Leaf spring exercise: A safe quadriceps strengthening exercise after anterior cruciate ligament reconstruction.

BACKGROUND: Leg extensions should be avoided in the early stages after anterior cruciate ligament reconstruction because the force exerted by the quadriceps muscle leads to anterior tibial displacement. To allow for safe quadriceps training in the knee extension range during this period, we devised the leaf spring exercise, which involves placing subjects in the prone position with their knee slightly flexed and instructing them to perform maximum isometric quadriceps contractions while supporting the proximal region of the lower leg's anterior surface and immobilizing the femur's posterior surface to prevent lifting. The current study aimed to examine the safety of Leaf spring exercise by determining the femur-tibia relationship using ultrasound imaging. METHODS: This controlled laboratory study included patients with unilateral anterior cruciate ligament-deficient knees (8 men and 8 women; age, 24.2 ± 8.3 years) who were instructed to perform Leaf spring exercise of both lower limbs. We measured the femur-tibia-step-off, which indicates the distance between the last point of the medial and lateral condyles of the femur and posterior margin of the tibial plateau, as a parameter to evaluate anterior tibial displacement via ultrasound diagnostic device. Further, peak torque of the quadriceps muscle was calculated using force measurement device. FINDINGS: No difference in anterior tibial displacement and peak torque was observed between the uninjured and injured sides during Leaf spring exercise. INTERPRETATION: Leaf spring exercise may add some strain on the reconstructed anterior cruciate ligament; hence, it can be considered a safe quadriceps exercise in the knee extension range.

Retrograde Flow Into the Internal Jugular Vein in a Hemodialysis Patient Mimicking Dural Arteriovenous Fistula: A Case Report.

Arterial spin labeling (ASL) and three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) are sensitive tools to detect dural arteriovenous fistula (DAVF), but hyperintensity in these images is also caused by jugular venous reflux. We present a case of a patient with renal failure on hemodialysis with retrograde flow into the internal jugular vein (IJV) mimicking DAVF. A 74-year-old man with a radial arteriovenous fistula for hemodialysis experienced transient dizziness. The TOF MRA and ASL revealed high signal intensity, suggesting the presence of a DAVF in the left transverse and sigmoid sinuses and the IJV. Digital subtraction angiography (DSA) revealed no evidence of a DAVF but showed retrograde flow into the IJV via his radial shunt. In hemodialysis patients, a high-flow shunt can cause fast retrograde flow into the dural sinuses and might lead to intracranial hypertension. The ASL images are useful for early detection and careful observation.

Current status of stroke in hemodialysis patients on a remote island.

OBJECTIVES: Hemodialysis patients have a higher incidence of stroke than healthy individuals. Hemodialysis patients living on remote islands are subject to additional distance and transportation difficulties. Therefore, we aimed to study the association between stroke and hemodialysis in patients living on remote islands. MATERIALS AND METHODS: We conducted a retrospective cohort study based on the medical records of maintenance hemodialysis patients in Shinkamigoto-Cho, Nagasaki, Japan, between June 1, 2005, and June 31, 2022. The clinical characteristics, probability of hemorrhagic stroke, acute ischemic stroke-free rate, and survival probability with or without a history of anticoagulant/antiplatelet use were evaluated. The survival probability among the hemorrhagic stroke, acute ischemic stroke, and non-stroke groups was also evaluated. RESULTS: This study involved 142 patients. Nine patients (6.3%) had intracerebral hemorrhage, one (0.7%) had subarachnoid hemorrhage, eight (5.6%) had acute ischemic stroke, and 124 (87.3%) had no stroke. The number of patients with severe disabilities (modified Rankin Scale 5/6) was significantly higher in the hemorrhagic stroke group. The probability of hemorrhagic stroke and acute ischemic stroke-free rate, or survival probability with or without a history of anticoagulant/antiplatelet use, were not significantly different. The acute ischemic stroke group was not associated with a lower survival probability than the other groups. The hemorrhagic stroke group had a significantly lower survival probability than the acute ischemic stroke group. CONCLUSIONS: This is the first study to report the status of stroke in hemodialysis patients living on remote islands, thus providing valuable information for improved stroke management in such patients.

