High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.

Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

Apixaban versus Aspirin for Embolic StrokeIn a trial of 352 patients with embolic stroke of undetermined source, 5 mg of apixaban administered twice daily was compared with 100 mg of aspirin administered once daily for the prevention of recurrent ischemic strokes. At 12 months, 13.6% of patients given apixaban had new ischemic lesions on magnetic resonance imaging compared with 16.0% of patients given aspirin, and the rates of clinically relevant bleeding were also comparable.

KCNA2 IgG autoimmunity in neuropsychiatric diseases.

BACKGROUND: Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice. DESIGN / METHODS: We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses. RESULTS: KCNA2 autoantibody-positive patients (n = 35, median age at disease onset of 65 years, range of 16-83 years, 74 % male) mostly presented with cognitive impairment and/or epileptic seizures but also ataxia, gait disorder and personality changes. Serum autoantibodies belonged to IgG3 and IgG1 subclasses and titers ranged from 1:32 to 1:10,000. KCNA2 IgG was found in the CSF of 8/21 (38 %) patients and in the serum of 4/96 (4.2 %) healthy blood donors. KCNA2 autoantibodies bound to characteristic anatomical areas in the cerebellum and hippocampus of mammalian brain and juxtaparanodal regions of peripheral nerves but reacted exclusively with intracellular epitopes. A subset of four KCNA2 autoantibody-positive patients responded markedly to immunotherapy alongside with conversion to seronegativity, in particular those presenting an autoimmune encephalitis phenotype and receiving early immunotherapy. An available brain biopsy showed strong immune cell invasion. KCNA2 autoantibodies occurred in less than 10 % in association with an underlying tumor. CONCLUSION: Our data suggest that KCNA2 autoimmunity is clinically heterogeneous. Future studies should determine whether KCNA2 autoantibodies are directly pathogenic or develop secondarily. Early immunotherapy should be considered, in particular if autoantibodies occur in CSF or if clinical or diagnostic findings suggest ongoing inflammation. Suspicious clinical phenotypes include autoimmune encephalitis, atypical dementia, new-onset epilepsy and unexplained epileptic seizures.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

No evidence for neuronal damage or astrocytic activation in cerebrospinal fluid of Neuro-COVID-19 patients with long-term persistent headache.

Headache is one of the most common neurological manifestations of COVID-19, but it is unclear whether chronic headache as a symptom of Post-COVID-19 is associated with ongoing CNS damage. We compared cerebrospinal fluid (CSF) levels of markers of CNS damage and inflammation in Post-COVID-19 patients with persistent headache to hospitalized acute COVID-19 patients with neurological symptoms and to non-COVID-19 disease-controls. CSF levels of neurofilament light chain, Ubiquitin carboxyl-terminal hydrolase L1 and Tau were similar in patients with persistent headache in post-COVID-19 compared to acute COVID-19 patients and all control groups. Levels of glial fibrillary astrocytic protein were lower in patients with persistent headache in post-COVID-19 compared to some control groups of patients with neurological disease. Therefore, our pilot study of CSF markers indicates that persistent post-COVID-19 headache is not a sign of underlying neuronal damage or glial activation.

Clinical significance and prevalence of subarachnoid hyperdensities on flat detector CT after mechanical thrombectomy: does it really matter?

BACKGROUND: Subarachnoid hyperdensities after mechanical thrombectomy (MT) are a common finding. However, it is often regarded as clinically insignificant. OBJECTIVE: With this single-center investigation, to identify the prevalence of subarachnoid hyperdensities following MT, associated predictors, and the impact on the clinical outcome of the patients. METHODS: 383 patients from the stroke registry were analyzed for the presence of subarachnoid hyperdensities on flat detector CT (FDCT) directly after the completion of MT, and on follow-up dual-energy CT, then classified according to a visual grading scale. 178 patients were included with anterior circulation occlusions. Regression analysis was performed to identify significant predictors, and Kruskal-Wallis analysis and Χ2 test were performed to test the variables among the different groups. The primary outcome was the modified Rankin Scale (mRS) score at 90 days and was analyzed with the Wilcoxon-Mann-Whitney rank-sum test. RESULTS: The prevalence of subarachnoid hyperdensities on FDCT was (66/178, 37.1%) with patients experiencing a significant unfavorable outcome (P=0.035). Significantly fewer patients with subarachnoid hyperdensities achieved a mRS score of ≤3 at 90 days 25/66 (37.9%) vs 60/112 (53.6%), P=0.043). In addition, mortality was significantly higher in the subarachnoid hyperdensities group (34.8% vs 19.6%, P=0.024). Distal occlusions and a higher number of device passes were significantly associated with subarachnoid hyperdensities (P=0.026) and (P=0.001), respectively. Patients who received intravenous tissue plasminogen activator had significantly fewer subarachnoid hyperdensities (P=0.029). CONCLUSIONS: Postinterventional subarachnoid hyperdensities are a frequent finding after MT and are associated with neurological decline and worse functional outcome. They are more common with distal occlusions and multiple device passes.

