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Jun Karasawa, Hajime Touho, Hideyuki Ohnishi, Susumu Miyamoto and Haruhiko Kikuchi

✓ Between January, 1986, and October, 1990, 30 children with moyamoya disease, aged from 2 to 17 years, underwent omental transplantation to either the anterior or the posterior cerebral artery territory. The mean follow-up period was 3.8 years, ranging from 1.6 to 6.4 years. Seventeen patients had symptoms of monoparesis, paraparesis, and/or urinary incontinence and were treated using unilateral or bilateral omental transplantation to the anterior cerebral artery territory. Eleven patients had visual symptoms and were treated with unilateral or bilateral omental transplantation to the posterior cerebral artery territory.

Two patients had symptoms associated with both the anterior and the posterior cerebral arteries, and were treated with dual omental transplantations. All 19 patients treated with omental transplantation to the anterior cerebral artery and 11 (84.6%) of the 13 treated with omental transplantation to the posterior cerebral artery showed improvement in their neurological state. Patients with more collateral vessels via the omentum had more rapid and complete improvement in their neurological state. Patients with severe preoperative neurological deficits associated with the posterior cerebral artery had persistence of their symptoms.

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Susumu Miyamoto, Haruhiko Kikuchi, Jun Karasawa and Yoshihiro Kuriyama

✓ A case of spontaneous carotid artery dissection is presented. In the case described, superficial temporal artery-middle cerebral artery anastomosis was performed because of impending stroke. Surgical revascularization is indicated in a case that shows such a rapid evolution of stroke that spontaneous resolution of the dissection cannot be awaited.

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Susumu Miyamoto, Takeshi Funaki, Koji Iihara and Jun C. Takahashi

Object

The authors evaluated the efficacy of a new flow reduction strategy for giant partially thrombosed upper basilar artery (BA) aneurysms, for which proximal parent artery occlusion is not always effective.

Methods

Eight consecutive patients with severely symptomatic, partially thrombosed, giant upper BA aneurysms were treated with a tailored flow reduction strategy, or received conservative therapies. The flow reduction strategy comprised isolation of several branches from the upper BA at their origins with bypasses in addition to parent artery occlusion.

Results

The median follow-up period of all 8 patients was 15.0 months (range 4–31 months). In 6 patients treated with flow reduction, the mean decrease in residual blood lumen was −10.7 mm (95% CI −19.7 to −1.7 mm; p = 0.029) and the mean decrease in diameter of the aneurysms was −11.5 mm (95% CI −25.1 to 2.1 mm; p = 0.082). Complete or virtually complete thrombosis was achieved in all but 1 aneurysm (83%) and shrinkage was observed in 4 (67%). In those in whom complete or virtually complete thrombosis was achieved, significant shrinkage of the aneurysm was observed (mean decrease in diameter −14.8 mm; 95% CI −28.8 to −0.8 mm; p = 0.043). Improvement or stabilization of symptoms occurred in 67% of the patients who received flow reduction treatment. Both patients who received conservative treatment had unfavorable outcomes.

Conclusions

The flow reduction strategy is effective at promoting complete thrombosis of the aneurysm. This strategy can also induce shrinkage of the aneurysm if successful thrombosis is achieved. Although the neurological outcome of the treatment appears favorable considering its intractable nature, further study of the treatment is necessary to confirm its clinical efficacy and safety.

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Jun Karasawa, Hajime Touho, Hideyuki Ohnishi, Susumu Miyamoto and Haruhiko Kikuchi

✓ Between May, 1974, and March, 1991, 104 patients with moyamoya disease, all under 16 years old at the time of first surgery, underwent superficial temporal-to-middle cerebral artery anastomosis and/or encephalomyosynangiosis. The mean follow-up period was 9.6 years (range 4.8 to 16.0 years). Hemiplegia was the most frequent symptom before the first operation. Transient ischemic attacks (TIA's) were noted in 57 patients and minor stroke with hemiplegia in 44. The most frequent type of cortical dysfunction was aphasia (21 cases). Postoperatively, the incidence of TIA's and/or completed stroke with motor weakness of the extremities was markedly decreased, but visual disturbance progressed and major or minor stroke with visual disturbance was found in two cases. In patients under the age of 3 years, a major stroke prior to surgery resulted in a poor outcome in 36% of cases. Preoperative major stroke in patients between the ages of 3 and 7 years was less frequent, and poor outcomes were seen in 17% of this group. There were no major preoperative strokes in patients with surgery after the age of 7 years, and no poor outcomes were recorded in this group. A major preoperative stroke prior to surgery had adverse impact on the ultimate patient intelligence quotient (IQ) following surgery. All patients operated on after the age of 7 years had a normal or borderline IQ at follow-up examination.

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Mauro Bergui and Gianni B. Bradac

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Keisuke Yamada, Susumu Miyamoto, Motohiro Takayama, Izumi Nagata, Nobuo Hashimoto, Yoshito Ikada and Haruhiko Kikuchi

Object. In their pursuit of a better substitute for dura mater in neurosurgical procedures, the authors review their experience with GM972.

Methods. A newly developed synthetic dural substitute composed of bioabsorbable polymers (GM972) was placed in 53 patients during neurosurgical procedures. The handling properties of the material, surgical wound features, and findings of hematological, computerized tomography, and/or magnetic resonance imaging examinations were evaluated. The average follow-up period was 35.5 months. The handling properties and biocompatibility of this new dural substitute were highly satisfactory, and no significant complication was observed. In patients who underwent a second surgery performed more than 18 months after the initial operation, this new dural substitute was found to have been replaced by autologous collagenous tissue. Because of its bioabsorbability, chronic foreign body reactions to this synthetic dural substitute were negligible.

