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Purpose: Pilomyxoid astrocytomas (PMA) are pediatric brain tumors predominantly located in the suprasellar region, third ventricle and posterior fossa, which are considered to be more clinically aggressive than pilocytic astrocytomas (PA). Another entity, intermediate pilomyxoid tumors (IPT), exists within the spectrum of pilocytic/pilomyxoid astrocytomas. The 2021 WHO CNS classification refrained from assigning grade 1 or 2 status to PMA, thereby reflecting the need to further elucidate their clinical and imaging characteristics., Methods: We included a total of 15 patients with PMA, IPT and suprasellar PA. We retrospectively evaluated immunohistochemistry, imaging findings and diffusion characteristics within these tumors as well as whole exome sequencing for three of the cases., Results: 87% of the tumors were supratentorial with 11 cases suprasellar in location, 1 case located in the frontal white matter and 1 in the hippocampus. 6 cases demonstrated intraventricular extension. ADC values were higher in PMA and IPT than PA. 3 cases demonstrated KIAA1549-BRAF-fusion, 2 had BRAF[Formula: see text]-mutation and 6 were BRAF-wildtype. All cases had recurrence/progression on follow-up., Conclusion: PMA and IPT do not demonstrate aggressive imaging characteristics in respect to their diffusion imaging with ADC values being higher than PA. Lack of BRAF-alteration in PMA corresponded to atypical location of tumors with atypical driver mutations and mechanisms., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective:  Treatment for newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) includes maximum safe resection, followed by adjuvant radio(chemo)therapy (RCx) with temozolomide. There is evidence that it is safe for GBM patients to prolong time to irradiation over 4 weeks after surgery. This study aimed at evaluating whether this applies to GBM patients with different levels of residual tumor volume (RV)., Methods:  Medical records of all patients with newly diagnosed GBM at our department between 2014 and 2018 were reviewed. Patients who received adjuvant radio (chemo) therapy, aged older than 18 years, and with adequate perioperative imaging were included. Initial and residual tumor volumes were determined. Time to irradiation was dichotomized into two groups (≤28 and >28 days). Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression., Results:  One hundred and twelve patients were included. Adjuvant treatment regimen, extent of resection, residual tumor volume, and O 6 -methylguanine DNA methyltransferase (MGMT) promoter methylation were statistically significant factors for overall survival (OS). Time to irradiation had no impact on progression-free survival ( p  = 0.946) or OS ( p  = 0.757). When stratified for different thresholds of residual tumor volume, survival predication via Cox regression favored time to irradiation below 28 days for patients with residual tumor volume above 2 mL, but statistical significance was not reached., Conclusion:  Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Perifocal edema of brain tumors is associated with survival and neurological symptoms. The present study sought to elucidate the association between edema volume and tumor infiltrating lymphocytes (TIL) in brain metastasis., Methods: 25 patients with brain metastasis were included into the retrospective study. TILs expressing CD45 was analyzed with leucocyte common antigen staining. MRI was used to semiautomatically estimate tumor and edema volumes., Results: No correlation between tumor volume and edema volume was identified. A positive correlation was identified between tumor volume and TILs expressing CD45 of the stromal compartment (r = 0.46, p = 0.02). No correlations were identified between TILs expressing CD45 and edema volume., Conclusions: The present study identified correlations between TILs expressing CD45 and volume of BM. The tumor growth of BM might lead to a recruitment of TIL, which could be assessed by MRI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Biomechanical changes are critical for cancer progression. However, the relationship between the rheology of single cells measured ex-vivo and the living tumor is not yet understood. Here, we combined single-cell rheology of cells isolated from primary tumors with in vivo bulk tumor rheology in patients with brain tumors. Eight brain tumors (3 glioblastoma, 3 meningioma, 1 astrocytoma, 1 metastasis) were investigated in vivo by magnetic resonance elastography (MRE), and after surgery by the optical stretcher (OS). MRE was performed in a 3-Tesla clinical MRI scanner and magnitude modulus | G* |, loss angle φ , storage modulus G ', and loss modulus G '' were derived. OS experiments measured cellular creep deformation in response to laser-induced step stresses. We used a Kelvin-Voigt model to deduce two parameters related to cellular stiffness ( μ KV ) and cellular viscosity ( η KV ) from OS measurements in a time regimen that overlaps with that of MRE. We found that single-cell μ KV was correlated with | G* | ( R = 0.962, p < 0.001) and G'' ( R = 0.883, p = 0.004) but not G' of the bulk tissue. These results suggest that single-cell stiffness affects tissue viscosity in brain tumors. The observation that viscosity parameters of individual cells and bulk tissue were not correlated suggests that collective mechanical interactions ( i.e. emergent effects or cellular unjamming) of many cancer cells, which depend on cellular stiffness, influence the mechanical dissipation behavior of the bulk tissue. Our results are important to understand the emergent rheology of active multiscale compound materials such as brain tumors and its role in disease progression.

