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The goal of this survey is to investigate the indications for preoperative digital subtraction angiography (DSA) before clipping of ruptured and unruptured intracranial aneurysms in an international panel of neurovascular specialists.An anonymous survey of 23 multiple-choice questions relating to indications for DSA before clipping of an intracranial aneurysm was distributed to the international panel of attendees of the European-Japanese Cerebrovascular Congress (EJCVC), which took place in Milan, Italy on 7-9 June 2018. The survey was collected during the same conference. Descriptive statistics were used to analyze the data.A total of 93 surveys were distributed, and 67 (72%) completed surveys were returned by responders from 13 different countries. Eighty-five percent of all responders were neurosurgeons. For unruptured and ruptured middle cerebral artery (MCA) aneurysms without life-threatening hematoma, approximately 60% of responders perform surgery without preoperative DSA. For aneurysms in other locations than MCA, microsurgery is done without preoperative DSA in 68% of unruptured and in 73% of ruptured cases. In cases of ruptured MCA or ruptured non-MCA aneurysms with life-threatening hematoma, surgery is performed without DSA in 97% and 96% of patients, respectively. Factors which lead to preoperative DSA being performed were: aneurysmal shape (fusiform, dissecting), etiology (infectious), size (25 mm), possible presence of perforators or efferent vessels arising from the aneurysm, intra-aneurysmal thrombus, previous treatment, location (posterior circulation and paraclinoid aneurysm) and flow-replacement bypass contemplated for final aneurysm treatment. These are all factors that qualify an aneurysm as a complex aneurysm.There is still a high variability in the surgeons' preoperative workup regarding the indication for DSA before clipping of ruptured and unruptured intracranial aneurysms, except for ruptured aneurysms with life-threatening hematoma. There is a general consensus among cerebrovascular specialists that any angioanatomical feature indicating a complex aneurysm should lead to a more detailed workup including preoperative DSA.

In Japan, hybrid neurosurgeons who perform both open surgical clipping as well as endovascular embolization for the treatment of intracranial aneurysms are common. Although many Japanese neurosurgeons can perform surgical clipping of middle cerebral artery aneurysms or internal carotid artery-posterior communicating artery aneurysms and coil embolization of cerebral aneurysms using simple techniques-only a limited number of neurosurgeons are able to perform surgical clipping and endovascular procedures for anterior communicating artery aneurysms, paraclinoid, or posterior circulation aneurysms using both treatment modalities equally and safely.The senior author's personal experience of more than 500 cases each of surgical clipping and endovascular embolization over the past 25 years included 110 cases of basilar tip aneurysms and 104 cases of paraclinoid internal carotid artery (ICA) aneurysms.The safety and efficacy of both treatments appears to be the same, while the durability of surgical clipping is superior to that of endovascular embolization. Among the 110 basilar tip aneurysms, 18 patients were treated by surgical clipping and 94 were treated by endovascular embolization. The initial results of endovascular therapy seemed to be better than those of surgical clipping, although the rate of retreatment was higher. Among the 104 cases of paraclinoid ICA aneurysm, 23 patients were treated by surgical clipping and 81 were treated by endovascular embolization. The results of both treatments seemed to be same, while surgical clipping had apparently good long-term durability. Over the past 15 years, the frequency of surgical clipping for basilar tip aneurysms has decreased, and the procedure may eventually be abandoned for this type of aneurysm. However, surgical clipping still offers several advantages in the treatment of paraclinoid aneurysms.Hybrid neurosurgeons can make reasonable decisions concerning the choice of treatment for cerebral aneurysms, as they perform both treatments and understand the benefits and drawbacks of each modality.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Objective: In Japan, hybrid neurosurgeons who perform both open surgical clipping as well as endovascular embolization for the treatment of intracranial aneurysms are common. Although many Japanese neurosurgeons can perform surgical clipping of middle cerebral artery aneurysms or internal carotid artery—posterior communicating artery aneurysms and coil embolization of cerebral aneurysms using simple techniques—only a limited number of neurosurgeons are able to perform surgical clipping and endovascular procedures for anterior communicating artery aneurysms, paraclinoid, or posterior circulation aneurysms using both treatment modalities equally and safely. Materials and methods: The senior author’s personal experience of more than 500 cases each of surgical clipping and endovascular embolization over the past 25 years included 110 cases of basilar tip aneurysms and 104 cases of paraclinoid internal carotid artery (ICA) aneurysms. Results: The safety and efficacy of both treatments appears to be the same, while the durability of surgical clipping is superior to that of endovascular embolization. Among the 110 basilar tip aneurysms, 18 patients were treated by surgical clipping and 94 were treated by endovascular embolization. The initial results of endovascular therapy seemed to be better than those of surgical clipping, although the rate of retreatment was higher. Among the 104 cases of paraclinoid ICA aneurysm, 23 patients were treated by surgical clipping and 81 were treated by endovascular embolization. The results of both treatments seemed to be same, while surgical clipping had apparently good long-term durability. Over the past 15 years, the frequency of surgical clipping for basilar tip aneurysms has decreased, and the procedure may eventually be abandoned for this type of aneurysm. However, surgical clipping still offers several advantages in the treatment of paraclinoid aneurysms. Conclusions: Hybrid neurosurgeons can make reasonable decisions concerning the choice of treatment for cerebral aneurysms, as they perform both treatments and understand the benefits and drawbacks of each modality.