Impact of immediate general anesthesia in the emergency room on prevention of rebleeding after subarachnoid hemorrhage.

BACKGROUND: Aneurysm rebleeding is fatal in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate whether immediate general anesthesia (iGA) management in the emergency room, upon arrival, prevents rebleeding after admission and reduces mortality following aSAH. METHODS: The clinical data of 3033 patients with World Federation of Neurosurgical Societies (WFNS) grade 1, 2, or 3 aSAH from the Nagasaki SAH Registry Study between 2001 and 2018 were retrospectively analyzed. iGA was defined as sedation and analgesia using intravenous anesthetics and opioids combined with intubation induction. We calculated crude and adjusted odds ratios to evaluate the associations between iGA and the risk of rebleeding/death using multivariable logistic regression models with fully conditional specification for multiple imputations. In the analysis of the relationship between iGA and death, we excluded patients with aSAH who died within 3 days after the onset of symptoms. RESULTS: Of the 3033 patients with aSAH who met the eligibility criteria, 175 patients (5.8%) received iGA (mean age, 62.4 years; 49 were male). Heart disease, WFNS grade, and lack of iGA were independently associated with rebleeding in the multivariable analysis with multiple imputations. Among the 3033 patients, 15 were excluded due to death within 3 days after the onset of symptoms. After excluding these cases, our analysis revealed that age, diabetes mellitus, history of cerebrovascular disease, WFNS grade, Fisher grade, lack of iGA, rebleeding, postoperative rebleeding, no shunt operation, and symptomatic spasm were independently associated with mortality. CONCLUSIONS: Management by iGA was associated with a 0.28-fold decrease in the risks of both rebleeding and mortality in patients with aSAH, even after adjusting for the patient's history of diseases, comorbidities, and aSAH status. Thus, iGA can be a treatment for the prevention of rebleeding before aneurysmal obliteration treatment.

Stent retriever angioplasty for acute atherosclerotic occlusion of vertebral artery.

The established effectiveness of mechanical thrombectomy using a stent retriever or aspiration catheter for emergent large-vessel occlusion caused by cardiogenic embolic stroke is widely recognized. However, in cases of acute artery occlusion resulting from atherosclerotic disease, mechanical thrombectomy often encounters challenges in achieving consistent recanalization, and aggressive percutaneous transluminal angioplasty (PTA) with a balloon and/or stenting can potentially lead to arterial dissection or additional perforator infarction. We present the case of an 88-year-old man who experienced sudden unconsciousness and tetra-paresis, diagnosed with cerebral infarction resulting from right vertebral artery occlusion. During the mechanical thrombectomy procedure, we identified atheromatous disease. Considering the circumstances, we made the decision to maintain the stent placement for 30 min following the loading of dual antiplatelet drugs. As a result, the right vertebral artery was successfully recanalized, although severe stenosis persisted. Two weeks after the initial procedure, we performed wingspan stent placement with a favorable outcome. Stent retriever angioplasty, using the deploy and re-sheath method, appears to be a viable option for managing acute atherosclerotic occlusion. This case highlights the challenges encountered in mechanical thrombectomy for atherosclerotic occlusion and demonstrates a potential approach to address this issue. By keeping the stent in place for a specific duration, combined with appropriate pharmacological intervention, recanalization was achieved, offering a promising therapeutic strategy for similar cases. Stent retriever angioplasty utilizing the deploy and re-sheath method emerges as a potential option for addressing acute atherosclerotic occlusion.

Treatment of new-onset primary central nervous system lymphoma in elderly patients using RMPV chemotherapy: a single-institution experience.

