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Stroke: From Pathophysiology to Therapy

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A special issue of Neurology International (ISSN 2035-8377).

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 31653

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Dr. Vishal K. Chavda

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Department of Medicine, Multispeciality, Trauma and ICCU Center, Sardar Hospital, Ahmedabad, Gujarat, India
Interests: ischemic stroke and brain injury; neurovascular aneurysms; traumatic brain injury; stroke and vesicular trafficking; pediatric stroke and epilepsy; brain cancer (GBM) and brain metastasis; cognitive decline and neurodegeneration; neurodegeneration and AD; computational modeling (in-silico)
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Dr. Nicola Montemurro

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Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56100 Pisa, Italy
Interests: brain tumor; glioblastoma; low-grade glioma; meningioma; neuro-oncology; augmented reality; virtual reality; tractography; spine tumor; traumatic brain injury; hydrocephalus
Special Issues, Collections and Topics in MDPI journals

Dr. Bipin Chaurasia

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Department of Neurosurgery, Bhawani Hospital and Research Center, Birgunj, Nepal
Interests: neurodegenerative disorders; stroke; meningioma

Special Issue Information

Dear Colleagues,

Stroke or ischemia is a potentially fatal occurrence that causes a number of co-morbidities linked to neurological problems. Although there are some post-stroke treatments available, very few people have successfully recovered from such a traumatic brain injury. There are incredibly few medications or technologies that have progressed to the clinical trial stage after tPA. Clinical procedures such as cardiac transplants and kidney transplants can result in gradual, life-threatening damage to the brain and ischemic brain injury. The present Special Issue is focused on improvements in stroke research, treatment, and cures; however, the submission of case reports, in-depth reviews, and unique molecular mechanistic research is also encouraged. Manuscript submissions that concern such conditions that result in ischemia injury (novel animal models and clinical cases) and progressive brain damage with novel approaches and treatment alternatives are also encouraged. The goal of the Special Issue is to publish articles regarding diseases or associated pathologies that turn into ischemia events and the current treatments for them.

Dr. Vishal K Chavda
Dr. Nicola Montemurro
Dr. Bipin Chaurasia
Guest Editors

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Keywords

ischemia reperfusion injury
stroke therapies
medical devices
stroke treatments
stroke pathologies

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Published Papers (10 papers)

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Research

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10 pages, 1510 KiB

Open AccessArticle

Clinical Features of Acute Ischemic Stroke Patients with Hypoesthesia as an Initial Symptom

by Takayoshi Akimoto, Katsuhiko Ogawa, Makoto Hara, Satoko Ninomiya, Masaki Ishihara, Akihiko Morita, Satoshi Kamei and Hideto Nakajima

Neurol. Int. 2023, 15(1), 508-517; https://doi.org/10.3390/neurolint15010030 - 15 Mar 2023

Viewed by 2248

Abstract

This study aimed to evaluate the clinical characteristics of acute ischemic stroke (AIS) patients who experienced hypoesthesia as the initial symptom. We retrospectively analyzed the medical records of 176 hospitalized AIS patients who met our inclusion and exclusion criteria and evaluated their clinical features and MRI findings. Among this cohort, 20 (11%) patients presented with hypoesthesia as the initial symptom. MRI scans of these 20 patients identified lesions in the thalamus or pontine tegmentum in 14 and brain lesions at other sites in 6. The 20 hypoesthesia patients had higher systolic (p = 0.031) and diastolic blood pressure (p = 0.037) on admission, and a higher rate of small-vessel occlusion (p < 0.001) than patients without hypoesthesia. The patients with hypoesthesia had a significantly shorter average hospital stay (p = 0.007) but did not differ significantly from those without hypoesthesia in National Institutes of Health Stroke Scale scores on admission (p = 0.182) or the modified Rankin Scale scores for neurologic disability on discharge (p = 0.319). In the patients with acute onset hypoesthesia, high blood pressure, and neurological deficits were more likely to be due to AIS than other causes. Since most of the lesions in AIS patients with hypoesthesia as the initial symptom were found to be small, we recommend performing MRI scans with such patients to confirm AIS. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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9 pages, 924 KiB

