Total small vessel disease score and functional outcomes following acute intracerebral hemorrhage.

BACKGROUND: Individual cerebral small vessel disease (SVD) markers are independent predictors for poor prognosis following intracerebral hemorrhage (ICH), however, the impact of the cumulative SVD burden on outcomes remains unclear. We aimed to investigate the association between the global SVD burden and functional outcomes following ICH. METHODS: We retrospectively evaluated a consecutive cohort of patients with ICH who underwent brain magnetic resonance imaging and magnetic resonance angiography, from a prospective registry. We identified the presence and severity of the SVD markers (cerebral microbleeds, lacunar infarctions, periventricular hyperintensities, and deep white matter hyperintensities) and summed them to obtain the modified total SVD score (0-4). Poor functional outcomes were defined as a modified Rankin Scale score at discharge ≥ 3. A multivariate logistic regression model was used to assess the association between patient outcomes and the SVD score. RESULTS: A total of 144 patients were included (65.0 ± 12.2 years, 67.4% male). The modified total SVD score was potentially associated with poor functional outcomes (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.97-3.03) after adjustment for age, sex, history of stroke, chronic kidney disease, prior use of antithrombotic agents, the National Institutes of Health Stroke Scale score on admission, the non-lobar location of ICH, and hematoma volume on admission. Moreover, among older patients (≥ 65 years), the SVD score was associated with poor outcomes (OR 3.11, 95% CI 1.01-9.55). Among those with supratentorial ICH, the score remained significant (OR 2.06, 95% CI 1.11-3.83). CONCLUSIONS: The modified total SVD score may have predictive value for poor functional outcomes following ICH.

Effect of Enzyme Replacement Therapy on Basilar Artery Diameter in Male Patients With Fabry Disease.

Background and Purpose- The effect of enzyme replacement therapy (ERT) on cerebrovascular complications remains largely unexplored. We aimed to investigate the relationship between basilar artery (BA) diameter and long-term ERT in patients with Fabry disease. Methods- We obtained baseline magnetic resonance imaging data from 30 patients (40.5±16.3 years, male: 14) in the single institution; among them, 21 patients prospectively had follow-up magnetic resonance imaging assessments. The short axis of BA diameter was measured at the midpons level on axial T2-weighted images. Brain magnetic resonance imaging measurements included markers of cerebral small vessel disease (lacunas, white matter hyperintensities, and cerebral microbleeds). We assessed variables associated with baseline BA diameter and annual BA diameter change using linear regression analyses. Results- Hypertension, left ventricular hypertrophy, estimated glomerular filtration rate, and white matter hyperintensities correlated with the initial BA diameter. After a mean interval of 7.2±4.6 years, the annual BA diameter change correlated positively with severe white matter hyperintensities and inversely with the duration of ERT (ß=-0.48, P=0.033). After stratifying patients by sex, a significant correlation between the duration of ERT and BA diameter was found only in men (ß=-0.72, P=0.019). Conclusions- Our results show a possible relationship between ERT and changes in BA diameter. Future studies to elucidate the clinical impact of BA changes as a potential surrogate marker are needed.

Magnetic Resonance Imaging Findings Related to Stroke Risk in Japanese Patients With Fabry Disease.

Background and Purpose- Stroke is the most frequent severe clinical event in patients with Fabry disease. We aimed to evaluate the cerebral magnetic resonance imaging findings of patients with Fabry disease and assess their association with future stroke risk after enzyme replacement therapy (ERT) induction. Methods- We retrospectively reviewed the magnetic resonance imaging findings of 25 patients with Fabry disease. Of these, 12 adult patients without prior stroke or ERT were enrolled to evaluate the association between baseline magnetic resonance imaging findings and stroke occurrence after ERT initiation. We assessed white matter hyperintensities, periventricular hyperintensities, and basilar artery diameter as neuroimaging markers. Results- The mean age of participants was 38.8±16.8 years. Fourteen patients (56.0%) were women. White matter hyperintensities and periventricular hyperintensities were observed in 15 and 13 cases, respectively. The mean basilar artery diameter was 3.2±0.55 mm. Two patients demonstrated old infarct lesions. Three of 12 patients in whom ERT was initiated had symptomatic stroke after baseline magnetic resonance imaging. Of these, 2 developed stroke within 6-month post-ERT initiation. The baseline basilar artery diameter was larger in patients who developed stroke than in those who did not (4.0±0.40 versus 2.9±0.49 mm, P=0.02). Conclusions- Basilar artery diameter may be associated with stroke risk after ERT initiation among Japanese patients with Fabry disease.

