Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery, genetics, and localization.

INTRODUCTION: Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT). Functional preservation and pain relief are the major goals in treating these tumors. METHODS: This retrospective observational study investigates the clinical and functional outcome of 205 operated peripheral (n = 148, 72%) and intraspinal (n = 57, 28%) schwannomas in 85 patients (53 NF2, 32 SWNT) treated at our department between 2006 and 2017. Associated factors such as genetics, age, and location were evaluated. RESULTS: Persisting drug-resistant pain was the most common symptom (84%, n = 173) and indication for surgery (54%, n = 110). Improvement in pain intensity was postoperatively seen in 81%. Peripheral nerve schwannomas exhibited worse pain intensity preoperatively compared to intraspinal lesions (p = 0.017 NF2, p = 0.029 SWNT). More total resections could be achieved in 93% of SWNT vs. 82% of NF2-associated tumors, p = 0.030). NF2 patients with intraspinal lesions were more neurologically affected (p < 0.05). Perioperative comparison of both tumor syndromes showed more neurological deficits (p = 0.027), and less pain (p = 0.024) in NF2-associated tumors. Mosaic NF2 patients had worse pain levels before surgery, and SWNT patients had a worse neurological function and more pain compared to non-mosaic or non-mutated cases. CONCLUSIONS: Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity. The influence of mutations needs to be further investigated in larger cohorts.

Managing NF2-associated vestibular schwannomas in children and young adults: review of an institutional series regarding effects of surgery and bevacizumab on growth rates, tumor volume, and hearing quality.

We reviewed our experience in managing of NF2-associated vestibular schwannoma (VS) in children and young adults regarding the effect of surgery and postoperative bevacizumab treatment. A total of 579 volumetric and hearing data sets were analyzed. The effect of surgery on tumor volume and growth rate was investigated in 46 tumors and on hearing function in 39 tumors. Long-term hearing follow-up behavior was compared with 20 non-operated ears in additional 15 patients. Sixteen operated VS were treated with bevacizumab. Mutation analysis of the NF2 gene was performed in 25 patients. Surgery significantly slowed down VS growth rate. Factors associated with a higher growth rate were increasing patient age, tumor volume, and constitutional truncating mutations. Immediately after surgery, functional hearing was maintained in 82% of ears. Deterioration of hearing was associated with initial hearing quality, larger tumor volumes, and larger resection amounts. Average hearing scores were initially better in the group of non-operated VS. Over time, hearing scores in both groups worsened with a similar dynamic. During bevacizumab treatment of residual tumors, four different patterns of growth were observed. Decompression of the internal auditory canal with various degrees of tumor resection decreases the postoperative tumor growth rates. Carefully tailored BAEP-guided surgery does not cause additional hearing deterioration. Secondary bevacizumab treatment showed heterogenous effects both regarding tumor size and hearing preservation. It seems that postoperative tumor residuals, that grow slower, behave differently to bevacizumab than reported for not-operated faster growing VS.

Role, function and challenges of multidisciplinary centres for rare diseases exemplified for neurofibromatosis type 1 syndrome.

PURPOSE: Neurofibromatosis type 1 (NF1) syndrome is a common rare/orphan disease that manifests itself early in the paediatric age. It imposes a considerable burden upon patients as well as on caregivers. Decisions regarding optimal care often rely on several medical instances working together as a team. METHODS: The authors reviewed the literature and supplied a description of their own clinical work at the NF1 centres. RESULTS: The experience of a multidisciplinary teamwork of three NF centres was summarized in order to enhance awareness for possible multidisciplinary ways of delivery of health and health-related aspects of care to NF1 patients. Both population-focused research centres and family-focused centres were reviewed. CONCLUSIONS: Chronic rare diseases that start in the paediatric age mandate long-term follow-up most often by several disciplines. NF1 syndrome is an example of a multidisciplinary centre in order to enhance the quality of care.

