Yong Bum Kim

Serum Vitamin D Status as a Predictor of Prognosis in Patients with Acute Ischemic Stroke

Background: Low 25-hydroxyvitamin D (25(OH)D) concentrations have been shown to predict risk of cardiovascular disease and all-cause mortality. Although the prevalence of 25(OH)D deficiency is high in patients with acute stroke, the prognostic value of 25(OH)D in stroke has not been clearly established. The purpose of this study was to determine whether the baseline serum 25(OH)D level was associated with the functional outcome in patients with acute ischemic stroke. Methods: From June 2011 to January 2014, consecutive patients with acute ischemic stroke within 7 days of symptom onset were enrolled in this study from a prospectively maintained stroke registry. Serum 25(OH)D level was measured at admission. Clinical and laboratory data including stroke severity using the National Institute of Health Stroke Scale (NIHSS) score were collected during admission, and the functional outcome at 3 months was assessed by modified Rankin scale (mRS). The association between the baseline 25(OH)D level and a good functional outcome (mRS 0-2) at 3 months was analyzed by multiple logistic regression models. Results: A total of 818 patients were enrolled in this study. Mean age was 66.2 (±12.9) years, and 40.5% were female. The mean 25(OH)D level was 47.2 ± 31.7 nmol/l, and the majority of patients met vitamin D deficient status (<50 nmol/l; 68.8%), while an optimal vitamin D level (≥75 nmol/l) was present in only 13.6% of the patients, and 436 (53.3%) patients showed good functional outcome at 3 months. Serum 25(OH)D levels in patients with good outcomes were significantly higher than those with poor outcome (50.2 ± 32.7 vs. 43.9 ± 30.0 nmol/l, p = 0.007). The 3-month functional outcome was significantly associated with month-specific 25(OH)D quartiles in multivariable logistic regression analysis. After adjustment for age and sex, the highest 25(OH)D quartile group had higher tendency for good functional outcome at 3 months (odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.13-2.51). After fully adjusting for other potential confounders, such as stroke severity and vascular risk factors, the association was further strengthened with an OR (95% CI) of 1.90 (1.14-3.16). Other factors associated with good functional outcome in multivariable analysis were younger age, lower initial NIHSS score and absence of diabetes. Conclusions: This study suggests that serum 25(OH)D level is an independent predictor of functional outcome in patients with acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.

25-Hydroxyvitamin D Status Is Associated With Chronic Cerebral Small Vessel Disease

Background and Purpose— The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease. Methods— We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses. Results— Mean age was 68 (±13) years. Mean level of 25(OH)D was 34.1±17.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02–0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41–3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01–1.63). Also, 25(OH)D deficiency (⩽25 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04–0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31–6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03–2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients. Conclusions— 25(OH)D is inversely associated with lacunes, white matter hyperintensity, and deep CMB. Our findings suggest that 25(OH)D is linked to small vessel disease, and in future trials it should be tested whether 25(OH)D supplementation can prevent small vessel disease.

Leukoaraiosis predicts poor outcome after spontaneous supratentorial intracerebral hemorrhage.

Background and Aims: Leukoaraiosis (LA) is associated with aging and vascular risk factors, and is a risk factor of intracerebral hemorrhage (ICH) after treatment with warfarin or thrombolytic treatment for ischemic stroke. In this study, we sought to examine whether LA is a predictor of outcome after spontaneous ICH. Methods: We retrospectively analyzed 238 consecutive patients with spontaneous supratentorial ICH identified by a database search. Patients were divided into two groups according to neurological outcome at 90 days: patients with good outcomes (Glasgow Outcome Scale ≧4) and patients with poor outcomes. Demographic features, ICH characteristics, and LA severity as assessed by van Swieten score on brain CT were compared between the two groups. Results: Overall, 105 (44.1%) of the patients analyzed had poor outcomes. In univariate analysis, LA severity, ICH volume on initial brain CT, initial Glasgow Coma Scale (GCS), presence of intraventricular hemorrhage (IVH), old age, surgical treatment, and higher admission serum glucose level were associated with poor outcome. Multiple logistic regression analysis showed that severity of LA, initial GCS score, hematoma volume, presence of IVH, and surgical treatment were independent predictors of poor outcome. Conclusion: LA is an independent predictor of poor neurological outcome in patients with spontaneous supratentorial ICH.

