A Perspective on the 6th International Conference on Sports Concussion.

The International Conference on Sports Concussion, held every four years since 2001, has been instrumental in forming the international consensus on sports-related concussions. However, due to the unprecedented global pandemic of COVID-19, not only the Tokyo Olympics 2020, but also the initially scheduled sixth conference was postponed multiple times. Finally, the 6th International Conference on Sports Concussion took place in Amsterdam at the end of October 2022. In July 2023, the Amsterdam Declaration, reflecting the outcomes of this sixth conference, was released. This paper provides an overview of the conference, in which significant updates were revealed and introduced, including revisions to the definition of sports-related concussions, as well as the latest version of the Sports Concussion Assessment Tool (SCAT), known as SCAT6, the Office Assessment Tool (SCOAT), and the updated staged return-to-play protocol.

Comparative Study of Postmortem MRI and Pathological Findings in Malignant Brain Tumors.

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.

Evaluation of Treatment Strategies for Male Prolactin-Secreting Pituitary Neuroendocrine Tumors.

Prolactin-secreting pituitary neuroendocrine tumors (PitNETs) are more common in women. Male patients may also have few symptoms and have macroadenomas extending outside the sella turcica. This study aimed to report the results of cabergoline treatment in male patients with prolactin-secreting PitNET. The study included nine male patients aged 26-65 years (median, 46 years) diagnosed with prolactin-secreting PitNETs. The age at onset, prolactin values, tumor size, symptoms, and treatment were assessed. The mean prolactin value at the initial presentation was 2734.6 ng/mL, and the mean maximum tumor diameter was 40.4 mm. Visual field disturbance was the most common symptom (44.4%), followed by headaches (33.3%), asymptomatic symptoms (11.1%), and galactorrhea (11.1%). Eight patients responded to cabergoline treatment with normalization of prolactin levels and tumor shrinkage. One patient did not respond to the cabergoline treatment and required surgical intervention. There were no cases of cerebrospinal fluid leakage. Cabergoline was found to be an effective treatment for male prolactin-secreting PitNETs.

Predictive Value of Acute Neurological Progression Using Bayesian CT Perfusion for Acute Ischemic Stroke with Large or Median Vessel Occlusion.

Objective: Since the efficacy of mechanical thrombectomy (MT) for acute cerebral infarction due to large vessel occlusion has been proven, the time available for treatment has gradually increased. Currently, under certain conditions, treatment is indicated up to 24 h from onset. Based on neurological signs and imaging diagnosis, Stroke Treatment Guideline 2021 recommends initiation of MT within 6-24 h from onset. Herein, we retrospectively investigated the relationship between cerebral perfusion imaging evaluation and prognosis in patients with acute cerebral infarction due to large or median vessel occlusion. Methods: Fifty-one patients diagnosed with acute cerebral infarction due to large or median vessel occlusions in anterior circulation between November 2019 and December 2021 were divided into medical care and reconstructive therapy (including tissue plasminogen activator [t-PA] therapy and MT) groups. The primary outcome was changes in the National Institutes of Health Stroke Scale (NIHSS) at admission and 1 week after onset. Patients in the medical care group were divided into those whose NIHSS did not worsen and those whose NIHSS worsened. Those in the reconstructive therapy group were divided into those whose NIHSS improved and those whose NIHSS did not improve. We evaluated the relationship between improvement factors in acute neurological symptoms and penumbral and core volumes from computed tomography perfusion performed at admission. Results: Of 45 eligible patients, 10 received medical care without t-PA or MT and 35 underwent reconstructive therapy, including t-PA and MT. Among the 10 patients in the medical care group, 3 had worsening symptoms and 7 did not. The mean and median (interquartile range [IQR]) penumbra volumes were significantly higher in patients with worsening symptoms than in those without. The receiver operating characteristic (ROC) curve showed a threshold value of 28.6 mL with an area under the curve (AUC) of 0.952. Among the 35 patients in the reconstructive therapy group, symptoms improved for 29 but did not improve for 6. The mean and median (IQR) core volumes were significantly higher in patients whose symptoms did not improve than in those whose symptoms improved. The ROC curve showed a threshold value of 25 mL and an AUC of 0.632. Conclusion: Evaluation of penumbra volumes could detect cases with worsening symptoms in cases where medical care was performed, and evaluation of core volumes may detect cases with non-improved symptoms in cases that received reconstructive therapy.

Genetic and Lineage Classification of Glioma-Initiating Cells Identifies a Clinically Relevant Glioblastoma Model.

The Cancer Genome Atlas (TCGA) project described a robust gene expression-based molecular classification of glioblastoma (GBM), but the functional and biological significance of the subclasses has not been determined. The present comprehensive analysis of 25 glioma-initiating cell (GIC) lines classifies GIC lines into four subtypes (classical, mesenchymal, proneural, and neural) that are closely related to the TCGA GBM subclasses and display distinct lineage characteristics and differentiation behavior that recapitulate neural development. More importantly, the GIC subtypes exhibit distinct biological phenotypes in relation to self-renewal capacity, proliferation, invasiveness, and angiogenic potential in vitro and in vivo. In addition, the GIC subtypes exhibit divergent patterns of signaling pathway activation and deactivation of the Wnt, Notch, and TGF-ß pathways. These results will improve drug discovery targeting certain genetic mutation in glioblastoma and improve the development of precision medicine.

Effect of Notch expression in glioma stem cells on therapeutic response to chemo-radiotherapy in recurrent glioblastoma.

Glioma stem cells (GSCs) have the capacity to repopulate tumors and mediate resistance to radiotherapy and chemotherapy. The Notch signaling pathway is important in proliferation, stem cell maintenance, cell differentiation, and tumorigenesis in GSCs. In this study, we compared CD133, Notch, and VEGF expressions in histological sections of primary and recurrent glioblastomas after radiotherapy and chemotherapy. In vitro study, the γ-secretase inhibitor inhibited NICD, Hes1 and pVEGFR2 expressions in GSCs. GSCs cultured under endothelial conditions undergo endothelial differentiation. Tumor samples were collected from 27 patients at the time of tumor recurrence. We used immunohistochemical techniques to compare expression of CD133, Notch-1 and VEGF. Expressions of CD133-, Notch-1-, and VEGF-positive glioma cells were higher in recurrent glioblastoma after radiotherapy and chemotherapy. To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy followed by a second surgery at recurrence. OS was significantly longer in cases with Notch-1 negativity (8.8 months) than in those with I Notch-1 positivity (6.8 months). We noted that GSCs have the potential for endothelial differentiation with Notch activity. We believe that Notch-1 is a potential target and/or biomarker for antiangiogenic treatments.