Hemodynamic stress and chronic inflammation are closely associated with the pathogenesis of intracranial aneurysms (IAs). However, the hemodynamic and biological mechanisms triggering IA formation remain to be elucidated. To clarify them, computational fluid dynamics (CFD) and histopathological analyses in the early phase of IA development using an experimentally induced IA model in rats were conducted. Histological changes in the early phase of IA development were observed under a scanning electron microscope (SEM) and a transmission electron microscope (TEM). Using data from 7-T magnetic resonance angiography (7T-MRA), CFD analyses were performed to determine wall shear stress (WSS) and wall pressure (WP) at the prospective site of IA. A bump-like protrusion named an “intimal pad” was located in the anterior cerebral artery (ACA) immediately distal to the apex of the bifurcation. TEM showed the degeneration of the internal elastic lamina (IEL) and longitudinally elongated smooth muscle cells (SMCs) that switched from the contractile to the proliferative phenotype and penetrated between two divided layers of the degenerated IEL in the prospective site of the IA. However, no inflammatory cells were observed. CFD analyses showed no particular pattern of WSS and WP at the prospective IA site. IEL degeneration and the phenotypic change and longitudinal elongation of SMCs were identified as the early events in IA development. CFD analyses and TEM data suggest that these biological events may be derived from increased circumferential wall stress due to increased blood pressure and increased longitudinal wall strain due to the existence of the intimal pad.
Genome engineering using programmable nucleases such as transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeat-associated protein nine facilitated the introduction of genetic alterations at specific genomic sites in various cell types. These tools have been applied to cancer modeling to understand the pathogenic effects of the growing catalog of mutations found in human cancers. Pertaining to brain tumors, neural progenitor cells derived from human induced pluripotent stem cells (iPSCs) engineered with different combinations of genetic driver mutations observed in distinct molecular subtypes of glioblastomas, the most common form of primary brain cancer in adults, give rise to brain tumors when engrafted orthotopically in mice. These glioblastoma models recapitulate the transcriptomic signature of each molecular subtype and authentically resemble pathobiology of glioblastoma, including inter- and intra-tumor heterogeneity, chromosomal aberrations, and extrachromosomal DNA amplifications. Similar engineering with genetic mutations found in medulloblastoma and atypical teratoid rhabdoid tumors in iPSCs have led to genetically trackable models that bear clinical relevance to these pediatric brain tumors. These models have contributed to improved comprehension of the genetic causation of tumorigenesis and offered a novel platform for therapeutic discovery. Studied in the context of three-dimensional cerebral organoids, these models have aided in the study of tumor invasion as well as therapeutic responses. In summary, modeling brain tumors through genome engineering enables not only the establishment of authentic tumor avatars driven by bona fide genetic mutations observed in patient samples but also facilitates functional investigations of particular genetic alterations in an otherwise isogenic background.
Cranial implants are commonly used throughout the world, yet the data on complications remain partly clarified. The aim of this study was to gather real data in 2018 on complications related to cranial implants in neurosurgery. The survey population consisted of 1103 institutes supplying neurosurgical treatment. The survey consisted of two-stage questionnaire. First the incidence of complications was investigated, then the secondary questionnaire was e-mailed to the respondents about the detailed of the complications. As the result, the annual incidence of complications related to cranial implants was 0.558% in Japan. Titanium plate and mesh were used predominantly in craniotomy and cranioplasty, respectively. The second survey collected data on 449 cases with complications (infection: 63%, implant exposure: 46%, multiple answer). Postoperative infection was associated with male sex, brain tumor, short interval between surgery and complication, usage of ceramics, hydroxyapatite, resin, and artificial dura, hyponutrition, multiple surgeries, dirty wound, and sinusitis as patient factors, and CSF leakage, ruptured sutures, and sinus maltreatment as surgery factors. Meanwhile, long hospital stay was associated with age, male sex, mRS 3–5 before complication, short interval between initial surgery and complication, large craniotomy, long operative time, usage of ceramics and artificial dura, multiple surgeries and dirty wound as patient factors, ruptured suture as a surgical factor, and bacterial infection, especially MRSA infection, as the complication and treatment consisting of removal as complication factors. In conclusion, this is the first Japanese national survey on complications related to cranial implants in neurosurgery. It is important to recall that complications may arise years after surgery and to be aware of the risk factors associated with complications.
