Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

Background: Distinguishing multiple system atrophy from other parkinsonian syndromes is challenging. Objectives: To evaluate vagus nerve ultrasonography for differentiating parkinsonian syndromes. Methods: A single-center, cross-sectional, observational study assessed 85 consecutive adult patients with de novo parkinsonism between June 2020 and December 2022, using 12 MHz ultrasonography of the vagus nerve cross-sectional area. Results: Bilateral vagus nerves were smaller in multiple system atrophy than in other parkinsonian syndromes. The area under the receiver operating characteristic curve for differentiating multiple system atrophy was 0.79 on the right side and 0.74 on the left. The cut-off values to diagnose multiple system atrophy were 0.71 and 0.86 mm2 on the right and left sides, respectively, with sensitivities of 82.6% and 87.0%, specificities of 74.2% and 64.5%, positive predictive values of 54% and 47.6%, and negative predictive values of 92.0% and 93.0%. Conclusions: Vagus nerve ultrasonography may differentiate multiple system atrophy from other parkinsonian syndromes.

Ultrasound evaluation of vagus nerve cross-sectional area in a community-dwelling elderly Japanese cohort.

OBJECTIVES: Although the vagus nerve (VN) is easily observed by ultrasonography, few studies have evaluated the cross-sectional area (CSA) of the VN in healthy older individuals from East Asia. In this study, we aimed to report reference values for the CSA of the VN in community-dwelling elderly Japanese individuals and to identify any associated medical history and/or lifestyle factors. METHODS: The present study included 336 participants aged ≥ 70 years from a prospective cohort study conducted in Yahaba, Japan from October 2021 to February 2022. The CSA of the VN was measured bilaterally at the level of the thyroid gland by ultrasonography. Simple linear regression analysis and generalized estimating equation were conducted to identify the associations between clinical and background factors and the CSA of the VN. RESULTS: In our cohort, the median CSA of the VN was 1.3 mm2 (interquartile range [IQR] 1.1-1.6) on the right side and 1.2 mm2 (IQR 1.0-1.4) on the left side. Generalized estimating equation showed that history of head injury (ß = 0.19, p < .01), current smoking habit (ß = -0.09, p = .03), and BMI (ß = 0.02, p < .01) were independently associated with the CSA of the VN. CONCLUSION: We have reported reference VN CSA values for community-dwelling elderly Japanese individuals. In addition, we showed that the CSA of the VN was positively associated with a history of head injury and BMI and inversely associated with current smoking habit.

Moyamoya Syndrome Presenting with Ischemic Stroke Caused by Rapid Worsening of Vessel Stenosis Associated with Triple-seropositive Antiphospholipid Syndrome.

Several case reports of patients with both moyamoya syndrome (MMS) and antiphospholipid syndrome (APS) have been published. However, the relationship between MMS and APS has not been clarified. We herein report a patient with MMS who had an ischemic stroke with rapid worsening of stenosis of the middle cerebral artery associated with APS. The patient was triple-positive for antiphospholipid antibodies. Patients with MMS complicated by APS should be closely followed up with vascular imaging.

Ischemic Stroke Due to Spontaneous Dissection of the Brachiocephalic to the Common Carotid Artery with a Fatal Course after Expansion to the Ascending Aorta.

Spontaneous dissection of the brachiocephalic artery is rare, and there is insufficient evidence for optimal treatment. We herein report a case of ischemic stroke due to spontaneous dissection of the brachiocephalic to the right common carotid artery. The patient was treated medically but died suddenly 18 days after the onset because of aortic dissection. Although almost all reported cases of spontaneous dissection of the brachiocephalic artery have had good outcomes with medical management, it is important to note that sudden development of aortic dissection might occur, even without initial findings suggestive of this condition.

Takayasu's Arteritis with a Thrombosed Aneurysm on the Common Carotid Artery Causing Ischemic Stroke.

Takayasu's arteritis is an inflammatory disease of unknown etiology that causes stenosis, occlusion, or dilatation of the aorta and its major branches, the pulmonary arteries, and the coronary arteries. The incidence of extracranial carotid artery aneurysm in patients with Takayasu's arteritis is reportedly 1.8-3.9%. We herein report a patient with Takayasu's arteritis who presented with transient left hemiplegia immediately after neck massage. Carotid ultrasonography revealed a thrombus within the fusiform aneurysm on the right common carotid artery. We speculated that fragmentation from the intra-aneurysmal thrombus was caused by neck massage.

