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Background Peripheral nerve injuries result in muscle denervation and apoptosis of the involved muscle, which subsequently reduces mitochondrial content and causes muscle atrophy. The local injection of mitochondria has been suggested as a useful tool for restoring the function of injured nerves or the brain. Objective To determine outcomes following the administration of isolated mitochondria into denervated muscle after nerve injury that have not been investigated. Methods Muscle denervation was conducted in a sciatic nerve crushed by a vessel clamp and the denervated gastrocnemius muscle was subjected to 195 μg hamster green fluorescent protein (GFP)-mitochondria intramuscular infusion for 10 min. Results The mitochondria were homogeneously distributed throughout the denervated muscle after intramuscular infusion. The increases in caspase 3, 8-oxo-dG, Bad, Bax, and ratio of Bax/Bcl-2 levels in the denervated muscle were attenuated by mitochondrial infusion, and the downregulation of Bcl-2 expression was prevented by mitochondrial infusion. In addition, the decrease in the expression of desmin and the acetylcholine receptor was counteracted by mitochondrial infusion; this effect paralleled the amount of distributed mitochondria. The restoration of the morphology of injured muscles and nerves was augmented by the local infusion of mitochondria. Mitochondrial infusion also led to improvements in sciatic functional indexes, compound muscle action potential amplitudes, and conduction latencies as well as the parameters of CatWalk (Noldus) gait analysis. Conclusion The local infusion of mitochondria can successfully prevent denervated muscle atrophy and augment nerve regeneration by reducing oxidative stress in denervated muscle.

Glioma surgery near the functional area is still a dilemma. Intraoperative neurophysiologic monitoring (IONM) and functional mapping can play a role to maximize the extent of resection (EOR), while minimizing the risk of sequelae. We herein review the utility of tailored intraoperative mapping and monitoring in patients undergoing glioma surgery in our institute. Patients were divided into two groups on the basis of application tailored IONM (group A, 2013–2017, n = 53) or not (group B, 2008–2012, n = 49) between January 2008 and December 2017. The setup, tailored IONM protocols, surgery, and clinical results of all patients with eloquent glioma were analyzed with the EOR, functionality scores, overall survival (OS) and progression-free survival (PFS) retrospectively. The 102 patients were considered eligible for analysis. High grade and low grade gliomas accounted for 73 (72%) and 29 (28%) cases, respectively. There was a positive association between the application of neuromonitor and post-operative functional preservation, but no significant statistical differences over the EOR, OS and PFS between the two groups. In our experience, tailored intraoperative functional mapping provides an effective neurological function preservation. Routine implementation of neurophysiological monitoring with adequate pre-operative planning and intraoperative teamwork in eloquent glioma can get more satisfied functional preservation. Due to the maturation and experience of our IONM team may also be the variation factor, prospective studies with a more prominent sample and proper multivariate analysis will be expected to determine the real benefit.

Objective Long-term effects of endoscopic endonasal transsphenoidal intracapsular debulking and adjuvant somatostatin analogs (SSAs) were evaluated in patients with growth hormone- (GH) secreting pituitary macroadenomas. Methods We retrospectively reviewed the medical records of 45 patients with acromegalic macroadenoma who underwent endonasal endoscopic transsphenoidal intracapsular debulking and received adjuvant SSAs (octreotide) between 2006 and 2015 who had >1 year of follow-up. To evaluate the predictive factors for 1 year and long-term biochemical outcomes, univariate and multivariate analyses were performed. Results Biochemical remission was achieved in 1 year in 20 of the 45 (44.4%) patients, and in 31 of the 45 patients after long-term adjuvant SSA treatment. Tumor control was achieved in 43 of the 45 (93.3%) patients. The univariate analysis showed age (≥55 years), tumor size (diameter ≤1.5 cm), premedication GH levels (≤2.8 ng/mL), premedication insulin-like growth factor 1 levels (≤2-fold of upper limit of normal range), cavernous sinus invasion (Knops grades 2, 3, and 4), and near-total tumor resection were associated with long-term outcomes. The multivariate analysis showed near-total resection was a significant predictor for long-term outcomes (P = 0.019). There were no new pituitary dysfunctions. The observed complications included one case of cerebrospinal fluid leakage and one case of epistaxis requiring intervention. Conclusions Intracapsular debulking and adjuvant SSAs are a safe and viable treatment for patients with GH secreting pituitary macroadenoma to achieve biochemical remission and tumor control. Although adjuvant SSA treatment enhances residual tumor control, cavernous sinus invasion impedes the remission of endocrine tumors.

