Thrombectomy patients with minor stroke: factors of early neurological deterioration.

BACKGROUND: A sizeable proportion of stroke patients with large vessel occlusion present with minor neurological deficits. Whether mechanical thrombectomy (MT) is beneficial in these patients is controversial. We aimed to investigate factors of early neurological deterioration (END) in thrombectomy patients with minor stroke and hypothesized that END is linked to unfavorable functional outcomes. METHODS: Multicenter cohort study screening all patients prospectively enrolled in the German Stroke Registry-Endovascular Treatment (n=13 082) between 2015 and 2021. Patients who underwent MT for anterior circulation vessel occlusion with baseline National Institutes of Health Stroke Scale (NIHSS) score of <6 were included. END was defined as an increase in NIHSS score of ≥4 within the first 24 hours after MT. Multivariable regression analyses were performed to investigate factors associated with END and its association with unfavorable functional outcomes 90 days after treatment (modified Rankin Scale (mRS) score ≥2). RESULTS: Among 817 patients included, 24% exhibited END and 48% had unfavorable functional outcomes. Prestroke mRS (adjusted odds ratio (aOR) [95% CI] 1.42 [1.13 to 1.78]), baseline NIHSS (aOR [95% CI] 0.83 [0.73 to 0.94]), time from admission to groin puncture (aOR [95% CI] 1.04 [1.02 to 1.07]), general anesthesia (aOR [95% CI] 1.68 [1.08 to 2.63]), number of passes (aOR [95% CI] 1.15 [1.03 to 1.29]), adverse events during treatment (aOR [95% CI] 1.89 [1.19 to 3.01]), successful recanalization (aOR [95% CI] 0.29 [0.17 to 0.50]), and intracranial hemorrhage on follow-up imaging (aOR [95% CI] 3.40 [1.90 to 6.07]) were independently associated with END. END was independently linked to unfavorable functional outcomes (aOR [95% CI] 7.51 [4.57 to 12.34]). CONCLUSIONS: Almost a quarter of thrombectomy patients with minor stroke developed END. These patients had twice the odds of experiencing unfavorable functional outcomes.

Reduced olfactory bulb volume accompanies olfactory dysfunction after mild SARS-CoV-2 infection.

Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Kidney dysfunction predicts 90 days mortality after stroke thrombectomy independent of cardiovascular risk factors and chronic kidney disease.

INTRODUCTION: Kidney dysfunction (KD) is a risk factor for cerebrovascular events and has been shown to have a detrimental effect on outcome after stroke. We evaluated the influence of KD at admission and pre-existing diagnosis of chronic kidney disease (CKD) before thrombectomy for anterior circulation stroke on functional independence and mortality 90 days after stroke in this cross-sectional study. PATIENTS AND METHODS: We included patients with acute ischemic stroke in the anterior circulation treated with thrombectomy at our hospital between June 2015 and May 2022. We analyzed clinical characteristics, laboratory values and pre-existing diagnosis of CKD. KD at admission was defined as glomerular filtration rate (GFR) <60 ml/min/1.73 m2. Outcomes were defined as a modified Rankin Scale Score of 0-2 for functional independence and mortality at 90 days. We fitted multivariate regression analysis to examine the influence of pre-treatment KD and pre-diagnosed CKD on outcome. RESULTS: Nine hundred fifty-three patients were included in this analysis (mean age 73.8 years, 54.2% female). KD was present in 31.8%, and patients with KD were older and more often female, presented more often with comorbidities such as arterial hypertension, diabetes, and atrial fibrillation, and were less often independent before the index stroke. In multivariate analysis adjusted for age, independence before the index stroke, diabetes, hypertension, atrial fibrillation, initial NIHSS, thrombolysis treatment, and recanalization outcome, KD on admission had no significant influence on functional independence 90 days after stroke, but predicted mortality with an odds ratio of 1.80 (95% CI 1.23-2.63, p = 0.003). This influence also persisted when controlling for pre-diagnosed CKD (OR 1.60, 95% CI 1.05-2.43, p = 0.027). DISCUSSION: KD might function as a surrogate parameter for comorbidity burden and thus increased risk of mortality in this cohort. CONCLUSIONS: KD on admission is associated with an 80% higher risk of mortality at 90 days after stroke thrombectomy independent of cardiovascular risk factors and CKD awareness. KD on admission should not exclude patients from thrombectomy but might support prognostic evaluation.

