Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19-A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan.

Background and Objectives: The incidence of coronavirus disease 2019 (COVID-19) has increased in Wakayama, Japan, due to the spread of the highly infectious B.1.1.7 variant. Before this event, the medical systems were almost unaffected. We aimed to assess the clinical characteristics of patients hospitalized with COVID-19 and the risk factors for therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. Materials and Methods: This single-center retrospective study enrolled 185 patients with mild to moderate COVID-19 hospitalized in our hospital without intensive care between 14 March and 31 May 2021. Results: In this period, 125 (67.6%) of the 185 patients had the B.1.1.7 variant. Sixty-three patients (34.1%) required remdesivir treatment. Age upon admission and length of hospitalization were significantly different between remdesivir treatment and careful observation groups (mean (standard deviation); 59.6 (14.7) versus 45.3 (20.6) years; p < 0.001 and median (interquartile range); 10 (9-12) versus 9 (8-10) years; p < 0.001). One patient was transferred to another hospital because of disease progression. At hospital admission, age ≥60 years (odds ratio (OR) 6.90, p < 0.001), a previous history of diabetes mellitus (OR 20.9, p = 0.002), B.1.1.7 variant (OR 5.30; p = 0.005), lower respiratory symptoms (OR 3.13, p = 0.011), headache (OR 3.82, p = 0.011), and fever ≥37.5 °C (OR 4.55, p = 0.001) were independent risk factors to require remdesivir treatment during the admission. Conclusions: Many patients with mild to moderate COVID-19 required the therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. From the clinical data obtained at admission, these risk factors could contribute to a prediction regarding the requirement of remdesivir treatment in cases of mild to moderate COVID-19.

MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes.

Mismatch repair genes mutS homologs 6/2 (MSH6/2) expressions are involved in tumor growth and programmed cell death 1 ligand 1 (PD-L1) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is not well understood. We aimed to clarify the effects of MSH6/2 and PD-L1 expression on tumor proliferation and invasiveness in nonfunctioning (NF) PAs. We performed immunohistochemistry to classify the NFPAs into gonadotroph adenoma (GAs), silent corticotroph adenomas (SCAs), null cell adenoma (NCAs), and pituitary transcription factor 1 (PIT1) lineage PAs. We evaluated MSH6/2 and PD-L1 mRNA expressions in NFPAs by real-time PCR (n = 73), and statistically analyzed the expressions and clinicopathological factors. We also investigated the effect of MSH6 knockout on PD-L1 expression in AtT-20ins and GH3. MSH6/2 expressions were significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. MSH6/2 expressions were positively associated with PD-L1 expression. PD-L1 expression was significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. Although MSH6/2 expressions also tended to be lower in PIT1 lineage PAs than in GAs, PIT1 lineage PAs expressed PD-L1 equivalently to GA, which was unlike SCAs and NCAs. MSH6 knockout in AtT-20ins and GH3 significantly decreased PD-L1 expression (75% and 34% reduction, respectively) with cell proliferation promotion. In conclusion, differences in MSH6/2 and PD-L1 expressions of SCAs, NCAs, and PIT1-lineage PAs from those of GAs appear to contribute to their clinically aggressive characteristics, such as more proliferation and invasiveness.

Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors.

INTRODUCTION: This study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas. METHODS: We collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival. RESULTS: Included in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis. CONCLUSIONS: This community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.

Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information.

[Percutaneous Transluminal Sinus Stenting for Sigmoid Sinus Stenosis Associated with Transverse-Sigmoid Sinus Dural Arteriovenous Fistula:A Case Report].

We report a case of transverse sinus-sigmoid sinus dural arteriovenous fistula(T-S dAVF)with venous flow congestion, which was accompanied by sigmoid sinus stenosis and treated with percutaneous transluminal sinus stenting. A 76-year-old woman presented with dementia and disturbance of consciousness. Magnetic resonance imaging(MRI)on admission revealed subcortical edema in the left occipital lobe and angiography demonstrated a left T-S dAVF with right transverse sinus occlusion and sigmoid sinus stenosis. Hemodynamics of the shunt flow from several feeders demonstrated retrograde flow to the straight sinus and superior sagittal sinus, and antegrade flow into the left internal jugular vein. These hemodynamics caused cortical venous congestion and intracranial venous hypertension. We performed percutaneous transluminal sinus stenting for left sigmoid sinus stenosis. Immediately after stent placement, retrograde shunt flow to the straight sinus and superior straight sinus dramatically disappeared and cortical venous congestion improved. Follow-up angiography 1 year after treatment showed neither new development of T-S dAVF nor re-stenosis of the stent in the left sigmoid sinus, although some shunt flow remained. Percutaneous transluminal sinus stenting for sinus stenosis associated with dAVF appears effective to improve venous congestion and intracranial venous hypertension.

