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Background and Purpose: This study aimed to investigate the value of d -dimer levels in predicting recurrent stroke in patients with embolic stroke of undetermined source. We also evaluated the underlying causes of recurrent stroke according to d -dimer levels. Methods: A total of 1431 patients with undetermined source were enrolled in this study and divided into quartiles according to their baseline plasma d -dimer levels. The primary outcome measure was the occurrence of recurrent stroke (ischemic or hemorrhagic) in the year following the stroke event. Results: The risk of recurrent stroke increased significantly with the increasing d -dimer quartile (log-rank P =0.001). Patients in the higher d -dimer quartiles had a higher probability of recurrent embolic stroke because of covert atrial fibrillation, hidden malignancy, or undetermined sources. Most recurrent strokes in Q3 and Q4 were embolic but not in Q1 or Q2. Multivariate analysis revealed that patients in Q3 and Q4 had a significantly increased risk of recurrent stroke compared with those in Q1 (hazard ratio, 3.12 [95% CI, 1.07−9.07], P =0.036; hazard ratio, 7.29 [95% CI, 2.59−20.52], P P trend d -dimer level above normal range and the risk of recurrent stroke (hazard ratio, 2.48 [95% CI, 1.31−4.70], P =0.005). In subgroup analyses, a high d -dimer level was associated with a significantly higher risk of recurrent stroke in men than in women ( P =0.039). Conclusions: Our findings suggest that d -dimer levels can be a useful risk assessment biomarker for predicting recurrent stroke, especially embolic ischemic stroke, in patients with undetermined source.

Isolated central positional vertigo (CPV) due to cerebellar infarction is often difficult to differentiate from benign paroxysmal positional vertigo (BPPV). Here, we aimed to evaluate whether vascular risk factors and serum vitamin D level can differentiate between positional vertigo types. A total of 78 consecutive patients were consecutively enrolled from January 2017. All CPV patients had a National Institutes of Health Stroke Scale score of 0 and cerebellar infarctions confirmed by brain MR imaging. Vascular risk factors and serum 25-hydroxyvitamin D levels were compared between the two groups of patients. The proportion of men was higher in the CPV than in the BPPV group (p = 0.004). Atrial fibrillation was common in the CPV group on univariate analysis (p = 0.046). However, there were no independent differentiating factors between the two groups. The proportion of patients according to the number of risk factors was significantly different between the two groups (linear by linear association test, p = 0.02). The mean serum 25-hydroxyvitamin D level did not differ. Also, the proportions of vitamin D insufficiency and deficiency did not differ significantly between the two groups. Increased number of vascular risk factors including male sex suggested more CPV than BPPV. However, the serum vitamin D level was below the normal range in both groups. Our results demonstrate that serum vitamin D level has little value in the differential diagnosis of positional vertigo. Efforts to identify differentiating factors are warranted, and accumulating evidences including our research may lead to a diagnostic algorithm for isolated positional vertigo.

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently established neurodegenerative disease entity. LATE neuropathological change (LATE-NC) is characterized by a TDP-43 proteinopathy that mainly involves the amygdala and medial temporal structures, with or without hippocampal sclerosis. LATE-NC is typically observed in individuals aged 80 years or older and manifests clinically as amnestic memory decline. Herein, we report a case of LATE diagnosed by brain autopsy in an 82-year-old male who had an 11-year history of memory impairment. Pathological examination revealed high Alzheimer disease neuropathological changes, as well as amygdala-predominant Lewy body pathology. In addition, immunohistochemistry for TDP-43 revealed neuronal and glial cytoplasmic inclusions in the dentate gyrus of the hippocampus, amygdala, and inferior temporal cortex. Increasing awareness of the newly defined entity LATE will enhance our understanding of the neurodegenerative processes that occur in the oldest individuals.

Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1-42 (Aβ1-42), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential.Methods: We measured NFL and Aβ1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum.Results: With disease progression, concentrations of NFL increased, and those of Aβ1-42 were decreases. The plasma and CSF values of NFL/Aβ1-42 were strongly correlated (r = 0.558). In addition, the plasma value of NFL/Aβ1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ1-42 changed more rapidly than did either the t-Tau or the p-Tau181 values measured in the CSF.Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

Brain aging is becoming an increasingly important topic, and the norms of brain structures are essential for diagnosing neurodegenerative diseases. However, previous studies of the aging brain have mostly focused on Caucasians, not East Asians. The aim of this paper was to examine ethnic differences in the aging process of brain structures or to determine to what extent ethnicity affects the normative values of lobar and subcortical volumes in clinically normal elderly and the diagnosis in multi-racial patients with Alzheimer's disease (AD). Lobar and subcortical volumes were measured using FreeSurfer from MRI data of 1,686 normal Koreans (age range 59–89) and 851 Caucasian, non-Hispanic subjects in the ADNI and OASIS datasets. The regression models were designed to predict brain volumes, including ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and MRI scanner manufacturers as independent variables. Ethnicity had a significant effect for all lobar (|β| > 0.20, p < 0.001) and subcortical regions (|β| > 0.08, p < 0.001) except left pallidus and bilateral ventricles. To demonstrate the validity of the z-score for AD diagnosis, 420 patients and 420 normal controls were selected evenly from the Korean and Caucasian datasets. The four validation groups divided by race and diagnosis were matched on age and sex using a propensity score matching. We analyzed whether and to what extent the ethnicity adjustment improved the diagnostic power of the logistic regression model that was built using the only z-scores of six regions: bilateral temporal cortices, hippocampi, and amygdalae. The performance of the classifier after ethnicity adjustment was significantly improved compared with the classifier before ethnicity adjustment (ΔAUC = 0.10, D = 7.80, p < 0.001; AUC comparison test using bootstrap). Korean AD dementia patients may not be classified by Caucasian norms of brain volumes because the brain regions vulnerable to AD dementia are bigger in normal Korean elderly peoples. Therefore, ethnicity is an essential factor in establishing normative data for regional volumes in brain aging and applying it to the diagnosis of neurodegenerative diseases.

Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer’s diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no β-amyloid pathology.

Patients with Parkinson's disease (PD) are liable to experience impairment in their activities of daily living (ADL), which include ambulating, eating, dressing, bathing, and personal hygiene. The aim of this study is to assess which clinical characteristics contribute significantly to instrumental ADL (IADL) in PD patients without dementia. We included 106 PD patients in our study, and each patient's motor and non-motor status and basic and instrumental ADL were assessed using the appropriate scales. Of the 106 PD patients, 31 (29.2%) had abnormal Korean IADL (K-IADL) scores. These patients were older and had higher scores in terms of the modified Hoehn and Yahr (mHY) staging scale, Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III, UPDRS part IV motor fluctuation, Beck Depression Inventory (BDI), and total Non-Motor Symptoms assessment scale for PD (NMSS), as well as lower scores in the Mini-Mental State Examination (MMSE). Pearson's correlation analysis showed significant associations between the scores of K-IADL and each of the following characteristics of the patients: age, mHY stage, UPDRS parts II and III, UPDRS part IV motor fluctuation, BDI, total NMSS, and MMSE. Multivariate linear regression analysis showed that the significant clinical characteristics associated with the K-IADL scores were determined to be the UPDRS part II, MMSE, and BDI scores. The results of our study revealed that the cognitive, depression, and motor symptoms were the significant predictors of IADL in PD patients without dementia.

We investigated the relationship between the mean blood pressure (BP) at 24–72 h and the clinical outcomes after acute ischemic stroke (AIS) in patients treated with reperfusion therapy. The primary outcome was measured using the modified Rankin Scale (mRS) at 3 months after AIS, and was based on the mean systolic BP at 24–72 h post-AIS. Favorable outcome was defined as mRS scores of 0–2. A total of 1,540 patients treated with reperfusion therapy were enrolled in the study. Favorable outcomes occurred more frequently in patients with BP ≤ 130/80 mmHg, and the risks of symptomatic intracranial hemorrhage and early neurological deterioration were lower in this optimal BP group. Multivariable analysis showed a significant association between mean BP ≤ 130/80 mmHg at 24–72 h and favorable outcomes at 3 months after AIS (odds ratio 2.95, 95% confidence interval 2.32–3.77, p

Background and Purpose— The purpose of this study was to investigate the association between adiposity using adipose tissue imaging and stroke outcomes in acute ischemic stroke patients treated with intravenous thrombolysis. Methods— A total of 127 patients with acute ischemic stroke treated with intravenous thrombolysis who underwent abdominal computed tomography on admission were enrolled in this prospective cohort study. Patients were grouped according to their visceral adipose tissue (VAT) proportion tertile. The primary outcome was measured using the modified Rankin Scale 3 months after symptom onset. Favorable and excellent outcomes were defined as modified Rankin Scale scores of 0 to 2 and 0 to 1, respectively. Results— As VAT proportion tertile increased, the number of patients exhibiting a favorable or excellent outcome decreased. In the final multivariable analysis after adjustments for confounders, patients in the highest VAT proportion tertile showed a decreased probability of a favorable and excellent outcome compared with those in the lowest tertile (odds ratio=0.18; 95% CI, 0.05−0.60; P =0.005 and odds ratio=0.13; 95% CI, 0.02−0.64; P =0.012, respectively). Obese patients (body mass index ≥25) also showed an excellent outcome compared with nonobese patients (odds ratio=4.88; 95% CI, 1.47−7.85; P =0.011). Among obese patients, those with an excellent outcome presented a significantly lower VAT proportion than those without (38.2% versus 46.1%, P =0.006). Conclusions— Results of this study indicate that low visceral abdominal fat proportion is associated with a favorable and excellent outcome in acute ischemic stroke patients treated with intravenous thrombolysis. Better clinical outcomes in obese patients were also associated with a lower proportion of VAT.

Background and Purpose— We analyzed the association between cerebral microbleeds (CMBs) and clinical outcome in acute ischemic stroke patients and especially in a subgroup of patients with successful recanalization. Methods— A total of 1532 acute ischemic stroke patients treated with intravenous thrombolysis or mechanical thrombectomy were enrolled in this prospective cohort study. The primary outcome was measured using the modified Rankin Scale at 3 months, according to the CMB status based on magnetic resonance imaging at admission. Favorable outcome was defined as functional independence with modified Rankin Scale scores of 0 to 2. Secondary outcomes included the occurrence of symptomatic intracranial hemorrhage. Results— There was no statistically significant association between the presence of CMB and favorable outcome at 3 months when considering all patients (44.3% versus 37.6%; P =0.121). In patients with recanalization, the number of patients with favorable outcomes was significantly higher in the CMB-negative than in the CMB-positive group (57.0% versus 36.0%; P P =0.038) and symptomatic intracranial hemorrhage (odds ratio=3.21; 95% CI, 1.37−7.49; P =0.007) in patients with recanalization. In the analysis of subgroups, a statistically significant interaction was found between CMB presence and recanalization in predicting functional outcomes at 3 months. Conclusions— These results indicate that the presence of CMBs, and especially high burden and lobar location, are independent predictors of poor 3-month clinical outcomes and may increase symptomatic intracranial hemorrhage risk in acute ischemic stroke patients with recanalization. Our findings suggest that CMBs lead to more unfavorable effects in patients with recanalization after large vessel occlusion than in those without recanalization.