Age and Functional Outcomes in Patients With Large Ischemic Stroke Receiving Endovascular Thrombectomy.

Importance: Randomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials. Objective: To provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct. Design, Setting, and Participants: This retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes. Exposure: Age. Main Outcomes and Measures: Primary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6). Results: A total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27). Conclusions and Relevance: In this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition.

The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

Predictors of Futile Recanalization in Ischemic Stroke Patients with low baseline NIHSS.

BACKGROUND: There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] <6). Prior studies of patients with admission NIHSS scores >6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases. AIM: The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors. METHODS: Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n=13082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3). FR was defined by a modified Rankin Scale (mRS) score of 2-6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR. RESULTS: A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio: 1.04 [95% confidence interval: 1.02-1.06]), pre-stroke mRS 1 (aOR: 2.70 [1.51-4.84]), transfer from admission hospital to comprehensive stroke center (aOR: 1.67 [1.08-2.56]), longer time from symptom onset/last seen well to admission (aOR: 1.02 [1.00-1.04]), MT under general anesthesia (aOR: 1.78 [1.13-2.82]), higher NIHSS after 24 hours (aOR: 1.09 [1.05-1.14]), and symptomatic intracranial hemorrhage (aOR: 16.88 [2.03-140.14]) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI 2b or 3. CONCLUSIONS: Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke. DATA ACCESS STATEMENT: The data that support the findings of our study are available on reasonable request after approval of the GSR steering committee.

Fluid excess on intensive care unit after mechanical thrombectomy after acute ischemic stroke is associated with unfavorable neurological and functional outcomes: An observational cohort study.

INTRODUCTION: Endovascular thrombectomy stands as a pivotal component in the standard care for patients experiencing acute ischemic stroke with large vessel occlusion. Subsequent care for patients often extends to a neurological intensive care unit. While fluid management is integral to intensive care, the association between early fluid balance and neurological and functional outcomes post-thrombectomy has not yet been thoroughly investigated. METHODS: In a retrospective analysis of an observational, single-center study spanning from 2015 to 2021 at the University Medical Center Hamburg-Eppendorf, Germany, we enrolled stroke patients who underwent thrombectomy and received subsequent treatment in the ICU. Unfavorable functional and neurological outcome was defined as a mRS > 2 on day 90 after admission (mRS d90) or NIHSS > 5 at discharge, respectively. A multivariate regression model, adjusting for confounders, utilized the average fluid balance in the first 5 days to predict outcomes. Patients were dichotomized by their average fluid balance (>1 L vs <1 L) within the first 5 days, and a multivariate mRS d90 shift analysis was conducted after adjusting for covariates. RESULTS: Between 2015 and 2021, 1252 patients underwent thrombectomy, and 553 patients met the inclusion criteria (299 women [54%]). Unfavorable functional outcome was significantly associated with a higher daily average fluid balance in the first 5 days in the ICU (mRS d90 ⩽ 2: 0.3 ± 0.5 L, mRS d90 > 2: 0.7 ± 0.7 L, p = 0.02). The same association was observed for the NIHSS at discharge (NIHSS ⩽ 5: 0.3 ± 0.5 L; NIHSS > 5: 0.6 ± 0.6 L; p = 0.03). The mRS d90 shift analysis revealed significance for patients with an average fluid balance <1 L for better functional outcomes (adjusted odds ratio [AOR] 2.17; 95% confidence interval [CI] 1.54-3.07; p < 0.01). DISCUSSION: Fluid retention in post-thrombectomy stroke patients in the ICU is associated with poorer functional and neurological outcomes. Consequently, fluid retention emerges as an additional potential predictor for post-intervention stroke outcomes. Our findings provide an initial indication that preventing excessive fluid retention in stroke patients after endovascular thrombectomy could be beneficial for both functional and neurological recovery. Therefore, fluid retention might be an element to consider in optimizing fluid management for stroke patients.

Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes.

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (ß estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.

Markers of Biological Brain Aging Mediate Effects of Vascular Risk Factors on Cognitive and Motor Functions: A Multivariate Imaging Analysis of 40,579 Individuals.

The increasing global life expectancy brings forth challenges associated with age-related cognitive and motor declines. To better understand underlying mechanisms, we investigated the connection between markers of biological brain aging based on magnetic resonance imaging (MRI), cognitive and motor performance, as well as modifiable vascular risk factors, using a large-scale neuroimaging analysis in 40,579 individuals of the population-based UK Biobank and Hamburg City Health Study. Employing partial least squares correlation analysis (PLS), we investigated multivariate associative effects between three imaging markers of biological brain aging - relative brain age, white matter hyperintensities of presumed vascular origin, and peak-width of skeletonized mean diffusivity - and multi-domain cognitive test performances and motor test results. The PLS identified a latent dimension linking higher markers of biological brain aging to poorer cognitive and motor performances, accounting for 94.7% of shared variance. Furthermore, a mediation analysis revealed that biological brain aging mediated the relationship of vascular risk factors - including hypertension, glucose, obesity, and smoking - to cognitive and motor function. These results were replicable in both cohorts. By integrating multi-domain data with a comprehensive methodological approach, our study contributes evidence of a direct association between vascular health, biological brain aging, and functional cognitive as well as motor performance, emphasizing the need for early and targeted preventive strategies to maintain cognitive and motor independence in aging populations.

Thrombectomy in ischemic stroke patients with large core but minor ischemic changes on non-enhanced computed tomography.

PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is regularly used to guide patient selection for mechanical thrombectomy (MT). Similarly, penumbral imaging based on computed tomography perfusion (CTP) may serve as neuroimaging tool to guide treatment. Yet, patients with a large ischemic core on CTP may show only minor ischemic changes resulting in a high ASPECTS. AIM: We hypothesized twofold: (1) the treatment effect of vessel recanalization in patients with core volume > 50 mL but ASPECTS ⩾ 6 is not different compared to high ASPECTS patients with core volume < 50 mL, and (2) recanalization is associated with core overestimation. METHODS: We conducted an observational study analyzing ischemic stroke patients consecutively treated with MT after triage by multimodal CT. Functional endpoint was the rate of functional independence at Day 90 defined as modified Rankin Scale (mRS) 0-2. Imaging endpoint was core overestimation, which was considered when CTP-derived core was larger than the final infarct volume assessed on follow-up imaging. Recanalization was evaluated with the extended Thrombolysis in Cerebral Infarction (eTICI) scale. Multivariable logistic regression analysis and propensity score matching (PSM) were used to assess the association of recanalization (eTICI ⩾ 2b) with functional outcome and core overestimation. RESULTS: Of 630 patients with ASPECTS ⩾ 6, 91 patients (14.4%) had a large ischemic core. Following 1:1 PSM, the treatment effect of recanalization was not different in patients with large core and ASPECTS ⩾ 6 (+ 25.8%, 95% CI: 16.3-35.4, p < 0.001) compared to patients with ASPECTS ⩾ 6 and core volume < 50 mL (+ 14.9%, 95% CI: 5.7-24.1, p = 0.002). Recanalization (aOR: 3.46, 95% CI: 1.85-6.47, p < 0.001) and higher core volume (aOR: 1.03, 95% CI: 1.02-1.04, p < 0.001) were significantly associated with core overestimation. CONCLUSION: In patients with ASPECTS ⩾ 6, core volumes did not significantly modify outcomes following recanalization. Reperfusion and higher core volume were significantly associated with core overestimation which may explain the treatment effect of MT for patients with a large ischemic core but minor ischemic changes on non-enhanced CT. DATA ACCESS STATEMENT: The data analyzed in this study will be available and shared on reasonable request from any qualified researcher for the purpose of replicating the results after clearance by the local ethics committee.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. METHODS: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. FINDINGS: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). INTERPRETATION: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. FUNDING: European Union Horizon 2020 Research and Innovation Programme.