Targeting the microenvironment in the treatment of arteriovenous malformations.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31+ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects.

Detection of virus-specific T cells via ELISpot corroborates early diagnosis in human Borna disease virus 1 (BoDV-1) encephalitis.

BACKGROUND: Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. CASE PRESENTATION: Here, we report the new case of a 40 - 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. RESULTS: Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. CONCLUSION: This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.

[Measuring the cochlea using a tablet-based software package: influence of imaging modality and rater background]. / Vermessung der Cochlea mittels eines Tablet-basierten Softwarepakets: Einfluss der Bildgebungsmodalität und des Untersucherhintergrunds.

BACKGROUND: Cochlear duct length (CDL) is subject to significant individual variation. In the context of cochlear implantation, adapting the electrode array length to the CDL is of potential interest, as it has been associated with improvements in both speech recognition and sound quality. Using a tablet-based software package, it is possible to measure CDL at the level of the organ of Corti (CDLOC) to select appropriate electrode array lengths based on individual cochlear anatomy. OBJECTIVE: To identify effects of imaging modality and rater background on CDL estimates. METHODS: Magnetic resonance imaging (MRI) and flat-panel volume CT (fpVCT) scans of 10 patients (20 cochleae) were analyzed using the OTOPLAN software package (MED-EL, Innsbruck, Austria). Raters were an otorhinolaryngology (ORL) specialist, an ORL resident, and an audiologist. To analyze effects of rater background and imaging modality on CDL measurements, linear mixed models were constructed. RESULTS: Measurements showed mean CDLOC(fpVCT) = 36.69 ± 1.78 mm and CDLOC(MRI) = 36.81 ± 1.87 mm. Analyses indicated no significant effect of rater background (F(2, 105) = 0.84; p = 0.437) on CDL estimates. Imaging modality, on the other hand, significantly affected CDL (F (1, 105) = 20.70; p < 0.001), whereby estimates obtained using MRI were 0.89 mm larger than those obtained using fpVCT. CONCLUSION: No effect of rater background on CDL estimates could be identified, suggesting that comparable measurements could be obtained by personnel other than specially trained neurootologists. While imaging modality (fpVCT vs. MRI) did impact CDL results, the difference was small and of questionable clinical significance.

Bornavirus Encephalitis Shows a Characteristic Magnetic Resonance Phenotype in Humans.

OBJECTIVE: The number of diagnosed fatal encephalitis cases in humans caused by the classical Borna disease virus (BoDV-1) has been increasing, ever since it was proved that BoDV-1 can cause human infections. However, awareness of this entity is low, and a specific imaging pattern has not yet been identified. We therefore provide the first comprehensive description of the morphology of human BoDV-1 encephalitis, with histopathological verification of imaging abnormalities. METHODS: In an institutional review board-approved multicenter study, we carried out a retrospective analysis of 55 magnetic resonance imaging (MRI) examinations of 19 patients with confirmed BoDV-1 encephalitis. Fifty brain regions were analyzed systematically (T1w, T2w, T2*w, T1w + Gd, and DWI), in order to discern a specific pattern of inflammation. Histopathological analysis of 25 locations in one patient served as correlation for MRI abnormalities. RESULTS: Baseline imaging, acquired at a mean of 11 ± 10 days after symptom onset, in addition to follow-up scans of 16 patients, revealed characteristic T2 hyperintensities with a predilection for the head of the caudate nucleus, insula, and cortical spread to the limbic system, whereas the occipital lobes and cerebellar hemispheres were unaffected. This gradient was confirmed by histology. Nine patients (47.4%) developed T1 hyperintensities of the basal ganglia, corresponding to accumulated lipid phagocytes on histology and typical for late-stage necrosis. INTERPRETATION: BoDV-1 encephalitis shows a distinct pattern of inflammation in both the early and late stages of the disease. Its appearance can mimic sporadic Creutzfeldt-Jakob disease on MRI and should be considered a differential diagnosis in the case of atypical clinical presentation. ANN NEUROL 2020;88:723-735.

Does Device Selection Impact Recanalization Rate and Neurological Outcome?: An Analysis of the Save ChildS Study.

Background and Purpose- The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods- The Save ChildS cohort study (January 2000-December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (<18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results- Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions- Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration- URL: https://www.drks.de/; Unique identifier: DRKS00016528.

