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Purpose Although pathogenic mechanisms of moyamoya disease (MMD) remain unknown, recent studies suggest that it is a caveolae disease. This study evaluated the effect of udenafil, a phosphodiesterase-5 inhibitor, on angiogenesis in in vitro and in vivo MMD models. Methods Angiogenesis and vessel maturation were assessed in in vitro models, caveolin- 1 (Cav-1) knockdown human umbilical vessel endothelial cells (HUVECs) and coronary artery smooth muscle cells (CASMCs), and in in vivo model of bilateral internal carotid artery occlusion (bICAo). Udenafil was administered (1,3,10, and 30 μM) in cell culture conditions, and functional studies (migration and tube formation assay) were performed and vessel maturation factors and cyclic guanosine monophosphate (cGMP) accumulation were measured. Results Udenafil (3 and 10 mg/kg) was orally administered once daily for 4 weeks in bICAo rat model, and histological analysis for angiogenesis and vessel maturation was performed. Udenafil increased vessel formation in both Cav-1 knockdown HUVEC and bICAo models without increased migration/proliferation of HUVECs and CASMCs. Udenafil increased CD31+ vessel density and NG2/Col4+ mural cell density in bICAo models. Cav-1 knockdown inhibited accumulation of cGMP, and udenafil treatment restored cGMP levels in Cav-1 knockdown HUVEC models. Vessel maturation factors (angiopoietin- 1 and platelet-derived growth factor receptor-β) and angiogenic factors (endothelial nitric oxide synthase) were increased after treatment with udenafil in vitro. Conclusion Our results indicate that udenafil reversed cellular levels of cGMP related to Cav-1 deficiency and induced angiogenesis and vessel maturation. Further studies are warranted to confirm the therapeutic effects of this strategy in MMD.

Fibromuscular dysplasia (FMD) is a noninflammatory and nonatherosclerotic disease that predominantly affects the renal and internal carotid arteries. However, the cause of this disease remains unclear. Radiological studies are important diagnostic methods, which generally involve luminal features on computed tomographic angiography, magnetic resonance angiography, and digital subtraction angiography. However, the high-resolution magnetic resonance imaging (HR-MRI) features of FMD have not yet been reported. Herein, we report the HR-MRI features of patients with FMD who showed typical involvement of the internal carotid arteries. Although both patients presented a beading appearance typical of medial fibroplasia, HR-MRI nevertheless showed distinct features. HR-MRI revealed concentric wall thickening and circular enhancement with dystrophic calcification in one and wall thickening, but no enhancement in the others. Further studies are required to determine whether these HR-MRI features are related to the type of FMD or patient prognosis.

In case of any embolic event, treatment strategy should be established according to the pathomechanisms of failure of non-vitamin K oral anticoagulants (NOAC). A 72-year-old man was referred to our hospital with a sudden speech disturbance. Diffusion-weighted imaging revealed cerebral infarction in the left middle cerebral artery territory. The patient had been diagnosed with nonvalvular atrial fibrillation 3 years ago and was administered a dose of 60 mg edoxaban/day. Anti-Xa and factor Xa activity assay confirmed the effect of this drug. A detailed transthoracic and transesophageal echocardiography revealed fibroelastoma of mitral valve, atrial septal defect, and spontaneous echo contrast in the left atrial appendage. Although the drug was effective, cardioembolism occurred and hence we decided to perform surgery. As the etiology of NOAC failure varies, anti-Xa and factor Xa activity assays help to determine the cause modifying the treatment strategy accordingly.

Diffusion-weighted image (DWI) is widely used in acute care hospitals and provides diverse, valuable information about acute stroke. DWI is the gold standard for identifying the infarct core. The DWI infarct pattern is correlated with the pathogenic mechanisms underlying stroke and may predict stroke recurrence and outcome. Therefore, a deeper understanding of DWI is necessary for physicians treating patients with acute ischemic stroke. In this review, the application and interpretation of DWI for acute stroke and future perspectives are discussed.

A silent brain infarct (SBI) is defined as imaging or neuropathological evidence of brain infarction without a history of acute neurological dysfunction attributable to the lesion. The number of patients with SBIs is estimated as several-fold higher than the number with clinical stroke. In addition, SBIs have important clinical implications. The presence of SBIs more than doubles the risk of subsequent stroke and dementia. Although most SBIs are lacunes, for which hypertensive small vessel disease is thought to be the main cause, some of them could be embolic in origin. The pathological mechanisms of SBIs and most effective strategies for prevention of future stroke may differ depending on the cause of the SBI. The literature reviewed and cases presented herein underscore the need for application of appropriate workups and therapeutic strategies in patients with SBIs. In this review, the definition, causes, and clinical impact of SBIs are discussed, together with the questions that remain open and recent advances (e.g., machine learning techniques) in the study of SBIs.