Derivation and validation of a screening tool for stroke-associated sepsis.

BACKGROUND: Post-stroke infections may cause sepsis, which is associated with poor clinical outcome. Sepsis is defined by life-threatening organ dysfunction that can be identified using the Sequential Organ Failure Assessment (SOFA) score. The applicability of the SOFA score for patients not treated on an intensive care unit (ICU) is limited. The aim of this study was to develop and validate an easier-to-use modification of the SOFA score for stroke patients. METHODS: Using a registry-based cohort of 212 patients with large vessel occlusion stroke and infection, potential predictors of a poor outcome indicating sepsis were assessed by logistic regression. The derived score was validated on a separate cohort of 391 patients with ischemic stroke and infection admitted to our hospital over a period of 1.5 years. RESULTS: The derived Stroke-SOFA (S-SOFA) score included the following predictors: National Institutes of Health stroke scale ≥ 14, peripheral oxygen saturation < 90%, mean arterial pressure < 70 mmHg, thrombocyte count < 150 109/l and creatinine ≥ 1.2 mg/dl. The area under the receiver operating curve for the prediction of a poor outcome indicating sepsis was 0.713 [95% confidence interval: 0.665-0.762] for the S-SOFA score, which was comparable to the standard SOFA score (0.750 [0.703-0.798]), but the prespecified criteria for non-inferiority were not met (p = 0.115). However, the S-SOFA score was non-inferior compared to the SOFA score in non-ICU patients (p = 0.013). CONCLUSIONS: The derived S-SOFA score may be useful to identify non-ICU patients with stroke-associated sepsis who have a high risk of a poor outcome.

Independent and additive contribution of white matter hyperintensities and Alzheimer's disease pathology to basal forebrain cholinergic system degeneration.

OBJECTIVES: Degeneration of the cholinergic basal forebrain nuclei (CBFN) system has been studied extensively in Alzheimer's disease (AD). White matter hyperintensities are a hallmark of aging as well as a common co-morbidity of AD, but their contribution to CBFN degeneration has remained unclear. Therefore, we explored the influence of white matter hyperintensities within cholinergic subcortical-cortical projection pathways on CBFN volumes and regional gray matter volumes in AD and age- and gender-matched controls. METHODS: We analyzed magnetic resonance images (MRI) from 42 patients with AD and 87 age- and gender-matched control subjects. We assessed the white matter hyperintensity burden within the cholinergic projection pathways using the Cholinergic Pathways Hyperintensities Scale (CHIPS), and applied probabilistic anatomical maps for the analysis of CBFN volumes, i.e. the Ch1-3 compartment and the Ch4 cell group (nucleus basalis of Meynert), by diffeomorphic anatomical registration using exponentiated lie algebra analysis of voxel-based morphometry. Using multiple linear regression analyses, we explored correlations between regional gray matter volumes and the extent of white matter hyperintensities or CBFN volumes in both groups. RESULTS: In AD, all CBFN volumes were significantly smaller than in controls, and white matter hyperintensity burden within the cholinergic projection pathways was not correlated with CBFN volume. In controls, white matter hyperintensity burden within the cholinergic projection pathways was inversely correlated with CBFN volume when corrected for sex and total intracranial volume, but this correlation was no longer significant after correction for age. Voxel-wise multiple linear regression analyses using threshold-free cluster enhancement revealed that in controls, cholinergic pathway hyperintensities correlated with gray matter loss in perisylvian areas, whereas the were no effects in AD. Moreover, we found that CBFN volumes correlated with distinct regional cortical atrophy patterns in both groups. CONCLUSION: Our results indicate that white matter hyperintensities and AD pathology contribute independently but additively to the degeneration of cholinergic basal forebrain structures. Whereas AD is primarily associated with CBFN volume loss, cholinergic degeneration associated with white matter hyperintensities appears to involve disruption of cholinergic cortical projection fibers with less pronounced effects on CBFN volumes.

