Publications by authors named "Horst Urbach"

273 Publications

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial.

Trials 2021 Apr 15;22(1):285. Epub 2021 Apr 15.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Background: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer's solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH.

Methods: This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0-3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints.

Discussion: New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer's solution.

Trial Registration: Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645 . Registered on 8 May 2019.
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http://dx.doi.org/10.1186/s13063-021-05208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048077PMC
April 2021

Machine Outputs Must Be Checked.

Clin Neuroradiol 2021 Apr 9. Epub 2021 Apr 9.

Dept. of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1007/s00062-021-01012-6DOI Listing
April 2021

Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.

Brain 2021 Apr 3. Epub 2021 Apr 3.

Department of Nuclear Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.
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http://dx.doi.org/10.1093/brain/awab009DOI Listing
April 2021

Novel Neuronal Autoantibodies in Huntington's Disease.

Biol Psychiatry 2021 Mar 12. Epub 2021 Mar 12.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.biopsych.2020.12.032DOI Listing
March 2021

FET-PET radiomics in recurrent glioblastoma: prognostic value for outcome after re-irradiation?

Radiat Oncol 2021 Mar 3;16(1):46. Epub 2021 Mar 3.

German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg, Heidelberg, Germany.

Purpose: The value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET)-radiomics in the outcome assessment of patients with recurrent glioblastoma (rGBM) has not been evaluated until now. The aim of this study was to evaluate whether a prognostic model based on FET-PET radiomics features (RF) is feasible and can identify rGBM patients that would most benefit from re-irradiation.

Methods: We prospectively recruited rGBM patients who underwent FET-PET before re-irradiation (GLIAA-Pilot trial, DRKS00000633). Tumor volume was delineated using a semi-automatic method with a threshold of 1.8 times the standardized-uptake-value of the background. 135 FET-RF (histogram parameters, shape and texture features) were extracted. The analysis involved the characterization of tumor and non-tumor tissue with FET-RF and the evaluation of the prognostic value of FET-RF for time-to-progression (TTP), overall survival (OS) and recurrence location (RL).

Results: Thirty-two rGBM patients constituted our cohort. FET-RF discriminated significantly between tumor and non-tumor. The texture feature Small-Zone-Low-Gray-Level-Emphasis (SZLGE) showed the best performance for the prediction of TTP (p = 0.001, satisfying Bonferroni-multiple-test significance level). Additionally, two radiomics signatures could predict TTP (TTP-radiomics-signature, p = 0.001) and OS (OS-radiomics-signature, p = 0.038). SZLGE and the TTP-radiomics-signature additionally predicted RL. Specifically, high values for TTP-radiomics-signature and for SZLGE indicated not only earlier progression, but also a RL within the initial FET-PET active volume.

Conclusion: Our findings suggest that FET-PET radiomics could contribute to the prognostic assessment and selection of rGBM-patients benefiting from re-irradiation. Trial registration DRKS00000633. Registered on 8th of December in 2010. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000633 .
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http://dx.doi.org/10.1186/s13014-020-01744-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931514PMC
March 2021

Dural Arteriovenous Fistula Formation Secondary to Cerebral Venous Thrombosis: Longitudinal Magnetic Resonance Imaging Assessment Using 4D-Combo-MR-Venography.

Thromb Haemost 2021 Mar 3. Epub 2021 Mar 3.

Department of Neuroradiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background And Purpose:  Dural arteriovenous fistulae (DAVFs) can develop secondary to cerebral venous thrombosis (CVT). The incidence of DAVF has not yet been investigated prospectively.

Methods:  Between July 2012 and January 2018, combined static and dynamic 4D MR venography (4D-combo-MRV) was performed in 24 consecutive patients at diagnosis of CVT and after 6 months. 3 Tesla magnetic resonance imaging with time of flight and contrast-enhanced magnetization-prepared rapid acquisition with gradient echo were performed at baseline to evaluate the extent of thrombosis and affected vessel segments. Baseline and follow-up 4D-combo-MRV were assessed for signs of DAVF. Interrater reliability of DAVF detection and the extent of recanalization were analyzed with kappa statistics.

Results:  DAVFs were detected in 4/30 CVT patients (13.3%, 95% confidence interval [CI] 3.3-26.7). Two of 24 patients (8.3%, 95% CI: 0-20.8) had coincidental DAVF with CVT on admission. At follow-up, de novo formation of DAVF following CVT was seen in 2/24 patients (8.3%, 95% CI: 0-20.8). Both de novo DAVFs were low grade and benign fistulae (Cognard type 1, 2a), which had developed at previously thrombosed segments. Endovascular treatment was required in two high degree lesions (Cognard 2a + b) detected at baseline and in one de novo DAVF (Cognard 1) because of debilitating headache and tinnitus. Thrombus load, vessel recanalization, and frequency of cerebral lesions (hemorrhage, ischemia) were not associated with DAVF occurrence.

Conclusion:  This exploratory study showed that de novo DAVF formation occurs more frequently than previously described. Although de novo DAVFs were benign, 75% of all detected DAVFs required endovascular treatment. Therefore, screening for DAVF by dynamic MRV, such as 4D-combo-MRV, seems worthwhile in CVT patients.
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http://dx.doi.org/10.1055/s-0041-1723991DOI Listing
March 2021

External validation of automated focal cortical dysplasia detection using morphometric analysis.

