長谷川 光広

The decoy receptor 3 (DcR3) gene is amplified at high frequency in human lung, colon, and liver cancers. DcR3 has been demonstrated to produce a secreted member of the tumor necrosis factor receptor superfamily that negatively regulates Fas-mediated apoptosis. In this study we examined DcR3 gene amplification, DcR3 mRNA expression, and DcR3 protein expression in 46 human astrocytic brain tumors by quantitative genomic PCR, quantitative reverse transcription-PCR, and immunohistochemistry, respectively. The DcR3 gene amplification was detected in none of 6 (0%) low-grade astrocytomas, 1 of 16 (6%) anaplastic astrocytomas, and 6 of 24 ( 25%) glioblastomas. Six of 7 (86%) cases with gene amplification exhibited both mRNA overexpression and/or protein overexpression, suggesting that DcR3 mRNA and protein were expressed more abundantly in the cases with gene amplification. We thus concluded that high DcR3 mRNA expression and protein expression may be positively related to the gene amplification in astrocytic brain tumors, especially glioblastomas. Further, we speculated that the DcR3 gene amplification with overexpression may be responsible for malignant features in glioblastomas.

Objective: This study was aimed to understand ultrastructural pathology of nerves of tumor origin of spinal schwannomas, which has not been reported so far, in order to understand the mechanism of the postoperative functional restoration after the nerve transection. Methods: From 13 patients who underwent sacrifice of an affected nerve root at total removal of spinal schwannomas (C2 conus), the proximal (spinal cord side, n = 12) and distal (dorsal root ganglion side, n = 10) stumps of the nerves of the tumor origin were collected and examined by light and electron microscope, followed by morphometric analysis (n = 9). Results: Almost all of affected nerves at both proximal and distal to the lesion were composed of well-preserved myelin sheath and axons with mild disturbance of endo- and perineurial structures at light microscopic level except one case, which showed severe fibrosis. Electron-microscopically, regenerated axons with thin myelin were found in part in the proximal and distal nerves with few macrophages in three cases. The area of nerves (mm(2)), density of myelinated axons (axons/mm(2)) and total number of myelinated axons in the proximal stump (0.552 +/- 0.430, 10,400 +/- 5,240 and 5,480 +/- 4,790) was approximately 70 %, 80 % and 60 %, respectively, of those in the distal stump (0.765 +/- 0.333, 12,400 +/- 5,180 and 9,970 +/- 8,630). Conclusions: This data combined with no permanent deficits after nerve transection suggest that the nerves of tumor origin are in the processes of slowly progressed deterioration with repeated degeneration and regeneration/remyelination, and the postoperative rapid recovery from the transient neurological deficit may be explained by functional compensation by the adjacent non-affected nerves with slow tumor growth.

Cyanotic breath-holding spell is a benign and self-limiting disease of young children but occasionally associated with sudden, unexpected death. The authors report a rare case in a 2-year-old girl with a severe form that started after radical resection of a cervicomedullary ganglioglioma. She was admitted to our hospital because of delayed and unstable gait. Since magnetic resonance imaging showed a cervicomedullary tumor, she underwent a radical resection and histology showed the tumor to be a ganglioglioma. Postoperatively, the function of the lower cranial nerves and cerebellum deteriorated and hemiparesis on the left became apparent, but she returned to the preoperative state in a few months. In addition, mild sleep apnea (Ondine curse) and severe cyanotic breath-holding spells occurred. The former responded to medication but the latter failed and continued several times per day with a rapid onset and progression of hypoxemia, loss of consciousness, sweating and opisthotonos. Five months after the operation, the patient returned home with a portable oxygen saturation monitor equipped with an alarm. This case indicates that cyanotic breath-holding spell, as well as sleep apnea, is critical during the early postoperative period. This is the first report observing that such spells may occur as a complication of radical resection of a cervicomedullary tumor. Copyright © 2005 S. Karger AG, Basel.

Solitary fibrous tumor (SFT) is a benign and rare neoplasm. To date, only 37 patients with intracranial SFTs have been reported. Although a number of the tumors were recurrent and some later underwent malignant transformation, none of these lesions progressed to cerebrospinal fluid (CSF) dissemination. In this paper the authors report a case of SFT in which the lesion recurred several times and ultimately was disseminated by the CSF. The patient was a 63-year-old woman with multiple intracranial and spinal tumors. Fifteen years before this presentation, at the age of 48 she had been hospitalized for resection of a falcotentorial tumor. During the ensuing 15 years she underwent multiple surgeries and sessions of radiation therapy for recurrent lesions. The exclusive location of her tumors in the subarachnoid space at the end of this 15-year period indicate CSF dissemination of the tumor. The tumor that was resected when the patient was 48 years old and the latest resected lesion were analyzed by performing immunohistological CD34, epithelial membrane antigen, vimentin, S100 protein, and reticulin staining, and determining the MIB-1 labeling index (LI). Most of the results were identical, and both tumors were diagnosed as SFT according to a staining pattern that showed a strong and diffuse positive reaction for CD34. Nevertheless, the authors noted that the MIB-1 LI increased from less than 1% in the original tumor to 13% in the latest tumor. The increased proliferation of MIB-1 indicates that the malignant transformation could have occurred during tumor recurrence with CSF dissemination.

