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Introduction: Patients with a large vessel occlusion (LVO) stroke who are transferred to a comprehensive stroke center (CSC) for endovascular thrombectomy (EVT) often experience infarct growth. We aimed to investigate the clinical predictors of fast infarct growth and its effect on clinical outcomes. Methods: We retrospectively collected EVT data of patients with LVO transferred to our center between March 14, 2019, and June 28, 2022. The absolute rate of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) decay was defined as (ASPECTS primary CT − ASPECTS repeat CT)/elapsed hours. The ratio of relative ASPECTS deterioration was defined as (ASPECTS primary CT − ASPECTS repeat CT)/ASPECTS primary CT. In the primary analysis, the study population was dichotomized into absolute slow progressors and absolute fast progressors using the median absolute rate of ASPECTS decay. Secondary analysis was also conducted using the median relative ASPECTS deterioration ratio, and the study population was categorized into relative fast progressors and relative slow progressors. Favorable outcome was defined as a 90-day modified Rankin Scale (mRS) score ≤ 2. Results: We included 309 patients: median age 72 years (IQR 65–77); median National Institutes of Health Stroke Scale (NIHSS) 14 (IQR 11–18). The median absolute rate of ASPECTS decay was 0.42 points/hour and the median relative ASPECTS deterioration ratio was 11.1%. Overall, fast infarct growth was independently associated with worse 90-day outcome (absolute rate of ASPECTS decay: OR = 3.395; 95% CI 1.844–6.250; P < 0.001; relative ASPECTS deterioration ratio: OR = 3.754; 95% CI 2.050–6.873; P < 0.001). In multivariable analysis, fast infarct growth was independently associated with high admission NIHSS, proximal occlusions, and poor collateral status, while intravenous thrombolysis before transfer was negative with fast inter-hospital infarct growth. Conclusions: For patients with LVO stroke who are transferred from a PSC to CSC for EVT, the infarct growth rate is highly variable and is strongly associated with 90-day outcomes. Initiation of intravenous bridging therapy before transfer may limit the infarct growth during inter-hospital transfer. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic extradural haematoma (EDH) is one of the neurosurgical emergencies in the paediatric population. One of the rare complications of extradural haematoma is adjacent parenchymal infarct from the compressive effect of haematoma leading to further morbidity. We aimed to evaluate the incidence and outcomes of this rare complication in paediatric trauma patients. Methods: We undertook a retrospective review of all operative extradural haematoma cases in single centre paediatric neurosurgical unit between the years 2008 and 2024. Cases with postoperative imaging were analysed for demographics, age, sex, dimensions of haematoma and underlying infarct, pre-operative GCS and pupillary abnormality and time interval from scan to surgery. Infarct was defined as well-defined parenchymal hypodensity corresponding to vascular territory and not attributable to contusions on postoperative CT head performed at 24–72 h. All patients suspected of stroke had further MRI brain for evaluation. Statistical analysis was then performed comparing groups with and without infarct. Results: Overall, 115 cases of extradural haematoma were identified during the study period. Eighty cases had adequate postoperative imaging to allow assessment for infarcts; 7.5% demonstrated evidence of infarct underlying extradural haematoma. Mean age in the infarct group was 1.8 years (M:F ratio 2:1) with mean EDH dimensions of 77 mm × 31.4 mm × 79.7 mm). Mean age in the non-infarct group was 8.6 years (M:F ratio 2:1) with mean EDH dimensions of (57.5 mm × 19.6 mm × 62.6 mm). Children with infarcts were significantly younger with larger haematoma dimensions and had a higher proportion of pupillary abnormalities. There was no significant difference in pre-operative GCS and scan-to-surgery time-lapse between the groups with and without infarct. Conclusion: Compressive effect of EDH can lead to underlying parenchymal infarct. Children with extradural haematoma-related infarct were younger with larger haematoma size and a higher proportion of pupillary abnormalities. [ABSTRACT FROM AUTHOR]

Introduction: Pituitary apoplexy has historically been considered an emergent condition that necessitates surgical intervention when there is acute symptomatic onset. This potentially serious condition often occurs in the setting of an underlying adenoma, cystic lesion, or other sellar mass. When these mass lesions hemorrhage within the confined space of the sella turcica, the pituitary gland is subjected to hemorrhagic ischemia. Furthermore, critical neurovasculature in close proximity to the sella can sustain collateral damage. In the present study, we investigate whether early versus delayed surgical intervention (in terms of three timelines: before versus after 48 h, 72 h, and 7 days, respectively) results in differences in visual outcomes for patients experiencing pituitary apoplexy with acute onset neurological and/or neuro-opthalmic symptoms. Furthermore, we compare the efficacy of surgical decompression versus expectant management of this condition. Methods: Accordingly, we queried the PubMed, Scopus, and Embase databases in adherence to PRISMA guidelines. Quantitative meta-analysis was performed according to the Mantel–Haenszel method and forest plots were generated using Review Manager v5.4. P-values < 0.05 were defined as the threshold for statistical significance. Results: Twenty-nine studies remained eligible for review following initial search and screen, including 16 studies describing the role of intervention timing and 15 studies comparing intervention modality. Most patients presented with a visual deficit, and all patients underwent surgery – most commonly via the endoscopic endonasal (EEA) approach. Two hundred and twenty patients were included in the sub-analysis for the 7-day cutoff point. Furthermore, 81 patients underwent surgical decompression of the sella prior to 48 h, and 32 patients underwent surgical decompression between 48–72 h following presentation. Almost all patients exhibited improved vision post-decompression, including 19/19 patients (100%) in the post-72-h cohort. On meta-analysis using the Mantel–Haenszel method, there was a significant difference in vision outcomes in favor of patients who underwent surgical decompression before 7 days as compared to after seven days (OR 5.88, 95% CI [1.77, 19.60], I2 = 0%, p < 0.01). In a separate sub-analysis, there was a total of 288 patients across 15 studies comparing surgical versus conservative management of pituitary apoplexy. These management options proved equivocal on meta-analysis (p > 0.05). Conclusion: In the present study, timing of surgical intervention for pituitary apoplexy was predictive of visual function recovery only at the 7-day timepoint, as has been reported by previous studies. Ultimately, this suggests that pituitary apoplexy involving severe visual deficits or altered mental status is best addressed within the first seven days post-presentation, and that both surgery and conservative management can offer similar outcomes. When apoplexy is suspected, IV corticosteroids should be administered independent of acuity or severity to prevent secondary adrenal crisis. Subsequently, for patients presenting without severe visual or other neurological deficits, expectant management is recommended. Management should be patient-specific and dependent upon the severity of symptoms present at onset. [ABSTRACT FROM AUTHOR]

Objectives: The few voxel-wise lesion-symptom mapping (VLSM) studies aimed at identifying the anatomy of executive function are limited by the absence of a model and by small populations. Using Trail Making Test (TMT) and verbal fluency and a model of their architectures, our objective was to identify the key structures underlying two major executive processes, set-shifting and strategic word search. Methods: We applied a validated VLSM analysis to harmonized cognitive and imaging data from 2009 ischemic stroke patients as a part of the Meta VCI Map consortium. All contrast analyses used an adjusted threshold with 2000 Freedman–Lane permutations (p ≤ 0.05). Results: The TMT parts A and B were associated with structures involved in visual-spatial processing, the motor system, the frontal lobes, and their subcortical connections. Set-shifting depended on the left dorsomedial frontal region. Both semantic and phonemic fluency tests depended on verbal output abilities and processing speed with similar slopes in different languages. The strategic search process depended on Broca's area, F2 and related tracts, temporal and deep regions. Lastly, the lesion map of set-shifting did not overlap with those of strategic word search processes. Interpretation: Our results identify the anatomical substrates of two main executive processes, revealing that they represent only a specific subpart of previously reported structures. Finally, our results indicate that executive functions depend on several specific, anatomically separable executive processes mainly operating in various parts of the frontal lobes. [ABSTRACT FROM AUTHOR]