The prognosis of primary central nervous system lymphoma (PCNSL) in the elderly remains poor. We aimed to evaluate the outcome of rituximab, methotrexate, procarbazine, and vincristine (RMPV) chemotherapy in elderly patients with new-onset PCNSL. Twenty-eight patients aged ≥ 70 years treated for PCNSL between 2010 and 2020 were examined retrospectively. Nineteen patients received RMPV and nine did not qualify. Patients received five to seven cycles of RMPV plus response-adapted whole-brain radiotherapy (WBRT) and cytarabine. Ten of the 19 patients who received RMPV (52.6%) completed the induction, but only four patients (21.1%) completed RMPV chemotherapy, WBRT 23.4 Gy, and cytarabine. Median progression-free survival (PFS) and overall survival (OS) in the RMPV group was 54.4 and 85.0 months, respectively. Both PFS and OS were significantly longer in patients who received RMPV chemotherapy than in those who did not, and in patients who started but did not complete RMPV than in those who did not receive RMPV. Patients who received incomplete RMPV tended to have a favorable prognosis. Initial treatment with RMPV chemotherapy was effective in elderly patients with PCNSL. Adjusting the number of courses of RMPV may improve the prognosis of elderly patients with PCNSL, but further verification is necessary.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

The effect of the Kasuya CKD network on prevention of the progression of chronic kidney disease: successful collaboration of a public health service, primary care physicians and nephrologists-community based cohort study.

BACKGROUND: In 2012, we established a CKD network in collaboration with the public health service, primary care physicians, and nephrologists in the Kasuya area. The aim of this study was to clarify if our CKD network was effective in preventing CKD progression. METHODS: 1591 subjects, who had CKD in health checks in 2012 were included in this study. The slope of estimated glomerular filtration rate (eGFR) was compared before and after 2012. Parameters at the first health check visit before 2012, visit in 2012, and the last visit after 2012, were compared. Paired t test, analysis of variance for repeated measurements, and the Friedman test were used for the analysis. RESULTS: Mean age was 65 years. There were 781 men and 810 women. Mean eGFR was 59 ml/min/1.73 m2. The mean slope of eGFR before 2012 was -1.833 ml/min/1.73 m2/year and significantly reduced to - 0.297 after 2012. Low-density lipoprotein cholesterol showed a significant serial lowering. Uric acid was significantly elevated in 2012 compared to the first visit and had decreased by the last. The dipstick urinary protein significantly increased in 2012 compared to the first visit and decreased by the last. The number of current smokers showed a significant reduction over time. On the other hand, systolic blood pressure (SBP) and HbA1c significantly elevated at the last visit. CONCLUSION: The Kasuya CKD network may be effective in preventing CKD progression.

Do neutrophil extracellular traps implicate in atheromatous plaques from carotid endarterectomy? Re-analyzes of cDNA microarray data by surgeons.

Background: Carotid artery stenosis is the cause of 15% of strokes. Neutrophil extracellular traps (NETs) and peptidyl arginine deiminase 4 (PAD4) are believed to be involved in thrombosis. This pilot study described the differential expression profile of NETs between atheromatous plaques and surrounding tissues. Methods: Microarray datasets of carotid plaques were obtained from Gene Expression Omnibus. The normalized data were processed into comma-separated value matrix files using spreadsheet software. Analyzes of microarray data were conducted using integrated differential expression and pathway analysis. Result: The clustering results illustrated that the classifications of plaque and control had reasonable biological validity. Pathway analysis revealed the relevance of immune response, cell signaling, and other pathways. Differentially expressed genes were detected between carotid plaques and control specimens. However, enrichment analyzes did not reveal a difference in PAD4 expression between the groups and that NET implication was only found in one cDNA microarray dataset. Discussion: This pilot study does not necessarily dismiss the possibility of a relationship between NETs and atherothrombotic stroke. Gene expression could differ between endothelial cells and atheromas, and further studies are needed.

