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Purpose: This retrospective monocentric study aimed to evaluate long-term auditory brainstem implant (ABI) function in patients with neurofibromatosis type 2, and to investigate the prognostic factors for ABI use., Methods: Between 1997 and 2022, 27 patients with at least five years of follow-up underwent implantation with 32 ABIs. At 1- and 5-years post-implantation and at last follow-up, ABIs were classified as used or non-used and the size of the ipsilateral tumor was recorded. For patients who used their ABIs, we assessed speech perception (disyllabic words, MBAA sentences) in quiet conditions with the ABI only, by lip-reading (LR), and with a combination of the two (ABI + LR). Hearing improvement was calculated as Δ ABI = (ABI + LR)-LR scores. Predictive factors for ABI use were analyzed., Results: One year post-implantation, 74% patients were ABI-users and 66% of the ABIs were used. Two of these patients were non-users at five years, and another two at last follow-up (14 ± 5.2 years); 54% of the patients were ABI-users at last follow-up. Δ ABI revealed a hearing improvement of 32-41% (disyllabic words) and 28-37% (MBAA sentences). Among 16 ABIs with at least LR improvement at 1-year post-implantation, 4 decreased their performance, coinciding with a large growing ipsilateral tumor in 3/4 ABIs. We identified no significant prognostic factors for ABI use., Conclusions: ABIs are indicated in case of bilateral deafness with a non-functional cochlear nerve. Half the patients with ABIs used their implants and auditory performance remained stable over time, except in cases of ipsilateral tumor growth., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Competing Interests: M. Kalamarides déclare n’avoir aucun lien d’intérêts.

Objectives: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis., Methods: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing., Results: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm 3 /year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001)., Conclusions: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate long-term hearing outcomes following cochlear implantation in patients with neurofibromatosis type 2 and ipsilateral vestibular schwannoma., Study Design: Retrospective study., Setting: Tertiary general hospital., Methods: Twenty-two patients undergoing cochlear implantation between 2004 and 2018 with at least 1 year of follow-up were included. Patients were categorized as "users" or "nonusers" of their cochlear implant (CI). For users, speech perception (disyllabic words) without lip-reading was assessed in quiet conditions 1-year postimplantation, and annually thereafter. CI users were classified into 2 groups on the basis of speech intelligibility (≥40% or <40%). Demographic data, treatment options, and tumor size were also recorded., Results: One year after implantation, 16 (73%) patients used their CI daily. Twelve of these patients had a speech intelligibility ≥40% (mean: 74 ± 21.9%). Three had a Koos stage IV tumor. At the last visit (mean duration of follow-up: 6 ± 5 years), 12 of these 16 patients were still using their implant daily, and 6 had a speech intelligibility ≥40%. No predictive factors for good performance at 1 year or performance stability were identified., Conclusion: Neurofibromatosis type 2 is a complex disease profoundly affecting patient quality of life, and cochlear implantation should always be considered on a case-by-case basis. In some individuals, cochlear implantation can provide good speech intelligibility for extended periods, even posttreatment or in cases of large tumors., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

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.)

Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most common of which are the vestibular schwannomas (VS). These tumors arise from Schwann cells of the vestibulocochlear nerve and their main cause is the loss of function of NF2, with 95 % of cases being sporadic and 5 % being part of the rare neurofibromatosis type 2 (NF2)-related Schwannomatosis. Genetic variations in NF2 do not fully explain the clinical heterogeneity of VS, and interactions between Schwann cells and their microenvironment appear to be critical for tumor development. Preclinical in vitro and in vivo models of VS are needed to develop prognostic biomarkers and targeted therapies. In addition to VS, other tumors can affect hearing. Meningiomas and other masses in the cerebellopontine angle can compress the vestibulocochlear nerve due to their anatomic proximity. Gliomas can disrupt several neurological functions, including hearing; in fact, glioblastoma multiforme, the most aggressive subtype, may exhibit early symptoms of auditory alterations. Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Tethered spinal cord syndrome (TCS) is characterized by cutaneous attachments on the filum terminale that stretch the spinal cord, leading to musculoskeletal and urogenital sequelae. While the neurocutaneous associations with TCS remain undefined, a recent study reports a high incidence of TCS among a pediatric neurofibromatosis (NF) cohort. This present study utilizes a population-level database to estimate TCS incidence among pediatric patients with neurofibromatosis types 1 and 2 (NF1, NF2)., Methods: The TriNetX Research Network was queried to identify patients diagnosed with NF and/or TCS before the age of 21. Symptomatic TCS requiring surgical intervention was identified using corresponding procedural codes within 12 months following TCS diagnosis. Odds ratios (OR) were calculated to measure the associations of NF1/NF2 with TCS., Results: 19,426 pediatric NF patients were evaluated (NF1: 18,383, NF2: 1042). The average ages of TCS diagnosis among NF1, NF2, and non-NF patients were 12, 16, and 9 years, respectively. The incidence of TCS was 1.2% in NF1 patients and 7.3% in NF2 patients, compared to 0.074% in the general population. The associations of NF incidence with TCS were significantly increased in both NF1 (OR 16.42; 14.38-18.76) and NF2 (OR 105.58; 83.56-133.40) patients compared to the general population. Symptomatic TCS requiring surgical intervention was not significantly associated with NF1/NF2 patients compared to the general TCS population., Conclusion: This analysis demonstrates a high incidence of TCS but delayed intervention in pediatric NF patients. Considering TCS counseling, spinal MRI, and earlier intervention may be warranted for NF patients experiencing musculoskeletal symptomatology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Concurrent occurrence of schwannoma and meningiomas are rare, and are found especially in association with neurofibromatosis type 2 (NF2). Occurrence of mixed tumor without the aforementioned conditions is extremely rare. We present three cases of mixed tumor in different locations, including two with NF2 and one without NF2. We analyse the relationship of mixed tumor with NF2 and its clinical implications. Presence of mixed schwannoma-meningioma should prompt screening for NF2. Thus aids in early diagnosis of unsuspected NF2 cases. We observed that irrespective of different locations, cases with NF2 showed frequent recurrence of schwannoma as compared to case who did not fit in the existing clinical criteria for NF2. Collision tumor and thereby NF2 mutations indicates the prognosis and recurrence of the tumor, thereby guides in deciding the management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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).)