Background: Several neurovascular procedures require temporary occlusion of cerebral arteries, leading to ischemia of unpredictable length, occasionally causing brain infarction. Experimental models of cerebral ischemia–reperfusion injury have established that platelet adhesion and coagulation play detrimental roles in reperfusion injury following transient cerebral ischemia. Therefore, in a model of cerebral ischemia–reperfusion injury (IRI), we investigated the therapeutic potential of a dual antiplatelet and anticoagulant (APAC) heparin proteoglycan mimetic which is able to bind to vascular injury sites. Methods: Brain ischemia was induced in mice by transient occlusion of the right middle cerebral artery for 60 min. APAC, unfractionated heparin (UFH) (both at heparin equivalent doses of 0.5 mg/kg), or vehicle was intravenously administered 10 min before or 60 min after the start of ischemia. At 24 h later, mice were scored for their neurological and motor behavior, and brain damage was quantified. Results: Both APAC and UFH administered before the onset of ischemia reduced brain injury. APAC and UFH pretreated mice had better neurological and motor functions (p < 0.05 and p < 0.01, respectively) and had significantly reduced cerebral infarct sizes (p < 0.01 and p < 0.001, respectively) at 24 h after transient occlusion compared with vehicle-treated mice. Importantly, no macroscopic bleeding complications were observed in either APAC- or UFH-treated animals. However, when APAC or UFH was administered 60 min after the start of ischemia, the therapeutic effect was lost, but without hemorrhaging either. Conclusions: Pretreatment with APAC or UFH was safe and effective in reducing brain injury in a model of cerebral ischemia induced by transient middle cerebral artery occlusion. Further studies on the use of APAC to limit ischemic injury during temporary occlusion in neurovascular procedures are indicated. [ABSTRACT FROM AUTHOR]

H2S-donors are cardioprotective in ischemia/reperfusion (I/R) injury. Some H2S-donors exert their beneficial effects in a nitric oxide (NO)-dependent manner, while others act using NO-independent pathways. The aims of the present study were to (i) evaluate whether H2S-donors with distinct pharmacodynamic properties act synergistically in I/R injury and (ii) determine if H2S-donors remain cardioprotective in obese mice. C57BL/6 mice were subjected to 30 min of ischemia followed by 120 min of reperfusion. Donors were administered intravenously at the end of ischemia (Na2S: 1 μmol/kg, GYY4137: 25 μmol/kg, AP39: 0,25 μmol/kg), while the 3-mercaptopyruvate sulfurtransferase (10 mg/kg) inhibitor was given intraperitonially 1 h prior to ischemia. Infarct size was estimated by 2,3,5-triphenyltetrazolium staining, while the area at risk was calculated using Evans blue. All three donors reduced infarct size when administered as a sole treatment. Co-administration of Na2S/GYY4137, as well as Na2S/AP39 reduced further the I/R injury, beyond what was observed with each individual donor. Since inhibition of the H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase is known to reduce infarct size, we co-administered C3 with Na2S to determine possible additive effects between the two agents. In this case, combination of C3 with Na2S did not yield superior results compared to the individual treatments. Similarly, to what was observed in healthy mice, administration of a H2S-donor (Na2S or AP39) reduced I/R injury in mice rendered obese by consumption of a high fat diet. We conclude that combining a NO-dependent with a NO-independent H2S-donor leads to enhanced cardioprotection and that H2S-donors remain effective in obese animals. [ABSTRACT FROM AUTHOR]

Purpose: Previous work suggests that Dihydroorotate dehydrogenase (DHODH) inhibition via teriflunomide (TERI) may provide protection in multiple disease models. To date, little is known about the effect of TERI on the heart. This study was performed to assess the potential effects of TERI on cardiac ischemia reperfusion injury. Methods: Male and female rat hearts were subjected to global ischemia (25 min) and reperfusion (120 min) on a Langendorff apparatus. Hearts were given either DMSO (VEH) or teriflunomide (TERI) for 5 min prior to induction of ischemia and during the reperfusion period. Left ventricular pressure, ECG, coronary flow, and infarct size were determined using established methods. Mitochondrial respiration was assessed via respirometry. Results: Perfusion of hearts with TERI led to no acute effects in any values measured across 500 pM–50 nM doses. However, following ischemia–reperfusion injury, we found that 50 nM TERI-treated hearts had an increase in myocardial infarction (p < 0.001). In 50 nM TERI-treated hearts, we also observed a marked increase in the severity of contracture (p < 0.001) at an earlier time-point (p = 0.004), as well as reductions in coronary flow (p = 0.037), left ventricular pressure development (p = 0.025), and the rate-pressure product (p = 0.008). No differences in mitochondrial respiration were observed with 50 nM TERI treatment (p = 0.24–0.87). Conclusion: This study suggests that treatment with TERI leads to more negative outcomes following cardiac ischemia reperfusion, and administration of TERI to at-risk populations should receive special considerations. [ABSTRACT FROM AUTHOR]

Background: Capsular warning syndrome (CWS) is a rare clinical syndrome characterised by recurrent and transient episodes of focal neurological deficits with high risk of infarction. The exact physiological mechanism of CWS remains unclear but is most commonly believed to be a result of haemodynamic insufficiency in diseased, small penetrating vessels. There are no defined treatment guidelines or established effective therapy. Case presentation: We describe the case of a 65-year-old man who presented to the emergency department with recurrent episodes of dysarthria coupled with right facial droop and right-sided weakness. Symptoms recurred a total of ten times within a span of 3 h. He had new onset atrial fibrillation. An initial cerebral angiogram showed mild intracranial atherosclerotic disease with no proximal large vessel occlusion or acute infarct. Magnetic resonance imaging 1 h later demonstrated an infarct in the left corona radiata. Conclusions: This case illustrates an uncommon etiology of CWS. We will also discuss the lack of consensus in treatment options for CWS to mitigate a complete stroke. [ABSTRACT FROM AUTHOR]