Although, both neurological examination and neuroimaging represent the main methods for the anatomical localization of lesions in stroke patients, atypical anatomical-functional representation of cortical lateralized syndromes can occur. Herein, we introduce three cases of atypical representation of left hemispheric syndromes with right hemispheric lesions and we explore the possible mechanisms underlying such disorders and their clinical implications.

Superficial siderosis is a rare disease of the central nervous system, which is characterized by chronic intrathecal hemorrhage leading to hemosiderin deposition on the leptomeninges and subpial layers of the brain and spinal cord. Patients with the syndrome typically present with sensorineural hearing loss, myelopathy, cerebellar ataxia, pyramidal signs, and cognitive impairment. The most common etiologies of the disease include bleeding of unknown cause, ruptured aneurysms, arteriovenous malformation, and traumatic injury of the brain. Here, we describe two patients diagnosed with superficial siderosis caused by spinal lesions, which is an unusual cause of chronic bleeding due to the presence of the disease.

Stroke is one of the leading causes of death and most common cause of disability in adult. Despite of recent advances in the recanalization therapy for acute ischemic stroke, the need for neuroprotectants is substantial, to extend the window for recanalization therapy and to prevent neuronal death by ischemic brain injury or by reperfusion injury after successful therapy. Herein, the possible reasons for the failure of neuroprotectants trials during the past two decades and current status of neuroprotective strategies for acute ischemic stroke are discussed. This review will also address the recent advances and future perspectives in preclinical and clinical trials of neuroprotective agents, including the efforts of high quality of transition of preclinical results to clinical trial, genetic studies to trigger neuroprotectants development, application of neuroprotectants at optimal time and duration after stroke, adjuvant approaches, and biomarker-based triage.

The targeted cancer therapies that have been introduced in recent years are directed against cancer-specific molecules and signaling pathways, and thus, they have limited nonspecific toxicities. However, major vascular events, including stroke, are common in patients receiving tyrosine kinase inhibitors (TKIs). Inhibition of vascular endothelial growth factor receptor by some TKIs probably explains such events. Moreover, venous and arterial thromboses, atherosclerosis, and bleeding have been reported. Ischemic lesions can also occur due to impaired angiogenesis or endothelial dysfunction. However, the exact mechanisms of arterial stroke in patients with cancer receiving TKIs are unknown. Here, we have report two cases of non-thrombotic ischemic cerebrovascular events related to TKIs and described the high-resolution magnetic resonance imaging findings.

Infectious diseases and stroke are common and a great health problem worldwide. However, relatively few studies have focused on direct infectious causes of acute stroke, and the exact mechanisms of acute stroke associated with infections are poorly understood. Herein, we present several infectious organisms that are probable causes of stroke. Different pathomechanisms of stroke and neuroimaging features of infection by these organisms are discussed. Specifically, the distribution of cerebral infarction suggests that infections could be a direct cause of acute stroke. These include cerebral convexity probably due to vasculitis in bacterial meningitis, deep infarcts due to endarteritis and inflammation in neurocysticercosis, and exudates in tuberculous meningitis, as well as hemodynamic borderzone infarct due to large vessel vasculitis by direct invasion of fungal infection. We suggest that prompt and appropriate control of these organisms could prevent ischemic stroke.

Churg-Strauss syndrome (CSS) is known to mainly involve small vessels; thus, in the event of large-vessel disease, other causes must be taken into consideration. We report a case of CSS with recurrent arterial dissection of the cervicocephalic arteries. A 74-year-old man with CSS visited the emergency department because of sudden left hemiparesis. He had been taking corticosteroids as CSS treatment for 12 years. He had a confirmed right vertebral dissection 10 years before and a right distal internal carotid artery dissection 1 year before. As the arterial dissection occurred in the same vessel region a year before, a stent was deployed in the region. A large cervicocephalic artery dissection in patients with CSS that is well regulated with immunotherapy is likely caused by the long-term corticosteroid therapy weakening the vessel wall; therefore, replacement with the appropriate immunotherapy should be considered.

Cardiac amyloidosis is characterized by the extracellular fibril deposition of amyloid protein in the myocardium. Cerebral embolism caused by cardiac amyloidosis is rare. We report a case of 59-year-old woman with multiple myeloma who developed cerebral infarction probably related to cardiac involvement of amyloidosis, and discuss the pathophysiological mechanisms based on kidney biopsy and characteristic echocardiographic and cardiac magnetic resonance imaging features.

Stroke is one of the leading causes of death and the most common cause of disability in adults. Remarkable advances in stroke research have been achieved during the past decades. Stroke fatalities have decreased significantly worldwide owing to improved stroke care because of increased public awareness of stroke symptoms, improved acute stroke therapy, and improved stroke prevention approaches. There are currently significant developments in new technologies with the potential to be used daily in clinical practice in patients with stroke. In this review, we have selected and discussed some of the key areas related to stroke, namely big data, artificial intelligence, precision medicine, medical devices, and stem cells.