Abstract WP204: Genetic Variant in VCAM1 Mediates Acute Infarct Size in Ischemic Stroke Patients

Introduction: Even though neuroinflammation is increasingly recognized as an essential contributor to ischemic brain injury, the exact underlying mechanisms remain unclear. Higher expression of the vascular cell adhesion molecule 1 (VCAM-1) increases leukocyte-brain endothelium interaction and has been associated with larger infarct size following acute ischemic stroke (AIS). The activation of the TGF-β signaling pathways can down-regulate VCAM-1 expression and ameliorate deleterious tissue outcome during neuroinflammation. Hypothesis: We sought to investigate whether genetic variation in the TGF-beta pathway and adhesion molecule genes is associated with acute stroke lesion size. Methods: We completed genome-wide association (GWA) testing and diffusion-weighted imaging lesion volume (DWIv) analysis in a discovery cohort of 532 AIS patients of European ancestry enrolled within 48 hours of symptom onset. An independent European ancestry cohort of 724 AIS patients with GWA data and automated DWIv served as replication cohort. GWA testing per SNP was performed using linear regression modeling of natural log-transformed DWIv adjusted for age, sex and relevant principal components. We selected 42 inflammatory genes in the TGF-beta pathway for a gene-based analysis using VEGAS (Versatile Gene-based -Association Study) software. A pre-specified discovery phase Bonferroni-corrected threshold was set at p<0.001. In the replication phase, 14 SNPs overlapping were tested at the Bonferroni-corrected p-value threshold of p<0.004. Results: Of all genes in the TGF-beta pathway, VCAM1 (p=0.0006) was significantly associated with DWIv in the discovery AIS cohort (age: 66 ± 14.9 years, sex: 63.4% male, DWIv: 2.2cm 3 (IQR: 0.6-11.7cm 3 )). A single SNP within the VCAM1 gene boundaries (rs3176876 (BETA=0.2341, p=0.003)) was significantly associated with DWIv in the replication AIS cohort (age: 65 ± 14.1 years, sex: 68.6% male, DWIv: 4cm 3 (IQR: 1.3-17.2cm 3 )). Conclusion: The genetic variant rs3176876 in the VCAM1 gene is associated with larger infarct lesion size measured on brain MRI of AIS patients. These findings suggest genetic contribution to the pro-inflammatory mechanisms in acute cerebral ischemia and warrant further investigation.

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Abstract 136: Genetics of White Matter Hyperintensity Burden in Patients With Ischemic Stroke: The MRI-GENIE Study

Stroke ◽

10.1161/str.48.suppl_1.136 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Anne-Katrin Giese ◽

Huichun Xu ◽

Kathleen Ryan ◽

Markus D Schirmer ◽

Adrian V Dalca ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Brain Mri ◽

Genome Wide Association ◽

European Ancestry ◽

White Matter Hyperintensity ◽

Chromosome 2 ◽

Association Testing ◽

Genome Wide ◽

Mri Scans

Introduction: The MRI-Genetics Interface Exploration (MRI-GENIE) study is the first international collaboration that aims to facilitate genetic discoveries in clinical cohorts of patients with acute ischemic stroke (AIS). We have amassed the largest-to-date collection of AIS cases with brain MRI scans and genome-wide genotyping to test the role of genetic susceptibility in MRI-based cerebrovascular traits. Objective/Hypothesis: To elucidate the genetic architecture of white matter hyperintensity (WMH) burden in AIS patients. Methods: Using a novel automated algorithm, we extracted WMH volume (WMHv) from clinical MRI scans of 2704 AIS patients (age 63.1 ± 14.7 years, 60.6% male) of European ancestry. Quality control (QC) measures were undertaken per subject and per SNP, excluding subjects with non-European ancestry and poor genotyping, as well as SNPs deviating from Hardy-Weinberg equilibrium and high levels of missingness. Imputation to the Haplotype Reference Consortium (HRC version r1.1) was conducted for 1712 remaining subjects with 2.8 million SNPs on the Michigan Imputation Server. After exclusion of poorly imputed SNPs (R 2 <0.5) and SNPs with minor allele frequency < 1%, 7.7 million SNPs remained for further analysis. Genome-wide association testing of natural log-transformed WMHv on the allelic dosage per SNP was adjusted for age, sex and principal components 1-10. Results: Genome-wide association testing has identified a novel locus on chromosome 2 (T allele at rs72856504) near the LDL Receptor related Protein 1B gene (LRP1B) that was significantly associated with WMHv burden in AIS (β=0.54, SE=0.098, p=3.65*10 -8 ). Conclusion: We have identified a novel locus (T allele rs72856504) on chromosome 2 near the LRP1B gene, which is specific for WMH in AIS and has not been previosuly described in stroke-free WMH cohorts. A replication effort involving additional independent cohorts of AIS patients with brain MRI and genome-wide genotyping is ongoing.

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ASSESSMENT OF THE SERUM INTERLEUKIN-6, INTERCELLULAR ADHESION MOLECULE-1, NITRIC OXIDE AND C-REACTIVE PROTEIN IN ACUTE ISCHEMIC STROKE

Zagazig University Medical Journal ◽

10.21608/zumj.2014.4405 ◽

2014 ◽

Vol 20 (4) ◽

pp. 1-9

Author(s):

El-Shazly SMA ◽

Abdel-Gawad EA ◽

Omar HM ◽

El-Khatib TH

Keyword(s):

Nitric Oxide ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Adhesion Molecule ◽

Interleukin 6 ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

C Reactive Protein ◽

Intercellular Adhesion Molecule 1 ◽

Reactive Protein

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Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort

Journal of Alzheimer s Disease ◽

10.3233/jad-201080 ◽

2021 ◽

pp. 1-9

Author(s):

Janice L. Atkins ◽

Luke C. Pilling ◽

Christine J. Heales ◽

Sharon Savage ◽

Chia-Ling Kuo ◽

...

