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Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations.

ABSTRACT: Arteriovenous malformations (AVMs) of the central nervous system are considered as congenital disorders. They are composed of abnormally developed dilated arteries and veins and are characterized microscopically by the absence of a capillary network. We previously reported DNA fragmentation and increased expression of apoptosis-related factors in AVM lesions. In this article, we used microarray analysis to examine differential gene expression in relation to clinical manifestations in 11 AVM samples from Japanese patients. We categorized the genes with altered expression into four groups: death-related, neuron-related, inflammation-related, and other. The death-related differentially expressed genes were MMP9, LIF, SOD2, BCL2A1, MMP12, and HSPA6. The neuron-related genes were NPY, S100A9, NeuroD2, S100Abeta, CAMK2A, SYNPR, CHRM2, and CAMKV. The inflammation-related genes were PTX3, IL8, IL6, CXCL10, GBP1, CHRM3, CXCL1, IL1R2, CCL18, and CCL13. In addition, we compared gene expression in those with or without clinical characteristics including deep drainer, embolization, and high-flow nidus. We identified a small number of genes. Using these microarray data we are able to generate and test new hypotheses to explore AVM pathophysiology. Microarray analysis is a useful technique to study clinical specimens from patients with brain vascular malformations.

SUBMITTER: Takagi Y

PROVIDER: S-EPMC4533425 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations.

Takagi Yasushi Y Aoki Tomohiro T Takahashi Jun C JC Yoshida Kazumichi K Ishii Akira A Arakawa Yoshiki Y Kikuchi Takayuki T Funaki Takeshi T Miyamoto Susumu S

Neurologia medico-chirurgica 20131025 3

Arteriovenous malformations (AVMs) of the central nervous system are considered as congenital disorders. They are composed of abnormally developed dilated arteries and veins and are characterized microscopically by the absence of a capillary network. We previously reported DNA fragmentation and increased expression of apoptosis-related factors in AVM lesions. In this article, we used microarray analysis to examine differential gene expression in relation to clinical manifestations in 11 AVM samp ...[more]

PMID: 24162243

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Project description:ObjectiveWe aimed to evaluate the clinical characteristics and long-term prognosis of brain arteriovenous malformations (bAVMs) treated with multimodality management of one-staged hybrid operation.MethodsWe identified bAVM patients treated with one-staged hybrid operation from a multicenter prospective cohort study (NCT03774017) between January 2016 and June 2020. Patients were divided into unruptured and ruptured groups by the hemorrhagic presentation. Long-term (>12 months) neurological disability, postoperative complications of stroke, and nidus obliteration were evaluated and compared between groups. Prognostic predictors associated with outcomes were analyzed.ResultsA total of 130 patients were identified in the study receiving one-staged hybrid operations, including 61 unruptured cases and 69 ruptured cases. Mean age was 29.1 years old, with 78 (60.0%) being male. Patients included in the study were followed up for a mean period of 37.4 (11.07) months. The annual hemorrhagic risk was 4.2% per year. Thirteen postoperative stroke events were detected in 11 patients (8.5%). Long-term disability occurred in 6.9% of cases, and 86.2% of patients experienced an unchanged or improved neurological status at the last follow-up. All patients achieved complete obliteration on follow-up angiographies. Increased AVM volume was associated with a higher risk of postoperative stroke (odds ratio (OR) 1.021, 95% confidence interval (CI) 1.006-1.037, and P = 0.006). Poor neurological status (OR 6.461, 95% CI 1.309-31.889, and P = 0.022) and infratentorial location (OR 5.618, 95% CI 1.158-27.246, and P = 0.032) were independent predictors for long-term disability.ConclusionsOne-staged hybrid operation of embolization combined microsurgical resection can be performed as a safe and effective strategy for bAVM treatments. Long-term prognosis of complete obliteration with low rates of morbidity and mortality can be achieved. Unruptured and ruptured bAVMs acquired similar favorable outcomes after the multimodality treatment.

Project description:BackgroundBrain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one-fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiosurgery, endovascular embolization, and staged combinations of these interventions. This is an update of a Cochrane Review first published in 2006, and last updated in 2009.ObjectivesTo determine the effectiveness and safety of the different interventions, alone or in combination, for treating brain AVMs in adults compared against either each other, or conservative management, in randomized controlled trials (RCTs).Search methodsThe Cochrane Stroke Group Information Specialist searched the Cochrane Stroke Group Trials Register (last searched 7 January 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library, MEDLINE Ovid (1980 to 14 January 2019), and Embase OVID (1980 to 14 January 2019). We searched international registers of clinical trials, the contents pages of relevant journals, and bibliographies of relevant articles (November 2009). We also contacted manufacturers of interventional treatments for brain AVMs (March 2005).Selection criteriaWe sought RCTs of any intervention for brain AVMs (used alone or in combination), compared against each other or against conservative management, with relevant clinical outcome measures.Data collection and analysisOne author screened the results of the updated searches for potentially eligible RCTs for this updated review. Both authors independently read the potentially eligible RCTs in full and confirmed their inclusion according to the inclusion criteria. We resolved disagreement by discussion. We assessed the risk of bias in included studies and applied GRADE.Main resultsWe included one trial with 226 participants: A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA), comparing intervention versus conservative management for unruptured brain AVMs (that had never bled). The quality of evidence was moderate because we found just one trial that was at low risk of bias other than a high risk of performance bias due to participants and treating physicians not being blinded to allocated treatment. Data on functional outcome and death at a follow-up of 12 months were provided for 218 (96%) of the participants in ARUBA. In this randomized controlled trial (RCT), intervention compared to conservative management increased death or dependency (modified Rankin Scale score ≥ 2, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.28 to 4.98; 1 trial, 226 participants; moderate-quality evidence) and the proportion of participants with symptomatic intracranial haemorrhage (RR 6.75, 95% CI 2.07 to 21.96; 1 trial, 226 participants; moderate-quality evidence), but there was no difference in the frequency of epileptic seizures (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 226 participants; moderate-quality evidence). Three RCTs are ongoing.Authors' conclusionsWe found moderate-quality evidence from one RCT including adults with unruptured brain AVMs that conservative management was superior to intervention with respect to functional outcome and symptomatic intracranial haemorrhage over one year after randomization. More RCTs will help to confirm or refute these findings.

Dataset Information

Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations.

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Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations.

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