Transdural Revascularization by Multiple Burrhole After Erythropoietin in Stroke Patients With Cerebral Hypoperfusion: A Randomized Controlled Trial.

BACKGROUND: In patients with acute symptomatic stroke, reinforcement of transdural angiogenesis using multiple burr hole (MBH) procedures after EPO (erythropoietin) treatment has rarely been addressed. We aimed to investigate the efficacy and safety of cranial MBH procedures under local anesthesia for augmenting transdural revascularization after EPO treatment in patients with stroke with perfusion impairments. METHODS: This prospective, randomized, blinded-end point trial recruited patients with acute ischemic stroke with a perfusion impairment of grade ≥2 within 14 days of symptom onset, steno-occlusive mechanisms on imaging examinations, and absence of transdural collaterals on transfemoral cerebral angiography. Patients were randomly assigned to receive MBH + EPO or MBH alone. The primary and secondary outcomes were revascularization success (trans-hemispheric and trans-burr hole) at 6 months and adverse events, respectively. RESULTS: We evaluated 42 of the 44 targeted patients, with 2 patients lost to follow-up. The combined and MBH-only (n=21 each) groups showed no differences in demographic characteristics and baseline perfusion parameters. Significantly, more cases of trans-hemispheric (19/21 [90.5%] versus 12/21 [57.1%]) and trans-burr hole (42/58 [72.4%] versus 30/58 [51.7%]) revascularization and significant improvements in perfusion parameters were observed in the combined group relative to the MBH-only group. No differences in treatment-related complications were observed between groups. Even after adjustment for potential covariates, EPO usage was an independent factor of successful hemispheric revascularization in this study (odds ratio, 6.41 [95% CI, 1.08-38.02]). CONCLUSIONS: The combination of MBH and EPO is safe and feasible for reinforcing transdural revascularization in acute steno-occlusive patients with perfusion impairments. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02603406.

Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial.

BACKGROUND: Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy. METHODS: This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received-placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 12 weeks. RESULTS: Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; P=0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92-2.60) between the placebo and low-dose groups and 1.61 (0.94-2.76) between the placebo and high-dose groups. No serious adverse events were reported. CONCLUSIONS: The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0-2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.

Null variants in DYSF result in earlier symptom onset.

We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18-30] and 36 years [IQR: 27-48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype-phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17-25]) than the N/M group (median: 29 years [IQR: 23-35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56-92]) than in the N/M group (median: 89 [IQR: 78-98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.

The Clinical Usefulness of Targeted Temperature Management in Acute Ischemic Stroke with Malignant Trait After Endovascular Thrombectomy.

BACKGROUND/OBJECTIVE: Targeted temperature management (TTM) may be more beneficial after endovascular treatment (EVT) in patients with a large ischemic core. Therefore, we assessed the usefulness of TTM for such patients from a multicenter endovascular registry. METHODS: Anterior circulation stroke patients who underwent endovascular recanalization were included; acute ischemic stroke with malignant traits was designated as (1) baseline Alberta Stroke Program Early CT Score (ASPECTS) below 6 and (2) diffusion-weighted imaging (DWI) lesion volume measurement (> 82 ml) or National Institutes of Health Stroke Scale score > 20 and item Ia > 0. TTM (34.5 °C) was maintained for at least 48 h. RESULTS: We evaluated baseline demographics, risk factors, EVT parameters, and clinical outcomes between the TTM and non-TTM groups. Among the 548 patients, the TTM group (n = 91) significantly had a lower baseline ASPECTS (p < 0.001) and a higher DWI volume (p < 0.001) than the non-TTM group (n = 457). TTM group had a lower prevalence of favorable outcome (0-2 of modified Rankin Scale at 3 months; p = 0.008) than the non-TTM group. In a subgroup analysis of malignant trait patients (n = 80), TTM patients (n = 28) had more favorable outcome (32.1% vs. 7.7% p = 0.009) and less hemorrhagic transformation (none vs. any hemorrhage, p = 0.007) than non-TTM patients (n = 52). After adjusting for potential outcome predictors, TTM (odds ratio [OR] 4.63; confidence interval [CI] 1.20-17.89; p = 0.026) and hypertension (OR 0.18; CI 0.04-0.74; p = 0.018) were found to be independent determinants. CONCLUSIONS: Our data suggest that TTM attenuates impending hemorrhagic transformation and leads to favorable clinical outcomes in EVT patients with malignant trait.