[Tentorial Dural Arteriovenous Fistula Presenting with Ocular Symptoms:A Case Report].

Tentorial dural arteriovenous fistula(dAVF)is classified as Cognard 4 with a high risk of aggressive feature, such as intracranial hemorrhage, venous infarction, and intracranial hypertension. We report a rare case presenting with ocular symptoms caused by tentorial dAVF. A 59-year-old man presented with progressive chemosis and exophthalmos of his left eye. Angiography showed a tentorial dAVF that was primarily fed by the middle meningeal artery and the meningohypophyseal artery. The AVF drained into the superior ophthalmic vein and the cerebellar cortical vein via an enlarged petrosal vein. Because transarterial Onyx embolization resulted in incomplete obliteration of the fistula, he underwent microsurgery via a suboccipital approach to obliterate the shunt. Postoperative angiography showed complete obliteration of the shunt. His ocular symptoms rapidly cured. We present this rare case and discuss the pathomechanism associated with the development of ocular symptoms secondary to a tentorial dAVF from the viewpoint of microvascular anatomy.

Atypical pituitary adenoma with MEN1 somatic mutation associated with abnormalities of DNA mismatch repair genes; MLH1 germline mutation and MSH6 somatic mutation.

The mechanism of pituitary tumorigenesis remains largely unknown. Lynch syndrome is an autosomal, dominantly inherited syndrome caused by a defective mismatch repair (MMR) mechanism involved in the development of various tumors at an early age. In this case study, we showed the occurrence of pituitary tumors associated with Lynch syndrome for the first time and performed genetic and immunohistochemical analysis to evaluate the genetic aberrations that might be related to the tumorigenesis and proliferation. A 68-year-old female patient with Lynch syndrome due to mutL homolog 1 (MLH1) gene mutation suffered from hypersecretion of adrenocorticotrophic hormone (ACTH), hypercortisolism and a rapidly progressive pituitary tumor. We performed genetic analysis by whole genome sequencing with genomic DNA of the pituitary tumor and peripheral blood leukocytes, as well as immunohistochemical analysis of MMR proteins. Genetic analysis revealed that the tumor had homozygous gene mutation of MEN1 associated with pituitary tumorigenesis and mutS homolog 6 (MSH6) gene. Furthermore, immunohistochemical analysis showed that MLH1 and MSH6 immunoexpression were negative. We reveal for the first time that MMR abnormality could cause somatic mutation of MEN1 and pituitary tumor occurrence is associated with Lynch syndrome. We suggest that the identified gene mutations, especially those of MSH6 and MLH1 genes, may be involved in the pathogenesis and proliferation of pituitary tumor. The knowledge obtained from our case study is important to elucidate the pathogenesis and proliferation mechanisms of pituitary tumors.

[A Case of Tentorial Dural Arteriovenous Fistula Treated with Transvenous Embolization Using NBCA].

We report a case of tentorial dural arteriovenous fistula(dAVF)treated with transarterial and transvenous embolization using n-butyl-2-cyanoacrylate(NBCA). A 70-year-old man presented with dysarthria and trunk ataxia. Computed tomography(CT)on admission revealed right cerebellar hemorrhage. Right external carotid angiography demonstrated a tentorial dAVF fed by the marginal tentorial artery, petrosquamous branch of the middle meningeal artery, ascending pharyngeal artery, and artery of foramen rotundum. Right internal carotid angiography demonstrated a shunt fed by the meningohypophyseal trunk. The draining vein was the right basal vein with a varix, which drained into the straight sinus. Thin-slice axial images on magnetic resonance angiography demonstrated a shunt point located on the right tentorial incisura. The lesion was diagnosed as Cognard type IV tentorial dAVF. It was initially treated with transarterial embolization using 25% NBCA, which was injected into the marginal tentorial artery and the petrosquamous branch of the middle meningeal artery. However, owing to partial persistence of the shunt after the procedure, transvenous embolization using NBCA was performed. A microcatheter was navigated through the straight sinus into the basal vein, and a balloon catheter was also navigated to the confluence of the straight sinus and the basal vein to interrupt blood flow and prevent the NBCA from flowing back to the sinus. 80% NBCA was injected into the draining vein near the shunt point. Angiography performed immediately after the procedure revealed complete occlusion of the shunt, and postoperative CT showed no evidence of hemorrhage. Transvenous embolization of tentorial dAVF can be an effective method if a microcatheter can be safely advanced close to the shunt point.

