Estimation of prognosis in patients after decompressive craniectomy after malignant hemispheric infarction: multifactorial scoring scale.

BACKGROUND: Patient's age is considered to be one of the most relevant factors in selecting surgical candidates for decompressive hemicraniectomy after malignant hemispheric infarction. However, questions about surgical indication in older patients, patients with consciousness disorder or patients with large infarctions remain unanswered. OBJECTIVE: Our aim was to design a multifactorial scoring scale based on a combination of patient-specific factors in order to optimize the assessment of prognosis in patients after hemicraniectomy malignant strokes. METHODS: In this prospective observational study with a one-year follow-up, we assessed clinical and imaging data of patients who underwent decompressive hemicraniectomy due to malignant brain infarction. Barthel index was used as a single outcome measure to distinguish favorable vs. unfavorable outcomes. Associations between multiple variables and clinical outcome were assessed. Subsequently, a design of a predictive scoring system was proposed. RESULTS: Age of the patient, preoperative level of consciousness, midline shift, and volume of infarction showed a significant association with postoperative Barthel index. According to the identified factors, a multifactorial prognostic scoring system was introduced, aimed to distinguish between favorable and unfavorable outcomes. Using ROC analysis, it has achieved an AUC of 0.74 (95%CI 0.58‒0.89, p=0.01)CONCLUSIONS: Prediction of postoperative outcome should be based on multiple variables. Our scale, based on the clinical and imaging data, can be used during decision-making to estimate potential benefit of decompressive craniectomy in patients after malignant brain infarction (Tab. 5, Fig. 1, Ref. 32). Text in PDF www.elis.sk Keywords: decompressive hemicraniectomy, malignant hemispheric infarction, indication, outcome, prediction.

Unusual and Rare Causes of Monocular Elevation Deficit.

INTRODUCTION: To study the rare and unusual causes of monocular elevation deficit. METHODS: Five patients presenting to us with diplopia and elevation deficit were thoroughly examined and were found to have monocular elevation deficit due to rare causes. OBSERVATIONS: All five were found to have different underlying etiologies - iatrogenic, sphenoid wing meningioma, cysticercosis, sarcoidosis and mid brain infarct, and were managed appropriately. DISCUSSION: Monocular Elevation Deficit can occur due to a variety of causes. Having a high index of suspicion for the more serious etiologies is of utmost importance. Thorough clinical examination and imaging help clinch the diagnosis.

Internuclear ophthalmoplegia as a presentation of procedural stroke: a case report.

BACKGROUND: Cardiac catheterization and endovascular procedures are extensively used in modern medicine, and procedural stroke is one of the major complications that the catheterization laboratory team may face in their everyday work. Recognizing the signs and symptoms of procedural stroke is crucial to ensuring appropriate management. We herein report a case of internuclear ophthalmoplegia that caused blurred vision, diplopia, and dizziness on lateral gaze as an unusual presentation of procedural stroke. CASE PRESENTATION: A 60-year-old Thai woman underwent right partial colectomy and was diagnosed with stage IV diffuse large B-cell lymphoma. Pre-chemotherapy echocardiography revealed mild left ventricular systolic dysfunction, and she therefore underwent diagnostic catheterization. Coronary angiography revealed normal coronary arteries, leading to a diagnosis of non-ischemic cardiomyopathy. After the procedure, she immediately developed dizziness and diplopia. During the right lateral gaze, she exhibited impaired adduction of the left eye and horizontal nystagmus of the right eye. A diagnosis of left internuclear ophthalmoplegia was made. Magnetic resonance imaging revealed a tiny area exhibiting characteristics of an acute infarct in the left paramedian midbrain, including the left medial longitudinal fasciculus, which explained the clinical picture. Another region of restricted diffusion indicating an acute infarct was detected in the right inferior cerebellar hemisphere. Magnetic resonance angiography revealed no significant cerebral artery disease. The patient achieved full neurological recovery 6 weeks after symptom onset. CONCLUSION: This report describes an uncommon presentation of procedural stroke that is likely to be misdiagnosed, especially by medical staff unfamiliar with internuclear ophthalmoplegia. Despite the good prognosis of internuclear ophthalmoplegia, appropriate stroke care is crucial in patients with procedural stroke because of the risk of multiple brain infarcts.

