scholarly journals DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yufeng Gao ◽  
Xiaojie Fu ◽  
Lie Yu ◽  
Di Zhang ◽  
Zhengfang Lu ◽  
...  

Objective. Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. Methods. Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. Results. A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (<10 mL), medium (10 to 30 mL), and large (>30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups ( P < 0.05 ). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups ( P < 0.05 ). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups ( P < 0.05 ). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups ( P < 0.05 ). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group ( P < 0.05 ). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group ( P < 0.05 ). Conclusion. The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

2021 ◽  
Vol 12 (1) ◽  
pp. 58-66
Author(s):  
Doan Nguyen ◽  
Vi Tran ◽  
Alireza Shirazian ◽  
Cruz Velasco-Gonzalez ◽  
Ifeanyi Iwuchukwu

Abstract Background Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. Methodology Blood samples from ICH patients (n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. Principle findings and results IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). Conclusions and significance Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Nerses Sanossian ◽  
Adrian M Burgos ◽  
David S Liebeskind ◽  
Sidney Starkman ◽  
Pablo Villablanca ◽  
...  

Background: Early neurologic deterioration (END) occurs commonly in intracerebral hemorrhage (ICH) patients being transported by EMS ambulances, but the imaging correlates of END have not been previously delineated. Methods: We analyzed consecutive ICH patients in the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial, a phase 3, multicenter of paramedic-initiated magnesium sulfate vs. placebo for stroke patients presenting within 2 hours of symptom onset. END was defined as a 2-point or greater decrease in the Glasgow Coma Scale (GCS) from paramedic evaluation to ED evaluation. Baseline imaging studies were independently analyzed by 2 neurologists for ICH location, volume, presence of intraventricular hemorrhage (IVH), heterogeneity (defined as >20 point difference in Hounsfield units), irregular hematoma borders, multilobulated appearance, and substantial edema (defined as >0.5cm thickness). Leukoaraiosis was graded using the Fazekas scale for periventricular and deep white matter changes (0-3 for each). Results: Among 127 patients, mean age was 66 (SD 14) years, 34% were women, 35% were Hispanic ethnicity, 83% white, and 84% had a history of HTN. Patients were evaluated by paramedics a median of 23 (IQR 16, 39) minutes after last known well time (LKWT). At that time, the median GCS was 15 (IQR 15-15) and mean SBP/DBP was 177/95 (SD 34/22). Initial post-arrival brain imaging was performed a median of 94 (IQR 77, 117) min after LKWT. Post-arrival study GCS scores were obtained at a median of 108 (IQR 70, 144) min after LWKT. Early neurologic deterioration occurred in 37 (29%) patients. Among these patients, median first ED GCS was 3 (IQR 3-10). On first imaging, compared with neurologically stable patients, END patients had larger hematoma volume (33 cc v 16 cc, p<0.0001), and more frequent presence of intraventricular extension (45% v 20%, p=0.003), midline shift (58% v 22%), substantial edema (54% v 26%, p=0.038), heterogeneous density (50% v 22%, p=0.006), multilobulated appearance (44% v 18%, p=0.002), and irregular border (39% v 14%, p=0.010). Leukoaraiosis and cortical v subcortical location did not affect rates of END. In multivariate analysis, hematoma volume and presence of IVH were imaging findings independently associated with early neurologic deterioration. Conclusions: About 3 in 10 patients with hyperacute ICH neurologically deteriorate during the prehospital and early emergency department course, often before neuroimaging is obtained. Patients with early neurologic deterioration have larger hematoma volume and occurrence of IVH on initial imaging. These findings suggest hematoma expansion prior to ED arrival drives early neurologic deterioration in ICH and emphasize the need for prehospital interventions.


Stroke ◽  
2018 ◽  
Vol 49 (7) ◽  
pp. 1618-1625 ◽  
Author(s):  
Sandro Marini ◽  
William J. Devan ◽  
Farid Radmanesh ◽  
Laura Miyares ◽  
Timothy Poterba ◽  
...  

2015 ◽  
Vol 3 (Suppl 1) ◽  
pp. A981
Author(s):  
HB Rotzel ◽  
A Serrano Lázaro ◽  
D Aguillón Prada ◽  
A Mesejo Arizmendi ◽  
C Sanchís Piqueras ◽  
...  

2012 ◽  
Vol 117 (4) ◽  
pp. 767-773 ◽  
Author(s):  
Justin A. Dye ◽  
Joshua R. Dusick ◽  
Darrin J. Lee ◽  
Nestor R. Gonzalez ◽  
Neil A. Martin

Object Surgical evacuation of spontaneous intracerebral hemorrhage (sICH) remains a subject of controversy. Minimally invasive techniques for hematoma evacuation have shown a trend toward improved outcomes. The aim of the present study is to describe a minimally invasive alternative for the evacuation of sICH and evaluate its feasibility. Methods The authors reviewed records of all patients who underwent endoscopic evacuation of an sICH at the UCLA Medical Center between March 2002 and March 2011. All patients in whom the described technique was used for evacuation of an sICH were included in this series. In this approach an incision is made at the superior margin of the eyebrow, and a bur hole is made in the supraorbital bone lateral to the frontal sinus. Using stereotactic guidance, the surgeon advanced the endoscopic sheath along the long axis of the hematoma and fixed it in place at two specific depths where suction was then applied until 75%–85% of the preoperatively determined hematoma volume was removed. An endoscope's camera, then introduced through the sheath, was used to assist in hemostasis. Preoperative and postoperative hematoma volumes and reduction in midline shift were calculated and recorded. Admission Glasgow Coma Scale and modified Rankin Scale (mRS) scores were compared with postoperative scores. Results Six patients underwent evacuation of an sICH using the eyebrow/bur hole technique. The mean preoperative hematoma volume was 68.9 ml (range 30.2–153.9 ml), whereas the mean postoperative residual hematoma volume was 11.9 ml (range 5.1–24.1 ml) (p = 0.02). The mean percentage of hematoma evacuated was 79.2% (range 49%–92.7%). The mean reduction in midline shift was 57.8% (p < 0.01). The Glasgow Coma Scale score improved in each patient between admission and discharge examination. In 5 of the 6 patients the mRS score improved from admission exam to last follow-up. None of the patients experienced rebleeding. Conclusions This minimally invasive technique is a feasible alternative to other means of evacuating sICHs. It is intended for anterior basal ganglia hematomas, which usually have an elongated, ovoid shape. The approach allows for an optimal trajectory to the long axis of the hematoma, making it possible to evacuate the vast majority of the clot with only one pass of the endoscopic sheath, theoretically minimizing the amount of damage to normal brain.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Frieder Schlunk ◽  
Johannes Kuthe ◽  
Peter Harmel ◽  
Heinrich Audebert ◽  
Uta Hanning ◽  
...  