Objective: Cochlear implants (CIs) are a well-established treatment modality for hearing loss due to neurofibromatosis type 2 (NF2). Our aim is to investigate variables that affect longitudinal performance of CIs among patients with NF2., Study Design: Retrospective review at a single academic institution consisting of patients who have received cochlear implants following hearing loss due to NF2., Methods: The primary outcome examined was CI disuse or explantation. Associated clinical and surgical variables were analyzed using descriptive statistics. These included postoperative pure tone average (PTA) at 500, 1000, and 2000 Hz, tumor size, previous surgery, and comorbid depression., Results: A total of 12 patients and 14 cochlear implants received at our institution from 2001 to 2022 were included. Notably, 35.7% of CIs (5 out of 14 cases) resulted in disuse or explantation. The average interval until explant was 9.4 years (range 3-14 years). In explanted CI cases, 20% had previous surgery and 80% had a diagnosis of comorbid depression as compared to 22.2% and 22.2%, respectively, in intact CI cases. Maximum tumor diameter was the only variable found to impact CI usage outcome (p = 0.028). Long-term data showed that on average, patients benefit from 13.85 years of CI utility and a maximum PTA improvement of 45.0 ± 29.0 dB., Conclusion: Despite the recurrent nature of NF2, patients continue to receive audiological benefit from cochlear implants. We found that larger tumor size may be associated with longitudinal CI failure., Level of Evidence: 4 Laryngoscope, 134:1847-1853, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Meningioma is the second most frequent tumor in patients with neurofibromatosis type 2 (NF2). The presence of meningioma is believed to be a negative prognostic marker in these patients. However, the molecular mechanisms involved in the tumorigenesis of NF2-associated meningioma are not well characterized. Epigenetic regulation, including microRNAs (miRNAs), may be involved in the development of different tumor types in patients with NF2. The objective of this study is to explore the different characteristics of serum miRNA expression depending on the presence or absence of meningioma in patients with NF2. Nine patients with NF2 who were treated at the Department of Neurosurgery, Hiroshima University Hospital, were included. Total RNA (including small RNAs) was extracted from serum samples for the preparation of a small RNA library for next-generation sequencing analysis. Differentially expressed miRNAs (DEMs) were analyzed using the DESeq2 package to compare the characteristic miRNA expression profiles of patients with and without meningioma. In small RNA sequencing analysis, out of a total of 1,879 miRNAs registered in the database, the expressions of 657 miRNAs were observed. In DEM analysis, the expressions of four miRNAs, namely, hsa-miR-664b, hsa-miR-7706, hsa-miR-590, and hsa-miR-6513, were downregulated in patients with NF2 with meningioma compared with patients with NF2 without meningioma. Hsa-miR-193a was identified as the only upregulated miRNA in patients with NF2 with meningioma. In conclusion, we identified different circulating miRNA expression characteristics depending on the presence or absence of meningioma in patients with NF2.

