Ischemic Brain Lesions Research Articles

The excessive tonic inhibition of the peri-infarct cortex depresses low gamma rhythm power during post-stroke recovery.

The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex, harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates, remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the peri-infarct cortex prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking. Probing the local field potential activity of the forelimb primary sensory cortex (S1FL) located in the peri-infarct cortex of male adult mice, we found a constant, deep reduction of low-gamma oscillation power (L-gamma; 30-50 Hz) precisely during the critical time window for recovery (1 to 3 weeks after stroke). The collapse of L-gamma power negatively corelated with behavioral progress in affected forelimb use. Mapping astrocyte reactivity and GABA-like immunoreactivity in the peri-infarct cortex revealed a parallel high signal, which gradually increased when approaching the lesion. Increasing tonic inhibition with local infusion of GABA or by blocking its recapture reduced L-gamma oscillation power in a magnitude similar to stroke. Conversely, the negative allosteric modulation of tonic GABA conductance using L655,708 or the gliopeptide ODN rescued the L-gamma power of the peri-infarct cortex. Altogether the present data point-out that the chronic excess of ambient GABA in the peri-infarct cortex limits the generation of L-gamma oscillations in the repairing cortex and suggests that rehabilitative interventions aimed at normalizing low-gamma power within the critical period of stroke recovery could optimize the restitution of lost functions.Significance Statement After a stroke, the recovery of lost motor function depends on the reorganization of surviving neural networks. However, the excitation/inhibition balance in the repairing area is suboptimal as it leans excessively towards inhibition. In this work, using an in vivo approach, we demonstrate here that this imbalance, occurring during the critical window for recovery, leads to the collapse of gamma oscillations, a crucial cerebral rhythm for organizing neural communication. This study reinforces the concept of timely therapeutic interventions aimed at correcting the pathological oscillatory regimen of stroke recovery to enhance plasticity.

Oxygen Extraction Fraction Mapping on Admission Magnetic Resonance Imaging May Predict Recovery of Hyperacute Ischemic Brain Lesions After Successful Thrombectomy: A Retrospective Observational Study.

In acute stroke, diffusion-weighted imaging (DWI) is used to assess the ischemic core. Dynamic-susceptibility contrast perfusion magnetic resonance imaging allows an estimation of the oxygen extraction fraction (OEF), but the outcome of DWI lesions with increased OEF postrecanalization is unclear. This study investigated the impact of OEF on the fate of DWI lesions in patients achieving recanalization after thrombectomy. This was a retrospective analysis of the HIBISCUS-STROKE cohort (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke; NCT: 03149705), a single-center observational study that prospectively enrolled patients who underwent magnetic resonance imaging triage for thrombectomy and a day-6 T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging. Automated postprocessing of admission dynamic-susceptibility contrast perfusion magnetic resonance imaging generated OEF maps. At visual analysis, the OEF status within DWI lesions was assessed in comparison to the contralateral side and correlated with volume changes (difference of ischemic lesion between admission DWI and registered day-6 T2-FLAIR). At voxel-based analysis, recovered DWI regions (lesions present on the admission DWI but absent on the registered day-6 T2-FLAIR) and nonrecovered regions were segmented to extract semiquantitative OEF values. Of the participants enrolled from 2016 to 2022, 134 of 321 (41.7%) were included (median age, 71.0 years; 58.2% male; median baseline National Institutes of Health Scale score, 15.0). At visual analysis, 46 of 134 (34.3%) patients had increased OEF within DWI lesions. These patients were more likely to show a reduction in ischemic lesion volumes compared with those without increased OEF (median change, -4.0 versus 4.8 mL; P<0.0001). Multivariable analysis indicated that increased OEF within DWI lesions was associated with a reduction in ischemic lesion volumes from admission DWI to day-6 T2-FLAIR (odds ratio, 0.68 [95% CI, 0.49-0.87]; P=0.008). At voxel-based analysis, recovered DWI regions had increased OEF, while nonrecovered regions had decreased OEF (median, 126.9% versus -27.0%; P<0.0001). Increased OEF within hyperacute DWI lesions was associated with ischemic lesion recovery between admission DWI and day-6 T2-FLAIR in patients achieving recanalization after thrombectomy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03149705.

