TCCD Fusion Imaging to Estimate Intracranial Pressure and Tissue Displacement with Large Hemispheric Infarction.

BACKGROUND: Despite breakthroughs in stroke treatment, some patients still experience large infarctions of the cerebral hemispheres resulting in mass effect and tissue displacement. The evolution of mass effect is currently monitored using serial computed tomography (CT) imaging. However, there are patients who are ineligible for transport, and there are limited options for bedside monitoring of unilateral tissue shift. METHODS: We used fusion imaging for overlaying transcranial color duplex with CT angiography. This method allows overlay of live ultrasound on top of CT or magnetic resonance imaging scans. Patients with large hemispheric infarctions were eligible to participate. Position data from the source files were used and matched with live imaging and correlation to magnetic probes on the patient's forehead and ultrasound probe. Shift of cerebral parenchyma, displacement of the anterior cerebral arteries, basilary artery and third ventricle were analyzed, as well as pressure on the midbrain, and the displacement of the basilar artery on the head were analyzed. Patients received multiple examinations in addition to standard care of treatment with CT imaging. RESULTS: The sensitivity for diagnosing a shift of 3 mm with fusion imaging was 100%, with a specificity of 95%. No side effects or interactions with critical care equipment were recorded. CONCLUSIONS: Fusion imaging is an easy method to access and acquire measurements for critical care patients and follow-up of tissue and vascular displacement after stroke. Fusion imaging may be a decisive support for indicating hemicraniectomy.

Detection of microemboli in patients with acute ischaemic stroke and atrial fibrillation suggests poor functional outcome.

INTRODUCTION: We investigated the burden of microembolic signals (MES) in patients with acute ischaemic stroke (AIS) and atrial fibrillation (AF), assessing their impact on functional outcomes. PATIENTS AND METHODS: This multicentre international prospective cohort study involved patients with AIS and either a known or newly diagnosed anticoagulant-naïve AF. All centres utilised the same transcranial Doppler machine for 1-h monitoring with bilateral 2 MHz probes within 24 h of symptom onset. Recordings underwent MES analysis by a blinded central reader. The primary objectives were to ascertain the MES proportion and its association with functional outcomes assessed by the modified Rankin scale (mRS) score at 90 days. RESULTS: Between September 2019 and May 2021, we enrolled 61 patients, with a median age of 78 years (interquartile range 73-83) and a median stroke severity score of 11 (interquartile range 4-18). MES were observed in 14 patients (23%), predominantly unilateral (12/14, 86%), with a median rate of 6 counts/hour (interquartile range 4-18). MES occurrence was higher post-thrombectomy and among those with elevated brain natriuretic peptide levels (p < 0.05). A worse mRS score of 3-6 was more frequent in patients with MES, occurring in 11/14 (79%), compared to those without MES, 20/47 (43%), with an adjusted odds ratio of 5.04 (95% CI, 1.15-39.4), p = 0.04. CONCLUSIONS: Nearly a quarter of patients with AIS and AF exhibited silent microembolization after the index event. Detecting MES within 24 h post-stroke (using transcranial Doppler) could signify a marker of poor functional outcomes. Subsequent trials will assess if very early antithrombotic treatment might enhance outcomes in this highly selective group of cardioembolic stroke patients. (Clinicaltrials.gov ID: NCT06018090).

[Specialization of Acute Stroke Care in Germany: Structural Changes During 2006-2017]. / Spezialisierung der Schlaganfallversorgung in Deutschland: Strukturveränderungen im Zeitraum von 2006­2017.

