NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics.

Background: Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable. Methods: A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed. Results: IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed. Conclusion: NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.

Breakouts-A Radiological Sign of Poor Prognosis in Patients With Brain Metastases.

Purpose: Brain metastases (BM) can present a displacing or infiltrating growth pattern, independent of the primary tumor type. Previous studies have shown that tumor cell infiltration at the macro-metastasis/brain parenchyma interface (MMPI) is correlated with poor outcome. Therefore, a pre-therapeutic, non-invasive detection tool for potential metastatic cell infiltration at the MMPI would be desirable to help identify patients who may benefit from a more aggressive local treatment strategy. The aim of this study was to identify specific magnetic resonance imaging (MRI) patterns at the MMPI in patients with BM and to correlate these patterns with patient outcome. Patients and Methods: In this retrospective analysis of a prospective BM registry, we categorized preoperative MR images of 261 patients with BM according to a prespecified analysis system, which consisted of four MRI contrast enhancement (CE) patterns: two with apparently regularly shaped borders (termed "rim-enhancing" and "spherical") and two with irregular delineation (termed "breakout" and "diffuse"). The primary outcome parameter was overall survival (OS). Additionally analyzed prognostic parameters were the Karnofsky Performance Index, tumor size, edema formation, extent of resection, and RPA class. Results: OS of patients with a breakout pattern was significantly worse than OS of all other groups. Conclusion: Our data show that BM with a breakout pattern have a highly aggressive clinical course. Patients with such a pattern potentially require a more aggressive local and systemic treatment strategy.

Development of cerebrospinal fluid fistula after incidental durotomy in spinal decompression surgery.

BACKGROUND: Incidental durotomy (ID) during spinal surgery is a risk factor for the development of cerebrospinal fluid (CSF) fistula. The rates of ID with or without consecutive CSF fistula vary according to the extent of the surgical procedure. Revision surgery has the highest rates of dural tears. However, not every case of ID leads to CSF fistula requiring revision surgery. The objective of this study was to analyze the predictors for the development of CSF fistula after ID. METHODS: This retrospective study included 6024 consecutive patients who had been surgically treated for degenerative spinal disease at our clinic over the past 15 years. Patients who had undergone surgical revision for CSF fistula were assigned to the CSF fistula group. A matched 3:1 control group (ID group) was formed of patients with ID but without CSF fistula. Charts, surgical reports, and radiographic data were reviewed and statistically analyzed for demographics, duration of symptoms, comorbidities, surgical strategy, and pre- and postoperative neurological performance. RESULTS: The 15-year incidence of CSF fistula in the overall population was 0.36% (N.=22). The following locations were affected: N.=18 lumbar (81.8%), N.=2 cervical (9.1%), and N.=2 thoracic (9.1%). The extent of ID was similar in both groups. The two groups did not significantly differ with regard to the intraoperative management of dural repair with primary suturing (P=0.345), dural patches, sealant, or collagen matrix (P=0.228; P=0.081; P=0.081). In the postoperative period, bed rest in supine position for 48 hours (P=0.037) and laxative therapy (P=0.034) were the most beneficial treatment modalities for preventing CSF fistula. Patients with CSF fistula were hospitalized significantly longer (21 days vs. 10 days in the control group; P<0.001). CONCLUSIONS: This large test group showed a low incidence of postoperative CSF fistula after intraoperative ID. Bed rest and laxative treatment were important approaches to preventing CSF fistula.

Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage-a feasibility series.

The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1-10. CGRP levels were determined via competitive enzyme immunoassay and calculated as "area under the curve" (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11-35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

Symptomatic Postoperative Spinal Epidural Hematoma after Spinal Decompression Surgery: Prevalence, Risk Factors, and Functional Outcome.