Background and Purpose— We analyzed the relationship between HbA1c (glycated hemoglobin) levels and clinical outcomes in patients with large vessel occlusion treated with mechanical thrombectomy (MT). Methods— A total of 534 patients with acute ischemic stroke (AIS) treated with MT were enrolled in this prospective cohort study. The primary outcome measured was the modified Rankin Scale score at 3 months, according to HbA1c level. High HbA1c levels were defined as a plasma level of HbA1c >6.5%. Favorable outcomes were defined as functional independence, with modified Rankin Scale scores of 0 to 2. Secondary functional outcomes included mortality, early clinical outcomes, and intracranial hemorrhage. Results— The number of patients with a favorable outcome was significantly lower in patients with HbA1c >6.5% than in those with HbA1c ≤6.5% (28.8% versus 42.1%; P =0.006). In multivariate analysis, high HbA1c levels (especially >7.0% HbA1c) were significantly associated with poor functional outcomes 3 months after AIS in patients with large vessel occlusion treated with MT. High HbA1c was also significantly associated with increased mortality and worse early clinical outcomes after AIS in patients treated with MT. Subgroup analyses showed that HbA1c >6.5% was associated with significantly lower odds of functional independence at 3 months after AIS, when comparing the recanalized group with nonrecanalized patients. Conclusions— These results suggest that high HbA1c level is an independent predictor of a poor outcome at 3 months after AIS in patients with large vessel occlusion treated with MT, particularly in those with recanalization, and may augment the risk of mortality and early clinical worsening after AIS.

Some patients with Parkinson's disease (PD) report hand tremors in their relatives. This study aimed to compare the clinical characteristics of early PD in patients with and without a family history of hand tremor. This study included 337 early and drug-naive patients with PD. The family history of hand tremor was obtained from the patients and their caregivers. Motor and non-motor symptoms of PD were assessed using the appropriate scales. A family history of hand tremor was present in 27 of 337 patients with PD (8.0%). Patients with a family history of hand tremor had significantly higher scores for rest tremors than those without. No significant differences were found in action tremor, bradykinesia, rigidity, gait, or posture scores between the two groups. The proportion of tremor-dominant subtypes was higher in patients with a family history of hand tremor than in those without (51.8% vs. 28.7%). Patients with PD, with a family history of hand tremor, had significantly lower scores in the urinary and sexual subdomains of the Non-Motor Symptoms Scale for PD than in those without. A family history of hand tremor affects the motor and non-motor symptoms in patients with early PD. It is necessary to investigate the family history of hand tremor in patients with PD.

Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.

The aging of the brain is a well-investigated topic, but existing analyses have mainly focused on Caucasian samples. To investigate brain aging in East Asians, we measured cortical and subcortical volumes from magnetic resonance imaging (MRI) scans of 1,008 cognitively normal elderly Koreans from the Gwangju Alzheimer’s and Related Dementia cohort and 342 Caucasians from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To determine whether the aging effect varies with ethnicity and sex, beta coefficients of age and confidence intervals (CIs) were estimated in each ethnicity–sex group using a bootstrap method and a regression analysis using the relative volume to intracranial volume as predicted. The betas or aging slopes largely were not significantly different between ethnicity and sex groups in most types of brain structures. However, ethnic differences between the two female groups were found in the brain, most cortical regions, and a few subcortical regions. Ethnic differences in brain aging are likely due in large part to genetic factors; thus, we compared carriers and non-carriers of a gene relevant to longevity and neurodegenerative diseases, such as apolipoprotein E (APOE) ε4. The regions with ethnic differences in women also showed significant differences between Korean APOE ε4 non-carriers and Caucasian APOE ε4 carriers. Furthermore, Caucasian women showed significant APOE ε4 effects in the largest number of regions. These results illustrate that much of the ethnic differences in females may be explained by synergistic effects of ethnic background and APOE ε4 carrier status. Our results suggest that sex-dependent differences of aging between ethnic backgrounds may be due to ethnicity-dependent effects of genetic risk factors, such as APOE ε4. We also presented the normative information on volume estimates of the brain structures of the elderly Korean people in the subdivided age groups. This normative information of the aging brain stratified by ethnicity provides the age-related reference ranges quantified to replace visual judgment and facilitate precise clinical decision-making.

Background and Purpose: We investigated the impact of the presence, burden, and location of cerebral microbleeds (CMBs) on the risk of major adverse cerebrovascular and cardiovascular events (MACCE) in patients with acute ischemic stroke and atrial fibrillation treated with oral anticoagulants (OACs). We also examined whether the clinical effect of CMBs differs according to the type of OACs. Methods: A total of 1742 patients with acute ischemic stroke and atrial fibrillation treated with OACs were enrolled in this cohort study. The primary composite outcome was the occurrence of MACCE (a composite of stroke, acute myocardial infarction, or vascular death) over a 2-year period according to CMB status. Results: CMB presence was significantly associated with the risk of future MACCE (hazard ratio, 1.89 [95% CI, 1.23–2.88]; P =0.003) after adjustment for confounders in patients with acute ischemic stroke and atrial fibrillation taking OACs. Patients with exactly 1 CMB had a similar rate of MACCE compared with those without CMBs ( P =0.461). However, patients with multiple CMBs (≥2), particularly high burden CMBs (≥5), had a significantly higher proportion of MACCE. Both CMB-positive groups with lobar and deep CMB had more frequent MACCE than the CMB-negative group, and the rate of MACCE was not different according to CMB location. In patients treated with warfarin, CMB was significantly associated with a risk of MACCE ( P =0.002), but not in patients treated with direct OACs ( P =0.517). Conclusions: The study results indicate that the risk of future MACCE increased with increasing CMB burden in patients with AIS and atrial fibrillation taking OACs, while the anatomic location of CMBs did not influence the risk of future MACCE. This risk seemed to be more apparent in patients taking warfarin.

