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Kazuo Yonenobu, Sohei Ebara, Keiju Fujiwara, Kazuo Yamashita, Keiro Ono, Tomio Yamamoto, Norimasa Harada, Hiroshi Ogino and Shinzaburo Ojima

✓ The authors describe their experience with 26 cases of thoracic myelopathy secondary to hypertrophic ossification of the spinal ligament (posterior longitudinal ligament and/or ligamentum flavum). The clinical manifestations of this condition and results of its surgical treatment are described. The commonest symptoms were numbness or tingling in the legs and feet and gait disturbance. Most of the patients with involvement of the upper thoracic spine showed typical features of thoracic myelopathy: that is, sensory and motor deficits in both the trunk and lower extremities, sphincter disturbance, and exaggerated tendon reflexes. Several patients with involvement of the thoracolumbar junction presented with atypical symptoms of thoracic myelopathy and were sometimes misdiagnosed and treated inappropriately. Surgical treatment, particularly laminectomy, was not always successful. Inconsistencies in the surgical outcome were caused by either operative complications or reversal of the initial improvement during the follow-up period. The results of anterior surgery for the condition were more favorable; however, use of this procedure was rarely indicated.

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Susumu Ito, Ken'ichi Sekido, Hiroshi Kanno, Hironobu Sato, Masaaki Tanaka, Kazuo Yamaguchi and Isao Yamamoto

Object. The goal of this study was to elucidate the genotype—phenotype relationship in syndromic craniosynostoses by analyzing the mutations of the fibroblast growth factor receptor (FGFR) gene and its clinical manifestations in patients, particularly those in atypical cases.

Methods. Twenty patients with craniosynostoses unrelated to Apert syndrome were enrolled in this study. The phenotypes indicated the following syndromes: 12 patients with unrelated Crouzon syndrome, including nine sporadic and three familial cases; two with sporadic Pfeiffer syndrome; and one with Antley—Bixler syndrome. The Crouzon phenotype was subdivided into three clinical forms: regular, top, and bottom ones. Two patients who demonstrated craniofacial anomalies and bilateral elbow joint contractures were categorized as having an unspecified craniosynostosis. Three cases of unclassifiable cloverleaf skull malformation were also analyzed.

Methods. Fourteen mutations of the FGFR2 gene were identified in these patients; seven of the 10 cysteine-related mutations were substitutions of codon 342 in the third immunoglobulin-like domain of this gene. The phenotypes of these seven cases were three of regular Crouzon, two of unspecified craniosynostosis, and one each of top Crouzon and unclassifiable cloverleaf skull malformation. In addition, four of the seven patients were found to have the same genotype (Cys342Arg). The phenotypes of these patients, however, were quite variable, ranging from regular Crouzon to unclassifiable cloverleaf skull malformation.

Conclusions. The phenotypes of patients with craniosynostoses unrelated to Apert syndrome proved quite variable, even in cases in which patients demonstrated the same genotype. In view of the phenotypic diversity evident in cases in which the same mutation in the FGFR2 gene is present, it is possible that other disease-modifying genetic factors exist to control the abnormal gain-of-function that accompanies FGFR signaling.

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Keisuke Yamada, Susumu Miyamoto, Izumi Nagata, Haruhiko Kikuchi, Yoshito Ikada, Hiroo Iwata and Kazuo Yamamoto

✓ A new bioabsorbable composite sheet was developed to provide a substitute for the dura mater and was evaluated histologically and biomechanically using rats and rabbits. This composite, composed of two l-lactic acid-ϵ-caprolactone (50% l-lactic acid, 50% ϵ-caprolactone) copolymer films and a poly(glycolic acid) nonwoven fabric, displayed good mechanical properties and was completely absorbed 24 weeks after implantation in the back of rats. Histological evaluation of the composite sheet was undertaken by implanting it in 31 rabbits with dural defects and examining the sites of implantation 2 weeks to 26 months later. No infection, cerebrospinal fluid leakage, evidence of convulsive disorders, significant adhesion to underlying cortex, or calcification was noticed in any cases. In addition, the regenerated duralike tissue had a high pressure-resistant strength 2 weeks after implantation. The authors conclude that this new bioabsorbable composite sheet can be successfully used as a dural substitute.

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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.