Purpose: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows. Methods: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3–6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study. Results: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79–77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04–1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53–0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60–0.83, P < 0.001) in predicting poor outcome accurately. Conclusion: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinosarcomas are rare and carry a very poor prognosis. They usually present with extensive lymphatic spread. An acute presentation of a stroke may reveal the underlying diagnosis. Case presentation: A woman in her 50s with no reported medical history presented to the emergency department as a code stroke. She was found during the evening by her sister leaving the bathroom disheveled. At that time, she was found to be mute, not following commands, with left gaze deviation and right hemiparesis. Computed tomography (CT) imaging showed an acute infarct in the left middle cerebral artery M2 branch or frontoparietal territory consistent with acute stroke. Upon further review, the sister states that she has had significant vaginal bleeding and never had menopause. On admission, she had significant anemia. CT of the abdomen and pelvis showed a large right adnexal mass, endometrial thickening, diffuse lymphadenopathy, omental nodularity, and a pulmonary nodule concerning for gynecologic malignancy with metastasis. Surgical pathology showed high grade endometrial carcinosarcoma. She was outside of the tPA window, and neurology determined her not to be a candidate for thrombectomy. She was managed medically with antiplatelet agents, high dose atorvastatin, and blood transfusions. Conclusions: Endometrial carcinosarcoma can present with severe anemia and irregular menstrual bleeding. In patients without routine gynecologic care, endometrial carcinosarcoma can go unnoticed and only be identified after workup for another condition such as acute stroke. Endometrial biopsy for diagnosis may be challenging in a patient with severe anemia. Alternatively, transvaginal ultrasonography with Doppler study and magnetic resonance imaging may be used to support the diagnosis. Furthermore, endometrial carcinosarcoma can complicate ischemic stroke management as it can present with bleeding and make it difficult to use anticoagulating agents. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the accuracy of automated software (iStroke) on magnetic resonance (MR) apparent diffusion coefficient (ADC) and perfusion-weighted imaging (PWI) against ground truth in assessing infarct core, and compare the hypoperfusion volume and mismatch volume on iStroke with those on Food and Drug Administration-approved software (RAPID) in patients with acute ischemic stroke. Methods: We used the single-volume decomposition method to develop the iStroke (iStroke; Beijing Tiantan Hospital, Beijing, China) software. Patients with ischemic stroke were collected from two educational hospitals in China with MR-PWI performed in the emergency department within 24 h of symptom onset. Infarct core volume was defined as ADC < 620 × 10−6 mm2/s and hypoperfusion volume was defined as Tmax > 6 s. We compared the accuracy of infarct core volume using iStroke and RAPID (iSchema View Inc, Menlo Park, CA) software with ground truth. Results: We included 405 patients with acute ischemic stroke with MR ADC and PWI sequences. The infarct core volume on iStroke (median 2.43 ml, interquartile range [IQR] 0.60–10.32 ml) was not significantly different from the ground truth (median 2.89 ml, IQR 0.77–9.17 ml) (P = 0.07); Bland–Altman curves showed that the core volume of iStroke and RAPID software were comparable with each other on individual agreement with ground truth. The hypoperfusion volume and mismatch volume on iStroke were not statistically different from those on the RAPID software, respectively. In patients with large vessel occlusion (n = 74), the agreement between iStroke and RAPID was substantial (kappa = 0.76) according to DEFUSE 3 criteria (infarct core < 70 ml, mismatch volume ≥ 15 ml, and mismatch ratio ≥ 1.8). Conclusions: The iStroke automatic processing of ADC and PWI is a reliable software for the identification of diffusion–perfusion mismatch in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A singleton fetus was referred to fetal magnetic resonance imaging (MRI) at 25 weeks due to mild ventriculomegaly and an abnormal fetal echocardiogram showing cardiomegaly, right ventricular hypertrophy and tricuspid insufficiency. Patchy areas of ischemic infarction, extensive subacute and chronic hemorrhage not respecting vascular territories, encephaloclastic cysts and closed lip schizencephaly were identified. Cataract was detected postnatally. The anomalies were caused by a pathogenic mutation (c.353 G>A; p.G118D) in the COL4A1 gene. The phenotype seen in this case, i.e. small vessel cerebral disease with or without ocular anomalies caused by COL4A1 mutations, is likely an underrecognized cause of perinatal stroke. The pattern of abnormalities reported herein should prompt strong consideration for diagnosis and molecular testing. [ABSTRACT FROM AUTHOR]

Segmentation of infarcts is clinically important in ischemic stroke management and prognostication. It is unclear what role the combination of DWI, ADC, and FLAIR MRI sequences provide for deep learning in infarct segmentation. Recent technologies in model self-configuration have promised greater performance and generalizability through automated optimization. We assessed the utility of DWI, ADC, and FLAIR sequences on ischemic stroke segmentation, compared self-configuring nnU-Net models to conventional U-Net models without manual optimization, and evaluated the generalizability of results on an external clinical dataset. 3D self-configuring nnU-Net models and standard 3D U-Net models with MONAI were trained on 200 infarcts using DWI, ADC, and FLAIR sequences separately and in all combinations. Segmentation results were compared between models using paired t-test comparison on a hold-out test set of 50 cases. The highest performing model was externally validated on a clinical dataset of 50 MRIs. nnU-Net with DWI sequences attained a Dice score of 0.810 ± 0.155. There was no statistically significant difference when DWI sequences were supplemented with ADC and FLAIR images (Dice score of 0.813 ± 0.150; p = 0.15). nnU-Net models significantly outperformed standard U-Net models for all sequence combinations (p < 0.001). On the external dataset, Dice scores measured 0.704 ± 0.199 for positive cases with false positives with intracranial hemorrhage. Highly optimized neural networks such as nnU-Net provide excellent stroke segmentation even when only provided DWI images, without significant improvement from other sequences. This differs from-and significantly outperforms-standard U-Net architectures. Results translated well to the external clinical environment and provide the groundwork for optimized acute stroke segmentation on MRI., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Introduction: The coronavirus disease (COVID-19) pandemic has changed routine clinical practice worldwide with major impacts on the provision of care and treatment for stroke patients. Methods: This retrospective observational study included all patients admitted to the Royal Stoke University Hospital in Stoke-on-Trent, UK, with a stroke or transient ischaemic attack between March 15th and April 14th, 2020 (COVID). Patient demographics, characteristics of the stroke, treatment details and logistics were compared with patients admitted in the corresponding weeks in the year before (2019). Results: There was a 39.5% (n = 101 vs n = 167) reduction in admissions in the COVID cohort compared with 2019 with more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) 7 vs 4, p = 0.02), and fewer strokes with no visible acute pathology (21.8 vs 37.1%, p = 0.01) on computed tomography. There was no statistically significant difference in the rates of thrombolysis (10.9 vs 13.2%, p = 0.72) and/or thrombectomy (5.9 vs 4.8%, p = 0.90) and no statistically significant difference in time from stroke onset to arrival at hospital (734 vs 576 min, p = 0.34), door-to-needle time for thrombolysis (54 vs 64 min, p = 0.43) and door-to-thrombectomy time (181 vs 445 min, p = 0.72). Thirty-day mortality was not significantly higher in the COVID year (10.9 vs 8.9%, p = 0.77). None of the 7 stroke patients infected with COVID-19 died. Conclusions: During the COVID-19 pandemic, the number of stroke admissions fell, and stroke severity increased. There was no statistically significant change in the delivery of thrombolysis and mechanical thrombectomy and no increase in mortality. [ABSTRACT FROM AUTHOR]

Purpose: Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[18F]fluoro-d-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice. Procedures: The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins. Results: The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice. Conclusions: Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity. [ABSTRACT FROM AUTHOR]

We report the neuropathological findings of a patient who died from complications of COVID-19. The decedent was initially hospitalized for surgical management of underlying coronary artery disease. He developed post-operative complications and was evaluated with chest imaging studies. The chest computed tomography (CT) imaging results were indicative of COVID-19 and he was subsequently tested for SARS-CoV-2, which was positive. His condition worsened and he died after more than 2 weeks of hospitalization and aggressive treatment. The autopsy revealed a range of neuropathological lesions, with features resembling both vascular and demyelinating etiologies. Hemorrhagic white matter lesions were present throughout the cerebral hemispheres with surrounding axonal injury and macrophages. The subcortical white matter had scattered clusters of macrophages, a range of associated axonal injury, and a perivascular acute disseminated encephalomyelitis (ADEM)-like appearance. Additional white matter lesions included focal microscopic areas of necrosis with central loss of white matter and marked axonal injury. Rare neocortical organizing microscopic infarcts were also identified. Imaging and clinical reports have demonstrated central nervous system complications in patients' with COVID-19, but there is a gap in our understanding of the neuropathology. The lesions described in this case provide insight into the potential parainfectious processes affecting COVID-19 patients, which may direct clinical management and ongoing research into the disease. The clinical course of the patient also illustrates that during prolonged hospitalizations neurological complications of COVID may develop, which are particularly difficult to evaluate and appreciate in the critically ill. [ABSTRACT FROM AUTHOR]