Background Cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42), total tau protein (t-Tau), and phosphorylated Tau (p-Tau) are ATN biomarkers for Alzheimer's disease (AD) and reflect pathogenic changes in the brain. CSF biomarkers of AD are considered for inclusion in the diagnostic criteria for research and clinical purposes to reduce the uncertainty of clinical diagnosis and to distinguish among AD stages. Objective This study aims to compare two commercially available analytical platforms with respect to accuracy and the potential for early diagnosis of AD. Methods A total of 211 CSF samples from healthy control (HC) and AD subjects were analyzed using two analytical platforms, INNOTEST ELISA and INNOBIA AlzBio3 xMAP kits. The accuracy of diagnosis and AUC values distinguishing study groups were compared between the two analytical platforms. Results The absolute values for Aβ1-42, t-Tau, and p-Tau181 levels differed between the two platforms. The Aβ1-42 levels decreased, while t-Tau and p-Tau levels increased according to the AD stages. The AUC of Aβ1-42 and t-Tau, which distinguish the early stages of AD (preclinical and prodromal AD), were similar between the two platforms, whereas there were significant differences in p-Tau AUC values. CSF p-Tau using the INNOBIA was highly accurate for distinguishing both preclinical AD (AUC = 0.826, cut-off score≥38.89) and prodromal AD (AUC = 0.862, cut-off score≥41.88) from HC. Conclusion The accuracy of CSF p-Tau levels in the preclinical and prodromal AD is higher for the INNOBIA than the INNOTEST, and the early stage AD can be accurately distinguished from HC.

Background Clinical subtypes of Parkinson's disease (PD) have been empirically defined based on the prominent motor symptoms. The aim of this study was to compare the prevalence of non-motor symptoms across PD motor subtypes in patients with PD. Methods A total of 192 patients with de novo PD were included. The patients were classified into the tremor-dominant/mixed/akinetic-rigid (TD/mixed/AR) and tremor-dominant/mixed/postural instability and gait disturbance (TD/mixed/PIGD) subtypes, according to previous reports. Results In the TD/mixed/AR classification, scores for scales related to motor symptoms and activities of daily living (ADL) were significantly different among the groups, and patients with the AR subtype demonstrated more severe scores than patients with the TD subtype. In the TD/mixed/PIGD classification, age, age at symptom onset, scores on motor-related scales, ADL, and non-motor symptoms were significantly different among the groups. Scores including the modified Hoehn and Yahr stages, the motor and ADL subscores of the Unified Parkinson's Disease Rating Scale, the Beck Depression Inventory, and the Non-Motor Symptom Assessment Scale were significantly different after adjustments for age and age at symptom onset, and patients with the PIGD subtype obtained more severe scores than patients with the TD subtype. Conclusion The TD/mixed/PIGD classification seems to be more suitable for identifying non-motor abnormalities than the TD/mixed/AR classification.

Pain is a frequent and troublesome non-motor symptom of Parkinson's disease (PD) and has a negative impact on quality of life (QoL). The aim of this study was to investigate the relative impact of pain or a specific pain subtype on the QoL of patients with PD. We included 161 patients with PD. Pain was assessed using the patients' descriptions, a structured interview, and a detailed neurological examination. QoL was assessed using the 39-item Parkinson's Disease Questionnaire (PDQ-39). One hundred and twenty (74.5%) patients with PD had chronic pain. Musculoskeletal pain was the most prevalent type, followed by radicular/neuropathic, dystonic, and central pain. PD patients with pain, regardless of the pain subtype, had a worse PDQ-39 score than those without pain. Multivariate regression analysis after adjusting for disease-related factors and motor characteristics showed that younger PD onset age and the high scores of part II of Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, and Visual Analogue Scale were significant predictors of the poor PDQ-39 score. Pain along with depression, poor activities of daily living, and younger age of PD symptom onset are associated with poor QoL. All subtypes of pain affect QoL of patients with PD. Pain should be considered during the management of patients with PD.

Magnetic resonance (MR) measurements of brainstem structures have been reported to be useful in differentiating patients with progressive supranuclear palsy (PSP) from those with Parkinson’s disease (PD). The aim of this study was to determine whether quantitative measurements of brainstem structures on MR images can help differentiate vascular parkinsonism (VaP) from degenerative parkinsonism (PD and PSP). Areas of the midbrain and pons, and widths of the superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) were measured in 62 patients with PD, 25 patients with PSP (11 probable and 14 possible), and 24 patients with VaP on T 1-weighted MR images. The midbrain-to-pons area ratio (M/P ratio), MCP-to-SCP width ratio (MCP/SCP ratio), and MR parkinsonism index (MRPI; P/M × MCP/SCP) were calculated. The midbrain area and M/P ratio of patients with VaP (104 and 0.22 mm2, respectively) were smaller than those in patients with PD (121 and 0.24 mm2, respectively) and larger than those in patients with PSP (90 and 0.19 mm2, respectively). The MRPI was significantly larger in patients with PSP (13.6) in comparison with those with PD (10.1) and VaP (10.7). However, the MRPI of patients with VaP was not significantly different from patients with PD. Our study showed that MRPI was useful in differentiating PSP from VaP or PD. Thus, MR imaging measurements of brainstem structures may help differentiate patients with VaP from those with PD and PSP.

Background: Pain and osteoporosis are common in Parkinson's disease (PD), and lower bone mineral density (BMD) or osteoporosis may be associated with an increased risk of reporting to have pain in the general population. The aim of this study was to determine whether there is an association between the pain subtypes and the BMD in patients with PD. Methods: We included 162 PD patients. Pain was assessed using the patients' descriptions, a structured interview, a detailed neurologic examination, and the Visual Analogue Scale. BMD was measured using dual energy X-ray absorptiometry scans. Results: Of the 162 PD patients, 120 had chronic pain, while 42 reported no pain. The most prevalent type of pain was musculoskeletal, followed by radicular/neuropathic, dystonic, and central. PD patients with musculoskeletal pain had a lower BMD than PD patients without pain. Multivariate regression analysis showed that the low BMD of the lumbar spine, hip, and femoral neck were related to old age, female gender, low MBI, and the presence of musculoskeletal pain. Conclusion: PD patients with musculoskeletal pain have low BMD and are at risk for developing osteoporosis. If a PD patient has musculoskeletal pain and other risk factors related to low BMD, clinicians should consider screening for osteoporosis.