Amide proton transfer MRI differentiates between progressive multifocal leukoencephalopathy and malignant brain tumors: a pilot study.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nerve system caused by the John Cunningham virus. On MRI, PML may sometimes appear similar to primary central nervous system lymphoma (PCNSL) and glioblastoma multiforme (GBM). The purpose of this pilot study was to evaluate the potential of amide proton transfer (APT) imaging for differentiating PML from PCNSL and GBM. METHODS: Patients with PML (n = 4; two men; mean age 52.3 ± 6.1 years), PCNSL (n = 7; four women; mean age 74.4 ± 5.8 years), or GBM (n = 11; 6 men; mean age 65.0 ± 15.2 years) who underwent APT-CEST MRI between January 2021 and September 2022 were retrospectively evaluated. Magnetization transfer ratio asymmetry (MTRasym) values were measured on APT imaging using a region of interest within the lesion. Receiver operating characteristics curve analysis was used to determine diagnostic cutoffs for MTRasym. RESULTS: The mean MTRasym values were 0.005 ± 0.005 in the PML group, 0.025 ± 0.005 in the PCNSL group, and 0.025 ± 0.009 in the GBM group. There were significant differences in MTRasym between PML and PCNSL (P = 0.023), and between PML and GBM (P = 0.015). For differentiating PML from PCNSL, an MTRasym threshold of 0.0165 gave diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of 100% (all). For differentiating PML from GBM, an MTRasym threshold of 0.015 gave diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 90.9%, 80.0%, and 100%, respectively. CONCLUSION: MTRasym values obtained from APT imaging allowed patients with PML to be clearly discriminated from patients with PCNSL or GBM.

Ruptured basilar artery perforator aneurysm: a novel mechanism of pure subarachnoid hemorrhage in moyamoya disease. Illustrative case.

BACKGROUND: Pure subarachnoid hemorrhage (SAH) in patients with moyamoya disease is a rare occurrence. Three underlying mechanisms have been described previously, except for ruptured aneurysm of the circle of Willis. Herein, the authors describe a novel mechanism: rupture of a perforator aneurysm in moyamoya disease. OBSERVATIONS: A 51-year-old man experienced sudden onset of severe headache and vomiting. Computed tomography showed diffuse SAH. Digital subtraction angiography (DSA) showed unilateral moyamoya disease without remarkable etiology of SAH. The patient underwent conservative management with antihypertensive agents. The second DSA on day 17 revealed a slow-filling aneurysm emerging from the basilar top perforating artery. The diagnosis of SAH due to unknown origin was changed to ruptured basilar artery perforator aneurysm (BAPA). The third follow-up DSA on day 159 revealed the resolution of BAPA. LESSONS: In the case of pure SAH, it is crucial to consider the possibility of perforator aneurysms due to hemodynamic stress caused by moyamoya disease. Repeated DSA is essential for detecting the lesion.

Endovascular treatment of an aneurysm arising from the minor limb of an upper basilar artery fenestration: illustrative case.

BACKGROUND: An aneurysm arising in an upper basilar artery (BA) fenestration is extremely rare. The authors reported a case involving successful endovascular treatment of an aneurysm arising from the minor limb of an upper BA fenestration. OBSERVATIONS: A 65-year-old woman presented with an incidentally detected upper BA aneurysm arising from the minor limb of an upper BA fenestration. The irregularly shaped aneurysm was 6.0 × 2.7 mm in diameter, and the minor limb had several perforators. The aneurysm was nearly completely occluded with a catheter-assisted technique. The authors preserved both limbs of the BA fenestration. The postoperative course was uneventful, and the patient had an excellent clinical course with no neurological deficits or aneurysmal recanalization. LESSONS: The case is the first report of an unruptured aneurysm arising at the minor limb of an upper BA fenestration. In this case, the authors preserved the minor limb with endovascular treatment. The authors believe catheter-assisted coil embolization to be a feasible endovascular technique in such cases.

Quantitative Chemical Exchange Saturation Transfer Imaging of Amide Proton Transfer Differentiates between Cerebellopontine Angle Schwannoma and Meningioma: Preliminary Results.