Value of fluid-attenuated inversion recovery MRI data analyzed by the lesion segmentation toolbox in amyotrophic lateral sclerosis.

BACKGROUND: MRI fluid-attenuated inversion recovery (FLAIR) studies reported hyperintensity in the corticospinal tract and corpus callosum of patients with amyotrophic lateral sclerosis (ALS). PURPOSE: To evaluate the lesion segmentation toolbox (LST) for the objective quantification of FLAIR lesions in ALS patients. STUDY TYPE: Retrospective. POPULATION: Twenty-eight ALS patients (eight females, mean age: 50 range: 24-73, mean ALSFRS-R sum score: 36) were compared with 31 age-matched healthy controls (12 females, mean age: 45, range: 25-67). ALS patients were treated with riluzole and additional G-CSF (granulocyte-colony stimulating factor) on a named patient basis. FIELD STRENGTH/SEQUENCE: 1.5 T, FLAIR, T1 -weighted MRI. ASSESSMENT: The lesion prediction algorithm (LPA) of the LST enabled the extraction of individual binary lesion maps, total lesion volume (TLV), and number (TLN). Location and overlap of FLAIR lesions across patients were investigated by registration to FLAIR average space and an atlas. ALS-specific functional rating scale revised (ALSFRS-R), disease progression, and survival since diagnosis served as clinical correlates. STATISTICAL TESTS: Univariate analysis of variance (ANOVA), repeated-measures ANOVA, t-test, Bravais-Pearson correlation, Chi-square test of independence, Kaplan-Meier analysis, Cox-regression analysis. RESULTS: Both ALS patients and healthy controls exhibited FLAIR alterations. TLN significantly depended on age (F(1,54) = 24.659, P < 0.001) and sex (F(1,54) = 5.720, P = 0.020). ALS patients showed higher TLN than healthy controls depending on sex (F(1, 54) = 5.076, P = 0.028). FLAIR lesions were small and most pronounced in male ALS patients. FLAIR alterations were predominantly detected in the superior and posterior corona radiata, anterior capsula interna, and posterior thalamic radiation. Patients with pyramidal tract (PT) lesions exhibited significantly inferior survival than patients without PT lesions (P = 0.013). Covariate age exhibited strong prognostic value for survival (P = 0.015). DATA CONCLUSION: LST enables the objective quantification of FLAIR alterations and is a potential prognostic biomarker for ALS. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:552-559.

Incidence of Arterial Hypotension in Patients Receiving Peroral or Continuous Intra-arterial Nimodipine After Aneurysmal or Perimesencephalic Subarachnoid Hemorrhage.

BACKGROUND: Oral nimodipine is used for prophylaxis and treatment of delayed cerebral ischemia in patients with aneurysmal or perimesencephalic subarachnoid hemorrhage (SAH). In cases of serious refractory cerebral vasospasm, a continuous intra-arterial (IA) infusion of nimodipine (CIAN) may be required to avoid cerebral ischemia. Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of the present study was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion. METHODS: In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography-tandem mass spectrometry. RESULTS: The intended full dose of 60 mg of nimodipine given orally every 4 h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14 days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration. CONCLUSIONS: Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1 mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60 mg every 4 h.

Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

BACKGROUND: Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. METHODS: All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. RESULTS: Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. CONCLUSIONS: Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

Early postoperative tumor progression predicts clinical outcome in glioblastoma-implication for clinical trials.

Molecular markers define the diagnosis of glioblastoma in the new WHO classification of 2016, challenging neuro-oncology centers to provide timely treatment initiation. The aim of this study was to determine whether a time delay to treatment initiation was accompanied by signs of early tumor progression in an MRI before the start of radiotherapy, and, if so, whether this influences the survival of glioblastoma patients. Images from 61 patients with early post-surgery MRI and a second MRI just before the start of radiotherapy were examined retrospectively for signs of early tumor progression. Survival information was analyzed using the Kaplan-Meier method, and a Cox multivariate analysis was performed to identify independent variables for survival prediction. 59 percent of patients showed signs of early tumor progression after a mean time of 24.1 days from the early post-surgery MRI to the start of radiotherapy. Compared to the group without signs of early tumor progression, which had a mean time of 23.3 days (p = 0.685, Student's t test), progression free survival was reduced from 320 to 185 days (HR 2.3; CI 95% 1.3-4.0; p = 0.0042, log-rank test) and overall survival from 778 to 329 days (HR 2.9; CI 95% 1.6-5.1; p = 0.0005). A multivariate Cox regression analysis revealed that the Karnofsky performance score, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, and signs of early tumor progression are prognostic markers of overall survival. Early tumor progression at the start of radiotherapy is associated with a worse prognosis for glioblastoma patients. A standardized baseline MRI might allow for better patient stratification.