BACKGROUND In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival but it has failed to improve overall survival (OS) in controlled trials. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients. METHODS The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis. RESULTS We found that among these GBM patients, the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. CONCLUSIONS This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patientsaccording to bevacizumab sensitivity.

Glioblastoma (GBM) is a common, malignant brain tumor. While it rarely metastasizes to distant organs, the diffuse invasion of glioma cells within the brain makes it difficult to resect. P21 (Waf-1) is a cyclin-dependent kinase inhibitor that plays an essential role in cell growth arrest, terminal differentiation, and apoptosis. Thus, the existence of natural variants of p21 could be linked to specific cancer. The purpose of this study was to identify the polymorphism variants of p21 codon 31 (Ser31Arg) and to explore its role in the therapy of glioblastoma multiforme. A total of unrelated 99 GBM subjects, were enrolled in the study, and genomic DNA was obtained from each tumor sample for genotyping. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR-RFLP analysis. Odds ratios (Ors) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. We found that among these GBM patients, the distribution of codon 31 polymorphisms was 20.2% for Serine homozygotes (Ser/Ser), 32.3% for arginine homozygotes (Arg/Arg), and 47.5% for Serine/arginine heterozygotes (Ser/Arg). Although the polymorphisms of p21 codon 31 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Ser genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. Our findings suggest that the p21 Ser31Arg polymorphism may play an important role in the pathogenesis and initiation of GBM. Moreover, the polymorphism seems to contribute to a significant prediction at early diagnosis for bevacizumab therapy.

A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear. In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis. The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro. Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment.

Gamma knife treatment outcome of large pituitary tumors which are only partially irradiated secondary to immediate proximity to critical structures such as the optic apparatus have not been rigorously studied.From July 2003 to December 2013, there were 41 cases of recurrent or residual nonfunctioning pituitary macroadenoma partially treated with gamma knife radiosurgery (GKRS) because the adenoma obscured part of the optic apparatus on planning SRS MR imaging.The follow up period after GKRS was 92.3 ± 5.6 months. The percentage of tumor coverage with the full dose was 88.5 ± 0.7%. Five of 43 (11.6%) patients experienced a transient visional decrease and one patient experienced a permanent visual field defect. During the follow up, two patients underwent transphenoidal surgery and one patient had a craniotomy due to tumor progression. Seven patients (16.2%) developed cortisol and thyroxine deficiencies. In multiple variant analyses, transient visual decline was correlated to the tumor volume ( 3.5 cc), percentage of tumor coverage ( 90%), the distance from the optic apparatus to the pituitary stalk ( 15 mm) and percentage of tumor above the orbital apex (65%).In the limited case of this cohort, we found that partially treated pituitary nonfunctioning macroadenoma yielded a high tumor control rate. However, visual decline as a result of tumor progression or radiation effect can occur in a minority of patients. The radiosurgical technique warrants further study to better define the long-term risk to benefit profile for its use in complex pituitary macroadenoma obscuring part of the optic apparatus.