OBJECTIVE: Postoperative spinal epidural hematoma (pSEH) with symptomatic compression of nervous structures after spinal decompression surgery is a rare complication. Delayed evacuation may result in severe neurologic impairment. We present a large single-center analysis of the prevalence, potential risk factors, and functional recovery after pSEH. METHODS: A retrospective review of our institutional database of spinal decompression surgery over 15 years yielded 6,024 consecutive patients. A total of 42 patients who had undergone surgical revision due to postoperative neurologic deterioration or intractable radiating pain and radiographically confirmed pSEH were allocated to the pSEH group. A matched 3:1 control group was formed (126 patients with the same surgical procedure, same year, same sex, and similar age). Charts, surgical reports, and radiographic data were reviewed for demographics, duration of symptoms, history of medical treatment, medication, comorbidities, radiographic extension, surgical strategy, and pre- and postoperative neurologic performance. Median follow-up was 3 months. Risk factors for pSEH, complete recovery, and recovery of neurologic symptoms were analyzed with univariable and multivariable logistic regression models. RESULTS: The prevalence of pSEH in this population was 0.69% (n = 42) with these locations: 7 of 1,284 (0.54%) cervical, 1 of 774 (0.12%) thoracic, and 34 of 3,966 (0.85%) lumbar. Use of anticoagulants (p = 0.003), pathologic coagulation values in the preoperative blood test (p = 0.034), and cigarette smoking (p = 0.003) were identified as independent risk factors of pSEH. Surgery in more than one level showed a trend toward an increased risk of pSEH. Pain as the only symptom (p = 0.0001) was a significant predictor of complete recovery. Patients symptomatic with paraplegia (p = 0.026) had a significantly higher risk of a poor neurologic outcome without full recovery of neurologic symptoms. CONCLUSION: The prevalence of pSEH was lower than previously reported incidences. Use of anticoagulants, pathologic coagulation values, and cigarette smoking were identified as independent risk factors of pSEH. Functional outcome was related to the duration between hematoma evacuation and the clinical presentation of symptomatic pSEH.

III. Ventricle diameter increase during ventricular drainage challenge - A predictor of shunt dependency after subarachnoid hemorrhage.

Hydrocephalus with the need for shunt placement is a common sequela after aneurysmal subarachnoid hemorrhage (aSAH). In 2009 Chan et al. published a formula to predict shunt dependency in SAH patients, the failure risk index (FRI). We reevaluated the FRI within the aSAH population in our hospital and wanted to identify easier measurements forecast shunt dependency. We retrospectively analyzed data from patients with aSAH treated in our neuro-intensive care unit and calculated the FRI according to the paper by Chan et al. 2013 and data were compared to the results of Chan et al. 38 patients were included in this study, 24 female and 14 male. 38% suffered a SAH WFNS I, 19% WFNS II, 24% WFNS III, 5% WFNS IV and 14% WFNS V. 17 patients underwent a shunt implantation (group 1), 21 patients did not (group 2). The calculated FRI Index did not correlate with the expectancy of shunt implantation in 22% of the cases (group 1). In group 2 the FRI index and the prediction of shunt dependency did not match in 33% of the cases. Furthermore, we found the increase of the third ventricle diameter to be predictive in 67% for failed EVD challenge and the decrease of the third ventricle diameter predictive in 67% for successful EVD challenge. In this study, we were not able to confirm the results of the FRI designed by Chan et al within our patient population. Furthermore, we consider the increase of the third ventricle diameter to be a simpler and more reliable predictor of shunt dependency.

Clinical Benefits of Combining Different Visualization Modalities in Neurosurgery.

The prevailing philosophy in oncologic neurosurgery, has shifted from maximally invasive resection to the preservation of neurologic function. The foundation of safe surgery is the multifaceted visualization of the target region and the surrounding eloquent tissue. Recent advancements in pre-operative and intraoperative visualization modalities have changed the face of modern neurosurgery. Metabolic and functional data can be integrated into intraoperative guidance software, and fluorescent dyes under dedicated filters can potentially visualize patterns of blood flow and better define tumor borders or isolated tumor foci. High definition endoscopes enable the depiction of tiny vessels and tumor extension to the ventricles or skull base. Fluorescein sodium-based confocal endomicroscopy, which is under scientific evaluation, may further enhance the neurosurgical armamentarium. We aim to present our institutional workup of combining different neuroimaging modalities for surgical neuro-oncological procedures. This institutional algorithm (IA) was the basis of the recent publication by Haj et al. describing outcome and survival data of consecutive patients with high grade glioma (HGG) before and after the introduction of our Neuro-Oncology Center.