Predicting Endovascular Treatment Outcomes in Acute Vertebrobasilar Artery Occlusion: A Model to Aid Patient Selection from the ASIAN KR Registry.

Background The decision to perform endovascular treatment (EVT) for stroke related to vertebrobasilar occlusion (VBO) remains controversial. Purpose To identify preprocedural predictors of good outcomes and to develop a model to aid patient selection for VBO. Materials and Methods For this retrospective study using a Korean multicenter registry, a predictive model for good outcomes (modified Rankin scale score, 0-2) was generated based on a derivation sample of patients with VBO (January 2011-February 2016). Preprocedural parameters, including onset-to-puncture time, infarct volume, occlusion type as a surrogate marker of intracranial atherosclerotic stenosis-related occlusion or embolic occlusion (truncal-type occlusion vs branching site occlusion), and collateral status, were analyzed. Continuous variables were dichotomized based on receiver operating characteristic analysis. Multiple logistic regression analysis was performed to generate a predictive model. The model was internally validated with the bootstrap method and was externally validated with a single-center sample (April 2016-December 2018). Results A predictive model was generated from 71 patients (mean age, 67 years ± 11 [standard deviation]; 41 [58%] men) and was externally validated in 32 patients (mean age, 72 years ± 13; 19 [59%] men). The composite of initial DW imaging volume of less than 10 mL (odds ratio [OR], 19.3; 95% confidence interval [CI]: 3.0, 126.4; P = .002), onset-to-puncture time of less than 8 hours (OR, 8.7; 95% CI: 1.8, 42.0; P = .007), and branching-site occlusion (OR, 6.1; 95% CI: 1.5, 26.0; P = .01) could be used to predict good outcomes, with a median area under the receiver operating characteristic curve of 0.86 (interquartile range [IQR], 0.77-0.95; bootstrap optimism-corrected C statistic, 0.837) in the derivation sample and 0.78 (IQR, 0.62-0.95) in the validation sample. Results failed to show an association between collateral status and outcome (P = .67). Conclusion When selecting patients with vertebrobasilar occlusion for endovascular treatment, the combination of onset-to-puncture time of less than 8 hours, initial infarct volume of less than 10 mL, and presence of branching-site occlusions is indicative of a good outcome. © RSNA, 2020 Online supplemental material is available for this article.

Optic nerve sheath diameter change in prediction of malignant cerebral edema in ischemic stroke: an observational study.

BACKGROUND: In acute large anterior circulation infarct patients with large core volume, we evaluated the role of optic nerve sheath diameter (ONSD) change rates in prediction of malignant progression. METHODS: We performed a retrospective observational study including patients with anterior circulation acute ischemic stroke with large ischemic cores from January 2010 to October 2017. Primary outcome was defined as undergoing decompressive surgery or death due to severe cerebral edema, and termed malignant progression. Patients were divided into malignant progressors and nonprogressors. Malignant progression was divided into early progression that occurred before D1 CT, and late progression that occurred afterwards. Retrospective analysis of changes in mean ONSD/eyeball transverse diameter (ETD) ratio, and midline shifting (MLS) were evaluated on serial computed tomography (CT). Through analysis of CT at baseline, postprocedure, and at D1, the predictive ability of time based change in ONSD/ETD ratio in predicting malignant progression was evaluated. RESULTS: A total of 58 patients were included. Nineteen (32.8%) were classified as malignant; 12 early, and 7 late progressions. In analysis of CTpostprocedure, A 1 mm/hr. rate of change in MLS during the CTbaseline-CTpostprocedure time phase lead to a 6.7 fold increased odds of early malignant progression (p < 0.05). For ONSD/ETD, 1%/hr. change lead to a 1.6 fold increased odds, but this association was trending (p = 0.249). In the CTD1, 1%/day change of ONSD/ETD in the CTbaseline-CTD1 time phase lead to a 1.4 fold increased odds of late malignant progression (p = 0.021) while 1 mm/day rate of change in MLS lead to a 1.5 fold increased odds (p = 0.014). CONCLUSIONS: The rate of ONSD/ETD changes compared to baseline at D1 CT can be a predictor of late malignant progression along with MLS. ONSD/ETD change rates evaluated at postprocedure did not predict early malignant progression.

