Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes.

OBJECTIVE: The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated. METHODS: Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next-generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age-matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days. RESULTS: In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age-matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83-33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (ß = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH-], aOR = 5.63, 95% CI = 3.24-9.77, p < 0.001) and 90-day functional disability (72/110 [CH+] vs 99/270 [CH-], aOR = 2.15, 95% CI = 1.20-3.88, p = 0.011). INTERPRETATION: CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836-847.

The impact of statin treatment duration on the risk of new-onset diabetes mellitus and recurrent vascular events in ischemic stroke patients: a linked data analysis.

INTRODUCTION: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. METHODS: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). RESULTS: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes. CONCLUSION: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

The effect of audiovisual feedback of monitor/defibrillators on percentage of appropriate compression depth and rate during cardiopulmonary resuscitation.

BACKGROUND: High quality cardiopulmonary resuscitation (CPR) is one of the key elements of the survival chain in cardiac arrest. Audiovisual feedback of chest compressions have been suggested to be beneficial by increasing the quality of CPR in the simulated cardiac arrests. METHODS: A prospective before and after study was performed to investigate the effect of a real-time audiovisual feedback system on CPR quality during in-hospital cardiac arrest in intensive care units from November 2018 to February 2022. In the feedback period, CPR was performed with the aid of the real-time audiovisual feedback system. The primary outcome was the percentage of compressions with both adequate depth (5.0-6.0 cm) and rate (100-120/minute). RESULTS: A total of 27,295 compressions in 30 cardiac arrests in the no-feedback period and 27,965 compressions in 30 arrests in the feedback period were analyzed. The percentage of compressions with both adequate depth and rate was 11.8% in the feedback period and 16.8% in the no-feedback period (P < 0.01). The percentage of compressions with adequate rate in the feedback period was lower than that in the no-feedback period (67.3% vs. 75.5%, P < 0.01). The percentage of beyond-target depth with the feedback was significantly higher than that without feedback (64.2% vs. 51.4%, P < 0.01). CONCLUSION: Real-time audiovisual feedback system did not increase CPR quality and was associated with a higher percentage of compression depth deeper than the recommended 5.0-6.0 cm. It is essential to explore more effective ways of implementing feedback in real clinical settings to improve of the quality of CPR. TRIAL REGISTRATION: NCT03902873 (study start: Nov. 2018, initial release April 2019, retrospectively registered).

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

BACKGROUND: Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. METHODS: We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. RESULTS: Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). CONCLUSION: Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). METHODS: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). RESULTS: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. DISCUSSION/CONCLUSION: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.

Dynamic change of neutrophil-to-lymphocyte ratio and symptomatic intracerebral hemorrhage after endovascular recanalization therapy.

OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) is a known marker of systemic inflammation. Recent studies demonstrated its applicability as a marker of poor prognosis for stroke patients. In this study, we evaluated the relationship between dynamic changes in the NLR and sICH in patients with successful recanalization following ERT. MATERIALS AND METHODS: This study included 128 patients with acute ischemic stroke who underwent successful ERT between January 2013 and November 2019. We evaluated the NLR pre-ERT (at admission) and post-ERT (at 24-36 h after ERT). The symptomatic ICH and miserable outcomes at 3 months after ERT were analyzed as outcomes. sICH was defined as type-2 parenchymal hematoma with neurological deterioration (defined as National Institute of Health Stroke Scale score ≥4). Moreover, a modified Rankin Scale score of 5-6 at 3 months was considered a miserable outcome. RESULTS: Among the included patients, sICH occurred in 12 (9.4%). The sICH group had significantly higher post-ERT NLR (P < 0.001) and ∆NLR (calculated as the difference between pre-ERT NLR and post-ERT NLR) (P = 0.004). In the multivariate analysis, the post-ERT NLR was independently associated with sICH (odds ratio [OR], 1.166; 95% confidence interval [CI], 1.041-1.306; P = 0.008) and miserable outcome at 3 months (OR, 1.101; 95% CI, 1.002-1.210; P = 0.045). CONCLUSIONS: This study demonstrated that temporal elevation of the NLR is associated with sICH events after successful ERT in patients with acute ischemic stroke. The temporal variation in NLR may help to identify high-risk patients with sICH after ERT.

Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes in patients with vascular brain injury; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. The primary objective of the INTREPID (Impact of Fever Prevention in Brain-Injured Patients) trial is to test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury. METHODS: INTREPID is a prospective randomized open blinded endpoint study of fever prevention versus usual care in patients with ischemic or hemorrhagic stroke. The fever prevention intervention utilizes the Arctic Sun System and will be compared to standard care patients in whom fever may spontaneously develop. Ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage patients will be included within disease-specific time-windows. Both awake and sedated patients will be included, and treatment is initiated immediately upon enrollment. Eligible patients are expected to require intensive care for at least 72 h post-injury, will not be deemed unlikely to survive without severe disability, and will be treated for up to 14 days, or until deemed ready for discharge from the ICU, whichever comes first. Fifty sites in the USA and worldwide will participate, with a target enrollment of 1176 patients (1000 evaluable). The target temperature is 37.0 °C. The primary efficacy outcome is the total fever burden by °C-h, defined as the area under the temperature curve above 37.9 °C. The primary secondary outcome, on which the sample size is based, is the modified Rankin Scale Score at 3 months. All efficacy analyses including the primary and key secondary endpoints will be primarily based on an intention-to-treat population. Analysis of the as-treated and per protocol populations will also be performed on the primary and key secondary endpoints as sensitivity analyses. DISCUSSION: The INTREPID trial will provide the first results of the impact of a pivotal fever prevention intervention in patients with acute stroke ( www.clinicaltrials.gov ; NCT02996266; registered prospectively 05DEC2016).

Senolytic Therapy for Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke is one of the leading causes of death, and even timely treatment can result in severe disabilities. Reperfusion of the ischemic stroke region and restoration of the blood supply often lead to a series of cellular and biochemical consequences, including generation of reactive oxygen species (ROS), expression of inflammatory cytokines, inflammation, and cerebral cell damage, which is collectively called cerebral ischemia-reperfusion (IR) injury. Since ROS and inflammatory cytokines are involved in cerebral IR injury, injury could involve cellular senescence. Thus, we investigated whether senolytic therapy that eliminates senescent cells could be an effective treatment for cerebral IR injury. To determine whether IR induces neural cell senescence in vitro, astrocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced astrocyte senescence and senescent cells in OGD/R-injured astrocytes were effectively eliminated in vitro by ABT263, a senolytic agent. IR in rats with intraluminal middle cerebral artery occlusion induced cellular senescence in the ischemic region. The senescent cells in IR-injured rats were effectively eliminated by intravenous injections of ABT263. Importantly, ABT263 treatment significantly reduced the infarct volume and improved neurological function in behavioral tests. This study demonstrated, for the first time, that senolytic therapy has therapeutic potential for cerebral IR injury.

Regional Arterial Spin Labeling Perfusion Defect Is Associated With Early Ischemic Recurrence in Patients With a Transient Ischemic Attack.

