An interdisciplinary integrated specialized one-stop outpatient clinic for idiopathic intracranial hypertension - an assessment of sick leave, presenteeism, and health care utilization.

BACKGROUND: Management of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop- concept. Here, we aimed to evaluate effects of this concept on sick leave, presenteeism, and health care utilization. METHODS: In a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding economic outcome parameters assessed over 6 months. Multivariate binary logistic regression models were used to adjust for confounders. RESULTS: Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, the IC group showed significantly fewer days with sick leave or presenteeism (-5 days/month), fewer unscheduled contacts for IIH-specific problems (-2.3/month), and fewer physician or hospital contacts in general (-4.1 contacts/month). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of the IC concept in these groups. CONCLUSIONS: Interdisciplinary integrated management significantly improves the burden of IIH in terms of sick leave, presenteeism and healthcare consultations - particularly in socioeconomically underprivileged patient groups.

The additive value of complementing diagnostic idiopathic intracranial hypertension criteria by MRI - an external validation study.

BACKGROUND: Recently, diagnostic criteria including a standardized MRI criterion were presented to identify patients suffering from idiopathic intracranial hypertension (IIH) proposing that IIH might be defined by two out of three objective findings (papilledema, ≥ 25 cm cerebrospinal fluid opening pressure (CSF-OP) and ≥ 3/4 neuroimaging signs). METHODS: To provide independent external validation, we retrospectively applied the proposed diagnostic criteria to our cohort of patients with clinical suspicion of IIH from the Vienna IIH database. Neuroimaging was reevaluated for IIH signs according to standardized definitions by a blinded expert neuroradiologist. We determined isolated diagnostic accuracy of the neuroimaging criterion (≥ 3/4 signs) as well as overall accuracy of the new proposed criteria. RESULTS: We included patients with IIH (n = 102) and patients without IIH (no-IIH, n = 23). Baseline characteristics were balanced between IIH and no-IIH groups, but papilledema and CSF-OP were significantly higher in IIH. For the presence of ≥ 3/4 MRI signs, sensitivity was 39.2% and specificity was 91.3% with positive predictive value (PPV) of 95.2% and negative predictive value (NPV) 25.3%. Reclassifying our cohort according to the 2/3 IIH definition correctly identified 100% of patients without IIH, with definite IIH and suggested to have IIH without papilledema by Friedman criteria, respectively. CONCLUSION: The standardized neuroimaging criteria are easily applicable in clinical routine and provide moderate sensitivity and excellent specificity to identify patients with IIH. Defining IIH by 2/3 criteria significantly simplifies diagnosis without compromising accuracy.

Multi-Dynamic-Multi-Echo-based MRI for the Pre-Surgical Determination of Sellar Tumor Consistency: a Quantitative Approach for Predicting Lesion Resectability.

PURPOSE: Pre-surgical information about tumor consistency could facilitate neurosurgical planning. This study used multi-dynamic-multi-echo (MDME)-based relaxometry for the quantitative determination of pituitary tumor consistency, with the aim of predicting lesion resectability. METHODS: Seventy-two patients with suspected pituitary adenomas, who underwent preoperative 3 T MRI between January 2020 and January 2022, were included in this prospective study. Lesion-specific T1-/T2-relaxation times (T1R/T2R) and proton density (PD) metrics were determined. During surgery, data about tumor resectability were collected. A Receiver Operating Characteristic (ROC) curve analysis was performed to investigate the diagnostic performance (sensitivity/specificity) for discriminating between easy- and hard-to-remove by aspiration (eRAsp and hRAsp) lesions. A Mann-Whitney-U-test was done for group comparison. RESULTS: A total of 65 participants (mean age, 54 years ± 15, 33 women) were enrolled in the quantitative analysis. Twenty-four lesions were classified as hRAsp, while 41 lesions were assessed as eRAsp. There were significant differences in T1R (hRAsp: 1221.0 ms ± 211.9; eRAsp: 1500.2 ms ±â€¯496.4; p = 0.003) and T2R (hRAsp: 88.8 ms ± 14.5; eRAsp: 137.2 ms ± 166.6; p = 0.03) between both groups. The ROC analysis revealed an area under the curve of 0.72 (95% CI: 0.60-0.85) at p = 0.003 for T1R (cutoff value: 1248 ms; sensitivity/specificity: 78%/58%) and 0.66 (95% CI: 0.53-0.79) at p = 0.03 for T2R (cutoff value: 110 ms; sensitivity/specificity: 39%/96%). CONCLUSION: MDME-based relaxometry enables a non-invasive, pre-surgical characterization of lesion consistency and, therefore, provides a modality with which to predict tumor resectability.