This is an open access proceeding book of 9th European-Japanese Cerebrovascular Congress at Milan 2018. Since many experts from Europe and Japan had very important and fruitful discussion on the management of Cerebrovascular diseases, the proceeding book is very attractive for the physician and scientists of the area.

Introduction: The goal of this survey is to investigate the indications for preoperative digital subtraction angiography (DSA) before clipping of ruptured and unruptured intracranial aneurysms in an international panel of neurovascular specialists.Methods: An anonymous survey of 23 multiple-choice questions relating to indications for DSA before clipping of an intracranial aneurysm was distributed to the international panel of attendees of the European-Japanese Cerebrovascular Congress (EJCVC), which took place in Milan, Italy on 7–9 June 2018. The survey was collected during the same conference. Descriptive statistics were used to analyze the data.Results: A total of 93 surveys were distributed, and 67 (72%) completed surveys were returned by responders from 13 different countries. Eighty-five percent of all responders were neurosurgeons. For unruptured and ruptured middle cerebral artery (MCA) aneurysms without life-threatening hematoma, approximately 60% of responders perform surgery without preoperative DSA. For aneurysms in other locations than MCA, microsurgery is done without preoperative DSA in 68% of unruptured and in 73% of ruptured cases. In cases of ruptured MCA or ruptured non-MCA aneurysms with life-threatening hematoma, surgery is performed without DSA in 97% and 96% of patients, respectively. Factors which lead to preoperative DSA being performed were: aneurysmal shape (fusiform, dissecting), etiology (infectious), size (>25 mm), possible presence of perforators or efferent vessels arising from the aneurysm, intra-aneurysmal thrombus, previous treatment, location (posterior circulation and paraclinoid aneurysm) and flow-replacement bypass contemplated for final aneurysm treatment. These are all factors that qualify an aneurysm as a complex aneurysm.Conclusion: There is still a high variability in the surgeons’ preoperative workup regarding the indication for DSA before clipping of ruptured and unruptured intracranial aneurysms, except for ruptured aneurysms with life-threatening hematoma. There is a general consensus among cerebrovascular specialists that any angioanatomical feature indicating a complex aneurysm should lead to a more detailed workup including preoperative DSA.

Trochlear nerve neurinomas are rare and solitary tumors without neurofibromatosis are extremely rare. We report a case of trochlear nerve neurinoma presenting with pathological laughter and diplopia. A 40-year-old male patient presented with diplopia and pathological laughter 2 months before admission. MRI showed a multicystic enhanced mass in the left tentorial incisura compressing the midbrain and the upper pons. The tumor was excised using the left trans-Sylvian approach with partial uncal resection. After excision of the tumor, the left trochlear nerve was identified on the surface of the lateral midbrain. The nerve was connected to the tumor. Pathological laughter completely resolved after the operation. This is the second reported case of trochlear nerve neurinoma presenting with pathological laughter. The lesion responsible for pathological laughter could be the midbrain, upper pons, diencephalon, or all of these.