Cortical Cerebral Microinfarcts on 3T Magnetic Resonance Imaging in Patients With Carotid Artery Stenosis.

Background and Purpose- Carotid artery stenosis is common in the elderly and contributes to cognitive impairment and dementia. Cortical cerebral microinfarcts (CMIs) play an important role in vascular cognitive impairment and dementia. We aimed to investigate the association between CMIs on 3T magnetic resonance imaging and clinical and radiological features, including plaque morphology, and cognitive function in patients with carotid stenosis. Methods- Eighty-nine patients with >30% carotid stenosis on ultrasound were prospectively enrolled, and underwent brain and carotid artery magnetic resonance imaging. CMIs were rated according to predetermined criteria based on 3D-double inversion recovery and fluid-attenuated inversion recovery images. Results- CMIs were identified in 26 patients (29%; median number 0, range 0-9). Poisson regression models adjusted for age and sex revealed that CMIs were associated with intraplaque hemorrhage (rate ratio, 1.95; 95% CI, 1.26-3.18), lacunar infarcts (rate ratio, 1.54; 95% CI, 1.00-2.44), and cortical infarcts (rate ratio, 3.22; 95% CI, 2.20-5.00). These associations were also observed in asymptomatic patients (n=64). Of 81 patients with unilateral carotid stenosis, the prevalence and number of CMIs were significantly higher in the hemisphere ipsilateral to the carotid stenosis than in the contralateral hemisphere ( P=0.005 and P<0.001, respectively). The presence of CMIs was associated with poor cognitive function. Conclusions- Our results indicate that vulnerable carotid plaque increases the risk of CMIs and subsequent cognitive impairment. Carotid atherosclerosis could be a potential therapeutic target for cognitive impairment.

Successful Reperfusion with Endovascular Therapy Has Beneficial Effects on Long-Term Outcome Beyond 90 Days.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. METHODS: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. RESULTS: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score. CONCLUSIONS: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.

Isolated cortical vasogenic edema and hyperintense vessel signs may be early features of reversible cerebral vasoconstriction syndrome: Case reports.

Background The temporal and anatomical features of vasoconstriction in patients with reversible cerebral vasoconstriction syndrome within hours after symptom onset, in the hyperacute phase, are unclear. Case result Herein we report the cases of two patients with acute severe headache who were diagnosed with reversible cerebral vasoconstriction syndrome. Magnetic resonance imaging within hours after symptom onset revealed multiple areas of isolated cortical vasogenic edema and hyperintense vessel signs of the distal cerebral arteries. Follow-up imaging performed four days later in both cases showed diffuse segmental arterial vasoconstriction in the proximal regions of the cerebral arteries. Both patients received antivasoconstrictive therapy shortly after admission, and neither had neurological sequelae at discharge. The magnetic resonance imaging findings improved gradually within three months after symptom onset. Conclusion Isolated cortical vasogenic edema and hyperintense vessel signs, when observed within hours from sudden severe headache onset, may be useful early markers of reversible cerebral vasoconstriction syndrome.

