Establishing an MSU service in a medium-sized German urban area-clinical and economic considerations.

Background and purpose: Mobile stroke units (MSU) have been demonstrated to improve prehospital stroke care in metropolitan and rural regions. Due to geographical, social and structural idiosyncrasies of the German city of Mannheim, concepts of established MSU services are not directly applicable to the Mannheim initiative. The aim of the present analysis was to identify major determinants that need to be considered when initially setting up a local MSU service. Methods: Local stroke statistics from 2015 to 2021 were analyzed and circadian distribution of strokes and local incidence rates were calculated. MSU patient numbers and total program costs were estimated for varying operating modes, daytime coverage models, staffing configurations which included several resource sharing models with the hospital. Additional case-number simulations for expanded catchment areas were performed. Results: Median time of symptom onset of ischemic stroke patients was 1:00 p.m. 54.3% of all stroke patients were admitted during a 10-h time window on weekdays. Assuming that MSU is able to reach 53% of stroke patients, the average expected number of ischemic stroke patients admitted to MSU would be 0.64 in a 10-h shift each day, which could potentially be increased by expanding the MSU catchment area. Total estimated MSU costs amounted to € 815,087 per annum. Teleneurological assessment reduced overall costs by 11.7%. Conclusion: This analysis provides a framework of determinants and considerations to be addressed during the design process of a novel MSU program in order to balance stroke care improvements with the sustainable use of scarce resources.

[Potential Impact of Public Communication on Emergency Presentations due to Headache during the Covid-19 Pandemic]. / Epidemiologische Untersuchung zu möglichen Auswirkungen öffentlicher Kommunikation im Rahmen der COVID-19-Pandemie auf Notfallvorstellungen von Kopfschmerzpatient*innen.

Headache is a frequent presenting symptom in the emergency department. While most cases are of benign aetiology, it is crucially important to identify potentially dangerous underlying disorders. We hypothesized an increase in headache-related emergency presentations after venous thrombosis of cerebral sinuses had been identified as a rare side effect of vaccination with adenovirus vector-based Coronavirus-disease 2019 (COVID-19) vaccines and that information had been publicly communicated by the Paul Ehrlich Institute. Data from patients with the diagnosis of primary headache disorders or unspecified headache presenting to the Interdisciplinary Emergency Department of the University Medicine Mannheim were retrospectively analysed. Based on vaccination dashboard data published by the Federal Ministry of Health, calendar weeks 14-30 and 47-48, on the one hand, and 1-13 and 31-46, on the othe, were categorized into a variable "vaccination epoch" (14-30, 47-48: high vaccination activity if≥3 million weekly vaccinations in Germany; 1-13, 31-46: low vaccination activity if<3 million weekly vaccinations). The number of patients with headache was the dependent variable. A Poisson regression was performed to analyze whether the frequency of events, i. e., patient presentations, was a function of year (2019, 2021), epoch (high, low) and an interaction of year and epoch - the latter reflecting an impact of vaccination activity during the pandemic and expressed as incidence rate ratio. Compared to 2019, there was a more than 70% increase in presentations due to headache during periods of high vaccination activity in 2021 (p<0.001; 95% confidence interval 1.272-2.316), in 25% of presentations in 2021, patients considered their headache as vaccination-associated. Public communication and resulting nocebo effects may, among other factors, have contributed to our observation of increased numbers of emergency headache presentations, illustrating the impact of public distribution of medical information on practical aspects of emergency care during crises.

Left atrial area index provides the best prediction of atrial fibrillation in ischemic stroke patients: results from the LAETITIA observational study.