Brain lesion and echocardiogenic predictors of newly detected atrial fibrillation in acute ischemic stroke

ObjectivesAtrial fibrillation (AF) is one of the notorious risk factors in acute ischemic stroke (AIS), and the use of anticoagulants has been shown to be effective in preventing ischemic stroke in AF patients. Therefore, identifying AF in AIS patients has become increasingly important. However, the impact of brain imaging and cardiac indices on the development of new AF after stroke remains unclear. MethodsA consecutive series of AIS patients who were admitted to the Ulsan University Hospital between January 2013 and December 2019 were identified. Patients with relevant ischemic brain lesions on MRI were included, and those without echocardiography data were excluded. We included and classified the AF patients who had the disease prior to or during hospitalization or met the criteria for cryptogenic stroke (CS). Differences in baseline characteristics, stroke risk factors, stroke severity, insular lesion, and echocardiographic data were investigated among each group. ResultsA total of 850 patients were enrolled in the study, comprising 231 patients with AF detected after stroke (AFDAS), 287 patients with known AF (KAF), and 350 patients with CS. Compared with KAF, patients with AFDAS had a lower prevalence of underlying coronary heart disease and stroke history. They had greater right insular cortex lesions and lesser left atrial enlargement in unadjusted analysis. Following adjusted analysis, the involvement of the right insular cortex was found to be associated with the AFDAS patient group (odds ratio, 1.57). When compared to the CS group, AFDAS patients were older, experienced more severe initial strokes, and had similar rates of pre-stroke anticoagulation prescription. Additionally, they demonstrated a higher prevalence of both insular lesions, increased left atrium volume index, reduced ejection fraction, and elevated e/e′ ratio. After adjustment, age, initial stroke severity, insular involvement, left atrium volume index, ejection fraction, and e/e′ ratio were found to be significant. ConclusionsThese results suggest that the right insular cortex lesion on acute stroke may be a cause of AFDAS.

Ischemic core detection threshold of computed tomography perfusion (CTP) in acute stroke.

This study aimed to determine the accuracy of detecting ischemic core volume using computed tomography perfusion (CTP) in patients with suspected acute ischemic stroke compared to diffusion-weighted magnetic resonance imaging (DW-MRI) as the reference standard. This retrospective monocentric study included patients who underwent CTP and DW-MRI for suspected acute ischemic stroke. The ischemic core size was measured at DW-MRI. The detectability threshold volume was defined as the lowest volume detected by each method. Clinical data on revascularization therapy, along with the clinical decision that influenced the choice, were collected. Volumes of the ischemic cores were compared using the Mann-Whitney U test. Of 83 patients who underwent CTP, 52 patients (median age 73years, IQR 63-80, 36 men) also had DW-MRI and were included, with a total of 70 ischemic cores. Regarding ischemic cores, only 18/70 (26%) were detected by both CTP and DW-MRI, while 52/70 (74%) were detected only by DW-MRI. The median volume of the 52 ischemic cores undetected on CTP (0.6mL, IQR 0.2-1.3mL) was significantly lower (p < 0.001) than that of the 18 ischemic cores detected on CTP (14.2mL, IQR 7.0-18.4mL). The smallest ischemic core detected on CTP had a volume of 5.0mL. Among the 20 patients with undetected ischemic core on CTP, only 10% (2/20) received thrombolysis treatment. CTP maps failed in detecting ischemic cores smaller than 5mL. DW-MRI remains essential for suspected small ischemic brain lesions to guide a correct treatment decision-making.

DXA-Measured Abdominal Adipose Depots and Structural Brain Integrity in Postmenopausal Women.

This study extends prior research from the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat. The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.6]) enrolled in WHIMS-MRI who had undergone DXA scans. DXA scans were completed at years 0, 3, and 6, and MRI scans were conducted ~8 years after baseline. Adjusted linear regression models were used to analyze the association between adiposity averaged across the 3-time points and volumes of brain regions previously linked to dementia. Higher levels of total body fat, TAT, VAT, SAT, gynoid, and overall leg fat were associated with larger hippocampal volume (β 0.02 [95% CI, 0.004-0.04]; 0.11 [0.02-0.21]; 0.26 [0.04-0.47]; 0.18 [0.03-0.33]; 0.18 [0.05-0.30]; 0.07 [0.009-0.12], respectively). No other significant associations were observed. Higher levels of adiposity were positively associated with hippocampal volume. Additional research with larger sample sizes is needed to ascertain the significance of this association.

