Hidenori Oishi

Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia–reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.

Complications Associated with Transvenous Embolisation of Cavernous Dural Arteriovenous Fistula

Summary¶ Results are presented of transvenous embolisation, via either the inferior petrosal sinus (IPS) or the superior ophthalmic vein (SOV), for 19 patients with cavernous dural arteriovenous fistula with special emphasis on complications. In 17 patients (89%) there was complete angiographic elimination of the shunts and resolution of the symptoms. The remaining two patients also improved clinically, regardless of the minimal residual shunts. Complications included forehead dysaesthesia in one patient, blepharoptosis in two, and transient abducens nerve palsy in three. Injury of the supra-orbital nerve and levator muscle occurred in association with the exposure of the SOV in the patient with dysaesthesia of the forehead and in those with blepharoptosis, respectively. In two patients, abducens nerve palsy resulted from coil over-packing in the cavernous sinus and from dissection of the clival dura during guidewire penetration of the thrombosed IPS in one patient. We found that the complication rate decreased with time, because we became better with this procedure. We believe that transvenous embolisation is the best available treatment modality if one pays careful attention to avoid complications related to the procedure.

Transvenous Embolization of Dural Carotid Cavernous Fistulas: A Series of 44 Consecutive Patients

BACKGROUND AND PURPOSE: Endovascular TVE for DCCF is used for curative purposes, but serious complications can be caused with inadequate embolization. Our aim was to report clinical characteristics, angiographic findings, and results of endovascular TVE in patients presenting with DCCF. MATERIALS AND METHODS: We performed a retrospective analysis of 44 consecutive patients with DCCF treated by TVE. Approach routes, angiographic results, clinical outcomes, and complications were assessed. RESULTS: An approach via the internal jugular vein and inferior petrosal sinus was possible in 90% of patients, with complete occlusion of the fistula in 81.6% of patients. A minor residual shunt remained in 13.6% of patients, while a significant shunt remained in 4.5%. In 4 patients, add-on management with transarterial embolization was useful, and in 2 patients with residual shunt, radiosurgery was used. With long-term follow-up (6–40 months), we encountered recanalization/recurrence in 4 patients (9.1%). Complications were seen in the form of permanent morbidity in 3 patients (7%) and transient morbidity in 6 patients (14%). CONCLUSIONS: For endovascular treatment of DCCF, a transvenous approach was effective in most of our patients; however, some adverse effects were encountered. If AV shunts remain after transvenous treatment, additional modalities must be considered.

Determinants of Poor Outcome After Aneurysmal Subarachnoid Hemorrhage when both Clipping and Coiling Are Available: Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) in Japan

OBJECTIVE To examine current determinants of poor outcome after aneurysmal subarachnoid hemorrhage (SAH) when ruptured aneurysms are treated with either microsurgery (clipping) or endovascular treatment (coiling) depending on each patients characteristics. METHODS Between March 2006 and February 2007, 534 patients with SAH were enrolled in the Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) project. Patients were treated according to the preference of investigators who were experienced in performing both clipping and coiling. Factors influencing poor outcome (12-month modified Rankin Scale [mRS], 3-6) were determined using multivariate logistic regression analyses. RESULTS In this cohort, 32.4% of patients were World Federation of Neurosurgical Societies (WFNS) grade IV-V, and 28.1% had a poor outcome. Clipping was preferably performed for small aneurysms with a wide neck and for middle cerebral artery (MCA) aneurysms, whereas coiling was preferred for larger, internal carotid artery (ICA) and posterior circulation aneurysms. In addition to increasing age, admission WFNS grade IV-V, preadmission aneurysmal rerupture, vasospasm-induced cerebral infarct, pneumonia, sepsis, shunt-dependent hydrocephalus and seizure, postclipping hemorrhagic complications (odds ratio 4.8, 95% confidence interval 1.5-15.3, P < 0.01), and postcoiling ischemic complications (odds ratio 4.4, 95% confidence interval 1.3-15.2, P < 0.05) significantly caused poor outcomes, although the complications did not affect mortality. Type of treatment modality and size and location of aneurysms did not influence outcome. CONCLUSIONS Introducing an endovascular treatment option has made aneurysm characteristics less important to outcome, but procedural complications are problematic and should be reduced to improve outcome.