Presenting symptoms in children with neurofibromatosis type 2.

PURPOSE: The hallmark of neurofibromatosis type 2 (NF2) is the presence of bilateral vestibular schwannomas (VS) which however have not yet developed or grown to large size in children and young adolescents. Therefore, early diagnosis in pediatric patients without family history of NF2 has to be made by signs and symptoms not related to VS which will be reviewed in this study. METHODS: A total of 70 children diagnosed for NF2 at an age of < 18 years were identified from our patient cohort. Age and symptoms, signs and pathology at symptom onset, age at NF2 diagnosis and symptoms leading to diagnosis as well as genetic findings were retrospectively reviewed. RESULTS: The average age at symptom/sign onset was 8 ± 6 (range 0-17) years and 11 ± 5 (range 1-17) years at time of diagnosis. Fifteen children had a positive family history and were diagnosed upon additional clinical symptoms. The most frequent first presenting symptom/signs were ophthalmological abnormalities (49%), followed by cutaneous features (40%), non-VS-related neurological deficits (33%), and symptoms attributable to VS (21%). VS were not only the most common symptomatic neoplasm but also the most frequent pathological evidence for the diagnosis (72%). In 42 patients with available genetic testing results, pathogenic mutations were most frequently identified (n = 27). CONCLUSION: The presenting symptoms in NF2 children appear "unspecific" or less specific for classical NF2 compared with adult NF2 patients, posing a challenge particularly for cases without family history. In children, ophthalmological and cutaneous features should raise clinical suspicion for NF2 and referral to an NF2 specialized center is recommended.

Surgical management of peripheral nerve sheath tumours in children, with special consideration of neurofibromatoses.

INTRODUCTION: Peripheral nerve sheath tumours in children are a rare and heterogeneous group, consisting mostly of benign tumours as well as malignant neoplasms. Especially in the paediatric population, diagnostics and indication for therapy pose relevant challenges for neurosurgeons and paediatric neurologists alike. Most paediatric cases that need surgical intervention are associated to neurofibromatosis type 1 (NF1). METHODS: We retrospectively reviewed all paediatric cases treated at the Department of Neurosurgery in Tübingen between 2006 and 2017 for peripheral nerve sheath tumours. We analysed clinical signs, symptoms, histology, association to an underlying phacomatosis and sensory/motor function. RESULTS: Of the 82 identified patients, the majority had NF1 (76.8%). Nine children bore a sporadic tumour without underlying phacomatosis (11%), 8 had NF2 (9.8%) and 2 schwannomatosis (2.4%), A total of 168 surgical interventions were performed, and 206 tumours were removed. Indication for surgery was in most instances significant tumour growth (45.2%) followed by pain (33.9%). New deficits led to surgery in 12.5% of interventions; malignancy was suspected in 8.3%. Histopathology revealed mostly neurofibromas (82.5%), divided into cutaneous neurofibromas (10.7%), infiltrating plexiform neurofibromas (25.7%) and peripheral nerve-born neurofibromas (46.1%). 12.1% of tumours were schwannomas, 2.9% MPNST, 1.5% ganglioneuroma (n = 3) and 1 hybrid-neurofibroma and perineurinoma each. Leading symptoms, such as pain and motor and sensory deficits, improved after 125/166 interventions (74.4%), remained unchanged following 39 interventions (23.2%) and worsened in 4 occasions (2.4%). CONCLUSION: Surgery is safe and effective for (neurofibromatosis associated) peripheral nerve sheath tumours in the paediatric population; however, management needs a multidisciplinary setting. We propose early surgical resection in paediatric patients with peripheral nerve sheath tumours with significant growth, or pain, or motor deficit, or suspected malignancy.

Planar single plane area determination is a viable substitute for total volumetry of CSF and brain in childhood hydrocephalus.