Definition, prediction, prevention and management of patients with severe ischemic stroke and large infarction.

ABSTRACT: Severe ischemic stroke carries a high rate of disability and death. The severity of stroke is often assessed by the degree of neurological deficits or the extent of brain infarct, defined as severe stroke and large infarction, respectively. Critically severe stroke is a life-threatening condition that requires neurocritical care or neurosurgical intervention, which includes stroke with malignant brain edema, a leading cause of death during the acute phase, and stroke with severe complications of other vital systems. Early prediction of high-risk patients with critically severe stroke would inform early prevention and treatment to interrupt the malignant course to fatal status. Selected patients with severe stroke could benefit from intravenous thrombolysis and endovascular treatment in improving functional outcome. There is insufficient evidence to inform dual antiplatelet therapy and the timing of anticoagulation initiation after severe stroke. Decompressive hemicraniectomy (DHC) <48 h improves survival in patients aged <60 years with large hemispheric infarction. Studies are ongoing to provide evidence to inform more precise prediction of malignant brain edema, optimal indications for acute reperfusion therapies and neurosurgery, and the individualized management of complications and secondary prevention. We present an evidence-based review for severe ischemic stroke, with the aims of proposing operational definitions, emphasizing the importance of early prediction and prevention of the evolution to critically severe status, summarizing specialized treatment for severe stroke, and proposing directions for future research.

Knockout of Rnf213 Ameliorates Cerebral Ischemic-reperfusion Injury by Inhibiting Neuronal Apoptosis Through the Akt/GSK-3ß/ß-catenin/Bcl-2 Pathway.

Previous studies by us and others have shown that RING finger protein 213 (RNF213) is associated with cerebrovascular disease and systemic vasculopathy. Indeed, Rnf213 mRNA expression is increased in cerebral ischemia reperfusion injury (CIRI). The purpose of the present study was to investigate the role of Rnf213 in CIRI. Using the middle cerebral artery occlusion (MCAO) model, we confirmed that the expression of RNF213 protein was significantly upregulated in neurons in the ischemic penumbra. Rnf213 knockout mice were successfully generated using CRISPR/Cas9 technology. According to TTC staining and Bederson neurological scale, removal of Rnf213 decreased brain infarct volume and improved neurological deficit score, although the restoration of cerebral blood flow after MCAO was similar in WT and Rnf213-/- mice. In addition, the levels of p-Akt, p-GSK-3ß, ß-catenin and Bcl-2 were significantly increased 24 h after MCAO in the ischemic penumbra of the Rnf213-/- mice compared to WT mice, indicating that Rnf213 removal may ameliorate neuronal apoptosis by regulating the Akt/GSK-3ß/ß-catenin/Bcl-2 signaling pathway. Taken together, our study reveals that Rnf213 regulates neuronal apoptosis in CIRI, therefore impacting on brain infarct volume in brain ischemia.

Diagnóstico y Tratamiento de la Enfermedad Cerebro Vascular Aguda Isquémica (Código Ictus) / Diagnosis and Treatment of Acute Ischemic Cerebrovascular Disease (Stroke Code)

La Enfermedad Cerebrovascular Isquémica (ECV-Isquémica) provoca alteraciones neurológicas agudas, causadas por la dis-función del flujo sanguíneo cerebral, lo que determina la pre-sencia de injuria neuronal.1Los factores de riesgo se clasifican en modificables y no modi-ficables entre estos últimos, los más frecuentes son: la hiperten-sión arterial, diabetes mellitus, obesidad, tabaco y sedentarismo, y su frecuencia es notablemente mayor después de los 65 años de edad (Anexo 1).1La Enfermedad Cerebrovascular Isquémica se caracteriza por ser la segunda causa de mortalidad a nivel mundial, y la ter-cera en causar discapacidad. En 2019, según el reporte del Ins-tituto Nacional de Estadísticas y Censos (INEC), se registraron 4577 fallecimientos producto de esta patología; y se reportó como la tercera causa de fallecimiento en hombres y mujeres en Ecuador.2El impacto económico que genera la ECV-Isquémica es con-siderable, puesto que se ha evidenciado que aproximadamente supone un gasto promedio de 4330 dólares en los primeros 3 meses posterior a presentar esta patología, sin considerar otras consecuencias como la pérdida laboral.3