Background and Purpose- With the lack of confirmatory examinations, the distinction of a transient ischemic attack (TIA) from various TIA-mimicking diseases is difficult, particularly in diffusion-weighted imaging (DWI)-negative TIAs. In this study, we aimed to evaluate the relationship between arterial spin labeling (ASL) perfusion defects and early ischemic recurrence (FU-DWI [+]) in patients with DWI-negative TIAs. Methods- We assessed consecutive patients with a DWI-negative TIA within 24 hours of symptom onset, who underwent both ASL images and follow-up magnetic resonance imaging during the acute period. As markers of the ASL images, we evaluated the ASL perfusion defects in each hemisphere. Arterial transit artifact (ATA) and intraarterial high-intensity signal (IAS) were also rated as markers of collateral status and blood stagnation due to large vessel occlusion, respectively. Results- Among the 136 patients with a DWI-negative TIA, 33 patients had FU-DWI (+) lesions in 36 hemispheres. In the multivariable analysis, ASL defects remained an independent predictor of FU-DWI (+) (adjusted odds ratio, 13.94 [95% CI, 5.77-33.70], P<0.001). In the evaluation of the interactive relationship between ASL defects and ATA/IAS, the (ASL [+] ATA [-]) group showed the highest frequencies of FU-DWI (+) events (55.6%) with the highest adjusted odds ratio values (adjusted odds ratio, 14.86 [95% CI, 5.63-39.24], P<0.001), indicating a negative synergistic effect between the ASL defects and ATA. Meanwhile, the (ASL [+] IAS [+]) group showed higher frequencies of FU-DWI (+) and higher adjusted odds ratio values than those of the (ASL [+] IAS [-]) and (ASL [-] IAS [-]) groups, indicating a positive synergistic effect. Conclusions- We demonstrated that ASL perfusion defects were associated with ipsilateral FU-DWI (+) in patients with a DWI-negative TIA. Furthermore, this association was enhanced with IASs and attenuated with ATAs.

Blood pressure variability and hemorrhagic transformation in patients with successful recanalization after endovascular recanalization therapy: A retrospective observational study.

OBJECTIVE: Although blood pressure (BP) variability has been regarded as a risk factor for hemorrhagic transformation (HTF) after intravenous thrombolysis, its effect on HTF after endovascular recanalization therapy (ERT) remains to be elucidated. We aimed to study the relationship between BP variability and symptomatic intracerebral hemorrhage (sICH) after successful recanalization with ERT. METHODS: A total of 211 patients with acute ischemic stroke and successful recanalization (thrombolysis in cerebral infarction 2b or 3) after ERT were included between January 2013 and May 2017. The BP data following ERT was obtained over the first 24 hours using parameters including mean, maximum, minimum, difference between maximum and minimum, standard deviation, coefficient of variation, successive variations, and time rate (TR) of BP variation for systolic BP (SBP) and diastolic BP. sICH was defined as parenchymal hemorrhage type 2 with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale. RESULTS: Among the included patients, 20 (9.5%) developed sICH after successful ERT. The parameters linked with BP fluctuation over time were significantly related to sICH. After adjusting for confounders, the TR of SBP (per 0.1 mmHg/min increase) variation was independently associated with sICH (odds ratio = 1.71, 95% confidence interval = 1.013-2.886). INTERPRETATION: Time-related BP variability in the first 24 hours following successful ERT was more correlated with sICH than other absolute BP levels. This suggests that maintaining a stable BP may be an important factor in preventing sICH after successful ERT. Ann Neurol 2019;85:574-581.

Focal hyperemia in Wernicke's encephalopathy: a preliminary arterial spin labeling MRI study.

Although a perturbed cerebral blood flow (CBF) has been reported in patients with Wernicke's encephalopathy (WE), its clinical meaning is still elusive. A retrospective analysis of 10 patients (male, 6; mean age, 57.7 years) with WE between October 2012 and May 2018 was performed. Brain imaging was performed using fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), arterial spin labeling (ASL) perfusion-weighted imaging (PWI), and contrasted enhanced T1-weighted imaging. All patients had symmetric high signal intensity lesions in the vulnerable areas on FLAIR or DWI with focal hyperintensity on ASL-PWI (100% sensitivity). CBFlesion was variable (from 70 mL/100 g/min to 190.0 mL/100 g/min). CBFlesion/CBFwhite matter was elevated, ranging from 2.5 to 5.5. Focal hyperintensity on ASL in the vulnerable areas can be a diagnostic clue for WE.

Neurological Pupil Index as an Indicator of Neurological Worsening in Large Hemispheric Strokes.

BACKGROUND/OBJECTIVE: Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes. METHODS: Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening. RESULTS: In this study, 2442 quantitative pupillary assessments were performed (n = 30; mean age, 67.9 years; males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 ± 0.65 vs. 4.45 ± 0.46, P < 0.001; and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration. CONCLUSIONS: Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients.