Background and aims: Left atrial (LA) enlargement has been repeatedly shown to be associated with the diagnosis of atrial fibrillation (AF). In clinical practice, several parameters are available to determine LA enlargement: LA diameter index (LADI), LA area index (LAAI), or LA volume index (LAVI). We investigated the predictive power of these individual LA parameters for AF in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: LAETITIA is a retrospective observational study that reflects the clinical reality of acute stroke care in Germany. Consecutive patient cases with acute ischemic cerebrovascular event (CVE) in 2019 and 2020 were identified from the Mannheim stroke database. Predictive power of each LA parameter was determined by the area under the curve (AUC) of receiver operating characteristic curves. A cutoff value was determined. A multiple logistic regression analysis was performed to confirm the strongest LA parameter as an independent predictor of AF in patients with acute ischemic CVE. Results: A total of 1,910 patient cases were included. In all, 82.0% of patients had suffered a stroke and 18.0% had a TIA. Patients presented with a distinct cardiovascular risk profile (reflected by a CHA2DS2-VASc score ≥2 prior to hospital admission in 85.3% of patients) and were moderately affected on admission [median NIHSS score 3 (1; 8)]. In total, 19.5% of patients had pre-existing AF, and 8.0% were newly diagnosed with AF. LAAI had the greatest AUC of 0.748, LADI of 0.706, and LAVI of 0.719 (each p < 0.001 vs. diagonal line; AUC-LAAI vs. AUC-LADI p = 0.030, AUC-LAAI vs. AUC-LAVI p = 0.004). LAAI, increasing NIHSS score on admission, and systolic heart failure were identified as independent predictors of AF in patients with acute ischemic CVE. To achieve a clinically relevant specificity of 70%, a cutoff value of ≥10.3 cm2/m2 was determined for LAAI (sensitivity of 69.8%). Conclusion: LAAI revealed the best prediction of AF in patients with acute ischemic CVE and was confirmed as an independent risk factor. An LAAI cutoff value of 10.3 cm2/m2 could serve as an inclusion criterion for intensified AF screening in patients with embolic stroke of undetermined source in subsequent studies.

PSEN1/SLC20A2 double mutation causes early-onset Alzheimer's disease and primary familial brain calcification co-morbidity.

Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF ß-amyloid parameters and FBB-PET suggested cortical ß-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.

Use of Prognostication Instruments in Prognostication Procedures of Postanoxic Coma Patients over Time: A Retrospective Study.

BACKGROUND: Many survivors of cardiovascular arrest remain in a postanoxic coma. The neurologist's task is to provide the most accurate assessment of the patient's neurologic prognosis through a multimodal approach of clinical and technical tests. The aim of this study is to analyze differences and developments in the concept of neurological prognosis assessment and in-hospital outcome of patients over a five year-period. METHODS: This retrospective observational study included 227 patients with postanoxic coma treated in the medical intensive care unit of the University Hospital, Mannheim from January 2016 to May 2021. We retrospectively analyzed patient characteristics, post-cardiac arrest care, and the use of clinical and technical tests for neurological prognosis assessment and patient outcome. RESULTS: Over the observation period, 215 patients received a completed neurological prognosis assessment. Regarding the multimodal prognostic assessment, patients with poor prognosis (54%) received significantly fewer diagnostic modalities than patients with very likely poor (20.5%), indeterminate (24.2%), or good prognosis (1.4%; p = 0.001). The update of the DGN guidelines in 2017 had no effect on the number of performed prognostic parameters per patient. The finding of bilaterally absent pupillary light reflexes or severe anoxic injury on CT contributed most to a poor prognosis category (OR 8.38, 95%CI 4.01-7.51 and 12.93, 95%CI 5.55-30.13, respectively), whereas a malignant EEG pattern and NSE > 90 µg/L at 72 h resulted in the lowest OR (5.11, 95%CI 2.32-11.25, and 5.89, 95%CI 3.14-11.06, respectively) for a poor prognosis category. Assessment of baseline NSE significantly increased over the years (OR 1.76, 95%CI 1.4-2.22, p < 0.001), and assessment of follow-up NSE at 72 h trended to increase (OR 1.19, 95%CI 0.99-1.43, p = 0.06). In-hospital mortality was high (82.8%), remained unchanged over the observation period, and corresponded to the number of patients in whom life-sustaining measures were discontinued. CONCLUSIONS: Among comatose survivors of cardiac arrest, the prognosis remains poor. Prognostication of a poor outcome led nearly exclusively to withdrawal of care. Prognostic modalities varied considerably with regard to their contribution to a poor prognosis category. Increasing enforcement of a standardized prognosis assessment and standardized evaluation of diagnostic modalities are needed to avoid false-positive prognostication of poor outcomes.

Current diagnosis and treatment practice of central retinal artery occlusion: results from a survey among German stroke units.

