A case of immunocompetent intracranial cryptococcoma in which intraoperative rapid pathological diagnosis and polymerase chain reaction led to early treatment: What to know to avoid misdiagnosis as brain tumor.

Background: Cryptococcal infections of the central nervous system are infrequent in immunocompetent hosts and usually present as meningitis. However, a fungal mass called a cryptococcoma may form, requiring caution in therapeutic intervention. Here, we report a rare case in which treatment of intraventricular cryptococcoma in an immunocompetent patient was facilitated by rapid pathological diagnosis. Case Description: A 58-year-old previously healthy man was admitted to our hospital with fever, headache, and gradually worsening hearing loss over 1 month. Cerebrospinal fluid analysis showed moderately elevated levels of protein and lymphocytic cells and decreased glucose. In addition, ß2-microglobulin was highly elevated. Magnetic resonance imaging showed homogeneously enhanced lesions in lateral ventricles of the left and right hemispheres and the subarachnoid space, and 18F-fluorodeoxyglucose positron emission tomography revealed abnormal uptake corresponding to the lesion. A surgical excision was performed to achieve a definitive diagnosis. Intraoperative rapid pathology, including immunohistochemistry (IHC), yielded negative results for malignant tumor, suggesting the possibility of inflammatory granuloma. Additional targeted pathological diagnosis was immediately performed. Paraffin-embedded histopathological examination showed fibrocaseous granuloma and numerous fungal spores. Cryptococcus neoformans within the granuloma were suggested by Fontana-Masson and Grocott staining and confirmed by polymerase chain reaction (PCR), leading to a diagnosis of cryptococcoma. Antifungal agents were started 3 days postoperatively. The patient has since been doing well, with no recurrence. Conclusion: This pathology can be difficult to distinguish from a brain tumor, so early pathological diagnosis, including rapid pathology with IHC and PCR, may be crucial.

Optimal treatment strategy for low-grade spinal cord astrocytoma: a retrospective, multicenter analysis by the Neurospinal Society of Japan.

OBJECTIVE: Primary spinal cord gliomas are rare, and among these astrocytomas (WHO grade II) are much rarer. The optimal treatment strategy thus remains unclear. The authors conducted a multicenter study led by the Neurospinal Society of Japan (NSJ) to analyze treatment policies and outcomes. The aim was to present optimal treatment methods for spinal cord astrocytoma and to identify predictors of better outcomes. METHODS: Among 1033 consecutive cases of spinal cord intramedullary tumors treated surgically at 58 centers affiliated with the NSJ, 57 patients were diagnosed with diffuse astrocytoma (WHO grade II) and were enrolled in the present study. Among these 57 patients, treatment methods, outcomes, and tumor proliferation rate as evaluated by the MIB-1 staining index (SI) were analyzed, and the optimal treatment method for spinal cord astrocytomas (grade II) was determined. In addition, the authors searched for factors predicting better treatment outcomes. RESULTS: Treatment for spinal cord astrocytoma comprised three methods: surgery alone in 30 patients, adjuvant radiation therapy in 13 patients, and adjuvant chemoradiotherapy in 13 patients. One patient who did not undergo surgery was excluded from survival analysis. Treatment with surgery alone or surgery with radiotherapy was associated with significantly longer overall and progression-free survivals than that with adjuvant chemoradiotherapy. Patients treated with radiation therapy had a higher MIB-1 SI than those treated with surgery alone. The extent of tumor resection tended to correlate with longer survival. In contrast, postoperative neurological worsening showed the inverse order. Adjuvant chemoradiotherapy was associated with the shortest survival in both total cases and recurrent cases. The optimal cutoff value of MIB-1 SI for predicting longer survival by surgery alone was less than 4.0%. CONCLUSIONS: The optimal treatment for spinal cord astrocytoma is maximal tumor resection without neurological impairment. When some tumor remains in patients with an MIB-1 SI less than 4.0%, a wait-and-see approach is optimal. If the MIB-1 SI is higher than 4.0%, local radiation therapy is recommended. Adjuvant chemotherapy is not recommended for the treatment of grade II spinal cord astrocytoma.