Background: Neurofibromatosis type 2-related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and cataracts. Mild to profound hearing loss and tinnitus are common symptoms reported by individuals with neurofibromatosis type 2. While tinnitus is known to have a significant and negative impact on the quality of life of individuals from the general population, the impact on individuals with neurofibromatosis type 2 is unknown. Consensus regarding the selection of suitable patient-reported outcome measures for assessment could advance further research into tinnitus in neurofibromatosis type 2 patients. The purpose of this work is to achieve a consensus recommendation by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration for patient-reported outcome measures used to evaluate quality of life in the domain of tinnitus for neurofibromatosis type 2 clinical trials., Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis Patient-Reported Outcomes Communication Subgroup systematically evaluated patient-reported outcome measures of quality of life in the domain of tinnitus for individuals with neurofibromatosis type 2 using previously published Response Evaluation in Neurofibromatosis and Schwannomatosis rating procedures. Of the 19 identified patient-reported outcome measures, 3 measures were excluded because they were not validated as an outcome measure or could not have been used as a single outcome measure for a clinical trial. Sixteen published patient-reported outcome measures for the domain of tinnitus were scored and compared on their participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials., Results: The Tinnitus Functional Index was identified as the most highly rated measure for the assessment of tinnitus in populations with neurofibromatosis type 2, due to strengths in the areas of item content, psychometric properties, feasibility, and available scores., Discussion: Response Evaluation in Neurofibromatosis and Schwannomatosis currently recommends the Tinnitus Functional Index for the assessment of tinnitus in neurofibromatosis type 2 clinical trials., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Facial paralysis secondary to neurofibromatosis type 2 (NF2) presents the reconstructive surgeon with unique challenges because of its pathognomonic feature of bilateral acoustic neuromas, involvement of multiple cranial nerves, use of antineoplastic agents, and management. Facial reanimation literature on managing this patient population is scant., Methods: A comprehensive literature review was performed. All patients with NF2-related facial paralysis who presented in the past 13 years were reviewed retrospectively for type and degree of paralysis, NF2 sequelae, number of cranial nerves involved, interventional modalities, and surgical notes., Results: Twelve patients with NF2-related facial paralysis were identified. All patients presented after resection of vestibular schwannoma. Mean duration of weakness before surgical intervention was 8 months. On presentation, one patient had bilateral facial weakness, 11 had multiple cranial nerve involvement, and seven were treated with antineoplastic agents. Two patients underwent gracilis free functional muscle transfer, five underwent masseteric-to-facial nerve transfer (of whom two were dually innervated with a crossfacial nerve graft), and one patient underwent depressor anguli oris myectomy. Trigeminal schwannomas did not affect reconstructive outcomes if trigeminal nerve motor function on clinical examination was normal. In addition, antineoplastic agents such as bevacizumab and temsirolimus did not affect outcomes if stopped in the perioperative period., Conclusions: Effectively managing patients with NF2-related facial paralysis necessitates understanding the progressive and systemic nature of the disease, bilateral facial nerve and multiple cranial nerve involvement, and common antineoplastic treatments. Neither antineoplastic agents nor trigeminal nerve schwannomas associated with normal examination affected outcomes., Clinical Question/level of Evidence: Therapeutic, V., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disease (frequency 1 in 25-90 000) characterized by the formation of tumors of the central nervous system due to a mutation in the NF2 gene on chromosome 22q12. Bilateral vestibular schwannomas are recognized as absolute diagnostic criteria of NF2 and occur in 95% of patients, are accompanied by hearing impairment, manifest at the age of 18-24 years. Skin manifestations can precede vestibular schwannomas for several years and predict the course of the disease: neurofibromas, cafe-au-lait macules, hypopigmented spots, recently described mesh capillary malformations. Despite the benign nature of schwannomas, they can lead to hearing loss, vestibular dysfunction, facial nerve paralysis, gait disorders, pain and convulsions, there is a risk of early death from compression of the brain stem. The probability of progressive hearing loss is partly determined by the type of mutation. We described a clinical case of NF2 in a 21-year-old patient with bilateral vestibular schwannomas without hearing loss, whose skin examination by ENT specialist revealed this disease. The importance of the presented observation is that the doctor should assume neurofibromatosis type 2 in a young patient with bilateral vestibular schwannomas. It is necessary to undertake a further examination of this patient, including: skin examination for the identification of characteristic neurofibromas and cafe-au-lait macules, consultation with an ophthalmologist, neurologist, MRI of the brain and spinal cord with contrast, genetic analysis - for timely initiation of therapy that prevents hearing loss and vestibular disorders.

Purpose: Neurofibromatosis type 2 (NF2) is intractable because of multiple tumors involving the nervous system and is clinically diverse and genotype-dependent. Stereotactic radiosurgery (SRS) for NF2-associated schwannomas remains controversial. We aimed to investigate the association between radiosurgical outcomes and mutation types in NF2-associated schwannomas., Methods: This single-institute retrospective study included consecutive NF2 patients with intracranial schwannomas treated with SRS. The patients' types of germline mutations ("Truncating," "Large deletion," "Splice site," "Missense," and "Mosaic") and Halliday's genetic severity scores were examined, and the associations with progression-free rate (PFR) and overall survival (OS) were analyzed., Results: The study enrolled 14 patients with NF2 with 22 associated intracranial schwannomas (median follow-up, 102 months).　The PFRs in the entire cohort were 95% at 5 years and 90% at 10-20 years. The PFRs tended to be worse in patients with truncating mutation exons 2-13 than in those with other mutation types (91% at 5 years and 82% at 10-20 years vs. 100% at 10-20 years, P = 0.140). The OSs were 89% for patients aged 40 years and 74% for those aged 60 years in the entire cohort and significantly lower in genetic severity group 3 than in the other groups (100% vs. 50% for those aged 35 years; P = 0.016)., Conclusion: SRS achieved excellent PFR for NF2-associated intracranial schwannomas in the mild (group 2A) and moderate (group 2B) groups. SRS necessitates careful consideration for the severe group (group 3), especially in cases with NF2 truncating mutation exons 2-13., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: NF2-schwannomatosis (NF2) is an autosomal dominant disorder prone to hearing loss. Auditory brainstem implants (ABIs) offer a promising solution for hearing rehabilitation in NF2., Objective: To synthesize existing literature on ABI implantation in NF2, focusing on audiological outcomes and ABI-related complications., Methods: The systematic review followed PRISMA guidelines and was registered in the PROSPERO database (CRD42022362155). Relevant studies were identified by searching PubMed, EMBASE, CENTRAL, CMB, and CNKI from inception to August 2023. Data on environmental sound discrimination, open-set discrimination, closed-set discrimination, and ABI-related complications were extracted and subjected to meta-analysis. Publication bias was evaluated using funnel plots and Egger's test., Results: Thirty-three studies were included. The pooled estimate was 58% (95% CI 49-66%) for environmental sound discrimination and 55% (95% CI 40-69%) for closed-set discrimination. Regarding open-set discrimination, the pooled estimates were 30% (95% CI 19-42%) for sound only, 46% (95% CI 37-54%) for lip-reading only, and 63% (95% CI 55-70%) for sound plus lip-reading. The pooled occurrence of ABI-related complications was 33% (95% CI 15-52%)., Conclusion: This meta-analysis underscores the effectiveness and safety of ABIs in NF2, providing valuable insights for evidence-based decision-making and hearing rehabilitation strategies.