Although central nervous system (CNS) metastases are common in advanced cancer, CNS involvement solely by intravascular tumor cells, known as intravascular carcinomatosis, is extremely rare. We report two cases of brain metastasis in which tumor cells were restricted to the vascular lumina without parenchymal involvement, resulting in ischemic lesions. The first patient is a previously healthy young woman who presented with symptoms of community-acquired pneumonia and progressed to respiratory failure. Computed tomography of the brain showed infarcts of differing ages. At autopsy, she was found to have widely metastatic cervical squamous cell carcinoma and cerebral tumor emboli with multifocal infarcts, mainly microinfarcts. The second patient is an elderly man with cognitive impairment and mild Parkinsonism who presented with symptoms of a urinary tract infection. Magnetic resonance imaging of the brain showed atrophy and changes suggestive of chronic microvascular ischemic disease. Postmortem examination demonstrated prostatic adenocarcinoma and cerebral tumor emboli with multifocal infarcts. These cases illustrate that this pattern of intracranial metastasis may rarely be a cause of cerebral ischemic lesions and emphasize the importance of thorough pathologic examination of the brain. [ABSTRACT FROM AUTHOR]

Pituitary adenomas are rare in children, and often present with symptoms of headache, nausea or emesis, visual disturbance, or hormonal hypersecretion. With large tumors, mass effect from the lesion can lead to severe endocrinopathy and compression of intracranial neurovascular structures. In this case report, we describe an unusual presentation of an ischemic stroke in the territory of the right middle cerebral artery resulting from a prolactin-secreting macroadenoma. The patient's primary symptoms were headache, left facial droop, and left hemibody weakness. She was successfully managed with cabergoline, a dopamine agonist, with a reduction in the size of the tumor and normalization of serum prolactin levels. She remained clinically stable throughout her hospitalization, and was safely discharged without surgical intervention. In her recent 2-year follow-up, her tumor and prolactin levels were stable and she had dramatic improvements in her left-sided muscle strength. [ABSTRACT FROM AUTHOR]

Multimodal magnetic resonance imaging (MRI) has emerged as a promising tool for diagnosing ischemic stroke and for determining treatment strategies in the acute phase. The detection and quantification of the penumbra and the infarct core regions aid the assessment of the potential risks and benefits of thrombolysis by providing information on salvageable tissue or ischemic lesion age. In this study, we proposed a fully automated and real-time algorithm to compute parameter maps of perfusion-weighted images (PWIs) and to identify an infarct core from diffusion-weighted images (DWIs). DWI and PWI were obtained using a 1.5 Tesla MRI scanner for 15 patients with acute ischemic stroke. Parameter maps of PWI were computed using restricted gamma-variate curve fitting and Fourier-based deconvolution. The ischemic penumbra was identified using time-to-maximum (Tmax) > 6 s as the mutual optimal threshold, while the infarct core was segmented using an adaptive thresholding on DWI. When the penumbra on PWI was compared with that generated using commercial software Pearson's linear correlation coefficient between penumbra volumes was 0.601 (p = 0.030), and the Dice coefficient was 0.51 ± 0.15. The infarct core on DWI was compared with the manually segmented gold standard. Dice coefficient between the manually drawn and automated segmented infarct cores was 0.62 ± 0.18. The processing times for PWI and DWI were 222.9 ± 16.4 and 53.4 ± 4.8 s, respectively. In conclusion, we demonstrate a fully automated and real-time algorithm to segment the penumbra and the infarct core regions based on PWI and DWI. [ABSTRACT FROM AUTHOR]

Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The cerebellar flocculus is a critical structure involved in the control of eye movements. Both static and dynamic abnormalities of the vestibulo-ocular reflex (VOR) have been described in animals with experimental lesions of the flocculus/paraflocculus complex. In humans, lesions restricted to the flocculus are rare so they can become an exceptional model to contrast with the clinical features in experimental animals or in patients with more generalized cerebellar diseases. Here, we examined a 67-year-old patient with an acute vestibular syndrome due to an isolated infarct of the right flocculus. We evaluated him multiple times over 6 months—to follow the changes in eye movements and vestibular function—with caloric testing, video-oculography and head-impulse testing, and the anatomical changes on imaging. Acutely, he had an ipsilateral-beating spontaneous nystagmus, bilateral gaze-evoked nystagmus, borderline impaired smooth pursuit, and a complete contraversive ocular tilt reaction. The VOR gain was reduced for head impulses directed contralateral to the lesion, and there was also an ipsilesional caloric weakness. All abnormalities progressively improved at follow-up visits but with a considerable reduction in volume of the affected flocculus on imaging. The vestibular and ocular motor findings, qualitatively similar to a previously reported patient, further clarify the “acute floccular syndrome” in humans. We also add new information about the pattern of recovery from such a lesion with corresponding changes in the size of the affected flocculus on imaging. [ABSTRACT FROM AUTHOR]

The injury caused by myocardial reperfusion after ischemia can be contained by interventions aimed at reducing the inflammation and the oxidative stress that underlie exacerbation of tissue damage. Sphingolipids are a class of structural and signaling lipid molecules; among them, the inflammation mediator ceramide accumulates in the myocardium upon ischemia/reperfusion. Here, we show that, after transient coronary occlusion in mice, an increased de novo ceramide synthesis takes place at reperfusion in the ischemic area surrounding necrosis (area at risk). This correlates with the enhanced expression of the first and rate-limiting enzyme of the de novo pathway, serine palmitoyltransferase (SPT). The intraventricular administration at reperfusion of myriocin, an inhibitor of SPT, significantly protected the area at risk from damage, reducing the infarcted area by 40.9 % relative to controls not treated with the drug. In the area at risk, myriocin downregulated ceramide, reduced the content in other mediators of inflammation and reactive oxygen species, and activated the Nrf2–HO1 cytoprotective response. We conclude that an enhanced ceramide synthesis takes part in ischemia/reperfusion injury and that myriocin treatment can be proposed as a strategy for myocardial pharmacological postconditioning. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to analyse MR imaging features and lesion patterns as defined by compromised vascular territories, correlating them to different clinical syndromes and aetiological aspects. Methods: In a 19.8-year period, clinical records and magnetic resonance imaging (MRI) features of 55 consecutive patients suffering from spinal cord ischemia were evaluated. Results: Aetiologies of infarcts were arteriosclerosis of the aorta and vertebral arteries (23.6 %), aortic surgery or interventional aneurysm repair (11 %) and aortic and vertebral artery dissection (11 %), and in 23.6 %, aetiology remained unclear. Infarcts occurred in 38.2 % at the cervical and thoracic level, respectively, and 49 % of patients suffered from centromedullar syndrome caused by anterior spinal artery ischemia. MRI disclosed hyperintense pencil-like lesion pattern on T2WI in 98.2 %, cord swelling in 40 %, enhancement on post-contrast T1WI in 42.9 % and always hyperintense signal on diffusion-weighted imaging (DWI) when acquired. Conclusion: The most common clinical feature in spinal cord ischemia is a centromedullar syndrome, and in contrast to anterior spinal artery ischemia, infarcts in the posterior spinal artery territory are rare. The exclusively cervical location of the spinal sulcal artery syndrome seems to be a likely consequence of anterior spinal artery duplication which is observed preferentially here. [ABSTRACT FROM AUTHOR]

Gas detection in the bowel wall and in portomesenteric venous vessels in adults has long been related to intestinal infarction and poor outcome; many case reports have shown that pneumatosis may be associated with a large variety of pathological situations, ranging from absolutely benign and asymptomatic forms to abdominal catastrophes. Several studies have been conducted on this topic with different conclusions, probably due to differences in population so that the clinical value of these signs is still questioned. Intestinal pneumatosis, especially if presenting with a band-like pattern and if associated with portomesenteric vein gas, when observed in an acute abdominal setting should raise the suspicion of mesenteric infarct and prompt a careful search for other signs of intestinal involvement, so as not to miss cases of life-threatening intestinal infarct or allow them to further evolve into extensive necrosis with worse prognosis. In this review we illustrate the most relevant aspects of these debated but significant radiological signs. [ABSTRACT FROM AUTHOR]