nua and weakness of left limbs. Other symptoms included nausea, vomiting, photophobia, and phonophobia. Brain computed tomography (CT) with CT angiography revealed high attenuation change with filling defect at the right internal jugular vein, right transverse sinus, and superior sagittal sinus. Magnetic resonance angiography of brain disclosed engorged cortical veins at right temporo-parietooccipital lobe and left frontoparietal lobe. Thrombosis of superior sagittal sinus, right transverse sinus, right sigmoid sinus, and right internal jugular vein were noted (Fig. 1a and b). Anticoagulant treatment was initiated but failed with rapid progression symptoms after 1 day. Glasgow Coma Scale (GCS) decreased from 15 to 11–12. The patient was immediately transferred to the angiography suite where cerebral angiography and venography studies disclosed sinus thrombosis with venous hypertension (Fig. 1c and d). Multi-modality endovascular thrombolysis was applied. Intravenous local mechanical thrombolysis was performed with a large-bore guiding catheter and balloon to break the clot. Using the NEURON Intracranial Access System (Penumbra, San Leandro, CA) as a large-bore guide catheter, direct aspiration for clot disruption was performed as far as the distal sagittal sinus by Sterling monorail balloon catheter (Boston Scientific, Boston, MT) (Fig. 2a and b). At the same time, urokinase (600,000 IU) was infused to dissolve the venous thrombi. After partial recanalization by mechanical thrombolysis, the guiding catheter was left inside the superior sagittal sinus for continuous local urokinase infusion (15,000 IU/h) for 48 h. We removed the catheter and repeated cerebral angiography and venography later. The final follow-up angiogram (Fig. 2c and d) showed patency of the sinuses. She was discharged without residual neurologic deficit and was prescribed warfarin orally for 6 months. Neurologic outcomes, GCS, and neuroimaging results were improved. Introduction

Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors, with dismal prognosis. More than 70% of GBM patients die within 2 years after diagnosis, even under intensive multimodality chemoradiation with an oral alkylating agent, temozolomide (TMZ).1 Identifying and understanding the biology behind novel chemo- and radioresistant markers in GBM would shed light on improving the current therapeutic approaches. Clinically, the methylation status of the methylguanine-DNA-methyltransferase (MGMT) gene promoter is a strong indicator of survival benefits of radiotherapy and TMZ.2 Besides, mutation at codon 132 of isocitrate dehydrogenase 1, which was strongly associated with codeletion of 1p or 19q, was prognostic as well for secondary GBM.3,4 However, the incidence of isolated 1p or 19q deletions among primary GBM has been low, at 6.2% and 5.3%, respectively.5 Ataxia telangiectasia mutated kinase (ATM) responds to DNA double-stranded breaks (DSBs) immediately following radiation exposure. In gliomas, ATM plays a critical role in radiation resistance,6 and the expression level of ATM dramatically alters radiosensitivity in GBM.7,8 Since ATM became an attractive target for tumor radiosensitization, several inhibitors of ATM activity have been developed, aimed to improve radiotherapy. However, ATM inhibitors were reported to be effective in eliminating only cancer cells that express functional ATM protein with already compromised DNA repairs.9 Recently, ATM was found to be tightly associated with mitochondrial homeostasis, and it has been suggested that ataxia-telangiectasia could be considered as a part of mitochondrial disease.10 Mitochondria play essential roles in cancer progression, in particular in metabolically remodeled phenotypes, which predominantly use aerobic glycolysis as an energy source (Warburg effect).11 Accumulated evidence indicates that some nucleus-encoded mitochondrial proteins are involved in tumorigenesis.12 An altered mitochondrial genome has been frequently found in GBM and shown to adapt to bioenergetic stress.13,14 Furthermore, mitochondrial dysfunction was reported to be associated with increasing damage to reactive oxygen species and the onset of several neurodegenerative diseases and neoplasms.15 Therefore, mitochondrial proteins indeed might be novel therapeutic targets to implement the existing treatments of GBM.16 The ATPase family, AAA domain containing 3A (ATAD3A; 66 kDa) is an essential mitochondrial enzyme involved in maintaining mitochondrial functions and communication between endoplasmic reticulum (ER) and mitochondria.17–19 ATAD3A was first identified as a tumor-specific antigen20,21 and was later shown to have roles in lung adenocarcinoma,19 uterine cervical cancer,22 and prostate cancer.23 Its clinical significance was further supported by in vitro data, in which cancer cells with ATAD3A overexpression were more resistant to anticancer drugs.21 Interestingly, the ATAD3A gene is located on human chromosome 1p36.33 and has been shown in human glioma cell lines to be correlated with cell growth and resistance to genotoxic drugs.24 Although deletion/alteration in the distal short arm of chromosome 1 (1p) has been associated with chemo- and radiosensitivity in oligodendrogliomas and other brain tumors, no specific tumor-related gene to date has been identified as conferring this to a treatment-resistant phenotype.25,26 In this report, we demonstrate that ATAD3A expression correlates with treatment response in a primary GBM chemoradiation cohort, implicating ATAD3A as a possible prognostic marker and therapeutic target in GBM. We also investigated the ATAD3A-associated chemo- and radioresistant mechanisms in GBM.