BACKGROUND: Central retinal artery occlusion (CRAO) is a neuro-ophthalmological emergency whose optimal management is still under debate and due to the absence of definite guidelines, practice is expected to vary. We aimed to characterize early evaluation as well as acute treatment and diagnostic approaches in German hospitals with a stroke unit (SU). METHODS: In 07/2021, all 335 certified German SUs were invited to participate in an anonymous online survey endorsed by the German Stroke Society on emergency department care organization, diagnostic procedures, and treatment of patients with unilateral vision loss (UVL) subsequently diagnosed with CRAO. RESULTS: One hundred and sixty-three (48.6%) of the 335 eligible centers responded. Most (117/135; 86.7%) stated that UVL patients were treated as an emergency, in 62/138 (44.9%) hospitals according to specific guidelines. First-line evaluation was performed by neurologists in 85/136 (62.5%) hospitals, by ophthalmologists in 43/136 (31.6%) hospitals. Seventy of 135 (51.9%) respondents indicated a lack of on-site ophthalmological expertise. Seventy-four of 129 (57.4%) respondents performed thrombolysis in CRAO and 92/97 (94.8%) stated that patients with CRAO-if admitted to neurology-were treated on a SU. CONCLUSIONS: Our findings reflect notable heterogeneity in early intrahospital care of CRAO in German SUs but demonstrate a preference for work-up and management as acute stroke by the involved neurologists. Streamlining interdisciplinary emergency evaluation is essential for ongoing and future prospective trials.

The remains of the day: neuropsychological findings in postacute transient global amnesia.

INTRODUCTION: Current clinical diagnostic criteria of transient global amnesia (TGA) require the episode to completely resolve within 24 h. Small case series investigating the neuropsychological profiles obtained during the first days after TGA are inconclusive, with some suggesting the persistence of memory deficits. METHODS: In this retrospective observational study, neuropsychological data of 185 TGA patients obtained during the first days following an attack were analysed. Data of cognitive functions assessed in at least 50 patients were evaluated and dichotomised according to z-values as "impaired" or "unimpaired". Moreover, the results of magnetic resonance imaging (MRI) were collected. RESULTS: Neuropsychological assessment was performed within the first 3 days after TGA in 158 (85.4%) of all patients. The majority of patients showed no significant neuropsychological sequelae in the postacute phase of TGA. However, Mini-Mental Status Examination showed impairment in 22.6% of 159 patients, and we found subtle reductions of patients' performance in tests of verbal long-term memory and executive function in 16.3-24.6% of patients. Patients with hippocampal diffusion-weighted imaging (DWI) lesions performed significantly worse in a verbal recognition task than those without DWI lesions. DISCUSSION: Our findings reflect subtle performance reductions in different cognitive domains in a small subgroup of TGA patients. This implies that the gradual resolution of subclinical symptoms may take longer than the 24 h required as maximum episode duration by current diagnostic criteria.

Measuring of Advanced Glycation End Products in Acute Stroke Care: Skin Autofluorescence as a Predictor of Ischemic Stroke Outcome in Patients with Diabetes Mellitus.

Background: Patients with diabetes mellitus (DM) are known to show poor recovery after stroke. This specific burden might be due to acute and chronic hyperglycemic effects. Meanwhile, the underlying mechanisms are a cause of discussion, and the best measure to predict the outcome is unclear. Skin autofluorescence (SAF) reflects the in-patient load of so-called advanced glycation end products (AGEs) beyond HbA1c and represents a valid and quickly accessible marker of chronic hyperglycemia. We investigated the predictive potential of SAF in comparison to HbA1c and acute hyperglycemia on the functional outcome at 90 days after ischemic stroke in a cohort of patients with DM. Methods: We prospectively included 113 patients with DM type 2 hospitalized for acute ischemic stroke. SAF was measured on each patient's forearm by a mobile AGE-Reader mu© in arbitrary units. HbA1c and the area under the curve (AUC) of the blood sugar profile after admission were assessed. Functional outcome was assessed via phone interview after 90 days. A poor outcome was defined as a deterioration to a modified Rankin Scale score ≥ 3. A good outcome was defined as a modified Rankin Scale score < 3 or as no deterioration from premorbid level. Results: Patients with a poor outcome presented with higher values of SAF (mean 3.38 (SD 0.55)) than patients with a good outcome (mean 3.13 (SD 0.61), p = 0.023), but did not differ in HbA1c and acute glycemia. In logistic regression analysis, age (p = 0.021, OR 1.24 [1.12−1.37]) and SAF (p = 0.021, OR 2.74 [1.16−6.46]) significantly predicted a poor outcome, whereas HbA1c and acute glycemia did not. Patients with a poor 90-day outcome and higher SAF experienced more infections (4.2% vs. 33.3% (p < 0.01)) and other various in-hospital complications (21.0% vs. 66.7% (p < 0.01)) than patients with a good outcome and lower SAF levels. Conclusions: SAF offers an insight into glycemic memory and appears to be a significant predictor of poor stroke outcomes in patients with DM exceeding HbA1c and acute glycemia. Measuring SAF could be useful to identify specifically vulnerable patients at high risk of complications and poor outcomes.