Local tirofiban infusion for remnant stenosis in large vessel occlusion: tirofiban ASSIST study.

BACKGROUND: Compared with embolic occlusions, intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusions (LVOs) often require rescue treatment following mechanical thrombectomy (MT). Herein, we hypothesized that local tirofiban infusion can be effective and safe for remnant stenosis in LVO during endovascular treatment and can improve clinical outcomes. METHODS: This observational multicenter registry study (January 2011 to February 2016) included patients with ICAS who underwent endovascular treatment for LVO within 24 h after stroke onset. An underlying fixed focal stenosis at the occlusion site observed on cerebral angiography during and after MT was retrospectively determined as a surrogate marker of ICAS. Procedural and clinical outcomes were compared between the tirofiban and non-tirofiban groups. RESULTS: Of 118 patients, 59 received local tirofiban infusion. Compared to the non-tirofiban group, patients were older (non-tirofiban group versus tirofiban group; median, 63 years vs. 71 years, p = 0.015) and the onset-to-puncture time was longer (median, 275 min vs. 395 min, p = 0.036) in the tirofiban group. The median percent of residual stenosis prior to rescue treatment tended to be higher in the tirofiban group (80 [71-86] vs. 83 [79-90], p = 0.056). Final reperfusion success (modified Treatment In Cerebral Ischemic 2b-3) was more frequent (42.4%vs. 86.4%, p = 0.016) and post-procedure parenchymal hematoma type 2 and/or thick subarachnoid hemorrhages were less frequent (15.3%vs. 5.1%, p = 0.068) in the tirofiban group. The frequency of favorable outcomes 3 months after endovascular treatment (modified Rankin Scale 0-2) was significantly higher in the tirofiban group (32.2% vs. 52.5%, p = 0.025), and tirofiban administration was an independent predictor of favorable outcomes (odds ratio, 2.991; 95% confidence interval, 1.011-8.848; p = 0.048). CONCLUSIONS: Local tirofiban infusion can be a feasible adjuvant treatment option for patients with ICAS-LVO.

Immediate effects of first-line thrombectomy devices for intracranial atherosclerosis-related occlusion: stent retriever versus contact aspiration.

BACKGROUND: Although stent retriever (SR) is recommended as a frontline device of endovascular treatment (EVT) for embolic large artery occlusion causing acute ischemic stroke, contact aspiration (CA) device showed similar efficacy in the recent trials. However, the efficacy of the both devices as first-line therapy for intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion has not yet been established. Therefore, we compared the immediate effects and final outcomes of SR and CA as first-line devices for treating ICAS-related occlusions. METHODS: We retrospectively analyzed the data of patients who underwent EVT for acute ischemic stroke from the registry of three Korean hospitals. Patients with ICAS-related occlusion who were treated within 24 h of onset of the symptoms were included. We investigated immediate reperfusion performance, immediate safety outcomes, and 3-month clinical outcomes for the two first-line devices. RESULTS: Of the 720 registered patients, 111 were eligible for this study. Forty-nine patients (44.1%) used SR and 62 (55.9%) used CA as the first-line device. Achieving successful reperfusion immediately after first-line thrombectomy was more frequent in the SR group than that in the CA group (77.6% vs. 43.5%, p = 0.001), with fewer additional rescue treatments (12.2% vs. 59.7%, p < 0.001). The incidence of iatrogenic dissection or rupture was lower in the SR group than that in the CA group (8.2% vs. 29.0%, p = 0.012). After additional rescue treatments, however, the final successful reperfusion rate did not differ between the two groups (SR 87.8% vs. CA 77.4%, p = 0.247), and there was no significant difference in the 3-month good outcomes (modified Rankin Scale, p = 0.524). CONCLUSIONS: First-line SR thrombectomy showed higher immediate reperfusion and less vessel injury for ICAS-related occlusions than CA. However, there was no significant difference in the final reperfusion status or 3-month outcomes from additional rescue treatments.

Ischemic Diffusion Lesion Reversal After Endovascular Treatment.

