PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas.

Gene rearrangement in the form of an intragenic deletion is the primary mechanism of oncogenic mutation of the epidermal growth factor receptor (EGFR) gene in gliomas. However, the incidence of platelet-derived growth factor receptor-α (PDGFRA) gene rearrangement in these tumors is unknown. We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified two rearrangements, including the first case of a gene fusion between kinase insert domain receptor (KDR) (VEGFRII) and the PDGFRA gene, and six cases of PDGFRA(Δ8, 9), an intragenic deletion rearrangement. The PDGFRA(Δ8, 9) mutant was common, being present in 40% of the glioblastoma multiformes (GBMs) with PDGFRA amplification. Tumors with these two types of PDGFRA rearrangement displayed histologic features of oligodendroglioma, and the gene products of both rearrangements showed constitutively elevated tyrosine kinase activity and transforming potential that was reversed by PDGFR blockade. These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated.

A nationwide survey of hypertrophic pachymeningitis in Japan.

OBJECTIVES: To clarify the prevalence, frequent causes and distinct features of hypertrophic pachymeningitis (HP) according to background conditions in a nationwide survey in Japan. METHODS: The study began with a preliminary survey to determine the approximate number of HP patients diagnosed from 1 January 2005 to 31 December 2009, and was followed by a questionnaire survey for clinical and laboratory findings. HP was defined as a condition with thickening of the cranial or spinal dura mater with inflammation, evidenced by MRI or histology. RESULTS: Crude HP prevalence was 0.949/100 000 population. The mean age at onset was 58.3±15.8 years. Among 159 cases for whom detailed data were collated, antineutrophil cytoplasmic antibody (ANCA)-related HP was found in 54 cases (34.0%) and IgG4/multifocal fibrosclerosis (MFS)-related HP in 14 cases (8.8%). Seventy cases (44.0%) were classified as 'idiopathic' and 21 (13.2%) as 'others'. ANCA-related HP cases showed a female preponderance, a higher age of onset, and higher frequencies of otological symptoms and elevated systemic inflammatory biomarkers, but lower frequencies of diplopia compared with idiopathic HP. IgG4/MFS-related HP cases showed a marked male predominance; all had cranial HP while none had isolated spinal HP or decreased sensation. CONCLUSIONS: HP is not extremely rare. ANCA-related HP is the most frequent form, followed by IgG4/MFS-related HP. Both forms have unique features, which may help to differentiate background causes.

Investigation of IgG4-positive cell infiltration in biopsy specimens from cases of hypertrophic pachymeningitis.

This study was an immunohistological study of IgG4-positive cell infiltration in 6 cases of hypertrophic pachymeningitis excluding secondary hypertrophic pachymeningitis caused by infectious diseases such as aspergillosis. The cases included 5 males and 1 female, ranging in age from 36 to 82 years (mean, 55 years). A biopsy was performed in all of the cases for diagnostic purposes, revealing fibrous dural hyperplasia with nonspecific inflammatory cell infiltration histologically. Two of the 6 patients had been treated with steroids before the biopsy, which was taken for poor response to steroid treatment. In these two cases, some IgG-positive cell infiltration of the thickened dura was observed; however, most of the cells were IgG4-negative. In the remaining four cases, many IgG- and IgG4-positive cells infiltrated the thickened dura and the IgG4-positive/IgG-positive cell ratio exceeded 40%. One of these patients was finally diagnosed with IgG4-related sclerosing disease, since he was diagnosed subsequently with retroperitoneal fibrosis. There was no evidence of any other lesions associated with IgG4-related sclerosing disease, other than in the dura. It is not rare for IgG4-positive cells to appear in the dura in cases of hypertrophic pachymeningitis; however, no IgG4-related systemic disease is present in these cases. Hypertrophic pachymeningitis with IgG4-positive cells may have some kind of relation to other systemic autoimmune diseases.

Linear fractures occult on skull radiographs: a pitfall at radiological screening for mild head injury.