Sex-Specific Differences in Pre-Stroke Characteristics Reveal Vulnerability of Elderly Women.

While the sexually dimorphic character of ischemic stroke has been acknowledged along several dimensions, age-specific sex disparities regarding pre-stroke characteristics in particular have received comparatively little attention. This study aimed to identify age-dependent associations between sex and risk factors, premorbidity, and living situation in patients with ischemic stroke to foster the continuing development of dedicated preventative strategies. In a retrospective single-center study, data of patients with acute ischemic stroke (AIS) admitted to the Department of Neurology, University Hospital Mannheim, Germany, between June 2004−June 2020 were included; AIS frequency, vascular risk factors, premorbidity, living situation, and stroke etiology were analyzed across sexes and different age spectra. From a total of 11,003 patients included in the study, 44.1% were female. Women aged >70−≤90 years showed a pronounced increase in stroke frequency, lived alone significantly more frequently, and had a significantly higher degree of pre-stroke disability than men; however, only hypertension and atrial fibrillation were more prevalent in women in this age segment. The seventh and eighth decades are a critical time in which the pre-stroke risk profile changes resulting in an increase in stroke morbidity in women. This emphasizes the relevance of and need for an approach to stroke prevention that is both targeted and integrative.

Impaired semantic memory during acute transient global amnesia.

As a clinical model of hippocampal dysfunction, transient global amnesia (TGA) causes reversible memory disturbance. While episodic memory deficits in TGA patients have been extensively described, data regarding semantic memory involvement are sparse and contradictory. We report impaired semantic fluency performance in 16 patients with hippocampal lesions on MRI during acute TGA compared to their performance one day later and to that of 20 healthy subjects. Our findings support the involvement of the hippocampus in semantic retrieval.

Chronobiology of transient global amnesia.

INTRODUCTION: The etiology of transient global amnesia (TGA) is still a matter of debate. Based, among others, on the observation of a close temporal relation between certain events and subsequent TGA episodes, recent proposals discuss the relevance of stress-associated processes impacting on hippocampal functioning. Circadian, infra- and ultradian rhythmicity has been found to play a relevant role in the multifactorial pathomechanisms of various disorders but has not been thoroughly studied in TGA. METHODS: Data of patients with a final diagnosis of TGA were collected in Mannheim, Germany (06/1999-01/2018, n = 404), and in the Kansai district, Japan (04/2006-03/2018, n = 261). Chronological patterns of TGA occurrence were determined. RESULTS: Significant circadian rhythmicity of TGA occurrence with bimodal peaks (mid-morning, late afternoon) was found for the entire population (p = 0.002) and for either sub-cohort (Mannheim: p = 0.003, Kansai: p = 0.007). This finding was confirmed for either sex (women: p = 0.004, men: p = 0.004) and different age groups (< 65 years: p = 0.0009, ≥ 65 years: p = 0.003). There was no variation according to day of the week, month or season, but the proportion of patients with a weekday episode was significantly higher in the Mannheim cohort (p = 0.002). DISCUSSION: We identified a robust circadian rhythm in TGA occurrence which remarkably applied to either of the two study sites located on different continents and which was independent of sex and age. In light of abundant evidence of circadian rhythmicity of both, components of the human stress response system and memory, chronobiological analyses may provide an opportunity to further uncover the mechanisms underlying TGA.

Skin Autofluorescence is an Independent Predictor of Post Stroke Infection in Diabetes.