QEVO® - A new digital endoscopic microinspection tool - A cadaveric study and first clinical experiences (case series).

BACKGROUND: The use of endoscopes in neurosurgery is well established, but the integration of a full high definition signaling, 45° angled endoscopic tool into a digital surgical microscope, is new. We report our first experiences in a cadaveric study and a clinical case series using the new microinspection tool QEVO® that serves as a plug-in feature for the recently launched KINEVO 900 digital visualization platform (CARL ZEISS MEDITEC, Oberkochen, Germany). For illustration purposes, we offer video footage. METHODS: The handling, workflow, and visualization patterns of the QEVO® microinspection tool were critically evaluated in cadaver specimens by simulating four standardized neurosurgical approaches: (1) pterional, (2) retrosigmoidal, (3) transsphenoidal, (4) and transcallosal. Similarly, we evaluated the QEVO® tool in corresponding clinical cases of (1) aneurysm clipping, (2) removal of cerebellar cavernoma, (3) and pituitary adenomectomy. RESULTS: In both the cadaveric study and clinical case series, the QEVO® tool was found to be beneficial in terms of high-quality visualization of fine structures and for displaying hidden anatomical details ("looking around the corner"). The handling was good, and the workflow was easy. However, the use of this tool was restricted by the lack of an external fixation and a working channel, the shortness of the tool, and the impossibility to switch to a 0° or 30° optic. CONCLUSION: Despite some restrictions, the QEVO® microinspection tool is an innovative, handheld, endoscopic tool that allows excellent additional visualization of the surgical field. In our opinion, this tool effectively enhances the modern neurosurgical armamentarium.

Long-Term Follow-Up of Cerebral Amyloid Angiopathy-Associated Intracranial Hemorrhage Reveals a High Prevalence of Atrial Fibrillation.

GOAL: Cerebral amyloid angiopathy (CAA) is the second-most common cause of nontraumatic intracerebral hemorrhages (ICH), surpassed only by uncontrolled hypertension. We characterized the percentage, risk factors, and comorbidities of patients suffering from CAA-related ICH in relation to long-term outcomes. MATERIAL AND METHODS: We performed retrospective analyses and clinical follow-ups of individuals suffering from ICH who were directly admitted to neurosurgery between 2002 and 2016. FINDINGS: Seventy-four of 174 (42%) spontaneous nontraumatic lobar ICH cases leastwise satisfied the modified Boston criteria definition for at least "possible CAA." Females suffered a higher risk of CAA-caused ICH (42 of 74, 56.8%, P= .035). Atrial fibrillation as a major comorbidity was observed in 19 patients (25.7%). Recovery (decrease of modified Rankin scale [mRS]) was highest during hospitalization in the acute clinic. One-year mortality was as follows: 14 of 25 patients (56%) with probable CAA without supporting pathology, 6 of 18, and 8 of 31 patients with supporting pathology and possible CAA, respectively. Only 10 of 74 (13.6%) had favorable long-term outcomes (mRS ≤2). Increasing numbers of lobar hemorrhages, low initial Glasgow Coma Scale, and subarachnoid hemorrhage were significantly associated with poor survivability, whereas statins, antithrombotic agents, an intraventricular hemorrhage, and midline shift played seemingly minor roles. CONCLUSIONS: Symptomatic ICH is a serious stage in CAA progression with high mortality. The high incidence of concurrent atrial fibrillation in these patients may support data on more widespread vascular pathology in CAA.

Retrosigmoid Craniotomy for Cerebellopontine Epidermoid Cyst.

Epidermoid cysts are benign lesions. The goal of this surgery is complete removal while preserving cranial nerves. Here, we illustrate the case of a 31-year-old male who presented with persistent headache following a short period of impaired consciousness. Imaging revealed a mass at the cerebellopontine angle (CPA) which at surgery proved to be an epidermoid cyst. In this video, we present the key steps of surgery. The postoperative course was uneventful and the patient was symptom-free at the 3 months of follow-up. The link to the video can be found at: https://youtu.be/0xwpkKwQoLI .