A Comparison of 7 Tesla MR Spectroscopic Imaging and 3 Tesla MR Fingerprinting for Tumor Localization in Glioma Patients.

This paper investigated the correlation between magnetic resonance spectroscopic imaging (MRSI) and magnetic resonance fingerprinting (MRF) in glioma patients by comparing neuro-oncological markers obtained from MRSI to T1/T2 maps from MRF. Data from 12 consenting patients with gliomas were analyzed by defining hotspots for T1, T2, and various metabolic ratios, and comparing them using Sørensen-Dice similarity coefficients (DSCs) and the distances between their centers of intensity (COIDs). The median DSCs between MRF and the tumor segmentation were 0.73 (T1) and 0.79 (T2). The DSCs between MRSI and MRF were the highest for Gln/tNAA (T1: 0.75, T2: 0.80, tumor: 0.78), followed by Gly/tNAA (T1: 0.57, T2: 0.62, tumor: 0.54) and tCho/tNAA (T1: 0.61, T2: 0.58, tumor: 0.45). The median values in the tumor hotspot were T1 = 1724 ms, T2 = 86 ms, Gln/tNAA = 0.61, Gly/tNAA = 0.28, Ins/tNAA = 1.15, and tCho/tNAA = 0.48, and, in the peritumoral region, were T1 = 1756 ms, T2 = 102 ms, Gln/tNAA = 0.38, Gly/tNAA = 0.20, Ins/tNAA = 1.06, and tCho/tNAA = 0.38, and, in the NAWM, were T1 = 950 ms, T2 = 43 ms, Gln/tNAA = 0.16, Gly/tNAA = 0.07, Ins/tNAA = 0.54, and tCho/tNAA = 0.20. The results of this study constitute the first comparison of 7T MRSI and 3T MRF, showing a good correspondence between these methods.

The Vienna idiopathic intracranial hypertension database-An Austrian registry.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is becoming increasingly more prevalent bearing the risk of visual impairment and affecting the quality of life. Clinical presentation and outcome are heterogeneous. Large, well-characterized cohorts are scarce. OBJECTIVE: To characterize the clinical spectrum, diagnostic findings, therapeutic management, and outcome of IIH. METHODS: We identified patients with IIH according to modified Friedman criteria treated at our center between 2014 and 2021. The Vienna IIH database is described in detail. RESULTS: Of 113 patients 89% were female (mean age 32.3 years). Median body mass index (BMI) was 31.8, with 85% overweight (BMI > 25) and 5% were classified as IIH without papilledema. Headache was present in 84% and showed migraine features in 43%. Median opening pressure in lumbar puncture was 31 cmH2O. Pharmacotherapy (predominantly acetazolamide) was established in 99%, 56% required at least 1 therapeutic lumbar puncture and 13% a surgical intervention. After a median 3.7 years follow-up, 57% had achieved significant weight loss, papilledema was present in 59% and headache in 76% (58% improved). Comparing initial presentation to follow-up, perimetry was abnormal in 67% vs. 50% (8% worsened, 24% improved) and transorbital sonography in 87% vs. 65% with a median optic nerve sheath diameter of 5.4 mm vs. 4.9 mm. Median peripapillary retinal nerve fiber layer thickness decreased from 199 µm to 99 µm and ganglion cell layer volume from 1.13 mm3 to 1.05 mm3. CONCLUSION: The large representative Vienna IIH cohort characterizes IIH-related symptoms, diagnostic findings, treatment, and outcome emphasizing substantial long-term sequelae of IIH. Future analyses will aim to refine phenotyping and identify factors predicting outcome.

