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Meningioma has the second highest incidence among primary intracranial tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. Sp1 (specificity protein 1) is a transcription factor that regulates tumor growth, but the literature describing the relationship between Sp1 and meningioma is scarce. The purpose of this study was to investigate the relationship between Sp1 expression and the clinicopathological parameters in meningioma by immunohistochemical staining.We collected samples from 74 patients from 2008-2012 in Kaohsiung Medical University Hospital, with staging and prognosis of the pathological section of the meningioma.Our results show that Sp1 expression was significantly associated with World Health Organization grade, malignancy, and recurrence in patients with meningioma.High expression of Sp1 in patients with meningioma was linked to poor prognosis of recurrence-free time. Therefore Sp1 may be a candidate biomarker of prognosis and therapy target in meningioma.

Spinal venous malformations are vascular malformations of the central nervous system. Progressive or sudden neurological deficits can result in the deterioration of the quality of life, owing to the nature of the disease. Surgery is recommended after 2–6 weeks in patients with acute symptoms, to facilitate better surgical planning. Steroids are administered during the preoperative planning and rehabilitation period. However, the patient reported in this study developed a perforated peptic ulcer 1 week after surgery and died due to sepsis. Therefore, we questioned the optimum time for surgery, i.e., we considered whether early or delayed surgery would result in better patient outcomes.

Glioblastoma multiforme is the most common and aggressive primary malignant brain tumor and usually invades the intracranial space. Extracranial invasion is uncommon, and skin invasions are even less common. Here, we present an extremely rare case of aggressive skin invasion by glioblastoma multiforme. Once skin invasion occurs, its spread is too rapid to be resectable in only a few weeks and is often accompanied by deterioration of the primary lesion and short-term survival. Recognizing small cutaneous tumors adjacent to a previous surgical site is vital at the initial stage of skin invasion. Early recognition of cutaneous lesions, resection, and pathological confirmation, followed by chemotherapy and radiotherapy, may be beneficial for these patients.

Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas.

A 53-year-old man presented with a history of slight weakness in the right lower limb. Giant invasive cauda equina schwannoma was diagnosed according to the criteria of Sridhar et al. Schwannomas are usually benign and common tumors arising from nerve sheath cells, particularly from sensory nerves. Giant invasive schwannomas, however, are rare, and most of patients with them present with severe neurologic deficits independent of daily activity, although in the case presented here, in spite of the large size of the tumor causing pedicle erosion, expansive destruction of the vertebral body and widening of the neural foramina, there were only minimal neurologic deficits. We have therefore decided to report this case, with a review of the relevant English literature emphasizing clinical presentations, plain film images and magnetic resonance image findings of giant invasive cauda equina schwannoma for early diagnosis and differential diagnosis.

Background Coldness, numbness, or causalgia usually affects the lower limbs in patients after back surgeries. The treatment of causalgia is still the source of continuing debate. We treated patients presenting with causalgia secondary to LD with CT-guided CLS and determined the therapeutic outcome at long-term follow-up. Methods From January 2002 to December 2002, a total of 15 patients (16 limbs) with causalgia after LD underwent the percutaneous CT-guided CLS. There were 7 male patients and 8 female patients, with an average age of 49.1 years. A total of 14 patients underwent unilateral procedures, and 1 patient underwent staged bilateral procedures. We followed up our patients for at least 24 months (24-36 months). Results There were 13 patients (14 limbs) diagnosed as Drucker stage I and 2 patients as stage II. There were 88% (14 limbs) that had an early satisfactory outcome after CLS and 75% (12 limbs) that had a late satisfactory outcome (more than 24 months after CLS). Stage I patients had more satisfying early and late outcome than stage II patients ( P = .014 and P = .039, respectively). Female patients were more likely to have satisfactory late outcome than male patients ( P = .034). There was no operative mortality. A patient had a complication of genitofemoral neuralgia, which had recovered in a month. Conclusions We concluded that the percutaneous CT-guided CLS is an easy, safe, and reproducible technique, and it carries long-term benefit to patients with pain after LD presenting with causalgia, especially for patients with Drucker stage I and female patients.