Ischemic Cerebrovascular Disease (Ischemic-CVD) causes acute neurological alterations, caused by cerebral blood flow dysfunction, which determines the presence of neuronal injury.1Risk factors are classified as modifiable and non-modifiable, among the latter, the most frequent are: arterial hypertension, diabetes mellitus, obesity, smoking and sedentary lifestyle, and their frequency is notably higher after 65 years of age (Anexo 1).1Ischemic Cerebrovascular Disease is characterized as the second leading cause of mortality worldwide, and the third leading cause of disability. In 2019, according to the report of the National Ins-titute of Statistics and Census (INEC), 4577 deaths were regis-tered as a result of this pathology; and it was reported as the third leading cause of death in men and women in Ecuador.2The economic impact of CVD-ischemic stroke is considerable, since it has been shown that approximately US$ 4330 is spent on average in the first 3 months after the onset of this pathology, without considering other consequences such as loss of work.3

PFT-α protects the blood-brain barrier through the Wnt/ß-catenin pathway after acute ischemic stroke.

The dysfunction of blood-brain barrier (BBB) plays a pivotal role in brain injury and subsequent neurological deficits of ischemic stroke. The current study aimed to examine the potential correlation between p53 inhibition and the neuroprotective effect of on the BBB. Rat middle cerebral artery occlusion and reperfusion model (MCAO/R) and oxygen-glucose deprivation/re-oxygenation model (OGD/R) were employed to simulate cerebral ischemia-reperfusion (CI/R) injury occurrence in vivo and in vitro. mNSS and TTC staining were applied to evaluate neurological deficits and brain infarct volumes. Evans blue (EB) staining was carried out to examine the permeability of BBB. RT-qPCR and Western blot to examine the mRNA and protein levels. Cell viabilities were detected by CCK-8. Flow cytometry and ELISA assay were employed to examine apoptosis and neuroinflammation levels. TEER value and sodium fluorescein were carried out to explore the permeability of HBMEC cells. PFT-α inhibited P53 and promoted the expression of ß-catenin and cyclin D1, which were reversed by DKK1. PFT-α inhibited neurological deficits, brain infarct volume, neuroinflammation, apoptosis, and BBB integrity than the MCAO/R rats; however, this inhibition was reversed by DKK1. PFT-α promoted OGD/R-induced cell viability in NSCs, and suppressed inflammation and apoptosis, but DKK1 weakened the effect of PFT-α. PFT-α increased OGD/R-induced TEER values in cerebrovascular endothelial cells, inhibited sodium fluorescein permeability, and increased the mRNA levels of tight junction protein, but they were all attenuated by DKK1. PFT-α protects the BBB after acute ischemic stroke via the Wnt/ß-catenin pathway, which in turn improves neurological function.

Activating Transcription Factor 3 Diminishes Ischemic Cerebral Infarct and Behavioral Deficit by Downregulating Carboxyl-Terminal Modulator Protein.

Activating transcription factor 3 (ATF3) is a stress-induced transcription factor and a familiar neuronal marker for nerve injury. This factor has been shown to protect neurons from hypoxic insult in vitro by suppressing carboxyl-terminal modulator protein (CTMP) transcription, and indirectly activating the anti-apoptotic Akt/PKB cascade. Despite prior studies in vitro, whether this neuroprotective pathway also exists in the brain in vivo after ischemic insult remains to be determined. In the present study, we showed a rapid and marked induction of ATF3 mRNA throughout ischemia-reperfusion in a middle cerebral artery (MCA) occlusion model. Although the level of CTMP mRNA was quickly induced upon ischemia, its level showed only a mild increase after reperfusion. With the gain-of-function approach, both pre- and post-ischemic administration of Ad-ATF3 ameliorated brain infarct and neurological deficits. Whereas, with the loss-of-function approach, ATF3 knockout (KO) mice showed bigger infarct and worse functional outcome after ischemia. In addition, these congenital defects were rescued upon reintroducing ATF3 to the brain of KO mice. ATF3 overexpression led to a lower level of CTMP and a higher level of p-Akt(473) in the ischemic brain. On the contrary, ATF3 KO resulted in upregulation of CTMP and downregulation of p-Akt(473) instead. Furthermore, post-ischemic CTMP siRNA knockdown led to smaller infarct and better behaviors. CTMP siRNA knockdown increased the level of p-Akt(473), but did not alter the ATF3 level in the ischemic brain, upholding the ATF3→CTMP signal cascade. In summary, our proof-of-principle experiments support the existence of neuroprotective ATF3→CTMP signal cascade regulating the ischemic brain. Furthermore, these results suggest the therapeutic potential for both ATF3 overexpression and CTMP knockdown for stroke treatment.

