An exploratory prospective phase II study of preoperative neoadjuvant bevacizumab and temozolomide for newly diagnosed glioblastoma.

PURPOSE: This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB). METHODS: Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy. RESULTS: Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively. CONCLUSION: Preoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively. TRIAL REGISTRATION NUMBER: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233 . Registration Date: Jan. 16, 2017.

Yield of Whole Body Computed Tomography in Hyper-Acute Stroke Patients With Large Vessel Occlusion.

PURPOSE: In the majority of cases, large vessel occlusion (LVO) in ischemic stroke patients has an embolic origin. Systemic embolism can occur simultaneously with brain thrombosis. This retrospective study evaluated the frequency and locations of systemic embolism in LVO stroke patients receiving revascularization therapy. MATERIALS AND METHODS: In our facility, we use contrast-enhanced computed tomography (CE-CT) to assess suspected stroke patients and routinely perform CE-CT from the chest to the abdomen after brain CT angiography to rule out contraindications like aortic dissection and trauma for thrombolysis. Systemic embolism is also assessed using these images, while myocardial infarction is evaluated based on electrocardiograms and laboratory findings. Other relevant clinical features of each patient are also analyzed. RESULTS: In total, 612 consecutively admitted stroke patients and 32 LVO patients who underwent revascularization therapy were included in the present study. Systemic embolism was identified in four patients (13%). The spleen was the most commonly affected organ, followed by the heart, kidneys, limbs, and lungs. All four patients with systemic embolism exhibited LVO resulting from embolism as the underlying mechanism. CONCLUSION: Systemic embolism was observed in 13% of our LVO patients, all of whom had LVO of embolic origin.

Rupture of the internal carotid artery pseudoaneurysm resulting from fungal sinusitis.

Although vasculitis due to infection with fungi, including Aspergillus, causes aneurysm formation, reports of internal carotid artery aneurysm formation resulting from fungal sinusitis are few. We report on a patient who experienced massive epistaxis from rupture of an internal carotid artery pseudoaneurysm, caused by fungal sinusitis. We treated the aneurysm with endovascular coil embolization, followed by endoscopic sinus surgery to remove the fungal mass. Intraoperative findings included a torn internal carotid artery and exposure of the coil to the sinus. Performing endoscopic sinus surgery before the embolization procedure would have increased the risks of massive intraoperative bleeding and mortality. Even after achieving hemostasis, serious sequelae, such as cerebral infarction, might occur. In this type of case, otorhinolaryngologists and neurosurgeons should collaborate, and an aneurysm should be treated before endoscopic sinus surgery. Although the treatment strategy for fungal internal carotid artery aneurysms is controversial, this case suggested the use of the embolization procedure followed by endoscopic debridement and antifungal therapy to treat a pseudoaneurysm of the internal carotid artery caused by fungal sinusitis.

Therapeutic efficacy and complications of radial versus femoral access in endovascular treatment of unruptured intracranial aneurysms.

PURPOSE: The transradial approach (TRA) in neuroendovascular treatment is known to have a lower risk of complications than the transfemoral approach (TFA). However, little research has focused on assessments of efficacy and risk of complications in the treatment of intracranial aneurysms. This study aimed to compare the efficacy and complications of TRA and TFA in coil embolization of unruptured intracranial aneurysms (UIAs) at our institution. METHODS: Consecutive patients who underwent endovascular surgery via TRA or TFA at a single institution from 1 April 2019, to 28 February 2022, were retrospectively analyzed. Patients were classified into TRA and TFA groups and assessed using propensity-adjusted analysis for outcomes including fluoroscopy time, volume embolization ratio (VER), and complications. RESULTS: A total of 163 consecutive UIAs were treated with coil embolization during the 35-months study period. The incidence of minor access site complications (ASCs) was significantly higher with TFA (20%, 25/126) than with TRA (2.7%, 1/37; p = 0.01). Propensity-adjusted analysis (matched for age, sex, aneurysm volume, embolization technique, and sheath size) revealed that TRA was associated with a lower risk of minor ASCs (odds ratio, 0.085; 95% confidence interval 0.0094-0.78; p = 0.029). However, TRA did not differ significantly from TFA with respect to fluoroscopy time, VER, major ASCs, and non-ASCs. CONCLUSIONS: Coil embolization for UIAs via TRA can reduce risk of minor ASCs without increasing the risk of non-ASCs compared with conventional TFA, and can achieve comparable results in term of efficacy and fluoroscopy time.