The Motor Optimality Score-Revised Improves Early Detection of Unilateral Cerebral Palsy in Infants with Perinatal Cerebral Stroke.

Neonatal cerebral stroke includes a range of focal and multifocal ischemic and hemorrhagic brain lesions, occurring in about one of 3000 live births. More than 50% of children with neonatal stroke develop adverse outcomes, mainly unilateral cerebral palsy. Asymmetries in segmental movements at three months have been proven to be an early sign of CP in infants with unilateral brain damage. Recognition of additional early signs could enhance prognostic assessment and enable an early and targeted intervention. The aim of the study was to assess early signs of CP in infants with arterial cerebral stroke through the General Movements Assessment and the Motor Optimality Score-Revised (MOS-R). Twenty-four infants born at term (12 females and 12 males) diagnosed with ACS, and 24 healthy infants (16 females and 8 males) were assessed. The GMs (fidgety movements) and MOS-R were assessed from videos recorded at 11-14 weeks of post-term age. Cognitive and motor outcomes were assessed at 24 months using the Griffiths III developmental quotient and Amiel-Tison neurological examination. The gross motor function classification system expanded and revised (GMFCS-E&R) was adopted to categorize CP. Among infants with ACS, 21 (87.5%) developed unilateral CP. Most of them showed non-disabling CP (14 had GMFCS-E&R grade 1 [66.6%], 6 grade 2 [28.6%], and 1 grade 5 [4.8%]). Fidgety movements (FMs) were absent in 17 (70.8%), sporadic in 4 (16.7%) infants, and normal in 3 (12.5%). Segmental movement asymmetry was found in 22/24 (91.7%). According to the MOS-R, motor items (kicking, mouth movements), postural patterns (midline centered head, finger posture variability), and movement character (monotonous and stiff) were statistically different among infants with ACS and healthy infants. The MOS-R median global score was lower in the group with ACS compared to the control group (6 vs 26; p < 0.01). FMs, segmental movement asymmetry, and MOS-R global score were significantly correlated with abnormal outcome. MOS-R global scores less than or equal to 13 had 100% specificity and sensitivity in predicting GMFCS-E&R grade ≥ 2 CP in infants with ACS. The rate of CP was high among infants with ACS, but in most cases it showed low GMFCS-E&R grades. The study highlighted a significant correlation between MOS-R, together with absent FMs and unilateral CP in infants with ACS. Moreover, the MOS-R showed high sensitivity and specificity in the prediction of CP. Combined assessment of FMs and MOS-R could help to better identify infants at high risk of developing UCP in a population of infants with ACS. Early identification of precocious signs of unilateral CP is fundamental to providing an early individualized intervention.

Mini-strokes after awake surgery for glioma resection: are there anesthesia related factors?

Awake surgery is now a common approach for the resection of glioma. One of the surgical complications is mini-stroke which take the form of periresectional small areas of brain ischemic lesions. The main objective of this study is to evaluate the association between factors related to anesthetic management and the risk of mini-stroke, in awake surgery for glioma resection. In this single-center retrospective study, all patients who were operated on, between 2011 and 2022, in awake conditions for a glioma resection, were retrospectively included. The studied anesthetic parameters included hemodynamic variables, fluid intake and urinary output. The primary endpoint was the presence of mini-stroke on a magnetic resonance imaging performed within the first 48h postoperatively. A total of 176 surgeries were included. Mini-stroke was present in 120/171 surgeries (70%), with a median volume of 1.2 interquartile range [0.4-2.2] cubic centimeters (cc). In a multivariable analysis, only the per operative urinary output was significantly associated with the incidence of postoperative mini-strokes (adjusted odd-ratio 0.65, 95% confidence interval 0.45-0.94, p = 0.02). No variables related to the anesthetic management were associated with the volume of postoperative mini-strokes. In particular, the time spent below 90% of the baseline systolic blood pressure was not associated with either the risk or the volume of mini-strokes. During awake surgery for glioma resection, among several anesthesia related factors, only the per operative urinary output was associated with the incidence of postoperative mini-stroke.

Troponin I as a Predictor of Transcranial Doppler Sonography Defined Vasospasm in Intensive Care Unit Patients After Spontaneous Subarachnoid Hemorrhage.

