Kazuya Kanemaru

Effects of cilostazol on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a multicenter prospective, randomized, open-label blinded end point trial

OBJECT Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a major cause of subsequent morbidity and mortality. Cilostazol, a selective inhibitor of phosphodiesterase 3, may attenuate cerebral vasospasm because of its antiplatelet and vasodilatory effects. A multicenter prospective randomized trial was conducted to investigate the effect of cilostazol on cerebral vasospasm. METHODS Patients admitted with SAH caused by a ruptured anterior circulation aneurysm who were in Hunt and Kosnik Grades I to IV and were treated by clipping within 72 hours of SAH onset were enrolled at 7 neurosurgical sites in Japan. These patients were assigned to one of 2 groups: the usual therapy group (control group) or the add-on 100 mg cilostazol twice daily group (cilostazol group). The group assignments were done by a computer-generated randomization sequence. The primary study end point was the onset of symptomatic vasospasm. Secondary end points were the onset of angiographic vasospasm and new cerebral infarctions related to cerebral vasospasm, clinical outcome as assessed by the modified Rankin scale, and length of hospitalization. All end points were assessed for the intention-to-treat population. RESULTS Between November 2009 and December 2010, 114 patients with SAH were treated by clipping within 72 hours from the onset of SAH and were screened. Five patients were excluded because no consent was given. Thus, 109 patients were randomly assigned to the cilostazol group (n = 54) or the control group (n = 55). Symptomatic vasospasm occurred in 13% (n = 7) of the cilostazol group and in 40% (n = 22) of the control group (p = 0.0021, Fisher exact test). The incidence of angiographic vasospasm was significantly lower in the cilostazol group than in the control group (50% vs 77%; p = 0.0055, Fisher exact test). Multiple logistic analyses demonstrated that nonuse of cilostazol is an independent factor for symptomatic and angiographic vasospasm. The incidence of new cerebral infarctions was also significantly lower in the cilostazol group than in the control group (11% vs 29%; p = 0.0304, Fisher exact test). Clinical outcomes at 1, 3, and 6 months after SAH in the cilostazol group were better than those in the control group, although a significant difference was not shown. There was also no significant difference in the length of hospitalization between the groups. No severe adverse event occurred during the study period. CONCLUSIONS Oral administration of cilostazol is effective in preventing cerebral vasospasm with a low risk of severe adverse events. Clinical trial registration no. UMIN000004347, University Hospital Medical Information Network Clinical Trials Registry.

Endoscopic indocyanine green video angiography in aneurysm surgery: an innovative method for intraoperative assessment of blood flow in vasculature hidden from microscopic view

Recently, intraoperative fluorescence video angiography using indocyanine green (ICG) has been widely used in aneurysm surgery. This is a simple and useful method to confirm complete occlusion of the aneurysm lumen and preservation of blood flow in the arteries around the aneurysm. However, the observation field of ICG video angiography is limited under a microscope, making it difficult to confirm the flow in the arteries behind the parent arteries or aneurysm. The authors developed a new technique of intraoperative endoscopic ICG video angiography to assess the blood flow in perforating arteries hidden by the parent arteries or aneurysm. The endoscope emits excitation light with a wavelength of approximately 800 nm, and video images were obtained through a cut filter. The authors used this ICG fluorescence endoscope in treating 3 patients with unruptured cerebral aneurysms. During clip placement, the endoscope was inserted to confirm aneurysm occlusion. Then, ICG was intravenously administered, and the fluorescence in the vessels was observed via the endoscope as well as under the microscope. The blood flow in the perforating arteries was clearly identified, and no procedural complication occurred. The authors conclude that the technique is very useful and facilitates intraoperative real-time assessment of the patency of perforating arteries behind parent arteries or aneurysms.