In 1995 a government-supported Universal National Health care system was implemented in Taiwan, which in 2008 was available to 98% of the population. This system offers affordable, rapid medical attention. A multi-center retrospective study was conducted to assess the prognosis of malignant glioma patients under this system. In 2005 and 2006, patients at 14 independent neuro-oncology centers with newly diagnosed malignant glioma were enrolled. The patient profile, pathology, treatment modalities, and prognosis were collected by questionnaire at each center. The Taiwan Neuro-Oncology Society was responsible for the data analysis. The overall median survival period, 1-year survival rate, and 2-year survival rate for patients with World Health Organization grade III glioma were 33.8 months, 81.4%, and 58.2%, respectively, and 15 months, 57.3%, and 33.9% in patients with grade IV glioma. The median survival period, 1-year survival rate, and 2-year-survival rate in patients receiving temozolomide adjuvant therapy was 36 months, 84.2%, and 61.8%, respectively, for patients with grade III glioma and 19.8 months, 73.1%, and 43.7%, for patients with grade IV glioma. The universal health care system in Taiwan offers a comparable prognosis with an affordable premium relative to other large series in developed countries.

Background We performed endoscope-assisted MVD or fully endoscopic MVD for minimizing the risks of brain retraction and extensive dissection and got good results. In addition, we highlighted the value of endoscopy in the diagnosis and therapy for cranial nerve pathologic condition in the posterior fossa. Methods Among 300 consecutive patients with microsurgically treated HFS, 32 patients underwent endoscope-assisted MVD or fully endoscopic MVD through the retromastoid approach between July 1998 and December 2002, at the Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. The use of endoscopes is indicated for patients who had difficulty in identifying the nerve-vessel conflicts. Results The procedure was successful in 96.9% of patients and improved in 3.1%. No failure or recurrence was noted. The postoperative complications were found in 2 patients who were treated by endoscope-assisted MVD. One patient (3.1%) showed delayed facial palsy on the seventh day but was fully recovered 2 months later. Hearing impairment was noticed in one patient (3.1%). There was no perioperative mortality. Conclusion From our experience, we conclude that the endoscope's superior visualization more accurately identifies neurovascular conflicts and provides a comprehensive evaluation of the completeness of the decompression. In addition, this method minimizes the risks of brain retraction and extensive dissection often required for microscopic exposure. Endoscopes are good as an adjunctive imaging modality to confirm nerve-vessel conflicts identified by the microscope and to reveal others that escaped from microscopic survey.

Background Spinal osteomyelitis and epidural abscess are complicated medical conditions. Diagnosis is often delayed because of cormorbidity. The time of instrumentation is still controversial. However, there is no doubting the indication of spinal hardware implantation when spinal fusion is needed. Long segment osteomyelitis and extended epidural abscess are rare. The treatment is challenging for neurosurgeons. We report a case of extended epidural abscesses and long segments of osteomyelitis. Methods One-stage meticulous debridement, anterior cervical corpectomies, and spinal fusion with mesh cage and titanium plate were performed on the patient. Hyperbaric oxygenation and 6 weeks of intravenous antibiotics were prescribed as adjuvant therapy. Results Both clinical presentations and imaging studies showed a good response to the treatment. The patient returned to his life 3 months later. Conclusions This case illustrates that spinal instrumentation is not an absolute contraindication in the presence of epidural abscesses and vertebral osteomyelitis. Combined surgical debridement at a critical level, with adjuvant antibiotics and hyperbaric oxygenation, is a safe and effective therapy in those with neurologic deficits, spinal instability, and extended epidural abscess.