BACKGROUND: Skull radiography is widely used to screen for fractures in patients with mild head injury. However, the clear depiction of a fracture requires a gap in the skull separated by the fracture that is wide enough to allow the passage of x-rays. We studied atypical linear fractures that were not visualized clearly, because a specific anatomical configuration hampered the passage of x-rays. METHODS: We retrospectively evaluated 278 patients with mild head injuries who had undergone routine skull radiography (anteroposterior and lateral views) and head computed tomography (CT). We found that some patients negative for linear fracture on skull radiographs were positive on bone window CT scans. RESULTS: Of the 278 patients aged between 2 months and 66 years, 8 (2.9%) manifested a linear fracture on CT scans that presented as a cross section of the fracture oblique to the direction of the x-rays. Four of the 8 developed acute epidural hematoma; 2 of these patients underwent craniotomy. CONCLUSIONS: Radiographic study returned false-negative results, because x-rays were absorbed by the double-layered skull along fractures whose cross section was oblique to the direction of the x-rays. The evaluation of head injury by radiography only may miss these fractures and their undetected presence may result in sequelae such as intracranial hematoma.

Effectiveness of interferon-beta therapy for recurrent glioblastoma: a case report.

AIMS AND BACKGROUND: Glioblastoma has a poor prognosis, with few therapeutic options if it recurs. We report a case in which we were able to inhibit the growth of a recurrent glioblastoma by weekly single-dose administration of interferon-beta. CASE REPORT: A patient with recurrent glioblastoma after radiation and chemotherapy was treated with nimustine and interferon-beta. After 2 cycles of nimustine, the patient's leukocyte, neutrophil, and platelet counts showed grade 4 toxicity according to the National Cancer Institute's Common Toxicity Criteria. The patient was treated with a weekly single dose of interferon-beta at 6 x 10(6) IU. The tumor showed no remarkable changes after 18 months, and the patient's Karnofsky performance status remained at 50%. CONCLUSIONS: The administration of interferon-beta produced long-term control in one case of glioblastoma and may be an effective therapy.

Utility of intraoperative fluorescent diagnosis of residual hemangioblastoma using 5-aminolevulinic acid.

Hemangioblastoma is a benign tumor of the cerebellum, and treatment involves surgical excision, both as the initial treatment and also in case of recurrence. Recurrence of hemangioblastoma can be local due to incomplete resection or can be distant and separate from the tumor resection region. Local recurrence can largely be avoided by verifying for any residual tumor intraoperatively before closure. In this study, we used intraoperative fluorescent diagnosis using 5-aminolevulinic acid (5-ALA) to verify the presence of a residual tumor during surgical resection. Nine patients with hemangioblastoma were given 1 g of 5-ALA orally before surgery, and a laser beam of 405 nm was focused on the tumor during resective surgery. Fluorescence of protoporphyrin IX (PPIX) was observed in the core of tumor in all the cases. Fluorescence of PPIX was observed in the peritumoral cyst wall in two patients after tumor resection, and in both of them fluorescent parts of PPIX were resected and histological examination showed tumor cells. Usually, there are no tumor cells in the peritumoral cyst of a hemangioblastoma, yet hemangioblastomas may sometimes recur from an unresected cyst wall. It is thus necessary to excise an infiltrating cyst of tumor cells to prevent recurrence. Intraoperative fluorescent diagnosis using 5-ALA is a useful method to discern whether tumor cells are present in the peritumoral cyst wall of a hemangioblastoma.

[Effect of Chai-ling-tang (Sairei-to) for methotrexate concentration degradation delay by methotrexate high-dose therapy].

