Potential of GSPT1 as a novel target for glioblastoma therapy.

Glioblastoma is the most common malignant brain tumor in adults, the survival rate of which has not significantly improved over the past three decades. Therefore, there is an urgent need to develop novel treatment modalities. We previously reported that G1 to S phase transition 1 (GSPT1) depletion induces delayed cell cycle in primary astrocytes. Herein, we examined the potential of GSPT1 as a novel target for glioblastoma therapy. CC-885, a cereblon modulator that degrades GSPT1 by bridging GSPT1 to the CRL4 E3 ubiquitin ligase complex, was administered to nude mice with transplanted brain tumors of U87 glioblastoma cells. The survival period was significantly longer in CC-885 treated mice than in control mice. Furthermore, we generated GSPT1-knockout (KO) U87 cells and GSPT1-KO U87 cells with stable overexpression of FLAG-tagged GSPT1 (Rescued GSPT1-KO). Mice with transplanted GSPT1-KO U87 cells and Rescued GSPT1-KO U87 cells showed significantly longer and similar survival periods, respectively, as those with wild-type (WT) U87 cells. GSPT1-KO U87 cells showed enhanced apoptosis, detected by cleaved PARP1, compared to WT U87 cells. Brain tumors with transplantation of GSPT1-KO U87 cells also showed enhanced apoptosis compared to those with transplantation of WT and Rescued GSPT1-KO U87 cells. GSPT1 expression was confirmed in patients with glioblastoma. However, the clinical study using 87 glioblastoma samples showed that GSPT1 mRNA levels were not associated with overall survival. Taken together, we propose that GSPT1 is an essential protein for glioblastoma growth, but not its malignant characteristics, and that GSPT1 is a potential target for developing glioblastoma therapeutics.

Predicting impaired cerebrovascular reactivity and risk of hyperperfusion syndrome in carotid artery stenosis using BeamSAT magnetic resonance imaging.

Pencil-beam presaturation (BeamSAT) magnetic resonance imaging (MRI) produces selective magnetic resonance angiography (MRA) images of specific arteries, including the unilateral internal carotid artery (ICA-selective MRA) or vertebral artery (VA-selective MRA). We evaluate the influence of flow pattern, visualized using BeamSAT MRI, on preoperative cerebral hemodynamic status and postoperative hyperperfusion syndrome (HPS). Patients undergoing carotid artery stenting or carotid endarterectomy were categorized into two groups to evaluate flow pattern. Patients with neither crossflow on BeamSAT MRI nor mismatch in middle cerebral artery (MCA) signal intensity between ICA-selective and conventional MRA were classified into Group I, comprising 29 patients. Group II included all other patients comprising 19 patients, who were suspected of experiencing changes in intracranial flow patterns. Cerebral blood flow and cerebrovascular reactivity (CVR) were assessed using single-photon emission computed tomography, and potential HPS symptoms were retrospectively assessed by chart review. Preoperative ipsilateral CVR was significantly lower in Group II than in Group I (18.0% ± 20.0% vs. 48.3% ± 19.5%; P < 0.0001). Group II showed significantly impaired CVR (odds ratio 17.7, 95% confidence interval 1.82-171; P = 0.013) in multivariate analysis. The partial areas under the curve of the BeamSAT logistic model (0.843) were significantly larger than those of the conventional logistic model (0.626) over the range of high sensitivity (0.6-1) (P = 0.04). The incidence of postoperative HPS symptoms was significantly higher in Group II than in Group I (8/19 vs. 1/29; P = 0.001). BeamSAT MRI may be a valuable and non-invasive tool for assessing cerebral hemodynamics and predicting postoperative HPS.

Multiple Synchronous Spinal Dural Arteriovenous Fistulas: A Systematic Literature Review.

BACKGROUND AND OBJECTIVES: Spinal dural arteriovenous fistulas (SDAVFs) lead to progressive neurological decline with symptoms such as paraparesis, bowel and bladder dysfunction, and sensory disturbances because of impaired spinal cord venous drainage. This study aimed to systematically review the literature on multiple synchronous SDAVFs and present 2 cases from our institution. METHODS: A comprehensive search was performed to identify all published cases of multiple synchronous SDAVFs. Overall, 23 patients with multiple synchronous SDAVFs were identified, including 21 from 19 articles and 2 from this study. The clinical presentation, lesion location, radiographic features, surgical treatment, and outcomes were analyzed in each patient. RESULTS: All patients in this study were male, and the duration from symptom onset to diagnosis in many of these patients was longer than that previously reported. Previous studies suggested that multiple SDAVFs typically occurred within 3 or fewer vertebral levels. However, >50% of the examined patients had remote lesions separated by more than 3 vertebral levels. Patients with remote lesions had a significantly worse outcome (1/7 vs 8/11, 95% CI 0.001-0.998; P = .049). CONCLUSION: Accurately locating fistulas before spinal angiography is critical for managing multiple remote SDAVFs. Considering the possibility of multiple remote SDAVFs, careful interpretation of imaging findings is essential for an accurate diagnosis and appropriate treatment planning.