Silent Brain Infarction, Delirium, and Cognition in Three Invasive Cardiovascular Procedures: a Systematic Review.

Silent brain infarctions (SBIs) are brain lesions noted on neuroimaging that are not associated with clinical symptoms. SBIs are associated with a number of vascular risk factors and are common following invasive cardiovascular procedures such as atrial fibrillation (AF) ablation, coronary artery bypass graft (CABG), and transcatheter aortic valve replacement (TAVR). Although not eliciting signs of clinical stroke, SBIs are associated with increased frailty, and motor and mood features. Less is known, however, about the relationship between SBI, cognition, and delirium following invasive cardiac procedures and most investigations into these relationships have been reported in large-scale epidemiological studies. In the current paper, we conducted a systematic review to evaluate evidence of a relationship between SBI, delirium, and cognitive decline following CABG, AF ablation, and TAVR. Twenty studies met inclusion criteria. In general, our review identified conflicting results for each cardiac procedure, with some studies suggesting a relationship between SBI, cognitive impairment, and delirium, whereas others showed no relationship between SBI, cognitive impairment, and delirium. Potential reasons for this discrepancy as well as suggestions for future research are discussed.

Effects of Three Different Doses of Inter-Alpha Inhibitor Proteins on Severe Hypoxia-Ischemia-Related Brain Injury in Neonatal Rats.

Hypoxia-ischemia (HI)-related brain injury is an important cause of morbidity and long-standing disability in newborns. We have previously shown that human plasma-derived inter-alpha inhibitor proteins (hIAIPs) attenuate HI-related brain injury in neonatal rats. The optimal dose of hIAIPs for their neuroprotective effects and improvement in behavioral outcomes remains to be determined. We examined the efficacy of 30, 60, or 90 mg/kg of hIAIPs administered to neonatal rats after exposure to HI for 2 h. Postnatal day 7 (P7) Wistar rats were exposed to either sham-surgery or unilateral HI (right carotid artery ligation, 2 h of 8% O2) brain injury. A placebo, 30, 60, or 90 mg/kg of hIAIPs were injected intraperitoneally at 0, 24 and 48 h after HI (n = 9-10/sex). We carried out the following behavioral analyses: P8 (righting reflex), P9 (negative geotaxis) and P10 (open-field task). Rats were humanely killed on P10 and their brains were stained with cresyl violet. Male extension/contraction responses and female righting reflex times were higher in the HI placebo groups than the sham groups. Female open-field exploration was lower in the HI placebo group than the sham group. hIAIPs attenuated these behavioral deficits. However, the magnitude of the responses did not vary by hIAIP dose. hIAIPs reduced male brain infarct volumes in a manner that correlated with improved behavioral outcomes. Increasing the hIAIP dose from 30 to 90 mg/kg did not further accentuate the hIAIP-related decreases in infarct volumes. We conclude that larger doses of hIAIPs did not provide additional benefits over the 30 mg/kg dose for behavior tasks or reductions in infarct volumes in neonatal rats after exposure to severe HI.

Decompressive hemicraniectomy for space-occupying brain infarction: Nationwide population-based registry study.