Background/aim: Tumor infiltrating lymphocytes (TILs) are an important prognostic factor in brain metastasis (BM). This study elucidated associations between apparent diffusion coefficient (ADC) texture analysis and TIL in BM., Patients and Methods: Eleven patients with BM were retrospectively included into the study. TIL levels were analyzed with Leucocyte-common antigen staining. Clinical routine magnetic resonance imaging was used to calculate the texture features., Results: ADC GrayLevelNonUniformity correlated with TILs of the stromal compartment (r=0.67, p=0.02). ADC HighGrayLevelRunEmphasis and ADC Coarseness showed associations with TILs of the tumoral compartment (r=-0.60, p=0.04 and r=0.68, p=0.02, respectively)., Conclusion: ADC texture features correlated with TIL levels in BM. ADC texture features could aid in reflecting the complex tumor-micromilieu in a non-invasive manner., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Glioblastoma and anaplastic astrocytoma represent the most commonly encountered high-grade-glioma (HGG) in adults. Although both neoplasms are very distinct entities in context of epidemiology, clinical course and prognosis, their appearance in conventional magnetic resonance imaging (MRI) is very similar. In search for additional information aiding the distinction of potentially confusable neoplasms, histogram analysis of apparent diffusion coefficient (ADC) maps recently proved to be auxiliary in a number of entities. Therefore, our present exploratory retrospective study investigated whether ADC histogram profile parameters differ significantly between anaplastic astrocytoma and glioblastoma, reflect the proliferation index Ki-67, or are associated with the prognostic relevant MGMT (methylguanine-DNA methyl-transferase) promotor methylation status., Methods: Pre-surgical ADC volumes of 56 HGG patients were analyzed by histogram-profiling. Association between extracted histogram parameters and neuropathology including WHO-grade, Ki-67 expression and MGMT promotor methylation status was investigated due to comparative and correlative statistics., Results: Grade IV gliomas were more heterogeneous than grade III tumors. More specifically, ADCmin and the lowest percentile ADCp10 were significantly lower, whereas ADCmax, ADC standard deviation and Skewness were significantly higher in the glioblastoma group. ADCmin, ADCmax, ADC standard deviation, Kurtosis and Entropy of ADC histogram were significantly correlated with Ki-67 expression. No significant difference could be revealed by comparison of ADC histogram parameters between MGMT promotor methylated and unmethylated HGG., Conclusions: ADC histogram parameters differ significantly between glioblastoma and anaplastic astrocytoma and show distinct associations with the proliferative activity in both HGG. Our results suggest ADC histogram profiling as promising biomarker for differentiation of both, however, further studies with prospective multicenter design are wanted to confirm and further elaborate this hypothesis., Competing Interests: The authors have declared that no competing interests exist.