Central neurocytoma is a rare intraventricular brain tumor that affects young adults and presents with increased intracranial pressure secondary to obstructive hydrocephalus. Typically, it has a favorable prognosis after adequate surgical intervention, but in some cases the clinical course is more aggressive. In this report, we describe the diagnosis and treatment of central neurocytoma in a series of patients at our institution.Our series of nine patients (M:F=2:7, mean age, 28.2 years) with ventricular tumors showed typical radiological, histologic and immunohistochemical features of central neurocytoma. Most patients received craniotomy with removal of the tumor through transcallosal or transcortical approach. The surgical and histopathologic data of these patients were reviewed and analyzed.The prognosis is generally favorable. Although most patients were alive and well at the last follow-up, two developed recurrence. Typical histologic features of recurrent neurocytoma include high proliferative activity (MIB-1 labeling index: 2.0-6.8%), prominent vascular proliferation and remarkable synaptophysin expression. Two patients (non-recurrent) died during follow-up due to sepsis or central failure. The MIB-1 labeling indices were as high as 2.2-5.4% for these two patients.Although central neurocytoma is generally a benign neoplasm, some variant forms of recurrence are also present. Complete resection provides favorable long-term prognosis in most cases. Recurrent tumors are often local and the patients seem to recover well after a second resection followed by radiotherapy. Histologic features such as tumor proliferation (MIB-1 labeling index), vascular proliferation, and synaptophysin expression are often prominent in the recurrent tumor. We recommend that these histologic features be considered for tumor recurrence during treatment and follow-up of these patients.

Background: Gamma knife radiosurgery (GKS) has been an effective treatment for meningiomas. Nevertheless, it still has certain risks. We present 2 cases of parasagittal meningioma after GKS complicated with radiation necrosis and peritumoral edema. The results of histologic examination are discussed. Case Description: Two cases of parasagittal meningioma received GKS. Symptomatic peritumoral edema developed 3–4 months after GKS. Both of them underwent surgical resection of their tumor afterwards. Histologic examination showed necrotic change inside the tumor and infiltration of inflammatory cells in both cases. Hyalinization of blood vessels was seen in the 2nd case. The patients had improvement of neurologic function after surgical resection. Imaging performed 3 months after surgical resection showed alleviation of brain edema. Conclusion: After radiosurgery peritumoral edema tends to occur in meningiomas with a parasagittal position. Radiation necrosis, infiltration of inflammatory cells, and radiation injury to the vasculature causing hyalinization of blood vessels are suggested as the underlying histopathology.

Cavernous hemangiomas rarely occur in the cerebral ventricles. Those occurring at the foramen of Monro are even less frequent. So far, only eight cases of cavernous hemangioma at the foramen of Monro have been reported in the literature. Here, we present a similar case and correlated the radiographic with the histopathologic findings of the patient. A 51-year-old woman was admitted with obstructive hydrocephalus-related symptoms. The computed tomography (CT) and magnetic resonance imaging (MRI) revealed a partly calcified lesion with slight contrast enhancement located in the area of the right foramen of Monro. The lesion was completely removed by surgical resection with a transfrontal transventricular approach. The resected mass was histologically diagnosed as cavernous hemangioma. The patient's symptoms resolved immediately after operation. Cavernous hemangioma at the foramen of Monro in the present case had common MRI features as previously reported. Although MRI can provide initial diagnosis for such unusually localized tumor, it should be confirmed histopathologically.

