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Tomohito Hishikawa, Koji Tokunaga, Kenji Sugiu, and Isao Date

Object

There is no description of the change in the posterior cerebral artery (PCA) in the diagnostic criteria of moyamoya disease (MMD). However, PCAs are often involved in the clinical setting, and an understanding of the significance of PCA lesions is therefore of great importance when evaluating the disease progression and predicting prognosis. The aim of this study was to assess the difference in posterior circulation involvement in pediatric and adult patients with MMD.

Methods

The records of 120 consecutive patients with MMD were reviewed. The clinical manifestations at diagnosis were evaluated on the basis of symptoms and CT and MRI findings. The degree of steno-occlusive internal carotid artery (ICA) lesions and the existence of steno-occlusive PCA lesions were evaluated by observing a total of 240 ICAs and PCAs on angiography. Angiographic correlation between anterior and posterior circulation was assessed in pediatric and adult patients with MMD.

Results

Seventeen (26%) of 66 pediatric patients and 18 (33%) of 54 adult patients exhibited steno-occlusive PCA lesions. There was no significant difference in the prevalence of PCA lesions between pediatric and adult patients with MMD (p = 0.36). The prevalence of infarction in pediatric and adult patients with PCA involvement was significantly higher than that in pediatric and adult patients without PCA involvement (p = 0.0003 and p = 0.003, respectively). There was no significant difference in the distribution of infarction areas between pediatric and adult patients with PCA involvement (p = 0.62). On the basis of the staging system used, steno-occlusive lesions in ICAs ipsilateral to PCAs with lesions were in significantly advanced stages compared with lesions in ICAs ipsilateral to PCAs without lesions in both pediatric and adult cases (p < 0.0001 and p = 0.0008, respectively). Pediatric patients had less advanced steno-occlusive lesions in ICAs ipsilateral to PCAs with lesions compared with adults (p < 0.05).

Conclusions

The clinical significance of posterior circulation involvement in MMD was similar between pediatric and adult patients. The only significant difference was that less advanced ICA lesions could complicate posterior circulation involvement in pediatric patients.

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Koji Tokunaga, Krisztina Barath, Jean-Baptiste Martin, and Daniel A. Rüfenacht

✓ Transarterial particulate embolization is indicated for benign intracranial dural arteriovenous fistulas (DAVFs) that have no dangerous venous reflux. This treatment, however, does not cure these lesions. In this case report the authors describe a spontaneously occurring DAVF that was treated by implanting coils through a transarterial microcatheter into the affected venous channel. The channel was separate from the normal dural sinuses. The pathological architecture of the fistula and the usefulness of this approach are discussed.

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Hernando Rafael

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Kenji Sugiu, Kazushi Kinugasa, Shinya Mandai, Koji Tokunaga, and Takashi Ohmoto

✓ Experimental aneurysms were created using a microsurgical technique to produce anastomosed venous pouches in the bilateral common carotid arteries of 12 dogs. The 24 aneurysms were then thrombosed via an endovascular approach with injection of a cellulose acetate polymer (CAP) solution that the authors have developed for use as a liquid thrombotic material. Angiography performed 1 to 4 weeks after CAP injection revealed complete thrombosis of the aneurysm with patency of the parent artery in 16 aneurysms. Histological analysis disclosed that the aneurysmal orifice in these cases was completely covered with newly formed endothelial cells 2 weeks after CAP thrombosis. Three other aneurysms exhibited parent artery occlusion caused by protrusion of the CAP mass through the aneurysmal orifice into the parent artery; this was thought to be caused by over-injection of the CAP solution. Histological analysis of the remaining five aneurysms, initially shown to have incomplete occlusion, revealed that they each possessed a residual neck that was partially covered with endothelial cells. No rupture of the aneurysms or migration of CAP into the distal arteries was observed.

These results suggest that using an endovascular approach, direct thrombosis of cerebral aneurysms with CAP is safe and effective. This technique may prove to be an alternative treatment for such aneurysms. However, there is a potential risk of regrowth or rupture of aneurysms that retain a residual neck and long-term follow-up studies will be required to evaluate this issue.

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Koji Tokunaga, Kenji Sugiu, Masahiro Kameda, Kyoji Sakai, Kaoru Terasaka, Toru Higashi, and Isao Date

✓ Intracerebral hemorrhage occurred in this 61-year-old woman with preexisting diplopia and proptosis. Results of angiography demonstrated a persistent primitive trigeminal artery (PPTA)—cavernous sinus fistula with cortical venous reflux. Two microcatheters were introduced transarterially through the PPTA into the two draining pathways in the cavernous sinus. Coils were delivered in both pathways simultaneously to prevent further venous overload on either path. The fistula was successfully occluded without complication while the PPTA was preserved. The authors describe this double-catheter technique for coil embolization of a fistula and review the literature concerning PPTA—cavernous sinus fistulas.