HINTERGRUND: Um die Schlaganfallversorgung zu optimieren, wurden in Deutschland in den letzten Jahren verschiedene qualitätsfördernde Maßnahmen (qfM) in regional unterschiedlichem Maß eingeführt. Ob sich diese Maßnahmen über die Jahre flächendeckend etabliert haben, ist unklar. METHODE: Für die strukturbezogenen Analysen der Schlaganfallversorgung in Deutschland wurden alle relevanten dokumentierten Schlaganfälle (ICD-10) aus den Qualitätsberichten (QB) deutscher Krankenhäuser und eine repräsentative Stichprobe von Krankenversicherungsdaten (AOK) im Zeitraum von 2006 (QB)/2007 (AOK) bis 2017 verwendet. Diese Informationen wurden u. a. durch Angaben zu zertifizierten Stroke Units der Deutschen Schlaganfall-Gesellschaft (DSG) und Daten zur Führung von regionalen Schlaganfall-Registern der Arbeitsgemeinschaft Deutschsprachiger Schlaganfall-Register (ADSR) ergänzt. Zur Verfolgung der Veränderungen des Versor-gungsgeschehens im deutschen Bundesgebiet wurden die Daten mit geografischen Daten (Bundesamt für Kartographie und Geodäsie) verknüpft. Es erfolgten univariate Analysen der Daten und eine Trend-Analyse der verschiedenen qfM im Jahresverlauf (Konkordanzkoeffizient nach Kendall). ERGEBNISSE: Die QB Analysen zeigten einen Anstieg kodierter Schlaganfälle in Krankenhäusern mit qfM um 14-20%. In 2006 wurden 80% der Schlaganfälle (QB) in einem Krankenhaus mit min. einer qfM kodiert, in 2017 95%. Diese Entwicklungen spiegelten sich auch in den AOK-Routinedaten wider, wobei in 2007 89% und in 2017 97% der Patient:innen unter mindestens einer qfM behandelt wurden. Dabei waren in 2007 bei 55% der behandelnden Krankenhäuser qfM vorhanden, in 2017 bei 72%. SCHLUSSFOLGERUNG: Patient:innen werden inzwischen signifikant häufiger in Krankenhäusern mit Spezialisierung auf die Schlaganfallversorgung behandelt. Auch die verschiedenen qfM haben sich im Laufe der Jahre im gesamten Bundesgebet verbreitet, jedoch existieren noch Versorgungslücken, die geschlossen werden sollten, damit in Zukunft alle Patient:innen qualitativ hochwertig behandelt werden können. BACKGROUND: In order to optimize stroke care, various quality-enhancing measures (qfM) have been introduced in Germany in recent years to varying degrees across regions, with the aim of achieving the best possible quality of care. It is unclear whether these measures have become established nationwide over the years. METHOD: For the structural analyses of stroke care in Germany, all relevant documented strokes (ICD-10) from the quality reports (QB) of German hospitals and a representative sample of health insurance data (AOK) for the period from 2006 (QB)/2007 (AOK) to 2017 were used. This information was supplemented by data on certified stroke units from the German Stroke Society (DSG) and data on the maintenance of regional stroke registries from the Working Group of German-Speaking Stroke Registers (ADSR), among others. To track changes in patterns of care in Germany, the data were linked with geographic data (Federal Agency for Cartography and Geodesy). Univariate analyses of the data and a trend analysis of the different qfM over the year (Kendall concordance coefficient) were performed. RESULTS: The analyses (QB) showed an increase in coded strokes in hospitals with qfM between 14-20%. In 2006, 80% of strokes (QB) were coded in hospitals with at least one qfM and 95% in 2017. Comparing years, AOK data showed similar trends: in 2007, 89% of patients were treated in hospitals with at least one qfM and 97% in 2017. In 2007, 55% of treating hospitals had qfM and 72% in 2017. CONCLUSION: Meanwhile, patients are more often treated in hospitals that specialise in stroke care. In addition, the various qfM have spread across the nation over the years, but there are still gaps in care that should be addressed to ensure quality care for all patients in the future.

Long-term outcomes of stroke unit care in older stroke patients: a retrospective cohort study.

BACKGROUND: older patients are less frequently treated in stroke units (SUs). Clinicians do not seem convinced that older patients benefit from specialised treatment in SU similarly to younger patients. OBJECTIVE: our study aimed to compare older patients' long-term outcomes with and without SU treatment. METHODS: this study used routinely collected health data of 232,447 patients admitted to hospitals in Germany between 2007 and 2017 who were diagnosed with ischaemic stroke (ICD 10 I63). The sample included 29,885 patients aged ≥90 years. The outcomes analysed were 10-, 30- and 90-day, and 1-, 3- and 5-year mortality and the combinations of death or recurrence, inpatient treatment and increase in long-term care needs. Bivariate chi-square tests and multivariable logistic regression analyses were used, adjusting for the covariates age, sex, co-morbidity, long-term care needs before stroke and socioeconomic status of the patients' region of origin. RESULTS: between 2007 and 2017, 57.1% of patients aged <90 years and 49.6% of those aged ≥90 years were treated in a SU. The 1-year mortality rate of ≥90-year-olds was 56.9 and 61.9% with and without SU treatment, respectively. The multivariable-adjusted risk of death in ≥90-year-olds with SU treatment was odds ratio (OR) = 0.67 (95% confidence interval [CI] = 0.62-0.73) 10 days after the initial event and OR = 0.76 (95% CI = 0.71-0.82) 3 years after stroke. CONCLUSIONS: even very old patients with stroke benefit from SU treatment in the short and long term. Therefore, SU treatment should be the norm even in older patients.

