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      Early neurological deterioration in patients with acute ischemic stroke: a prospective multicenter cohort study

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          Abstract

          Background:

          There is still no precise knowledge of the causes of progression in patients with acute ischemic stroke (AIS), and we are unable to predict patients at risk.

          Objective:

          To explore the frequency, predictive factors, and the prognosis of early neurological deterioration (END) in patients with AIS

          Methods:

          In this prospective multicenter observational study, we assessed patients with AIS admitted to 18 hospitals in Henan, China. We defined END as an increase of ⩾2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ⩾1 point in the motor items of the NIHSS within 7 days after admission. Risk factors were analyzed using multivariate logistic regression models. Prognosis was evaluated using the modified Rankin Scale (mRS), with poor prognosis defined as mRS 3–6.

          Results:

          A total of 9114 patients with AIS within 24 h of symptom onset were enrolled in the study. END occurred in 1286 (14.1%) patients. The highest incidence (62.5%) of END occurred within 24 h after admission. After adjusting potential confounders, age, body mass index, waist–hip ratio, systolic blood pressure, baseline NIHSS, disabled at baseline, history of atrial fibrillation, diabetes mellitus, intracranial arterial stenosis, infarct location in the lenticulostriate artery area and cerebral watershed, neutrophils, lymphocytes, uric acid, and triglycerides were identified as independent predictors for END. END was significantly associated with poor prognosis at 90 days, and the adjusted OR was 1.74 (95% CI: 1.53–1.97).

          Conclusion:

          One in seven hospitalized patients with AIS may experience END within 24 h of onset. The highest incidence of END occurred within 24 h of admission and decreased steeply with time. Easily identifiable risk factors predict END and could help understand the causal mechanisms and thereby prevent END.

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          Most cited references43

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          The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke

          Background and purpose To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. Results Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238–1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009–1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560–0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643–0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. Conclusions NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02090-6.
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            The pathophysiology of watershed infarction in internal carotid artery disease: review of cerebral perfusion studies.

            In carotid disease, infarcts can occur in the cortical as well as internal watershed (WS), or both. Better understanding the pathophysiology of WS infarcts would guide treatment. Two distinct hypotheses, namely low-flow and micro-embolism, are equally supported by neuropathological and physiological studies. Here we review the evidence regarding the mechanisms for WS stroke in carotid disease and whether they differ between cortical and internal WS infarcts. After a brief account of the anatomy of the WS and the cerebrovascular physiology in circumstances of low perfusion pressure, the literature concerning the mechanisms of WS infarction in carotid disease is reviewed and discussed with emphasis on imaging and ultrasound studies of the cerebral hemodynamics. The evidence strongly favors a hemodynamic mechanism for internal WS infarction, especially regarding the so-called rosary-like pattern in the centrum semiovale. However, the relationships between cortical WS infarction and hemodynamic compromise appear more complicated. Thus, although severe hemodynamic compromise appears to underlie combined cortical and internal WS infarction, artery-to-artery embolism may play an important role in isolated cortical WS infarcts. Based on the high prevalence of microembolic signals documented by ultrasound in symptomatic carotid disease, a recent hypothesis postulates that embolism and hypoperfusion play a synergetic role, according to which small embolic material prone to lodge in distal field arterioles would be more likely to result in cortical micro-infarcts when chronic hypoperfusion prevails. Future studies combining imaging of brain perfusion, diffusion-weighted imaging, and ultrasound detection of microembolic signals should help resolve these issues.
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              Proinflammatory Cytokines and Early Neurological Worsening in Ischemic Stroke

              Background and Purpose —The mechanisms for clinical deterioration in patients with ischemic stroke are not completely understood. Several proinflammatory cytokines are released early after the onset of brain ischemia, but it is unknown whether inflammation predisposes to neurological deterioration. We assessed the implication of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in early neurological worsening in ischemic stroke. Methods —Two hundred thirty-one patients consecutively admitted with first-ever ischemic cerebral infarction within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale (CSS) score fell at least 1 point during the first 48 hours after admission. IL-6 and TNF-α were determined in plasma and cerebrospinal fluid (CSF; n=81) obtained on admission. Results —Eighty-three patients (35.9%) deteriorated within the first 48 hours. IL-6 in plasma (>21.5 pg/mL; OR 37.7, CI 11.9 to 118.8) or in CSF (>6.3 pg/mL; OR 13.1, CI 2.2 to 77.3) were independent factors for early clinical worsening, with multiple logistic regression. The association was statistically significant in all ischemic stroke subtypes as well as in subjects with cortical or subcortical infarctions. IL-6 in plasma was highly correlated with body temperature, glucose, fibrinogen, and infarct volume. CSF and plasma concentrations of TNF-α were also higher in patients who deteriorated, but the differences observed did not remain significant on multivariate analysis. Conclusions —In addition to participating in the acute-phase response that follows focal cerebral ischemia, IL-6 levels on admission are associated with early clinical deterioration. The association between IL-6 and early neurological worsening prevails without regard to the initial size, topography, or mechanism of the ischemic infarction.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curation
                Role: Formal analysis
                Role: ResourcesRole: Software
                Role: Formal analysis
                Role: ResourcesRole: Software
                Role: ResourcesRole: SoftwareRole: Supervision
                Role: SupervisionRole: ValidationRole: Visualization
                Role: ResourcesRole: SoftwareRole: Supervision
                Role: ResourcesRole: SoftwareRole: Supervision
                Role: ResourcesRole: SoftwareRole: Supervision
                Role: ResourcesRole: SoftwareRole: Supervision
                Role: ResourcesRole: SoftwareRole: Supervision
                Role: ConceptualizationRole: Data curationRole: ResourcesRole: SoftwareRole: Supervision
                Journal
                Ther Adv Neurol Disord
                Ther Adv Neurol Disord
                TAN
                sptan
                Therapeutic Advances in Neurological Disorders
                SAGE Publications (Sage UK: London, England )
                1756-2856
                1756-2864
                24 January 2023
                2023
                : 16
                : 17562864221147743
                Affiliations
                [1-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [2-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [3-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [4-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [5-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [6-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [7-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [8-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [9-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [10-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [11-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [12-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 450052, Henan, China
                [13-17562864221147743]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 450052, Henan, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-7718-3288
                Article
                10.1177_17562864221147743
                10.1177/17562864221147743
                9880581
                36710721
                bd51cb68-dbc7-4639-81ca-6008c01b5f66
                © The Author(s), 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 18 August 2022
                : 8 December 2022
                Funding
                Funded by: Technology Projects of Henan Province in 2020, ;
                Award ID: (Grant No. 201300310300)
                Categories
                Original Research
                Custom metadata
                January-December 2023
                ts1

                incidence,ischemic stroke,neurological deterioration,prognosis,risk factor

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