions: Applying this endoscopic approach concurrently with conventional microscopic surgery can enable the safe resection of as many lesions as possible during one operation.

There have been anecdotal reports of vasculopathy associated with Neurofibromatosis Type 2 (NF2). Given the increasing use of bevacizumab, a vascular endothelial growth factor inhibitor which results in an increased risk of bleeding, it is important to ascertain if there is a predisposition to vascular abnormalities in NF2. In our unit NF2 patients undergo annual MRI brain and internal auditory meatus imaging. We noted incidental intracranial aneurysms in some patients and sought to determine the prevalence of intracranial aneurysms in our cohort of NF2 patients. We conducted a retrospective audit of the MRI images of 104 NF2 patients from 2014 to 2016. Axial T2 brain MRI images were assessed for vascular abnormalities by two neuroradiologists blinded to patient's clinical details. Intracranial aneurysms were detected in four patients and an aneurysm clip related to previous surgery was noted in one additional patient. Using standard MRI imaging sequences alone we provide evidence of intracranial aneurysms in 4.4% of our cohort. This compares with an estimated overall prevalence of 3% in the general population. We discuss these findings as well as other evidence for a vasculopathy associated with NF2., (© 2017 Wiley Periodicals, Inc.)

Background: Although the natural history of vestibular schwannomas (VS) has been previously studied, few studies have investigated associated epidemiological factors, primarily because of the lack of large available cohorts., Objective: The objective of this study was to perform a multi-scale geographical analysis of the period prevalence of VS in West Scotland from 2000 to 2015., Methods: Adults diagnosed with sporadic VS were identified through the National Health Services of West Scotland database and geocoded to the unit postcode. To assess whether the cohort of VS cases could be pooled into a period prevalence measure, the locations of VS cases were analyzed by sex using Cross-L and Difference-K functions. VS period prevalence was examined at two aggregate spatial scales: the postcode district and a coarser scale of NHS Health Boards. The spatial structure of period prevalence within each level of spatial aggregation was measured using univariate global and local Moran's I. Bivariate local Moran's I was used to examine the between-scale variability in period prevalence from the postcode district level to the NHS Health Boards levels. Prior to spatial autocorrelation analyses, the period prevalence at the postcode district was tested for stratified spatial heterogeneity within the NHS Health Boards using Wang's q-Statistic., Results: A total of 512 sporadic VS were identified in a population of over 3.1 million. Between 2000 and 2015, VS period prevalence was highest within the NHS Health Boards of Greater Glasgow and Clyde, Ayrshire and Arran and the Western Isles. However, at the NHS scale, period prevalence exhibited no spatial autocorrelation globally or locally. At the district scale, Highland exhibited the most unusual local spatial autocorrelation. Bivariate local Moran's I results indicated general stability of period prevalence across the postcode district to Health Boards scales. However, locally, some postcode districts in Greater Glasgow and Clyde, Ayrshire and Arran exhibited unusually low district to zone spatial autocorrelation in period prevalence, as did the southern parts of the Western Isles. Some unusually high period prevalence values between the postcode district to Health Board scale were found in Tayside, Forth Valley and Dumfries and Galloway., Conclusion: Geographic variability in VS in West Scotland was identified in this patient population, showing that there are areas, even remote, with unusually high or low period prevalence. This can be partially attributed to links between primary and tertiary care. Potential genetic or environmental risk factors that may contribute to geographic variation in this disease within Scotland are also a possibility but require further investigation.

Objective: The neurofibromatoses (NF) type 1 and 2 are hereditary tumor predisposition syndromes caused by germline mutations in the NF1 and NF2 tumor suppressor genes. In NF1 and 2, peripheral nerve tumors occur regularly. For further characterizing nerve ultrasound was performed in patients with NF1 and 2., Methods: Patients with established diagnosis of NF1 (n=27) and NF2 (n=10) were included. Ultrasound of peripheral nerves and cervical roots was performed during routine follow-up visits. Healthy volunteers were studied for comparison., Results: In patients with NF1, median cross-sectional area (CSA) of most nerves was significantly increased compared to controls and to NF2 due to generalized plexiform tumors, which arose out of multiple fascicles in 23 of 27 patients (85%). These were often accompanied by cutaneous or subcutaneous neurofibromas. In NF2, the overall aspect of peripheral nerves consisted of localized schwannomas (80%) and, apart from that, normal nerve segments., Conclusion: Nerve ultrasound is able to visualize different nerve pathologies in NF1 and NF2. It is a precise and inexpensive screening method for peripheral nerve manifestation in neurofibromatosis and should be considered as the first choice screening imaging modality for all peripheral nerves within reach of non-invasive ultrasound techniques., Significance: Ultrasound patterns of peripheral nerve pathologies are described for the first time in a large cohort of patients with NF1 and NF2. It is a suitable screening tool and enables targeted MRI analysis., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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.