Frederick Palm

Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH).To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption.Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption.Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment.Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome.Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%).Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies.clinicaltrials.gov Identifier: NCT01829581.

Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach.Within a 1-year recruitment period, patients suspected of having acute (symptom onset<4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic.The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke [median (interquartile range) 1.91 μg/L (0.41-17.66) vs 0.08 μg/L (0.02-0.14), P<0.001]. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high [area under the curve 0.915 (95% CI 0.847-0.982), P<0.001]. A GFAP cutoff of 0.29 μg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic.Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.

We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe.We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons.In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions.Primary preventive strategies for ischemic stroke in young adults-having high rate of modifiable risk factors-should be targeted according to sex and age at continental level.

Background and purpose Risk factors for IS in young adults differ between genders and evolve with age, but data on the age‐ and gender‐specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. Methods Stroke etiology was reported in detail for 3331 patients aged 15–49 years with first‐ever IS according to Trial of Org in Acute Stroke Treatment ( TOAST ) criteria: large‐artery atherosclerosis ( LAA ), cardioembolism ( CE ), small‐vessel occlusion ( SVO ), other determined etiology, or undetermined etiology. CE was categorized into low‐ and high‐risk sources. Other determined group was divided into dissection and other non‐dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. Results Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE , the most frequent high‐risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA , high‐risk sources of CE , and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. Conclusions The etiology of IS in young adults has clear gender‐specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates.The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke.Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 ± 12.6 years) than men (n = 299; 69.7 ± 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20-1.56) than in women (1.12; 95% CI 0.97-1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), small-artery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and 'probable atherothrombotic stroke' (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p < 0.001), coronary artery disease (p = 0.0015) and peripheral artery disease (p = 0.024) was significantly more common in men than in women. Overall, 1-year survival was not different between both sexes; however, a significant age-sex interaction with higher mortality in elderly women (>85 years) was detected.Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men.

The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established.To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).Surgical hematoma evacuation vs conservative treatment.The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH.Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02).Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake &lt;48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICH any ), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICH ECASS-II ) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICH NINDS ); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICH any was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICH ECASS-II and sICH NINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH.We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03).Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.

Background Patients with recent stroke or transient ischaemic attack are at high risk for a further vascular event, possibly leading to permanent disability or death. Although evidence-based treatments for secondary prevention are available, many patients do not achieve recommended behavioural modifications and pharmaceutical prevention targets in the long-term. We aimed to investigate whether a support programme for enhanced secondary prevention can reduce the frequency of recurrent vascular events. Methods INSPiRE-TMS was an open-label, multicentre, international randomised controlled trial done at seven German hospitals with acute stroke units and a Danish stroke centre. Patients with non-disabling stroke or transient ischaemic attack within 2 weeks from study enrolment and at least one modifiable risk factor (ie, arterial hypertension, diabetes, atrial fibrillation, or smoking) were included. Computerised randomisation was used to allocate patients (1:1) either to the support programme in addition to conventional care or to conventional care alone. The support programme used feedback and motivational interviewing strategies with eight outpatient visits over 2 years aiming to improve adherence to secondary prevention targets. The primary outcome was the composite of major vascular events consisting of stroke, acute coronary syndrome, and vascular death, assessed in the intention-to-treat population (all patients who underwent randomisation, did not withdraw study participation, and had at least one follow-up). Outcomes were assessed at annual follow-ups using time-to-first-event analysis. All-cause death was monitored as a safety outcome. This trial is registered with ClinicalTrials.gov, NCT01586702. Findings From Aug 22, 2011, to Oct 30, 2017, we enrolled 2098 patients. Of those, 1048 (50·0%) were randomly assigned to the support programme group and 1050 (50·0%) patients were assigned to the conventional care group. 1030 (98·3%) patients in the support group and 1042 (99·2%) patients in the conventional care group were included in the intention-to-treat analysis. The mean age of analysed participants was 67·4 years and 700 (34%) were women. After a mean follow-up of 3·6 years, the primary outcome of major vascular events had occurred in 163 (15·8%) of 1030 patients of the support programme group and in 175 (16·8%) of 1042 patients of the conventional care group (hazard ratio [HR] 0·92, 95% CI 0·75–1·14). Total major vascular event numbers were 209 for the support programme group and 225 for the conventional care group (incidence rate ratio 0·93, 95% CI 0·77–1·12; p=0·46) and all-cause death occurred in 73 (7·1%) patients in the support programme group and 85 (8·2%) patients in the conventional care group (HR 0·85, 0·62–1·17). More patients in the support programme group achieved secondary prevention targets (eg, in 1-year-follow-up 52% vs 42% [p<0·0001] for blood pressure, 62% vs 54% [p=0·0010] for LDL, 33% vs 19% [p<0·0001] for physical activity, and 51% vs 34% [p=0·0010] for smoking cessation). Interpretation Provision of an intensified secondary prevention programme in patients with non-disabling stroke or transient ischaemic attack was associated with improved achievement of secondary prevention targets but did not lead to a significantly lower rate of major vascular events. Further research is needed to investigate the effects of support programmes in selected patients who do not achieve secondary prevention targets soon after discharge. Funding German Federal Ministry of Education and Research, Pfizer, and German Stroke Foundation.

<h2>Summary</h2><h3>Background</h3> Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. <h3>Methods</h3> In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov, NCT02204267, and is completed and closed for participants. <h3>Findings</h3> Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9–1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0–2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 <i>vs</i> 249 [14·5%] of 1717; HR 0·9 [0·8–1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5–0·9]). <h3>Interpretation</h3> Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. <h3>Funding</h3> Bayer Vital. <h3>Translation</h3> For the German translation of the abstract see Supplementary Materials section.

Background and Purpose— Considerable locoregional differences in stroke incidence exist even within countries. Based on data from a statewide stroke care quality monitoring project, we hypothesized a high stroke incidence mainly among younger age groups in the industrial city of Ludwigshafen am Rhein, Germany. To test this hypothesis and to provide data on stroke incidence and case-fatality rates, a population-based stroke register was initiated. Methods— The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke register among the 167 906 inhabitants of Ludwigshafen am Rhein. Starting on January 1, 2006, standard definitions and multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Results— In 2006 and 2007, 1231 cases with stroke or transient ischemic attack including 725 patients with first-ever stroke were identified. The crude annual incidence rate per 1000 for first-ever stroke was 2.16 (95% CI 2.10 to 2.32). After age adjustment to the European population, incidence for first-ever stroke was 1.46 (95% CI 1.35 to 1.57; men: 1.63; 95% CI 1.46 to 1.81; women: 1.29; 95% CI 1.15 to 1.43). Crude annual incidence rates per 1000 were 1.86 for ischemic stroke, 0.19 for intracerebral hemorrhage, 0.05 for subarachnoid hemorrhage, and 0.05 for undetermined stroke. Case-fatality rates for first-ever stroke were 13.6%, 16.4%, and 23.2% at Days 28, 90, and 365, respectively. Conclusions— High crude incidence rates in our study reflect the rising burden of stroke in our aging population. Age-adjusted incidence rates were somewhat higher than those reported by recent studies from Western Europe, mainly due to higher incidence in subjects &lt;65 years.