The human dynamin-like protein, HdynIV, has recently been cloned and shown to be involved in the formation and trafficking of coated vesicles. In particular, one of the HdynIV variant overexpressions has been suggested to contribute to the pathogenesis of brain tumors. In this paper, we report on the genomic organization of the human HdynIV gene. The gene was found to correspond to 20 exons of genomic sequence on human chromosome 12, distributed over 64 kb of genomic DNA. The two exons, numbers 15 and 16, are subjected to differential splicing, generating four different transcripts of a perfect match to our recent report on the four different spliced HdynIV variants [DNA Cell Biol. 19 (2000) 189]. We have also characterized the 5′ regulatory region of the HdynIV gene in order to understand the molecular mechanisms regulating its expression. The transcriptional initiation site was identified by 5′-RACE. The 5′-flanking sequence of the HdynIV gene contains three GC boxes that concatenate Ap2- and Sp1-binding motifs, but that does not contain either the TATA or CAAT consensus sequence. A region between −140 and +92 contributed to high promoter activity. Deletion analysis demonstrated that the minimal promoter activity required the region of −110 to −100. Electrophoretic mobility shift assay demonstrated that a putative transcriptional factor bound to the region of −119 to −90. Site-directed mutagenesis analysis of this region revealed that nucleotides at −108 to −100 were essential for transactivation mediated by this transcriptional factor. In conclusion, we have characterized the minimal HdynIV promoter and shown that CTCCCAGCA (−108 to −100) sequence may act as a novel transcriptional element for regulating HdynIV gene expression.

Aims. Rac1 is a member of the Ras superfamily of small GTPase and plays a fundamental role in cytoskeleton reorganization, regulation of gene expression and cell proliferation, and cellular transformation. Though recent studies point to an involvement of rac1 in tumorigenesis, little is known about the alteration of rac1 gene in human brain tumours. Methods. Reverse transcription-polymerase chain reaction (RT-PCR), TA cloning, and DNA sequencing were performed to detect rac1 gene mutations in the surgical specimens of 45 human brain tumours. Results. Twelve of 45 cases had base changes in the rac1 gene. The frequency of rac1 alterations was seven of 18 meningiomas, three of 14 astrocytomas, one of seven pituitary adenomas, and one of four metastatic brain tumours. No mutation was detected in acoustic neurilemomas. The subtypes of seven meningiomas include three meningotheliomatous, two atypical, one transitional and one angioblastic meningioma. Three astrocytomas had rac1 gene mutation, including one grade II, one grade III, and one grade IV astrocytoma. All of single base changes were transitions, five of them being T to C transitions. Sites of rac1 mutation were found in codons 34, 41 (two cases), 42 (two cases), 43, 44, 46 and 58. These mutations are mainly localized in the putative effector-domain of rac1 gene and may enhance the activity of rac1, which increases the survival of brain tumours. Conclusion. Our results suggest that rac1 gene may play a role in some brain tumours of divergent histogenesis and that the alterations of rac1 gene may contribute to tumorigenesis and/or metastasis.

The purpose of this study was to demonstrate the existence of a newly recognized midline posterior column pathway that mediates the perception of visceral pain resulting from hepatobiliary or pancreatic cancer. A punctate midline myelotomy (PMM) of T(3) level was performed in 6 patients who experienced severe visceral pain caused by hepatobiliary or pancreatic cancer. Preoperatively, the pain was refractory to strong opioids. Clinical efficacy of PMM was evaluated by comparing patient pain rating on a visual analogue scale. Follow-up periods ranged from 2-18 weeks after operation. All 6 patients had immediate pain relief after operation. Although the pain recurred from 2-12 weeks later in 3 patients, the severity of recurrent cancer pain markedly decreased. No adverse neurological sequelae were observed. Our results of high thoracic PMM offer clinical support for the concept that neurosurgical interruption of midline visceral pain pathway can effectively control severe visceral pain without causing adverse neurological sequelae in patients with hepatobiliary or pancreatic cancer.

Breast carcinoma has a high predisposition to metastasize to the brain parenchyma. An association between carcinoma of the breast and intracranial meningioma has been reported. The available published articles regarding patients with intracranial meningioma and breast carcinoma have been reviewed. To the best of our knowledge, 86 cases including our 4 cases have so far been reported. All cases were female, and the mean age was 62.4 years when intracranial meningioma was diagnosed. The mean interval of the 2 tumours was 4.5 years. Twenty-five cases of breast tumour were infiltrating duct carcinomas. The location of intracranial meningioma and pathologic subtype showed no specific predominance. Hormone receptor study was performed in 28 cases. In meningioma, the positive rate of progesterone receptor (32.1%) is higher than oestrogen receptor (7.1%); while the positive rate of oestrogen receptor (53.6%) is higher than the progesterone receptor (42.9%) in breast cancer. A review of this study is presented with emphasis on the existence of intracranial meningioma and breast cancer in one patient at different periods. Lesions of the central nervous system in patients with breast cancer should not be immediately labeled as metastases. Intracranial meningioma should be excluded. Likewise, patients with meningioma should have periodic physical examinations and mammographies whereby disease may be diagnosed and treated at an early stage

Summary Esthesioneuroblastoma is a rare neoplasm arising from the olfactory epithelium, and shows intracranial extension in the advanced disease. We report here a 40-year-old female, who had initially been diagnosed to have a Kadish stage C esthesioneuroblastoma. Recurrence presented about 10 months after the first operation, radiotherapy and chemotherapy, with pure bilateral subdural extension but without local signs. Although recurrence is common in advanced esthesioneuroblastoma, such a pattern of presentation is rare, with only three similar cases reported previously. We discuss the possible pathophysiology of such an event and propose possible means of prevention.

