Preface In 2005, intravenous (IV) thrombolysis using alteplase, a recombinant tissue, type plasminogen activator (rt-PA), for patients with acute ischemic stroke was approved in Japanon the basis of ...the results of the Japan Alteplase Clinical Trial (J-ACT) with a specific low-dose regimen. Over the 10 years after approval, intravenous thrombolysis has become common as standard therapy for acute ischemic stroke. During this period, the Japan Stroke Society published the Guldlines forIntravenous Application of rt-PA (Alteplese) in 2005, independently of the Japanese Guidelines fpr the Management of Stroke in an effort to promote safe, widespread use of intravenous thrombolysis, and revised the present guidelines repeatedly according to subsequent accumulated evidence and changing therapeutic attitudes, The Japan Stroke Society also orgallized training sessions for proper use using the treatment guidelines as the textbook all over Japan every year and conducted a widespread awareness campaign. This effort was unique in Japan but was highly assessed outside Japan. Since 2018, e-learning has made it easier to participate in these training sessions.
The revised Japan Stroke Society Guidelines for the Treatment of Stroke were published in Japanese in July 2021. In this article, the extracted recommendation statements are published. The revision ...keeps pace with the great progress in stroke control based on the recently enacted Basic Act on Stroke and Cardiovascular Disease in Japan. The guideline covers the following areas: primary prevention, general acute management of stroke, ischemic stroke and transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, asymptomatic cerebrovascular disease, other cerebrovascular disease, and rehabilitation.
Preface from the Guidelines for Mechanical Thrombectomy in Japan, the First Edition (April 2014) Acute cerebral artery occlusion is associated with very poor outcomes. Early recanalization of ...occluded arteries, however, may improve the outcome, and recanalization therapy has been attempted with a variety of approaches. The most well-known approach is intravenous therapy with the recombinant tissue-plasminogen activator (IV rt-PA), alteplase. The efficacy of IV rt-PA has been established through many randomized controlled trials (RCTs). IV rt-PA is classified as a Class I therapy in the Guidelines for the Early Management of Patients with Acute Ischemic Stroke of the American Heart Association/American Stroke Association (AHA/ASA) and a Grade A recommendation in the Japanese Guidelines for the Management of Stroke. Even as cerebrovascular medical technology has progressed, IV rt-PA remains the priority therapy for patients with acute ischemic stroke. Currently, IV rt-PA is indicated for acute ischemic stroke within 4.5 hours of onset with no contraindications.
The current standard of diagnosing central nervous system (CNS) lymphoma is stereotactic biopsy, however the procedure has a risk of surgical complication. Liquid biopsy of the CSF is a less ...invasive, non‐surgical method that can be used for diagnosing CNS lymphoma. In this study, we established a clinically applicable protocol for determining mutations in MYD88 in the CSF of patients with CNS lymphoma. CSF was collected prior to the start of chemotherapy from 42 patients with CNS lymphoma and matched tumor specimens. Mutations in MYD88 in 33 tumor samples were identified using pyrosequencing. Using 10 ng each of cellular DNA and cell‐free DNA (cfDNA) extracted from the CSF, the MYD88 L265P mutation was detected using digital PCR. The conditions to judge mutation were rigorously determined. The median Target/Total value of cases with MYD88 mutations in the tumors was 5.1% in cellular DNA and 22.0% in cfDNA. The criteria to judge mutation were then determined, with a Target/Total value of 0.25% as the cutoff. When MYD88 mutations were determined based on these criteria, the sensitivity and specificity were 92.2% and 100%, respectively, with cellular DNA; and the sensitivity and specificity were 100% with cfDNA. Therefore, the DNA yield, mutated allele fraction, and accuracy were significantly higher in cfDNA compared with that in cellular DNA. Taken together, this study highlights the importance of detecting the MYD88 L265P mutation in cfDNA of the CSF for diagnosing CNS lymphoma using digital PCR, a highly accurate and clinically applicable method.
Development of a liquid biopsy for less invasive diagnosis of CNS lymphoma is in progress. In this study, the conditions for detecting the MYD88 L265P mutation by digital PCR were set, and extremely high accuracy was confirmed. This method is fully clinically feasible.
Objective
To build a prediction model that estimates the 3‐year rupture risk of unruptured saccular cerebral aneurysms.
Methods
Survival analysis was done using each aneurysm as the unit for ...analysis. Derivation data were from the Unruptured Cerebral Aneurysm Study (UCAS) in Japan. It consists of patients with unruptured cerebral aneurysms enrolled between 2000 and 2004 at neurosurgical departments at tertiary care hospitals in Japan. The model was presented as a scoring system, and aneurysms were classified into 4 risk grades by predicted 3‐year rupture risk: I, < 1%; II, 1 to 3%; III, 3 to 9%, and IV, >9%. The discrimination property and calibration plot of the model were evaluated with external validation data. They were a combination of 3 Japanese cohort studies: UCAS II, the Small Unruptured Intracranial Aneurysm Verification study, and the study at Jikei University School of Medicine.
Results
The derivation data include 6,606 unruptured cerebral aneurysms in 5,651 patients. During the 11,482 aneurysm‐year follow‐up period, 107 ruptures were observed. The predictors chosen for the scoring system were patient age, sex, and hypertension, along with aneurysm size, location, and the presence of a daughter sac. The 3‐year risk of rupture ranged from <1% to >15% depending on the individual characteristics of patients and aneurysms. External validation indicated good discrimination and calibration properties.