Objective: To compare cochlear implant (CI) and auditory brainstem implant (ABI) performance in patients with NF2-related schwannomatosis (NF2)., Study Design: Historical cohort., Setting: Tertiary academic center., Patients: A total of 58 devices among 48 patients were studied, including 27 ABIs implanted from 1997 to 2022 and 31 CIs implanted from 2003 to 2022. Three patients had bilateral ABIs, three had bilateral CIs, three had an ABI on one side and a CI on the other, one had a CI that was later replaced with an ipsilateral ABI, and one had an ABI and CI concurrently on the same side., Interventions: CI or ABI ipsilateral to vestibular schwannoma., Main Outcome Measures: Open-set speech perception, consonant-nucleus-consonant word scores, and AzBio sentence in quiet scores., Results: Among all patients, 27 (47%) achieved open-set speech perception, with 35 (61%) daily users at a median of 24 months (interquartile range [IQR], 12-87 mo) after implantation. Comparing outcomes, CIs significantly outperformed ABIs; 24 (77%) CIs achieved open-set speech perception compared with 3 (12%) ABIs, with median consonant-nucleus-consonant and AzBio scores of 31% (IQR, 0-52%) and 57% (IQR, 5-83%), respectively, for CIs, compared with 0% (IQR, 0-0%) and 0% (IQR, 0-0%), respectively, for ABIs. Patients with ABIs were younger at diagnosis and at implantation, had larger tumors, and were more likely to have postoperative facial paresis., Conclusion: Many patients with NF2-associated vestibular schwannoma achieved auditory benefit with either a CI or an ABI; however, outcomes were significantly better in those patients who were able to receive a CI. When disease and anatomy permit, hearing rehabilitation with a CI should be considered over an ABI in these patients. Tumor management strategies that increase the ability to successfully use CIs should be strongly considered given the high risk of losing bilateral functional acoustic hearing in this population., (Copyright © 2023, Otology & Neurotology, Inc.)

Purpose: Large individual differences and poor speech recognition outcomes are routinely observed in most patients who have received auditory brainstem implants (ABIs). A case report of an ABI recipient with exceptionally good speech recognition outcomes presents an opportunity to better understand the core information processing mechanisms that underlie variability and individual differences in outcomes., Method: A case study is reported of an adult ABI recipient (ID-006) with postlingually acquired, Neurofibromatosis Type 2 (NF2)-related hearing loss who displayed exceptional postoperative speech recognition scores. A novel battery of assessment measures was used to evaluate ID-006's auditory, cognitive, and linguistic information processing skills., Results: Seventeen years following ABI activation, ID-006 scored 77.6% correct on the AzBio Sentences in quiet. On auditory processing tasks, ID-006 scored higher on tasks with meaningful sentences and much lower on tasks that relied exclusively on audibility. ID-006 also demonstrated exceptionally strong abilities on several cognitive and linguistic information processing tasks., Conclusions: Results from a novel battery of information processing tests suggest that ID-006 relies extensively on top-down predictive processing and cognitive control strategies to efficiently encode and process auditory information provided by his ABI. Results suggest that current measures of outcomes and benefits should be expanded beyond conventional speech recognition measures to include more sensitive and robust measures of speech recognition as well as neurocognitive measures such as executive function, working memory, and lexical access.

Intracochlear schwannomas (ICS) are very rare benign tumours of the inner ear. We present histopathological proof of the extremely rare bilateral occurrence of intracochlear schwannomas with negative blood genetic testing for neurofibromatosis type 2 (NF2). Bilateral schwannomas are typically associated with the condition NF2 and this case is presumed to have either mosaicism for NF2 or sporadic development of bilateral tumours. For progressive bilateral tumour growth and associated profound hearing loss, surgical intervention via partial cochleoectomy, tumour removal, preservation of the modiolus, and simultaneous cochlear implantation with lateral wall electrode carrier with basal double electrode contacts was performed. The right side was operated on first with a 14-month gap between each side. The hearing in aided speech recognition for consonant-nucleus-consonant (CNC) phonemes in quiet improved from 57% to 83% 12 months after bilateral cochlear implantation (CI). Bilateral intracochlear schwannomas in non-NF2 patients are extremely rare but should be considered in cases of progressive bilateral hearing loss. Successful tumour removal and cochlear implantation utilizing a lateral wall electrode is possible and can achieve good hearing outcomes., (© 2023. The Author(s).)