Vestibular schwannomas are the most common tumor at the common cerebellopontine angle, followed by meningiomas. Differentiation of these tumors is critical because of the different surgical approaches required for treatment. Recent studies have demonstrated the utility of amide proton transfer (APT)-chemical exchange saturation transfer (CEST) imaging in evaluating malignant brain tumors. However, APT imaging has not been applied in benign tumors. Here, we explored the potential of APT in differentiating between schwannomas and meningiomas at the cerebellopontine angle. We retrospectively evaluated nine patients with schwannoma and nine patients with meningioma who underwent APT-CEST MRI from November 2020 to April 2022 pre-operation. All 18 tumors were histologically diagnosed. There was a significant difference in magnetization transfer ratio asymmetry (MTRasym) values (0.033 ± 0.012 vs. 0.021 ± 0.004; p = 0.007) between the schwannoma and meningioma groups. Receiver operative curve analysis showed that MTRasym values clearly differentiated between the schwannoma and meningioma groups. At an MTRasym value threshold of 0.024, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTRasym were 88.9%, 77.8%, 80.0%, and 87.5%, respectively. Our results demonstrated the ability of MTRasym values on APT-CEST imaging to discriminate patients with schwannomas from patients with meningiomas.

Long-term imaging course of Chiari malformation type I due to fibrous dysplasia/McCune-Albright syndrome.

INTRODUCTION: McCune-Albright syndrome (MAS) and fibrous dysplasia (FD) have been reported to cause Chiari type I malformation (CM1) and skull base invagination (BI). CASE: A 6-year-old girl was diagnosed with MAS and FD. She was diagnosed with CM1 at age 8 years, and the syringomyelia had gradually increased by age 20 years. We performed foramen magnum decompression and C1 laminectomy, and the syringomyelia stopped spreading after surgery. DISCUSSION: This patient underwent long-term radiological observation and morphological evaluations, which revealed that the skull thickening was progressing, while the posterior cranial fossa volume (PCFV) remained unchanged for 14 years. Therefore, although PCFV did not decrease, it was considered to be relatively inadequate due to the increase in brain volume with growth, resulting in posterior fossa overcrowding, causing CM1. CONCLUSION: In patients with FD/MAS, long-term evaluation of bone thickening, odontoid position, and PCFV is necessary.

Asymmetric epileptic spasms after corpus callosotomy in children with West syndrome may be a good indicator for unilateral epileptic focus and subsequent resective surgery.

OBJECTIVE: This retrospective study was designed to observe differences in ictal movements of epileptic spasm (ES) before and after corpus callosotomy (CC). We hypothesized that asymmetric expression of ES is more clarified after CC and would be a good indicator for the epileptic hemisphere. METHODS: We selected 16 patients with intractable ES in West syndrome who were seizure-free after CC and subsequent resection or disconnective surgery of the unilateral hemisphere. We retrospectively reviewed their behavioral ES recorded at video-electroencephalography monitoring before and after CC. Asymmetric neck flexion (NF) and involuntary muscular contraction of the upper and lower extremities (MCU and MCL, respectively) were primarily described correlating their laterality and the responsible hemisphere proved by surgical resection. RESULTS: Asymmetric NF, MCU, and MCL could be found both before and after CC. However, the percentage of those movements to the total number of ES increased after CC; asymmetric NF, 82.9% vs. 20.1%; unilaterally predominant MCU, 81% vs. 39.3%; and unilaterally predominant MCL, 77.6% vs. 29.9%. Regarding asymmetric NF, the direction in which the neck flexed or the head turned was significantly ipsilateral to the responsible hemisphere in 9 of 12 patients after CC (75%). The predominant side of MCU and MCL were significantly contralateral to the responsible hemisphere in 11 of 11 and 7 of 9 patients (100% and 77.8%, respectively). SIGNIFICANCE: Asymmetric NF, MCU, and MCL were clarified in patients with ES who were successfully treated with CC and subsequent surgery. Those changes in ictal behaviors after CC may indicate the lateralization of epileptic activity and encourage more curative surgical treatment.

Effects of fasudil on blood-brain barrier integrity.

BACKGROUND: Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. METHODS: BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6 h OGD/24 h reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. RESULTS: We found that treatment with 0.3-30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. CONCLUSIONS: Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.

