Diastolic Dysfunction as a Positive Predictor of Recurrent Vascular Events in Patients With Noncardioembolic Stroke.

BACKGROUND: This study aimed to assess the effects of left ventricular diastolic dysfunction (LVDD) on vascular outcomes among patients with stroke of noncardioembolic origins. METHODS: This prospective observational study enrolled 563 patients with noncardioembolic stroke (mean age, 67.9 years; 66.7% men and 33.3% women individuals) registered in the Tokyo Women's Medical University Stroke Registry between 2013 and 2020. Then, patients were divided into the LVDD and non-LVDD groups. The primary outcome was a composite of major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death 1 year after stroke onset. The effect of LVDD on vascular events was assessed using multivariable Cox regression analyses. RESULTS: A total of 130 (23.1%) patients had any grade of LVDD, and patients with LVDD had a higher risk of major adverse cardiovascular event at 1 year than those without LVDD (annual rate, 20.9% versus 10.8%; log-rank P=0.001). The multivariable Cox proportional hazards regression model demonstrated that the presence of LVDD was independently associated with the major adverse cardiovascular event risk (hazard ratio, 1.79 [95% CI, 1.02-3.12]; P=0.019). Furthermore, the LVDD grade was proportional to the risk of major adverse cardiovascular events and recurrent stroke. CONCLUSIONS: LVDD may be associated with further vascular events after a noncardioembolic stroke, suggesting the importance of LVDD evaluations in risk stratification and secondary prevention in patients with noncardioembolic stroke. REGISTRATION: URL: https://upload.umin.ac.jp; Unique identifier: UMIN000031913.

Association of circulating CD34+ cells level and prognosis after ischemic stroke.

BACKGROUND: CD34 is a transmembrane phosphoglycoprotein and a marker of hematopoietic and nonhematopoietic stem/progenitor cells. In experimental studies, CD34+ cells are rich sources of endothelial progenitor cells and can promote neovascularization and endothelial repair. The potential role of CD34+ cells in stroke patients remains unclear. AIMS: We aimed to assess the prognostic effect of circulating CD34+ cell levels on the risk of vascular events and functional prognosis in stroke patients. PATIENTS AND METHODS: In this prospective observational study, patients with ischemic stroke were consecutively enrolled within 1 week of onset and followed up for 1 year. Patients were divided into three groups according to tertiles of the level of circulating CD34+ cells (Tertile 1, <0.51/µL; Tertile 2, 0.51-0.96/µL; and Tertile 3, >0.96/µL). The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. The secondary outcomes included the modified Rankin scale (mRS) scores. RESULTS: A total of 524 patients (mean age, 71.3 years; male, 60.1%) were included. High CD34+ cell levels were associated with younger age (p < 0.001) and low National Institutes of Health Stroke Scale scores at admission (p = 0.010). No significant differences were found in the risk of MACEs among the three groups (annual rates: 15.0%, 13.4%, and 12.6% in Tertiles 1, 2, and 3, respectively; log-rank p = 0.70). However, there were significant differences in the mRS scores at 3 months (median (interquartile range); 2 (1-4), 1 (1-3), and 1 (0-2) in Tertiles 1, 2, and 3, respectively; p = 0.010) and 1 year (3 (1-4), 2 (1-4), and 1 (0-3); p < 0.001) among these groups. After multivariable adjustments, a higher CD34+ cell level was independently associated with good functional outcomes (mRS score of 0-2) at 3 months (adjusted odds ratio (OR), 1.43; 95% confidence interval (CI), 1.01-2.05) and 1 year (adjusted OR, 1.53; 95% CI, 1.09-2.16). CONCLUSION: Although no correlations were found between circulating CD34+ cell levels and vascular event risk, elevated CD34+ cell levels were associated with favorable functional recovery in stroke patients. DATA ACCESS STATEMENT: Data supporting the findings of this study are available from the corresponding author on reasonable request. CLINICAL TRIAL REGISTRATION: The TWMU Stroke Registry is registered at https://upload.umin.ac.jp as UMIN000031913.

Relationship between quadriceps muscle computed tomography measurement and motor function, muscle mass, and sarcopenia diagnosis.