Vascular Imaging Techniques to Diagnose and Monitor Patients with Takayasu Arteritis: A Review of the Literature.

Takayasu arteritis (TA) is a large vessel vasculitis that causes stenosis, occlusion, and sometimes the aneurysm of the aorta and its major branches. TA often occurs in young women, and because the symptoms are not obvious in the early stages of the disease, diagnosis is difficult and often delayed. In approximately 10% to 20% of patients, TA is reportedly complicated by ischemic stroke or transient ischemic attack. It is important to diagnose TA early and provide appropriate treatment to prevent complications from stroke. Diagnostic imaging techniques to visualize arterial stenosis are widely used in clinical practice. Even if no signs of cerebrovascular events are present at the time of the most recent evaluation of patients with TA, follow-up vascular imaging is important to monitor disease progression and changes in the cerebrovascular risk. However, the optimal imaging technique for monitoring of TA has not been established. Therefore, the purpose of this review is to describe newly available evidence on the usefulness of conventional imaging modalities (digital subtraction angiography, computed tomography angiography, magnetic resonance imaging/angiography, duplex ultrasound, and positron emission tomography) and novel imaging modalities (optical coherence tomography, infrared thermography, contrast-enhanced ultrasonography, and superb microvascular imaging) in the diagnosis and monitoring of TA.

Cross-sectional area of the vagus nerve on carotid duplex ultrasound and atrial fibrillation in acute stroke: A retrospective analysis.

INTRODUCTION: The autonomic nervous system, including the vagus nerve, is associated with the development of atrial fibrillation (AF). However, the association between the cross-sectional area (CSA) of the vagus nerve on ultrasound and the presence of AF has not been fully clarified. This study investigated the association between vagus nerve CSA and the presence of AF in patients with acute stroke. METHODS: We retrospectively reviewed 150 consecutive patients with ischemic stroke or transient ischemic attack. Vagus nerve CSA was evaluated by carotid ultrasonography on the axial view at the thyroid gland level. Univariate and multivariable analyses were performed to examine the association between vagus nerve CSA and AF. RESULTS: Of 133 patients included in the analysis, 31 (23.3%) were diagnosed with AF before hospital discharge. The median right vagus nerve CSA was significantly smaller in patients with AF than in patients without AF (p = 0.03). However, there was no significant difference in median left vagus nerve CSA. Multivariable logistic regression analysis revealed that log transformed and quintiled brain natriuretic peptide level (odds ratio [OR], 5.03; 95% confidence interval [CI], 2.43-10.40) and right vagus nerve CSA (OR, 0.33; 95% CI, 0.12-0.91) were independent predictors of AF. DISCUSSION/CONCLUSION: Smaller right vagus nerve CSA in carotid ultrasonography was an independent predictor of AF in patients with ischemic stroke or transient ischemic attack, suggesting that patients with small right vagus nerve CSA should be closely monitored for development of AF.

Superb Microvascular Imaging Ultrasound for Cervical Carotid Artery Stenosis for Prediction of the Development of Microembolic Signals on Transcranial Doppler during Carotid Exposure in Endarterectomy.