A 53-year-old female with a functioning pituitary adenoma was found to also have an unruptured asymptomatic aneurysm in the cavernous sinus portion of the internal carotid artery on MRI. The adenoma had a suprasellar extension with optic chiasm compression and extended into the right cavernous sinus. An aneurysm-like flow-void adjacent to the left internal carotid artery in the sella and embedded in the adenoma was also found. The aneurysm was confirmed by conventional angiography. We used a right fronto-pterional approach to clip the aneurysm and to remove the pituitary tumor in a one-stage procedure. The outcome was good on long-term follow-up. It is important to thoroughly evaluate the anatomic relations around the sella turcica prior to procedures with limited exposure, including transsphenoidal surgery, to avoid unrecognized complications and morbidity.

We report a case of calcified chronic encapsulated intracerebral haematoma (ICH) in a 29-year-old female who presented with progressive left sided weakness and intermittent seizures since childhood. The preoperative magnetic resonance (MR) imaging of the head initially suggested that a partially thrombosed aneurysm or vascular malformation was present. However, no vascular stain was found on the digital subtraction angiography (DSA) of both the carotid and vertebral arteries. The excised mass was histologically diagnosed as a chronic ICH. We traced the patient's medical history and found that at the age of one she sustained a head injury after a fall. So far, to our knowledge, no case of epilepsy secondary to a calcified chronic encapsulated ICH occurring 28 years after head injury has been reported. Calcified chronic encapsulated ICH concomitant with new bone formation within is even rarer. The possible pathogenesis of this case is discussed.

We present a 68-year-old male patient with an exceptionally aggressive tumour which invaded to the skull base, cavernous sinus, nasopharynx, sphenoid sinus, pituitary fossa, bilateral parasellar regions, premedullary cistern, and left infratemporal fossa. Headache was the only symptom. The serum prolactin level was 95,973 ng/ml. The patient was treated by right subfrontal craniotomy with removal of the tumour. Because it did not respond well to surgical treatment and the electron micrograph showed abundant secretory granules in some parts of the specimen, post-operative radiotherapy and bromocriptine therapy were instituted. After combined therapies and a long-term follow-up, only little residual pituitary tumour was seen with serum prolactin progressively dropped to 717 ng/ml with no obvious symptoms. The histological findings, the ideal treatments and the clinical course of multi-invasive giant prolactinoma will be discussed.

In this study, we investigated the dose-effect relationship and safety of tissue plasminogen activator (tPA) for the treatment of intraventricular hemorrhage/hematoma (IVH) in rats. Adult male Sprague-Dawley rats were injected with autologous blood into the left lateral ventricle to establish IVH. Two hours later, Ringer's saline or 0.25-2 microg of tPA were administered directly to the IVH over 3 h. The regional cerebral blood flow (rCBF) on the surface of the left parietal cortex was measured with laser Doppler flowmetry. Twenty-four hours after the build-up of IVH, the brains were removed for morphometrical and histological studies. A dose of 0.5-2 microg tPA significantly diminished the IVH in a dose-dependent manner (p0.001). However, only the dose of 0.5 microg tPA significantly ameliorated the reduction of rCBF 24 h after IVH (p0.01). TPA did not improve the ventricular dilatation on the side with IVH. Instead, 1-2 microg of tPA caused additional injuries, including intraventricular leukocytosis and edema of periventricular tissues and choroid plexus on both hemispheres. These results indicate that higher doses of tPA may have detrimental effects on the brain. The dosage rate of 0.5 microg seems beneficial to treat 5 microl of IVH (equals to a dose of 0.1 mg/ml blood) in our model in terms of the satisfactory fibrinolysis and less damage to the brain.

Treatment of a dural arteriovenous fistula (AVF), which is difficult to access by either the surgical or endovascular approach, is challenging. A hybrid technique, combining a microsurgical approach and endovascular embolization, can provide less invasive management of dural AVFs in a modern neurosurgical hybrid operating suite. We present a case of intracerebral hemorrhage in the left cerebellum secondary to dural AVF, Cognard type IV with numerous tiny feeders from the ascending pharyngeal artery branches. No adequate arterial or venous route for endovascular embolization was found by neuroangiography. The hybrid technique, combining keyhole pterional craniotomy and embolization with n-butyl cyanoacrylate glue injection via direct cannulation of the periclival venous plexus, succeeded in obliterating the dural AVF. Intraoperative angiography showed successful embolization of the dural AVF without any complication. This report illustrates the usefulness of the neurosurgical hybrid operating suite for the treatment of difficult dural AVFs.

