Ultra-High-Molecular-Weight Polyethylene Merlon Shape: Novel Fixation of Artificial Bone for Cranioplasty.

BACKGROUND: Cranioplasty is a surgical procedure widely performed for repairing cranial defects caused by external decompression surgery for cerebrovascular disease or traumatic brain injury. We devised a new cranioplasty method using artificial bone made up of ultra-high molecular-weight polyethylene, with serrated wings on the edge. We named this newly designed artificial bone as Merlon shape. OBJECTIVE: To describe our initial experience with the Merlon shape and evaluate its usefulness and safety in cranioplasty. METHODS: The serrated wings of the Merlon shape were preoperatively designed for solid fixation and improving cosmetic results by reducing the thickness of the artificial bone. We evaluated 25 patients who underwent cranioplasty with the Merlon shape between December 2018 and December 2021. The causes of bone defects in these patients (male: 9, female: 16; median age: 62 years) were subarachnoid hemorrhage (n = 14), cerebral infarction (n = 8), and traumatic brain injury (n = 3). RESULTS: There were no postoperative adverse events such as infection, bone resorption, implant exposure, or graft sinking in 24 patients during an average follow-up period of 19 months. One patient experienced acute epidural hemorrhage and required reoperation. CONCLUSION: This is the first report on the use of the ultra-high molecular-weight polyethylene Merlon shape. Our initial 4-year case series showed good outcomes with this method.

Fatal Cerebral Venous Thrombosis in a Pregnant Woman with Inherited Antithrombin Deficiency after BNT162b2 mRNA COVID-19 Vaccination.

Antithrombin deficiency is a high-risk factor for venous thromboembolism during pregnancy, whereas cerebral venous thrombosis is rare. Cerebral venous thrombosis related to coronavirus disease 2019 (COVID-19) vaccines has been reported; however, there are a few reports of cerebral venous thrombosis after a messenger RNA (mRNA) vaccination. A 25-year-old female in her sixth week of pregnancy presented with headache 24 days after BNT162b2 mRNA COVID-19 vaccination. The following day, she presented with altered sensorium and was diagnosed with severe cerebral venous thrombosis. She demonstrated heparin resistance and was found to have an inherited antithrombin deficiency. A heterozygous missense variant in SERPINC1 (c.379T>C, p.Cys127Arg, 'AT Morioka') was detected by DNA analysis. Despite intensive care with unfractionated heparin, antithrombin concentrate, and repeated endovascular treatments, she died on the sixth day of hospitalization. Cerebral venous thrombosis in pregnant women with an antithrombin deficiency can follow a rapid and fatal course. Treatment with unfractionated heparin and antithrombin concentrate may be ineffective in severe cerebral venous thrombosis cases with antithrombin deficiency. Early recognition of antithrombin deficiency and an immediate switch to other anticoagulants may be required. Although the association between cerebral venous thrombosis and the vaccine is uncertain, COVID-19 vaccinations may require careful evaluation for patients with prothrombic factors.

A low score on the National Institutes of Health Stroke Scale with eye movement disorder may indicate a good candidate for acute mechanical thrombectomy for posterior circulation large vessel occlusion: illustrative cases.

BACKGROUND: Basilar artery occlusion (BAO) accounts for 1% of all strokes, and its natural prognosis is extremely poor. There is no consensus on the treatment strategy for mild BAO. OBSERVATIONS: Between August 2015 and May 2021, 429 patients received mechanical thrombectomy (MT) in the authors' hospital. Three patients had a BAO with a National Institutes of Health Stroke Scale (NIHSS) score of ≤6 and showed eye movement disorder as the main symptom. MT immediately improved ocular symptoms in all three cases, and the patients were discharged with a modified Rankin Scale ≤2. LESSONS: Lesions responsible for the eye movement disorder are distributed from the midbrain to the pontine tegmentum. These lesions are supplied by the arteries of the interpeduncular fossa, which is impaired by BAO. Symptoms due to problems with the arteries of the interpeduncular fossa can be rapidly improved by MT, and it is useful for preventing neurological deterioration in mild cases. BAO with a low NIHSS score in the presence of eye movement disorder as the main symptom may be a good indication for MT.

