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Introduction: Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP‐43 pathology. Methods: We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β‐amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP‐43 pathology in GRN carriers and non‐carriers. Results: Pathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP‐43 deposits. Twenty‐two rare, pathogenic GRN variants were observed in the family cohort. Discussion: GRN mutations in clinical and neuropathological AD increase the burden of tau‐related brain pathology but show no specific association with β‐amyloid load or AD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if clinically asymptomatic compression of the middle cerebellar tract by extracerebral posterior fossa tumors can produce changes in diffusion tensor imaging (DTI) parameters and if these changes return to normal after Gamma Knife radiosurgery (GKRS). Material and methods: In 22 patients (12 female, mean age 53.8 years) with posterior fossa tumors (14 schwannomas and 8 meningiomas), the middle cerebellar tract was tracked using DTI data. DTI parameters, such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) within these tracts were determined separately on the tumor side and on the contra-lateral side. As a surrogate parameter of tract compression, we used the distance between a tangential line extending between the anterior, not affected part of the pons and the cerebellum, and the furthest extension of the tumor into the lateral rim of the pons. In a subgroup of 15 patients, DTI parameters were recorded after a follow-up of more than 2 years (mean follow-up time 37.5 months) after GKRS and compared to initial findings. Results: Before GKRS, all DTI parameters within the compressed tract had increased. The increase in MD correlated significantly with the degree of tract compression (c = 0.443, p < 0.05). Followup examinations after GKRS showed reduction in FA and AD, whereas MD and RD increased. After correction for time elapsed after treatment and tumor type, the changes of MD and AD following treatment correlated significantly with the reduction of tract compression, but not with radiation dose. Conclusion: Although without obvious clinical symptoms, disorders of the middle cerebellar tract, as in the case of posterior fossa tumors, persist after reduction of tumor size. Because of the significant correlation between the change of parameters and the reduction of tract compression, initial compression and consequent relief are regarded as the main factors responsible for persistent disorders of the middle cerebellar tract. Radiosurgery dose did not contribute significantly to changes in DTI parameters. [ABSTRACT FROM AUTHOR]

Introduction: In Gamma Knife Radiosurgery (GKRS) of suprasellar lesions, the exact localization of the visual pathways is important to avoid radiation induced optic neuropathy (RION). Reliable identification of the optic nerve, chiasm and tracts can be challenging using routine magnetic resonance imaging, especially in patients with lesions compressing the optic structures or in patients who had prior operation of suprasellar tumors. This study investigates the application of inversion recovery sequences (Fast gray and white matter acquisition T1 inversion recovery, FGATIR) to improve identification of the optic pathway. Methods: Inversion recovery sequences were performed on 5 healthy volunteers, varying their inversion times between 400 and 500 ms, and between 800 and 1100 ms. Inversion times were optimized to either suppress or to preserve the signal of the optic structures, while increasing or suppressing the signal of processes within the surrounding cisterns. Inversion recovery sequences were performed before radiosurgery on 10 patients with suprasellar tumors that were compressing or displacing the optic structures. Signal intensities of gray and white matter, of CSF and tumors were measured and subtraction images were calculated. Results: Compared to a standard T1-weighted sequence, delineation of the visual pathways was superior on inversion recovery images, both on images with suppression of the optic structures as well on images with suppression of its surrounding tissues, and was rated best on subtraction images. Conclusion: For radiosurgery of suprasellar tumors, inversion recovery sequences can be of valuable benefit for accurate delineation of optic pathway and radiosurgical dose planning in order to avoid radiation-induced normal tissue effects. [ABSTRACT FROM AUTHOR]

