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.