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Book ; Thesis: Is novel always better? - the effects of warfarin and dabigatran anticoagulation in the event of traumatic brain injury

Schäfer, Jan Hendrik

2016

Author's details	vorgelegt von Jan Hendrik Schäfer
Language	English
Size	37 Seiten, Illustrationen, Diagramme
Publishing place	Frankfurt am Main
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Dissertation, Johann Wolfgang Goethe-Universität Frankfurt am Main, 2016
Note	Zusammenfassung in deutscher und englischer Sprache ; Enthält einen Sonderabdruck
HBZ-ID	HT019265136
Database	Catalogue ZB MED Medicine, Health

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Article: Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy.

Schaefer, Jan Hendrik / Lieschke, Franziska / Urban, Hans / Bohmann, Ferdinand O / Gatzke, Florian / Miesbach, Wolfgang

Frontiers in neurology

2024 Volume 15, Page(s) 1361751

Abstract: Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been ... ...

Abstract	Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated Results: Between February and July 2023, 20 blood samples ( Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.
Language	English
Publishing date	2024-02-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2024.1361751
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Article ; Online: Prevalence, recovery and phenotype of dysphagia in patients with ischaemic cerebellar stroke.

Schaefer, Jan Hendrik / Luft, Felix / Seiler, Alexander / Harborth, Elena / Kaffenberger, Sara / Polkowski, Christoph / Foerch, Christian / Lapa, Sriramya

European journal of neurology

2024 , Page(s) e16303

Abstract: Background and purpose: Swallowing is a complex task, moderated by a sophisticated bilateral network including multiple supratentorial regions, the brainstem and the cerebellum. To date, conflicting data exist about whether focal lesions to the ... ...

Abstract	Background and purpose: Swallowing is a complex task, moderated by a sophisticated bilateral network including multiple supratentorial regions, the brainstem and the cerebellum. To date, conflicting data exist about whether focal lesions to the cerebellum are associated with dysphagia. Therefore, the aim of the study was to evaluate dysphagia prevalence, recovery and dysphagia pattern in patients with ischaemic cerebellar stroke. Methods: A retrospective analysis of patients consecutively admitted to an academic stroke centre with ischaemic stroke found only in the cerebellum was performed. The presence of dysphagia was the primary end-point and was assessed by a speech-language pathologist, according to defined criteria. Dysphagia pattern was evaluated by analysing the videos of the flexible endoscopic evaluation of swallowing. Brain imaging was used to identify lesion size and location associated with dysphagia. Results: Between January 2016 and December 2021, 102 patients (35.3% female) with a mean age of 52.8 ± 17.3 years were included. Thirteen (12.7%) patients presented with dysphagia. The most frequently observed flexible endoscopic evaluation of swallowing phenotype was premature spillage (n = 7; 58.3%), whilst significant residues or aspiration did not occur. One patient died (7.7%); the other patients showed improvement of dysphagia and one patient (7.7%) was discharged with dietary restrictions. Conclusions: Although the involvement of the cerebellum in deglutition has become increasingly evident, isolated lesions to the cerebellum are less likely to cause clinically relevant and persisting dysphagia compared to other brain regions. The observed dysphagia pattern shows a lack of coordination and control, resulting in premature spillage or fragmented bolus transfer in some patients.
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.16303
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Article ; Online: Distribution Pattern Analysis of Cortical Brain Infarcts on Diffusion-Weighted Magnetic Resonance Imaging: A Hypothesis-Generating Approach to the Burden of Silent Embolic Stroke.

Schaller-Paule, Martin A / Fritz, Daniel / Schaefer, Jan Hendrik / Hattingen, Elke / Foerch, Christian / Seiler, Alexander

Journal of the American Heart Association

2022 Volume 11, Issue 19, Page(s) e026438

Abstract: Background In patients with covert cerebrovascular disease or proximal source of embolism, embolic silent brain infarction may precede major stroke events. Therefore, characterization of particularly cortical silent brain infarction is essential for ... ...