Additive prognostic impact of the cerebrospinal fluid arginine/ornithine ratio to established clinical scores in aneurysmal subarachnoid hemorrhage.

Cerebrospinal fluid (CSF) metabolites are increasingly recognized as prognostic factors in aneurysmal subarachnoid hemorrhage (SAH). The CSF arginine/ornithine ratio (Arg/Orn) was shown to predict cerebral vasospasms and clinical outcome in SAH. The additive prognostic value of Arg/Orn over established prognostic scores has not been investigated. CSF Arg/Orn and the established prognostic scores SAH, FRESH, SAH-PDS, HAIR, Rosen-McDonald, Hunt and Hess, WFNS and modified Fisher scale were determined in a prospective cohort of patients with aneurysmal SAH. Logistic regression models to predict a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 3 months follow-up, were constructed for each score, both with and without the addition of Arg/Orn. The impact of Arg/Orn was assessed comparing logistic regression models containing the respective score with and without Arg/Orn with the likelihood ratio chi-squared test. CSF Arg/Orn and clinical scores were determined in 38 SAH patients. Arg/Orn was an independent predictor of clinical outcome when added to established prognostic scores (p < 0.05) with the exception of HAIR (p = 0.078). All models were significantly improved if Arg/Orn was added as a covariable (p < 0.05). The results of this study confirm Arg/Orn as an independent prognostic factor and its addition improves established prognostic models in SAH.

Ability of patients with acute ischemic stroke to recall given information on intravenous thrombolysis: Results of a prospective multicenter study.

Introduction: Intravenous thrombolysis (IVT) is an on label treatment for selected patients with acute ischemic stroke (AIS). As major bleeding or allergic shock may occur, the need to ensure patients' informed consent for IVT is a matter of debate. Patients and methods: Prospective investigator-initiated multi-center observational study to assess the ability of AIS patients to recall information, provided by a physician during a standardized educational talk (SET) on IVT use. The recall of 20 pre-defined items was assessed in AIS after 60-90 min (n = 93) or 23-25 h (n = 40) after SET. About 40 patients with subacute stroke, 40 non-stroke patients, and 23 relatives of AIS patients served as controls, and were surveyed 60-90 min after SET. Results: Within 60-90 min after SET, AIS patients (median age 70 years, 31% female, median NIHSS score on admission 3 points) who were considered capable to provide informed consent recalled 55% (IQR 40%-66.7%) of the provided SET items. In multivariable linear regression analysis recapitulation by AIS patients was associated with their educational level (ß = 6.497, p < 0.001), self-reported excitement level (ß = 1.879, p = 0.011) and NIHSS score on admission (ß = -1.186, p = 0.001). Patients with subacute stroke (70 years, 40% female, median NIHSS = 2) recalled 70% (IQR 55.7%-83.6%), non-stroke patients (75 years, 40% female) 70% (IQR 60%-78.7%), and AIS relatives (58 years, 83% female) 70% (IQR 60%-85%). Compared to subacute stroke patients, AIS patients less often recalled the frequency of IVT-related bleeding (21% vs 43%), allergic shock (15% vs 39%), and bleeding-related morbidity and mortality (44% vs 78%). AIS patients recalled 50% (IQR 42.3%-67.5%) of the provided items 23-25 h after SET. Conclusion: AIS patients eligible for IVT remember about half of all SET-items after 60-90 min or 23-25 h, respectively. The fact that the recapitulation of IVT-associated risks is particularly poor should be given special consideration.

Intravenous thrombolysis upon flow restoration improves outcome in endovascular thrombectomy.

