Long Sleep Duration and Dissatisfaction with Sleep Quality Are Associated with Ischemic Stroke in Young Patients.

INTRODUCTION: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients. METHODS: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (<45 years) ischemic stroke patients in 8 tertiary hospitals in Korea. A total of 225 patients and 225 age- and sex-matched controls were enrolled in the same period. Detailed information about patients' demographics, socioeconomic state, and traditional and nontraditional risk factors including sleep-related factors were obtained using structured questionnaires. Risk of ischemic stroke was estimated using conditional logistic regression analysis. RESULTS: Although average sleep duration was similar in patients and controls, patients were more likely to have long (≥9 h) or extremely short (<5 h) sleep durations. In addition, the proportion of subjects with dissatisfaction with sleep quality was higher in patients than controls (66.2 vs. 49.3%, p < 0.001). In multivariable conditional logistic regression analysis, long sleep duration (OR: 11.076, 95% CI: 1.819-67.446, p = 0.009) and dissatisfaction with sleep quality (OR: 2.116, 95% CI: 1.168-3.833, p = 0.013) were independently associated with risk of ischemic stroke. CONCLUSIONS: Long sleep duration and dissatisfaction with sleep quality may be associated with increased risk of ischemic stroke in young adults. Improving sleep habit or quality could be important for reducing the risk of ischemic stroke.

An interesting case of crossed syndrome: ipsilateral facial paralysis with contralateral glossoplegia.

BACKGROUND: Stroke is rarely accompanied with peripheral facial paralysis and supranuclear palsy of the hypoglossal nerve. Both sides of the motor cortex innervate the hypoglossal nucleus; therefore, unilateral lesions of the upper motor neurons rarely result in contralateral lingual paresis. We report a rare case of crossed syndrome with associated hyperacute peripheral hemifacial paralysis and contralateral lingual paresis after a lower pontine tegmentum ischemic stroke. CASE PRESENTATION: A 73-year-old man presented with symptoms of hyperacute peripheral hemifacial paralysis. Upon protrusion, the patient's tongue deviated to the contralateral side, without fasciculation or atrophy. Brain imaging showed focal ischemic stroke in the pontine tegmentum. However, lingual hemiparesis and multimodal neuroimaging findings differed. CONCLUSIONS: We suggest that cortico-hypoglossal fibers pass through the dorsal pontine. This case of crossed syndrome is a rare report of a lower pontine tegmentum ischemic stroke resembling an upper motor neuron lesion of the contralateral hypoglossal nerve.

Effects of Dose Titration on Dipyridamole-Induced Headache: A Randomized, Double-Blind Clinical Trial.

PURPOSE: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. RESULTS: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different. CONCLUSION: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache.

Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.

OBJECTIVE: Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA. METHODS: This was a phase 2, 2-part, multicenter trial in stroke patients (19-80 years old) receiving rtPA. Intravenous otaplimastat was administered <30 minutes after rtPA. Stage 1 was a single-arm, open-label safety study in 11 patients. Otaplimastat 80 mg was administered twice daily for 3 days. Stage 2 was a randomized, double-blind, placebo-controlled study involving 69 patients, assigned (1:1:1) to otaplimastat 40 mg, otaplimastat 80 mg, or a placebo. The primary endpoint was the occurrence of parenchymal hematoma (PH) on day 1. Secondary endpoints included serious adverse events (SAEs), mortality, and modified Rankin scale (mRS) distribution at 90 days (clinicaltrials.gov identifier: NCT02787278). RESULTS: No safety issues were encountered in stage 1. The incidence of PH during stage 2 was comparable: 0 of 22 with the placebo, 0 of 22 with otaplimastat 40 mg, and 1 of 21 with the 80 mg dose. No differences in SAEs (13%, 17%, 14%) or death (8.3%, 4.2%, 4.8%) were observed among the 3 groups. Three adverse events (chills, muscle rigidity, hepatotoxicity) were judged to be related to otaplimastat. INTERPRETATION: Intravenous otaplimastat adjunctive therapy in patients receiving rtPA is feasible and generally safe. The functional efficacy of otaplimastat needs to be investigated with further large trials. ANN NEUROL 2020;87:233-245.

