Hye Sun Lee

A randomized trial of mesenchymal stem cells in multiple system atrophy

Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA‐cerebellar type (MSA‐C).

In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum

To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image‐based tau staging in the Alzheimer disease (AD) spectrum.

Effects of nurse staffing, work environments, and education on patient mortality: an observational study.

BACKGROUND While considerable evidence has been produced showing a link between nursing characteristics and patient outcomes in the U.S. and Europe, little is known about whether similar associations are present in South Korea. OBJECTIVE To examine the effects of nurse staffing, work environment, and education on patient mortality. METHODS This study linked hospital facility data with staff nurse survey data (N=1024) and surgical patient discharge data (N=76,036) from 14 high-technology teaching hospitals with 700 or more beds in South Korea, collected between January 1, 2008 and December 31, 2008. Logistic regression models that corrected for the clustering of patients in hospitals were used to estimate the effects of the three nursing characteristics on risk-adjusted patient mortality within 30 days of admission. RESULTS Risk-adjusted models reveal that nurse staffing, nurse work environments, and nurse education were significantly associated with patient mortality (OR 1.05, 95% CI 1.00-1.10; OR 0.52, 95% CI 0.31-0.88; and OR 0.91, CI 0.83-0.99; respectively). These odds ratios imply that each additional patient per nurse is associated with an 5% increase in the odds of patient death within 30 days of admission, that the odds of patient mortality are nearly 50% lower in the hospitals with better nurse work environments than in hospitals with mixed or poor nurse work environments, and that each 10% increase in nurses having Bachelor of Science in Nursing Degree is associated with a 9% decrease in patient deaths. CONCLUSIONS Nurse staffing, nurse work environments, and percentages of nurses having Bachelor of Science in Nursing Degree in South Korea are associated with patient mortality. Improving hospital nurse staffing and work environments and increasing the percentages of nurses having Bachelor of Science in Nursing Degree would help reduce the number of preventable in-hospital deaths.

Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson's disease

Background Parkinsons disease with mild cognitive impairment (PD-MCI) is a heterogeneous entity in terms of cognitive profiles and conversion to dementia. However, the risk factors for ongoing cognitive decline in patients with PD-MCI are not clearly defined. Methods 51 patients with PD-MCI were prospectively followed-up for a minimum of 2 years. Subjects were classified as MCI converters (n=15) or MCI non-converters (n=36) based on whether they were subsequently diagnosed with PD dementia. We explored cognitive profiles and neuroanatomical characteristics of PD-MCI converters using voxel based morphometry (VBM) of grey matter (GM) density and region of interest based volumetric analysis of the substantia innominata (SI). Results PD-MCI converters showed more severe cognitive deficits in frontal executive functions, immediate verbal memory and visual recognition memory compared with PD-MCI non-converters. VBM analysis revealed that PD-MCI converters had significantly lower GM density in the left prefrontal areas, left insular cortex and bilateral caudate nucleus compared with that in PD-MCI non-converters. The mean normalised SI volume was significantly smaller in both PD-MCI converters (1.19±0.35, p<0.001) and PD-MCI non-converters (1.52±0.27, p<0.001) compared with that in controls (1.87±0.19). PD-MCI converters had a significantly smaller normalised SI volume than PD-MCI non-converters (p<0.001). Conclusions Our data show that atrophy in the frontostriatal areas and cholinergic structures, as well as frontal lobe associated cognitive performance, may act as predictors of dementia in PD-MCI patients, suggesting distinctive patterns of cognitive profiles and a neuroanatomical basis for progressive PD-MCI.

Acute ophthalmoplegia (without ataxia) associated with anti-GQ1b antibody

Background: Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody. Methods: We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia. Results: AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia. Conclusions: Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.

Red blood cell distribution width is associated with poor clinical outcome in acute cerebral infarction

Increased red blood cell distribution width (RDW), which is a marker of anisocytosis, is associated with mortality and cardiovascular events in the general population and in patients with heart failure or coronary heart disease. We investigated whether RDW in acute cerebral infarction is predictive of functional outcome and mortality. A total of 847 consecutive patients with first-ever acute cerebral infarction who presented to the emergency department within seven days of symptom onset were enrolled in this study. We investigated the association of RDW with poor functional outcome (modified Rankin Scale >2) and all-cause mortality at three months, as well as survival time for one year after stroke onset. Multivariate logistic regression revealed that higher RDW was independently associated with poor functional outcome (adjusted odds ratio [OR], 1.222 per 1% increment in RDW, 95% confidence interval [CI] 1.059-1.409, p=0.006) and all-cause death (adjusted OR, 1.395 per 1% increment in RDW, 95% CI 1.168-1.665, p<0.001) at three months after stroke onset. RDW was an independent predictor of survival in multivariate Cox-proportional regression model (adjusted hazard ratio, 1.328 per 1% increment in RDW, 95%CI 1.178-1.498, p<0.001). The addition of RDW to a survival model significantly increased predictability for survival across the entire follow-up period (weighted average of the area-under the curves, 0.858 vs. 0.841, p<0.05). In conclusion, higher RDW measured in cases of acute stage cerebral infarction was associated with poor functional outcome and mortality. RDW may be used as a biomarker for the prediction of long-term outcomes in patients with acute cerebral infarction.

Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction

OBJECTIVE We aimed to investigate the relationship of each white blood cells (WBC) subtype with neurologic severity and outcome in acute stroke. METHODS We included 779 patients with first-ever acute cerebral infarction within 72 h after symptom onset. We investigated the association between counts for WBC subtypes in peripheral blood at admission and (1) initial stroke severity; (2) early change in stroke severity within one week; and (3) functional outcome at three months. RESULTS Higher total WBC and neutrophil counts were associated with more severe stroke at admission (p<0.001). In contrast, lower lymphocyte counts were associated with a lesser improvement during the first week after admission (p<0.05) and with poor functional outcome at three months (OR=0.706 per 1000 lymphocyte counts/mm(3), p=0.020). CONCLUSIONS Our study merits further investigation on the role of each WBC subtype in ischemic injury and different prognostic value of WBC subtypes measured at admission in acute stroke.

Increases in Cerebral Atherosclerosis According to CHADS2 Scores in Patients With Stroke With Nonvalvular Atrial Fibrillation

Background and Purpose— The CHADS2 score is used for risk stratification of ischemic stroke in patients with nonvalvular atrial fibrillation and high CHADS2 scores are associated with increased risk of stroke. Most components of the CHADS2 score are also risk factors for atherosclerosis. Therefore, high CHADS2 scores can be associated with concomitant cerebral atherosclerosis and subsequently atherothrombotic stroke. The aim of this study was to determine whether there are differences in the presence and burden of concomitant cerebral atherosclerosis according to CHADS2 scores in patients with stroke with nonvalvular atrial fibrillation. Methods— We included 780 consecutive patients with nonvalvular atrial fibrillation who had undergone angiographic studies at index stroke between August 1994 and March 2010 in the present study. We investigated the relationships between the CHADS2 score and the presence, severity, and pattern of cerebral atherosclerosis and stroke mechanism. Results— Of the 780 patients, concomitant arterial stenosis (≥50%) was found in 231 patients (29.6%). The number of arteries with atherosclerosis increased as the CHADS2 score increased (P<0.001) as did the proportion of combined extracranial and intracranial atherosclerosis (P<0.001). Multivariate analyses showed that high risk based on the CHADS2 score was an independent predictor of concomitant cerebral atherosclerosis (OR, 3.121; 95% CI, 1.770 to 5.504) and the presence of proximal stenosis at the symptomatic artery (OR, 3.043; 95% CI, 1.458 to 6.350). Conclusions— The CHADS2 score can predict the presence of concomitant cerebral artery atherosclerosis. Increased risk of stroke in patients with high CHADS2 scores may be partly explained by increased frequency and burden of cerebral atherosclerosis.

Long-Term Mortality in Patients With Stroke of Undetermined Etiology

Background and Purpose— The determination of stroke etiology is essential for planning treatment for stroke prevention. However, the etiology of stroke is undetermined in many patients. Methods— During a 10-year period, consecutive patients with acute ischemic stroke were enrolled. The stroke etiology was determined based on the Trial of ORG 10172 in Acute Stroke Treatment classification. Long-term mortality and causes of death were identified using death certificates. The standardized mortality ratio was calculated to compare the mortality in patients with stroke and that in the general Korean population. Results— In total, 3278 patients were enrolled and followed-up for a median of 3.4 years (interquartile range, 1.5–5.7). The stroke subtype was undetermined in 37% because of negative evaluation (21.2%), multiple causes (10.6%), and incomplete evaluation (4.8%). Poor functional outcome at 3 months (modified Rankin scale score >2) was more frequent in patients with an incomplete evaluation than in those with the other stroke subtypes (49.6% vs 24.5%; P<0.001). During follow-up, 781 patients (23.8%) died. The overall cumulative death rate was highest in patients with an incomplete evaluation (12.7% within 30 days, 25.5% within 1 year, and 35.7% within 3 years), followed by those with cardioembolism. Multivariate analysis after adjusting for covariates including initial stroke severity, the mortality of patients with an incomplete evaluation was second lowest after cardioembolism, whereas that in patients with a negative evaluation was low. Conclusions— Long-term mortality in patients with an incomplete evaluation was quite high. Etiologic work-up helps to better define the stroke subtype and determine the prognosis.

Association of cerebral microbleeds with mortality in stroke patients having atrial fibrillation

Objectives: We investigated the association of cerebral microbleeds (CMBs) with long-term mortality in patients with nonvalvular atrial fibrillation (NVAF) according to burden and distribution of CMBs. Methods: This was a retrospective, hospital-based, observational study. In total, 504 consecutive ischemic stroke patients with NVAF who underwent brain T2-weighted, gradient-recalled echo MRI were included. Data for the date and causes of death were based on the death certificates from the Korean National Statistical Office. We determined the association of the presence, burden, and distribution of CMBs with mortality from all-cause, ischemic heart disease, ischemic stroke, and hemorrhagic stroke. Results: CMBs were found in 30.7% of patients (155/504). During a median follow-up of 2.5 years, 176 patients (34.9%) died (ischemic stroke, 81; hemorrhagic stroke, 12; ischemic heart disease, 32). Patients with CMBs died more frequently than those without (41.9% vs 31.8%, p = 0.028). After adjusting for age, sex, and other significant variables, the presence of multiple (≥5) CMBs was as an independent predictor for all-cause (hazard ratio [HR]: 1.99) and ischemic stroke (HR: 3.39) mortality. Patients with strictly lobar CMBs had an increased risk of hemorrhagic stroke mortality (HR: 5.91). Conclusions: The presence and burden of CMBs were associated with increased mortality in stroke patients with NVAF. Patients with lobar CMBs were at increased risk of death due to hemorrhagic stroke. The diagnosis of CMBs is of value in predicting long-term prognosis in stroke patients with NVAF.