Point-of-Care Ultrasound in Neurology - Report of the EAN SPN/ESNCH/ERcNsono Neuro-POCUS Working Group.

In the last decade, ultrasound examination in neurology has been undergoing a significant expansion of its modalities. In parallel, there is an increasing demand for rapid and high-quality diagnostics in various acute diseases in the prehospital setting, the emergency room, intensive care unit, and during surgical or interventional procedures. Due to the growing need for rapid answers to clinical questions, there is particular demand for diagnostic ultrasound imaging. The Neuro-POCUS working group, a joint project by the European Academy of Neurology Scientific Panel Neurosonology, the European Society of Neurosonology and Cerebral Hemodynamics, and the European Reference Centers in Neurosonology (EAN SPN/ESNCH/ERcNsono Neuro-POCUS working group), was given the task of creating a concept for point-of-care ultrasound in neurology called "Neuro-POCUS". We introduce here a new ultrasound examination concept called point-of-care ultrasound in neurology (Neuro-POCUS) designed to streamline conclusive imaging outside of the ultrasound center, directly at the bedside. The aim of this study is to encourage neurologists to add quick and disease-oriented Neuro-POCUS to accompany the patient in the critical phase as an adjunct not a substitution for computed tomography, magnetic resonance imaging, or standard comprehensive neurosonology examination. Another goal is to avoid unwanted complications during imaging-free periods, ultimately resulting in advantages for the patient.

Autoantibodies from patients with complex regional pain syndrome induce pro-inflammatory effects and functional disturbances on endothelial cells in vitro.

ABSTRACT: Complex regional pain syndrome (CRPS) is an inadequate local response after a limb trauma, which leads to severe pain and autonomic and trophic changes of the affected limb. Autoantibodies directed against human ß2 adrenergic and muscarinic M2 receptors (hß2AR and hM2R) have been described in CRPS patients previously. We analyzed sera from CRPS patients for autoantibodies against hß2AR, hM2R, and endothelial cells and investigated the functional effects of purified IgG, derived from 13 patients with CRPS, on endothelial cells. Eleven healthy controls, 7 radial fracture patients without CRPS, and 10 patients with peripheral arterial vascular disease served as control subjects. The CRPS-IgG, but not control IgG, bound to the surface of endothelial cells ( P < 0.001) and to hß2AR and hM2R ( P < 0.05), the latter being reversed by adding ß2AR and M2R antagonists. The CRPS-IgG led to an increased cytotoxicity and a reduced proliferation rate of endothelial cells, and by adding specific antagonists, the effect was neutralized. Regarding second messenger pathways, CRPS-IgG induced ERK1/2, p38, and STAT1 phosphorylation, whereas AKT phosphorylation was decreased at the protein level. In addition, increased expression of adhesion molecules (ICAM-1 and VCAM-1) on the mRNA level was induced by CRPS-IgG, thus inducing a pro-inflammatory condition of the endothelial cells. Our results show that patients with CRPS not only develop autoantibodies against hß2AR and hM2R, but these antibodies also interfere with endothelial cells, inducing functional effects on these in vitro, and thus might contribute to the pathophysiology of CRPS.

Neuromuscular sonography detects changes in muscle echotexture and nerve diameter in ICU patients within 24 h.