Elevation of Troponin I (TnI) in spontaneous subarachnoid hemorrhage (SAH) patients is a well-known phenomenon and associated with cardiopulmonary complications and poor outcome. The present study was conducted to investigate the association of the TnI value on admission, and the occurrence of cerebral vasospam in SAH patients. A total of 142 patients with SAH, who were admitted to the neurosurgical intensive care unit (ICU) between December 2014 and January 2021 were evaluated. Blood samples were drawn on admission to determine TnI value. Each patient's demographic, radiological and medical data on admission, the modified Ranking Scale score at discharge as well as continuous measurements of transcranial Doppler sonography were analyzed. A maximum mean flow velocity (MMFV) > 120 cm/sec was defined as any vasospasm. These were stratified into severe vasospasms, which were defined as at least two measurements of MMFVs > 200 cm/sec or an increase of MMFV > 50 cm/sec/24 h over two consecutive days or a new neurological deterioration and mild vasospasm defined as MMFVs > 120 cm/sec in absence of severe vasospasm criteria. The total study population was dichotomized into patients with an initially elevated TnI (>0.05 µg/L) and without elevated TnI (≤0.05 μg/L). A total of 52 patients (36.6%) had an elevated TnI level upon admission, which was significantly associated with lower GCS score (p < 0.001), higher WFNS score (p < 0.001) and higher Fisher grade (p = 0.01) on admission. In this context a higher rate of ischemic brain lesions (p = 0.02), a higher modified Rankin Scale score (p > 0.001) and increased mortality (p = 0.02) at discharge were observed in this group. In addition, TnI was identified as an independent predictor for the occurrence of any vasospasm and severe vasospasm. An initially elevated TnI level is an independent predictor for the occurrence of any and severe vasospasm in patients with SAH.

Stroke and Stroke-Like Episodes: Recurrent Manifestations in GLUT1 Deficiency Syndrome

BackgroundSince the initial description of glucose transporter-1 deficiency syndrome (Glut1-DS) the phenotype of the condition has expanded, even leading to the recognition of atypical manifestations. We report on eight patients with Glut1-DS who experienced at least one episode of acute focal neurological deficits. MethodsWe conducted a retrospective analysis, collecting clinical, electrophysiological, neuroradiological, and genetic information. We focused in particular on three well-documented cases. ResultsAmong 42 patients with Glut1-DS, eight individuals aged between six and 38 years presented with an acute onset of neurological disturbances: dysarthria/aphasia, oral dyskinesia, swallowing difficulties, paresthesia, facial palsy, hemi/monoplegia, vomiting, headache, and behavioral disturbances. When performed, magnetic resonance imaging (MRI) revealed signs of venous congestion and hypoperfusion and electroencephalography showed focal contralateral slowing. Deficits were transient in all patients but one. Four patients (50%) were on a ketogenic diet (KD), and two of these patients had lower than usual ketonemia levels during the episode. In two patients, MRI demonstrated the presence of an ischemic brain lesion. ConclusionsIn Glut1-DS, stroke-like episodes are a recurrent manifestation, particularly during early adulthood, and they were reported in 19% of the patients in our cohort. Stroke mimics should be considered a key feature of Glut1-DS, as other paroxysmal disorders. It remains to be established whether a KD can prevent the recurrence of episodes and, if so, at what level of ketosis. Further observations are needed to confirm the correlation between Glut1-DS and ischemic stroke.

Pharmacological neuroprotection in cerebrovascular insufficiency: Possible approaches

This review analyzed the literature data and results of our research on the experimental and clinical studies of the possibilities of pharmacological neuroprotection in ischemic brain lesions. Neuroprotection is one of the strategic directions of specific pharmacotherapy for cerebrovascular insufficiency. Different approaches to pharmacological neuroprotection are possible, considering the main pathogenetic pathways of the ischemic cascade and physiological mechanisms of neuroprotection. Pharmacological neuroprotection can be achieved by blocking the pathogenetic links of the ischemic cascade (primarily glutamate excitotoxicity and oxidant stress) and inducing physiological processes associated with neuroplasticity and neurotrophy. The issues related to the use of various pharmacotherapeutic groups for primary and secondary neuroprotection are discussed. The optimal choice of pathogenetic and physiological targets for primary and secondary pharmacological neuroprotection is an important component in the development of pharmacotherapy strategies for ischemic brain lesions because it consistently increases the resistance of brain cells to ischemia/hypoxia and stimulates reparative recovery processes in the central nervous system. Rationally selected pathways and drugs for pharmacological neuroprotection determine their effectiveness in ischemic brain lesions.