BACKGROUND: We hypothesized that ongoing IV thrombolysis (IVT) at flow restoration in patients with acute ischemic stroke (AIS) treated with IVT and endovascular thrombectomy (ET) is associated with improved outcome. METHODS: We included patients with IVT and successful recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b) after ET from an observational multicenter cohort, the German Stroke Registry - Endovascular Treatment trial. Procedural characteristics and functional outcome at discharge and 90 days were compared between patients with and without ongoing IVT at flow restoration. To determine associations with functional outcome, adjusted ORs were calculated using ordinal multivariable logistic regression models adjusted for potential baseline confounder variables. RESULTS: Among 1303 patients treated with IVT and ET who achieved successful recanalization, IVT was ongoing in 13.8% (n=180) at flow restoration. Ongoing IVT was associated with better functional outcome at discharge (adjusted OR 1.61; 95% CI 1.13 to 2.30) and at 90 days (adjusted OR 1.52; 95% CI 1.06 to 2.18). CONCLUSION: These results provide preliminary evidence for a benefit of ongoing IVT at flow restoration in patients with AIS treated with ET.

First Experience with the Nimbus Stentretriever : A Novel Device to Handle Fibrin-rich Clots.

PURPOSE: To share our first experience with the Nimbus stentretriever, a multizone device designed to assist neurointerventionalists in handling fibrin-rich clots in endovascular stroke treatment. METHODS: We retrospectively analyzed the data of patients who were treated with the Nimbus stentretriever at our high-volume stroke center between May 2021 and May 2022. We evaluated the number of passes before Nimbus was used, the number of passes with nimbus, as well as the recanalization success before and after Nimbus according to the modified treatment in cerebral ischemia (mTICI) scale. Also, patient characteristics, procedural times and clinical outcomes were documented. RESULTS: A total of 21 consecutive patients were included in the study. An mTICI 2b/3 could be achieved in 76.2% and mTICI 2c/3 could be achieved in 57.1%. The mean number of passes was 3.4 before the use of Nimbus, 2.2 with Nimbus, and 5.4 for all passes with and without Nimbus and 4 occlusions (19.0%) were successfully recanalized with direct aspiration after the use of Nimbus. We observed seven subarachnoid hemorrhages (33.3%) and two cases of vasospasm. CONCLUSION: In our series, the use of Nimbus resulted in successful recanalization in half of the patients after otherwise unsuccessful thrombectomy maneuvers; therefore, it should be considered as a rescue option if the maneuver with conventional stent retrievers was unsuccessful.

Endovascular thrombectomy in young patients with stroke.

BACKGROUND: Endovascular treatment (ET) is standard of care in patients with acute ischemic stroke due to large vessel occlusion, but data on ET in young patients remain limited. AIM: We aim to compare outcomes for young stroke patients undergoing ET in a matched cohort. METHODS: We analyzed patients from an observational multicenter cohort with acute ischemic stroke and ET, the German Stroke Registry-Endovascular Treatment trial. Baseline characteristics, procedural parameters, and functional outcome at 90 days were compared between young (<50 years) and older (⩾50 years) patients with and without nearest-neighbor 1:1 propensity score matching. RESULTS: Out of 6628 acute ischemic stroke patients treated with ET, 363 (5.5%) were young. Young patients differed with regard to prognostic outcome characteristics. Specifically, National Institutes of Health Stroke Scale (NIHSS) at admission was lower (median 13, interquartile range (IQR) 8-17 vs. 15, IQR 9-19, p < 0.001), and prestroke dependence was less frequent (2.9% vs. 12.2%, p < 0.001) than in older patients. Compared to a matched cohort of older patients, ET was faster (time from groin puncture to flow restoration, 35 vs. 45 min, p < 0.001) and intracranial hemorrhage was less frequent in young patients (10.0% vs. 25.9%, p < 0.001). Good functional outcome (modified Rankin Scale (mRS) 0-2) at 3 months was achieved more frequently in young patients (71.6% vs. 44.1%, p < 0.001), and overall mortality was lower (6.7% vs. 25.4%, p < 0.001). Among previously employed young patients (n = 177), 37.9% returned to work at 3-month follow-up, while 74.1% of the remaining patients were still undergoing rehabilitation. CONCLUSION: Young stroke patients undergoing ET have better outcomes compared to older patients, even when matched for prestroke condition, comorbidities, and stroke severity. Hence, more liberal guidelines to perform ET for younger patients may have to be established by future studies.

