a review of medical records upon the first admission.
Survey items included demographic data and presence of cerebrovascular risk factors using standardized, struc- tured questionnaires. The items were classified accord- ing to the current guidelines ofthe American Heart Association . Comorbidities were assessed using the Charlson comorbidity index . Initial stroke severity was recorded at the time of hospital arrival using the Korean National Institute of Health Stroke Scale (K- NIHSS) for ischemic strokes . Physical examin- ation findings and laboratory measures were also re- corded. The course ofthe disease during admission was documented including information on medication use, treatments such as intravenous or arterial thrombolysis, and complications. Patients that re- ceived rehabilitation at 3 months were transferred to the rehabilitation center to initiate active rehabilita- tion after acute management at the neuroscience cen- ter. The remaining patients that did not receive any rehabilitation treatments were discharged or trans- ferred to other hospitals instead of being transferred to the Rehabilitation Medicine Department.
licenses/by-nc/3.0) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose: In this study, we investigated thestroke mechanism and the factors associ- ated with ischemicstrokein patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. Materials and Methods: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between Janu- ary 2007 and December 2011. The controls were patients with NVAF without isch- emic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms ofstrokein cases. Results: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemicstroke were independently associated with cases. High CHADS 2 score (≥3) or CHA 2 DS 2 -VASc score (≥5), in particular, with previous ischemicstroke along with ≥1 point of other components of CHADS 2 score or ≥3 points of other components of CHA 2 DS 2 -VASc score was a significant predictor for development ofischemicstroke. Conclusion: NVAF patients with high CHADS 2 /CHA 2 DS 2 -VASc scores and a previous ischemicstroke or smoking history are at high risk ofstroke despite optimal warfarin treatment. Some other measures to reduce the risk ofstroke would be necessary in those specific groups of patients.
ischemicstroke. (O'Gara et al., 2013) Therefore, primary percutaneous coronary intervention was recommended than IVT in patients with acute myocardial infarction.
To find the factors related with RBC ratio, we arranged the patients with available thrombi according to the RBC ratio. Consequently, we analyzed clinical and radiological characteristics among the patients divided into three groups according to the RBC ratio. As the RBC ratio increased, the proportion of patients with vessel signs and symptomatic hemorrhage increased. There was a tendency of good response to IVT related with increase of RBC ratio. Clinical outcome at 3 months was worse with increase of RBC ratio, related with symptomatic hemorrhage. RBC dominance was related with vessel signs on imaging studies and might be related with symptomatic hemorrhage. This is line with previous studies, and worse outcome in patients with vessel signs is generally accepted. (Qureshi et al., 2006) Even the response to IVT was more prevalent in RBC-dominant group, considering clinical outcome and symptomatic hemorrhage, theuseof IVT should be cautious in patients with vessel signs.
Our study has several limitations that are worth mentioning including the fact that it had a retrospective, small-sized, nonrandomized study design. Clinical and angiographic outcomes were obtained from follow up patients only. Therefore, the patients included in this study may constitute a high-risk group who experienced recurrent strokes after index strokes. Although treatment with anticoagulant and antiplatelet agents does not show a different outcome in large artery atherosclerosis,  the lack of standardization oftheuseof therapeutic agents including dose and duration of antithrombotics and statin within subjects is also a limitation.
We collected all capillary glucose data during hospital admission. Several studies suggested that glucose excursions inthe acute period are more important than those inthe chronic period, when evaluating clinical outcomes [41,42]. However, post-stroke hyperglycemia could develop more than 48 hours after symptom onset . Hypoglycemia may develop during the chronic period as iatrogenic hypoglycemia due to the persistent useof anti-diabetic treatment or the relative paucity of glucose monitoring during this period. The glucose range reflects the fluctuations inthe entire glucose profile in a simple manner. Moreover, the glucose range is easier to calculate and use to make clinical decisions, as compared to the SD or CV ofthe glu- cose values. In fact, a reduction inthe glucose range by 10 points is more intuitive as compared to a reduction of 10% inthe SD or CV ofthe glucose values. In this perspectives, reducing range of glucose during hospital admission might be effective management strategy in reduc- ing the development of hypoglycemia and in finally improving functional outcomes in patients with an acute ischemicstroke.
