Reo Kawaguchi

Expression of Mitogen-Activated Protein Kinases in Chronic Subdural Hematoma Outer Membranes

Growth factors and inflammatory cytokines activate the mitogen-activated protein kinase (MAPK) cascade. Previous studies have shown that chronic subdural hematoma (CSDH) fluid contains these factors and cytokines. In this study, expression of three major MAPK cascade transmitters in the outer membrane of CSDH was assessed. Eleven patients whose outer membrane and CSDH fluid were successfully obtained during trepanation surgery were included in this study. Expression of extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK), p-JNK, and actin was examined by Western blot and immunostaining. We examined whether CSDH fluid could activate MAPKs in cultured endothelial cells (ECs) or fibroblasts in vitro. Western blot analysis showed that p-ERK was present in all samples, whereas p-p38 and p-JNK were detected, but not in all cases. Immunostaining showed that all three p-MAPKs were expressed in vascular endothelium. However, only p-ERK was expressed in fibroblasts. Expression of p-extracellular signal-regulated kinase kinase (MEK) and p-ERK in ECs and fibroblasts was significantly induced immediately after treatment with CSDH fluid, whereas p-p38 and p-JNK expression was significantly induced in ECs 60 min after treatment, but not in fibroblasts. Activation of MEK was significantly inhibited by treatment with antibodies directed against interleukin-6 and vascular endothelial growth factor in ECs, but not in fibroblasts. Inflammatory cytokines and growth factors in CSDH fluids might activate major MAPKs in ECs, which might be associated with neovascularization in the outer membrane of CSDH. These MAPK pathways could become novel targets for treatment of CSDHs.

Activation of Nuclear Factor-kappa B in Endothelial Cells of Chronic Subdural Hematoma Outer Membranes

BACKGROUND Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Nuclear factor-kappa B (NF-κB) induces the production of inflammatory cytokines and adhesion molecules, which play an essential role in angiogenesis and inflammation. Recently, the double-stranded RNA-activated protein kinase (PKR) was shown to directly interact with NF-κB subunits to influence its transcriptional activity. OBJECTIVE To examine the expression of NF-κB signaling pathway components and PKR in CSDH outer membranes. METHODS Eight patients whose outer membranes were successfully obtained during trepanation surgery were included in this study. The IκBα, IKKβ, IKKγ, NF-κB, phosphorylated ( p )-NF-κB, and PKR expression levels were examined using western blotting analysis. NF-κB expression was also examined using immunohistochemistry. We investigated whether CSDH fluid could activate NF-κB in cultured endothelial cells in Vitro. RESULTS The IκBα, IKKβ, IKKγ, and NF-κB levels were approximately the same. Additionally, p -NF-κB and PKR were detected at similar levels. Immunostaining showed that NF-κB was expressed in the vascular endothelium. p -NF-κB expression in endothelial cells was significantly induced immediately after treatment with CSDH fluid. Furthermore, NF-κB activation was significantly inhibited by treatment with antibodies directed against vascular endothelial growth factor. CONCLUSION PKR might activate NF-κB through vascular endothelial growth factor in endothelial cells, which might be associated with endothelial cell proliferation in the CSDH outer membrane. Thus, the NF-κB signaling pathway could play a critical role in CSDH growth.

Experimental Direct Measurement of Clot-Capturing Ability of Stent Retrievers

BACKGROUND Stent retrievers (SRs) can be used to perform mechanical thrombectomy for the treatment of acute major arterial occlusion. Recanalization is faster, and outcomes are better with treatment involving these devices than with internal treatment. Although several SRs are available, their clot-capturing abilities are unclear. Therefore in the present study, we numerically evaluated the clot-capturing abilities of SRs in an experimental vascular model. METHODS A sham clot (urethane foam) was fixed with sutures at the middle of a vascular model (polyvinyl chloride tube). One end of the tube was connected to a measuring instrument. From the other end, an SR was inserted and deployed over the sham clot. The delivery wire of the stent was then withdrawn at a constant velocity using an automatic withdrawal machine. The maximum frictional force before the stent left the clot was measured. Five stents (Trevo ProVue [2 sizes], Revive, and Solitaire [2 sizes]) and three stent-deployment techniques (standard, push-and-fluff, and wire-push techniques) were evaluated. RESULTS The clot-capturing ability (maximum withdrawing force [N: newton]) was greater for large-diameter stents than for small-diameter stents (mean 0.39 ± 0.11 vs. 0.56 ± 0.18). For Trevo and Revive, the clot-capturing ability was highest with the push and fluff technique (mean 0.43 ± 0.05). For Solitaire, the ability was the highest with the simple wire-push technique (mean 0.705 ± 0.16). CONCLUSIONS We successfully numerically evaluated the clot-capturing abilities of SRs. The clot-capturing ability differed among SRs and among stent-deployment techniques.

