Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.

BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

Assessment of head-mounted display for exoscopic neurosurgery.

Background: Head-mounted display (HMD) arises as an alternative display system for surgery. This study aimed to assess the utility of a stereoscopic HMD for exoscopic neurosurgery. Methods: The leading operator and assistants were asked to assess the various aspects of the HMD characteristics compared to the monitor display using a visual analog scale (VAS)-based questionnaire. The VAS score ranged from 0 to 10 (0, HMD was significantly inferior to the monitor; 5, HMD and monitor display were equal; and 10, HMD was significantly superior to the monitor). Results: The surgeons and assistants used and evaluated HMD in seven exoscopic surgeries: three tumor removal, one aneurysm clipping, one anterior cervical discectomy and fusion, and two cervical laminectomy surgeries. The leading operators' assessment of HMD-based surgery was not different from monitor-based surgery; however, the assistants evaluated the field of view, overall image quality, and the assisting procedure as better in MHD-based surgery than monitor-based surgery (P = 0.039, 0.045, and 0.013, respectively). Conclusion: HMD-based exoscopic neurosurgery can be performed at a similar quality as monitor-based surgery. Surgical assistants may benefit from using HMD-based surgery.

Intraventricular pituicytoma: illustrative case.

BACKGROUND: Pituicytoma is a rare glial neoplasm from pituicytes of the neurohypophysis or infundibulum. It occurs in the sella and suprasellar area, and it is extremely uncommon to observe intraventricular pituicytoma without affecting the infundibulum or infundibular recess. OBSERVATIONS: A 69-year-old man had suffered progressive dementia for 6 months. Magnetic resonance imaging revealed a solid, homogeneously enhancing mass with flow voids within the anterior third ventricle. The sella, suprasellar area, infundibulum, and infundibular recess were unaffected. The patient underwent a transcallosal transchoroidal approach, which ended in partial removal of the tumor due to significant tumoral bleeding. A second surgery resulted in its subtotal removal. The tumor had bipolar cells, and their nuclei were immunoreactive for thyroid transcription factor-1. A DNA methylation analysis corresponded to the methylation class of pituicytoma, granular cell tumor, and spindle cell oncocytoma. Pituicytoma was the diagnosis based on these results. A systematic review identified 5 intraventricular pituicytoma cases. LESSONS: Intraventricular pituicytoma can grow without involvement of the infundibulum or infundibular recess. The current case suggests that pituicytes of the hypothalamic tuber cinereum can also give rise to pituicytoma. Because of the hypervascular nature of intraventricular pituicytomas, it is imperative to control intraoperative bleeding with attention to the adjacent hypothalamus. https://thejns.org/doi/10.3171/CASE24247.

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Postoperative vasospasm and cerebral infarction in a patient with large pituitary adenoma and cerebral superficial siderosis.

Background: Cerebral vasospasm and infarction are rare complications of transsphenoidal surgery for pituitary adenoma. Cerebral superficial siderosis may result from subarachnoid hemorrhage from a pituitary adenoma. The constellation of cerebral superficial siderosis, cerebral vasospasm, and pituitary adenoma is rare. We describe an extremely rare clinical constellation of immediately postoperative cerebral vasospasm and consequent cerebral infarction in a case with a large pituitary adenoma and cerebral superficial siderosis. Case Description: A 70-year-old man presented with a pituitary adenoma causing a worsening headache. Preoperative magnetic resonance (MR) images revealed cerebral superficial siderosis, suggesting subarachnoid hemorrhage from pituitary apoplexy. MR angiography (MRA) showed no vasospasm. During the transsphenoidal surgery, an intratumoral hematoma was found. The arachnoid membrane was partially torn and intratumoral hematoma entered the subarachnoid space. Intraoperatively, the intracranial vessels remained intact. The suprasellar tumor was almost entirely resected; however, the patient remained comatose postoperatively. Computed tomography revealed ischemic lesions in the bilateral insular and frontotemporal cortex. MRA revealed cerebral vasospasm in the bilateral middle cerebral arteries. The patient was treated with levetiracetam for nonconvulsive status epilepticus and underwent a lumbar peritoneal shunt surgery for secondary hydrocephalus. However, the patient remained listless. Conclusion: Postoperative cerebral vasospasm and infarction are severe but rare complications for a pituitary adenoma after transsphenoidal surgery. Preoperative and intraoperative subarachnoid hemorrhage might have been a risk factor in our case. Similar cases should be warranted to analyze whether cerebral superficial siderosis may also indicate the risk of severe postoperative vasospasm immediately after transsphenoidal surgery for pituitary adenoma.

Carotid Micromesh Stent for the Cervical Carotid Artery Dissecting Aneurysm in a Patient with Vascular Eagle Syndrome.