Abstract Background Follow-up imaging in intracerebral hemorrhage is not standardized and radiologists rely on different imaging modalities to determine hematoma growth. This study assesses the volumetric accuracy of different imaging modalities (MRI, CT angiography, postcontrast CT) to measure hematoma size. Methods 28 patients with acute spontaneous intracerebral hemorrhage referred to a tertiary stroke center were retrospectively included between 2018 and 2019. Inclusion criteria were (1) spontaneous intracerebral hemorrhage (supra- or infratentorial), (2) noncontrast CT imaging performed on admission, (3) follow-up imaging (CT angiography, postcontrast CT, MRI), and (4) absence of hematoma expansion confirmed by a third cranial image within 6 days. Two independent raters manually measured hematoma volume by drawing a region of interest on axial slices of admission noncontrast CT scans as well as on follow-up imaging (CT angiography, postcontrast CT, MRI) using a semi-automated segmentation tool (Visage image viewer; version 7.1.10). Results were compared using Bland–Altman plots. Results Mean admission hematoma volume was 18.79 ± 19.86 cc. All interrater and intrarater intraclass correlation coefficients were excellent (1; IQR 0.98–1.00). In comparison to hematoma volume on admission noncontrast CT volumetric measurements were most accurate in patients who received postcontrast CT (bias of − 2.47%, SD 4.67: n = 10), while CT angiography often underestimated hemorrhage volumes (bias of 31.91%, SD 45.54; n = 20). In MRI sequences intracerebral hemorrhage volumes were overestimated in T2* (bias of − 64.37%, SD 21.65; n = 10). FLAIR (bias of 6.05%, SD 35.45; n = 13) and DWI (bias of-14.6%, SD 31.93; n = 12) over- and underestimated hemorrhagic volumes. Conclusions Volumetric measurements were most accurate in postcontrast CT while CT angiography and MRI sequences often substantially over- or underestimated hemorrhage volumes.


2021 ◽  
Author(s):  
Yuefan Yang ◽  
Pan Wang ◽  
Anlai Liu ◽  
Xiuquan Wu ◽  
Zedong Yan ◽  
...  

Abstract Background: Intracerebral hemorrhage causes high mortality and morbidity, but its therapy methods are limited. In the present study, pulsed electromagnetic fields (PEMFs) were demonstrated to have beneficial effects on an intracerebral hemorrhage (ICH) model. This study explored the effects and underlying mechanism of PEMFs in a mouse model of ICH and cultured BV2 cells.Methods: PEMFs were applied 24 hours after collagenase-induced ICH and 4 hours per day for seven consecutive days. The levels of proinflammatory factors were assessed by ELISA kits and western blotting. Hematoma volume was measured by histological analysis. The effects of PEMFs on phagocytosis of the erythrocytes was observed in cultured BV2 cells.Results: Seven days after ICH, the hematoma volume was significantly reduced in PEMF-treated animals compared to nontreated mice. We found that PEMFs decreased the hematoma volume and the levels of proinflammatory factors after ICH. To evaluate the mechanisms underlying the effects of PEMFs on ICH, we analyzed the transcriptome profile three days after ICH, and we found that PEMFs reversed the changes in inflammation-related pathways and alleviated neurological deficits. Furthermore, PEMFs enhanced the erythrophagocytosis of microglia via CD36. Thus, the PEMF-mediated promotion of neurological functions may at least partly involve anti-inflammatory processes and hematoma clearance.Conclusions: These results suggest that PEMF treatment is a possible adjuvant therapy for ICH patients.


2014 ◽  
Vol 61 (4) ◽  
pp. 17-20
Author(s):  
Aleksandra Milosevic ◽  
Nikola Repac ◽  
Igor Nikolic ◽  
Igor Coric ◽  
Aleksandar Janicijevic ◽  
...  

The study included 39 patients treated in a Special hospital for the prevention and treatment of cerebrovascular diseases ? Sveti Sava? in Belgrade in the period from October 2010 to January 2012. The criteria for inclusion in the study is the moment of diagnosis of spontaneous intracerebral hemorrhage (ICH) in the basal ganglia of the brain (BG). The results: we analyzed 25 male patients and 14 female patients, aged 54 years to 95 years. In deceased group - 22 (56.4%), 20 (90.9%) were the age group 60 to 80 years., GCS: 3-5 -12 patients (54.5%) died, GCS 6 -8 -10 patients (45.5%), 20 patients (90.9%) also had intracerebral and intraventricular hemorrhage complicated by acute hydrocephalus. Conclusion: predisposing factors for mortality within one year in patients with spontaneous intracerebral hemorrhage in the basal ganglia of the brain are: males older than 60 years, unregulated hypertension and penetration of blood in the chamber system.


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