BACKGROUND: In the treatment of childhood hydrocephalus, 3D volumetry seems to have many advantages over classical planar index measurements for dedicated monitoring of changes in cerebrospinal fluid and brain volume. Nevertheless, this method requires extensive technical effort and access to the complete three-dimensional data set. Against this background, we evaluated the possibility of planar area determination in a single plane and the correlation to volumetry. METHODS: 138 routinely performed true FISP MRI sequences (1 mm isovoxel) were analyzed retrospectively in 68 patients with pediatric hydrocephalus. After preprocessing, the 3D-data sets were skull stripped to estimate the inner skull volume. A 2-class segmentation into different tissue types (brain matter and CSF) was performed, and the volumes of CSF (VCSF) and brain matter (VBrain) were calculated. A plane at the level of the foramina of Monro was manually identified in the ac-pc oriented data. In this plane, the areas of brain (ABrain) and CSF (ACSF) in cm2 were calculated and used for further correlation analysis. RESULTS: Mean VCSF was 340 ± 145 cm3 and VBrain 1173 ± 254 cm3. In the selected plane, ACSF was 26 ± 14 cm2, and ABrain was 107 ± 25 cm2. There was a very strong positive correlation between both ACSF and VCSF (r = 0.895) and between ABrain and VBrain (r = 0.846). The prediction equations for VBrain and VCSF were highly significant. CONCLUSION: Planar area determination of brain and CSF correlates excellently with both VCSF and VBrain. Thus, areas can serve as a surrogate marker for total brain and CSF volumes for a quantitated objective tracking of changes during treatment of childhood hydrocephalus.

Occurrence and management of postoperative pneumocephalus using the semi-sitting position in vestibular schwannoma surgery.

BACKGROUND: The semi-sitting position in neurosurgical procedures is still under debate due to possible complications such as venous air embolism (VAE) or postoperative pneumocephalus (PP). Studies reporting a high frequency of the latter raise the question about the clinical relevance (i.e., the incidence of tension pneumocephalus) and the efficacy of a treatment by an air replacement procedure. METHODS: This retrospective study enrolled 540 patients harboring vestibular schwannomas who underwent posterior fossa surgery in a supine (n = 111) or semi-sitting (n = 429) position. The extent of the PP was evaluated by voxel-based volumetry (VBV) and related to clinical predictive factors (i.e., age, gender, position, duration of surgery, and tumor size). RESULTS: PP with a mean volume of 32 ± 33 ml (range: 0-179.1 ml) was detected in 517/540 (96%) patients. The semi-sitting position was associated with a significantly higher PP volume than the supine position (40.3 ± 33.0 ml [0-179.1] and 0.8 ± 1.4 [0-10.2], p < 0.001). Tension pneumocephalus was observed in only 14/429 (3.3%) of the semi-sitting cases, while no tension pneumocephalus occurred in the supine position. Positive predictors for PP were higher age, male gender, and longer surgery duration, while large (T4) tumor size was established as a negative predictor. Air exchange via a twist-drill was only necessary in 14 cases with an intracranial air volume > 60 ml. Air replacement procedures did not add any complications or prolong the ICU stay. CONCLUSION: Although pneumocephalus is frequently observed following posterior fossa surgery in semi-sitting position, relevant clinical symptoms (i.e., a tension pneumocephalus) occur in only very few cases. These cases are well-treated by an air evacuation procedure. This study indicates that the risk of postoperative pneumocephalus is not a contraindication for semi-sitting positioning.

Semantic segmentation of cerebrospinal fluid and brain volume with a convolutional neural network in pediatric hydrocephalus-transfer learning from existing algorithms.