Detection of Left Ventricular Thrombus by Cardiac Magnetic Resonance in Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: We aimed to use contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging to elucidate the prevalence of left ventricular (LV) thrombus in patients suspected of embolic stroke of undetermined source (ESUS) with previous myocardial infarction or LV dysfunction (LV ejection fraction [LVEF] <50%). METHODS: We prospectively investigated 797 consecutive patients who presented to our hospital with acute ischemic stroke between 2014 and 2015. Patients with myocardial infarction or LVEF<50% underwent CE-CMR imaging. ESUS was diagnosed according to proposal criteria based on transthoracic echocardiography findings. RESULTS: The prevalence of ESUS was 22% (178 of 797) on initial diagnosis. Among 60 patients with myocardial infarction or LVEF<50%, the stroke subtypes were as follows: small artery disease, 17% (10 of 60); large artery atherosclerosis, 5% (3 of 60); cardioembolic stroke, 49% (29 of 60); ESUS, 23% (14 of 60); and undetermined causes other than ESUS, 6% (4 of 60). Of 60 patients examined via CE-CMR, LV thrombus was confirmed in 12 patients, whereas only 1 had been detected on transthoracic echocardiography (P=0.04). Importantly, 29% (4 of 14) of patients with ESUS had LV thrombus. A prediction model based on CE-CMR findings showed higher performance in LV thrombus detection, permitting a net improvement of 0.46 (95% confidence interval, 0.08-0.82; P=0.016) in cardioembolic stroke reclassification. Compared with patients without LV thrombus, those with LV thrombus had lower LVEF (median: 26% versus 40%; P=0.003). Notably, 42% (5 of 12) of patients with LV thrombus had LVEF≥30%. CONCLUSIONS: When ESUS-suspected patients have myocardial infarction or LV dysfunction, CE-CMR may help improve detection of cardioembolic stroke and provide relevant information for anticoagulation therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665.

Relationship Between Infarct Volume and Prothrombin Time-International Normalized Ratio in Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: In Japan, warfarin treatment at prothrombin time-international normalized ratio (PT-INR) of 1.60-2.60 is recommended for elderly patients with nonvalvular atrial fibrillation (NVAF). But it remains unknown whether PT-INR 1.60-1.99 has a similar effect on stroke severity as a value >2.0. The purpose of this study was to clarify the association between infarct volume and PT-INR levels.Methods and Results:The 180 patients (mean age, 76 years [SD, 10 years], 53% male) selected from 429 consecutive ischemic stroke patients admitted within 48 h of onset between 2004 and 2014 with NVAF were included. We classified them into 4 groups according to their PT-INR values on admission: no warfarin (NW), 129 patients; PT-INR <1.60 (poor control: PC), 29 patients; PT-INR 1.60-1.99 (low-intensity control: LC), 14 patients; and PT-INR ≥2.00 (high-intensity control: HC), 8 patients. Median (interquartile range: IQR) of infarct volume was 55 mL (IQR 14-175) in the NW, 42 mL (IQR 27-170) in the PC, 36 mL (IQR 6-130) in the LC, and 11 mL (IQR 0-39) in the HC groups. The infarct volume of the HC group was significantly smaller than in the other 3 groups, but no difference existed between the LC and PC groups or the LC and NW groups. CONCLUSIONS: Warfarin control at PT-INR of 1.60-1.99 is not effective for reducing the severity of ischemic stroke in NVAF patients.

Validation of an algorithm that determines stroke diagnostic code accuracy in a Japanese hospital-based cancer registry using electronic medical records.

BACKGROUND: This study aimed to validate an algorithm that determines stroke diagnostic code accuracy, in a hospital-based cancer registry, using electronic medical records (EMRs) in Japan. METHODS: The subjects were 27,932 patients enrolled in the hospital-based cancer registry of Osaka University Hospital, between January 1, 2007 and December 31, 2015. The ICD-10 (international classification of diseases, 10th revision) diagnostic codes for stroke were extracted from the EMR database. Specifically, subarachnoid hemorrhage (I60); intracerebral hemorrhage (I61); cerebral infarction (I63); and other transient cerebral ischemic attacks and related syndromes and transient cerebral ischemic attack (unspecified) (G458 and G459), respectively. Diagnostic codes, both "definite" and "suspected," and brain imaging information were extracted from the database. We set the algorithm with the combination of the diagnostic code and/or the brain imaging information, and manually reviewed the presence or absence of the acute cerebrovascular disease with medical charts. RESULTS: A total of 2654 diagnostic codes, 1991 "definite" and 663 "suspected," were identified. After excluding duplicates, the numbers of "definite" and "suspected" diagnostic codes were 912 and 228, respectively. The proportion of the presence of the disease in the "definite" diagnostic code was 22%; this raised 51% with the combination of the diagnostic code and the use of brain imaging information. When adding the interval of when brain imaging was performed (within 30 days and within 1 day) to the diagnostic code, the proportion increased to 84% and 90%, respectively. In the algorithm of "definite" diagnostic code, history of stroke was the most common in the diagnostic code, but in the algorithm of "definite" diagnostic code and the use of brain imaging within 1 day, stroke mimics was the most frequent. CONCLUSIONS: Combining the diagnostic code and clinical examination improved the proportion of the presence of disease in the diagnostic code and achieved appropriate accuracy for research. Clinical research using EMRs require outcome validation prior to conducting a study.