Surgical management of aneurysms of the bifurcation of the internal carotid artery

Internal carotid artery (ICA) bifurcation aneurysms are rare and easily bleed in younger patients, but are difficult to treat surgically, due to perforators surrounding and adherent to the aneurysm. A series of 25 patients treated by clipping under the operating microscope are analyzed and compared with previous cases. Twenty-five patients, 11 men and 14 women (mean age 51 years), were treated by the same neurosurgeon. Seventeen patients presented with subarachnoid hemorrhage (Hunt & Kosnik Grade I in three, II in five, III in two, IV in seven), five with unruptured ICA bifurcation aneurysms, and three with unruptured ICA bifurcation aneurysms but another ruptured aneurysm. There were 23 small, one large, and one giant ICA bifurcation aneurysms. The projection was superior in 12, anterior in seven, and posterior in six cases. Pterional approach was employed for all cases. Outcomes were evaluated at discharge with the Glasgow Outcome Scale. Favorable outcomes (good recovery (GR) and moderate disability (MD)) were obtained in ten of 17 patients with ruptured ICA bifurcation aneurysm. Favorable outcomes were significantly greater in Grades I and II (three in I, four in II) than in Grades III and IV (one in III, two in IV; P=0.0498). Seven of eight patients with unruptured ICA bifurcation aneurysm had favorable outcomes. Temporary clipping and projection of the aneurysm did not affect the outcome. Causative factors of unfavorable outcomes were primary brain damage in cases of small and large aneurysms and perforator damage in the case of giant aneurysm. Poor clinical grade and vasospasm are the causative factors of poor outcome in patients with ruptured ICA bifurcation aneurysm. Preservation of perforators is crucial in cases of giant aneurysm. Clipping of unruptured ICA bifurcation aneurysms is recommended since they tend to bleed at a lower age than other aneurysms.

Intra-arterial injection fluorescein videoangiography in aneurysm surgery.

BACKGROUND: To visualize blood flow in the arteries and aneurysm during surgery, intravenous fluorescence videoangiography has been used. However, the image contrast with this procedure is diminished by repeated study because the dye remains for about 10 minutes after injection. OBJECTIVE: To determine the optimal dye concentration and to clarify the usefulness of fluorescein videoangiography by intra-arterial dye injection. METHODS: In the pilot study, fluorescein sodium dissolved at various concentrations was illuminated with excitation light, and fluorescence was detected by cameras. The fluorescence of 0.001% fluorescein sodium solution mixed with plasma at various concentrations was then examined. In 13 aneurysm patients, dye solution was administered through the catheter for intraoperative digital subtraction angiography. The intravenous injection method was also performed, and the findings were compared. RESULTS: Dye was clinically used at a concentration of 0.005% to 0.1% on the basis of the results of the pilot study. Fluorescence emission from the vessels and aneurysms was clearly observed by both methods; however, arterial injection provided brighter emission, resulting in clearer demonstration of the bloodstream than venous injection. Dye clearance was also quicker, which allowed repeat injections without delay. Dye filling in the aneurysm indicating incomplete occlusion was detected in 2 cases, and occlusion of the perforating artery was observed in 2 cases. CONCLUSION: Intra-arterial fluorescein videoangiography provides brighter and clearer imaging of blood flow with a smaller dose of dye than intravenous videoangiography. It can be repeated within a short time and is useful for detecting incomplete clipping or unexpected obstruction of arteries. ABBREVIATIONS: AcomA, anterior communicating artery DSA, digital subtraction angiography ICA, internal carotid artery ICG, indocyanine green MEP, motor evoked potential

Indocyanine green videoangiography to detect aneurysm and related vascular structures buried in subarachnoid clots

This 44-year-old woman presented with a ruptured anterior communicating artery aneurysm. Intraoperative indocyanine green (ICG) videoangiography demonstrated the aneurysm neck and dome, which were buried in subarachnoid clots. Dissection and aspiration of the clots around the neck were safely performed without touching the ruptured points. The aneurysm was successfully clipped. The patients postoperative course was excellent. This case illustrates the use of intraoperative ICG videoangiography to provide information about the anatomical location of the aneurysm neck and dome despite their being completely obscured by subarachnoid clots. Intraoperative ICG videoangiography allowed safer dissection of the ruptured aneurysm from the blood clots.

Intracranial Pial Arteriovenous Fistula Caused by Dural Tenting: Case Report

We describe a rare case where a patient developed intracranial pial arteriovenous (AV) fistula due to dural tenting. The patient was a 63-year-old woman who had undergone neck clipping for an unruptured middle cerebral artery (MCA) aneurysm. The surgery was performed without any problems and her postoperative course was uneventful. Two weeks after cerebral angiography operation revealed a pial AV fistula fed by the right MCA and drained into the vein of Trolard through the Sylvian vein which had not existed before surgery. Being diagnosed as de novo pial AV fistula, surgical repair was performed. The AV fistula was located just beneath the dural tenting. The fistulous point was confirmed with fluorescein video angiography and obliterated using a clip. Although rare, we should pay attention to the AV fistula due to dural tenting as the complications of cranial surgery.