Survival in amyotrophic lateral sclerosis varies considerably. About one third of the patients die within 12 months after first diagnosis. The early recognition of fast progression is essential for patients and neurologists to weigh up invasive therapeutic interventions. In a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany, we identified significant prognostic factors at time of diagnosis that allow prediction of early death within first 12 months.Incident cases, diagnosed between October 2009 and September 2012 were enrolled and followed up at regular intervals of 3 to 6 months. Univariate analysis utilized the Log-Rank Test to identify association between candidate demographic and disease variables and one-year mortality. In a second step we investigated a multiple logistic regression model for the optimal prediction of one-year mortality rate.In the cohort of 176 ALS patients (mean age 66.2 years; follow-up 100%) one-year mortality rate from diagnosis was 34.1%. Multivariate analysis revealed that age over 75 years, interval between symptom onset and diagnosis below 7 months, decline of body weight before diagnosis exceeding 2 BMI units and Functional Rating Score below 31 points were independent factors predicting early death.Probability of early death within 12 months from diagnosis is predicted by advanced age, short interval between symptom onset and first diagnosis, rapid decline of body weight before diagnosis and advanced functional impairment.ClinicalTrials.gov (NCT01955369, registered September 28, 2013).

<h3>Objective</h3> To report the effects of anti-NMDA receptor (NMDAR) encephalitis in pregnant patients and their babies. <h3>Methods</h3> We studied a retrospective cohort of patients who developed anti-NMDAR encephalitis during pregnancy or became pregnant while recovering from the encephalitis. In addition, we reviewed the English literature between 2010 and 2019 related to this topic. <h3>Results</h3> We studied 11 patients; 6 developed anti-NMDAR encephalitis during pregnancy, and 5 became pregnant while recovering. There were no obstetrical complications, but 6 (55%) babies were premature. Ten newborns were healthy, and 1 (9%) developed transient respiratory distress. Nine infants had assessable follow-up (median 18 months; range, 7–96 months), and all showed normal development. We identified 21 cases in the English literature. Obstetrical complications occurred in 7 (33%) pregnancies. Two patients died of septic shock (1 baby successfully delivered), another 2 had miscarriages, and in 2, the pregnancy was terminated. Sixteen babies (76%) were delivered, 9 (56%) premature. At birth, 13/16 (81%) newborns were healthy, 2/16 (13%) had transient neurologic or respiratory symptoms, and 1 (6%) died of brain edema. Follow-up (median 12 months; range, 6–36 months) was reported for 8 children: 7 (88%) showed normal development and behavior, and 1 (13%) cortical dysplasia. Immunotherapy was used during pregnancy in 7 (64%) of our patients and 18 (86%) of the reported cases, including rituximab in 4 cases, without adverse effects. <h3>Conclusions</h3> Patients who develop anti-NMDAR encephalitis during pregnancy or become pregnant during recovery often have obstetrical complications, but most of the newborns are healthy and appear to have normal development.

In the early stages of the global COVID-19 pandemic hospital admissions for acute ischemic stroke (AIS) decreased substantially. As health systems have become more experienced in dealing with the pandemic, and as the proportion of the population vaccinated rises, it is of interest to determine whether the prevalence of AIS hospitalization and outcomes from hospitalization have returned to normal.In this observational, retrospective cohort study, we compared the prevalence and outcomes of AIS during the first four waves of the pandemic to corresponding pre-pandemic periods in 2019 using administrative data collected from a nationwide network of 76 hospitals that manages 7% of all in-hospital cases in Germany.We included 25,821 AIS cases in the study period (2020/2021) and used 26,295 AIS cases as controls (2019). Compared to pre-pandemic numbers, mean daily AIS admissions decreased only during wave 1 (from 39.6 to 34.1; p < 0.01) and wave 2 (from 39.9 to 38.3; p = 0.03) and returned to normal levels during waves 3 and 4. AIS case fatality increased in wave 1 only (from 6.0% to 7.6%; p = 0.03). We observed a consistent decrease in the prevalences of arterial hypertension, diabetes, and obesity among AIS cases throughout the pandemic and no changes in rates of systemic thrombolysis, mechanical thrombectomy, or decompressive craniectomy. The rate of transfer to stroke units increased only during waves 2 (by 4.6%; p < 0.01) and 3 (by 3.0%; p < 0.01). The proportion of patients with coinciding SARS-CoV-2 and AIS was low, peaking at 3.4% in wave 2 and subsequently decreasing to 0.4% in wave 4.In Germany, the COVID-19 pandemic seems to have had a larger effect on nationwide in-hospital AIS care during the early pandemic stages, in which AIS case numbers decreased and case fatality rose. This may reflect a nationwide "learning curve" within health care systems in providing AIS care in times of a pandemic.

Periodontitis is a common infectious disease associated with increased risk for ischemic stroke though presently unclear mechanisms. In a case-control study, we investigated salivary levels of four periodontal pathogens, as well as systemic and local inflammatory markers. The population comprised 98 patients with acute ischemic stroke (mean ± SD, 68.2 ± 9.7 yrs; 45.9% women) and 100 healthy controls (69.1 ± 5.2 yrs; 47.0% women). Patients were more often edentulous and had fewer teeth than controls (13.8 ± 10.8 versus 16.6 ± 10.1). After adjusting for stroke risk factors and number of teeth, controls had higher saliva matrix metalloproteinase-8 (MMP-8), myeloperoxidase (MPO), IL-1β, Aggregatibacter actinomycetemcomitans, and serum LPS activity levels. Patients had higher serum MMP-8 and MPO, and they were more often qPCR-positive for A. actinomycetemcomitans (37.9% versus 19.0%) and for ≥3 periodontopathic species combined (50.0% versus 33.0%). We conclude that controls more often had evidence of current periodontal infection with higher periodontal pathogen amount, endotoxemia, local inflammation and tissue destruction. Stroke patients more often had evidence of end-stage periodontitis with edentulism and missing teeth. They were more often carriers of several periodontopathic pathogens in saliva, especially A. actinomycetemcomitans. Additionally, inflammatory burden may contribute to high systemic inflammation associated with elevated stroke susceptibility.

In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke.Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored.In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients.NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.

Post-stroke delirium (POD) in patients on stroke units (SU) is associated with an increased risk for complications and poorer clinical outcome. The objective was to reduce the severity of POD by implementing an interprofessional delirium-management.Multicentric quality-improvement project on five SU implementing a delirium-management with pre/post-comparison. Primary outcome was severity of POD, assessed with the Nursing Delirium Screening Scale (Nu-DESC). Secondary outcome parameters were POD incidence, duration, modified Rankin Scale (mRS), length of stay in SU and hospital, mortality, and others.Out of a total of 799 patients, 59.4% (n = 475) could be included with 9.5% (n = 45) being delirious. Implementation of a delirium-management led to reduced POD severity; Nu-DESC median: pre: 3.5 (interquartile range 2.6-4.7) vs. post 3.0 (2.2-4.0), albeit not significant (p = 0.154). Other outcome parameters were not meaningful different. In the post-period, delirium-management could be delivered to 75% (n = 18) of delirious patients, and only 24 (53.3%) of delirious patients required pharmacological treatments. Patients with a more severe stroke and POD remained on their disability levels, compared to similar affected, non-delirious patients who improved.Implementation of delirium-management on SU is feasible and can be delivered to most patients, but with limited effects. Nursing interventions as first choice could be delivered to the majority of patients, and only the half required pharmacological treatments. Delirium-management may lead to reduced severity of POD but had only partial effects on duration of POD or length of stay. POD hampers rehabilitation, especially in patients with more severe stroke.DRKS, DRKS00021436. Registered 04/17/2020, www.drks.de/DRKS00021436 .

