[Polypharmacy in patients with dementia]. / Polypharmazie bei Demenzerkrankten.

The number of patients with dementia is expected to grow in the coming years due to an aging population and an increasing life-expectancy. At the same time, in an aging society there will be an increase in multimorbidity and therefore polypharmacy. This combination presents numerous challenges particularly for people with dementia, as the correct administration of the drugs can frequently no longer be guaranteed. The drug treatment of neuropsychiatric symptoms of dementia are often treated with antipsychotics with potentially severe side effects and with limited efficacy. Moreover, many drugs have an anticholinergic potential, which may worsen the cognitive function even further in patients with dementia. The use of anticholinergic drugs should be handled with care and when possible be avoided in patients with dementia.

Analysis of Frailty in Geriatric Patients as a Prognostic Factor in Endovascular Treated Patients with Large Vessel Occlusion Strokes.

Frailty is associated with an increased risk of adverse health-care outcomes in elderly patients. The Hospital Frailty Risk Score (HFRS) has been developed and proven to be capable of identifying patients which are at high risk of adverse outcomes. We aimed to investigate whether frail patients also face adverse outcomes after experiencing an endovascular treated large vessel occlusion stroke (LVOS). In this retrospective observational cohort study, we analyzed patients ≥ 65 years that were admitted during 2015-2019 with LVOS and endovascular treatment. Primary outcomes were mortality and the modified Rankin Scale (mRS) after three months. Regression models were used to determine the impact of frailty. A total of 318 patients were included in the cohort. The median HFRS was 1.6 (IQR 4.8). A total of 238 (75.1%) patients fulfilled the criteria for a low-frailty risk with a HFRS < 5.72 (22.7%) for moderate-frailty risk with an HFRS from 5-15 and 7 (2.2%) patients for a high-frailty risk. Multivariate regression analyses revealed that the HFRS was associated with an increased mortality after 90 days (CI (95%) 1.001 to 1.236; OR 1.112) and a worse mRS (CI (95%) 1.004 to 1.270; OR 1.129). We identified frailty as an impact factor on functional outcome and mortality in patients undergoing thrombectomy in LVOS.

Comparing the diagnostic value of Echocardiography In Stroke (CEIS) - results of a prospective observatory cohort study.

BACKGROUND: Echocardiography is one of the main diagnostic tools for the diagnostic workup of stroke and is already well integrated into the clinical workup. However, the value of transthoracic vs. transesophageal echocardiography (TTE/TEE) in stroke patients is still a matter of debate. Aim of this study was to characterize relevant findings of TTE and TEE in the management of stroke patients and to correlate them with subsequent clinical decisions and therapies. METHODS: We evaluated n = 107 patients admitted with an ischemic stroke or transient ischemic attack to our stroke unit of our university medical center. They underwent TTE and TEE examination by different blinded investigators. RESULTS: Major cardiac risk factors were found in 8 of 98 (8.2%) patients and minor cardiac risk factors for stroke were found in 108 cases. We found a change in therapeutic regime after TTE or TEE in 22 (22.5%) cases, in 5 (5%) cases TEE leads to the change of therapeutic regime, in 4 (4%) TTE and in 13 cases (13.3%) TTE and TEE lead to the same change in therapeutic regime. The major therapy change was the indication to close a patent foramen ovale (PFO) in 9 (9.2%) patients with TTE and in 10 (10.2%) patients with TEE (p = 1.000). CONCLUSION: Major finding with clinical impact on therapy change is the detection of PFO. But for the detection of PFO, TTE is non inferior to TEE, implicating that TTE serves as a good screening tool for detection of PFO, especially in young age patients. TRIAL REGISTRATION: The trial was registered and approved prior to inclusion by our local ethics committee (1/3/17).

The Retrobulbar Spot Sign and Prominent Middle Limiting Membrane as Prognostic Markers in Non-Arteritic Retinal Artery Occlusion.

Central retinal artery occlusion (CRAO) is characterized by the sudden, painless loss of vision. Typical sonographic and optic coherence tomography (OCT) findings are a retrobulbar spot sign and prominent middle limiting membrane (p-MLM) sign. It remains uncertain whether the retrobulbar spot sign alone or coinciding with the appearance of p-MLM sign is a prognostic marker for visual acuity and the development of secondary retinal ischemia after CRAO. In our prospective cohort study, we included patients with a non-arteritic central artery occlusion < 4 weeks. We examined the following parameters at prespecified time points: ultrasound examination of orbital cavity, Spectral Domain-OCT examination, visual acuity test, and fundoscopy and ultra-widefield angiography to diagnose retinal vascularization. The presence of p-MLM sign in SD-OCT after CRAO was accompanied by significantly better vision during the first four weeks (2.3 (IQR 0.75) vs. 2.6 (IQR 0.33); p = 0.006). Moreover, the spot sign seems to be a prognostic factor for developing secondary retinal ischemia (8 (100%) vs. 0 (0%); p = 0.036). A retrobulbar spot sign seems to be a negative prognostic factor and is associated with secondary retinal ischemia, whereas a p-MLM sign is a somewhat positive prognostic factor for visual acuity.

