There are very few organ transplants from brain-dead donors (BD transplants) in Japan compared with other countries. The neuroemergency section of the Japanese Society of Neurology (JSN) conducted a survey on the participation of neurologists in BD determination. The target of the survey was educational and quasi-educational institutions of the JSN. It was found that neurologists served as doctors to legally declare BD in 38% of institutions. Many institutions had neurological staffs with the skills required for BD determination, such as EEG reading (97%), neurological evaluations of BD (93%), judgment of the apnea test (75%), or interpretation of auditory brainstem responses (67%). As many as 96% of the responders considered that neurologists should participate in legal BD determination, although 20% felt that the lack of human resources prevented them from active participation. An inquiry to the Japan Organ Transplant Network revealed that neurologists served as a doctor to legally declare BD in around 80% of legal BD determination cases so far. The neuroemergency section conducted another survey regarding the duration of high-sensitivity and bipolar recording in EEG for BD determination. This was because simplification of EEG recording was planned for the revision of the official manual for legal BD determination. It was found that high-sensitivity and bipolar recording was conducted for 15 minutes or shorter in 52% of institutions. Many existing overseas as well as Japanese guidelines require 30-minute EEG recording for BD determination. However, the only basis was the reports of two cases with drug intoxication in whom EEG reappeared after 20 minutes' electrocerebral inactivity: such patients would not be candidates for donors according to the Japanese guideline. Based on the present results, the minimal required duration of (high-sensitivity and bipolar) EEG recording for legal BD determination was shortened to 15 minutes in the revised manual.

【背景および目的】併存疾患がある脳卒中患者に対する複種類のリハビリテーション(複合リハ)の実施,転院状況は不明である.【方法】一次脳卒中センター(PSC)に,施設情報,リハ体制,複合リハ,転院状況についてアンケート調査を実施した.【結果】414施設が解析対象となった.リハ体制では言語聴覚士が最も少なく,専従・専任看護師はほぼいなかった.また脳卒中リハ(脳卒中看護)認定看護師を含め,専門資格をもつ看護師も少なかった.リハでは認知症リハの対応ができていなかった.また診療報酬にかかわらず実施できるリハは,脳血管疾患リハ以外に1種類である施設が多かった.複合リハ必要例では,大学病院で転院までに時間がかかる施設が多かった.【結論】本邦のPSCの多くは複合リハが十分に実施されていない可能性がある.複合リハの実施には,言語聴覚士,専門看護師の増員,認知症への対応,診療報酬の見直しなどが必要と考えられる.

The ratio of the internal carotid artery (ICA) to the common carotid artery (CCA), especially the “AcT ratio,” which is a modified measurement method of acceleration time, is useful for diagnosing ICA-origin stenosis. However, previous studies were single-center studies. Therefore, this multicenter, retrospective, cross-sectional study aimed to determine whether a method using the AcT ratio is useful for estimating stenosis rates. This study included 461 vessels subjected to carotid artery ultrasonography and evaluation for ICA-origin stenosis via NASCET at four hospitals. The duration from the steep rise point to the inflection point or the first peak was defined as AcT on pulsed wave Doppler. The AcT ratio was calculated as AcT of ICA/AcT of ipsilateral CCA. The AcT ratio and rate of ICA-origin stenosis were analyzed using Pearson's correlation coefficient, simple regression analysis, and ROC curve. A significant positive correlation was observed between the AcT ratio and NASCET stenosis. NASCET stenosis of ≥ 50

Aims: Atherogenic dyslipidemia (AD) is regarded as a residual risk of cardiovascular diseases characterized by low high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) levels and related to the intracranial stenosis of atheromatous thrombotic brain infarction (ATBI). Further, atherosclerosis is possibly related to another stroke subtype, including cryptogenic stroke (CS). In particular, an aortic complicated lesion (ACL) is a notable embolic source of CS, since recurrence of aortogenic brain embolism is not rare. This study aimed to clarify the underlying association between AD and CS. Methods: CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for ESUS/CS) had extensive data from CS patients who underwent transesophageal echocardiography (TEE). AD was defined as HDL-C <= 40 mg/dl and TG >= 150 mg/dl. Based on these criteria, patients were divided into an AD group and a non-AD group to compare the clinical features. Results: Of 664 CS patients (446 men, 68.7 +/- 12.8 years), 68 (10.2%) met the criteria of AD (AD group), and 596 (89.8%) were in the non-AD group. On multiple logistic regression analysis, body mass index (unit OR 1.11, 95%CI 1.04-1.19, p = 0.002), diabetes mellitus (OR 2.23, 95%CI 1.28-3.87, p = 0.004), ACL in the arch (OR 1.89, 95%CI 1.09-3.31, p = 0.025), and deterioration during hospitalization (OR 3.96, 95%CI 1.32-10.68, p = 0.009) were independently associated with AD. Conclusion: AD was not rare in the present CS population. Moreover, AD was crucially related to ACL in CS. Therefore, intensive and pleiotropic lipid-modifying therapy would be efficacious for further treatment of aortogenic brain embolism.