When methotrexate (MTX) salvage chemotherapy is performed for primary brain malignant lymphoma, use of leucovonrin rescue must often be extended due to delays in the degradation of blood concentration. We examined whether delay in MTX blood concentration degradation could be prevented by chai-ling-tang (Sairei-to) which has diuretic action. In the five cases examined were MTX blood concentration 72 hours after MTX administration was more than 1 x 10(-7) M. A single dose of 3 g of chai-ling-tang was administered three times on the day the MTX salvage chemotherapy was subsequently performed. MTX blood concentration at 72 hours post MTX administration and subsequent chai-ling-tang administration was less than 1 x 10(-7) M in all five cases. In addition, urea nitrogen and creatinine levels in serum increased and creatinine clearance decreased following MTX administration, however these changes induced by MTX administration were reduced by chai-ling-tang administration. Chai-ling-tang was effective in preventing an MTX deferent delay in MTX high-dose therapy by improving renal blood flow.

Proteomics of tumor-specific proteins in cerebrospinal fluid of patients with astrocytoma: usefulness of gelsolin protein.

Changes in cerebrospinal fluid (CSF) composition have been shown to accurately reflect pathological processes in the CNS, and are potential indicators of abnormal CNS states, such as tumor growth. To detect biomarkers in high-grade astrocytomas, the differential expression of proteins in the cerebrospinal fluid was analyzed from two cases each of diffuse astrocytoma (grade II), and glioblastoma (grade IV) using agarose 2-D gel electrophoresis (2-DE). It was found that the expression of gelsolin protein decreased with histological grade. To examine whether gelsolin is a useful indicator of tumor aggressiveness or patient outcome, its expression was further studied on immunohistochemistry in 41 formalin-fixed and paraffin-embedded astrocytomas. The positive cell rate of gelsolin in tumors was 59.4% in grade II, 30.0% in grade III and 29.4% in grade IV, respectively. Gelsolin expression was significantly lower in high-grade astrocytomas (grade III or IV) than in low-grade astrocytomas (grade II; P < 0.05). Moreover, in astrocytomas the overall survival of patients in the low-expression group was significantly poorer than in the high expression group (P < 0.05). These data suggest that gelsolin is a prognostic factor in astrocytoma.

Brachial plexopathy due to massive swelling of the neck associated with craniotomy in the park bench position.

BACKGROUND: During prolonged neurosurgical procedures, anesthetized patients are at risk for position-related complications. We report a rare combination of neck swelling and brachial plexopathy as operative position-related complications. CASE DESCRIPTION: This 56-year-old woman was placed in the left park bench position for removal of a tentorial meningioma in the right posterior fossa. At 2 hours after the 10-hour procedure, her left neck began to swell with progression during the next 10 hours to involve the face on the same side and the face and neck on the opposite side. Computed tomography showed swelling of the muscles and deep soft tissue primarily on the left. No brain edema was observed. She was conservatively treated with orotracheal intubation, placed in the head-up position, and received anticoagulants. Her swelling subsided by the 20th postoperative day; however, she manifested weakness in the proximal muscles of the left upper extremity. Magnetic resonance imaging revealed swelling of the brachial plexus on the left; electrophysiologic studies were compatible with damage to the upper trunk of the brachial plexus. She was discharged 2 months after surgery with improved weakness. CONCLUSION: Possible pathologic mechanisms are kinking of the jugular vein due to extremely flexed neck position during surgery and associated delayed swelling of the neck and brachial plexus. The cerebral venous return may have been maintained by anastomosis between the internal jugular and the vertebral venous system. To prevent such complications, we must take great care of the anesthetized patients when placed in the forced neck position.

Spinal cord tethering by aberrant nerve root in myelomeningocele: case report.

INTRODUCTION: A 2,796-gram male baby was born at 40 weeks gestation by vaginal delivery. Soon after, he was admitted at our department for treatment of a dorsal appendage. RESULTS AND DISCUSSION: Magnetic resonance (MR) imaging showed a low-position spinal cord, skin-covered myelomeningocele, syringomyelia, and a tethered cord. Resection of the caudal appendage and tethering tissue was performed 22 days after birth under electrophysiological monitoring. Histopathological examination of the caudal appendage that was covered with skin revealed the presence of spinal cord tissue and peripheral nerve tissue. The string-like tethering tissue that extended from the spinal cord to the caudalis was a nerve root, and there was fiberization of the caudalis. The syringomyelia was improved at postoperative MR imaging. To our knowledge, there is no report of a similar case in the literature. We report rare combination of myelomeningocele and spinal cord tethering by aberrant nerve root with thoracic syringomyelia.