Efficacy of a High-definition Three-dimensional Exoscope in Simultaneous Transcranial and Endoscopic Endonasal Surgery: A Case Report.

Owing to recent advances in medical optical technology, a high-definition (4K) three-dimensional (3D) exoscope has been developed as an alternative tool to using conventional microscopes for microscopic surgery, and its efficacy for neurosurgery has been reported. We report a case who underwent simultaneous surgery aiming for en bloc resection of an anterior skull base malignancy with concurrent exoscopic transcranial and endoscopic endonasal approaches using a 4K 3D exoscope. The patient was a 76-year-old woman who underwent en bloc resection for an anterior skull base olfactory neuroblastoma 13 years ago. After confirming the recurrence of progressive olfactory neuroblastoma, tumor resection was again decided to be performed. As with the first procedure, surgery was performed in an en bloc manner, using both transcranial and endonasal approaches. Exoscope provided enough space above the surgical field to allow us to perform transcranial and endonasal surgeries simultaneously. Moreover, the surgeons could maintain a comfortable posture throughout the procedure, and total tumor removal was successfully achieved without any abnormal event. To our knowledge, this is the first report of the introduction of an exoscope aiming for en bloc resection of an anterior skull base malignancy while performing simultaneous surgery with both transcranial and endonasal approaches. We believe that the more cases are accumulated, the more efficacy of a 4K 3D exoscope will be elucidated.

Fibrous granulation mimicking cranial intraosseous tumor.

A cranial intraosseous lesion is a rare disease with a limited number of subtypes. We report a case of a cranial intraosseous fibrous granulation that mimicked an intraosseous tumor. A 57-year-old man was incidentally found to have a cranial intraosseous lesion on brain computed tomography. Total resection was performed to establish a pathological diagnosis and to achieve cosmesis, and the pathological diagnosis was fibrosis and fibrous granulation in the medullary cavity. Fibrous granulation tissue occurs in the calvarium due to bone defects secondary to acquired factors, including trauma. Since its pathological diagnosis is established through surgery, surgery should be carefully considered based on the patient's chief complaint, location of the lesion, and suspicion of malignancy based on imaging findings.

Acute Occlusion of the Ventriculoperitoneal Shunt Due to Factor XIII Deficiency-related Postoperative Hemorrhage: A Case Report.

Coagulation factor XIII (F13) deficiency has been known to be a rare disease with estimated one per two million and one of the possible reasons of postoperative hemorrhage; however, it still remains unpenetrated to physicians. We report a case of acute ventriculoperitoneal (VP) shunt dysfunction due to delayed intraventricular hemorrhage, which could be because of F13 deficiency. The patient was a 48-year-old man with a history of post-meningitis hydrocephalus followed by VP shunt placement. He was found unconscious and transferred to our hospital. A brain CT scan demonstrated shunt malfunction, and he underwent emergency shunt revision. The postoperative course was uneventful except for unexpected neck bruises and continuous minor bleeding from the surgical wound. Three days after surgery, he suddenly became comatose and a CT scan revealed the recurrence of hydrocephalus with newly identified small volume of intraventricular hemorrhage. Emergency shunt revision was performed again. The shunt valve was filled with a hematoma and bloody cerebrospinal fluid was drained from the ventricle. Postoperative blood sample examination demonstrated no abnormal findings but a decreased level of F13 activity, which was thought to be a possible cause of postoperative hemorrhage and the shunt valve hematoma. F13 deficiency causes delayed intracranial hemorrhage 24-48 h after neurological surgery. It can only be diagnosed by checking F13 activity with suspicion. If diagnosed accurately beforehand, unexpected postoperative bleeding can be preventable with proper treatment, such as F13 concentrate and cryoprecipitate. The actual number of the patient with F13 deficiency may be more than estimated ever.

[Posterior Approach for Cervical Spondylotic Myelopathy in Patients Older than 80 Years of Age].