OBJECTIVES: An elongated styloid process may cause vascular Eagle syndrome that includes cervical carotid artery (CCA) dissection with stenosis and aneurysm formation. There are only four reported cases with vascular Eagle syndrome-related CCA dissecting aneurysm treated with carotid artery stenting (CAS). This is the first report of applying a dual-layer nitinol micromesh stent (CASPER) for vascular Eagle syndrome-related CCA dissecting aneurysm. CASE PRESENTATION: A 38-year-old man presented with a sudden onset of aphasia and right hemiplegia. Cerebral angiography demonstrated the left CCA dissecting aneurysm. The superior trunk of the left middle cerebral artery (MCA) was also occluded, and emergent thrombectomy was performed. Computed tomography with angiography (CTA) revealed that a 33 mm-long styloid process compressed the CCA at the aneurysm formation. Three weeks later, a CASPER stent was applied for the CCA aneurysm under the flow reversal system. Immediately after stent placement, blood flow in the aneurysm became stagnant, and postoperative CTA demonstrated regression of the aneurysm. The aneurysm did not recur for 6 months with no styloid process resection. CONCLUSIONS: The dual-layer nitinol micromesh stent (CASPER) was useful to treat vascular Eagle syndrome-related CCA dissecting aneurysm.

Stromal cells of hemangioblastomas exhibit mesenchymal stem cell-derived vascular progenitor cell properties.

Hemangioblastoma is composed of neoplastic stromal cells and a prominent capillary network. To date, the identity of stromal cells remains unclear. Mesenchymal stem cells can give rise to committed vascular progenitor cells, and ephrin-B2/EphB4 and Notch signaling have crucial roles in these steps. The aim of our study was to elucidate that stromal cells of central nervous system hemangioblastomas have mesenchymal stem cell-derived vascular progenitor cell properties. Ten hemangioblastomas were investigated immunohistochemically. CD44, a mesenchymal stem cell marker, was detected in stromal cells of all cases, suggesting that stromal cells have mesenchymal stem cell-like properties. Neither CD31 nor α-SMA was expressed in stromal cells, suggesting that stromal cells have not acquired differentiated vascular cell properties. Both ephrin-B2 and EphB4, immature vascular cell markers, were detected in stromal cells of all cases. Jagged1, Notch1, and Hesr2/Hey2, which are known to be detected in both immature endothelial cells and mural cells, were expressed in stromal cells of all cases. Notch3, which is known to be detected in differentiating mural cells, was also expressed in all cases. These results suggest that stromal cells also have vascular progenitor cell properties. In conclusion, stromal cells of hemangioblastomas exhibit mesenchymal stem cell-derived vascular progenitor cell properties.

Role of Endothelial-to-Mesenchymal Transition in the Pathogenesis of Central Nervous System Hemangioblastomas.

OBJECTIVE: Hemangioblastomas (HBs) are benign vascular tumors of the central nervous system and histologically contain abundant microvessels. Therefore, they clinically exhibit vascular malformation-like characteristics. It has been described that endothelial-to-mesenchymal transition (EndMT) contributes to the pathogenesis of cerebral cavernous malformations. However, it remains unknown whether EndMT contributes to the pathogenesis of central nervous system HBs. The aim of our study was to investigate whether EndMT occurs in central nervous system HBs. METHODS: Ten central nervous system HBs were immunohistochemically investigated. RESULTS: Cluster of differentiation (CD) 31 (an endothelial marker) and EndMT markers, such as α-smooth muscle actin (a mesenchymal marker) and CD44 (a mesenchymal stem cell marker), were expressed in the endothelial layer of microvessels in all cases. These findings suggest that endothelial cells (ECs) of microvessels in central nervous system HBs have acquired mesenchymal and stem cell-like characteristics and undergone EndMT. In all cases, both ephrin-B2 and EphB4, which are not detected in adult normal brain vessels, were expressed in the endothelial layer of microvessels. These data suggest that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. CONCLUSIONS: To our knowledge, this is the first report showing the possibility that EndMT contributes to the pathogenesis of central nervous system HBs. It is likely that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. EndMT is expected to be a new therapeutic target in central nervous system HBs.

Intramedullary spinal cord abscess and subsequent granuloma formation: a rare complication of vertebral osteomyelitis detected by diffusion-weighted magnetic resonance imaging.