Interpretation
A simple scoring system that only needs easily available patient and aneurysmal information was constructed. This can be used in clinical decision making regarding management of unruptured cerebral aneurysms. Ann Neurol 2015;77:1050–1059
Abstract
BACKGROUND
Giant fusiform and dolichoectatic aneurysms of the basilar trunk and vertebrobasilar junction (BTVBJ-GFDA) are extremely difficult to treat.
OBJECTIVE
To evaluate factors ...influencing survival and outcome of BTVBJ-GFDA by performing a retrospective multicenter cohort study.
METHODS
A total of 32 patients with BTVBJ-GFDA were included in this study. Clinicopathological characteristics, treatment measures, and outcomes were collected from medical records and imaging studies. Autopsy and histological findings of the aneurysm and adjacent brain tissue were also obtained in 9 cases.
RESULTS
A total of 11 patients did not undergo surgery, of whom 10 died; 3 from progressive brainstem compression, 4 from subarachnoid hemorrhage, 2 from brainstem infarction, and 1 from associated atherosclerotic disease. The remaining 21 patients underwent a surgical treatment, consisting of immediately proximal parent artery occlusion, remotely proximal parent artery occlusion, clip reconstruction, and distal bypass and achieved significantly longer overall survival compared with those who received conservative therapy (adjusted hazard ratio 1.508, 95% CI 1.058-2.148, P = .02). Histological examination of the aneurysms demonstrated staged clots, open lumen, and intrathrombotic channels with endothelial lining. The patients younger than 45 yr of age showed statistically longer survival than those equal and older than 45 yr (P = .03).
CONCLUSION
Surgical intervention achieved greater survival than conservative management in BTVBJ-GFDA. Narrow ideal treatment window of the blood flow within the aneurysm to maintain sufficient but not excess supply should be targeted based on the hemodynamics of both the posterior communicating arteries and perforating vessel collaterals.
Graphical Abstract
Graphical Abstract
The traditional apprenticeship approach to surgical skill education for young surgeons has drastically changed to more systematic surgical training using cadavers. Cadavers fixed with formalin are ...not suitable for surgical training because of their associated health hazards and overhardening. Recently, we established a formalin-free soft preservation method for human cadavers using
N
-vinyl-2-pyrrolidone. Since 2012, 61 cadavers have been embalmed with pyrrolidone in our institution. Tissues of pyrrolidone-embalmed cadavers are soft and pliable, and their bodies can be preserved for as long as 37 months without any signs of corruption. In this review, we introduce our recent attempts to apply pyrrolidone-embalmed cadavers in surgical and medical procedure training, including endotracheal intubation, motion physiology of the vocal folds, laparoscopic surgery, endoscopic skull base surgery, and development of novel medical devices. Future research perspectives on pyrrolidone embalming are discussed.
This study aimed to assess the number of patients with acute stroke seeking medical emergency care since the declaration of the state of emergency in the COVID-19 pandemic in the Tokyo metropolitan ...area of Japan.
In this combined retrospective and prospective multicenter survey, data on the numbers of hospital admissions due to acute ischemic stroke, of large vessel occlusion (LVO) cases, and of reperfusion therapies performed from February to July 2020, restrictions of the medical care system, and comprehensive stroke center (CSC) scale scores were collected in 19 stroke centers in Tokyo.
In the survey period, 3,456 patients were admitted with acute stroke. There was a decrease in the number of admissions (-22%), LVO (-22%), thrombolysis (-6%), and thrombectomy (-23%) during the state of emergency, but the ratio of thrombectomy to LVO cases was not different. The acceptance of acute stroke cases by emergency transport and emergent operations in the central eastern area of Tokyo, was also significantly decreased to <50% and remains <60%. According to CSC scores, each hospital restricted their infrastructure or educational activities according to their medical resources. There was only one stroke case with COVID-19 (thrombectomy case) in all 3,456 patients in this study.
The COVID-19 pandemic had a major impact on stroke care in Tokyo, including stroke admissions and medical care systems, resulting in a significant reduction in thrombolysis and thrombectomy. The extent of the drop may be the result of the number of COVID-19 patients.
A 51-year-old man with a history of renal cell carcinoma presented with sudden aphasia, right hemiparesis, and dysesthesia. MRA showed left middle cerebral artery occlusion, and he was diagnosed with ...acute ischemic stroke and treated with intravenous recombinant tissue plasminogen activator and endovascular thrombectomy. The pathological diagnosis of the retrieved thrombus was consistent with the already-known pathological findings of the primary renal cell carcinoma. Therefore, a diagnosis of cerebral embolism caused by tumor cells was made. The pathological findings of the retrieved thrombi were important in determining the cause of ischemic stroke.
Abstract
Backgrounds
Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent ...glioblastoma setting.
Methods
A total of 171 patients with newly diagnosed glioblastoma, either ‘primary’ glioblastoma or ‘secondary’ glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122).
Results
IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with ‘primary’ glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When ‘primary’ glioblastoma and ‘secondary’ glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035).
Conclusions
These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with ‘primary’ glioblastoma and pretreated ‘secondary’ glioblastoma, and further warrant investigation in prospective studies.
Overall survival after first progression of patients with primary glioblastoma was not significantly different between those with mutant IDH1 and wild-type IDH1. O6-methylguanine-DNA methyltransferase status and Karnofsky Performance status were independent better prognosticators.
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