Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the Acute Brain Bleeding Analysis study

BACKGROUND AND PURPOSE: The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear. We examined the risk of HS associated with the use of NANSAIDs in Koreans. METHODS: We performed a nationwide, multicenter case-control study from 2002 to 2004. This study included 940 nontraumatic acute HS cases in patients aged 30 to 84 years, with an absence of a history of stroke or hemorrhage-prone brain lesions, alongside 940 community controls, matched to each case by age and sex. Pretrained interviewers obtained information on prescription drugs as well as over-the-counter drugs taken within 14 days before the onset of stroke. We adjusted potential confounders, including family histories of stroke, histories of hypertension, smoking, alcohol consumption, high salt intake, and laborious work hours. The adjusted ORs and their 95% CIs were calculated by conditional logistic regression. RESULTS: The proportion of NANSAIDs exposure within 14 days was 2.9% for HS patients and 2.0% for the controls. The adjusted odds ratios of stroke in NANSAIDs users compared with nonusers was 1.12 (95% CI, 0.77 to 1.65) for all HS, 1.03 (95% CI, 0.49 to 2.18) for subarachnoid hemorrhage, and 1.19 (95% CI, 0.76 to 1.87) for intracerebral hemorrhage. CONCLUSIONS: No increased risk of HS either subarachnoid hemorrhage or intracerebral hemorrhage was found among NANSAIDs users.This study was partially supported by the Korean Food and Drug Administration

NINJ2 SNP may affect the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions

<p>Abstract</p> <p>Background</p> <p>To investigate if single nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene <it>NINJ2 </it>would be associated with earlier-onset (vs. late-onset) first-ever ischemic stroke and increase silent cerebrovascular lesions prior to the manifestation of the stroke.</p> <p>Methods</p> <p>We prospectively enrolled 164 patients (67.6 ± 12.9 years, 92 men) admitted with first-ever ischemic strokes. All patients underwent genotyping of rs11833579 and rs12425791 as well as systemic investigations including magnetic resonance (MR) imaging and other vascular workup. Stroke-related MR lesions were registered on a brain-template-set using a custom-built software package 'Image_QNA': high-signal-intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery (FLAIR) MR images, and low signal intensity hemorrhagic lesions on gradient-echo MR images.</p> <p>Results</p> <p>The rs11833579 A/A or G/A genotype was independently associated with the first-ever ischemic stroke before the age 59 vs. 59 or over, after adjusting for cardiovascular risk factors and prior medication of antiplatelet or anticoagulant drugs, increasing the risk by about 2.5 fold. In the quantitative MR lesion maps from age-sex matched subgroups (n = 124 or 126), there was no difference between the patients with the rs11833579 A/A or G/A genotype and those with the G/G genotype. Unexpectedly, the extent of leukoaraiosis on FLAIR-MR images tended to be smaller in the corona radiata and centrum semiovale of the patients with the rs12425791 A/A or G/A genotype than in those with the G/G genotype (<it>P </it>= 0.052). Neither the rs11833579 nor the rs12425791 genotype significantly affected initial stroke severity; however the latter was associated with relatively low modified Rankin scale scores at 1 year after stroke.</p> <p>Conclusions</p> <p>The rs11833579 A/A or G/A genotype may bring forward the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions prior to the stroke. Further studies are required to confirm our preliminary findings.</p

Abstract 142: Safety and Efficacy of PCSK9 inhibitor injection in Pathients immediately before mechanical thrombectomy

Introduction Statins are lipid‐lowering agents and have beneficial effects in patients with acute ischemic stroke, including in the hyperacute period around mechanical thrombectomy.Evolucumab, a PCSK9 inhibitor, is a fast‐acting drug that lowers serum LDL with beneficial effects during chronic stroke period. During an hyperacute ischemic stroke, the brain can be vulnerable, especially around reperfusion therapy. However, the clinical effect of PCSK9 inhibitor injection around mechanical thrombectomy is still unknown. Here we showed the efficacy and safety of PCSK9 inhibitor injection immediately prior to mechanical thrombectomy for these patients. Methods The subjects were stroke patients who underwent mechanical thrombectomy at Inha University Hospital from April 2019 to March 2023. Clinical profiles between the evolucumab group and the non‐user group were analyzed. Results Of the 263 patients enrolled, 112 (42.6%) were male and the mean age was 69.1 years. Of these, 42 patients received a single dose of a PCSK9 inhibitor immediately prior to intervention and additional injections were not made due to insurance issues. Evolukumab injection was determined according to physician preference. There were no significant differences between the two groups in age, gender ratio, major risk factors, stroke etiology, or prior statin treatment. Evolucumab group had a higher stent recovery rate than the non‐user group (70.7 vs 53.4%, p = 0.04). However, there were no significant difference in TICI grade, or symptomatic hemorrhage. Compared with non‐user group, Evolucumab group had the lower NIHSS score on discharge (12.41 vs 8.83, p=0.03) and seemed to have the lower in‐hopital mortality(12.2 vs 2.4% p=0.06) Mean LDL‐C levels at admission and 3 months after stroke did not differ between the two groups. Cardiovascular and other adverse events within 3 months were similar in both groups. Conclusion Evolocumab added to conventional high‐intensity statin therapy was well tolerated and appeared to be associated with lower in‐hospital mortality and lower NIHSS scores at discharge without additional side effects. Further large randomized clinical trials might be needed to investigate the beneficial effects of PCSK9i during hyperacute stroke period

Total small vessel disease burden and functional outcome in patients with ischemic stroke.