An isolated fourth ventricle (IFV) is characterized by fourth ventricular dilation due to obstruction of its inlet and outlet. A disproportionately large communicating fourth ventricle (DLCFV) is a rare subtype of IFV, characterized by dilation of the fourth ventricle, regardless of the size of the lateral ventricles, with no apparent obstruction of the cerebral aqueduct. To our knowledge, this is the first case series describing endoscopic diagnosis and treatment strategy for DLCFV. We retrospectively reviewed six cases of DLCFV in which endoscopic surgery was performed at our institution and affiliated facilities between June 2013 and March 2017. DLCFV was diagnosed using radiographic imaging and intraoperative endoscopy. We also conducted a PubMed search and included only original studies related to DLCFV treatment written in English in our review of the literature. Endoscopic third ventriculostomy (ETV) was performed in all patients. Additional endoscope-assisted placement of a fourth ventriculoperitoneal (VP) shunt was performed in two patients who could not be managed with ETV alone because of severe adhesion of the interpeduncular cistern due to subarachnoid hemorrhage (SAH). The patients’ symptoms and the size of the fourth ventricle improved with surgical treatment, without complications. Endoscopic surgery for DLCFV appears to be a safe and effective treatment. Based on our treatment strategy, ETV is the first-line treatment for DLCFV. Endoscope-assisted placement of the fourth VP shunt can be treatment for severe adhesion of the interpeduncular cistern.
Some of the pediatric moyamoya patients spend their childhood without diagnosed as moyamoya disease (MMD) because of their mild ischemic attacks and emerge again with ischemic or hemorrhagic stroke in their adulthood. This study was aimed to clarify the clinical characteristics of adult moyamoya patients with childhood onset and elucidate the impact of long disease period on their clinical features. Present study included 116 untreated hemispheres of 69 adult patients with MMD. They were divided into two groups: childhood onset group (26 hemispheres of 14 patients) and adult onset group (90 hemispheres of 55 patients). Clinical features were compared between the two groups. The incidence of hemorrhagic stroke was significantly higher in childhood onset group (P = 0.0091). Lenticulostriate and choroidal channels were more developed in childhood onset group (P = 0.044 and P <0.001, respectively). Vault moyamoya was more frequently observed in childhood onset group (P <0.001). The development of surgical collaterals through indirect bypass was more marked in childhood onset group (P = 0.0019). Multivariate analysis revealed that childhood onset and developed choroidal channels were significantly associated with the occurrence of hemorrhagic stroke (OR 4.31 [95% CI 1.21–15.4], P = 0.025 and OR 6.78 [95% CI 1.78–25.8], P = 0.0050, respectively). This study clearly shows that adult moyamoya patients with childhood onset have more developed spontaneous collaterals, which may, in turn, highly causes hemorrhagic stroke. Adult moyamoya patients with “childhood onset” should be recognized as a novel and important concept when elucidating the underlying mechanisms of hemorrhagic stroke in MMD.
Lumbar disc herniation (LDH) elicits low back pain (LBP) and lower-limb symptoms. Paralumbar spine disease (PLSD), for example, superior cluneal nerve/middle cluneal nerve entrapment (SCN-EN, MCN-EN) and sacroiliac joint pain (SIJ), may be attributable to LDH whose treatment may not ameliorate their symptoms. We treated LDH patients and addressed their coexisting PLSDs. We retrospectively analyzed the effects of targeted block therapy for PLSD in 47 patients with LDH. They were 23 men and 24 women ranging in age from 21 to 79 years. They were seen between August 2014 and October 2018, within 3 weeks of LDH onset. PLSD was diagnosed based on the symptoms of patients whose pain was not controlled by oral medications. The treatment outcome was assessed by comparing the numerical rating scale (NRS) and the Roland-Morris Disability Questionnaire (RDQ) score recorded before and 2 weeks after last block treatment. Of the 47 patients with LDH, 2 suffered no LBP and 30 reported tenderness in the low back. We performed block therapy in 13 patients; 9 (19.1%) had concurrent PLSD and experienced pain relief. Their NRS improved from 8.1 ± 1.8 before- to 1.3 ± 0.9 after treatment; their RDQ score fell from 11.2 ± 6.0 to 0.9 ± 1.2 (both, p < 0.01). In an LDH patient with MCN-EN alone, MCN neurolysis was performed 2 weeks after a single MCN block proved to be only transiently effective. Paralumbar diseases may coexist in patients with LDH; treatment of the former may alleviate their LBP.