Dural Arteriovenous Fistula Mimicking Acute Encephalitis.

We herein report a case of acute neurological symptoms and a fever initially suspected of being encephalitis but later revealed to be dural arteriovenous fistula (dAVF). An 84-year-old woman had a fever and cerebral edema and was initially treated for encephalitis. A review of her magnetic resonance imaging findings revealed abnormal blood flow signals. After cerebral angiography, the patient was finally diagnosed with left transverse-sigmoid sinus dAVF. The present case showed that dAVF can also present with an acute onset and a fever, mimicking acute encephalitis. Because the treatments for encephalitis and dAVF differ greatly, the possibility of dAVF should also be considered when diagnosing encephalitis.

A Novel Hemostatic Peptide Solution for Common Acute Gastrointestinal Bleeding Diseases: First Case Series Study on the Treatment Results of Endoscopic Hemostasis by Nonexpert Endoscopists.

INTRODUCTION: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy. METHODS: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023. RESULTS: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases. CONCLUSION: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH. METHODS: Overall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study. Following SAH onset, 136 patients were managed with continuous CSF drainage, whereas 68 were managed with intermittent CSF drainage. Logistic regression analyses were used to calculate the age-adjusted and multivariate odds ratios for the development of sCH. The Cox proportional hazards regression model were used to compare the effects of intermittent and continuous CSF drainage on sCH development. RESULTS: Overall, 96 patients developed sCH among the 204 patients with SAH. In total, 74 (54.4%) of the 136 patients managed with continuous CSF drainage developed sCH, whereas 22 (32.4%) of the 68 patients managed with intermittent CSF drainage developed sCH. This demonstrated that the rate of sCH development was significantly lower among patients managed with intermittent CSF drainage. Compared with continuous CSF drainage, intermittent CSF drainage exhibited a multivariate odds ratio (95% confidential interval) of 0.25 (0.11-0.57) for sCH development. Intermittent CSF drainage was more effective (0.20, 0.04-0.95) in patients with severe-grade SAH than in those with mild-grade SAH (0.33, 0.12-0.95). Intermittent CSF drainage was ineffective in patients with acute hydrocephalus (8.37, 0.56-125.2), but it was effective in patients without acute hydrocephalus (0.11, 0.04-0.31). CONCLUSIONS: Compared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset.

Japanese nationwide questionnaire survey on delayed cerebral infarction due to vasospasm after subarachnoid hemorrhage.

Background and purpose: Various prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021. Methods: In 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan. Of them, 162 hospitals (29% response rate) responded to the questionnaire. Of these, 158 were included in this study, while four hospitals that responded insufficiently were excluded. The efficacy of treatments for reducing DCI were examined through a logistic regression analysis. Results: Among 3,093 patients treated with aneurysmal SAH, 281 patients (9.1%) were diagnosed with DCI related to cerebral vasospasm. Coil embolization had significantly lower DCI frequency (6.9%), compared to microsurgical clipping (11.8%, odds ratio, 0.90; 95% confidential intervals, 0.84-0.96; P, 0.007). In addition, cilostazol administration was associated with significantly lower DCI frequency (0.48; 0.27-0.82; 0.026). The efficacy of cilostazol in reducing DCI remained unchanged after adjustment for covariates. The most effective combination of multiple prophylactic drugs in reducing DCI related to cerebral vasospasm was cilostazol, fasudil, and statin (0.38; 0.22-0.67; 0.005). Conclusions: This study elucidated the trends in prophylactic drugs to prevent cerebral vasospasm and frequency of DCI after aneurysmal SAH in Japan. Coil embolization and cilostazol administration showed effectiveness in reducing DCI related to cerebral vasospasm in 2021.

Secular trends and features of thalamic hemorrhages compared with other hypertensive intracerebral hemorrhages: an 18-year single-center retrospective assessment.