Impact of shaggy aorta on intraoperative cerebral embolism during carotid artery stenting.

Careful selection of patients for carotid stenting is necessary. We suggest that patients with a shaggy aorta syndrome may be at higher risk for perioperative embolic complications. The study is a retrospective subanalysis of the SIBERIA Trial. We included 72 patients undergoing transfemoral carotid artery stenting. Patients were monitored during the procedures using multifrequency transcranial Doppler with embolus detection and differentiation. Pre- and postprocedural (2 and 30 days) cerebral diffusion-weighted cerebral MRIs were performed. Forty-six patients had shaggy aorta syndrome. Intraoperative embolisms were recorded in 82.6% and 46.1% of patients with and without shaggy aorta syndrome, respectively (P=0.001). New asymptomatic ischemic brain lesions in the postoperative period occurred in 78.3% and in 26.9% of patients with and without shaggy aorta syndrome, respectively (P<0.001). There were no cases of stroke within 2 days in both groups. 3 (6.5%) cases of stroke within 30 days after the procedure were observed only in patients with shaggy aorta syndrome. There were no cases of contralateral stroke. Shaggy aorta syndrome (OR 5.54 [1.83:16.7], P=0.001) and aortic arch ulceration (OR 6.67 [1.19: 37.3], P=0.02) were independently associated with cerebral embolism. Shaggy aorta syndrome (OR 9.77 [3.14-30.37], P<0.001) and aortic arch ulceration (OR 12.9 [2.3: 72.8], P=0.003) were independently associated with ipsilateral new asymptomatic ischemic brain lesions. Shaggy aorta syndrome and aortic arch ulceration significantly increase the odds of intraoperative embolism and new asymptomatic ischemic brain lesions. Carotid endarterectomy or transcervical carotid stent should be selected in patients with shaggy aorta syndrome.

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990–2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep–wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population—all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (</>median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.

Fat Embolism Syndrome from Bone Marrow Necrosis Following Peg-Filgrastim in a Patient with Primary Mediastinal B-Cell Lymphoma

Background: The mechanism of atraumatic fat embolization syndrome (FES) is poorly understood. However, mechanical and biochemical processes are the two plausible theories that exist. FES from bone marrow necrosis caused by hemoglobinopathies, use of chemotherapy in hematopoietic malignancies and from use of G-CSF has been reported. In our case, a young male patient with primary mediastinal large B-cell lymphoma presented with microhemorrhages and punctiform ischemic brain lesions after receiving chemoimmunotherapy and pegylated G-CSF. Case: A 29-year-old male recently diagnosed with primary mediastinal large B-cell lymphoma presented to our ED with severe bone pain after receiving his first cycle etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin, and rituximab (DA R-EPOCH) with peg-filgrastim support. He was discharged with pain control and subsequently received his second cycle of DA-R-EPOCH (20% increase in etoposide, doxorubicin, and cyclophosphamide) with a retrial of peg-filgrastim. His WBC count rose to a peak of 41,100K/UL on the seventh day of his second cycle. Ten days after receipt of his 2 nd peg-filgrastim, he presented to the ED with complaints of generalized weakness, decreased oral intake and mild imbalance with his gait. His blood pressure was 103/71 mmHg, heart rate was 138 beats per minute, respiratory rate was 22 breaths per minute and oxygen saturation was 91% on room air; and he required 2 liters of supplemental oxygen. Laboratory studies showed Hb of 8.1 gm/dL, PLT of 47,000k/UL and WBC of 10,100k/UL. The WBC differential was consistent with myeloid predominance with a left shift and some enucleated RBC consistent with use of peg- filgrastim. LDH was 2874 U/L, albumin was 3.8 g/L, PTT 23.1 seconds, PT 13.8 seconds, INR 1.2. A CT with angiography of the chest showed no pulmonary embolism but an anterior mediastinal soft tissue mass, which decreased in size compared to his prior image, with erosive changes of sternum. Mediastinal and axillary lymphadenopathy also overall decreased in size. Due to developing confusion and mild left-sided facial weakness, MRI with and without intravenous contrast of the brain demonstrated numerous petechial microhemorrhages throughout the brain parenchyma in the supratentorial compartment and posterior cranial fossa with involvement of superficial and deep parenchymal regions. Many were seen clustered in the internal/external watershed regions. Transthoracic echocardiogram with bubble study demonstrated a patent foramen ovale (PFO). Prophylactic low molecular weight heparin was started and he was discharged after improvement of symptoms. He proceeded to complete 4 more cycles of standard dose R-EPOCH with prophylactic levofloxacin instead of peg-GCSF. His neurologic symptoms resolved and did not recur. Conclusion: This case highlights a rare but severe complication of BMN causing fat embolization syndrome in a patient receiving G-CSF following R-EPOCH for high PMBCL with sternal bone involvement. We hypothesize that the rapid proliferation of myeloid cell lines induced by G-CSF led to vascular occlusion and relative hypoxemia. Furthermore, the prolonged incorporation of corticosteroids is known to cause adipose tissue disruption. His underlying disease involved invasion into his sternum which further would support the theory of bone marrow necrosis being able to dislodge into the vasculature. This case is important to alert physicians to be cognizant of this severe complication and to provide some evidence for continuing curative intent treatment with the omission of G-CSF support.