Post-Stroke Depressive Symptoms: Varying Responses to Escitalopram by Individual Symptoms and Lesion Location.

OBJECTIVE: The efficacy of antidepressants in post-stroke depressive symptoms (PSD) varies. We aimed to examine whether the effect of escitalopram on PSD differs according to individual depressive symptoms and stroke lesion location. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram on depression in acute stroke patients (237 with placebo, 241 with escitalopram). Depressive symptoms were evaluated with the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Changes in MADRS and individual item scores at 12 weeks were compared between the treatment groups and among the stroke lesion location groups. Stroke lesion locations were grouped according to the anatomical distribution of serotonin fibers that originate from the midbrain/pons and spread to the forebrain via subcortical structures: "Midbrain-Pons," "Frontal-Subcortical," and "Others." Least-squares means were calculated to demonstrate the independent effect of lesion location. RESULTS: Total MADRS scores decreased more significantly in the escitalopram than in the placebo group, while a significant effect of escitalopram was observed in only 3 items: apparent sadness, reported sadness, pessimistic thoughts. In the lesion location analyses, escitalopram users in the Frontal-Subcortical group showed significant improvement in total MADRS scores (placebo [n = 130] vs. escitalopram [n = 148], least-square mean [95% CI]: -2.3 [-3.5 to -0.2] vs. -4.5 [-5.5 to -3.4], p = .005), while those in the Midbrain-Pons and Others groups did not. CONCLUSIONS: The effect of escitalopram on PSD may be more prominent in patients with particular depressive symptoms and stroke lesion locations, suggesting the need for tailored treatment strategies.

Mechanism of Stroke According to the Severity and Location of Atherosclerotic Middle Cerebral Artery Disease.

BACKGROUND AND PURPOSE: Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease. METHODS: We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated. RESULTS: A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p < 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005). CONCLUSIONS: The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion.

Are Genetic Variants Associated with the Location of Cerebral Arterial Lesions in Stroke Patients?

BACKGROUND: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. METHODS: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. RESULTS: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. CONCLUSION: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis.

Depressive Symptoms in Stroke Patients: Are There Sex Differences?

BACKGROUND: We aimed to examine sex differences in symptom characteristics and pharmacological responses in post-stroke depressive (PSD) symptoms. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram for 3 months on depression in patients with acute stroke. Depressive symptoms were evaluated using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Baseline characteristics, clinical variables, and treatment responses to escitalopram were compared between male and female patients. Treatment responses were defined as changes in MADRS (total score and its components) between baseline and 3 months and were compared between the escitalopram and placebo groups within each sex group. The least square mean was calculated to determine the independent effect of escitalopram, of which interaction was evaluated with patient sex. RESULTS: Of the 478 patients (intention-to-treat population), 187 (39%) were female. Female patients were significantly older than male patients and demonstrated more severe depressive symptoms at baseline (male vs. female, MADRS score, mean [SD]: 9.7 ± 8.0 vs. 12.2 ± 8.4, p = 0.001), especially in apparent sadness, reported sadness, and reduced appetite items. These differences were significant after adjustment for age and the severity of neurologic deficits. The female escitalopram group showed a significant 3-month improvement in MADRS scores (placebo [n = 86] vs. escitalopram [n = 101], least square mean [95% CI] -2.7 [-4.1 to -1.2] vs. -5.0 [-6.4 to -3.6], p = 0.007), and this efficacy was prominent in apparent sadness, reported sadness, and pessimistic thoughts items. However, there was no significant effect of escitalopram on depressive symptoms in the male group. The treatment responses of escitalopram tended to be more pronounced in the female group, particularly in alleviating a subset of depressive symptoms such as apparent sadness (p for interaction = 0.009). CONCLUSION: PSD may differ according to sex in its symptom characteristics and treatment responses to escitalopram, and tailored treatment strategies for PSD may therefore be needed.

Prediction of deep vein thrombosis by ultrasonography and D-dimer in Asian patients with ischemic stroke.