Prediction of hepatocellular carcinoma in patients with Fontan-associated liver disease using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid magnetic resonance imaging.

AIM: The unique feature of Fontan circulation is elevated central venous pressure, which causes Fontan-associated liver disease (FALD). FALD is associated with a high incidence of hepatocellular carcinoma (HCC). Performing biopsies in patients with FALD is difficult as a result of warfarinization; gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), a noninvasive examination, is useful for characterizing liver disease and detecting HCC. However, few studies have reported the detailed features of Gd-EOB-DTPA MRI, and the association between these findings and prognosis. Thus, this study aimed to investigate the utility of Gd-EOB-DTPA MRI to predict HCC development in patients with FALD. METHODS: This study enrolled 44 patients with FALD (mean age 25 years) who underwent Gd-EOB-DTPA MRI. The hepatobiliary phase images were scored semiqualitatively, and the patients were classified into the mild (0-1 point) or severe group (≥2 points). The endpoint was HCC, and event-free survival was analyzed using Kaplan-Meier and log-rank tests. RESULTS: The severe group included 19 patients. During a mean follow-up of 58 months, HCC developed in six patients. Kaplan-Meier analysis revealed that patients in the severe group had a significantly poorer prognosis than those in the mild group (p = 0.0053). The Fibrosis-4 index and liver-to-spleen ratio of patients with HCC were moderate. CONCLUSIONS: Gd-EOB-DTPA MRI can be used to classify disease severity and predict the prognosis of patients with FALD.

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.

Reliable intraoperative diagnostic methods for PCNSL: utility of combining intraoperative immunohistochemistry, cytology, and flow cytometry in achieving optimal treatment.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rapidly growing malignant tumor that typically shows sensitivity to high-dose methotrexate-based chemotherapy. Rapid diagnosis and early chemotherapy are thus essential to obtain the best outcome. To accomplish this, we have performed intraoperative rapid immunohistochemistry (IHC) as an examination method for obtaining accurate diagnosis during surgery. Here, to markedly enhance the accuracy of intraoperative rapid IHC, the utility of adding intraoperative rapid examinations of cytology and flow cytometry (FCM) in addition to rapid IHC was investigated. METHODS: From April 2020 to January 2024, we performed intraoperative rapid IHC in 35 patients with intracranial lesions, including PCNSL. In the last 17 of these cases, intraoperative cytology and FCM were also performed simultaneously. We examined the utility of examination methods in determining treatment strategies for brain tumors, particularly early therapeutic intervention for PCNSL. RESULTS: Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: 20 PCNSLs, 9 glioblastomas, 4 diffuse gliomas, 1 meningioma, and 1 inflammatory disorder. In all cases, results from intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In two cases, results from conventional intraoperative rapid pathological diagnoses based on morphological assessments using frozen sections changed with the addition of intraoperative rapid IHC. Further, the time from surgery to initiation of chemotherapy for PCNSL was significantly reduced by adding cytology and FCM to rapid IHC alone (only rapid IHC group: 7.3 days, combination group: 1.6 days; p = 0.015). CONCLUSIONS: The combination of rapid intraoperative IHC, cytology, and FCM contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. These examination methods may allow new therapeutic strategies for not only PCNSL, but also other brain tumors.

Gated SPECT-Derived Myocardial Strain Estimated From Deep-Learning Image Translation Validated From N-13 Ammonia PET.

