[Internal Carotid Artery:Development and Anomalies].

This chapter outlines the cerebrovascular developmental anatomy with emphasis on the internal carotid artery(ICA), which is important for optimal endovascular treatment of cerebrovascular system disorders. Gene expression, neural crest cells, and pharyngeal arches play key roles in the embryonic development of the carotid arteries. Evolutionary inheritance in vertebrates contributes to the formation, regression, and segmental structure of these arteries. We present examples of current mutations with regard to their segmental nature; ICA mutations are discussed primarily with regard to their developmental origin from the first to third pharyngeal arches and the role of the ductus caroticus. This comprehensive review highlights the importance of understanding the developmental and anatomical nuances of the ICA to aid with accurate diagnosis and management of vascular anomalies in the clinical setting. We have focused on the complexity associated with ICA mutations, particularly those associated with the third pharyngeal arch and the need for a solid foundation of developmental and anatomical knowledge to accurately identify and interpret their significance in the adult phenotype.

Vascular Ehlers-Danlos syndrome with a Novel missense COL3A1 gene mutation present with bilateral spontaneous carotid-cavernous fistula: a case report.

This report describes a unique case of vascular Ehlers-Danlos syndrome (vEDS) characterized by multiple spontaneous direct carotid-cavernous sinus fistulas (CCF). The patient initially presented with ocular symptoms and was effectively treated with transarterial coil embolization. Five years later, the patient developed recurrent contralateral CCF that required complex endovascular techniques. Genetic testing identified a novel mutation in the COL3A1 gene, confirming the diagnosis of vEDS. This case report provides a near-term perspective on the identification of structural abnormalities in the COL3A1 protein to ensure the safety of endovascular therapy for patients with vEDS.

Clinical Significance of Early Venous Filling Detected via Preoperative Angiography in Glioblastoma.

Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between 1 April 2013 and 31 March 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of the 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angiography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, p = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.

Outcomes of Intramedullary Spinal Cord Tumor Surgery in Older Versus Younger Adults: A Multicenter Subanalysis Study by the Neurospinal Society of Japan.

OBJECTIVE: Intramedullary spinal cord tumors (IMSCTs) are uncommon and difficult to treat. Studies examining the efficacy of rare IMSCT surgery in the elderly are limited. We conducted a subanalysis using multicenter retrospective-historical data provided by the Japan Neurospinal Society to compare surgical outcomes between older and younger adults with IMSCTs. METHODS: We classified patients with IMSCTs into younger (aged 18-64 years) or older ( ≥ 65 years) groups. The primary outcomes of "improved" or "worsened" from the preoperative period to 6 months after surgery were evaluated using the modified McCormick scale (mMCs). A favorable outcome was defined as an mMCs grade of I/II at 6 months. RESULTS: Among 841 patients registered, there were 658 younger (78.2%) and 183 older patients (21.8%) evaluated using mMCs at 6 months. Median preoperative mMCs grades were significantly worse in older patients than in younger patients. Neither the "improved" nor "worsened" rate differed significantly between the groups (28.1% vs. 25.1%; crude odds ratio [cOR], 0.86; 95% confidence interval [CI], 0.59-1.25; adjusted OR [aOR], 0.84; 95% CI, 0.55-1.28; 16.9% vs. 23.0%; cOR, 1.47; 95% CI, 0.98-2.20; aOR, 1.28; 95% CI, 0.83-1.97). Favorable outcomes were significantly less common among older adults in the univariate analysis but were not significant in the multivariate analysis (66.4% vs. 53.0%; cOR, 0.57; 95% CI, 0.41-0.80; aOR, 0.77; 95% CI, 0.50-1.19). In both younger and older patients, preoperative mMCs accurately predicted favorable outcomes. CONCLUSION: Age alone is not a sufficient reason to prohibit surgery for IMSCTs.

Spinal Cord Subependymoma: A Subanalysis of the Neurospinal Society of Japan's Multicenter Study of Intramedullary Spinal Cord Tumors.