Rationale: Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose-response study in a transient ischemic stroke model is lacking. Objectives: We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats. Methods: Cerebral ischemia was induced in 13-month-old male Sprague-Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke. Results: Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved ( p < 0.05) spatial memory performance. The P8 and P16 groups showed maximum improvement in long-term memory compared to vehicle. Significant ( p < 0.05) gait impairments were observed in the vehicle group compared to shams. Animals receiving the P8 dose showed maximum gait improvement compared to vehicle. Post hoc analysis revealed that the P8 and P16 groups showed significant attenuation in infarct volume compared to vehicle. Animals receiving the P32 dose did not show any effect on infarct volume. Conclusions: Although all doses were somewhat effective, progesterone given at 8 mg/kg led to the most consistent improvements across a panel of behavioral/functional tests and reduced the severity of ischemic infarct injury. [ABSTRACT FROM AUTHOR]

The purpose of the study is feasibility of dynamic CT perfusion imaging to detect and differentiate ischemic and infarcted myocardium in a large porcine model. 12 Country pigs completed either implantation of a 75 % luminal coronary stenosis in the left anterior descending coronary artery simulating ischemia or balloon-occlusion inducing infarction. Dynamic CT-perfusion imaging (100 kV, 300 mAs), fluorescent microspheres, and histopathology were performed in all models. CT based myocardial blood flow (MBF), blood volume (MBV) and transit constant (K), as well as microsphere's based myocardial blood flow (MBF) were derived for each myocardial segment. According to histopathology or microsphere measurements, 20 myocardial segments were classified as infarcted and 23 were ischemic (12 and 14 %, respectively). Across all perfusion states, MBF strongly predicted MBF (β 0.88 ± 0.12, p < 0.0001). MBF, MBV, and K were significantly lower in ischemic/infarcted when compared to reference myocardium (all p < 0.01). Relative differences of all CT parameters between affected and non-affected myocardium were higher for infarcted when compared to ischemic segments under rest (48.4 vs. 22.6 % and 46.1 vs. 22.9 % for MBF, MBV respectively). Under stress, MBF was significantly lower in infarcted than in ischemic myocardium (67.8 ± 26 vs. 88.2 ± 22 ml/100 ml/min, p = 0.002). In a large animal model, CT-derived parameters of myocardial perfusion may enable detection and differentiation of ischemic and infarcted myocardium. [ABSTRACT FROM AUTHOR]

The increasing numbers of obese and morbidly obese individuals in the community are having a direct effect on forensic facilities. In addition to having to install more robust equipment for handling large bodies, the quality of autopsy examinations may be reduced by the physical difficulties that arise in trying to position bodies correctly so that normal examinations can proceed. Accelerated putrefaction is often an added complication. Metabolic disturbances resulting from obesity increase susceptibility to a range of conditions that are associated with sudden and unexpected death, and surgery may have increased complications. The rates of a number of different malignancies, including lymphoma, leukemia, melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon, gallbladder, thyroid, prostate, breast and endometrium, are increased. In addition, obese individuals have higher rates of diabetes mellitus, and sepsis. The unexpected collapse of an obese individual should raise the possibility of a wide range of conditions, many of which may be more difficult to demonstrate at autopsy than in an individual with a normal body mass index. Although sudden cardiac death due to cardiomegaly, pulmonary thromboembolism, or ischemic heart disease may be the most probable diagnosis in an unexpected collapse, the range of possible underlying conditions is extensive and often only determinable after full postmortem examination. [ABSTRACT FROM AUTHOR]

Subarachnoid haemorrhage (SAH) is a devastating disease and a major burden on society. Despite this, pharmacological treatment options are limited. Appropriate animal modelling of SAH is essential for the development of neuroprotective drugs, but experimental SAH often fails to produce widespread neuronal loss, as frequently seen in humans. We report that a recently described modification of the endovascular perforation model in rat produced widespread heterogeneous infarcts 72 h after SAH. Cerebral blood flow (CBF) was monitored, with or without intracranial pressure (ICP) measurement, for 1 h after induction of SAH. Blood load size was assessed, and brain injury was quantified at 72 h using histological staining, blood brain barrier breakdown assessment and immunofluorescent imaging of neuronal viability and microglial activation. Results showed that ICP measurement allowed for faster recovery of CBF, potentially reducing brain injury. Larger subarachnoid blood loads predicted more extensive neuronal damage which was easily quantified with the combination of histological and immunohistochemical techniques. Thus, for the investigation of neuroprotective strategies after SAH, the present protocol produces quantifiable, clinically relevant, heterogeneous patterns of infarct due to large blood loads, high ICP and low CBF. [ABSTRACT FROM AUTHOR]

We report a case of a 41-year-old man with a splenic abscess caused by methicillin-resistant Staphylococcus aureus (MRSA). He had been treated with antimicrobials and corticosteroids for interstitial pneumonia caused by Mycoplasma pneumoniae and hemolytic anemia. He developed catheter-related (MRSA) bacteremia during his stay in the ICU and was treated with teicoplanin for 2 weeks. After 4 weeks of outpatient follow-up, he was readmitted to the hospital with fever and pain in the left upper quadrant. A thoracoabdominal CT scan showed subcapsular collection in areas of splenic infarction that had been detected on his first admission. CT-guided percutaneous aspiration resulted in the isolation of MRSA. The patient was treated successfully with teicoplanin for 6 weeks. Our aim in presenting this quite rare case is to highlight the tendency of infarcts that develop as a result of hemolytic attacks during systemic infections to be a focus of infection for nosocomial bacteremia. [ABSTRACT FROM AUTHOR]

Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of the several common, objective and predefined histological abnormalities of the placenta as identified by pathologists blinded to all clinical information. A total 1,153 women were recruited from an unselected population delivering at 34-43 weeks. Histological findings in common obstetric outcome groups were compared to those of the unselected population, and odds ratios and predictive values were calculated. Normal histological findings were present in 72.1% of pregnancies with normal outcomes and in 79.1%, 66.6%, 80%, and 74.8% of pregnancies affected by pre-eclampsia (PET), pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small for gestational age (SGA), respectively. Chronic placental underperfusion was seen more frequently in PIH (odds ratio (OR) 2) and SGA (OR 1.4), while villitis of unknown aetiology was observed more commonly in cases with PIH (OR 3.2). Fetal thrombotic vasculopathy was twice as common in cases with GDM whilst massive perivillous fibrin deposition was much more frequent in those with PET (OR 20.2) and SGA (OR 8.9). Chorangiomata were 13 times more common in pregnancies with PET. However, in all cases, positive predictive values were low, with the majority of cases with histological abnormalities being associated with normal outcome. At term, specific placental histological lesions are significantly more common in complicated pregnancies, but the clinical significance of such lesions in a specific case remains uncertain, since the majority will be identified from clinically uncomplicated normal pregnancies. [ABSTRACT FROM AUTHOR]