Diagnostic Utility of Contrast-enhanced 3D T1-weighted Imaging in Acute Cerebral Infarction Associated with Graves Disease.

Graves disease is rarely complicated with cerebrovascular steno-occlusive diseases. Previous studies have suggested several hypotheses for this occurrence, including excess thyroid hormone, which stimulates the sympathetic nervous system, which in turn causes an abnormal hemodynamic response with consequent atherosclerotic changes, and antithyroid antibodies cause local vascular inflammation in patients with Graves disease. However, radiological findings of vasculitis in patients with Graves disease and cerebral infarction remain less known. We report the case of a 30-year-old Japanese woman with acute cerebral infarction due to vasculitis associated with Graves disease. She was admitted to our hospital with a 4-day history of intermittent transient dysarthria and limb shaking of the left leg when standing. Three weeks before admission, she went to a local hospital because of general malaise and was diagnosed with Graves disease. Neurological examination revealed paralytic dysarthria, left central facial nerve palsy, and left hemiparesis (manual muscle testing, 4 of 5). Blood examinations showed hyperthyroidism (thyroid-stimulating hormone ≤.010 µU/mL; free T3 ≥25.0 pg/mL; free T4 ≥8.0 ng/dL) and elevation of antithyroid antibody levels (thyroid peroxidase antibody, 87 IU/mL). The vessel wall of the right internal carotid artery was markedly enhanced on contrast-enhanced three-dimensional T1-weighted magnetic resonance imaging, suggesting vasculitis. Magnetic resonance angiography revealed right internal carotid artery occlusion after the branching ophthalmic artery. Arterial stenosis due to vasculitis was considered the cause of hemodynamic ischemic stroke. Vessel wall imaging such as high-resolution contrast-enhanced T1-weighted imaging seems useful for assessing the underlying mechanism of stroke in patients with Graves disease.

Recurrent Stroke Due to Metastatic Pulmonary Tumor Emboli as an Important Clinical Entity.

We present an autopsy case of repetitive stroke due to tumor emboli, indistinguishable from thromboembolism with a hypercoagulable state in its clinical course. A 72-year-old man diagnosed with stage IVA oropharyngeal squamous cell carcinoma received chemoradiotherapy. Follow-up imaging revealed mediastinal lymph nodes and pulmonary metastasis. One year later, the patient experienced right arm weakness, and brain magnetic resonance imaging showed acute ischemic lesions in multiple vascular territories. He was diagnosed with paradoxical cerebral embolism due to cancer-associated venous thrombosis and treated with rivaroxaban. However, newly developed cerebral infarcts were confirmed 1 month later. Then, rivaroxaban treatment was switched to subcutaneous unfractionated heparin injection. He was admitted again for stroke recurrence and died of respiratory failure 8 days after admission. Autopsy demonstrated pulmonary metastasis invading the veins and tumor emboli in the culprit cerebral arteries. D-dimer was kept constant at a slightly higher level, ranging from 1 to 3 µg/mL during the course of recurrence. We should consider tumor embolism in the differential diagnosis of recurrent stroke along with pulmonary tumor and resistance to heparin preparations with unchanged D-dimer levels.

Brachial-Ankle Pulse Wave Velocity as a Predictor of Silent Cerebral Embolism after Carotid Artery Stenting.

BACKGROUND: In neuroendovascular therapy, the effect of arterial stiffness on postprocedural cerebral thromboembolism is unknown. In this observational study, we examined the relationship between cerebral thromboembolism after carotid artery stenting and arterial stiffness. METHODS: From April 2015 to February 2017, we enrolled consecutive patients undergoing scheduled carotid artery stenting in our institution. In all patients, preprocedural brachial-ankle pulse wave velocity was used to assess arterial stiffness, whereas the number of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging was assessed after treatment. We also analyzed patient data and details of procedures in patients with carotid artery stenting. RESULTS: Twenty-one patients completed the study. The mean brachial-ankle pulse wave velocity was 1879 cm/s. There was no association of cerebral thromboembolisms with age, unstable plaque, protection device, or type of stent. However, the brachial-ankle pulse wave velocity was an independent predictor of cerebral thromboembolisms (P = .0017). CONCLUSIONS: Brachial-ankle pulse wave velocity is predictive of silent cerebral embolisms on diffusion-weighted magnetic resonance imaging after carotid artery stenting.