Background and Purpose- Several studies have reported partial reversal of diffusion-weighted imaging (DWI) lesions after acute stroke reperfusion treatment. However, factors associated with DWI reversal have not yet been systematically investigated. We evaluated the factors associated with DWI reversal after endovascular treatment (EVT). Methods- We retrospectively analyzed consecutively encountered patients with acute ischemic stroke who underwent EVT at 3 comprehensive stroke centers in Korea from January 2011 to February 2016. Patients who received EVT within 24 hours of anterior circulation infarction and had both baseline and follow-up DWIs were included. DWI reversal was defined as a decrease in DWI volume from baseline to follow-up. We compared the characteristics and outcomes between patients with and without DWI reversal and assessed independent factors associated with DWI reversal. Results- Of 720 patients encountered during the time period, 404 patients (56.1%) met the study criteria, with 63 patients (15.5%) showing DWI reversal after EVT. The mean time interval between baseline and follow-up DWI was 4.7±2.4 days. Mean baseline DWI volumes of patients with and without DWI reversal were 30.1±36.7 versus 22.0±30.7 mL ( P=0.106), and follow-up DWI volumes were 17.8±24.9 versus 68.7±77.5 mL ( P<0.001). Patients with DWI reversal showed better functional outcomes at 3 months than those without DWI reversal (modified Rankin Scale [interquartile range], 1 [0-3] versus 2 [1-4]; P=0.001). In a multivariate analysis, complete reperfusion (odds ratio, 1.954; 95% CI, 1.063-3.582) and shorter time from baseline DWI to final reperfusion (odds ratio, 0.991; 95% CI, 0.983-0.998) were independently associated with DWI reversal. Conclusions- Complete reperfusion and shorter imaging time to recanalization were independently associated with DWI reversal among patients with acute ischemic stroke who received EVT.

Cranial burr hole with erythropoietin administration induces reverse arteriogenesis from the enriched extracranium.

It is challenging to revitalize ischemic penumbra after an acute stroke with intracranial perfusion insufficiency. To evaluate whether cranial burr hole and erythropoietin (EPO) generate effective revascularization, we investigated the efficacy of the augmentation method for reverse arteriogenesis from the healthy extracranial milieu. An intracranial perfusion insufficiency was created through bilateral internal carotid artery ligation (bICAL) in Sprague-Dawley rats. We administered recombinant human EPO (5000 U/kg) or saline intraperitoneally for 3 days after bICAL. Mechanical barrier disruption (MBD) was performed through a cranial burr hole with small dural cracks in the right hemisphere. The ipsilateral hemisphere with MBD grossly showed vascular networks between the extra- and intra-cranial spaces 2 weeks after the MBD procedure. It also showed significantly increased vessels in the intracranial vasculature adjacent to the MBD region (p = 0.0006). The levels of pro-angiogenic and inflammatory factors with prominent markers of vessel permeability were also significantly increased (MBD-only vs. control; Tnf-α, p = 0.0007; Vegf, p = 0.0206). In the EPO-administered group, such elevations in inflammation were significantly mitigated (combined vs. MBD-only; Tnf-α, p = 0.0008). The ipsilateral hemisphere with MBD-EPO (vs. MBD-only) showed significantly increased vessels (RECA-1, p = 0.0182) and their maturation (RECA-1/α-SMA, p = 0.0046), with upregulation of tumor growth factor-ß1 (Tgf-ß1, p = 0.037) and matrix metalloproteinase-2 (Mmp-2, p = 0.0488). These findings were completely blocked by minocycline (MIC) administration during in vivo (Tgf-ß1, p = 0.0009; Mmp-2, p < 0.0001) and in vitro experiments (tube formation, p < 0.0001). Our data suggest that the MBD procedure (for angiogenic routes) and EPO administration (for an arteriogenic booster) are complimentary and can facilitate successfully "reverse arteriogenesis" in subjects with intracranial perfusion insufficiency.

Prevalence and Socioeconomic Status of Patients with Genetic Myopathy in Korea: A Nationwide, Population-Based Study.