Background We used initial plain computed tomography to delineate acutely occluded internal carotid arteries or horizontal segments of middle cerebral arteries. If affected arteries could be delineated using initial plain computed tomography, useful information might be obtained that could support endovascular thrombectomies. Methods In 15 patients with occluded internal carotid arteries or horizontal segments of middle cerebral arteries, the affected middle cerebral artery was automatically traced using the extender function for blood vessel tracing with reference to the default value (window setting, 40; window width, 90) on Ziostation 2 (Ziosoft Inc., Tokyo, Japan) based on initial plain computed tomography data. Results The horizontal and sylvian segments of the middle cerebral artery were delineated in 15 and nine patients, respectively, based on plain computed tomography volume data. Images of occluded vessels delineated by plain computed tomography closely correlated with digital subtraction angiography. Conclusions Initial plain computed tomography combined with a new generation workstation enabled the rapid delineation of occluded segments of intracranial vessels and could provide useful information that might improve the safety of endovascular thrombectomy.

Introduction It has not been reported how long the follow-up study after carotid artery stenting (CAS) should be continued. The purpose of the present study is to clarify the dynamic change of the in-stent neointimal layer and residual arterial lumen by two years following CAS using three-dimensional computed tomography angiography (3D CTA) with volume rendering. Methods Thirty-six stented carotid arteries in 34 consecutive patients were examined by 3D CTA with volume rendering at two weeks and 3, 6, 12, 24 months of follow-up. Results An in-stent hypodense area could be detected in 10 of 36 (27.8%) carotid arteries at two weeks after CAS. In-stent hypodense areas gradually declined thereafter by three months. In the course of longer follow-up, the layer of the in-stent hypodense area (neointimal hyperplasia) continued to grow in size for up to 24 months. Patients with an in-stent hypodense area at two weeks have a thicker layer of neointimal hyperplasia at 24 months than patients without in-stent hypodense area at two weeks’ follow-up. The predictive factors for growing neointimal hyperplasia at 24 months in multiple regression analysis are ulcer formation in pretreatment stenosis and the thickness of in-stent hypodense area at two weeks following CAS. Conclusion Our results suggest that follow-up study should be continued for a longer period even if in-stent restenosis could not be detected at one year following CAS. Especially in cases with ulcer formation in pretreatment stenosis and with a subacute in-stent hypodense area after CAS, longer follow-up is strongly recommended.

The superficial temporal artery to middle cerebral artery (STA-MCA) bypass procedure has continually evolved and new strategies have been advocated to reduce anesthetic or surgical mortality and morbidity. Further simplifying and decreasing the invasiveness of STA-MCA bypass by performing this operation without endotracheal general anesthesia was deemed feasible in certain subsets of patients.We performed STA-MCA bypass using local anesthesia using a sedative in 45 patients with hemodynamically compromised cerebrovascular occlusive disease as well as multiple comorbidities in the period between February 2010 and April 2016. The technique is based on preoperative identification of the point at which the donor and recipient vessels are in closest proximity. The preoperative use of computed tomography angiography allowed us to identify the target point precisely and use a minimally invasive procedure. All patients received dexmedetomidine as the sole sedative agent, together with scalp block local anesthesia with an unsecured airway.Successful STA-MCA bypass surgeries were achieved via a preselected minimally invasive approach in all cases. There was good hemodynamic stability throughout surgery. No airway/ventilation complications occurred and no patient was converted to general anesthesia. The patients subjectively tolerated this technique well with a high rate of satisfaction. Postoperative magnetic resonance angiography confirmed patent bypass in 44 of 45 patients (patency rate of 97.8%). There were two postoperative hyper-perfusion syndromes and one cerebral ischemia with transient neurological symptoms (postoperative complication rate of 6.3%). No recurrence of ipsilateral cerebral ischemia was observed during the follow-up periods. There was one contralateral cardiogenic cerebral embolism during the follow-up period. The overall stroke rate was calculated as 1%/patient/year.Our initial experience confirms the feasibility of performing STA-MCA bypass under local anesthesia without endotracheal general anesthesia.

