Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an ...abnormal vascular network at the base of the brain. These diagnostic criteria of the moyamoya disease, stated by the Research Committee on Spontaneous Occlusion of the Circle of Willis (moyamoya disease) in Japan, are well established and generally accepted as the definition of this rare entity. On the contrary to the diagnosis of definitive moyamoya disease, there is some confusion in the terminology and understanding of quasi-moyamoya disease; moyamoya disease in association with various disease entities, such as atherosclerosis, autoimmune diseases, Down syndrome, etc. Although the clinical management is not affected by these semantic distinctions, terminological confusion may interfere with the international collaboration of the clinical investigation of these rare conditions. In this article, we sought to review the international standard and regional differences in the diagnosis of moyamoya disease and quasi-moyamoya disease.
In this report, we, the Research Committee on Moyamoya Disease (Spontaneous Occlusion of the circle of Willis), describe in detail the changes in the new "Diagnostic Criteria 2021" for moyamoya ...disease and its scientific basis to make it widely known to the world. The revised criteria cover all aspects of the disease, including a definition of the disease concept, diagnostic imaging, and the concept of quasi-moyamoya disease (moyamoya syndrome).
Clazosentan has been investigated globally for the prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). The authors evaluated its effects on vasospasm-related morbidity ...and all-cause mortality following aSAH in Japanese patients.
Two similar double-blind, placebo-controlled phase 3 studies were conducted in 57 Japanese centers in patients with aSAH, after aneurysms were secured by endovascular coiling in one study and surgical clipping in the other. In each study, patients were randomly administered intravenous clazosentan (10 mg/hr) or placebo (1:1) starting within 48 hours of aSAH and for up to 15 days after aSAH. Stratified randomization based on World Federation of Neurosurgical Societies grade was performed using a centralized interactive web response system. Vasospasm-related morbidity and all-cause mortality within 6 weeks post-aSAH, including new cerebral infarcts and delayed ischemic neurological deficits as well as all-cause mortality, were the first primary endpoint in each study. The second primary endpoint was all-cause morbidity (new cerebral infarct or delayed ischemic neurological deficit from any causes) and all-cause mortality (all-cause morbidity/mortality) within 6 weeks post-aSAH. The incidence of individual components of the primary morbidity/mortality endpoints within 6 weeks and patient outcome at 12 weeks post-aSAH (including the modified Rankin Scale scores) were also evaluated. The above analyses were also performed in the population pooled from both studies.
In each study, 221 patients were randomized and 220 were included in the full analysis set of the primary analysis (109 in each clazosentan group, 111 in each placebo group). Clazosentan significantly reduced the incidence of vasospasm-related morbidity and all-cause mortality after aneurysm coiling (from 28.8% to 13.6%; relative risk reduction 53%; 95% CI 17%-73%) and after clipping (from 39.6% to 16.2%; relative risk reduction 59%; 95% CI 33%-75%). All-cause morbidity/mortality and poor outcome (dichotomized modified Rankin Scale scores) were significantly reduced by clazosentan after preplanned study pooling. Treatment-emergent adverse events were similar to those reported previously.
Clazosentan significantly reduced the combined incidence of vasospasm-related morbidity and all-cause mortality post-aSAH with no unexpected safety findings. Clinical trial registration nos.: JapicCTI-163368 and JapicCTI-163369 (https://www.clinicaltrials.jp).
Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an ...abnormal vascular network at the base of the brain. Recent advances in molecular biology and genetic research have provided better understanding of the pathophysiology of moyamoya disease, but surgical revascularization still remains the preferred treatment for this entity. The present study investigated the clinical course of 106 consecutive patients with moyamoya disease who underwent superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis in 150 hemispheres. The outcomes of surgery on the operated hemisphere were favorable, with no cerebrovascular event during the outpatient follow-up period (mean 58.4 months) in 89.3% (134/150). Two patients suffered hemorrhagic events on the operated hemisphere during the follow-up period (2/150, 1.33%), one of whom suffered deteriorated neurological status after hemorrhage. Despite the favorable long-term outcome, the incidence of temporary neurological deterioration due to cerebral hyperperfusion was 18.0% (27/150), but no patients suffered permanent neurological deterioration directly caused by hyperperfusion. In conclusion, direct/indirect revascularization surgery is a safe and effective treatment for moyamoya disease, although the issue of bleeding/re-bleeding remains to be solved. Postoperative cerebral hyperperfusion and peri-operative infarction are potential complications of this procedure, so we recommend intensive postoperative care and cerebral blood flow measurement in the acute stage, because the management of hyperperfusion is contradictory to that of ischemia.
Moyamoya disease is a chronic cerebrovascular disease with unknown etiology, which is characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an ...abnormal vascular network formation at the base of the brain. Moyamoya disease is known to have unique and dynamic nature to convert the vascular supply for the brain from internal carotid (IC) system to the external carotid (EC) system, as indicated by Suzuki’s angiographic staging established in 1969. Insufficiency of this ‘IC-EC conversion system’ may result in cerebral ischemia, as well as in intracranial hemorrhage from inadequate collateral vascular network, both of which represent the clinical presentation of moyamoya disease. Therefore, surgical revascularization by extracranial-intracranial bypass is the preferred procedure for moyamoya disease to complement ‘IC-EC conversion’ and thus to avoid cerebral infarction and/or intracranial hemorrhage. Long-term outcome of revascularization surgery for moyamoya disease is favorable, but rapid increase in cerebral blood flow on the affected hemisphere could temporarily cause unfavorable phenomenon such as cerebral hyperperfusion syndrome. We would review the current status of revascularization surgery for moyamoya disease based on its basic pathology, and sought to discuss the significance of measuring cerebral blood flow in the acute stage and intensive perioperative management.
RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function ...are not yet comprehended. To understand RNF23 function, we performed gene knockdown (KD) in vascular cells and performed various phenotypical analysis as well as extensive transcriptome and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted angiogenesis in HUVEC, in part due to downregulation of DNA replication and proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced inflammation after RNF213 KD, leading to retarded cell migration and enhanced macrophage transmigration. This was evident at the level of transcriptome as well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led to alteration in cytoskeletal organization, contractility, and vSMCs function related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication in co-culture models. Overall, our results indicate that RNF213 KD sensitizes endothelial cells to inflammation, leading to altered angiogenesis. Our results shed the light on the important links between RNF213 mutations and inflammatory/immune inducers of MMD and on the unexplored role of epitranscriptome in MMD.
We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major ...diseases, such as cancer and cardiovascular diseases.
We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely.
As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex.
This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.
Despite the plethora of published studies on intracranial aneurysms (IAs) hemodynamic using computational fluid dynamics (CFD), limited progress has been made towards understanding the complex ...physics and biology underlying IA pathophysiology. Guided by 1733 published papers, we review and discuss the contemporary IA hemodynamics paradigm established through two decades of IA CFD simulations. We have traced the historical origins of simplified CFD models which impede the progress of comprehending IA pathology. We also delve into the debate concerning the Newtonian fluid assumption used to represent blood flow computationally. We evidently demonstrate that the Newtonian assumption, used in almost 90% of studies, might be insufficient to describe IA hemodynamics. In addition, some fundamental properties of the Navier–Stokes equation are revisited in supplementary material to highlight some widely spread misconceptions regarding wall shear stress (WSS) and its derivatives. Conclusively, our study draws a roadmap for next-generation IA CFD models to help researchers investigate the pathophysiology of IAs.
Following stress, transfer RNA (tRNA) is cleaved to generate tRNA halves (tiRNAs). These tiRNAs have been shown to repress protein translation. Angiogenin was considered the main enzyme that cleaves ...tRNA at its anticodon to generate 35–45 nucleotide long tiRNA halves, however, the recent reports indicate the presence of angiogenin‐independent cleavage. We previously observed tRNA cleavage pattern occurring away from the anticodon site. To explore this noncanonical cleavage, we analyze tRNA cleavage patterns in rat model of ischemia–reperfusion and in two rat cell lines. In vivo mitochondrial tRNAs were prone to this noncanonical cleavage pattern. In vitro, however, cytosolic and mitochondrial tRNAs could be cleaved noncanonically. Our results show an important regulatory role of mitochondrial stress in angiogenin‐mediated tRNA cleavage. Neither angiogenin nor RNH1 appear to regulate the noncanonical tRNA cleavage. Finally, we verified our previous findings of the role of Alkbh1 in regulating tRNA cleavage and its impact on noncanonical tRNA cleavage.
During oxidative stress, transfer RNA (tRNA) is cleaved at the anticodon via angiogenin to generate 35–45 nt long tiRNAs. This process regulates protein translation. Rashad et al. show a noncanonical form of tRNA cleavage, occurring away from the anticodon and is angiogenin in dependent. This noncanonical cleavage is in‐part regulated by tRNA methylation (via Alkbh1). Moreover, they show an important role of mitochondrial stress in regulating canonical and noncanonical tRNA cleavage.
Traumatic acute subdural hematoma (ASDH) is a major clinical entity in traumatic brain injury (TBI). It acts as a space occupying lesion to increase intracranial pressure, and is often complicated by ...co-existing lesions, and is modified by cerebral blood flow (CBF) changes, coagulopathy, and delayed hematomas. Because of its complicated pathophysiology, the mortality of ASDH is still remaining high. In this review article, its epidemiology, pathophyiology, surgical treatment, and salvage ability are described. With regard to epidemiology, as the population ages, growing number of elderly patients with ASDH, especially patients with prehospital anticoagulant and antiplatelets, increase. Concerning pathophysiology, in addition to well-known initial intracranial hypertension and subsequent ischemia, delayed hyperemia/hyperperfusion, or delayed hematoma is being recognized frequently in recent years. However, optimal treatments for these delayed phenomenons have not been established yet. With regard to surgical procedures, all of craniotomy, decompressive craniectomy, and initial trephination strategies seem to be effective, but superiority of each procedure have not been established yet. Since Glasgow Coma Scale (GCS) scores, age, papillary reaction, and computed tomographic findings are strongly correlated to outcome, each factor has been investigated as an indicator of salvage ability. None of them, however, has been defined as such one. In future studies, epidemiological changes as population ages, management of delayed pathophysiology, superiority of each surgical procedures, and salvage ability should be addressed.
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