Explanatory Power and Prognostic Implications of Factors Associated with Troponin Elevation in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). METHODS: This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. RESULTS: Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040-0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698-0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. CONCLUSION: Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.

RNF213 rs112735431 polymorphism in intracranial artery steno-occlusive disease and moyamoya disease in Koreans.

BACKGROUND: The rs112735431 polymorphism of the RNF213, a susceptibility variant for moyamoya disease (MMD), may be associated with non-MMD intracranial artery steno-occlusive disease of non-MMD type (non-MMD ICAD) in Asian. We investigated whether the rs112735431 polymorphism of the RNF213 affect the development of non-MMD ICAD in Koreans compared to MMD and control group. METHODS: We included 31 patients with non-MMD ICAD, 25 patients with MMD, and 100 participants as control group. The rs112735431 polymorphism of the RNF213 was evaluated by polymerase chain reaction amplification of target and detection by restriction fragment length polymorphism analysis. Clinical phenotype was compared between patients with and without the rs112735431 polymorphism in non-MMD ICAD and MMD. RESULTS: The rs112735431 polymorphism of the RNF213 was significantly associated with non-MMD ICAD (p=0.001; odds ratio, 14.3; 95% confidence interval, 2.80-73.2) and MMD (p<0.0001; odds ratio, 126.0; 95% confidence interval, 24.2-656.0). The rate of hypertension was more frequent in MMD with the rs112735431 polymorphism than MMD without polymorphism (p=0.010). CONCLUSIONS: The rs112735431 polymorphism of the RNF213 is highly associated not only with MMD but also with non-MMD ICAD in Koreans. Also, our study suggests that the rs112735431 polymorphism of the RNF213 may be linked to the hypertension in MMD. Further studies are needed to clarify the relationship between the rs112735431 polymorphism of the RNF213 and hypertension in patients with MMD.

Low serum TNF-related apoptosis-inducing ligand (TRAIL) levels are associated with acute ischemic stroke severity.

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor receptor superfamily and its serum level is known to be closely associated with future cardiovascular events and prognosis of various cardiovascular diseases. We investigated whether serum TRAIL levels are associated with the severity of acute ischemic stroke and specific stroke subtype. METHODS: We used an enzyme-linked immunosorbent assay to measure the serum TRAIL levels of 293 patients with acute ischemic stroke within 7 days of onset. Stroke subtype was classified as large artery atherosclerosis, cardioembolism, small vessel occlusion and other determined etiology. We used National Institute of Health Stroke Scale (NIHSS) score of first hospital day and stroke volume on diffusion-weighted imaging within 7 days of stroke onset for measuring the severity of acute ischemic stroke. RESULTS: The level of serum TRAIL showed significant negative correlations with NIHSS score and stroke volume. Serum TRAIL levels significantly decreased as the tertile of NIHSS score and stroke volume increased. The relative risk of patients with serum TRAIL<64.0 pg/mL for the presence of highest tertile of NIHSS score was significantly increased (adjusted OR [95%CI]; 7.07 [3.64-13.74]). Regarding stroke volume, the relative risk of patients with serum TRAIL<71.5 pg/mL for the presence of highest tertile of stroke volume was also significantly increased (adjusted OR [95%CI]; 2.81 [1.61-4.92]). There are no significant differences of serum TRAIL level among stroke subtypes. CONCLUSIONS: Low serum TRAIL levels were significantly associated with the acute ischemic stroke severity. This finding suggests that serum TRAIL might also have a role in acute ischemic stroke as well as other cardiovascular diseases.

Intracranial fibromuscular dysplasia presenting as various ocular manifestations.

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that mainly affects renal, extracranial carotid, and vertebral arteries. Intracranial FMD is uncommon unlike extracranial or renal FMD, and the primary manifestation of intracranial FMD is intracranial aneurysm. We report an unusual case of intracranial FMD showing various ocular manifestations, including central retinal artery occlusion, transient monocular blindness, and oculomotor nerve palsy without renal involvement.

Change in cortical vessel signs on susceptibility-weighted images after full recanalization in hyperacute ischemic stroke.

BACKGROUND: The cortical vessel signs (CVSs) on susceptibility-weighted images (SWIs) have been reported in patients with hyperacute ischemic stroke. We evaluated the change of this susceptibility sign on the immediate SWI after full recanalization and its clinical implications. METHODS: Nineteen hyperacute ischemic stroke patients who had acute large artery occlusion and underwent post-recanalization SWI were enrolled in this study. The patients had ICA (internal carotid artery, 2 cases), M1 (M1 segment of middle cerebral artery, 7 cases), M2 (M2 segment of middle cerebral artery, 1 cases), T (intracranial ICA bifurcation, 2 cases), ICA/M1 (4 cases) and basilar artery (3 cases) occlusion on imaging studies before thrombolysis and they underwent immediate magnetic resonance imaging, including the SWI, after full recanalization. The recanalization status was evaluated using the thrombolysis in cerebral infarction (TICI) score before and after thrombolysis. The SWI images were evaluated for the presence of asymmetry of veins over the ischemic territory and this was correlated with the site of stenosis or occlusion. The veins in the ischemic territory were classified as 'prominent' if there were more numerous veins and/or large veins with a greater signal loss observed compared with the opposite normal hemisphere, 'equal' if there were no significant difference in appearance in both the cerebral hemispheres, and 'less' if the veins were decreased in the affected area as compared with that of the normal cortex. Baseline clinical parameters and clinical outcomes were reviewed. RESULTS: The initial TICI grades were 0 in all cases. After thrombolysis, TICI grades were 3 in all cases. The pre-recanalization SWIs were obtained in 10 of 19 patients and all 10 showed prominent CVSs over the affected side, which disappeared on the post-recanalization SWI. On the post-recanalization SWI, the observed veins in the affected area were equal (10/19), less (5/19), and both equal and less (4/19). Patients with equal cortical veins in the affected area had small lesions on diffusion-weighted image (DWI) (10/19), while patients with less cortical veins had medium to large lesions on DWI (9/19). CONCLUSION: The prominent CVSs on SWI can be indicative of acute thromboembolic occlusion and its change immediately after recanalization can be used to reflect the metabolic status. After recanalization, the appearance of the equal CVS (return to normal) on SWI was associated with a favorable clinical outcome and infarction was avoided in our small series study.