Lack of Association between Low Cumulative Dose of Hydroxyethyl Starch and Acute Kidney Injury in Patients with Acute Ischemic Stroke.

BACKGROUND: Hydroxyethyl starch (HES, 6% 130/0.4) has been used as a volume expander for the treatment of cerebral hypoperfusion in acute ischemic stroke. Although HES use was associated with renal failure in sepsis or critical illness, it still remains to be elucidated whether HES is linked to renal adverse events in patients with acute ischemic stroke. METHODS: A total of 524 patients with acute ischemic stroke within 7 days of onset were included between January 2012 and May 2016. Renal function on admission and follow-up on day 7 ± 2 was assessed using serum creatinine (SCr) and estimated glomerular filtration rate (eGFR). Propensity score matching (PSM) was used to perform a 1:1 matched-pair analysis to minimize the group differences caused by covariates. The percentage of patients with new-onset acute renal injury (AKI) using the Kidney Disease: Improving Global Outcomes or good functional outcome (modified Rankin Scale 0-2) at 90 days were compared between HES cohort and controls. RESULTS: Among the included patients (mean age, 68.6 years; male, 56.5%), 81 patients (15.5%) were HES cohort (median cumulative dose, 1,450 mL). Baseline renal function was better in HES cohort compared to that in the controls (SCr, 0.87 ± 0.43 mg/dL vs. 1.15 ± 1.15 mg/dL, P < 0.001; eGFR, 86.91 ± 24.27 mL/min vs. 74.55 ± 29.58 mL/min, P < 0.001), which became not significant in PSM cohort (72 pairs). The percentage of new-onset AKI did not differ between the HES cohort and controls (1.4% vs. 1.4%, P = 1.000). In addition, new-onset AKI was not related to HES (odds ratio, 1.422; 95% confidence interval, 0.072-28.068; P = 0.817) after adjusting for confounders. HES cohort tended to have higher percentage of good functional outcome at 90 days compared to controls, which failed to reach statistical significance (68.1% vs. 54.2%, P = 0.087). CONCLUSION: A low cumulative dose of HES was not associated with renal adverse events in patients with acute ischemic stroke.

Impact of the Dedicated Neurointensivists on the Outcome in Patients with Ischemic Stroke Based on the Linked Big Data for Stroke in Korea.

BACKGROUND: Neurocritical care by dedicated neurointensivists may improve outcomes of critically ill patients with severe brain injury. In this study, we aimed to validate whether neurointensive care could improve the outcome in patients with critically ill acute ischemic stroke using the linked big dataset on stroke in Korea. METHODS: We included 1,405 acute ischemic stroke patients with mechanical ventilator support in the intensive care unit after an index stroke. Patients were retrieved from linking the Clinical Research Center for Stroke Registry and the Health Insurance Review and Assessment Service data from the period between January 2007 and December 2014. The outcomes were mortality at discharge and at 3 months after an index stroke. The main outcomes were compared between the centers with and without dedicated neurointensivists. RESULTS: Among the included patients, 303 (21.6%) were admitted to the centers with dedicated neurointensivists. The patients treated by dedicated neurointensivists had significantly lower in-hospital mortality (18.3% vs. 26.8%, P = 0.002) as well as lower mortality at 3-month (38.0% vs. 49.1%, P < 0.001) than those who were treated without neurointensivists. After adjusting for confounders, a treatment without neurointensivists was independently associated with higher in-hospital mortality (odds ratio [OR], 1.59; 95% confidence intervals [CIs], 1.13-2.25; P = 0.008) and 3-month mortality (OR, 1.48; 95% CIs, 1.12-1.95; P = 0.005). CONCLUSION: Treatment by dedicated neurointensivists is associated with lower in-hospital and 3-month mortality using the linked big datasets for stroke in Korea. This finding stresses the importance of neurointensivists in treating patients with severe ischemic stroke.

