優秀論文獎

糖尿病合併高血壓患者使用Telmisartan與失智的發生風險：全人口世代研究
劉濟弘 1、宋碧姍 2、李晏榮 3、黃文冠 4、李泰衛 5、黃錦章 1、李宗海 1、陳天心 6、魏怡嘉 7
1
林口長庚神經內科部、 2成大醫院神經科、 3林口長庚新陳代謝科、 4林口長庚腫瘤科
5
基隆長庚臨床統計中心、 6基隆長庚心臟科、 7基隆長庚神經科

Telmisartan Use and Risk of Dementia in Type 2 Diabetes Patients with

Hypertension: A Population-based Cohort Study
Chi-Hung Liu1, Pi-Shan Sung2, Yan-Rong Li3, Wen-Kuan Huang4, Tay-Wey Lee5, Chin-Chang Huang1,
Tsong-Hai Lee1, Tien-Hsing Chen6, Yi-Chia Wei7
1
Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
2
Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National
Cheng Kung University, Tainan, Taiwan.
3
Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung
Memorial Hospital, Taoyuan, Taiwan.
4
Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial
Hospital, Taoyuan, Taiwan.
5
Biostatistical Consultation Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
6
Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital,
Chang Gung University College of Medicine, Keelung, Taiwan.
7
Department of Neurology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.

Background: Angiotensin receptor blockers (ARBs) may have protective effects against
dementia occurrence in patients with hypertension (HTN). However, whether telmisartan,
an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has
additional benefits compared to other ARBs remains unclear.
Methods and findings: Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM)
patients were identified from the National Health Insurance Research Database of Taiwan.
Patients with HTN using ARBs were included in the study. Patients with a history of stroke,
traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided
into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score
matching (1:4) was used to balance the distribution of baseline characteristics and medications.
The primary outcome was the diagnosis of dementia. The secondary outcomes included the
diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS,
and all-cause mortality. The risks between groups were compared using a Cox proportional
hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients
in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan
group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19%
versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia
diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022)
and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97;
p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%;
HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations
included potential residual confounding by indication, interpretation of causal effects in an
observational study, and bias caused by using diagnostic and medication codes to represent real
clinical data.
Conclusions: The current study suggests that telmisartan use in hypertensive T2DM patients
may be associated with a lower risk of dementia and any IS events in an East-Asian population.

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血中神經絲輕鏈可預測接受血栓移除術中風病患之預後
陳志昊1、朱海瑞2、黃怡婷3、林彥亨4、李崇維4、湯頌君1、鄭建興1
1
台大醫院神經部
2
恩主公醫院神經部
3
台北大學統計學系
4
台大醫院影像醫學部

Plasma Neurofilament Light Chain Level Predicts Outcomes in Stroke Patients

Receiving Endovascular Thrombectomy
Chih-Hao Chen*1, Hai-Jui Chu*2, Yi-Ting Huang3, Yen-Heng Lin4, Chung-Wei Lee4, Sung-Chun Tang1,
Jiann-Shing Jeng1 (*co-first)
1
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
2
Department of Neurology, En Chu Kong Hospital, New Taipei City, Taiwan.
3
Department of Statistics, National Taipei University, New Taipei City, Taiwan.
4
Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.

Background: Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients

with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central
nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated
the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS
undergoing EVT.
Methods: We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma
biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and
ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule
array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of
interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3-6) and types
of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage).
Results: Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP,
and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four
biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly
higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared
with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex,
National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status,
higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03-4.08), T2 (OR, 2.08;
95% CI, 1.05-4.01), and T3 (OR, 3.94; 95% CI, 1.44-10.79) were independent predictors of death or
disability at 90 days.
Conclusion: Among patients with AIS who received EVT, those with hemorrhagic transformation
exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were
predictive of unfavorable functional outcomes.

