Yuko Tanaka

Background: Delayed cerebrovascular complications after radiotherapy have been well-documented. However, optimal management of acute ischemic stroke secondary to radiation-induced intracranial arterial stenosis remains unclear. Case Description: A 17-year-old girl developed an acute ischemic stroke secondary to delayed middle cerebral artery stenosis following radiotherapy for recurrent craniopharyngioma after tumor resection. Intravenous alteplase (rt-PA) was administered 4 h after symptom onset, resulting in neurological improvement, and she was discharged with a modified Rankin Scale score of 0. Conclusion: This case suggests that rt-PA may be an effective treatment option for acute ischemic stroke associated with post-radiotherapy arterial stenosis, provided that the standard eligibility criteria are met.

Background: Septic cerebral embolisms (SCE) are serious neurological complications of sepsis. An embolic occlusion due to infected thrombi can precipitate ischemic stroke and a spectrum of secondary pathologies, including intracerebral hemorrhages, mycotic aneurysms, meningitis, and brain abscesses, which are a major complication of SCE. However, delayed abscess formation following cerebral infarction is rarely encountered, and the underlying mechanisms remain poorly understood. Here, we present a rare case of SCE in a patient who underwent a mechanical thrombectomy (MT) for large-vessel occlusion and developed delayed abscess formation following cerebral infarction. Case Description: A 46-year-old man with a history of aortic stent graft implantation presented with sudden impairment of consciousness and right hemiparesis. Neuroradiological imaging revealed a left middle cerebral artery territory infarction due to occlusion of the left internal carotid artery. We performed emergency MT and achieved partial reperfusion. Histopathological evaluation of the retrieved thrombi revealed the presence of bacterial aggregates, confirming the diagnosis of SCE. Despite initial empiric antibiotic therapy, the patient developed a delayed brain abscess in the infarcted territory during the subacute phase. This unexpected course required further therapeutic intervention, including neurosurgical procedures and subsequent antibiotic therapy. Conclusion: This case highlights both the diagnostic value of retrieved thrombi in SCE and the potential for delayed abscess formation after recanalization therapy using MT. In addition, this finding suggests the importance of ongoing vigilance for delayed brain abscess formation following SCE. In a severe clinical condition of sepsis, early diagnosis and tailored interventions are essential to improve outcomes.

Background: Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of amyloid β (Aβ)-mediated small vessel disease associated with prior neurosurgical exposure, such as cadaveric dura mater grafting or other Aβ-contaminated materials. The condition generally manifests decades later, presenting as intracerebral hemorrhage (ICH), seizures, or cognitive decline. While the presence of inflammatory forms of sporadic cerebral amyloid angiopathy (CAA) is well-documented, an inflammatory variant of iCAA has not been previously documented. The aims of this report are to present the first case of inflammatory iCAA, integrating clinical, radiological, and pathological findings, and to highlight its therapeutic implications. Case Description: A 38-year-old man with a medical history of cadaveric dura mater grafting in infancy presented with recurrent ICHs and progressive cognitive decline. A brain magnetic resonance imaging revealed extensive cortical superficial siderosis, leptomeningeal enhancement, and arterial wall enhancement. These features are suggestive of inflammatory CAA. Brain Biopsy revealed cortical vessel Aβ deposition and mild parenchymal lymphocytic infiltration. We diagnosed inflammatory form of iCAA with the clinical findings. Steroid pulse therapy followed by a taper of oral prednisolone led to clinical and radiological improvement, with no recurrence of symptoms or hemorrhage during 24-month period of follow-up. Conclusion: This case offers the first neuroradiological evidence of an inflammatory phenotype in iCAA. The favorable response to immunosuppressive therapy indicates that inflammation may play a pathogenic role in this case. Early immunosuppressive therapy should be considered when inflammatory features are present in iCAA.

We examined whether synchronizing and analyzing three data sources, active personal dosimeter (APD) information, in-room monitoring camera footage, and the operator’s main angiography panel video, could identify opportunities to reduce occupational radiation exposure during cerebral angiography without therapeutic intervention. We analyzed the behavior of eight physicians and radiation doses measured outside the lead apron during 12 diagnostic cerebral angiography procedures performed between January and April 2024. Appropriate use of a ceiling-suspended radiation protective shield (CSRPS) was associated with approximately 70% exposure reduction. In addition, exposure during femoral arteriography (catheter advancement from femoral artery puncture to the aortic arch) accounted for approximately 50% of the total exposure, identifying both as effective intervention points. This approach identified operators’ incorrect use of radiation protection equipment and enabled clear feedback to operators on areas for improvements in radiation protection practices.

Background: Visual field defect and visual impairment are important but poorly characterized complications after flow-diverter (FD) stent placement for internal carotid artery (ICA) aneurysms. Methods: We retrospectively analyzed 31 consecutive patients with 32 ICA aneurysms treated by FD stent implantation between October 2015 and April 2021. Aneurysms were classified into two groups those with visual symptoms before and after FD stenting (symptomatic group) and those without (asymptomatic group). We analyzed patients’ background characteristics, treatment details, and imaging findings. Results: Visual symptoms were present in 25% (8/32) of aneurysms and worsened after treatment in 9.4% (3/32). Aneurysm enlargement was more common in the symptomatic group than the asymptomatic group (50% vs. 4.1%; odds ratio 23.0, 95% confidence interval [CI] 2.0–262.6, P = 0.0086). Poor visualization of the ophthalmic artery after procedure was observed in 50% versus 12.5% (odds ratio 7.0, 95% confidence interval 1.1–44.1, P = 0.047). No central retinal artery occlusion or cerebral ischemic events were observed. All three deteriorating cases improved after high dose steroids: one required additional FD stenting. Conclusion: In this single-center retrospective cohort, visual symptoms after FD stenting were relatively common but were usually reversible. Aneurysm enlargement and early loss of ophthalmic-artery flow identify patients at higher visual risk. Early steroid therapy and, when necessary, further endovascular treatment may mitigate visual deterioration.