A 44-year-old man presented with a rare subfrontal schwannoma with headache. He had undergone radiation therapy for a pineal lesion 30 years previously, but the histology was not verified. On admission, neurological examination revealed no focal deficits including hyposmia. Computed tomography demonstrated a mass measuring 5 x 3 cm in the right anterior cranial fossa. Magnetic resonance imaging revealed a heterogeneously enhanced mass with multiple cysts. The tumor, which was clearly separable from the surrounding normal brain, was totally resected through a right frontal craniotomy. There was no adhesion between the tumor and the olfactory groove or cribriform plate. The frontal base dura was suspected to be the tumor attachment. The patient was discharged without hyposmia. Histological examination revealed a typical pattern of schwannoma consisting of Antoni type A and type B. Immunohistochemical staining was positive for S-100 protein but negative for epithelial membrane antigen. Subfrontal schwannoma not associated with the olfactory groove or cribriform plate is extremely rare. The operative findings and absence of hyposmia suggest that the meningeal branch of the trigeminal nerve was the origin of the tumor. However, the possibility of radiation-induced reactive Schwann cells cannot be excluded.

Objective and importance. Amniotic membrane can be used as autologous reconstruction graft material when aseptically obtained. We introduce here a novel repair technique using autologous amnion graft, and report a case presentation of myelomeningocele successfully treated with this graft material. Technique. Amniotic membrane, which was composed of amnion and chorion, was aseptically harvested at cesarean section. Removing chorionic tissue, amnion containing monolayer of amniotic epithelial cells and underlining fibrous tissue was isolated. After the procedure of reconstruction of neural and meningeal elements, the membrane was placed as onlay autograft over the reconstructed neural structure followed by suture of undermined skin flap without any myocutaneous flap transfer technique or fascial transposition from paraspinal muscles. Results. The postoperative healing process of the wound was excellent. Conclusion. Autograft of amniotic tissue has no risks of rejection, foreign body reaction, or transmission of slow virus infection to reconstruct the lesion of newborn patient. Amnion autograft would be a biologic rationale to promote wound healing, being applied as a part of a variety of pediatric neurosurgical procedure. (C) 2003 Elsevier Ltd. All rights reserved.

Objective-To describe our experience with selective chemical rhizotomy of facial nerves using adriamycin (ADM) in a patient with hemifacial spasm (HFS). This unique technique is less invasive than intracranial neurosurgery and enables one to perform a permanent nerve block under local anesthesia. Patient-The patient, a 73-year-old female had difficulty opening her left eye. Following unsuccessful treatment with antiepileptic medicine, she received selective intraneural injections of ADM under local anesthesia. One week after the surgery the spasms had disappeared completely. No major complications were caused by this procedure and there had been no recurrence of spasms 3 years after the surgery. Results-It is thought that recurrence of HFS should be observed after simple neurotomy due to regrowth of nerve fibers. However. this did not occur after chemical rhizotomy with ADM. This method clearly differs from previously used varieties of simple neurotomy because the latter technique does not cause severe destructive changes in the facial motor nucleus. Conclusion-Selective facial nerve chemical rhizotomy with ADM under local anesthesia may be effective in treating a subgroup of patients with HFS, especially elderly patients and those in the high-risk group for general anesthesia and intracranial neurosurgery.