BACKGROUND: Genetic myopathy is a clinically and genetically heterogeneous group of genetic disorders characterized by progressive degeneration of skeletal muscles. Epidemiological studies of genetic myopathy have not yet been performed in Korea. OBJECTIVES: This study used data from the national health insurance claims database to determine the prevalence and socioeconomic status of patients with genetic myopathy in Korea. METHODS: We analyzed the Health Insurance Review and Assessment database from 2007 to 2011. Patients with genetic myopathy were defined based on diagnostic and procedure codes. We then evaluated the prevalence, types of health insurances, and medical expenses of these patients. RESULTS: During the 11-year study period, 2,988 patients with genetic myopathy were enrolled. Among them, 1,762 were men and 1,226 were women. The prevalence per 100,000 population in 2017 was 3.09 (3.94 for men and 2.24 for women). The prevalence of genetic myopathy among men <35 years old (8.33 per 100,000 population) was approximately twice that among women <35 years old (4.06 per 100,000 population). However, there was no significant difference in the prevalence of genetic myopathy among those ≥35 years old according to sex. The ratio of patients using medical aid among all genetic myopathy patients was approximately 4 times than that among the general population in Korea. The medical expenses per person for genetic myopathy increased from USD 2,027 in 2007 to USD 4,810 in 2017. CONCLUSIONS: Our study was the first nationwide epidemiologic study of the prevalence and socioeconomic status of patients with genetic myopathy in Korea. Our results confirmed a sex divergence in a younger population and those with low socioeconomic status among patients with genetic myopathy.

Erythrocyte Fraction Within Retrieved Thrombi Contributes to Thrombolytic Response in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Recent advent of endovascular thrombectomy (EVT) enables us to provide a new perspective on the use of tPA (tissue-type plasminogen activator) through histological analysis of retrieved thrombus. We investigated the responsiveness of intravenous thrombolysis (IVT) according to the thrombus composition in EVT-attempted patients with acute ischemic stroke. METHODS: We reviewed 92 consecutive patients with anterior circulation stroke who received combined IVT and EVT for 2 years. IVT responsiveness is defined as any decrease in the clot burden from baseline computed tomographic angiography to digital subtraction angiography during EVT. We histologically analyzed the relative fractions of red blood cells (RBCs), congregated fibrin and platelets, and white blood cells in the retrieved thrombi using semiautomated color-based segmentation method. Clinical characteristics according to the RBC fraction were investigated, and associated factors with IVT responsiveness were explored. RESULTS: Fifty-two patients with histological analyses were stratified into lowest, middle, and highest tertiles of RBC fraction. Toward higher RBC fraction, there was more common susceptibility vessel signs on magnetic resonance imaging (50.0% versus 66.7% versus 91.7%; P=0.022) and prevalent IVT responsiveness (25.0% versus 41.7% versus 75.0%; P=0.010). IVT-responsive group (n=23) had higher RBC fraction (45.7±15.5% versus 35.9±12.2%; P=0.010), lower fibrin and platelet (50.4±14.0% versus 58.5±11.1%; P=0.027), and lower white blood cells fraction (3.9±2.1% versus 5.5±3.0%; P=0.027) than IVT-unresponsive group (n=29). After adjusting for potential variables, RBC fraction (odds ratio, 1.05; 95% confidence interval, 1.01-1.10) remained only independent determinant of IVT responsiveness. CONCLUSIONS: In EVT-attempted patients with acute ischemic stroke, IVT responsiveness would be closely associated with RBC fraction.

Feasibility of Multiple Burr Hole With Erythropoietin in Acute Moyamoya Patients.

BACKGROUND AND PURPOSE: In patients with acute symptomatic moyamoya (<2 weeks), the feasibility of a combination therapy of multiple burr hole procedure under local anesthesia and intravenous erythropoietin pretreatment was assessed. We also identified the factors associated with transdural revascularization. METHODS: In this prospective single-arm study, perfusion-impaired patients presenting with transient ischemic attack or acute cerebral infarction were assessed. Combination therapy was performed to patients lacking transdural collaterals. Primary outcomes were evaluated clinically with modified Rankin Scale scores and radiologically with revascularization success (transhemispheric, trans-burr hole, and sufficient revascularizations [filling ≥33% of ipsilateral supratentorium]) at 6 months. Treatment-related adverse events were analyzed in 3 phases: pre burr hole, post burr hole, and after-discharge as secondary outcome. Factors associated with sufficient revascularization were investigated. RESULTS: Fifty hemispheres from 37 patients were included. Compared with discharge, modified Rankin Scale score at 6 months significantly improved (2.0 [0.0-5.0] versus 1.0 [0.0-4.0]; P<0.001). Majority had successful revascularization: trans-burr hole arteriogenesis (89.5%), transhemispheric arteriogenesis (98.0%), and sufficient revascularization (52.0%). There was no significant pre burr hole or post burr hole complication. Two (5.4%) transient ischemic attack and 1 (2.7%) cerebral infarction occurred after discharge. Presentation with acute infarction (odds ratio, 4.8; 95% confidence interval, 1.1-21.4), ipsilateral basal moyamoya vessels (odds ratio, 13.9; 95% confidence interval, 1.3-144.2), and delayed mean transit time (odds ratio, 3.9; 95% confidence interval, 1.3-12.2) predicted sufficient revascularization. CONCLUSIONS: Combination therapy allows safe and effective revascularization in moyamoya patients with acute ischemic presentation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03162588.