ABO-Incompatible Platelet Transfusion Is Associated with Ischemic Lesions on Brain MRI in Patients with Intracerebral Hemorrhage

Background: We have identified that major ABO-incompatible platelet transfusions are associated with poor intracerebral hemorrhage (ICH) outcomes. The underlying drivers for the relationship of these incompatible platelet units on outcome are unknown, yet do not appear to be related to impaired hemostasis. Conversely, ICH patients are known to encounter remote, “silent” ischemic lesions, thought to be from microthrombosis, during their hospitalization. Though these ischemic lesions are well known to associate with poor ICH outcomes, risk factors for its formation are unknown. We explored whether major ABO-incompatible platelet transfusions are associated with acute ischemic lesions on brain MRI during an ICH hospitalization. Methods: Consecutive spontaneous ICH patients enrolled into a single-center, prospective cohort study between 2009 and 2018 were assessed. Patients who received a single platelet transfusion within 24 hours of ICH admission and had a brain MRI during the hospitalization were included in the analysis. Major ABO incompatible platelet transfusion (vs minor mismatch/identical) was defined as the exposure. Presence of remote ischemic lesions, defined as diffusion restriction &amp;gt;10 mm away from the hematoma detected on brain MRI, was the outcome. Regression models were used to assess relationships between major ABO-incompatible platelet unit exposure and acute ischemic brain lesions, adjusting for time from ICH onset to MRI or ICH severity. Results: We identified 40 ICH patients receiving an acute platelet transfusion and having a brain MRI performed during the ICH hospitalization. The mean age was 67.1 (SD 14.1), 37.5% were female, and 20% received a major ABO incompatible platelet unit. Patients receiving a major incompatible platelet unit were more likely to encounter ischemic lesions (62.5% vs 21.9%). We also identified an association of major ABO-incompatible platelets units with acute ischemic brain lesions in our regression models after adjusting for time from ICH symptom onset to MRI (OR 5.45, 95%CI 1.01-29.30, p=0.048) and ICH severity (OR 9.15, 95%CI 1.37-62.67, p=0.024). Additional sensitivity analysis adjusting for patient blood type did not alter this relationship (OR 17.1, 95%CI 1.34-217.9, p = 0.029). Conclusions: Among ICH patients receiving acute platelet transfusions and MRI neuroimaging, major ABO incompatible units were associated with remote ischemic lesions on brain MRI. Further work is needed to address the generalizability of our data and to clarify relationships of platelet unit characteristics, cerebral microthrombosis, and clinical outcomes after ICH.