Fluorescein sodium-guided resection of cerebral metastases-an update.

BACKGROUND: Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients. METHODS: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25-85 years); 5 mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events. RESULTS: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course. CONCLUSIONS: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

[Cerebellar Infarction After Carbon Monoxide Poisoning and Hyperbaric Oxygen Therapy]. / Kleinhirninfarkt nach CO-Intoxikation und hyperbarer Sauerstofftherapie.

We report on a patient who developed a space-occupying cerebellar infarction with occlusive hydrocephalus after a poisoning with carbon monoxide with the intention to commit suicide. A neurosurgical and intensive care therapy were needed. The patient's survival without severe neurological deficits could be secured due to the early detection of the intracerebral lesions.

Adverse event grading following CTCAE v3.0 underestimates hypertensive side effects in patients with glioma treated with Bevacizumab.

Anti-VEGF therapy with Bevacizumab (BEV) is widely used in cases of relapsed high-grade glioma (HGG). Arterial hypertension is a known side effect of anti-VEGF therapy. 42 Patients with relapsed HGG were treated with BEV 10 mg/kg on days 1 and 15 of 28-day cycles in addition to treatment with 40 mg TMZ daily until disease progression, based on magnetic resonance imaging and/or worsening of clinical status. In a retrospective analysis, hypertensive side effects were evaluated as the primary endpoint, while survival information in addition to toxicity was analyzed as secondary endpoint. Grading which employs the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 detected hypertensive events with a significantly higher sensitivity than CTCAE version 3.0. The rate of severe hypertensive events observed as CTCAE ≥ °3 were 9.5 % in version 3.0 and 45.2 % in version 4.0. The results presented here indicate that CTCAE version 3.0 may underreport the incidence and grade of BEV-induced hypertension within clinical trials. As hypertension has not only long-term, but also severe short-term side effects, we suggest that arterial hypertension under BEV should be scored according to CTCAE version 4.0 to avoid clinically relevant hypertension-related adverse events in these patients.

Diffusion-weighted imaging in oral squamous cell carcinoma using 3 Tesla MRI: is there a chance for preoperative discrimination between benign and malignant lymph nodes in daily clinical routine?

BACKGROUND: Preoperative staging of cervical lymph nodes is important to determine the extent of neck dissection in patients with oral squamous cell carcinoma (OSCC). PURPOSE: To evaluate whether a preoperative discrimination of benign and malignant cervical lymph nodes with diffusion-weighted imaging (DWI) (3T) is feasible for clinical application. MATERIAL AND METHODS: Forty-five patients with histological proven OSCC underwent preoperative 3T-MRI. DWI (b = 0, 500, and 1000 s/mm(2)) was added to the standard magnetic resonance imaging (MRI) protocol. Mean apparent diffusion coefficients (ADCmean) were measured for lymph nodes with 3 mm or more in short axis by two independent readers. Finally, these results were matched with histology. RESULTS: Mean ADC was significantly higher for malignant than for benign nodes (1.143 ± 0.188 * 10(-3) mm(2)/s vs. 0.987 ± 0.215 * 10(-3) mm(2)/s). Using an ADC value of 0.994 * 10(-3) mm(2)/s as threshold results in a sensitivity of 80%, specificity of 65%, positive predictive value of 31%, and negative predictive value of 93%. CONCLUSION: Due to a limited sensitivity and specificity DWI alone is not suitable to reliably discriminate benign from malignant cervical lymph nodes in daily clinical routine. Hence, the preoperative determination of the extent of neck dissection on the basis of ADC measurements is not meaningful.

Fluorescein sodium-guided resection of cerebral metastases­experience with the first 30 patients.

BACKGROUND: Surgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW 560 nm (Zeiss Meditec, Germany) in patients with CM. METHODS: Thirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1 years); 200 mg of FL was intravenously injected directly before CM resection. A YELLOW 560 nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects. RESULTS: Most patients (90.0%, n = 27) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0%) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0%) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3% (n = 25) of patients. No adverse effects were registered over the postoperative course. CONCLUSIONS: FL and the YELLOW 560 nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results.