INTRODUCTION: During exposure of the carotid arteries, embolism from the surgical site is recognized as a primary cause of neurological deficits or new cerebral ischemic lesions following carotid endarterectomy (CEA), and associations have been reported between histological neovascularization in the carotid plaque and both plaque vulnerability and the development of artery-to-artery embolism. Superb microvascular imaging (SMI) enables accurate visualization of neovessels in the carotid plaque without the use of intravenous contrast. This study aimed to determine whether preoperative SMI ultrasound for cervical carotid artery stenosis predicts the development of microembolic signals (MES) on transcranial Doppler (TCD) during exposure of the carotid arteries in CEA. METHODS: Preoperative cervical carotid artery SMI ultrasound followed by CEA under TCD monitoring of MES in the ipsilateral middle cerebral artery was conducted in 70 patients previously diagnosed with internal carotid artery stenosis (defined as ≥70%). First, observers visually identified intraplaque microvascular flow (IMVF) signals as moving enhancements located near the surface of the carotid plaque within the plaque on SMI ultrasonograms. Next, regions of interest (ROI) were manually placed at the identified IMVF signals (or at arbitrary places within the plaque when no IMVF signals were identified within the carotid plaque) and the carotid lumen, and time-intensity curves of the IMVF signal and lumen ROI were generated. Ten heartbeat cycles of both time-intensity curves were segmented into each heartbeat cycle based on gated electrocardiogram findings and averaged with respect to the IMVF signal and lumen ROI. The difference between the maximum and minimum intensities (ID) was calculated based on the averaged IMVF signal (IDIMVF) and lumen (IDl) curves. Finally, the ratio of IDIMVF to IDl was calculated. RESULTS: MES during exposure of the carotid arteries were detected in 17 patients (24%). The incidence of identification of IMVF signals was significantly greater in patients with MES (94%) than in those without (57%; p = 0.0067). The IDIMVF/IDl ratio was significantly greater in patients with MES (0.108 ± 0.120) than in those without (0.017 ± 0.042; p < 0.0001). The specificity and positive predictive value for the IDIMVF/IDl ratio for prediction of the development of MES were significantly higher than those for the identification of IMVF signals. Logistic regression analysis revealed that only the IDIMVF/IDl ratio was significantly associated with the development of MES (95% CI 101.1-3,628.9; p = 0.0048). CONCLUSION: Preoperative cervical carotid artery SMI ultrasound predicts the development of MES on TCD during exposure of the carotid arteries in CEA.

Impact of Introducing the Pletaal Assist System on Drug Adherence in Outpatients with Ischaemic Stroke: A Pilot Study.

PURPOSE: The effectiveness of Electronic Medication Packaging devices for monitoring drug adherence has been widely reported. However, conventional devices are expensive for routine use and cannot confirm whether the medication was administered. We aimed to determine, in a pilot and feasibility study, the impact of introducing a new medication support device, the Pletaal Assist System®, to monitor and improve cilostazol adherence for stroke prevention at an outpatient clinic. PATIENTS AND METHODS: We assessed consecutive patients treated with cilostazol for >3 months at our stroke outpatient clinic from January 2018 to March 2020. The adherence rate was assessed as follows: (the number of pills prescribed minus the number of remaining pills)/the number of pills prescribed. We compared the adherence rates before, during, and after Pletaal Assist System® usage, respectively. RESULTS: Overall, 25 patients (median age, 68.5 years; range, 51-86 years; male, 64%) were enrolled. All participants were prescribed cilostazol (100 mg) twice a day. There was no significant difference in the adherence rate among the three periods. However, in 10 patients with adherence rate below 100%, the adherence rate during Pletaal Assist System® usage was higher than before usage (99.5% vs 95%, p=0.04), and the rate after using the Pletaal Assist System® tended to be lower compared to the rate during usage (99.5% vs 96%, p=0.05). CONCLUSION: Our preliminary evidence suggest that the Pletaal Assist System® could further improve cilostazol adherence in outpatients with poor drug adherence and may reduce the risk of recurrent strokes by improving adherence of patients with a history of stroke.

Influence of PAR-1 in patients with non-valvular atrial fibrillation: The antiplatelet effect of dabigatran.

INTRODUCTION: Dabigatran, a direct thrombin inhibitor, has been widely used in patients with non-valvular atrial fibrillation (NVAF) and is considered to have an antiplatelet effect. However, the mechanisms remain unclear. We evaluated protease-activated receptor-1 (PAR-1) expression and activation by thrombin on platelets from NVAF patients, before and after dabigatran treatment, in addition to the expression of platelet activation marker CD62P. MATERIALS AND METHODS: The study included 18 NVAF patients. We used flow cytometry to measure the binding of PAR-1 monoclonal antibodies (SPAN12 and WEDE15) and the expression of CD62P with and without thrombin stimulation, before, 14 days after, and 28 days after treatment with dabigatran. Coagulation fibrinolysis markers were also measured. RESULTS: PAR-1 expression was significantly lower in NVAF patients than in healthy controls (HC); it was further reduced by thrombin stimulation. CD62P expression was almost absent on the platelets in NVAF patients, but was significantly increased by thrombin stimulation. PAR-1 expression was not significantly different before and after treatment; CD62P expression was inhibited by dabigatran. The levels of coagulation markers were significantly higher in NVAF patients than in HC, and decreased after treatment. CONCLUSIONS: Lower expression of PAR-1 in NVAF patients resulted from the cleavage of PAR-1 on some platelets, by exposure to small amounts of thrombin in vivo. The therapeutic effect of dabigatran in NVAF patients was demonstrated by inhibition of CD62P expression on the platelet upon thrombin stimulation in vitro. Our results indicate that dabigatran may reveal antithrombotic activity with antiplatelet and anticoagulant effects.

Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA.

OBJECTIVES: The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. RESULTS: In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. CONCLUSIONS: We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

Thrombin-induced platelet aggregation -effect of dabigatran using automated platelet aggregometry.

Dabigatran, a direct oral thrombin inhibitor, has two therapeutic effects: anticoagulation; and antiplatelet activity. In the clinical field, evaluation of the effect of dabigatran on thrombin-induced platelet aggregation is difficult because of fibrin clot formation and platelet aggregation. The aim of this study was to establish a new platelet aggregation method and to investigate the effects of dabigatran on thrombin-induced platelet aggregation. Platelet aggregation with thrombin was performed with automated light transmission aggregometry (CS2400; Sysmex, Kobe, Japan) in 40 healthy subjects. Thrombin-induced platelet aggregation was performed using thrombin and platelet-rich plasma (PRP), and thrombin-induced fibrin polymerization was inhibited by adding the peptide Gly-Pro-Arg-Pro (GPRP). The effect of dabigatran was then evaluated using the above method. Thrombin at < 0.2 U/mL did not induce platelet aggregation in most normal subjects. Median maximum aggregation percent (MA%) (25th-75th percentile) with 0.5 and 1.0 U/mL of thrombin was 87.0% (79.3-90.8%), and 90.2% (86.5-92.2%), respectively. The anti-platelet effects of dabigatran were then evaluated with these concentrations of thrombin. Dabigatran (final concentration, 2.5-1000 nM) inhibited platelet aggregation by 0.2-1.0 U/mL of thrombin in a concentration-dependent manner in vitro. Dabigatran showed potent inhibitory effects against platelet aggregation induced by 0.5 and 1.0 U/mL thrombin with half maximal inhibitory concentrations of 10.5 and 40.4 nM, respectively. A standard for thrombin-induced platelet aggregation was developed using the CS2400 in healthy subjects, and dabigatran was confirmed to inhibit thrombin-induced platelet aggregation in vitro with PRP.

Evaluation of Intraplaque Neovascularization Using Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography.

BACKGROUND: Several studies have shown a linkage between intraplaque neovascularization (IPN) and plaque instability. Although contrast-enhanced ultrasonography (CEUS) may help visualize IPN in the carotid artery, its benefits are limited in Japan, where there is no health insurance coverage for contrast agents in medical imaging. Superb microvascular imaging (SMI), however, enables the depiction of low-velocity blood flow. The current study compares the diagnostic accuracy of SMI and CEUS in the evaluation of IPN. METHODS: The SMI and CEUS video images were transferred to a workstation and then analyzed to determine whether intraplaque blood flow signals were detected with SMI and whether plaques were contrast-enhanced with carotid artery CEUS. The images generated were independently interpreted by 2 radiologic technologists and 1 neurologist. RESULTS: Intraplaque enhancement was observed in 19 patients using CEUS while intraplaque blood flow signals were observed in 12 patients using SMI. A 100% specificity was recorded for SMI (all 12 patients with SMI-detected intraplaque blood flow showed contrast-enhanced plaques), while its sensitivity was 63% (8 of the 15 patients with no SMI-detected intraplaque blood flow showed contrast-enhanced plaques on CEUS). CONCLUSIONS: The results of this study show that patients with SMI-detected blood flow will tend to have plaque enhancement using CEUS. This suggests that SMI, as a simpler, safer, and noninvasive technique, can facilitate the visualization of carotid artery IPN without the use of a contrast agent, as well as in the clinical evaluation of plaque instability.