Background and purpose Atrial fibrillation ( AF ) is amongst the most important etiologies of ischaemic stroke. In a population‐based stroke registry, we tested the hypothesis of low adherence to current guidelines as a main cause of high rates of AF ‐associated stroke. Methods Within the L udwigshafen Stroke Study (Lu SS t), a prospective ongoing population‐based stroke register, we analyzed all patients with a first‐ever ischaemic stroke ( FEIS ) owing to AF in 2006 and 2007. We determined whether AF was diagnosed before stroke and assessed pre‐stroke CHADS 2 and CHA 2 DS 2 ‐ VAS c scores. Results In total, 187 of 626 patients with FEIS suffered from cardioembolic stroke owing to AF , which was newly diagnosed in 57 (31%) patients. Retrospective pre‐stroke risk stratification according to CHADS 2 score indicated low/intermediate risk in 34 patients (18%) and high risk ( CHADS 2 ≥ 2) in 153 patients (82%). Application of CHA 2 DS 2 ‐ VAS c score reduced number of patients at low/intermediate risk ( CHA 2 DS 2 ‐ VAS c score 0–1) to five patients (2.7%). In patients with a CHADS 2 score ≥ 2 and known AF ( n = 106) before stroke, 38 (36%) were on treatment with vitamin K antagonists on admission whilst only in 16 patients (15%) treatment was in therapeutic range. Conclusions Our study strongly supports the hypothesis that underuse of oral anticoagulants in high‐risk patients importantly contributes to AF ‐associated stroke. CHA 2 DS 2 ‐ VAS c score appears to be a more valuable risk stratification tool than CHADS 2 score. Preventive measures should focus on optimizing pre‐stroke detection of AF and better implementation of present AF ‐guidelines with respect to anticoagulation therapy.

Objectives The clinical spectrum of amyotrophic lateral sclerosis (ALS) is characterized by a considerable variation. Different phenotypes have been described by previous studies. We assessed clinical variability and prognostic relevance of these phenotypes in a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany. Methods Incident ALS cases, diagnosed between October 2009 and September 2012, were prospectively enrolled and classified according to established ALS phenotype classification (bulbar, classic, flail arm, flail leg, pyramidal, respiratory). Survival probability was described using Kaplan–Meier method. Moreover, the influence of an additional frontotemporal dementia (FTD) was analysed. Results Phenotypes of all 200 patients were determined. Bulbar and classic phenotypes accounted for 75% of all cases. Deterioration of functional impairment during disease progression was lowest in flail leg and pyramidal variants, and most pronounced in bulbar and classic phenotypes. A poor survival prognosis was observed for bulbar, classic or respiratory phenotypes. Patients with an additional FTD showed an even worse outcome. Conclusions Results suggest that ALS is a heterogeneous disease, as ALS phenotypes differ in disease progression and survival time. Patients classified as suffering from bulbar, classic and respiratory ALS, as well as those with an additional FTD, show a marked reduction of survival time.

Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies.(1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions.Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient-control pairs enrolled by the end of 2018.SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

Background and aims Infectious diseases contribute to stroke risk, and are associated with socioeconomic status (SES). We tested the hypotheses that the aggregate burden of infections increases the risk of ischemic stroke (IS) and partly explains the association between low SES and ischemic stroke. Methods In a case–control study with 470 ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population, antibodies against the periodontal microbial agents Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, against Chlamydia pneumonia, Mycoplasma pneumoniae (IgA and IgG), and CagA-positive Helicobacter pylori (IgG) were assessed. Results IgA seropositivity to two microbial agents was significantly associated with IS after adjustment for SES (OR 1.45 95% CI 1.01–2.08), but not in the fully adjusted model (OR 1.32 95% CI 0.86–2.02). By trend, cumulative IgA seropositivity was associated with stroke due to large vessel disease (LVD) after full adjustment (OR 1.88, 95% CI 0.96–3.69). Disadvantageous childhood SES was associated with higher cumulative seropositivity in univariable analyses, however, its strong impact on stroke risk was not influenced by seroepidemiological data in the multivariable model. The strong association between adulthood SES and stroke was rendered nonsignificant when factors of dental care were adjusted for. Conclusions Infectious burden assessed with five microbial agents did not independently contribute to ischemic stroke consistently, but may contribute to stroke due to LVD. High infectious burden may not explain the association between childhood SES and stroke risk. Lifestyle factors that include dental negligence may contribute to the association between disadvantageous adulthood SES and stroke.

Background and aims Matrix metalloproteinase (MMP)-8 and myeloperoxidase (MPO) may contribute to cerebral damage in acute ischemic stroke. We tested the hypothesis that levels of MPO, MMP-8 and the ratio between MMP-8 and its regulator, tissue inhibitor of metalloproteinase (TIMP-1), are increased in acute ischemic stroke and its etiologic subgroups and they correlate with stroke severity. Methods In a cross-sectional case–control study, serum concentrations of MMP-8, MPO and TIMP-1 were assessed within 24 h after admission in 470 first-ever ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population. Odds ratios (OR) per decade of log transformed dependent variables were calculated and adjusted for age, sex and vascular risk factors. Results Levels of MMP-8 (OR 4.9; 95% CI 3.4–7.2), MMP-8/TIMP-1 ratio (3.0; 2.2–4.1) and MPO (6.6; 4.0–11.0) were independently associated with ischemic stroke. MMP-8 levels differed between etiologic stroke subgroups (p = 0.019, ANOVA), with higher levels in cardioembolic stroke and stroke due to large vessel disease, and lower levels in microangiopathic stroke. MMP-8, MMP-8/TIMP-1 ratio and MPO (p < 0.001) concentrations showed positive associations with stroke severity independent of stroke etiology. Conclusions Concentrations of serum neutrophil markers are increased after ischemic stroke and associate with stroke severity and etiology. The value of these biomarkers in diagnostics and prognostics is worth being evaluated.

Background and Purpose— The association between socioeconomic status in adulthood and the risk of stroke is well established; however, the independent effects of socioeconomic conditions in different life phases are less understood. Methods— Within a population-based stroke registry, we performed a case–control study with 470 ischemic stroke patients (cases) aged 18 to 80 years and 809 age- and sex-matched stroke-free controls, randomly selected from the population (study period October 2007 to April 2012). We assessed socioeconomic conditions in childhood, adolescence, and adulthood, and developed a socioeconomic risk score for each life period. Results— Socioeconomic conditions were less favorable in cases regarding paternal profession, living conditions and estimated family income in childhood, school degree, and vocational training in adolescence, last profession, marital status and periods of unemployment in adulthood. Using tertiles of score values, low socioeconomic conditions during childhood (odds ratio 1.77; 95% confidence interval 1.20–2.60) and adulthood (odds ratio 1.74; 95% confidence interval 1.16–2.60) but not significantly during adolescence (odds ratio 1.64; 95% confidence interval 0.97–2.78) were associated with stroke risk after adjustment for risk factors and other life stages. Medical risk factors attenuated the effect of childhood conditions, and lifestyle factors reduced the effect of socioeconomic conditions in adolescence and adulthood. Unfavorable childhood socioeconomic conditions were particularly associated with large artery atherosclerotic stroke in adulthood (odds ratio 2.13; 95% confidence interval 1.24–3.67). Conclusions— This study supports the hypothesis that unfavorable childhood socioeconomic conditions are related to ischemic stroke risk, independent of established risk factors and socioeconomic status in adulthood, and fosters the idea that stroke prevention needs to begin early in life.

Stroke is among the most common causes of death and persisting disability and therefore represents a great social and economic burden worldwide. In order to lower this burden it is essential to identify risk factors and respective preventive strategies. Besides the established stroke risk factors (e.g. hypertension, diabetes, hypercholesterolemia, atrial fibrillation) both acute and chronic infectious diseases have emerged as risk factors for stroke. Mainly acute respiratory tract infection but also urinary tract infections independently increase the risk of ischemic stroke. Such additional risk was shown to be highest for infection within 3 days before ischemia and the risk steadily declines with increasing time intervals between infection and stroke. Associations between stroke incidence and mortality and influenza epidemics have been demonstrated. Observational studies showed an inverse association between influenza vaccination and stroke risk; however, interventional studies in this field have not been performed so far. Chronic infections, presently discussed as stroke risk factors mainly include periodontitis and infections with Helicobacter pylori (Hp) and Chlamydia pneumoniae (Cp). Although most respective studies identified these infectious diseases as independent stroke risk factors interventional trials have not been performed so far and causality is not proven, yet. There is preliminary evidence that the number of pathogens to which a subject had been exposed to rather than single pathogens are associated with the risk of stroke or other cardiovascular diseases. Chronic infectious diseases are treatable conditions and their identification as causal contributors to stroke risk could offer new avenues in stroke prevention.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.