Low Testosterone Level as a Predictor of Poststroke Emotional Disturbances: Anger Proneness and Emotional Incontinence.

BACKGROUND: The role of sex hormones in poststroke mood and emotional disturbances is unclear. We aimed to evaluate the impact of sex hormones on poststroke emotional disturbance, especially anger proneness (AP) and emotional incontinence (EI). We also investigated whether statins, which are widely used for stroke prevention, affect sex hormone levels or the presence of poststroke AP/EI based on the hypothesis that intensive treatment with statins would inhibit the synthesis of cholesterol, the preferred substrate of testosterone. METHODS: We prospectively enrolled 40 patients who experienced ischemic stroke at least 3 months prior to study enrollment. We performed clinical and laboratory evaluations, including hormone-level measurements and neuropsychological tests. Poststroke AP and EI were assessed using interviews, then patients were divided into 2 groups: AP/EI-present or absent. RESULTS: Of the 40 patients (30 men, mean age 58.8 years), 16 (40.0%) were classified as AP/EI-present group. AP/EI were not related to stroke severity or location; however, the testosterone level was significantly lower in patients with AP/EI than in those without AP/EI (2.1 ± 1.7 vs. 3.9 ± 2.5 ng/mL, P = .023). After adjusting for potential confounding variables, low testosterone levels were a significant independent predictor of AP/EI (odds ratio .68, 95% confidence interval .49-.96, P = .027). In contrast, sex hormone levels and AP/EI prevalence did not differ between statin users and nonusers. CONCLUSIONS: AP/EI were associated with low testosterone levels in patients with previous ischemic stroke, but statin use did not affect AP/EI prevalence.

Feasibility of improved motion-sensitized driven-equilibrium (iMSDE) prepared 3D T1-weighted imaging in the diagnosis of vertebrobasilar artery dissection.

BACKGROUND AND PURPOSE: This study was to evaluate the diagnostic value of improved motion-sensitized driven-equilibrium (iMSDE)-prepared 3D T1-weighted magnetic resonance imaging (MRI) (iMSDE-3DMRI) in intracranial vertebrobasilary dissection (VBD) and to compare iMSDE-3DMRI images with those obtained using 2D high-resolution (HR) MRI with respect to their diagnostic performance in VBD. MATERIALS AND METHODS: We retrospectively reviewed 105 lesions from 102 patients who underwent multimodal imaging and contrast-enhanced iMSDE-3DMRI (CE-iMSDE-3DMRI). The 2D-HRMRI protocol comprised four axial HR images. The CE-iMSDE-3DMRI images were reformatted in the axial, coronal, and sagittal planes. The 2D-HRMRI-based diagnosis was compared with the final diagnosis. The 2D-HRMRI and CE-iMSDE-3DMRI images were examined independently for the diagnosis performance of dissection. RESULTS: VBD was confirmed in 66 lesions in 63 patients; 17 patients had confirmed atherosclerosis, and 22 had no lesions in the vertebrobasilar artery. Diagnostic performances of 2D-HRMRI (AUC, 0.839±0.04; sensitivity, 94.0; specificity, 79.5; diagnostic accuracy, 88.6) CE-iMSDE-3DMRI (AUC, 0.847±0.04; sensitivity, 84.8; specificity, 84.6; diagnostic accuracy, 84.7) and 2D-HRMRI+CE-iMSDE-3DMRI (AUC, 0.893±0.03; sensitivity, 97.0; specificity, 85.0; diagnostic accuracy, 92.5) were good. Comparisons of the diagnostic performance of 2D-HRMRI andCE-iMSDE-3DMRI showed that combined interpretation of 2D-HRMRI and iMSDE-3DMRI yields a significantly higher diagnostic performance than that of 2D-HRMRI (P=0.042). CONCLUSIONS: CE-iMSDE-3DMRI showed good diagnostic performance for the diagnosis of intracranial VBD. These results suggest that CE-iMSDE-3DMRI can be used in combination with 2D-HRMRI for the diagnosis of intracranial VBD.