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反應性星狀細胞增生對於腦中風後認知功能障礙的影響
黃國倫 1、蕭穎聰 2、何孟洋 1、徐榮隆 3、張寓智 1、張庭瑜 1、劉濟弘 1、張健宏 1、吳逸民 4、
吳冠毅 5、魏孝萍 2、閻紫宸 2、Nobuyuki Okamura 6、李宗海 1、林昆儒 2
1
林口長庚神經內科部
2
林口長庚核醫部及分子影像中心
3
新北市土城醫院神經部
4
林口長庚放射部
5
林口長庚精神部
6
日本仙台市東北大學發長,老化及癌症研究所神經影像科

Investigation of Reactive Astrogliosis Effect on Post-Stroke Cognitive Impairment

Kuo-Lun Huang1, Ing-Tsung Hsiao2, Meng-Yang Ho1, Jung-Lung Hsu3, Yeu-Jhy Chang1,
Ting-Yu Chang1, Chi-Hung Liu1, Chien-Hung Chang1, Yi-Ming Wu4, Kuan-Yi Wu5, Shiaw-Pyng Wey2,
Tzu-Chen Yen2, Nobuyuki Okamura6, Tsong-Hai Lee1, Kun-Ju Lin2
1
Department of Neurology, Linkou Chang Gung Memorial Hospital, and College of Medicine, Chang
Gung University, Taoyuan, Taiwan.
2
Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial
Hospital, Taoyuan, Taiwan.
3
Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital,
Chang Gung University, New Taipei City, Taiwan.
4
Department of Radiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
5
Department of Psychiatry, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
6
Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

Background: To investigate the associations between post-stroke cognitive impairment

(PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-
emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke.
Methods: We prospectively enrolled 63 amyloid-negative patients with first-ever stroke.
Neurocognitive evaluation, MRI, 18F-THK-5351 and 18F-florbetapir PET were performed
around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using
a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole
brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume,
leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery
to obtain composite cognitive scores, and defined PSCI as a general cognitive function
score < -1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for
demographic, vascular, and neurodegenerative variables.
Results: Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower
education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores
were significantly associated with general cognitive and executive functions at multiple
regression models. Path analyses showed that stroke can exert cognitive influence directly by
stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in
patients with either right or left hemisphere stroke.
Conclusion: The patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients
with first-ever stroke were associated with PSCI manifestations, which suggests that RA
presents a modulating effect in PSCI development.

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簡易但有組織的神經科住院醫師訓練課程可增進急性腦中風照顧品質：短期至
長期成效
張育銘 1、王淳民 1、林伯昱 1、宋碧姍 1, 2、林聖翔 2, 3、陳志弘 1
1
國立成功大學醫學院附設醫院神經部
2
國立成功大學醫學院臨床醫學研究所
3
國立成功大學醫學院附設醫院生物統計諮詢中心

Simple but Organized Neurology Residency Training Improves the Quality of

Acute Stroke Care: From the Outset to Long-Term Effect
Yu-Ming Chang1, Chun-Min Wang1, Po-Yu Lin1, Pi-Shan Sung1, 2, Sheng-Hsiang Lin2, 3, Chih-Hung Chen1
1
Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National
Cheng Kung University, Tainan, Taiwan.
2
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
3
Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine,
National Cheng Kung University, Tainan, Taiwan.

Acute stroke management had became more and more important nowadays. Minimizing the
time of tissue plasminogen(tPA) administration for acute stroke patietns indicated saving
more brain tissues. However, we often had drug administration time delay and variance
clinical performance by each neurology residents in the past. Besides renewal of acute stroke
protocol in our hospital, we further conducted a serial stroke lectures and simulation training
for our residents since 2018. The final goal was to diminish the door-to-needle(DTN) time and
escalate the proportion of DTN ≤ 60 minutes.
Between August 2015 and October 2020, we divided the residents into two groups: the control
group (C group) comprised residents who had not received the new educational program prior
to attending the ED work shift, whereas the intervention group (I group) comprised residents
who had completed the requirement. Regarding tPA administration in junior residency
year, the I group displayed a lower mean DTN time (I:C group = 53:65 minutes, P<0.05)
and a higher percentage of patients with a DTN ≤60 minutes than the C group (I:C group =
78%:53%, P<0.05). We had also proved that the average DTN time significantly improved
after introducing the training programs with a trend of time decrement. Furthermore, I group
even demonstrated a more steady and better performance of tPA administration by long-term
tracking in comparison with the C group.
Our results suggest that organized educational intervention regarding acute stroke enhance the
clinical performance of neurology residents since junior residency, and thereby the quality of
acute stroke care.