BACKGROUND: Deep vein thrombosis (DVT) is an important complication of ischemic stroke, although the incidence of DVT is regarded as being lower in Asian than in non-Asian patients. Here, we investigated the incidence and factors associated with DVT in Asian patients with ischemic stroke. METHODS: Acute ischemic stroke patients received lower extremity ultrasonography (LEUS) to diagnose the presence of DVT. Clinical characteristics and laboratory results, including D-dimer level, were compared between patients with and without DVT. Independent risk factors for DVT were investigated using multivariable analysis. Similar analysis was performed to identify factors associated with elevated D-dimer level (> 0.5 mg/dl) in acute ischemic stroke patients. RESULTS: During the study period, 289 patients were enrolled, and 38 (13.1%) showed DVT. Female sex (OR = 2.579, 95% CI = 1.224-5.432; p = 0.013) and a high National Institutes of Health Stroke Scale (NIHSS) score (OR = 1.191 95% CI = 1.095-1.294; p = 0.005) were independently associated with the presence of DVT, although D-dimer level was not. Stroke mechanism, especially cardioembolic stroke (OR = 3.777, 95% CI = 1.532-9.313; p = 0.004; reference: large artery atherosclerosis), NIHSS score (OR = 1.087, 95% CI = 1.002-1.179; p = 0.001) and thrombolysis (OR = 12.360, 95% CI 2.456-62.213; p = 0.002) were independently associated with elevated abnormal D-dimer levels. CONCLUSION: The severity of ischemic stroke, but not the D-dimer level, was associated with the presence of DVT in Asian ischemic stroke patients. D-dimer level was influenced by the stroke mechanism. LEUS in patients with severe neurological deficit, rather than screening with D-dimer, may be more beneficial for diagnosing DVT in Asian patients with acute ischemic stroke.

Atherosclerotic plaque locations may be related to different ischemic lesion patterns.

BACKGROUND: Atherosclerosis of the internal carotid artery (ICA) is an important cause of ischemic stroke. Artery-to-artery embolism is the major stroke mechanism in patients with atherosclerotic carotid disease. This study hypothesized that the atherosclerotic ICA geometry and plaque location would be associated with lesion pattern in patients with acute ischemic stroke. METHODS: Ischemic stroke patients with symptomatic proximal ICA disease (> 50% diameter stenosis) were enrolled. The carotid plaque location was divided into high-apical and low-body types. The geometric parameters of the ICA (angles between arteries) were measured, and ischemic lesion patterns were classified according to the number, location, and size of the lesions. Factors associated with plaque location and lesion pattern, dichotomized by size, were investigated. RESULTS: Of the 93 acute ischemic stroke patients enrolled, 31 had high-apical and 62 had low-body plaques. Hyperlipidemia was more prevalent and the common carotid artery (CCA)-ICA angle was wider (167.7 ± 10.4° vs 162.3 ± 9.8°, p = 0.019) in patients with low-body than high-apical plaques. Low-body plaques were more frequently associated with small scattered or cortical lesions (54.8% vs. 32.3%, p = 0.040), whereas high-apical plaques were more frequently associated with large lesions having additional lesions (38.7% vs. 11.3%, p = 0.002). The presence of low-body plaques (odds ratio: 3.106, 95% confidence interval: 1.105-8.728, p = 0.032) was independently associated with the small lesion-only pattern. CONCLUSIONS: Low-body plaques are more frequently associated with small scattered lesions, whereas high-apical plaques are more frequently associated with large lesions having additional lesions. A wide CCA-ICA angle is associated with low-body plaque of the carotid artery.

Distal versus Proximal Middle Cerebral Artery Occlusion: Different Mechanisms.