RATIONALE AND OBJECTIVES: This study investigated the use of deep learning-generated virtual positron emission tomography (PET)-like gated single-photon emission tomography (SPECTVP) for assessing myocardial strain, overcoming limitations of conventional SPECT. MATERIALS AND METHODS: SPECT-to-PET translation models for short-axis, horizontal, and vertical long-axis planes were trained using image pairs from the same patients in stress (720 image pairs from 18 patients) and resting states (920 image pairs from 23 patients). Patients without ejection-fraction changes during SPECT and PET were selected for training. We independently analyzed circumferential strains from short-axis-gated SPECT, PET, and model-generated SPECTVP images using a feature-tracking algorithm. Longitudinal strains were similarly measured from horizontal and vertical long-axis images. Intraclass correlation coefficients (ICCs) were calculated with two-way random single-measure SPECT and SPECTVP (PET). ICCs (95% confidence intervals) were defined as excellent (≥0.75), good (0.60-0.74), moderate (0.40-0.59), or poor (≤0.39). RESULTS: Moderate ICCs were observed for SPECT-derived stressed circumferential strains (0.56 [0.41-0.69]). Excellent ICCs were observed for SPECTVP-derived stressed circumferential strains (0.78 [0.68-0.85]). Excellent ICCs of stressed longitudinal strains from horizontal and vertical long axes, derived from SPECT and SPECTVP, were observed (0.83 [0.73-0.90], 0.91 [0.85-0.94]). CONCLUSION: Deep-learning SPECT-to-PET transformation improves circumferential strain measurement accuracy using standard-gated SPECT. Furthermore, the possibility of applying longitudinal strain measurements via both PET and SPECTVP was demonstrated. This study provides preliminary evidence that SPECTVP obtained from standard-gated SPECT with postprocessing potentially adds clinical value through PET-equivalent myocardial strain analysis without increasing the patient burden.

Right Ventricular Strain With 4-Dimensional Computed Tomography Identifies Pulmonary Hypertension in Adults With Repaired Tetralogy of Fallot.

BACKGROUND: This study evaluated right ventricular (RV) volume, strain, and morphology using cardiac 4-dimensional computed tomography (4D-CT) to detect pulmonary hypertension (PH) in adults with repaired tetralogy of Fallot (TOF) scheduled for transcatheter pulmonary valve implantation (TPVI). METHODS AND RESULTS: Using cardiac 4D-CT data, we calculated RV strain in 3 different geometries and RV outflow tract (RVOT) mass in 42 patients with repaired TOF. We compared RV strain and RVOT mass between patients with and without PH. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance of these measurements for identifying PH. Four-chamber (4ch) strain was significantly smaller for patients with (n=10) than without (n=32) PH (8.8±1.7% vs. 11.1±2.4%, respectively; P<0.01), whereas RVOT mass was significantly larger in the PH group (12.5±3.5 vs. 9.2±3.2 cm2; P<0.01). ROC analysis of the diagnostic performance revealed that the respective sensitivity and specificity was 70% and 84% (area under the curve [AUC]=0.784) for 4ch strain of 8.8%; 80% and 69% (AUC=0.766) for RVOT mass of 10.7 cm2; and 80% and 81% (AUC=0.844) for a 4ch strain/RVOT mass ratio of 0.97. CONCLUSIONS: RVOT mass and 4ch strain obtained from cardiac 4D-CT may be helpful for identifying PH in patients with repaired TOF.

Transarterial and Transvenous Approach for the Embolization of Arteriovenous Fistula between the Hepatic Arteries and Inferior Vena Cava Associated with Liver Abscess Due to Cholangitis.

An 87-year-old woman was hospitalized for liver abscesses and cholangitis due to common bile duct stones. She developed worsening anemia and abdominal pain. Contrast-enhanced computed tomography revealed an intrahepatic pseudoaneurysm and an arteriovenous fistula between the hepatic arteries and inferior vena cava. The initial endovascular treatment was transarterial embolization. The pseudoaneurysm was embolized with an N-butyl-2-cyanoacrylate mixture, and the inflow arteries of the arteriovenous fistula were embolized with microcoils. However, the residual perfusion of the arteriovenous fistula remained. A second endovascular treatment was performed using the transarterial and transvenous approaches. The inflow arteries were embolized using microcoils and gelatin sponges and the dominant outflow vein was embolized using microcoils, resulting in the disappearance of the perfusion in the arteriovenous fistula.

Glucose metabolic rate from four-dimensional [18F]FDG PET/CT to differentiate sarcoid lesions from malignant lesions.