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Takashi Tamiya, Shuji Hamazaki, Yasuhiro Ono, Koji Tokunaga, Kengo Matsumoto, Tomohisa Furuta, and Takashi Ohmoto

✓ A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor—polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.

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Noboru Kusaka, Kenji Sugiu, Koji Tokunaga, Atsushi Katsumata, Ayumi Nishida, Katsunari Namba, Hirofumi Hamada, Hiroyuki Nakashima, and Isao Date

Object. Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks.

Methods. A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group.

Conclusions. In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.

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Keiichi Iseda, Shigeki Ono, Keisuke Onoda, Motoyoshi Satoh, Hiroaki Manabe, Mitsuhisa Nishiguchi, Kenji Takahashi, Koji Tokunaga, Kenji sugiu, and Isao Date

Object

Inflammation in the subarachnoid space and apoptosis of arterial endothelial cells have been implicated in the development of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). The authors investigated mechanisms of possible antivasospastic effects of N-benzyl-oxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), a caspase inhibitor that can inhibit both inflammatory and apoptotic systems, in animal models of SAH.

Methods

Rabbits were assigned to three groups of eight animals each and were subjected to SAH by injection of blood into the cisterna magna. The experiments were performed in the following groups: SAH only, SAH + vehicle, and SAH + Z-VAD-FMK. The Z-VAD-FMK (1 mg) or vehicle (5% dimethyl sulfoxide) was intrathecally administered before SAH induction. Diameters of the basilar artery (BA) were measured on angiograms obtained before and 2 days after SAH. The BA diameter on Day 2 was expressed as a percentage of that before SAH. Interleukin (IL)–1β in the cerebrospinal fluid (CSF) was examined using Western blotting, and brains were immunohistochemically examined for caspase-1 and IL-1β. In a separate experiment, 20 rats were subjected to SAH and their brains were immunohisto-chemically assessed for caspase-1, IL-1β, and macrophages.

Results

In rabbits, Z-VAD-FMK significantly attenuated cerebral vasospasm (the BA diameter on Day 2 in SAH-only, SAH + vehicle, and SAH + Z-VAD-FMK groups was 66.6 ± 3.2%, 66.3 ± 3.7%, and 82.6 ± 4.9% of baseline, respectively), and suppressed IL-1β release into the CSF and also suppressed immunoreactivities of caspase-1 and IL-1β in macrophages infiltrating into the subarachnoid space. Immunoreactivities for caspase-1 and IL-1β were observed in immunohistochemically proven infiltrating macrophages in rats.

Conclusions

These results indicate that caspase activation may be involved in the development of SAH-induced vasospasm through inflammatory reaction.

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Kazushi Kinugasa, Ichiro Kamata, Nobuyuki Hirotsune, Koji Tokunaga, Kenji Sugiu, Akira Handa, Hiroyuki Nakashima, Takashi Ohmoto, Shinya Mandai, and Yuzo Matsumoto

✓ Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had diffuse or localized thick subarachnoid blood clots, two had diffuse thin clots, and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome.

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Reiichiro Tanaka, Tetsuya Yumoto, Naoki Shiba, Motohisa Okawa, Takao Yasuhara, Tomotsugu Ichikawa, Koji Tokunaga, Isao Date, and Yoshihito Ujike

Magnetic resonance imaging is used with increasing frequency to provide accurate clinical information in cases of acute brain injury, and it is important to ensure that intracranial pressure (ICP) monitoring devices are both safe and accurate inside the MRI suite. A rare case of thermal brain injury during MRI associated with an overheated ICP transducer is reported.

This 20-year-old man had sustained a severe contusion of the right temporal and parietal lobes during a motor vehicle accident. An MR-compatible ICP transducer was placed in the left frontal lobe. The patient was treated with therapeutic hypothermia, barbiturate therapy, partial right temporal lobectomy, and decompressive craniectomy. Immediately after MRI examination on hospital Day 6, the ICP monitor was found to have stopped working, and the transducer was subsequently removed. The patient developed meningitis after this event, and repeat MRI revealed additional brain injury deep in the white matter on the left side, at the location of the ICP transducer. It is suspected that this new injury was caused by heating due to the radiofrequency radiation used in MRI because it was ascertained that the tip of the transducer had been melted and scorched. Scanning conditions—including configuration of the transducer, MRI parameters such as the type of radiofrequency coil, and the specific absorption rate limit—deviated from the manufacturer's recommendations. In cooperation with the manufacturer, the authors developed a precautionary tag describing guidelines for safe MR scanning to attach to the display unit of the product.

Strict adherence to the manufacturer's guidelines is very important for preventing serious complications in patients with ICP monitors undergoing MRI examinations.