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer’s disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10−94, GT: OR = 15.87, p = 2.62 × 10−9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10−108, GT: OR = 12.63, p = 3.44 × 10−64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.

Background Coffee consumption represents a negative risk factor for Parkinson’s disease (PD) and seems to affect PD motor symptoms. We aimed to investigate the association between coffee consumption and motor symptoms in de novo PD patients. Methods In total, 284 patients with de novo PD were included in the current study. Motor and non-motor symptoms were evaluated using various scales. History of coffee consumption was obtained via a semi-structured interview. Results In total, 204 patients were categorized as coffee drinkers and 80 as non-coffee drinkers. Coffee drinkers were predominantly male and had early symptom onset; in addition, they were younger, reported more years in formal education, and had better motor and non-motor scores than did non-coffee drinkers. After adjustments, coffee drinkers had lower tremor scores than did non-coffee drinkers, and coffee consumption was related to tremors in a dose-dependent manner. These relationships were statistically significant in case of rest tremor but not in case of action tremor. The dose-dependent relationship between coffee consumption and tremor severity was significant only in men. Non-motor symptom scores were not significantly different between coffee drinkers and non-coffee drinkers. Conclusions Coffee consumption and tremor severity are inversely related in male patients with de novo PD.

We investigated the association between retinal changes measured using optical coherence tomography (OCT) and diverse clinical grading scales in patients with Parkinson’s disease (PD). Seventy-four eyes of 74 patients with de novo PD and 53 eyes of age-matched control subjects were included. The thickness of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) were measured. We analyzed the correlations between the clinical PD grading scales and OCT parameters, and between the OCT parameters and volumetric data in the cerebral cortical and subcortical structures. The area under the receiver operating characteristic curve (AUC) was calculated for diagnosing cognitive impairment in patients with PD. Statistically significant reductions in the thickness of average, temporal, and inferior pRNFL and overall mGCIPL were observed in patients with PD. The Montreal Cognitive Assessment score was significantly associated with mGCIPL thinning. The AUC of the mGCIPL parameters for diagnosing cognitive impairment in patients with PD ranged from 0.651 to 0.760. Moreover, thinning of the mGCIPL was significantly associated with the volumetric parameters of associated brain structures. Our findings highlight the clinical implications of OCT measurements as a potential biomarker for early detection of cognitive impairment in patients with PD.

Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes’ tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits.

Background/Aims: Disease-modifying therapy for Alzheimer’s disease (AD) has led to a need for biomarkers to identify prodromal AD and very early stage of AD dementia. We aimed to identify the cutoff values of cerebrospinal fluid (CSF) biomarkers for detecting prodromal AD. Methods: We assessed 56 patients with amnestic mild cognitive impairment (aMCI) who underwent lumbar puncture. Additionally, 87 healthy elderly individuals and 34 patients with AD dementia served as controls. Positron emission tomography was performed using florbetaben as a probe. We analyzed the concentration of Aβ1–42, total tau protein (t-Tau), and tau protein phosphorylated at threonine 181 (p-Tau181) in CSF with INNOTEST enzyme-linked immunosorbent assay. Results: For the detection of prodromal AD in patients with aMCI, the cutoff values of CSF Aβ1–42, t-Tau, and p-Tau181 were 749.5 pg/mL, 225.6 pg/mL, and 43.5 pg/mL, respectively. To discriminate prodromal AD in patients with aMCI, the t-Tau/Aβ1–42 and ­p-Tau181/Aβ1–42 ratios defined cutoff values at 0.298 and 0.059, respectively. Conclusions: CSF biomarkers are very useful tools for the differential diagnosis of prodromal AD in aMCI patients. The concentration of CSF biomarkers is well correlated with the stages of the AD spectrum.

Freezing of gait (FOG) is a common and debilitating problem in patients with Parkinson’s disease (PD). The aim of this study was to estimate the prevalence of FOG, and to identify factors that independently contribute to FOG in patients with PD. We included 157 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q). Patients with or without FOG were defined as item 3 in the FOG-Q. One hundred eleven (70.7%) out of 157 PD patients presented with FOG. Patients with FOG were older, had long disease duration, were taking higher doses of dopaminergic agents, and had higher motor and non-motor scores than those without FOG. Multivariate linear regression analysis showed that high modified Hoehn and Yahr (mHY) stage, Unified PD Rating Scale (UPDRS) part II score, and non-motor symptom assessment scale for PD (NMSS) total score were significant predictors of a high FOG-Q score. Patients with FOG had significantly higher scores for cardiovascular, gastrointestinal tract, urinary, and miscellaneous NMSS domains than those without FOG. FOG in PD was associated with higher mHY stage, UPDRS part II score, and total NMSS score. Therefore, clinicians should consider non-motor, motor features and activities of daily living states for the proper management of FOG.

Objective Coffee consumption has an inverse association with the risk of Parkinson's disease (PD). The aim of this study was to investigate the association between coffee consumption and non-motor symptoms (NMSs) in patients with PD. Methods In this cross-sectional study, we included 196 early-stage, treatment-naive PD patients. Coffee consumption history was obtained via semi-structured interviews. NMSs were assessed using the Non-Motor Symptom assessment scale (NMSS). Results Of the 196 patients with PD, 136 (69.3%) were categorized as coffee drinkers and 60 (30.6%) were non-drinkers. Coffee drinkers were younger, predominantly male, were younger in age at symptom onset, had lower Unified Parkinson's Disease Rating Scale motor and Beck Depression Inventory scores, and higher Mini-Mental State Examination scores than non-coffee drinkers. After adjustment, coffee drinking was significantly inversely associated with the prevalence of lack of motivation, anhedonia, and lack of pleasure, which were less frequent in coffee drinkers. Total NMSS scores were lower in coffee drinkers than in non-drinkers (p = 0.047). In particular, coffee drinking was significantly associated with a reduced severity of the mood/cognition domain of NMSS (p = 0.003). After correcting for multiple testing, there were no significant differences in the prevalence of NMSs, but there were significant differences in the severity of NMSs between coffee drinkers and non-drinkers. Conclusion There is a negative association between coffee consumption and the severity of the mood/cognition domain of NMSS in patients with PD. Clinicians should consider the history of coffee consumption in the assessment of NMSs in PD.