PURPOSE: During an ICU stay, changes in muscles and nerves occur that is accessible via neuromuscular sonography. METHODS: 17 patients recruited from the neurological and neurosurgical ICU (six women; 66 ± 3 years) and 7 healthy controls (three women, 75 ± 3 years) were included. Muscle sonography (rectus abdominis, biceps, rectus femoris and tibialis anterior muscles) using gray-scale values (GSVs), and nerve ultrasound (peroneal, tibial and sural nerves) analyzing the cross-sectional area (CSA) were performed on days 1 (t1), 3 (t2), 5 (t3), 8 (t4), and 16 (t5) after admission. RESULTS: Time course analysis revealed that GSVs were significantly higher within the patient group for all of the investigated muscles (rectus abdominis: F = 7.536; p = 0.011; biceps: F = 14.761; p = 0.001; rectus femoris: F = 9.455; p = 0.005; tibialis anterior: F = 7.282; p = 0.012). The higher GSVs were already visible at t1 or, at the latest, at t2 (tibialis anterior muscles). CSA was enlarged in all of the investigated nerves in the patient group (peroneal nerve: F = 7.129; p = 0.014; tibial nerve: F = 28.976, p < 0.001; sural nerve: F = 13.051; p = 0.001). The changes were visible very early (tibial nerve: t1; peroneal nerve: t2). The CSA of the motor nerves showed an association with the ventilation time and days within the ICU (t1 through t4; p < 0.05). DISCUSSION: We detected very early changes in the muscles and nerves of ICU-patients. Nerve CSA might be a useful parameter to identify patients who are at risk for difficult weaning. Therefore our observations might be severity signs of neuromuscular suffering for the most severe patients.

Quality Assurance Measures and Mortality After Stroke.

BACKGROUND: Quality assurance for acute in-hospital care in Germany is based on compulsory comparisons between institutions, so-called external quality assurance (EQA). The effectiveness of EQA has not yet been adequately studied. The purpose of the QUASCH project, which is supported by the Innovation Fund of the Federal Joint Committee, is to investigate the association between EQA and health care outcomes, specifically with respect to stroke. METHODS: The analyses were based on data from 379 825 patients insured by the AOK health insurance fund who were acutely admitted to a hospital because of stroke over the period 2007-2017. Data on 47 659 patients were derived from EQA documentation in the state of Hesse, in which stroke EQA had already been introduced in 2003; data on the remaining 332 166 patients were from other federal states, where 117 734 of these patients had been treated under EQA conditions. The association of EQA with mortality over the period of observation was analyzed by multivariate Cox regression, with the following covariates: age, sex, comorbidities, time period of occurrence, nursing care level, type of stroke, socio-economic deprivation in the region of origin, and treatment in a stroke unit. RESULTS: Compared to treatment without EQA, mortality risk under EQA in the state of Hesse was significantly lower (hazard ratio [HR]: 0.93; 95% confidence interval: [0.92; 0.95]). The reduction in mortality risk with EQA was somewhat lower in the other federal states (HR: 0.96 [0.95; 0.97]). Treatment in a stroke unit was associated with a mortality risk that was lower still (HR: 0.86 [0.85; 0.87]). Mortality risk rose with age, comorbidities, and need for nursing care; it was lower in women and in persons whose stroke occurred in a later period. CONCLUSION: Quality assurance measures are associated with lower mortality risk after stroke. The concentration of care in specially qualified institutions is associated with stronger effects than EQA alone.

Microbubble-mediated sonothrombolysis with BR38 of a venous full blood thrombus in a rat embolic stroke model.