This study has certain limitations. Despite the cohort study design, we could not exclude the effects of possible confounders that might have affected both nephrolithiasis and stroke. Because we do not have data regarding body mass index, smoking, and history of alcohol use, we could not adjust for these factors. Certain patients might not have visited a clinic for treatment of nephrolithiasis and/or stroke, and these patients might have been missed. Visits for nephrolithiasis might have increased the chance ofstroke detection. Therefore, we performed an additional analysis for between > 3 months and 1 year after the detection of nephrolithiasis. The results of this analysis were consistent with our aforementioned findings (adjusted HR ofischemicstroke = 1.22, 95%
However, the main limitations for studying the effectiveness of OAC + AP treatment in contemporary cohorts of AIS and AF patients are the major selection bias for which it can be only partly adjusted, since there will be measured and unmeasured confounders related to why these patients were taking OAC + AP inthe first place.
Nonetheless, in a recent study, an analysis restricted to patients with AF and ipsilateral stroke with significant large artery stenosis, not complete occlusion, showed that OAC + AP was less likely to be associated with 3-month vascular events than OAC alone (weighted HR 0.25 [0.07–0.89]) 17 . Therefore, the results should be interpreted with caution and limited to a hypothesis generation function. These findings, however, suggest that future trials Table 4. Association of OAC vs OAC + AP with primary outcome according to the CHA2DS2-VASc score subgroup. *Adjusted variables: age, NIHSS scores, dyslipidemia, smoking, prior anticoagulant use, prior statin use, prior antihypertensive use, prior antidiabetic use, LAD, glucose, SBP, LDL-cholesterol, multiple lesions, reperfusion therapy, stroke mechanism, CHA2DS2-VASc score. a Weighted Cox proportional hazards model with robust standard errors.
Our study has several limitations. First, due to the non-randomised nature ofthe study, our results may be influenced by several confounders including a selection bias for treatment, even if adjusted statistical models were used inthe attempt to control them. Second, a central adjudication ofthe outcome events was not performed but rather, these events were assessed by the local investigators. Third, in observational studies it is not possible to adjust for physician biases associ- ated with prescription of oral anticoagulant timings and agents. Another potentially important factor is the difference in time period between posterior strokes and anterior strokes; the former being recent and the latter being from previously published studies with enrolment before 2014 (the RAF and RAF-DOAC studies). There could therefore be important secular trends accounting for different event rates (e.g. changes in NOAC use), improved general stroke care (e.g. pos- sibly less bridging) or different OAT timing. In fact, regarding changes in oral anticoagulant type use, inthe posterior stroke population, which was more recently collected, 66% ofthe patients were treated with NOACs compared to 55% ofthe patients inthe anterior stroke population. Conversely, 27% ofthe patients with anterior stroke were treated with warfa- rin, compared to 19% ofthe patients inthe posterior stroke population.
While further studies will be needed to clarify which one ofthe above listed possible explana- tions are true and/or more important, the Stroke-MR interval appears to be an important fac- tor to be considered inthe interpretation of ASL-II finding.
There were some limitations inthe current study. Given its retrospective nature, the pres- ence of sampling bias cannot be ruled out. Our findings were based on small number of patients only and that there was a high number of dropout patients due to missing DSC perfu- sion which raises a high suspicion of selection bias. Missing CBF quantification is a major limi- tation as no precise comparison of CBF between ASL and DSC was possible in our study. In addition, our departmental protocol was to use a post-labeling delay of 1,600 msec for ASL imaging, which could have resulted in ASL-II in some brain areas as discussed above. The author ofthe previous paper  described 2000 msec post-labeling delay as the most appro- priate for CBF quantification for the clinical adult population, but before proceeding with this study, we performed a visual assessment by applying various post-labeling delays in our center and then selected 1600 msec as the most appropriate for visual assessment. Although a 1600 msec delay did not prevent the hyperintense spot, we could split the grade II and III by analyz- ing this spot and parenchymal signal together, and it is clear that at least in our proposed algo- rithm, grade II is better perfusion status than grade III. If we develop the research using CBF quantification inthe future, it seems necessary to adjust the post-labeling delay and to analyze the ASL image base on the calculated CBF value. Despite these limitations, the statistical results were strong. Further, an inter-observer agreement for interpretation of ASL imaging was very high with a weighted kappa value of 0.98. These results indicate that the new visual ranking system is objective and reproducible. For these reasons, we believe that our new visual ranking system can be potentially valuable and practical and that future researchesare warranted in a larger cohort with ischemicstroke.