Background: The quadriceps muscle is one of the human body's largest and most clinically important muscles and is evaluated using mid-thigh computed tomography (CT); however, its relationship with motor function and sarcopenia remains unclear. Herein, we investigated the relationship between the cross-sectional area (CSA) of the quadriceps muscle, CT attenuation value (CTV), dual-energy X-ray absorptiometry muscle mass measurements, and muscle strength and motor function to evaluate the relationship between muscle mass loss and motor function decline, determine the diagnostic ability for sarcopenia, and confirm the usefulness of quadriceps muscle CT evaluation. Methods: A total of 472 middle-aged and older community dwellers (254 men and 218 women) aged ≥40 years (mean age: 62.3 years) were included in this study. The quantity and quality of the quadriceps muscle were assessed using CSA and CTV (CSA×CTV) as a composite index multiplied by quality and quantity. Age-adjusted partial correlations by sex with eight motor functions (knee extension muscle strength, power, normal walking speed, fast walking speed, grip strength, sit-up ability, balance ability, and reaction time) were evaluated, including correction methods for height, weight, and body mass index (BMI). Further, the accuracy of sarcopenia diagnosis was evaluated using appendicular muscle mass with dual-energy X-ray absorptiometry measurements, grip strength, and walking speed as the gold standard, and receiver operating characteristic curves were plotted to evaluate diagnostic performance. Results: In men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p<0.05), excluding only balance ability. BMI-corrected CSA was significantly correlated with all eight motor functions in men and women (p<0.05). In the diagnosis of sarcopenia based on skeletal muscle index, CSA (area under the curve (AUC) 0.935) and CSA×CTV (AUC 0.936) and their correction by height (CSA/height (AUC 0.917) and CSA×CTV/height (AUC 0.920)) were highly accurate and useful for diagnosis in men but moderately accurate in women (CSA (AUC 0.809), CSA×CTV (AUC 0.824), CSA/height (AUC 0.799), CSA×CTV/height (AUC 0.814)). Conclusion: The present results showed that a single CT image of the quadriceps muscle at the mid-thigh is useful for diagnosing sarcopenic changes, such as loss of muscle mass, muscle weakness, and muscle function.

Potential of patellar height measurement methods in predicting recurrent patellar dislocation incidence: a case-control study.

BACKGROUND: Recurrent patellar dislocation (RPD) is a multifactorial disease that affects young and active people. Patellar height measurements are used clinically to screen and diagnose knee conditions. However, there are no known studies that have assessed and compared the performance of patellar height indices for predicting the incidence of RPD, which could be used to recommend surgical treatment after primary patellar dislocation. This case-control study aimed to determine if the patellar height index could be used to predict the incidence of RPD, and to identify the optimal method in terms of its diagnostic ability for RPD. METHOD: Altogether, 133 patients (52 patients with RPD [Group R] and 81 sex- and age-matched controls [Group C]) were enrolled in this study. The Insall-Salvati (IS), Blackburne-Peel (BP), Caton-Deschamps (CD), and modified IS (mIS) methods were used to measure the patellar height index. The intra-observer and inter-observer reliabilities of these four methods were determined using intraclass correlation coefficients. A receiver operating characteristic curve analysis was performed to evaluate the predictive ability of each index and identify the cut-off values that indicated significantly increased risk of RPD. RESULTS: Patient demographics were similar between the two groups. The inter-observer and intra-observer reliabilities were good for all four methods. In patients with RPD, the mean index values for the four methods were significantly higher than those in the matched controls. The area under the curve (AUC) values for IS, BP, CD, and mIS were 0.91 (standard error [SE], 0.03; 95% confidence interval [CI], 0.84-0.96), 0.72 (SE, 0.05; 95% CI, 0.63-0.81), 0.86 (SE, 0.03; 95% CI, 0.79-0.92), and 0.96 (SE, 0.01; 95% CI, 0.94-0.99), respectively. CONCLUSION: Patellar height indices had high predictive performance for the incidence of RPD. The mIS method had the highest AUC.

Stroke in Patients With Common Noncancerous Gynecologic Diseases: A Multicenter Study in Japan.