Outcome of Stroke Patients with Unknown Onset and Unknown Time Last Known Well Undergoing Endovascular Therapy.

PURPOSE: Endovascular treatment (ET) in patients with large vessel occlusion stroke (LVOS) with unknown onset or an extended time window can be safe and effective if patients are selected by defined clinical and imaging criteria; however, it is unclear if these criteria should also be applied to patients with unknown onset and unknown time last known well. In this study, we aimed to assess whether absent information on the time patients were last known to be well impacts outcome in patients with unknown onset LVOS. METHODS: We analyzed patients who were enrolled in the German Stroke Registry-Endovascular Treatment between 2015 and 2019. Patients with unknown onset and unknown time last known well (LKWu) were compared to patients with known onset (KO) and to patients with unknown onset but known time last known well (LKWk) regarding clinical and imaging baseline characteristics and outcome. RESULTS: Out of 5909 patients, 561 presented with LKWu (9.5%), 1849 with LKWk (31.3%) and 3499 with KO (59.2%). At 90 days, functional independency was less frequent in LKWu (27.0%) compared to KO (42.6%) and LKWk patients (31.8%). These differences were not significant after adjusting for confounders. A main confounder was the initial Alberta stroke program early CT score. CONCLUSION: The LKWu patients had a similar outcome after ET as KO and LKWk patients after adjusting for confounders. Thus, ET should not be withheld if the time last known well is unknown. Instead, LKWu patients may be selected for ET using the same criteria as in LKWk patients.

No serological evidence for neuronal damage or reactive gliosis in neuro-COVID-19 patients with long-term persistent headache.

Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation.

Pregabalin improves axon regeneration and motor outcome in a rodent stroke model.

Ischaemic stroke remains a leading cause of death and disability worldwide. Surviving neurons in the peri-infarct area are able to establish novel axonal projections to juxtalesional regions, but this regeneration is curtailed by a growth-inhibitory environment induced by cells such as reactive astrocytes in the glial scar. Here, we found that the astroglial synaptogenic cue thrombospondin-1 is upregulated in the peri-infarct area, and hence tested the effects of the anticonvulsant pregabalin, a blocker of the neuronal thrombospondin-1 receptor Alpha2delta1/2, in a mouse model of cortical stroke. Studying axonal projections after cortical stroke in mice by three-dimensional imaging of cleared whole-brain preparations, we found that pregabalin, when administered systemically for 5 weeks after stroke, augments novel peri-infarct motor cortex projections and improves skilled forelimb motor function. Thus, the promotion of axon elongation across the glial scar by pregabalin represents a promising target beyond the acute phase after stroke to improve structural and functional recovery.

Antithrombotic treatment and outcome after endovascular treatment and acute carotid artery stenting in stroke patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation (OAC) is the mainstay of secondary prevention in ischemic stroke patients with atrial fibrillation (AF). However, in AF patients with large vessel occlusion stroke treated by endovascular therapy (ET) and acute carotid artery stenting (CAS), the optimal antithrombotic medication remains unclear. METHODS: This is a subgroup analysis of the German Stroke Registry-Endovascular Treatment (GSR-ET), a prospective multicenter cohort of patients with large vessel occlusion stroke undergoing ET. Patients with AF and CAS during ET were included. We analyzed baseline and periprocedural characteristics, antithrombotic strategies and functional outcome at 90 days. RESULTS: Among 6635 patients in the registry, a total of 82 patients (1.2%, age 77.9 ± 8.0 years, 39% female) with AF and extracranial CAS during ET were included. Antithrombotic medication at admission, during ET, postprocedural and at discharge was highly variable and overall mortality in hospital (21%) and at 90 days (39%) was high. Among discharged patients (n = 65), most frequent antithrombotic regimes were dual antiplatelet therapy (DAPT, 37%), single APT + OAC (25%) and DAPT + OAC (20%). Comparing DAPT to single or dual APT + OAC, clinical characteristics at discharge were similar (median NIHSS 7.5 [interquartile range, 3-10.5] vs 7 [4-11], p = 0.73, mRS 4 [IQR 3-4] vs. 4 [IQR 3-5], p = 0.79), but 90-day mortality was higher without OAC (32 vs 4%, p = 0.02). CONCLUSIONS: In AF patients who underwent ET and CAS, 90-day mortality was higher in patients not receiving OAC. REGISTRATION: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03356392.