OBJECTIVES: On 18F-Fludeoxyglucose (FDG) PET/CT, active sarcoid lesions are often difficult to differentiate from malignant lesions. We investigated the potential of the glucose metabolic rate (MRglc, mg/min/100 mL), a new quantification of glucose metabolic kinetics derived from direct reconstruction based on linear Patlak analysis, to distinguish between sarcoidosis and malignant lesions. MATERIALS AND METHODS: A total of 100 patients with cardiac sarcoidosis (CS) and 67 patients with cancer who underwent four-dimensional FDG PET/CT were enrolled. The lesions with a standardized uptake value (SUV) ≥ 2.7 on the standard scan were included as active lesions in the analysis. SUV and MRglc were derived using data acquired between 30 min and 50 min on four-dimensional FDG PET/CT. The mean value in the volume of interest (size 1.5 cm3) was measured. The diagnostic performance of sarcoidosis using MRglc and SUV was evaluated using receiver-operating-characteristic (ROC) analysis. RESULTS: A total of 90 sarcoidosis lesions from 44 CS patients (18 males, 63.4 ± 12.2 years) and 87 malignant lesions from 57 cancer-bearing patients (32 males, 65 ± 14 years) were analyzed. SUV and MRglc for sarcoid lesions were significantly lower than those for malignant lesions (SUV, 4.98 ± 2.00 vs 6.21 ± 2.14; MRglc, 2.52 ± 1.39 vs 3.68 ± 1.61; p < 0.01). ROC analysis indicated that the ability to discriminate sarcoid patients from those with malignancy yielded areas under the curves of 0.703 and 0.754, with sensitivities of 64% and 77% and specificities of 75% and 72% for SUV 5.025 and MRglc 2.855, respectively. CONCLUSION: MRglc was significantly lower in sarcoid lesions than malignant lesions, and improved sarcoid lesions identification over SUV alone. CLINICAL RELEVANCE STATEMENT: MRglc improves sarcoid lymph node identification over SUV alone and is expected to shorten the examination time by eliminating delayed scans. KEY POINTS: Active sarcoid lesions are sometimes associated with FDG accumulation and should be differentiated from malignant lesions. SUV and metabolic rate of glucose (MRglc) strongly positively correlated, and MRglc could differentiate sarcoid and malignant lesions. MRglc allows for accurate evaluation and staging of malignant lesions.

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.

Prediction of cardiac allograft vasculopathy using splenic switch-off on myocardial PET.

BACKGROUND: Heart transplantation (HTx) is a definitive therapy for refractory heart failure. Cardiac allograft vasculopathy (CAV), characterized by diffuse arteriopathy involving the epicardial coronary arteries and microvasculature, is the major cause of death for patients with HTx. 13N-ammonia positron emission tomography (NH3-PET) can offer diagnostic and prognostic utility for CAV. The splenic switch-off (SSO) detected in NH3-PET is a hemodynamic indicator of favorable response to adenosine. We hypothesized that both CAV and SSO reflected a pathology that progresses in parallel with systemic vascular endothelial dysfunction. Therefore, we quantitatively evaluated splenic adenosine reactivity measured using NH3-PET as an index of endothelial function, and examined its predictability for CAV. METHODS: Forty-eight patients who underwent NH3-PET after HTx were analyzed. The spleen ratio was calculated as the mean standardized uptake value, measured by placing an ROI on the spleen, at stress divided by that at rest. SSO was defined by a cutoff determined using receiver operating characteristic (ROC) analysis for the spleen ratio. The endpoint was appearance or progression of CAV. Predictability of SSO was analyzed using Kaplan-Meier analysis. RESULTS: The endpoint occurred in 9 patients during a mean follow-up of 45 ±â€¯17 months. ROC curve analysis demonstrated a cutoff of 0.94 for spleen ratio. Patients without SSO displayed a significantly higher CAV rate than those with SSO (p = 0.022). CONCLUSIONS: SSO reflects the endothelial function of systemic blood vessels and was a predictor of CAV in patients with HTx.

An extremely rare case of primary alveolar rhabdomyosarcoma in the central nervous system.