Open AccessEditor’s ChoiceArticle

Post-Stroke Pneumonia in Real-World Practice: Background, Microbiological Examination, and Treatment

by Takayoshi Akimoto, Makoto Hara, Masaki Ishihara, Katsuhiko Ogawa and Hideto Nakajima

Neurol. Int. 2023, 15(1), 69-77; https://doi.org/10.3390/neurolint15010006 - 9 Jan 2023

Cited by 2 | Viewed by 2412

Abstract

Post-stroke pneumonia (PSP) has an impact on acute ischemic stroke (AIS). Although predictive scores for PSP have been developed, it is occasionally difficult to predict. Clarifying how PSP was treated after its onset in clinical practice is important. Admitted patients with AIS over a 2-year period were retrospectively reviewed. Of 281 patients with AIS, 24 (8.5%) developed PSP. The integer-based pneumonia risk score was higher in patients with PSP. The onset of PSP was frequently seen up to the 4th day of hospitalization. Of patients with PSP, sputum examination yielded Geckler 4 or 5 in only 8.3%. Angiotensin-converting enzyme inhibitor (ACE-I) was more frequently administered to patients with PSP; however, all these cases were started with ACE-I following PSP onset. Nasogastric tubes (NGTs) were inserted in 16 of the patients with PSP, of whom 11 were inserted following PSP onset. Multivariate analysis showed that PSP onset was a poor prognostic factor independent of the female sex, urinary tract infection, and National Institutes of Health Stroke Scale. PSP treatment would benefit from the administration of antimicrobials and ACE-I, as well as NGT insertion. To select effective agents for PSP and evaluate the indications for NGT insertion, further case studies are needed. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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10 pages, 1870 KiB

Open AccessArticle

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy

by Soichiro Shibata, Kenzo Sakurai, Keiji Tachikawa, Riyoko Ko, Sakae Hino, Takayuki Fukano, Kenji Isahaya, Takafumi Haraguchi, Junji Yamauchi, Kenichiro Tanabe, Misako Nagasaka, Yuta Hagiwara, Takahiro Shimizu, Hisanao Akiyama, Yasuyuki Kobayashi, Yasuhiro Hasegawa and Yoshihisa Yamano

Neurol. Int. 2022, 14(4), 981-990; https://doi.org/10.3390/neurolint14040077 - 21 Nov 2022

Cited by 2 | Viewed by 2245

Abstract

Purpose: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. Methods: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0–5) in population #2. Results: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. Conclusions: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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20 pages, 1962 KiB

Open AccessArticle

Association of Lesion Topography with Functional Outcomes in Acute Ischemic Stroke Patients Considered for, or Receiving, Reperfusion Therapy: A Meta-Analysis

by Shuyue Chen, Kevin J. Spring, Murray C. Killingsworth, Zeljka Calic, Roy G. Beran and Sonu M. M. Bhaskar

Neurol. Int. 2022, 14(4), 903-922; https://doi.org/10.3390/neurolint14040073 - 7 Nov 2022