Abstract	Background In patients with covert cerebrovascular disease or proximal source of embolism, embolic silent brain infarction may precede major stroke events. Therefore, characterization of particularly cortical silent brain infarction is essential for identifying affected patients and commencing adequate secondary prevention. This study aimed to investigate differences in the distribution pattern of cortical ischemic stroke lesions to assess potential predilection sites of cortical silent brain infarction. Methods and Results We prospectively included all consecutive patients with stroke presenting from January 1 to December 31, 2018. Diffusion-weighted imaging lesions were used to generate voxel-based lesion maps and assigned to atlas-based cortical regions of interest in middle cerebral artery territories. Each region-of-interest lesion frequency was related to the respective region-of-interest volume to identify frequently affected and underrepresented cerebral cortex areas. Diffusion-weighted imaging data for voxel-based lesion maps were available in 334 out of 633 patients. Primary analysis revealed that small- (<0.24 cc) and medium-sized (0.24-2640 cc) lesions distributed predominantly along regions associated with sensorimotor or language function. Detailed analysis within middle cerebral artery territories showed an approximated frequency of missed cortical stroke lesions of up to 67% in the right and 69% in the left hemisphere. In particular, the frontal, temporal, and occipital cortices were underrepresented. Larger lesion size and areas associated with higher cortical function led to hospital admission. Conclusions Cortical brain infarcts in hospitalized patients are not dispersed equally but are predominantly located in brain structures associated with motor control and sensory and language function. Matching underrepresented cerebral cortex regions to symptoms not yet associated with stroke warrants further exploration.
MeSH term(s)	Brain Infarction ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/pathology ; Diffusion Magnetic Resonance Imaging ; Embolic Stroke ; Embolism/complications ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Stroke/complications ; Stroke/etiology
Language	English
Publishing date	2022-09-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.122.026438
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Article ; Online: Divergence and Convergence of Sex-Specific Time Trends in Ischemic Stroke: 10-Year Analysis of a State-Wide Registry in Germany.

Schaefer, Jan Hendrik / Bohmann, Ferdinand O / Lieschke, Franziska / Misselwitz, Björn / Foerch, Christian

Journal of the American Heart Association

2022 Volume 11, Issue 20, Page(s) e027130

Abstract: Background The incidence of ischemic stroke was previously expected to rise among countries with an aging population. Lately, several studies from developed countries have reported a decline in certain cohorts. Whether this applies to all sexes, however, ...

Abstract	Background The incidence of ischemic stroke was previously expected to rise among countries with an aging population. Lately, several studies from developed countries have reported a decline in certain cohorts. Whether this applies to all sexes, however, is uncertain, with limited data on the temporal development in incidence, treatment, and recovery. Methods and Results We analyzed a prospective stroke inpatient quality-assurance registry of the federal state of Hesse, Germany. Recruitment of all patients with a final diagnosis of ischemic stroke at hospital discharge (
MeSH term(s)	Humans ; Male ; Female ; Aged ; Atrial Fibrillation/epidemiology ; Ischemic Stroke/diagnosis ; Ischemic Stroke/epidemiology ; Ischemic Stroke/therapy ; Stroke/diagnosis ; Stroke/epidemiology ; Stroke/etiology ; Germany/epidemiology ; Registries ; Incidence ; Risk Factors ; Brain Ischemia/diagnosis ; Brain Ischemia/epidemiology ; Brain Ischemia/therapy
Language	English
Publishing date	2022-10-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.122.027130
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Article ; Online: Differences in characteristics between patients from Egypt and Germany presenting with lacunar stroke.

Maged, Mohamed / Aref, Hany / Nahas, Nevine El / Hamid, Eman / Fathy, Mai / Roushdy, Tamer / Schaefer, Jan Hendrik / Foerch, Christian / Spitzer, Daniel

Scientific reports

2023 Volume 13, Issue 1, Page(s) 22925

Abstract: Despite the enormous health burden of lacunar stroke, data from low- and middle-income countries on lacunar stroke characteristics and its comparison with that of high-income countries are scarce. Thus, we aimed to investigate and compare the variable ... ...