Background: The use of radiotherapy (RT) for the treatment of vestibulocochlear schwannomas is standard in patients with type 2 neurofibromatosis (NF2). In the general population, fractionated RT (FRT) can achieve good results compared to single-dose radiosurgery (SRS). We aimed to assess whether this is true for NF2 patients as well., Methods: This retrospective cohort study included 34 patients and 54 lesions treated between 2010 and 2023 in a single university hospital., Results: Thirty-four patient charts were assessed. The median follow-up was 62.6 months (range, 7.1-135.8 months). Lesion size (median larger diameter, 2.5 cm) was correlated with the use of FRT (P > 0.001). Younger age also was correlated with FRT (P = 0.006). Median overall survival and progression-free survival (PFS) were not reached. The overall control rate was 76.5%, and the mean PFS was 49.8 months, compared with . 90.5% and 57.2 months, respectively, for SRS and 66.7% and 44.9 months, respectively, for FRT. There were no differences between the 2 groups in hearing loss, tinnitus, and facial palsy., Conclusions: In the NF2 population, FRT may yield worse control rates than SRS. Whenever possible, it is preferable to not fractionate treatment for these patients. Nevertheless, the FRT results were still good. More and larger prospective trials are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm 3 /year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages., (© 2023. The Author(s).)

Objective: To review a single-center experience with hearing rehabilitation in patients with neurofibromatosis type 2 (NF2) and to describe the auditory outcomes of cochlear implants (CIs) and auditory brainstem implants (ABI) in this population., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Twelve adult patients with NF2 who received a CI (n = 10) and/or an ABI (n = 5) between 2000 and 2021., Interventions: Insertion of a CI and/or an ABI in NF2 patients with bilateral vestibular schwannomas (VSs)., Main Outcome Measures: Patients' demographic data, treatment history, hearing evolution, hearing rehabilitation methods, implant details, and auditory outcomes after implantation., Results: Among those who received a CI, five patients had a stable untreated VS, one patient underwent a cochlear nerve preserving surgery, and four patients received radiotherapy treatments. Six patients became regular users of their device. The median open-set sentence recognition scores were as follows: 0.5% preoperatively, 60% at 1 year postoperatively, and 80% on the most recent audiological evaluation. All patients with an ABI were implanted concomitantly with VS surgical excision, and three of them also received radiotherapy treatments. The median open-set sentence recognition scores were as follows: 4% preoperatively, 26% at 1 year postoperatively, and 0% on the most recent evaluation. Three patients became regular ABI users., Conclusion: Despite major technological advances, auditory outcomes with ABIs remain deceiving. Considering the overall improvement in postoperative auditory performances provided by CIs compared with ABIs, cochlear implantation standouts as a primary mean of hearing rehabilitation in NF2 patients., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: Compare cochlear implant (CI) performance between patients with ipsilateral sporadic vestibular schwannoma (VS) and NF2-related schwannomatosis (NF2). Compare CI performance according to VS management modality., Study Design: Historical cohort., Setting: Tertiary academic center., Patients: Forty-nine patients (52 ears) undergoing cochlear implantation in the setting of ipsilateral sporadic (n = 21) or NF2-associated VS (n = 28)., Interventions: CI ipsilateral to VS., Main Outcome Measures: Auditory thresholds, consonant-nucleus-consonant (CNC) word scores, and AzBio sentences in quiet scores., Results: Among all patients, median post-CI pure tone average was 28 dB HL (interquartile range [IQR], 21-38), CNC word score was 39% (IQR, 6-62), and AzBio sentences in quiet score was 60% (IQR, 11-83) at a median of 12.5 months postimplantation. Despite the NF2 cohort having larger tumors, when comparing patients with sporadic versus NF2-associated VS, there were no statistically significant differences in CNC word (49% [30-70] vs. 31% [0-52]) or AzBio sentences in quiet (66% [28-80] vs. 57% [5-83]) scores. Regardless of NF2 status, all patients managed with observation, and radiosurgery achieved open-set speech. In patients who underwent microsurgery, 6 (46%) of 13 with NF2 achieved open-set speech recognition compared with 4 (67%) of 6 with sporadic disease., Conclusion: Select patients with VS achieve successful hearing rehabilitation with a CI. In this cohort, tumor management strategy significantly influenced CI performance, whereas differences in NF2 status exhibited less effect. Specifically, all patients managed with observation or radiosurgery achieved open-set speech perception, whereas approximately half of people with NF2-related VS and two-thirds of people with sporadic VS achieved this outcome after tumor microsurgery. When disease permits, observation and radiosurgery should be considered in patients who may later pursue a CI., Competing Interests: Conflict of interest: MLC receives research support from Advanced Bionics Corp., Cochlear Corp., and MED-EL GmbH., (Copyright © 2023, Otology & Neurotology, Inc.)

