Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases.

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

Visualization of the lenticulostriate arteries, long insular arteries, and long medullary arteries on intra-arterial computed tomography angiography with ultrahigh resolution in patients with glioma.

PURPOSE: The anatomical association between the lesion and the perforating arteries supplying the pyramidal tract in insulo-opercular glioma resection should be evaluated. This study reported a novel method combining the intra-arterial administration of contrast medium and ultrahigh-resolution computed tomography angiography (UHR-IA-CTA) for visualizing the lenticulostriate arteries (LSAs), long insular arteries (LIAs), and long medullary arteries (LMAs) that supply the pyramidal tract in two patients with insulo-opercular glioma. METHODS: This method was performed by introducing a catheter to the cervical segment of the internal carotid artery. The infusion rate was set at 3 mL/s for 3 s, and the delay time from injection to scanning was determined based on the time-to-peak on angiography. On 2- and 20-mm-thick UHR-IA-CTA slab images and fusion with magnetic resonance images, the anatomical associations between the perforating arteries and the tumor and pyramidal tract were evaluated. RESULTS: This novel method clearly showed the relationship between the perforators that supply the pyramidal tract and tumor. It showed that LIAs and LMAs were far from the lesion but that the proximal LSAs were involved in both cases. Based on these results, subtotal resection was achieved without complications caused by injury of perforators. CONCLUSION: UHR-IA-CTA can be used to visualize the LSAs, LIAs, and LMAs clearly and provide useful preoperative information for insulo-opercular glioma resection.

Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.

Convection-enhanced delivery (CED) delivers agents directly into tumors and the surrounding parenchyma. Although a promising concept, clinical applications are often hampered by insufficient treatment efficacy. Toward developing an effective CED-based strategy for delivering drugs with proven clinical efficacy, we performed a basic characterization study to explore the locally delivered characteristics of the water soluble nitrosourea nimustine hydrochloride (ACNU). First, ACNU distribution after CED in rodent brain was studied using mass spectrometry imaging. Clearance of 14C-labeled ACNU after CED in striatum was also studied. ACNU was robustly distributed in rodent brain similar to the distribution of the hydrophilic dye Evans blue after CED, and locally delivered ACNU was observed for over 24 h at the delivery site. Subsequently, to investigate the potential of ACNU to induce an immunostimulative microenvironment, Fas and transforming growth factor-ß1 (TGF-ß1) was assessed in vitro. We found that ACNU significantly inhibited TGF-ß1 secretion and reduced Fas expression. Further, after CED of ACNU in 9L-derived intracranial tumors, the infiltration of CD4/CD8 lymphocytes in tumors was evaluated by immunofluorescence.CED of ACNU in xenografted intracranial tumors induced tumor infiltration of CD4/CD8 lymphocytes. ACNU has a robust distribution in rodent brain by CED, and delayed clearance of the drug was observed at the local infusion site. Further, local delivery of ACNU affects the tumor microenvironment and induces immune cell migration in tumor. These characteristics make ACNU a promising agent for CED.

Hepatitis B virus reactivation during temozolomide administration for malignant glioma.

INTRODUCTION: The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. METHOD: We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. RESULTS: In one of two HBV carriers, HBV DNA turned positive 8 months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). CONCLUSION: Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections.

Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.

Incidence of initial spinal metastasis in glioblastoma patients and the importance of spinal screening using MRI.