Bridging therapy is associated with improved cognitive function after large vessel occlusion stroke - an analysis of the German Stroke Registry.

BACKGROUND: The targeted use of endovascular therapy (EVT), with or without intravenous thrombolysis (IVT) in acute large cerebral vessel occlusion stroke (LVOS) has been proven to be superior compared to IVT alone. Despite favorable functional outcome, many patients complain about cognitive decline after EVT. If IVT in addition to EVT has positive effects on cognitive function is unclear. METHODS: We analyzed data from the German Stroke Registry (GSR, an open, multicenter and prospective observational study) and compared cognitive function 90 days after index ischemic stroke using MoCA in patients with independent (mRS ≤ 2 pts) and excellent (mRS = 0 pts) functional outcome receiving combined EVT and IVT (EVT + IVT) vs. EVT alone (EVT-IVT). RESULTS: Of the 2636 GSR patients, we included 166 patients with mRS ≤ 2 at 90 days in our analysis. Of these, 103 patients (62%) received EVT + IVT, 63 patients (38%) were treated with EVT alone. There was no difference in reperfusion status between groups (mTICI ≥ 2b in both groups at 95%, p = 0.65). Median MoCA score in the EVT + IVT group was 20 pts. (18-25 IQR) vs. 18 pts. (16-21 IQR) in the EVT-IVT group (p = 0.014). There were more patients with cognitive impairment (defined as MoCA < 26 pts) in the EVT-IVT group (54 patients (86%)) compared to the EVT + IVT group (78 patients (76%)). EVT + IVT was associated with a higher MoCA score at 90 days (mRS ≤ 2: p = 0.033, B = 2.39; mRS = 0: p = 0.021, B = 4.38). CONCLUSIONS: In Patients with good functional outcome after LVOS, rates of cognitive impairment are lower with combined EVT and IVT compared to EVT alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03356392.

One-Stop Management of 230 Consecutive Acute Stroke Patients: Report of Procedural Times and Clinical Outcome.

BACKGROUND AND PURPOSE: Rapid thrombectomy for acute ischemic stroke caused by large vessel occlusion leads to improved outcome. Optimizing intrahospital management might diminish treatment delays. To examine if one-stop management reduces intrahospital treatment delays and improves functional outcome of acute stroke patients with large vessel occlusion. METHODS: We performed a single center, observational study from June 2016 to November 2018. Imaging was acquired with the latest generation angiography suite at a comprehensive stroke center. Two-hundred-thirty consecutive adults with suspected acute stroke presenting within 6 h after symptom onset with a moderate to severe National Institutes of Health Stroke Scale (≥10 in 2016; ≥7 since January 2017) were directly transported to the angiography suite by bypassing multidetector CT. Noncontrast flat-detector CT and biphasic flat-detector CT angiography were acquired with an angiography system. In case of a large vessel occlusion patients remained in the angiography suite, received intravenous rtPA therapy and underwent thrombectomy. As primary endpoints, door-to-reperfusion times and functional outcome at 90 days were recorded and compared in a case-control analysis with matched prior patients receiving standard management. RESULTS: A total of 230 patients (123 women, median age of 78 years (Interquartile Range (IQR) 69-84)) were included. Median symptom-to-door time was 130 min (IQR 70-195). Large vessel occlusion was diagnosed in 166/230 (72%) patients; 64/230 (28%) had conditions not suitable for thrombectomy. Median door-to-reperfusion time for M1 occlusions was 64 min (IQR 56-87). Compared to 43 case-matched patients triaged with multidetector CT, median door-to-reperfusion time was reduced from 102 (IQR 85-117) to 68 min (IQR 53-89; p < 0.001). Rate of good functional outcome was significantly better in the one-stop management group (p = 0.029). Safety parameters (mortality, sICH, any hemorrhage) did not differ significantly between groups. CONCLUSIONS: One-stop management for stroke triage reduces intrahospital time delays in our specific hospital setting.

Heart Failure Is Not Associated with a Poor Outcome after Mechanical Thrombectomy in Large Vessel Occlusion of Cerebral Arteries.