Background: Alterations in thyroid hormone (TH) levels may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia. Cognitive deficits are common in Parkinson's disease (PD) patients. The aim of this study was to investigate whether variations within the normal ranges of thyroid function are related to cognitive function in early PD without dementia. Methods: Eighty-four euthyroid patients with early PD underwent evaluation of their thyroid status, including measures of thyroid-stimulating hormone (TSH), total triiodothyronine (tT3) and free thyroxine (fT4), and comprehensive neuropsychological tests. Results: The 46 patients of the PD-MCI group did not differ in the serum levels of TH compared to the 38 patients of the PD-normal cognition group. fT4 levels were inversely associated with the Mini-Mental State Examination (MMSE) score and neuropsychological tests of attention and visuospatial and executive function. TSH and tT3 levels were not related to cognitive performances. After controlling for demographic and clinical variables, multiple regression analyses indicated statistically significant associations between fT4 concentrations and MMSE score and neuropsychological tests of executive function. Conclusions: This study supports a relationship between the thyroid status and cognitive function in euthyroid early PD patients, with higher concentrations of fT4 being associated with a poor performance of executive function.

있는 추체외로증상을 감별하기 위해 병전 증상에 대해 문진하 였고 이러한 증상은 떨림과 함께 시작된 것으로 확인되었다. 파 킨슨 증상에 대해 시행한 통합파킨슨척도(Unified Parkinson’s Disease Rating Scale, UPDRS) 운동기능검사점수는 21점이었 으며 호엔야 2단계였다. 추가적인 선별검사에서 말초혈액검사 백혈구 6,100/mm, 혈색소 13.7 g/dL, 혈소판 79,000/mm이었 다. 생화학검사에서 C-반응단백질 8.61 mg/dL, 알부민 3.5 g/dL, AST 122 IU/L, ALT 57 IU/L, ALP 58 IU/L, 총빌리루빈 0.7 mg/dL, 직접빌리루빈 0.2 mg/dL이었으며 혈청 페리틴이 5,788.08 ng/mL (남자 참고치 20-320 ng/mL)로 크게 증가되어 있었다. 내원 당시 시행한 뇌자기공명영상은 경미한 뇌위축이

Aspergillosis in the central nervous system (CNS) is a very rare disease in immune-competent patients. There was a case of a healthy man without a history of immune-compromised disease who had invasive aspergillosis with unusual radiologic findings. A 48-year-old healthy man with diabetes mellitus, presented with complaints of blurred vision that persisted for one month. Brain magnetic resonance imaging (MRI) showed multiple nodular enhancing lesions on the right cerebral hemisphere. The diffusion image appeared in a high-signal intensity in these areas. Cerebrospinal fluid examination did not show any infection signs. An open biopsy was done and intraoperative findings showed grayish inflammatory and necrotic tissue without a definitive mass lesion. The pathologic result was a brain abscess caused by fungal infection, morphologically aspergillus. Antifungal agents (Amphotericin B, Ambisome and Voriconazole) were used for treatment for 3 months. The visual symptoms improved. There was no recurrence or abscess pocket, but the remaining focal enhanced lesions were visible in the right temporal and occipital area at a one year follow-up MRI. This immune-competent patient showed multiple enhancing CNS aspergillosis in the cerebral hemisphere, which had a good outcome with antifungal agents.

BACKGROUND AND PURPOSE Juxtacortical spots are detected frequently on fluid-attenuated inversion recovery (FLAIR) images, but have not been extensively researched in patients with transient ischemic attack (TIA). We hypothesized that juxtacortical spots on FLAIR images are partly associated with right-to-left shunt (RLS) in TIA without clear etiology. The possibility of an association between the presence of RLS and juxtacortical spots on FLAIR images in patients with TIA without clear etiology was investigated, and the imaging findings of patients with and without RLS were compared. METHODS This was a retrospective study of TIA patients who visited our tertiary stroke center consecutively within 72 hours of TIA onset. Cryptogenic TIA was defined as no clear etiology despite a routine diagnostic workup. The presence of RLS was examined by transcranial Doppler with an agitated saline test or transesophageal echocardiography. Juxtacortical spots were defined as small and round hyperintensities in the juxtacortex on FLAIR images, excluding white-matter hyperintensities. RESULTS Of the 132 patients with cryptogenic TIA examined for this study, 70 (53.0%) had RLS. Juxtacortical spots on FLAIR images were detected more frequently in patients with RLS than in those without. The independent factors for the presence of juxtacortical spots were RLS [odds ratio (OR)=3.802, 95% confidence interval (95% CI)=1.74-8.2; p=0.001] and age (OR=1.058, 95% CI=1.01-1.10; p=0.004) by multivariate analysis. The number of juxtacortical spots was significantly higher among patients with a moderate-to-large RLS than in those with a small or no RLS. CONCLUSIONS The findings of the present study demonstrate a significant association between the presence of RLS and the occurrence of juxtacortical spots on FLAIR images in patients with cryptogenic TIA.

Recently, a number of cryptographic security measures for random network coding (RNC) has been proposed in literature in response to the security treats to RNC; however most of them are computationally heavy. In this paper, we evaluate the performance of a secure network coding scheme based on a homomorphic encryption scheme and discuss how to minimize its computational cost. Via experimental results, we argue that our method reduces computational overhead significantly in some settings.