The neuroprotective effect of rosiglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, has been investigated using both in vivo and in vitro models of global ischemia in CD1 mice. Behavioral tests were carried out prior to and at various times (up to 14 days) subsequent to bilateral common carotid artery occlusion followed by reperfusion. Mice at each time point were euthanized under anesthesia and the brain was removed, serially sliced and stained with 1% triphenyltetrazolium (TTC) to quantify infarct size. Administration of rosiglitazone (5 or 10 mg/kg, i.p.) 10 min prior to occlusion significantly reduced the postsurgical mortality rate (10-11 vs. 36%, P < 0.05). The higher dose of rosiglitazone (10 mg/kg) also significantly reduced the mean area of brain infarct at 1, 3, 7 and 14 days post-ischemia, reduced post-occlusion deficits in limb grasping and forelimb placing at various time points, and reduced total nitrite concentration in serum and brain homogenate at day 7 post-occlusion. To model global ischemia in vitro, coronal brain slices were incubated in oxygenated artificial cerebrospinal fluid (ACSF) in the presence of either glutamate (1 mM) or hydrogen peroxide (HO) (5 μM) for 30 min. Both HO and glutamate caused significant tissue damage, and co-incubation with rosiglitazone (5 μM) significantly reduced HO-induced damage but did not significantly reduce glutamate-induced brain damage in this model. Our observations provide further evidence for a neuroprotective effect of rosiglitazone in rodent models of ischemia. [ABSTRACT FROM AUTHOR]

The purpose of the study was to determine the ability to predict infarct age based on decrease in apparent diffusion coefficient (ADC) values. We retrospectively identified 94 individuals (age range 16 years to 91 years; mean 63.7 + 14.1 years) who underwent magnetic resonance diffusion-weighted imaging at our institution over a course of 14 months whose infarct age could be reliably determined within 1 h. A single observer measured ADC values within the center of the infarct and compared them against values in contralateral normal tissue. We examined the ability of four ADC decrease thresholds (i.e., >50%, >40%, >30%, and >20%) to predict infarct age of <24 and <48 h. Levels of ADC decrease in infarcts were as follows: <20%, n = 9; 20–29%, n = 21; 30–39%, n = 25; 40–49%, n = 23; >50%, n = 16. For prediction of infarct age <24 h, sensitivity for the four ADC decrease thresholds ranged from 25% to 94%, specificity ranged from 10% to 85%, positive predictive value (PPV) ranged from 18% to 25%, and negative predictive value (NPV) ranged from 85% to 89%. For prediction of infarct age <48 h, sensitivity ranged from 23% to 98%, specificity ranged from 15% to 87%, PPV ranged from 46% to 56%, and NPV ranged from 60% to 89%. Test performance characteristics for predicting infarct age of <24 and <48 h were relatively poor. In particular, PPV was very low for predicting infarcts <24 h old. [ABSTRACT FROM AUTHOR]

The Na+–K+–2Cl− cotransporter localized in the brain vascular endothelium has been shown to be important in the evolution of cerebral edema following experimental stroke. Previous in vivo studies have demonstrated that bumetanide, a selective Na+–K+–2Cl− cotransport inhibitor, attenuates ischemia-evoked cerebral edema. Recently, bumetanide has been shown to also inhibit water permeability via aquaporin-4 (AQP4) expressed in Xenopus laevis oocytes. We tested the hypothesis that the perivascular pool of AQP4 plays a significant role in the anti-edema effect of bumetanide by utilizing wild-type (WT) mice as well as mice with targeted disruption of α-syntrophin (α-Syn−/−) that lack the perivascular pool of AQP4. Isoflurane-anesthetized adult male WT C57Bl6 and α-Syn−/− mice were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by 24 or 48 h of reperfusion. Adequacy of MCAO and reperfusion was monitored with laser-Doppler flowmetry over the ipsilateral parietal cortex. Infarct volume (tetrazolium staining), cerebral edema (wet-to-dry ratios), and AQP4 protein expression (immunoblotting) were determined in different treatment groups in separate sets of experiments. Bumetanide significantly attenuated infarct volume and decreased ipsilateral hemispheric water content in WT mice compared to vehicle treatment. In α-Syn−/− mice, bumetanide treatment had no effect on infarct volume or ischemia-evoked cerebral edema. Bumetanide-treated WT mice had a significant attenuation of AQP4 protein expression at 48 h post-MCAO compared to vehicle-treated WT mice. These data suggest that bumetanide exerts its neuroprotective and anti-edema effects partly via blockade of the perivascular pool of AQP4 and may have therapeutic potential for ischemic stroke in the clinical setting. [ABSTRACT FROM AUTHOR]

Lesions located in the basal ganglia (BG) are thought to be involved in the fatigue observed in neurological disorders. However, the significance of the location of infarcts in poststroke fatigue (PSF) is unknown. This study examined the association between BG infarcts and PSF. A total of 334 Chinese patients with acute ischemic stroke consecutively admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. At admission, a host of demographic and clinical characteristics was collected and the number and location of acute infarcts were evaluated with MRI. All participants were assessed for PSF with the fatigue severity scale (FSS) 3 months after their index stroke. PSF was defined as a mean FSS score of 4.0 or more. Depressive symptoms were measured by the geriatric depression scale (GDS). Seventy-eight (23.4%) patients had PSF. In the univariate analysis, the PSF group included more females, had higher GDS scores, and a higher number of acute infarcts, and the PSF patients were more likely to have acute infarcts at the BG. Acute BG infarct remained an independent predictor of PSF in the multivariate analysis. In conclusion, these results suggest that BG infarcts may play a role in the development of PSF. [ABSTRACT FROM AUTHOR]

Infarction in the artery of Percheron territory is a rare phenomenon in which occlusion of an unpaired perforating artery arising from the P1 segment on one side results in infarcts in the bilateral paramedian thalami with or without midbrain infarcts. We describe the case of a 40-year-old male who developed this complication following re-exploratory trans-sphenoidal surgery for a pituitary adenoma. In this first report of its kind in endoscopic pituitary surgery, the pathogenesis and clinico-radiological features of this rare vascular event are discussed. [ABSTRACT FROM AUTHOR]

We present the case of a 2-week-old male infant who presented with an asymptomatic liver mass and underwent surgical resection because of suspicion of malignancy after extensive radiological study with ultrasonography, computed tomography, and MRI. Pathological examination revealed a peripheral hepatic infarct with calcifications and a rim of peripheral organization suggestive of being at least 2 weeks old. This case reviews the scarce cases of hepatic infarct in newborns and highlights the fact that, although untreated perinatal hepatic infarction usually progresses to atrophy of the affected area with compensation by the unaffected liver, surgical resection remains an option in cases of complications or uncertain diagnosis. [ABSTRACT FROM AUTHOR]

Maximal cardiac output is reduced in severe acute hypoxia but also in chronic hypoxia by mechanisms that remain poorly understood. In theory, the reduction of maximal cardiac output could result from: (1) a regulatory response from the central nervous system, (2) reduction of maximal pumping capacity of the heart due to insufficient coronary oxygen delivery prior to the achievement of the normoxic maximal cardiac output, or (3) reduced central command. In this review, we focus on the effects that acute and chronic hypoxia have on the pumping capacity of the heart, particularly on myocardial contractility and the molecular responses elicited by acute and chronic hypoxia in the cardiac myocytes. Special emphasis is put on the cardioprotective effects of chronic hypoxia. (Part of a multi-author review.) [ABSTRACT FROM AUTHOR]

Blood pressure (BP) is the major determinant of cerebral perfusion yet blood pressure management in acute stroke is complex and controversial. Optimized blood pressure management may improve outcomes in patients with ischemic and hemorrhagic stroke although the available data are conflicting and target BP goals are not well defined. We review the current literature, published guidelines, and emerging research on this important topic. Additionally, the treatment algorithm which we employ is discussed.Journal of Human Hypertension (2009) 23, 559–569; doi:10.1038/jhh.2008.164; published online 15 January 2009 [ABSTRACT FROM AUTHOR]