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肝細胞癌患者與較高一年腦中風風險之相關性研究：全國登記資料庫之世代研究
許晉譯 1, 2、劉品崧 1, 3、劉安邦 2, 4、黃暉凱 2, 5, 6、羅慶徽 1, 2, 5
1
花蓮慈濟醫院高齡健康中心
2
慈濟大學醫學系
3
慈濟大學醫學科學研究所
4
花蓮慈濟醫院神經內科部
5
花蓮慈濟醫院家庭醫學部
6
花蓮慈濟醫院研究部

High 1-year Risk of Stroke in Patients with Hepatocellular Carcinoma: A

Nationwide Registry-based Cohort Study
Jin-Yi Hsu1, 2, Peter Pin-Sung Liu1, 3, An-Bang Liu2, 4, Huei-Kai Huang2, 5, 6, Ching-Hui Loh1, 2, 5
1
Center for Aging and Health, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation,
Hualien, Taiwan.
2
School of Medicine, Tzu Chi University, Hualien, Taiwan.
3
Institute of Medical Sciences Tzu Chi University Hualien Taiwan.
4
Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien,
Taiwan.
5
Department of Family Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation,
Hualien, Taiwan.
6
Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation,
Hualien, Taiwan.

Background: Patients with hepatocellular carcinoma (HCC) might be more vulnerable to

develop stroke than other cancer patients because of HCC-associated coagulation dysfunction.
However, limited studies have investigated the relationship between HCC and stroke.
Methods: This nationwide population-based cohort study enrolled all patients with HCC
diagnosed between 2011 and 2015 from the Taiwan Cancer Registry and Taiwan National
Health Insurance Research Database; an age- and sex-matched cohort without cancer was
included. The primary outcome was the 1-year risk for first-ever stroke after the index date.
The Fine and Gray competing risk regression model was used to estimate the 1-year stroke
risk with adjusted hazard ratios (aHRs).
Results: After propensity score matching, each cohort has 18,506 patients with similar
baseline characteristics. Compared with the cancer-free cohort, the aHRs in the HCC cohort
for overall, ischemic, and hemorrhagic strokes were 1.59 [95% confidence interval (CI), 1.35–
1.88], 1.38 [95% CI, 1.15–1.65], and 2.62 [95% CI, 1.79–3.84], respectively. On subgroup
analysis, HCC patients without cirrhosis, those with stage 3 or 4 cancer had a higher stroke
risk than cancer-free cohort.
Conclusions: Therefore, stroke prevention should be considered in patients with HCC,
especially in those without cirrhosis and with stage 3 or 4 cancer.

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混和位置腦出血與微出血病患之長期血管預後研究
蔡欣熹 1, 2, 3、陳思汝 1, 2、蔡力凱 2、Marco Pasi 4、羅彥伶 1、陳雅芳 5、湯頌君 2、鄭建興 2
1
台大醫院北護分院神經內科
2
台大醫院神經內科
3
台大醫學院臨床醫學研究所
4
法國里爾大學附設醫院神經內科
5
台大醫院影像醫學科

Long-Term Vascular Outcomes in Patients With Mixed Location Intracerebral

Hemorrhage and Microbleeds
Hsin-Hsi Tsai1, 2, 3, Szu-Ju Chen1, 2, Li-Kai Tsai2, Marco Pasi4, Yen-Ling Lo1, Ya-Fang Chen5,
Sung-Chun Tang2, Jiann-Shing Jeng2
1
Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
2
Departments of Neurology, National Taiwan University College of Medicine and Hospital, Taipei,
Taiwan.
3
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei,
Taiwan.
4
Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, F-59000 Lille,
France.
5
Department of Medical Imaging, National Taiwan University College of Medicine and Hospital,
Taipei, Taiwan.

