Validation of Signal Intensity Gradient from TOF-MRA for Wall Shear Stress by Phase-Contrast MR.

To validate the correlation between the signal intensity gradient (SIG) from time-of-flight magnetic resonance angiography (TOF-MRA) and wall shear stress (WSS) determined by phase contrast magnetic resonance (PC-MR), we conducted both experimental and human studies. In the experimental study, we measured WSS in four tubes of different sizes with variable flow rates using PC-MR and TOF-MRA. The flow rates of water in the experimental study ranged from 0.06 to 12.75 mL/s, resulting in PC-WSS values between 0.1 and 1.6 dyne/cm2. The correlation between PC-WSS and SIG was statistically significant, showing a coefficient of 0.86 (P < 0.001, R2 = 0.75). The line fit provided the conversion equation as Y = 1.6287X - 1.1563 (Y = PC-WSS, X = SIG). For the human study, 28 subjects underwent TOF-MRA and PC-MR examinations of carotid and vertebral arteries. Arterial PC-WSS and SIG were determined in the same segment for each subject. The arterial PC-WSS ranged from 1.9 to 21.0 dyne/cm2. Both carotid and vertebral arteries showed significant correlations between PC-WSS and SIG, with coefficients of 0.85, 0.86, 0.91, and 0.81 in the right and left carotid and vertebral arteries, respectively. Our results show that SIG from TOF-MRA and SIG-WSS derived from the conversion equation provide concurrent in vivo hemodynamic information on arterial shear stress. This study was registered on ClinicalTrials.gov with the identifier NCT04585971 on October 14, 2020.

Cerebral artery signal intensity gradient from Time-of-Flight Magnetic Resonance Angiography and clinical outcome in lenticulostriate infarction: a retrospective cohort study.

Purpose: Lenticulostriate infarction requires further research of arterial hemodynamic factors, as the disease is diagnosed in the absence of major arterial stenosis or cardioembolism. Methods: In this multicenter retrospective cohort study, we included patients who were hospitalized for lenticulostriate infarction from January 2015 to March 2021 at three stroke centers in South Korea. We obtained hemodynamic information on cerebral arteries using signal intensity gradient (SIG), an in-vivo approximated wall shear stress (WSS) derived from Time-of-Flight Magnetic Resonance Angiography (TOF-MRA). A favorable outcome was defined as a modified Rankin Scale of 0 to 2 at hospital discharge. Results: A total of 294 patients were included, of whom 146 (49.7%) had an unfavorable outcome. The unfavorable outcome group showed significantly lower SIG in both middle cerebral arteries (MCAs) than the favorable group (5.2 ± 1.2 SI/mm vs. 5.9 ± 1.2, p < 0.001), and similar findings were observed in other cerebral arteries. The SIGs in both MCAs were independently associated with favorable outcome, with an odds ratio of 1.42 (95% confidence interval, 1.11-1.80; p = 0.005) for the right MCA and 1.49 (95% CI, 1.15-1.93; p = 0.003) for the left MCA, after adjusting for potential confounders. Similar findings were observed in other cerebral artery SIGs. Conclusion: Cerebral artery SIG from TOF-MRA was significantly associated with short-term functional outcomes in patients with lenticulostriate infarction. Further studies are needed to investigate the temporal relationships of SIG in patients with cerebral infarction.

Geometric versus Hemodynamic Indexes for Rupture-Destined Aneurysms: A Retrospective Cohort and a Repeated-Measures Study.

INTRODUCTION: A proper stratification of intracranial aneurysms is critical in identifying rupture-destined aneurysms and unruptured intracranial aneurysms. We aimed to determine the utility of geometric and hemodynamic indexes in differentiating two types of aneurysms and to examine the characteristics of natural evolutionary changes of unruptured aneurysms. METHODS: Rupture-destined aneurysm refers to an aneurysm that undergoes subsequent aneurysmal subarachnoid hemorrhage (SAH). On the other hand, an unruptured intracranial aneurysm is characterized by an aneurysm that does not experience rupture during serial time-of-flight magnetic resonance angiography (TOF-MRA). In addition to geometric indexes, signal intensity gradient (SIG), an in vivo approximated wall shear stress from TOF-MRA, was measured in aneurysms. The difference between the maximum and minimum values of SIG in an aneurysm compared to parent arterial values was designated as the delta-SIG ratio. RESULTS: This study analyzed 20 rupture-destined aneurysms in 20 patients and 45 unruptured intracranial aneurysms in 41 patients with follow-up TOF-MRA. While geometric indexes did not show differences between the two groups, the delta-SIG ratio was higher in the rupture-destined aneurysms (1.5 ± 0.6 vs. 1.1 ± 0.3, p = 0.032). The delta-SIG ratio showed a higher area under the receiver operating characteristic curve for SAH than the size ratio (0.72 [95% CI, 0.58-0.87] vs. 0.56 [95% CI, 0.41-0.72], p = 0.033). The longitudinal re-examination of TOF-MRA in the unruptured intracranial aneurysms revealed evidence of aneurysmal growth, while concurrently exhibiting hemodynamic stability. CONCLUSION: The delta-SIG ratio showed higher discriminatory results between the two groups compared to geometric indexes. Aneurysmal rupture risk should be assessed by considering both geometric and hemodynamic information. This study was registered on ClinicalTrials.gov (NCT05450939).

