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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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown., Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes., Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores., Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups., Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

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 (&lt;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 (&lt;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 &lt; 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., (© 2023 S. Karger AG, Basel.)

Two different stroke mechanisms are involved in small vessel disease: branch atheromatous disease (BAD) and lipohyalinotic degeneration (LD). We compared mechanisms of stroke in lenticulostriate arteries (LSA) vs. anterior pontine arteries (APA) and verified factors associated with stroke mechanisms, including shape of middle cerebral artery (MCA) and basilar artery (BA). We retrospectively reviewed patients with acute ischemic stroke with penetrating artery territory confirmed by MRI. The mechanisms of stroke were categorized based on diffusion-weighted imaging; BAD was defined as lesion larger than 10 mm in LSA and lesions involving basal pontine in APA. Other lesions were classified as LD. The shapes of MCA and BA were classified as straight, with one angle, or with two angles (U, C or S shape, respectively) using anterior-posterior view. The study included 221 patients. LD was more common in LSA infarcts, but BAD was more common in APA infarcts (p < 0.001). Low initial National Institutes of Health Stroke Scale [Adjusted Odds ratio (aOR) = 0.78; p < 0.001], absence of hyperlipidemia [aOR = 0.31; p = 0.002], previous statin use [aOR = 4.35; p = 0.028] LSA infarcts [reference = APA territory; aOR = 11.07; p < 0.001], and S-shaped vessels (reference = straight shaped vessels; aOR = 3.51; p = 0.004) were independently associated with LD. Angulations in the mother vessels may be more associated with true small vessel disease more with LD than BAD., (© 2022. The Author(s).)

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., (© 2022 S. Karger AG, Basel.)

Background and Purpose: Antiphospholipid syndrome (APS) is one of the uncommon causes of ischemic stroke, and is associated with young and female patients. However, the significance of antiphospholipid antibody (aPL) in older ischemic stroke patients is uncertain. We aimed to examine the significance of aPLs in ischemic stroke in these older patients., Materials and Methods: A total of 739 patients with acute ischemic stroke within 7 days of initial symptoms were collected consecutively. Clinical and laboratory data were obtained from medical records. aPLs (lupus anticoagulant, anti-cardiolipin antibody, anti-β2glycoprotein-I antibody) were measured the day after admission and the presence of at least one antibody was regarded as positive aPL. Patients with positive aPL were rechecked after at least 12 weeks for confirmation of APS., Result: Of the 739 patients, 103 (13.9%) had at least one aPL initially. These patients were older, had more atrial fibrillation and higher levels of inflammatory markers. Among the 103 aPL positive patients, 41 remained positive at 3 months, 23 showed negative conversion, and 39 were not available for follow-up. Patients diagnosed with APS had higher numbers of aPL and had specifically anti-β2glycoprotein-I IgG antibody. The patients with aPLs did not differ significantly from the others in terms of stroke subtype., Conclusion: aPL was rather common in ischemic stroke patients regardless of age. Although the influence of transient positive aPL on ischemic stroke remains uncertain, two or more aPLs and the presence of anti-β2glycoprotein-I IgG may predict a diagnosis of APS.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The factors associated with clopidogrel resistance in patients with stroke recurrence receiving single or dual antiplatelet treatment (SAPT or DAPT) may differ. This study compared the high on-treatment platelet reactivities (HPRs) and the factors associated with clopidogrel resistance in recurrent ischemic stroke patients receiving clopidogrel or aspirin and clopidogrel. Methods: We enrolled and allocated 275 recurrent ischemic stroke patients to the clopidogrel and DAPT groups and compared their demographics, conventional risk factors, and P2Y12 reaction units (PRUs). Clopidogrel resistance was categorized as PRU higher than 275. We performed a multivariate logistic regression analysis to determine the factors underlying clopidogrel resistance during SAPT and DAPT. Results: In total, 145 (52.7%) and 130 (47.3%) patients received clopidogrel and DAPT, respectively at recurrence. The risk factors of the two groups were not significantly different, except that coronary artery disease was more frequent in the DAPT group. The PRU was higher (255 ± 91 vs. 221 ± 84; p = 0.002) and clopidogrel resistance was more frequent (45.5 vs. 31.5%; p = 0.018) in the SAPT than in the DAPT group. Hyperlipidemia was associated with clopidogrel resistance during SAPT, and smoking (Odds ratio = 0.426, 95% confidence interval 0.210–0.861; p = 0.018) had a protective effect against clopidogrel resistance. For those receiving DAPT, old age, female, low hemoglobin A1c level, and high ARU were associated with clopidogrel resistance. Conclusions: HPR and clopidogrel resistance were more frequent in recurrent ischemic stroke patients receiving clopidogrel than in those receiving DAPT. Smoking was independently associated with less clopidogrel resistance among those receiving clopidogrel SAPT but not in those receiving DAPT. [ABSTRACT FROM AUTHOR]