Concomitant radiosurgical and targeted oncological treatment improves the outcome of patients with brain metastases from gastrointestinal cancer.

BACKGROUND: So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT). METHODS: Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported. RESULTS: Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT. CONCLUSION: Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management.

MRI features of idiopathic intracranial hypertension are not prognostic of visual and headache outcome.

BACKGROUND: In idiopathic intracranial hypertension (IIH), certain MRI features are promising diagnostic markers, but whether these have prognostic value is currently unknown. METHODS: We included patients from the Vienna-Idiopathic-Intracranial-Hypertension (VIIH) database with IIH according to Friedman criteria and cranial MRI performed at diagnosis. Presence of empty sella (ES), perioptic subarachnoid space distension (POSD) with or without optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) was assessed and multivariable regression models regarding visual outcome (persistent visual impairment/visual worsening) and headache outcome (headache improvement/freedom of headache) were fitted. RESULTS: We included 84 IIH patients (88.1% female, mean age 33.5 years, median body mass index 33.7). At baseline, visual impairment was present in 70.2% and headache in 84.5% (54.8% chronic). Persistent visual impairment occurred in 58.3%, visual worsening in 13.1%, headache improvement was achieved in 83.8%, freedom of headache in 26.2%. At least one MRI feature was found in 78.6% and 60.0% had ≥3 features with POSD most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.0%) and PGF (23.8%). In multivariable models, there was no association of any single MRI feature or their number with visual impairment, visual worsening, headache improvement or freedom. Visual impairment at baseline predicted persistent visual impairment (odds ratio 6.3, p<0.001), but not visual worsening. Chronic headache at baseline was significantly associated with lower likelihood of headache freedom (odds ratio 0.48, p=0.013), but not with headache improvement. CONCLUSIONS: MRI features of IIH are neither prognostic of visual nor headache outcome.

Impact of rater experience and referral question on detecting magnetic resonance imaging features of idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: In idiopathic intracranial hypertension (IIH), magnetic resonance imaging (MRI) features are promising diagnostic markers, but the impact of rater experience and the specific referral question is unknown. METHODS: From the Vienna Idiopathic Intracranial Hypertension database, patients were included with definitive IIH and routine cranial MRI performed during diagnostic work-up. Frequencies of partial empty sella (ES), optic nerve sheath distension (ONSD), optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) were compared in three settings: (i) real-world rating, (ii) junior neuroradiologist without special IIH training and (iii) senior neuroradiologist with experience in IIH imaging (gold standard). RESULTS: Magnetic resonance imaging scans of 84 IIH patients (88% female, mean age 33.5 years) were evaluated. By gold standard, ONSD was the most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.4%) and PGF (23.8%). Compared to the gold standard, IIH features were described significantly less frequently in routine MRI reports (ONSD 28.6%, ONT 13.1%, PGF 4.8%, TSS 42.9%, p < 0.01 respectively) except for ES (42.9%, p = 0.9). A specific referral question regarding IIH increased detection rates in routine reports, but rates remained significantly lower than by gold standard. In contrast, a rating by a neuroradiologist without special training produced significantly higher frequencies of ONSD (81.0%, p < 0.01) and ONT (60.7%, p < 0.01) but not of ES (47.6%), PGF (29.8%) and TSS (68.1%). CONCLUSIONS: Idiopathic intracranial hypertension MRI features are underestimated in routine MRI reports and partly overcalled by less experienced neuroradiologists, driven by features less well known or methodologically difficult. Reevaluation of MRI scans by an experienced rater (and to a lesser degree a specific referral question) improves diagnostic accuracy.

Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension.