BACKGROUND: For the segmentation of medical imaging data, a multitude of precise but very specific algorithms exist. In previous studies, we investigated the possibility of segmenting MRI data to determine cerebrospinal fluid and brain volume using a classical machine learning algorithm. It demonstrated good clinical usability and a very accurate correlation of the volumes to the single area determination in a reproducible axial layer. This study aims to investigate whether these established segmentation algorithms can be transferred to new, more generalizable deep learning algorithms employing an extended transfer learning procedure and whether medically meaningful segmentation is possible. METHODS: Ninety-five routinely performed true FISP MRI sequences were retrospectively analyzed in 43 patients with pediatric hydrocephalus. Using a freely available and clinically established segmentation algorithm based on a hidden Markov random field model, four classes of segmentation (brain, cerebrospinal fluid (CSF), background, and tissue) were generated. Fifty-nine randomly selected data sets (10,432 slices) were used as a training data set. Images were augmented for contrast, brightness, and random left/right and X/Y translation. A convolutional neural network (CNN) for semantic image segmentation composed of an encoder and corresponding decoder subnetwork was set up. The network was pre-initialized with layers and weights from a pre-trained VGG 16 model. Following the network was trained with the labeled image data set. A validation data set of 18 scans (3289 slices) was used to monitor the performance as the deep CNN trained. The classification results were tested on 18 randomly allocated labeled data sets (3319 slices) and on a T2-weighted BrainWeb data set with known ground truth. RESULTS: The segmentation of clinical test data provided reliable results (global accuracy 0.90, Dice coefficient 0.86), while the CNN segmentation of data from the BrainWeb data set showed comparable results (global accuracy 0.89, Dice coefficient 0.84). The segmentation of the BrainWeb data set with the classical FAST algorithm produced consistent findings (global accuracy 0.90, Dice coefficient 0.87). Likewise, the area development of brain and CSF in the long-term clinical course of three patients was presented. CONCLUSION: Using the presented methods, we showed that conventional segmentation algorithms can be transferred to new advances in deep learning with comparable accuracy, generating a large number of training data sets with relatively little effort. A clinically meaningful segmentation possibility was demonstrated.

Automatic volumetry of cerebrospinal fluid and brain volume in severe paediatric hydrocephalus, implementation and clinical course after intervention.

BACKGROUND: In childhood hydrocephalus, both the amount of cerebrospinal fluid and the brain volume are relevant for the prognosis of the development and for therapy monitoring. Since classical planar measurements of ventricular size are subject to strong limitations, imprecise and neglect brain volume, 3D volumetry is most desirable. We used and evaluated the robust segmentation algorithms of the freely available FSL-toolbox in paediatric hydrocephalus patients before and after specific therapy. METHODS: Retrospectively 76 pre- and postoperative high-resolution T2-weighted MRI sequences (true FISP, 1 mm isovoxel) were analyzed in 38 patients with paediatric hydrocephalus (mean 4.4 ± 5.1 years) who underwent surgical treatment (ventriculo-peritoneal (VP) shunt n = 22, endoscopic third ventriculostomy (ETV) n = 16). After preprocessing, the 3D-datasets were skull stripped to estimate the inner skull surface. Following, a 2 class segmentation into different tissue types (brain matter and CSF) was performed. The volumes of CSF and brain were calculated. RESULTS: The method could be implemented in an automated fashion in all 76 MRIs. In the VP shunt cohort, the amount of CSF (p < 0.001) decreased. Consecutively brain volume increased significantly (p < 0.001). Following ETV, CSF volume (p = 0.019) decreased significantly (p = 0.012) although the reduction was less pronounced than after shunt implantation. Brain volume expanded (p = 0.02). CONCLUSION: A reliable automated segmentation of CSF and brain could be performed with the implemented algorithm. The method was able to track changes after therapy and detected significant differences in CSF and brain volumes after shunting and after ETV.

Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2.

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.

Comprehensive anatomical and functional imaging in patients with type I neurofibromatosis using simultaneous FDG-PET/MRI.