Objective: To determine whether mixed location intracerebral hemorrhages/microbleeds

(Mixed-ICH) is a risk factor for vascular unfavorable outcome compared to cerebral amyloid
angiopathy-related ICH (CAA-ICH) or strictly deep hypertensive intracerebral hemorrhage/
microbleeds (HTN-ICH).
Methods: 300 patients with spontaneous ICH were included. Clinical data, neuroimaging
markers and follow-up outcomes (recurrent ICH, ischemic stroke and vascular death) were
compared between Mixed-ICH (n=148), CAA-ICH (n=32) and HTN-ICH (n=120). The
association between follow-up events and neuroimaging markers were explored using
multivariable Cox regression models.
Results: Patients with Mixed-ICH are older (65.6±12.1 years vs 58.1±13.3 years, p<0.001)
than HTN-ICH, but younger than CAA-ICH (73.3±13.8 years, p=0.001). Compared to CAA-
ICH, Mixed-ICH has similar incidence of vascular event (all p>0.05). Compared to HTN-
ICH, Mixed-ICH is associated with higher ICH recurrence (hazard ratio [HR]=3.0, 95%
confidence interval [CI]: 1.2-7.7), more ischemic stroke (HR=8.2, 95% CI: 1.0-65.8), and
vascular composite outcome (HR=3.5, 95% CI: 1.5-8.2) after adjustment for age and sex. In
patients with Mixed-ICH, the presence of cortical superficial siderosis (cSS) is associated the
development of ICH recurrence (HR=4.8, 95% CI 1.0-23.2), ischemic stroke (HR=8.8, 95%
CI: 1.7-45.5), and vascular composite outcome (HR=6.2, 95% CI: 1.9-20.2). The association
between cSS and ischemic stroke (p=0.01) or vascular composite outcome (p=0.003)
remained significant after further adjustment for other radiological markers.
Conclusions: Mixed-ICH harbors higher risk of unfavorable vascular outcome than HTN-
ICH. Presence of cSS in Mixed-ICH independently predicts vascular event, suggesting the
contribution of detrimental effect due to coexisting CAA.

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大血管阻塞患者電腦斷層灌流不足指數與電腦斷層血管攝影側枝循環分數之關
聯性研究
王淳民、張育銘、宋碧姍、陳志弘
國立成功大學醫學院附設醫院神經部

Hypoperfusion Index Ratio as a Surrogate of Collateral Scoring on CT

Angiogram in Large Vessel Stroke
Chun-Min Wang, Yu-Ming Chang, Pi-Shan Sung, Chih-Hung Chen
Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National
Cheng Kung University, Tainan, Taiwan.

Background: This study was to evaluate the correlation of the hypoperfusion intensity ratio
(HIR) with the collateral score from multiphase computed tomography angiography (mCTA)
amongpatients with large vessel stroke.
Method: From February 2019 to May 2020, we retrospectively reviewed the patients with
large vessel strokes (intracranial carotid artery or proximal middle cerebral artery occlusion).
HIR was defined as a Tmax > 10 s lesion volume divided by a Tmax > 6 s lesion volume,
which was calculated by automatic software (Syngo.via, Siemens). The correlation between
the HIR and mCTA score was evaluated by Pearson’s correlation. The cutoff value predicting
the mCTA score was evaluated by receiver operating characteristic analysis.
Result: Ninety-four patients were enrolled in the final analysis. The patients with good
collaterals had a smaller core volume (37.3 ± 24.7 vs. 116.5 ± 70 mL, p < 0.001) and lower
HIR (0.51 ± 0.2 vs. 0.73 ± 0.13, p < 0.001) than those with poor collaterals. A higher HIR
was correlated with a poorer collateral score by Pearson’s correlation. (r = −0.64, p < 0.001).
The receiver operating characteristic (ROC) analysis suggested that the best HIR value for
predicting a good collateral score was 0.68 (area under curve: 0.82).
Conclusion: HIR is a good surrogate of collateral circulation in patients with acute large
artery occlusion.