Visual Impairment due to a large paraclinoid aneurysm treated with parent artery occlusion and bypass: A case report.

INTRODUCTION: Paraclinoid internal carotid artery (ICA) aneurysms can sometimes cause visual field disturbances due to their size, and it is challenging to treat either surgically or using endovascular techniques. Flow diverters generally have positive outcomes, but sometimes in symptomatic aneurysms, we see the thrombosed section becomes enlarged. Therefore, optimal treatment strategies are difficult to determine. CASE: A 68-year-old woman presented with a chief complaint of vision loss in the left eye. A large wide-necked saccular aneurysm was found on the left ICA paraclinoid portion. Under general anesthesia, a Pipeline Flex was inserted along with coil embolization. After treatment, the aneurysm showed thrombotic expansion, and the visual impairment worsened. One year later, aneurysm recanalization was evident; therefore, another Pipeline was inserted to overlap the stent. However, her visual impairment worsened again, and parent artery occlusion with high flow bypass was performed 20 months after her first treatment. Two weeks postoperatively, improved peripheral vision was confirmed. Further, no enlargement of the aneurysm was observed using magnetic resonance imaging 6 months later. CONCLUSION: This case examined a symptomatic, large paraclinoid aneurysm in a patient, which continued to enlarge after Pipeline stent placement, but was later treated successfully using direct parent artery occlusion in combination with high-flow bypass.

Tandem Lesions of the Vertebrobasilar System Treated by Thrombectomy and Vertebral Artery Stenting: A Case Report.

Objective: There are few reports on endovascular treatment of tandem lesions in the posterior circulation and no consensus on treatment strategies has been reached. We report a case of tandem lesions of basilar artery occlusion and vertebral artery stenosis treated by thrombectomy and vertebral artery stenting. Case Presentation: We present the case of a 73-year-old man who developed consciousness disorder and tetraplegia. Head and neck CTA revealed tandem left vertebral artery stenosis and basilar artery occlusion. The patient was treated using a reverse technique, which involves performing thrombectomy first and then vertebral artery stenting, along with Carotid Guardwire PS. Postoperative impairment of consciousness and improvement of tetraplegia were achieved. Conclusion: The reverse technique combined with Carotid Guardwire PS may be a useful treatment strategy for tandem lesions in the posterior circulation.

Use of Contralateral Trans-Anterior Communicating Artery Snare to Rescue Lost Access to a Pipeline Embolization Device Unsheathed in an Aneurysm.

Objective: A pipeline embolization device (PED; Medtronic, Minneapolis, MI, USA) is a new vascular reconstruction device used to treat large internal carotid artery (ICA) aneurysms in Japan. We herein present a PED-related complication and describe its rescue strategy. Rescue therapy using a snare via the posterior communicating artery from the contralateral side has already been reported. However, this is the first report of therapy via the anterior communicating artery (AcomA). Case Presentation: A 49-year-old woman underwent vascular reconstruction with a PED for a large cavernous ICA aneurysm. During the placement of the PED, the proximal side of the PED slipped into the aneurysm. It was impossible to enter the true lumen of the PED from the proximal side because the orifice of the stent faced the aneurysmal wall. Contralateral trans-AcomA access to the PED was obtained through the distal ICA. The microwire from the distal ICA was connected with Goose Neck snares (Medtronic) from the proximal ICA. Pulling the snares to the proximal side, the PED was straightened and distal access was regained. Another PED was deployed such that it overlapped with the first PED to achieve vascular reconstruction. The patient finally recovered from aphasia, but paralysis of the right upper limb remained after rehabilitation. Conclusion: If the stent slips into the aneurysm, distal access through the true stent lumen may be very difficult. We presented a rescue technique for this complication, through the AcomA from the contralateral side.

Effect of Preoperative Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor on Carotid Artery Stenting.

BACKGROUND: Perioperative embolic stroke is one of the most serious complications during carotid artery stenting (CAS). Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is a low-density lipoprotein-lowering drug that inhibits proprotein convertase subtilisin/kexin type 9, which normally binds to the low-density lipoprotein cholesterol (LDL-C) receptor. Its combination with statin significantly decreases LDL-C levels. PCSK9i is expected to achieve lower LDL-C levels than single use of statin. This study aimed to investigate whether perioperative PCSK9i administration stabilizes carotid artery plaque and reduces perioperative complications of CAS. METHODS: Nine patients with symptomatic stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50%) or asymptomatic stenosis (NASCET ≥ 80%) were included. PCSK9i was administered at least twice (once in 2 weeks) in the outpatient clinic before CAS. Perioperative complications; results from blood tests, magnetic resonance imaging (MRI), magnetic resonance angiography, and carotid ultrasonography (US); and modified Rankin scale score at discharge were assessed. RESULTS: High intensity on diffusion-weighted imaging was not observed in 8 patients. Changes in carotid plaque characteristics were found with MRI and/or carotid US in 7 patients. The plaque to muscle ratio decreased in 3 patients. The carotid plaque became hyperechoic in 2 patients, and the fibrous cap was seen more clearly on carotid US. Two patients had findings of stabilized plaque on MRI and carotid US, which indicates that plaque transformation was more stable. CONCLUSIONS: Lowering LDL-C level could reduce ischemic complications, and low LDL-C level affects plaque stability and antithrombus formation. PCSK9i can possibly stabilize carotid plaque and reduce perioperative complications of CAS.

Efficacy of superficial temporal artery-middle cerebral artery double anastomoses in a patient with rapidly progressive moyamoya disease: case report.

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction.

Safety and feasibility of convection-enhanced delivery of nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain.

OBJECTIVES: Convection-enhanced delivery (CED) has been developed as an effective drug-delivery strategy for brain tumors. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain tissue. We previously showed the anti-tumor efficacy of nimustine hydrochloride (ACNU) delivered via CED against a rodent intracranial xenografted tumor model. Here, we developed a method to monitor the drug distribution using a non-human primate brain. METHODS: CED of a mixture of ACNU with gadodiamide was performed using three non-human primates under real-time magnetic resonance imaging monitoring. Animals were clinically observed for any toxicity after infusion. Two months later, their brains were subjected to histological examination for the evaluation of local toxicity. Another one animal was euthanized immediately after CED of a mixture of ACNU, gadodiamide, and Evans blue dye to evaluate the concordance between ACNU and gadodiamide distributions. The harvested brain was cut into blocks and the ACNU content was measured. RESULTS AND DISCUSSION: Real-time magnetic resonance imaging monitoring of co-infused gadodiamide confirmed the success of the infusion maneuver. In the monkey that also received Evans blue, the distribution of Evans blue was similar to that of gadodiamide and paralleled the measured ACNU content, suggesting concordance between ACNU and gadodiamide distributions. Histological examination revealed minimum tissue damage with the infusion of ACNU at 1 mg/ml, determined as a safe dose in our previous rodent study. CED of ACNU can be co-administered with gadodiamide to ensure successful infusion and monitor the distribution volume.

Efficacy of intraoperative irrigation with saline for preventing shunt infection.