Background and Objectives: Gynecologic diseases such as uterine fibroids, endometriosis, and adenomyosis are common in women of reproductive age. Case reports and small case series have reported ischemic stroke in women with such common noncancerous gynecologic diseases, and their cause of stroke is frequently attributed to cryptogenic stroke or unconventional mechanisms related to hypercoagulability. However, stroke etiology and prognosis are not well known. We assessed the prevalence of and stroke mechanisms related to common noncancerous gynecologic diseases using hospital-based clinical data. Methods: We retrospectively identified consecutive female patients with common noncancerous gynecologic diseases (uterine fibroids, endometriosis, and adenomyosis) diagnosed with ischemic stroke/transient ischemic attack (TIA) between the ages of 20 and 59 years admitted to 10 stroke centers in Japan by reviewing prospectively collected data between 2017 and 2019. The clinical, laboratory, and neuroimaging features were evaluated and compared between patients with conventional stroke mechanisms (CSMs) (large artery atherosclerosis, small vessel occlusion, cardioembolism, and other determined etiology) and non-CSMs (cryptogenic stroke and causes related to hypercoagulability such as nonbacterial thrombotic endocarditis and paradoxical embolism) according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Results: Of the 470 female patients with ischemic stroke/TIA, 39 (8%) (37 ischemic stroke and 2 TIA) had common noncancerous gynecologic diseases. The most common gynecologic diseases were uterine fibroids in 24 (62%) patients, followed by endometriosis in 9 (23%) and adenomyosis in 6 (15%). Twenty patients (51%) were assigned to the non-CSMs group, and 19 patients (49%) were assigned to the CSMs group. Adenomyosis and endometriosis were more frequent in the non-CSMs group than in the CSMs group. CA125 and D-dimer levels were higher in the non-CSMs group than in the CSMs group. Multiple vascular territory infarcts were frequent in patients with adenomyosis (60%) and endometriosis (43%) in the non-CSMs group. No stroke recurrence or death was observed within 3 months after discharge in both the CSMs and non-CSMs groups. Outcomes at 3 months after discharge were similar in both groups. Discussion: In patients with common noncancerous gynecologic diseases, hypercoagulopathy may play a role in the pathogenesis of ischemic stroke/TIA without CSMs.

Hyperhomocysteinemia Increases Vascular Risk in Stroke Patients with Chronic Kidney Disease.

AIMS: We aimed to assess the prognostic impact of hyperhomocysteinemia (HHcy) on the recurrent vascular event risk in stroke patients with or without chronic kidney disease (CKD). METHODS: In this prospective observational study, 621 patients (mean age, 69.5 years; male, 62.2%) with ischemic stroke or transient ischemic attack were consecutively enrolled within 1 week of onset and followed-up for 1 year. HHcy was defined as elevated levels of fasting total homocysteine ＞15 µmol/L. CKD was defined as an estimated glomerular filtration rate of ＜60 mL/min/1.73 m2 or a history of renal replacement therapy. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. RESULTS: The prevalence of HHcy was 18.5%. Patients with HHcy were more likely to have intracranial (37.4% versus 24.8%; p=0.008) and extracranial (20.9% versus 13.0%; p=0.037) artery stenosis than were those without HHcy. At 1 year, patients with HHcy were at a greater risk of MACE than were those without HHcy (annual rate, 17.8% versus 10.4%; log-rank p=0.033). In the Cox proportional hazard regression models, HHcy was independently associated with an increased risk of MACE in patients with CKD (adjusted hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.02-4.20), whereas HHcy was not predictive of MACE in those without CKD (adjusted HR, 1.00; 95% CI, 0.30-3.32). CONCLUSIONS: Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.

Long-Term Outcome in Patients With Acute Ischemic Stroke and Heart Failure.

BACKGROUND: This study aimed to identify the association between long term functional outcomes and acute ischemic stroke (AIS) in patients with heart failure (HF) in Japan and whether 1-year event risks can be related to these patients.Methods and Results: This was a prospective observational study, and 651 patients registered in the Tokyo Women's Medical University Stroke Registry were classified into the HF and non-HF groups. Functional outcome at 1 year after stroke onset was defined as either good (modified Rankin Scale [mRS] score of 0-2) or poor (mRS score of 3-6). The primary outcome was a composite of major adverse cardiovascular events (MACE), including non-fatal stroke, non-fatal acute coronary syndrome, and vascular death. Patients with HF had a higher poor functional outcome rate at 1 year than those without HF (54.7% vs. 28.2%, P<0.001). Multivariate logistic regression analysis also demonstrated the prevalence of HF was an independent predictor of an mRS score of ≥3 at 1 year after stroke onset (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; P=0.036). Furthermore, patients with HF tended to have a higher risk of MACE and all-cause mortality than those without HF. CONCLUSIONS: AIS patients with HF were associated with poor functional outcome at the 1-year follow up. Further multicenter studies involving a larger number of patients are warranted to verify these results.

Reclassification and risk stratification of embolic stroke of undetermined source by ASCOD phenotyping.