Thromboelastography 6s for assessment of platelet function during coil embolization of unruptured intracranial aneurysms.

OBJECTIVES: Methods for assessing platelet function in patients with neurovascular disease remain controversial and poorly studied. This study aimed to assess associations between thromboelastography 6s (TEG6s) measurements and postoperative ischemic complications in patients with unruptured intracranial aneurysms (UIAs) treated by coil embolization. METHODS: Eighty-four patients with UIAs taking a combined aspirin and clopidogrel protocol were retrospectively reviewed from January 2021 to May 2022. Blood samples were obtained for TEG6s to assess platelet function on the day of coil embolization. To identify acute ischemic complications, diffusion-weighted imaging (DWI) was performed within 24 h after coil embolization. Multivariate logistic regression analysis was conducted to identify potential risk factors for postoperative positive DWI (DWI (+)) lesions. RESULTS: Forty-three of the 84 patients (51%) with DWI (+) lesions were identified. Compared with patients without DWI (+) lesions, Adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAADP) was significantly higher (53.6 mm [Interquartile range (IQR): 48.3-58.3 mm] vs 46.7 mm [IQR: 36.8-52.2 mm]; p=0.001) and ADP inhibition rate (ADP%) was significantly lower (19% [IQR: 11-31%] vs 31% [IQR: 21-44%]; p=0.001) in DWI (+) patients. Multivariate analysis identified MAADP, ADP%, and procedure time as significant independent predictors of subsequent DWI (+) lesions (odds ratios: 1.07, 0.96, and 1.02, respectively). Based on receiver operating characteristic curve analysis, MAADP >50.9 mm and ADP% <28.8% were associated with postoperative DWI (+) lesions in patients undergoing coil embolization for UIAs. CONCLUSIONS: MAADP and ADP% as assessed by TEG6s can offer reliable parameters to predict postoperative ischemic complications after coil embolization of UIAs. Lower MAADP values and higher ADP% may decrease the risk of postoperative ischemic complications.

Risk factors for recanalization of dense coil packing for unruptured cerebral aneurysms in endovascular coil embolization: Analysis of a single center's experience.

In coil embolization of cerebral aneurysms, inadequate packing is known to increase the probability of recanalization. Even tightly embolized aneurysms may be recanalized, but predictive factors for recanalization have not been fully investigated. This retrospective study aimed to identify risk factors for recanalization of treated aneurysms with a volume embolization ratio (VER) ≥ 25%. A total of 301 unruptured aneurysms in 248 patients who underwent coil embolization between March 2012 and January 2021 were analyzed. Cases involving dissecting aneurysm, intraluminal thrombosis, parent artery occlusion, intraoperative rupture, re-treatment, rupture the day after surgery, postoperative coil migration, and postoperative parent artery occlusion were excluded due to the inaccuracy of VER. A total of 105 aneurysms (34.9%) treated with VER ≥ 25% were extracted. Clinical features (age, sex, medical history, family history), anatomical features (shape, location, aneurysm size, inflow angle, and volume), procedural features (stent-assisted, Raymond-Roy occlusion classification [RROC] immediately after treatment, re-treatment rate), and follow-up period were compared between Recanalization and Non-recanalization groups. Predictors of recanalization were determined using logistic regression and receiver operating characteristic (ROC) curve analyses. Eleven aneurysms were recanalized. In multivariate analysis, RROC class 3 (odds ratio [OR] 11.0; 95% confidence interval [CI] 2.03-59.4) and aneurysm volume (OR 1.005; 95%CI 1.001-1.008) were independent predictors of recanalization. ROC curve analysis showed optimal cutoff values for aneurysm volume of 69.5 mm3 (sensitivity, 81.8%; specificity, 72.3%). In coil embolization of unruptured aneurysms that VER ≥ 25%, cases with RROC class 3 or high aneurysm volume may be associated with a higher risk of recanalization, and should be carefully followed-up.