Deep brain stimulation: Connectivity profile for bradykinesia alleviation.

OBJECTIVE: Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. METHODS: We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. RESULTS: Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. INTERPRETATION: Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.

Clinical Experience with Hemopatch® as a Dural Sealant in Cranial Neurosurgery.

BACKGROUND: Herein, we report our clinical experience with the novel polyethylene glycol-covered matrix dural onlay, Hemopatch® (Baxter Deutschland GmbH, Unterschleißheim, Germany) for the prevention of postoperative cerebrospinal fluid (CSF) fistulas. METHODS: Retrospectively, 22 consecutive patients (11 females, 11 males, mean age: 49.8 years, range: 15-77 years) with oncological and vascular intracranial lesions were included in this study. In all patients, the Hemopatch was applied as the dural onlay. The accuracy of the primary dural sutures was distinguished into 1) no visible gaps, 2) small gaps < 3 mm, and 3) large gaps > 3 mm. We evaluated the patient charts, surgical reports, and postoperative images. The median follow-up was three months. We recorded any wound healing disorder, such as infection or CSF fistula, and postoperative hemorrhage resulting in surgical revision. RESULTS: Supratentorial, infratentorial, and transsphenoidal approaches were conducted in 17, four, and one patient, respectively. Accurate sutures without visible gaps, small gaps, and large gaps were covered with the Hemopatch in 11, eight, and three patients. One patient developed a CSF fistula (4.5%), one patient had a wound infection (4.5%), and in one patient, a remote cerebellar hemorrhage occurred (unrelated to the dural closure) (4.5%). Thus, the surgical revision rate due to wound healing disorders was 9% (2/22). CONCLUSION: It is safe and feasible to use the Hemopatch as a dural sealant. The rate of postoperative wound healing disorders in our population was in the lower range of reported surgical revision rates after supra-/infratentorial craniotomies. However, prospective and controlled clinical trials are still warranted.

Fluorescein Sodium in the Surgical Treatment of Recurrent Glioblastoma Multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor and has a high recurrence rate. Maximizing the extent of resection (EOR) in recurrent GBM has proved to be the cornerstone of neurosurgical retreatment. The development of surgical microscopes fitted with fluorescein-specific filters has facilitated fluorescein-guided microsurgery and the identification of tumor tissue. Use of fluorescein sodium (FL) in primary high-grade glioma resection has shown promising results. Here, we present our experience with FL and the dedicated surgical microscope filter YELLOW 560 nm in 106 patients with recurrent GBM. METHODS: A total of 106 patients with recurrent GBM were included (53 women, 53 men; mean age, 53 years). A total of 5 mg/kg bodyweight of FL was intravenously injected approximately 45 minutes before craniotomy. A YELLOW 560 nm filter (PENTERO 900 [Carl Zeiss Meditec, Oberkochen Germany]) was used for microsurgical tumor resection and resection control. Surgical reports were reviewed regarding the degree of fluorescent staining. Postoperative magnetic resonance images were examined within 48 hours after surgery regarding the EOR and postoperative course regarding neurologic outcome, complications, and any adverse events. RESULTS: Bright fluorescent staining was present in all patients, which markedly enhanced tumor visibility and was deemed helpful for tumor resection. Seventeen patients (16%) showed residual tumor tissue on postoperative magnetic resonance imaging (MRI). Therefore, gross total resection was achieved in 89 patients (84%). No adverse events were registered postoperatively. CONCLUSIONS: FL and YELLOW 560 nm are readily available methods for fluorescence-guided tumor resection, similar to contrast enhancement in T1-weighted MRI. FL may improve resection in recurrent GBM with minimal risk, and tumor margins are clearly visualized. FL and the YELLOW 560 nm filter are safe and feasible tools for safe maximal resection of recurrent glioblastoma.

Degenerative symptomatic spinal synovial cysts: Clinical presentation and functional outcome.

