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      Severe Lesions Involving Cortical Cholinergic Pathways Predict Poorer Functional Outcome in Acute Ischemic Stroke

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          Abstract

          Supplemental Digital Content is available in the text.

          Abstract

          Background and Purpose—

          The aim of the study was to assess the effect of lesion severity in cortical cholinergic pathways in acute ischemic stroke patients on functional outcomes.

          Methods—

          The study sample consisted of 214 men (70.9%) and 88 women (29.1%) with acute ischemic stroke. We used the Cholinergic Pathways Hyperintensities Scale (CHIPS) to assess the severity of lesions in cortical cholinergic pathways using brain magnetic resonance imaging. The other magnetic resonance imaging parameters included infarction, white matter lesions, and medial temporal lobe atrophy. Functional outcome was assessed using the Lawton activities of daily living (ADL) scale at 3 and 6 months after the index stroke. We also assessed disability status using the modified Rankin Scale.

          Results—

          Univariate analysis showed that patients with poor functional outcomes were older, more likely to be men, had a higher National Institutes of Health Stroke Scale (NIHSS) score on admission, and had more frequent histories of previous stroke and infection complications. They also had significantly more frequent cortical infarcts, left subcortical infarcts, a larger infarct volume, more severe medial temporal lobe atrophy, and periventricular hyperintensities, and higher CHIPS scores. In the multiple regression analysis, model 1 showed that age and NIHSS score on admission were significant predictors of poor ADL at 3 months, with an R 2 of 45.4% fitting the model. Age, NIHSS score on admission and stroke subtype were also significant predictors of poor ADL at 6 months, with an R 2 of 37.9% fitting the model. In model 2, sex, previous stroke, NIHSS score on admission, right cortical infarcts, left subcortical infarcts and CHIPS score were significant predictors for poor ADL at 3 months, with an R 2 of 53.5%. NIHSS score on admission, stroke subtype, and CHIPS score were significant predictors for poor ADL at 6 months, with an R 2 of 40.2%. After adjustment for confounders, CHIPS score was also a significant predictor for poor modified Rankin Scale, both at 3 and 6 months. Even after removing patients with moderate-to-severe white matter lesions, higher CHIPS scores still correlated with poorer ADL and modified Rankin Scale both at both 3 and 6 months.

          Conclusions—

          In patients with acute ischemic stroke, cortical cholinergic pathways impairment is common, and the severity of lesions in the cortical cholinergic pathways may significantly predict a poorer functional outcome.

          Clinical Trial Registration—

          URL: http://www.chictr.org.cn/index.aspx. Unique identifier: ChiCTR1800014982.

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          Most cited references13

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          The cholinergic innervation of the human cerebral cortex.

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            A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia.

            One possible mechanism of cognitive decline in individuals with subcortical vascular disease is disruption of cholinergic fibers by ischemic lesions, such as strategically located white matter hyperintensities (WMH). The authors applied a new MRI visual rating scale to assess WMH within cholinergic pathways in patients with Alzheimer Disease (AD) and subcortical ischemic microvascular disease. Subjects included 60 AD patients with and without WMH, matched for age, as well as 15 control subjects. A visual rating scale was developed based on published immunohistochemical tracings of the cholinergic pathways in humans. On 4 selected axial images, the severity of WMH in the cholinergic pathways was rated on a 3-point scale for ten regions, identified with major anatomical landmarks. A published, consensus-derived, general WMH scale was also applied. All subjects underwent standardized neuropsychological testing. The Cholinergic Pathways HyperIntensities Scale showed reliability and was validated with volumetry of strategic WMH. After accounting for age and education in a multiple linear regression model, The Cholinergic Pathways HyperIntensities Scale ratings were associated with impaired performance on the Mattis Dementia Rating Scale (r=0.40; P=0.02) and accounted for 12% of the variance (corrected r2). A similar model was not significant for general WMH scores. The new MRI rating scale for WMH in cholinergic pathways is reliable and shows stronger correlations with cognitive performance than a general WMH rating scale in AD with WMH. This new rating scale provides indirect evidence that localization of WMH within neurotransmitter systems may contribute to cognitive decline.
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              Cortical hubs and subcortical cholinergic pathways as neural substrates of poststroke dementia.

              A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia.
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                Author and article information

                Journal
                Stroke
                Stroke
                STR
                Stroke
                Lippincott Williams & Wilkins
                0039-2499
                1524-4628
                December 2018
                01 November 2018
                : 49
                : 12
                : 2983-2989
                Affiliations
                [1 ]From the Department of Neurology, Dongguan People’s Hospital (Affiliated Dongguan Hospital, South Medical University), Guangdong Province, China (J.-F.Q., Y.-K.C., G.-P.L., J.-H.Z., H.-H.Z., H.-P.Y.)
                [2 ]Faculty of Neurology, Guangdong Medical University, Zhanjiang, China (H.-H.Z.).
                Author notes
                Correspondence to Yang-Kun Chen, MD, PhD, Department of Neurology, Dongguan People’s Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan City, Guangdong Province, China. Email cykun78@ 123456163.com
                Article
                00028
                10.1161/STROKEAHA.118.023196
                6257508
                30571427
                d12b9a62-cc71-4954-8799-89ffcdc650c8
                © 2018 The Authors.

                Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

                History
                : 9 August 2018
                : 5 October 2018
                : 10 October 2018
                Categories
                10178
                Original Contributions
                Clinical Sciences
                Custom metadata
                TRUE

                activities of daily living,brain ischemia,infarction,magnetic resonance imaging,stroke

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