Object. Because of their histological similarities, it is occasionally difficult to differentiate neurocytoma and dysembryoplastic neuroepithelial tumor (DNT) from oligodendroglial tumors. This study was conducted to investigate genetic differences among these tumor types in terms of loss of heterozygosity on chromosomes 1p and 19q, and p53 gene mutation. Methods. A total of 24 tumors were analyzed, consisting of eight central neurocytomas, three DNTs, seven oligodendrogliomas, four oligoastrocytomas, and two undetermined extraventricular tumors with neurocytoma features (ETNFs). Allelic loss was determined using microsatellite markers that cover the common deletions on chromosomes 1p and 19q in oligodendrogliomas. A p53 gene mutation was identified using polymerase chain reaction-single-strand conformation polymorphism analysis and subsequent direct sequencing. Immunohistochemical studies with synaptophysin and electron microscopy investigations were also conducted. Allelic loss on 1p and 19q was detected in six oligodendrogliomas (86%) and in three oligoastrocytomas (75%), but in none of the central neurocytomas or DNTs. A p53 missense mutation was detected at codon 161 (GCC-->ACC, Ala-->Thr) in only one oligoastrocytoma. without allelic loss. Synaptophysin was expressed in all central neurocytomas and DNTs, in three oligodendrogliomas (43%), and in three oligoastrocytomas (75%). Of the ETNFs, one demonstrated synaptophysin expression and neural ultrastructures but lacked genetic alterations, whereas the other showed allelic loss on 1p and 19q but was negative immunohistochemically and ultrastructurally. The former was diagnosed as a potential intraparenchymal neurocytoma and the latter as an oligodendroglioma. Conclusions. Despite histological similarities, central neurocytomas and DNTs are genetically distinct from oligodendroglial tumors. Examination for allelic loss on 1p and 19q and for p53 mutation can be useful for making this distinction.

Metastasis of systemic cancer to intracranial tumors is a rare event. The authors report a case of 49-year-old woman with such occurrence, whose breast cancer metastasized to a preexisting parasagittal meningioma at a postoperative interval of 1.5 years. She was admitted to our hospital because of progressive right hemiparesis. Magnetic resonance imaging revealed newly emerged perifocal edema and inhomogeneous contrast enhancement of the meningioma. High choline/creatine ratio and lactate/lipid peak on proton magnetic resonance spectroscopy suggested malignancy. She underwent a tumor resection, and pathologic examination revealed intratumoral metastasis of breast cancer in a transitional meningioma. Immunoreactivity of E-cadherin was detected in both meningioma and breast cancer cells. It is suggested that abrupt appearance of symptoms, inhomogeneous enhancement, and perifocal edema of meningioma is a sign of intratumoral metastasis from systemic cancers.

Object. It has been reported that due to premature synostosis of the lambdoid suture in the first 24 months of life, more than 70% of patients with Crouzon syndrome concurrently suffer from chronic tonsillar herniation (Chiari Type I malformation) and some (20%) associated syringomyelia. The goal of the present study was to examine mutations in the fibroblast growth factor receptor (FGFR) genes in Crouzon syndrome and its related conditions. Methods. Five patients were studied: three with Crouzon syndrome (one sporadic and two familial), one with sporadic Chiari I with syringomyelia. and one with unilateral lambdoid synostosis. Deoxyribonucleic acid was screened for FGFR1-3 mutations by using single-strand conformational polymorphism and subsequent direct sequencing. Two types of missense mutations were detected in the FGFR2 gene, Cys342Trp (1205, TGC --> TGG) in a patient with sporadic Crouzon syndrome and Tyr281Cys (1021, TAC --> TGC) in two siblings (brother and sister) with familial Crouzon syndrome, respectively. The former has been reported only in sporadic cases but the latter has not previously been identified. A polymorphism in the FGFR3 gene, Asn294Asn (882, AAT --> AAC), was also detected in three patients. No mutation was found in the patient with sporadic Chiari I with syringomyelia. Conclusions. The FGFR2 missense mutation was detected in Crouton syndrome but not in sporadic Chiari I with syringomyelia or lambdoid synostosis. A novel FGFR2 Mutation. Tyr281Cys, was found in familial Crouton syndrome with Chiari I and syringomyelia. It may be informative to look for this in patients with Crouton syndrome and associated syringomyelia.

The subject of this report is a rare case of a 5-year-old girl who developed an arachnoid cyst with a bony and dural defect in the parietal convexity. She had no history of head trauma or infection. Surgical exploration revealed the bulging lesion to consist of cerebrospinal fluid-containing spongy subcutaneous tissue and to extend into the bony and dural defect. The arachnoid cyst cavity was found beneath the subcutaneous lesion and was not connected to the adjacent subarachnoid space. Histologically, the subcutaneous tissue contained a complex of sinusoidal channels formed by an abundance of migrating arachnoidal cells, thus mimicking meningocele. Copyright (C) 2002 S. Karger AG, Basel.

