Cerebral infarction following administration of andexanet alfa for anticoagulant reversal in a patient with traumatic acute subdural hematoma.

Background: Anticoagulants prevent thrombosis in patients with atrial fibrillation (AF) and venous thromboembolism but increase the risk of hemorrhagic complications. If severe bleeding occurs with anticoagulant use, discontinuation and rapid reversal are essential. However, the optimal timing for resuming anticoagulants after using reversal agents remains unclear. Here, we report early cerebral infarction following the use of andexanet alfa (AA), a specific reversal agent for factor Xa inhibitors, in a patient with traumatic acute subdural hematoma (ASDH). The possible causes of thromboembolic complication and the optimal timing for anticoagulant resumption are discussed. Case Description: An 84-year-old woman receiving rivaroxaban for AF presented with impaired consciousness after a head injury. Computed tomography (CT) revealed right ASDH. The patient was administered AA and underwent craniotomy. Although the hematoma was entirely removed, she developed multiple cerebral infarctions 10 h after the surgery. These infarctions were considered cardiogenic cerebral embolisms and rivaroxaban was therefore resumed on the same day. This case indicates the possibility of early cerebral infarction after using a specific reversal agent for factor Xa inhibitors. Conclusion: Most studies suggest that the safest time for resuming anticoagulants after using reversal agents is between 7 and 12 days. The present case showed that embolic complications may develop much earlier than expected. Early readministration of anticoagulant may allow for adequate prevention of the acute thrombotic syndromes.

Association of intravenous administration of human Muse cells with deficit amelioration in a rat model of spinal cord injury.

OBJECTIVE: Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells, which can be harvested from the bone marrow. After transplantation, Muse cells can migrate to an injured site of the body and exert repair effects. However, it remains unknown whether Muse cell transplantation can be an effective treatment in spinal cord injury (SCI). METHODS: The authors used a rat model of thoracic spinal cord contusion injury. For Muse cell transplantation, the clinical product CL2020 containing 300,000 Muse cells was administered intravenously 1 day after midthoracic SCI. Animals were divided into CL2020 (n = 11) and vehicle-treated (n = 15) groups. Behavioral and histological evaluations were conducted over a period of 8 weeks to see whether intravenous CL2020 administration provided therapeutic effects for SCI. The effects of human-selective diphtheria toxin on reversion of the therapeutic effects of CL2020 were also investigated. RESULTS: Hindlimb motor function significantly improved after CL2020 transplantations. Importantly, the effects were reverted by the human-selective diphtheria toxin. In immunohistochemical analyses, the cystic cavity formed after the injury was smaller in the CL2020 group. Furthermore, higher numbers of descending 5-hydroxytryptamine (5-HT) fibers were preserved distal to the injury site after CL2020 administration. Eight weeks after the injury, Muse cells in CL2020 were confirmed to differentiate most predominantly into neuronal cells in the injured spinal cord. CONCLUSIONS: Following SCI, Muse cells in CL2020 can reach the injured spinal cord after intravenous administration and differentiate into neuronal cells. Muse cells in CL2020 facilitated nerve fiber preservation and exerted therapeutic potential for severe SCI.

A Case of Telangiectatic Osteosarcoma in the Frontal Bone.

Telangiectatic osteosarcoma (TOS) is a subtype of osteosarcoma. TOS in the elderly and TOS in the skull are very rare. Here, we report a case of TOS in the frontal bone of an elderly patient. The patient was a 79-year-old woman who was identified as having a right frontal bone lesion. The patient was initially diagnosed with an intradiploic epidermoid cyst (IEC). A 60mm cystic lesion with bone destruction appeared 5 years later, which enlarged over 2 months. The fluid in the cyst seemed to be blood that had lost its clotting ability. Tumor and the surrounding tissue were resected. The postoperative course was favorable. Postoperative magnetic resonance imaging (MRI) showed no evidence of residual lesions. There was no metastases. Histopathologically, the cyst wall was composed of fibrous connective tissue and did not contain epithelial components. There were no skin appendages and keratinized tissues in the lesion. Based on these findings, the diagnosis changed to aneurysmal bone cyst (ABC). Subsequent immunohistochemical examinations confirmed that the MIB-1 index was 50% in some sections and there were atypical cells showing osteogenic properties in other sections. Based on these results, the patient was finally diagnosed with TOS. The differential diagnoses for cystic lesion presenting bone destruction include TOS, ABC, and IEC. In case of cystic lesion with bone destruction, early diagnosis based on histopathological study is important and complete resection with surrounding tissues is required, given the possibility of TOS.

Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model.