Background and aims. The superficial temporal artery to middle cerebral artery (STA-MCA) bypass procedure has continually evolved and new strategies have been advocated to reduce anesthetic or surgical mortality and morbidity. Further simplifying and decreasing the invasiveness of STA-MCA bypass by performing this operation without endotracheal general anesthesia was deemed feasible in certain subsets of patients.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Posterior cerebral artery (PCA) aneurysms are rare, and direct surgery of these is considered difficult. Coil embolization of PCA aneurysms is becoming popular. However, it is difficult to completely obliterate the aneurysm while preserving the flow of the parent artery in large or giant PCA aneurysms with a wide neck with this technique. We report a case of a large and wide-necked PCA aneurysm with multiple recurrences following successful surgical clipping and coil embolization. A 77-year-old man with a large unruptured right PCA (P2) aneurysm was successfully treated by surgical clipping. Postoperative digital subtraction angiography (DSA) showed complete aneurismal occlusion. Four years afterward, the aneurysm recurred and grew toward the contralateral. Surgical retreatment of this complicated aneurysm was considered difficult, with a substantial risk of complications. Therefore, the aneurysm was treated with an endovascular procedure. Because simple coil embolization was not expected to achieve satisfactory obliteration of the aneurysm with preservation of parent artery patency, we used stent-assisted coil embolization. The patient tolerated the treatment well. On DSA obtained six months after the first endovascular treatment, coil compaction and recanalization of the aneurysm were detected. A second coil embolization was successfully performed without any complications. The aneurysm was stable during the next six-month follow-up. Stent-assisted coil embolization may be feasible and effective for such postoperatively complicated aneurysms.

The surgical treatment of intrinsic brainstem lesions remains a major challenge. In this article we present the results of using an infratentorial-supracerebellar (ITSC) approach for the resection of intrinsic ponto-mesencephalic lesions.The authors reviewed the cases of 16 patients. In seven of them, a paramedian ITSC transcollicular approach was used to resect intrinsic mid-brain lesions, and in the other nine patients, an intermediate or lateral ITSC infra-trochlear approach was used for ponto-mesencephalic lesions.All 16 lesions were completely removed. There was no recurrence of bleeding during the follow-up period, and no mortality. In seven patients with mid-brain lesions, the preoperative ocular symptoms improved in three of them, and the neurological deficits - other than ocular symptoms improved - in five of them. The preoperative modified Rankin Scale score of 1.8 improved to 1.3 postoperatively. In nine patients with a ponto-mesencephalic lesion, the preoperative ocular symptoms improved in four of nine patients, and the neurological deficits other than ocular symptoms improved in five of them, while one patient exhibited venous infarction in a cerebellar hemisphere that caused neurological deterioration. The preoperative modified Rankin Scale score of 3.75 improved to 2.5 postoperatively in these patients.The ITSC transcollicular or infra-trochlear approach provide a wide operative entry zone and minimize the functional damage to the surrounding structures for access to ponto-mesencephalic lesions.

Cerebral revascularization strategies may become necessary in select patients who present with challenging cerebral aneurysms. In this study, we present the techniques of a moderate-flow extra-intracranial bypass using a short interposition vein graft and concurrent aneurysm management.The short interposition vein graft was used for the reconstruction of complex cerebral aneurysms in nine patients. In eight of them, the superficial temporal artery (STA) main trunk was used as a donor site for the anastomosis of a short interposition vein graft, and an extracranial vertebral artery (VA) was used in one case. The vein grafts were implanted into the M2 of the middle cerebral artery (MCA) for the adjunctive treatment of internal carotid artery (ICA) aneurysms in three patients, into the A3 of the anterior cerebral artery (ACA) in one patient, into the P2 of the posterior cerebral artery (PCA) for the adjunctive treatment of complex PCA aneurysms in three patients, into the P3 of the PCA for the adjunctive treatment of a basilar artery (BA) trunk giant aneurysm in 1 patient, and into the postero-inferior cerebellar artery (PICA) for the adjunctive treatment of the VA dissecting aneurysm in one patient.All of the bypasses were patent. Intraoperative flow measurements confirmed a moderate flow-carrying capacity of the short interposition short vein graft (30-70 ml; mean: 43 ml/min).The STA main trunk to proximal MCA/PCA bypass and the extracranial VA to PICA bypass using short interposition vein grafts can provide sufficient blood flow and may be a reasonable alternative to the conventional EC-IC bypass/high-flow bypass.