OBJECTIVE: We analyzed data from the Norwegian Stroke Registry (NSR) to study access to and outcomes of decompressive hemicraniectomy for brain infarction in a nationwide routine clinical setting. We also discretionary assessed whether the outcomes were comparable with those achieved in randomized controlled trials (RCTs), and whether the use was in accordance with guidelines. METHODS: The NSR is a nationwide (population 5.3 million) clinical quality registry. We included all stroke-cases operated in 2017 through 2019, and retrieved data on baseline characteristics, treatment and functional outcome after three months (dichotomized modified Rankin Scale score; favorable (0-3) or unfavorable (4-6)). Crude treatment rates and the expected proportion of patients transferred from a local hospital to a stroke-center for the operation were estimated, based on the total population's distribution of residency. RESULTS: The 68 cases were 17 (25%) women and 51 (75%) men with a median National Institute of Health Stroke Scale (NIHSS) score on admission of 14.0 (inter-quartile range (IQR) 11.0) and a median time from onset to hemicraniectomy of 34.3 (IQR 40.9) hours. The crude treatment rate varied between regions from 0.29 to 1.40 operations per 100,000 population per year, and the proportion transferred from a local hospital (50%) was lower than expected (68%). A favorable outcome was achieved in 20/52 (38.5%) cases. CONCLUSIONS: The findings indicate gender- and geographic-inequalities in access. Among operated cases, outcomes were comparable with those reported from RCTs, and the use in accordance with recommendations in the current guidelines from the American Stroke Association.

Brain infarction following meningioma surgery-incidence, risk factors, and impact on function, seizure risk, and patient-reported quality of life.

In this study, we seek to explore the incidence of and potential risk factors for postoperative infarctions after meningioma surgery, in addition to the possible association with new neurological deficits, seizures, and health-related quality of life (HRQoL). A single-center cohort study was conducted, where all patients operated for an intracranial meningioma at our institution between 2007 and 2020 were screened for inclusion. Clinical data were prospectively collected in a local tumor registry, and HRQoL was assessed using both generic and disease-specific instruments. In total, 327 meningioma operations were included, and early postoperative MRIs showed peritumoral infarctions in 114 (34.9%). Median infarction volume was 4.5 ml (interquartile range 2.0-9.5) and 43 (37.7%) of the infarctions were rim-shaped, 44 (38.6%) were sector-shaped, 25 (21.9%) were a combination of rim- and sector-shaped, and two (1.8%) were remote infarctions. Permanent neurological deficits were seen in 22 patients (6.7%) and deficits were associated with infarctions (p < 0.001). There was no difference in frequency of registered postoperative epilepsy between patients with versus without infarctions. Patients with infarctions reported more future uncertainty; otherwise, there were no significant differences in disease specific HRQoL between patients with versus without infarctions. In this study, we found that peritumoral infarctions after meningioma resection are common. Most patients with permanent neurological deficits had infarctions. Yet, most infarctions were small, and although sometimes symptomatic on individual level, infarctions did not lead to significant deterioration of HRQoL on group level.

Characterization of Astrocytes in the Minocycline-Administered Mouse Photothrombotic Ischemic Stroke Model.

Astrocytes, together with microglia, play important roles in the non-infectious inflammation and scar formation at the brain infarct during ischemic stroke. After ischemia occurs, these become highly reactive, accumulate at the infarction, and release various inflammatory signaling molecules. The regulation of astrocyte reactivity and function surrounding the infarction largely depends on intercellular communication with microglia. However, the mechanisms involved remain unclear. Furthermore, recent molecular biological studies have revealed that astrocytes are highly divergent under both resting and reactive states, whereas it has not been well reported how the communication between microglia and astrocytes affects astrocyte divergency during ischemic stroke. Minocycline, an antibiotic that reduces microglial activity, has been used to examine the functional roles of microglia in mice. In this study, we used a mouse photothrombotic ischemic stroke model to examine the characteristics of astrocytes after the administration of minocycline during ischemic stroke. Minocycline increased astrocyte reactivity and affected the localization of astrocytes in the penumbra region. Molecular characterization revealed that the induced expression of mRNA encoding the fatty acid binding protein 7 (FABP7) by photothrombosis was enhanced by the minocycline administration. Meanwhile, minocycline did not significantly affect the phenotype or class of astrocytes. The expression of Fabp7 mRNA was well correlated with that of tumor-necrosis factor α (TNFα)-encoding Tnf mRNA, indicating that a correlated expression of FABP7 from astrocytes and TNFα is suppressed by microglial activity.

Pre- and post-conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta-analysis.