Abstract	Despite the enormous health burden of lacunar stroke, data from low- and middle-income countries on lacunar stroke characteristics and its comparison with that of high-income countries are scarce. Thus, we aimed to investigate and compare the variable characteristics and vascular status in patients from Egypt and Germany suffering lacunar stroke. Two cohorts of lacunar stroke patients from Ain Shams University Hospital, Egypt and Goethe University Hospital Frankfurt, Germany were retrospectively collected between January 2019 and December 2020 and analyzed for demographics, risk factors, mode of presentation, neuroimaging features, treatment protocols and outcomes. MRI showed a different distribution pattern of lacunar strokes between cohorts, detecting posterior circulation lacunar infarctions preponderantly in patients from Egypt and anterior circulation lacunar infarctions preponderantly in patients from Germany. Complementary MR/CT angiography revealed a significantly higher proportion of intracranial and combined intracranial and extracranial arterial stenosis in patients from Egypt than in patients from Germany, suggesting differences in pathological processes. Younger age, higher NIHSS on admission, and posterior circulation lacunar infarction were predictors of Egyptian origin, whereas hypertension was a predictor of German origin. Our results support the idea of clinical and neuroimaging phenotype variations in lacunar stroke, including different sources of lacunar stroke in patients of different populations and geographical regions. This implies that guidelines for management of lacunar stroke might be tailored to these differences accordingly.
MeSH term(s)	Humans ; Stroke, Lacunar/diagnostic imaging ; Stroke, Lacunar/epidemiology ; Egypt/epidemiology ; Retrospective Studies ; Hypertension ; Risk Factors ; Stroke/diagnostic imaging ; Stroke/epidemiology
Language	English
Publishing date	2023-12-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50269-z
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Article ; Online: Large-vessel-occlusion in patients with previous ischemic stroke: an analysis of adherence to secondary preventive medication for different etiologies.

Kohlhase, Konstantin / Schäfer, Jan Hendrik / Tako, Lisa Marie / Willems, Laurent M / Hattingen, Elke / Bohmann, Ferdinand O / Grefkes, Christian / Rosenow, Felix / Strzelczyk, Adam

Neurological research and practice

2023 Volume 5, Issue 1, Page(s) 22

Abstract: Background: Large vessel occlusion (LVO) is a severe condition that carries a high risk of morbidity and mortality, underscoring the importance of effective prevention strategies. This retrospective study aimed to analyze the intake of preventive ... ...

Abstract	Background: Large vessel occlusion (LVO) is a severe condition that carries a high risk of morbidity and mortality, underscoring the importance of effective prevention strategies. This retrospective study aimed to analyze the intake of preventive medication at the time of hospitalization in a cohort of recurrent stroke patients presenting with acute LVO. Methods: The study assessed the intake of either platelet aggregation inhibitors (PAI), oral anticoagulants (OAC) or statins at admission in patients with recurrent stroke and correlated it with the final classification of LVO. The frequency of those secondary preventive medication in recurrent stroke patients was defined as primary endpoint. The Modified Rankin Scale (mRS) at discharge was used as a functional outcome and defined as a secondary outcome measure. Results: This study included 866 patients who were treated for LVO between 2016 and 2020, of whom 160 (18.5%) had a recurrent ischemic stroke. OAC (25.6% vs. 14.1%, p < 0.01), PAI (50.0% vs. 26.0%, p < 0.01), or statin therapy (50.6% vs. 20.8%, p < 0.01) at admission were significantly more frequent in recurrent stroke patients compared to patients with a first-time stroke. Concerning LVO etiology in recurrent stroke patients, OAC at admission was taken in 46.8% of cardioembolic LVO, whereas PAI and statin at admission in macroangiopathic LVO were administered to 40.0%; neither PAI nor OAC was taken in 26.0%, 28.3%, and 31.6% of cardioembolic, macroangiopathic, or cryptogenic strokes, respectively. Regardless of stroke recurrence or etiology, there was an increase in mRS at discharge. Conclusions: Despite high-quality healthcare, this study suggested a significant proportion of patients with recurrent stroke who were either non-adherent or insufficiently adherent to secondary preventive medication. Given the disability associated with LVO, improving patients' medication adherence and identifying unknown stroke causes are crucial for effective prevention strategies.
Language	English
Publishing date	2023-05-25
Publishing country	England
Document type	Journal Article
ISSN	2524-3489
ISSN (online)	2524-3489
DOI	10.1186/s42466-023-00247-7
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Article ; Online: Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury.

Schaller-Paule, Martin A / Maiworm, Michelle / Schäfer, Jan Hendrik / Friedauer, Lucie / Hattingen, Elke / Wenger, Katharina Johanna / Weber, Frank / Jakob, Jasmin / Steffen, Falk / Bittner, Stefan / Yalachkov, Yavor / Foerch, Christian

Journal of neurology

2024

Abstract: Background: Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS ... ...

Abstract	Background: Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)). Methods: We recruited 77 patients with relapsing-remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse. Results: After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (p Conclusions: Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.
Language	English
Publishing date	2024-03-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-024-12299-z
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Article ; Online: Evaluating the utility of serum NfL, GFAP, UCHL1 and tTAU as estimates of CSF levels and diagnostic instrument in neuroinflammation and multiple sclerosis.