Background The “drip and ship” approach can facilitate an early initiation of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) at community hospitals. New endovascular treatment modalities, such as stent retrieval, have further improved the rate of safe and successful recanalization. We assessed the clinical outcomes of on-demand endovascular therapy in patients with AIS who were transported to a comprehensive stroke center under the “drip and ship” paradigm. Methods This retrospective study evaluated prospectively registered patients with acute large vessel occlusions in the anterior circulation who underwent endovascular recanalization after IVT at our regional comprehensive stroke center between January 2011 and April 2014. Clinical outcomes and neuroradiological findings were compared between patients who received IVT at the center (direct visit, DV) and at a community hospital (drip and ship, DS). Results Baseline characteristics such as age, initial National Institutes of Health Stroke Scale (NIHSS) score, and risk factors for stroke were similar, and most patients underwent endovascular therapy with a Solitaire stent (81.9% vs. 89.3% for DV and DS, respectively, P = 0.55). The average initial NIHSS score was 12.15±4.1 (12.06 vs. 12.39 for DV and DS, respectively, P = 0.719). The proportions of long-term favorable outcomes (modified Rankin Scale score ≤2 at 90 days) and successful recanalization (Thrombolysis in Cerebral Ischemia score ≥2b) were not significantly different (P = 0.828 and 0.158, respectively). The mortality rates and occurrences of symptomatic intracerebral hemorrhage were not significantly different (P = 0.999 and 0.267, respectively). Conclusions The “drip and ship” approach with subsequent endovascular therapy is a feasible treatment concept for patients with acute large vessel occlusion in the anterior circulation that could help improve clinical outcomes in patients with AIS.

Network coding has been shown to improve various performance metrics in network systems. However, if network coding is implemented as software a huge time delay may be incurred at encoding/decoding stage so it is imperative for network coding to be parallelized to reduce time delay when encoding/decoding. In this paper, we compare the performance of parallelized decoders for random linear network coding (RLC) and pipeline network coding (PNC), a recent development in order to alleviate problems of RLC. We also compare multi-threaded algorithms on multi-core CPUs and massively parallelized algorithms on GPGPU for PNC/RLC.

Background Some recent studies have shown that poor outcomes after acute ischemic stroke (AIS) were closely related to lower serum triglyceride (TG) levels, not hypertriglyceridemia. However, hypertriglyceridemia has been shown to be an independent predictor for poor outcome in patients with coronary artery disease. This study attempted to evaluate the association between serum TG levels and early prognosis of AIS. Methods We enrolled 736 consecutive patients with AIS. Based on the TG level, patients were divided into 5 groups based on the guidelines of the National Cholesterol Education Program (NCEP). We defined early neurological deterioration (END) as a 4-point or greater deterioration of the NIH stroke scale (NIHSS) score and early clinical improvement (ECI) as a 4-point reduction of NIHSS within a week after symptom onset. We compared patients with END, ECI, and neither END nor ECI. Results The risk of END was significantly higher in the hyperTG and hypoTG groups compared with the normal group. The percentages of ECI were significantly lower in the hypoTG, borderline, and hyperTG groups compared with the normal group. For END, the multivariable adjusted odds ratios were significantly higher in the hypoTG, borderline, and hyperTG groups compared with the low normal group (50 to 100 mg/dl). Conclusions TG had a nonlinear, J-shaped association with poor outcome and a reverse J-shaped association with good outcome in AIS. This study suggests that both hyperTG and hypoTG can be risk factors for poor early outcome in AIS.

Non-contrast enhanced computed tomography (NCCT) is usually performed to estimate bleeding complications immediately after procedures. However, hyperdense areas on NCCT have not yet been understood; different interpretations have been reported in the literature. It remains unclear whether NCCT performed immediately after intra-arterial revascularization (IAR) could be useful for predicting hemorrhagic transformation (HT) or clinical outcomes. Therefore, we investigated the diagnostic values of hyperdense areas on NCCT images obtained immediately after IAR. This was a retrospective study of acute ischemic stroke patients who underwent IAR between October 2007 and December 2010. NCCT scans were routinely obtained immediately after IAR and additional follow-up imaging protocols included diffusion weighted imaging (DWI)/gradient echo imaging (GRE) 24 h after IAR. HT was assessed by means of GRE obtained 24 h after IAR. Hounsfield Unit (HU) of the hyperdensity was measured in the manually drawn regions of interest. A total of 68 patients were analyzed in this study. Twenty-nine patients (42.6%) developed HT on follow-up images. Thirty-eight patients had hyperdense areas on NCCT immediately after IAR. Hyperdensity on NCCT performed immediately after IAR revealed 23 (60.5%) of the 38 patients with six false negative areas. NCCT performed immediately after IAR showed a sensitivity of 79.3%, a specificity of 61.5%, a positive predictive value of 60.5% and a negative predictive value of 80% for HT. The HU value was a predictor of HT without statistical significance (area under curve of 0.629; 95% CI: 0.49–0.76; p = 0.068). In addition, an HU of >90 poorly predicted HT with a low sensitivity (23%) and a high specificity (94%). In conclusion, our results showed that although hyperdensity on NCCT images obtained immediately after IAR had a moderate predictive value for HT, there were limitations to the prediction of subsequent parenchymal hematoma and symptomatic intracranial hemorrhage, with a low specificity and a low positive predictive value.

Background Early neurological deterioration (END) of acute ischemic stroke may be important because it can predict clinical outcomes. We described several cases with similar clinical findings but different outcomes and analyzed the characteristics of their imaging studies. We retrospectively analyzed minor stroke patients with severe arterial stenosis within 6 hours of stroke onset. We defined END as 4 or more deterioration of the National Institutes of Health Stroke Scale score. Diffusion-weighted imaging (DWI) lesions were classified as lesions of the pial artery (PI), perforating artery (PAI) and border-zone (BZ). Results We consecutively analyzed a total of 12 subjects in this study. The patterns of initial DWI lesions were internal BZ (50%), PI (50%), PAI (25%), and cortical BZ (16.7%). Among them, the number of subjects with END was 5, and the frequency of internal BZ on initial DWI was significantly higher in patients with END than in those without. Conclusions In conclusion, the results of this study suggest that when internal BZ infarcts are detected in patients with acute minor strokes accompanied by severe arterial stenosis, close observation and careful management should be performed because END can be induced at an early stage.