The impact of heart failure on outcome in stroke patients is not fully understood. There is evidence for an increased mortality and morbidity, but it remains uncertain whether thrombectomy in patients with large vessel occlusion (LVO) in the anterior circulation is less effective in patients with heart failure compared to patients without. Retrospectively, we analyzed echocardiographic data of all patients in our stroke database, who underwent mechanical thrombectomy (n=668) for the presence of heart failure. Furthermore, we collected baseline characteristics and neurological and neuroradiological parameters. In the analysis, 373 of the 668 patients of our stroke database underwent echocardiography. Of these 373 patients, 90 patients (24%) suffered from heart failure with reduced left ventricular ejection fraction measured by echocardiography according to the current guidelines. After adjustment for age, the Alberta stroke program early CT score (ASPECTS), and time from symptom onset to recanalization, the analysis revealed that thrombectomy in patients with heart failure and LVO is not associated with less favorable outcome measured by the modified Rankin Scale after 90 days (3 (0-6) vs. 3 (1-5); p=0.380). Moreover, we could not find a significant difference in mortality compared to patients without heart failure (11.0% vs. 7.4%; p=0.313).

Clot reduction prior to embolectomy: mSAVE as a first-line technique for large clots.

INTRODUCTION: The "Stent retriever Assisted Vacuum-locked Extraction" (SAVE) technique is a promising embolectomy method for intracranial large vessel occlusion (LVO). We report our experience using a modified SAVE (mSAVE) approach for clot reduction prior to embolectomy in acute ischemic stroke patients with large clots. MATERIALS AND METHODS: We retrospectively analyzed 20 consecutive patients undergoing mSAVE in our center due to intracranial LVO. Angiographic data (including first-pass and overall complete reperfusion, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 3, rate of successful reperfusion (eTICI ≥2c), number of passes, time from groin puncture to reperfusion) and clinical data (favorable outcome at 90 days, defined as modified Rankin Scale (mRS) ≤2) were assessed. RESULTS: First-pass and overall eTICI 3 reperfusion was reached in 13/20 (65%) and 14/20 (70%), respectively. The rate of successful reperfusion (eTICI ≥2c) after one pass was 85% and on final angiogram 90% with an average number of 1.1 ± 0.3 attempts. Eight out of 11 (73%) ICA occlusions were reperfused successfully and 5 (46%) completely after a single pass. Median groin to reperfusion time was 33 minutes (IQR 25-46). A favorable clinical outcome was achieved in 9/20 (45%) patients at discharge and after 90 days, respectively. CONCLUSION: Clot reduction followed by embolectomy (mSAVE) is feasible and may be an important tool in the treatment of large clots.

Low flow in the left atrial appendage assessed by transesophageal echocardiography is associated with increased stroke severity-Results of a single-center cross-sectional study.

BACKGROUND: About 25% of strokes are thought to be cryptogenic. There is growing evidence that most of these cryptogenic strokes are thromboembolic and caused by an undetected atrial fibrillation. Measured slow flow in the left atrial appendage has been proposed to be an indicator for the thromboembolic risk since it is possibly associated with undetected atrial fibrillation. METHODS: We evaluated all patients (n = 909; mean of 62 years, 39% female) admitted with an ischemic stroke (84%) or transient ischemic attack to our university medical center who underwent transesophageal echocardiography examination 2012-2014. Baseline characteristics, cardio-/neurovascular risk factors, electrocardiogram monitoring data, National Institute of Health Stroke Scale values, the localization of the stroke, as well as transesophageal echocardiography findings were analyzed. RESULTS: Stroke severity measured by the National Institute of Health Stroke Scale in patients with a low flow in the left atrial appendage was significantly higher than in patients without left atrial appendage low flow (p < 0.001). There was a threshold phenomenon in flow velocity at about 60 cm/s above which no significant change in National Institute of Health Stroke Scale values could be observed. These patients were significantly different concerning incidence of heart failure (10.6% vs. 2.3%; p < 0.001) and atrial fibrillation (32.2% vs. 8.8%; p < 0.001). However, threshold phenomenon of left atrial appendage flow was unchanged when excluding atrial fibrillation and heart failure patients. CONCLUSIONS: A low flow in the left atrial appendage was associated with clinically elevated stroke severity and could be indicated as an independent stroke risk factor. Further prospective studies are warranted to evaluate beneficial effects of therapeutic options in these patients also in the assumed absence of atrial fibrillation.

Outcome Prediction Using Perfusion Parameters and Collateral Scores of Multi-Phase and Single-Phase CT Angiography in Acute Stroke: Need for One, Two, Three, or Thirty Scans?