PURPOSE: To demonstrate the clinical use of FDG-PET/MRI for monitoring enlargement and metabolism of plexiform neurofibromas (PNF) in patients with neurofibromatosis type 1 (NF1), in whom the development of a malignant peripheral nerve sheath tumor (MPNST) is often a life limiting event. METHODS: NF1 patients who underwent a simultaneous FDG-PET/MRI examination in our institution from September 2012 to February 2018 were included. Indication was suspicion of malignant transformation of a PNF to MPNST. A maximum of six peripheral nerve lesions per patient were defined as targets. Standardized uptake values (SUV) and apparent diffusion coefficients (ADC) were measured. The presence of target sign and contrast-medium enhancement was visually recorded. Growth rates were estimated comparing prior or follow-up examinations and correlated with FDG uptake and ADC values. The presence of CNS lesions in cerebral T2 weighted images was recorded. RESULTS: In 28 NF1 patients a total number of 83 peripheral nerve tumors, 75 benign PNFs and eight MPNSTs, were selected as target lesions. The SUVs of MPNSTs were significantly higher than the SUVs of PNF (3.84 ± 3.98 [SUVmean MPNSTs] vs. 1.85 ± 1.03 [SUVmean PNF], P < .01). Similarly, lesion SUVmean-to-liver SUVmean ratios significantly differed between MPNSTs and PNF (3.20 ± 2.70 [MPNSTs] vs. 1.23 ± 0.61 [PNF]; P < .01). For differentiation between still benign PNF and MPNSTs, we defined SUVmax ≥ 2.78 as a significant cut-off value. Growth rate of PNF correlated significantly positively with SUVmean (rs = .41; P = .003). MRI parameters like ADCmean (1.87 ± 0.24 × 10-3 mm2/s [PNF] vs. 1.76 ± 0.11 × 10-3 mm2/s [MPNSTs]; P > .05], contrast medium enhancement (P = .50) and target sign (P = .86) did not differ between groups. CONCLUSION: Simultaneous FDG-PET/MRI is a comprehensive imaging modality for monitoring PNF in NF1 patients. The combined acquisition of both morphologic information in MRI and metabolic information in PET enables the correlation of lesion growth rates with metabolic activity and to define SUV thresholds of significance to identify malignant transformation, which is of utmost clinical significance.

Ki-67 labeling index and expression of p53 are non-predictive for invasiveness and tumor size in functional and nonfunctional pituitary adenomas.

BACKGROUND: It is still controversial whether an increased proliferation index is correlated with the tumor invasiveness of pituitary adenomas. A homogeneous large monocentric series of pituitary adenomas was retrospectively analyzed. The correlation between the proliferation indices (Ki-67 and p53 expression levels) and invasiveness and size of pituitary adenomas was investigated in primary operated and recurrent adenomas. METHOD: Four hundred thirty-nine patients after resection of pituitary adenomas were retrospectively included (43 recurrent tumors, 196 null cell adenomas, 86 somatotroph adenomas, 55 corticotroph adenomas, 55 prolactinomas, 4 thyreotroph adenomas). The maximum tumor diameter and tumor invasiveness in Knosp grading were assessed and Ki-67 and p53 immunostaining was performed. The role of invasiveness was evaluated using a cumulative odds ordinal logistic regression. For calculating the effect of tumor size, a one-way analysis of variance (ANOVA) was conducted. RESULTS: Overall and in the subgroups, no significant correlation between proliferation indices and mean tumor diameter was found. No significant predictive expression value of Ki-67 and p53 on tumor invasiveness and in recurrent tumors could be demonstrated. There was a tendency that Ki-67 LI and p53 LI are higher in recurrent corticotroph adenomas and lactotroph adenomas but values did not reach the significant level. CONCLUSION: Invasive character of pituitary adenomas is neither correlated with increased Ki-67 LI nor with increased p53 expression. Proliferation parameters are independent from adenoma size at initial presentation. The partly elevated expression of Ki-67 in recurrent tumors underlines the clinical importance of the marker.