Cerebral lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). Its pathological mechanism remains ambiguous despite several investigations. In Case 1, a 67-year-old man with hepatocellular carcinoma (HCC) experienced neurological deficits soon after undergoing a fourth session of TACE. Computed tomography (CT) scan showed multiple hyperdense lesions along the gyrus of frontal lobes and in the subcortical white matter. Transcranial Doppler (TCD) and transesophageal echocardiogram performed during the intravenous injection of agitated saline documented the presence of a right-to-left shunt (RLS) by demonstrating microbubbles in the left middle cerebral artery and left atrium. In Case 2, a 63-year-old woman underwent a third TACE due to a large HCC. After the procedure, her mental status deteriorated. Brain CT showed multiple hyperdense lesions on the cerebral and cerebellar cortex. TCD with agitated saline showed multiple microembolic signals shortly after the injection of agitated saline. The risk of cerebral lipiodol embolism may increase with recurrence and progression of HCC in patients who have a pre-existing RLS in the heart or lung. A test for the detection of an RLS may be necessary to identify patients with a heightened risk of cerebral embolism when multiple TACE procedures are required. TACE for HCC can cause pulmonary embolism or infarction.(1,2) However, cerebral lipiodol embolism is rare after TACE. There have been several reports of cerebral embolism after TACE, but their exact mechanism has not yet been fully elucidated. We report herein 2 patients who developed cerebral lipiodol embolism after undergoing multiple TACE procedures for remnant HCC through a pre-existing RLS.

Background: Possible factors associated with early outcome after thrombolysis are the recanalization time and the status of tissue. We assessed whether combined intravenous (IV) and intra-arterial (IA) thrombolysis performed according to the status of tissue based on perfusion computed tomography (PCT) is beneficial for the early outcome in patients with acute ischemic stroke. Methods: To improve the recanalization time, we assumed that combined IA thrombolysis after IV thrombolysis would be beneficial. Eligible patients for combined thrombolysis were selected according to the status of tissue based on PCT. Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3. ‘Good functional outcome’ was defined as a Modified Rankin Scale (mRS) score of 2 or less at discharge. Results: Eighteen patients (11 men) underwent combined IV/IA thrombolysis. The recanalization rate after combined IV/IA thrombolysis was 88.9% (TIMI 2, 4; TIMI 3, 12). A good functional outcome at discharge was noted in 12 patients (66.7%). The incidence of symptomatic intracranial hemorrhage was 5.6% (1/18). Conclusions: The results of this study suggest that combined IV/IA thrombolysis based on the presence of mismatches on PCT might have a relatively high rate of recanalization and a favorable early outcome. In addition, the incidence of symptomatic intracranial hemorrhage was acceptable.

The existing approaches for the music application have not considered a real-time multi-tasking model. So, it suffers from a high complexity and a low flexibility in design as well as lack of predictability for the timely execution of critical tasks. In this paper, we design a new concurrent tasking architecture for a real-time embedded music system and examine if all real-time tasks can finish execution within their respective time constraints. The design is implemented on the Linux based Xhyper272 Board that uses the Intel Bulverde microprocessor. Key Words:Music Embedded System, Real-Time, Concurrent Tasks, DARTS, Scheduling 1) 1. 서 론 마이크로프로세서의 가격이 저렴해짐에 따라 특정 분야에 관심이 있는 사용자의 요구를 만족시킬 수 있는 임베디드시스템 개발에 대한 관심이 증가하고 있다[2]. 이러한 예로 여러 가지 악기를 이용한 연주, 편곡 혹은 작곡에 관심이 있는 사람들에게 컴퓨터 음악을 할 수 있는 환경을 제공하는 뮤직 임베디드시스템이 있다. 뮤직 시스템을 이용하면 오선지를 이용한 수작업 대신에 미디(MIDI: Musical Instrument Digital Interface) 케이블로 연결된 전자악기들을 한 파트씩 연주 및 녹음하고 음정, 속도, 피치 등을 정밀하게 편집하여 ※ 본 연구는 한국과학재단 특정기초연구(R01-2005-000-10671-0287)지원으로 수행되었음 †준 회 원:울산대학교 대학원 컴퓨터공학 석사과정 ††정 회 원:울산대학교 컴퓨터정보통신공학부 부교수(교신저자)논문접수:2007년 11월 5일, 른심사완료：2008년 2월 22일

Background and Purpose— Time-dependent changes in individual platelet reactivity have been detected in patients with coronary artery disease. Therefore, we sought to evaluate the time-dependent changes in platelet reactivity to aspirin during the acute stage after ischemic stroke and the clinical implications of variable patient responses to aspirin in acute ischemic stroke. Methods— We conducted a single-center, prospective, observational study. The acute aspirin reaction unit (ARU) was measured after 3 hours of aspirin loading, with higher values indicating increased platelet reactivity despite aspirin therapy. The follow-up ARU was measured on the fifth day of consecutive aspirin intake. The numeric difference between the follow-up ARU and the acute ARU was defined as ΔARU and was stratified into quartiles. Early neurological deterioration was regarded as an early clinical outcome. Results— Both the acute ARU (476±69 IU) and the follow-up ARU (451±68 IU) were measured in 349 patients in this study. Early neurological deterioration was observed in 72 patients (20.6%). Changes in aspirin platelet reactivity over time showed an approximately Gaussian distribution. The highest ΔARU quartile was independently associated with early neurological deterioration (odds ratio, 3.19; 95% confidence interval, 1.43–7.10; P =0.005) by multivariate logistic regression analysis. Conclusions— The results of our study showed that the increase in platelet reactivity to aspirin over time is independently associated with early neurological deterioration in patients with acute ischemic stroke. In addition, during the acute stage of ischemic stroke, serial platelet reactivity assays may be more useful than a single assay for identifying the clinical implications of aspirin platelet reactivity after ischemic stroke.