BackgroundCerebral small vessel disease (SVD) is comprised of lacunes, cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and enlarged perivascular space (EPVS). We investigated the cumulative effect of SVD on 3-month functional outcome following ischemic stroke using the total SVD score.MethodsThe total SVD score of 477 acute ischemic stroke patients with adequate brain MRI was analyzed. We used multivariable ordinal logistic regression analysis to investigate the independent impact of total SVD score on ordinal modified Rankin Scale (mRS) score at 3-month after ischemic stroke.ResultsMean age was 66±14 years, and 61% were men. The distribution of the total SVD score from 0 to 4 was 27%, 24%, 26%, 16%, and 7%, respectively. The proportion of mRS scores 2 or greater was 16% and 47% in total SVD score 0 and 4, respectively. Multivariable ordinal logistic regression analysis results showed that compared with the total SVD score of 0, total SVD scores of 2, 3, and 4 were independently associated with higher mRS scores with adjusted odds ratios (95% confidence intervals) of 1.68 (1.02-2.76), 2.24 (1.25-4.00), and 2.00 (1.02-4.29). Lacunes, CMBs, WMHs but not EPVS were associated with mRS scores at 3 months. However, the impact of each SVD marker on stroke outcome was smaller than that of the total SVD score.ConclusionWe found an independent association between total SVD scores and functional outcome at 3 months following ischemic stroke. The total SVD score may be useful for stratification of patients who are at a high-risk of unfavorable outcomes

Aphasia following striatocapsular infarction may be explained by concomitant small cortical infarct on diffusion-weighted imaging

BACKGROUND: The underlying mechanism of aphasia following striatocapsular infarction (SCI) remains controversial. We hypothesized that aphasia resulting from SCI might be associated with concomitant cortical lesions, which can be demonstrated by diffusion-weighted imaging (DWI). METHODS: We analyzed 24 patients with left SCI who underwent DWI and MR angiography within 2 days after the onset. Aphasia was assessed by the modified Korean version of the Boston Diagnostic Aphasia Examination test. RESULTS: DWI showed the presence of additional ischemic lesions involving the cortical areas in 13 of 24 SCI patients (54%). Ten patients (42%) showed aphasia. All 10 patients with aphasia had cortical lesions in addition to SCI (p = 0.0002), whereas 21% (3/14) of the nonaphasic patients had additional cortical lesions. Conventional MRI did not reveal the presence of corresponding acute cortical lesions in any of the aphasic patients. There was no difference between the patients with and without aphasia in terms of their stroke etiology. CONCLUSIONS: Our data suggest that aphasia due to SCI in the acute stage may be attributed to direct cortical injury, whose presence can be demonstrated by DWI, even though it might be invisible on conventional imaging

Molecular Imaging of Cathepsin B Proteolytic Enzyme Activity Reflects the Inflammatory Component of Atherosclerotic Pathology and Can Quantitatively Demonstrate the Antiatherosclerotic Therapeutic Effects of Atorvastatin and Glucosamine

Inflammation in atherosclerotic plaques causes plaque vulnerability and rupture, leading to thromboembolic complications. Cathepsin B (CatB) proteases secreted by macrophages play a major role in plaque inflammation. We used a CatB-activatable near-infrared fluorescence (NIRF) imaging agent to demonstrate the inflammatory component in mice atheromata and the atherosclerosis-modulating effects of atorvastatin or glucosamine treatments. Apolipoprotein E knockout mice (n = 35) were fed normal chow, a Western diet, a Western diet + atorvastatin, a Western diet + glucosamine, or a Western diet + atorvastatin + glucosamine for 14 weeks. Twenty-four hours after the intravenous injection of a CatB-activatable probe, ex vivo NIRF imaging of the aortas and brains was performed, followed by histology. The CatB-related signal, observed in the aortas but not in the cerebral arteries, correlated very well with protease activity and the presence of macrophages on histology. Animals on Western diets could be distinguished from animals on a normal diet. The antiatherosclerotic effects of atorvastatin and glucosamine could be demonstrated, with reduced CatB-related signal compared with untreated animals. Plaque populations were heterogeneous within individuals, with some plaques showing a high and others a lower CatB-related signal. These differences in signal intensity could not be predicted by visual inspection of the plaques but did correlate with histologic evidence of inflammation in every case. This suggests that vulnerable inflamed plaques can be identified by optical molecular imaging