Cilostazol improves endothelial function in acute cerebral ischemia patients: a double-blind placebo controlled trial with flow-mediated dilation technique.

BACKGROUND: In order to evaluate the impact of cilostazol on endothelial function, we compared the changes of flow-mediated dilation (FMD) between aspirin and cilostazol groups in patients with acute cerebral ischemia. METHODS: Patients presenting with acute cerebral ischemic events were randomly assigned into aspirin (n = 40) or cilostazol (n = 40) group in a double-blinded manner. FMD was measured at baseline (T0) and 90 days (T1). We measured L-arginine at baseline (a precursor of biologically active nitric oxides). Serious and non-serious adverse events were described. RESULTS: Despite no difference in the baseline FMD values (p = 0.363), there was a significant increase of FMD values in cilostazol group (7.9 ± 2.4 to 8.9 ± 2.3%, p = 0.001) and not in aspirin group (8.5 ± 2.6 to 9.3 ± 2.8%, p = 0.108). In the multiple regression analysis performed in cilostazol group, serum L-arginine levels were inversely correlated with FMD at T1 (ß = -0.050, SE: 0.012, p < 0.001) with age, total cholesterol levels, and C-reactive protein as confounders. While T0 FMD values in both aspirin and cilostazol groups did not show any correlation with serum L-arginine levels, the correlation is restored in the cilostazol group at T1 (r = 0.467, p = 0.007), while such is not shown in the aspirin group. There was no difference of serious adverse events between the two groups (p = 0.235). Adverse events were more common in the cilostazol group (35/40 vs. 25/40, p = 0.010), due to frequent headaches (14/40 vs. 3/30, p = 0.003) which was well tolerated. CONCLUSION: Cilostazol improved endothelial function in acute cerebral ischemia patients. It also restored an inverse correlation between 3-month FMD and baseline L-arginine levels. TRIAL REGISTRATION: NCT03116269 , 04/12/2017, retrospectively registered.

Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes.

BACKGROUND: Diabetes mellitus (DM) is a risk factor for early neurological deterioration (END) in acute ischemic stroke. The prothrombotic protein fibrinogen is frequently elevated in patients with diabetes, and may be associated with poorer prognoses. We evaluated whether fibrinogen is associated with END in patients with diabetes after acute ischemic stroke. METHODS: We included 3814 patients from a single hospital database admitted within 72 h of onset of ischemic stroke. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥2 within 7 days post-admission. In the total population (END, n = 661; non-END, n = 3153), univariate and multivariate analyses were performed to assess fibrinogen as an independent predictor for END. We then performed propensity score matching and univariate analyses for DM (END, n = 261; non-END, n = 522) and non-DM populations (END, n = 399; non-END, n = 798). Multiple logistic analyses were performed after matching for fibrinogen as a risk factor in each subgroup. RESULTS: Fibrinogen levels were higher in the END group than in the non-END group (367 ± 156 mg/dL vs. 347 ± 122 mg/dL, p = 0.002), though they were not associated with END in logistic regression analyses. Fibrinogen levels were found to be an independent predictor for END, but only in the DM population (fibrinogen levels 300-599 mg/dL, odds ratio: 1.618, 95% confidence interval: 1.037-2.525, p = 0.034, fibrinogen levels ≥600 mg/dL, 2.575, 1.018-6.514, p = 0.046; non-DM population, p = 0.393). The diabetes-fibrinogen interaction for the entire cohort was p = 0.101. CONCLUSIONS: Elevated fibrinogen is dose-dependently associated with END in patients with diabetes following acute ischemic stroke.

Cigarette smoking is an independent risk factor for post-stroke delirium.