BACKGROUND: Clinical and radiological characteristics of middle cerebral artery (MCA) infarction may differ according to the location of occlusion. OBJECTIVES: We investigated the difference between proximal and distal symptomatic MCA occlusion (MCAO) in patients with ischemic stroke. The factors associated with the imaging characteristics were also analyzed. METHODS: Patients with ischemic stroke due to MCAO were consecutively enrolled. The location of MCAO was determined by the ratio of the length of the ipsilesional MCA to that of the contralateral MCA and dichotomized to proximal and distal MCAO. Clinical and radiological characteristics were compared between patients with proximal and distal MCAO. Factors associated with the basal ganglia (BG) involvement, hemorrhagic transformation (HT), and neurological change during admission were investigated. RESULTS: Among 181 included patients, MCAO location showed a bimodal peak (at the proximal [n = 99] and distal MCA [n = 82]). Proximal MCAO was more frequently associated with hyperlipidemia and large artery atherosclerosis, whereas distal MCAO was more frequently associated with hypertension, atrial fibrillation, and cardioembolic stroke. BG involvement was similar between the 2 groups (48 vs. 39%; p = 0.21), whereas HT was more frequent in distal MCAO (10 vs. 23%; p = 0.02). Among patients with proximal MCAO, hyperintense vessel sign was less frequently observed in those with a BG involvement than those without (38 vs. 60%; p = 0.03). Among those without BG involvement, the presence of HT was very low and similar between patients with proximal and distal MCAOs (1.9 vs. 2.0%). However, in patients with BG involvement, HT was more frequently observed in those with distal MCAO than in those with proximal MCAO (54.8 vs. 15.7%; p < 0.001). The presence of hyperintense vessel sign (OR 0.172, 95% CI 0.051-0.586; p = 0.005) and distal MCAO (OR 0.200, 95% CI 0.059-0.683; p = 0.011) was independently associated with improvement during admission. CONCLUSION: Proximal MCAO is more frequently associated with atherosclerosis, whereas distal MCAO is more frequently associated with cardioembolism. In proximal MCAO, the status of collateral flow presented by hyperintense vessel sign may affect the involvement of BG. In distal MCAO, distal migration of the embolus, which first impacted at the proximal MCA causing BG ischemia, may explain the high rate of HT by reperfusion injury. Hyperintense vessel sign and distal MCAO were independently associated with neurological improvement during admission.

Subclinical Peripheral Arterial Disease in Patients with Acute Ischemic Stroke: A Study with Ultrasonography.

BACKGROUND: Peripheral arterial disease (PAD) is an advanced form of atherosclerosis defined by an abnormal ankle-brachial index (ABI). However, the ABI provides no information about the location of atherosclerosis. We investigated the clinical implication of PAD confirmed using lower-extremity ultrasonography (LEUS), with consideration of the atherosclerosis location. METHODS: Patients with acute ischemic stroke who underwent LEUS were enrolled. Patients with PAD were further divided into those with PAD at the proximal (above-popliteal artery, PADP) and distal (below-tibialis artery, PADD) segments. The clinical outcome was compared between patients with and without PAD, and between PADP and PADD. The atherosclerosis location in the cerebral artery was also compared between groups. RESULTS: Among 289 patients, PAD was observed in 108 (37.4%) patients (43 had PADP and 65 had PADD). Patients with PAD were slightly older (P < .001) and had more significant carotid artery stenosis (30.6% versus 12.7%, P < .001) than those without. Patients with PAD had poor 3-month functional outcome than those without (modified-Rankin Scale score: 3 [interquartile range, 1-4] versus 2 [1-3], respectively, P = .003). Diabetes, high-stroke severity, and the presence of PADP (odds ratio, 3.893; 95% confidence interval, 1.454-10.425; P = .007) were independently associated with poor functional outcome at 3 months. Patients with PADP showed higher prevalence of extracranial stenosis than those with PADD (41.9% versus 23.1%; P = .038). CONCLUSIONS: Our study suggests that subclinical PAD, especially PADP, is associated with poor functional outcome at 3 months after stroke onset. Interestingly, the location of cerebral atherosclerosis differed according to the location of PAD.