BACKGROUND AND PURPOSE: Collateral status is an important factor determining outcome in acute ischemic stroke (AIS). Hence, different collateral scoring systems have been introduced. We applied different scoring systems on single- and multi-phase computed tomography (CT) angiography (spCTA and mpCTA) and compared them to CT perfusion (CTP) parameters to identify the best method for collateral evaluation in patients with AIS. METHODS: A total of 102 patients with AIS due to large vessel occlusion in the anterior circulation who underwent multimodal CT imaging and who were treated endovascularly were included. Collateral status was assessed on spCTA and mpCTA using four different scoring systems and compared to CTP parameters. Logistic regression was performed for predicting favorable outcome. RESULTS: All collateral scores correlated well with each other and with CTP parameters. Comparison of collateral scores stratified by extent of perfusion deficit showed relevant differences between groups (P<0.01 for each). An spCTA collateral score discriminated best between favorable and unfavorable outcome as determined using the modified Rankin Scale 3 months after stroke. CONCLUSION: s Collateral status evaluated on spCTA may suffice for outcome prediction and decision making in AIS patients, potentially obviating further imaging modalities like mpCTA or CTP.

Influence of beta-blocker therapy on the risk of infections and death in patients at high risk for stroke induced immunodepression.

BACKGROUND: Stroke-induced immunodepression is a well characterized complication of acute ischemic stroke. In experimental studies beta-blocker therapy reversed stroke-induced immunodepression, reduced infection rates and mortality. Recent, heterogeneous studies in stroke patients could not provide evidence of a protective effect of beta-blocker therapy. Aim of this study is to investigate the potential preventive effect of beta-blockers in subgroups of patients at high risk for stroke-induced immunodepression. METHODS: Data from a prospectively derived registry of major stroke patients receiving endovascular therapy between 2011-2017 in a tertiary stroke center (University Medical Center Göttingen. Germany) was used. The effect of beta-blocker therapy on pneumonia, urinary tract infection, sepsis and mortality was assessed using multivariate logistic regression analysis. RESULTS: Three hundred six patients with a mean age of 72 ± 13 years and a median NIHSS of 16 (IQR 10.75-20) were included. 158 patients (51.6%) had pre-stroke- and continued beta-blocker therapy. Beta-blocker therapy did not reduce the incidence of pneumonia (OR 0.78, 95% CI 0.31-1.92, p = 0.584), urinary tract infections (OR 1.51, 0.88-2.60, p = 0.135), sepsis (OR 0.57, 0.18-1.80, p = 0.334) or mortality (OR 0.59, 0.16-2.17, p = 0.429). Strokes involving the insula and anterio-medial cortex increased the risk for pneumonia (OR 4.55, 2.41-8.56, p<0.001) and sepsis (OR 4.13, 1.81-9.43, p = 0.001), while right hemispheric strokes increased the risk for pneumonia (OR 1.60, 0.92-2.77, p = 0.096). There was a non-significantly increased risk for urinary tract infections in patients with beta-blocker therapy and insula/anterio-medial cortex strokes (OR 3.12, 95% CI 0.88-11.05, p = 0.077) with no effect of beta-blocker therapy on pneumonia, sepsis or mortality in both subgroups. CONCLUSIONS: In major ischemic stroke patients, beta-blocker therapy did not lower post-stroke infection rates and was associated with urinary tract infections in a subgroup with insula/anterio-medial strokes.

Clinical Relevance of Patent Foramen Ovale and Atrial Septum Aneurysm in Stroke: Findings of a Single-Center Cross-Sectional Study.

BACKGROUND: A significant proportion of ischemic strokes are cryptogenic. In this context, the clinical pertinence of patent foramen ovale (PFO) with and without atrial septum aneurysm (ASA) remains controversial. The aim of this study was to identify how PFO +/-ASA and cryptogenic stroke are associated in a representative sample of stroke patients. METHODS: We enrolled all patients (n = 909) with ischemic stroke or transient ischemic attack admitted to the certified stroke unit or neurological intensive care unit of our university medical center who underwent transesophageal echocardiography (TEE) between 2012 and 2014. The baseline characteristics, cardio-/neurovascular risk factors, clinical parameters and TEE findings were analyzed. RESULTS: PFO was present in 26.2%, and PFO was combined with an ASA in 9.9%. In cryptogenic stroke, the prevalence of PFO was higher compared to other etiologies (30.9 vs. 21.9%; p < 0.002). Patients with PFO had lower National Institute of Health Stroke Score (NIHSS) values at admission than those without (2 [0-5] vs. 3 [1-7]; p = 0.001; 95% CI [0.62-0.88]). No difference was found in NIHSS values of PFO patients with or without ASA (2 [0-5] vs. 2 [0-5]; p = 0.683; 95% CI 0.94 [0.68-1.28]). CONCLUSIONS: Our study indicates that a detected PFO +/-ASA could exhibit a stroke-relevant finding, if classical risk factors for the stroke were lacking.