A 69-year-old woman with hypertension presented to the emergency room with severe pulsatile pain around the left orbital area and diplopia for 2 days. Neurological examination revealed paresthesia over the upper two-thirds of left face innervated by the ophthalmic and maxillary divisions of trigeminal nerve and diplopia secondary to left abducens nerve palsy. Brain noncontrast computed tomography (CT) showed a 2.5 × 2.5 × 2.0 cm hyperdense mass over left cavernous sinus suggestive of thrombus formation (Fig. 1a). CT angiography (CTA) showed a giant, partially thrombosed aneurysm arising from the intracavernous internal carotid artery (ICA) (Fig. 1b). Digital subtraction angiography (DSA) showed a large persistent primitive trigeminal artery (PPTA) connecting the ICA to the distal part of the hypoplastic middle basilar artery (BA), with a 1.2 × 1.2 × 1.0 cm aneurysm sac at the origin of PPTA and hypoplasia in the left vertebral artery (VA). (Fig. 1c–f) Steroid therapy was prescribed initially and endovascular surgery was arranged. Aspirin (400 mg) and clopidogrel (300 mg) were administered before the treatment. All procedures were performed under general anesthesia and full heparinization. The covered stent, Jostent stent graft (previously JoMed, Helsingborg, Sweden; now Abbott Vascular, Redwood City, California, USA), was successfully deployed at left ICA to cover the orifice of persistent primitive trigeminal artery (Fig. 2). The postoperative course was uneventful. Trigeminal neuralgia improved immediately after treatment but diplopia persisted. One-year follow-up of left ICA DSA showed ICA patency was preserved and there was no recurrent aneurysm. In addition, the right VA DSA showed a small remnant of PPTA supplied by the vertebrobasilar artery (Fig. 3). The clinical situation at one-year follow-up showed complete resolution of trigeminal neuralIntroduction

Background: Some complex dural arteriovenous fistulas (DAVFs) are lesions that typically have numerous arterial feeders. Surgery, including resection of fistulas or skeletonization of the diseased sinus, is still one of the important treatments for these lesions. However, major blood loss is usually encountered during craniotomy because of abundant arterial feeders from the scalp and transosseous vessels. We present a novel approach for obliteration of the fistulas with less blood loss. Methods: Our first case was a 52-year-old male who suffered from syncope and seizure. Cerebral digital subtraction angiography (DSA) revealed complex DAVFs with numerous arterial feeders from bilateral external carotid arteries (ECAs) and drainage into the superior sagittal sinus with cerebral venous reflux. The second case was a 48-year-old male presenting with chronic headache. His DSA also showed complex DAVFs along the superior sagittal sinus with cerebral venous reflux. In both cases, we performed the surgical procedure to obliterate the pathological fistulas after temporary clamping of bilateral ECAs and noted less blood loss than in the conventional surgery. Results: The follow-up DSA showed successful obliteration of the complex DAVFs on the first case and partial improvement on the second case followed by transarterial embolization (TAE). The symptoms of the both patients were relieved after surgery with good recovery. Conclusion: Temporary clamping of bilateral ECAs can improve the safety and ease the surgical excision for complex DAVFs. By using this technique, neurosurgeons can deal with aggressive DAVFs more confidently and calmly.