Background and purpose: The aortic complicated lesion (ACL) is a notable embolic source of cryptogenic stroke (CS) observed in 10-60 % of patients. Although the antithrombotic and statin therapy are certainly effective, the recurrence of aortogenic stroke is not rare. Atherogenic dyslipidemia (AD) is regarded as the significant residual risk of cardiovascular diseases even under the statin remedy and characterized by low high-density lipoprotein (HDL) and high triglyceride (TG). In the present study, we aimed to clarify the underlying association between ACL and AD. Methods: Clinical data of CS patients admitted between April 2014 and December 2016 in Japanese 8 institutes and underwent transesophageal echocardiography (TEE) were analyzed in the present study. Low HDL was defined as ≤ 40 mg/dl and high TG was defined as ≥ 150 mg/dl in the fasting condition, respectively. Furthermore, AD must satisfy both cut-off values. Based on these criteria, patients were divided into 4 groups as AD group, HDL group, TG group, and non-AD group to compare the clinical features. Results: Of 664 CS patients, 68 (57 men, 68.6 ± 11.1 years) met the criteria of AD (AD group), and 108 (90 men, 68.5 ±13.7 years) fulfilled the low HDL only (HDL group), 115 (76 men, 66.9 ± 11.7 years) merely met the high TG (TG group), 373 (223 men, 69.4 ± 13.1 years) satisfied the neither (non-AD group). In a univariate analysis, ACL in arch revealed with TEE was significantly more frequent in AD group (55.9 vs 38.0 vs 39.1 vs 33.8 %, p=0.007). In a multiple regression analysis, male (OR 2.57, 95%CI 1.23-5.38, p=0.012), body mass index (unit OR 1.16, 95%CI 1.08-1.25, p<0.001), diabetes (OR 2.52, 95%CI 1.41-4.53, p=0.002), ACL in arch (OR 2.12, 95%CI 1.19-3.80, p=0.011) were independently, and past history of stroke (OR 0.35, 95%CI 0.14-0.90, p=0.030) was inversely associated with AD group. Conclusions: Although the previous study exhibited that AD was predominantly associated with intracranial stenosis in atherothrombotic brain infarction, AD was also crucially related to ACL in CS in the present study. Concerning the aortogenic stroke, more intensive and pleiotropic lipid-lowering therapy would be efficacious for further treatment.

Aim: Various embolic sources and pathogenetic mechanisms underlie cryptogenic stroke (CS). We investigated the association of etiological diversity with short-term outcomes in patients with CS using a modified atherosclerosis (A), small-vessel disease (S), cardiac pathology (C), other causes (O), and dissection (D) (ASCOD) system.Methods: Patients with CS who underwent transesophageal echocardiography were registered in this multicenter, observational study. In the modified classification system, O and D were inapplicable and thus excluded. Instead, atherosclerosis, small-vessel disease, cardiac pathology-CS classification was specifically constructed for the etiological diagnosis of CS. We utilized this system to explore the mechanism of CS by grading each pathology and evaluated its association with poorer modified Rankin Scale scores of 3-6 at hospital discharge.Results: A total of 672 patients (68.7 +/- 12.8 years, 220 females) were analyzed. In the multiple logistic regression model, female sex (odds ratio [OR], 1.87 [1.15-3.04]; P=0.012), body mass index (OR, 0.93 [0.88-0.99]; P=0.025), National Institute of Health Stroke Scale score (OR, 1.16 [1.12-1.21]; P<0.001), CHADS2 score (OR, 1.56 [1.30-1.86]; P<0.001), D-dimer (OR, 1.04 [1.01-1.08]; P=0.015), diffusion-weighted image (DWI) lesion size (OR, 1.44 [1.10-1.89]; P=0.009), and S+C score (OR, 1.26 [1.03-1.56]; P=0.029) were associated with poor functional outcome at discharge whereas the S+C score was marginally associated with poor functional outcome after excluding 137 patients with a premorbid modified Rankin Scale score of >= 3. Conclusions: The coexistence of small-vessel disease and cardiac pathology might be associated with poor in-hospital functional outcome in CS.

Hyperuricemia often accompanies hypertension, diabetes, dyslipidemia, metabolic syndrome, and chronic renal disease; it is also closely related to cardiovascular disease. Moreover, several epidemiological studies have linked hyperuricemia and ischemic stroke. However, uric acid may also have neuroprotective effects because of its antioxidant properties. An association between low uric acid levels and neurodegenerative diseases has been suggested, which may be attributed to diminished neuroprotective effects as a result of reduced uric acid. This review will focus on the relationship between uric acid and various neurological diseases including stroke, neuroimmune diseases, and neurodegenerative diseases. When considering both the risk and pathogenesis of neurological diseases, it is important to consider the conflicting dual nature of uric acid as both a vascular risk factor and a neuroprotective factor. This dual nature of uric acid is important because it may help to elucidate the biological role of uric acid in various neurological diseases and provide new insights into the etiology and treatment of these diseases.

