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      Tumor-related neurocognitive dysfunction in patients with diffuse glioma: a retrospective cohort study prior to antitumor treatment

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          Abstract

          Background

          Impairments in neurocognitive functioning (NCF) frequently occur in glioma patients. Both the tumor and its treatment contribute to these impairments. We aimed to quantify NCF in glioma patients before treatment and to investigate which factors influence NCF.

          Methods

          We performed a retrospective cohort study in diffuse glioma patients according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) criteria. All patients had undergone neuropsychological assessment as part of routine clinical care, before awake surgery. We studied “overall NCF” and NCF in 5 neurocognitive domains separately. For “overall NCF” and per domain, we performed analyses at 2 different levels of outcome measures: (1) group level: mean cognitive functioning of the study sample, and (2) individual level: the percentage of impaired patients. We performed multivariable logistic regression analyses to investigate which factors were associated with the occurrence of cognitive impairments.

          Results

          From our cohort of glioma patients (2010-2016), 168 patients met all the inclusion criteria. All cognitive domains were significantly affected at the group level. The percentages of neurocognitive impairments (–2SD) were highest for Executive Functioning, Psychomotor Speed, and Memory (26.5%, 23.2%, and 19.3%, respectively). Patients with high-grade glioma were affected more severely than patients with low-grade glioma. Tumor volume, isocitrate dehydrogenase status, WHO grade, and histology were associated with the occurrence of domain-specific impairments.

          Conclusions

          Cognitive impairment occurs in the majority of treatment-naive glioma patients. The domains Executive Functioning, Speed, and Memory are involved most frequently. These impairments in NCF are explained not only by tumor location and volume, but also by other (biological) mechanisms.

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          Most cited references24

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          IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection.

          IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas-World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma. Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry. IDH1 mutation was independently associated with complete resection of enhancing disease (93% complete resections among mutants vs 67% among wild-type, P 5 cc residual vs not reached for <5 cc, P = .025). The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status.
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            Cognitive Disorders in Acute Stroke: Prevalence and Clinical Determinants

            Background: Although cognitive impairment early after stroke is a powerful predictor of long-term functional dependence and dementia, little is known about the characteristics and determinants of cognitive dysfunction in acute stroke. Methods: We administered a neuropsychological examination covering 7 cognitive domains to 190 patients within 3 weeks after a first stroke. We also assembled lesion characteristics, clinical factors at admission, demographic characteristics and vascular risk factors. Multivariate logistic regression adjusted for age, gender and education was performed to examine determinants of acute cognitive impairment. Results: Overall, 74% of patients with a cortical stroke, 46% with a subcortical stroke and 43% with an infratentorial stroke demonstrated acute cognitive impairment.Disorders in executive functioning (39%) and visual perception/construction (38%) were the most common. The prevalence and severity of deficits in executive functioning, language, verbal memory and abstract reasoning was more pronounced following left compared to right cortical stroke (all p < 0.05). Intracerebral haemorrhage (OR = 5.6; 95% CI = 1.2–25.4) and cortical involvement of the stroke (OR = 3.6; 95%, CI = 1.3–9.9) were independent determinants of acute cognitive impairment, whereas premorbid moderate alcohol consumption exerted a protective effect (OR = 0.4; 95% CI = 0.1–1.1). Conclusions: Cognitive impairment is common in the first weeks after stroke, with executive and perceptual disorders being the most frequent. Intracerebral haemorrhage, cortical involvement of the lesion and premorbid moderate alcohol consumption are independently associated with acute cognitive impairment.
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              Network measures predict neuropsychological outcome after brain injury.

              Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as "cortical hubs" of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six "target" hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two "control" hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.
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                Author and article information

                Journal
                Neurooncol Pract
                Neurooncol Pract
                nop
                Neuro-Oncology Practice
                Oxford University Press (US )
                2054-2577
                2054-2585
                December 2019
                22 April 2019
                22 April 2019
                : 6
                : 6
                : 463-472
                Affiliations
                [1 ] University Medical Center Utrecht/Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery , The Netherlands
                [2 ] Helmhotz Institute, Utrecht University , The Netherlands
                Author notes
                Corresponding Author: Emma van Kessel, MD, University Medical Center Utrecht/Brain Center Rudolf Magnus, Department of Neurology, internal address G03.232, PO Box 85500, 3508 XC Utrecht, The Netherlands ( e.vankessel-2@ 123456umcutrecht.nl ).

                These authors contributed equally to this work.

                Article
                npz008
                10.1093/nop/npz008
                6899056
                31832216
                4cb06421-d3c2-4c3d-89d6-7aaafe0e4235
                © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 10 September 2018
                : 16 November 2018
                : 13 February 2019
                Page count
                Pages: 11
                Funding
                Funded by: Ton & Patricia Bohnenn
                Categories
                Original Articles

                brain tumor,cognition,glioma,idh,isocitrate dehydrogenase,neurocognitive functioning,neuropsychology

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