BACKGROUND: Post-stroke delirium is a common problem in the care of stroke patients, and is associated with longer hospitalization, high short-term mortality, and an increased need for long-term care. Although post-stroke delirium occurs in approximately 10 ~ 30% of patients, little is known about the risk factors for post-stroke delirium in patients who experience acute stroke. METHODS: A total of 576 consecutive patients who experienced ischemic stroke (mean age, 65.2 years; range, 23-93 years) were screened for delirium over a 2-year period in an acute stroke care unit of a tertiary referral hospital. We screened for delirium using the Confusion Assessment Method. Once delirium was suspected, we evaluated the symptoms using the Korean Version of the Delirium Rating Scale-Revised-98. Neurological deficits were assessed using the National Institutes of Health Stroke Scale at admission and discharge, and functional ability was assessed using the Barthel Index and modified Rankin Scale at discharge and 3 months after discharge. RESULTS: Thirty-eight (6.7%) patients with stroke developed delirium during admission to the acute stroke care unit. Patients with delirium were significantly older (70.6 vs. 64.9 years of age, P = .001) and smoked cigarettes more frequently (40% vs. 24%, P = .033) than patients without delirium. In terms of clinical features, the delirium group experienced a significantly higher rate of major hemispheric stroke (55% vs. 26%, P < .001), exhibited poorer functional performance at discharge and 3 months after discharge, and stayed in hospital significantly longer. Independent risk factors for delirium were older age, history of cigarette smoking, and major hemispheric stroke. CONCLUSION: Abrupt cessation of cigarette smoking may be a risk factor for post-stroke delirium in ischemic stroke patients. The development of delirium after stroke is associated with worse outcome and longer hospitalization.

Useful Computed Tomography Score for Estimation of Early Neurologic Outcome in Post-Cardiac Arrest Patients With Therapeutic Hypothermia.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) is used to assess early ischemic stroke damage. This study compared bilateral ASPECTS (ASPECTS-b) with the gray:white matter ratio (GWR) and quantitative regional abnormality (QRA) to evaluate the prognostic utility of early computed tomography (CT) findings in post-cardiac arrest patients.Methods and Results:Out-of-hospital cardiac arrest patients with return of spontaneous circulation (ROSC) who underwent brain CT (<6 h after onset) and therapeutic hypothermia were recruited from a university hospital over a 2-year period. General demographics, ROSC characteristics, ASPECTS-b (total score=20 points), GWR, and QRA were assessed. Multivariate logistic regression analysis was used to predict neurologic outcome using cerebral performance category (CPC) at 1 month. The study population was divided into good (n=20; CPC 1-2) and poor (n=47; CPC 3-5) outcome groups. The good (vs. poor) outcome group was younger (mean [±SD] age 46.7±11.8 vs. 60.3±17.2 years; P=0.002) and had more initial shockable rhythms (40.0% vs. 8.5%; P=0.002). In addition, the good outcome group had a higher mean ASPECTS-b score (15.3±2.7 vs. 9.0±4.9; P<0.001), despite no differences in QRA and mean GWR. Age and ASPECTS-b were independent predictors of outcome after adjusting for potential confounders. CONCLUSIONS: These findings suggest that an initial CT score (ASPECTS-b) could help estimate early neurologic outcomes in post-cardiac arrest patients treated with therapeutic hypothermia.

Olfactory dysfunction is related to postoperative delirium in Parkinson's disease.

Operations often lead to delirium in elderly patients, particularly those with impaired cognition, suggesting that underlying neuropathology may play a role in the development of postoperative delirium. Olfactory dysfunction is a well-known marker of underlying Lewy body pathology in Parkinson's disease (PD). However, the prognostic value of olfaction for the development of postoperative delirium in PD remains unclear. 34 PD patients with or without postoperative delirium following surgery under general anesthesia were included in this study (n = 17 for each group). Cross-Cultural Smell Identification scores were lower in PD patients with postoperative delirium (4.4 ± 1.5) relative to the delirium-free controls (6.8 ± 2.4, p < 0.005). Multivariate logistic regression analysis revealed that olfaction and operation time were significant predictors of the development of postoperative delirium. Impaired olfaction is significantly associated with postoperative delirium in PD. Olfaction may be useful for identifying PD patients susceptible to postoperative delirium.