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Kazuhiro Chiba, Itsuo Yamamoto, Hisashi Hirabayashi, Motoki Iwasaki, Hiroshi Goto, Kazuo Yonenobu and Yoshiaki Toyama

Object. Ossification of the posterior longitudinal ligament (OPLL) often progresses after surgery, and this may cause late-onset neurological deterioration. There have been few studies, however, to clarify any correlation between progression and clinical outcome, partly because of the lack of studies involving reliable and reproducible methods by which detection of progression is made possible. The authors conducted a multicenter study to investigate the occurrence of postoperative progression and to elucidate the possible risk factors in a large-scale patient population, and a novel computer-assisted measurement method was used to provide the basis for future clinical studies.

Methods. The authors analyzed lateral plain radiographs obtained immediately and at 1 and 2 years after surgery in 131 patients who underwent posterior decompression at 13 institutions. The x-ray films were transformed via scanner into digital images; the length and thickness of ossifications were measured using a new computer-assisted measurement system, and the incidence of progression was determined. Odds ratios for progression according to age group and types of OPLL were determined and compared to elucidate significant risk factors of progression.

Conclusions. This is the first multicenter study to investigate the incidence of OPLL progression after posterior decompression by using a standardized measurement method. The rate of postoperative progression at 2 years was 56.5%, which was comparable with results reported in other studies. Progression occurred more frequently in younger-age rather than in older-age patient populations at both 1 and 2 years postoperatively. Mixed-type and continuous-type OPLL progressed more frequently than the segmental-type lesion at 2 years. The results of the present study could serve as basis for future studies to assess the efficacy of drug therapy to prevent OPLL progression.

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Shigeki Yamada, Masatsune Ishikawa, Kazuo Yamamoto, Tadashi Ino, Toru Kimura, Shotai Kobayashi and Japan Standard Stroke Registry Study Group

OBJECT

The present study aimed to investigate aneurysm locations and treatments for ruptured cerebral aneurysms associated with secondary normal-pressure hydrocephalus (sNPH) after subarachnoid hemorrhage (SAH) by using comprehensive data from the Japanese Stroke DataBank.

METHODS

Among 101,165 patients with acute stroke registered between 2000 and 2013, 4693 patients (1482 men, 3211 women) were registered as having had an SAH caused by a ruptured saccular aneurysm. Of them, 1448 patients (438 men and 1010 women; mean age 61.9 ± 13.4 years) who were confirmed to have or not have coexisting acute hydrocephalus and sNPH were included for statistical analyses. Locations of the ruptured aneurysms were subcategorized into 1 of the following 4 groups: middle cerebral artery (MCA; n = 354), anterior communicating artery and anterior cerebral artery (ACA; n = 496), internal carotid artery (ICA; n = 402), and posterior circulation (n = 130). Locations of 66 of the ruptured aneurysms were unknown/unrecorded. Treatments included craniotomy and clipping alone in 1073 patients, endovascular coil embolization alone in 285 patients, and a combination of coiling and clipping in 17 patients. The age-adjusted and multivariate odds ratios from logistic regression analyses were calculated after stratification using the Fisher CT scale to investigate the effects of the hematoma volume of SAH.

RESULTS

Acute hydrocephalus was confirmed in 593 patients, and 521 patients developed sNPH. Patients with a ruptured ACA aneurysm had twice the risk for sNPH over those with a ruptured MCA aneurysm. Those with an ACA aneurysm with Fisher Grade 3 SAH had a 9-fold-higher risk for sNPH than those with an MCA aneurysm with Fisher Grade 1 or 2 SAH. Patients with a ruptured posterior circulation aneurysm did not have any significant risk for sNPH. Clipping of the ruptured aneurysm resulted in twice the risk for sNPH over coil embolization alone.

CONCLUSIONS

Patients with low-grade SAH caused by a ruptured MCA aneurysm had a low risk for the development of sNPH. In contrast, patients with high-grade SAH caused by a ruptured ACA aneurysm had a higher risk for sNPH. Endovascular coiling might confer a lower risk of developing sNPH than microsurgical clipping.

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Kintomo Takakura, Hiroshi Abe, Ryuichi Tanaka, Koichi Kitamura, Tetsuro Miwa, Kazuo Takeuchi, Shinjiro Yamamoto, Naoki Kageyama, Hajime Handa, Heitaro Mogami, Akira Nishimoto, Tohru Uozumi, Masao Matsutani and Kazuhiro Nomura

✓ A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area.

The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level.

This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.