Background: Prospective data on maintenance therapy with bevacizumab for persons with NF2-related schwannomatosis (NF2-SWN) is lacking. In this prospective multicenter phase II study, we evaluated the efficacy, safety, and tolerability of bevacizumab for maintenance therapy in children and adults with NF2-SWN and hearing loss due to vestibular schwannomas (VS)., Methods: Following induction therapy, participants received bevacizumab 5 mg/kg every 3 weeks for 18 months. Participants were monitored for changes in hearing, tumor size, and quality of life (QOL), and for adverse events. Hearing loss was defined as a statistically significant decline in word recognition score (WRS) or pure-tone average compared to the study baseline; tumor growth was defined as >20% increase in volume compared to baseline., Results: Twenty participants with NF2-SWN (median age 23.5 years; range, 12.5-62.5 years) with hearing loss in the target ear (median WRS 70%, range 2%-94%) received maintenance bevacizumab. Freedom from hearing loss in the target ear was 95% after 48 weeks, 89% after 72 weeks, and 70% after 98 weeks. Freedom from tumor growth in the target VS was 94% after 48 weeks, 89% after 72 weeks, and 89% after 98 weeks. NF2-related QOL remained stable for 98 weeks whereas tinnitus-related distress decreased. Maintenance bevacizumab was well tolerated, with 3 participants (15%) discontinuing treatment due to adverse events., Conclusions: Maintenance bevacizumab (5 mg/kg every 3 weeks) is associated with high rates of hearing and tumor stability during 18 months of follow-up. No new unexpected adverse events related to bevacizumab were identified in this population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Solitary circumscribed neuroma formerly known as palisaded encapsulated neuroma is a rare, benign neural tumor that usually presents as a painless firm nodule or papule on the face and within oral cavity, although they can occur elsewhere on the body. No association with neurofibromatosis has been reported in the literature. Herein, we report, a previously unreported unique association of neurofibromatosis type 2 (NF-2) with multiple cutaneous solitary circumscribed neuromas in a 24-year-old female. A 24-year-old female with history of NF-2 presented with two slow-growing soft-to-firm papules on the chin and forehead that had been gradually increasing in size over a period of 5 years. The papule on the chin was increasingly tender to palpation. Histologic sections demonstrated a dermal based almost encapsulated, smoothly contoured tumefactive mass composed of spindle cell proliferation with neuroid structures and foci of palisaded growth (resembling schwannoma) and intralesional cleft like spaces. By immunohistochemistry, the lesional cells were strongly and diffusely positive for S-100 and SOX10 with multifocal neurofilament expression while the "capsule" was diffusely reactive for epithelial membrane antigen. The overall features were considered prototypic for solitary circumscribed neuroma. The patient is 18-months post-surgical resection with no evidence of recurrence. In summary, we report for the first time a case of multiple solitary circumscribed neuromas in a patient with known NF2. We highlight pertinent diagnostic clues relevant to surgical pathologist to facilitate recognition (as this tumor is often mistaken for schwannoma or neurofibroma). The clinical behavior is excellent and surgical resection is considered curative.

Purpose: Pediatric meningioma differs not only in its rare incidence from the adult meningioma, but also in its clinical characteristics. Many treatment approaches of pediatric meningioma are based on the study results of adult meningioma studies. The aim of this study was to explore the clinical and epidemiological characteristics of pediatric meningioma., Methods: Data on pediatric patients diagnosed between 1982 and 2021 with NF2-associated or sporadic meningioma and recruited in the trials/registries HIT-ENDO, KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 were retrospectively analyzed for clinical characteristics, etiology, histology, therapy, and outcome., Results: One hundred fifteen study participants were diagnosed with sporadic or NF2-associated meningioma at a median age of 10.6 years. There was a 1:1 sex ratio, with 14% of study participants suffering from NF2. 46% of the meningiomas were located hemispherically, 17% at the optic nerve/ intraorbital and 10% ventricularly. Multiple meningiomas were detected in 69% of NF2 patients and in 9% of sporadic meningiomas. 50% of the meningiomas were WHO grade I, 37% WHO grade II and 6% WHO grade III. Progressions or recurrences occurred after a median interval of 1.9 years. Eight patients (7%) died, 3 of them due to disease. The event-free survival was higher for WHO grade I than for WHO grade II meningioma patients (p = 0.008)., Conclusions: The major difference to the preceding literature could be found in the distribution of different WHO grades and their influence on event-free survival. Prospective studies are warranted to assess the impact of different therapeutic regimens., Clinical Trial Registration Numbers: NCT00258453; NCT01272622; NCT04158284., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by a mutation in the NF2 suppressor gene and is characterized by the development of multiple benign tumors throughout the central nervous system. Bilateral vestibular schwannomas (VSs) are pathognomonic for NF2 and are associated with progressive hearing loss and eventual deafness in most patients. This review presents current management options for NF-2-associated VSs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cochlear implantation offers significantly better hearing outcomes than auditory brainstem implantation in patients with vestibular schwannoma. Neither the primary treatment modality nor the cause of the tumor (neurofibromatosis type 2 related or sporadic) seems to have a significant effect on hearing outcome with cochlear implantation. Some uncertainty remains regarding long-term hearing outcomes; however, cochlear implantation in vestibular schwannoma serves to offer patients, with a functioning cochlear nerve, the probability of open set speech discrimination with a consequent positive impact on quality of life., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role and safety., Objective: To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS., Methods: We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male., Results: A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 [95% CI: 1.01-1.05]; P = .02) and bilateral VSs (hazards ratio: 4.56 [95% CI: 1.05-19.78]; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort., Conclusion: Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