Background: Alveolar rhabdomyosarcoma (ARMS) shows a predilection for the peripheral extremities and is very rarely identified as a primary in the brain. Here, we report a case of ARMS with multiple lesions exclusively within the central nervous system (CNS). Case Description: A 20-year-old man presented to our hospital with a gradually increasing headache and disturbance of consciousness. Neuroimaging showed hydrocephalus and multiple tumor lesions, including in the brainstem and cerebellum, with uniform gadolinium enhancement on T1-weighted magnetic resonance imaging, as well as spinal cord seeding. Cerebrospinal fluid (CSF) analysis showed a slightly elevated cell count (6/µL; normal, <5/µL) and highly elevated protein (153 mg/dL). In addition, atypical cells were cytologically identified in the CSF. No other laboratory findings were abnormal. Emergency ventricular drainage was performed to control cerebral pressure, followed by a biopsy to confirm the diagnosis. Histological examination revealed a fascicular arrangement of oval cells with eosinophilic cytoplasm and tumor cells with pleomorphic nuclei and prominent nucleoli. Immunohistochemical studies showed negative results for glial fibrillary acidic protein and positive results for desmin and myogenin. In addition, molecular analysis revealed that this tumor had the H3F3A p.Lys28Met mutation and no paired box (PAX)3-forkhead box O1 (FOXO1) or PAX7-FOXO1 fusion genes. ARMS was, therefore, diagnosed. Chemotherapy and radiotherapy were subsequently initiated, but tumor growth could not be controlled, and the patient died 6 months after surgery. Conclusion: This report describes an extremely rare case of ARMS arising exclusively within the CNS.

Berberine as a potential enhancer for 5-ALA-mediated fluorescence in glioblastoma: increasing detectability of infiltrating glioma stem cells to optimize 5-ALA-guided surgery.

OBJECTIVE: The prognosis of glioblastoma (GBM) correlates with residual tumor volume after surgery. In fluorescence-guided surgery, 5-aminolevulinic acid (ALA) has been used to maximize resection while avoiding neurological morbidity. However, not all tumor cells, particularly glioma stem cells (GSCs), display 5-ALA-mediated protoporphyrin IX (PpIX) fluorescence (5-ALA fluorescence). The authors searched for repositioned drugs that affect mitochondrial functions and energy metabolism, identifying berberine (BBR) as a potential enhancer of 5-ALA fluorescence. In this study, they investigated whether BBR can enhance 5-ALA fluorescence in GSCs and whether BBR can be applied to clinical practice as a 5-ALA fluorescence enhancer. METHODS: The effects of BBR on 5-ALA fluorescence in glioma and GSCs were evaluated by flow cytometry (fluorescence-activated cell sorting [FACS]) analysis. As 5-ALA is metabolized for heme synthesis, the effects of BBR on mRNA expressions of 7 enzymes in the heme-synthesis pathway were analyzed. Enzymes showing significantly higher expression than control in all cells were identified and protein analysis was performed. To examine clinical availability, the detectability and cytotoxicity of BBR in tumor-transplanted mice were analyzed. RESULTS: Fluorescence microscopy revealed much more intense 5-ALA fluorescence in both GSCs and non-stem cells with 5-ALA and BBR than with 5-ALA alone. FACS showed that BBR greatly enhanced 5-ALA fluorescence compared with 5-ALA alone, and enhancement was much higher for GSCs than for glioma cells. Among the 7 enzymes examined, BBR upregulated mRNA expressions of ALA synthetase 1 (ALAS1) more highly in all cells, and activated ALAS1 through deregulating ALAS1 activity inhibited by the negative feedback of heme. An in vivo study showed that 5-ALA fluorescence with 5-ALA and BBR was significantly stronger than with 5-ALA alone, and the sensitivity and specificity of BBR-enhanced fluorescence were both 100%. In addition, BBR did not show any cytotoxicity for normal brain tissue surrounding the tumor mass. CONCLUSIONS: BBR enhanced 5-ALA-mediated PpIX fluorescence by upregulating and activating ALAS1 through deregulation of negative feedback inhibition by heme. BBR is a clinically used drug with no side effects. BBR is expected to significantly augment fluorescence-guided surgery and photodynamic therapy.

Essentials for early diagnosis of primary intramedullary spinal cord lymphoma. How to suspect primary intramedullary spinal cord lymphoma early and proceed to invasive biopsy? A case report and literature review.