PURPOSE: Intracranial glioblastomas with simultaneous spinal lesions prior to chemoradiation therapy or craniotomy, defined as initial spinal metastasis, are not well understood. Herein, we investigated intracranial glioblastoma and demonstrated the importance of spinal screening using gadolinium enhanced spinal magnetic resonance imaging (Gd-MRI). METHODS: Consecutive adult patients with intracranial glioblastoma were treated between 2010 and 2014 and received spinal screening using Gd-MRI. Spinal screening was performed regardless of spine-related symptoms, and patients presenting with and without initial spinal metastasis (spinal and non-spinal groups, respectively) were compared based on patient demographics, tumor characteristics, radiological and molecular features, and overall survival (OS). RESULTS: During the study period, 116 glioblastoma cases were treated and 87 of these (76%) underwent spinal screening. Among these patients, 11 (13%) were included in the spinal group, and 76 (87%) were included in the non-spinal group. All patients of the spinal group were free of symptoms related to spinal lesions. Compared with the non-spinal group, intracranial lesions of the spinal group presented higher incidences of intracranial dissemination and were located at subventricular zones (P = 0.0012 and 0.020, respectively). MIB-1 labeling index, molecular alterations such as IDH1 mutation, TERT promoter mutation, and immunoreactivity of ATRX and MGMT did not differ between two groups. OS was significantly shorter in the spinal group than in the non-spinal group (P = 0.0054). CONCLUSIONS: This study revealed a relatively high incidence of spinal metastasis. A subset of glioblastoma patients benefited from spinal screening, through which early detection of asymptomatic spinal metastasis was achieved.

Paradoxical worsening of ocular symptoms after transvenous embolization of cavernous sinus dural arteriovenous fistula due to coil-induced perifocal inflammation: A case report.

Ocular symptoms usually completely resolve after successful transvenous embolization of cavernous sinus dural arteriovenous fistulas (CS-dAVFs). Herein, we report a case of CS-dAVF in which sinus packing of the superior ophthalmic vein (SOV) caused coil-induced inflammation in orbital tissue, leading to deteriorating ocular symptoms. A 73-year-old woman presented with right-eye exophthalmos and chemosis. Cerebral angiography demonstrated right CS-dAVF, which retrogradely drained into the right SOV. We conducted sinus packing with coils via the right inferior petrosal sinus, resulting in obliteration of the shunts. One day after sinus packing, right exophthalmos and chemosis progressed, suggesting dAVF recurrence. However, no residual angiographic shunts were observed. Orbital magnetic resonance imaging (MRI) revealed edema in intraorbital tissue and gadolinium contrast enhancement of SOV wall. We presumed that the coils in SOV induced perifocal inflammation at the venous wall and surrounding orbital tissue, leading to aggravation of ocular symptoms. Following steroid therapy for 2 months, ocular symptoms and contrast enhancement on orbital MRI significantly improved without anticoagulant treatment. Posttreatment paradoxical worsening of ocular symptoms could be caused by coil-induced inflammation of the SOV wall near the orbital tissue. Steroid therapy could be effective in reducing orbital inflammatory reactions.

Flow diverter therapy for immunosuppressant-resistant vertebral artery fusiform aneurysm due to eosinophilic granulomatosis with polyangiitis: illustrative case.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by the presence of asthma and eosinophilia. Because cerebral aneurysm formation induced by EGPA is a rare occurrence, there is no established treatment strategy for this condition. OBSERVATIONS: A 67-year-old female who was diagnosed with idiopathic eosinophilia 3 months ago developed de novo fusiform aneurysms in the left vertebral, left internal carotid, and bilateral superficial temporal arteries, as noted during a regular follow-up examination of a convexity meningioma. Pathological examination of the resected superficial temporal artery revealed eosinophilic granulomas, which led to the diagnosis of EGPA, as well as EGPA-induced aneurysm formation. As the partially thrombosed vertebral artery fusiform aneurysm enlarged, the compression of the medulla oblongata occurred despite intensive immunosuppressive therapy for 1 year. The patient underwent flow diversion therapy administered using the pipeline embolization device, resulting in complete disappearance of the aneurysm. LESSONS: Considering that the entire circumference of the aneurysmal wall is affected by necrotizing vasculitis, flow diverter therapy would be a reasonable and efficient approach for the treatment of EGPA-related aneurysms in cases in which the patient is nonresponsive to immunosuppressants.

H3K27M and TERT promoter mutations are poor prognostic factors in surgical cases of adult thalamic high-grade glioma.