Serotonin transporter gene polymorphisms may be associated with poststroke neurological recovery after escitalopram use.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) putatively improve neurological recovery after stroke. We aimed to investigate whether serotonin transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs in the poststroke neurological recovery. METHODS: This was a post hoc analysis of the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo-controlled, double-blind trial examining the efficacy of escitalopram on emotional and neurological disturbances after acute stroke. Patients with no/minimal disability initially (modified Rankin Scale (mRS) 0-1) were excluded. Of the participants, 301 underwent genetic studies of the STin2 (a variable number tandem repeat (VNTR) in intron 2) (STin2 12/10 and STin2 12/12 genotypes) and 5-HTTLPR (a variable-length repeat in the promoter region) polymorphisms of SERT. We explored whether neurological function (National Institutes of Health Stroke Scale (NIHSS) score and mRS) at 3 months would differ according to SERT polymorphisms within each treatment arm (escitalopram and placebo). RESULTS: Among the escitalopram users (n=159), neurological function in subjects with STin2 12/10 (n=29) improved significantly more than that in STin2 12/12 carriers (n=130) at 3 months. After adjusting for age, initial NIHSS and depression, STin2 12/10 independently predicted a good clinical outcome (mRS 0-1) (OR 2.99, 95% CI 1.04 to 8.58) at 3 months. However, differences between STin2 polymorphisms were not shown in the placebo group (n=142). 5-HTTLPR polymorphisms were not associated with neurological recovery in any treatment group. CONCLUSION: STin2 VNTR polymorphisms may be associated with poststroke neurological recovery after SSRI therapy. Further studies are needed to identify the role of serotonin in neurological recovery after stroke.

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. RESULTS: Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. CONCLUSIONS: Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268.

Predictors of Hemorrhage Volume after Intravenous Thrombolysis.

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) is one of the most feared complications after administration of intravenous recombinant tissue plasminogen activator (IV rtPA). The aim of this study was to determine correlations between hemorrhage volume (HV) after IV rtPA treatment and risk factors for sICH. METHODS: We analyzed 318 patients from the stroke registries of 4 hospitals in Korea. We confirmed hemorrhage by computed tomography (CT) or magnetic resonance imaging within 36 hours. Patient groups were classified by HV (0, 0-10, 10-25, and greater than 25 mL). Based on the HV, we evaluated the following: (1) predictors for hemorrhage; (2) rates of sICH according to various sICH definitions; and (3) 3-month functional outcomes after IV rtPA treatment. RESULTS: Among the 318 patients, hemorrhage occurred in 72 patients. HV was significantly correlated with atrial fibrillation (OR = 3.38, 95% CI = 1.87-6.09), early CT changes (OR = 3.17, 95% CI = 1.69-5.93), and dense artery sign (OR = 1.90, 95% CI = 1.07-3.39). Compared with the groups with HV less than 25 mL, patients with an HV of greater than 25 mL were more likely to have higher mortality rates (33.3% versus 11.8%) and worse outcomes at 3 months (good: 8.3% versus 50.3%; excellent: 0% versus 33.7%). CONCLUSIONS: HV after IV rtPA is an important predictor of clinical outcomes. Atrial fibrillation, early CT changes, and dense artery sign were significantly associated with large HVs; therefore, these patient factors might be considered before and after thrombolytic treatment.

Protocol of the Stroke in Korean Young Adults Study: A Multicenter Case-Control Study and Prospective Cohort Study.

BACKGROUND: The incidence of ischemic stroke in young adults has been rising over recent decades, but there is still limited information on its risk factors, etiologies, and outcomes. Because these patients generally participate in social life, risk factors associated with lifestyle may have a great impact and need to be identified. METHODS: The SKY (Stroke in Korean Young Adults) study is a multicenter case-control study and a prospective cohort study in 8 tertiary medical centers in the Republic of Korea. The case subjects are patients aged 18-44 years with first-ever ischemic stroke occurring within 1 month of stroke onset, and the control subjects are age- and gender-matched community controls. Our aim is to include 470 cases and 470 controls. The main objective of our study is to determine the risk factors and the causes of ischemic stroke in Korean young adults. Both well-documented risk factors and little-known lifestyle-related risk factors such as lifestyle habits and psychological distress including job strain will be evaluated by comparing cases and controls using a structured questionnaire. Secondary objectives are to determine the risks of mortality, recurrent vascular events, and poststroke epilepsy in these patients. Conditional logistic regression analysis will be used to estimate odds ratios and 95% confidence intervals. CONCLUSIONS: The SKY study is designed to obtain more insights into relatively little-known risk factors in young Korean adults with ischemic stroke. The results may also help identify the frequencies of uncommon etiologies and outcomes in these patients.

Increased VEGF and decreased SDF-1α in patients with silent brain infarction are associated with better prognosis after first-ever acute lacunar stroke.