Long-Lasting Unruptured Large Intracranial Aneurysm in Bilateral Moyamoya Disease: Case Report.

Introduction: The rupture risk of intracranial aneurysms in patients with moyamoya disease is higher than that in the general population. We report a confirmed case of moyamoya disease with bilateral middle cerebral artery (MCA) occlusion with a large and long-lasting aneurysm. Case: A 71-year-old woman visited the clinic with a large intracranial aneurysm. The patient was diagnosed with an ischemic stroke 2 months ago. She exhibited weakness in the left upper and lower extremities and dysarthria and was taking aspirin. The brain magnetic resonance imaging showed complete occlusion in the bilateral MCA proximal (M1) and a large 11 × 11 mm nonruptured cerebral aneurysm in the A3 segment of the left anterior cerebral artery. On transfemoral cerebral angiography, the patient was diagnosed with Suzuki grade VI moyamoya disease with bilateral MCA occlusion. After 7 years, the cerebral aneurysm size further increased, but it remained unruptured. Conclusions: Here, the patient had moyamoya disease with a large aneurysm, but aneurysmal rupture did not occur even after 7 years. Our case report might help in understanding the mechanisms of cerebral aneurysm occurrence and rupture in moyamoya patients.

Rapid Regression of Carotid Artery Stenosis Shortly after Intensive Medical Therapy.

Carotid artery stenosis (CAS) is mainly caused by atherosclerosis. Intensive medical therapy is effective in preventing stroke in CAS. To date, there has been no published report of rapid regression of CAS. A woman with untreated hyperlipidemia visited our emergency room with left hemiparesis. She exhibited facial palsy, left hemiparesis, and dysarthria immediately after the visit. Brain magnetic resonance (MR) diffusion-weighted imaging confirmed acute infarction in the right middle cerebral artery (MCA) territory due to severe stenosis of the right internal carotid artery (ICA), which was revealed by MR angiography and carotid duplex ultrasonography. The patient started intensive statin therapy and dual antiplatelet agent therapy. Carotid artery stenting was not performed until hospitalization day 16 due to pleural effusion. On day 16, digital subtraction angiography was performed, and spontaneous regression of severe stenosis was observed. Only mild stenosis with ulcerative plaque was evident. The rapid CAS regression in this case may be caused by M2 macrophage polarization as a result of intensive statin therapy. This rapid regression may also result from reduced foam cell formation by statin and aspirin and thereby increased endogenous thrombolysis. Our patient demonstrated the efficacy of short-term intensive statin and aspirin therapy on atherosclerosis with untreated hyperlipidemia.

Hemorrhagic Transformation after Intravenous Tissue Plasminogen Activator Administration in Acute Distal Middle Cerebral Artery Occlusion.

Atrial fibrillation and cerebral embolism are known to increase the risk of hemorrhagic transformation (HT). In addition, a sufficient number of collateral vessels in acute ischemic stroke can maintain the ischemic penumbra and prevent progression to the ischemic core, while an insufficient number of collateral vessels increase the HT risk after therapeutic recanalization. In this case, when the middle cerebral artery is recanalized, reperfusion injury may occur in the basal ganglia due to insufficient collateral vessels.

Factors Distinguishing Proximal and Distal Internal Carotid Artery Occlusions in Patients with Acute Ischemic Stroke.