In this series of consecutive post-tPA/MT plus stenting patients receiving early antiplatelet therapy, there were zero instances of symptomatic ICH. In the absence of widely-accepted treatment guidelines for patients with tandem occlusions or refractory intracranial stenosis and AIS, there is ongoing debate for the role of acute stenting in this population due to the potentially increased risk of ICH with requisite antiplatelets, 3)6)13)16)40) especially in pa- tients that received prior tPA. Antiplatelet strategies by those advocating stenting in this setting typically involve pre- or peri-procedural dual oral antiplatelet or intrave- nous glycoprotein IIb/IIIa inhibitor loading followed by maintenance therapies, 4)13)34) although holding antiplate- lets for 24 hours after tPA despite stent placement has also been described. 22) This latter approach likely derives from the current stroke guidelines that advise against the administration of antiplatelets within 24 hours of tPA, 33) and are based on RCTs that demonstrated increased ICH risk without improved outcomes for the early admin- istration of aspirin after tPA. 41) However, these studies did not account for the increased thrombotic risk in patients undergoing MT or stent placement, a consider- ation highlighted by thein-stent thrombosis seen inthe one patient in this study that had delayed initiation of post-procedural antiplatelets. While stent placement in our patient sample provided a compelling rationale for expedited post-tPA/MT antiplatelet initiation, 10)16) this population is also an effective proxy for assessing the theoretical safety of early post-tPA/MT antiplatelet usein non-stented patients at high risk for re-occlusion (i.e., those with large vessel occlusions from ICAD versus embolic disease, elevated platelets, and residual embolic
However, CM might be less frequently used because evidence for theuseof clopidogrel is limited inthe context of acute ischemicstroke 22 , and a recent study suggested that the antiplatelet regimen inthe first few days after ischemicstroke should include aspirin 23 . Other antiplatelet drugs did not reduce the risk or severity of early recurrent stroke 23 . However, as the combination therapy was only supported in patients with symptomatic high-grade intracranial stenosis or acute minor stroke or TIA over 3 months in randomized trials 3,24 , our results regarding physicians’ preference for AC after aspirin failure were somewhat unexpected. Therefore, these findings may address the need for a randomized clinical trial to explore the optimal antiplatelet strategy in aspirin failure.
1. 출처논문 소개
사망률 분석을 위해 선정한 출처논문은 2012년 8월 28일 남 효석 등이 발표한 ‘원인불명 뇌졸중 환자의 장기 사망률 연구 (long-term mortality in patients with strokeof undetermined etiology)’로 정하였다 (4) . 연구대상은 1997년부터 2007년 사이 에 국내 한 대학병원에서 급성 허혈성 뇌졸중으로 치료받고 한 국뇌졸중등록사업 자료은행에 등록된 환자 3,965명을 대상으 로 하였고 입원기간 동안 병력조사, 임상양상 및 혈관성 위험 요인 등에 대한 조사와 기초혈액검사 및 심전도를 비롯하여 CT, MRI와 같은 영상의학적 검사를 통해 확진하였다. 이 중 재 발성 뇌졸중이나 다른 유형의 뇌졸중, 기타 자료 부족 등을 이 유로 687명을 배제하여 최종 3,278명에 대하여 뇌졸중의 세부 유형을 구분하고 분석을 시행하였다.
Our study has some limitations. First, this study is subject to all ofthe limitations inherent to a retrospective analysis. Second, we only included a selective group of patients with NVAF and ischemicstroke who underwent all following examinations; TEE, cardiac CT, carotid duplex sonography, and brain imaging. This retrospective non-consecutive inclusion has inherent risk of selection bias. Therefore, the findings of our study cannot be generalized to the entire NVAF population with ischemicstroke. However, the CHA 2 DS 2 -VASc score distribution of non-consecutively enrolled AF patients with strokein this study was similar to that of consecu- tively enrolled AF patients with strokeinthe previously published Yonsei Stroke Registry data ofthe same institution (S1 Fig) . Third, we investigated only a limited number of CE and non-CE risk factors, which may not be representative ofthe total burden of risk. Fourth, it is unclear whether non-CE risk factors in high risk NVAF patients are associated phenomenon or have causal result relationship with stroke event because it was difficult to classify the mech- anisms ofstroke, CE or non-CE, in many patients.