Association between Cerebral Arterial Calcification and Brachial-Ankle Pulse Wave Velocity in Patients with Acute Ischemic Stroke

Background/Aims: Vascular calcification is known to be associated with cardiovascular mortality, and arterial stiffness measured by pulse wave velocity is associated with major cardiovascular risk factors. The aim of the present study was to elucidate the correlation between arterial stiffness and cerebral arterial calcification. Methods: Arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), and cerebral arterial calcification, as measured by CT angiography using a 40-multidetector scanner, were examined in patients with acute ischemic stroke. Sixty-seven subjects who were free of renal disease or peripheral arterial disease were included in the analysis. Results: Univariate analysis revealed that baPWV was significantly correlated with cerebral arterial calcification (r = 0.524, p < 0.001) and age (r = 0.452, p < 0.001), and multiple linear regression analysis indicated that age and cerebral arterial calcification were independent determinants of baPWV. Conclusion: We report that increased baPWV is closely associated with the degree of cerebral arterial calcification in patients with acute ischemic stroke. Our results suggest that the severity of cerebral arterial calcification is representative of the degree of systemic arterial stiffness.

Increased cardiovascular mortality in subjects with metabolic syndrome is largely attributable to diabetes and hypertension in 159,971 Korean adults

CONTEXT Metabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD) mortality. OBJECTIVE This study aimed to evaluate the association of MetS with all-cause and cardiovascular mortality in apparently healthy young Korean subjects. DESIGN A retrospective study of 155,971 participants (mean age, 41.8 y) in a health screening program, followed up for 3.7 years (597,628.2 person-years). The risk for all-cause mortality and CVD mortality were analyzed according to the presence or absence of MetS. MAIN OUTCOMES A total of 542 subjects died during followup. Women with MetS showed a significantly increased age-adjusted hazard ratio (HR) for all-cause mortality compared with women without MetS, even after adjustment for confounding factors (HR, 1.82; 95% confidence interval [CI], 1.15-2.88). Subjects with MetS showed a significantly increased risk for CVD mortality compared with those without MetS, even after adjustment for confounding factors (HR, 1.60; 95% CI, 1.02-2.20), of which significance disappeared when subjects with diabetes or hypertension at baseline were excluded from the analysis (HR, 0.95; 95% CI, 0.29-3.12). CONCLUSIONS The presence of MetS increased the risk for all-cause mortality in women and the risk for CVD mortality in total population. These increased HR attributed to the pre-existing diabetes or hypertension in this population.

Increased Pulsatility Index Is Associated with Intracranial Arterial Calcification

Background/Aims: An increase in the pulsatility index (PI) has been suggested to reflect distal vascular resistance. The purpose of the present study was to investigate the association between intracranial arterial calcification and intracranial PIs. Methods: Consecutive patients with acute ischemic stroke or transient ischemic attack were included. The PIs of both middle cerebral arteries (MCAs) were measured by transcranial Doppler ultrasonography. Intracranial carotid artery calcification (ICAC) was assessed on computed tomography angiography, and then compared with the mean PI of both MCAs. Patients with internal carotid artery steno-occlusion were excluded from this study. Results: A total of 156 patients were finally enrolled. The prevalence of diabetes increased as the PI value increased (p for trends; p = 0.025). PI was correlated with ICAC score (r = 0.413, p < 0.001) and age (r = 0.507, p < 0.001). Multiple linear regression analysis indicated that aging and ICAC were independent determinants of the PI of MCA after adjusting for sex, systolic blood pressure, smoking, and the presence of diabetes. Conclusions: This study shows that an increase in PI was correlated with the severity of ICAC, which suggests calcification-related vascular resistance might have a role in the elevation of PI.

Large-Artery Stenosis Predicts Subsequent Vascular Events in Patients with Transient Ischemic Attack

Background and purpose We investigated subsequent vascular events in patients with transient ischemic attack (TIA) and determined the predictors of such events among vascular risk factors including large-artery disease, TIA-symptom duration, and acute ischemic lesions on diffusion-weighted imaging (DWI). Methods We identified 98 consecutive patients with TIA who visited a tertiary university hospital and underwent DWI and brain magnetic resonance angiography within 48 hours of symptom onset. We reviewed the medical records to assess the clinical characteristics of TIA, demographics, and the subsequent vascular events including acute ischemic stroke, TIA, and myocardial infarction. Results Large-artery disease was detected in 55 patients (56%). Ten patients (10%) experienced TIA symptoms for longer than 1 hour, and acute infarctions on DWI were identified in 30 patients (31%). During the mean follow-up period of 19 months, seven patients (7%) had an acute ischemic stroke and 20 patients (20%) had TIA. Retinal artery occlusion in two patients, spinal cord infarction in one patient, and peripheral vascular claudication in one patient were also recorded. Cox proportional-hazards multivariate analysis revealed that large-artery disease was an independent predictor of subsequent cerebral ischemia (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.1-7.1; p=0.02) and subsequent vascular events (HR, 2.9; 95% CI, 1.2-6.7; p=0.01). Conclusions In patients with TIA, large-artery disease is an independent predictor of subsequent vascular events. Acute infarction on DWI and a symptom duration of more than 1 hour are not significantly correlated with a higher risk of subsequent vascular events. These findings suggest that the underlying vascular status is more important than symptom duration or acute ischemic lesion on DWI.

Association between Small Deep Cerebellar Ischemic Lesion and Small-Vessel Disease.

