It has been reported that Mizoribine is an immunosuppressant used to suppress rejection in renal transplantation, nephrotic syndrome, lupus nephritis, and rheumatoid arthritis. The molecular chaperone HSP60 alone induces inflammatory cytokine IL-6 and the co-chaperone HSP10 alone inhibits IL-6 induction. HSP60 and HSP10 form a complex in the presence of ATP. We analyzed the effects of Mizoribine, which is structurally similar to ATP, on the structure and physiological functions of HSP60–HSP10 using Native/PAGE and transmission electron microscopy. At low concentrations of Mizoribine, no complex formation of HSP60–HSP10 was observed, nor was the expression of IL-6 affected. On the other hand, high concentrations of Mizoribine promoted HSP60–HSP10 complex formation and consequently suppressed IL-6 expression. Here, we propose a novel mechanism of immunosuppressive action of Mizoribine.

Background: Since clazosentan was approved for insurance coverage in Japan, the postoperative management of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has changed as each facility gains experience. Here, we investigate the prevention, treatment, and management of DCI after SAH throughout Japan in 2023. Methods: In 2024, we conducted an anonymous questionnaire survey—emailed to certified neurosurgeons in hospitals across Japan—regarding management for preventing DCI after aneurysmal SAH. Of them, 78 hospitals responded and were included in this study. These results were compared with the findings of a survey conducted prior to the approval of clazosentan in Japan (2022). Results: The proportion of institutions with a standardized protocol for DCI after aneurysmal SAH at a level of ≥50% was 93.0%. For both craniotomy and endovascular surgery, clazosentan was used most frequently, followed by cilostazol, fasudil, and statins. The most common drug for both direct and endovascular procedures was clazosentan. The predominant reason for discontinuing clazosentan was respiratory complications—such as pulmonary edema—followed by cardiac complications. However, 62.1% of facilities felt that the number of cases wherein clazosentan was discontinued was deceasing. While 77.5% of respondents felt that clazosentan was effective for preventing DCI after aneurysmal SAH, only 49.3% felt that it improved outcomes. Conclusions: Since its approval, clazosentan has been the most common treatment for DCI prevention after aneurysmal SAH. The impression of the effectiveness in preventing DCI and the outcomes of clazosentan have been mixed. As data accumulate, clazosentan use and management protocols will be refined and developed.

Background: Diffuse midline glioma (DMG) is an invasive astrocytic tumor arisen from midline structures, such as the pons and thalamus. Five cases of DMG in the pineal region have been reported, but the clinical course was poor; there was no case of survival for more than 2 years. Case Description: We report the case of a 12-year-old boy with DMG in the pineal region who is living a normal daily life for more than 6 years following multimodal treatment. He complained of a headache accompanied by vomiting that had gradually worsened 1 month previously, and initial magnetic resonance imaging revealed a pineal tumor. Germinoma was initially suspected; however, a combination of chemotherapy using carboplatin and etoposide was ineffective. The first surgery was performed through the left occipital transtentorial approach (OTA); the diagnosis was DMG. After 60 Gy radiotherapy concomitant with temozolomide (TMZ), the tumor enlarged. Second surgery was performed through bilateral OTAs, and 90% of the tumor was removed. In addition, stereotactic radiotherapy (30 Gy, six fractions) was administered, and the local equivalent dose in 2 Gy/fraction reached 97.5 Gy. Maintenance chemotherapy using TMZ and bevacizumab was continued for 2 years. After finishing chemotherapy, the enhancing lesion enlarged again, and bevacizumab monotherapy was effective. Now, at 6 years after diagnosis, the patient leads an ordinary life as a student. Conclusion: Maximum resection and high-dose radiotherapy followed by bevacizumab may have been effective in the present case.

Intracranial carotid artery dissection causing cerebral ischemia is a rare but important cause of cerebral infarction in children and adolescents. Although endovascular therapy has been reported to be effective, questions regarding the indications for intervention are yet to be addressed. Therefore, this study aimed to evaluate factors related to clinical outcomes through a nationwide survey. Overall, 35 neurosurgical centers reported patients within 2 weeks after ischemic onset due to intracranial carotid artery dissection causing cerebral ischemia treated between January 2015 and December 2020. Data on clinical and radiological findings were statistically analyzed. Twenty-eight patients met the inclusion criteria. The median age was 36 years (range, 7-59 years), without sex differences. Headache at onset was documented in 60.7% of the patients. Dissection findings were categorized into stenosis (71.4%) or occlusion (28.6%). Initial treatments, including various antithrombotic agent combinations in 23 (82.1%) patients, effectively improved or prevented aggravation in half of the patients. The patients with stenotic dissection were significantly more likely to experience aggravation during the initial treatment than did those with occlusive dissection (P = 0.03). In addition, the patients with moderate to severe neurological deficits on admission had poorer outcomes at discharge more frequently than did those with mild neurological deficits on admission. Eight patients undergoing endovascular therapy had no procedural complications or further aggravation after intervention. In conclusion, patients with intracranial carotid dissection causing cerebral ischemia who had a stenotic dissection were at risk of further aggravation, and endovascular therapy effectively improved or prevented aggravation.