OBJECTIVE: This study aimed to analyze the clinical characteristics, treatment strategies, and surgical outcomes of subependymoma patients from the 2022 Neurospinal Society of Japan multicenter intramedullary spinal cord tumor study. METHODS: Twenty-six patients with spinal cord subependymoma who were included in the index study of 1,033 patients were retrospectively analyzed. RESULTS: Mean patient age was 49.4 years. Seventeen patients were men and 9 were women. Sensory disturbance was reported in 22 patients and motor weakness in 18. Median duration of symptoms was 24 months. The tumor was eccentrically located in 19 patients (73.1%) and unilateral in 17 (65.4%). Gross total resection was achieved in 6 patients (23.1%). The same rate for ependymoma patients in the index study was significantly higher (74.8%). Median follow-up was 40.5 months (interquartile range, 18-68 months). In 2 patients who underwent only partial resection, reoperation was required owing to progression 68 and 90 months after surgery, respectively. No recurrence occurred in patients who underwent gross total resection. Five patients experienced neurological worsening after surgery. CONCLUSION: Although spinal cord subependymoma can be difficult to distinguish from other intramedullary spinal cord lesions before surgery, it is characterized by an indolent clinical course and eccentric location. Surgical treatment should prioritize functional preservation because the prognosis is good even after subtotal resection.

Intravenous Administration of Human Amniotic Mesenchymal Stem Cells in the Subacute Phase of Cerebral Infarction in a Mouse Model Ameliorates Neurological Disturbance by Suppressing Blood Brain Barrier Disruption and Apoptosis via Immunomodulation.

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

Accuracy of Pedicle Screw Placement Comparing an Electronic Conductivity Device and a Multi-axis Angiography Unit with C-arm Fluoroscopy in Lumbar Fixation Surgery for Safety.

The aim of this study was to compare the accuracy, safety, and usefulness of percutaneous pedicle screw (PPS) placement for lumbar fixation using a multi-axis angiography unit (MAU) and an electronic conductivity device (ECD) with a cannulated Jamshidi needle with that using a conventional C-arm. Of 65 cases that underwent lumbar fixation (region between L1-S1) during April 2013 to March 2019, 57 cases that could be followed-up for more than 12 months after the procedure were included. Among them, 31 patients (150 screws) received treatment with MAU and ECD (MAU+ECD group) and 26 (117 screws) were treated with the conventional C-arm. We performed a retrospective study of the surgical techniques used in each group at our institute by assessing the accuracy of PPS using Gertzbin-Robbins classification and the Japanese Orthopedic Association (JOA) score for recovery. There was no significant difference in surgery outcome based on the JOA recovery rate. There was a significant difference between the two groups in terms of Accuracy-1 (Group A indicating accuracy and Groups B-E indicating inaccuracy), where the rates were 85.3% and 72.0% in the MAU+ECD group and C-arm group, respectively (P = 0.008). There was also a significant difference between the two groups in terms of Accuracy-2 (Groups A-B indicating accuracy; Groups C-E indicate inaccuracy), where the rates were 98.0% and 92.4% in the MAU+ECD and C-arm groups, respectively (P = 0.036). A combination of MAU and ECD is a safe and accurate method for inserting screws into the pedicle.

Differences in Acute Ischemic Stroke Management and Prognosis between Multiple Large-Vessel Occlusion and Single Large-Vessel Occlusion: Subanalysis of the RESCUE-Japan Registry 2.