Introduction: Trends regarding the locations of hypertensive cerebral hemorrhages are unclear. To clarify hypertensive hemorrhage trends, we investigated intracerebral hemorrhages (ICHs) over an 18-year period, focusing on thalamic hemorrhages compared with other sites of hemorrhages. Methods: We reviewed the cases of patients hospitalized for hypertensive ICH in 2004-2021 at our hospital; 1,320 eligible patients were registered with a primary ICH/intraventricular hemorrhage. After exclusion criteria were applied, we retrospectively analyzed 1,026 hypertensive ICH cases. Results: The proportions of thalamic and subcortical hemorrhages increased over the 18-year period, whereas putaminal hemorrhage decreased. Multivariate logistic regression analyses revealed that for thalamic hemorrhage, ≥200 mmHg systolic blood pressure (p = 0.031), bleeding <15 mL (p = 0.001), and higher modified Rankin scale (mRS) score ≥ 4 at discharge (p = 0.006) were significant variables in the late period (2013-2021) versus the early period (2004-2012), whereas for putaminal hemorrhage, significant factors in the late period were triglyceride <150 mg/dL (p = 0.006) and mRS score ≥ 4 at discharge (p = 0.002). Among the features of the thalamic hemorrhages in the late period revealed by our group comparison with the putaminal and subcortical hemorrhages, the total and subcortical microbleeds were more notable in the thalamic hemorrhages than in the other two types of hemorrhage, whereas cerebellar microbleeds were more prominent when compared only with subcortical hemorrhages. Discussion: Our findings revealed an increasing trend for thalamic hypertensive hemorrhage and a decreasing trend for putaminal hemorrhage. The thalamic hemorrhage increase was observed in both young and older patients, regardless of gender. The main features of thalamic hemorrhage in the late period versus the early period were decrease in larger hemorrhage (≥15 mL) and an increase in cases with higher systolic blood pressure (at least partially involved a small number of untreated hypertensive patients who developed major bleeding). The total and subcortical microbleeds were more notable in the thalamic hemorrhages of the late period than in the putaminal and subcortical hemorrhages. These results may contribute to a better understanding of the recent trends of hypertensive ICHs and may help guide their appropriate treatments for this condition.

Minimally invasive treatment for glioblastoma through endoscopic surgery including tumor embolization when necessary: a technical note.

Background: Although there have been some reports on endoscopic glioblastoma surgery, the indication has been limited to deep-seated lesions, and the difficulty of hemostasis has been a concern. In that light, we attempted to establish an endoscopic procedure for excision of glioblastoma which could be applied even to hypervascular or superficial lesions, in combination with pre-operative endovascular tumor embolization. Methods: Medical records of six consecutive glioblastoma patients who received exclusive endoscopic removal between September and November 2020 were analyzed. Preoperative tumor embolization was performed in cases with marked tumor stain and proper feeder arteries having an abnormal shape, for instance, tortuous or dilated, without passing through branches to the normal brain. Endoscopic tumor removal through a key-hole craniotomy was performed by using an inside-out excision for a deep-seated lesion, with the addition of an outside-in extirpation for a shallow portion when needed. Results: Endoscopic removal was successfully performed in all six cases. Before resection, endovascular tumor embolization was performed in four cases with no resulting complications, including ischemia or brain swelling. Gross total resection was achieved in three cases, and near total resection in the other three cases. Intraoperative blood loss exceeded 1,000 ml in only one case, whose tumor showed a prominent tumor stain but no proper feeder artery for embolization. In all patients, a smooth transition to adjuvant therapy was possible with no surgical site infection. Conclusion: Endoscopic removal for glioblastoma was considered to be a promising procedure with minimal invasiveness and a favorable impact on prognosis.

Endoscope-Controlled High Frontal Approach for Dural Arteriovenous Fistula in Anterior Cranial Fossa.