Phenotypic and genotypic overlap between mosaic NF2 and schwannomatosis in patients with multiple non-intradermal schwannomas.

Schwannomatosis and neurofibromatosis type 2 (NF2) are both characterized by the development of multiple schwannomas but represent different genetic entities. Whereas NF2 is caused by mutations of the NF2 gene, schwannomatosis is associated with germline mutations of SMARCB1 or LZTR1. Here, we studied 15 sporadic patients with multiple non-intradermal schwannomas, but lacking vestibular schwannomas and ophthalmological abnormalities, who fulfilled the clinical diagnostic criteria for schwannomatosis. None of them harboured germline NF2 or SMARCB1 mutations as determined by the analysis of blood samples but seven had germline LZTR1 variants predicted to be pathogenic. At least two independent schwannomas from each patient were subjected to NF2 mutation testing. In five of the 15 patients, identical somatic NF2 mutations were identified (33%). If only those patients without germline LZTR1 variants are considered (n = 8), three of them (37.5%) had mosaic NF2 as concluded from identical NF2 mutations identified in independent schwannomas from the same patient. These findings imply that a sizeable proportion of patients who fulfil the diagnostic criteria for schwannomatosis, are actually examples of mosaic NF2. Hence, the molecular characterization of tumours in patients with a clinical diagnosis of schwannomatosis is very important. Remarkably, two of the patients with germline LZTR1 variants also had identical NF2 mutations in independent schwannomas from each patient which renders differential diagnosis of LZTR1-associated schwannomatosis versus mosaic NF2 in these patients very difficult.

Fibrolipomatous hamartomas of the median nerve in infancy and early childhood-imaging hallmarks, symptomatology, and treatment.

A fibrolipomatous hamartoma (FLH) is a rare lesion leading to an enlargement of the affected nerve and commonly manifests at the median nerve. Symptomatic patients are mostly adolescents or adults. In children below 10 years, this entity is rather unknown and likely to be misdiagnosed. We report three children with FLH, two severely and one mildly symptomatic, all below 4 years of age at the time of first presentation. Two of three children were initially misdiagnosed. We provide a review of the pertinent clinical and radiological findings of the entity. Two patients had a characteristic macrodactyly. The two symptomatic children underwent surgical carpal tunnel decompression. The intervention relived their symptoms with a long-lasting effect. Surgical reduction of the hamartoma mass is not indicated and medical treatment non-existent. CONCLUSION: A symptomatic FLH of the median nerve is rare in children below the age of 5 years but has to be kept in mind as differential diagnosis in case of wrist and/or palm swelling, macrodactyly, and pain in hand or forearm. MRI is diagnostic, with very characteristic features, which can also be identified in high-resolution nerve ultrasound. This article aims to increase the knowledge about the entity including the diagnostic features and the management options. What is Known: • Fibrolipomatous hamartomas (FLHs) of the median nerve are rare, possibly associated with macrodactyly and tissue growth at the wrist and thenar side of the palm. • An associated carpal tunnel syndrome typically occurs, if at all, in adulthood. What is New: • We describe two children below 4 years with symptomatic carpal tunnel syndrome, experiencing a long-lasting favorable outcome after carpal tunnel decompression. In this age group, only one other child undergoing surgery has been published so far. • MRI and high-resolution ultrasound demonstrate the characteristic features of FLHs and are the diagnostic modalities of choice. Biopsy is not recommended.

Development of a vestibular schwannoma tumor slice model for pharmacological testing.