BACKGROUND: In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists (GLP-1-RAs) could present an attractive treatment option. METHODS: In this open-label, single-center, case-control pilot study, patients with IIH (pwIIH) and a body mass index (BMI) of ≥ 30 kg/m2 were offered to receive a GLP-1-RA (semaglutide, liraglutide) in addition to the usual care weight management (UCWM). Patients electing for UCWM only served as a control group matched for age-, sex- and BMI (1:2 ratio). The primary endpoint was the percentage weight loss at six months (M6) compared to baseline. Secondary endpoints included the rate of patients with a weight loss of ≥ 10%, monthly headache days (MHD), the rate of patients with a ≥ 30% and ≥ 50% reduction in MHD, visual outcome parameters, and adverse events (AEs). RESULTS: We included 39 pwIIH (mean age 33.6 years [SD 8.0], 92.3% female, median BMI 36.3 kg/m2 [IQR 31.4-38.3]), with 13 patients being treated with GLP-1-RAs. At M6, mean weight loss was significantly higher in the GLP-1-RA group (-12.0% [3.3] vs. -2.8% [4.7]; p < 0.001). Accordingly, weight loss of ≥ 10% was more common in this group (69.2% vs. 4.0%; p < 0.001). Median reduction in MHD was significantly higher in the GLP-1-RA group (-4 [-10.5, 0.5] vs. 0 [-3, 1]; p = 0.02), and the 50% responder rate was 76.9% vs. 40.0% (p = 0.04). Visual outcome parameters did not change significantly from baseline to M6. Median reduction in acetazolamide dosage was significantly higher in the GLP-1-RA group (-16.5% [-50, 0] vs. 0% [-25, 50]; p = 0.04). AEs were mild or moderate and attributed to gastrointestinal symptoms in 9/13 patients. None of the AEs led to premature treatment discontinuation. CONCLUSIONS: This open-label, single-center pilot study suggests that GLP-1-RAs are an effective and safe treatment option for achieving significant weight loss with a favorable effect on headache, leading to reduced acetazolamide dosage in pwIIH.

Evaluation of Gliomas with Magnetic Resonance Fingerprinting with PET Correlation-A Comparative Study.

OBJECTIVES: Advanced MR imaging of brain tumors is still mainly based on qualitative imaging. PET imaging offers additive metabolic information, and MR fingerprinting (MRF) offers a novel approach to quantitative data acquisition. The purpose of this study was to evaluate the ability of MRF to predict tumor regions and grading in combination with PET. METHODS: Seventeen patients with histologically verified infiltrating gliomas and available amino-acid PET data were enrolled. ROIs for solid tumor parts (SPo), perifocal edema (ED1), and normal-appearing white matter (NAWM) were selected on conventional MRI sequences and aligned to the MRF and PET images. The predictability of gliomas by region and grading as well as intermodal correlations were assessed. RESULTS: For MRF, we calculated an overall predictability by region (SPo, ED1, and NAWM) for all of the MRF parameters of 76.5%, 47.1%, and 94.1%, respectively. The overall ability to distinguish low- from high-grade gliomas using MRF was 88.9% for LGG and 75% for HGG, with an accuracy of 82.4%, a ppV of 85.71%, and an npV of 80%. PET positivity was found in 13/17 patients for solid tumor parts, and in 3/17 patients for the edema region. However, there was no significant difference in region-specific MRF values between PET positive and PET negative patients. CONCLUSIONS: MRF and PET provide quantitative measurements of the tumor tissue characteristics of gliomas, with good predictability. Nonetheless, the results are dissimilar, reflecting the different underlying mechanisms of each method.

Idiopathic intracranial hypertension presenting with migraine phenotype is associated with unfavorable headache outcomes.