An intramedullary spinal cord abscess, which is usually associated with discitis, is an uncommon but potentially important complication of vertebral osteomyelitis. The authors describe a rare case of an intramedullary conus medullaris abscess and lumbar osteomyelitis sparing the intervertebral discs and without discitis. The patient also developed a granuloma in the cauda equina during treatment. Diffusion-weighted MRI was useful for differentiating the granulomatous lesion from the relapse of infection. A 65-year-old immunocompetent man with moderately controlled diabetes presented with progressive lowerextremity numbness and weakness with urinary dysfunction. He had progressive paraparesis, bilateral leg paresthesia, and sphincter compromise. Magnetic resonance imaging revealed an intramedullary ring-enhanced lesion, which was hyperintense on diffusion-weighted images. The lesion, an intramedullary spinal cord abscess, was surgically drained. During antibiotic treatment, serial MRI showed an enlarging enhanced lesion in the cauda equina, and a recurrent infection was suspected. A second-look surgery confirmed the formation of a granuloma and the absence of a relapse of the abscess. Although the enhanced lesion increased in size, its intensity on diffusion-weighted images remained unchanged. After 3 months of antibiotic treatment, all enhanced lesions were diminished. An intramedullary spinal cord abscess is a rare but important complication of vertebral osteomyelitis, and it requires immediate treatment. Diffusion-weighted MRI was useful for the initial diagnosis as well as for monitoring treatment efficacy.

Lumbar alignment and clinical outcome after single level asymmetrical transforaminal lumbar interbody fusion for degenerative spondylolisthesis with local coronal imbalance.

Transforaminal lumbar interbody fusion (TLIF) is widely accepted for the treatment of lumbar arthrodesis. However, the exact characteristics of TLIF depend on the number, location, shape, or materials of the interbody implants, and the type of posterior instrument. Clinical and biomechanical characteristics of each TLIF procedure are still unclear. The present study investigated the clinical and radiological improvements after single level asymmetrical TLIF, in which a single box-shaped spacer was obliquely inserted into the intervertebral space, for lumbar degenerative spondylolisthesis in patients with or without local coronal imbalance (LCI) at the operated level. The clinical records of 60 patients who underwent single level asymmetrical TLIF augmented with the pedicle screw fixation system from January 2005 to January 2011, were retrospectively reviewed. The patients were divided into the LCI group (n = 19) and non-LCI group (n = 41), based on segmental lateral translation or disc wedging at the operated site. Clinical recovery was significantly good in both groups at 2 years after surgery, but improvement of low back pain was significantly worse in the LCI group. Radiological examination revealed that the mean lumbar scoliotic angle was significantly worse in the LCI group postoperatively. Preoperative greater scoliotic angle and coronal off balance of the lumbar spine were related to unfavorable radiological outcomes. The present study showed that single level asymmetrical TLIF is an acceptable method for achieving good clinical and radiological outcomes for patients with symptomatic degenerative spondylolisthesis, however, the clinical benefits and realignment are limited if the patient has LCI at the operated site with greater scoliotic angle or coronal off balance of the lumbar spine.

[Systematic review of complications for proper informed consent(12)decompression or fixation surgery of the lumbar spine].

A systematic review of the English- and Japanese-language literature related to complications and reoperation rates of spinal surgery for degenerative lumbar disease was undertaken for articles published between 1993 and 2012. From these references, key articles were selected to determine the incidence of clinical perioperative and postoperative adverse events for different types of degenerative lumbar diseases. The mortality rate after lumbar degenerative spinal surgery was 0.20% in the large-scale clinical studies evaluated. In this review series, the complication rates for lumbar canal stenosis(LCS), degenerative spondylolisthesis(DS), and lumbar disc herniation(LDH)were 7.6%, 8.5%, and 3.5%, respectively. The reoperation rates for LCS, DS, and LDH were 8.1%, 8.0%, and 6.2%, respectively. These data are helpful for spinal surgeons to apprise patients who have spinal surgery for degenerative lumbar disease of the possible risks of surgical procedures and reoperation rates.

Coexistence of multiple cavernous angiomas in the spinal cord and skin: a unique case of Cobb syndrome.

Cobb syndrome is a rare, noninherited, neurocutaneous disease characterized by vascular abnormality of the spinal cord and is associated with vascular lesions in the skin at the same metamere. The majority of spinal vascular lesions are arteriovenous malformations, and skin lesions are mostly port-wine angiomas. The authors report the first case of multiple intramedullary cavernous angiomas (CAs) accompanied by skin CAs within the same metamere. A 42-year-old man presented with an acute onset of gait disturbance, low-back pain, and urinary incontinence. Magnetic resonance imaging of the thoracolumbar spine showed homogeneously enhanced lesions on a contrast-enhanced T1-weighted image and a hypointense area on a T2*-weighted image surrounding this enhanced lesion, between the T-12 and S-1 levels. Purple protruding skin lesions were detected on the left side of his gluteal region. The patient received a laminectomy followed by evacuation of a hematoma and partial removal of the tumor, which completely resolved his neurological symptoms. Pathological examinations showed that the spinal and skin lesions were CAs, suggesting that these vascular lesions developed congenitally. Cavernous angiomas associated with Cobb syndrome present with multiple lesions spanning more than 3 vertebral levels, making it difficult to completely resect these tumors. Although Cobb syndrome is an uncommon disease entity, it should be considered if a patient manifesting with neurological deficits has skin vascular lesions, including CAs.