Chronic Elevation of Tumor Necrosis Factor-α Mediates the Impairment of Leptomeningeal Arteriogenesis in db/db Mice.

BACKGROUND AND PURPOSE: Leptomeningeal collateral growth is a key factor that defines the severity of ischemic stroke. Patients with stroke generally have vascular risk factors, such as diabetes mellitus; however, consensus is lacking on how diabetes mellitus affects leptomeningeal arteriogenesis. We investigate the influence of diabetes mellitus on the leptomeningeal arteriogenesis. METHODS: We measured the vessel diameter of the leptomeningeal anastomoses 14 days after the common carotid artery occlusion in db/db, db/+, and streptozotocin-induced hyperglycemic mice. In another set of these mice, we measured the infarct volume attributed to subsequent middle cerebral artery occlusion 14 days after the common carotid artery occlusion. Mac-2-positive cells on the dorsal brain surface and the mRNA expression of several macrophage-related factors in the cerebral cortex were examined. Finally, we tested whether the leptomeningeal arteriogenesis could be restored by pharmaceutical intervention in the db/db mice. RESULTS: Cerebral hypoperfusion led to significant ipsilateral leptomeningeal collateral growth in db/+ mice and streptozotocin-induced hyperglycemic mice. The collateral growth contributed to reduced infarct volume. In contrast, leptomeningeal arteriogenesis was impaired in the db/db mice. The number of Mac-2-positive cells was increased and tumor necrosis factor-α mRNA expression was induced after common carotid artery occlusion in the db/+ mice. However, these responses were not observed in the db/db mice. Administration of the tumor necrosis factor-α inhibitor etanercept before common carotid artery occlusion restored the hypoperfusion-induced leptomeningeal collateral growth in db/db mice. CONCLUSIONS: These results indicate that leptomeningeal arteriogenesis is impaired in db/db mice and that suppression of the tumor necrosis factor-α response to hypoperfusion is the major contributing factor.

Prevalence of positive diffusion-weighted imaging findings and ischemic stroke recurrence in transient ischemic attack.

BACKGROUND: The relationship between transient ischemic attack (TIA) clinical etiology, positive diffusion-weighted imaging (DWI) findings, and stroke recurrence is controversial. This study aimed to clarify the prevalence of positive DWI findings and TIA recurrence in relation to TIA patient characteristics. METHODS: The subjects were patients admitted to our stroke unit within 7 days after symptom onset between January 2006 and July 2013. We examined DWI findings and TIA recurrence according to etiologic subtypes. RESULTS: We enrolled 139 patients with lacunar TIA (n = 17), atherothrombotic TIA (n = 35), cardioembolic TIA (n = 25), TIA due to other causes (n = 32), or TIA with undetermined etiology (n = 30). The prevalence of positive DWI findings was highest among the cardioembolic TIA patients (56.0%). No association was found between the prevalence of positive DWI findings and symptom duration, motor presence, or ABCD(2) score. Plasma d-dimer level was significantly higher in the DWI-positive group than that in the DWI-negative group (P = .01). The prevalence of TIA recurrence was highest (5 of 35, 14.3%) among the atherothrombotic TIA patients, regardless of positive DWI findings. None of the patients treated with the anticoagulant and antiplatelet combination therapy experienced a recurrence. In contrast, almost all patients with cardioembolic TIA received anticoagulant treatment and none experienced recurrence. CONCLUSIONS: The prevalence of positive DWI findings was high among the cardiogenic TIA patients. TIA recurrence was often observed among the atherothrombotic TIA patients treated with antiplatelets. Management of patients with atherothrombotic TIA requires further aggressive antithrombotic strategy.

Association of interleukin-6 with the progression of carotid atherosclerosis: a 9-year follow-up study.