Shortening of ventricular shunt catheter associated with cranial growth: effect of the frontal and parieto-occipital access route on long-term shunt patency.

OBJECT: The authors present the difference of shortening the ventricular shunt catheter associated with growth of the cranium between the frontal and parieto-occipital access, a key for long patency of the shunt implanted in children. MATERIALS AND METHOD: Our retrospective study included 28 children. In group A (n=9), the catheter was inserted through a frontal burr hole and in group B (n=19), through a parieto-occipital burr hole. To compare changes that occurred in the interval between the time of insertion and follow-up in the length of the ventricular catheter in the cranium and to assess displacement of the burr used for catheter entry. RESULTS: The results show that ventricular catheter shortening and burr-hole displacement were more pronounced in group A. CONCLUSIONS: This study documents that insertion of the ventricular catheter via the frontal route in children resulted in a higher incidence of shortening due to greater displacement of the burr hole adjacent to the coronal suture. Therefore, we recommend that the parieto-occipital route be used to maintain long-term shunt function.

Usefulness of gamma knife pituitary surgery to control thalamic pain after treatment of thalamic malignant lymphoma and report of pathology of gamma knife lesions.

Here, we describe the first reported autopsy findings following gamma knife surgery for thalamic pain. A 62-year-old man presented with thalamic pain after treatment for thalamic malignant lymphoma. He was treated with narcotic drugs, but his pain was uncontrollable. Treatment using gamma knife surgery on the pituitary gland using a maximum dose of 180 Gy, led to the control of his intractable pain with lower doses of drugs. His death was pain-free and was caused by a recurrence of the tumor, six months after gamma knife surgery. An autopsy was performed and necrosis was present in the area of the pituitary gland where it borders the pituitary stalk. Half of the adenohypophysis was not necrotic, and necrosis was not found in the pituitary stalk.

Auditory alert system for fluorescence-guided resection of gliomas.

Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection using 5-aminolevulinic acid labeling is one of the most valuable tools available to determine the extent of glioma infiltration, but requires repeated spectroscopic evaluation of the tissue. The present method informs the surgeon of residual tumor in real time using spectrum analysis of PPIX fluorescence and an audible alert system. The target region was illuminated with a laser with a peak wavelength of 405 +/- 1 nm in addition to the usual microscope halogen lamp during tumor resection. Analysis of the spectrum detected the PPIX peak using a difference in relative intensity exceeding 500 at 636 nm and 632 nm, when an audible alert was transmitted to the surgeon. Using this method, infiltration of glioma was detected and confirmed histologically in three of six glioblastomas. The surgeon can detect tumor infiltration far more objectively and with less effort using this system during tumor resection.

[Retro-odontoid disc herniation extracted using the posterior-lateral transdural approach: case report].

A 73-year-old woman suffered from neck pain, progressive m tor weakness and sensory disturbance in all extremities. Neuroradiological studies revealed a retro-odontoid mass with posterior compression of the upper cervical spinal cord. Decompression of the mass was performed via a postero-lateral transdural approach, and the patient exhibited marked improvement of the symptoms. Histological examination revealed that the mass was composed of degenerative cartilaginous tissue, consistent with disc material, but the lesion was not neoplastic. Retro-odontoid disc herniation causing cervical myelopathy is very rare. We primarily discuss the surgical management of retro-odontoid disc herniation.

Malignant transformation of intracranial mature teratoma to yolk sac tumor after late relapse. Case report.