INTRODUCTION: The management and prognosis of acute ischemic stroke due to multiple large-vessel occlusion (LVO) (MLVO) are not well scrutinized. We therefore aimed to elucidate the differences in patient characteristics and prognosis of MLVO and single LVO (SLVO). METHODS: The Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) enrolled 2,420 consecutive patients with acute LVO who were admitted within 24 h of onset. We compared patient prognosis between MLVO and SLVO in the favorable outcome, defined as a modified Rankin Scale (mRS) score ≤2, and in mortality at 90 days by adjusting for confounders. Additionally, we stratified MLVO patients into tandem occlusion and different territories, according to the occlusion site information and also examined their characteristics. RESULTS: Among the 2,399 patients registered, 124 (5.2%) had MLVO. Although there was no difference between the 2 groups in terms of hypertension as a risk factor, the mean arterial pressure on admission was significantly higher in MLVO (115 vs. 107 mm Hg, p = 0.004). MLVO in different territories was more likely to be cardioembolic (42.1 vs. 10.4%, p = 0.0002), while MLVO in tandem occlusion was more likely to be atherothrombotic (39.5 vs. 81.3%, p < 0.0001). Among MLVO, tandem occlusion had a significantly longer onset-to-door time than different territories (200 vs. 95 min, p = 0.02); accordingly, the tissue plasminogen activator administration was significantly less in tandem occlusion (22.4 vs. 47.9%, p = 0.003). However, interestingly, the endovascular thrombectomy (EVT) was performed significantly more in tandem occlusion (63.2 vs. 41.7%; adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1-5.0). The type of MLVO was the only and significant factor associated with EVT performance in multivariate analysis. The favorable outcomes were obtained less in MLVO than in SLVO (28.2 vs. 37.1%; aOR, 0.48; 95% CI, 0.30-0.76). The mortality rate was not significantly different between MLVO and SLVO (8.9 vs. 11.1%, p = 0.42). DISCUSSION/CONCLUSION: The prognosis of MLVO was significantly worse than that of SLVO. In different territories, we might be able to consider more aggressive EVT interventions.

Relationship Between Acute Neurological Function and Long-Term Prognosis in Patients with Large Arterial Occlusions.

OBJECTIVES: To clarify the relationship between early neurological symptoms and long-term functional outcomes of acute ischemic stroke, which would be beneficial for patient management and determining clinical study criteria of novel therapeutic interventions. MATERIALS AND METHODS: We retrieved data from the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) and investigated the association between 24- and 72-hour National Institutes of Health Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores, stratified by the site of occlusion (carotid or vertebrobasilar circulatory large arterial occlusion [ACO or PCO, respectively]) and endovascular recanalization therapy (EVT) performance. We examined the correlation using Spearman's rank correlation coefficient (rho). Predictive accuracies of 24- and 72-hour NIHSS scores for good outcomes at 90 days (defined as mRS score of 0-2) were evaluated by receiver operating characteristic (ROC) analyses and the corresponding areas under the curves (AUCs). RESULTS: Among the 2420 patients, 1745 had ACO (971 with EVT, 774 without EVT) and 263 had PCO (127 with EVT, 136 without EVT). The 24- and 72-hour NIHSS scores were significantly associated with 90-day mRS scores and accurately predicted good outcomes (all rhos ≥0.76, all AUCs ≥0.86). In the ACO group, there were differences in rho and AUC depending on EVT performance and the time from onset to NIHSS acquisition, but no differences were observed in the PCO group. CONCLUSIONS: EVT performance and time frame should be considered when determining the criteria of novel therapeutic interventions, especially for patients with ACO.

Adipose-derived stem cell therapy inhibits the deterioration of cerebral infarction by altering macrophage kinetics.

INTRODUCTION: We previously established a method to isolate and culture human adipose-derived stem cells (hADSCs) using fetal bovine serum and showed the therapeutic impact on cerebral infarction. Recently, we modified the culture method with the use of serum-free media for future clinical applications. This study aims to evaluate whether intravenous administration of hADSCs induced by the serum-free culture method would improve neurobehavioral deficits in mice with cerebral infarction. RESULTS: Induced hADSCs possessed the characteristics of mesenchymal stem cells and withstood a freeze-thaw process. hADSC administration improved neurobehavioral deficits in MCAO-treated mice and suppressed brain atrophy at the chronic phase. Although hADSC administration did not affect serum cytokine profiles, it decreased the number of CD11b+ monocytes in the spleen. Concomitantly, hADSC administration increased the local accumulation of CD11b+CD163+ M2 macrophages into the border zone of the cerebral infarction at 4 days post-MCAO (the acute phase). DISCUSSION: Our data indicate that the systemic administration of hADSCs can improve the neurobehavioral deficits that occur after cerebral infarction by modulating the acute immune response mediated by CD11b+CD163+ M2 macrophages in infarcted lesions.

Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain.