Critical cerebellar hemorrhage due to pilocytic astrocytoma in a child: A case report.

BACKGROUND: Cerebellar hemorrhage is rare in children, and its cause is usually vascular disorders such as arteriovenous malformations or hematological disorders. CASE DESCRIPTION: A previously healthy 10-year-old girl presented with a loss of consciousness following sudden headache and vomiting. A non-contrast brain computed tomography (CT) scan revealed a massive cerebellar hemorrhage with obstructive hydrocephalus; however, subsequent CT angiography (CTA) showed no vascular abnormalities. An emergency craniotomy was performed to evacuate the hematoma, and histological analysis of the specimen obtained from the tissue surrounding the hematoma revealed a pilocytic astrocytoma (PA). Six months after the ictus, her recovery was scored at 2 on the modified Rankin Scale. CONCLUSION: PA can be a cause of critical cerebellar hemorrhage. In this case of life-threatening massive hematoma, CTA was useful to exclude a major vascular pathology and to save time.

Avoidance and Improvement in Visual Field Defect After Surgery for Metastatic Brain Tumors in the Parietal and the Occipital Lobe.

OBJECTIVE: Visual field defects occasionally occur secondary to tumors in the parietal and the occipital lobes. The aim of this study was to analyze the efficacy of improvement in hemianopsia after surgery for metastatic brain tumors involving or adjacent to the optic radiation (OR). METHODS: The study included 49 patients with brain metastasis in the parietal and occipital lobes in the present study. Preoperative and postoperative neurological assessments included visual field, Mini-Mental State Examination, and Karnofsky performance scale. RESULTS: Of 49 patients, 33 (67.3%) presented with preoperative homonymous hemianopsia. Of these 33 patients, the visual field was improved postoperatively in 17 patients (51.5%). In all patients regardless of preoperative hemianopsia, postoperative visual fields did not deteriorate. Tractography demonstrated that the OR was split by the tumor (n = 6) and fanning of fibers expanded along the lateral side of the tumor (n = 11). All tumors were removed via surgical access toward the medial side of the tumor. Gross total resection was achieved in most tumors in the group with visual improvement (n = 16/17; 94.1%). Improvement in the visual field was attributed to tumor location in the subcortical white matter, removal rate of the tumor, and higher postoperative Karnofsky performance scale score. CONCLUSIONS: The OR tended to deviate to the lateral side of the tumor in the parieto-occipital junction. The postoperative visual field improved even in cases of an occipital tumor. Based on the present study, total resection via an appropriate surgical route should be considered to preserve the OR, leading to improvement in the postoperative visual field.

MRI characteristics of syringomyelia associated with foramen magnum arachnoiditis: differentiation from Chiari malformation.

BACKGROUND: It is important to distinguish foramen magnum arachnoiditis (FMA) from Chiari malformation (CM) before surgery because the operative strategies for these diseases differ. In the current study, we compared pretreatment magnetic resonance imaging (MRI) of FMA with CM and investigated the MRI findings useful to differentiate between these diseases. METHODS: We retrospectively reviewed patients with FMA or CM aged ≥ 18 years who underwent surgeries at our institution between 2007 and 2019. The morphologies of the syrinx, neural elements, and posterior cranial fossa were preoperatively evaluated with MRI. We used the receiver operating characteristic (ROC) curve for the fourth ventricle-to-syrinx distance (FVSD). RESULTS: Ten patients with FMAs and 179 with CMs were included. FVSD in the FMA group was significantly shorter than that in the CM group (7.5 mm [IQR, 2.8-10 mm] in FMA vs. 29.9 mm [IQR, 16.3-52.9 mm] in CM, p < 0.0001). The other MRI findings that showed the height, size, and length of the syrinx; size of the foramen magnum; degree of cerebellar tonsillar descent; shape of the cerebellar tonsil; and dorsal subarachnoid space at the foramen magnum differed significantly between the two groups. The ROC curve analysis showed that patients whose FVSD was less than 11 mm could be diagnosed with FMA with a specificity of 90% and sensitivity of 96%. CONCLUSIONS: A more cranial syrinx development (FVSD < 11 mm) appears to be the characteristic MRI finding in FMA.