BACKGROUND: Common vascular diseases underlying stroke, including atherosclerosis, small-vessel disease (SVD), and cardioembolic pathology, can be present in patients with embolic stroke of undetermined source (ESUS), although these are not direct causes of stroke. AIMS: To describe the frequency and degree of the three major diseases using atherosclerosis, SVD, cardiac pathology, other causes, and dissection (ASCOD) phenotyping and to assess their prognostic implications in ESUS. METHODS: In this prospective observational study, 221 patients with ESUS within 1 week of onset were consecutively enrolled and followed up for 1 year. Vascular diseases associated with stroke were assessed using the ASCOD classification. The primary outcome was a composite of nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: Among 221 patients (mean age, 69.6 years; male, 59.7%), 135 (61.1%), 102 (46.2%), and 107 (48.4%) had any grade of atherosclerosis (A2 or A3), SVD (S3), and cardiac pathology (C2 or C3), respectively. ESUS patients graded as A2 or A3 (i.e. ipsilateral atherosclerotic plaque, contralateral ⩾ 50% stenosis, or aortic arch plaque) were at a significantly higher risk of composite vascular events than those graded as A0 (i.e. no atherosclerotic disease) (adjusted hazard ratio (95% confidence interval), 2.40 (1.01-5.72). No differences were observed in the event risk between patients with S3 (i.e. magnetic resonance imaging evidence of SVD) and S0 (i.e. no SVD) and between those with C2 or C3 (i.e. presence of any cardiac pathology) and C0 (i.e. no cardiac abnormalities). CONCLUSIONS: Atherosclerotic diseases corresponding to ASCOD grade A2 or A3 were predictive of recurrent vascular events in ESUS patients. Reclassification of ESUS using ASCOD phenotyping provides important clues for risk prediction and may guide optimal management strategies.

Triglyceride-glucose index as a prognostic marker after ischemic stroke or transient ischemic attack: a prospective observational study.

BACKGROUND: Triglyceride-glucose (TyG) index has been proposed as a simple and credible surrogate for insulin resistance and an independent predictor of cardiovascular outcomes. Due to lack of data on TyG index in stroke, we aimed to evaluate the predictive value of the index for recurrent vascular event risk among stroke patients. METHODS: This was a prospective observational study, in which 866 patients (mean age, 70.1 years; male, 60.9%) with ischemic stroke (n = 781) or transient ischemic attack (n = 85) within 1 week of onset were consecutively enrolled and followed up for 1 year. The TyG index was calculated as ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Patients were divided into 3 groups according to the tertile of TyG index levels: tertile 1, < 8.48; tertile 2, 8.48-9.01; and tertile 3, > 9.01. The primary outcome was a composite of major adverse cardiovascular events (MACE), including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: The median TyG index was 8.74 (interquartile range, 8.34-9.16). Higher levels of TyG index were significantly associated with increased prevalence of ipsilateral extracranial carotid (P = 0.032) and intracranial (P = 0.003) atherosclerotic stenosis. There were significant differences in the MACE risk between the three groups (annual rate, 8.6%, 11.6%, and 17.3% in the tertile 1, tertile 2, tertile 3 groups, respectively; log-rank P = 0.005). After multivariable adjustments, the TyG index remains to be a significant predictor of MACE, with an adjusted hazard ratio for tertile 3 versus tertile 1 groups (95% confidence interval) of 2.01 (1.16-3.47). Similar results were also found for the risk of recurrent stroke. CONCLUSIONS: TyG index is associated with cervicocerebral atherosclerosis and the MACE risk after a stroke, suggesting the potential value of TyG index to optimize the risk stratification of stroke patients. Trial registration URL:  https://upload.umin.ac.jp . Unique identifier: UMIN000031913.

Influence of vitamin D on sarcopenia pathophysiology: A longitudinal study in humans and basic research in knockout mice.

