1 KoreanRe, 2 Design hospital
Hyeyun Ahn, FLMI, FALU 1 , Kwang-il Park, MD, PhD, FLMI 1 , Sinhyung Lee, MD, FLMI 2
Worldwide, stroke is the 2nd or 3rd leading cause of death and a major health problem. Recent advances in medical technology have significantly improved diagnosis and treatment strategies ofischemicstroke. The ischemicstroke subtype is an important determinant of mortality and long-term prognosis of patients. To estimate excess-risks oftheischemicstroke subtype, recently published article, Korean cohort study ofstroke, was used as a source article.
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.
patients who achieved final reperfusion were enrolled inthe study, and other important vari- ables that may affect the outcome were adjusted, we believe that temporary opening improved clinical outcome. Second, as the choice of ERT modality was not randomized, there is a possi- bility of confounding bias. However, treatment allocation was mainly decided by specific time and the baselines characteristics between the patients with temporary opening and those with- out were comparable except for the initial occlusion site. Multivariate analysis was also per- formed to adjust for confounding variables. Third, the time dependent decrease of reperfusion benefit in patients without temporary opening and the beneficial effect of temporary opening in patients with good collaterals had the borderline of statistical significance. It may attribute to relatively small sample size of this study. Finally, this study was retrospective analysis of sin- gle center data. Inevitable limitations with the study design should be considered when inter- preting the study results.
reduced arterial reflexes, and behavioral and emotional responses. These features of high BPV would demonstrate the detrimental effect on stroke prognosis.
There are several limitations. First, this study was retrospectively conducted using a single hospital database, and had a risk of bias. However, our subjects were consecutively identified from a prospective stroke registry and large amounts of BP data would increase the statistical power. Second, this study only showed an association between BPV and END on a daily basis, and could not explain a causal relationship. Because we aimed to identify the course and impact of short-term BPV, a different study design and more precise analytic tools are needed.
We collected all capillary glucose data during hospital admission. Several studies suggested that glucose excursions intheacute 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 use of 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 acuteischemicstroke.
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.
Therefore, early and late PSSi groups were compared in this study. Different prognostic factors including seizure recurrence rate are regarded as a reflection of underlying pathomechanism associated with the en- during predisposition. Early seizures are thought to result from acute disruption of brain integrity, meta- bolic homeostasis, and excitatory glutamate release, leading to secondary neuronal injury and electrically irritable tissue. In contrast, late seizures are related to neuronal circuit reorganization by aberrant gliosis and development of hyperexcitable cicatrix, eventually resulting in spontaneous seizures [23, 36]. We hy- pothesized that clinical characteristics of PSSi patients might reflect the epileptogenic predisposition of post- stroke brain. Our results suggested that different epi- lepsy pathogenesis might be involved in early and late PSSi because the adjusted ORs of recurrence related factors did not match each other.
‘malignant MCA infarction’. Malignant middle cerebral artery (MCA) infarction is associated with a dismal prognosis regardless of maximum intensive care and timely carrying decompressive hemicranietomy.
Due to evolution of treatment modality about EVT, the treatment direction to reduce reperfusion injury has come to a new horizon. After recanalization, reperfusion injury, which is expressed by edema and hemorrhagic transformation occurs, and several medical therapies that minimize such neuronal damage have been studied. One of them is a therapeutic hypothermia, and there are not many studies that have been verified as a multi-center trial. Therefore, we aimed to evaluate the efficacy of therapeutic hypothermia inacuteischemicstroke patients after endovascular recanalization therapy. We also investigated the therapeutic hypothermia effect in subgroups that included only malignant MCA infarct patients.
Although middle cerebral artery occlusion increases the expression of interleukin-1 β and tissue necrosis factor- α, this elevation is suppressed by both hypothermia and glycyrrhizin treatment. We show that hypothermia reduces the production of inflammatory cytokines and helps salvage peri-infarct regions from the propagation ofischemic injury via HMGB1 blockade. In addition to suggesting a potential mechanism for hypothermia ’s therapeutic effects, our results suggest HMGB1 modulation may lengthen the therapeutic window for stroke treatments.
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 ofacute 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 use in 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 thrombolytic therapy might not be helpful, if the vascular obstruction is not related with the thrombus.