BACKGROUND: Currently, surgical obliterations are a mainstay for treating dural arteriovenous fistula (DAVF) in the anterior cranial fossa (ACF), which has high risks of hemorrhage and functional disorder. By introducing an endoscope into a high frontal approach and utilizing its advantages, we attempted to establish it as a new surgical procedure that eliminates the drawbacks of various approaches that have been used to date. METHODS: By using 30 clinical datasets of venous-phase head computed tomography angiogram, measurements and comparisons on a 3-dimensional workstation were performed to identify the appropriate positioning of keyhole craniotomy for endoscope-controlled high frontal approach (EHFA). Based on these data, a cadaver-based surgery was simulated to verify the feasibility of EHFA and develop an efficient procedure. RESULTS: In EHFA, though raising the position of the keyhole craniotomy made the operative field deeper, significant advantages were obtained in the angle between the operative axis and the medial-anterior cranial base and the amount of bone removal required at the anterior edge of craniotomy. Minimally invasive EHFA, performed through a keyhole craniotomy without opening the frontal sinus, proved to be feasible on 10 sides of 5 cadaver heads. Moreover, 3 patients with DAVF in ACF were successfully treated by clipping the fistula via EHFA. CONCLUSIONS: EHFA, which provided a direct corridor to the medial ACF at the level of the foramen cecum and crista galli and the minimum necessary operative field, was found to be a suitable procedure for clipping the fistula of DAVF in ACF.

Clinical utility of paced finger tapping assessment in idiopathic normal pressure hydrocephalus.

Background: The Finger Tapping (F-T) test is useful for assessing motor function of the upper limbs in patients with idiopathic normal pressure hydrocephalus (iNPH). However, quantitative evaluation of F-T for iNPH has not yet been established. The purpose of this study was to investigate the usefulness of the quantitative F-T test and optimal measurement conditions as a motor evaluation and screening test for iNPH. Methods: Sixteen age-matched healthy controls (mean age 73 ± 5 years; 7/16 male) and fifteen participants with a diagnosis of definitive iNPH (mean age 76 ± 5 years; 8/15 male) completed the study (mean ± standard deviation). F-T performance of the index finger and thumb was quantified using a magnetic sensing device. The performance of repetitive F-T by participants was recorded in both not timing-regulated and timing-regulated conditions. The mean value of the maximum amplitude of F-T was defined as M-Amplitude, and the mean value of the maximum velocity of closure of F-T was defined as cl-Velocity. Results: Finger Tapping in the iNPH group, with or without timing control, showed a decrease in M-Amplitude and cl-Velocity compared to the control group. We found the only paced F-T with 2.0 Hz auditory stimuli was found to improve both M-Amplitude and cl-Velocity after shunt surgery. Conclusion: The quantitative assessment of F-T with auditory stimuli at the rate of 2.0 Hz may be a useful and potentially supplemental screening method for motor assessment in patients with iNPH.

Single-stage repair for ascending aortic aneurysm, artery stenosis and occlusion of neck vessels caused by Takayasu arteritis.

Takayasu arteritis results in a variety of vascular symptoms, and there are some cases in which progressive vascular lesions require surgical intervention. We present a case with ascending aortic aneurysm, right common carotid artery stenosis, left common carotid artery occlusion and left subclavian artery stenosis caused by Takayasu arteritis that was successfully treated with total arch replacement and ascending aorta to right internal carotid artery bypass.

New Cortical Spot Cerebral Infarction Out of Border Zone in ICA Occlusion Suggests Recanalization: A Case Report.

Internal carotid artery occlusion rarely recanalizes spontaneously. Awareness of signs of recanalization is important, as it may necessitate changing the treatment strategy. We report a case of new cortical infarction outside the border zone, which led to the realization of internal carotid artery recanalization and revascularization. A 76-year-old woman presented with mild dysarthria. Magnetic resonance imaging showed cerebral infarction in the left-hemispheric border zone and occlusion of the internal carotid artery origin. Cerebral angiography performed showed complete occlusion of the internal carotid artery origin and intracranial collateral blood flow from the external carotid artery through the ophthalmic artery. She was diagnosed with infarction due to a hemodynamic mechanism caused by internal carotid artery occlusion and was treated with supplemental fluids and antithrombotic drugs. Four days after hospitalization, the right paralysis worsened and a new cerebral infarction was observed in the cortex, outside the border zone. This infarction appeared to be embolic rather than hemodynamic; thus, we suspected recanalization of the internal carotid artery. The patient underwent emergency cerebral angiography again, which revealed slight recanalization. Thus, emergency revascularization and carotid artery stenting were performed. New cortical infarcts outside the border zone in patients with complete internal carotid artery occlusion is an important finding, suggesting spontaneous recanalization of the occluded internal carotid artery.