BACKGROUND: Vitamin D is an essential nutrient in musculoskeletal function; however, its relationship to sarcopenia remains ambiguous, and the mechanisms and targets of vitamin D activity have not been elucidated. This study aimed to clarify the role of vitamin D in mature skeletal muscle and its relationship with sarcopenia. METHODS: This epidemiological study included 1653 community residents who participated in both the fifth and seventh waves of the National Institute for Longevity Sciences, Longitudinal Study of Aging and had complete background data. Participants were classified into two groups: vitamin D-deficient (serum 25-hydroxyvitamin D < 20 ng/mL) and non-deficient (serum 25-hydroxyvitamin D ≥ 20 ng/mL); they underwent propensity-score matching for background factors (age, sex, height, weight, comorbidities, smoker, alcohol intake, energy intake, vitamin D intake, steps, activity, season and sarcopenia). Changes in muscle strength and mass over the 4-year period were compared. For basic analysis, we generated Myf6CreERT2 Vitamin D Receptor (VDR)-floxed (VdrmcKO ) mice with mature muscle fibre-specific vitamin D receptor knockout, injected tamoxifen into 8-week-old mice and analysed various phenotypes at 16 weeks of age. RESULTS: Grip strength reduction was significantly greater in the deficient group (-1.55 ± 2.47 kg) than in the non-deficient group (-1.13 ± 2.47 kg; P = 0.019). Appendicular skeletal muscle mass reduction did not differ significantly between deficient (-0.05 ± 0.79 kg) and non-deficient (-0.01 ± 0.74 kg) groups (P = 0.423). The incidence of new cases of sarcopenia was significantly higher in the deficient group (15 vs. 5 cases; P = 0.039). Skeletal muscle phenotyping of VdrmcKO mice showed no significant differences in muscle weight, myofibre percentage or myofibre cross-sectional area; however, both forelimb and four-limb muscle strength were significantly lower in VdrmcKO mice (males: forelimb, P = 0.048; four-limb, P = 0.029; females: forelimb, P < 0.001; four-limb, P < 0.001). Expression profiling revealed a significant decrease in expression of sarcoendoplasmic reticulum Ca2+ -ATPase (SERCA) 1 (P = 0.019) and SERCA2a (P = 0.049) genes in the VdrmcKO mice. In contrast, expression of non-muscle SERCA2b and myoregulin genes showed no changes. CONCLUSIONS: Vitamin D deficiency affects muscle strength and may contribute to the onset of sarcopenia. Vitamin D-VDR signalling has minimal influence on the regulation of muscle mass in mature myofibres but has a significant influence on muscle strength.

IgG4-related brain pseudotumor mimicking CNS lymphoma. A case report.

Here, we report a case of IgG4-related brain pseudotumor (IgG4-BP) in a 39-year-old woman, mimicking central nervous system (CNS) lymphoma. She presented with headache, fever, and fatigue. Her medical history was notable for appearance of a tumefactive brain lesion seven years before. Brain biopsy performed at the age of 32 revealed nonspecific inflammatory changes, and her condition improved with oral low-dose steroid therapy. Magnetic resonance imaging performed at the age of 39 identified a hyperintensity lesion with edema located at the medial temporal lobe region adjacent to the inferior horn of the left lateral ventricle on fluid-attenuated inversion recovery images, which showed gadolinium-contrast enhancement on T1-weighted images and a slightly hyperintensity signal on diffusion-weighted images. Methionine-positron emission tomography (PET) depicted a high methionine uptake in the lesion. Additionally, soluble levels of interleukin (IL)-2 receptor (sIL-2R) and IL-10 were increased in cerebrospinal fluid (CSF). Based on these findings, we suspected CNS lymphoma and performed partial resection of the brain lesion. Pathological examination revealed prominent lymphocytic infiltration associated with plasma cell infiltration. Most of the plasma cells were immunoreactive for IgG4. Storiform fibrosis and partially obliterative phlebitis were concomitantly observed. Thus, the patient was diagnosed as having IgG4-BP. To the best of our knowledge, this is the first case report of IgG4-BP with detailed findings obtained by CSF testing, methionine-PET, and pathological examination. Because IgG4-related diseases can present as a pseudotumor that mimics CNS lymphoma, it is essential to carefully differentiate IgG4-BP from CNS lymphoma.

Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial.

Background: Remote ischemic conditioning (RIC) refers to the application of repeated short periods of ischemia intended to protect remote areas against tissue damage during and after prolonged ischemia. Aim: We aim to evaluate the efficacy of RIC, determined by the modified Rankin Scale (mRS) score at 90 days after stroke onset. Design and methods: This study is an investigator-initiated, multicenter, prospective, randomized, open-label, parallel-group clinical trial. The sample size is 400, comprising 200 patients who will receive RIC and 200 controls. The patients will be divided into three groups according to their National Institutes of Health Stroke Scale score at enrollment: 5-9, mild; 10-14, moderate; 15-20, severe. The RIC protocol will be comprised of four cycles, each consisting of 5 min of blood pressure cuff inflation (at 200 mmHg or 50 mmHg above the systolic blood pressure) followed by 5 min of reperfusion, with the cuff placed on the thigh on the unaffected side. The control group will only undergo blood pressure measurements before and after the intervention period. This trial is registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/: UMIN000046225). Study outcome: The primary outcome will be a good functional outcome as determined by the mRS score at 90 days after stroke onset, with a target mRS score of 0-1 in the mild group, 0-2 in the moderate group, and 0-3 in the severe group. Discussion: This trial may help determine whether RIC should be recommended as a routine clinical strategy for patients with ischemic stroke.