Background: In previous studies, we analyzed the potential of both Diffusion Tensor Imaging and of Texture Analysis of Magnetic Resonance Imaging to predict the volumetric response of benign meningiomas to Gamma Knife radiosurgery (GKRS). In this study, we analyzed the value of meningioma morphology in the prediction of volumetric changes induced by GKRS. Methods: The retrospective prediction model of meningioma responsiveness to GKRS included T1- weighted, non-contrast enhanced MRI scans obtained from 93 patients before GKRS. Imaging data was processed and analyzed through the QMENTA cloud platform and meningioma morphology was quantified by calculation of 337 shape, first-order and second order radiomic features. This analysis was performed on original 3D unfiltered MR images and images modified by Laplacian of Gaussian (LoG), logarithm and exponential filters. Results: Sixty calculated features significantly correlated with the outcome defined as meningioma volume change per month. The predictive model was created based on all radiomic and twelve non-radiomic features using the LASSO regression machine learning method. Thereby, LoG-sigma-1-0-mm-3D_firstorder_InterquartileRange (coefficient weight = -9.916) and logarithm_ngtdm_ Busyness (coefficient = 0.002) were selected as the most predictively robust and non-redundant features. The radiomic score based on these two radiomic features produced an AUC = 0.81. Its values ranged between -2.89 and 2.48, whereby score values up to -1.31 defined a subgroup of 50 patients with consistent absence (0%) of tumor progression. Conclusions: This is the first report of a strong association between the MRI radiomic features and the volumetric meningioma response to radiosurgery. The clinical importance of the early and reliable prediction of meningioma responsiveness to GKRS is based on its potential to guide individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Hypofractionated radiosurgery (HFSRS) has been recently considered as an alternative to single fraction stereotactic radiosurgery (SFSRS) for perioptic lesions. To estimate and quantify a possible benefit from HFSRS versus SFSRS, the value of the alpha/beta ratio must be known, for both lesions and organs at risk. Recently the a/ß ratio for the anterior visual pathway (AVP) has been found to be relatively small (1.03Gy). While a/ß ratios for Meningiomas and Chordomas have been investigated, a/ß ratios for Pituitary Adenomas (PA) or Craniopharyngiomas (CFG) have never been published to the best of our knowledge. Method and materials: The a/ß ratios were estimated from meta-analyses of studies on treatments performed including SFSRS, HFSRS, and radiotherapy (RT), using the Fraction Equivalent (FE) method. Physical doses were corrected for repair effects during treatment, based on the biphasic repair process of sublethal damage, with repair halftimes of 0.19h and 2.16h. While treatment times during a RT fraction are generally sufficiently shorter than one halftime of fast repair of sublethal damage, repair effects need to be considered for HFSRS and particularly for SFSRS. 35 studies fulfilling the equivalency criteria with fraction numbers 1-30 were included to assess the a/ß ratio of PA, while 19 studies with fraction numbers 1-31 were included to assess the a/ß ratio of CFG. Clinical data provided from our center were added, including HFSRS for 41 PA and 10 CFG, and SRS for 84 PA and 8 CFG, with a mean follow-up period of 23m (HFSRS) and 27m (SRS). Results: The FE plot method revealed an a/ß ratio for non-functional PA of 2.47Gy, confidence interval [2.29- 2.64Gy], while for functional PA an a/ß ratio of 4.91Gy was found, confidence interval [4.45-5.34Gy]. For CFG we found a low a/ß ratio of 0.83Gy, confidence interval [0.67-1.03Gy]. Conclusion: Pondering the concept of the biphasic repair process of sublethal damage, a/ß ratios can be much smaller than calculated with the traditional uncorrected FE method. As expected, a/ß ratios for both functional and nonfunctional PA are much larger compared to the a/ß ratio of the AVP. Theoretically, an increased Single Fraction Equivalent Dose (SFED) to the lesion of more than 14% for functional PA and of almost 6% for nonfunctional PA can be achieved with optimized HFSRS schedules, while maintaining constant the risk of visual deterioration from RION, by widening the therapeutic ratio. No therapeutic gain can be expected from hypofractionation for CFG. [ABSTRACT FROM AUTHOR]

Background: Although intracranial Rosai-Dorfman disease is a principally benign lymphohistiocytosis, some patients run a relapsing or progressive course. However, reports about long-term follow-up are extremely rare. Case Description: In two patients, initial tumor resection was incomplete or followed by recurrences over 3 years, which finally subsided after application of chemotherapy, and patients remained tumor-free for more than 7 years thereafter. Conclusion: Up to now there is no agreement on how to treat complicated cases of intracranial Rosai-Dorfman disease; our good experience with adjuvant chemotherapy and long-term follow-up will contribute to treatment planning in complicated cases. [ABSTRACT FROM AUTHOR]

Introduction: Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology., Methods: We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers., Results: Pathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP-43 deposits. Twenty-two rare, pathogenic GRN variants were observed in the family cohort., Discussion: GRN mutations in clinical and neuropathological AD increase the burden of tau-related brain pathology but show no specific association with β-amyloid load or AD., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)