Direct Advancement of Balloon-Guide Catheter Distal to the Carotid Free-Floating Thrombus Achieves Smart Mechanical Thrombectomy.

A 68-year-old man with bladder cancer developed sudden dysarthria and left hemiplegia. MRI revealed occlusion of the right middle cerebral artery (MCA). Cerebral angiography revealed a large carotid free-floating thrombus (CFFT) at the origin of the right internal carotid artery (ICA) and right M1 occlusion. A balloon-guide catheter (BGC) was directly guided distal to the CFFT. Mechanical thrombectomy (MT) was performed on the M1 occlusion while the balloon was inflated to block antegrade blood flow, and good recanalization was achieved. To continue processing the CFFT, the deflated BGC was pulled to the common carotid artery, and the thrombus dispersed into the external carotid artery (ECA). Subsequently, the patient's symptoms improved. Directly advancing a BGC distally to a CFFT may be a useful treatment strategy for tandem lesions with carotid free-floating thrombi.

Successful Mechanical Thrombectomy for Acute Middle Cerebral Artery Occlusion in a Centenarian.

Clinical trials have proven the efficacy and beneficial therapeutic outcomes of endovascular therapy in patients with major arterial occlusion. However, its efficacy for very elderly patients, such as nonagenarians or centenarians, is not well established. In this case report, we describe the successful use of mechanical thrombectomy for the management of stroke in a centenarian. The 100-year-old woman with severe right-sided paralysis and total aphasia was admitted to our hospital approximately 30 min from the onset of symptoms. The National Institutes of Health Stroke Scale score was 24 at admission, and three-dimensional computed tomography angiography revealed occlusion in the M1 segment of left middle cerebral artery. She had persistent atrial fibrillation and was diagnosed with colon cancer one month prior to the admission. The modified Rankin Scale score before the stroke was 1, and she was generally independent. The patient successfully underwent mechanical thrombectomy, and recanalization with thrombolysis in cerebral infarction grade 3 was accomplished 129 minutes after the onset. The patient made a remarkable recovery with a National Institutes of Health Stroke Scale score of 4 at 48 h and was discharged home with a modified Rankin Scale score of 2 on day 8. Thus, mechanical thrombectomy can be performed with a good outcome even in centenarians.

Aplastic or twig-like middle cerebral artery and cardiogenic cerebral embolism mimicking moyamoya disease with RNF213 polymorphism: A case report.

Progressive stenosis and occlusion of the bilateral internal carotid artery terminals and circle of Willis are typical features of Moyamoya disease. However, aplastic or twig-like middle cerebral artery (Ap/T-MCA)-wherein the unilateral main trunk of the middle cerebral artery (MCA) is not depicted, and a plexiform arterial network is formed-is similar to the findings of Moyamoya disease. Here, we describe a 78-year-old man who presented with mild right paralysis and aphasia. Magnetic resonance angiography (MRA) at admission did not show the bilateral MCAs. The findings were similar to those of Moyamoya disease, and his symptoms worsened after hospitalization. Endovascular treatment was performed, and the left MCA was completely recanalized. Later, paroxysmal atrial fibrillation was detected, and we finally determined that left MCA occlusion had occurred due to embolism. The right MCA was completely occluded at its origin, indicating an Ap/T-MCA. Embolic occlusion of the unilateral MCA and contralateral Ap/T-MCA made this case resemble Moyamoya disease in the acute stage. Even when chronic occlusion is suspected on MRA in acute cerebral infarction, endovascular treatment should be considered. Additionally, a heterotypic R4810K polymorphism was later found in the RNF213 gene. To our knowledge, this is the second report of Ap/T-MCA with the RNF213 gene polymorphism; however, their association remains unclear and requires further analyses.

The Feasibility of Mechanical Thrombectomy on Single-Plane Angiosuite: An In-Depth Analysis of Procedure Time.