Acute internal carotid artery (ICA) occlusions cause extensive brain ischemia. Accurate determination of the occlusion site facilitates rapid revascularization interventions and improves prognosis. However, proximal ICA occlusions, as determined with computed tomography (CT) angiography, often are located more distally. Therefore, we assessed clinical and imaging factors associated with the accurate determination of occlusion sites. In this observational study, we evaluated 102 patients who presented acute ischemic stroke symptoms and had a CT angiography within 6 h, showing proximal ICA occlusion. The participants were divided into two groups, depending on whether there was correspondence between digital subtraction angiography and CT angiography regarding the occlusion location. Proximal occlusions were, accordingly, categorized as "true" (correspondence) or "false" (no correspondence; distal). Demographic, clinical, and imaging features were analyzed. Multivariate regression analysis was performed to identify factors predicting the correspondence between actual ICA occlusion sites and those detected by CT angiography. The shape (Odds ratios, OR = 646.584; Confidence interval, CI = 21.703-19263.187; p < 0.001) and the length (OR = 0.696; CI = 0.535-0.904; p = 0.007) of the ICA occlusion and atrial fibrillation (OR = 0.024; CI = 0.002-0.340; p = 0.006) were significant factors. The cut-off length of ICA stump at 6.2 mm, the sensitivity was 71%, and the specificity was 70% (area under the ROC curve = 0.767).

Factors Affecting Post-Stroke Depression in Acute Ischemic Stroke Patients after 3 Months.

Post-stroke depression (PSD) affects approximately one-third of stroke patients. PSD not only impairs recovery and lowers quality of life, but has also serious neurological consequences, high mortality, and stroke recurrence risks. Studies on PSD-related prognostic factors are still lacking, especially environmental factors. Moreover, relieving factors after PSD in stroke patients has not been reported. This study aimed to investigate (study design 1) risk factors for PSD diagnosis after three months, and (study design 2) related factors for the relieving of early PSD after three months. This retrospective study included 227 patients hospitalized for acute ischemic stroke within three days at Jeonbuk National University Hospital from January to December 2019. The depressive status was assessed using the Hamilton Depression Rating Scale (HDRS) at admission and after three months. Clinical and laboratory data were analyzed for relevant prognostic factors. (Study design 1) HDRS score at admission (adjusted odds ratio (aOR) 1.22, 95% confidence interval (CI) 1.14-1.31; p < 0.001) and hospitalization period (aOR 1.11, 95% CI 1.02-1.20; p = 0.013) were confirmed as prognostic factors of PSD after three months. (Study design 2) The National Institute of Health Stroke Scale (NIHSS) score at discharge (aOR 0.80, 95% CI 0.68-0.94; p = 0.006) and HDRS score at admission (aOR 0.80, 95% CI 0.71-0.89; p < 0.001) were confirmed as prognostic factors of depression improvement after three months. In conclusion, environmental factors such as hospitalization period could be important in managing PSD. Factors related to PSD improvement are expected to be helpful in establishing a strategy for PSD recovery.

Aconitine Neurotoxicity According to Administration Methods.

We evaluated the toxic effects of aconitine on the human nervous system and its associated factors, and the general clinical characteristics of patients who visited the emergency room due to aconitine intoxication between 2008 and 2017. We also analyzed the differences related to aconitine processing and administration methods (oral pill, boiled in water, and alcohol-soaked), and the clinical characteristics of consciousness deterioration and neurological symptoms. Of the 41 patients who visited the hospital due to aconitine intoxication, 23 (56.1%) were female, and most were older. Aconitine was mainly used for pain control (28 patients, 68.3%) and taken as oral pills (19 patients, 46%). The patients showed a single symptom or a combination of symptoms; neurological symptoms were the most common (21 patients). All patients who took aconitine after processing with alcohol showed neurological symptoms and a higher prevalence of consciousness deterioration. Neurological symptoms occurred most frequently in patients with aconitine intoxication. Although aconitine intoxication presents with various symptoms, its prognosis may vary with the processing method and prevalence of consciousness deterioration during the early stages. Therefore, the administration method and accompanying symptoms should be comprehensively investigated in patients who have taken aconitine to facilitate prompt and effective treatment and better prognoses.

Comparison of clinical and biological differences between patent foramen ovale subtypes in ischemic stroke.