Objective: Perifocal edema of brain tumors is associated with survival and neurological symptoms. Our aim was to analyze associations between perifocal edema and immunohistochemical features including proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis (BM)., Methods: 35 patients with BM were included into the retrospective study. The tumors were localized supratentorial in 25 lesions (71.4%) and infratentorial in 10 lesions (28.6%). The following immunohistochemical features were calculated on histopathological specimens: microvessel density, proliferation index Ki 67, matrix-metallopeptidase 9 (MMP9) extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) expression. Tumor and edema volumes were estimated semiautomatically on magnetic resonance images., Results: There were no correlations between tumor volume and edema volume. Moreover, no correlation was identified between the investigated immunohistochemical features and tumor/edema volume. In the non-small cell lung cancer subgroup, a positive correlation between tumor volume and VEGF expression was observed (r = 0.52, P = 0.02) and edema volume correlated inversely with MMP9 expression (r = -0.53, P = 0.02)., Conclusion: In BM, no linear associations exist between tumor volumes, edema volumes and immunohistochemical features reflecting proliferation potential, neoangiogenesis, microvessel density and MMP9 expression. However, in the subgroup of non-small cell lung cancer, there might be associations between MMP9 expression and edema volume as well as between tumor volume and angiogenesis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The ability to visualize the brain's fiber connections noninvasively in vivo is relatively young compared with other possibilities of functional magnetic resonance imaging. Although many studies showed tractography to be of promising value for neurosurgical care, the implications remain inconclusive. An overview of current applications is presented in this systematic review. A search was conducted for (("tractography" or "fiber tracking" or "fibre tracking") and "neurosurgery") that produced 751 results. We identified 260 relevant articles and added 20 more from other sources. Most publications concerned surgical planning for resection of tumors ( n  = 193) and vascular lesions ( n  = 15). Preoperative use of transcranial magnetic stimulation was discussed in 22 of these articles. Tractography in skull base surgery presents a special challenge ( n  = 29). Fewer publications evaluated traumatic brain injury (TBI) ( n  = 25) and spontaneous intracranial bleeding ( n  = 22). Twenty-three articles focused on tractography in pediatric neurosurgery. Most authors found tractography to be a valuable addition in neurosurgical care. The accuracy of the technique has increased over time. There are articles suggesting that tractography improves patient outcome after tumor resection. However, no reliable biomarkers have yet been described. The better rehabilitation potential after TBI and spontaneous intracranial bleeding compared with brain tumors offers an insight into the process of neurorehabilitation. Tractography and diffusion measurements in some studies showed a correlation with patient outcome that might help uncover the neuroanatomical principles of rehabilitation itself. Alternative corticofugal and cortico-cortical networks have been implicated in motor recovery after ischemic stroke, suggesting more complex mechanisms in neurorehabilitation that go beyond current models. Hence tractography may potentially be able to predict clinical deficits and rehabilitation potential, as well as finding possible explanations for neurologic disorders in retrospect. However, large variations of the results indicate a lack of data to establish robust diagnostical concepts at this point. Therefore, in vivo tractography should still be interpreted with caution and by experienced surgeons., Competing Interests: None declared., (Thieme. All rights reserved.)

Mechanical properties of biological tissues and, above all, their solid or fluid behavior influence the spread of malignant tumors. While it is known that solid tumors tend to have higher mechanical rigidity, allowing them to aggressively invade and spread in solid surrounding healthy tissue, it is unknown how softer tumors can grow within a more rigid environment such as the brain. Here, we use in vivo magnetic resonance elastography (MRE) to elucidate the role of anomalous fluidity for the invasive growth of soft brain tumors, showing that aggressive glioblastomas (GBMs) have higher water content while behaving like solids. Conversely, our data show that benign meningiomas (MENs), which contain less water than brain tissue, are characterized by fluid-like behavior. The fact that the 2 tumor entities do not differ in their soft properties suggests that fluidity plays an important role for a tumor's aggressiveness and infiltrative potential. Using tissue-mimicking phantoms, we show that the anomalous fluidity of neurotumors physically enables GBMs to penetrate surrounding tissue, a phenomenon similar to Saffman-Taylor viscous-fingering instabilities, which occur at moving interfaces between fluids of different viscosity. Thus, targeting tissue fluidity of malignant tumors might open horizons for the diagnosis and treatment of cancer., Competing Interests: The authors declare no competing interest.