Object Superficial temporal artery (STA)–middle cerebral artery (MCA) bypasses have continually evolved, and new strategies have been advocated for reducing anesthetic or surgical morbidity and mortality. Further simplifying, and decreasing the invasiveness of, STA-MCA bypass by performing this operation without endotracheal general anesthesia was believed to be feasible in certain subsets of patients. Methods The authors performed STA-MCA bypass using local anesthesia with a sedative in 10 patients with hemodynamically compromised occlusive cerebrovascular disease, as well as multiple comorbidities, between February 2010 and September 2011. The technique is based on the preoperative identification of the point at which the donor and recipient vessels are in closest proximity. Preoperative use of CT angiography allowed the authors to identify the target point precisely and use a minimally invasive procedure. All patients received dexmedetomidine as the sole sedative agent, together with scalp-blocking local anesthesia, with an unsecured airway. Results Successful STA-MCA bypass surgeries were achieved via a preselected minimally invasive approach in all cases. There was good hemodynamic stability throughout surgery. No airway or ventilation complications occurred, and no patients were converted to general anesthesia. Subjectively, patients tolerated the technique well with a high rate of satisfaction. There were no perioperative morbidities or deaths. Postoperative MR angiography confirmed a patent bypass in all patients. All patients remained symptom free and returned to normal daily life following the operation. Conclusions This initial experience confirms the feasibility of performing STA-MCA bypass without endotracheal general anesthesia. This novel technique produced a high degree of patient satisfaction.

A 63-year-old patient presented with cerebral hyperperfusion manifesting as transient aphasia and general tonic convulsions 3 and 4 days after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. Diffusion-weighted magnetic resonance (MR) imaging revealed a focal low-intensity area at the site of anastomosis in the left temporal lobe, with high apparent diffusion coefficient, together with focal intense increase in cerebral blood flow in the same region. This lesion was considered to be pure vasogenic edema caused by cerebral hyperperfusion. Additional treatment with intravenous drip infusion of free radical scavenger and reduction in blood pressure with nicardipine improved the patient's symptoms and brain edema. The brain edema gradually decreased on MR imaging and completely disappeared at 3 months after bypass surgery. Cerebral hyperperfusion is often encountered after recanalization of occlusive arteries, removal of arteriovenous malformations, and carotid endarterectomy, but may also occur after STA-MCA anastomosis.

Background and Aims The surgical treatment of intrinsic brainstem lesions remains a major challenge. In this article we present the results of using an infratentorial-supracerebellar (ITSC) approach for the resection of intrinsic ponto-mesencephalic lesions.

Background and Aims Cerebral revascularization strategies may become necessary in select patients who present with challenging cerebral aneurysms. In this study, we present the techniques of a moderate-flow extra-intracranial bypass using a short interposition vein graft and concurrent aneurysm management.

It has been believed that clinical outcomes of the elderly subarachnoid hemorrhage (SAH) patients in poor grades are quite unsatisfactory. Recently, endovascular coil embolization is available for such patients as a less invasive treatment. In this study, we retrospectively analyzed clinical outcome of SAH patients in poor grades who were treated with endovascular coil embolization. Among 54 patients (≧75 years) presenting aneurysmal SAH who underwent early endovascular coil embolization, 24 patients in WFNS Grade IV or V were analyzed. Nineteen patients were in Grade IV, and 5 patients in Grade V. In all the patients, the dome of the aneurysm was successfully embolized with detachable coils. The degree of occlusion of the treated aneurysm was complete occlusion in 21%, neck remnant in 33%, dome filling in 25%, and partial in 21%. The rate of procedural complication was 8.3%. Outcome after 6 months was favorable in 37% of Grade IV and 40% in Grade V, respectively. Endovascular coil embolization was successfully performed in elderly SAH patients in poor neurological grades with a high level of technical success and acceptable clinical outcomes.

A 71-year-old man presented with right hemiparesis and aphasia due to cerebral infarction in the frontal lobe. Computed tomography (CT) revealed a high-density mass, 12 mm in diameter, in the stem of the left sylvian fissure. Carotid angiography demonstrated occlusion of the left ascending frontal artery complex and retention of contrast medium at the bifurcation of the left middle cerebral artery (MCA). The diagnosis was cerebral infarction caused by occlusion of the ascending frontal artery complex resulting from thrombosed left MCA aneurysm. The patient was managed conservatively and his neurological symptoms gradually improved. One month later, he lapsed into a coma. CT revealed subarachnoid hemorrhage. Carotid angiography showed a large left MCA aneurysm with branch occlusion of the left ascending frontal artery complex. A left frontotemporal craniotomy was performed. The MCA aneurysm was opened and the intramural thrombi removed, and finally neck clipping was performed. The patient made a good postoperative recovery.