BACKGROUND: Pre-existing silent brain infarctions (SBIs) have been reported to be associated with better outcomes after first-ever symptomatic ischemic stroke, although the mechanism of this remains unclear. We investigated the association between SBIs, outcomes of acute lacunar infarction, and biomarkers including vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), macrophage migration inhibitory factor (MIF), and high-mobility group box-1 (HMGB1). METHODS: A total of 68 consecutive patients diagnosed with first-ever lacunar infarction (<20 mm) within 24 hours of symptom onset were included in this study. Clinical, laboratory, and imaging data were obtained. Plasma levels of VEGF, SDF-1α, MIF, and HMGB1 were assessed using Enzyme-Linked Immunosorbent Assay kits. RESULTS: SBIs were noted in 31 of the 68 patients. Although the initial National Institutes of Health Stroke Scale scores were not related with the presence of SBIs (P = .313), patients with SBIs had better outcomes at 3 months (P = .029). Additionally, plasma VEGF levels were higher (P = .035) and SDF-1α levels were lower (P < .001) in patients with SBIs. Logistic regression analysis indicated that VEGF and SDF-1α were independently associated with the presence of SBIs. CONCLUSIONS: SBIs are associated with favorable outcomes in patients with first-ever acute lacunar infarction and higher levels of VEGF, and lower levels of SDF-1α in these patients may contribute to their more favorable prognosis.

Effects of uric acid levels on outcome in severe ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator.

Uric acid (UA) has been known to be a neuroprotective antioxidant because of its free radical scavenger activity. We studied the influence of UA in patients with acute ischemic stroke after thrombolytic therapy. Two hundred eighteen consecutive patients treated with intravenous thrombolysis were included in this analysis. We analyzed the relationship between serum UA levels obtained at the emergency department and clinical outcomes. Early improvement and excellent functional outcomes were measured using the National Institutes of Health Stroke Scale (NIHSS) 24 h after onset and the modified Rankin scale after 3 months. There was no significant relationship between serum UA levels and early improvement or excellent functional outcome in the total patients (p = 0.583 and p = 0.082, respectively). However, in patients with severe baseline stroke deficits (NIHSS score ≥15), higher-tertile UA levels were significantly associated with excellent functional outcomes (p = 0.003). Excellent functional outcomes in patients with severe baseline disability might have a significant association with serum UA levels particularly in men but not in women (p = 0.007 in men and p = 0.621 in women). Increased serum UA levels might be associated with better outcomes in ischemic stroke patients treated with intravenous thrombolysis, but the effectiveness of UA can differ by initial stroke severity and gender.

A Multimodal Ensemble Deep Learning Model for Functional Outcome Prognosis of Stroke Patients.

BACKGROUND AND PURPOSE: The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. METHODS: We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3-6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3-6. RESULTS: Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3-6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). CONCLUSION: The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

Blood viscosity associated with stroke mechanism and early neurological deterioration in middle cerebral artery atherosclerosis.

Blood viscosity may affect the mechanisms of stroke and early neurological deterioration (END). We aimed to investigate the relationship between blood viscosity, stroke mechanisms, and END in patients with middle cerebral artery (MCA) infarction. Patients with symptomatic MCA atherosclerosis (≥ 50% stenosis) were recruited. Blood viscosity was compared across patients with different mechanisms of symptomatic MCA disease: in situ thrombo-occlusion (sMCA-IST), artery-to-artery embolism (sMCA-AAE), and local branch occlusion (sMCA-LBO). END was defined as four points increase in the National Institutes of Health Stroke Scale score from baseline during the first week. The association between blood viscosity and END was also evaluated. A total of 360 patients (76 with sMCA-IST, 216 with sMCA-AAE, and 68 with sMCA-LBO) were investigated. Blood viscosity was highest in patients with sMCA-IST, followed by sMCA-AAE and sMCA-LBO (P < 0.001). Blood viscosity was associated with END in patients with MCA disease. Low shear viscosity was associated with END in patients with sMCA- LBO (adjusted odds ratio, aOR 1.524; 95% confidence interval, CI 1.035-2.246), sMCA- IST (aOR 1.365; 95% CI 1.013-1.839), and sMCA- AAE (aOR 1.285; 95% CI 1.010-1.634). Blood viscosity was related to END in patients with stroke caused by MCA disease.