Treatment of Ruptured Vertebral Artery Dissection and Abdominal Hemorrhage Associated with Segmental Arterial Mediolysis Using Endovascular Coil Embolization

BACKGROUND Segmental arterial mediolysis is a rare disease characterized by idiopathic noninflammatory vasculopathy involving small to medium arteries. Here, we report a case of ruptured cerebral and abdominal aneurysms, which were successfully treated using emergency endovascular coil embolization. CASE DESCRIPTION A 45-year-old male suffered subarachnoid hemorrhage caused by the rupture of the right vertebral artery dissecting aneurysm, which was treated using emergency endovascular coiling. Iatrogenic dissection of the left vertebral artery occurred during the procedure. A stent was placed, and antivasospasm therapy was initiated after operation. Eight days after admission, the patient experienced sudden hypovolemic shock because of an abdominal hemorrhage, which was diagnosed as the rupture of an aneurysm in the accessory middle colic artery and treated with urgent coil embolization. CONCLUSIONS It is extremely rare for a subarachnoid and an abdominal hemorrhage to occur simultaneously during hospitalization. Here, owing to the vulnerability of the unaffected vertebral artery during the initial procedure, segmental arterial mediolysis was diagnosed.

Neonatal Intracranial Pial Arteriovenous Fistula Treated with Endovascular Embolization: A Case Report

BACKGROUND Pial arteriovenous fistulas (PAVFs) are rare vascular malformations, especially in neonates. The purpose of this report is to discuss the treatment strategy and its associated challenges. We present a case of prenatal intracranial PAVF treated by endovascular embolization in the neonatal period. CASE DESCRIPTION The patient was born through Cesarean delivery and then treated twice using transarterial embolization with detachable platinum coils and n-butyl cyanoacrylate due to intractable heart failure. Even though angiography findings showed dramatical reduction in the shunt, the patient did not recover from heart failure and died at day 49 after birth. CONCLUSIONS Despite current developments in medical technology and therapies, the effective treatment of critical PAVFs still poses a challenge. Therefore, more indications and effective alternative treatments must be discussed.

Bilateral Vertebral Artery Dissection and Unilateral Carotid Artery Dissection in a Case of Ehlers–Danlos Syndrome Type IV

BACKGROUND Ehlers-Danlos syndrome (EDS) is a rare genetic connective tissue disorders, but the vascular type (type IV) typically poses the greatest risk to patients. We report a case of multiple cranial artery dissection, which was successfully treated with carotid artery stenting. CASE DESCRIPTION A 50-year-old woman presented with recurrent severe headaches caused by bilateral vertebral artery dissections that were treated conservatively at our hospital. However, she developed right cervical pain and dizziness at 3 days after admission, and a magnetic resonance angiogram revealed dissection of the right internal carotid artery. Because the dissected portion of the artery had narrowed, a stent was placed. The pearl and string formations in the bilateral vertebral arteries then improved spontaneously. Subsequently, the patient was diagnosed with EDS type IV via a skin biopsy, and review of her family history revealed that multiple family members had suffered from subarachnoid hemorrhages. No neurologic deficits were observed, and the patient was discharged without further events at 30 days after admission. CONCLUSIONS It is extremely rare for multiple artery dissections to occur at the same time. EDS type IV should be considered as an important differential diagnosis in similar cases, even in adult patients without a known history of connective tissue disease or vascular complications.

Novel Vertebral Artery Flow Reversal Method for Preventing Ischemic Complication during Endovascular Intervention

BACKGROUND AND PURPOSE We report a secure endovascular approach for the treatment of vascular lesions of the posterior circulation. Even if a large profile guide catheter is wedged in the unilateral vertebral artery (VA), our VA flow reversal method can prevent ischemic complications, including the spinal cord infarction. CASE PRESENTATION The patient was a 64-year-old woman who had been followed up for arteriovenous malformation (AVM) and an unruptured aneurysm of the basilar artery-superior cerebellar artery bifurcation. Endovascular treatment was performed because minor bleeding occurred from the AVM. When a 6-French guide catheter was navigated into the right VA, the guide catheter became completely wedged, and blood flow between the tip of the catheter and the VA union was fully stagnated. Because ischemia of the anterior spinal artery and right posterior inferior cerebellar artery could persist for a few hours during the endovascular procedure, we built a continuous reversal circulation from the guiding catheter tip to the femoral vein. The flow stagnation disappeared immediately. There was no complication during embolization of both the AVM and aneurysm. CONCLUSIONS The VA flow reversal method was secure in this case in which the tip of the guide catheter became wedged in the VA during the endovascular procedure.