Successful Endovascular Trapping for Symptomatic Thrombosed Giant Unruptured Aneurysms of the V1 and V2 Segments of the Vertebral Artery: Case Report and Literature Review.

A thrombosed giant aneurysm of the V1 and V2 segments of the vertebral artery (VA) is rare. Therefore, there is controversy regarding its optimal treatment. A case of a symptomatic giant VA aneurysm located in the V1 to V2 segments on the left treated successfully by endovascular trapping of the VA is reported. A 68-year-old woman presented with swelling in the left anterior neck. Computed tomography angiography (CTA) showed a giant aneurysm measuring 47 × 58 × 47 mm3 in the left neck. Ten days after her first visit, she presented with sudden onset of left anterior neck pain. Repeated CTA showed a partial thrombus in the aneurysm. Angiography showed two thrombosed giant aneurysms located in the V1 to V2 segments of the left VA. After endovascular trapping for the aneurysms, the anterior neck pain resolved and the aneurysm gradually shrank. This case demonstrates that endovascular surgery is better than open surgery because it is less invasive. When performing endovascular treatment, trapping will be an alternative strategy for a symptomatic giant thrombotic aneurysm of the V1 and V2 segments of the VA if the patient can tolerate ischemia.

Alteration of FOXM1 expression and macrophage polarization in refractory meningiomas during long-term follow-up.

Malignant progression of grade I meningioma with a long latency period is rare. We experienced grade II/III meningiomas with refractoriness and recurrence from grade I meningiomas through multiple surgeries. Three patients with atypical/anaplastic meningioma experienced long-latent recurrence after initial surgery for grade I (meningothelial) meningioma without following adjuvant radiotherapy were included in the present study. Histological findings of the initial tumors in all cases (case 1, 2, and 3) revealed meningothelial meningioma with 1%, 5%, and 0.1% MIB-1 positive cells, respectively. Surprisingly, magnetic resonance imaging (MRI) detected a recurrent tumor 2, 12, and 12 years after the initial operation, respectively. Case 1 was atypical meningioma after third recurrence, and case 2 and 3 were anaplastic meningioma after second and third recurrence, respectively. The patient in case 2 received adjuvant radiotherapy. In case 2, the tumor recurred intracranial and distant metastasis to the lung with huge substantial pleural effusion was detected. To investigate the pathogenesis of malignant progression from benign to malignant meningioma, CD163/CD68 expression by immunohistochemically and FOXM1 mRNA expression by RT-PCR were compared using surgical specimens from initial and recurrent tumors in all three patients. The ratio of CD163/CD68 positivity and FOXM1 mRNA expression were increased in recurrent tumors compared with matched initial tumors. CD163 and FOXM1 expression levels were induced even in recurrent grade I meningioma, suggesting that macrophage polarization and pro-mitotic transcriptional factor might be associated with clinical behavior of meningioma and be useful as a prediction marker for malignant progression. Careful long-term follow-up is important for early diagnosis of malignant progression in meningiomas, even if grade I meningioma is completely resected. Development of a multidisciplinary approach including radiation and novel molecular targeted therapy is expected for recurrent and malignant meningiomas.

[Technical "Tips" for Epidural Tenting Using DuraGen® for Surgical Management of Large Dural Defects:A Technical Note].