Induction of vascular endothelial growth factor and matrix metalloproteinase-9 via CD47 signaling in neurovascular cells.

Neurovascular injury comprises a wide spectrum of pathophysiology that underlies the progression of brain injury after cerebral ischemia. Recently, it has been shown that activation of the integrin-associated protein CD47 mediates the development of blood-brain barrier injury and edema after cerebral ischemia. However, the mechanisms that mediate these complex neurovascular effects of CD47 remain to be elucidated. Here, we compare the effects of CD47 signaling in brain endothelial cells, astrocytes, and pericytes. Exposure to 4N1 K, a specific CD47-activating peptide derived from the major CD47 ligand thrombospondin-1, upregulated two major neurovascular mediators, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), in brain endothelial cells and astrocytes. No changes were detected in pericytes. These findings may provide a potential mechanism for CD47-induced changes in blood-brain barrier homeostasis, and further suggest that CD47 may be a relevant neurovascular target in stroke.

Statistical parametric mapping and statistical probabilistic anatomical mapping analyses of basal/acetazolamide Tc-99m ECD brain SPECT for efficacy assessment of endovascular stent placement for middle cerebral artery stenosis.

INTRODUCTION: Statistical parametric mapping (SPM) and statistical probabilistic anatomical mapping (SPAM) were applied to basal/acetazolamide Tc-99m ECD brain perfusion SPECT images in patients with middle cerebral artery (MCA) stenosis to assess the efficacy of endovascular stenting of the MCA. METHODS: Enrolled in the study were 11 patients (8 men and 3 women, mean age 54.2 +/- 6.2 years) who had undergone endovascular stent placement for MCA stenosis. Using SPM and SPAM analyses, we compared the number of significant voxels and cerebral counts in basal and acetazolamide SPECT images before and after stenting, and assessed the perfusion changes and cerebral vascular reserve index (CVRI). RESULTS: The numbers of hypoperfusion voxels in SPECT images were decreased from 10,083 +/- 8,326 to 4,531 +/- 5,091 in basal images (P = 0.0317) and from 13,398 +/- 14,222 to 7,699 +/- 10,199 in acetazolamide images (P = 0.0142) after MCA stenting. On SPAM analysis, the increases in cerebral counts were significant in acetazolamide images (90.9 +/- 2.2 to 93.5 +/- 2.3, P = 0.0098) but not in basal images (91 +/- 2.7 to 92 +/- 2.6, P = 0.1602). The CVRI also showed a statistically significant increase from before stenting (median 0.32; 95% CI -2.19-2.37) to after stenting (median 1.59; 95% CI -0.85-4.16; P = 0.0068). CONCLUSION: This study revealed the usefulness of voxel-based analysis of basal/acetazolamide brain perfusion SPECT after MCA stent placement. This study showed that SPM and SPAM analyses of basal/acetazolamide Tc-99m brain SPECT could be used to evaluate the short-term hemodynamic efficacy of successful MCA stent placement.

Phenotypic variability in Kennedy's disease: implication of the early diagnostic features.

OBJECTIVES: The clinical diagnosis of Kennedy's disease (KD) is not easy when the typical manifestations are lacking, especially in early stage of the disease. In our study, we tried to identify the relative frequency of common clinical features and early symptoms in KD. METHOD: Eighteen Korean patients with KD were included. Clinical findings were subdivided into two parts: the age at onset of each clinical symptoms and characteristic signs on investigations. With detailed clinical examinations, the serum creatine kinase (CK) level, electrophysiologic study and DNA analysis were performed and analyzed in detail. RESULTS: In KD, the most consistent clinical findings at evaluations included perioral fasciculation with variable bulbar paresis, limb weakness with wasting, hyporeflexia, hand tremor, and elevated CK level. Some distinguishing features, such as X-linked family history, gynecomastia, and sensory abnormalities were absent in a half of cases. Frequent initial clinical findings include tremor (50%) and symptoms other than weakness, such as cramps and fatigability (33.3%). CONCLUSION: We conclude that KD shows variable clinical and electrophysiological features. Our description on the onset and subsequent progression of each clinical finding might help to identify KD in early stage and avoid misdiagnosis.