Citations

Abstract Please see the full-text version of this guideline (https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_3) for the target population of each recommendation listed below. STEREOTACTIC RADIOSURGERY Question 1 What is the overall probability of maintaining serviceable hearing following stereotactic radiosurgery utilizing modern dose planning, at 2, 5, and 10 yr following treatment? Recommendation Level 3 : Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled that there is moderately high probability (>50%-75%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 2 Among patients with AAO-HNS (American Academy of Otolaryngology-Head and Neck Surgery hearing classification) class A or GR (Gardner-Robertson hearing classification) grade I hearing at baseline, what is the overall probability of maintaining serviceable hearing following stereotactic radiosurgery, utilizing modern dose planning, at 2, 5, and 10 yr following treatment? Recommendation Level 3 : Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled that there is a high probability (>75%-100%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 3 What patient- and tumor-related factors influence progression to nonserviceable hearing following stereotactic radiosurgery using ≤13 Gy to the tumor margin? Recommendation Level 3: Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled regarding the probability of successful hearing preservation based on the following prognostic data: the most consistent prognostic features associated with maintenance of serviceable hearing are good preoperative word recognition and/or pure tone thresholds with variable cut-points reported, smaller tumor size, marginal tumor dose ≤12 Gy, and cochlear dose ≤4 Gy. Age and sex are not strong predictors of hearing preservation outcome. MICROSURGERY Question 4 What is the overall probability of maintaining serviceable hearing following microsurgical resection of small to medium-sized sporadic vestibular schwannomas early after surgery, at 2, 5, and 10 yr following treatment? Recommendation Level 3 : Individuals who meet these criteria and are considering microsurgical resection should be counseled that there is a moderately low probability (>25%-50%) of hearing preservation immediately following surgery, moderately low probability (>25%-50%) of hearing preservation at 2 yr, moderately low probability (>25%-50%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 5 Among patients with AAO-HNS class A or GR grade I hearing at baseline, what is the overall probability of maintaining serviceable hearing following microsurgical resection of small to medium-sized sporadic vestibular schwannomas early after surgery, at 2, 5, and 10 yr following treatment? Recommendation Level 3: Individuals who meet these criteria and are considering microsurgical resection should be counseled that there is a moderately high probability (>50%-75%) of hearing preservation immediately following surgery, moderately high probability (>50%-75%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 6 What patient- and tumor-related factors influence progression to nonserviceable hearing following microsurgical resection of small to medium-sized sporadic vestibular schwannomas? Recommendation Level 3: Individuals who meet these criteria and are considering microsurgical resection should be counseled regarding the probability of successful hearing preservation based on the following prognostic data: the most consistent prognostic features associated with maintenance of serviceable hearing are good preoperative word recognition and/or pure tone thresholds with variable cut-points reported, smaller tumor size commonly less than 1 cm, and presence of a distal internal auditory canal cerebrospinal fluid fundal cap. Age and sex are not strong predictors of hearing preservation outcome. CONSERVATIVE OBSERVATION Question 7 What is the overall probability of maintaining serviceable hearing with conservative observation of vestibular schwannomas at 2, 5, and 10 yr following diagnosis? Recommendation Level 3: Individuals who meet these criteria and are considering observation should be counseled that there is a high probability (>75%-100%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 8 Among patients with AAO-HNS class A or GR grade I hearing at baseline, what is the overall probability of maintaining serviceable hearing with conservative observation at 2 and 5 yr following diagnosis? Recommendation Level 3: Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled that there is a high probability (>75%-100%) of hearing preservation at 2 yr, and moderately high probability (>50%-75%) of hearing preservation at 5 yr. Insufficient data were available to determine the probability of hearing preservation at 10 yr for this population subset. Question 9 What patient and tumor-related factors influence progression to nonserviceable hearing during conservative observation? Recommendation Level 3: Individuals who meet these criteria and are considering observation should be counseled regarding probability of successful hearing preservation based on the following prognostic data: the most consistent prognostic features associated with maintenance of serviceable hearing are good preoperative word recognition and/or pure tone thresholds with variable cut-points reported, as well as nongrowth of the tumor. Tumor size at the time of diagnosis, age, and sex do not predict future development of nonserviceable hearing during observation. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-manage-ment-patients-vestibular-schwannoma/chapter_3.

Abstract QUESTION 1 What is the expected diagnostic yield for vestibular schwannomas when using a magnetic resonance imaging (MRI) to evaluate patients with previously published definitions of asymmetric sensorineural hearing loss? TARGET POPULATION These recommendations apply to adults with an asymmetric sensorineural hearing loss on audiometric testing. RECOMMENDATION Level 3: On the basis of an audiogram, it is recommended that MRI screening on patients with ≥10 decibels (dB) of interaural difference at 2 or more contiguous frequencies or ≥15 dB at 1 frequency be pursued to minimize the incidence of undiagnosed vestibular schwannomas. However, selectively screening patients with ≥15 dB of interaural difference at 3000 Hz alone may minimize the incidence of MRIs performed that do not diagnose a vestibular schwannoma. QUESTION 2 What is the expected diagnostic yield for vestibular schwannomas when using an MRI to evaluate patients with asymmetric tinnitus, as defined as either purely unilateral tinnitus or bilateral tinnitus with subjective asymmetry? TARGET POPULATION These recommendations apply to adults with subjective complaints of asymmetric tinnitus. RECOMMENDATION Level 3: It is recommended that MRI be used to evaluate patients with asymmetric tinnitus. However, this practice is low yielding in terms of vestibular schwannoma diagnosis (<1%). QUESTION 3 What is the expected diagnostic yield for vestibular schwannomas when using an MRI to evaluate patients with a sudden sensorineural hearing loss? TARGET POPULATION These recommendations apply to adults with a verified sudden sensorineural hearing loss on an audiogram. RECOMMENDATION Level 3: It is recommended that MRI be used to evaluate patients with a sudden sensorineural hearing loss. However, this practice is low yielding in terms of vestibular schwannoma diagnosis (<3%). The full guideline can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_2.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

AbstractOligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein‐coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood. Enhancements in spinal cord myelin with PAR2 loss‐of‐function were accompanied by increased numbers of Olig2‐ and CC1‐positive oligodendrocytes, as well as in levels of cyclic adenosine monophosphate (cAMP), and extracellular signal related kinase 1/2 (ERK1/2) signaling. Parallel promyelinating effects were observed after blocking PAR2 expression in purified oligodendrocyte cultures, whereas inhibiting adenylate cyclase reversed these effects. Conversely, PAR2 activation reduced PLP expression and this effect was prevented by brain derived neurotrophic factor (BDNF), a promyelinating growth factor that signals through cAMP. PAR2 knockout mice also showed improved myelin resiliency after traumatic spinal cord injury and an accelerated pattern of myelin regeneration after focal demyelination. These findings suggest that PAR2 is an important controller of myelin production and regeneration, both in the developing and adult spinal cord.

PurposeThis work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well‐defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam.MethodsA novel silicon microdosimeter with well‐defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/μm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread‐out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth‐dose distribution from the treatment planning system (TPS) and to compare the simulated dose‐mean lineal energy to the experimental results.ResultsFor a 131 MeV PBS spot (124.6 mm R90 range in water), the measured dose‐mean lineal energy increased from 2 keV/μm at the entrance to 8 keV/μm in the BP, with a maximum value of 10 keV/μm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP.ConclusionsThe SOI microdosimeter with its well‐defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy.