Publications by authors named "Stefan Schwab"

316 Publications

Land-Use System and Forest Floor Explain Prokaryotic Metacommunity Structuring and Spatial Turnover in Amazonian Forest-to-Pasture Conversion Areas.

Front Microbiol 2021 21;12:657508. Epub 2021 Apr 21.

National Agrobiology Research Center, Embrapa Agrobiologia, Seropédica, Brazil.

Advancing extensive cattle production is a major threat to biodiversity conservation in Amazonia. The dominant vegetation cover has a drastic impact on soil microbial communities, affecting their composition, structure, and ecological services. Herein, we explored relationships between land-use, soil types, and forest floor compartments on the prokaryotic metacommunity structuring in Western Amazonia. Soil samples were taken in sites under high anthropogenic pressure and distributed along a ±800 km gradient. Additionally, the litter and a root layer, characteristic of the forest environment, were sampled. DNA was extracted, and metacommunity composition and structure were assessed through 16S rRNA gene sequencing. Prokaryotic metacommunities in the bulk soil were strongly affected by pH, base and aluminum saturation, Ca + Mg concentration, the sum of bases, and silt percentage, due to land-use management and natural differences among the soil types. Higher alpha, beta, and gamma diversities were observed in sites with higher soil pH and fertility, such as pasture soils or fertile soils of the state of Acre. When taking litter and root layer communities into account, the beta diversity was significantly higher in the forest floor than in pasture bulk soil for all study regions. Our results show that the forest floor's prokaryotic metacommunity performs a spatial turnover hitherto underestimated to the regional scale of diversity.
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http://dx.doi.org/10.3389/fmicb.2021.657508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097146PMC
April 2021

Influence of Early Enteral Nutrition on Clinical Outcomes in Neurocritical Care Patients With Intracerebral Hemorrhage.

Front Neurol 2021 20;12:665791. Epub 2021 Apr 20.

Department of Neurology, University Hospital Erlangen-Nuremberg, Erlangen, Germany.

Early enteral nutrition (EEN) represents the current standard of care for patients treated in general intensive care units (ICU). Specific nutritional recommendations for patients receiving dedicated neurocritical care are not established. This study investigated associations of EEN with clinical outcomes for patients suffering from intracerebral hemorrhage treated at a neurological ICU (NICU). This retrospective cohort study included patients admitted to the NICU with atraumatic ICH over a 4-year period. Nutritional data, demographic, clinical, radiological, and laboratory characteristics were assessed. EEN was defined as any enteral nutrition within 48 hours after admission. Comparisons were undertaken for patients with EEN vs. those without, further propensity score (PS) matching (caliper 0.2; one: many) was used to account for baseline imbalances. Primary outcome was the modified Rankin Scale (0-3 = favorable, 4-6 = unfavorable) at 12 months, secondary outcomes comprised perihemorrhagic edema (PHE) volume, infectious complications during the hospital stay, and mRS at 3 months, as well as mortality rates at 3 and 12 months. Of 166 ICH-patients treated at the NICU, 51 (30.7%) patients received EEN, and 115 (69.3%) patients received no EEN (nEEN). After propensity score matching, calories delivered from enteral nutrition (EEN 161.4 [106.4-192.3] kcal/day vs. nEEN 0.0 [0.0-0.0], < 0.001) and the total calories (EEN 190.0 [126.0-357.0] kcal/day vs. nEEN 33.6 [0.0-190.0] kcal/day, < 0.001) were significantly different during the first 48 h admitted in NICU. Functional outcome at 12 months (mRS 4-6, EEN 33/43 [76.7%] vs. nEEN, 49/64 [76. 6%]; = 1.00) was similar in the two groups. There were neither differences in mRS at 3 months, nor in mortality rates at 3 and 12 months between the two groups. EEN did not affect incidence of infective complications or gastrointestinal adverse events during the hospital stay; however, EEN was associated with significantly less extent of PHE evolution [maximum absolute PHE (OR 0.822, 95% CI 0.706-0.957, = 0.012); maximum relative PHE (OR 0.784, 95% CI 0.646-0.952, = 0.014)]. In our study, EEN was associated with reduced PHE in ICH-patients treated at a NICU. However, this observation did not translate into improved survival or functional outcome at 3 and 12 months.
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http://dx.doi.org/10.3389/fneur.2021.665791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093818PMC
April 2021

Alpha power decrease in quantitative EEG detects development of cerebral infarction after subarachnoid hemorrhage early.

Clin Neurophysiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.

Objective: In subarachnoid hemorrhage (SAH), transcranial Doppler/color-coded-duplex sonography (TCD/TCCS) is used to detect delayed cerebral ischemia (DCI). In previous studies, quantitative electroencephalography (qEEG) also predicted imminent DCI. This study aimed to compare and analyse the ability of qEEG and TCD/TCCS to early identify patients who will develop later manifest cerebral infarction.

Methods: We analysed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artefact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as significant EEG event. Median reduction and duration of alpha power decrease in each channel was determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory.

Results: 34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I-V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters.

Conclusions: There was a moderate correlation of TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction.

Significance: qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction.
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http://dx.doi.org/10.1016/j.clinph.2021.03.005DOI Listing
March 2021

Pearls & Oy-sters: Moyamoya Vasculopathy and Its Association With Congenital Heart Disease.

Neurology 2021 Apr 14. Epub 2021 Apr 14.

Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.

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http://dx.doi.org/10.1212/WNL.0000000000012049DOI Listing
April 2021

Effects of a 4-Step Standard Operating Procedure for the Treatment of Fever in Patients With Acute Stroke.

Front Neurol 2021 4;12:614266. Epub 2021 Mar 4.

Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Fever in the acute phase of stroke leads to an unfavorable clinical outcome and increased mortality. However, no specific form of effective fever treatment has been established, so far. We analyzed the effectiveness of our in-house standard operating procedure (SOP) of fever treatment. This SOP was analyzed for a period of 33 weeks. Patients with cerebral ischemia (ischemic stroke, transient ischemic attack) or cerebral hemorrhage (intracerebral, subarachnoid) and body temperature elevation of ≥ 37.5°C within the first 6 days after admission were eligible for inclusion in the analysis. The results of SOP group, who's data have been collected prospectively were then compared with a historical control group that had been treated conventionally 1 year earlier in the same period. The data of control group have been collected in retrospect. The primary endpoint was the total duration of the fever for the first 6 days after admission to the stroke unit. A total of 130 patients (mean age of 78 ± 12) received 370 antipyretic interventions. Sequential application of paracetamol ( = 245), metamizole ( = 53) and calf compress ( = 15) led to significant reduction in body temperature. In patients who did not respond to these applications, normothermia could be achieved after infusion of the cooled saline solution. Normothermia could be achieved within 120 min in more than 90% of the cases treated by the SOP. The SOP reduced the fever duration in the 6 days significantly, from 12.2 ± 2.7 h [95% confidence interval (CI) for mean] in the control group to 3.9 ± 1.0 h (95% CI) in the SOP group ( < 0.001). The SOP was rated to be reasonable and effective. Our in-house SOP is cost-efficient and effective for fever treatment in stroke patients, that can be implemented by local health care professionals.
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http://dx.doi.org/10.3389/fneur.2021.614266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970170PMC
March 2021

Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020.

Eur J Neurol 2021 Feb 22. Epub 2021 Feb 22.

Department of Neurology, University Hospital Würzburg, Würzburg, Germany.

Background And Purpose: The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany.

Methods: In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in-hospital and (telemedical) stroke care during the pandemic was conducted.

Results: Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID-19 measures in May/June 2020 were observed. Compared to 2018-2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID-19, there were no relevant shortcomings reported regarding in-hospital stroke treatment or telemedical stroke care.

Conclusions: Telemedical stroke care in Germany was able to provide full service despite the COVID-19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID-19 measures in Germany.
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http://dx.doi.org/10.1111/ene.14787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013200PMC
February 2021

The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial - A post hoc analysis.

Eur Stroke J 2020 Dec 23;5(4):370-373. Epub 2020 Apr 23.

Heidelberg University Hospital, Department of Neurology, Heidelberg, Germany.

Introduction: To investigate the impact of a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) on functional outcome in patients with acute stroke in a prolonged time window or unknown time of symptom onset randomized to intravenous thrombolysis or placebo.

Patients And Methods: We performed a post-hoc analysis of the European Cooperative Acute Stroke Study-4 (ECASS-4) trial. ECASS-4 was an investigator driven, phase 3, multi-center, double-blind, placebo-controlled study which randomized ischemic stroke patients presenting within 4.5 and 9h of stroke onset or unknown time-window to either rt-PA or placebo after MR-imaging. Two subgroups "no mismatch" (nMM) and "any mismatch" (aMM) were created by applying a DWI-FLAIR-mismatch criterion. We calculated frequency of nMM and aMM and performed a univariate analysis (Fisher's Test) for excellent clinical outcome (mRS 0-1) and mortality (mRS=6).

Results: MR-Imaging of n=111/119 (93.2%) patients was suitable for this analysis. DWI-FLAIR mismatch was found in 49 patients (44.1%). Proportions of mismatch nMM and aMM were comparable in treatment-groups (aMM: Placebo 46.3%, Alteplase 42.1%; p=0.70). Patients with nMM showed no benefit of rt-PA-treatment (OR (95%CI) mRS 0-1: 0.95 (0.29-3.17)). Patients with aMM showed a point estimate of the odds ratio in favour of a treatment benefit of rt-PA (mRS 0-1: OR (95%CI) 2.62 (0.68-11.1)). Mortality within 90 days was not different in patients treated with rt-PA if nMM (15.2%) or aMM (12.5%) was present.

Discussion: In this analysis no significant evidence, but subtle indication towards patients treated with rt-PA in a prolonged time window reaching an excellent clinical outcome if a DWI-FLAIR-mismatch is present on initial stroke MR-imaging.

Conclusion: A DWI-FLAIR mismatch in the region of ischemia as imaging based surrogate parameter for patient selection for i.v. rt-PA should be strongly pursued.
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http://dx.doi.org/10.1177/2396987320920114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856579PMC
December 2020

Temporal assessment of root and shoot colonization of elephant grass (Pennisetum purpureum Schum.) host seedlings by Gluconacetobacter diazotrophicus strain LP343.

Microbiol Res 2021 Mar 25;244:126651. Epub 2020 Nov 25.

Embrapa Agrobiologia, Rodovia BR 465, km 7, CEP 23891-000, Seropédica, RJ, Brazil. Electronic address:

Gluconacetobacter diazotrophicus is a species of great agronomic potential due to its growth-promotion traits. Its colonization process in different plants has been reported. However, there have been no studies regarding its structural colonization in elephant grass. This is a fast-growing C4-Poaceae plant, and its application in Brazil is mainly aimed at feeding dairy cattle, due to its high nutritional value. Also, in the last decade, this grass has been applied in the production of biofuels. The present study aimed to monitor the colonization process of strain LP343 of G. diazotrophicus inoculated in elephant grass seedlings of PCEA genotype, by using a mCherry-tagged bacterium. Samples of roots and shoots collected at different periods were visualized by confocal laser-scanning microscopy. The colony-counting assay was used to compare the number of cells recovered in different niches and a qPCR was performed for the quantification of endophytic cells in root and shoot tissues. Results suggested that the strain LP343 quickly recognized the PCEA roots as host, attached to the elephant grass roots at 6 h, and 7 days after inoculation were able to colonize the xylem vessels of roots and shoots of elephant grass. This study advances our knowledge about the colonization process of G. diazotrophicus species in elephant grass, contributing to future studies involving the plant-bacteria interaction cultivated under gnotobiotic conditions.
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http://dx.doi.org/10.1016/j.micres.2020.126651DOI Listing
March 2021

Automated Pupillometry Identifies Absence of Intracranial Pressure Elevation in Intracerebral Hemorrhage Patients.

Neurocrit Care 2020 Dec 24. Epub 2020 Dec 24.

Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.

Introduction: Although automated pupillometry is increasingly used in critical care settings, predictive value of automatically assessed pupillary parameters during different intracranial pressure (ICP) levels and possible clinical implications are unestablished.

Methods: This retrospective cohort study at the neurocritical care unit of the University of Erlangen-Nuremberg (2016-2018) included 23 nontraumatic supratentorial (intracerebral hemorrhage) ICH patients without signs of abnormal pupillary function by manual assessment, i.e., absent light reflex. We assessed ICP levels by an external ventricular drain simultaneously with parameters of pupillary reactivity [i.e., maximum and minimum apertures, light reflex latency (Lat), constriction and redilation velocities (CV, DV), and percentage change of apertures (per-change)] using a portable pupillometer (NeurOptics®). Computed tomography (CT) scans were analyzed to determine lesion location, size, intraventricular hemorrhage, hydrocephalus, midline shift, and compression or absence of the basal cisterns. We performed receiver operating characteristics analysis to investigate associations of ICP levels with pupillary parameters and to determine best cutoff values for prediction of ICP elevation. After dichotomization of assessments according to ICP values (normal: < 20 mmHg, elevated: ≥ 20 mmHg), prognostic performance of the determined cutoff parameters of pupillary function versus of CT-imaging findings was analyzed by calculating sensitivity, specificity, positive and negative predictive values (logistic regression, corresponding ORs with 95% CIs).

Results: In 23 patients (11 women, median age 59.0 (51.0-69.0) years), 1,934 assessments were available for analysis. A total of 74 ICP elevations ≥ 20 mmHg occurred in seven patients. Best discriminative thresholds for ICP elevation were: CV < 0.8 mm/s (AUC 0.740), per-change < 10% (AUC 0.743), DV < 0.2 mm/s (AUC 0.703), and Lat > 0.3 s (AUC 0.616). Positive predictive value of all four parameters to indicate ICP elevation ranged between 7.2 and 8.3% only and was similarly low for CT abnormalities (9.1%). We found high negative predictive values of pupillary parameters [CV: 99.2% (95% CI 98.3-99.6), per-change: 98.7% (95% CI 97.8-99.2), DV: 98.0% (95% CI 97.0-98.7), Lat: 97.0% (95% CI 96.0-97.7)], and CT abnormalities [99.7% (95% CI 99.2-99.9)], providing evidence that both techniques adequately identified ICH patients without ICP elevation.

Conclusions: Our data suggest an association between noninvasively detected changes in pupillary reactivity and ICP levels in sedated ICH patients. Although automated pupillometry and neuroimaging seem not sufficient to noninvasively indicate ICP elevation, both techniques, however, adequately identified ICH patients without ICP elevation. This finding may facilitate routine management by saving invasive ICP monitoring or repeated CT controls in patients with specific automated pupillometry readings.
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http://dx.doi.org/10.1007/s12028-020-01146-4DOI Listing
December 2020

Automatic dementia screening and scoring by applying deep learning on clock-drawing tests.

Sci Rep 2020 11 30;10(1):20854. Epub 2020 Nov 30.

Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058, Erlangen, Germany.

Dementia is one of the most common neurological syndromes in the world. Usually, diagnoses are made based on paper-and-pencil tests and scored depending on personal judgments of experts. This technique can introduce errors and has high inter-rater variability. To overcome these issues, we present an automatic assessment of the widely used paper-based clock-drawing test by means of deep neural networks. Our study includes a comparison of three modern architectures: VGG16, ResNet-152, and DenseNet-121. The dataset consisted of 1315 individuals. To deal with the limited amount of data, which also included several dementia types, we used optimization strategies for training the neural network. The outcome of our work is a standardized and digital estimation of the dementia screening result and severity level for an individual. We achieved accuracies of 96.65% for screening and up to 98.54% for scoring, overcoming the reported state-of-the-art as well as human accuracies. Due to the digital format, the paper-based test can be simply scanned by using a mobile device and then be evaluated also in areas where there is a staff shortage or where no clinical experts are available.
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http://dx.doi.org/10.1038/s41598-020-74710-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704614PMC
November 2020

Multicenter Validation of the max-ICH Score in Intracerebral Hemorrhage.

Ann Neurol 2021 03 21;89(3):474-484. Epub 2020 Dec 21.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Objective: Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max-ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long-term outcomes after ICH.

Methods: This multicenter validation study compared the prognostication of the max-ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German-wide studies (RETRACE I + II; anticoagulation-associated ICH only) conducted at 22 participating centers, one German prospective single-center study (UKER-ICH; nonanticoagulation-associated ICH only), and 1 US-based prospective longitudinal single-center study (MGH; both anticoagulation- and nonanticoagulation-associated ICH), treated between January 2006 and December 2015.

Results: Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% [440 of 2,377]; MGH: 31.0% [577 of 1,283]). Validation of long-term functional outcome prognostication by the max-ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve [AUROC], German cohort: 0.81 [0.78-0.83] vs 0.74 [0.72-0.77], p < 0.01; MGH: 0.85 [0.81-0.89] vs 0.78 [0.74-0.82], p < 0.01), and for the entire cohort (AUROC, German cohort: 0.84 [0.82-0.86] vs 0.80 [0.77-0.82], p < 0.01; MGH: 0.83 [0.81-0.85] vs 0.77 [0.75-0.79], p < 0.01). Both scores showed no evidence of poor calibration. The clinical utility investigated by decision curve analysis showed, at high threshold probabilities (0.8, aiming to avoid false-positive poor outcome attribution), that the max-ICH Score provided a clinical net benefit compared with the ICH Score (14.1 vs 2.1 net predicted poor outcomes per 100 patients).

Interpretation: The max-ICH Score provides valid and improved prognostication of functional outcome after ICH. The associated clinical net benefit in minimizing false poor outcome attribution might potentially prevent unwarranted care limitations in patients with ICH. ANN NEUROL 2021;89:474-484.
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http://dx.doi.org/10.1002/ana.25969DOI Listing
March 2021

Parenchymatous hematoma in patients with atraumatic subarachnoid hemorrhage: Characteristics, treatment, and clinical outcomes.

Int J Stroke 2020 Nov 19:1747493020971878. Epub 2020 Nov 19.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Data regarding the influence of concomitant parenchymatous hematoma (PH) on long-term outcomes in patients with atraumatic subarachnoid hemorrhage (SAH) are scarce. Further, it is not established if these patients benefit from surgical intervention.

Aim: The aim of this study was to determine the influence of concomitant PH in SAH patients on functional long-term outcome, and whether these patients may benefit from surgical hematoma evacuation.

Methods: Over a 5-year period, all consecutive patients with SAH treated at the Departments of Neurology, Neuroradiology, and Neurosurgery, at the University Hospital Erlangen (Germany) were recorded. In addition to the clinical and imaging characteristics of SAH, we documented the presence, location, and volume of PH as well as treatment parameters. Outcome assessment at 12 months included functional outcome (modified Rankin scale (mRS), favorable = 0-2), health-related quality of life, and long-term complications. For outcome analysis, a propensity score matching (ratio 1:1, caliper 0.1) was performed to compare SAH patients with and without PH. Sub-analyses were performed regarding PH treatment (surgical evacuation vs. conservative).

Results: A total of 494 patients with atraumatic SAH were available. Eighty-five (17.2%) had PH on initial imaging. SAH patients with PH had a worse clinical condition on admission and had a greater extent of subarachnoid/intraventricular hemorrhage. Median PH volume was 11.0 ml (5.4-31.8) with largest volumes observed in patients with ruptured middle cerebral artery (MCA)-aneurysm (31.7 ml (16.3-43.2)). After propensity-score matching (PSM), patients with PH had worse functional outcomes at 12 months (modified Rankin scale (mRS) 0-2: PH 31.8% vs. ØPH57.7% p < 0.001), and a lower rate of self-reported health compared to patients without PH (EQ-5D VAS: PH 50(30-70) vs. ØPH 80(65-95); p < 0.001). In PH patients, surgical evacuation was associated with a higher rate of favorable outcome at 12 months compared to those treated conservatively (surgery 14/28 (50.0%) vs. conservative 14/57 (24.6%); adjusted odds-ratio (OR; 95%CI): 1.34 (1.08-1.66); p = 0.001), irrespective of aneurysm location. Subgroup-analysis revealed positive associations of surgical hematoma evacuation with outcome in subgroups with larger PH volumes (>10 ml; OR (95%CI): 1.39 (1.09-1.79)), frontal PH location (OR 1.59 (1.14-2.23)), and early surgery (within 600 min after onset; OR 1.42 (1.03-1.94)).

Conclusions: Concomitant PH occurs frequently in patients with SAH and is associated with functional impairment after 1 year. Surgical evacuation of PH may improve outcomes in these patients, irrespective of aneurysm-location.
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http://dx.doi.org/10.1177/1747493020971878DOI Listing
November 2020

Psychosocial long-term outcome in patients with psychogenic non-epileptic seizures.

Seizure 2020 Dec 24;83:187-192. Epub 2020 Sep 24.

Epilepsy Center, Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.

Purpose: To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up.

Methods: Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002-2016 were contacted by phone 1-16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL.

Results: Of 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up.

Conclusion: Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL.
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http://dx.doi.org/10.1016/j.seizure.2020.09.014DOI Listing
December 2020

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Ex vivo radiosensitivity is increased in non-cancer patients taking valproate.

BMC Neurol 2020 Oct 24;20(1):390. Epub 2020 Oct 24.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Universitaetsstraße 27, 91054, Erlangen, Germany.

Background: Valproate (VPA) is a commonly prescribed antiepileptic drug for patients experiencing epileptic seizures due to brain tumors. VPA increases radiation sensitivity in various tumor cells in vitro due to complex mechanisms. This could make tumors more vulnerable to ionizing radiation or overcome radioresistance. Yet, clinical data on possible improvement of tumor control by adding VPA to tumor therapy is controversial. Potentially radiosensitizing effects of VPA on healthy tissue remain unclear. To determine individual radiosensitivity, we analyzed blood samples of individuals taking VPA.

Methods: Ex vivo irradiated blood samples of 31 adult individuals with epilepsy were studied using 3-color fluorescence in situ hybridization. Aberrations in chromosomes 1, 2 and 4 were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M) and compared to age-matched (2:1) healthy donors.

Results: The patient cohort (n = 31; female: 38.7%) showed an increase of their average B/M value compared to healthy individuals (n = 61; female: 56.9%; B/M: 0.480 ± 0.09 vs. 0.415 ± 0.07; p = .001). The portion of radiosensitive (B/M >  0.500) and distinctly radiosensitive individuals (B/M >  0.600) was increased in the VPA group (54.9% vs. 11.3 and 9.7% vs. 0.0%; p < .001). In 3/31 patients, radiosensitivity was determined prior to and after VPA treatment and radiosensitivity was increased by VPA-treatment.

Conclusions: In our study, we confirmed that patients treated with VPA had an increased radiosensitivity compared to the control group. This could be considered in patients taking VPA prior to the beginning of radiotherapy to avoid toxic side effects of VPA-treatment.
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http://dx.doi.org/10.1186/s12883-020-01966-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585294PMC
October 2020

Multimodal CT or MRI for IV thrombolysis in ischemic stroke with unknown time of onset.

Neurology 2020 12 21;95(22):e2954-e2964. Epub 2020 Oct 21.

From the Departments of Neurology (K.M., G.S., S.S., B.K.) and Neuroradiology (P.H., M.K., A.D., T.E.), University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nuremberg (FAU), Erlangen, Germany.

Objective: To investigate differences in procedure times, safety, and efficacy outcomes comparing 2 different protocols to enable thrombolysis in the extended or unknown time window after stroke onset with either multimodal CT or MRI.

Methods: Patients with ischemic stroke in the extended or unknown time window who received IV thrombolysis between January 2011 and May 2019 were identified from an institutional registry. Imaging-based selection was done by multimodal CT or MRI according to institutional treatment algorithms.

Results: IV thrombolysis was performed in 100 patients (54.3%) based on multimodal CT imaging and in 84 patients (45.7%) based on MRI. Baseline clinical data, including stroke severity and time from last seen normal to hospital admission, were similar in patients with CT and MRI. Door-to-needle times were shorter in patients with CT-based selection (median [interquartile range] 45 [37-62] minutes vs 75 [59-90] minutes; mean difference [95% confidence interval (CI)] -28 minutes [-35 to -21]). No differences were detected regarding the incidence of symptomatic intracranial hemorrhage (2 [2.0%] vs 4 [4.8%]; adjusted odds ratio [aOR] [95% CI] 0.47 [0.08-2.83]) and favorable outcome at day 90 (25 [33.8%] vs 33 [42.9%]; aOR 0.95 [0.45-2.02]).

Conclusion: IV thrombolysis in ischemic stroke in the unknown or extended time window appeared safe in CT- and MRI-selected patients, while the use of CT imaging led to faster door-to-needle times.

Classification Of Evidence: This study provides Class IV evidence that for patients with ischemic stroke in the extended or unknown time window, imaging-based selection for IV thrombolysis by multimodal CT compared to MRI led to shorter door-to-needle times.
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http://dx.doi.org/10.1212/WNL.0000000000011059DOI Listing
December 2020

Management of Stroke in Patients with Left Ventricular Assist Devices.

J Stroke Cerebrovasc Dis 2020 Nov 12;29(11):105166. Epub 2020 Aug 12.

Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.

Introduction: The number of patients with left ventricular assist devices (LVAD) is rapidly growing in industrialized countries. While cerebrovascular events comprise a significant complication, data on stroke etiology, clinical management and functional outcome are scarce.

Methods: Consecutive LVAD patients with ischemic or hemorrhagic stroke receiving treatment at an university stroke center between 2010 and 2018 were included into an institutional registry. Clinical characteristics, causes, management and functional outcome of stroke occurring within this cohort are reported. Acceptable functional outcome was defined as mRS 0-3.

Results: N = 30 acute strokes occurred in 20 patients (77% ischemic, 23% hemorrhagic, mean age 57 ± 13 years, 10% female, 8 patients (40%) had more than one event). 87% of all events happened with non-pulsatile devices, on average 9 (IQR 3-22) months after the implantation. All patients used oral anticoagulation with a Vitamin-K antagonist in combination with anti-platelets. The international normalized ratio (INR)-values were outside the therapeutic range in 39% of ischemic strokes and in 57% of hemorrhagic strokes. Ischemic strokes were predominantly of cardioembolic origin (92%) and of mild to moderate clinical severity (median NIHSS 6 (IQR 4-10). None qualified to receive intravenous thrombolysis or intra-arterial endovascular therapy. 61% of IS-patients showed an acceptable functional outcome after three months. 4/7 patients with hemorrhagic stroke received immediate reversal of anticoagulation without any thrombotic complications.

Conclusion: The majority of LVAD patients with ischemic stroke had an acceptable functional outcome after three months. Future clinical research is warranted to improve therapeutic strategies for acute care and stroke prevention.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105166DOI Listing
November 2020

Genome-based reclassification of Sp245 as the type strain of sp. nov.

Int J Syst Evol Microbiol 2020 Dec;70(12):6203-6212

Embrapa Agrobiologia, BR 465 Km 7, 23891-000, Seropédica, Rio de Janeiro, Brazil.

sp. strain Sp245, originally identified as belonging to , is recognized as a plant-growth-promoting rhizobacterium due to its ability to fix atmospheric nitrogen and to produce plant-beneficial compounds. sp. Sp245 and other related strains were isolated from the root surfaces of different plants in Brazil. Cells are Gram-negative, curved or slightly curved rods, and motile with polar and lateral flagella. Their growth temperature varies between 20 to 38 °C and their carbon source utilization is similar to other species. A preliminary 16S rRNA sequence analysis showed that the new species is closely related to Sp7 and CC-Nfb-7. Housekeeping genes revealed that sp. Sp245, BR 12001 and Vi22 form a separate cluster from strain CC-Nfb-7, and a group of strains closely related to Sp7. Overall genome relatedness index (OGRI) analyses estimated based on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) between sp. Sp245 and its close relatives to other species type strains, such as Sp7 and CC-Nfb-7 revealed values lower than the limit of species circumscription. Moreover, core-proteome phylogeny including 1079 common shared proteins showed the independent clusterization of Sp7, CC-Nfb-7 and sp. Sp245, a finding that was corroborated by the genome clustering of OGRI values and housekeeping phylogenies. The DNA G+C content of the cluster of Sp245 was 68.4-68.6 %. Based on the phylogenetic, genomic, phenotypical and physiological analysis, we propose that strain Sp245 together with the strains Vi22 and BR12001 represent a novel species of the genus , for which the name sp. nov. is proposed. The type strain is Sp245 (=BR 11005=IBPPM 219) (GCF_007827915.1, GCF_000237365.1, and GCF_003119195.2).
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http://dx.doi.org/10.1099/ijsem.0.004517DOI Listing
December 2020

Cerebral lipogranuloma: A penetrating traumatic brain injury.

Neurology 2020 12 14;95(22):1019-1020. Epub 2020 Oct 14.

From the Departments of Neurology (M.H., S.S., F.S.), Neuropathology (R.C.), and Neuroradiology (T.E.), University Hospital Erlangen, Germany.

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http://dx.doi.org/10.1212/WNL.0000000000011071DOI Listing
December 2020

Quantitative H and Na muscle MRI in Facioscapulohumeral muscular dystrophy patients.

J Neurol 2021 Mar 12;268(3):1076-1087. Epub 2020 Oct 12.

Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.

Objective: Our aim was to assess the role of quantitative H and Na MRI methods in providing imaging biomarkers of disease activity and severity in patients with Facioscapulohumeral muscular dystrophy (FSHD).

Methods: We imaged the lower leg muscles of 19 FSHD patients and 12 controls with a multimodal MRI protocol to obtain STIR-Tw images, fat fraction (FF), water T (wT), water T (wT), tissue sodium concentration (TSC), and intracellular-weighted sodium signal (inversion recovery (IR) and triple quantum filter (TQF) sequence). In addition, the FSHD patients underwent muscle strength testing.

Results: Imaging biomarkers related with water mobility (wT and wT) and ion homeostasis (TSC, IR, TQF) were increased in muscles of FSHD patients. Muscle groups with FF > 10% had higher wT, wT, TSC, IR, and TQF values than muscles with FF < 10%. Muscles with FF < 10% resembled muscles of healthy controls for these MRI disease activity measures. However, wT was increased in few muscles without fat replacement. Furthermore, few STIR-negative muscles (n = 11/76) exhibited increased wT, TSC, IR or TQF. Increased wT as well as Na signals were also present in muscles with normal wT. Muscle strength was related to the mean FF and all imaging biomarkers of tibialis anterior except wT were correlated with dorsal flexion.

Conclusion: The newly evaluated imaging biomarkers related with water mobility (wT) and ion homeostasis (TSC, IR, TQF) showed different patterns compared to the established markers like FF in muscles of FSHD patients. These quantitative biomarkers could thus contain valuable complementary information for the early characterization of disease progression.
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http://dx.doi.org/10.1007/s00415-020-10254-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914168PMC
March 2021

Disseminated Multifocal Intracerebral Bleeding Events in Three Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation As Rescue Therapy.

Crit Care Explor 2020 Sep 15;2(9):e0218. Epub 2020 Sep 15.

Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Objectives: To describe three coronavirus disease 2019 patients suffering from acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation therapy and tight anticoagulation monitoring presenting a novel pattern of multifocal brain hemorrhage in various degrees in all cerebral and cerebellar lobes.

Design: Clinical observation of three patients. Post mortem examinations.

Setting: Two ICUs at the University Hospital Erlangen.

Patients: Three patients (medium age 56.6 yr, two male with hypertension and diabetes, one female with no medical history) developed severe acute respiratory distress syndrome on the basis of a severe acute respiratory syndrome coronavirus 2 infection. All required mechanical ventilation and venovenous extracorporeal membrane oxygenation support.

Interventions: Clinical observation, CT, data extraction from electronic medical records, and post mortem examinations.

Main Results: We report on an unusual multifocal bleeding pattern in the white matter in three cases with severe acute respiratory distress syndrome due to coronavirus disease 2019 undergoing venovenous extracorporeal membrane oxygenation therapy. Bleeding pattern with consecutive herniation was found in CT scans as well as in neuropathologic post mortem examinations. Frequency for this unusual brain hemorrhage in coronavirus disease 2019 patients with extracorporeal membrane oxygenation therapy at our hospital is currently 50%, whereas bleeding events in extracorporeal membrane oxygenation patients generally occur at 10-15%.

Conclusions: Multifocality and high frequency of the unusual white matter hemorrhage pattern suggest a coherence to coronavirus disease 2019. Neuropathological analyses showed circumscribed thrombotic cerebrovascular occlusions, which eventually led to microvascular and later on macrovascular disseminated bleeding events. However, signs of cerebrovascular inflammation could not be detected. Polymerase chain reaction analyses of brain tissue or cerebrospinal fluid remained negative. Increased susceptibility for fatal bleeding events should be taken into consideration in terms of systemic anticoagulation strategies in coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCE.0000000000000218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498131PMC
September 2020

Quantitative Corticospinal Tract Assessment in Acute Intracerebral Hemorrhage.

Transl Stroke Res 2020 Sep 21. Epub 2020 Sep 21.

Department of Neuroradiology, University of Erlangen-Nuremberg, Erlangen, Germany.

Intracerebral hemorrhage (ICH) prognostication during the acute phase is often subjective among physicians and often affects treatment decisions. The present study explores objective imaging parameters using quantitative corticospinal tract (CST) fiber reconstruction during the acute phase of ICH and correlates these parameters with functional outcome and patient recovery. We prospectively enrolled nonsurgical spontaneous supratentorial ICH patients and obtained an MRI scan on day 5 ± 1. Q-space diffeomorphic reconstruction was performed using DSI Studio, and quantitative anisotropy (QA) was calculated. The CST was reconstructed based on QA. The dichotomized modified Rankin Scale score on day 90 (favorable outcome = 0-2) and Barthel Index (favorable recovery = 100 on day 90 or improvement between discharge and day 90 > 60%) were assessed. Thirty-three patients, median age 72 years (interquartile range (IQR) 64-83), 21 female (64%), 21 (64%) with lobar hemorrhage, median ICH volume on admission 15.0 (IQR 7.0-27.4) mL, were included. Sixteen patients (48%) had a favorable outcome and 24 (73%) had a favorable recovery. The mean number of ipsilesional reconstructed CST fiber pathways was higher in patients with favorable outcomes (153 (standard deviation (SD) 103) vs. 60 (SD 39), p = 0.003) and predicted outcome after adjustment (Exp(B) = 1.016 (95% CI = 1.002-1.030)). QA in the ipsilesional posterior limb of the internal capsule showed a trend towards an association with favorable outcome (Exp(B) = 1.194 (95% CI = 0.991-1.439 (adjusted))). The total (ipsilesional + contralesional) number of reconstructed fiber pathways was associated with favorable recovery (Exp(B) = 1.025 (95% CI = 1.003-1.047 (adjusted))). Quantitative tractography parameters assessed in the acute phase of ICH may represent a promising predictor of long-term outcome and recovery. This might facilitate prognostic evaluation and organization of rehabilitation.
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http://dx.doi.org/10.1007/s12975-020-00850-9DOI Listing
September 2020

Dexamethasone in Patients with Spontaneous Intracerebral Hemorrhage: An Updated Meta-Analysis.

Cerebrovasc Dis 2020 15;49(5):495-502. Epub 2020 Sep 15.

Department of Neurology, University Hospital Erlangen, Erlangen, Germany.

Background: Spontaneous intracerebral hemorrhage (ICH) is a frequent cerebrovascular disorder and still associated with high mortality and poor clinical outcomes. The purpose of this review was to update a 15-year-old former meta-analysis on randomized clinical trials (RCTs) addressing the question of whether ICH patients treated with dexamethasone have better outcomes than controls.

Methods: The electronic databases PubMed, SCOPUS, and Cochrane as well as web platforms on current clinical trials were searched for the years 1970-2020 without constriction on language. Data were extracted and outcomes were pooled for conventional and cumulative meta-analysis using a commercial software program (www.Meta-Analysis.com).

Results: Finally, 7 RCTs were identified and analyzed including 248 participants in the dexamethasone groups and 242 in the control groups. Five studies showed a high risk of bias. The overall relative risk (RR) for death was 1.32 (95% confidence interval [CI] 0.99-1.76; p = 0.06) and did not differ significantly between the 2 groups. After exclusion of studies with high risk of bias, the RR for death was 1.37 (95% CI 0.54-3.42; p = 0.51). The RR for poor outcome did not differ significantly between the 2 groups analyzed for all included studies (RR = 0.69; 95% CI 0.47-1; p = 0.05) and after exclusion of studies with high risk of bias (RR = 0.7; 95% CI 0.45-1.08; p = 0.11). The RR for complications did not differ significantly including all studies (RR = 1.29; 95% CI 0.77-2.17; p = 0.34) and after exclusion of studies with high risk of bias (RR = 1.27; 95% CI 0.18-8.89; p = 0.81). The cumulative statistics delivered no other results; however, it pointed out fewer complications over time in the dexamethasone group.

Conclusion: Clear evidence of a beneficial or negative effect of dexamethasone is still lacking. Modern RCTs or observational studies with propensity design are necessary to evaluate the efficacy and safety of treatment with dexamethasone in patients with ICH.
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http://dx.doi.org/10.1159/000510040DOI Listing
November 2020

Bedside Catheter Hematoma Evacuation in Vitamin K Antagonist-Related Intracerebral Hemorrhage: A Safe and Feasible Approach.

Front Neurol 2020 14;11:807. Epub 2020 Aug 14.

Department of Neurology, University of Freiburg, Freiburg im Breisgau, Germany.

Although outcome in intracerebral hemorrhage (ICH) patients is generally not improved by surgical intervention, the use of minimally invasive surgery (MIS) has shown promising results. However, vitamin K antagonist (VKA)-related ICH patients are underrepresented in surgical treatment trials. We therefore assessed the safety and efficacy of a bedside MIS approach including local application of urokinase in VKA-related ICH. Patients with a VKA-related ICH > 20 ml who received bedside hematoma evacuation treatment ( = 21) at the University Medical Center Freiburg were retrospectively included for analysis and compared to a historical control group ( = 35) selected from an institutional database (University Medical Center Erlangen) according to identical inclusion criteria. Propensity score matching was performed to obtain comparable cohorts. The evolution of hematoma and peri-hemorrhagic edema (PHE) volumes, midline shift, and the occurrence of adverse events were analyzed. Furthermore, we assessed the modified Rankin Scale and NIHSS scores recorded at discharge. Propensity score matching resulted in 16 patients per group with well-balanced characteristics. Median ICH volume at admission was 45.7 (IQR: 24.2-56.7) ml in the control group and 48.4 (IQR: 28.7-59.6) ml in the treatment group ( = 0.327). ICH volume at day 7 was less pronounced in the treatment group [MIS: 23.2 ml (IQR: 15.8-32.3) vs. control: 43.2 ml (IQR: 27.5-52.4); = 0.013], as was the increase in midline shift up to day 7 [MIS: -3.75 mM (IQR: -4.25 to -2) vs. control: 1 mM (IQR: 0-2); < 0.001]. No group differences were observed in PHE volume on day 7 [MIS: 42.4 ml (IQR: 25.0-72.3) vs. control: 31.0 ml (IQR: 18.8-53.8); = 0.274] or mRS at discharge [MIS: 5 (IQR: 4-5) and 5 (IQR: 4-5); = 0.949]. No hematoma expansion was observed. The catheter had to be replaced in 1 patient (6%). Bedside catheter-based hematoma evacuation followed by local thrombolysis with urokinase appears to be feasible and safe in cases of large VKA-related ICH. Further studies that assess the functional outcome associated with this technique are warranted. DRKS00007908 (German Clinical Trial Register; www.drks.de).
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http://dx.doi.org/10.3389/fneur.2020.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456824PMC
August 2020

Twenty-Year Time Trends in Long-Term Case-Fatality and Recurrence Rates After Ischemic Stroke Stratified by Etiology.

Stroke 2020 09 19;51(9):2778-2785. Epub 2020 Aug 19.

Interdisciplinary Centre for Health Technology Assessment (HTA) and Public Health, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany (M.W., M.H., C.S., P.L.K.-R.).

Background And Purpose: Data on long-term survival and recurrence after stroke are lacking. We investigated time trends in ischemic stroke case-fatality and recurrence rates over 20-years stratified by etiological subtype according to the Trial of ORG 10172 in Acute Stroke Treatment classification within a population-based stroke register in Germany.

Methods: Data was collected within the Erlangen Stroke Project, a prospective, population-based stroke register covering a source population of 105 164 inhabitants (2010). Case fatality and recurrence rates for 3 months, 1 year, and 5 years were estimated with Kaplan-Meier estimates. Sex-specific time trends for case-fatality and recurrence rates were estimated with Cox regression. We adjusted for age, sex, and year of event and stratified for etiological subtypes. A sensitivity analysis with competing risk analysis for time trends in recurrence were performed.

Results: Between 1996 and 2015, 3346 patients with first ischemic stroke were included; age-standardized incidence per 100 000 was 75.8 in women and 131.6 in men (2015). Overall, 5-year survival probabilities were 50.4% (95% CI, 47.9-53.1) in women and 59.2% (95% CI, 56.4-62.0) in men; 5-year survival was highest in patients with first stroke due to small-artery occlusion (women, 71.8% [95% CI, 67.1-76.9]; men, 75.9% [95% CI, 71.3-80.9]) and lowest in cardioembolic stroke (women, 35.7% [95% CI, 31.0-41.1]; men, 47.8% [95% CI, 42.2-54.3]). Five-year recurrence rates were 20.1% (95% CI, 17.5-22.6) in women and 20.1% (95% CI, 17.5-22.7) in men; 5-year recurrence rate was lowest in women in stroke due to small artery occlusion 16.0% (95% CI, 11.7-20.1) and in men in large-artery atherosclerosis 16.6% (95% CI, 8.7-23.9); highest risk of recurrence was observed in undefined strokes (women, 22.3% [95% CI, 17.8-26.6]; men, 21.4% [95% CI, 16.7-25.9]). Cox regression revealed improvements in case-fatality rates over time with differences in stroke causes. No time trends in recurrence rates were observed.

Conclusions: Long-term survival and recurrence varied substantially by first stroke cause. Survival probabilities improved over the past 2 decades; no major trends in stroke recurrence rates were observed.
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http://dx.doi.org/10.1161/STROKEAHA.120.029972DOI Listing
September 2020

Dressing Apraxia as Initial Manifestation of Creutzfeldt-Jakob Disease.

Tremor Other Hyperkinet Mov (N Y) 2020 07 7;10:14. Epub 2020 Jul 7.

Department of Neurology, University Hospital Erlangen, DE.

Background: Creutzfeldt-Jakob disease (CJD) is a rare prion disease characterized by rapidly progressive dementia.

Case Report: A 76-year-old woman exhibited pronounced signs and symptoms of dressing apraxia for about seven weeks before the disease progressed and probable CJD was diagnosed supported by imaging and CSF findings.

Discussion: Dressing apraxia as the initial manifestation of CJD has been sparsely reported. This remarkably focal syndrome should be considered with view on movement and neuropsychological disorders in early CJD.
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http://dx.doi.org/10.5334/tohm.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394209PMC
July 2020

Letter by Kallmünzer et al Regarding Article, "Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: a Systematic Review and Meta-Analysis".

Stroke 2020 07 16;51(7):e130-e131. Epub 2020 Jun 16.

Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Germany (B.K., S.S.). Department of Neurology, Klinikum Bayreuth GmbH, Bayreuth, Germany.

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http://dx.doi.org/10.1161/STROKEAHA.120.029631DOI Listing
July 2020

Automated ASPECT scoring in acute ischemic stroke: comparison of three software tools.

Neuroradiology 2020 Oct 8;62(10):1231-1238. Epub 2020 May 8.

Department of Neuroradiology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.

Purpose: Various software applications offer support in the diagnosis of acute ischemic stroke (AIS), yet it remains unclear whether the performance of these tools is comparable to each other. Our study aimed to evaluate three fully automated software applications for Alberta Stroke Program Early CT (ASPECT) scoring (Syngo.via Frontier ASPECT Score Prototype V2, Brainomix e-ASPECTS® and RAPID ASPECTS) in AIS patients.

Methods: Retrospectively, 131 patients with large vessel occlusion (LVO) of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy (EVT), were included. Pre-interventional non-enhanced CT (NECT) datasets were assessed in random order using the automated ASPECT software and by three experienced neuroradiologists in consensus. Interclass correlation coefficient (ICC), Bland-Altman, and receiver operating characteristics (ROC) were applied for statistical analysis.

Results: Median ASPECTS of the expert consensus reading was 8 (7-10). Highest correlation was between the expert read and Brainomix (r = 0.871 (0.818, 0.909), p < 0.001). Correlation between expert read and Frontier V2 (r = 0.801 (0.719, 0.859), p < 0.001) and between expert read and RAPID (r = 0.777 (0.568, 0.871), p < 0.001) was high, respectively. There was a high correlation among the software tools (Frontier V2 and Brainomix: r = 0.830 (0.760, 0.880), p < 0.001; Frontier V2 and RAPID: r = 0.847 (0.693, 0.913), p < 0.001; Brainomix and RAPID: r = 0.835 (0.512, 0.923), p < 0.001). An ROC curve analysis revealed comparable accuracy between the applications and expert consensus reading (Brainomix: AUC = 0.759 (0.670-0.848), p < 0.001; Frontier V2: AUC = 0.752 (0.660-0.843), p < 0.001; RAPID: AUC = 0.734 (0.634-0.831), p < 0.001).

Conclusion: Overall, there is a convincing yet developable grade of agreement between current ASPECT software evaluation tools and expert evaluation with regard to ASPECT assessment in AIS.
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http://dx.doi.org/10.1007/s00234-020-02439-3DOI Listing
October 2020

Neck cooling induces blood pressure increase and peripheral vasoconstriction in healthy persons.

Neurol Sci 2020 Sep 26;41(9):2521-2529. Epub 2020 Mar 26.

Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.

Introduction: Noninvasive temperature modulation by localized neck cooling might be desirable in the prehospital phase of acute hypoxic brain injuries. While combined head and neck cooling induces significant discomfort, peripheral vasoconstriction, and blood pressure increase, localized neck cooling more selectively targets blood vessels that supply the brain, spares thermal receptors of the face and skull, and might therefore cause less discomfort cardiovascular side effects compared to head- and neck cooling. The purpose of this study is to assess the effects of noninvasive selective neck cooling on cardiovascular parameters and cerebral blood flow velocity (CBFV).

Methods: Eleven healthy persons (6 women, mean age 42 ± 11 years) underwent 90 min of localized dorsal and frontal neck cooling (EMCOOLS Brain.Pad™) without sedation. Before and after cooling onset, and after every 10 min of cooling, we determined rectal, tympanic, and neck skin temperatures. Before and after cooling onset, after 60- and 90-min cooling, we monitored RR intervals (RRI), systolic, diastolic blood pressures (BPsys, BPdia), laser Doppler skin blood flow (SBF) at the index finger pulp, and CBFV at the proximal middle cerebral artery (MCA). We compared values before and during cooling by analysis of variance for repeated measurements with post hoc analysis (significance: p < 0.05).

Results: Neck skin temperature dropped significantly by 9.2 ± 4.5 °C (minimum after 40 min), while tympanic temperature decreased by only 0.8 ± 0.4 °C (minimum after 50 min), and rectal temperature by only 0.2 ± 0.3 °C (minimum after 60 min of cooling). Index finger SBF decreased (by 83.4 ± 126.0 PU), BPsys and BPdia increased (by 11.2 ± 13.1 mmHg and 8.0 ± 10.1 mmHg), and heart rate slowed significantly while MCA-CBFV remained unchanged during cooling.

Conclusions: While localized neck cooling prominently lowered neck skin temperature, it had little effect on tympanic temperature but significantly increased BP which may have detrimental effects in patients with acute brain injuries.
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http://dx.doi.org/10.1007/s10072-020-04349-xDOI Listing
September 2020

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation.

J Neurol 2020 Jul 23;267(7):2007-2012. Epub 2020 Mar 23.

Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.

Background: Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced doses is common.

Methods: Data from an observational registry including patients admitted with acute cerebral ischemia while taking oral Factor Xa inhibitors for atrial fibrillation between April 2016 and December 2018 were investigated. The dose regimen of the Xa inhibitor was classified as "appropriate", "underdosed" and "overdosed" in conformity with the European Medicines Agency labelling. The effect of underdosing on the functional factor Xa plasma level on admission, the clinical stroke severity and the functional outcome after 3 months were investigated.

Results: 254 patients with cerebral ischemia while on Factor Xa inhibitors were included. The dose regimen of the Factor Xa inhibitor was appropriate in 166 patients (65%), underdosed in 67 patients (26%) and overdosed in 21 patients (8%). Underdosing was associated with female sex, diabetes mellitus and higher CHADS-Vasc scores. Underdosing independently predicted lower anti-Xa plasma levels on admission [median 69.4 ng/ml (IQR 0.0-121.6) vs. 129.2 ng/ml (65.5-207.2); p < 0.001], was associated with higher NIHSS scores on admission [median 5 (IQR 1-10) vs. 3 (1-7); p = 0.041] and worse functional outcome after 3 months (favorable outcome 26.9% vs. 46.9%; p = 0.025).

Conclusion: One in three patients with ischemic stroke during treatment with oral Xa inhibitors used inappropriate dose regimens. Underdosing was associated with lower functional plasma levels, higher clinical stroke severity and worse functional outcome.
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http://dx.doi.org/10.1007/s00415-020-09795-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320957PMC
July 2020