Kampei SHIMIZU, Mika KUSHAMAE, Tohru MIZUTANI, Tomohiro AOKI
Subarachnoid hemorrhage (SAH) is mainly attributable to the rupture of intracranial aneurysms (IAs). Although the outcome of SAH is considerably poor in spite of the recent intensive medical care, mechanisms regulating the progression of IAs or triggering rupture remain to be clarified, making the development of effective preemptive medicine to prevent SAH difficult. However, a series of recent studies have been expanding our understanding of the pathogenesis of IAs. These studies have suggested the crucial role of macrophage-mediated chronic inflammation in the pathogenesis of IAs. In histopathological analyses of IA lesions in humans and induced in animal models, the number of macrophages infiltrating in lesions is positively correlated with enlargement or rupture of IAs. In animal models, a genetic deletion or an inhibition of monocyte chemotactic protein-1, a major chemoattractant for macrophages, or a pharmacological depletion of macrophages consistently suppresses the development and progression of IAs. Furthermore, a macrophage-specific deletion of Ptger2 (gene for prostaglandin E receptor subtype 2) or a macrophage-specific expression of a mutated form of IκBα which inhibits nuclear translocation of nuclear factor κB significantly suppress the development of IAs, supporting the role of macrophages and the inflammatory signaling functioning there in the pathogenesis of IAs. The development of drug therapies suppressing macrophage-mediated inflammatory responses in situ can thus be a potential strategy in the pre-emptive medicine targeting SAH. In this manuscript, we summarize the experimental evidences about the pathogenesis of IAs focused on inflammatory responses and propose the definition of IAs as a macrophage-mediated inflammatory disease.
The “cerebrospinal fluid (CSF) circulation theory” of CSF flowing unidirectionally and circulating through the ventricles and subarachnoid space in a downward or upward fashion has been widely recognized. In this review, observations of CSF motion using different magnetic resonance imaging (MRI) techniques are described, findings that are shared among these techniques are extracted, and CSF motion, as we currently understand it based on the results from the quantitative analysis of CSF motion, is discussed, along with a discussion of slower water molecule motion in the perivascular, paravascular, and brain parenchyma. Today, a shared consensus regarding CSF motion is being formed, as follows: CSF motion is not a circulatory flow, but a combination of various directions of flow in the ventricles and subarachnoid space, and the acceleration of CSF motion differs depending on the CSF space. It is now necessary to revise the currently held concept that CSF flows unidirectionally. Currently, water molecule motion in the order of centimeters per second can be detected with various MRI techniques. Thus, we need new MRI techniques with high-velocity sensitivity, such as in the order of 10 μm/s, to determine water molecule movement in the vessel wall, paravascular space, and brain parenchyma. In this paper, the authors review the previous and current concepts of CSF motion in the central nervous system using various MRI techniques.
Dramatic breakthroughs in the treatment and assessment of neurological diseases are lacking. We believe that conventional methods have several limitations. Computerized technologies, including virtual reality, augmented reality, and robot assistant systems, are advancing at a rapid pace. In this study, we used Parkinson’s disease (PD) as an example to elucidate how the latest computerized technologies can improve the diagnosis and treatment of neurological diseases. Dopaminergic medication and deep brain stimulation remain the most effective interventions for treating PD. Subjective scales, such as the Unified Parkinson’s Disease Rating Scale and the Hoehn and Yahr stage, are still the most widely used assessments. Wearable sensors, virtual reality, augmented reality, and robot assistant systems are increasingly being used for evaluation of patients with PD. The use of such computerized technologies can result in safe, objective, real-time behavioral assessments. Our experiences and understanding of PD have led us to believe that such technologies can provide real-time assessment, which will revolutionize the traditional assessment and treatment of PD. New technologies are desired that can revolutionize PD treatment and facilitate real-time adjustment of treatment based on motor fluctuations, such as telediagnosis systems and “smart treatment systems.” The use of these technologies will substantially improve both the assessment and the treatment of neurological diseases before next-generation treatments, such as stem cell and genetic therapy, and next-generation assessments, can be clinically practiced, although the current level of artificial intelligence cannot replace the role of clinicians.