BACKGROUND:Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies.OBJECTIVE:In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan.METHODS:This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation.RESULTS:Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023.CONCLUSIONS:The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan.TRIAL REGISTRATION:UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/39307.

Background: High-risk patent foramen ovale (PFO) could be pathological in cryptogenic stroke (CS), but its clinical characteristics have not been fully studied, especially in elderly patients.Methods: Patients with CS were enrolled in the CHALLENGE ESUS/CS registry, a multicenter registry of CS patients undergoing transesophageal echocardiography. Clinical characteristics were compared among three groups: high-risk PFO group, large shunt PFO (>= 25 microbubbles) or PFO with atrial septal aneurysm (ASA); right-to-left shunt (RLS) group, RLS including PFO with <25 microbubbles or without ASA; and no-RLS group.Results: In total, 654 patients were analyzed: 91, 221, and 342 in the high-risk PFO, RLS, and no-RLS groups, respectively. In multinomial logistic regression analysis, the male sex (odds ratio [OR] 1.825 [1.067-3.122]) was independently associated with high-risk PFO, but hypertension (OR, 0.562 [0.327-0.967]), multiple infarctions (OR, 0.601 [0.435-0.830]), and other cardioaortic embologenic risks (OR, 0.514 [0.294-0.897]) were inversely associated with high-risk PFO compared with non-RLS. In 517 patients aged >= 60 years, multiple infarctions (OR, 0.549 [0.382-0.788]) and other cardioaortic embologenic risks (OR, 0.523 [0.286-0.959]) were inversely associated with high-risk PFO. Conclusions: High-risk PFO had specific clinical characteristics and possible mechanistic associations, and this trend was consistent among CS patients aged >= 60 years.Clinical Trial Registration Information: http://www.umin.ac.jp/ctr/ (UMIN000032957).

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.

ABSTRACT Objectives: We collected opinions about the use of a stroke-specific regional clinical pathway for facilitating collaboration between acute and rehabilitation hospitals in Japan. Methods: The study surveys were administered in acute hospitals designated as primary stroke centers and certified by the Japan Stroke Association (n=961) and in rehabilitation hospitals affiliated with the Kaifukuki Rehabilitation Ward Association (n=1237). The survey collected information on interfacility collaboration when caring for patients admitted during the acute phase following non-traumatic stroke from April 2020 to March 2021. We examined the pathway’s usefulness and challenges relative to facility type using the χ2 test. Results: Of 422 acute hospitals and 223 rehabilitation hospitals that responded to our survey, 259 (62.1%) acute hospitals and 164 (85.4%) rehabilitation hospitals used the pathway. Fewer rehabilitation hospitals than acute hospitals considered that the pathway was useful (52.0% vs. 63.8%, P=0.02). Fewer rehabilitation hospitals did not experience pathway-related problems when compared with acute hospitals (38.0% vs. 55.8%, P<0.01). Conclusions: Personnel at rehabilitation hospitals were less satisfied with the regional clinical care pathway than those in acute hospitals. These results suggest that the current stroke-specific regional clinical pathway could be improved.

Stroke requires rapid determination of the cause to provide timely and appropriate initial management. Various ultrasonographic techniques have been evaluated as ways to determine the cause of stroke; among them, carotid artery ultrasonography is particularly useful since it provides considerable information within a short time period when used to evaluate a specific site. In the emergency room, carotid artery ultrasonography can be used to diagnose internal carotid artery stenosis, predict an occluded vessel, and infer the cause of ischemic stroke. Additionally, carotid artery ultrasonography can diagnose different conditions including subclavian artery steal syndrome, bow hunter’s stroke, Takayasu’s arteritis, moyamoya disease, and dural arteriovenous fistula. Furthermore, patients with ischemic stroke with a pulse deficit or hypotension must be differentiated from acute type A aortic dissection, which requires emergency surgery; carotid artery ultrasonography can immediately differentiate between the two conditions by identifying the intimal flap of the common carotid artery. The following article provides an overview of carotid artery ultrasonography performed as point-of-care ultrasound in the emergency room in patients with suspected stroke.