OBJECT: The rate of infection following shunt procedures is unacceptably high. The authors have hypothesized that the key to reducing the shunt infection rate is in reducing bacteria in the operating field and wound. This hypothesis has been tested in a prospective nonrandomized controlled manner. METHODS: Data obtained in all patients undergoing shunt insertions or revisions for hydrocephalus performed between October 1, 2003, and June 12, 2009, were reviewed. Starting in August 2006, we began routinely irrigating the operating field and wound with saline solution from a syringe. Prior to this, we had not used any irrigation techniques, providing an adequate control group (Group A) for the effect of the irrigation technique. Prior to November 2007, we used saline containing amikacin for irrigation (Group B). After that date, we used saline only for irrigation (Group C). RESULTS: A total of 150 shunt procedures were performed in 79 girls and 71 boys during the study period. The mean age of all patients was 44.0 +/- 59.1 months. Groups A, B, and C comprised 61, 40, and 49 shunt procedures, respectively. There was no statistical difference in age among the 3 groups. Nine infections occurred within 90 days in the postoperative period. The overall infection rate was 6.0%. Eight infections occurred before introducing the irrigation procedure (infection rate 13.1%). One infection was noted after introducing irrigation (Group B [0.0%] + Group C [2.0%]; combined B and C infection rate = 1.1%). There was a statistical difference in the infection rate between Group A and Groups B and C combined (p = 0.003), Groups A and B (p = 0.021), and Groups A and C (p = 0.035). In contrast, no statistical difference was observed between Groups B and C (p > 0.99). Six of the 9 infections were due to staphylococcal species. CONCLUSIONS: An irrigation technique used to reduce bacteria in the operating field and wound is effective for preventing shunt infection. Irrigation alone, and not antibiotics, contributed to the prophylaxis of shunt infection.

Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts.

Prognosis for the patients with glioblastoma, the most common malignant brain tumor, remains dismal. A major barrier to progress in treatment of glioblastoma is the relative inaccessibility of tumors to chemotherapeutic agents. Convection-enhanced delivery (CED) is a direct intracranial drug infusion technique to deliver chemotherapeutic agents to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED can provide wider distribution of infused agents compared to simple diffusion. We have reported that CED of a polymeric micelle carrier system could yield a clinically relevant distribution of encapsulated agents in the rat brain. Our aim was to evaluate the efficacy of CED of polymeric micellar Am80, a synthetic agonist with high affinity to nuclear retinoic acid receptor, in a rat model of glioblastoma xenografts. We also used systemic administration of temozolomide, a DNA-alkylating agent, which has been established as the standard of care for newly diagnosed malignant glioma. U87MG human glioma cells were injected into the cerebral hemisphere of nude rats. Rats bearing U87MG xenografts were treated with CED of micellar Am80 (2.4 mg/m(2)) on day 7 after tumor implantation. Temozolomide (200 mg/m(2)/day) was intraperitoneally administered daily for 5 days, starting on day 7 after tumor implantation. CED of micellar Am80 provided significantly longer survival than the control. The combination of CED of micellar Am80 and systemic administration of temozolomide provided significantly longer survival than single treatment. In conclusion, temozolomide combined with CED of micellar Am80 may be a promising method for the treatment of malignant gliomas.

O(6)-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma.

OBJECTIVE: The prognostic significance of O(6)-methylguanine DNA methyltransferase (MGMT) was evaluated by analysis of both MGMT promoter methylation and protein expression in a series of patients with newly diagnosed glioblastoma. METHODS: Seventy-three patients with glioblastomas treated with alkylating agents were analyzed for MGMT expression by immunohistochemistry. Genomic DNA was isolated from frozen surgical specimens obtained from 62 of 73 patients. MGMT promoter methylation was determined by methylation-specific polymerase chain reaction. The prognostic significance of MGMT was evaluated together with other well-known prognostic factors. RESULTS: MGMT promoter hypermethylation was detected in 35 of 62 patients (56.4%). MGMT immunoreactivity was low in 26 (35.6%) tumors, moderate in 24 (32.9%), and high in 23 (31.5%). Significant correlation was observed between MGMT expression and MGMT promoter methylation (P < 0.001). Both MGMT promoter methylation and low MGMT expression were independently associated with better progression-free survival but not with longer overall survival. However, in the subgroup analysis, MGMT promoter hypermethylation was significantly associated with longer overall survival in patients treated with temozolomide (TMZ) after nimustine hydrochloride (ACNU) treatment. CONCLUSIONS: Low MGMT expression and MGMT promoter methylation are both predictive markers for slower tumor progression in patients with glioblastoma.