Spinal synovial cysts (SSC) are a rare but important differential diagnosis for degenerative or space-occupying spinal lesions. There is controversy about the most beneficial treatment, which can be conservative or surgical. We provide a review of our surgical data for purposes of quality assessment and improvement. 5313 patients with surgically treated degenerative spinal diseases were analyzed retrospectively. The incidence of SSC was 1.14%. 61 patients (31 women, 30 men; mean age 65.3 years) with SSC were included in this study. The charts, surgical reports, and radiographic data were reviewed for demographics, duration of symptoms, size of SSC, anatomical site, surgical approach, Visual Analog Scale (VAS), and neurological performance including the Japanese Orthopedic Association Score (JOA score) and the Frankel score. Laminotomy was the most common surgical approach in 93.4% of the patients followed by hemilaminectomy in 6.6%. The predominant site of SSC was the lumbar spine in 86.9%. 95.1% had experienced local and radicular pain as the predominant symptom and 47.5% preoperative sensory and motor deficits. At discharge, the JOA score was significantly increased compared to admission (median value of 17). At follow-up, 94.4% had normal neurological function and 5.6% showed grade 1 neurological deficits. Leg pain had decreased in 94.4% and back pain in 70.6%. At long-term follow-up, all patients presented neurologically stable. The median value for pain classified with the VAS had decreased from 6 at admission to 1 at long-term follow-up. During long-term follow-up, 6 patients (9.8%) had developed spinal instability requiring stabilization, 5 patients had received facet joint infiltration due to symptomatic facet joint syndrome. The epidemiological and clinical patterns of symptomatic SSC are similar to those of other degenerative spinal diseases. Thus, SSC should always be considered as a rare but important differential diagnosis. Surgical outcome was excellent with immediate symptom relief and recovery, which further improved over time. Our data support the benefit of surgical treatment and may be useful in recommending neurosurgical therapy to patients with SSC.

Excessive release of endogenous neuropeptide Y into cerebrospinal fluid after treatment of spontaneous subarachnoid haemorrhage and its possible impact on self-reported neuropsychological performance - results of a prospective clinical pilot study on good-grade patients.

OBJECTIVES: Neuropsychological dysfunction after treatment of spontaneous subarachnoid haemorrhage (sSAH) is common but underreported. The vasoconstrictor neuropeptide Y (NPY) is excessively released after sSAH and in psychiatric disorders. We prospectively analysed the treatment-specific differences in the secretion of endogenous cerebrospinal fluid (CSF) NPY during the acute stage after sSAH and its impact on cognitive processing. METHODS: A total of 26 consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Ventricular CSF was drawn daily from day 1-10. CSF NPY levels were determined with competitive enzyme immunoassay. All patients underwent neuropsychological self-report assessment [36-Item Short Form Health Survey (SF-36) and ICD-10-Symptom-Rating questionnaire (ISR)] after the onset of sSAH (day 11-35; t1) and at the 6-month follow-up (t2). RESULTS: At t1, increased mean levels of NPY in CSF significantly correlated with impaired performance in most ISR scores (ISR total p = .018, depression p = .035, anxiety p = .008, nutrition disorder p = .047, supplementary items p = .038) and in several psychological SF-36 items (vitality p = .019, general mental health p = .001, mental component summary p = .025). DISCUSSION: To the best of our knowledge, this study is the first to correlate the levels of endogenous NPY in supratentorial CSF with cognitive outcome in good-grade sSAH patients. Excessive NPY release into CSF may have a short-term influence on the pathogenesis of neuropsychological deficits. The impact of cerebrovascular manipulation on NPY release has to be further elucidated. ABBREVIATIONS: ANOVA: analysis of variance; aSAH: aneurysmal subarachnoid haemorrhage; AUC: area under the curve; CBF: cerebral blood flow; CSF: cerebrospinal fluid; CT (scan): computed tomography (scan); CV: cerebral vasospasm; DIND: delayed ischemic neurological deficit; DSA: digital subtraction angiography; EIA: enzyme immunoassay; EV: endovascular aneurysm occlusion; EVD: external ventricular drainage; FU: 6-month follow-up; GCS: Glasgow Coma Scale; Ghp: general health perceptions; GOS: Glasgow Outcome Scale; h: hour/s; HH: Hunt and Hess; ICU: intensive care unit; ISR: ICD-10-Symptom-Rating questionnaire; MCS: mental component summary; Mhi: general mental health; min: minute/s; min-max: minimum - maximum; ml: millilitre; mRS: modified Ranking Scale; MS: microsurgical clipping, microsurgical aneurysm occlusion; ng: nanograms; no. [n]: number; NPY: Neuropeptide Y; p: p value; Pain: bodily pain; PCS: physical component summary; Pfi: physical functioning; pSAH: perimesencephalic subarachnoid haemorrhage; PTSD: posttraumatic stress disorder; QoL: quality of life; Rawhtran: health transition item; Rolem: role limitations because of emotional problems; Rolph: role limitations due to physical health problems; SAH: subarachnoid haemorrhage; SD: standard deviation; SF-36: 36-Item Short Form Health Survey; Social: social functioning; sSAH: spontaneous subarachnoid haemorrhage; TCD: trans-cranial Doppler ultrasound; (test) t1: test in the sub-acute phase after the onset of bleeding (between day 11 and 35 after subarachnoid haemorrhage); (test) t2: test in the short-term (chronic phase) after treatment at 6-month follow-up; test t1 - t2: intergroup development from t1 to t2; Vital: vitality; vs: versus.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation.