Background: Primary intramedullary spinal cord lymphoma (PISCL) is an extremely rare condition. Early diagnosis is very difficult due to the nonspecific clinical and imaging findings. A biopsy is essential for a definitive diagnosis, but courage is required to perform the surgery. Here, we present a case of PISCL and suggest useful indicators for accurate diagnosis of this pathological entity. Case Description: A 70-year-old woman presented with subacute bilateral lower-limb paralysis, disturbance of warm and pain sensations, and vesicorectal disturbance. Magnetic resonance imaging showed a contrast-enhanced mass from C7 to Th2 and large, edematous lesions from the upper cervical to lower thoracic spinal cord. Elevated uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) was identified in the enhanced regions on FDG-positron emission tomography (PET). Cerebrospinal fluid (CSF) analysis revealed highly elevated levels of ß2-microglobulin (ß2-MG). Steroid pulse therapy and therapeutic plasma exchange were performed for suspected myelitis, but symptoms did not improve. Spinal cord biopsy was, therefore, performed for treatment-resistant myelopathy. Histopathological examination revealed diffuse large B-cell lymphoma, which was diagnosed as PISCL because systemic examination showed no other findings suggestive of malignant lymphoma. Conclusion: In cases with poor response to treatment and a progressive course, PISCL should be considered, and spinal cord biopsy should be performed if PET shows increased 18F-FDG uptake and ß2-MG is elevated in CSF.

[A New Preoperative Simulation Using Magnetic Resonance Imaging Bone-Like Imaging with Zero-Echo-Time Sequence].

This study aimed to evaluate the clinical usefulness of zero-echo time(ZTE)-based magnetic resonance imaging(MRI)in planning an optimal surgical approach and applying ZTE for anatomical guidance during transcranial surgery. P atients who underwent transcranial surgery and carotid endarterectomy and for whom ZTE-based MRI and magnetic resonance angiography(MRA)data were obtained, were analyzed by creating ZTE/MRA fusion images and 3D-ZTE-based MRI models. We examined whether these images and models could be substituted for computed tomography imaging during neurosurgical procedures. Furthermore, the clinical usability of the 3D-ZTE-based MRI model was evaluated by comparing it with actual surgical views. ZTE/MRA fusion images and 3D-ZTE-based MRI models clearly illustrated the cranial and intracranial morphology without radiation exposure or the use of an iodinated contrast medium. The models allowed the determination of the optimum surgical approach for cerebral aneurysms, brain tumors near the brain surface, and cervical internal carotid artery stenosis by visualizing the relationship between the lesions and adjacent bone structures. However, ZTE-based MRI did not provide useful information for surgery for skull base lesions, such as vestibular schwannoma, because bone structures of the skull base often include air components, which cause signal disturbances in MRI. ZTE sequences on MRI allowed distinct visualization of not only the bone but also the vital structures around the lesion. This technology is minimally invasive and useful for preoperative planning and guidance of the optimum approach during surgery in a subset of neurosurgical diseases.

Role of amide proton transfer imaging in maximizing tumor resection in malignant glioma: a possibility to take the place of 11C-methionine positron emission tomography.

BACKGROUND: Amide proton transfer (APT) imaging has been proposed as a technique to assess tumor metabolism. However, the relationship between APT imaging and other quantitative modalities including positron emission tomography (PET) has not been investigated in detail. This study aimed to evaluate the clinical usefulness of APT imaging in determining the metabolic status of malignant glioma and to compare findings with those from 11C-methionine (Met)-PET. METHODS: This research analyzed APT imaging data from 20 consecutive patients with malignant glioma treated between January 2022 and July 2023. Patients underwent tumor resection and correlations between tumor activity and intensity of APT signal were investigated. We also compared 11C-Met-PET and APT imaging for the same regions of the perifocal tumor invasion area. RESULTS: Clear, diagnostic APT images were obtained from all 20 cases. Mean APT intensity (APTmean) was significantly higher in the glioblastoma (GBM), IDH wild type group (27.2 ± 12.8%) than in other gliomas (6.0 ± 4.7%; p < 0.001). The cut-off APTmean to optimally distinguish between GBM and other malignant gliomas was 12.8%, offering 100% sensitivity and 83.3% specificity. These values for APTmean broadly matched the tumor-to-contralateral normal brain tissue ratio from 11C-Met-PET analysis (r = 0.66). The APT signal was also observed in the gadolinium non-contrast region on T1-weighted imaging, appearing to reflect the surrounding tumor-infiltrated area. CONCLUSIONS: APT imaging can be used to evaluate the area of tumor invasion, similar to 11C-Met-PET. APT imaging revealed low invasiveness in patients and was useful in preoperative planning for tumor resection, facilitating maximum tumor resection including the tumor invasive area.