(1) Background: This study aimed to evaluate the efficacy and treatment-related toxicity of proton radiotherapy (PRT) for vestibular schwannoma (VS) in patients with neurofibromatosis type 2-related schwannomatosis (NF2). (2) Methods: Consecutive NF2 patients treated with PRT for VS between 2004 and 2016 were retrospectively evaluated, focusing on tumor volume, facial and trigeminal nerve function, hearing, tinnitus, vestibular symptoms, and the need for salvage therapy after PRT. (3) Results: Eight patients were included (median age 36 years, 50% female). Median follow-up was 71 months. Five (63%) patients received fractionated PRT and three (38%) received PRT radiosurgery for VS. Six patients (75%) received prior VS surgery; three also received bevacizumab. Six patients (75%) did not require salvage therapy after PRT. Two patients (25%) with residual hearing lost it after PRT, and six had already lost ipsilateral hearing prior to PRT. Tumor and treatment-related morbidity could be evaluated in six patients. Following PRT, conditions that occurred or worsened were: facial paresis in five (83%), trigeminal hypoesthesia in two (33%), tinnitus in two (33%), and vestibular symptoms in four patients (67%). (4) Conclusion: After PRT for VS, the majority of the NF2 patients in the cohort did not require additional therapy. Tumor and/or treatment-related cranial nerve deficits were common. This is at least partly explained by the use of PRT as a salvage treatment after surgery or bevacizumab, in the majority of cases. There remains the further opportunity to elucidate the efficacy and toxicity of proton radiotherapy as a primary treatment.

Objective: To investigate the results of cochlear implantation in subjects with neurofibromatosis type 2 (NF2) and bilateral vestibular schwannomas (VS)., Study Design: Retrospective case series., Setting: University-based tertiary referral center., Subjects: Five subjects with NF2 and severe-to-profound sensorineural hearing loss., Intervention: Cochlear implantation., Main Outcome Measure: Surgical outcomes and audiometric performance after cochlear implantation., Results: Five subjects (3 female, 2 male) were included in the study. The mean age at the time of implantation was 54 years old (range 35-78 years). Follow-up after cochlear implantation averaged 38 months (range 21-106 months). In the 5 implanted ears, 2 had no prior treatment, 1 had undergone prior radiation therapy, 1 underwent prior microsurgical removal, and 1 underwent prior microsurgical removal with adjuvant radiation therapy. The mean ipsilateral VS dimensions at time of implantation were 14 mm × 7.2 mm × 6.1 mm (mediolateral × anteroposterior × craniocaudal). Following cochlear implant activation, all 5 subjects achieved sound awareness, open set speech recognition, and 4 continue to be daily users of the devices., Conclusion: Cochlear implantation is a viable hearing rehabilitation option for subjects with NF2 and severe-to-profound sensorineural hearing loss. All subjects reported benefit with their cochlear implant, including open set speech recognition, enhanced lip-reading skills and environmental awareness of sound. Four subjects continued to demonstrate improved open-set speech recognition at the time of their last evaluations.

Purpose: People with pre-existing conditions may be more susceptible to severe COVID-19 when infected by SARS-CoV-2. The relative risk and severity of SARS-CoV-2 infection in people with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) is unknown., Methods: We investigated the proportions of people with NF1, NF2, or SWN in the National COVID Cohort Collaborative (N3C) electronic health record data set who had a positive test result for SARS-CoV-2 or COVID-19., Results: The cohort sizes in N3C were 2501 (NF1), 665 (NF2), and 762 (SWN). We compared these with N3C cohorts of patients with other rare diseases (98-9844 individuals) and the general non-NF population of 5.6 million. The site- and age-adjusted proportion of people with NF1, NF2, or SWN who had a positive test result for SARS-CoV-2 or COVID-19 (collectively termed positive cases) was not significantly higher than in individuals without NF or other selected rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts. The proportion of patients experiencing severe outcomes was no greater for people with NF1 than in cohorts with other rare diseases or the general population., Conclusion: Having NF1, NF2, or SWN does not appear to increase the risk of being SARS-CoV-2 positive or of being a patient with COVID-19 or of developing severe complications from SARS-CoV-2., Competing Interests: Conflict of Interest J.T.J. is a recipient of royalties from Elsevier and consulting fees from Navio Theragnostics, Inc; CereXis; and Recursion. S.P. is a cofounder of NFlection Therapeutics and NF2 Therapeutics, Inc; consults for Akouos; and serves on the Scientific Advisory Board of and holds stock in SonALAsense. All other authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

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.)

Competing Interests: The authors report no conflicts of interest.

Objective: Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5'-triphosphate-competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models., Methods: Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees., Results: Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment., Conclusions: The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.