BACKGROUND AND PURPOSE: Limited information is available on the long-term effects of interleukin-6 (IL-6) on systemic atherosclerosis. The purpose of the present study was to clarify the relationship between chronic elevation of IL-6 and the long-term progression of carotid atherosclerosis. METHODS: We prospectively evaluated 210 patients with ≥1 vascular risk factors for 9.0±1.0 years. Carotid mean-maximal intima-media thickness (mmIMT), the serum high-sensitivity C-reactive protein (hs-CRP) level, and the serum IL-6 level were measured at baseline and every 3 years. The associations between the progression of mmIMT and the long-term average levels of hs-CRP and IL-6 were analyzed. RESULTS: Carotid mmIMT increased throughout the study period (0.031±0.026 mm/y). Baseline mmIMT was significantly associated with baseline hs-CRP (P=0.002) and baseline IL-6 (P<0.001) levels. Progression of mmIMT was positively correlated with average hs-CRP (P=0.001) and average IL-6 (P<0.001) levels. When adjusted for age, sex, traditional risk factors, and baseline mmIMT, mmIMT progression remained significantly associated only with the average IL-6 level (standardized ß=0.17; P=0.02), but not with the average hs-CRP level (standardized ß=0.10; P=0.18). CONCLUSIONS: Chronic elevation of serum IL-6 was associated with the progression of atherosclerosis in patients with vascular risk factors. IL-6 could be used as a quantitative marker and a potential therapeutic target for accelerated atherosclerosis.

Echogenicity of medium-to-large carotid plaques predicts future vascular events.

BACKGROUND: Although the echolucent plaque in carotid stenosis is associated with future ischemic stroke, the predictive value of echogenicity in small and medium size carotid plaques on vascular events has not been thoroughly examined. Thus, we prospectively tested the hypothesis that plaque echogenicity of carotid atheroma can predict the future total cardiovascular events in patients with vascular risk factors. METHODS: Ultrasound assessment of carotid intima-media complex thickness (IMT) and plaque echogenicity using integrated backscatter (IBS) analysis was performed in 596 patients aged 40 or more, with any history of vascular events or with at least 1 risk factor, who were enrolled between 2001 and 2006 in the Osaka Follow-up Study for Carotid Atherosclerosis, part 2 (OSACA2). We followed the incidence of total cardiovascular events including cerebrovascular events, coronary heart disease (CHD), and peripheral artery disease (PAD) for 6.4 years. We divided the patients into two groups according to the IBS index above (echorich plaques) and under (echolucent plaque) the median value, and calculated the hazard ratios (HR) of the echolucent group compared with the echogenic group in the risk of cardiovascular events. RESULTS: Among 596 patients, carotid stenosis was found only in 87 patients. During the follow-up period, we observed 121 cardiovascular events including 63 cerebrovascular events, 45 CHD cases, and 13 PAD cases. The patients with incident cardiovascular events had larger plaque thickness and lower IBS index than those without incident vascular events. The relative risk of vascular events for echolucent versus echorich plaques was 1.45 (95% confidence interval [CI] 0.99-2.13, p = 0.058) after adjustment for risk factors and plaque thickness. In patients with plaque size above the median value (>2.1 mm), the relative risk of vascular events for echolucent plaques was 1.72 (95% CI 1.06-2.85, p = 0.029), but this association was not observed in patients with plaque size <2.0 mm. CONCLUSIONS: The association between echogenicity of carotid plaque and incident vascular events is dependent on the plaque size. Echolucent medium-to-large plaques, but not small plaques, are associated with the risk of future total cardiovascular events. This finding suggests that measurement of echolucency in medium-to-large carotid plaques may improve selection of patients at high risk for total vascular events.

Association between interleukin-6 levels and first-ever cerebrovascular events in patients with vascular risk factors.