Fast, accurate and automatic segmentation of acute ischemic stroke lesions is important for clinical trials and has potential for efficient stroke management. To identify stroke slices, stroke hemisphere, and segment stroke regions in diffusion-weighted magnetic resonance imaging (DWI), divergence based algorithms are proposed. The study used 57 DWI volumes with inter 0.94–2.42 mm and intra 5–14 mm plane resolutions. We used ratio of intensity probability density functions (pdf) as a divergence measure. For slice identification, this measure is the ratio of pdfs of slice and the volume; for hemisphere and infarct segmentation, it is the ratio of the difference of the pdfs of the left and right hemispheres to the sum of their pdfs. The median and cross over points are thresholds for slice and region segmentation while hemisphere identification is threshold free. Descriptive statistics were determined and ROC analysis was performed. The median sensitivity, specificity, and Dice statistical index for segmentation are 86.34%, 99.83%, 0.72, respectively. For slice and hemisphere identification sensitivity and specificity are (90.05%; 68.78%) and (94.74%; 94.74%), respectively. The algorithm implemented in VC++ takes 3–5 s per volume. This automatic, accurate and fast method is potentially useful in clinical setting and clinical trials to localize and quantify the stroke regions, eliminate inter- and intra-variability, and laborious and time consuming, operator-dependent manual segmentation. [ABSTRACT FROM AUTHOR]

Retrospective studies suggested that cerebral microbleeds (MB) on magnetic resonance images (MRI) increase risk of intracerebral haemorrhage (ICH). To compare the benefit of anti-thrombotic agents in stroke prevention (absolute risk reduction 2.49 –6 %) versus risk of ICH in ischaemic stroke patients with MB. We prospectively studied patients admitted consecutively for acute ischaemic stroke between 1999 and 2004. MB on MRI were documented. Primary end points were subsequent ICH, recurrent cerebral infarct (CI) and mortality. A total of 908 patients were recruited. MB were identified in 252 (27.8 %) patients. Mean follow-up period was 26.6 ± 15.4 months. Risk of subsequent ICH increased significantly with quantity of MB: 0.6 % (no MB), 1.9 % (1 MB), 4.6 % (2–4 MB) and 7.6 % (≥ 5 MB) (p < 0.001). There was also a significant increase in mortality from ICH: 0.6 %, 0.9 %, 1.5 % and 3.8 % respectively (p = 0.054). Rate of recurrent CI was 9.6 %, 5.6 %, 21.5 % and 15.2 % respectively (p = 0.226). Mortality from CI and myocardial infarction did not increased with quantity of MB. Survival analyses showed that age, presence of MB, mixed cortical-subcortical distribution of MB were independent predictors of subsequent ICH. Risk and mortality of ICH increased with quantity of MB. As tendency to recurrent CI exceed that of ICH, anti-thrombotic agents are still warranted. However, in patients with ≥ 5 MB, the high risk and mortality of ICH seem to outweigh the modest benefit of antithrombotic agents. Extra precautions should be taken to minimize risk of ICH. Further studies in patients on Coumadin and assessment of functional outcome are warranted to support these preliminary findings. [ABSTRACT FROM AUTHOR]

Accurate and rapid quantification of infarcts from DWI scans is critical in acute ischemic stroke. Acquisition artifacts lead to hyperintense regions in DWI MR scans resulting in false positives. Discriminating infarcts and artifacts helps in reducing infarct segmentation errors. An algorithm based on two-dimensional symmetry of artifacts about the midsagittal plane and three-dimensional spatial coherence of infarct regions is proposed to characterize and separate infarcts from artifacts. The two dimensional symmetry is quantified by propagating Poisson errors in the intensity space of each pixel, and distant and spatially incoherent regions in a volume are considered as artifacts. The combination of two criteria enhances the confidence in the decision whether a hyperintense region is an infarct or artifact. The validity of the proposed algorithm is demonstrated using 51 cases. The improvement in results is demonstrated in three situations: (1) automatic infarct slice identification resulting in an average increase in (specificity, Dice Statistical Index (DSI)) by (15.2%, 6.9%) while the sensitivity decrease is by only 1.5% and (2) automatic infarct segmentation using two different algorithms: first resulting in an average DSI increase by 7.6% and second by 5.1%. On a matlab platform, the processing time is < 1 s. The proposed algorithm is useful as a fast post-processing tool to reduce artifacts in infarct processing applications. [ABSTRACT FROM AUTHOR]

Natriuretic peptides are regulatory autacoids in the mammalian myocardium whose functions, mediated via particulate guanylyl cyclase/cGMP, may include cytoprotection against ischaemia-reperfusion injury. Previous work has identified that B-type natriuretic peptide (BNP) limits infarct size when administered prior to and during coronary occlusion through a KATP channel-dependent mechanism. The present study examined the hypothesis that the protection afforded by BNP is mediated specifically at reperfusion in a postconditioning-like manner. Langendorff-perfused rat hearts were subjected to 35 min coronary artery occlusion and 120 min reperfusion, and infarct size was determined by tetrazolium staining. Postconditioning was effected by applying six 10-second periods of global ischaemia at the onset of reperfusion.Treatment with either BNP 10 nM or the NO donor S-nitroso-N-acetylpenicillamine (SNAP) 1–10 μM was commenced 5 min prior to reperfusion and continued until 10 min after reperfusion. Control infarct size (% of ischaemic risk zone) was 40.8 ± 3.7%.BNP at reperfusion induced a significant limitation of infarct size (BNP 22.9 ± 4.1% P<0.05 vs. control). Co-treatment at reperfusion with BNP and the KATP channel blockers 5-hydroxydecanote (5HD, 100 μM), glibenclamide (Glib; 10 μM) or HMR1098 (10 μM) abolished the infarct-limiting effect of BNP (BNP + 5HD 41.0 ± 3.9%, BNP + Glib 39.8 ± 5.6%, BNP + HMR 1098 46.0 ± 7.1%,P < 0.05 vs. BNP). BNP given together with L-NAME (100 μM) at reperfusion resulted in a marked loss of protection (BNP + L-NAME 53.1 ± 3.8% P < 0.001 vs. BNP). In a second series of experiments, SNAP (1–10 μM) given at reperfusion was found not to be protective (SNAP 1 μM 30.2 ± 4.9%, SNAP 2 μM 27.5 ± 9.5%, SNAP 5 μM 39.2 ± 5.7%, SNAP 10 μM 33.7 ± 6.4%, not significant vs. control). In a third series of experiments, postconditioning significantly limited infarct size (14.9 ± 3.6 % vs. control 34.5 ± 4.9%, P < 0.01) and this effect of postconditioning was abolished in the presence of isatin (100 μM), a non-specific blocker of particulate guanylyl cyclases (35.1 ± 6%, P < 0.05 vs. postconditioning). In conclusion, pharmacological activation of pGC by BNP can effectively induce protection against reperfusion injury, by mechanisms involving KATP channel opening and endogenous NO synthase activation. Furthermore, endogenous activation of pGC could play a role in the mechanism of postconditioning. [ABSTRACT FROM AUTHOR]