Objectives: Brain metastasis (BM) is a major complication of different cancers. There is increasing evidence for influence of vascular factors on BM in patients with non-small cell lung cancer (NSCLC). It is not known if the same is true for other tumors that might rely on different forms of vasculogenesis. The objective of this retrospective study was to evaluate a possible negative association of vascular white matter lesions and vascular risk factors (vasRF) with brain metastases in patients with melanoma., Patients and Methods: 3D-brain magnetic resonance imaging (MRI) of 30 patients with BM from malignant melanoma and screening MRI of 31 BM negative patients were analysed. Number of metastases was calculated and T2 hyperintensive white matter lesions (WML) were classified according to Fazekas-Score (grade I-III) per patient and compared between BM+ and BM- patients., Results: Patients without BM showed more pronounced WML (median = WML 1, mean = 1.3; SD = 1.04,) than patients with BM (median = WML 0, mean = 0.6; SD = 0.8, p = 0.017). With respect to vascular risk factors, BM were more likely (p x2  = 0.019) in patients without vasRF., Conclusions: WML and possibly vasRF may reduce the risk of BM in different malignant tumors including melanoma. Presence of WML in patients with BM could potentially influence treatment choice regarding local or whole brain treatment after further multicentric prospective validation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: There is increasing evidence that cerebral microangiopathy reduces number of brain metastases. Aim of this study was to analyse if vascular risk factors (arterial hypertension, diabetes mellitus, smoking, and hypercholesterolemia) or the presence of peripheral arterial occlusive disease (PAOD) can have an impact on number or size of brain metastases., Patients and Methods: 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Mean number of metastases (NoM) and mean diameter of metastases (mDM) were compared between patients with/without vascular risk factors (vasRF)., Results: No general correlation of vascular risk factors with brain metastases was found in this monocentric analysis of a patient cohort with several tumor types. Arterial hypertension, diabetes mellitus, hypercholesterolemia and smoking did not show an effect in uni- and multivariate analysis. In patients with PAOD the number of BM was lower than without PAOD. This was the case independent from cerebral microangiopathy but did not persist in multivariate analysis., Conclusion: From this first screening approach vascular risk factors do not appear to strongly influence brain metastasation. However, larger prospective multi-centric studies with better characterized severity of vascular risk are needed to more accurately detect effects of individual factors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Brain metastases are major complications of common cancers. Tumor type and proneness to the CNS are thought to define the number and size of brain metastases. It is not known if intrinsic vascular factors can also have an effect. Restricted perfusion due to cerebral small vessel disease is frequent in elderly patients and causes white matter lesions (WML). The aim of this analysis was to evaluate a possible negative effect of WML and patient age on the number and size of brain metastases (BM) of different tumor entities. Pre-therapeutic 3 T brain magnetic resonance imaging (MRI) of 200 patients with BM were analyzed. Location, size and number of BM (NoM) were determined. T2 hyperintensive WML were scored according to Fazekas-Score (grade I-III). Patients with WML grade 1 (NoM: 5.59; p = 0.009) and grade 2 (NoM: 3.68; p = 0.002) had significantly less BM than patients without WML (NoM: 6.99). This effect was present in subgroups of different tumors: NSCLC (p = 0.05), other tumors than NSCLC (p = 0.048). Age (≤65 or >65 years) was positively correlated with the degree of WML but not with number (pNoM = 0.832) or mean diameter (pmDM = 0.662) of brain metastases. While patient age did not appear to be relevant, increasing WML were associated with lower number of brain metastases in different tumor types.