BACKGROUND: Early recanalization of an occluded vessel is associated with a better clinical outcome in acute ischemic stroke. Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only available in a minority of patients and often fails to reopen the occluded vessel. Mechanical recanalization is more effective in this matter but only available for selected patients when a thrombectomy centre can be reached. Therefore, sonothrombolysis might represent an alternative or complementary approach. Here, we tested microbubble-mediated sonothrombolysis (mmSTL) in a thromboembolic stroke model for middle cerebral artery occlusion (MCAO) in rats. METHODS: Sixty-seven male Wistar rats underwent MCAO using an autologous full blood thrombus and were randomly assigned to four groups receiving rt-PA, mmSTL, a combination of both, or a placebo. Diagnostic workup included neurological examination, assessment of infarct size, and presence of intracerebral haemorrhage by magnetic resonance imaging (MRI) and presence of microbleedings in histological staining. RESULTS: Neurological examination revealed no differences between the treatment groups. In all treatment groups, there was a reduction in infarct size 24 hours after MCAO as compared to the placebo (P≤0.05), but there were no differences between the active treatment groups (P>0.05) (placebo 0.75±0.10 cm3; mmSTL 0.43±0.07 cm3; rt-PA 0.4±0.07 cm3; mmSTL + rt-PA 0.27±0.08 cm3). Histological staining displayed intracerebral microbleedings in all animals. The frequency of gross bleeding detected by MRI did not differ between the groups (placebo 3; mmSTL 4; rt-PA 2; mmSTL + rt-PA 2; P>0.05) and was not associated with worse performance in clinical testing (P>0.05). There were no statistical differences in the mortality between the groups (P>0.05). CONCLUSIONS: Our study showed the efficacy and safety of mmSTL with or without rt-PA in an embolic rat stroke model using a continuous full blood thrombus. Sonothrombolysis might be useful for patients who need to be transported to a thrombectomy centre or for those with distal vessel occlusion.

Quality assurance data for regional drip-and-ship strategies- gearing up the transfer process.

BACKGROUND: Stroke patients with large vessel occlusion (LVO) require endovascular therapy (EVT) provided by comprehensive stroke centers (CSC). One strategy to achieve fast stroke symptom 'onset to treatment' times (OTT) is the preclinical selection of patients with severe stroke for direct transport to CSC. Another is the optimization of interhospital transfer workflow. Our aim was to investigate the dynamics of the OTT of 'drip-and-ship' patients as well as the current 'door-in-door-out' time (DIDO) and its determinants at representative regional German stroke units. METHODS: We determined the numbers of all EVT treatments, 'drip-and-ship' and 'direct-to-center' patients and their median OTT from the mandatory quality assurance registry of the federal state of Hesse, Germany (2012-2019). Additionally, we captured process time stamps from primary stroke centers (PSC) in a consecutive registry of patients referred for EVT in our regional stroke network over a 3 months period. RESULTS: Along with an increase of the EVT rate, the proportion of drip-and-ship patients grew steadily from 19.4% in 2012 to 31.3% in 2019. The time discrepancy for the median OTT between 'drip-and-ship' and 'direct-to-center' patients continuously declined from 173 to 74 min. The largest share of the DIDO (median 92, IQR 69-110) is spent with the organization of EVT and consecutive patient transfer. CONCLUSIONS: 'Drip-and-ship' patients are an important and growing proportion of stroke patients undergoing EVT. The discrepancy in OTT for EVT between 'drip-and-ship' and 'direct-to-center' patients has been reduced considerably. Further optimization of the DIDO primarily aiming at the processes after the detection of LVO is urgently needed to improve stroke patient care.

Outpatient care in acute and prehospital emergency medicine by emergency medical and patient transport service over a 10-year period: a retrospective study based on dispatch data from a German emergency medical dispatch centre (OFF-RESCUE).

BACKGROUND: The number of operations by the German emergency medical service almost doubled between 1994 and 2016. The associated expenses increased by 380% in a similar period. Operations with treatment on-site, which retrospectively proved to be misallocated (OFF-Missions), have a substantial proportion of the assignment of the emergency medical service (EMS). Besides OFF-Missions, operations with patient transport play a dominant role (named as ON-Missions). The aim of this study is to work out the medical and economic relevance of both operation types. METHODS: This analysis examined N = 819,780 missions of the EMS and patient transport service (PTS) in the catchment area of the emergency medical dispatch centre (EMDC) Bad Kreuznach over the period from 01/01/2007 to 12/31/2016 in terms of triage and disposition, urban-rural distribution, duration of operations and economic relevance (p < .01). RESULTS: 53.4% of ON-Missions are triaged with the indication non-life-threatening patient transport; however, 63.7% are processed by the devices of the EMS. Within the OFF-Mission cohort, 78.2 and 85.8% are triaged or dispatched for the EMS. 74% of all ON-Missions are located in urban areas, 26% in rural areas; 81.3% of rural operations are performed by the EMS. 66% of OFF-Missions are in cities. 93.2% of the remaining 34% of operations in rural locations are also performed by the EMS. The odds for both ON- and OFF-Missions in rural areas are significantly higher than for PTS (ORON 3.6, 95% CI 3.21-3.30; OROFF 3.18, 95% CI 3.04-3.32). OFF-Missions last 47.2 min (SD 42.3; CI 46.9-47.4), while ON-Missions are processed after 79.7 min on average (SD 47.6; CI 79.6-79.9). ON-Missions generated a turnover of more than € 114 million, while OFF-Missions made a loss of almost € 13 million. CONCLUSIONS: This study particularly highlights the increasing utilization of emergency devices; especially in OFF-Missions, the resources of the EMS have a higher number of operations than PTS. OFF-Missions cause immensely high costs due to misallocations from an economic point of view. Appropriate patient management appears necessary from both medical and economic perspective, which requires multiple solution approaches.