OBJECTIVE: To assess the prognostic impact of migraine headache in idiopathic intracranial hypertension (IIH). BACKGROUND: Migraine headache is common in IIH, but it is unclear whether it has prognostic relevance. METHODS: We investigated patients with IIH from the Vienna-IIH-database and differentiated migraine (IIH-MIG) from non-migraine headache (IIH-nonMIG) and without headache (IIH-noHA). Using multivariable models, we analyzed the impact of IIH-MIG on headache and visual outcomes 12 months after diagnosis. RESULTS: Among 97 patients (89% female, mean [SD] age 32.9 [11.1] years, median body mass index 32.0 kg/m2 , median cerebrospinal fluid opening pressure 310 mm), 46% were assigned to IIH-MIG, 37% to IIH-nonMIG (11% tension-type, 26% unclassifiable), and 17% to IIH-noHA. Overall, headache improvement was achieved in 77% and freedom of headache in 28%. The IIH-MIG group showed significantly lower rates for headache improvement (67% vs. 89% in IIH-nonMIG, p = 0.019) and freedom of headache (11% vs. 33% in IIH-nonMIG and 63% in IIH-noHA, p = 0.015). These differences persisted when only analyzing patients with resolved papilledema at follow-up. In contrast, visual worsening was significantly less common in IIH-MIG (9% vs. 28% in IIH-nonMIG and 31% in IIH-noHA, p = 0.045). In multivariable models, IIH-MIG was associated with a significantly lower likelihood of achieving headache improvement (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40-0.78, p < 0.001) and freedom of headache (OR 0.29, 95% CI 0.12-0.46, p < 0.001), but also a lower risk for visual worsening (OR 0.26, 95% CI 0.04-0.82, p < 0.001). CONCLUSIONS: In IIH, migraine headache is associated with unfavorable outcomes for headache, even when papilledema has resolved, and possibly favorable visual outcome.

Does High-Definition 3-Dimensional Imaging Improve Orientation During Endoscopic Transsphenoidal Surgery? A Prospective Trial.

BACKGROUND: Endoscopy has evolved as the standard visualization tool for endonasal transsphenoidal resection of sellar lesions. The most widely used 2-dimensional (2D) endoscopes harbor the problem of limited depth perception. Therefore, 3-dimensional (3D) endoscopes have been developed to enable depth perception through a stereoscopic view. OBJECTIVE: To evaluate the impact of high-definition (HD) 2D vs 3D HD endoscopes on spatial orientation within the sphenoid sinus. METHODS: In this prospective single-center study, 21 patients have been investigated (2021-2022). Eleven standardized anatomic landmarks, which were preoperatively defined on neuronavigation imaging, were intraoperatively targeted with a navigation probe using either 2D HD or 3D HD endoscopes for visualization. RESULTS: Overall, 3D HD endoscopes provided a statistically significant higher accuracy of identification of sphenoid sinus landmarks (median deviation: 5.2 mm vs 4.2 mm, P < .001). In detail: tuberculum sellae (3.0 mm vs 4.3 mm, P = .047), most anterior point of sella (3.3 mm vs 4.8 mm, P = .049), and clivus indentation (3.8 mm vs 5.3 mm, P = .035). Anatomic variations such as a complex sphenoid sinus configuration had no influence on identifying sphenoid sinus landmarks. CONCLUSION: According to our data, stereoscopic 3D HD endoscopy enhances intraoperative orientation by improved depth perception within the sphenoid sinus. This may add to the safety of endoscopic skull base procedures, especially in extended approaches and cases with distorted anatomy.

Incidence, risk factors, and treatment of incidental durotomy during decompression in degenerative lumbar spine conditions.

BACKGROUND: The purpose of this study was to identify independent risk factors for incidental durotomy (ID) during decompressive lumbar spine surgery, and to describe its treatment. METHODS: This retrospective review includes 650 patients who underwent lumbar decompression at a tertiary institution between January 2015 and October 2019. Data collection was obtained through one independent researcher. The incidence rate and treatment of ID was evaluated by a chart review of operative notes, patient charts, physiotherapy reports, and nursing reports. RESULTS: The incidence rate of ID was 12.6%. The most common reason for admission was disc herniation (63.2%), followed by vertebral stenosis (22.1%). ID resulted in significantly longer operation time (P=0.0001) and length of hospitalization (P=0.0001). A correlation between ID and patient's diagnosis (P=0.0078) as well as the chosen type of surgery (P=0.0404) with an Odds Ratio to cause ID of 1.9 for laminectomy and 1.6 for undercutting compared to microdiscectomy were found. However, age, sex, surgeon experience, lumbar level, revision surgery, as well as multilevel surgery were not significantly correlated with the incidence of ID. Dural tears were closed with dural sealant (47.2%), polyester 4-0 sutures (11.1%) or a combination of both (37.5%) and the majority of patients had bed rest of at least two days. By usage of these treatment methods no patient needed reoperation. CONCLUSIONS: Diagnosis of vertebrostenosis as well as laminectomy were significantly correlated with the incidence of ID. Treatment with intraoperative closure and postoperative bed rest even though not standardized led to complication free outcomes.