There is compelling evidence that the mature central nervous system (CNS) harbors stem cell populations outside conventional neurogenic regions. We previously demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. PCs are found throughout the CNS, including cerebellum, but it remains unclear whether cerebellar PCs also form ischemia-induced multipotent stem cells (iSCs). In this study, we demonstrate that putative iSCs can be isolated from poststroke human cerebellum (cerebellar iSCs [cl-iSCs]). These cl-iSCs exhibited multipotency and differentiated into electrophysiologically active neurons. Neurogenic potential was also confirmed in single-cell suspensions. DNA microarray analysis revealed highly similar gene expression patterns between PCs and cl-iSCs, suggesting PC origin. Global gene expression comparison with cerebral iSCs revealed general similarity, but cl-iSCs differentially expressed certain cerebellum-specific genes. Thus, putative iSCs are present in poststroke cerebellum and possess region-specific traits, suggesting potential capacity to regenerate functional cerebellar neurons following ischemic stroke.

Intravenous administration of human adipose-derived stem cells ameliorates motor and cognitive function for intracerebral hemorrhage mouse model.

Even today, intracerebral hemorrhage (ICH) is a major cause of death and disabilities. Rehabilitation is preferentially applied for functional recovery although its effect is limited. Recent studies have suggested that intravenous administration of mesenchymal stem cells would improve the post-ICH neurological deficits. Human adipose-derived stem cells (hADSCs) have been established in our laboratory. We aimed to evaluate the therapeutic efficacy of the hADSCs on the post-ICH neurological deficits using a clinical-relevant ICH mouse model. We also evaluated immune responses to clarify the underlying mechanisms. The hADSCs expressed MSC markers at high levels. The hADSCs administration into the ICH-bearing mice improved the neurological deficits during the subacute phases, which was shown by neurobehavioral experiments. Besides, the hADSC administration decreased the number of CD11+CD45+ cells and increased the proportion of CD86+ and Ly6C+ cells in the ICH lesions. In summary, intravenous administration of hADSCs during the acute phase improved ICH-induced neurological deficits during the subacute phase because of the suppression of acute inflammation mediated by CD11+CD45+ subpopulations. Our data suggest that hADSCs can be served as a novel strategy for ICH treatment.

Angiographic and Clinical Characteristics of Thoracolumbar Spinal Epidural and Dural Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: The purpose of this study is to compare the angiographic and clinical characteristics of spinal epidural arteriovenous fistulas (SEAVFs) and spinal dural arteriovenous fistulas (SDAVFs) of the thoracolumbar spine. METHODS: A total of 168 cases diagnosed as spinal dural or extradural arteriovenous fistulas of the thoracolumbar spine were collected from 31 centers. Angiography and clinical findings, including symptoms, sex, and history of spinal surgery/trauma, were retrospectively reviewed. Angiographic images were evaluated, with a special interest in spinal levels, feeders, shunt points, a shunted epidural pouch and its location, and drainage pattern, by 6 readers to reach a consensus. RESULTS: The consensus diagnoses by the 6 readers were SDAVFs in 108 cases, SEAVFs in 59 cases, and paravertebral arteriovenous fistulas in 1 case. Twenty-nine of 59 cases (49%) of SEAVFs were incorrectly diagnosed as SDAVFs at the individual centers. The thoracic spine was involved in SDAVFs (87%) more often than SEAVFs (17%). Both types of arteriovenous fistulas were predominant in men (82% and 73%) and frequently showed progressive myelopathy (97% and 92%). A history of spinal injury/surgery was more frequently found in SEAVFs (36%) than in SDAVFs (12%; P=0.001). The shunt points of SDAVFs were medial to the medial interpedicle line in 77%, suggesting that SDAVFs commonly shunt to the bridging vein. All SEAVFs formed an epidural shunted pouch, which was frequently located in the ventral epidural space (88%) and drained into the perimedullary vein (75%), the paravertebral veins (10%), or both (15%). CONCLUSIONS: SDAVFs and SEAVFs showed similar symptoms and male predominance. SDAVFs frequently involve the thoracic spine and shunt into the bridging vein. SEAVFs frequently involve the lumbar spine and form a shunted pouch in the ventral epidural space draining into the perimedullary vein.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.