• Microglia are activated after ischemic stroke and sTREM2 levels are considered to reflect the activation of microglia. • Early increment of sTREM2 and late decrement of sTREM2 were more common in patients with poor outcome after ischemic stroke. • Early increment of sTREM2 were independently associated with poor outcome after ischemic stroke. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is derived from cleavage of TREM2, which is expressed on the cell surface of microlgia and other tissue-specific macrophages. In the present study, the changes in the sTREM2 levels after ischemic stroke (IS) and their association with clinical outcomes were evaluated. A total of 43 patients diagnosed with non-cardioembolic IS between June 2011 and May 2014 were consecutively included in this study. Patients treated with intravenous thrombolysis or intra-arterial thrombectomy were excluded. Plasma samples were collected three times (days 1, 7, and 90) after ictus. The sTREM2 level was measured in the samples using the highly sensitive solid-phase proximity ligation assay (SP-PLA). Among the 43 subjects, higher initial NIH stroke scale (NIHSS) score (P = 0.005), early increment of sTREM2 (P < 0.001), and late decrement of sTREM2 (P = 0.002), were more common in patients with poor outcome. Based on multivariate analysis, initial NIHSS score (P = 0.015) and early increment of sTREM2 (P = 0.032) were independently associated with poor outcome. The results from the present study indicate that increment of sTREM2 level at the early phase was a predictor of poor outcome. Serial follow-up of sTREM2 may aid prognosis after stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Stromal cell-derived factor-1α (SDF-1α) provides neurotrophic support to neurons. In this prospective study, we investigated the association between SDF-1α and long-term outcome in patients with acute ischemic stroke. Methods: This study included 104 patients with first-ever ischemic stroke, identified within 24 h of symptom onset. Serum samples were collected immediately after admission and 3 months thereafter, as well as from age- and sex-matched normal controls. The correlation between acute-stage serum SDF-1α and stroke severity were analyzed. Finally, the relationship between serum SDF-1α and long-term outcome was evaluated by multivariate analysis. Results: Serum SDF-1α levels were only higher in acute-stage stroke patients compared with the normal control group (p = 0.011). The serum SDF-1α level was increased in proportion to infarct volume (r = 0.220, p = 0.025) and initial National Institutes of Health Stroke Scale score (r = 0.275, p = 0.005). After adjustment for covariates, a high initial serum SDF-1α level (OR 1.167, p = 0.023) or second and third tertiles of SDF-1α level compared to first tertile (OR 4.644, p = 0.044 and OR 9.396, p = 0.025, respectively) were significantly associated with a favorable long-term outcome. Conclusions: This prospective study demonstrated a correlation between serum SDF-1α and favorable long-term outcome in patients with acute ischemic stroke. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague–Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10min before the occlusion of the left middle cerebral artery (MCAo) for 2h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p &#60;0.05). Plasma MMP-9 increased maximally at 4h and then decreased rapidly, brain MMP-9 increased maximally at 24h and persisted until 72h, and NF-κB increased maximally at 24h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke. [Copyright &y& Elsevier]

Abstract: Objective: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke; however it is rather neglected. Vessel wall visualization by high resolution magnetic resonance imaging (HRMRI) might provide more accurate information. Methods: A total of 219 consecutive patients with acute ischemic stroke underwent MRI, MRA and proton-density weighted HRMRI. Using HRMRI, the patients were divided into 3 groups with respect to basilar plaques: no plaque (n = 85), minimal plaque (n = 72) and apparent plaque (n = 62). Demographics and characteristics were compared between the groups, and the extents of stenoses calculated from MRA versus HRMRI data were also compared. Factors potentially associated with basilar plaque were validated by multivariate analysis. Results: Patients with apparent plaque had higher frequencies of diabetes mellitus, lower high-density lipoprotein and higher hemoglobin A1c, erythrocyte sedimentation rate and homocysteine. Of the 62 cases of apparent plaque, severe stenosis (>50%) was observed in 10 (16%) by MRA and in 27 (43%) by HRMRI, which points to overestimation of plaques by HRMRI. In addition, no stenosis was evident on MRA in 13 patients with apparent plaque even though they had up to 72% stenosis on HRMRI. After adjusting for covariates, basilar artery apparent plaque was independently associated with old age, previous stroke, diabetes mellitus, low HDL and high levels of homocysteine. Conclusions: Basilar artery stenosis with plaque is more accurately detected using HRMRI than MRA. In addition, the associated risk factors differ somewhat. The use of HRMRI for evaluating ICAS deserves more attention. [Copyright &y& Elsevier]