Cardiac papillary fibroelastoma (CPF) is often of valvular origin, but rarely forms in coumadin ridge (CR) and may cause cerebral embolism. We present an unusual 79-year-old man with cerebral embolism caused by CPF in CR. The patient presented with right upper limb paresis and was diagnosed with left centrum ovale infarction. Atrial fibrillation and severe stenosis of the cerebral and carotid artery were not found in various examinations. Although transthoracic echocardiography showed no abnormalities, transesophageal echocardiography (TEE) revealed a mobile string-like structure measuring approximately 11 mm at the tip of the CR. We suspected a thrombus attached to the CR, and anticoagulation therapy was administered, however the structure did not disappear. Therefore, the patient was diagnosed as cardiac tumor and underwent tumor excision and surgical closure of the left atrial appendage. The tumor was confirmed to be CPF on histopathology. Warfarin therapy was continued, and there was no recurrence of tumor or cerebral embolism at 4 months after surgery. CPF should be considered in cryptogenic stroke, especially in embolic stroke of undetermined sources cerebral embolism.

Carotid artery ultrasonography is capable of diagnosing or inferring the presence or absence of stenosis or occlusion of the internal carotid artery (ICA) and vertebral artery (VA), as well as the not directly observable distal ICA, middle cerebral artery (MCA), and basilar artery (BA). Stenosis at the origin of the ICA is mainly evaluated using the parameter peak systolic velocity (PSV), with values of ≥ 200–230 cm/s indicating severe stenosis. Recently, the acceleration time ratio has been reported for diagnosis of ICA origin stenosis. An indicator called the end-diastolic (ED) ratio can be used for diagnosing occlusion of the distal ICA or the M1 segment of the MCA. The PSV of stenosis can be used to diagnose stenosis at the beginning of the VA or V1, and mean flow velocity, mean ratio, and diameter ratio can be used to diagnose distal VA occlusion. Furthermore, the usefulness of the VA pulsatility index and resistance index has been suggested for diagnosing stenosis or occlusion of the BA. This review outlines diagnostic sonography criteria for stenosis and occlusion of extracranial and intracranial arteries.

The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been studied. CHALLENGE ESUS/CS is a multicenter registry of cryptogenic stroke patients undergoing transesophageal echocardiography. Twelve-lead electrocardiogram, continuous cardiac monitoring, and 24-h Holter electrocardiogram were all used for the detection of AF. Early and late detection of AF was determined with an allocation ratio of 1:1 among patients with AF. A total of 677 patients (68.7 ± 12.8 years; 455 men) were enrolled, and 64 patients developed AF during hospitalization. Four days after admission was identified as the approximate median day to classify early and late phases to detect AF: ≤ 4 days, 37 patients; > 4 days, 27 patients. Multiple logistic regression analysis showed that spontaneous echo contrast (SEC) (OR 5.91; 95% CI 2.19-15.97; p < 0.001) was associated with AF ≤ 4 days, whereas a large infarction > 3 cm in diameter (OR 3.28; 95% CI 1.35-7.97; p = 0.009) was associated with AF > 4 days. SEC and large infarctions were important predictors of in-hospital AF detection, particularly in the early and late stages, respectively; thus, they could serve as indications for recommending ICM.

Objective: Some cardiac abnormalities could be a substrate for potential embolic source in cryptogenic stroke (CS). We evaluated whether cardiac and echocardiographic markers were associated with CS in patients with incidental patent foramen ovale (PFO) as defined using the Risk of Paradoxical Embolism (RoPE) score. Materials and methods: Among 677 patients enrolled in a multicenter observational CS registry, 300 patients (44%) had PFOs detected by transesophageal echocardiography. They were classified into probable PFO-related stroke (RoPE score>6, n = 32) and stroke with incidental PFO (RoPE score<6, n = 268) groups, and clinical characteristics, laboratory findings, cardiac and echocardiographic markers (i.e. brain natriuretic peptide, left atrial [LA] diameter, ejection fraction, early transmitral flow velocity/early diastolic tissue Doppler imaging velocity [E/e'], LA appendage flow velocity, spontaneous echo contrast, atrial septal aneurysm, substantial PFO, and aortic arch plaques), stroke recurrence, and excellent outcome (modified Rankin scale score <2) at discharge were compared. Risk factors for low RoPE scores were determined using multiple logistic regression analysis. Results: Higher brain natriuretic peptide levels (p = 0.032), LA enlargement (p < 0.001), higher E/e' (p = 0.001), lower LA appendage flow velocity (p < 0.001), non-substantial PFO (p = 0.021), and aortic arch plaques (p = 0.002) were associated with the low RoPE score group. Patients with high RoPE scores had excellent outcomes (58% versus 78%, p = 0.035). LA enlargement (age- and sex-adjusted odds ratio, 1.15; 95 % confidence interval, 1.00-1.32; p = 0.039) was an independent predictor of low RoPE scores. Conclusions: Abnormal cardiac substrate could be associated with CS occurrence in a subset of patients with PFO. Patients with CS who had incidental PFO may be at risk of cardioembolism.