Relationship between sarcopenia classification and thigh muscle mass, fat area, muscle CT value and osteoporosis in middle-aged and older Japanese adults.

Sarcopenia is one of the most important health issues in today's ageing society. As an evaluation method, computed tomography (CT) is an effective means of assessing not only the quantity but also the quality of skeletal muscle. We aimed to examine the relationship between sarcopenia severity and muscle/fat area, and osteoporosis. 321 patients (116 men and 205 women, mean age 77.2 ± 7.1 years, age range 53-96 years) who visited the Integrated Healthy Aging Clinic from 2016 to 2017 were included in this study. Based on the Asia Working Group for Sarcopenia2019 criteria, patients were divided into four groups: normal group, low-functional group (with normal skeletal muscle mass, but reduced muscle strength or physical function), sarcopenia group, and severe sarcopenia group. We measured the skeletal muscle (SM), intermuscular adipose tissue (IMAT), and subcutaneous adipose tissue (SAT) areas and the CT attenuation values (CTV) using cross sections of the mid-thigh CT. We also measured bone mineral density. Then, we compared each result among the four groups. We found a significant decrease in SM area in both men and women with sarcopenia (p < 0.001 for both sexes). In women, a decrease in SAT area was observed in the sarcopenia group (p < 0.001), and an increase in IMAT was observed in the low functional group (p < 0.001). The CTV decreased in men with sarcopenia and severe sarcopenia; similarly, women in the low functional and severe sarcopenia groups had decreased CTV (p < 0.001 for both sexes). An association between sarcopenia and osteoporosis in men was detected (p = 0.004). By using not only muscle mass but also fat mass and CTV, we were able to better examine the pathogenesis of sarcopenia and differences between men and women in Japanese middle-aged and older adults.

[A case of cardioembloic stroke with wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome].

Here, we report a case of an 85-year-old man who presented sudden onset of diplopia, dysarthria, and gait disturbance. On admission, he exhibited bilateral adduction palsy, convergence palsy, and binocular exotropia in the forward gaze showing wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. He had a history of chronic nonvalvular atrial fibrillation. DWI-MRI revealed acute ischemic lesions in the paramedian pontine tegmentum, lower midbrain, both cerebellar hemispheres, and left frontal cortex. He was thus diagnosed with an acute phase of cardioembolic stroke. Subsequently, the right eye adduction palsy in the forward gaze was slightly improved, but other eye movement disorders persisted during discharge from the hospital. The pathology was suspected to involve bilateral damages to both medial longitudinal fasciculus and the paramedian pontine reticular formation. WEBINO syndrome was not only ascribed to lacunar infarction and large artery atherosclerosis but also cardioembolic stroke. The presence of other non-eye symptoms and multiple ischemic lesions could be the characteristics of WEBINO syndrome following cardioembolic stroke.

Prognostic Role of Hypertriglyceridemia in Patients With Stroke of Atherothrombotic Origin.

BACKGROUND AND OBJECTIVES: Hypertriglyceridemia is perceived to promote atherosclerotic pathology, but its role in stroke has not been well defined. Our aim was to assess the contribution of hypertriglyceridemia to residual vascular risk in patients with atherothrombotic stroke. METHODS: The Tokyo Women's Medical University Stroke Registry is an ongoing prospective, observational registry in which 870 patients with acute ischemic stroke or TIA within 1 week of onset were consecutively enrolled and followed up for 1 year. Hypertriglyceridemia was defined as serum triglycerides levels of ≥150 mg/dL under fasting conditions. Significant stenosis of the cervicocephalic arteries was defined as having ≥50% stenosis or occlusion. The primary outcome was major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: Of 870 patients (mean age 70.1 years, male 60.9%), 217 (24.9%) had hypertriglyceridemia. High triglycerides levels were significantly associated with an increased prevalence of intracranial artery stenosis, particularly in the anterior circulation, rather than extracranial artery stenosis. Patients with hypertriglyceridemia had a greater risk of major adverse cardiovascular events than those without (annual rate 20.9% vs 9.7%; p < 0.001), even after adjustment for potential confounders, including baseline low-density lipoprotein cholesterol and statin use (adjusted hazard ratio 2.46, 95% CI 1.62-3.74). The higher risk of vascular events in patients with hypertriglyceridemia vs without hypertriglyceridemia was observed among patients with stroke of atherothrombotic origin (n = 174, annual rate 35.1% vs 14.2%; p = 0.001), those with significant intracranial artery stenosis (n = 247, annual rate 29.9% vs 14.7%; p = 0.006), and those with significant extracranial carotid artery stenosis (n = 123, annual rate 23.0% vs 9.4%; p = 0.042). In contrast, hypertriglyceridemia was not predictive of recurrent vascular events in patients with cardioembolic stroke (n = 221, annual rate 19.1% vs 10.5%; p = 0.18). DISCUSSION: Hypertriglyceridemia is an important modifiable risk factor that drives residual vascular risk in patients with stroke of atherothrombotic origin, even while on statin therapy. TRIAL REGISTRATION INFORMATION: UMIN000031913 at upload.umin.ac.jp. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with atherothrombotic stroke, hypertriglyceridemia is associated with an increased risk of major cardiovascular events.