BACKGROUND: Our goal was to develop a 3D tumor slice model, replicating the individual tumor microenvironment and for individual pharmaceutical testing in vestibular schwannomas with and without relation to NF2. METHODS: Tissue samples from 16 VS patients (14 sporadic, 2 NF2-related) were prospectively analyzed. Slices of 350 µm thickness were cultured in vitro, and the 3D tumor slice model underwent thorough evaluation for culturing time, microenvironment characteristics, morphology, apoptosis, and proliferation rates. Common drugs - Lapatinib (10 µM), Nilotinib (20 µM), and Bevacizumab (10 µg/ml) - known for their responses in VS were used for treatment. Treatment responses were assessed using CC3 as an apoptosis marker and Ki67 as a proliferation marker. Standard 2D cell culture models of the same tumors served as controls. RESULTS: The 3D tumor slice model accurately mimicked VS ex vivo, maintaining stability for three months. Cell count within the model was approximately tenfold higher than in standard cell culture, and the tumor microenvironment remained stable for 46 days. Pharmacological testing was feasible for up to three weeks, revealing interindividual differences in treatment response to Lapatinib and intraindividual variability in response to Lapatinib and Nilotinib. The observed effects were less pronounced in tumor slices than in standard cell culture, indicating the model's proximity to in vivo tumor biology and enhanced realism. Bevacizumab had limited impact in both models. CONCLUSION: This study introduces a 3D tumor slice model for sporadic and NF2-related VS, demonstrating stability for up to 3 months, replication of the schwannoma microenvironment, and utility for individualized pharmacological testing.

Management of Sporadic Vestibular Schwannomas in Children-Volumetric Analysis and Clinical Outcome Assessment.

Vestibular schwannomas (VS) usually manifest between the 5th and 8th decade of life. Most pediatric cases are associated with Neurofibromatosis type 2 and sporadic VS are rare in this age group. Few case series have been published. We report on our institutional series of sporadic VS in children. We included all cases between 2003 and 2021; 28 of 1635 patients harbored a sporadic VS and were younger than 21 years old. A retrospective review of clinical parameters and surgical data as well as outcomes was performed. All procedures were performed via a retrosigmoid approach. Preoperative imaging was assessed, and tumor volumetry was performed. Mean follow-up was 28 months, symptomatology was diverse. Most children and adolescents presented with hearing loss and tinnitus. All cases with multiple preoperative magnetic resonance imaging scans showed volumetric tumor growth between 1 and 18%/month (mean 8.9 ± 5.6%). Cystic tumor morphology and bone erosion was seen in larger tumors. Gross total resection was possible in 78% of patients and no recurrence was observed. All patients with subtotal resection showed tumor regrowth. Sporadic VS in children are rare and present with a high clinical variability. Surgical resection is the primary therapy and is feasible with favorable results comparable to the adult age group.

Surgical Management of Sporadic Peripheral Nerve Schwannomas in Adults: Indications and Outcome in a Single Center Cohort.

Most sporadic peripheral nerve sheath tumors in adults are schwannomas. These tumors usually present with significant pain but can also cause neurological deficits. Symptomatology is diverse, and successful surgical interventions demand interdisciplinarity. We retrospectively reviewed 414 patients treated between 2006 and 2017 for peripheral nerve sheath tumors. We analyzed clinical signs, symptoms, histology, and neurological function in the cohort of adult patients with schwannomas without a neurocutaneous syndrome. In 144 patients, 147 surgical interventions were performed. Mean follow-up was 3.1 years. The indication for surgery was pain (66.0%), neurological deficits (23.8%), significant tumor growth (8.8%), and suspected malignancy (1.4%). Complete tumor resection was achieved on 136/147 occasions (92.5%). The most common location of the tumors was intraspinal (49.0%), within the cervical neurovascular bundles (19.7%), and lower extremities (10.9%). Pain and neurological deficits improved significantly (p ≤ 0.003) after 131/147 interventions (89.1%). One patient had a persistent decrease in motor function after surgery. Complete resection was possible in 67% of recurrent tumors, compared to 94% of primary tumors. There was a significantly lower chance of complete resection for schwannomas of the cervical neurovascular bundle as compared to other locations. The surgical outcome of sporadic schwannoma surgery within the peripheral nervous system is very favorable in experienced peripheral nerve surgery centers. Surgery is safe and effective and needs a multidisciplinary setting. Early surgical resection in adult patients with peripheral nerve sheath tumors with significant growth, pain, neurological deficit, or suspected malignancy is thus recommended.