Objective To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH. Methods Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. Results IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04–1.93) vs non-LDSH: 1.32 (0.33–3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38–4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4–6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume &lt;4.4 mL: 0.18 (0.04–0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS &lt;4: 0.29 (0.11–0.78); p=0.014) were significantly associated with fewer IHC. Conclusions Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Background During the covid-19 pandemic, a non-funded, nurse-led quality improvement project on delirium management was in progress on four Stroke Units (SU). Two sites experienced pandemic-related delays; we set out to learn lessons based on the impact for delivering multicentre trials. Methods Secondary analysis of a prospective quality improvement project. We compared data quality from centres with vs. without delay. Unplanned modifications in study management were classified as a) fatal modifications (ending the study), b) serious modifications (requiring a revision of the registration and/or ethic approval, c) moderate modifications (revising study management), d) minor modifications (improving study performance). Local study coordinators summarised lessons learned. Results The study had an overall delay of 14 months. Centres without delay delivered better data quality and had less loss of patients due to missing primary outcome data in 0.3% vs 28.8% in centres with delay (p&lt;0.001). There were no fatal modifications, two serious (exchange of study centre, adding new outcome parameters), six moderate (e.g. delayed start in two centres, change from in-person to virtual meetings), and one minor modification (four local study coordinators taking parental leave). Lessons learned were frequent communication with study coordinators, attention to data quality, protocolisation of recruitment rates, and adapted education in quality improvement projects. Conclusions Pandemic-related disruption can be substantial, with poorer data quality, but only in a few cases were registration and/or ethic approval modifications required. Facilitators are flexible, including changed time frames, frequent virtual communication, and critical reflection.

The possibility to survive with amyotrophic lateral sclerosis (ALS) varies considerably and survival extends from a few months to several years. A number of demographic and clinical factors predicting survival have been described; however, existing data are conflicting. We intended to predict patient survival in a population-based prospective cohort of ALS patients from variables known up to the time of diagnosis.Incident ALS patients diagnosed within three consecutive years were enrolled and regularly followed up. Candidate demographic and disease variables were analysed for survival probability using the Kaplan-Meier method. The Cox proportional hazard regression model was used to assess the influence of selected predictor variables on survival prognosis.In the cohort of 193 patients (mean age 65.8, standard deviation 10.2 years), worse prognosis was independently predicted by older age, male gender, bulbar onset, probable or definite ALS according to El Escorial criteria, shorter interval between symptom onset and diagnosis, lower Functional Rating Scale, diagnosis of frontotemporal dementia, and living without a partner.Taking into account these predictor variables, an approximate survival prognosis of individual ALS patients at diagnosis seems feasible.

There is a lack of prospective and population based epidemiological data on amyotrophic lateral sclerosis in Germany to date. The ALS registry Rhineland-Palatinate was established to investigate the incidence, course and phenotypic variety of ALS in this south-west German state of about 4 million inhabitants. During the period 2010–2011, consecutive incident patients with amyotrophic lateral sclerosis according to the revised El Escorial criteria were included and followed up using multiple overlapping sources of case ascertainment. One hundred and forty-six patients were enrolled. The annual crude incidence for amyotrophic lateral sclerosis in Rhineland-Palatinate was 1.8/100,000 person-years (95% CI 1.6–2.2). Male to female ratio was 1.1:1. Incidence increased with age reaching a peak in the 70–74 years age group and declined thereafter. Late-onset ALS (≥ 75 years) was found in 14.4% of patients. About 32% of patients presented with bulbar onset. In conclusion, incidence rate of amyotrophic lateral sclerosis in Rhineland-Palatinate is within the range of other prospective population based registers in Europe and North America. Gender ratio is nearly balanced.

Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution.The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks.Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1-3) as well as 225 cooperating hospitals (per network: median 9, IQR 4-17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319-2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6-14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5-8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states.Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future.HINTERGRUND UND ZIEL: Telemedizinische Schlaganfall-Netzwerke tragen dazu bei, die Schlaganfallversorgung und insbesondere den Zugang zu zeitkritischen Schlaganfalltherapien in vorrangig strukturschwachen, ländlichen Regionen zu gewährleisten. Ziel ist eine Darstellung der Nutzungsfrequenz und regionalen Verteilung dieser Versorgungsstruktur.Die Kommission „Telemedizinische Schlaganfallversorgung“ der Deutschen Schlaganfall-Gesellschaft führte eine Umfragestudie in allen Schlaganfall-Netzwerken durch.In Deutschland sind 22 telemedizinische Schlaganfall-Netzwerke aktiv, welche insgesamt 43 Zentren (pro Netzwerk: Median 1,5, Interquartilsabstand [IQA] 1–3) sowie 225 Kooperationskliniken (pro Netzwerk: Median 9, IQA 4–17) umfassen und an einem unmittelbaren Zugang zur Schlaganfallversorgung für 48 Mio. Menschen teilhaben. Im Jahr 2018 wurden 38.211 Telekonsile (pro Netzwerk: Median 1340, IQA 319–2758) durchgeführt. Die Thrombolyserate betrug 14,1 % (95 %-Konfidenzintervall 13,6–14,7 %), eine Verlegung zur Thrombektomie wurde bei 7,9 % (95 %-Konfidenzintervall 7,5–8,4 %) der ischämischen Schlaganfallpatienten initiiert. Das Finanzierungssystem ist uneinheitlich mit einem Vergütungssystem für die Zentrumsleistungen in nur drei Bundesländern.Etwa jeder 10. Schlaganfallpatient wird telemedizinisch behandelt. Die telemedizinischen Schlaganfall-Netzwerke erreichen vergleichbar hohe Lyseraten und Verlegungen zur Thrombektomie wie neurologische Stroke-Units und tragen zur Sicherstellung einer flächendeckenden Schlaganfallversorgung bei. Eine netzwerkübergreifende Sicherstellung der Finanzierung und einheitliche Erhebung von Qualitätssicherungsdaten haben das Potenzial diese Versorgungsstruktur zukünftig weiter zu stärken.