Retractorless surgery for a pineal region tumor through an occipital transtentorial approach.

This video demonstrates surgical techniques of the occipital transtentorial approach to a pineal region tumor without using a fixed brain retractor, which may cause functional impairment or even tissue injury to the occipital visual cortex. There are several ways to facilitate retractorless surgery through this approach. A lateral-semiprone positioning of the patient can induce gravity retraction. The brain is relaxed by draining CSF fluid through lumbar drainage or lateral ventricular tap in the case of obstructive hydrocephalus. Dynamic retraction with handheld instruments after extensive dissection of the deep venous system, including basal veins, can provide a sufficient working space. The video can be found here: https://youtu.be/kQvEHiNcRow .

[A Case of Percutaneous Transluminal Angioplasty and Stenting for Dacron Bypass Graft Stenosis with Cerebral Infarction].

A 62-year-old man presented to the emergency room with mild dysarthria and right motor weakness. The patient was diagnosed with aortic dissection (DeBakey type III) in the cardiovascular department of our institution two years ago and was then treated with left carotid-bilateral subclavian bypass with collagen-seated Dacron graft followed by thoracic endovascular aortic repair (TEVER) with stent-graft placement. Magnetic resonance imaging on admission showed cerebral infarction with left proximal middle cerebral artery occlusion in the left cerebral hemisphere. Three-dimensional computed tomography angiography (3D-CTA) demonstrated a stenotic lesion at the anastomosis of the right subclavian artery and the bypass graft. It also showed the partial left common carotid artery, suggestive of an endoleak in the thoracic stent graft. The patient was diagnosed with artery-to-artery embolism due to bypass graft stenosis or endoleak in the thoracic stent graft and was treated with conservative therapy. He gradually recovered from the neurological deficit and underwent endovascular angioplasty with a balloon-expandable stent for bypass graft stenosis by using the distal balloon protection method and the left proximal common carotid artery occlusion with coils 1 month later. One-year follow-up 3D-CTA showed good patency of the stent in the bypass graft. No recurrence of cerebral infarction was observed during the postoperative course.

Extremely slow-growing cerebellar ganglioglioma in an elderly patient.

Background: Gangliogliomas account for 0.4% of primary brain tumors. They mainly occur in the supratentorial compartment and typically affect only children and young adults. We present an especially rare case of cerebellar ganglioglioma in an elderly patient. Case Description: A 76-year-old Japanese woman presented with headache and nausea from 1 month previously. She had been diagnosed with a cerebellar tumor in her childhood, but the lesion was asymptomatic at that time, and there was no evidence of an increase in size, so it had been monitored without surgery. At the time of presentation, she had not been examined for approximately ten years. On admission, magnetic resonance imaging indicated a T2 hypertense cyst in the cerebellar vermis. Post-contrast T1 imaging showed an enhanced mural nodule in the cyst. Cerebral angiography showed that none of the vertebral arteries were significant feeders. The tumor was removed through posterior fossa craniotomy. The histopathological diagnosis was ganglioglioma. The patient's headache and nausea improved after surgery. Conclusion: Our patient presented a very rare case of extremely slow-growing elderly ganglioglioma in the cerebellum. In patients with gangliogliomas, long-term follow-up is important because the disease may become symptomatic at an older age.

Profiling of Unfolded Protein Response Markers and Effect of IRE1α-specific Inhibitor in Pituitary Neuroendocrine Tumor.