Background: Pathologic investigations showed that lacunar infarction could develop in the deep cerebellar region. However, the etiology of small deep cerebellar ischemic lesions (SDCI) has not been adequately studied. The aim of this study was to investigate the relationship between SDCI and small-vessel disease. Methods: We studied 100 consecutive patients who had both (1) acute ischemic stroke (index stroke) confirmed by diffusion-weighted MRI and (2) evidence of a chronic small cerebellar ischemic lesion (<15 mm). Small-vessel-related MRI findings, risk factors and subtype of index stroke were compared between the patients with SDCI and those with small cortical cerebellar ischemic lesions (SCCI). Results: Eighty patients had SCCI, and 20 patients had SDCI. Cardioembolic sources (38.8 vs. 5%, p = 0.003) and vertebrobasilar artery stenosis (61.3 vs. 35%, p = 0.034) were more frequent in patients with SCCI. In a multivariate model including traditional risk factors, patients with SDCI had significantly more lacunar infarcts (odds ratio, 1.18; 95% confidence interval, 1.02–1.37) and cerebral microbleeds (odds ratio, 10.92; 95% confidence interval, 2.16–55.32) than those with SCCI. Patients with SDCI frequently had the small-artery disease subtype of index stroke (odds ratio, 5.84; 95% confidence interval, 1.71–19.9). Conclusions: The results suggest that SDCI are frequently associated with small-vessel disease.

IL-1β Induction and IL-6 Suppression Are Associated with Aggravated Neuronal Damage in a Lipopolysaccharide-Pretreated Kainic Acid-Induced Rat Pup Seizure Model

Objectives: Reportedly, hippocampal neuronal degeneration by kainic acid (KA)-induced seizures in rats <14 days old was enhanced by lipopolysaccharide (LPS). This study was to test the hypothesis that cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α are associated with aggravated neuronal damage. Materials and Methods: Sixty male Sprague-Dawley, 14-day-old rats were used. Experiments were conducted in saline, LPS + saline, saline + KA and LPS + KA groups. Intraperitoneal LPS injections (0.04 mg/kg) were administered 3 h prior to KA injection (3 mg/kg). Results: The LPS + KA group showed a tendency toward shorter latency to seizure onset (p = 0.086) and significantly longer seizure duration (p < 0.05) compared with the KA group. Induction of the proconvulsant cytokine IL-1β in rat pup brains was significantly greater in the LPS + KA group compared to the KA group (38.8 ± 5.5 vs. 9.2 ± 1.0 pg/µg; p < 0.05); however, IL-6 levels were higher in the KA group than in the LPS + KA group (108.7 ± 6.8 vs. 60.9 ± 4.7 pg/µg; p < 0.05). The difference in tumor necrosis factor-α between the LPS + KA group and the KA group was insignificant (12.1 ± 0.6 vs. 10.9 ± 2.3 pg/µg; p = 0.64). Conclusions: Our results showed an increase in the proconvulsant cytokine IL-1β and a decrease in a potentially neuroprotective cytokine, IL-6, in rat pups treated with LPS + KA. These results warrant further investigation into the possible role of IL-1β induction and IL-6 suppression in LPS-promoted neuronal damage.

Post-interventional microembolism: cortical border zone is a preferential site for ischemia.

Background: Previous diffusion-weighted MRI (DWI) studies have indicated that 10–40% of patients have silent embolism during neurointerventional procedures. However, lesion patterns of the embolisms have not been adequately investigated. Methods: DWI was taken within 7 days before and 48 h after cerebral angioplasty and stent procedures. New lesions on the follow-up DWI were analyzed in the non-treated arterial territories. Based on the arterial territories, supratentorial lesions were classified into cortical lesions and subcortical lesions. Cortical lesions were subdivided into cortical border zone and cortical proper lesions. Subcortical lesions were divided into deep perforator and internal border zone lesions. Infratentorial lesions were divided into brainstem and cerebellar lesions. Results: 72 patients were included in this study. There were 223 new DWI lesions (1–23 lesions) in the non-treated arterial territories of 37 patients. There were 154 cortical lesions, 45 cerebellar lesions, 21 subcortical lesions and 3 brainstem lesions. Analysis of the distribution pattern of cortical lesions showed that 88 of 154 lesions were located at the cortical border zone. Of the subcortical lesions, 13 of 21 lesions were located at the internal border zone area, within the corona radiata and centrum ovale. Only 4 lesions were located at the deep perforator territory. Infratentorial lesions were mostly located at the cerebellar hemisphere (45/48). Most lesions were tiny infarcts (<5 mm diameter); 7 of 223 lesions were >10 mm in diameter. Conclusions: Interventional-angiography-related microembolisms mostly lodge in the cerebral cortical border zone area and cerebellar hemisphere. Microembolisms to the deep perforating artery territory are distinctly rare.