Endovascular Therapy of 500 Small Asymptomatic Unruptured Intracranial Aneurysms

BACKGROUND AND PURPOSE: Although the natural course of UIAs remains unclear, the risk of aneurysmal SAH due to small (<10 mm) asymptomatic UIAs is low. Endovascular therapy for UIAs has increased because of device development and the need for less invasive treatment. We report the results, safety, and efficacy of endovascular therapy of small asymptomatic UIAs. MATERIALS AND METHODS: A total of 457 patients with 500 small asymptomatic UIAs (maximum diameter < 10 mm) underwent endosaccular coil embolization at Juntendo University Hospital and affiliated hospitals. We retrospectively evaluated the technical feasibility, immediate and short-to-midterm follow-up anatomic results, procedure-related complications, and clinical outcomes. RESULTS: Endosaccular coil embolization was completed in 481 aneurysms (96.2%) and attempted in 19 (3.8%). Completed aneurysms were treated with the simple (39.5%), balloon-assisted (51.4%), and double-catheter (9.1%) techniques. Immediate angiographic outcomes were CO for 309 (64.2%) aneurysms, RN for 72 (15.0%), and RA for 100 (20.8%). Procedure-related complications occurred in 38 aneurysms (7.6%): 19 ischemic, 11 hemorrhagic, and 8 others. Permanent morbidity and mortality were 0.8% and 0.2%, respectively. Anatomic outcome of 427 aneurysms followed up for >6 months with conventional catheter or MR angiographies showed recanalization in 72 (16.9%) aneurysms, necessitating retreatment in 9.9% (mean, 31.4 months). No patients had aneurysmal SAH during the clinical follow-up period (mean, 34.7 months). CONCLUSIONS: In this series, endovascular therapy of small asymptomatic UIAs was highly feasible with low morbidity and mortality rates.

Successful surgical treatment of a dural arteriovenous fistula at the craniocervical junction with reference to pre- and postoperative MRI

Abstract We report a 62-year-old woman who presented with a myelopathy at the lower thoracic level. Left vertebral angiography revealed a dural arteriovenous fistula (DAVF) at the craniocervical junction, draining into an anterior spinal vein. Below the T 7 level, the spinal cord gave high signal on T 2-weighted images and enhanced with Gd-DTPA. The patient was successfully treated by simple clipping of vein draining the DAVF. The abnormal signal intensity and contrast enhancement rapidly regressed, except in the conus medullaris. Regression of the parenchymal abnormality on serial MRI following treatment corresponded closely with postoperative improvement of neurological function.

Pathophysiological dual action of adiponectin after transient focal ischemia in mouse brain.

BACKGROUND Adiponectin, an adipocyte-derived bioactive protein, provides vascular protection. Recent clinical studies have suggested that plasma adiponectin plays a role in cerebrovascular disease (CVD). The present study was designed to determine the serial changes in adiponectin expression in the brain and plasma after transient focal cerebral ischemia in mice. METHODS C57BL/6 mice (n=100) were subjected to 60 min of middle cerebral artery occlusion followed by 1, 3, 6, 12, 24, 48, 72 h and 7-day reperfusion. Plasma adiponectin levels were determined by ELISA kit, and expression of adiponectin was assessed by immunohistochemistry, western blot analysis, and reverse transcription-polymerase chain reaction. RESULTS Cerebral ischemia-reperfusion injury resulted in a transient rise in the acute phase and decrease in the late phase, in plasma adiponectin levels (P<0.05). The same insult resulted in upregulation of adiponectin expression, with two peaks at 3 and 24 h after reperfusion (P<0.05). Adiponectin protein was negligible in nonischemic contralateral hemispheres, but relatively high levels of the protein were detected in the ischemic hemisphere. Adiponectin mRNA was detected in neither nonischemic nor ischemic hemisphere. Adiponectin accumulated only in endothelial cells of ischemic brain in response to cerebral ischemia. CONCLUSIONS Our results indicate that ischemic insult results in a transient rise in plasma adiponectin level during the acute phase, and that circulating adiponectin then accumulates in damaged vessels in the ischemic brain during the late phase. These findings suggest that time-targeting administration of adiponectin could be potentially useful in the treatment of stroke.

