OBJECTIVE: Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.
METHODS: We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).
RESULTS: Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (\"first hit\") but distinct \"second hit\" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.
CONCLUSIONS: Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.

We report partial response (PR) to novel therapy with selumetinib in a patient with neurofibromatosis type 2 (NF2). A 25-year-old male presented with bilateral vestibular schwannomas, spinal cord intramedullary ependymomas, cranial and spinal meningiomas, spinal nerve root mixed schwannoma-neurofibromas, and peripheral nerve sheath tumors. He tested negative for germline NF2, SWItch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and leucine zipper-like transcription regulator 1 (LZTR1) mutations. Molecular analysis of a resected cervical spine schwannoma-neurofibroma demonstrated an isolated somatic SMARCB1 mutation. Due to progression of all tumors, he was treated medically with both everolimus (10 mg/day) and selumetinib (25 mg/kg twice a day), but he rapidly transitioned to selumetinib monotherapy due to everolimus toxicity. 3 months of treatment resulted in PR in one spinal ependymoma and stable disease in other tumors. This PR was quantified by the differences in units of intensity in pre- and post-treatment magnetic resonance image. To the best of our knowledge, this is the first reported case for using selumetinib in NF2-associated tumors or ependymomas.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: To describe the characteristics, management, and outcomes of pediatric patients with sporadic vestibular schwannoma (sVS).
METHODS: This was a case series at a tertiary care center. Patients were identified through a research repository and chart review. Interventions were microsurgery, stereotactic radiosurgery (SRS), and observation. Outcome measures were tumor control, facial nerve function, and hearing.
RESULTS: Eight patients over 2006-2022 fulfilled inclusion criteria (unilateral VS without genetic or clinical evidence of neurofibromatosis type 2 (NF2); age ≤ 21) with a mean age of 17 years (14-20). Average greatest tumor length in the internal auditory canal was 9.7 mm (4.0-16.1). Average greatest tumor dimension (4/8 tumors) in the cerebellopontine angle was 19.1 mm (11.3-26.8). Primary treatment was microsurgery in five (62.5%) patients, observation in two (25%), and SRS in one (12.5%). Four (80%) surgical patients had gross total resections, and one (20%) had regrowth post-near total resection and underwent SRS. One observed patient and the primary SRS patient have remained radiographically stable for 3.5 and 7 years, respectively. The other observed patient required surgery for tumor growth after 12 months of observation. Two surgical patients had poor facial nerve outcomes. All post-procedural patients developed anacusis. Mean follow-up was 3 years (0.5-7).
CONCLUSIONS: We describe one of the largest reported cohorts of pediatric sVS in the USA. Diligent exclusion of NF2 is critical. Given the high likelihood of eventually requiring intervention and known adverse effects of SRS, microsurgery remains the preferred treatment. However, observation can be considered in select situations.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a multifaceted disease characterized primarily by benign CNS tumors, especially meningiomas and vestibular schwannomas. There have been several cases of brainstem ischemic stroke in young NF2 patients reported in the literature. To date, there is no unified theory about the connection between NF2 and pediatric stroke.
METHODS: We present a case of ischemia in the left cerebellar peduncle of a young patient with NF2, as well as a narrative review of the literature of previous cases.
RESULTS: Serial magnetic resonance images (MRIs) displayed an initial area of restricted diffusion in the left cerebellar peduncle with peripheral enhancement which did improve over several months, consistent with maturing infarct.
CONCLUSIONS: Our case joins several others with similar presentations and findings. The primary theory for the cause of brainstem ischemia in juvenile NF2 is a microvascular cause due to deficiency of neurofibromin 2, a regulator of endothelial development. Multicenter studies with large NF2 cohorts are needed to better characterize this syndrome.

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(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.

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.
To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS.
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.
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.
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.