BACKGROUND Carotid aneurysms of the paraclinoid segment are usually located in the intradural space, but can infrequently straddle the intra- and extradural space. CASE DESCRIPTION We present 2 cases of unruptured carotid dural ring aneurysms with an aneurysmal sac that straddled the distal dural ring. Each paraclinoid aneurysm projected superiorly from the anterior surface of the internal carotid artery with a relatively flattened dome and central indentation on angiography. The aneurysmal domes were circumscribed by the distal dural ring and straddled the intra- and extradural space. After broad opening of the distal dural ring, aneurysms were successfully obliterated by clip application in parallel with the internal carotid artery. CONCLUSION These cases underscore the significance of an aneurysmal dome indentation on angiographic images as a reflection of aneurysmal circumscription by the distal dural ring. Aneurysms that straddle the intra- and extradural space may require broad opening of the distal dural ring for adequate control and clipping.

Percutaneous transluminal angioplasty (PTA) has been a useful therapy to treat stenosis of cervical internal carotid artery (ICA) or vertebral artery (VA). Here we show that our clinical results regarding preventive effect of stenting on restenosis after PTA in the ICA and VA origin. We also show our experimental studies with gene transfer techniques aiming reduction of restenosis after balloon-injury in rat carotid artery. It has been reported that drug-eluting stent inhibits restenosis after coronary angioplasty. Further understanding of the mechanism of restenosis and application of these new modalities may lead to better clinical results in angioplasty of the craniocervical arteries.

We previously reported that hepatocyte growth factor (HGF) promoted proliferation of neurospheres and neuronal differentiation of neural stem cells (NSCs) derived from mouse embryonic brain. In this study, spheres from mouse embryonic stem (ES) cells were generated by floating culture following co-culture on PA6 stromal cells. In contrast to the behavior of the neurospheres derived from embryonic brain, addition of HGF to the growth medium of the floating cultures decreased the number of spheres derived from ES cells. When spheres were stained using a MAP-2 antibody, more MAP-2-positive cells were observed in spheres cultured with HGF. When HGF was added to the growth and/or differentiation medium, more MAP-2-positive cells were also obtained. These results suggest that HGF promotes neuronal differentiation of NSCs derived from ES cells.

We used a paramedian, infratentorial-supracerebellar, transcollicular approach to resect 6 intrinsic midbrain cavernous malformations. The route of access to the lesions was designed to minimize the anatomic and functional damage to the surrounding structures. Access was through one superior colliculus in 2 cases, through one inferior colliculus in 2 cases, and through the superior and inferior colliculi of one side in 2 cases. All 6 lesions were completely removed; the preoperative ocular symptoms improved in 4 of these 6 patients and did not change in 2. The neurological deficits except ocular symptoms improved in 2 patients. No recurrence of bleeding was observed during the follow-up period (mean 52 months). We conclude that the paramedian, infratentorial-supracerebellar, transcollicular approach permits safe removal of intrinsic midbrain cavernous malformations. Resection of the superior or inferior colliculus, or both, on one side appears to be neurologically well tolerated.

Hepatocyte growth factor (HGF), originally cloned as a hepatocyte mitogen, has recently been reported to exhibit neurotrophic activity in addition to being expressed in different parts of the nervous system. At present, the effects of HGF on neural stem cells (NSCs) are not known. In this study, we first report the promoting effect of HGF on the proliferation of neurospheres and neuronal differentiation of NSCs. Medium containing only HGF was capable of inducing neurosphere formation. Addition of HGF to medium containing fibroblast growth factor 2 or epidermal growth factor increased both the size and number of newly formed neurospheres. More neurons were also obtained when HGF was added in differentiation medium. In contrast, neurosphere numbers were reduced after repeated subculture by mechanical dissociation, suggesting that HGF-formed neurospheres comprised predominantly progenitor cells committed to neuronal or glial lines. Together, these results suggest that HGF promotes proliferation of neurospheres and neuronal differentiation of NSCs derived from mouse embyos.