Purpose: In recent years Magnetic Resonance Elastography (MRE) emerged into a clinically applicable imaging technique. It has been shown that MRE is capable of measuring global changes of the viscoelastic properties of cerebral tissue. The purpose of our study was to evaluate a spatially resolved three-dimensional multi-frequent MRE (3DMMRE) for assessment of the viscoelastic properties of intracranial tumours., Methods: A total of 27 patients (63 ± 13 years) were included. All examinations were performed on a 3.0 T scanner, using a modified phase-contrast echo planar imaging sequence. We used 7 vibration frequencies in the low acoustic range with a temporal resolution of 8 dynamics per wave cycle. Post-processing included multi-frequency dual elasto-visco (MDEV) inversion to generate high-resolution maps of the magnitude |G*| and the phase angle φ of the complex valued shear modulus., Results: The tumour entities included in this study were: glioblastoma (n = 11), anaplastic astrocytoma (n = 3), meningioma (n = 7), cerebral metastasis (n = 5) and intracerebral abscess formation (n = 1). Primary brain tumours and cerebral metastases were not distinguishable in terms of |G*| and φ. Glioblastoma presented the largest range of |G*| values and a trend was delineable that glioblastoma were slightly softer than WHO grade III tumours. In terms of φ, meningiomas were clearly distinguishable from all other entities., Conclusions: In this pilot study, while analysing the viscoelastic constants of various intracranial tumour entities with an improved spatial resolution, it was possible to characterize intracranial tumours by their mechanical properties. We were able to clearly delineate meningiomas from intraaxial tumours, while for the latter group an overlap remains in viscoelastic terms.

Objective: To generate high-resolution maps of the viscoelastic properties of human brain parenchyma for presurgical quantitative assessment in glioblastoma (GB)., Methods: Twenty-two GB patients underwent routine presurgical work-up supplemented by additional multifrequency magnetic resonance elastography. Two three-dimensional viscoelastic parameter maps, magnitude |G*|, and phase angle φ of the complex shear modulus were reconstructed by inversion of full wave field data in 2-mm isotropic resolution at seven harmonic drive frequencies ranging from 30 to 60 Hz., Results: Mechanical brain maps confirmed that GB are composed of stiff and soft compartments, resulting in high intratumor heterogeneity. GB could be easily differentiated from healthy reference tissue by their reduced viscous behavior quantified by φ (0.37±0.08 vs. 0.58±0.07). |G*|, which in solids more relates to the material's stiffness, was significantly reduced in GB with a mean value of 1.32±0.26 kPa compared to 1.54±0.27 kPa in healthy tissue (P = 0.001). However, some GB (5 of 22) showed increased stiffness., Conclusion: GB are generally less viscous and softer than healthy brain parenchyma. Unrelated to the morphology-based contrast of standard magnetic resonance imaging, elastography provides an entirely new neuroradiological marker and contrast related to the biomechanical properties of tumors.

Introduction: An integrated PET/MRI scanner has been used in selected cases of pediatric brain tumor patients to obtain additional metabolic information about lesions for preoperative biopsy planning and navigation., Patients and Methods: Four patients, age 9-16 years, received PET/MRI scans employing [(11)C]methionine positron emission tomography (PET) and contrast-enhanced 3D-MR sequences for neuronavigation. PET and MR sequences have been matched for neurosurgical guidance. An infrared camera-based neuronavigation system was employed with co-registered MR and PET images fused to hybrid images for preoperative planning, stereotactic biopsy planning, and/or intraoperative guidance., Results: All patients showed hot spots of increased amino acid transport in PET and contrast-enhancing lesions in MRI. In three of the four patients, PET hot spots were congruent with contrast-enhancing areas in MRI. In two patients, frame-based stereotactic biopsies were taken from thalamo-mesencephalic lesions. One patient underwent second-look surgery for the suspicion of recurrent malignant glioma of the posterior fossa. One incidental frontal mass lesion was subtotally resected. No complications occurred. Hybrid imaging was helpful during the procedures to obtain representative histopathologic specimens and for surgical guidance during resection. Co-registered images did match with intraoperative landmarks, tumor borders, and histopathologic specimens., Conclusion: The integrated PET/MRI scanner offers co-registered multimodal, high-resolution data for neuronavigation with reduced radiation exposure compared to PET/CT scans. One examination session provides all necessary data for neuronavigation and preoperative planning, avoiding additional anesthesia in the small patients. Hybrid multimodality imaging may improve safety and yield additional information when obtaining representative histopathologic specimens of brain tumors.