Validation of the German Version of Functional Oral Intake Scale (FOIS-G) for Flexible Endoscopic Evaluation of Swallowing (FEES).

The Functional Oral Intake Scale (FOIS) is the most frequently used scale for the evaluation of functional oral intake by dysphagia patients. FOIS was validated using data from Videofluoroscopic Swallowing Study (VFSS). Until now, a validated German version of FOIS for Flexible Endoscopic Evaluation of Swallowing (FEES) is lacking. The aim of this study was a cross-cultural validation of the German version of FOIS (FOIS-G) for FEES. The translation of the original FOIS was carried out according to the Translation, Review, Adjudication, Pretesting, Documentation (TRAPD) translation methodology. For the validation process, six experienced language therapists (SLT) retrospectively analyzed charts of 93 stroke patients. Inclusion criteria were comprised of stroke, clinical examination by an SLT within 24 h of admission, and FEES within 72 h of admission. The validity was calculated by comparison with Modified Rankin Scale (MRS), Barthel Index (BI), the Penetration-Aspiration-Scale (PAS), and a water swallow test. Spearman rank correlation of all paired raters ranged from rs = 0.96 to rs = 0.99, and percentage agreement ranged from 81 to 94%. The overall agreement between all raters was calculated by Fleiss kappa (0.83) (s.e. 0.02). There is a significant correlation between the BI and the MRS with the FOIS-G (rs = 0.301, p = 0.003 for BI; rs = - 0.366, p < 0.001 for MRS), between the PAS and the FOIS-G (rs = - 0.758, p < 0.001), as well as between the 70 ml-water-test and the FOIS-G (rs = 0.470, p < 0.001). FOIS-G is a valid instrument for the evaluation of the functional oral intake of food and liquids in dysphagia patients.

Flexible endoscopic evaluation of swallowing (FEES) to determine neurological intensive care patients' oral diet.

PURPOSE: Dysphagia is common in critically ill neurological patients and is associated with a high mortality and morbidity. Data on the usefulness of flexible endoscopic examination of swallowing (FEES) in neurological intensive care unit (ICU) patients are lacking, raising the need for evaluation. METHOD: FEES was performed in neurological intensive care patients suspected of dysphagia. We correlated findings with baseline data, disability status, pneumonia and duration of hospitalisation, as well as a need for mechanical ventilation or tracheotomy. RESULT: This analysis consisted of 125 patients with suspected dysphagia. Most of the patients (81; 64,8%) suffered from acute stroke. Dysphagia was diagnosed using FEES in 90 patients (72%). FEES results led to dietary modifications in 80 patients (64%). The outcome at discharge was worse in dysphagic stroke patients diagnosed by FEES as compared to non-dysphagic stroke patients (p = 0.009). Patients without oral diet had higher need for intubation (p = 0.007), tracheotomy (p = 0.032) and higher mortality (p < 0.001) in comparison to patients with at least small amounts of oral intake. CONCLUSION: As the clinical assessment of the patients often classified the dysphagia incorrectly, the broad use of FEES in ICU patients might help to adequately adjust patients' oral diet. This knowledge might contribute to lower mortality and morbidity.

BAFF serum and CSF levels in patients with multiple sclerosis and infectious nervous system diseases.