Epilepsia 2021 Apr 27;62(4):1005-1021. Epub 2021 Feb 27.

Department of Epileptology, University Hospital Bonn, Bonn, Germany.

Objective: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set.

Methods: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years).

Results: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%.

Significance: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy.
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http://dx.doi.org/10.1111/epi.16853DOI Listing
April 2021

SPECTRE-A novel dMRI visualization technique for the display of cerebral connectivity.

Hum Brain Mapp 2021 Feb 27. Epub 2021 Feb 27.

Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.

The visualization of diffusion MRI related properties in a comprehensive way is still a challenging problem. We propose a simple visualization technique to give neuroradiologists and neurosurgeons a more direct and personalized view of relevant connectivity patterns estimated from clinically feasible diffusion MRI. The approach, named SPECTRE (Subject sPEcific brain Connectivity display in the Target REgion), is based on tract-weighted imaging, where diffusion MRI streamlines are used to aggregate information from a different MRI contrast. Instead of using native MRI contrasts, we propose to use continuous template information as the underlying contrast for aggregation. In this respect, the SPECTRE approach is complementary to normative approaches where connectivity information is warped from the group level to subject space by anatomical registration. For the purpose of demonstration, we focus the presentation of the SPECTRE approach on the visualization of connectivity patterns in the midbrain regions at the level of subthalamic nucleus due to its importance for deep brain stimulation. The proposed SPECTRE maps are investigated with respect to plausibility, robustness, and test-retest reproducibility. Clear dependencies of reliability measures with respect to the underlying tracking algorithms are observed.
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http://dx.doi.org/10.1002/hbm.25385DOI Listing
February 2021

Interaction between cognitive reserve and age moderates effect of lesion load on stroke outcome.

Sci Rep 2021 Feb 24;11(1):4478. Epub 2021 Feb 24.

Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

The concepts of brain reserve and cognitive reserve were recently suggested as valuable predictors of stroke outcome. To test this hypothesis, we used age, years of education and lesion size as clinically feasible coarse proxies of brain reserve, cognitive reserve, and the extent of stroke pathology correspondingly. Linear and logistic regression models were used to predict cognitive outcome (Montreal Cognitive Assessment) and stroke-induced impairment and disability (NIH Stroke Scale; modified Rankin Score) in a sample of 104 chronic stroke patients carefully controlled for potential confounds. Results revealed 46% of explained variance for cognitive outcome (p < 0.001) and yielded a significant three-way interaction: Larger lesions did not lead to cognitive impairment in younger patients with higher education, but did so in younger patients with lower education. Conversely, even small lesions led to poor cognitive outcome in older patients with lower education, but didn't in older patients with higher education. We observed comparable three-way interactions for clinical scores of stroke-induced impairment and disability both in the acute and chronic stroke phase. In line with the hypothesis, years of education conjointly with age moderated effects of lesion on stroke outcome. This non-additive effect of cognitive reserve suggests its post-stroke protective impact on stroke outcome.
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http://dx.doi.org/10.1038/s41598-021-83927-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904829PMC
February 2021

Subcortical band heterotopia in a patient with phenylketonuria: Co-Existence or consequence?

Seizure 2021 Mar 15;86:144-146. Epub 2021 Feb 15.

Epilepsy Center, University Medical Center, Medical Faculty, University of Freiburg, Breisacher Str. 64, D-79106 Freiburg, Germany.

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http://dx.doi.org/10.1016/j.seizure.2021.02.016DOI Listing
March 2021

SVM-Based Normal Pressure Hydrocephalus Detection.

Clin Neuroradiol 2021 Jan 26. Epub 2021 Jan 26.

Department of Neuroradiology, Medical Center, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.

Background And Purpose: As magnetic resonance imaging (MRI) signs of normal pressure hydrocephalus (NPH) may precede clinical symptoms we sought to evaluate an algorithm that automatically detects this pattern.

Methods: A support vector machine (SVM) was trained in 30 NPH patients treated with ventriculoperitoneal shunts and 30 healthy controls. For comparison, four neuroradiologists visually assessed sagittal MPRAGE images and graded them as no NPH pattern, possible NPH pattern, or definite NPH pattern.

Results: Human accuracy to visually detect a NPH was between 0.85 and 0.97. Interobserver agreement was substantial (κ = 0.656). Accuracy of the SVM algorithm was 0.93 and AUROC 0.99. Among 272 prespecified regions, gray matter and CSF volumes of both caudate, the right parietal operculum, the left basal forebrain, and the 4th ventricle showed the highest discriminative power to separate a NPH and a no NPH pattern.

Conclusion: A NPH pattern can be reliably detected using a support vector machine (SVM). Its role in the work-up of asymptomatic patients or neurodegenerative disease has to be evaluated.
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http://dx.doi.org/10.1007/s00062-020-00993-0DOI Listing
January 2021

Health Economic Aspects of Aneurysmal Subarachnoid Hemorrhage: Factors Determining First Year In-Hospital Treatment Expenses.

J Neurol Surg A Cent Eur Neurosurg 2021 Jan 24. Epub 2021 Jan 24.

Department of Neurosurgery, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany.

Background:  Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a common neurosurgical emergency with a high case fatality rate. The clinical course of SAH generates high health economic expenses. Here we highlight possible cost-driving factors for in-hospital care expenses for the first year. Furthermore, results are compared with ischemic stroke treatment.

Methods:  One hundred and one patients with aneurysmal SAH treated in our hospital from 2007 through 2009 were included. The Hunt and Hess (HH) scale, World Federation of Neurosurgical Societies (WFNS) scale, Fisher Scale, and further outcome-relevant data were recorded. Expenses were calculated using the German fixed case rate classification system consisting of Diagnosis-Related Groups (DRG) and the Operation and Procedure catalogue (OPS). Overall acute length of stay (LOS) and LOS on the intensive care unit (ICU) were separately evaluated. Expenses were compared with formerly published first-year costs of ischemic stroke.

Results:  Fifty-four percent of the patients (median age 52 years, 69% females) received coiling and 46% clipping. Acute in-hospital treatment accounted for 82% of total in-hospital expenses, while consequential in-hospital treatment accounted only for 18%. Altogether, the total first-year in-hospital expenses for all patients were as high as €2,650,002, resulting in average SAH in-hospital treatment expenses of €26,238 per patient for the first year. Poor clinical condition on admission and longer stay in ICU are the main cost-driving factors. The impact of the aneurysm treatment method is debatable. Only a poor HH grade and longer ICU stay are independent cost-driving factors. SAH treatment expenses are far higher than treatment costs for ischemic stroke in the literature (€6,731 for first-year inpatient and €3,287 for outpatient treatment).

Conclusions:  Clinical condition and LOS determine in-hospital expenses after SAH. Aneurysmal SAH prevalently results in a relevant economic impact on the health system exceeding formerly published treatment expenses for ischemic stroke.
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http://dx.doi.org/10.1055/s-0040-1720982DOI Listing
January 2021

On the Way.

Authors:
Horst Urbach

Clin Neuroradiol 2020 Dec;30(4):657

Dept. of Neuroradiology, University Medical Center Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

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http://dx.doi.org/10.1007/s00062-020-00977-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728648PMC
December 2020

Recurrent Pontine Strokes in a Young Male.

J Stroke Cerebrovasc Dis 2020 Dec 22;29(12):105386. Epub 2020 Oct 22.

Department of Neurology, University of Bonn, Germany; Department of Neurology, GFO Kliniken Troisdorf, Germany. Electronic address:

A 34-year-old patient presented to the emergency department with recurrent neurologic symptoms of sudden onset. MRI showed white matter hyperintensities consistent with small vessel disease, predominantly in the pons. There were no known cardiovascular risk factors (CVRF) and extensive workup for vasculitis was negative. The preliminary diagnosis was small vessel primary central nervous system vasculitis, but immunosuppressive treatment did not stop a progression of the disease over 6 months. Repeated negative diagnostic workup for vasculitis, lack of response to therapy, young age, and predominant involvement of the pons were compatible with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), which is a very rare monogenic cause of cerebral small vessel disease due to upregulation of collagen type-IV. Correspondingly, a COL4A1 mutation was found. Therapy was immediately stopped in favour of more strict adjustment of the CVRF including lowering of LDL < 70 mg/dl and extensive monitoring of blood-pressure.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105386DOI Listing
December 2020

Apples and oranges.

Epilepsia 2021 01 25;62(1):279-280. Epub 2020 Nov 25.

Department of Neuroradiology, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Breisgau, Germany.

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http://dx.doi.org/10.1111/epi.16770DOI Listing
January 2021

SPectroscOpic prediction of bRain Tumours (SPORT): study protocol of a prospective imaging trial.

BMC Med Imaging 2020 11 23;20(1):123. Epub 2020 Nov 23.

Department of Neurosurgery, Medical Centre, University of Freiburg, Breisacher Str. 64, 79106, Freiburg im Breisgau, Germany.

Background: The revised 2016 WHO-Classification of CNS-tumours now integrates molecular information of glial brain tumours for accurate diagnosis as well as for the development of targeted therapies. In this prospective study, our aim is to investigate the predictive value of MR-spectroscopy in order to establish a solid preoperative molecular stratification algorithm of these tumours. We will process a 1H MR-spectroscopy sequence within a radiomics analytics pipeline.

Methods: Patients treated at our institution with WHO-Grade II, III and IV gliomas will receive preoperative anatomical (T2- and T1-weighted imaging with and without contrast enhancement) and proton MR spectroscopy (MRS) by using chemical shift imaging (MRS) (5 × 5 × 15 mm voxel size). Tumour regions will be segmented and co-registered to corresponding spectroscopic voxels. Raw signals will be processed by a deep-learning approach for identifying patterns in metabolic data that provides information with respect to the histological diagnosis as well patient characteristics obtained and genomic data such as target sequencing and transcriptional data.

Discussion: By imaging the metabolic profile of a glioma using a customized chemical shift 1H MR spectroscopy sequence and by processing the metabolic profiles with a machine learning tool we intend to non-invasively uncover the genetic signature of gliomas. This work-up will support surgical and oncological decisions to improve personalized tumour treatment.

Trial Registration: This study was initially registered under another name and was later retrospectively registered under the current name at the German Clinical Trials Register (DRKS) under DRKS00019855.
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http://dx.doi.org/10.1186/s12880-020-00522-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685595PMC
November 2020

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis.