A Spontaneous Extracranial Internal Carotid Artery Dissection with Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review.

Background and Objectives: Non-cystic manifestation of autosomal dominant polycystic kidney disease (ADPKD) is an important risk factor for cerebral aneurysms. In this report, we describe a rare spontaneous internal carotid artery (ICA) dissection in a patient with ADPKD. Observations: A 38-year-old woman with a history of ADPKD and acute myocardial infarction due to coronary artery dissection experienced severe spontaneous pain on the left side of her neck. Magnetic resonance imaging (MRI) revealed a severe left ICA stenosis localized at its origin. Carotid plaque MRI showed that the stenotic lesion was due to a subacute intramural hematoma. Close follow-up by an imaging study was performed under the diagnosis of spontaneous extracranial ICA dissection, and spontaneous regression of the intramural hematoma was observed uneventfully. Conclusions: When patients with a history of ADPKD present with severe neck pain, it is crucial to consider the possibility of a spontaneous ICA dissection. A carotid plaque MRI is beneficial in the differential diagnosis. Conservative management may benefit patients without ischemic symptoms.

Impact of Pre-operative Embolization With Onyx for Brain Arteriovenous Malformation Surgery.

Objective: To clarify the safety and efficacy of pre-operative embolization using Onyx liquid embolic agent (Onyx; ev3) compared with N-butyl cyanoacrylate (NBCA; Cordis Neurovascular, Inc.) or coils in cerebral arteriovenous malformation (AVM) surgery. Methods: This was a retrospective review of a prospectively collected clinical database of brain AVMs treated at our institute from January 2005 to March 2021. A total of 38 consecutive patients who underwent AVM resection after pre-operative embolization were included. Based on pre-operative embolization materials, the patients were divided into the pre-Onyx group (n = 16), in which NBCA or coils were used for embolization, and the Onyx group (n = 22). Patient characteristics and treatment results were compared between the two groups. Results: Patient characteristics were comparable between the two groups in terms of age, sex, and rupture status. While the Spetzler-Martin grade was also similar between the two groups, the location of the AVM nidus in the eloquent area was slightly higher in patients in the Onyx group (72.7%) than in patients in the pre-Onyx group (43.8%) (P = 0.09). The embolization rate was higher in the pre-Onyx group (mean: 63.0%; range: 12.7-100%) than in the Onyx group (mean: 50.0%; range: 15.8-100%), but the difference was not statistically significant (P = 0.06). The time needed for surgical removal was shorter in the Onyx group (mean: 354.8 min; range: 144-884 min) than in the pre-Onyx group (mean: 457.9 min; range: 240-1,294 min); however, this difference was not statistically significant (P = 0.13). The amount of intraoperative bleeding was significantly lower in the Onyx group (mean: 129.8 ml; range: 20-540 mL) than in the pre-Onyx group (mean: 448.8 mL; range: 120-1,550 ml) (P = 0.0008). The surgical complication rates were comparable between the two groups (pre-Onyx group, 18.8%; Onyx group, 4.5%; P = 0.29). Conclusions: Pre-operative embolization with Onyx can significantly reduce the amount of intraoperative bleeding in AVM resection and may contribute to safe AVM surgery.

Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain.

Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability. In this study, FUS/microbubble-assisted BBB opening was investigated for the intravenous delivery of mRNA-LNP to the brain. The intensity of FUS irradiation was optimized to 1.5 kW/cm2, at which BBB opening occurred efficiently without hemorrhage or edema. Exogenous protein (luciferase) expression by mRNA-LNP, specifically at the FUS-irradiated side of the brain, occurred only when FUS and microbubbles were applied. This exogenous protein expression was faster but shorter than that of plasmid DNA delivery. Furthermore, foreign protein expression was observed in the microglia, along with CD31-positive endothelial cells, whereas no expression was observed in astrocytes or neurons. These results support the addition of mRNA-LNP to the lineup of nanoparticles delivered by BBB opening.