Atherogenic Dyslipidemia and Residual Vascular Risk After Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Notwithstanding the current guideline-based management, patients with stroke retain a substantial risk of further vascular events. We aimed to assess the contribution of atherogenic dyslipidemia (AD) to this residual risk. METHODS: This was a prospective observational study, in which 792 patients (mean age, 70.1 years; male, 60.2%) with acute ischemic stroke (n=710) or transient ischemic attack (n=82) within 1 week of onset were consecutively enrolled and followed for 1 year. AD was defined as having both elevated levels of triglycerides ≥150 mg/dL and low HDL-C (high-density lipoprotein cholesterol) <40 mg/dL in men or <50 mg/dL in women, under fasting conditions. The primary outcome was a composite of major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: The prevalence of AD was 12.2%. Patients with AD more often had intracranial artery stenosis than those without (42.3% versus 24.1%; P=0.004), whereas no differences were observed in the prevalence of extracranial artery stenosis (17.7% versus 12.9%; P=0.62) or aortic plaques (33.3% versus 27.0%; P=0.87). At 1 year, patients with AD were at a greater risk of major adverse cardiovascular events (annual rate, 24.5% versus 10.6%; hazard ratio [95% CI], 2.33 [1.44-3.80]) and ischemic stroke (annual rate, 16.8% versus 8.6%; hazard ratio [95% CI], 1.84 [1.04-3.26]) than those without AD. When patients were stratified according to baseline LDL-C (low-density lipoprotein cholesterol) level, AD was predictive of major adverse cardiovascular events among those with LDL-C ≥100 mg/dL (n=509; annual rate, 20.5% versus 9.6%; P=0.036) as well as those with LDL-C <100 mg/dL (n=283; annual rate, 38.6% versus 12.4%; P<0.001). CONCLUSIONS: AD is associated with intracranial artery atherosclerosis and a high residual vascular risk after a stroke or transient ischemic attack. AD should be a promising modifiable target for secondary stroke prevention. Registration: URL: https://upload.umin.ac.jp; Unique identifier: UMIN000031913.

Characteristics and Prognosis of Stroke in Living Donor Renal Transplant Recipients.

AIMS: We aimed to determine the characteristics and vascular outcomes of stroke in renal transplant (RT) recipients and compare them with those in patients on hemodialysis (HD) and those with no renal replacement therapy (RRT). METHODS: In this prospective observational study, 717 patients (mean age, 70.8 years; male, 60.5%) with acute ischemic stroke within one week of onset were consecutively enrolled and followed for one year. The patients were classified into three groups: (1) living donor RT recipients (n=27); (2) patients on maintenance HD before the index stroke (n=39); and (3) those with no history of RRT (n=651). The primary outcome was a composite of major adverse cardiovascular events (MACE). RESULTS: Diabetic nephropathy was the most common reason for RRT in both RT and HD patients. RT patients were more likely to have embolic stroke of undetermined source (33.3%) than others, whereas HD patients more often had cardioembolism (51.3%). No difference was observed in the MACE risk between the patients in RT and non-RRT groups (annual rate, 11.3% vs. 13.1%; log-rank P=0.82; hazard ratio [95% confidence interval], 0.92 [0.29-2.98]). In contrast, HD patients had a greater risk of MACE than those with no RRT (annual rate, 28.2% vs. 13.1%; log-rank P=0.019; hazard ratio [95% confidence interval], 2.24 [1.16-4.3]). CONCLUSIONS: The underlying etiologies of stroke differed in RT and HD patients. The one-year risk of MACE for stroke patients who had received an RT was lower than that for patients undergoing HD and comparable with that of patients with no RRT.

Scapular Winging following Sports-Related Injury in a Rugby Player.