OBJECTIVE: The objective of this study was to examine the association of inflammatory markers with risk of first-ever cerebrovascular events (CVEs), while simultaneously evaluating subclinical vascular disease. METHODS AND RESULTS: We enrolled 464 outpatients who had vascular risk factors without any preexisting cardiovascular disease. We examined the presence of silent lacunar infarction (SLI) by magnetic resonance imaging; carotid intima-media thickness by ultrasound; and measured high-sensitivity C-reactive protein, interleukin (IL)-6, and IL-18 at baseline, and assessed their associations with CVEs using Cox proportional hazards models of 4.8±2.6 years follow-up. We further calculated measures of reclassification and discrimination. In age- and sex-adjusted analysis, IL-6, but neither high-sensitivity C-reactive protein nor IL-18, was associated with CVEs. The association remained significant after adjustment for conventional risk factors, intima-media thickness, and SLI (hazard ratios: 1.80, per 1-SD increase in log IL-6, P=0.03). Compared with the patients with below median IL-6 without SLI, those with above median IL-6 and SLI had a higher risk of CVEs (hazard ratios: 4.14, P=0.0014). The combination of IL-6 and SLI resulted in the net reclassification improvement of 14.3% (P=0.04), and the integrated discrimination improvement gain of 2.1% (P=0.05). CONCLUSIONS: IL-6 levels were independently associated with CVEs and could improve reclassification in those with SLI.

Basilar artery diameter is an independent predictor of incident cardiovascular events.

OBJECTIVE: Basilar arterial (BA) dolichoectasia is associated with cerebral small-vessel disease and stroke. However, the association between moderate dilation of the BA and cerebral small-vessel disease or subsequent cardiovascular events remains unclear. This study aims to clarify the factors related to BA diameter and to clarify whether the BA diameter is an independent predictor of cardiovascular events. APPROACH AND RESULTS: The study subjects comprised 493 outpatients with atherosclerotic risk factors. BA diameter, lacunar infarct, severity of deep white matter hyperintensities, and intracranial steno-occlusive lesions were assessed with MRI and magnetic resonance angiography. Then, we prospectively evaluated the association between BA diameter and cardiovascular events. The BA diameter ranged from 1.1 to 5.2 mm, and only 0.8% of the patients had dolichoectasia. Male sex, the presence of lacunar infarcts, the severity of deep white matter hyperintensities, the fetal-type variation of the circle of Willis, and intracranial steno-occlusive lesions were independently associated with BA diameter. In the mean follow-up of 6.0 years, 91 patients developed cardiovascular events. BA diameter was independently associated with total cardiovascular events after adjusting for age, sex, and conventional risk factors (hazard ratio, 1.55 per 1 mm increase in BA diameter; P=0.009). CONCLUSIONS: Increased BA diameter within the normal range is related to both large-vessel disease and cerebral small-vessel disease, and it could be a new predictor of cardiovascular events.

Clinical characteristics of stroke in SARS-CoV-2 infected patients in Japan: A prospective nationwide study.

INTRODUCTION: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan. METHODS: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately. RESULTS: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26). CONCLUSION: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log10 D-dimer. REGISTRATION: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226.

Treatment Results of Carotid Artery Stenting with an Open-Cell Stent: Analysis of 734 Consecutive Cases at a Single Center.

OBJECTIVE: In carotid artery stenting (CAS) for internal carotid artery stenosis, the stent is often selected according to the plaque properties and arterial tortuosity. In our institute, an open-cell stent is used as the first-line stent regardless of the characteristics of the lesion. This study was performed to examine the outcome of CAS with an open-cell stent as the real-world results. METHODS: In total, 811 CAS procedures using open-cell stents were performed for internal carotid artery stenosis from April 2002 to December 2019. Of these patients, we excluded those with hyperacute conditions for which CAS was performed within 3 days of onset, those in whom acute mechanical thrombectomy was performed simultaneously with CAS, and those with stenosis due to arterial dissection. Thus, 734 patients were retrospectively analyzed. Perioperative and long-term outcomes and risk factors for perioperative infarction were investigated. RESULTS: The periprocedural stroke rate and mortality rate were 3.7% (27/734) and 0.4% (3/734), respectively. Low-echoic plaque was a significant risk factor for periprocedural stroke in both univariate (P < 0.03) and multivariate (odds ratio, 2.69; 95% confidence interval, 1.14-6.66; P = 0.02) analyses. Cerebral infarction and high grade restenosis were observed in 15 (2.0%) and 17 (2.3%) patients during a median 50-month follow-up. CONCLUSIONS: CAS with open-cell stents showed good results in terms of both the postoperative stroke incidence and long-term severe restenosis rate. However, low-echoic plaque was a risk factor for perioperative stroke incidence, which should be considered when deciding on the indication for CAS with an open-cell stent.