Acquired Idiopathic Generalized Anhidrosis (AIGA) and Its Complications: Implications for AIGA as an Autoimmune Disease,

There is increasing evidence that acute bacterial and viral infection represent trigger factors that temporarily elevate the risk of ischemic stroke. During and after influenza epidemics vascular death rates and hospitalizations for stroke are increased. Influenza vaccination is an effective measure to reduce hospitalization and mortality in the elderly and work incapacity in adults of working age. Results of several observational studies support the hypothesis that influenza vaccination is associated with reduced odds of stroke. As randomized studies are lacking, a causal role of influenza vaccination in stroke prevention is not proven, however. According to current guidelines in many countries, that recommend the vaccination in all patients with chronic vascular disease, all patients with a history of stroke or TIA should receive an influenza vaccination annually. Furthermore, patients with diabetes mellitus or with a combination of risk factors that increase stroke risk should obtain the vaccination. In addition, there is evidence from observational data that the neuraminidase inhibitor oseltamivir reduces the risk of stroke within 6 months after influenza infection. Keywords: Acute infections, influenza, stroke, risk factor, cerebral ischemia, vascular disease, vaccination, antivirals

Cardioembolic stroke (CES) due to atrial fibrillation (AF) is associated with high stroke mortality. Oral anticoagulation (OAC) reduces stroke mortality, however, the impact of OAC-administration during hospital stay post ischemic stroke on mortality is unclear. We determined whether the timing of OAC initiation among other prognostic factors influenced mortality after CES.Within the Ludwigshafen Stroke Study (LuSSt), a prospective population-based stroke register, we analysed all patients with a first ever ischemic stroke or TIA due to AF from 2006 until 2010. We analysed whether treatment or non-treatment with OAC and initiation of OAC-therapy during and after hospitalization influenced stroke mortality within 500 days after stroke/TIA due to AF.In total 479 patients had a first-ever ischemic stroke (n = 394) or TIA (n = 85) due to AF. One-year mortality rate was 28.4%. Overall, 252 patients (52.6%) received OAC. In 181 patients (37.8%), OAC treatment was started in hospital and continued thereafter. Recommendation to start OAC post discharge was given in 110 patients (23.0%) of whom 71 patients received OAC with VKA (14.8%). No OAC-recommendation was given in 158 patients (33.0%). In multivariate Cox regression analysis, higher age (HR 1.04; 95% CI 1.02-1.07), coronary artery disease (HR: 1.6; 95% CI 1.1-2.3), higher mRS-score at discharge (HR 1.24; 95% CI 1.09-1.4), and OAC treatment ((no OAC vs started in hospital (HR: 5.4; 95% CI 2.8-10.5), were independently associated with stroke mortality. OAC-timing did not significantly influence stroke mortality (started post discharge vs. started in hospital (HR 0.3; 95% CI 0.07-1.4)).OAC non-treatment is the main predictor for stroke mortality. Although OAC initiation during hospital stay showed a trend towards higher mortality, early initiation in selected patients is an option as recommendation to start OAC post hospital was implemented in only 64.5%. This rate might be elevated by implementation of special intervention programs.

Introduction Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated. Materials and methods The assay to measure LPS-NC was set up by spiking serum samples with E. coli LPS. The LPS-NC, LPS-binding protein (LBP), soluble CD14 (sCD14), lipoprotein profiles, apo(lipoprotein) A-I, apoB, and phospholipid transfer protein (PLTP) activity, were determined in 98 ischemic stroke patients and 100 age- and sex-matched controls. Serum and saliva immune response to A. actinomycetemcomitans, its concentration in saliva, and serotype-distribution were examined. Results LPS-NC values ranged between 51–83% in the whole population. Although several of the LPS-NC determinants differed significantly between cases and controls (PLTP, sCD14, apoA-I, HDL-cholesterol), the levels did not (p = 0.056). The main determinants of LPS-NC were i) triglycerides (β = -0.68, p<0.001), and ii) HDL cholesterol (0.260, <0.001), LDL cholesterol (-0.265, <0.001), PLTP (-0.196, 0.011), and IgG against A. actinomycetemcomitans (0.174, 0.011). Saliva A. actinomycetemcomitans concentration was higher [log mean (95% CI), 4.39 (2.35–8.19) vs. 10.7 (5.45–21) genomes/ml, p = 0.023) and serotype D more frequent (4 vs. 0%, p = 0.043) in cases than controls. Serotypeablity or serotypes did not, however, relate to the LPS-NC. Conclusion Serum LPS-NC comprised low PLTP-activity, triglyceride and LDL cholesterol concentrations, as well as high HDL cholesterol and IgG against A. actinomycetemcomitans. The present findings let us to conclude that LPS-NC did not associate with stroke.

A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk.In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor β1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens).Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99-1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects.A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.

&lt;b&gt;&lt;i&gt;Background and Purpose:&lt;/i&gt;&lt;/b&gt; A recent surgery may be one of the trigger factors precipitating stroke and transient ischemic attack (TIA). While stroke in cardiac and carotid surgery has been well studied, less is known on stroke risk after surgery outside the heart and brain supplying arteries. We tested the hypothesis that preceding non-neurosurgical, non-cardiothoracic, and non-carotid surgery and other interventions temporarily increase the risk of stroke and transient ischemic attack (TIA) and investigated the risk related to different time periods between interventions and stroke/TIA. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In the Ludwigshafen Stroke Study, a population-based stroke registry, we assessed surgery and other interventions within the year preceding stroke and TIA. The risk factor profiles of patients with and without prior intervention were compared and rate ratios (RR) were calculated for different time periods with 91-365 days before stroke and TIA serving as reference period. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In 2006 and 2007, 803 patients without and 116 patients with non-neurosurgical, non-cardiothoracic, and non-carotid intervention within the preceding year were identified. Elective (n = 21) and posttraumatic orthopedic (n = 14), eye (n = 14), and visceral surgery (n = 11) dominated. Interventions within 0-30 days (n = 34; RR 4.72; 95% confidence interval (CI) 2.70-8.26) but not within 31-60 or 61-90 days before stroke/TIA were observed more often than in the reference period. Interventions were more common within day 8-30 before stroke/TIA (RR 3.26; 95% CI 1.66-6.39), particularly common within the preceding week (RR 9.52; 95% CI 3.77-24.1) and most common in the preceding 2 days (RR 27.1; 95% CI 5.97-123) as compared to the reference period. Atrial fibrillation (AF) but not other risk factors was more common in patients with interventions within 30 days (n = 15; 44.1%) as compared to patients with more antecedent interventions (n = 19; 23.2%, p = 0.022) and those without surgery (n = 222; 27.6%, p = 0.031). Interventions within 30 days before stroke/TIA, were associated with total ischemic stroke (RR 6.11; 95% CI 3.32-11.2), first-ever in a lifetime ischemic stroke (RR 5.62; 95% CI 2.83-11.1)&lt;b&gt; &lt;/b&gt;and recurrent ischemic stroke (RR 7.50; 95% CI 2.88-19.6). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Recent non-cardiothoracic, non-carotid, and non-neurosurgical interventions are associated with an increased risk of stroke lasting for about 1 month and being particularly high within the first days. AF may be among the mechanisms linking interventions and stroke besides induction of a procoagulant state and interruption of medication.

To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs).Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months.231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5-26] vs. 1 d [0-4], P<0.001).The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation.

Physical activity (PA) is associated with lower risk of stroke. We tested the hypothesis that lack of pre-stroke PA is an independent predictor of poor outcome after first-ever ischemic stroke. We assessed recent self-reported PA and other potential predictors for loss of functional independence - modified Rankin Scale (mRS) > 2 - one year after first-ever ischemic stroke in 1370 patients registered between 2006 and 2010 in the Ludwigshafen Stroke Study, a population-based stroke registry. After 1 year, 717 (52.3%) of patients lost their independence including 251 patients (18.3%) who had died. In multivariate logistic regression analysis lack of regular PA prior to stroke (Odds Ratio (OR) 1.7, Confidence Interval (CI) 1.1–2.5), independently predicted poor outcome together with higher age (65–74: OR 1.7; CI 1.1–2.8, 75–84 years: OR 3.3; CI 2.1–5.3; ≥85 years OR 14.5; CI 7.4–28.5), female sex (OR 1.5; CI 1.1–2.1), diabetes mellitus (OR 1.8; CI 1.3–2.5), stroke severity (OR 1.2; CI 1.1–1.2), probable atherothrombotic stroke etiology (OR 1.8; CI 1.1–2.8) and high leukocyte count (> 9.000/mm3; OR 1.4; CI 1.0–1.9) at admission. Subclassifying unknown stroke etiology, embolic stroke of unknown source (ESUS; n = 40, OR 2.2; CI 0.9–5.5) tended to be associated with loss of independence. In addition to previously reported factors, lack of PA prior to stroke as potential indicator of worse physical condition, high leukocyte count at admission as indicator of the inflammatory response and probable atherothrombotic stroke etiology might be independent predictors for non-functional independence in first-ever ischemic stroke.