Risk Stratification for Immediate Postoperative Hearing Loss by Preoperative BAER (Brainstem Auditory Evoked Response) and Audiometry in NF2-Associated Vestibular Schwannomas.

Both brainstem auditory evoked potentials (BAEP) and audiometry play a crucial role in neuro-oncological treatment decisions in Neurofibromatosis Type 2 associated (NF2) vestibular schwannoma (VS) as hearing preservation is the major goal. In this study, we investigated the risk of immediate postoperative hearing deterioration (>15 dB and/or 15% loss in pure-tone average [PTA]/ speech discrimination score [SDS] in a cohort of 100 operated VS (ears) in 72 NF2 patients by retrospective analysis of pre- and postoperative hearing data (PTA, SDS, American Association of Otolaryngology-Head and Neck Surgery [AAO-HNS], and brainstem auditory evoked potential [BAEP] class) taking into account relevant influencing factors, particularly preoperative audiometry and BAEP status and the extent of resection. Immediately after surgery, the hearing was preserved in 73% of ears and approximately ~60% of ears kept their hearing classes. Preoperative BAEP (p = 0.015) and resection amount (p = 0.048) significantly influenced postoperative hearing outcome. The prediction model for postoperative hearing deterioration/loss between preoperative BAEP and AAO-HNS class showed increased risk by increasing BAEP class. Twenty-one tumors/ears were identified with large BAEP and AAO-HNS class discrepancies (≥2 points) and were associated with a high (48-100%) risk of deafness after surgery in ears with preoperative available hearing. Overall, the results were heterogeneous but the better both BAEP and audiometry class before surgery, the higher the chance of hearing maintenance afterwards. Large resection amounts (e.g., 100% risk in near-total resections) exhibit a significant (p < 0.05) higher risk compared to smaller amounts (e.g., 10/20% in laser-coagulated/partially resected tumors). Our results emphasized the indispensable role of both hearing monitoring in form of audiometry and neurophysiology (BAEP) in the pre-and perioperative monitoring of NF2-associated VS. Both BAEP and audiometry are good prognostic markers for the postoperative hearing outcome. The extent of resection should be strictly guided by and adjusted to the intraoperative neurophysiological monitoring.

Age at Onset and Presenting Symptoms of Neurofibromatosis Type 2 as Prognostic Factors for Clinical Course of Vestibular Schwannomas.

The presenting symptoms of the tumor suppressor gene syndrome neurofibromatosis type 2 (NF2) are often non-specific and unrelated to the disease hallmark bilateral vestibular schwannomas (VS). However, age at onset and presenting symptoms may have predictive values for the clinical course of VS. In this retrospective single-center study, we addressed this issue by reviewing 106 patients with 194 VS. Presenting symptoms attributable to VS commonly occur in 87% of adults and 31% of children. Age at onset significantly correlates with tumor volumes at presentation (p = 0.034). In addition, age at onset significantly correlates with pure-tone average (p = 0.0001), speech discrimination scores (p = 0.001), age at beginning of hearing loss (p = 0.0001), age at deafness (p = 0.0001), and age at first surgery (p = 0.0001). Patients presenting with VS related symptoms had significantly (p < 0.05) worse hearing values at presentation and after surgery. These patients also exhibited higher growth rates and tumor volumes compared to patients with non-VS related presenting symptoms, but this difference did not reach the significance level of p < 0.05. Due to the late appearance of these symptoms, the time of beginning hearing loss, surgery and deafness is significantly delayed (p < 0.05) compared to patients not presenting with VS. In summary, age at onset and type of presenting symptom provide excellent prognostic parameters for predicting VS- and hearing-related clinical course.