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丙戊酸透過調節Akt磷酸化及減弱神經細胞凋亡來減少蛛網膜下腔出血老鼠的血
管痙攣
吳界欣、蔡易真、蔡泰欣、郭耿良、蘇裕峰、張智輝、林志隆
高雄醫學大學附設中和紀念醫院

Valproic Acid Reduces Vasospasm through Modulation of Akt Phosphorylation

and Attenuates Neuronal Apoptosis in Subarachnoid Hemorrhage Rats
Chieh-Hsin Wu, Yi-Cheng Tsai, Tai-Hsin Tsai, Keng-Liang Kuo, Yu-Feng Su, Chih-Hui Chang,
Chih-Lung Lin
Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan.

Background and Purpose: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating

emergent event associated with high mortality and morbidity. Survivors usually experience
functional neurological sequelae caused by vasospasm-related delayed ischemia. Therefore,
this study used a rat model of SAH to investigate whether valproic acid (VPA) attenuates
cerebral vasospasm or exerts a neuroprotective effect.
Methods: In this study, male Sprague-Dawley rats were randomly assigned to five groups:
sham (non-SAH) group, SAH group, and three groups with SAH treated with different doses
of valproic acid (VPA) (10, 20, 40 mg/kg, once-daily, for 7 days). The severity of vasospasm
was determined by the ratio of cross-sectional areas to intima-media thickness of the basilar
arteries (BA) on the seventh day after SAH.
Results: The BA showed decreased expression of phospho-Akt proteins. The dentate gyrus
showed increased expression of cleaved caspase-3 and Bax proteins and decreased expression
of Bcl-2, phospho-ERK 1/2, phospho-Akt and acetyl-histone H3 proteins. The incidence
of SAH-induced vasospasm was significantly lower in the SAH group treated with VPA 40
mg/kg (p < 0.001). Moreover, all groups treated with VPA showed reversal of the above-
mentioned protein expression in BA and the dentate gyrus. Treatment with VPA upregulated
histone H3 acetylation and conferred anti-vasospastic and neuro-protective effects by
enhancing Akt and/or ERK phosphorylation.
Conclusion: This study demonstrated that VPA could alleviate delayed cerebral vasospasm
induced neuro-apoptosis after SAH. 

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於腦出血患者中急性降血壓增加發生分水嶺腦梗塞之風險
陳思汝 1, 2、蔡欣熹 1, 2、蔡力凱 1、陳雅芳 3、湯頌君 1、鄭建興 1
1
台大醫院神經部
2
台大醫院北護分院神經部
3
台大醫院影像醫學部

Acute Blood Pressure Reduction Increases the Risk of Border Zone Ischemia in
Acute Hypertensive Intracerebral Hemorrhage
Szu-Ju Chen1, 2, Hsin-Hsi Tsai1, 2, Li-Kai Tsai1, Ya-Fang Chen3, Sung-Chun Tang1, Jiann-Shing Jeng1
1
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
2
Department of Neurology, National Taiwan University Bei-Hu Branch, Taipei, Taiwan.
3
Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.