Background and Purpose- Multilineage-differentiating stress-enduring cells are endogenous nontumorigenic reparative pluripotent-like stem cells found in bone marrow, peripheral blood, and connective tissues. Topically administered human multilineage-differentiating stress-enduring cells into rat/mouse stroke models differentiated into neural cells and promoted clinically relevant functional recovery. However, critical questions on the appropriate timing and dose, and safety of the less invasive intravenous administration of clinical-grade multilineage-differentiating stress-enduring cell-based product CL2020 remain unanswered. Methods- Using an immunodeficient mouse lacunar model, CL2020 was administered via the cervical vein in different doses (high dose=5×104 cells/body; medium dose=1×104 cells/body; low dose=5×103 cells/body) at subacute phase (≈9 days after onset) and chronic phase (≈30 days). Cylinder test, depletion of human cells by diphtheria toxin administration, immunohistochemistry, and human specific-genome detection were performed. Results- Tumorigenesis and adverse effects were not detected for up to 22 weeks. The high-dose group displayed significant functional recovery compared with the vehicle group in cylinder test in subacute-phase-treated and chronic-phase-treated animals after 6 weeks and 8 weeks post-injection, respectively. In the high-dose group of subacute-phase-treated animals, robust and stable recovery in cylinder test persisted up to 22 weeks compared with the vehicle group. In both groups, intraperitoneal injection of diphtheria toxin abrogated the functional recovery. Anti-human mitochondria revealed CL2020 distributed mainly in the peri-infarct area at 1, 10, and 22 weeks and expressed NeuN (neuronal nuclei)- and MAP-2 (microtubule-associated protein-2)-immunoreactivity. Conclusions- Intravenously administered CL2020 was safe, migrated to the peri-infarct area, and afforded functional recovery in experimental stroke.

Unruptured Saccular Aneurysm Arising from the Fenestrated A1 Segment of the Anterior Cerebral Artery: Report of 2 Cases.

Some cases of aneurysms originating from the fenestrated A1 segment of the anterior cerebral artery (ACA) have been reported, but the pitfalls of the surgical procedure have not been well determined. We herein report 2 cases of a saccular aneurysm arising from the fenestrated A1 segment. Case 1 was a 72-year-old man incidentally diagnosed with an unruptured left ACA aneurysm on magnetic resonance imaging (MRI). Cerebral angiography revealed a saccular aneurysm arising from the proximal end of the left A1 segment. He underwent surgical clipping via the left pterional approach. The aneurysm originated from the proximal bifurcation of the fenestrated left A1 segment. A fenestrated ring clip was applied to obliterate the aneurysmal neck and one small fenestrated trunk, preserving the other fenestrated trunk and perforators around the fenestration. Case 2 was a 73-year-old man incidentally diagnosed with an unruptured ACA aneurysm on MRI. Cerebral angiography revealed a saccular aneurysm arising from the proximal end of the fenestrated left A1 segment. He underwent surgical clipping via the interhemispheric approach. The aneurysm originated from the proximal bifurcation of the fenestrated left A1 segment. A fenestrated ring clip was applied to obliterate the aneurysmal neck and one hypoplastic fenestrated trunk, preserving the other fenestrated trunk and perforators around the aneurysm. Detailed intraoperative evaluations of the anatomical structure and hemodynamics around the fenestration are important. The intentional obliteration of a fenestrated trunk and application of fenestrated clips need to be considered in difficult cases in order to expose the aneurysmal neck.

SMART (stroke-like migraine attacks after radiation therapy) syndrome responded to steroid pulse therapy: Report of a case and review of the literature.

This report presents a case of stroke-like migraine attacks after radiation therapy (SMART) syndrome in a 31-year-old man in whom symptoms and radiological findings resolved with steroid pulsed therapy and reviews the literatures with special emphasis on the use of steroids against SMART syndrome. The patient had a past history of left temporal anaplastic astrocytoma and was treated with surgery followed by local 72 Gy radiation therapy and chemotherapy using Nimustine Hydrochloride. Four years after the surgery, he was suffering from subacute progressing symptoms of headache, right hemianopia, right hemiparesis and aphasia from 2 to 4 days before admission to our hospital. At first he was diagnosed as symptomatic epilepsy but after extensive examination, the final diagnosis was SMART syndrome. His symptoms soon improved with steroid pulse therapy. In the literature, steroid pulse therapy is not necessarily a standard of care for SMART syndrome, but it seemed to decrease the need of biopsy. As the lesions of SMART syndrome require differential diagnosis from recurrences, biopsy was performed in some cases. However, lack of benefit and possible detriment is reported with biopsy of SMART lesions. Through this experience we suggest that steroid pulse therapy may provide speedy recovery from symptoms, and it should be considered before other invasive investigations or treatments.