Post stroke infection occurs in 15-20% of acute stroke patients and is associated with a poor longterm outcome. In a prospective study on 113 acute ischemic stroke patients with diabetes mellitus 15.9% suffered nosocomial infection. We found chronic hyperglycemia measured by skin autofluorescence in arbitrary units to be an independent predictor of a nosocomial infection post stroke (OR = 3.24 [CI 95%: 1.13; 9.26], p = 0.029). Skin autofluorescence represents the glycemic memory beyond HbA1c. Potential mechanisms leading from increased skin autofluorescence to vulnerability for infectious complications include more severe strokes due to preexisting vasculopathy and exacerbated post stroke immunosuppression.

Sex-related differences in stressful events precipitating transient global amnesia - A retrospective observational study.

INTRODUCTION: Physically or emotionally charged events have consistently been reported as precipitating an episode of transient global amnesia (TGA). In conjunction with evidence of hippocampal involvement from neuroimaging, this has promoted the hypothesis that TGA is a stress-related disorder. METHODS: In this retrospective observational study, medical records of 389 patients with TGA were analysed regarding documented precipitating events, which were classified according to previously suggested criteria. Moreover, comorbidities and results of magnetic resonance imaging were collected. FINDINGS: In our cohort of TGA patients, 231 were female (59.4%). A precipitating factor was identified in 266 patients (68.4%). Of these, 136 patients (51.1%) reported physical triggers, the most common being physical exertion (64.0%). Another 122 patients (45.9%) presented with an emotional trigger, most frequently classified as an interpersonal conflict (42.7%). In 8 cases (2.1%), TGA was preceded by a medical procedure. Emotional triggers were more often experienced by women (37.2% vs 22.8%, p = 0.003), while physical stressors were more often present in men (30.7% vs 41.1%, p = 0.035). Women had a significantly higher number of hippocampal MRI lesions than men (mean 1.13 vs 0.92; p = 0.042). CONCLUSION: Our data suggest a female predominance in TGA occurrence and a sex-related difference in susceptibility to certain triggering events in TGA patients. In light of recent research on sex-specific differences in vulnerability to stress, these findings support the hypothesis that this might be a significant contributing factor in the pathogenesis of TGA.

Decreased admissions and change in arrival mode in patients with cerebrovascular events during the first surge of the COVID-19 pandemic.

BACKGROUND AND PURPOSE: Investigating clinical characteristics of patients presenting with cerebrovascular events during the pandemic may provide valuable insight into further understanding the phenomenon of decreased stroke admissions during the COVID-19 pandemic. METHOD: Data of patients presenting with a cerebrovascular event to the emergency department during weeks 12-17/2020 were compared to data from the respective weeks in 2019. RESULTS: A significant reduction in the number of admissions by 35.9% (p = 0.005) was observed during the COVID-19 epoch. In addition, significantly more patients arrived by ambulance during the COVID-19 epoch (2019: 75.7%, 2020: 94.2%; p = 0.001). CONCLUSION: Our data may have implications as to how campaigns raising awareness for serious medical conditions in the context of the pandemic should be framed.

Investigation of the "central vein sign" in infratentorial multiple sclerosis lesions.

BACKGROUND: Recently there has been an increasing interest in the "central vein sign" (CVS) in multiple sclerosis (MS) lesions. Infratentorial brain regions represent typical predilection sites for MS lesion development and are part of the current McDonald criteria to demonstrate dissemination in space, but only a few studies investigated the presence of the CVS in infratentorial MS lesions. The aim of this study was to investigate the CVS in infratentorial MS lesions. METHODS: 3T MRI data sets from 119 patients with relapsing MS were analysed. Chronic lesions were identified on T2-weighted images. Co-registered T2 / susceptibility-weighted images (SWI) were analysed for the presence of the CVS. RESULTS: A total of 527 lesions were analysed. A CVS was present in the majority of infratentorial lesions (62/88, 70%). There was no difference in the frequencies of the CVS of infratentorial lesions compared to paraventricular lesions (67/81, 83%; p = 0.06) or subcortical (150/209; 72%; p = 0.82) lesions. Infratentorial lesions showed a CVS more often than juxtacortical lesions (16/34; 47%; p = 0.02), while periventricular lesions showed a CVS more often than infratentorial lesions (97/115; 84%, p = 0.02). CONCLUSION: CVS is a frequent finding in infratentorial MS lesions that may increase the diagnostic value in MS.