CONTEXT: Inositol-requiring enzyme 1α (IRE1α) and PKR-like ER kinase (PERK), which are endoplasmic reticulum (ER) membrane proteins, regulate the unfolded protein response (UPR). These molecules have recently gained attention as a novel therapeutic target in secretory tumors. The roles of the UPR in pituitary neuroendocrine tumors (PitNETs) are unclear. OBJECTIVE: To clarify UPR profiling of PitNETs and to investigate the effect of pharmacological modulation of UPR by KIRA8, a newly developed IRE1α-specific inhibitor. METHODS: In 131 patients with PitNETs, we evaluated RNA expression of UPR markers in PitNETs and their clinical phenotypes. Using GH3 cells, we examined the effects of KIRA8 and its combination with octreotide on UPR profiling, cell growth, and apoptosis. RESULTS: Cytoprotective adaptive-UPR (A-UPR) markers were more increased in functioning PitNETs (FPitNETs, n = 112) than in nonfunctioning PitNETs (NFPitNETs, n = 19), while there was no difference in proapoptotic terminal-UPR (T-UPR) markers. Similarly, overt somatotroph tumors (STs, acromegaly, n = 11) increased A-UPR compared with silent STs (n = 10). In STs, serum IGF-1 levels were inversely correlated with Txnip mRNA expression, a representative T-UPR marker. KIRA8 inhibited cell growth and facilitated apoptosis in GH3 cells with increased expressions of T-UPR markers, which was enhanced by the combination with octreotide. Octreotide increased mRNA expression of Txnip and Chop, but decreased spliced Xbp1 under ER stress. Octreotide is suggested to inhibit activation of IRE1α but to reciprocally induce T-UPR under PERK. CONCLUSION: UPR markers in FPitNETs are implicated as dominant A-UPR but blunted T-UPR. KIRA8, enhanced with octreotide, unbalances the UPR, leading to antitumor effects. Targeting IRE1α may provide a novel strategy to treat PitNETs.

Factors Associated with Early and Late Seizure Related to Aneurysmal Subarachnoid Hemorrhage.

Post-stroke epilepsy may occur after aneurysmal subarachnoid hemorrhage (aSAH). Both early and late seizures could cause severe neurocognitive deficits if administration of appropriate antiseizure medication is delayed. Therefore, it is important to elucidate the risk factors for early and late seizures, which could be shared with medical teams to promptly manage seizures. There are aspects of both hemorrhage and ischemia in aSAH, and thus, numerous risk factors are considered for early and late seizures. We examined factors associated with aSAH-related early and late seizures. Among 297 patients who had aSAH and underwent direct or endovascular surgery, 25 had early seizures and 20 had late seizures. Patients who did not experience any seizures in at least 2-years of follow-up (n = 81) were used as the control group. Early seizures were associated with older age and acute severe nonneurological infection, whereas late seizures were associated with intraparenchymal lesion volume >10 mL and shunt placement. In patients with late seizures, consistency was frequently observed between electroencephalogram and the presence of intraparenchymal lesions. The frontopolar electrode on electroencephalogram was highly sensitive to abnormality in early seizures. Early seizures were induced by the patient's systemic factors, which may lower the threshold for cortical excitability. Patients with intraparenchymal lesions who undergo shunt placement should be carefully followed up for late seizures.

Management of non-benign meningiomas with Gamma Knife radiosurgery.

OBJECTIVE: Results of Gamma Knife radiosurgery (GKS) were retrospectively evaluated in 16 patients with histologically confirmed atypical and anaplastic intracranial meningiomas. MATERIALS AND METHODS: There were nine men and seven women (mean age 61.0 years). Atypical meningiomas were diagnosed in nine cases and anaplastic meningiomas in seven. In nine patients there was malignant transformation of a tumor that had initially proved to be benign. In total, 21 radiosurgical procedures were performed. The mean tumor volume at the time of GKS was 7.1 cm3. The mean marginal and maximum irradiation doses were 18.8 and 37.0 Gy, respectively. The mean length of follow-up after treatment was 37.1 months. FINDINGS: Of 21 radiosurgical procedures, 6 (29 %) led to stabilization of tumor growth during the mean follow-up of 40.5 months. It was significantly associated with small lesion volume (P = 0.02), and greater marginal (P = 0.04) and maximum (P = 0.02) irradiation doses. Seven patients underwent eight surgical resections of a progressing tumor during the mean period of 26.1 months after irradiation. Five patients (31 %) died because of tumor progression within the average time period of 16.8 months after GKS. Overall, at the time of the last follow-up just two patients (13 %) had no evidence of tumor regrowth, and only three patients (19 %) maintained good activities of daily living during 12, 59, and 69 months, respectively, after radiosurgery. CONCLUSION: GKS has limited efficacy in cases of non-benign meningioma. Better tumor control rates can be attained for small neoplasms treated with greater marginal and maximum irradiation doses.