Our study have several limitations. First, we reviewed the patients ’ medical records retrospectively, so seizure events could have been missed or under- diagnosed in some patients. Second, the observational nature of our study nature is prone to uncontrolled AED prescription, variable follow up duration, or bias of unmeasured factors. Lastly, the small number of patients in this study might have limited to derive ad- justed ORs with multiple predictor variables. How- ever, we tested the distribution of all continuous variables and confirmed that they are normally dis- tributed. Although we selected clinical variables using a modest statistical guideline of p < 0.3, we found that the validity of our scoring systems was improved with relatively good sensitivity and specificity. This kind of clinical scoring system for seizure recurrence in PSSi patients could be useful with further validation inthe future large scale prospective study.
blood brain barrier, however, limits diffusion of blood-derived molecules into the brain. 58, 59 Therefore, in many previous in vivo reports, various regions ofthe brain were transfected directly with a recombinant adenovirus instead of using intraventricular injections. 36-38, 60 Based on these reports, adenovirus was introduced into the both striatum and cortex stereotaxically. These regions were selected to examine the effects of a selective and temporal increase of APE/Ref-1 inthe mouse brain. Type 5 hexon, one ofthe major structural components ofthe capsid protein, was observed inthe injected hemisphere, indicating that the infected virus was well distributed (Fig. 3). In the western blot analysis ofthe Adv-APE/Ref-1 treatment group, the temporal profile of APE/Ref-1 (Fig. 4) and expression of APE/Ref-1 were determined to demonstrate the increasing amount of APE/Ref-1 protein during ischemic injury (Fig. 5). The data suggests that Adv-APE/Ref-1 increases APE/Ref-1 expression and compensates for the loss of APE/Ref-1 after I/R.
양이 실험대조군에 비해 유의하게 증가하였고, 그 양은 약 2 배 정도로 늘어났다. 또한 1 시간의 심각한 허혈손상 후 재관류 손상이 시작된 지 1 시간 후 역시 agmatine 은 허혈손상 시작 전 보다 약 2 배 이상 늘어났고 이와 같은 결과는 실험대조군과 ischemic preconditioning 군 에서 동일하게 관찰되었다. Agmatine 을 생성하는 알기닌탈탄소 효소(ADC) 의 발현을 조사한 결과 실험대조군과 ischemic preconditioning 군에서의 차이는 없었다. 다만 허혈손상 1 시간차에 실험대조군에서 더 많이 발현된 것으로 확인되었다. 재관류시의 ADC 의 발현은 실험대조군과 ischemic preconditioning 군에서 차이가 거의 없었다. 면역조직화학 결과에서 보면 ADC 의 발현은 ischemic preconditioning 에 의해 보호된 부위에서는 그 발현이 실험대조군에 비해 증가함을 보여주고 반면, 손상된 부위에서는 ADC 의 발현이 별 차이가 나지 않음을 확인하였으며, 이는 ADC 에 의해 생성되는 agmatine 이 연관되어 있음을 간접적으로 보여주는 것이라 생각된다. 허혈후 재관류 손상시 cell death 에 중요한 역할을 하는 것으로 알려져 있는 nNOS 와 iNOS 발현을 조사한 결과, ischemic preconditioning 으로 인해 nNOS 의 발현은 재관류 1 시간과 23 시간에 현격히 줄어들었으며, 반면 iNOS 는 실험대조군과 마찬가지로 발현됨을 확인하였다. 따라서 Ischemic preconditioning 에 의해 증가된 agmatine 이 nNOS 의 발현을 감소시킴으로써 신경보호작용을 나타내었을 것으로 생각되었다.
1H). She was discharged with no specific neurologic or clini- cal symptoms on day 20 after admission.
Dissection ofthe carotid artery might show an intimal flap and double lumen, but carotid artery dissection accom- panied by inflammation of vessel wall and its surrounding tissues has not been well characterized. In the present case, the crescent-shape ofthe irregular enhancement on the carotid wall and perivascular tissues was suggestive of ca- rotidynia. Neuroimaging findings of a double lumen inthe carotid artery might have been due to secondary dissection associated with inflammatory changes. We diagnosed the present case as carotidynia based on the criteria ofthe In- ternational Headache Society (IHS). 1 In addition, the patient had three other specific findings that are unusual among the well-known characteristics of carotidynia.