Fluids Barriers CNS 2020 Nov 11;17(1):67. Epub 2020 Nov 11.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: The importance of cerebrospinal fluid (CSF) diagnostics for psychiatry is growing. The CSF/blood albumin quotient (Q) is considered to be a measure of the blood-CSF barrier function. Recently, systematically higher Q in males than in females was described in neurological patients. The aim of this study was to investigate whether a sex difference could also be detected in a well-characterized psychiatric cohort.

Methods: The patient cohort comprised 989 patients, including 545 females and 444 males with schizophreniform and affective syndromes who underwent CSF diagnostics, including Q measurement. The basic CSF findings and antineuronal autoantibody data of this cohort have already been published. This re-analysis employed analysis of covariance with age correction for Q mean values and chi-testing for the number of increased age-corrected Q levels to investigate sex differences in Q.

Results: The Q levels were elevated above reference levels by 18% across all patients, and a comparison between male and female patients revealed a statistically significant sex difference, with increased values in 26% of male patients and a corresponding rate of only 10% in female patients (chi = 42.625, p < 0.001). The mean Q values were also significantly higher in males (6.52 ± 3.69 × 10) than in females (5.23 ± 2.56 × 10; F = 52.837, p < 0.001).

Discussion: The main finding of this study was a significantly higher Q level in male compared to female patients with psychiatric disorders, complementing previously described sex differences in neurological patient cohorts. This result indicates bias from some general factors associated with sex and could be partly explained by sex differences in body height, which is associated with spine length and thus a longer distance for CSF flow within the subarachnoid space down the spine from the occipital area to the lumbar puncture site in males compared to females. Hormonal influences caused by different estrogen levels and other sex-specific factors could also play a relevant role. The significance of the study is limited by its retrospective design, absence of a healthy control group, and unavailability of exact measures of spine length.
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http://dx.doi.org/10.1186/s12987-020-00223-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656685PMC
November 2020

Spontaneous Intracranial Hypotension.

Dtsch Arztebl Int 2020 Jul;117(27-28):480-487

Department of Neurosurgery, Universitätsklinikum Freiburg.

Background: Spontaneous intracranial hypotension (SIH) is an underdiagnosed disease. Its incidence is estimated at 5 per 100 000 persons per year.

Methods: This review is based on a selective literature search in PubMed covering the years 2000-2019, as well as on the authors' personal experience.

Results: The diagnostic and therapeutic methods discussed here are supported by level 4 evidence. SIH is caused by spinal leakage of cerebrospinal fluid (CSF) out of ventral dural tears or nerve root diverticula, or, in 2-5% of cases, through a fistula leading directly into the periradicular veins (CSF-venous fistula). In half of all patients, no CSF leak is demonstrable. A low CSF opening pressure on lumbar puncture is present in only one-third of patients; imaging studies are thus needed to confirm and localize a spinal CSF leak. Half of all patients in whom myelographic computed tomography (CT) reveals contrast medium reaching the epidural space have ventral dural tears, which tend to be located at upper thoracic spinal levels. Epidural blood patches applied under fluoroscopic or CT guidance can seal the CSF leak in 30-70% of patients, but 90% of patients with ventral dural tears will need operative closure. Some patients who have no visible epidural contrast medium on CT presumably do not have SIH, while others do, in fact, have a CSF leak from a diverticulum or a CSF-venous fistula and will need to have the site of the leak demonstrated with the aid of further studies, such as dynamic (subtraction) myelography in the lateral decubitus position.

Conclusion: The management of patients with SIH calls for complementary imaging studies to demonstrate the causative spinal CSF leak. Often, successful treatment requires surgical closure of the leak. In view of the sparse evidence available to date, controlled studies should be performed.
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http://dx.doi.org/10.3238/arztebl.2020.0480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575894PMC
July 2020

The correlation between apraxia and neglect in the right hemisphere: A voxel-based lesion-symptom mapping study in 138 acute stroke patients.

Cortex 2020 Nov 2;132:166-179. Epub 2020 Sep 2.

Department of Neurology and Clinical Neuroscience, University Medical Center Freiburg, University of Freiburg, Freiburg i.Br., Germany; Freiburg Brain Imaging Center, University of Freiburg, Freiburg i.Br., Germany.

Apraxia is frequently described after left hemisphere stroke and results from lesions to a complex network for motor cognition with dorso-dorsal, ventro-dorsal and ventral processing streams. Apraxia also occurs after right hemisphere stroke, but lesion correlates and underlying mechanisms remain to be elucidated. To clarify the role of the right hemisphere in apraxic deficits and the influence of neglect, we prospectively examined apraxia (imitation of meaningless postures and pantomime of tool use) and neglect in 138 acute right hemisphere stroke patients with first-ever ischemic stroke in the middle cerebral artery territory and identified corresponding lesion correlates using voxel-based lesion-symptom mapping. Imitation of meaningless postures was impaired as frequently as after left hemisphere stroke (38.4%) and was significantly associated with neglect. Imitation of meaningless postures was related to temporal (middle temporal gyrus, temporoparietal junction, superior temporal gyrus and sulcus), parietal (angular gyrus, parieto-occpitpial sulcus), secondary sensorimotor cortex and (peri-)insular lesions. Presence of neglect dichotomized the results: a lesion correlate for isolated imitation without neglect was found in the right parieto-occipital cortex, while imitation deficits, when co-occurring with neglect, were related to lateral occipito-temporal, superior temporal sulcus and (peri-)insular lesions. Pantomime of tool use deficits, typical for apraxia after left hemisphere lesions, were found in only 5 cases (3.6%) and only in the context of neglect, and were associated with occipital lobe, ventral and anterior temporal lobe, and inferior frontal (areas 45/47) lesions. The syndrome of apraxia after right hemisphere stroke differs from apraxia after left hemisphere stroke. Imitation deficits are found in both hemispheres after dorso-dorsal stream lesions. Neglect also leads to and explains deficits in imitation and pantomime in patients with right ventral stream lesions. Therefore, in right hemisphere lesions, apraxia can either be explained as impaired visuomotor transformation or as a result of visuospatial deficits.
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http://dx.doi.org/10.1016/j.cortex.2020.07.017DOI Listing
November 2020

Diagnosing Organic Causes of Schizophrenia Spectrum Disorders: Findings from a One-Year Cohort of the Freiburg Diagnostic Protocol in Psychosis (FDPP).

Diagnostics (Basel) 2020 Sep 14;10(9). Epub 2020 Sep 14.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Secondary schizophrenia spectrum disorders (SSDs) have clearly identifiable causes. The Department for Psychiatry and Psychotherapy at the University Hospital Freiburg has continued to expand its screening practices to clarify the organic causes of SSDs. This retrospective analysis was carried out to analyze whether a comprehensive organic diagnostic procedure could be informative in patients with SSDs. The "Freiburg Diagnostic Protocol in Psychosis" (FDPP) included basic laboratory analyses (e.g., thyroid hormones), metabolic markers, pathogens, vitamin status, different serological autoantibodies, rheumatic/immunological markers (e.g., complement factors), cerebrospinal fluid (CSF) basic and antineuronal antibody analyses, as well as cranial magnetic resonance imaging (cMRI) and electroencephalography (EEG). The findings of 76 consecutive patients with SSDs (55 with paranoid-hallucinatory; 14 with schizoaffective; 4 with hebephrenic; and 1 each with catatonic, acute polymorphic psychotic, and substance-induced psychotic syndromes) were analyzed. Overall, vitamin and trace element deficiency was identified in 92%. Complement factor analyses detected reduced C3 levels in 11%. Immunological laboratory alterations were detected in 76%. CSF analysis revealed general alterations in 54% of the patients, mostly with signs of blood-brain barrier dysfunction. cMRI analyses showed chronic inflammatory lesions in 4%. Combination of EEG, cMRI, and CSF revealed alterations in 76% of the patients. In three patients, autoimmune psychosis was suspected (4%). On the basis of these findings, we conclude that a comprehensive diagnostic procedure according to the FDPP in patients with SSD is worthwhile, considering the detection of secondary, organic forms of SSDs, as well as alterations in "modulating factors" of the disease course, such as vitamin deficiency. Larger studies using comprehensive diagnostic protocols are warranted to further validate this approach.
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http://dx.doi.org/10.3390/diagnostics10090691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555162PMC
September 2020

Derivo embolization device in the treatment of unruptured intracranial aneurysms: a prospective multicenter study.

J Neurointerv Surg 2020 Sep 8. Epub 2020 Sep 8.

Department of Intracranial Endovascular Therapy, Alfried Krupp Krankenhaus Essen, Essen, Germany.

Background: Flow diverters (FD) are used regularly for the endovascular treatment of unruptured intracranial aneurysms. We aimed to assess the safety and effectiveness of the Derivo embolization device (DED) with respect to long-term clinical and angiographic outcomes.

Methods: A prospective multicenter trial was conducted at 12 centers. Patients presenting with modified Rankin Score (mRS) of 0-1, treated for unruptured intracranial aneurysms with DED were eligible. Primary endpoint was the mRS assessed at 18 months with major morbidity defined as mRS 3-5. Satisfactory angiographic occlusion was defined as 3+4 on the Kamran scale.

Results: Between July 2014 and February 2018, 119 patients were enrolled. Twenty-three patients were excluded. Ninety-six patients, 71 (74%) female, mean age 54±12.0 years, were included in the analysis. Mean aneurysm size was 14.2±16.9 mm. The mean number of devices implanted per patient was 1.2 (range 1-3). Clinical follow-up at 18 months was available in 90 (94%) patients, resulting in a mean follow-up period of 14.8±5.2 months. At last available follow-up of 96 enrolled patients, 91 (95%) remained mRS 0-1. The major morbidity rate (mRS 3-5) was 3.1% (3/96), major stroke rate was 4.2% (4/96), and mortality was 0%. Follow-up angiographies were available in 89 (93%) patients at a median of 12.4±5.84 months with a core laboratory adjudicated satisfactory aneurysm occlusion in 89% (79/89).

Conclusion: Our results suggest that DED is a safe and effective treatment for unruptured aneurysms with high rates of satisfactory occlusion and comparably low rates of permanent neurological morbidity and mortality.

Trial Registration: DRKS00006103.
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http://dx.doi.org/10.1136/neurintsurg-2020-016303DOI Listing
September 2020

Characterization of longitudinal transformation of T2-hyperintensity in oligodendroglioma.

BMC Cancer 2020 Aug 27;20(1):818. Epub 2020 Aug 27.

Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.

Background: Oligodendroglioma (ODG) are CNS resistant tumors characterized by their unique molecular signature, namely a combined deletion of 1p and 19q simultaneously to an IDH1/2 mutation. These tumors have a more favorable clinical outcome compared to other gliomas and a long-time survival that ranges between 10 and 20 years. However, during the course of the disease, multiple recurrences occur and the optimal treatment at each stage of the disease remains unclear. Here we report a retrospective longitudinal observation study of 836 MRI examinations in 44 ODG patients.

Methods: We quantified the volume of T2-hyperintensity to compute growth behavior in dependence of different treatment modalities, using various computational models.

Results: The identified growth pattern revealed dynamic changes, which were found to be patient-specific an did not correlate with clinical parameter or therapeutic interventions. Further, we showed that, surgical resection is beneficial for overall survival regardless the WHO grad or timepoint of surgery. To improve overall survival, an extent of resection above 50% is required. Multiple resections do not generally improve overall survival, except a greater extent of resection than in previous surgeries was achieved.

Conclusions: Our data aids to improve the interpretation of MRI images in clinical practice.
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http://dx.doi.org/10.1186/s12885-020-07290-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450792PMC
August 2020

Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis.

Transl Psychiatry 2020 08 12;10(1):279. Epub 2020 Aug 12.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.

The central role played by cerebrospinal-fluid (CSF) examinations including antineuronal autoantibody (Ab) testing is increasingly recognized in psychiatry. The rationale of this study was to present a multimodally investigated group of patients. In total, 992 patients were analyzed for CSF alterations: 456 patients with schizophreniform and 536 with affective syndromes. Ab measurement included testing for established antineuronal IgG-Abs against intracellular antigens in serum (Yo/Hu/Ri/cv2[CRMP5]/Ma1/Ma2/SOX1/TR[DNER]/Zic4/amphiphysin/GAD65) and for cell surface antigens in the CSF (NMDAR/AMPA-1/2-R/GABA-B-R/LGI1/CASPR2/DPPX). In 30 patients with "red flags" for autoimmune psychosis, "tissue tests" were performed. Additional diagnostics included MRI and EEG analyses. CSF white-blood-cell counts were increased in 4% and IgG indices in 2%; CSF-specific oligoclonal bands were detected in 4%; overall, 8% displayed signs of neuroinflammation. In addition, 18% revealed increased albumin quotients. Antineuronal Abs against intracellular antigens were detected in serum in 0.6%. Antineuronal Abs against established cell surface antigens were detected in serum of 1% and in the CSF of 0.3% (CSF samples were only questionably positive). Abnormal IgG binding in "tissue tests" was detected in serum of 23% and in CSF of 27%. In total, 92% of the Ab-positive patients demonstrated at least one sign of brain involvement in additional diagnostics using CSF, MRI, EEG, and FDG-PET. In summary, CSF basic analyses revealed signs of blood-brain-barrier dysfunction and neuroinflammation in relevant subgroups of patients. Established antineuronal IgG-Abs were rare in serum and even rarer in the CSF. "Tissue tests" revealed frequent occurrences of Ab-binding; therefore, novel antineuronal Abs could play a relevant role in psychiatry.
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http://dx.doi.org/10.1038/s41398-020-00967-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419532PMC
August 2020

Accuracy and practical aspects of semi- and fully automatic segmentation methods for resected brain areas.

Neuroradiology 2020 Dec 20;62(12):1637-1648. Epub 2020 Jul 20.

Freiburg Brain Imaging, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Purpose: Precise segmentation of brain lesions is essential for neurological research. Specifically, resection volume estimates can aid in the assessment of residual postoperative tissue, e.g. following surgery for glioma. Furthermore, behavioral lesion-symptom mapping in epilepsy relies on accurate delineation of surgical lesions. We sought to determine whether semi- and fully automatic segmentation methods can be applied to resected brain areas and which approach provides the most accurate and cost-efficient results.

Methods: We compared a semi-automatic (ITK-SNAP) with a fully automatic (lesion_GNB) method for segmentation of resected brain areas in terms of accuracy with manual segmentation serving as reference. Additionally, we evaluated processing times of all three methods. We used T1w, MRI-data of epilepsy patients (n = 27; 11 m; mean age 39 years, range 16-69) who underwent temporal lobe resections (17 left).

Results: The semi-automatic approach yielded superior accuracy (p < 0.001) with a median Dice similarity coefficient (mDSC) of 0.78 and a median average Hausdorff distance (maHD) of 0.44 compared with the fully automatic approach (mDSC 0.58, maHD 1.32). There was no significant difference between the median percent volume difference of the two approaches (p > 0.05). Manual segmentation required more human input (30.41 min/subject) and therefore inferring significantly higher costs than semi- (3.27 min/subject) or fully automatic approaches (labor and cost approaching zero).

Conclusion: Semi-automatic segmentation offers the most accurate results in resected brain areas with a moderate amount of human input, thus representing a viable alternative compared with manual segmentation, especially for studies with large patient cohorts.
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http://dx.doi.org/10.1007/s00234-020-02481-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666677PMC
December 2020

neuroRAD 2020 Virtual.

Authors:
Horst Urbach

Clin Neuroradiol 2020 06;30(2):201

Klinik für Neuroradiologie, Universitätsklinikum Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1007/s00062-020-00924-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326527PMC
June 2020

Parkinsonian Syndrome with Frontal Lobe Involvement and Anti-Glycine Receptor Antibodies.

Brain Sci 2020 Jun 23;10(6). Epub 2020 Jun 23.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Atypical Parkinsonian syndromes with prominent frontal lobe involvement can occur in the 4R-taupathies progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Secondary forms of movement disorders may occur in the context of autoimmune encephalitis with antineuronal antibodies, such as anti-glycine receptor (anti-GlyR) antibodies, which are typically associated with Stiff-Person spectrum syndrome, or progressive encephalomyelitis with rigidity and myoclonus. Overlaps between neurodegenerative and immunological mechanisms have been recently suggested in anti-IgLON5 disease. In this case study, the authors describe a patient with a Parkinsonian syndrome with frontal lobe involvement and anti-GlyR antibodies. : The patient presented was a 63-year-old female. Her symptoms had begun with insomnia at the age of 60, after which, since the age of 61, increasing personality changes developed, leading to a diagnosis of depression with delusional symptoms. Severe cognitive deficits emerged, along with a left-side accentuated Parkinsonian syndrome with postural instability. The personality changes involved frontal systems. Magnetic resonance imaging (MRI) showed low-grade mesencephalon atrophy. [F]fluorodeoxyglucose positron emission tomography (FDG PET) depicted a moderate hypometabolism bilateral frontal and of the midbrain, while [I]FPCIT single-photon emission computed tomography (SPECT) revealed severely reduced dopamine transporter availability in both striata, indicating pronounced nigrostriatal degeneration. In addition, anti-GlyR antibodies were repeatedly found in the serum of the patient (max. titer of 1:640, reference: <1:20). Therefore, an anti-inflammatory treatment with steroids and azathioprine was administered; this resulted in a decrease of antibody titers (to 1:80) but no detectable clinical improvement. The cerebrospinal fluid (CSF) and electroencephalography diagnostics showed inconspicuous findings, and negative CSF anti-GlyR antibody results. : The patient presented here was suffering from a complex Parkinsonian syndrome with frontal lobe involvement. Because of the high anti-GlyR antibody titers, the presence of an autoimmune cause of the disorder was discussed. However, since no typical signs of autoimmune anti-GlyR antibody syndrome (e.g., hyperexcitability, anti-GlyR antibodies in CSF, or other inflammatory CSF changes) were detected, the possibility that the anti-GlyR antibodies might have been an unrelated bystander should be considered. Alternatively, the anti-GlyR antibodies might have developed secondarily to neurodegeneration (most likely a 4-repeat tauopathy, PSP or CBD) without exerting overt clinical effects, as in cases of anti-IgLON5 encephalopathy. In this case, such antibodies might also potentially modify the clinical course of classical movement disorders. Further research on the role of antineuronal antibodies in Parkinsonian syndromes is needed.
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http://dx.doi.org/10.3390/brainsci10060399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349831PMC
June 2020

Psychiatric Manifestation of Anti-LGI1 Encephalitis.

Brain Sci 2020 Jun 16;10(6). Epub 2020 Jun 16.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is typically characterized by limbic encephalitis, faciobrachial dystonic seizures and hyponatremia. The frequency with which milder forms of anti-LGI1 encephalitis mimic isolated psychiatric syndromes, such as psychoses, or may lead to dementia if untreated, is largely unknown.

Case Presentation: Here, the authors present a 50-year-old patient who had suffered from neurocognitive deficits and predominant delusions for over one and a half years. He reported a pronounced feeling of thirst, although he was drinking 10-20 liters of water each day, and he was absolutely convinced that he would die of thirst. Due to insomnia in the last five years, the patient took Z-drugs; later, he also abused alcohol. Two years prior to admission, he developed a status epilepticus which had been interpreted as a withdrawal seizure. In his serum, anti-LGI1 antibodies were repeatedly detected by different independent laboratories. Cerebrospinal fluid analyses revealed slightly increased white blood cell counts and evidence for blood-brain-barrier dysfunction. Magnetic resonance imaging showed hyperintensities mesio-temporally and in the right amygdala. In addition, there was a slight grey-white matter blurring. A cerebral [F] fluorodeoxyglucose positron emission tomography (FDG-PET) examination of his brain showed moderate hypometabolism of the bilateral rostral mesial to medial frontal cortices. Treatment attempts with various psychotropic drugs remained unsuccessful in terms of symptom relief. After the diagnosis of probable chronified anti-LGI1 encephalitis was made, two glucocorticoid pulse treatments were performed, which led to a slight improvement of mood and neurocognitive deficits. Further therapy was not desired by the patient and his legally authorized parents.

Conclusion: This case study describes a patient with anti-LGI1 encephalitis in the chronified stage and a predominant long-lasting psychiatric course with atypical symptoms of psychosis and typical neurocognitive deficits. The patient's poor response to anti-inflammatory drugs was probably due to the delayed start of treatment. This delay in diagnosis and treatment may also have led to the FDG-PET findings, which were compatible with frontotemporal dementia ("state of damage"). In similar future cases, newly occurring epileptic seizures associated with psychiatric symptoms should trigger investigations for possible autoimmune encephalitis, even in patients with addiction or other pre-existing psychiatric conditions. This should in turn result in rapid organic clarification and-in positive cases-to anti-inflammatory treatment. Early treatment of anti-LGI1 encephalitis during the "inflammatory activity state" is crucial for overall prognosis and may avoid the development of dementia in some cases. Based on this case, the authors advocate the concept-long established in many chronic inflammatory diseases in rheumatology-of distinguishing between an "acute inflammatory state" and a "state of organ damage" in autoimmune psychosis resembling neurodegenerative mechanisms.
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http://dx.doi.org/10.3390/brainsci10060375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348933PMC
June 2020

Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) - a phase II prospective randomized multicenter trial (NOA-14, ARO 2015-3, DKTK-ROG).