Viewed by 2295

Abstract

Background: The impact of lesion topography (LT), characterised by the Alberta Stroke Programme Early CT Score (ASPECTS), on outcomes after reperfusion therapy in acute ischemic stroke (AIS) is poorly elucidated. We investigated the prognostic accuracy of ASPECTS-based LT assessment and its association with clinical outcomes in AIS patients considered for reperfusion therapy or receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or none or both. Methods: Studies were identified from PubMed with additional studies added from Google Scholar. The prevalence of individual ASPECTS regions will also be determined. The association of individual ASPECTS regions with the functional outcome at 90 days will be assessed using random-effects modelling for various cut-offs, such as 6, 7 and 8. The association of continuous ASPECTS with the functional outcome at 90 days will also be undertaken. Forest plots of odds ratios (ORs) will be generated. Results: A total of 25 studies have been included in the final analysis, encompassing 11,404 patients. Pooled estimates indicate that the highest prevalence rates were in cases involving the insula and lentiform nucleus. Subgroup analysis for ASPECTS < 6 (OR 6.10; 95% CI 2.50–14.90; p < 0.0001), ASPECTS < 7 (OR 4.58; 95% CI 1.18–17.86; p < 0.0001) and ASPECTS < 8 (OR 2.26; 95% CI 1.32–3.89; p < 0.0001) revealed a significant association with poor functional outcome at 90 days. Decreasing ASPECTS significantly increased the odds of poor functional outcomes at 90 days (SMD −1.15; 95% CI −1.77–−0.52; p < 0.0001). Conclusions: Our meta-analysis demonstrates that decreasing ASPECTS is significantly associated with poor functional outcomes. Individual ASPECTS regions associated with the highest odds of poor functional outcomes were identified. Future studies on the association of LT and clinical outcomes specific to EVT are required. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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23 pages, 5602 KiB

Open AccessArticle

Is Composition of Brain Clot Retrieved by Mechanical Thrombectomy Associated with Stroke Aetiology and Clinical Outcomes in Acute Ischemic Stroke?—A Systematic Review and Meta-Analysis

by Joanna Huang, Murray C. Killingsworth and Sonu M. M. Bhaskar

Neurol. Int. 2022, 14(4), 748-770; https://doi.org/10.3390/neurolint14040063 - 20 Sep 2022

Cited by 12 | Viewed by 3544

Abstract

Background: Brain clots retrieved following endovascular thrombectomy in acute ischemic stroke patients may offer unique opportunities to characterise stroke aetiology and aid stroke decision-making in select groups of patients. However, the evidence around the putative association of clot morphology with stroke aetiology is limited and remains inconclusive. This study aims to perform a systematic review and meta-analysis to delineate the association of brain clot composition with stroke aetiology and post-reperfusion outcomes in patients receiving endovascular thrombectomy. Methods: The authors conducted a systematic literature review and meta-analysis by extracting data from several research databases (MEDLINE/PubMed, Cochrane, and Google Scholar) published since 2010. We used appropriate key search terms to identify clinical studies concerning stroke thrombus composition, aetiology, and clinical outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: The authors identified 30 articles reporting on the relationship between stroke thrombus composition or morphology and aetiology, imaging, or clinical outcomes, of which 21 were included in the meta-analysis. The study found that strokes of cardioembolic origin (SMD = 0.388; 95% CI, 0.032–0.745) and cryptogenic origin (SMD = 0.468; 95% CI, 0.172–0.765) had significantly higher fibrin content than strokes of non-cardioembolic origin. Large artery atherosclerosis strokes had significantly lower fibrin content than cardioembolic (SMD = 0.552; 95% CI, 0.099–1.004) or cryptogenic (SMD = 0.455; 95% CI, 0.137–0.774) strokes. Greater red blood cell content was also significantly associated with a thrombolysis in cerebral infarction score of 2b–3 (SMD = 0.450; 95% CI, 0.177–0.722), and a positive hyperdense middle cerebral artery sign (SMD = 0.827; 95% CI, 0.472–1.183). No significant associations were found between red blood cell, platelet, or white blood cell content and aetiology, or between clot composition and bridging thrombolysis. Conclusions: This meta-analysis found that fibrin composition is significantly higher in strokes of cardioembolic and cryptogenic origin, and that red blood cell content is positively associated with the hyperdense middle cerebral artery sign and better reperfusion outcomes. Important advances to stroke clinical workup can be derived from these findings, in which many aspects of stroke workflow remain to be optimised. As data are still limited in terms of the association of various thrombus components with stroke aetiology as well as a standardised method of analysis, further studies are required to validate these findings to guide their use in clinical decision-making. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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10 pages, 696 KiB