Posterior Meningeal Artery Origin Patterns among 300 Cases and Their Clinical Importance

BACKGROUND AND PURPOSE The posterior meningeal artery (PMA) is known as a dura mater-nourishing vessel. We encountered a patient with Wallenberg syndrome during transarterial embolization of the PMA associated with the dural arteriovenous fistula (DAVF). METHODS After development of Wallenberg syndrome in the patient, we assessed origins of the PMA patterns in 300 cases and divided them into 3 types. CASE PRESENTATION A 63-year-old man was incidentally diagnosed as having transverse-sigmoid sinus DAVF with a cortical venous reflux. During the transarterial embolization, the patient complained of vertigo and numbness of the right extremities. Postoperatively, the patient exhibited Wallenberg syndrome. Diffusion-weighted magnetic resonance imaging showed a high-intensity area on the lateral side of the right medulla. CONCLUSIONS While performing arterial embolization of the PMA that directly originates from the intracranial vertebral artery, the possibility of deficient brainstem nourishment must be considered.

Expressions of Eotaxin-3, Interleukin-5, and Eosinophil-Derived Neurotoxin in Chronic Subdural Hematoma Fluids

Eosinophils induce inflammation by releasing cytokines and cytotoxic granule proteins. Infiltration of eosinophilic granulocytes occurs in the outer membrane of chronic subdural hematomas (CSDHs). Eosinophils play an important role in the growth of CSDHs. However, the manner in which eosinophils accumulate within CSDH fluid remains undetermined. In the current study, we assessed the expression of eosinophil chemoattractants in CSDH fluids according to growth stage of CSDHs and examined the correlation between the two. CSDH fluids were obtained from 38 patients during trepanation surgery. Ecalectin, eotaxin-3, interleukin-5 (IL-5), and eosinophil-derived neurotoxin (EDN) concentrations were measured using enzyme-linked immunosorbent assay kits. For use as controls, serum samples were collected from 5 healthy adults, and cerebrospinal fluid (CSF) samples were collected from 5 adults with unruptured aneurysms. The percentage of eosinophils (%eosinophil) in CSDH fluids was calculated using Giemsa staining. Concentrations of ecalectin, eotaxin-3, IL-5, and EDN were nearly equivalent in serum and CSF samples; however, their concentrations were high in CSDH fluids. In particular, ecalectin and EDN levels in CSDH fluids were significantly higher than those in serum and CSF. Levels of eotaxin-3, IL-5, EDN, and %eosinophil were significantly higher in laminar type of CSDH, whereas that of ecalectin was not. The correlations between eotaxin-3 and IL-5, IL-5 and EDN, and EDN and %eosinophil were statistically significant (p < 0.01). Our data suggest that eotaxin-3 is a chemoattractant of eosinophils. IL-5 induces the activation of eosinophils subsequent to degranulation of EDN into CSDH fluids. These factors may serve as novel therapeutic targets for managing CSDH.

Novel Technique for Rapid and Accurate Insertion of a Microguidewire Tail Into Low-Profile Devices During Endovascular Procedures: The Paper Rail Method

Purpose: To report a novel technique (“paper rail”) to facilitate inserting the tail of a microguidewire into the tip of a low-profile device during endovascular procedures. Technique: A sterilized nonwoven fabric tape with a smooth glossy paper backing is used. The tape has several linear folds ideal for a paper rail. Holding each piece of equipment about 5 cm from its respective tip, both the tail of the guidewire and the tip of the catheter are navigated at a 30° angle toward each other in the crease until the guidewire enters the catheter. The paper rail technique was compared with the conventional freehand method under varying luminosities found in an operating room. The paper rail technique was most effective in suboptimal lighting, where the mean time was reduced from 83 seconds with the conventional method to 20 seconds with the paper rail maneuver. The times required to insert the wire with the paper rail method were comparable (~22 seconds) at all light levels. Conclusion: The paper rail method may help improve the speed and accurate insertion of the tail of a microguidewire into the tip of low-profile devices during endovascular procedures. It may be particularly useful for physicians in a low-light environment or trainees.