BMC Cancer 2020 Jun 8;20(1):532. Epub 2020 Jun 8.

Department of Radiation Oncology, Faculty of Medicine, Medical Center - University of Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany.

Background: Whole brain radiation therapy (WBRT) is the standard therapy for multiple brain metastases. However, WBRT has a poor local tumor control and is associated with a decline in neurocognitive function (NCF). Aim of this trial is to assess the efficacy and safety of a new treatment method, the WBRT with hippocampus avoidance (HA) combined with the simultaneous integrated boost (SIB) on metastases/resection cavities (HA-WBRT+SIB).

Methods: This is a prospective, randomized, two-arm phase II multicenter trial comparing the impact of HA on NCF after HA-WBRT+SIB versus WBRT+SIB in patients with multiple brain metastases. The study design is double-blinded. One hundred thirty two patients are to be randomized with a 1:1 allocation ratio. Patients between 18 and 80 years old are recruited, with at least 4 brain metastases of solid tumors and at least one, but not exceeding 10 metastases ≥5 mm. Patients must be in good physical condition and have no metastases/resection cavities in or within 7 mm of the hippocampus. Patients with dementia, meningeal disease, cerebral lymphomas, germ cell tumors, or small cell carcinomas are excluded. Previous irradiation and resection of metastases, as well as the number and size of metastases to be boosted have to comply with certain restrictions. Patients are randomized between the two treatment arms: HA-WBRT+SIB and WBRT+SIB. WBRT is to be performed with 30 Gy in 12 daily fractions and the SIB with 51 Gy/42 Gy in 12 daily fractions on 95% of volume for metastases/resection cavities. In the experimental arm, the dose to the hippocampi is restricted to 9 Gy in 98% of the volume and 17Gy in 2% of the volume. NCF testing is scheduled before WBRT, after 3 (primary endpoint), 9, 18 months and yearly thereafter. Clinical and imaging follow-ups are performed 6 and 12 weeks after WBRT, after 3, 9, 18 months and yearly thereafter.

Discussion: This is a protocol of a randomized phase II trial designed to test a new strategy of WBRT for preventing cognitive decline and increasing tumor control in patients with multiple brain metastases.

Trial Registration: The HIPPORAD trial is registered with the German Clinical Trials Registry (DRKS00004598, registered 2 June 2016).
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http://dx.doi.org/10.1186/s12885-020-07011-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281918PMC
June 2020

Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment.

Childs Nerv Syst 2020 10 7;36(10):2537-2552. Epub 2020 Jun 7.

Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.

Introduction: Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12-18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging.

Methods: The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center.

Results: Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy.

Conclusion: We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.
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http://dx.doi.org/10.1007/s00381-020-04712-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575510PMC
October 2020

Dissociation of visual extinction and neglect in the left hemisphere.

Cortex 2020 08 28;129:211-222. Epub 2020 Apr 28.

Department of Neurology and Neuroscience, University Medical Center Freiburg, Freiburg, Germany; Freiburg Brain Imaging Center, University Medical Center Freiburg, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University Medical Center Freiburg, Freiburg, Germany. Electronic address:

Visual neglect and extinction are two distinct visuospatial attention deficits that frequently occur after right hemisphere cerebral stroke. However, their different lesion profiles remain a matter of debate. In the left hemisphere, a domain-general dual-loop model with distinct computational abilities onto which several cognitive functions may project, has been proposed: a dorsal stream for sensori-motor mapping in time and space and a ventral stream for comprehension and representation of concepts. We wondered whether such a distinction may apply to visual extinction and neglect in left hemisphere lesions. Of 165 prospectively studied patients with acute left hemispheric ischemic stroke with a single lesion on MRI, 122 had no visuospatial attention deficit, 10 had extinction, 31 neglect and 2 had both, visual extinction and neglect. Voxel-based-lesion-symptom mapping (VLSM, FDR<.05) showed a clear anatomical dissociation. Extinction occurred after damage to the parietal cortex (anterior bank of the intraparietal sulcus, inferior parietal lobe, and supramarginal gyrus), while visual neglect occurred after damage mainly to the temporal lobe (superior and middle temporal lobe, anterior temporal pole), inferior ventral premotor cortex, frontal operculum, angular gyrus, and insula. Direct comparison of both conditions linked extinction to intraparietal sulcus and supramarginal gyrus (FDR<.05). Thus, in the left hemisphere extinction seems to be related to dorsal stream lesions, whereas neglect maps more on the ventral stream. These data cannot be generalized to the right hemisphere. However, a domain-general point-of-view may stimulate discussion on visuospatial attention processing also in the right hemisphere.
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http://dx.doi.org/10.1016/j.cortex.2020.04.010DOI Listing
August 2020