Sepsis in Patients With Large Vessel Occlusion Stroke-Clinical Characteristics and Outcome.

Background: Infections are an important complication after stroke and negatively affect clinical outcome. While pneumonia and urinary tract infections are well recognized after stroke, the incidence and consequences of sepsis remain unclear. The aim of this study was to evaluate the frequency and characteristics of sepsis in patients undergoing endovascular therapy for large vessel occlusion stroke, and its association with clinical outcome. Methods: We analyzed a cohort of patients who underwent endovascular therapy at a single center between 2016 and 2020. The diagnosis and timing of infections and Sequential Organ Failure Assessment scores were evaluated retrospectively to identify patients with sepsis. Patients with sepsis were compared to controls regarding clinical characteristics and outcome. Results: Fifty-four of 406 patients (13.3%) were found to have sepsis. The median onset of sepsis was 2 days after admission. The majority of cases (85.2%) was caused by pneumonia. At 3 months, 72.5% of patients with sepsis were bedridden or dead compared to 25.7 and 42.7% of controls and patients with an infection without sepsis, respectively. The adjusted odds ratio (95% confidence interval) for a poor outcome was 5.4 (1.6-17.6) for patients with sepsis vs. controls, and 2.0 (0.8-5.2) for patients with sepsis vs. patients with an infection without sepsis. Conclusions: Sepsis is a frequent complication after large vessel occlusion stroke, and may be associated with a poor clinical outcome. More studies are needed to determine specific risk factors and measures to early recognize and reduce the possibly negative impact of sepsis on outcome after stroke.

MotiQ: an open-source toolbox to quantify the cell motility and morphology of microglia.

Microglia are the primary resident innate immune cells of the CNS. They possess branched, motile cell processes that are important for their cellular functions. To study the pathways that control microglial morphology and motility under physiological and disease conditions, it is necessary to quantify microglial morphology and motility precisely and reliably. Several image analysis approaches are available for the quantification of microglial morphology and motility. However, they are either not automated, not freely accessible, and/or limited in the number of morphology and motility parameters that can be assessed. Thus, we have developed MotiQ, an open-source, freely accessible software for automated quantification of microglial motility and morphology. MotiQ allows quantification of a diverse set of cellular motility and morphology parameters, including the parameters that have become the gold standard in the microglia field. We demonstrate that MotiQ can be applied to in vivo, ex vivo, and in vitro data from confocal, epifluorescence, or two-photon microscopy, and we compare its results to other analysis approaches. We suggest MotiQ as a versatile and customizable tool to study microglia.

Structural retinal changes in cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is an important contributor to cognitive impairment and stroke. Previous research has suggested associations with alterations in single retinal layers. We have assessed changes of all individual retinal layers in CSVD using high-resolution optical coherence tomography (OCT) for the first time. Subjects with recent magnetic resonance imaging (MRI) underwent macular and peripapillary retinal imaging using OCT for this case-control study. Number and volume ratio index (WMRI) of white matter lesions (WML) were determined on MRI. Data were analyzed using multiple linear regression models. 27 CSVD patients and 9 control participants were included. Ganglion cell layer (GCL) volume was significantly reduced in patients with CSVD compared to age-matched controls (p = 0.008). In patients with CSVD, larger foveal outer plexiform layer (OPL) volume and decreased temporal peripapillary retinal nerve fiber layer (RNFL) thickness were significantly associated with a higher WMRI in linear regression when controlling for age (p ≤ 0.033). Decreased foveal GCL volume and temporal-inferior RNFL thickness at Bruch's membrane opening (MRW), and increased temporal MRW were associated with a higher WML burden (p ≤ 0.037). Thus, we identified alterations in several OCT layers in individuals with CSVD (GCL, OPL, MRW and RNFL). Their potential diagnostic value merits further study.