PURPOSE: Multiple sclerosis (MS) is the most common immune-mediated CNS disease, characterised by demyelination and progressive neurological disability. The B-cell activating factor BAFF has been described as one important factor in the pathophysiology of different autoimmune diseases. METHODS: We measured BAFF levels in the serum and cerebrospinal fluid (CSF) in 50 consecutive patients with MS and 35 patients with infectious CNS disease (ID). 52 patients with other, non-inflammatory disorders (OND), served as controls. RESULTS: BAFF-serum levels in ID patients were higher than in patients diagnosed with MS (ID 0.55 ± 0.24 ng/ml, MS 0.43 ± 0.14 ng/ml, OND 0.45 ± 0.24 ng/ml; p = 0.09). Interestingly, MS patients had lower BAFF CSF levels compared to the controls and ID patients, and the CSF levels in the latter were elevated compared to those of the controls (MS 0.17 ± 0.11 ng/ml, OND 0.25 ± 0.14 ng/ml, ID 0.97 ± 0.78 ng/ml; p < 0.001). CONCLUSIONS: The ID patients' having higher absolute BAFF levels in the CSF than in the serum indicates that the increased BAFF CSF levels were caused by intrathecal synthesis rather than passive transfer via a disturbed blood-brain-barrier. The significantly decreased BAFF CSF levels in MS patients were a surprising result of our study. Although it has been reported that astrocytes in active MS lesions can express BAFF, the soluble form was not increased in the CSF of MS patients. It remains unclear whether the inflammatory features of active MS plaques are truly represented by the CSF compartment.

Neuroprotective mechanisms of erythropoietin in a rat stroke model.

OBJECTIVE: This study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO). METHODS: One hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet-dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography. RESULTS: In the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment. CONCLUSIONS: Single-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

National Institutes of Health Stroke Scale (NIHSS) on admission predicts acute symptomatic seizure risk in ischemic stroke: a population-based study involving 135,117 cases.

The National Institutes of Health Stroke Scale (NIHSS) score is the most frequently used score worldwide for assessing the clinical severity of a stroke. Prior research suggested an association between acute symptomatic seizures after stroke and poorer outcome. We determined the frequency of acute seizures after ischemic stroke in a large population-based registry in a central European region between 2004 and 2016 and identified risk factors for acute seizures in univariate and multivariate analyses. Additionally, we determined the influence of seizures on morbidity and mortality in a matched case-control design. Our analysis of 135,117 cases demonstrated a seizure frequency of 1.3%. Seizure risk was 0.6% with an NIHSS score at admission <3 points and increased up to 7.0% with >31 score points. Seizure risk was significantly higher in the presence of acute non-neurological infections (odds ratio: 3.4; 95% confidence interval: 2.8-4.1). A lower premorbid functional level also significantly increased seizure risk (OR: 1.7; 95%CI: 1.4-2.0). Mortality in patients with acute symptomatic seizures was almost doubled when compared to controls matched for age, gender, and stroke severity. Acute symptomatic seizures increase morbidity and mortality in ischemic stroke. Their odds increase with a higher NIHSS score at admission.

Acute symptomatic seizures in intracerebral and subarachnoid hemorrhage: A population study of 19,331 patients.

BACKGROUND: Risk factors for acute symptomatic seizures after stroke demonstrated in retrospective analyses should be confirmed in large population studies. While seizures following ischemic stroke have been studied intensively, less is known about seizure predictors in hemorrhagic stroke. This study sought to identify risk factors of acute symptomatic seizures and to elucidate associated short-term (in-hospital) morbidity and mortality rates in primary intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). METHODS: We determined the frequency of all acute symptomatic seizures perceived by clinical staff after hemorrhagic stroke in a large population-based registry in a central European region between 2004 and 2016. Further, we analyzed risk factors for seizure occurrence, morbidity, and mortality in univariate and multivariate analyses. RESULTS: Of 297,120 stroke patients, 19,331 experienced a hemorrhagic stroke. Frequency of acute seizures (without semiological differentiation) in this subpopulation was 4% (4.0% in ICH and 3.6% in SAH). The risk for acute symptomatic seizures was significantly increased in both stroke types in the presence of an acute non-neurological infection (odds ratio: 2.0 for ICH and 4.2 for SAH). A lower premorbid functional level also significantly increased the seizure risk (odds ratio: 2.0 for ICH and 3.1 for SAH). The odds of in-hospital mortality in the presence of acute seizures were significantly reduced in ICH patients (odds ratio: 0.7) but not in SAH patients. CONCLUSION: Acute symptomatic seizures are equally common in ICH and SAH patients in this registry. Seizure risk is invariably increased in the presence of acute non-neurological infection. Mortality is reduced in ICH patients with seizures, but the exact reason for this relationship is not clear and might represent a biased finding.