A Narrative Review on CD44's Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence.

High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5-2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-ß, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5-5% O2) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence.

Identification of CD44 as a Reliable Biomarker for Glioblastoma Invasion: Based on Magnetic Resonance Imaging and Spectroscopic Analysis of 5-Aminolevulinic Acid Fluorescence.

Recurrent glioblastoma multiforme (GBM) is largely attributed to peritumoral infiltration of tumor cells. As higher CD44 expression in the tumor periphery correlates with higher risk of GBM invasion, the present study analyzed the relationship between CD44 expression and magnetic resonance imaging (MRI)-based invasiveness of GBM on a large scale. We also quantitatively evaluated GBM invasion using 5-aminolevulinic acid (5-ALA) spectroscopy to investigate the relationship between CD44 expression and tumor invasiveness as evaluated by intraoperative 5-ALA intensity. Based on MRI, GBM was classified as high-invasive type in 28 patients and low-invasive type in 22 patients. High-invasive type expressed CD44 at a significantly higher level than low-invasive type and was associated with worse survival. To quantitatively analyze GBM invasiveness, the relationship between tumor density in the peritumoral area and the spectroscopic intensity of 5-ALA was investigated. Spectroscopy showed that the 5-ALA intensity of infiltrating tumor cells correlated with tumor density as represented by the Ki-67 staining index. No significant correlation between CD44 and degree of 5-ALA-based invasiveness of GBM was found, but invasiveness of GBM as evaluated by 5-ALA matched the classification from MRI in all except one case, indicating that CD44 expression at the GBM periphery could provide a reliable biomarker for invasiveness in GBM.

Perioperative perampanel administration for early seizure prophylaxis in brain tumor patients.

Background: The efficacy of perioperative prophylactic antiepileptic drug therapy in "seizure-naïve" patients with brain tumor, including glioblastoma (GBM), remains controversial. This study investigated whether perampanel (PER) is effective and safe for preventing perioperative onset of epileptic seizures, so-called early seizure, in patients with brain tumors. Methods: Forty-five patients underwent tumor resection through craniotomy for a primary supratentorial brain tumor at Ehime University Hospital between April 2021 and July 2022. PER was administered from the 1st to the 6th day after surgery for seizure prophylaxis. Occurrence of early seizure, hematological toxicities, and various side effects were recorded on postoperative days 7 and 14. In addition, the clinical course of these patients was compared with 42 brain tumor patients under the same treatment protocol who received levetiracetam (LEV) for seizure prophylaxis between April 2017 and October 2018. Results: In 45 patients with brain tumor, including GBM, who received PER administration, no early seizures were identified within 7 days postoperatively. No adverse drug reactions such as hematological toxicity, liver or kidney dysfunction, or exanthematous drug eruption were observed in any cases. As side effects, somnolence was reported in 14 patients (31.1%), vertigo in 3 patients (6.7%), and headache in 3 patients (6.7%). Although somnolence and vertigo were difficult to assess in the case of intraparenchymal tumors, particularly GBM, these side effects were not identified in patients with extraparenchymal tumors such as meningiomas, epidermoid cysts, and pituitary adenomas. In addition, no significant differences were identified compared to patients who received LEV. Conclusion: The efficacy and safety of PER in preventing early seizures among patients with brain tumors were retrospectively evaluated. Perioperative administration of PER to patients with brain tumors may reduce the risk of early seizures without incurring serious side effects, showing no significant differences compared to patients who received LEV.