Early computed tomography-based scores to predict decompressive hemicraniectomy after endovascular therapy in acute ischemic stroke.

BACKGROUND: Identification of patients requiring decompressive hemicraniectomy (DH) after endovascular therapy (EVT) is crucial as clinical signs are not reliable and early DH has been shown to improve clinical outcome. The aim of our study was to identify imaging-based scores to predict the risk for space occupying ischemic stroke and DH. METHODS: Prospectively derived data from patients with acute large artery occlusion within the anterior circulation and EVT was analyzed in this monocentric study. Predictive value of non-contrast cranial computed tomography (ncCT) and cerebral blood volume (CBV) Alberta Stroke Program Early CT score (ASPECTS) were investigated for DH using logistic regression models and Receiver Operating Characteristic Curve analysis. RESULTS: From 218 patients with EVT, DH was performed in 20 patients (9.2%). Baseline- (7 vs. 9; p = 0.009) and follow-up ncCT ASPECTS (1 vs. 7, p<0.001) as well as baseline CBV ASPECTS (5 vs. 7, p<0.001) were significantly lower in patients with DH. ncCT (baseline: OR 0.71, p = 0.018; follow-up: OR 0.32, p = <0.001) and CBV ASPECTS (OR 0.63, p = 0.008) predicted DH. Cut-off ncCT-ASPECTS on baseline was 7-, ncCT-ASPECTS on follow-up was 4- and CBV ASPECTS on baseline was 5 points. CONCLUSIONS: ASPECTS could be useful to early identify patients requiring DH after EVT for acute large vessel occlusion.

Bridging-therapy with intravenous recombinant tissue plasminogen activator improves functional outcome in patients with endovascular treatment in acute stroke.

BACKGROUND: Although endovascular treatment for proximal cerebral vessel occlusion is very effective, it remains controversial if intravenous thrombolysis (IVT) prior to endovascular treatment is superior compared to endovascular treatment alone. In this study we compared functional outcomes and recanalization rates of endovascularly treated stroke patients with and without bridging IVT. METHODS: Patients with acute large artery occlusion within the anterior and posterior cerebral circulation eligible for intraarterial revascularization with and without prior IVT were included in this monocentric, prospective observational study. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) were determined at baseline, discharge and 90-days follow up after stroke. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3. RESULTS: Of the 109 patients included, 81 (74%) received bridging therapy with i.v.-rtPA prior to endovascular treatment, 28 (26%) received endovascular treatment alone. There was no difference in groin-to-reperfusion time between the groups (54 vs 50min; p=0.657), but a trend towards a higher reperfusion rate in patients with bridging therapy (69 vs 15 patients, p=0.099). Mean improvement of the NIHSS during hospitalization was 8 points (SD; ±8) in the bridging-group and 2 points (SD, ±7) in the non-bridging-group (p=0.001). Number of patients with discharge mRS 0-2 (34 vs 5; p=0.024) and 90-days mRS 0-2 (35 vs 6; p=0.061) was higher in the bridging-group compared to the non-bridging-group. CONCLUSIONS: This study provides evidence that bridging therapy with i.v.-rtPA improves functional outcome in patients eligible for endovascular treatment. Further studies are needed to confirm our findings and to identify patients most likely benefitting from bridging therapy.

BAG1 is neuroprotective in in vivo and in vitro models of Parkinson's disease.

Bcl-2-associated athanogene-1 (BAG1) is a multifunctional protein comprising co-chaperone function, increasing Hsp70 foldase activity and chaperone-dependent protein degradation of misfolded substrates, with anti-apoptotic activity. It is neuroprotective in different models of neurological diseases, like cerebral ischemia and Huntington's disease. In the context of Parkinson's disease, it has recently been shown to restore DJ-1 function in an in vitro model of hereditary Parkinson's disease. Here, we demonstrate that BAG1 overexpression in SH-SY5Y cells reduces toxicity after transfection of disease-related α-synuclein mutants. Furthermore, it protects from rotenone-induced cell death in vitro and ameliorates neuronal demise in an in vivo 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) model for Parkinson's disease after adeno-associated virus (AAV)-mediated BAG1 gene transfer into the substantia nigra in mice but showed no protective effects in an in vitro 6-hydroxidopamine model. In conclusion, we present BAG1 as a potential therapeutic target in Parkinson's disease.