Usefulness of Leksell GammaPlan for preoperative planning of brain tumor resection: delineation of the cranial nerves and fusion of the neuroimaging data, including diffusion tensor imaging.

Leksell GammaPlan (LGP) software was initially designed for Gamma Knife radiosurgery, but it can be successfully applied to planning of the open neurosurgical procedures as well. We present our initial experience of delineating the cranial nerves in the vicinity of skull base tumors, combined visualization of the implanted subdural electrodes and cortical anatomy to facilitate brain mapping, and fusion of structural magnetic resonance imaging and diffusion tensor imaging performed with the use of LGP before removal of intracranial neoplasms. Such preoperative information facilitated choosing the optimal approach and general surgical strategy, and corresponded well to the intraoperative findings. Therefore, LGP may be helpful for planning open neurosurgical procedures in cases of both extraaxial and intraaxial intracranial tumors.

Hemangioblastoma of the medulla oblongata that caused isolated fourth ventricle after stereotactic radiosurgery: A case report.

Isolated fourth ventricle is a rare complication following shunt insertion of the lateral ventricles for hydrocephalus. The present report describes a rare case of a hemangioblastoma of the medulla oblongata that caused isolated fourth ventricle due to intraventricular deposition of fibrin. A 34-year-old man presented with headache a month before admission. Magnetic resonance imaging indicated multiple tumors in the medulla oblongata and the bilateral cerebellar hemisphere with surrounding edema, and the patient was diagnosed with hemangioblastoma. The patient began to develop progressive headache and nausea after stereotactic radiosurgery, and computed tomography showed obstructive hydrocephalus. Endoscopic third ventriculostomy was performed, and the intraoperative view of this showed that the walls of the lateral and third ventricles were covered with a white membrane-like substance. Endoscopic third ventriculostomy and then ventriculoperitoneal shunt did not improve the hydrocephalus. The patient's consciousness deteriorated due to isolated fourth ventricle and upward herniation. The patient underwent posterior fossa craniotomy and the tumor in the medulla oblongata was removed via a telovelar approach. Intraoperatively, the fourth ventricle was filled with a white membrane-like substance, which was surgically removed and pathologically diagnosed as fibrin. The patient's consciousness and obstructive hydrocephalus improved after surgery. The present case suggests that isolated fourth ventricle may occur after VP shunt placement for the hydrocephalus with hyperproteinorachia.

Giant cell arteritis with severe intracranial involvement diagnosed and treated early.

Background: Ischemic cerebrovascular accidents (CVA) occur in 3.3-7.2% of patients with giant cell arteritis (GCA), and intracranial vessels are rarely affected. We, herein, report a case of intracranial GCA with rapidly progressive multiple intracranial vascular lesions. Case Description: A 76-year-old woman visited a local doctor due to a headache; then, it improved spontaneously. Three months later, she suddenly had cerebral infarctions of bilateral pons and cerebellum. Magnetic resonance angiography (MRA) revealed the left internal carotid artery (ICA) occlusion, the right vertebral artery (VA) occlusion, and the left VA stenosis. She was diagnosed with atherothrombotic stroke and dual antiplatelet therapy was administered. However, 2 weeks later, the left VA stenosis was aggravated. Therefore, we reviewed the data of MRA performed 3 months ago and noted no lesions in the ICA and VA. T1 black-blood post-gadolinium imaging sequence magnetic resonance imaging (MRI) revealed vessel wall enhancement in the bilateral VA, left ICA, and bilateral superficial temporal artery. We performed a temporal artery biopsy and diagnosed her with GCA. The progression of the intracranial vascular lesions was decelerated by oral glucocorticoid administration. Conclusion: Intracranial vascular lesions in GCA can be formed later than initial symptoms, such as headache, and aggravated despite improvement in headache. In patients with GCA, evaluating intracranial vessels as a control is useful for distinguishing them from arteriosclerotic lesions at the onset of CVA. Intracranial GCA is characterized by rapidly progressive vascular lesions in the bilateral ICA and VA. In addition, T1 black-blood post-gadolinium imaging sequence MRI may lead to early diagnosis and treatment.