Keyword(s):

Iron Reduction ◽

Brain Mri ◽

European Ancestry ◽

Uk Biobank ◽

Brain Iron ◽

Mri Features ◽

Incident Dementia ◽

Hfe Mutations ◽

The Uk

Background: Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. Objective: To estimated p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. Methods: UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2 * measures (lower values indicating more iron). Results: European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2 * measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Conclusion: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

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Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2016.013 ◽

2016 ◽

Vol 4 (1) ◽

pp. 139-141

Author(s):

Ali Yilmaz ◽

Zahir Kizilay ◽

Ayca Ozkul ◽

Bayram Çirak

Keyword(s):

Ischemic Stroke ◽

Head Trauma ◽

Distal Part ◽

Brain Mri ◽

Artery Occlusion ◽

Acute Ischemia ◽

Post Traumatic ◽

The Brain ◽

Perforating Arteries ◽

Pure Motor

BACKGROUND: The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood.CASE REPORT: Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner.CONCLUSION: Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood.

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Neuroprotective mechanisms of erythropoietin in a rat stroke model

Translational Neuroscience ◽

10.1515/tnsci-2020-0008 ◽

2020 ◽

Vol 11 (1) ◽

pp. 48-59

Author(s):

Martin Juenemann ◽

Tobias Braun ◽

Nadine Schleicher ◽

Mesut Yeniguen ◽

Patrick Schramm ◽

...

Keyword(s):

Blood Flow ◽

Infarct Size ◽

Cerebral Edema ◽

Infarct Volume ◽

Artery Occlusion ◽

Lesion Volume ◽

Ischemic Lesion ◽

Human Erythropoietin ◽

Male Wistar Rats ◽

Cerebral Artery Occlusion

AbstractObjectiveThis study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO).MethodsOne hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet–dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography.ResultsIn the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment.ConclusionsSingle-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

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The anesthetic approach for endovascular recanalization therapy depends on the lesion site in acute ischemic stroke

Neuroradiology ◽

10.1007/s00234-021-02762-3 ◽

2021 ◽

Author(s):

Kilian Fröhlich ◽

Gabriela Siedler ◽

Svenja Stoll ◽

Kosmas Macha ◽

Thomas M. Kinfe ◽

...

Keyword(s):

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Acute Ischemic Stroke ◽

Cerebral Artery ◽

Posterior Circulation ◽

Neurological Deficits ◽

Stroke Severity ◽

Lesion Volume ◽

Middle Cerebral Artery Territory ◽

Cerebral Lesion

Abstract Purpose Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician’s decision between GA and CS using voxel-based lesion symptom mapping (VLSM). Methods In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. Results One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. Conclusions The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician’s decision on using GA in EVT.

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The influence of lesion volume, perilesion resection volume, and completeness of resection on seizure outcome after resective epilepsy surgery for cortical dysplasia in children

Journal of Neurosurgery Pediatrics ◽

10.3171/2014.10.peds14282 ◽

2015 ◽

Vol 15 (6) ◽

pp. 644-650 ◽

Cited By ~ 30

Author(s):

Chima O. Oluigbo ◽

Jichuan Wang ◽

Matthew T. Whitehead ◽

Suresh Magge ◽

John S. Myseros ◽

...

Keyword(s):

Epilepsy Surgery ◽

Seizure Control ◽

Brain Mri ◽

Age At Onset ◽

Cortical Dysplasia ◽

Complete Resection ◽

Seizure Outcome ◽

Seizure Freedom ◽

Lesion Volume ◽

Resection Volume

OBJECT Focal cortical dysplasia (FCD) is one of the most common causes of intractable epilepsy leading to surgery in children. The predictors of seizure freedom after surgical management for FCD are still unclear. The objective of this study was to perform a volumetric analysis of factors shown on the preresection and postresection brain MRI scans of patients who had undergone resective epilepsy surgery for cortical dysplasia and to determine the influence of these factors on seizure outcome. METHODS The authors reviewed the medical records and brain images of 43 consecutive patients with focal MRI-documented abnormalities and a pathological diagnosis of FCD who had undergone surgical treatment for refractory epilepsy. Preoperative lesion volume and postoperative resection volume were calculated by manual segmentation using OsiriX PRO software. RESULTS Forty-three patients underwent first-time surgery for resection of an FCD. The age range of these patients at the time of surgery ranged from 2 months to 21.8 years (mean age 7.3 years). The median duration of follow-up was 20 months. The mean age at onset was 31.6 months (range 1 day to 168 months). Complete resection of the area of an FCD, as adjudged from the postoperative brain MR images, was significantly associated with seizure control (p = 0.0005). The odds of having good seizure control among those who underwent complete resection were about 6 times higher than those among the patients who did not undergo complete resection. Seizure control was not significantly associated with lesion volume (p = 0.46) or perilesion resection volume (p = 0.86). CONCLUSIONS The completeness of FCD resection in children is a significant predictor of seizure freedom. Neither lesion volume nor the further resection of perilesional tissue is predictive of seizure freedom.

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