In-stent Thrombosis after Carotid Artery Stenting Despite Sufficient Antiplatelet Therapy in a Bladder Cancer Patient

In-stent thrombosis (IST) after carotid artery stenting (CAS) is a rare but potentially devastating complication. We present a case of early IST after CAS despite sufficient antiplatelet therapy in a patient with bladder cancer. A 77-year-old man under preventive triple antiplatelet therapy underwent CAS without any intra- or periprocedural complications. However, the patient developed a large asymptomatic IST 6 days after CAS. Anticoagulant therapy with argatroban was reintroduced to treat IST concomitant with antiplatelet agents. Subsequently, the IST shrank and disappeared without any thrombotic symptoms. Malignancy is regarded as an acquired thrombophilic condition associated with a significant risk of thrombosis. In the field of coronary stents, cancer is associated with a significant increasing risk of IST. The cause of IST in our case was possibly related in hypercoagulable state because of the patients cancer. Attention for IST should be paid in CAS cases with these risk factors, and repeated examination is recommended.

Giant Serpentine Aneurysm of the Distal Anterior Cerebral Artery

We report a case of a 38-year-old man with a giant serpentine aneurysm arising from the distal anterior cerebral artery. This aneurysm grew from a fusiform aneurysm to a huge aneurysm within 5 months before manifesting as a mass lesion. The aneurysm was largely filled with thrombus, and 4 distal branches arose from the aneurysm dome. Selective balloon test occlusion of the distal anterior cerebral artery using an intravascular technique was performed to confirm the tolerance of the brain tissue. The balloon test occlusion elicited adequate leptomeningeal collateral circulation and no neurologic symptoms; thus, the aneurysm was treated with trapping and resection. The patient had no ischemic complications after the surgery and returned to his job 1 month later. No ischemia developed in the 2 years after surgery. Selective balloon test occlusion of the distal cerebral artery using an intravascular technique can be a very useful tool in planning the therapeutic strategy for a complicated distal cerebral aneurysm.

Phase II Trial of Intravenous Low-Dose Granulocyte Colony-Stimulating Factor in Acute Ischemic Stroke

BACKGROUND Granulocyte colony-stimulating factor (G-CSF) has shown neuroprotective and neurogenerative activities in experimental studies, and our previous phase I clinical study suggested the safety and potential efficacy of low-dose G-CSF in acute ischemic stroke patients. The present phase II trial is aimed to evaluate the effect of G-CSF administration on neurological function and infarct volume, compared with a placebo group. METHODS Forty-nine acute ischemic stroke patients (29 males, 20 females; 71 ± 10 years) within 24 hours after onset were recruited. Eligible patients were randomized 2:2:1 to receive G-CSF 150 µg/body/day, G-CSF 300 µg/body/day, and placebo, respectively. We evaluated clinical outcome in terms of the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index at 90 days after onset, together with changes in infarct volume on magnetic resonance imaging. RESULTS We found no serious adverse event, including change in leukocyte levels, which remained below 31,000/µL, at 150 and 300 µg G-CSF/body/day. Clinical outcome scores did not show any significant difference among the 3 groups. Chronological changes in infarct volume also showed no significant difference. CONCLUSIONS G-CSF was well-tolerated at 150 and 300 µg/body/day in patients with acute ischemic stroke. However, administration of G-CSF at both 150 and 300 µg/body/day neither contributed to functional recovery nor reduced infarct volume at 3 months after onset, compared with the control group. The apparent lack of effectiveness may have been due to the small sample size. A trial of combination therapy with recombinant tissue plasminogen activator and G-CSF is planned.

Hypoglossal canal dural arteriovenous fistula embolized under precise anatomical evaluation by selective intra-arterial injection computed tomography angiography

Dural arteriovenous fistula (DAVF) involving the hypoglossal canal is rare but increasingly reported. To achieve complete obliteration without a procedure-related complication, understanding of the precise anatomy of this DAVF is essential. Here, we describe a 72-year-old man who underwent selective intra-arterial injection computed tomography angiography which allowed us to understand the detailed anatomy of the complex DAVF regarding access routes and the target regions for transvenous embolization (TVE). With the aid of this novel neuroimaging technique successful target TVE was achieved safely and completely.