INTRODUCTION: Mechanical thrombectomy (MT) is usually performed on biplane (BP) angiosuites. When the BP angiosuite is not available, the single-plane (SP) angiosuite may be a substitute. However, the feasibility of MT performed on the SP angiosuite is yet to be elucidated. Therefore, we investigated the alternative effect of the SP angiosuite on the detailed division of procedure time, recanalization rate, and outcome in patients with anterior circulation infarction. METHODS: The subjects included 80 consecutive patients with anterior circulation infarction who underwent MT at our hospital between May 2015 and December 2020. Demographics and characteristics of the BP and SP groups were assessed and compared. The time from puncture to guiding catheter placement (P-G), time from guiding catheter placement to recanalization (G-R), and time from puncture to recanalization (P-R) were also extracted. A good outcome was defined as a modified Rankin scale score ≤2 at 3 months. RESULTS: Of the 80 patients, 67 and 13 were treated with BP and SP angiosuites, respectively. There were no differences in age, sex, complications, Alberta Stroke Program Early CT Score, National Institutes of Health Stroke Scale score at onset, occlusion site, rate of recombinant tissue-type plasminogen activator administration, stroke subtype, recanalization rate, and complications between the 2 groups. The rate of a good outcome was not different between the 2 groups. P-G was significantly longer in the SP group than in the BP group, whereas there was no significant difference in G-R and P-R between the 2 groups (P-G: BP 29.9 ± 21.8 vs. SP 48.5 ± 43.6 min, p = 0.04). CONCLUSION: MT performed on the SP angiosuite tended to prolong the time for guiding catheter placement. However, there was no difference in the overall procedure time, recanalization rate, or outcome between BP and SP angiosuites. Therefore, if the BP angiosuite is not available, the use of the SP angiosuite should be encouraged.

Balloon Test Occlusion of the Carotid Artery: Internal Validation of Predictive Results.

AIM: To develop a protocol of balloon test occlusion (BTO) to perform single-photon emission computed tomography (SPECT) only in cases that require it by using mean stump pressure (MSTP). MATERIAL AND METHODS: BTO was performed in 52 consecutive patients (derivation group). Using the derivation group data, a protocol was created and applied to 55 consecutive patients (validation group). RESULTS: In the derivation group, all patients with MSTP ≥65 mmHg had an ischemic tolerance, whereas those with MSTP ?45 mmHg were considered ischemic intolerant. Based on these results, we developed a protocol wherein MSTP between 45 mmHg and 65 mmHg was defined as "ischemic borderzone" and SPECT was performed in these cases. Using this protocol, BTO was performed in the validation group and 19 patients were treated with parent artery occlusion with or without bypass. In two cases that did not follow the protocol, the occurrence of hypoperfusion caused cerebral infarction after treatment. However, if this protocol had been followed for all cases, no false-negative cases of BTO would have occurred. CONCLUSION: By measuring MSTP and identifying the approximate ischemic tolerability, the current protocol can identify cases requiring SPECT, which is particularly reliable but complicated. Moreover, this protocol would be especially useful for reducing false-negative cases of BTO.

Successful treatment of advanced pancreatic leiomyosarcoma treated with gemcitabine plus nab-paclitaxel: a case report and literature review.

Pancreatic leiomyosarcoma (PLMS) is an extremely rare tumor that accounts for 0.1% of pancreatic malignancies, and its chemotherapy has yet to be established. Generally, soft-tissue sarcoma chemotherapy is standard treatment with doxorubicin (DXR) alone. However, the effectiveness of gemcitabine (GEM) plus docetaxel (DOC) has been shown in uterine leiomyoma. In contrast, the GEM plus nab-paclitaxel (PTX) regimen has been established as first-line chemotherapy for unresectable pancreatic cancer. For this study, we selected the GEM plus nab-PTX regimen for patients with PLMS, achieving success in approximately 10 months. From a search on PubMed, we found only 12 cases of PLMS (including this case) that underwent chemotherapy. Our case is the first reported patient to have survived more than 2 years with chemotherapy alone. In a nude mouse model, the GEM plus DOC regimen was shown to significantly decrease tumor size when compared with DXR in leiomyosarcoma, and the GEM plus nab-PTX regimen was reported to significantly reduce necrosis when compared with DXR alone, GEM alone, DOC alone, nab-PTX alone and GEM plus DOC in soft-tissue sarcoma. GEM plus nab-PTX therapy might therefore be the first choice for soft-tissue sarcoma and leiomyosarcoma. This is the first reported case of PLMS treated with GEM plus nab-PTX.