Long non-coding RNAs H19 and NKILA are associated with the risk of death and lacunar stroke in the elderly population

IntroductionDifferential expression of long non-coding RNAs (lncRNAs) is a hallmark of cardiovascular aging, cerebrovascular diseases, and neurodegenerative disorders. This research article investigates the association between a panel of lncRNAs and the risk of death and ischemic stroke in a cohort of non-institutionalized elderly subjects. MethodA total of 361 healthy individuals aged 75 years old, prospectively recruited in the Vienna Transdanube Aging (VITA) cohort, were included. Expression of lncRNAs at baseline was assessed using quantitative polymerase chain reaction PCR with pre-amplification reaction, using 18S for normalization. The primary endpoint was all-cause mortality; the secondary endpoint was the incidence of new ischemic brain lesions. Death was assessed over a 14-year follow-up, and ischemic brain lesions were evaluated by magnetic resonance imaging (MRI) over a 90-month follow-up. Ischemic brain lesions were divided into large brain infarcts (Ø≥ 1.5 cm) or lacunes (Ø< 1.5 cm) ResultsThe primary endpoint occurred in 53.5 % of the study population. The incidence of the secondary endpoint was 16 %, with a 3.3 % being large brain infarcts, and a 12.7 % lacunes.After adjustment for potential confounders, the lncRNA H19 predicted the incidence of the primary endpoint (HR 1.194, 95 % C.I. 1.012–1.409, p = 0.036), whereas the lncRNA NKILA was associated with lacunar stroke (HR 0.571, 95 % C.I. 0.375–0.868, p = 0.006). ConclusionIn a prospective cohort of non-institutionalized elderly subjects, high levels of lncRNA H19 are associated with a higher risk of death, while low levels of lncRNA NKILA predict an increased risk of lacunar stroke.

Nurse-driven protocol for the management and follow-up of subclinical atrial fibrillation episodes in pacemaker patients

Abstract Background Atrial high-rate episodes (AHREs) compatible with atrial fibrillation (AF) detected in pacemakers are associated with an increased risk of stroke. Nurses trained in pacemaker (PM) follow-up can detect theses AHREs during patient’ scheduled visits and provide the best care option to the patients. Purpose To evaluate a nurse protocol applied in these patients focused on a) identifying those with AHREs and taking into account the timing of these events and their duration, and b) provide the best care and follow-up then after. Methods and Results To create our protocol, we evaluated PM patients without a previous history of AF and classified the incidence of AHREs into 3 groups: &amp;gt;5 minutes to 24 hours; &amp;gt;24 hours and patients who are in clinical AF (documented on ECG) at the time of the visit. We also evaluate the time elapsed since PM implantation (£ 3 months vs &amp;gt; 3 months) and the type of atrial electrode fixation (active vs passive). In a prior study we analyzed 110 patients with AHREs &amp;gt;5 minutes and &amp;lt;24 hours (56% male, age 75 ± 9 years, mean CHA2DS2VACS scores of 3.5 ± 1.5). After 24 ± 9 months, 40 patients (36.4%) presented AHREs, and CT images showed ischemic brain lesions in 26 of them (23.6%). The presence of AHREs at 3 months was more frequent in patients with a recent MP implantation (17% vs 4.5%) and with a significant relationship with the type of active fixation of the electrode. The presence of ischemic lesions on CT was related to the detection of AHREs during follow-up, but not with AHREs in the first 3 months. Therefore, we designed a dedicated protocol for follow-up in these patients (AHREs &amp;gt;5 minutes and &amp;lt;24 hours) after PM implantation with repetitive follow-up visits assessing the evolution of AHREs. In cases of &amp;gt;24 hours and those with ECG documented AF, Guidelines recommendations were followed. Conclusions In PM patients, the presence of AHREs might be related to serious clinical complications. On the other hand, AHREs occur regularly during the first 3 months after PM implantation, maybe related to the procedure itself and the use of active fixation for the atrial lead. AHREs in this period may not be related to major complications and individual risk should be carefully assessed before starting anticoagulation. A dedicated protocol for closer follow-up visits in these patients might help to identify those at risk and prevent clinical events.

Detection of brain lesions after catheter ablation depends on imaging criteria: insights from AXAFA-AFNET 5 trial.