BACKGROUNDS: The patent foramen ovale (PFO) is an atrial septal tunnel with a flap-like opening, causing a right-to-left shunt (RLS) between the atrial chambers. There are few studies on ischemic stroke characteristics based on PFO subtypes. In this study, we investigated whether there are differences in clinical characteristics, RLS amount, and the etiology of stroke defined by the Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification between PFO subtypes. METHODS: We retrospectively analyzed consecutive ischemic stroke patients with PFO who were admitted to the Jeonbuk National University Hospital from November 2013 to February 2015, and performed a microbubble test to detect RLS. The patients were divided into two groups according to RLS characteristics: constant RLS group and provoked RLS group. We compared the clinical characteristics and degree of RLS between the PFO subtypes. RESULTS: Out of 144 ischemic patients evaluated in this study, 83 (58%) were classified into the constant RLS group and 61 (42%) into the provoked RLS group. The proportion of microembolic signal (MES) grades 3 and 4 was significantly higher in the constant RLS group than in the provoked RLS group. There were no statistical differences in the distribution of TOAST classification between the two groups. CONCLUSION: The constant RLS group showed a higher proportion of high-grade MES than the provoked RLS group.

Peripheral vasoreactivity in acute ischemic stroke with hemiplegia.

The association between vasomotor tone of the peripheral arteries and cerebral hemisphere function has not been established. This study analyzed the peripheral vasoreactivity of patients with acute ischemic stroke and hemiplegia using a modified Raynaud scan, which is a new technology for blood flow measurement. In this retrospective case-control study, we examined patients with unilateral weakness consistent with ischemic lesions who underwent brain magnetic resonance imaging and modified Raynaud scanning within five days from the onset of symptoms. The modified Raynaud scan was used to quantify the radioactivity of the bilateral fingertips during rest and cooling-heating thermal stress conditions and estimate vasoreactivity based on the change in the blood amount per time under rest-thermal stress. The subjects were classified into the preserved and impaired groups based on their degrees of vasomotor reaction. Based on the modified Raynaud scanning, 37 (mean age = 69.1 ± 10.6) and 32 (mean age = 62.6 ± 11.8) subjects were allocated to the preserved and impaired groups, respectively. Binary logistic regression showed that the affected limb edema (odds ratio (OR) 6.15; confidence interval (CI) 1.40-26.97; p = 0.016) and anterior circulation (OR 3.68; CI 1.01-13.48; p = 0.049) were associated with impaired vasoreactivity. The modified Raynaud scans confirmed that central lesions in the anterior circulation with hemiparesis may influence the vasoreactivity of edematous peripheral arteries. These results may inform treatment and rehabilitation for stroke patients with hemiparesis.

Association of Carotid Artery Endothelial Signal Intensity Gradient with Unilateral Large Artery Ischemic Stroke.

BACKGROUND: Common carotid artery (CCA) and internal carotid artery (ICA) are aligned linearly, but their hemodynamic role in ischemic stroke has not been studied in depth. OBJECTIVES: We aimed to investigate whether CCA and ICA endothelial shear stress (ESS) could be associated with the ischemic stroke of large artery atherosclerosis (LAA). METHODS: We enrolled consecutive patients with unilateral ischemic stroke of LAA and healthy controls aged >60 years in the stroke center of Jeonbuk National University Hospital. All patients and controls were examined with carotid artery time-of-flight magnetic resonance angiography, and their endothelial signal intensity gradients (SIGs) were determined, as a measure of ESS. The effect of right or left unilateral stroke on the association between carotid artery endothelial SIG and ischemic stroke of LAA was assessed. RESULTS: In total, the results from 132 patients with ischemic stroke of LAA and 121 controls were analyzed. ICA endothelial SIG showed significant and independent associations with the same-sided unilateral ischemic stroke of LAA, even after adjusting for the potential confounders including carotid stenosis, whereas CCA endothelial SIG showed a significant association with the presence of the ischemic stroke of LAA. CONCLUSION: Although CCA and ICA are located with continuity, the hemodynamics and their roles in large artery ischemic stroke should be considered separately. Further studies are needed to delineate the pathophysiologic roles of ESS in CCA and ICA for large artery ischemic stroke.

Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient. OBJECTIVES: The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD. METHODS: We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed. RESULTS: Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94-5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53-48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00-1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29-0.72, p = 0.001) was negatively associated. CONCLUSION: In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.

Characteristics of Symptomatic Basilar Artery Stenosis Using High-Resolution Magnetic Resonance Imaging in Ischemic Stroke Patients.