✓ The authors have recently performed a fluorescence-guided tumor resection procedure by using high-dose fluorescein sodium without any special surgical microscopes for the intraoperative visualization of glioblastoma multiforme (GBM), and they report on the actual procedure and clinicopathological findings. Thirty-two patients with GBMs underwent tumor resection during which this fluorescence-guided procedure was used. Fluorescein sodium (20 mg/kg) was intravenously injected after dural opening at the craniotomy site. The tumor was stained almost homogeneously yellow and the color was intense enough to be readily perceived for resection. The center of the solid lesion was stained a deep yellow and surrounded by a transition zone that was faintly stained. The colored lesion was clearly distinguishable from the unstained zone outside the GBM, particularly in the white matter. Both the deeply and faintly stained regions included endothelial proliferation and dense tumor cells. In the unstained region, less dense tumor cells were consistently revealed; however, no endothelial proliferation could be seen. Grosstotal resection (GTR) was successful in 84.4% of the patients who received an injection of fluorescein sodium, which accounted for 100% of those in whom all the visible yellow color (both the deeply and faintly stained regions) was judged to have been resected during operation. Gross-total resection was performed in 100% of the patients who underwent the fluorescence-guided procedure and assigned to Stage I, a GBM stage in which, as a therapeutic policy, the tumor should be resected as radically as possible. The GTR rates in patients who received fluorescein sodium were significantly higher than those in patients who did not (73 patients with GBMs who underwent tumor resection without the fluorescence-guided procedure). Although the extent of surgery was revealed to be one of the significant and independent prognostic factors for GBM, the fluorescein sodium—guided resection procedure was not a significant or independent prognostic factor in this series. This surgical procedure does not require any special surgical microscopic equipment and is simple, safe, useful, readily accomplished, and universally available for resection of GBMs. Its efficacy simplifies the surgical procedure of navigating the stained lesion from the unstained area to achieve GTR of GBMs, which can be demonstrated on magnetic resonance images.

We describe follow-up clinical and angiographic results in patients with cerebral aneurysms treated with IDC or GDC. In 175 patients, 116 patients with ruptured aneurysm and 59 patients with non-ruptured aneurysm who underwent endovascular occlusion of aneurysms, there was no mortality and nine cases (4.7%) with morbidity in the periprocedural period. During follow up period, four cases (2.3%) experienced bleeding, and three cases (1.7%) experienced thromboembolic events. On the follow-up angiograms (median angiographic follow-up period 24.8 months), 12.5% of incompletely obliterated aneurysms exhibited progressive thrombosis, 20% remained unchanged and 67.5% showed aneurysmal recanalization or regrowth. Histological examination of a small ruptured A-com aneurysm treated seven months before harvesting, demonstrated that formation of an incomplete endothelium-lined layer of connective tissue at the orifice, and no complete fibrous obliteration of the aneurysm lumen could be detected, various amounts of unorganized clot were still present in the center of the aneurysm. Coil embolization is a safe treatment for cerebral aneurysms with a lower incidence of periprocedural morbidity, wheareas follow-up results are less satisfactory in cases involving incompletely obliterated lesions.

The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.

We report two instructive cases of ruptured dissecting aneurysm of the basilar artery. Although stent-assisted endovascular treatment was successful, recurrent bleeding occurred 4 h after the procedure in one patient, and the other's basilar artery occluded 6 days after the procedure. These cases suggest that the high porosity of currently available stents may be insufficient to induce intraluminal thrombosis and merely stenting may fail to prevent bleeding, while postoperative anticoagulation alone may be inadequate to prevent occlusion of the stented vessel.

Object. It is well known that the central nervous system (CNS) is an immunologically privileged site. To characterize CD8+ tumor-infiltrating lymphocytes (TILs) recovered from the CNS, the authors compared these cells with TILs recovered from subcutaneous tissue by using a B7.1 gene—modified tumor implantation model. Methods. The authors established a B7.1 gene—modified EL4 murine lymphoma cell line (EL4-B7.1) and implanted the cells into the CNS to observe the duration of tumor-free survival. Although EL4-B7.1 cells were completely rejected in a subcutaneous implantation model, 40% of animals died after the CNS implantation (all animals in which the parent tumor was implanted died within 16 days). Therefore, the authors isolated TILs from each implantation site and analyzed the expressions of activation antigens CD25 and CD69 by performing the anti-CD8 magnetic beads separation method and flow cytometric analysis. After implantation of the parent tumor, there was no difference in the number of TILs from each site (CD25 1.7–3.2%, CD69 21.9–34.3%). After implantation of the B7.1-modified tumor, the CD25-expressing TIL population from the subcutaneous site was 4.68 times higher than that from the CNS site (17.8% compared with 3.8%). Based on these findings, the authors used a mitomycin C—treated EL4-B7.1 subcutaneous vaccination with various protocols. Vaccination before tumor challenge was sufficient to prevent the development of the tumor. For animals with established tumor, the vaccination protocol was able to prolong host survival (p = 0.0053). Conclusions. The data clearly demonstrate that the CNS environment fails to activate CD8+ TILs fully. These are the first data indicating in detail a difference between CD8+ TILs from the CNS and those from other sites based on a B7.1-modified tumor model.