The effect of chronic coronary artery occlusion on the content of rat myocardial coenzymes Q (CoQ) and evaluation of the applicability of CoQ10 for limiting postinfarct remodeling have been investigated. Left ventricle myocardium hypertrophy was characterized by the decrease in CoQ9 (−45%, p < 0.0001), CoQ10 (−43%, p < 0.001), and α-tocopherol (−35%, p < 0.05). There were no differences between the parameters of postinfarction and sham-operated rats in plasma. Administration of CoQ10 (10 mg/kg) via a gastric probe for 3 weeks before and 3 weeks after occlusion maintained higher levels of CoQ in the postinfarction myocardium: the decrease in CoQ9 and CoQ10 was 25% ( p < 0.05) and 23% ( p < 0.05), respectively (versus sham-operated animals). Plasma concentrations of CoQ10 were more than 2 times higher ( p < 0.05). In CoQ treated rats there was significant correlation between plasma levels of CoQ and the infarct size: r = −0.723 ( p < 0.05) and r = −0.839 ( p < 0.01) for CoQ9 and CoQ10. These animals were also characterized by earlier and more intensive scar tissue formation in the postinfarction myocardium and also by more pronounced cell regeneration processes. This resulted in the decrease in both the infarct size (16.2 ± 8.1 vs. 27.8 ± 12.1%) and also mass index of left ventricle (2.18 ± 0.24 vs. 2.38 ± 0.27 g/kg) versus untreated rats ( p < 0.05). Thus, long-term treatment with ubiquinone increases plasma and myocardial CoQ content and this can improve the survival of myocardial cells during ischemia and limit postinfarct myocardial remodeling. [ABSTRACT FROM AUTHOR]

The aim of this study was to retrospectively review the cases of hepatic infarction diagnosed at our institute using conventional, spiral and multislice computed tomography (CT) over the last decade in order to describe its morphological and density characteristics and define its possible etiopathogenesis. Twenty-three consecutive patients aged 27–65 years with hepatic infarction were studied by CT at our institute over a period of about 10 years. A conventional CT unit was used in seven patients, a helical CT scanner in ten and a multislice CT in six. CT was performed before and after the administration of 130–150 cc of contrast material infused at a rate of 3–3.5 ml/s. CT showed hepatic infarction due to arterial causes in 19 cases, 11 of which were in liver transplant patients. The infarction was related to right hepatic artery embolisation to control haemorrhage (one case), chemoembolisation of a multifocal hepatocarcinoma in a cirrhotic liver (one case), arterial mesenteric infarction due to thromboembolism (two cases), necrotising pancreatitis (one case), surgery in pancreatic cancer invading the hepatic artery (one case), pancreaticoduodenectomy (two cases), portal thrombosis in a young woman with pregnancy-related clotting disorder (one case), haemolytic anaemia, elevated liver enzymes, low platelet count (HELLP) syndrome (one case); eclampsia and disseminated intravascular coagulation (DIC) (one case) and acute exacerbation of Budd-Chiari syndrome (one case). At CT scans, hepatic infarction was depicted as a hypodense parenchymal area, at times triangular in shape, with sharp peripheral contours (12 cases) or as a rounded central or marginal area (four cases) with irregular appearance (three cases), with lobar extension (two cases) and ill-defined shape (two cases). Moreover, CT showed intralesional gas not correlated to bacterial infection (two cases). In all surgical cases, the results were confirmed by pathology. CT is the method of choice in the diagnosis of hepatic infarction, providing useful information regarding site, morphology, and extent of the lesion. Furthermore, in most cases, CT is able to suggest the possible aetiology and guide appropriate management. [ABSTRACT FROM AUTHOR]

Abstract We studied the microscopic features of 137 cases of human cerebral infarct. In each case, the age of the lesion was determined by measuring the time elapsed between initial clinical presentation and date of surgery or death. Multiple microscopic variables were analyzed on hematoxylin and eosin-stained sections. There were 104 (76%) male and 33 (24%) female patients with a median age of 64 years. The location of the infarcts included 129 cerebral, 5 cerebellar, and 1 each in the pons, midbrain and medulla. The age of the lesions ranged from 1 day to 53 years. All lesions were single and varied from lacunes to large infarcts in the distribution of one or more cerebral arteries. Key histologic features of the proposed classification are as follows: (1) phase of acute neuronal injury (11 cases studied), age 1-2 days, characterized by the presence of neuronal changes, and spongiosis of the neuropil and absence of neuronal ferrugination, chronic inflammation, macrophages, neo-vascularization and cavitation; (2) phase of organization subdivided into: (a) phase of acute inflammation (31 cases), age 3-37 days, characterized by coagulative necrosis, and frequent acute inflammation, and (b) phase of chronic inflammation (57 cases), age 10 days-53 years, characterized by the presence or absence of coagulative necrosis, neuronal injury, red neurons, macrophages, mononuclear inflammatory cells, perivascular cuffing, cavitation, gliosis, spheroids; absence of neutrophils; and (3) phase of resorption (38 cases), age 26 days-23 years, characterized by absence of an inflammatory response. Neuronophagia is not a feature of cerebral infarcts. [ABSTRACT FROM AUTHOR]

Interleukin-1 receptor antagonist (IL-1ra) has been shown previously to have neuroprotective effects in animal models of stroke. The effects of chronic overexpression of human soluble IL-1ra (hsIL-1ra) were studied in a mouse model of permanent focal cerebral ischemia. A transgenic mouse strain (Tg hsIL-1ra+/–) has been developed using the promoter for glial fibrillary acidic protein (GFAP) to limit the overexpression to the CNS. Analysis of the neurological scores, infarct volume and edema formation revealed no differences between Tg hsIL-1ra+/– and wild-type (WT) mice. The cerebral ischemia resulted in pronounced astrocyte proliferation and microglial activation, as well as induction of inflammatory markers in both Tg hsIL-1ra+/– and WT mice, with no major differences between the two genotypes. Interestingly, hsIL-1ra expression in astrocytes was reduced in infarcted areas as compared to non-ischemic regions and sham-operated controls. In conclusion, transgenic overexpression of hsIL1-ra was not neuroprotective in this cerebral ischemia model, possibly due to insufficient levels for protection against the extensive lesion, or an up-regulation of compensatory inflammatory signals due to the lifetime blockade of IL-1 receptors. [ABSTRACT FROM AUTHOR]

Postischemic spontaneous hyperthermia as a complication of occlusion of the middle cerebral artery with an intraluminal filament has been observed by some authors, but many other reports do not discuss this factor. The possible reasons why some of the authors have not seen severe hyperthermia in their experiments include differences in surgical technique, the strain of animals, the type of the anesthesia, and the occluder filament. The aim of this study was to examine the changes in the core temperature of rats using different types of filaments. The middle cerebral artery was occluded for 2 h with three different types of filaments. The changes in the temperature were continuously monitored during occlusion and for the next 4 h. Groups with uncontrolled hyperthermia and with controlled normal core temperature were used. In addition, the necrotic and penumbral areas were measured 4 and 48 h after the ischemia in both groups. Spontaneous postischemic hyperthermia was detected using all types of filaments. A close correlation was found between the size of the occluder filament and the time-course and degree of hyperthermia. Moreover, the size of the filament correlated well with the size of the infarct at both 4 and 48 h after the occlusion. We suggest that filament size is a major contributor to the degree of hyperthermia and the development of brain damage in the middle cerebral artery occlusion model. Our results call attention to the need to standardize the methods used to screen for therapeutic agents for stroke. [ABSTRACT FROM AUTHOR]

Cerebellar function has traditionally been viewed as limited to the control of voluntary movement. There is increasing clinical and experimental evidence that the cerebellum is involved in nonmotor behaviours and cognitive operations. In acquired and congenital cerebellar lesions such deficits can be demonstrated by appropriate testing. These nonmotor functions explain, at least in part, why many children with congenital cerebellar deficits or malformations first come to medical attention because of developmental delay. While the outcome of defined cerebellar syndromes, such as Dandy-Walker and Joubert, is documented, the relevance of cerebellar involvement related to prenatal (ischaemic) insults and of those observed in the context of more widespread CNS disorganization is not well understood. The cerebellum is vulnerable to prenatal infections and to many toxins and metabolic disorders, but not to perinatal and postnatal hypoxic-ischaemic injury. Consideration of cerebellar involvement and analysis of imaging patterns are crucial in recognizing many neuropaediatric disorders and helpful in guiding appropriate additional investigations. [ABSTRACT FROM AUTHOR]