Only a few reports have been published on molecular genetic alterations in primary central nervous system lymphomas (PCNSLs) of the diffuse large B-cell type and no reports have addressed the correlation between the genetic alterations and clinical course of the patients with this neoplasm. Thus, the molecular background of the PCNSL and its importance for the clinical course of the patients are still unclear. We investigated a series of 14 patients with PCNSL to determine structural alterations of the INK4a/ARF, MDM2, and TP53 genes, the status of bcl-2 and bcl-6 protein expression, and the clinical course of the patients (i.e. their survival time after diagnosis). No structural alterations of MDM2 and TP53 genes were found. Only INK4a/ARF genes whose expression affects both the p16INK4a-Rb and p14ARF-mdm2-p53 pathways in the regulation for cell cycle and apoptosis, showed an alteration of the homozygous deletions at a high frequency (nine of 14 patients: 64%). This specific alteration was not related with the bcl-6 expression, but a relation was shown with overexpression of the bcl-2 anti-apoptotic protein (p = 0.036, chi-square test), as well as a shorter patient survival (p = 0.044, Wilcoxon test). There was only a tendency, not a significant correlation, in which the patients with bcl-2 overexpression resulted in poor prognosis (p = 0.149). The present study is the first to suggest that the INK4a/ARF gene homozygous deletions and overexpression of the bcl-2 protein may be correlated with each other and together serve as important predictors for the prognosis of patients with PCNSL.

A gangliocytoma/ganglioglioma with no atypical or malignant features was subtotally resected from the right temporal lobe of a 16-year-old woman. A second resection was performed 8 years Inter to treat a locally recurrent lesion with increased cellularity that was diagnosed as a World Health Organization Grade II ganglioglioma on the basis of neuropathological examination. Molecular analysis of the recurrent tumor revealed a TP53 gene mutation, but no amplification of the epidermal growth factor receptor (EGFR) gene. Radiotherapy (60 Gy) was administered after the second resection. The patient returned 1 year later with a second focal recurrence. The specimen obtained during the third resection of tumor exhibited exclusively astrocytic differentiation, cellular pleomorphism with multinucleated cells, high mitotic activity, and endothelial proliferation. Therefore, the tumor was diagnosed to be a glioblastoma multiforme (GBM). Molecular analysis of tumor DNA from the second recurrent tumor demonstrated the presence of the TP53 mutation, which previously had been observed in the first recurrent tumor, but again no evidence of EGFR amplification. Findings demonstrate that the presence of TP53 mutation in progressed gangliogliomas should be interpreted as a progression-associated mutation rather than a consequence of treatment. This is the first report to indicate that the molecular pathways of gangliocytomas/gangliogliomas progressing to become GBMs may parallel those of diffuse astrocytomas progressing to become GBMs.

The authors report two cases of multicentric osteolytic lesions in the occipital bone without any history of head trauma. The excisional biopsy of the first case revealed that the lesion was multicentric but a continuous cavity with the subarachnoid space through various sizes of dural defect, and the cavities were covered by arachnoid lining. Together with the previously reported similar 5 cases, the characteristic common feature is multicentric osteolytic lesions in the occipital bone at advanced age without marginal sclerosis. "The cluster of arachnoid diverticula in the occipital bone (CADOB)" is probably the most appropriate term for these non-traumatic lesions with the following characteristics: elderly patients, occipital bone, midline, multiple, intact outer table, nonsclerotic margin and without history of trauma. Operation may not be indicated because of its non-progressive and benign nature.

INFANTILE MYOFIBROMATOSIS IS a rare clinical entity characterized by multiple mesenchymal tumors in the neonatal period. We describe a 15-month-old girl with multicentric cranial lesions involving the parietal and occipital bones associated with a single small subcutaneous lesion in the back. Magnetic resonance imaging clearly demonstrated the isointense lesions on T1-, T2-, and proton density-weighted images, which showed marked gadolinium enhancement of the tumors and adjacent dura mater. A histological examination of the resected temporal lesion revealed the myofibroblastic nature of the tumor cells. This is the first description of magnetic resonance features of multicentric infantile myofibromatosis in the cranium, and gadolinium-enhanced magnetic resonance images were useful in showing dural involvement. The importance of recognizing this disorder is emphasized because of its special clinical behavior.

Antiphospholipid antibodies have been reported to occur in ischemic stroke patients, but there have been no previous reports linking these antibodies to spinal cord infarction. A case of spinal cord infarction associated with primary antiphospholipid syndrome in a 6-year-old boy is reported. Magnetic resonance imaging clearly demonstrated marked swelling of the thoracolumbar spinal cord with gadolinium-diethylenetriamine penta-acetic acid enhancement at an acute stage, followed later by cord atrophy. Serological study disclosed positive lupus anticoagulant and immunoglobulin G anticardiolipin antibody. It is suggested that the role of antiphospholipid antibodies as an etiological factor for spinal cord ischemia should be recognized among causes that might have been categorized as either spontaneous spinal cord infarction or myelitis.