Diagnostic criteria of small sellar lesions with hyperprolactinemia: Prolactinoma or else.

Objective: To evaluate the combined predictive value of MRI criteria with the prolactin-volume-ratio (PVR) to differentiate prolactinoma from non-prolactinoma, in small sellar lesions with hyperprolactinemia. Methods: Retrospective analysis of 55 patients with sellar lesions of ≤15 mm diameter on MRI and hyperprolactinemia of ≤150 ng/mL, surgically treated between 2003 and 2020 at the Medical University of Vienna, with a conclusive histopathological report. Serum prolactin levels, extent of pituitary stalk deviation, size and volume of the lesion were assessed. The PVR was calculated by dividing the preoperative prolactin level by tumor volume. Results: Our study population consisted of 39 patients (71%) with a prolactin-producing pituitary adenoma (group A), while 16 patients (29%) had another type of sellar lesion (group B). Patients in group A were significantly younger (p=0.012), had significantly higher prolactin levels at diagnosis (p<0.001) as well as smaller tumor volume (p=0.036) and lower degree of pituitary stalk deviation (p=0.009). The median PVR was significantly higher in group A (243 ng/mL per cm3) than in group B (83 ng/mL per cm3; p=0.002). Furthermore, the regression operating characteristics analysis revealed a PVR >100 ng/mL per cm3 to be predictive for distinguishing prolactin-producing lesions from other small sellar lesions. Conclusion: In patients with small sellar lesions, Prolactin-Volume-Ratios >100 represents a possible predictive marker for the diagnosis of prolactin-producing pituitary adenomas.

Clinico-pathologic predictors of dismal course in atypical meningiomas: a retrospective single-centre analysis.

BACKGROUND: Despite continuous refinement of the WHO classification for meningiomas, the biological behaviour of atypical meningiomas remains difficult to predict on the basis of this grading system alone. The aim of this study was to investigate the prognostic significance of clinical and radiological parameters in a series of atypical meningioma with long follow-up of minimum 5 years. METHODS: Of 1675 meningiomas treated at the Medical University Vienna between 1993 and 2015, 179 were atypical meningioma. Of those, 93 patients were identified with follow-up of ≥5 years. Patients were grouped by recurrence and evaluated for overall and progression free survival as well as potential prognostic parameters such as age, gender, tumor size and location, edema, irregular surface, contrast enhancement, bone invasion and hyperostosis, necrosis, EOR and MIB-1. RESULTS: From 42 (45%) patients in group recurrent and 51 (55%) patients in group nonrecurrent, seven independent factors were associated with decreased progression-free survival in univariate analysis: size ≥5 cm, age ≥60 years, male gender, subtotal resection, irregular surface, and necrosis on magnetic resonance imaging, and MIB-1 ≥6%. In multivariable analysis, only larger size, older age, necrosis and higher MIB-1 remained independent prognostic risk factors for recurrence of atypical meningioma. CONCLUSIONS: We identified larger size, older age, presence of necrosis on magnetic resonance imaging, and higher MIB-1, as detrimental parameters for recurrence of atypical meningioma. Until molecular profiling of atypical meningioma becomes routinely available, these parameters may aid the clinician in decision making about surveillance intervals and adjuvant radiation treatment.

How to dose-stage large or high-risk brain metastases: an alternative two-fraction radiosurgical treatment approach.