Open AccessArticle

EEG Correlation Coefficient Change with Motor Task Activation Can Be a Predictor of Functional Recovery after Hemiparetic Stroke

by Fei Zheng, Shin Sato, Kenji Mamada, Naoto Ozaki, Jin Kubo and Wataru Kakuda

Neurol. Int. 2022, 14(3), 738-747; https://doi.org/10.3390/neurolint14030062 - 19 Sep 2022

Cited by 2 | Viewed by 2040

Abstract

Background: Recently, it was reported that the extent of cortico-cortical functional connections can be estimated by the correlation coefficient based on electroencephalography (EEG) monitoring. We aimed to investigate whether the EEG correlation coefficient change with motor task activation can predict the functional outcomes of hemiparetic stroke patients. Methods: Sixteen post-stroke hemiparetic patients admitted to our rehabilitation ward were studied. On admission, EEG recording to calculate the correlation coefficient was performed at rest and during motor task activation. For the analysis of the EEG data, the program software FOCUS (NIHON KOHDEN, Japan) was used. The motor function of paretic limbs was evaluated with the Fugl–Meyer Assessment (FMA) on admission and 4 weeks after admission. Results: Significant increases in the correlation coefficient with motor task activation were noted in C3-F3 or C4-F4, C3-F7 or C4-F8, and F3-F7 or F4-F8 of the lesional hemisphere. Among them, the rate of the correlation coefficient change in F3-F7 or F4-F8 in the lesional hemisphere was significantly correlated with the rate of the upper-limb FMA score change. Conclusion: The extent of the EEG correlation coefficient change with motor task activation in F3-F7 or F4-F8 of the lesional hemisphere may help predict the motor functional outcomes of hemiparetic upper limbs after stroke. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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Review

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16 pages, 985 KiB

Open AccessReview

Unexplored Roles of Erythrocytes in Atherothrombotic Stroke

by Charalampos Papadopoulos, Konstantinos Anagnostopoulos, Dimitrios Tsiptsios, Stella Karatzetzou, Eirini Liaptsi, Irene Zacharo Lazaridou, Christos Kokkotis, Evangelia Makri, Maria Ioannidou, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2023, 15(1), 124-139; https://doi.org/10.3390/neurolint15010011 - 23 Jan 2023

Cited by 6 | Viewed by 3581

Abstract

Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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34 pages, 2644 KiB

Open AccessReview

Diffusion Tensor Imaging as a Prognostic Tool for Recovery in Acute and Hyperacute Stroke

by Foteini Christidi, Dimitrios Tsiptsios, Aggeliki Fotiadou, Sofia Kitmeridou, Stella Karatzetzou, Konstantinos Tsamakis, Anastasia Sousanidou, Evlampia A. Psatha, Efstratios Karavasilis, Ioannis Seimenis, Christos Kokkotis, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 841-874; https://doi.org/10.3390/neurolint14040069 - 21 Oct 2022

Cited by 12 | Viewed by 4219

Abstract

Stroke represents a major cause of mortality and long-term disability among adult populations, leaving a devastating socioeconomic impact globally. Clinical manifestation of stroke is characterized by great diversity, ranging from minor disability to considerable neurological impairment interfering with activities of daily living and even death. Prognostic ambiguity has stimulated the interest for implementing stroke recovery biomarkers, including those provided by structural neuroimaging techniques, i.e., diffusion tensor imaging (DTI) and tractography for the study of white matter (WM) integrity. Considering the necessity of prompt and accurate prognosis in stroke survivors along with the potential capacity of DTI as a relevant imaging biomarker, the purpose of our study was to review the pertinent literature published within the last decade regarding DTI as a prognostic tool for recovery in acute and hyperacute stroke. We conducted a thorough literature search in two databases (MEDLINE and Science Direct) in order to trace all relevant studies published between 1 January 2012 and 16 March 2022 using predefined terms as key words. Only full-text human studies published in the English language were included. Forty-four studies were identified and are included in this review. We present main findings and by describing several methodological issues, we highlight shortcomings and gaps in the current literature so that research priorities for future research can be outlined. Our review suggests that DTI can track longitudinal changes and identify prognostic correlates in acute and hyperacute stroke patients. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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20 pages, 685 KiB