Cavernous sinus dural arteriovenous fistula accessed through a straightened superficial temporal vein.

Background: Transvenous embolization through the inferior petrosal sinus (IPS) is the most common treatment procedure for cavernous sinus dural arteriovenous fistula (CSDAVF). When the IPS is inaccessible or the CSDAVF cannot be treated with transvenous embolization through the IPS, the superficial temporal vein (STV) is used as an alternative access route. However, the approach through the STV is often challenging because of its tortuous and abruptly angulated course. We report a case of recurrent CSDAVF which was successfully treated using a chronic total occlusion (CTO)-dedicated guidewire and by straightening the STV. Case Description: A 63-year-old woman was diagnosed with CSDAVF on examination for oculomotor and abducens nerve palsy. She was initially treated with transvenous embolization through the IPS. However, CSDAVF recurred, and transvenous embolization was performed through the STV. A microcatheter could not be navigated because of the highly meandering access route through the STV. By inserting a CTO-dedicated guidewire into the microcatheter, the STV was straightened and the microcatheter could be navigated into a shunted pouch of the CS. Finally, complete occlusion of the CSDAVF was achieved. Conclusion: If an access route is highly meandering, the approach can be facilitated by straightening the access route with a CTO-dedicated guidewire.

Development of Internal Carotid Artery Dissection During Masturbation.

Sexual intercourse is known as one of the daily activities triggering spontaneous cervicocephalic artery dissection (sCAD), however, it has been unclear if masturbation can trigger the development of sCAD. Herein, we report a case of sCAD in association with masturbation. A 51-year-old right-handed man developed subarachnoid hemorrhage during masturbation. The dissection of the left internal carotid artery was evident on the 9th hospital day. Finally, he was treated with stenting and coiling and discharged with a good prognosis.

Differential Methylation Signatures in Severely Calcified Carotid Plaques by Genome-Wide Comprehensive Analysis.

BACKGROUND: The precise cellular behaviors of calcification, including its molecular and genetic activities, have not yet been fully established for carotid plaques. OBJECTIVE: We sought specific genes with tissue-specific differential methylation associated with carotid calcification status. METHODS: We classified eight plaques from carotid endarterectomy patients as high- or low-calcified based on their Agatston calcium scores. We analyzed differential DNA methylation and performed bioinformatics data mining. RESULTS: A high correlation of average methylation levels (ß-values) in promoter regions between high- and low-calcified plaque groups was observed. A principal component analysis of DNA methylation values in promoters of specimens revealed two independent clusters for high- and lowcalcified plaques. Volcano plots for methylation differences in promoter regions showed that significantly hypomethylated probes were more frequently found for high-calcified plaques than more methylated probes. Differential hypomethylation of receptor activity-modifying protein 1 (RAMP1) in high-calcified plaques was commonly extracted in both the promoter region and the cytosinephosphate- guanine (CpG) island shore region, where differential methylation had been reported to be more tissue-specific. Kyoto Encyclopedia of Genes and Genomes pathway analysis annotated a pathway associated with vascular smooth muscle contraction in the differentially methylated genes of the promoter and CpG island shore regions in high-calcified plaques. CONCLUSION: Among the extracted differentially methylated genes, hypomethylated genes were more dominant than more methylated genes. The augmentation of RAMP1 by hypomethylation may contribute to the enhancement of anti-atherosclerotic effects and hence stability in high-calcified plaques. These results contribute to our understanding of the genetic signatures associated with calcification status and cellular activity in carotid plaques.