Targeted Delivery of Iron Oxide Nanoparticle-Loaded Human Embryonic Stem Cell-Derived Spherical Neural Masses for Treating Intracerebral Hemorrhage.

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.

High Neutrophil-to-Lymphocyte Ratio Predicts Stroke-Associated Pneumonia.

Background and Purpose- Although there are a variety of risk factors and predictive models for stroke-associated pneumonia (SAP), more objective and easily accessible markers are still needed. In this study, we evaluated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and SAP in patients with acute ischemic stroke. Methods- We assessed 1317 consecutive patients with acute ischemic stroke. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. The severity of pneumonia was rated using scores from the Pneumonia Severity Index, the quick Sequential Organ Failure Assessment, and the Acute Physiology and Chronic Health Evaluation II. The NLR was calculated after dividing absolute neutrophil counts by absolute lymphocyte counts. Results- Among the total patients, SAP occurred in 112 (9.0%) patients. Using a multivariable analysis, the NLR (adjusted odds ratio=1.55; 95% confidence interval, 1.15-2.11; P=0.005) remained significant after adjusting for confounders. In addition, age, atrial fibrillation, previous stroke history, initial National Institutes of Health Stroke Scale score, and high-sensitivity C-reactive protein were also significant, independent of NLR. The NLR was higher in the severe pneumonia group when it was assessed by Pneumonia Severity Index ( P<0.001), quick Sequential Organ Failure Assessment ( P<0.001), and Acute Physiology and Chronic Health Evaluation II scores ( P=0.004). Furthermore, patients who had SAP had worse clinical outcomes both during hospitalization and after discharge. Conclusions- We demonstrated that a higher NLR predicted SAP in patients with acute ischemic stroke. The NLR may help to identify high-risk patients in time and provide clues for further studies about preventive antibiotic therapy.

Decompressive craniectomy for herpes simplex encephalitis complicated by frank intracerebral hemorrhage: a case report and review of the literature.

BACKGROUND: Herpes simplex encephalitis is the most common type of sporadic encephalitis worldwide. Frank intracerebral hemorrhage complicating the disease course in herpes simplex encephalitis patients is rare, especially cases where surgical decompression is necessary. Here, we report a previously healthy female with herpes simplex encephalitis who underwent surgical decompression due to temporal lobe hemorrhage. CASE PRESENTATION: A previously healthy 34-year-old Korean female presented with fever, myalgia and severe headache. Brain MRI showed a high T2 signal intensity change and diffuse swelling of the right temporal lobe. Polymerase chain reaction testing of the cerebrospinal fluid confirmed the presence of herpes simplex virus 1. The patient was admitted for close observation and intravenous acyclovir. On hospital day 3, she had a sudden onset of vomiting and severe headache. Brain CT showed frank temporal lobe hemorrhage. Despite aggressive medical treatment, she became increasingly drowsy. Ultimately, she underwent emergency right decompressive craniectomy, expansile duraplasty and intracranial pressure monitor insertion. The patient recovered fully without any neurological deficits or neuropsychological problems. She was discharged after completion of 2 weeks of acyclovir and returned 2 months later for cranioplasty. CONCLUSIONS: Patients with severe herpes simplex encephalitis complicated by intracerebral hemorrhage or malignant cerebral edema should undergo aggressive medical treatment. Surgical decompression should also be actively considered in these severe cases to prevent further neurological deterioration.

Building Linked Big Data for Stroke in Korea: Linkage of Stroke Registry and National Health Insurance Claims Data.