椎骨動脈閉塞慢性期に，椎骨動脈からPICAへの側副血行路にflow related aneurysmを生じ，くも膜下出血をきたした1例を経験したので報告する． 症例は51歳，男性．X年突然の左後頚部痛，めまいが出現し，救急受診．受診時，AICA症候群を認め，画像検査にて左椎骨動脈解離による閉塞，左小脳半球脳梗塞と診断した．抗血小板薬にて保存的加療を行い，左聴力低下のみ残存し，自宅退院となった．3年間の外来フォロー中のMRIでは，左椎骨動脈閉塞の再開通は認めなかった．X＋3年，突然の嘔気，嘔吐，めまい，後頭部痛が出現し，JCS 200の状態で当院救急搬送された．頭部CTでくも膜下出血を認め，脳血管撮影では，左椎骨動脈閉塞，V3 portionからPICAへ吻合する蛇行した側副血行路を認め，その途中に3mm程度の動脈瘤を認め，同部位の破裂と診断した．開頭トラッピング術を行い，術後経過良好にて，第66病日にmRS 2で転院となった． 椎骨動脈解離閉塞後，このようなまれな合併症を生じることがあるので慎重な経過観察が必要である．

Introduction: Multiple myeloma (MM) is one of the hematological malignancy that affects the plasma cells in bone marrow. The treatment of MM patients has been dramatically changed by new agents such as proteasome inhibitors and immunomodulatory drugs. However, most patients will relapse even if new agents provide therapeutic advantages. Therefore, a new strategy is still needed to increase MM patient survival. Insulin-like growth factor (IGF) cause intracellular signaling that ultimately results in cellular growth and proliferation. Because IGF signaling pathways have crucial functions in hematological malignancies and solid tumors, IGF pathways might regulate myeloma cell survival. Materials and Methods: In this study, we investigated whether IGF1R inhibitor could suppress myeloma cells. We also investigated whether IGF1 was involved in proteasome sensitivity against myeloma cells and cytokines were induced by IGF1 in human umbilical vein endothelial cells (HUVEC). Results: We first investigated the IGF signaling pathways by microarray gene expression data from the online Gene Expression Omnibus (GEO). IGF is tightly regulated by six related IGF-binding proteins (IGFBPs). Gene expression of IGF1, IGF1R, IGFBP2, IGFBP5, IGFBP7 and IGF2 are involved in myeloma and normal control samples from the public microarray datasets of GSE39754. We next investigated the proteasome inhibitor, bortezomib or carfilzomib activity. Proteasome inhibitors exhibit cell growth inhibition against myeloma cells. However, in the presence of IGF1, proteasome inhibitors activity was reduced. Linsitinib is an orally bioavailable small molecule inhibitor of the IGF1R. We investigated whether linsitinib could inhibit the proliferation of myeloma cells. We found linsitinib treatment inhibited the growth of myeloma cells in a dose dependent manner. Activity of Caspase 3/7 and cytotoxicity were also increased. Combined treatment of myeloma cells with carfilzomib and linsitinib caused more cytotoxicity than each drug alone. Caspase 3/7 activity and cellular cytotoxicity was also increased. We examined the intracellular signaling. Activity of caspase 3 and poly (ADP-ribose) polymerase (PARP) was increased after carfilzomib and linsitinib treatment. We next blocked IGF1R function by small interfering RNA (siRNA). We found drug sensitivity of the cells to the carfilzomib was increased compared to mock-transfected cells. Caspase 3/7 activity and cytotoxicity were increased after carfilzomib treatment in siRNA transfected cells. We next investigated the in vitro effects of IGF1 on cultured HUVEC. Because the entire bone marrow cavity is hypoxic condition, we investigated the IGF signaling pathways in the hypoxic condition by microarray gene expression data from GEO. Gene expression of IGF1R and IGF2 are increased in the hypoxia from the public microarray datasets of GSE36837. Gene amplification was confirmed by RT-PCR analysis. In the immunoblot analysis, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation was increased by IGF1 stimulation in the time dependent manner. We also found that gene expression of monocyte chemotactic protein-1 (MCP-1) was enhanced by IGF1 stimulation. Conclusion: The IGF1 signaling pathway is involved in proteasome inhibitor sensitivity and plays a key role in chemokine production of the HUVEC. Our data also suggested that administration of IGF1R inhibitor, linsitinib, might be a powerful strategy against myeloma cells and enhance cytotoxic effects of proteasome inhibitors in those residual MM cells. Disclosures: Ohyashiki: MSD,: Honoraria, Research Funding; Bristol Meyer Squibb KK,: Honoraria, Research Funding; Kyowakko Kirin KK,: Research Funding; Celegene KK,: Honoraria, Research Funding; Pfizer KK,: Honoraria, Research Funding; Novartis KK,: Honoraria, Research Funding; Taiho Pharmaceutical KK: Honoraria, Research Funding; Takeda Pharmaceutical KK,: Honoraria, Research Funding; Jansen Pharma KK,: Research Funding; Chugai KK,: Honoraria, Research Funding; Nihon-Seiyaku,: Research Funding; Ono Pharmaceutical KK,: Honoraria, Research Funding; Eizai,: Research Funding; Nippon-shinyaku,: Honoraria, Research Funding; Asahikase: Research Funding; Asteras KK,: Research Funding; Dainippon Sumitomo KK,: Honoraria, Research Funding.