This study, following Japanese Registry of NeuroEndovascular Treatment 1 and 2 (JR-NET 1 & 2), shows an annual trend of cases including adverse events and clinical outcomes at 30 days after NET. JR-NET3 was registered by 749 cumulative total number of physicians, certified by the Japanese Society of Neuroendovascular Therapy in 166 centers, between 2010 and 2014. Medical information about the patients was anonymized and retrospectively registered through a website. A total of 40,177 patients were recruited, 632 patients were excluded because data of preprocedural status were not available. So we analyzed 39,545 patients retrospectively. The proportion of octogenarians is increasing year-by-year and 14.7% in 2014 compared with 10.4% in 2010. Most frequent target disease is intracranial aneurysm. For the proportion of the treatment of intracranial aneurysm, 50.0% in 2010, but that has decreased to 44.8% in 2014. However, number of procedures were increased from 3150 in 2010 to 3419 in 2014. Although before the positive clinical evidence of mechanical thrombectomy for acute ischemic stroke (AIS) was established, the proportion of endovascular treatment for AIS increased 13.8% in 2014 compared with 6.3% in 2010. The number of patients requiring neuroendovascular treatment in Japan is increasing since 2010–2013, but that declined a little in 2014 caused by study operation suspended at the end of 2013. The outcomes of such therapy are clinically acceptable. Details of each type of treatment will be investigated in sub-analyses of the database.
The marked heterogeneity in glioblastoma (GBM) may be induced through dynamic differentiation and dedifferentiation process of glioma cells. The hypothesis that environmental stimuli induce these phenotypic changes, including dedifferentiation into the stem cell phenotype which contributes to the high invasiveness and resultant poor outcome in GBM patients, is recently being proven. In the process of cancer invasion and metastasis, the phenotypic change has also been described as epithelial-mesenchymal transition (EMT). This biological process is mainly dependent on hypoxic stimuli and also on transforming growth factor-β (TGF-β) released from glioma stem cells, mesenchymal stem cells, and myeloid cells recruited by hypoxia. The tumor microenvironment, especially hypoxia, inducing such dynamic phenotypic changes can be a good therapeutic target in the treatment of GBM.
Indocyanine green (ICG) emits fluorescence in the far-red domain under light excitation. ICG video angiography (ICG-VA) has been established as a useful method to evaluate blood flow in the operative field. We report the usefulness of ICG-VA for Sylvian fissure dissection in patients with subarachnoid hemorrhage (SAH). Subjects comprised 7 patients who underwent ICG-VA before opening the Sylvian fissure during neck clipping for ruptured cerebral aneurysm. We observed contrasted Sylvian veins before opening the Sylvian fissure using surgical microscopes. This procedure was termed “Sylvian ICG”. We observed ICG fluorescence quickly in all cases. Sylvian veins that appeared unclear in the standard microscopic operative field covered with subarachnoid hemorrhage were extremely clearly depicted. These Sylvian ICG findings were helpful in identifying entry points and the dissecting course of the Sylvian fissure. At the time of clipping, no residual fluorescence from Sylvian ICG was present, and aneurysm clipping was not impeded. Sylvian ICG for SAH patients is a novel technique to facilitate dissection of the Sylvian fissure. We believe that this technique will contribute to improved safety of clipping surgery for ruptured aneurysms.
The advent of magnetic resonance imaging (MRI) enables noninvasive measurement of cerebrospinal fluid (CSF) motion, and new information about CSF motion has now been acquired. The driving force of the CSF has long been thought to be choroid plexus (CP) pulsation, but to investigate whether this phenomenon actually occurs, CSF motion was observed in the ventricular system and subarachnoid space using MRI. Eleven healthy volunteers, ranging in age from 23 to 58 years, participated in this study. The MRI sequences used were four-dimensional phase-contrast (4D-PC) and time-spatial labeling inversion pulse (t-SLIP). The 4D-PC images included sagittal images in the cranial midline, coronal images focusing on the foramen of Monro (FOM), and oblique coronal images of the trigone to quantify CSF velocity and acceleration. These values were compared and analyzed as non-parametric data using the Kolmogorov-Smirnov test and the Mann-Whitney U test. 4D-PC showed that the median CSF velocity was significantly lower in the posterior part of the lateral ventricle than in other regions. The quantitative analysis of velocity and acceleration showed that they were decreased around the CP in the trigone. Image analysis of both velocity mapping and t-SLIP showed suppressed CSF motion around the CP in the trigone. These findings cast doubt on CP pulsation being the driving force for CSF motion.