Koerbel, Kimberly / Maiworm, Michelle / Schaller-Paule, Martin / Schäfer, Jan Hendrik / Jakob, Jasmin / Friedauer, Lucie / Steffen, Falk / Bittner, Stefan / Foerch, Christian / Yalachkov, Yavor

Multiple sclerosis and related disorders

2024 Volume 87, Page(s) 105644

Abstract: Background: This study aimed to evaluate the utility of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1) and total tau (tTAU) serum concentrations as approximation for cerebrospinal fluid ...

Abstract	Background: This study aimed to evaluate the utility of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1) and total tau (tTAU) serum concentrations as approximation for cerebrospinal fluid (CSF) concentrations of the respective biomarkers in the context of neuroinflammation and multiple sclerosis (MS). Methods: NfL, GFAP, UCHL1 and tTAU concentrations in serum and CSF were measured in 183 patients (122 with neuroinflammatory disease and 61 neurological or somatoform disease controls) using the single molecule array HD-1 analyzer (Quanterix, Boston, MA). Spearman's rank correlations were computed between serum and CSF concentrations. In a second step, the effects of age, BMI, gadolinium-enhancing lesions in MRI, integrity of the blood-brain barrier (BBB) and presence of acute relapse were accounted for by computing partial correlations. The analyses were repeated for a subsample consisting of MS phenotype patients only (n = 118). EDSS, MS disease activity and acute relapse were considered as additional covariates. Receiver operating characteristic (ROC) analysis was performed for each serum/CSF biomarker concentration to assess how well the particular biomarker concentration differentiates MS patients from somatoform disease controls. Correlations between serum and CSF levels as well as area under the curve (AUC) values were compared for the different biomarkers using z-test statistics. Results: Serum concentrations correlated positively with CSF levels for NfL (r = 0.705, p < 0.01) as well as for GFAP (r = 0.259, p < 0.01). Correlation coefficients were significantly higher for NfL than for GFAP (z = 5.492, p < 0.01). We found no significant serum-CSF correlations for UCHL1 or tTAU. After adjusting for covariates, the results remained unchanged. In the analysis focusing only on MS patients, the results were replicated. ROC analysis demonstrated similarly acceptable performance of serum and CSF NfL values in differentiating MS phenotype patients from somatoform disease controls. AUC values were significantly higher for serum and CSF NfL compared to other biomarkers. Conclusion: NfL and GFAP but not UCHL1 or tTAU serum concentrations are associated with CSF levels of the respective biomarker. NfL exhibits more robust correlations between its serum and CSF concentrations as compared to GFAP independently from BBB integrity, clinical and radiological covariates. Both serum and CSF NfL values differentiate between MS and controls.
Language	English
Publishing date	2024-04-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2024.105644
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Article: Measurement of D-dimer in cerebrospinal fluid using a luminescent oxygen channeling immunoassay.

Kohlhase, Konstantin / Schaefer, Jan Hendrik / Miesbach, Wolfgang / Hintereder, Gudrun / Kirchmayr, Konstantin / Zwinge, Birga / Yalachkov, Yavor / Foerch, Christian / Schaller-Paule, Martin A

Frontiers in neurology

2022 Volume 13, Page(s) 951802

Abstract: Background: Measurement of D-dimer in cerebrospinal fluid (CSF) allows insight into coagulation system activation in the central nervous system and can be utilized to monitor intracranial hemorrhage as well as acute phase processes beyond hemostasis in ... ...

Abstract	Background: Measurement of D-dimer in cerebrospinal fluid (CSF) allows insight into coagulation system activation in the central nervous system and can be utilized to monitor intracranial hemorrhage as well as acute phase processes beyond hemostasis in inflammatory and neoplastic diseases. So far, the measurability of D-dimer in low and very low concentrations in CSF was limited in conventional immunoassays. Novel high-sensitivity chemiluminescent immunoassays such as the luminescent oxygen channeling immunoassay (LOCI Methods: INNOVANCE LOCI hs D-dimer reagent cartridge was used for the measurement of D-dimer in CSF of patients with different neurological diseases. For the evaluation of linearity, dilution series were performed in a pooled CSF sample with the determination of intra-assay precision (CV, coefficient of variation) in 3 individual samples with 20 replicates. Furthermore, D-dimer concentrations measured by LOCI Results: Linear regression analysis of the LOCI Conclusion: D-dimer in CSF of patients with neurological disease can be reliably measured by the LOCI
Language	English
Publishing date	2022-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.951802
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