Purposes: First, to evaluate outcome, the benefit of concurrent chemotherapy and prognostic factors in a cohort of sixty-four high-grade glioma patients who underwent a second course of radiation therapy at progression. Second, to validate a new prognostic score for overall survival after reirradiation of progressive gliomas with an independent patient cohort., Patients and Methods: All patients underwent fractionated reirradiation with a median physical dose of 36 Gy. Median planned target volume was 110.4 ml. Thirty-six patients received concurrent chemotherapy consisting in 24/36 cases (67%) of carboplatin and etoposide and in 12/36 cases (33%) of temozolomide. We used the Kaplan Meier method, log rank test and proportional hazards regression analysis for statistical assessment., Results: Median overall survival from the start of reirradiation was 7.7 ± 0.7 months. Overall survival rates at 6 and 12 months were 60 ± 6% and 24 ± 6%, respectively. Despite relatively large target volumes we did not observe any major acute toxicity. Concurrent chemotherapy did not appear to improve outcome. In contrast, female gender, young age, WHO grade III histology, favorable Karnofsky performance score and complete resection of the tumor prior to reirradiation were identified as positive prognostic factors for overall survival. We finally validated a recent suggestion for a prognostic score with our independent but small patient cohort. Our preliminary findings suggest that its ability to discriminate between different prognostic groups is limited., Conclusions: Outcome of our patients was comparable to previous studies. Even in case of large target volumes reirradiation seems to be feasible without observing major toxicity. The benefit of concurrent chemotherapy is still elusive. A reassessment of the prognostic score, tested in this study, using a larger patient cohort is needed.

We report a case of a 24-year-old man with a right thalamic germinoma that initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis based on clinical symptoms, imaging results and histology of an endoscopically navigated biopsy. A second biopsy, prompted by clinical course, and performed openly from parieto-lateral revealed the underlying germinoma, obscured in the first biopsy by a granulomatous tissue response, particularly at the tumor edge. The present case highlights granulomatous inflammatory tissue response on the tumor edge of germinoma as a tumor-immanent diagnostic challenge. This diagnostic problem is aggravated by stereotactic and endoscopic approaches. We conclude that granulomatous inflammation in a specimen obtained by biopsy of a midline lesion should always be considered for the differential diagnosis of germinoma. Stereotactic and endoscopic surgery should sample several different target points within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy approach is advantageous compared to endoscopic or stereotactic techniques for germinoma and should be considered if a germinoma is in the differential diagnosis and if allowed by the clinical situation.

Background and Purpose: Differentiating between intracranial cysts or cyst-like structures and communicating or noncommunicating cysts is often not possible with cranial CT or nonfunctional MR imaging. We evaluated a retrospective ECG-gated fast imaging with steady-state precession (PSIF) MR sequence with optional cine mode to differentiate cystic masses from enlarged CSF spaces and to determine the accuracy of detecting communication between cysts and neighboring CSF spaces., Methods: Fourteen patients with intracranial cystic masses underwent CSF flow studies with an ungated and a retrospective ECG-gated cine-mode PSIF sequence in addition to spin-echo imaging. Findings were evaluated retrospectively by using a five-point rating scale and without knowledge of clinical or other imaging findings. Results were compared with intraoperative findings or with results of intrathecal contrast studies., Results: Eighteen arachnoid cysts and one enlarged cisterna magna were diagnosed. Improved differentiation between cysts and enlarged CSF spaces was obtained with cine-mode PSIF imaging in six lesions (six patients). Increased diagnostic certainty as to communication between cysts and CSF spaces was obtained in 18 cysts (13 patients). Diagnoses were verified by membranectomy in five lesions, by CT cisternography in five lesions, and indirectly by shunting in one cystic lesion. In one case, MR diagnosis was not confirmed by CT cisternography., Conclusion: Cine-mode MR imaging with a retrospective ECG-gated flow-sensitive PSIF sequence contributed to the certainty of communication between arachnoid cysts and neighboring CSF spaces with an accuracy of 90%, using surgical findings or intrathecal contrast studies as reference. Differentiation between intracranial cysts and enlargement of CSF spaces and other cystic masses was improved in 25% of cases.