Abstract Background and purpose The effects of the coronavirus disease 2019 (COVID‐19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. Methods In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in‐hospital and (telemedical) stroke care during the pandemic was conducted. Results Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical ( p &lt; 0.001) and telemedical stroke consultations ( p &lt; 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID‐19 measures in May/June 2020 were observed. Compared to 2018–2019, neither stroke patients' age ( p = 0.38), gender ( p = 0.44), nor severity of ischemic stroke ( p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID‐19, there were no relevant shortcomings reported regarding in‐hospital stroke treatment or telemedical stroke care. Conclusions Telemedical stroke care in Germany was able to provide full service despite the COVID‐19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID‐19 measures in Germany.

The INSPiRE-TMS trial (Intensified Secondary Prevention Intending a Reduction of Recurrent Events in Transient Ischemic Attack and Minor Stroke Patients) investigated effects of a multicomponent support program in patients with nondisabling stroke or transient ischemic attack. Although secondary prevention targets were achieved more frequently in the intensified care group, no significant differences were seen in rates of recurrent major vascular events. Here, we present the effects on prespecified patient-centered outcomes.In a multicenter trial, we randomized patients with modifiable risk factors either to the intensified or conventional care alone program. Intensified care was provided by stroke specialists and used feedback and motivational interviewing strategies (≥8 outpatient visits over 2 years) aiming to improve adherence to secondary prevention targets. We measured physical fitness, disability, cognitive function and health-related quality of life by stair-climbing test, modified Rankin Scale, Montreal Cognitive Assessment, and European Quality of Life 5 Dimension 3 Level during the first 3 years of follow-up.Of 2072 patients (mean age: 67.4years, 34% female) assessed for the primary outcome, patient-centered outcomes were collected in 1,771 patients (877 intensified versus 894 conventional care group). Physical fitness improved more in the intensified care group (mean between-group difference in power (Watt): 24.5 after 1 year (95% CI, 5.5-43.5); 36.1 after 2 years (95% CI, 13.1-59.7) and 29.6 (95% CI, 2.0-57.3 after 3 years). At 1 year, there was a significant shift in ordinal regression analysis of modified Rankin Scale in favor of the intensified care group (common odds ratio, 1.23 [95% CI, 1.03-1.47]) but not after 2 (odds ratio, 1.17 [95% CI, 0.96-1.41]) or 3 years (odds ratio, 1.16 [95% CI, 0.95-1.43]) of follow-up. However, Montreal Cognitive Assessment and European Quality of Life 5 Dimension scores showed no improvement in the intensified intervention arm after 1, 2, or 3 years of follow-up.Patients of the intensified care program group had slightly better results for physical fitness and modified Rankin Scale after 1 year, but none of the other patient-centered outcomes was significantly improved.URL: https://www.gov; Unique identifier: NCT01586702.

Abstract Background Risk diseases and risk factors for stroke include atrial fibrillation, hypertension, diabetes mellitus, smoking, and elevated LDL-cholesterol. Due to modern treatment options, the impact of these risk diseases on subsequent cardiovascular events or death after a first stroke is less clear and needs to be elucidated. We therefore aimed to get insights into the persistence of adverse prognostic effects of these risk diseases and risk factors on subsequent stroke or death events 1 year after the first stroke by using the new weighted all-cause hazard ratio. Methods This study evaluates the 1 year follow-up of 470 first ever stroke cases identified in the area of Ludwigshafen, Germany, with 23 deaths and 34 subsequent stroke events. For this purpose, the recently introduced “weighted all-cause hazard ratio” was used, which allows a weighting of the competing endpoints within a composite endpoint. Moreover, we extended this approach to allow an adjustment for covariates. Results None of these risk factors and risk diseases, most probably being treated after the first stroke, remained to be associated with a subsequent death or stroke [weighted hazard ratios (95% confidence interval) for diabetes mellitus, atrial fibrillation, high cholesterol, hypertension, and smoking are 0.4 (0.2–0.9), 0.8 (0.4–2.2), 1.3 (0.5–2.5), 1.2 (0.3–2.7), 1.6 (0.8–3.6), respectively]. However, when analyzed separately in terms of death and stroke, the risk factors and risk diseases under investigation affect the subsequent event rate to a variable degree. Conclusions Using the new weighted hazard ratio, established risk factors and risk diseases for the occurrence of a first stroke do not remain to be significant predictors for subsequent events like death or recurrent stroke. It has been demonstrated that the new weighted hazard ratio can be used for a more adequate analysis of cardiovascular risk and disease progress. The results have to be confirmed within a larger study with more events.

Persisting disability requiring professional healthcare or help in daily life activities can be expected in a third to a half of all stroke survivors. It is mainly the elderly that are affected. For the increasingly aging population of Western societies, stroke represents an increasing social and economic burden. Besides the existing therapeutic options, additional treatment and prevention strategies are needed. Traditional risk factors do not explain all clinical and epidemiological features of stroke. Recently, the association between infectious and inflammatory processes and the occurrence of vascular disease has been established. This review summarizes the current evidence of infections as stroke risk factors and of potential anti-infective strategies as future methods of stroke prevention.

Purpose . A transient painless monocular visual loss due to a decrease in retinal circulation—also known as “amaurosis fugax”—often precedes acute territorial cerebral ischaemia. The case we present underlines the importance of a comprehensive diagnostic workup in patients with amaurosis fugax. Case Report . A 44-year-old man who had suffered from a dissection of the ascending aorta (Stanford Type A) five months ago presented with recurrent monocular vision problems. Episodes with sectional vision loss mainly occurred in combination with low blood pressure levels. Furthermore, the haemoglobin level was chronically low (Hb 9.7 mg/dL), and the patient was by mistake on a simultaneous therapy with phenprocoumon and unfractionated heparin. Carotid artery duplex scanning revealed a high-grade stenosis of the proximal right common carotid artery. MR imaging corroborated hypoperfusion in brain area corresponding to the right MCA. Conclusion . Our patient is an example in whom transient retinal ischaemic attacks may originate from haemodynamic reasons.

Fragestellung: Durch verbesserte Behandlungsmethoden des Schlaganfalls ist eine Senkung der Mortalität zu erwarten. Populationsbasierte Schlaganfallregister sind für eine verlässliche Erhebung dieser Daten notwendig. Wir präsentieren hier Ergebnisse eines populationsbasierten Schlaganfallsregisters der in Südwestdeutschland gelegene Industriestadt Ludwigshafen am Rhein.

Warum dieser Fall? Häufigste Ursache einer Amaurosis fugax ist der transiente, meist embolisch bedingte Verschluss einer retinalen Arterie. Pathophysiologisch sind hierbei sowohl arterio-arterielle Embolien (z. B. im Rahmen einer Karotisstenose) sowie kardiale Embolien (z. B. als Folge eines Vorhofflimmerns) in Erwägung zu ziehen. Der vorgestellte Fall dokumentiert den seltenen Fall einer hämodynamischen Ursache als Folge einer Aortendissektion in Kombination mit einer Anämie sowie Hypotonie.

Fragestellung: Der Schlaganfall stellt zunehmend ein menschliches, medizinisches und sozioökonomisches Problem dar. Ziel unseres Schlaganfallregisters ist die Erfassung epidemiologischer Daten zur Häufigkeit des Schlaganfalls und seiner ätiologischen Subgruppen. Wir präsentieren wir Daten zu Inzidenzen, Subklassifikation sowie Pathogenese der im Jahr 2006 registrierten Schlaganfälle.