BACKGROUND: Thalamic high-grade gliomas (HGGs) are rare tumors with a dismal prognosis. H3K27M and telomerase reverse transcriptase promoter (TERTp) mutations reportedly contribute to poor prognoses in HGG cases. We investigated the outcomes of surgically treated adult thalamic HGGs to evaluate the prognostic significance of H3K27M and TERTp mutations. METHODS: We retrospectively analyzed 25 adult patients with thalamic HGG who underwent maximum surgical resection from January 1997 to March 2020. The histological and molecular characteristics, progression-free survival (PFS), and overall survival (OS) of the patients were compared. For molecular characteristics, target sequencing was used to determine the H3F3A, HIST1H3B, and TERTp mutations. RESULTS: H3K27M mutations were detected in 12/25 (48.0%) patients. TERTp mutations were not detected in H3K27M-mutant gliomas but were detected in 8/13 (61.5%) of H3 wild-type gliomas. Although it was not significant, H3K27M-mutant gliomas tended to have a shorter PFS (6.7 vs 13.1 months; P = .2928) and OS (22.8 vs 24.4 months; P = .2875) than H3 wild-type gliomas. Moreover, the prognosis of TERTp-mutant gliomas was as poor as that of H3K27M-mutant gliomas. Contrary, 5 gliomas harboring both H3 and TERTp wild-type showed a better median PFS (59.2 vs 6.4 months; P = .0456) and OS (71.8 vs 24.4 months; P = .1168) than those harboring H3K27M or TERTp mutations. CONCLUSIONS: TERTp-mutant gliomas included in the H3 wild-type glioma group limited patient survival as they exhibited an aggressive course similar to H3K27M-mutant gliomas. Comprehensive molecular work-up for the H3 wild-type cases may further confirm this finding.

Association between IDH mutational status and tumor-associated epilepsy or venous thromboembolism in patients with grade II and III astrocytoma.

In previous studies, isocitrate dehydrogenase (IDH) mutations were associated with tumor-associated epilepsy (TAE) and venous thromboembolism (VTE). We examined the relationship between IDH mutations in grade II/III astrocytomas and TAE/VTE according to the 2016 World Health Organization classification. The clinical data of patients with newly diagnosed grade II/III gliomas who were treated at Tohoku University Hospital from January 2010 to December 2018 were reviewed. Associations between TAE or VTE and the clinical/biological characteristics, histology, and IDH1/2 mutational status in patients with grade II/III gliomas were evaluated. Of the initial 137 patients (290 hospitalizations), 117 patients (203 hospitalizations) were included in the TAE group and 124 patients (213 hospitalizations) were included in the VTE group. Seventy-eight patients (66.7%) in the TAE group were diagnosed with astrocytoma and 38/78 (48.3%) presented with TAE. According to the multivariable analysis, the IDH mutational status and male sex were associated independently with an increased risk of TAE (p < 0.05). Eighty-five patients (68.5%) in the VTE group were diagnosed with astrocytoma. VTE was observed in 16/161 (9.9%) hospitalizations. According to the multivariable analysis, age, diffuse astrocytoma histology, and resection were associated independently with an increased risk of VTE. The decision tree analysis showed that TAE was more frequent in younger patients while VTE was more frequent in older patients. This study demonstrated that the IDH mutational status was associated with TAE but not with VTE. Therefore, a future large-scale study is needed to provide sufficient evidence. TAE was more common in young patients, while VTE was more common in the elderly.

Successful presurgical endovascular management of venous sinus thrombosis associated with high-grade cerebral arteriovenous malformation: A case report.

We report a case of a 39-year-old man presenting with a high-grade left parieto-occipital arteriovenous malformation (AVM) complicated by superior sagittal sinus (SSS) stenosis, seven years after the first presentation. Magnetic resonance imaging revealed a newly developed perilesional edema. Venous sinus stenosis acutely progressed to occlusion and induced multiple intracerebral hemorrhages. An emergent balloon venoplasty of the SSS successfully recanalized the thrombosed sinus. Further, multistage transarterial nidus embolization was performed followed by surgical resection, resulting in a complete eradication of the large AVM. The emergence of perilesional edema is a key radiological feature for the early recognition of a newly developed venous drainage route disturbance, which would result in hemorrhagic events. Venous sinus thrombosis is a rare cause of drainage route disturbance in cerebral AVMs. For such cases, the recanalization of venous drainage concomitant with flow reduction by performing transarterial embolization is effective in preventing further hemorrhage, which enables a safe performance of subsequent radical surgery.