BACKGROUND: Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear. METHODS: We evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion. RESULTS: Poly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre- and post-conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor-κB (NF-κB) [SMD = -1.78; CIs (-2.67, -0.88); p = 0.0)], and tumor necrosis factor alpha (TNF-α) [SMD = -16.83; CIs (-22.63, -11.02); p = 0.00]. CONCLUSION: We showed that poly I:C is neuroprotective and acts via the TLR3/NF-κB/TNF-α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.

Editor's Choice - Relevance of Infarct Size, Timing of Surgery, and Peri-operative Management for Non-ischaemic Cerebral Complications After Carotid Endarterectomy.

OBJECTIVE: To assess the incidence of post-operative non-ischaemic cerebral complications as a pivotal outcome parameter with respect to size of cerebral infarction, timing of surgery, and peri-operative management in patients with symptomatic carotid stenosis who underwent carotid endarterectomy (CEA). METHODS: Retrospective analysis of prospectively collected single centre CEA registry data. Consecutive patients with symptomatic carotid stenosis were subjected to standard patch endarterectomy. Brain infarct size was measured from the axial slice of pre-operative computed tomography/magnetic resonance imaging demonstrating the largest infarct dimension and was categorised as large (> 4 cm2), small (≤ 4 cm2), or absent. CEA was performed early (within 14 days) or delayed (15 - 180 days) after the ischaemic event. Peri-operative antiplatelet regimen (none, single, dual) and mean arterial blood pressure during surgery and at post-operative stroke unit monitoring were registered. Non-ischaemic post-operative cerebral complications were recorded comprising haemorrhagic stroke and encephalopathy, i.e., prolonged unconsciousness, delirium, epileptic seizure, or headache. RESULTS: 646 symptomatic patients were enrolled of whom 340 (52.6%) underwent early CEA; 367 patients (56.8%) demonstrated brain infarction corresponding to stenosis induced symptoms which was small in 266 (41.2%) and large in 101 (15.6%). Post-operative non-ischaemic cerebral complications occurred in 12 patients (1.9%; 10 encephalopathies, two haemorrhagic strokes) and were independently associated with large infarcts (adjusted odds ratio [OR] 6.839; 95% confidence interval [CI] 1.699 - 27.534) and median intra-operative mean arterial blood pressure in the upper quartile, i.e., above 120 mmHg (adjusted OR 13.318; 95% CI 2.749 - 64.519). Timing of CEA after the ischaemic event, pre-operative antiplatelet regimen, and post-operative blood pressure were not associated with non-ischaemic cerebral complications. CONCLUSION: Infarct size and unintended high peri-operative blood pressure may increase the risk of non-ischaemic complications at CEA independently of whether performed early or delayed.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Multimodal Medical Image Fusion Based on Multiple Latent Low-Rank Representation.

A multimodal medical image fusion algorithm based on multiple latent low-rank representation is proposed to improve imaging quality by solving fuzzy details and enhancing the display of lesions. Firstly, the proposed method decomposes the source image repeatedly using latent low-rank representation to obtain several saliency parts and one low-rank part. Secondly, the VGG-19 network identifies the low-rank part's features and generates the weight maps. Then, the fused low-rank part can be obtained by making the Hadamard product of the weight maps and the source images. Thirdly, the fused saliency parts can be obtained by selecting the max value. Finally, the fused saliency parts and low-rank part are superimposed to obtain the fused image. Experimental results show that the proposed method is superior to the traditional multimodal medical image fusion algorithms in the subjective evaluation and objective indexes.

Embolic Stroke of Undetermined Source (ESUS) and Stroke in Atrial Fibrillation Patients: not so Different after all?