Four novel small nucleolar RNAs (snoRNAs), h5sn1, h5sn2, h5sn3, and h5sn4, were successfully amplified from human total RNAs using RT-PCR. They exhibited the structural hallmarks of box H/ACA snoRNAs and formed sequence complementarity to 5S rRNA. The nucleotide sequences of the snoRNAs from different donors were highly conserved as evidenced by single-stranded conformational polymorphism and direct nucleotide sequence analysis. Although their host genes had no protein-coding potential, the expression of the snoRNAs was differentially displayed in different tissues. Noticeably, h5sn2 was highly expressed in normal brain, but its expression drastically decreased in meningioma. This opens the fascinating possibility of the relationship between the processing of snoRNAs and carcinogenesis.

To evaluate the incidence and influencing factors related to preoperative and postoperative seizures, a retrospective analysis was performed in 190 patients with astrocytic tumours. Preoperative seizures occurred in 50 (26%) patients and 27 (54%) of the m had recurrent seizures. Late-onset seizures developed after craniotomy in 11 (8%) of 140 patients. Seizures at presentation were significantly correlated with age at diagnosis (P=0.0204) and pathological grade of tumour (P=0.0040). The patients aged less than 40 years had a high risk of seizures at presentation (odds ratio=3.076, P=0.0134). Postoperative seizures were significantly associated with the presence of preoperative seizures (P

In a retrospective study of a consecutive series of 222 surgically treated meningiomas, it was found that 26.6% of the patients presented epilepsy as their initial symptom. In this group, surgical excision of the intracranial meningiomas stopped the epilepsy in about 62.7% of the patients. But approximately one-fifth of the patients with intracranial meningiomas and no history of preoperative epilepsy developed new onset postoperative seizures. Of the patients with early onset of postoperative epilepsy, epilepsy appeared in 66.7% within first 48 h after surgery. Of the patients with postoperative epilepsy, 71.2% were seizure-free following 1 year of anticonvulsant therapy. Regarding preoperative existing factors, intracranial meningiomas located at supratentorium, convexity, and with evidence of or severe peritumoral edema significantly contributed to preoperative epilepsy. And in patients with preoperative epilepsy, those tumors with evidence of or severe perifocal edema and cerebral edema at the operative site were significantly more likely to suffer from postoperative epilepsy.

The constellations have some connections with neuromedicine. As neurosurgeons, we can learn something from the night sky. Medical terms or descriptions are generously used from mythology or celestial lore. Neurosurgeons spend so much time on their professional careers that they may ignore something wonderful which is worthy of their attention. The puzzling issues between the constellations and neuromedicine can be exciting. Imagination allows neurosurgery to make great strides and progression. With that same imagination we can take an odyssey!

Top of pageAbstract Central nervous system (CNS) trauma, stoke, or neuron degeneration diseases can lead to permanent paralysis or other loss of function. However, it is becoming clear that the CNS is not incapable of regeneration. The adult mammalian CNS has a low potential of neuron regeneration because it consists of low levels of growth-promoting matrix molecules and high levels of inhibitory factors. The integrin family of transmembrane receptors may have the ability to active the neuron regeneration. The function of one member of the integrin family, which is G protein-coupled receptor kinase interacting protein 1 (GIT1), has been tested in an eye model of the rat. Briefly, the recombinant GIT1 and eGFP, luciferase, or eGFP adenoviral vectors (ADGIT1, ADLUC, or ADGFP) and DiI solution were injected into the left superior colliculus (SC) separately. The expression of luciferase or eGFP was monitored in rat eyes by using a molecular imaging technique. The right optical nerves were isolated and injured in some rats 3|[ndash]|5 days after virus injection. The retinal ganglion cell (RGC) layer and the right optical nerve will be tested at different time points. The luciferase gene expression in RGCs was detected in the eyes of live animals following local luciferin delivery using optical imaging techniques. No GFP expression was detected using fluorescent imaging techniques. The cell types that were expressed the foreign genes were mainly RGCs, which were confirmed by using luciferase immunohistochemistry and fluorescent microscopy. Because more than 95% RGCs will be dead in 2 weeks after rat optical nerve injury and the living RGCs are pre-required for axonal growth, the numbers of living RGCs were counted first. The living RGCs were labeled by DiI and shown in a red color under fluorescent microscopy. The samples of optical nerves have not been tested yet. The average numbers of RGCs in 140000 |[mu]|m2 on Days 10 and 15 post optical nerve injury were 179.6 |[plusmn]| 4.3 and 23.4 |[plusmn]| 1.7 in ADGIT1 group and 69.4 |[plusmn]| 4.6 and 11.9 |[plusmn]| 0.8 in ADGFP group. The numbers of living RGCs in ADGIT1 group were significantly higher than that in the ADGFP group at both time points (P