OBJECTIVE: The authors sought to evaluate clinical outcome in patients with large, high-risk brain metastases (BMs) treated with different dose strategies by use of two-fraction dose-staged Gamma Knife radiosurgery (GKRS). METHODS: A retrospective analysis was performed with data from 142 patients from two centers who had been treated with two-fraction dose-staged GKRS between June 2015 and January 2020. Depending on the changes in marginal dose between the first (GKRS1) and second (GKRS2) GKRS treatments, the study population was divided into three treatment groups: dose escalation, dose maintenance, and dose de-escalation. RESULTS: The 142 study patients underwent two-fraction dose-staged GKRS treatments for 166 large, high-risk BMs. The median tumor volume of 7.4 cm3 decreased significantly from GKRS1 to GKRS2 (4.4 cm3; p < 0.001), and to the last follow-up (1.8 cm3; p < 0.001). These significant differences in BM volume reduction were achieved in all three treatment groups. However, differences according to the primary tumor histology were apparent: while dose maintenance seemed to be the most effective treatment strategy for BMs from lung cancer or melanoma, dose escalation was the most beneficial treatment option for BMs from breast, gastrointestinal, or genitourinary cancer. Of note, the vast majority of patients who underwent dose-staged BM treatment did not show any significant postradiosurgical complications. CONCLUSIONS: In patients with large, high-risk BMs, dose-staged GKRS treatment represents an effective local treatment method with acceptable complication risks. Different dose-strategy options are available that may be chosen according to the primary tumor histology and treatment volume but may also be tailored to the findings at GKRS2.

MR Fingerprinting-A Radiogenomic Marker for Diffuse Gliomas.

(1) Background: Advanced MR imaging (MRI) of brain tumors is mainly based on qualitative contrast images. MR Fingerprinting (MRF) offers a novel approach. The purpose of this study was to use MRF-derived T1 and T2 relaxation maps to differentiate diffuse gliomas according to isocitrate dehydrogenase (IDH) mutation. (2) Methods: Twenty-four patients with histologically verified diffuse gliomas (14 IDH-mutant, four 1p/19q-codeleted, 10 IDH-wildtype) were enrolled. MRF T1 and T2 relaxation times were compared to apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV) within solid tumor, peritumoral edema, and normal-appearing white matter (NAWM), using contrast-enhanced MRI, diffusion-, perfusion-, and susceptibility-weighted imaging. For perfusion imaging, a T2* weighted perfusion sequence with leakage correction was used. Correlations of MRF T1 and T2 times with two established conventional sequences for T1 and T2 mapping were assessed (a fast double inversion recovery-based MR sequence ('MP2RAGE') for T1 quantification and a multi-contrast spin echo-based sequence for T2 quantification). (3) Results: MRF T1 and T2 relaxation times were significantly higher in the IDH-mutant than in IDH-wildtype gliomas within the solid part of the tumor (p = 0.024 for MRF T1, p = 0.041 for MRF T2). MRF T1 and T2 relaxation times were significantly higher in the IDH-wildtype than in IDH-mutant gliomas within peritumoral edema less than or equal to 1cm adjacent to the tumor (p = 0.038 for MRF T1 mean, p = 0.010 for MRF T2 mean). In the solid part of the tumor, there was a high correlation between MRF and conventionally measured T1 and T2 values (r = 0.913, p < 0.001 for T1, r = 0.775, p < 0.001 for T2), as well as between MRF and ADC values (r = 0.813, p < 0.001 for T2, r = 0.697, p < 0.001 for T1). The correlation was weak between the MRF and rCBV values (r = -0.374, p = 0.005 for T2, r = -0.181, p = 0.181 for T1). (4) Conclusions: MRF enables fast, single-sequence based, multi-parametric, quantitative tissue characterization of diffuse gliomas and may have the potential to differentiate IDH-mutant from IDH-wildtype gliomas.

Cost-Effectiveness of Endovascular Thrombectomy in Childhood Stroke: An Analysis of the Save ChildS Study.