The recurrence of intracranial mature teratomas as germ cell tumors of different histological types is rarely reported. The authors describe the first case of the malignant transformation of an intracranial mature teratoma into a yolk sac tumor in a 16-year-old boy who presented with a 1-month history of anorexia and somnolence. Seven years prior to this presentation, the boy had undergone surgery for extirpation of a mature pineal teratoma. Computed tomography images obtained at his second presentation revealed a homogeneously enhanced mass within the third ventricle. The tumor was resected and the results of a histological examination were consistent with a yolk sac tumor. After resection, the patient underwent radiation therapy followed by chemotherapy with cisplatin and etoposide but died of tumor progression 15 months after his second hospitalization.

Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study.

We performed a pathological study to identify the locus of production of protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA) perorally 2 h before undergoing surgery. The target region was exposed to laser light with a peak wavelength of 405 +/- 1 nm and an output of 40 mW. Tissue samples from the tumor bulk and surrounding areas were examined by histological and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX fluorescence can be observed in peritumoral edematous areas that are free of neoplastic cells, because PPIX produced by neoplastic cells leaks into the surrounding edematous area.

Confirmation of the initial pressure setting in Codman-Hakim programmable valves under magnification--technical note.

Codman-Hakim programmable valves allow neurosurgeons to adjust the opening pressure to the patient's particular clinical needs. However, the pressure control cam is extremely small, so identification of the pressure indicator and its operation is somewhat difficult when initially setting the opening pressure before implantation. We employed a commercial loupe on the program transmitter unit to sufficiently enlarge the view of the cam for clear identification. We recommend that the manufacturer to incorporate a loupe to provide a more sophisticated product.

Duraplasty in the posterior fossa using a boat-shaped sheet of expanded polytetrafluoroethylene.

Application of sutures between expanded polytetrafluoroethylene (ePTFE) dural substitutes and the dura mater is often frustrating in posterior fossa surgery because of the difficulty in holding the elastic graft in a deep and narrow field. To resolve this problem, we have developed a boat-shaped graft made from a triangular ePTFE sheet by pinching each angle using a suture. Formation of standing edges of the sheet facilitates holding of the flaps for secure and more rapid suturing than the conventional approach using a flat sheet.

Symptomatic Rathke's cleft cyst with cavernous sinus syndrome.

An 88-year-old man presented with Rathke's cleft cyst (RCC) manifesting as complete cavernous sinus syndrome. He had no headache, endocrinological symptom, or blood abnormality. Neuroimaging revealed a cystic intrasellar lesion with lateral extension. The patient underwent surgery by a transsphenoidal approach. Histological examination revealed squamous and cuboidal epithelium. The diagnosis was RCC. RCC is rarely symptomatic, but enlargement and compression of the surrounding structures usually causes headache, visual field defects, or symptoms of pituitary dysfunction. The present case shows that RCC may manifest as complete cavernous sinus syndrome.

Histological examination of false positive tissue resection using 5-aminolevulinic acid-induced fluorescence guidance.

Intraoperative 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance for resection of malignant brain tumors was correlated with histological examination to investigate false positive findings in 42 patients with malignant glioma and six patients with metastatic brain tumor. Patients received a single 1 g oral dose of 5-ALA 2 hours before surgery. The tumor site was illuminated with a laser with a peak wavelength of 405 +/- 1 nm and output of 40 mW. Samples with strong fluorescence were obtained from the tumor bulk and samples with weak fluorescence from the tumor cavity. Fluorescence was observed in 36 of the 42 malignant gliomas and four of the six metastatic brain tumors. No tumor cells were found in fluorescent samples from six of the 36 malignant gliomas and all four metastatic brain tumors. Five of the six malignant gliomas were recurrent cases. Fluorescence was found in areas of peritumoral edema or inflammatory cell and reactive astrocyte infiltration. Intraoperative 5-ALA-induced fluorescence guidance is useful for the resection of initial malignant glioma since false positive results are rare, but only non-eloquent weak positive areas should be resected. In contrast, all weak positive areas of recurrent malignant gliomas must be resected. Weak positive areas of the peritumoral edema surrounding metastatic brain tumors should be removed carefully as false positive results are common.