The most common cause of medial scapular winging is long thoracic nerve palsy (LTN) and subsequent serratus anterior muscle dysfunction. A 16-year-old right-handed male high-school rugby player developed severe right-sided neck and shoulder pain after tackling an opponent while playing rugby. Six weeks after initial injury, the patient observed shoulder muscle weakness when performing his daily activities. On physical examination, limited active elevation of the right shoulder in the scapular plane and scapular winging was observed. Magnetic resonance imaging revealed atrophy of both the SA and subclavius muscles on the right side, and we initially suspected an LTN injury sustained. However, while detailing his history, the patient explained that he also had noted difficulty sucking high viscosity drinks such as shakes and smoothies since childhood. In addition, physical examination showed weakness of the orbicularis oculi muscle. Considering the facial muscle weakness, facioscapulohumeral dystrophy (FSHD) was also suspected, and genetic testing showed chromosome 4q35 deletion with restriction fragments 17 kb and 3 tandem repeated DNA confirming the diagnosis of FSHD. Clinicians should be aware that FSHD could be one of the differential diagnoses of scapular winging after sports injury, and surgeons should rule out the diagnosis of FSHD before performing any surgical treatment for SA palsy.

Deep flexion helps to avoid popliteal artery injury during all-inside lateral meniscal repair: A cadaveric study.

BACKGROUND: Arthroscopic meniscus repair rarely leads to major complications such as popliteal artery injury. The distance between the suturing device and the popliteal artery, and the risk of popliteal artery injury at different knee flexion angles during all-inside lateral meniscal repair remain unclear. METHODS: All-inside devices were inserted into 10 human cadaveric knees at the posterior horn of the lateral meniscus through the anterolateral portal at 60°, 90°, and 120° knee flexion; posterior segment of the lateral meniscus through the anterolateral portal at 60°, 90°, and 120°; and anteromedial portal at 90°. Distance and positional relationship between the device and popliteal artery were measured radiographically. RESULTS: In posterior horn repair through the anterolateral portal, the median distance increased from 5.7 mm at 60° to 9.1 mm at 90° (P = 0.63) and 18.0 mm at 120° (P = 0.02). The device pushed the wire at 60° in three cases, 90° in one case, and 120° in 0 cases. In posterior segment repair through the anterolateral portal, the median distance was 12.6 mm at 60°, 10.4 mm at 90°, and 18.3 mm at 120° (P = 0.08). The median distance at 90° was 18.1 mm through the anteromedial portal, the same as that at 120° through the anterolateral portal (P = 0.43), but greater than that at 90° through the anterolateral portal (P = 0.04). The wire was not pushed in any case. CONCLUSION: Although all-inside repair of the posterior part of the lateral meniscus through the anterolateral portal is risky, deeper knee flexion reduces the risk of popliteal artery injury.

4-Methylumbelliferone suppresses catabolic activation in anterior cruciate ligament-derived cells via a mechanism independent of hyaluronan inhibition.

BACKGROUND: The anterior cruciate ligament (ACL) has a key role as a dynamic stabilizer of the knee joints, and ACL dysfunction caused by traumatic or degenerative rupture accelerates osteoarthritis progression. Thus, it is important to prevent the degenerative rupture of the ACL. 4-Methylumbelliferone (4-MU), a pre-approved drug, exerts anti-inflammatory effects in osteoarthritis chondrocytes. It was originally used as an inhibitor of hyaluronan synthesis in chondrocytes. METHODS: In this study, we investigated whether 4-MU affects the expression of catabolic factors, such as matrix metalloproteinase (MMP)-1, MMP-3, and interleukin (IL)-6, in ACL-derived cells and ACL explant cultures using immunohistochemistry, real-time RT-qPCR, and capillary western immunoassay. Furthermore, the hyaluronan concentration was evaluated using a colorimetric assay. Statistical analyses were conducted using analysis of variance for multi-group comparisons, followed by Tukey or Tukey-Kramer post hoc test. RESULTS: Our results revealed, for the first time, that 4-MU suppressed the IL-ß-induced upregulation of pro-catabolic factors, such as MMP-1, MMP-3, and IL-6, in ACL-derived cells. This suppressive effect was also observed in the cultured ligament tissues in ex vivo experiments. 4-MU also reversed an enhanced dependence on glycolysis in IL-1ß-activated ACL-derived cells. Furthermore, we found that the suppressive effects of 4-MU were exerted directly and not through the inhibition of hyaluronan synthesis. CONCLUSIONS: We conclude that 4-MU could be an effective and useful treatment for knee osteoarthritis, owing to its anti-inflammatory effect on, not only chondrocytes but also on ligament cells.