BACKGROUND: Linkage of public healthcare data is useful in stroke research because patients may visit different sectors of the health system before, during, and after stroke. Therefore, we aimed to establish high-quality big data on stroke in Korea by linking acute stroke registry and national health claim databases. METHODS: Acute stroke patients (n = 65,311) with claim data suitable for linkage were included in the Clinical Research Center for Stroke (CRCS) registry during 2006-2014. We linked the CRCS registry with national health claim databases in the Health Insurance Review and Assessment Service (HIRA). Linkage was performed using 6 common variables: birth date, gender, provider identification, receiving year and number, and statement serial number in the benefit claim statement. For matched records, linkage accuracy was evaluated using differences between hospital visiting date in the CRCS registry and the commencement date for health insurance care in HIRA. RESULTS: Of 65,311 CRCS cases, 64,634 were matched to HIRA cases (match rate, 99.0%). The proportion of true matches was 94.4% (n = 61,017) in the matched data. Among true matches (mean age 66.4 years; men 58.4%), the median National Institutes of Health Stroke Scale score was 3 (interquartile range 1-7). When comparing baseline characteristics between true matches and false matches, no substantial difference was observed for any variable. CONCLUSION: We could establish big data on stroke by linking CRCS registry and HIRA records, using claims data without personal identifiers. We plan to conduct national stroke research and improve stroke care using the linked big database.

Blood Pressure Management for Acute Ischemic and Hemorrhagic Stroke: The Evidence.

Hypertension is the most common modifiable risk factor for stroke (both ischemic and hemorrhagic types). In the hyperacute phase, a majority of patients shows an elevated blood pressure (BP) at the time of presentation because of sympathetic hyperactivity or a physiological response to tissue ischemia. Therefore, BP may decrease spontaneously in a few hours and may drop further when complete recanalization is achieved. In stroke guidelines, an elevated BP is usually left untreated up to a systolic BP (SBP) of 220 mm Hg and a diastolic BP of 120 mm Hg. This recommendation is based on the BP level that corresponds to the upper limit of the pressure autoregulation zone above which cerebral blood flow is directly dependent on BP. However, in patients in whom administration of recombinant tissue-type plasminogen activator is indicated, BP should be controlled to a level < 185/110 mm Hg before infusion and should be maintained at levels < 180/105 mm Hg to limit the risk of intracerebral hemorrhage (ICH). In cases where endovascular thrombectomy is considered, the optimal intra- and postprocedural BP target have not yet been clearly identified. Expert opinion recommends that intraprocedural BP reduction could be associated with a risk of poor outcomes, and therefore, SBP may be reduced only to 120 to 140 mm Hg after successful reperfusion therapy. However, this recommendation is primarily based on observational studies and requires validation in prospective trials. It has been observed that in patients presenting with an ICH, there is no perihematomal penumbra noted and rapid BP reduction is generally well tolerated without a risk of neurological worsening. Multiple trials describing acute reduction of BP recommend SBP reduction only to 140 mm Hg because while there is no benefit of better functional outcomes below that level, there exists a definite risk of increased renal complications.

Treatment of Cryptogenic Stroke with Active Cancer with a New Oral Anticoagulant.

BACKGROUND: Low-molecular weight heparin (LMWH) was shown to be effective and safe in treating venous thromboembolism, and generally used for stroke in cancer patients, but its effects on stroke are unclear. We compared clinical outcomes between LMWH and new oral anticoagulant (NOAC) in patients with cancer-related stroke. METHODS: We enrolled patients with cryptogenic ischemic stroke with active cancer who were treated with LMWH or NOAC between May 2012 and June 2015. The clinical outcomes, including early neurologic deterioration, early radiologic recurrence, 3-month modified Rankin scale score, 90-day mortality, cardio-cerebrovascular recurrence, and bleeding complications, were compared. RESULTS: Among 48 patients, 7 patients were treated with NOAC, and the remaining 41 patients with LMWH. Overall, the participants presented poor outcomes, including 20 (42%) early neurologic deteriorations, 28 (58%) early radiologic recurrences, 34 (71%) poor modified Rankin scale scores, 27 (56%) 90-day mortality events, 24 (50%) cardio-cerebrovascular recurrences, and 18 (38%) bleeding complications, that led to a change or temporary hold in medication in 12 cases. No statistical differences were found between the 2 groups in terms of demographic, clinical, or cardiovascular risk factors and clinical outcomes. CONCLUSIONS: NOAC showed the similar clinical outcomes and safety compared with LMWH in the treatment of cryptogenic ischemic stroke in active cancer patients.