Conclusions. In this report the authors support the effectiveness and safety of this bioabsorbable artificial dural substitute that provides a reduced risk of transmission of latent infection.

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Yasuhiko Tabata, Keisuke Yamada, Liu Hong, Susumu Miyamoto, Nobuo Hashimoto and Yoshito Ikada

Object. The feasibility of using a biodegradable hydrogel incorporating basic fibroblast growth factor (bFGF) to induce bone regeneration at the site of a skull defect in monkeys was investigated.

Methods. Basic fibroblast growth factor was incorporated into a bioabsorbable hydrogel, which was prepared through glutaraldehyde crosslinking of gelatin. Following treatment of monkey skull defects measuring 6 mm in diameter (six defects/experimental group) with gelatin hydrogel incorporating bFGF, skull bone regeneration was evaluated using soft x-ray studies, dual x-ray absorptometry, and histological examinations.

The water content of the hydrogels varied according to the glutaraldehyde concentration in the hydrogel preparation. Gelatin hydrogels incorporating 100 µg of bFGF significantly promoted bone regeneration and the skull defect was completely closed 21 weeks after implantation. This is in marked contrast with the effect of the same dose of bFGF in solution form. Bone mineral density (BMD) measured at the sites of skull defect was enhanced by the bFGF-incorporating hydrogels. The BMD enhancement was more prominent at lower water contents of hydrogel. Empty gelatin hydrogels neither induced nor interfered with skull bone regeneration.

Conclusions. The findings of this study indicate that bFGF coupled with bioabsorbable hydrogel is a very promising tool to assist in the regrowth of bone at the site of a skull defect, which clinically has been recognized as almost impossible.

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Liu Hong, Yasuhiko Tabata, Susumu Miyamoto, Masaya Yamamoto, Keisuke Yamada, Nobuo Hashimoto and Yoshito Ikada

Object. Skull bone regeneration induced by transforming growth factor—β1 (TGFβ1)—containing gelatin hydrogels (TGFβ1-hydrogels) was investigated using a rabbit skull defect model. Different strengths of TGFβ1 were examined and compared: different TGFβ1 doses in gelatin hydrogels with a fixed water content, different water contents in gelatin hydrogels with a fixed TGFβ1 dose, and TGFβ1 in solution form. In addition, regenerated skull bone was observed over long time periods after treatment.

Methods. Soft x-ray, dual energy x-ray absorptometry, and histological studies were performed to assess the time course of bone regeneration at a 6-mm-diameter skull defect in rabbits after treatment with TGFβ1-hydrogels or other agents. The influence of TGFβ1 dose and hydrogel water content on skull bone regeneration by TGFβ1-hydrogels was evaluated. Gelatin hydrogels with a water content of 95 wt% that incorporated at least 0.1 µg of TGFβ1 induced significant bone regeneration at the rabbit skull defect site 6 weeks after treatment, whereas TGFβ1 in solution form was ineffective, regardless of dose. The in vivo degradability of the hydrogels, which varied according to water content, played an important role in skull bone regeneration induced by TGFβ1-hydrogels. In our hydrogel system, TGFβ1 is released from hydrogels as a result of hydrogel degradation. When the hydrogel degrades too quickly, it does not retain TGFβ1 or prevent ingrowth of soft tissues at the skull defect site and does not induce bone regeneration at the skull defect. It is likely that hydrogel that degrades too slowly physically impedes formation of new bone at the skull defect. Following treatment with 0.1-µg TGFβ1-hydrogel (95 wt%), newly formed bone remained at the defect site without being resorbed 6 and 12 months later. The histological structure of the newly formed bone was similar to that of normal skull bone. Overgrowth of regenerated bone and tissue reaction were not observed after treatment with TGFβ1-hydrogels.

Conclusions. A TGFβ1-hydrogel with appropriate biodegradability will function not only as a release matrix for the TGFβ1, but also as a space provider for bone regeneration. The TGFβ1-hydrogel is a promising surgical tool for skull defect repair and skull base reconstruction.

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Keisuke Yamada, Yasuhiko Tabata, Kazuo Yamamoto, Susumu Miyamoto, Izumi Nagata, Haruhiko Kikuchi and Yoshito Ikada

✓ Biodegradable gelatin hydrogels incorporating basic fibroblast growth factor (bFGF) were evaluated for their efficacy in bone regeneration using a rabbit model. Hydrogels with water contents of 85% and 98% were prepared using chemical crosslinking of gelatin with an isoelectric point of 4.9 in aqueous solution and, after freeze drying, were impregnated with an aqueous solution of bFGF to obtain bFGF-incorporated gelatin hydrogels. When they were implanted into bone defects measuring 6 mm in diameter in rabbit skulls (six animals/group), complete closure of the defect was observed at 12 weeks after implantation, regardless of the water content of the hydrogels. In contrast, bFGF did not enhance bone regeneration when applied to the skull defect in solution with phosphate-buffered saline (PBS). Also, gelatin hydrogels lacking bFGF were not effective in inducing bone formation, with fibrous tissue growing into the defect instead, similar to the skull defect seen in control rabbits treated with PBS. This indicates that the presence of hydrogels did not interfere with bone regeneration at the skull defect, probably because of their disappearance during biodegradation. It is concluded that the gelatin hydrogel is a promising matrix for effective induction of biological activity of bFGF for bone regeneration in skull and sinus defects.