Hintergrund: Der Schlaganfall stellt ein zunehmendes menschliches, medizinisches und sozioökonomisches Problem dar. In der Anzahl der Schlaganfall-neuerkrankungen bestehen selbst innerhalb eines Landes deutliche lokale und regionale Unterschiede. Wir berichten über die Zwei-Jahres-Ergebnisse eines seit 2006 bestehenden Schlaganfallregisters aus einer überwiegend industriell geprägten Stadt im Südwesten Deutschlands.

Fragestellung: Angesichts der zunehmend älter werdenden Bevölkerung westlicher Industrienationen stellt der Schlaganfall ein zunehmendes menschliches, medizinisches und sozioökonomisches Problem dar. Ziel unseres Schlaganfallregisters ist die Erfassung epidemiologischer Daten zur Häufigkeit des Schlaganfalls und seiner ätiologischen Subgruppen sowie einer Veränderung der Inzidenzen über die Zeit, um Patienten zielgerichteter behandeln zu können. Hier präsentieren wir erste Daten einer industriell geprägten Stadt im Südwesten Deutschlands.

Zusammenfassung Hintergrund Demografischer Wandel, Urbanisierung sowie eine zunehmende Spezialisierung der Akutversorgung von Schlaganfallpatienten erfordern eine Anpassung von Versorgungsstrukturen mit dem Ziel, auch Patienten in ländlichen Regionen leitliniengerecht behandeln zu können. Methodik Im Frühjahr 2016 wurde ein landesweites telemedizinisches Schlaganfallnetzwerk unter Einbeziehung aller 6 überregionalen Stroke Units im Land Rheinland-Pfalz etabliert. Die Zuständigkeit für den Konsildienst wechselt täglich zwischen den Kliniken und steht rund um die Uhr zur Verfügung. Alle Kriterien des OPS 8.98b werden erfüllt. Am Netzwerk teilnehmen können alle regionalen Stroke Units und Kliniken, die prädefinierte Kriterien erfüllen und nicht in regionaler Konkurrenz mit etablierten Stroke Units stehen. Ergebnisse Zu Projektbeginn am 01.04. 2016 nahmen 6 Kliniken teil, die alle eine regionale Stroke Unit unter internistischer Leitung besitzen. Innerhalb des ersten Jahres erfolgten 1568 telemedizinische Konsile. Die Diagnosen waren ischämische Infarkte (n = 802 Patienten; 51,2 %), intrazerebrale Blutungen (n = 46; 2,9%), transitorisch ischämische Attacken (TIA; n = 319; 20,4 %) und nicht vaskuläre Ursachen (sog. Stroke Mimics; n = 400; 25,5 %). Die Latenz zwischen Klinikaufnahme und Konsilbeginn betrug im Median 21 Minuten (Interquartilrange (IQR) 22 Minuten), die mediane Konsildauer lag bei 24 Minuten (IQR 22 Minuten). Bei den Patienten mit ischämischen Schlaganfällen betrug die Lyserate 12,5 % (n = 100). Eine mechanische Thrombektomie wurde nach Weiterverlegung in eines der Zentren bei 4,6 % (n = 37) der Patienten durchgeführt. Schlussfolgerung Die telemedizinische Netzwerkbildung ist geeignet, die landesweite Versorgung von Schlaganfallpatienten sicherzustellen. Weitere Analysen, insbesondere zum Outcome, werden benötigt.

Hypohidrosis and anhidrosis can be caused by various diseases.Diabetes mellitus, Sjo ¨gren syndrome, pure autonomic failure, Fabry disease, Ross syndrome, thyroid dysfunction, paraneoplastic autonomic dysfunction, and congenital absence of sweat glands are possible diagnoses. 1 A less common cause of hypohidrosis/anhidrosis is the acquired idiopathic generalized anhidrosis (AIGA).Until now, 64 cases of AIGA have been reported, 62 being Japanese. 2 We here report a European patient with AIGA.Case report.A 39-year-old white man presented with a 6-month history of progressive heat intolerance and lack of sweating except for the axillary zone and parts of his face.The patient also reported tachycardia and general fatigue.He had no history of dry mouth, dry eyes, concomitant sharp pain, or urticaria.The patient's history and family history were unremarkable.The patient did not take any medications.Physical and neurologic examination including autonomic functional tests (heart rate variability, Valsalva maneuver, respiratory sinus arrhythmia, tilt table test) were normal.Axon reflex testing was not performed.The thermoregulatory as well as the pilocarpine sweating tests showed anhidrosis except for the axillary and periorbital zones (figure ,A).Cranial MRI, chest radiograph, and various laboratory tests (including anti-GM1 and anti-GQ1B antibodies, IgE level) revealed normal findings.A skin biopsy specimen from the sternum showed infiltration of sweat glands by CD3-positive lymphocytes (figure, C).Acquired idiopathic generalized anhidrosis was diagnosed, and methylprednisolone was administered (1,000 mg/day for 3 days IV followed by tapering oral doses for 2 weeks).One week after therapy initiation, the patient's sweat production improved.Two months later, the thermoregulatory sweating test was normal (figure, B).A repeated skin biopsy revealed no more CD3-positive lymphocyte infiltration (figure, D).Discussion.AIGA is an uncommon cause of hypohidrosis/ anhidrosis.Most of the reported cases were from Japan.Clinical features of AIGA are an acute or sudden onset of generalized anhidrosis with an onset early in life, the absence of other autonomic dysfunction, and a marked response to glucocorticoids.Concomitant sharp pain or cholinergic urticaria and elevated IgE levels have also been described in the majority of patients.These features were absent in our patient; however, the marked response to glucocorticoids and the histopathologic findings strongly support the diagnosis of AIGA.There are three subgroups of AIGA 1 : The idiopathic pure sudomotoric failure (IPSF), sudomotoric neuropathy, and sweat gland failure.Most cases of AIGA seem to represent IPSF, as in the case of our patient.Typical histopathologic findings here include CD3positive lymphocyte infiltrations of the sweat glands 3 and occlusion of proximal coiled ducts, 4 whereas CD3-positive lymphocyte infiltration seems to be a hallmark of IPSF.Although the etiology of AIGA is still unclear, immunologic mechanisms contribute to the disease.The facts that IPSF as a subgroup of AIGA is associated with CD3-positive lymphocyte infiltration of sweat glands and that CD3 plays an important role in the induction of cellmediated disorders support this hypothesis.This may also explain the improvement in sweat function with corticosteroids in 78% of patients with AIGA. 2 A deficit in the muscarinic cholinergic receptor in eccrine sweat glands or interference in transmission of acetylcholine to cholinergic receptors is supposed to be involved in the pathogenesis of IPSP.This might explain the persisting sweat production of the axilla, as seen in our patient.Sweat glands of the axilla are apocrine glands and are supposed to be under adrenergic control. 2 Another explanation would be the early stage of the disease in our patient, with not all sweat glands already being involved.The possibility that the CD3 cells might be directed to some parts of the eccrine sweat gland itself has to be considered as well.In cases of progressive hypohidrosis/anhidrosis with no other pathologic findings, the diagnosis of AIGA should be considered.In most cases, steroid pulse therapy is effective.