Comparison of Three-Dimensional T1-Weighted Magnetic Resonance and Contrast-Enhanced Ultrasound Plaque Images for Severe Stenosis of the Cervical Carotid Artery.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) and contrast-enhanced ultrasound assess characteristics and neovascularization, respectively, of the carotid plaque. The purpose of the present study was to clarify how findings of contrast-enhanced ultrasound plaque imaging are related to those of 3-dimensional (3D) fast spin echo (FSE) T1-weighted MR plaque imaging (WI) in severe stenosis (≥70%) of the cervical carotid artery. METHODS: Fifty-three patients underwent 3D FSE T1-WI and contrast-enhanced ultrasound. For each patient, the averaged contrast ratio on MR (CRMR) was calculated by dividing the averaged internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity; maximally enhanced intensities on the intraplaque and lumen time-intensity curves were obtained from contrast-enhanced ultrasound data, and the ratio of the maximal intensity of the intraplaque curve to that of the lumen curve was calculated and defined as contrast effect (CEUS). RESULTS: A linear correlation (r = .702; P <.0001) was observed between CRMR and CEUS. Receiver operating characteristic curve analyses to evaluate the ability of the CEUS to differentiate each category of CRMR from the other 2 categories showed that the sensitivity was significantly lower for category II (1.30 ≤ CRMR ≤ 1.60) than for category I (CRMR < 1.30) or III (1.60 < CRMR). The CEUS was lower in plaques with higher CRMR than in those with lower CRMR in a subgroup of category III (P = .0196). CONCLUSION: Findings of contrast-enhanced ultrasound plaque imaging are related to those of 3D FSE T1-WI MR plaque imaging according to the life history of arterial plaque and its neovascularization.

Preoperative cervical carotid artery contrast-enhanced ultrasound findings are associated with development of microembolic signals on transcranial Doppler during carotid exposure in endarterectomy.

BACKGROUND AND AIMS: Emboli from the surgical site during exposure of the carotid arteries cause new cerebral ischemic lesions or neurological deficits after carotid endarterectomy (CEA). The purpose of the present study was to determine whether preoperative contrast-enhanced ultrasound findings of the cervical carotid arteries are associated with the development of microembolic signals (MES) on transcranial Doppler, during exposure of the arteries in CEA, and to compare the predictive accuracy of contrast-enhanced ultrasound findings with that of gray-scale median (GSM). METHODS: Seventy patients with internal carotid artery stenosis (≥70%) underwent preoperative cervical carotid artery ultrasound and CEA under transcranial Doppler monitoring of MES in the ipsilateral middle cerebral artery. Maximally enhanced intensities on the intraplaque and lumen time-intensity curves, respectively, were obtained from contrast-enhanced ultrasonography data, and the ratio of the maximal intensity (EIp) of the intraplaque curve to that (EIl) of the lumen curve was calculated. The GSM value of the plaque was also measured. RESULTS: The area under the receiver operating characteristic curve to discriminate between the presence and absence of MES during exposure of the carotid arteries was significantly greater for EIp/EIl than for GSM (p = 0.0108). Multivariate statistical analysis demonstrated that only EIp/EIl was significantly associated with the development of MES during exposure of the carotid arteries (p = 0.0002). CONCLUSIONS: Preoperative contrast-enhanced ultrasound findings of the cervical carotid arteries are associated with development of MES on transcranial Doppler during exposure of the arteries in CEA, and the predictive accuracy of contrast-enhanced ultrasound is greater than that of GSM.

Carotid plaque characteristics on magnetic resonance plaque imaging following long-term cilostazol therapy.

BACKGROUND: Cilostazol is an antiplatelet agent that can induce the regression of atherosclerosis. However, its long-term effects on plaque involution of the cervical carotid arteries remain unknown. Thus, we aimed to evaluate the effect of long-term cilostazol administration on carotid plaques using quantitative magnetic resonance (MR) plaque imaging. METHODS: Sixteen consecutive patients with carotid stenosis were examined using T1-weighted MR plaque imaging at baseline, 6 months, and 12 months after initiation of 200 mg per day of cilostazol. We calculated the contrast ratio of the carotid plaque against the sternocleidomastoid muscle and percent areas of the intraplaque fibrous tissue, lipid/necrosis, and hemorrhage components using automated software. We also measured the volume and echogenicity of the plaques using 3-dimensional ultrasonography. RESULTS: The contrast ratio of the carotid plaque significantly decreased during the cilostazol administration (median 1.07, 1.04, and 1.00 at baseline, 6 months, and 12 months, respectively; P = .03). Furthermore, the area of the fibrous components significantly increased (73.9%, 80.3%, and 85.7%, respectively; P = .03) and that of the lipid/necrotic components significantly decreased (25.2%, 19.2%, and 14.3%, respectively; P = .04). There were no substantial changes in plaque volume or echogenicity on ultrasonography. CONCLUSIONS: Signal alterations on MR plaque imaging indicated the increase of fibrous components and the decrease of lipid/necrotic components in the carotid plaque during the cilostazol therapy.