Abstract Background: Stroke related to atrial fibrillation (AF) is associated with high recurrence and mortality rates. Embolic Stroke of Undetermined Source (ESUS) is associated with fewer vascular risk factors, less disability, and a high recurrence rate. Objective: To compare risk factors, functional outcomes and the occurrence of primary endpoint (a composite of recurrent stroke, cardiovascular death, and myocardial infarction) between AF stroke and ESUS patients. Method: A retrospective analysis was conducted including all consecutive patients with first-ever ischemic stroke admitted to the Hospital de Clinicas (Clinical Hospital) of the Federal University of Paraná from October 2012 to January 2017 (n=554). There were 61 patients with stroke due to AF and 43 due to ESUS. Both groups were compared for demographic characteristics and vascular risk factors. Logistic regression models were performed to assess the impact of each variable on the primary endpoint in a 12-month follow-up. Statistical significance was considered for p-values < 0.05. Results: ESUS patients, as compared to AF patients, were younger and more likely to be smokers. ESUS patients presented a mean CHADS2VASc score of 4, while the AF group presented a score of 5 (p <0.001). The primary endpoint was observed in 9 (20.9%) ESUS and 11 (18.0%) AF patients over a 12-month period (p=0.802). Higher glucose levels upon hospital admission (p=0.020) and a higher modified Rankin Scale upon hospital discharge (p=0.020) were predictors of the primary endpoint occurrence. Conclusion: AF and ESUS stroke patients presented very similar independence rates upon hospital discharge and outcomes after 12 months, despite some baseline differences, including stroke recurrence, vascular death, and myocardial infarction.

Effects of cerebral small vessel disease on the outcomes in cryptogenic stroke with active cancer.

Cerebral small vessel diseases (cSVDs) affect the prognosis of various types of ischemic stroke. Therefore, we evaluated the association between cSVD and the prognosis of cryptogenic stroke patients with active cancer. We enrolled patients diagnosed with cryptogenic stroke and active cancer from 2010 to 2016. Early neurological deterioration (END) was defined as a ≥ 2-point increase in the total NIHSS score or a ≥ 1-point increase in the motor NIHSS score within the first 72 h. We defined an unfavorable outcome as the modified Rankin Scale (mRS) score ≥ 3 points. We analyzed cSVD separately for each subtype including white matter hyperintensity (WMH), silent brain infarct (SBI), and cerebral microbleed (CMB). A total of 179 cryptogenic stroke patients with active cancer were evaluated. In the multivariable analysis, SBI was significantly associated with END (adjusted odds ratio = 3.97, 95% confidence interval: 1.53-10.33). This close relationship between SBI and END increased proportionally with an increase in SBI burden. However, WMH and CMB showed no significant association with END. None of the cSVD subtypes showed a statistically significant relationship with the 3-month unfavorable outcome. SBI was the only parameter closely associated with END in cryptogenic stroke patients with active cancer.

Brain infarctions after glioma surgery: prevalence, radiological characteristics and risk factors.

BACKGROUND: Prevalence, radiological characteristics, and risk factors for peritumoral infarctions after glioma surgery are not much studied. In this study, we assessed shape, volume, and prevalence of peritumoral infarctions and investigated possible associated factors. METHODS: In a prospective single-center cohort study, we included all adult patients operated for diffuse gliomas from January 2007 to December 2018. Postoperative infarctions were segmented using early postoperative MRI images, and volume, shape, and location of postoperative infarctions were assessed. Heatmaps of the distribution of tumors and infarctions were created. RESULTS: MRIs from 238 (44%) of 539 operations showed restricted diffusion in relation to the operation cavity, interpreted as postoperative infarctions. Of these, 86 (36%) were rim-shaped, 103 (43%) were sector-shaped, 40 (17%) were a combination of rim- and sector-shaped, and six (3%) were remote infarctions. Median infarction volume was 1.7 cm3 (IQR 0.7-4.3, range 0.1-67.1). Infarctions were more common if the tumor was in the temporal lobe, and the map shows more infarctions in the periventricular watershed areas. Sector-shaped infarctions were more often seen in patients with known cerebrovascular disease (47.6% vs. 25.5%, p = 0.024). There was a positive correlation between infarction volume and tumor volume (r = 0.267, p < 0.001) and infarction volume and perioperative bleeding (r = 0.176, p = 0.014). Moreover, there was a significant positive association between age and larger infarction volumes (r = 0.193, p = 0.003). Infarction rates and infarction volumes varied across individual surgeons, p = 0.037 (range 32-72%) and p = 0.026. CONCLUSIONS: In the present study, peritumoral infarctions occurred in 44% after diffuse glioma operations. Infarctions were more common in patients operated for tumors in the temporal lobe but were not more common following recurrent surgeries. Sector-shaped infarctions were more common in patients with known cerebrovascular disease. Increasing age, larger tumors, and more perioperative bleeding were factors associated with infarction volumes. The risk of infarctions and infarction volumes may also be surgeon-dependent.