Purpose: Neurofibromatosis (NF) is an incurable genetic neurological condition. Psychosocial interventions that promote resiliency are a promising approach to address the high emotional distress and low quality of life (QoL) associated with NF. However, no studies have examined the psychosocial needs of treatment-seeking adults with NF. Our goal was to explore, using data from the largest efficacy trial of a psychosocial intervention for NF, differences in QoL, emotional distress, resiliency, and pain-related outcomes compared to other chronic medical populations and within subtypes (NF1, NF2, schwannomatosis; SCHW)., Methods: Enrolled participants (N = 228) were geographically diverse adults with NF and elevated stress. We performed secondary analysis on baseline measures of QoL, emotional distress, resiliency, and pain-related outcomes. We reported descriptive statistics and normative comparisons to understand the psychosocial characteristics of the overall sample and performed between-group analyses to explore differences within NF type., Results: Our sample endorsed worse QoL, emotional distress, resilience, and pain-related outcomes than similar chronic illness populations. Within NF types, participants with NF1 reported lower QoL and resilience compared to those with NF2. Participants with SCHW reported higher pain intensity than those with NF1. Participants with SCHW reported higher pain interference and lower physical QoL compared to those with NF1 and NF2., Conclusions: Our findings support the urgent need for psychosocial interventions targeting deficits in QoL, emotional distress, resilience, and pain-related outcomes in adults with NF. We recommend efforts to enhance sample diversity, prepare clinicians to provide high-levels of support, and attune skills training to each NF type., Trial Registration: ClinicalTrials.gov NCT03406208; https://clinicaltrials.gov/ct2/show/NCT03406208 (Archived by WebCite at http://www.webcitation.org/72ZoTDQ6h )., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied., Objectives: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity., Methods: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved., Results: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque-like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque-like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype-based classes., Conclusions and Relevance: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose: Sporadic vestibular schwannoma (VS) is rare in children in contrast to adults, and detailed investigations of case series of these patients using a single fixed protocol are scarce. This study presents our surgical experience of pediatric VSs without clinical evidence of neurofibromatosis type 2 (NF2) at the initial diagnosis., Methods: Among 1385 consecutive sporadic VS surgeries, 18 pediatric patients (1.3%; 11-18 years old) were retrospectively investigated., Results: The most common initial symptom was hearing disturbance (72.2%), and 6 patients (33.3%) experienced a delayed diagnosis (over 2 years after initial symptom onset). Preoperative image characteristics of these tumors included a solid tumor, hypervascularity, and significant extension into the internal acoustic meatus, when compared with adults. Preoperative embolization was successfully accomplished for 2 recent hypervascular tumors. The tumor resection rate was 95-100% under sufficient intraoperative neuromonitoring, and no additional surgery was required during the follow-up period (average: 57.9 months). No patients experienced permanent facial nerve palsy, and serviceable hearing function was preserved in 6 of 11 patients. Signs of NF2, such as bilateral VSs, were not identified in any patients during the follow-up., Conclusion: Safe and sufficient tumor resection was achieved under detailed neuromonitoring in pediatric patients with sporadic VS, although this tends to be difficult owing to hypervascularity, a small cranium, and significant meatal extension. Preoperative embolization may help safe resection of hypervascular tumors. Subsequent development of NF2 has not been observed up to the most recent follow-up, but careful observation is essential for these younger patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tanycytic ependymomas are a rare spinal cord tumour arising from tanycyte cells lining the ventricle or spinal central canal. This is the first report of familial spinal tanycytic ependymoma occurring in two first degree relatives. Both patients underwent surgical resection of the intra-medullary tumours with good overall recovery. Genetic analysis identified that the brothers shared a previously unreported mutation in the NF-2 gene. NF-2 mutations in spinal tanycytic ependymomas may be more common than initially thought and consideration should be given to screening the neural axis for other tumours and genetic counselling., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Neurofibromatosis type 2 (NF2) is characterized by bilateral vestibular schwannoma (VS) more often in adults but a severe paediatric form with multiple neurological tumours is also described. In this population, a early diagnosis is important to prevent the onset of neurological complications but is difficult, particularly without a familial history. Cutaneous manifestations, which may precede VS or neurological tumours by several years, may contribute to an early diagnosis, but specific studies are lacking. The objective of this study was to characterize cutaneous manifestations of NF2 in a paediatric population., Results: This observational, descriptive and multicentric study was conducted from April 2019 to April 2020 in seven academic French hospitals. We included patients ≤ 18 years old who fulfilled the Manchester diagnostic criteria or had a pathogenic mutation identified in the NF2 gene. All patients underwent a dermatological examination guided by a standardized questionnaire. 21 children were included, of whom 20 had at least one skin tumour (mean number 5 ± 4.6 [range 0-15]), which led to a diagnosis in four cases. In the other 17 cases, the diagnosis of NF2 was based on neurosensory complications (n = 10), family screening (n = 4) or ocular signs (n = 3). Before the NF2 diagnosis, 15 children had at least one "undiagnosed" cutaneous tumour that did not lead to a specific management. Patients' dermatological examination also revealed < 6 non specific café au lait macules (n = 15), hypopigmented macules (n = 12) with more than 3 lesions in 4 cases, and purple reticulated macules of the trunk (n = 4)., Conclusion: Dermatological lesions are frequent and early in children with NF2 but rarely lead to the diagnosis. Cutaneous schwannomas are the most frequent but are often underdiagnosed. Café au lait macules are frequent, but atypical and mostly in small numbers. Multiple hypopigmented macules seem suggestive although inconsistent. The sensitivity of reticulated capillary malformation-like lesions remains to be assessed by further studies., (© 2022. The Author(s).)