Top of pageAbstract Mature mammalian neurons, except for olfactory neurons, are incapable of cell division. Promoting the regeneration of degenerated adult neurons is a major goal in neurological science. The human teratocarcinoma cell line (NTera 2 or NT2) is capable of neuronal differentiation following treatment with retinoic acid. These neurons (NT2N cells) have a stable neuronal phenotype. The effect of GIT1 overexpression in human NT2N cells was evaluated using an adenoviral vector. A recombinant GIT1 and GFP adenoviral vector (AdEGFP-GIT1) was constructed. The biologic activities of GIT1 were assessed according to the induction of neuronal spine formation, cell migration, and the amounts of GAP-43 and active Cdc42. Cells treated with AdEGFP-GIT1 were compared to untreated cells and to cells treated with AdEGFP. NT2N cells in the AdEGFP-GIT1 group demonstrated more spine formation and higher numbers of migrating cells than that either cells treated with AdEGFP or untreated NT2N cells. GAP-43 and active Cdc42 were quantified by dot ELISA method. The results showed that the amount of GAP-43 and active Cdc42 in the AdEGFP-GIT1 group was much higher than in AdEGFP and untreated NT2N groups. In conclusion, GIT1 overexpression promotes spine formation, migration, and expression of the growth factor GAP-43 and active Cdc42. The GIT1/|[beta]|-PIX/Cdc42/PAK pathway may play an important role in the biological activities of neurons. GIT1 also stimulates GAP-43 expression which may help promote regeneration of damaged axons and formation of new synapses. Therefore, GIT1 may have potential in the treatment of nerve injury.

Based on previous gene therapy studies in bone formation induced by BMP adenoviral vectors, the osteogenic potentials of different BMP adenoviral vectors (ADhBMP-2, -4, -6, -7, and -9) are very high in immunodeficient animals but vary significantly among immunocompetent animals. We have demonstrated that the amounts of bone formation in immunocompetent animals were not significantly affected by use of different generations of adenoviral vectors and different species of BMPs. The similar protein expression curves between immunodeficient and immunocompetent rats indicated that reduced amount of BMP expression was not the main factor limiting the bone formation. Nevertheless, some components of sera may specifically block the signal transduction pathways of particular BMPs, thus interrupting bone formation. We use the term |[ldquo]|bone formation inhibitors (BFIs)|[rdquo]| to describe these immune factors to distinguish them from |[ldquo]|BMP antagonists|[rdquo]|, which are mainly secreted by bone tissue. A mouse skeletal muscle myoblast cell line (C2C12) was used as a model. Reduction of alkaline phosphatase (AP) expression was used as an index to evaluate the inhibiting activity of serum. The distribution of BFIs among different animal species and strains was investigated. Sera from rabbit, rat, and mice were tested. Sera from two strains of rabbit included 14 normal control sera and five adenovirus-vaccinated sera. Most rabbit sera did not exhibit significant inhibiting activity on cell response to any BMP. Only one serum from adenovirus-vaccinated rabbit displayed inhibiting activity on cell response to BMP6. Two sera from NOD SCID mice did not show any inhibiting activity on cell response to BMP2, -6 and -9. Forty-four sera obtained from athymic nude, SD, and Wistar rats were tested. From athymic nude rats we obtained five normal and seven adenovirus-vaccinated sera. All the rat sera inhibited response of cells to BMP6. Two sera obtained from adenovirus (ADLUC)-vaccinated athymic nude rats 16 months after the vaccination inhibited cell response to BMP2, -6, and -9. Four sera from untreated Wistar rats demonstrated inhibiting activities to all three BMPs. Sera from 13 normal, and 15 adenovirus-vaccinated SD rats, all displayed inhibiting activity to BMP6. Some sera also showed inhibition of cell response to BMP2 and -9. The results indicate that BFIs are widely distributed among different animal species and strains. Adenovirus-vaccinated sera may have higher titers than normal sera. This finding will provide a new point of view to assess the relationship between the immune system and BMPs.