DuraGen®, an absorbable, engineered collagen-based artificial graft was introduced in Japan in September 2019 for cranial, transsphenoidal, and spinal surgeries. In addition to its efficacy and safety profile, owing to sutureless dural repair, DuraGen® is widely accepted by neurosurgeons. Direct tenting with DuraGen® is occasionally required in patients with large dural defects, particularly in cases of tumors adherent to the dura. To overcome this limitation, we introduced a surgical technique for epidural tenting using DuraGen®. A 78-year-old man with a history of alexia underwent craniotomy for resection of a left temporal lobe metastatic tumor. We completely removed the recurrent tumor, which was strongly adherent to the dura in the middle cranial fossa. A layer of DuraGen® was used as a subdural underlay beneath the autologous dura to close the wide dural defect. To avoid postoperative epidural fluid collection, we retracted the DuraGen® from the epidural aspect and interposed several pieces of muscle, which were sutured on the subdural aspect to ensure that the muscle pieces securely plugged the dural defect. We placed an additional overlay of DuraGen® along the autologous dura. The patient's postoperative course was uneventful without cerebrospinal fluid leakage, tension pneumocephalus, or wound infection. Reoperations for tumor resection, particularly surgical procedures for refractory meningiomas and malignant tumors cause increasing fragility and wide defects of the dura. DuraGen® placement enables sutureless closure and is less time-consuming. Our technique of epidural direct tenting with DuraGen® using muscle pieces sutured on the subdural aspect could be useful in patients with significantly large dural defects and can prevent postoperative epidural fluid collection to ensure complete dural sealing.

IgG4-Related Disease in the Frontal Convexity Concomitant with Smoldering Multiple Myeloma: A Case Report and Review of the Literature Regarding Therapeutic Implications.

BACKGROUND: We have reported an extremely rare case of a frontal convexity tumor diagnosed as IgG4-related disease (IgG4-RD) with unique neuroradiological images. CASE DESCRIPTION: A 64-year-old man with a history of monoclonal gammopathy of undetermined significance and conservative treatment had presented with a left facial spasm. Computed tomography showed a high-density round tumor with perifocal edema in the right frontal convexity. Magnetic resonance imaging demonstrated unique findings, including low signal intensity on T1- and T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images, with slight gadolinium enhancement. The tumor was totally removed via right frontal craniotomy. It had been located in the subdural space, was not adherent to the dura, and was less vascular than meningiomas. Histological investigation demonstrated plasma cells that were strongly positive for IgG4 and contained κ and λ light chains at a ratio of 1.5:1. The serum IgG4 level was elevated. The tumor met the diagnostic criteria for IgG4-RD. The patient was followed up for 3 years during postoperative adjuvant steroid therapy. The steroid therapy was discontinued, and during the next 4 years, neither tumor recurrence nor symptoms were observed. CONCLUSION: Intracranial IgG4-RD with smoldering monoclonal gammopathy of undetermined significance is extremely rare. We reviewed the differential diagnosis of plasma cell granuloma and plasmacytoma, therapeutic implications, and clinical outcomes. Complete resection of a conspicuous and solitary IgG4-RD lesion in the frontal convexity is simple and could provide a cure with less-aggressive adjuvant therapy.

Rapid Recurrence and Anaplastic Transformation of a Pilocytic Astrocytoma in an Elderly Patient: Case Report and Review of the Literature.

BACKGROUND: Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported. CASE DESCRIPTION: An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histologic examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was <1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, magnetic resonance imaging showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histologic findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed. CONCLUSIONS: It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy. A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.

Chronic Encapsulated Expanding Thalamic Hematoma Associated with Obstructive Hydrocephalus following Radiosurgery for a Cerebral Arteriovenous Malformation: A Case Report and Literature Review.

Chronic encapsulated intracerebral hematoma is a unique type of intracerebral hematoma accompanied by a capsule that is abundant in fragile microvasculature occasionally causing delayed regrowth. A 37-year-old man who had undergone radiosurgery for an arteriovenous malformation (AVM) causing intracerebral hematoma in the left parietal lobe presented with headache, vomiting, and progressive truncal ataxia due to a cystic lesion that had been noted in the left thalamus, leading to progressive obstructive hydrocephalus. He underwent left frontal craniotomy via a transsylvian fissure approach, and the serous hematoma was aspirated. The hematoma capsule was easy to drain and was partially removed. Pathological findings demonstrated angiomatous fibroblastic granulation tissue with extensive macrophage invasion. The concentration of vascular endothelial growth factor (VEGF) was high in the hematoma (12012 pg/mL). The etiology and pathogenesis of encapsulated hematoma are unclear, but the gross appearance and pathological findings are similar to those of chronic subdural hematoma. Based on the high concentration of VEGF in the hematoma, expansion of the encapsulated hematoma might have been caused by the promotion of vascular permeability of newly formed microvasculature in the capsule.