Physicians who care the patients with acuteischemicstroke must evaluate not only bleeding events and thrombogenic risk factors, but also the other obstructing causes except thrombus. We experienced a patient who was afflicted with the infected embolic myxoma.
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.
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, the use of IVT should be cautious in patients with vessel signs.
A recent European practical guide recommends the “1-3- 6-12 day rule” for the initiation of NOACs after transient ische- mic attack or acuteischemicstroke. 16 However, the recom- mendations are based on expert opinion and are not supported by clinical trial data. An analysis ofthe Virtual International Stroke Trials Archive (VISTA) database found that the early ini- tiation of anticoagulants (2-3 days after stroke) was associ- ated with substantially fewer recurrent events during the fol- lowing weeks without an increased risk of symptomatic intracerebral hemorrhages. 17 However, the finding is subject to substantial confounding by indication. In a prospective ob- servational study that enrolled 1029 consecutive patients with acuteischemicstroke and known or newly diagnosed AF with- out contraindications to anticoagulation, compared with ini- tiation of treatment before 4 days or more than 14 days after stroke onset, initiation of anticoagulants within 4 to 14 days ofstroke onset was associated with a significant reduction inthe composite ofstroke, transient ischemic attack, sympto- matic systemic embolism, symptomatic cerebral bleeding, and major extracranial bleeding within 90 days from acutestroke. 18 In a recent small, prospective observational study of 60 pa- tients initiating rivaroxaban at a median time of 3 days after mild to moderate cardioembolic stroke or transient ischemic attack, no patient developed symptomatic hemorrhagic trans- formation, and 8 patients had asymptomatic new hemor- rhagic transformation or worsening of hemorrhagic transfor- mation on results of follow-up MRI obtained 7 days after initiation of rivaroxaban, suggesting the safety of rivaroxa- ban treatment intheacute stage. 19 Our findings support the recommendations and are generally in accordance with the findings ofthe earlier observational studies.
Materials and methods Patients and evaluation
The study subjects were drawn from consecutive patients with acuteischemicstroke who had been registered inthe prospective stroke registry from January 2001 to June 2007. During admission, all patients with cerebral infarction within 7 days after symptom onset were thor- oughly investigated. Patients were evaluated with angiography, 12-lead electrocardiography, chest x-ray, lipid profile and standard blood tests. Transesophageal echocardiography, trans- thoracic echocardiography, heart CT, Holter monitoring and continuous EKG monitoring instroke unit were also performed. Among the study patients, 388 (72.1%) patients underwent continuous EKG monitoring and 246 (45.7%) patients underwent echocardiography. More detailed information about etiologic evaluations ofthe patients was described in S1 Table.
Proximal HV, which is frequently observed prox- imal to or within the Sylvian fissure, may have differ- ent implications in comparison to distal HV. In contrast to distal HV, 92% of patients with proximal MCA occlusion had proximal HV, regardless ofthe initial ischemic lesion volume, lesion volume pro- gression, and clinical severity. Proximal HV was not a useful prognostic indicator in this study. Proximal HV may be used as a marker for arterial occlusion, presumably the result ofthe thrombus inside the ar- terial lumen. 4,7 Distal HV is more likely related to either slow, anterograde flow at the site ofthe occlu- sion or retrograde collateral flow from arteries unaf- fected by occlusion, both having a relative delay in transit time with the latter owing to a more circui- tous route of delivery. In patients with similar perfu- sion lesion volumes, prominent distal HV may provide a mechanism for discriminating tissue kept viable for extended periods by way of a well- developed collateral network from tissue rapidly evolving as the result of marginalized flow distal to the site ofthe occlusion.
This study had limitations. We did not investigate blood samples from the general popula- tion. However, the main goals of our study were to demonstrate the association ofthe pres- ence, burden, and progression of cerebral SVD. Second, all of our blood samples and brain image findings were acquired from patients with acutestroke at the time of admission. There- fore, we were unable to investigate serial changes in Klotho concentration and progression in cerebral SVD findings of brain MRI. Third, we did not perform lumbar puncture for CSF study, although Klotho which is present in choroid plexus might be good to test for association Klotho with cerebral SVD. The reason was because lumbar puncture for CSF study was risky procedure inacuteischemicstroke patients because patients was taking medication including anti-thrombotic agent.
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.