BACKGROUND: Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone. METHODS: Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group. RESULTS: Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001). CONCLUSIONS: Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

11C-Choline PET/pathology image coregistration in primary localized prostate cancer.

PURPOSE: The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of (11)C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). METHODS: In 28 PC patients, (11)C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). RESULTS: PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71% of patients, and complete overlap in 4%. CONCLUSION: PET/pathology image coregistration can be used for evaluation of different imaging modalities. (11)C-Choline PET failed to distinguish tumour from nontumour tissue.

Amelioration of Parkinsonian tremor evoked by DBS: which role play cerebello-(sub)thalamic fiber tracts?

BACKGROUND: Current pathophysiological models of Parkinson's disease (PD) assume a malfunctioning network being adjusted by the DBS signal. As various authors showed a main involvement of the cerebellum within this network, cerebello-cerebral fiber tracts are gaining special interest regarding the mediation of DBS effects. OBJECTIVES: The crossing and non-decussating fibers of the dentato-rubro-thalamic tract (c-DRTT/nd-DRTT) and the subthalamo-ponto-cerebellar tract (SPCT) are thought to build up an integrated network enabling a bidimensional communication between the cerebellum and the basal ganglia. The aim of this study was to investigate the influence of these tracts on clinical control of Parkinsonian tremor evoked by DBS. METHODS: We analyzed 120 electrode contacts from a cohort of 14 patients with tremor-dominant or equivalence-type PD having received bilateral STN-DBS. Probabilistic tractography was performed to depict the c-DRTT, nd-DRTT, and SPCT. Distance maps were calculated for the tracts and correlated to clinical tremor control for each electrode pole. RESULTS: A significant difference between "effective" and "less-effective" contacts was only found for the c-DRTT (p = 0.039), but not for the SPCT, nor the nd-DRTT. In logistic and linear regressions, significant results were also found for the c-DRTT only (pmodel logistic = 0.035, ptract logistic = 0,044; plinear = 0.027). CONCLUSIONS: We found a significant correlation between the distance of the DBS electrode pole to the c-DRTT and the clinical efficacy regarding tremor reduction. The c-DRTT might therefore play a major role in the mechanisms of alleviation of Parkinsonian tremor and could eventually serve as a possible DBS target for tremor-dominant PD in future.

Attenuation of the BOLD fMRI Signal and Changes in Functional Connectivity Affecting the Whole Brain in Presence of Brain Metastasis.

To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage.

Limited capability of MRI radiomics to predict primary tumor histology of brain metastases in external validation.

Background: Growing research demonstrates the ability to predict histology or genetic information of various malignancies using radiomic features extracted from imaging data. This study aimed to investigate MRI-based radiomics in predicting the primary tumor of brain metastases through internal and external validation, using oversampling techniques to address the class imbalance. Methods: This IRB-approved retrospective multicenter study included brain metastases from lung cancer, melanoma, breast cancer, colorectal cancer, and a combined heterogenous group of other primary entities (5-class classification). Local data were acquired between 2003 and 2021 from 231 patients (545 metastases). External validation was performed with 82 patients (280 metastases) and 258 patients (809 metastases) from the publicly available Stanford BrainMetShare and the University of California San Francisco Brain Metastases Stereotactic Radiosurgery datasets, respectively. Preprocessing included brain extraction, bias correction, coregistration, intensity normalization, and semi-manual binary tumor segmentation. Two-thousand five hundred and twenty-eight radiomic features were extracted from T1w (±â€…contrast), fluid-attenuated inversion recovery (FLAIR), and wavelet transforms for each sequence (8 decompositions). Random forest classifiers were trained with selected features on original and oversampled data (5-fold cross-validation) and evaluated on internal/external holdout test sets using accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC). Results: Oversampling did not improve the overall unsatisfactory performance on the internal and external test sets. Incorrect data partitioning (oversampling before train/validation/test split) leads to a massive overestimation of model performance. Conclusions: Radiomics models' capability to predict histologic or genomic data from imaging should be critically assessed; external validation is essential.

SARS-CoV2 evokes structural brain changes resulting in declined executive function.

BACKGROUND: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus' neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model. METHODS: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed. RESULTS: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered. CONCLUSION: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as 'Post-COVID'.