Background: Patients with acute intracerebral hemorrhage (ICH) are commonly treated
with acute blood pressure (BP) reduction which has been suspected relating to cerebral
hypoperfusion and acute ischemic lesions (AILs). Here, we investigated the impact of acute
systolic BP (SBP) reduction on the risk of AILs at border-zone (BZ) areas in patients with
acute hypertensive ICH.
Methods: We enrolled patients with acute hypertensive ICH (hemorrhagic lesions restricted to
deep region [Strictly deep-ICH] or located at mixed lobar and deep areas [Mixed-ICH]) who
received brain MRI within 7 days after ICH onset. BZ AILs are lesions locating at BZ areas
that are hyperintense on DWI sequence and hypointense on ADC series. The degree of acute
SBP reduction was measured by the differences between the initial SBP and the SBP recorded
at 24 hours after ICH onset.
Results: Of the 274 enrolled participants (62.5 ± 12.7 years old, 65% male), 11 patients
developed BZ AILs. Compared to patients without BZ AILs, patients with lesions had
larger degree of acute SBP reduction (71.7 ± 33.6 vs. 43.0 ± 32.2 mmHg, P = 0.023), more
microbleeds (MB) and higher white matter hyperintensity volume (all p < 0.05). A multiple
logistic regression model revealed that larger degree of acute SBP drop was associated with
higher risk of AILs (OR 1.34, 95% CI 1.08 – 1.72, P = 0.012) after adjustment for age, sex,
and image markers of cerebral small vessel disease. In subgroup analysis, larger degree of
acute SBP reduction was an independent risk factor for development of BZ AILs in patients
with Mixed-ICH (OR 1.47, 95% CI 1.13 – 2.03, P = 0.008), but not in patients with strictly
deep-ICH (P = 0.715).
Conclusion: In acute hypertensive ICH, acute SBP reduction may lead to cerebral
hypoperfusion and increase the risk of AILs at BZ areas especially in patients with Mixed-
ICH.

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雙線與單線抗血小板藥物在大血管粥狀硬化所致之缺血性中風或暫時性腦缺血
之結果比較與分析：系統性回顧
曾子芸 1、Jeffrey L. Saver 2、林浚仁 1, 3
1
臺北榮民總醫院神經內科
2
美國加州大學洛杉磯分校大衛格芬醫學院腦中風中心及神經部
3
國立陽明大學醫學院

Dual versus Mono Antiplatelet Therapy for Acute Ischemic Stroke or Transient
Ischemic Attack with Evidence of Large Artery Atherosclerosis
Tzu-Yun Tseng1, Jeffrey L. Saver2, Chun-Jen Lin1, 3
1
Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital,
Taipei, Taiwan.
2
Comprehensive Stroke Center and Department of Neurology, David Geffen School of Medicine,
University of California, Los Angeles, USA.
3
School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Background and Purpose: Current evidences support the short-term use of dual antiplatelet
(DAPT) in minor ischemic stroke or transient ischemic attack (TIA) based on the studies
performed in patients with a broad range of non-cardioembolic stroke mechanisms.
However, the efficacy and safety of DAPT use in ischemic stroke patients with large artery
atherosclerosis (LAA) are still uncertain. We undertook a systemic search and formal meta-
analysis to compare DAPT vs mono-antiplatelet therapy (MAPT) in patients with etiology
specifically presumed to be symptomatic LAA.
Methods: We conducted a systemic online search for completed randomized controlled trials
that 1) compared DAPT vs MAPT in patients with acute ischemic stroke or TIA, 2) were
confined to or had available subgroup data regarding population with symptomatic extra- or
intracranial artery stenosis. Study-level meta-analysis was performed for outcomes including
ischemic stroke (IS) recurrence, intracranial hemorrhage (ICH), and major bleeding with
Mantel-Haenszel method and random effect models, and was described as risk difference (RD)
and 95% confidence interval (CI).
Results: Eight trials including 4,294 patients were pooled. Comparing to MAPT, DAPT
significantly reduced IS recurrence (6.2% vs 9.7%, RD: -3%, 95% CI: -5% to -1%). Across
all agents, out of 100 treated patients, 3 fewer had recurrent ischemic stroke with DAPT.
However, there was evidence of agent heterogeneity (pheterogeneity=0.03), with clopidogrel
added to aspirin and ticagrelor added to aspirin showing benefit but not cilostazol. The safety
endpoints including ICH (0.28% vs 0.19%, RD: 0%, 95% CI: -0% to 0%) and major bleeding
(0.57% vs 0.32%, RD: 0%, 95% CI: -0% to 0%) did not differ significantly.
Conclusions: In patients with symptomatic large artery extracranial or intracranial
atherosclerosis, DAPT was superior to MAPT in preventing IS recurrence without increasing
bleeding risks. The optimal DAPT regimens and duration of treatment in this population need
to be clarified in further studies.

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