OBJECTIVE: We aimed to investigate the characteristics and operative results of elderly patients with cervical spondylotic myelopathy(aged ≧80 years)treated using the posterior approach. METHODS: Between April 2010 and December 2018, 21 patients aged ≧80 years(older group:8 men and 13 women;age range, 80-90 years)who underwent laminoplasty were reviewed and compared with 23 patients aged <80 years(younger group;13 men and 10 women;age range, 42-79 years)who underwent laminoplasty. The following data were obtained from chart reviews:age;sex;cervical canal stenosis level;time to operation;symptoms(e.g., gait disturbance);comorbidities(hypertension, diabetes mellitus, cancer, heart disease, ischemic cerebrovascular disease, and lumbar canal stenosis);antithrombotic drug use;cardiac, pulmonary, and renal functions;operative time;volume of blood loss during the operation;postoperative delirium;and follow-up period. Neurological deficits before and after the surgery were assessed using the neurosurgical cervical spine scale(NCSS). Data were statistically analyzed, and p-values <0.05 were considered statistically significant. RESULTS: The operative time, symptoms(hypertension), renal function, and preoperative NCSS score were significantly different between the older and younger groups. Meanwhile, most variables showed no significant differences between the groups. Although the preoperative NCSS score was lower in the older group, there was no significant difference in the degree of improvement in the NCSS score after surgery. CONCLUSIONS: The findings of this study suggest that we should not hesitate to perform surgery for cervical spondylotic myelopathy in elderly patients with favorable cardiorespiratory function.

Delayed Rebleeding from Pseudoaneurysm After Mechanical Thrombectomy Using Stent Retriever Due to Small Artery Avulsion Confirmed by Open Surgery.

BACKGROUND: Pseudoaneurysm after mechanical thrombectomy (MT) is rare but is one of the potential complications associated with endovascular procedures. There is limited information regarding its mechanism of formation and the potential risk of delayed bleeding. CASE DESCRIPTION: An 84-year-old woman was admitted to our institution with right hemiplegia and global aphasia. Magnetic resonance imaging and angiography revealed occlusion of the M2 segment of the left middle cerebral artery with subtle acute ischemic change in this territory. After initiating intravenous thrombolysis, MT was performed for persistent occlusion of the M2. Successful revascularization was finally achieved with a single pass of a Trevo XP 3 mm × 20 mm stent retriever; significant deviation of the vessel occurred during withdrawal of the stent retriever. Anticoagulation was initiated after confirming resolution of a small amount of postprocedural subarachnoid hemorrhage 1 day after the procedure. However, 4 days after the procedure, computed tomography and angiography revealed a massive sylvian hematoma with de novo formation of a small pseudoaneurysm at the site where the stent retriever was deployed. Open surgery revealed a small artery avulsion at this site. The lesion was closed by microsurgical suturing. CONCLUSIONS: Angiographic and intraoperative findings showed that the mechanism of formation of the pseudoaneurysm was small artery avulsion resulting from deviation of the vessel during withdrawal of the stent retriever. When performing MT in a tortuous distal vessel, the possibility of small artery avulsion should be kept in mind to both prevent and manage critical hemorrhagic complications.

[Locked-in Syndrome due to Primary Brainstem Injury:A Case Report].

Most cases of the primary brainstem injuries(PBSI)are fatal, and disturbance of consciousness is often prolonged even if lifesaving is obtained. The mechanisms of PBSI are as follows: diffuse axonal injury from acceleration/deceleration, shear strain at the midbrain, direct injury of neurovascular structures by tentorial margin, and lower brainstem injury by hyperextension of the cervical vertebrae. Though we can use both CT and MRI to diagnose, MRI is more helpful than CT in detecting, localizing, and characterizing PBSI. When the location of PBSI is limited in the ventral side of pons, it may occasionally result in locked in syndrome(LIS). Generally it is difficult to diagnose LIS with severe trauma due to the rarity of this syndrome caused by head injury. Here, we report a case of an elderly man with traumatic brainstem hemorrhage, who transiently presented LIS and finally improved.

Strategy for patients with co-existence of meningioma and intracerebral aneurysm, especially unruptured aneurysm (-seven cases and review of the literature-).

BACKGROUND: Intracerebral aneurysms co-existing with meningiomas are rare. Treatment strategies for intracerebral aneurysms co-existing with meningiomas have not yet been established. METHODS: We studied 62 patients with intracerebral aneurysms co-existing with meningiomas in the literature including our seven cases, evaluated the various managements and outcomes, and discussed the strategy for intracerebral aneurysms, especially unruptured cases, co-existing with meningiomas. The aim of this study was to develop a guide for the management of non-subarachnoid hemorrhage (SAH) intracerebral aneurysms co-existing with meningiomas. RESULTS: Most intracerebral aneurysms co-existing with meningiomas are unruptured. Of course, aneurysms presenting with SAH should be treated first followed by the resection of meningiomas. In addition, intracerebral aneurysms inside or adjacent to meningiomas have a high risk of intraoperative rupture during the surgery for meningiomas, and it may be necessary to treat them first followed by the resection of meningiomas with one or two-step surgery. In nine out of 62 patients, ten intracerebral unruptured aneurysms were not treated; however, no intracerebral aneurysms ruptured during the follow-up period, and outcomes of these patients were good in eight and poor in only one. CONCLUSIONS: Intracerebral unruptured aneurysms remote from meningiomas may be treated according to the guidelines for unruptured aneurysms. In advance of microsurgery and endovascular techniques, both lesions should be treated, if possible.