BACKGROUND AND PURPOSE: The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. METHODS: In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. RESULTS: The model. RESULTS: yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. CONCLUSIONS: EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Combined standard bypass and parent artery occlusion for management of giant and complex internal carotid artery aneurysms.

BACKGROUND: Complex aneurysms do not have a standard protocol for treatment. In this study, we investigate the safety and efficacy of microsurgical revascularization combined with parent artery occlusion (PAO) in giant and complex internal carotid artery (ICA) aneurysms. METHODS: Between 1998 and 2017, 41 patients with 47 giant and complex ICA aneurysms were treated by an a priori planned combined treatment strategy. Clinical and radiological outcomes were stratified according to mRS and Raymond classification. Bypass patency was assessed. Median follow-up time was 3.9 years. RESULTS: After successful STA-MCA bypass, staged endovascular (n=37) or surgical (n=1) PAO was executed in 38 patients following a negative balloon occlusion test. Intolerance to PAO led to stent/coil treatments in two patients. Perioperative bypass patency was confirmed in 100% of completed STA-MCA bypass procedures. Long-term overall bypass patency rate was 99%. Raymond 1 occlusion and good outcome were achieved in 95% and 97% (mRS 0-2) of cases, respectively. No procedure-related mortality was encountered. Eighty-four percent of patients with preoperative cranial nerve compression syndromes improved during follow-up. CONCLUSIONS: The combined approach of STA-MCA bypass surgery followed by parent artery occlusion achieves high aneurysm occlusion and low morbidity rates in the management of giant and complex ICA aneurysms. This combined indirect approach represents a viable alternative to flow diversion in patients with cranial nerve compression syndromes or matricidal aneurysms, and may serve as a backup strategy in cases of peri-interventional complications or lack of suitable endovascular access.

Optimizing maximum resection of glioblastoma: Raman spectroscopy versus 5-aminolevulinic acid.

OBJECTIVE: The objective of this study was to assess and compare the potential of 5-aminolevulinic acid (5-ALA) and Raman spectroscopy (RS) in detecting tumor-infiltrated brain in patients with glioblastoma (GBM). METHODS: Between July 2020 and October 2021, the authors conducted a prospective clinical trial with 15 patients who underwent neurosurgical treatment of newly diagnosed and histologically verified GBM. A solid contrast-enhancing tumor core and peritumoral tissue were investigated intraoperatively for cancer cells by using 5-ALA and RS to achieve pathology-tailored maximum resection. In each case, a minimum of 10 biopsies were sampled from navigation-guided areas. Two neuropathologists examined the biopsies for the presence of neoplastic cells. The detection performance of 5-ALA and RS alone and in combination was assessed. Pre- and postoperative MRI, Karnofsky Performance Status (KPS), and National Institutes of Health Stroke Scale (NIHSS) scores were compared, and median progression-free survival (PFS) was evaluated. RESULTS: A total of 185 biopsy samples were harvested from the contrast-enhancing tumor core (n = 19) and peritumoral tissue (n = 166). In the tumor core, 5-ALA and RS each showed a sensitivity of 100%. In the peritumoral tissue, 5-ALA was less sensitive than RS in detecting cancer (46% vs 69%) but showed higher specificity (81% vs 57%). When the two methods were combined, the accuracy of tumor detection was increased by about 10%. Pathology-tailored resection led to a 52% increase in resection volume comparing the volume of preoperative contrast enhancement with the postoperative resection cavity on MRI (p = 0.0123). Eloquent brain involvement prevented gross-total resection in 4 patients. Four weeks after surgery, mean KPS (p = 0.7637) and NIHSS scores (p = 0.3146) were not significantly different from preoperative values. Of the 13 patients who had received postoperative chemoradiotherapy, 4 did not show any progression after a median follow-up of 14 months. The remaining 9 patients had a median PFS of 8 months. CONCLUSIONS: According to the study data, RS is capable of detecting tumor-infiltrated brain with higher sensitivity but lower specificity than the current standard of 5-ALA. With further technological and workflow advancements, RS in combination with protoporphyrin IX fluorescence may contribute to pathology-tailored glioma resection in the future.