Decreasing postoperative cognitive deficits after heart surgery: protocol for a randomized controlled trial on cognitive training.

BACKGROUND: The occurrence of postoperative cognitive deficits, especially after heart surgery, has been demonstrated in several studies. These deficits can clearly be noticed by the patients and by their close relatives in daily life. Furthermore, postoperative cognitive deficits can decrease quality of life in social functioning and earning capacity. The aim of this study is to investigate whether early postoperative cognitive training can reduce subjective and objective postoperative cognitive deficits. METHODS: The proposed study is a multicenter, two-arm, randomized controlled trial involving 144 elderly patients undergoing elective heart-valve surgery with extracorporeal circulation. Patients will be assigned to either a training group or a control group. The intervention involves paper-and-pencil-based cognitive training, which is conducted for 36 min over a period of 18 days. The training starts about 1 week after surgery and is carried out during the hospitalized rehabilitation phase. The control group will not receive cognitive training or a placebo intervention. A detailed assessment of psychological functions and health-related quality of life prior to surgery at discharge from rehabilitation and 3 and 12 months after discharge will be performed. The primary outcome of this trial is the training effect on objective cognitive functions at discharge from rehabilitation. Secondary outcomes are the training effect on objective and subjective cognitive functions (3 and 12 months after discharge), depression, health-related quality of life, and the impact of perioperative cerebral ischemia on the training effect. Perioperative cerebral ischemia will be measured with postoperative magnetic resonance imaging including diffusion-weighted sequences. DISCUSSION: Should it be shown that our cognitive training can improve postoperative cognitive deficits and quality of life, one possibility could be to integrate this intervention into early rehabilitation. Furthermore, we hope that the investigation of perioperative ischemia by diffusion-weighted magnetic resonance imaging will improve our understanding of neurobiological factors influencing the course of postoperative cognitive plasticity. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00015512. Retrospectively registered on 21 September 2018.

Adjustment of oral diet based on flexible endoscopic evaluation of swallowing (FEES) in acute stroke patients: a cross-sectional hospital-based registry study.

BACKGROUND: Diagnosing dysphagia in acute stroke patients is crucial, as this comorbidity determines morbidity and mortality; we therefore investigated the impact of flexible nasolaryngeal endoscopy (FEES) in acute stroke patients. METHODS: The FEES investigation as performed in acute stroke patients treated at a large university hospital, allocated as a standard procedure for all patients suspected of dysphagia. We correlated our findings with baseline data, disability status, pneumonia, duration of hospitalisation, necessity for mechanical ventilation and treatment on the intensive care unit. The study was designed as a cross-sectional hospital-based registry. RESULTS: We investigated 152 patients. The median age was 73; 94 were male. Ischemic stroke was diagnosed in 125 patients (82.2%); 27 (17.8%) suffered intracerebral haemorrhage. Oropharyngeal dysphagia was diagnosed in 72.4% of the patients, and was associated with higher stroke severity on admission (median NIHSS 11 [IQR 6-17] vs. 7 [4-12], p = .013; median mRS 5 [IQR 4-5] vs. 4 [IQR 3-5], p = .012). Short-term mortality was higher among patients diagnosed with dysphagia (7.2% vs. 0%, p = .107). FEES examinations revealed that only 30.9% of the patients had an oral diet appropriate for their swallowing abilities. A change of oral diet was associated with a better outcome at discharge (mRS; p = .006), less need of mechanical ventilation (p = .028), shorter period of hospitalisation (p = .044), and lower rates of pneumonia (p = .007) and mortality (p = .011). CONCLUSION: Due to the inability of clinical assessments to detect silent aspiration, FEES might be better suited to identify stroke patients at risk and may contribute to a better functional outcome and lower rates of pneumonia and mortality. Our findings also point to a low awareness of dysphagia, even in a specialised stroke centre. FEES in acute stroke patients helps to adjust the oral diet for the vast majority of stroke patients (69.1%) based on their swallowing abilities, potentially avoiding severe complications.