AIM: Arterial narrowing associated with the progression of atherosclerosis leads to serious conditions such as stroke, coronary artery disease, or even death. High-resolution magnetic resonance imaging (HR-MRI) is better for detecting arterial wall status and discriminating tissue characteristics than conventional imaging. We used HR-MRI to investigate the frequency of patients with basilar artery (BA) stenosis observed distinctively on routine angiography and identify the clinical features associated with this imaging. We analyzed the nature of the vessel wall causing the basal artery stenosis by HR-MRI, and related clinical factors. METHODS: Patients with BA stenosis underwent HR-MRI. The association between atherosclerosis (with or without intraplaque hemorrhage [IPH]) and dissection was analyzed. High signal intensity within a BA plaque on magnetization-prepared rapid acquisition with gradient echo was defined as an area with a signal intensity ＞200% that of the adjacent muscle. RESULTS: Fifteen patients were diagnosed with BA dissection on HR-MRI. IPH was identified in 14 patients. Patients with BA plaque with IPH were older and had higher prevalence of hypertension and hyperlipidemia than the other patients. The frequencies of alcohol drinking and number of current smokers were higher in the dissection group than in the other groups. Hyperlipidemia was identified as an influencing factor for IPH development in atherosclerotic plaque. Young age was identified as the influencing factor for the occurrence of BA dissection. CONCLUSIONS: The etiology of stenosis or occlusion was unclear until the development of HR-MRI. With HR-MRI, stroke etiology is better understood, and factors affecting each etiology can be identified. Further studies that clarify the etiology of posterior circulation stroke are required.

Association of Genetic Variation in a Wnt Signaling Pathway Gene (ß-Catenin) with Susceptibility to Leukoaraiosis.

Aim: Blood-brain barrier (BBB) disruption is the primary initiating cause of cerebral small-vessel diseases including leukoaraiosis (LA). ß-Catenin is a key regulator of the BBB and plays an important role in cell-cell adhesion at adherens junctions by interacting with cadherin molecules. Thus, ß-Catenin may be a good candidate gene for LA. We performed a genetic analyses to investigate the association between ß-catenin alleles and LA. Materials and Methods: A total of 339 LA cases and 203 controls were enrolled from individuals who underwent brain magnetic resonance imaging with obtainable vascular risk factors. Genotyping of ß-catenin single nucleotide polymorphisms (SNPs), including rs1880481 C > A, rs13072632 C > T, and rs4135385 A > G, was performed by real-time polymerase chain reaction using a LightCycler 2.0. Results: Two SNPs, rs1880481 and rs4135385, showed significant differences in their allelic frequencies between the control and LA groups and the combinatorial effects of the risk alleles for these two SNPs also significantly increased the risk of LA. The G-T-A, A-T-A, and A-T-G haplotypes for the three SNPs showed significant differences in both types of LA: LA-periventricular white matter and LA-deep white matter. However, the C-T-G haplotype was only significantly different for LA-PVWM, while the A-C-A was only significantly different for LA-DWM. The combination of diabetes mellitis, hypertension, and these risk alleles increased the likelihood of both types of LA. Conclusion: This study provides evidence that ß-catenin polymorphisms and their associated haplotypes are associated with susceptibility to LA.

Acute basilar artery occlusion with recurrent shivering: A case report.

RATIONALE: Shivering is an important physiological response of the body that causes muscle tremors to maintain temperature homeostasis. Traumatic brain injuries that affect the hypothalamus cause hypothermia, and physical removal of suprasellar tumors causes thermoregulation imbalance. However, no study has reported shivering due to ischemic stroke. PATIENT CONCERNS: A 58-year-old male patient was admitted to our emergency department to evaluate severe stenosis of the basilar artery. While waiting for further examination, he exhibited coarse shivering and severe dysarthria. DIAGNOSIS: Brain computed tomography angiography revealed occlusion of the entire basilar artery, and cerebral hypoperfusion was diagnosed in that area. INTERVENTIONS: Transfemoral cerebral angiography (TFCA) was immediately performed, followed by thrombectomy of the basilar artery. OUTCOMES: Neurological deficits, including shivering, were rapidly reversed. The same symptom reoccurred 5 hours later, and TFCA was performed for thrombectomy and stenting, and neurological symptoms immediately reversed. The patient's neurological symptoms did not worsen during hospitalization. LESSONS: Patients with acute basilar artery occlusion need prompt management because they have a higher mortality rate than those with other intracranial artery occlusions. When a patient exhibits neurological deficits accompanied by abrupt shivering for no specific reason, basilar artery occlusion must be considered.