Hypohidrosis and anhidrosis can be caused by various diseases.Diabetes mellitus, Sjo ¨gren syndrome, pure autonomic failure, Fabry disease, Ross syndrome, thyroid dysfunction, paraneoplastic autonomic dysfunction, and congenital absence of sweat glands are possible diagnoses. 1 A less common cause of hypohidrosis/anhidrosis is the acquired idiopathic generalized anhidrosis (AIGA).Until now, 64 cases of AIGA have been reported, 62 being Japanese. 2 We here report a European patient with AIGA.Case report.A 39-year-old white man presented with a 6-month history of progressive heat intolerance and lack of sweating except for the axillary zone and parts of his face.The patient also reported tachycardia and general fatigue.He had no history of dry mouth, dry eyes, concomitant sharp pain, or urticaria.The patient's history and family history were unremarkable.The patient did not take any medications.Physical and neurologic examination including autonomic functional tests (heart rate variability, Valsalva maneuver, respiratory sinus arrhythmia, tilt table test) were normal.Axon reflex testing was not performed.The thermoregulatory as well as the pilocarpine sweating tests showed anhidrosis except for the axillary and periorbital zones (figure ,A).Cranial MRI, chest radiograph, and various laboratory tests (including anti-GM1 and anti-GQ1B antibodies, IgE level) revealed normal findings.A skin biopsy specimen from the sternum showed infiltration of sweat glands by CD3-positive lymphocytes (figure, C).Acquired idiopathic generalized anhidrosis was diagnosed, and methylprednisolone was administered (1,000 mg/day for 3 days IV followed by tapering oral doses for 2 weeks).One week after therapy initiation, the patient's sweat production improved.Two months later, the thermoregulatory sweating test was normal (figure, B).A repeated skin biopsy revealed no more CD3-positive lymphocyte infiltration (figure, D).Discussion.AIGA is an uncommon cause of hypohidrosis/ anhidrosis.Most of the reported cases were from Japan.Clinical features of AIGA are an acute or sudden onset of generalized anhidrosis with an onset early in life, the absence of other autonomic dysfunction, and a marked response to glucocorticoids.Concomitant sharp pain or cholinergic urticaria and elevated IgE levels have also been described in the majority of patients.These features were absent in our patient; however, the marked response to glucocorticoids and the histopathologic findings strongly support the diagnosis of AIGA.There are three subgroups of AIGA 1 : The idiopathic pure sudomotoric failure (IPSF), sudomotoric neuropathy, and sweat gland failure.Most cases of AIGA seem to represent IPSF, as in the case of our patient.Typical histopathologic findings here include CD3positive lymphocyte infiltrations of the sweat glands 3 and occlusion of proximal coiled ducts, 4 whereas CD3-positive lymphocyte infiltration seems to be a hallmark of IPSF.Although the etiology of AIGA is still unclear, immunologic mechanisms contribute to the disease.The facts that IPSF as a subgroup of AIGA is associated with CD3-positive lymphocyte infiltration of sweat glands and that CD3 plays an important role in the induction of cellmediated disorders support this hypothesis.This may also explain the improvement in sweat function with corticosteroids in 78% of patients with AIGA. 2 A deficit in the muscarinic cholinergic receptor in eccrine sweat glands or interference in transmission of acetylcholine to cholinergic receptors is supposed to be involved in the pathogenesis of IPSP.This might explain the persisting sweat production of the axilla, as seen in our patient.Sweat glands of the axilla are apocrine glands and are supposed to be under adrenergic control. 2 Another explanation would be the early stage of the disease in our patient, with not all sweat glands already being involved.The possibility that the CD3 cells might be directed to some parts of the eccrine sweat gland itself has to be considered as well.In cases of progressive hypohidrosis/anhidrosis with no other pathologic findings, the diagnosis of AIGA should be considered.In most cases, steroid pulse therapy is effective.

Hypohidrosis and anhidrosis can be caused by various diseases.Diabetes mellitus, Sjo ¨gren syndrome, pure autonomic failure, Fabry disease, Ross syndrome, thyroid dysfunction, paraneoplastic autonomic dysfunction, and congenital absence of sweat glands are possible diagnoses. 1 A less common cause of hypohidrosis/anhidrosis is the acquired idiopathic generalized anhidrosis (AIGA).Until now, 64 cases of AIGA have been reported, 62 being Japanese. 2 We here report a European patient with AIGA.Case report.A 39-year-old white man presented with a 6-month history of progressive heat intolerance and lack of sweating except for the axillary zone and parts of his face.The patient also reported tachycardia and general fatigue.He had no history of dry mouth, dry eyes, concomitant sharp pain, or urticaria.The patient's history and family history were unremarkable.The patient did not take any medications.Physical and neurologic examination including autonomic functional tests (heart rate variability, Valsalva maneuver, respiratory sinus arrhythmia, tilt table test) were normal.Axon reflex testing was not performed.The thermoregulatory as well as the pilocarpine sweating tests showed anhidrosis except for the axillary and periorbital zones (figure ,A).Cranial MRI, chest radiograph, and various laboratory tests (including anti-GM1 and anti-GQ1B antibodies, IgE level) revealed normal findings.A skin biopsy specimen from the sternum showed infiltration of sweat glands by CD3-positive lymphocytes (figure, C).Acquired idiopathic generalized anhidrosis was diagnosed, and methylprednisolone was administered (1,000 mg/day for 3 days IV followed by tapering oral doses for 2 weeks).One week after therapy initiation, the patient's sweat production improved.Two months later, the thermoregulatory sweating test was normal (figure, B).A repeated skin biopsy revealed no more CD3-positive lymphocyte infiltration (figure, D).Discussion.AIGA is an uncommon cause of hypohidrosis/ anhidrosis.Most of the reported cases were from Japan.Clinical features of AIGA are an acute or sudden onset of generalized anhidrosis with an onset early in life, the absence of other autonomic dysfunction, and a marked response to glucocorticoids.Concomitant sharp pain or cholinergic urticaria and elevated IgE levels have also been described in the majority of patients.These features were absent in our patient; however, the marked response to glucocorticoids and the histopathologic findings strongly support the diagnosis of AIGA.There are three subgroups of AIGA 1 : The idiopathic pure sudomotoric failure (IPSF), sudomotoric neuropathy, and sweat gland failure.Most cases of AIGA seem to represent IPSF, as in the case of our patient.Typical histopathologic findings here include CD3positive lymphocyte infiltrations of the sweat glands 3 and occlusion of proximal coiled ducts, 4 whereas CD3-positive lymphocyte infiltration seems to be a hallmark of IPSF.Although the etiology of AIGA is still unclear, immunologic mechanisms contribute to the disease.The facts that IPSF as a subgroup of AIGA is associated with CD3-positive lymphocyte infiltration of sweat glands and that CD3 plays an important role in the induction of cellmediated disorders support this hypothesis.This may also explain the improvement in sweat function with corticosteroids in 78% of patients with AIGA. 2 A deficit in the muscarinic cholinergic receptor in eccrine sweat glands or interference in transmission of acetylcholine to cholinergic receptors is supposed to be involved in the pathogenesis of IPSP.This might explain the persisting sweat production of the axilla, as seen in our patient.Sweat glands of the axilla are apocrine glands and are supposed to be under adrenergic control. 2 Another explanation would be the early stage of the disease in our patient, with not all sweat glands already being involved.The possibility that the CD3 cells might be directed to some parts of the eccrine sweat gland itself has to be considered as well.In cases of progressive hypohidrosis/anhidrosis with no other pathologic findings, the diagnosis of AIGA should be considered.In most cases, steroid pulse therapy is effective.

Hintergrund: Leukozyten-Thrombozyten Aggregate spiegeln Thrombozytenaktivierung und einen prothrombotischen Zustand wieder. Dieser Parameter ist in Zusammenhang mit akuten zerebralen ischämischen Ereignissen bislang nicht untersucht worden.

Aims: Hypohidrosis/Anhidrosis can be caused by various aetiological factors. A less common cause of hypohidrosis/anhidrosis is the acquired generalized anhidrosis (AIGA). Until now, 64 cases of AIGA have been reported with 62 being identified in Japan. We report about the first European case of AIGA where the patient had no other associated disease.