Left atrial catheter ablation is well established in patients with symptomatic atrial fibrillation (AF) but associated with risk of embolism to the brain. The present analysis aims to assess the impact of diffusion-weighted imaging (DWI) slice thickness on the rate of magnetic resonance imaging (MRI)-detected ischaemic brain lesions after ablation. AXAFA-AFNET 5 trial (NCT02227550) participants underwent MRI using high-resolution (hr) DWI (slice thickness: 2.5-3 mm) and standard DWI (slice thickness: 5-6 mm) within 3-48 h after ablation. In 321 patients with analysable brain MRI (mean age 64 years, 33% female, median CHA2DS2-VASc 2), hrDWI detected at least one acute brain lesion in 84 (26.2%) patients and standard DWI in 60 (18.7%; P < 0.01) patients. High-resolution diffusion-weighted imaging detected more lesions compared to standard DWI (165 vs. 104; P < 0.01). The degree of agreement for lesion confirmation using hrDWI vs. standard DWI was substantial (κ = 0769). Comparing the proportion of DWI-detected lesions, lesion distribution, and total lesion volume per patient, there was no difference in the cohort of participants undergoing MRI at 1.5 T (n = 52) vs. 3 T (n = 269). The pre-specified AXAFA-AFNET 5 sub-analysis revealed significantly increased rates of MRI-detected acute brain lesions using hrDWI instead of standard DWI in AF patients undergoing ablation. In comparison to DWI slice thickness, MRI field strength had a no significant impact in the trial. Comparing the varying rates of ablation-related MRI-detected brain lesions across previous studies has to consider these technical parameters. Future studies should use hrDWI, as feasibility was demonstrated in the multicentre AXAFA-AFNET 5 trial.

Association of Cerebral Oximetry With Brain Ischemic Lesions and Functional Outcomes in Arch Repair

BackgroundThis exploratory analysis of the randomized controlled Aortic Surgery Cerebral Protection Evaluation CardioLink-3 trial sought to determine if cerebral oximetry desaturation during elective proximal arch repair is associated with detrimental postoperative neuroradiologic and neurofunctional outcomes. MethodsCerebral oximetry and pre- and postoperative brain magnetic resonance imaging data from 101 participants were analyzed. Oximetry data from the trial allocation groups were compared; the relationships between cerebral oximetry indices and new ischemic cerebral lesions on magnetic resonance imaging and neurologic outcomes were also evaluated. ResultsTotal cerebral desaturation events (>20% decrease from baseline) on the left (median [interquartile range], 1 [1-3] vs 1.5 [0.5-3] with innominate and axillary cannulation; P = .80) were comparable to those on the right (1 [1-3] vs 1 [0-3]; P = .75) as were the total area under the curve of desaturation (left, P = .61; right, P = .84). Seventy patients had new ischemic lesions, among whom 36 had new severe lesions. Total desaturation events and area under the curve of desaturation were similar in patients with and without new ischemic lesions or severe lesions. The nadir regional cerebral saturation was lower on the left (49% [41-56]) than the right (53% [44-59]); left desaturation episodes were associated with lower postoperative cognitive test scores (P = .004). ConclusionsThe innominate and axillary cannulation techniques for elective proximal arch repair with unilateral antegrade cerebral perfusion were associated with similar occurrences of cerebral oximetry desaturation and neither were associated with new ischemic lesions.

Ultrasonographic Vasospasm and Outcome of Posterior Reversible Encephalopathy and Cerebral Vasoconstriction Syndromes.

Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are often complicated by vasospasm and ischemia. Monitoring with transcranial color-coded Doppler (TCCD) could be useful, but its role is not established. We studied the incidence of ultrasonographic vasospasm (uVSP) in PRES/RCVS and its relationship with ischemic lesions and clinical outcome. We conducted a multicenter retrospective study of all patients with PRES/RCVS from 2008 to 2020 who underwent TCCD and magnetic resonance imaging (MRI). TCCD exams were analyzed for uVSP. Diffusion-weighted MRI was analyzed for positive lesions (DWI-positive). Functional outcome was assessed by modified Rankin scale (mRS) at 90 days. The associations with outcomes were determined by logistic regression. We included 80 patients (mean age of 46 (standard deviation, 17) years; 66% females; 41 with PRES, 28 with RCVS and 11 with overlap phenotype). uVSP was detected in 25 (31%) patients. DWI-positive lesions were more often detected in uVSP-positive than uVSP-negative patients (36% vs. 15%; adjusted odds ratio [aOR] 4.05 [95% CI 1.06 - 15.5], P=0.04). DWI-positive lesions were independently associated with worse functional prognosis (mRS 2-6, 43% vs. 10%; aOR, 10 [95% CI 2.6 - 43], P<0.01). Having additional uVSP further increased the odds of a worse outcome (P interaction=0.03). Ultrasonographic vasospasm was detected in a third of patients with PRES/RCVS and was associated with brain ischemic lesions. TCCD bedside monitoring can help to stratify patients at risk for cerebral ischemia, a strong predictor of functional outcome.