Open AccessEditor’s ChoiceReview

Stroke and Emerging Blood Biomarkers: A Clinical Prospective

by Aimilios Gkantzios, Dimitrios Tsiptsios, Stella Karatzetzou, Sofia Kitmeridou, Vaia Karapepera, Erasmia Giannakou, Penelope Vlotinou, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 784-803; https://doi.org/10.3390/neurolint14040065 - 22 Sep 2022

Cited by 23 | Viewed by 5312

Abstract

Stroke constitutes the primary source of adult functional disability, exhibiting a paramount socioeconomic burden. Thus, it is of great importance that the prediction of stroke outcome be both prompt and accurate. Although modern neuroimaging and neurophysiological techniques are accessible, easily available blood biomarkers reflecting underlying stroke-related pathophysiological processes, including glial and/or neuronal death, neuroendocrine responses, inflammation, increased oxidative stress, blood–brain barrier disruption, endothelial dysfunction, and hemostasis, are required in order to facilitate stroke prognosis. A literature search of two databases (MEDLINE and Science Direct) was conducted in order to trace all relevant studies published between 1 January 2010 and 31 December 2021 that focused on the clinical utility of brain natriuretic peptide, glial fibrillary acidic protein, the red cell distribution width, the neutrophil-to-lymphocyte ratio, matrix metalloproteinase-9, and aquaporin-4 as prognostic tools in stroke survivors. Only full-text articles published in English were included. Twenty-eight articles were identified and are included in this review. All studied blood-derived biomarkers proved to be valuable prognostic tools poststroke, the clinical implementation of which may accurately predict the survivors’ functional outcomes, thus significantly enhancing the rehabilitation efficiency of stroke patients. Along with already utilized clinical, neurophysiological, and neuroimaging biomarkers, a blood-derived multi-biomarker panel is proposed as a reasonable approach to enhance the predictive power of stroke prognostic models. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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Other

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29 pages, 856 KiB

Open AccessSystematic Review

The Clinical Utility of Leukoaraiosis as a Prognostic Indicator in Ischemic Stroke Patients

by Foteini Christidi, Dimitrios Tsiptsios, Anastasia Sousanidou, Stefanos Karamanidis, Sofia Kitmeridou, Stella Karatzetzou, Souzana Aitsidou, Konstantinos Tsamakis, Evlampia A. Psatha, Efstratios Karavasilis, Christos Kokkotis, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 952-980; https://doi.org/10.3390/neurolint14040076 - 17 Nov 2022

Cited by 8 | Viewed by 2456

Abstract

Stroke constitutes a major cause of functional disability with increasing prevalence among adult individuals. Thus, it is of great importance for both clinicians and stroke survivors to be provided with a timely and accurate prognostication of functional outcome. A great number of biomarkers capable of yielding useful information regarding stroke patients’ recovery propensity have been evaluated so far with leukoaraiosis being among them. Literature research of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 25 June 2022 that dealt with the clinical utility of a current leukoaraiosis as a prognostic indicator following stroke. Only full-text articles published in English language were included. Forty-nine articles have been traced and are included in the present review. Our findings highlight the prognostic value of leukoaraiosis in an acute stroke setting. The assessment of leukoaraiosis with visual rating scales in CT/MRI imaging appears to be able to reliably provide important insight into the recovery potential of stroke survivors, thus significantly enhancing stroke management. Yielding additional information regarding both short- and long-term functional outcome, motor recovery capacity, hemorrhagic transformation, as well as early neurological deterioration following stroke, leukoaraiosis may serve as a valuable prognostic marker poststroke. Thus, leukoaraiosis represents a powerful prognostic tool, the clinical implementation of which is expected to significantly facilitate the individualized management of stroke patients. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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