Comparison of the outcomes of patients with primary central nervous system lymphoma between the neurosurgery and hematology/oncology departments based on the relative dose intensity of methotrexate.

Primary central nervous system lymphoma (PCNSL) is an extranodal type of lymphoma, which is treated with methotrexate (MTX)-based induction therapy. Although PCNSL is a hematological malignancy, patients with PCNSL may be treated at neurosurgery or hematology/oncology departments; however, the outcomes of PCNSL treatment have not been compared between these two departments. The present study compared the outcomes of 26 patients with newly diagnosed PCNSL that were treated at the Department of Neurological Surgery or Department of Hematology/Oncology (Wakayama Medical University Hospital, Wakayama, Japan) between January 2011 and December 2021. The relative dose intensity (RDI) and relative treatment intensity of MTX were assessed as indicators of the intensity of chemotherapy. The median RDI of MTX was 67 and 93% in the neurosurgery and hematology/oncology groups, respectively (P<0.001). The proportion of patients that achieved a complete response after high-dose MTX-based therapy was significantly higher in the hematology/oncology group than in the neurosurgery group (P=0.038). The estimated 2-year overall survival was 72 and 100% in the neurosurgery and hematology/oncology groups, respectively (P=0.046). As with the difference in the outcomes observed between pediatrics and hematology departments for adolescents with acute lymphoblastic leukemia, the outcomes of patients with PCNSL may differ between neurosurgery and hematology/oncology departments.

Rituximab Monotherapy for Grade 2-3 Lymphomatoid Granulomatosis with Central Nervous System Involvement in a Patient Receiving Methotrexate for Rheumatoid Arthritis.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder (LPD). The optimal management strategy of methotrexate (MTX) related-LPD with central nervous system (CNS) involvement and histological features of LYG remains unclear. We herein report a case of grade 2-3 LYG in a rheumatoid arthritis patient, in which an intracranial mass accompanied by hemorrhaging and pulmonary and skin lesions developed. The patient received successful rituximab monotherapy. The tumor cells in the skin and brain showed monoclonal and oligoclonal proliferation, respectively. Our case suggests that rituximab monotherapy may be effective against MTX-LPD with CNS involvement, especially in cases with LYG histology.

Prognostic Factors and Histopathological Features of Pediatric Intracranial Ependymomas: Nationwide Brain Tumor Registry-based Study of Japan.

To assess the clinicopathological features and prognostic factors of pediatric intracranial ependymomas and to explore the current diagnostic practice, we analyzed clinical data from the Brain Tumor Registry of Japan (BTRJ). Data of fifty children under 18 years of age diagnosed with intracranial ependymoma were extracted from the BTRJ database. Cases were reviewed for overall survival (OS) and progression-free survival (PFS), with attention to gender, preoperative Karnofsky performance status score, location of the tumor, the extent of resection, World Health Organization (WHO) histopathological grading, and adjuvant therapy. The median age at diagnosis was 6.1 years, ranging from 7 months to 17.6 years. Based on the WHO histopathological grading, 27 patients were classified under grade 2 (54%) and 23 patients were classified under grade 3 (46%). Gross total resection (GTR) was achieved in 30 patients (60%). The median follow-up time was 65 months. Five-year PFS and OS were 47.2 ± 7.3% and 73.3 ± 6.7%, respectively. GTR was associated with longer OS (P = 0.02). The histopathological grading was not an independent prognostic factor for the OS. Mitosis and microvascular proliferation were higher among patients with grade 3 than in those with grade 2, which aided in deciding the WHO grade. This nationwide study revealed the characteristics and outcomes of patients with childhood ependymomas. GTR was the factor most consistently associated with improved survival. In contrast, the histopathological grading in this cohort was not a significant prognostic factor. More reproducible and practical criteria for the diagnosis of intracranial ependymomas should be further pursued in future studies.