Assessing Blood Flow in an Intracranial Stent: A Feasibility Study of MR Angiography Using a Silent Scan after Stent- Assisted Coil Embolization for Anterior Circulation Aneurysms

BACKGROUND AND PURPOSE: Blood flow in an intracranial stent cannot be visualized with 3D time-of-flight MR angiography owing to magnetic susceptibility and radiofrequency shielding. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). The purpose of this study was to determine whether Silent MRA could visualize flow in an intracranial stent placed in the anterior circulation. MATERIALS AND METHODS: Nine patients treated with stent-assisted coil embolization for anterior circulation aneurysms underwent MRAs (Silent MRA and TOF MRA) and x-ray digital subtraction angiography. MRAs were performed in the same session on a 3T unit. Two neuroradiologists independently reviewed the MRA images and subjectively scored flow in a stent as 1 (not visible) to 4 (excellent) by referring to the latest x-ray digital subtraction angiography image as a criterion standard. RESULTS: Both observers gave MRA higher scores than TOF MRA for flow in a stent in all cases. The mean score for Silent MRA was 3.44 ± 0.53, and for TOF MRA, it was 1.44 ± 0.46 (P < .001). CONCLUSIONS: Silent MRA was able to visualize flow in an intracranial stent more effectively than TOF MRA. Silent MRA might be useful for follow-up imaging after stent-assisted coil embolization, though these study results may be only preliminary due to some limitations.

Utility of time-resolved three-dimensional magnetic resonance digital subtraction angiography without contrast material for assessment of intracranial dural arterio-venous fistula

Background Intracranial dural arteriovenous fistula (DAVF) is an arteriovenous shunting disease of the dura. Magnetic resonance angiography (MRA) is expected to be a safer alternative method in evaluation of DAVF, compared with invasive intra-arterial digital subtraction angiography (IADSA). Purpose To evaluate the diagnostic use of time-spatial labeling inversion pulse (Time-SLIP) three-dimensional (3D) magnetic resonance digital subtraction angiography (MRDSA) without contrast material in six patients with DAVF. Material and Methods Images for 3D time-of-flight MRA, which has been a valuable tool for the diagnosis of DAVF but provide little or less hemodynamic information, and Time-SLIP 3D MRDSA, were acquired for each patient. The presence, side, and grade of the disease were evaluated according to IADSA. Results In all patients, the presence and side of the DAVF were correctly identified by both 3D time-of-flight MRA and Time-SLIP 3D MRDSA. Cortical reflux present in a patient with a grade 2b DAVF was not detected by Time-SLIP 3D MRDSA, when compared with IADSA findings. Conclusion Time-SLIP 3D MRDSA provides hemodynamic information without contrast material and is a useful complementary tool for diagnosis of DAVF.

Endovascular therapy of internal carotid artery bifurcation aneurysms

Background Internal carotid artery (ICA) bifurcation aneurysms are uncommon. Therefore, there have been only a few endovascular series on ICA bifurcation aneurysms published to date. The purpose of this study is to report the safety and efficacy of endovascular therapy for ICA bifurcation aneurysms. Methods There were 25 ICA bifurcation aneurysms (unruptured n=23, ruptured n=2) in 25 patients in this study. There were 14 women, with a mean age of 60.9±10.1 years. All patients underwent endosaccular coil embolization. Results Aneurysm size and neck size ranged from 2.5 to 10.0 mm (mean 5.4±1.5) and from 1.5 to 4.0 mm (mean 2.7±0.8), respectively. Regarding the clinical outcomes of the 23 patients with unruptured aneurysms, 22 patients had no change in their preprocedural modified Rankin Scale (mRS) score. The other patient died of ventilator associated aspiration pneumonia. Two patients with ruptured aneurysms each had scores of mRS 0. Overall morbidity and death rates were 0% and 4%, respectively. 15 aneurysms were treated with a simple technique. The 10 remaining aneurysms required adjunctive techniques: balloon assisted (n=9) and double catheter (n=1). The immediate anatomical outcomes were complete occlusion (n=19 (76.0%)), residual neck (n=4 (16.0%)) and residual aneurysm (n=2 (8.0%)). The overall follow-up of anatomical outcomes were unchanged (n=14 (63.7%)), improved (n=5 (22.7%)) and recurrence (n=3 (13.6%)). No patient suffered from aneurysmal subarachnoid hemorrhage after endovascular therapy. Thromboembolic events without clinical modification occurred in two patients. Conclusions Endovascular therapy of ICA bifurcation aneurysms is safe and effective, with a low risk of recanalization and re-treatment.