PURPOSE: Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. METHODS: To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. RESULTS: Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. CONCLUSIONS: MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

A Patient-Independent Significance Test by Means of False-Positive Rates in Selected Correlation Analysis of Brain Multimodal Monitoring Data.

Recently, we introduced a mathematical toolkit called selected correlation analysis (sca) that reliably detects negative and positive correlations between arterial blood pressure (ABP) and intracranial pressure (ICP) data, recorded during multimodal monitoring, in a time-resolved way. As has been shown with the aid of a mathematical model of cerebral perfusion, such correlations reflect impaired autoregulation and reduced intracranial compliance in patients with critical neurological diseases. Sca calculates a Fourier transform-based index called selected correlation (sc) that reflects the strength of correlation between the input data and simultaneously an index called mean Hilbert phase difference (mhpd) that reflects the phasing between the data. To reliably detect pathophysiological conditions during multimodal monitoring, some thresholds for the abovementioned indexes sc and mhpd have to be established that assign predefined significance levels to that thresholds. In this paper, we will present a method that determines the rate of false positives for fixed pairs of thresholds (lsc, lmhpd). We calculate these error rates as a function of the predefined thresholds for each individual out of a patient cohort of 52 patients in a retrospective way. Based on the deviation of the individual error rates, we subsequently determine a globally valid upper limit of the error rate by calculating the predictive interval. From this predictive interval, we deduce a globally valid significance level for appropriate pairs of thresholds that allows the application of sca to every future patient in a prospective, bedside fashion.

Fluorescence-guidance in non-Gadolinium enhancing, but FET-PET positive gliomas.

OBJECTIVES: We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging-MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). PATIENTS AND METHOD: Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. RESULTS: In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. DISCUSSION AND CONCLUSION: Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.

Efficacy of D,L-methadone in the treatment of glioblastoma in vitro.

AIM: Recently, D,L-methadone has been put forward as adjuvant treatment in glioblastoma (GBM). METHODS: We analyzed the µ-opioid receptor expression in a set of GBM cell lines and investigated the efficacy of D,L-methadone alone and in combination with temozolomide (TMZ). Results & conclusion: Expression of the µ-opioid receptor was similar in the tested cell lines. High concentrations of D,L-methadone induced apoptosis in all cell lines and showed treatment interaction with TMZ. However, in lower dosages, reflecting clinically attainable concentrations, D,L-methadone alone showed no efficacy, and induced even higher proliferation in one specific cell line. Also, no interaction with TMZ was observed. These results suggest caution to the premature use of D,L-methadone in the treatment of GBM patients.