Superficial temporal artery (STA) is the mainstay of donor vessels for extra-intracranial bypass (EC-IC bypass) in cerebral revascularization. However, the typically used STA frontal or parietal branch is not always adequate in its flow-carrying capacity. In the present study, we provide an update on an alternative strategy: the use of the STA main trunk as a donor vessel, with a short vein interposition graft.Seven patients in whom the STA main trunk was used as a donor site for anastomosis of a short interposition vein graft were included. The grafts were implanted into the M2 of the middle cerebral artery for adjunctive treatment of IC anterior wall blood-blister aneurysms in two patients, for revascularization of an internal carotid artery occlusion in one patient, into the P2/3 of the posterior cerebral artery (PCA) for adjunct treatment of complex PCA aneurysms in three patients and into the P3 of PCA for adjunct treatment of basilar artery (BA) trunk giant aneurysm in one patient.All the bypasses were patent. Intraoperative flow measurements confirmed a moderate flow-carrying capacity of the STA main trunk-interposition short vein graft (20-50 ml; mean 43 ml/min).The STA main trunk has a larger diameter than the distal branch; therefore, it would be expected to have a significantly higher flow capacity than its branches. STA main trunk to proximal MCA/PCA bypass using short interposition vein grafts can provide sufficient blood flow, and may be a reasonable alternative to ECA to MCA/PCA bypass using long vein grafts.

Background and Purpose— About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial–intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. Methods— This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial–intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Results— Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan–Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P =0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148–1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan–Meier survival analysis (2.7%/y versus 7.6%/y; P =0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125–1.009). Conclusions— Although statistically marginal, Kaplan–Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: C000000166.

The purpose of this study was to evaluate the usefulness of contrast-enhanced 3D MR angiography (CE-MRA) with an automated bolus-detection algorithm (SmartPrep technique) and the specialized phased-array coils for the patients suspected cerebrovascular disease. Forty-three patients with brain attack were examined with CE-MRA. A tracker volume of SmartPrep technique was placed along the ascending aorta in the coronal image. After the bolus injection of gadolinium, an increase in signal that corresponded to the arrival of gadolinium was used to trigger centric re-ordered spoiled gradient echo arterial selective MRA with imaging time of 20-40 sec. We were able to achieve a 100% successful triggering rate of SmartPrep technique and selectively arterial-phase carotid and vertebral arteries with almost no venous contamination could be delineated. These techniques enabled high resolution imaging of entire craniocervical arteries from aortic arch to the circle of Willis. This CE-MRA was useful to evaluate both occlusion of arteries and the collateral pathways and to measure stenosis and residual flow of dissection accurately. CE-MRA was a reliable less-invasive alternative to investigate the patients of cerebrovascular disease.

✓ The supracerebellar transtentorial (SCTT) approach, a modification of the infratentorial supracerebellar approach, facilitates simple and minimally invasive access to posterior temporomedial structures without requiring retraction of the temporal or occipital lobe. The SCTT approach was used in 16 patients over a 3-year period. Eleven patients harbored tumors confined to, or located mainly within, the posterior hippocampal formation, three patients harbored aneurysms (one ruptured posterior cerebral artery [PCA] aneurysm at the P2-P3 junction, one ruptured giant PCA [P2] aneurysm, and one giant basilar artery—superior cerebellar artery aneurysm), one patient had juvenile-type moyamoya disease, and one patient suffered from medically intractable epilepsy. In these patients, the SCTT approach enabled tumor removal, aneurysm clipping, and vascular bypass procedures. The authors' experience suggests that this approach can be used routinely in treating lesions in the posterior temporomedial region.