Background and Purpose— Intracerebral hemorrhage (ICH) is associated with high mortality and neurological deficits, and concurrent hyperglycemia usually worsens clinical outcomes. Aquaporin-4 (AQP-4) is important in cerebral water movement. Our aim was to investigate the role of AQP-4 in hyperglycemic ICH. Methods— Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) in adult Sprague–Dawley male rats. ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. One set of rats was repeatedly monitored by MRI at 1, 4, and 7 days after ICH induction so as to acquire information on the formation of hematoma and edema. Another set of rats was killed and brains were examined for differences in the degree of hemorrhage and edema, water content, blood–brain barrier destruction, and AQP-4 expression. Results— Hyperglycemia ICH rats exhibited increased brain water content, more severe blood–brain barrier destruction, and greater vasogenic edema as seen on diffusion-weighted MRI. Significant downregulation of AQP-4 was observed in STZ-treated rats after ICH as compared with non–STZ-treated rats. Apoptosis was greater on day 1 after ICH in STZ-treated rats. Conclusions— The expression of AQP-4 in the brain is downregulated in hyperglycemic rats as compared with normoglycemic rats after ICH. This change is accompanied by increased vasogenic brain edema and more severe blood–brain barrier destruction.

Background and importance Although medical treatment has been considered a dogma for chronic total occlusion (CTO) of the carotid artery, use of endovascular recanalization has also been reported. However, there are some difficulties in performing endovascular recanalization. We present the novel technical details and advantages of hybrid surgery for recanalization of symptomatic CTO of the internal carotid artery (ICA). Clinical presentation Three cases with recurrent ischemic attacks due to thrombotic occlusion of the right ICA above the bifurcation were successfully treated by this hybrid surgery, combining endarterectomy of the proximal ICA with endovascular angioplasty of the distal ICA. Using this hybrid technique, complete recanalization was achieved in all 3 cases. Follow-up computed tomography angiography with perfusion imaging showed improved brain perfusion. At 6-month follow-up, ischemic symptoms had not recurred. Conclusion We consider this hybrid surgery to be a feasible and good alternative surgical procedure for the treatment of CTO of the internal carotid artery.

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein kinase A (PKA) activity. Adenylyl cyclase activator forskolin attenuated, but PKA inhibitor H89 augmented, gefitinib-induced Bad dephosphorylation, Bax mitochondrial translocation, caspase-9/caspase-3 activation, and viability loss. Intriguingly, a nonselective protein phosphatase inhibitor okadaic acid alleviated gefitinib-induced alterations, except Bad dephosphorylation. In parallel with the higher basal PKA activity, response of U87 cells to gefitinib treatment was delayed and relatively resistant compared with that of H4 and T98G cells. Inactivation of PKA sensitized H4, T98G, and U87 cells to gefitinib cytotoxicity, Bad dephosphorylation in serine-112, and caspase-9/caspase-3 activation. Our findings suggest the involvement of the Bad/Bax signaling pathway in gefitinib-induced glioma apoptosis. Furthermore, the inactivation of PKA was shown to play a role in triggering the proapoptotic function of Bad.

Background: Esophageal dilatation is the most widely used treatment option for the management of esophageal strictures. Complications include bleeding, brain abscess, esophageal perforation and bacteremia. Nasopharyngeal gangrenous abscess after the esophageal dilatation is very rare. Endonasal endoscopic surgery was performed to treat the lesion and a successful result was obtained. Case Description: A 59-year-old woman with a previous history of dilatation for esophageal stricture was admitted with a low-grade fever, headache, neck pain and cranial nerve abnormalities including sixth nerve palsy. Imaging studies aroused suspicion of necrotic retropharyngeal tumor with clivus, condylar process and cavernous sinus invasion. Biopsy with a pharyngosope was performed by an ENT doctor. The pathology showed acute necrotic inflammation, tissue granulation and bacteria colonies. Navigation with endonasal endoscopic surgery was chosen to treat the skull base and nasopharyngeal abscess. Bacterial culture showed Escherichia coli. Symptoms improved after the operation and treatment with antibiotics. Conclusion: A nasopharyngeal gangrenous abscess with extension to the skull base in the case of esophageal reconstruction after esophageal dilatation is extremely rare. Physicians dealing with esophageal stricture should keep in mind that a nasopharyngeal abscess is a potential complication of esophageal dilatation.

Stereotactic aspiration of hematoma is an effective method for the treatment of basal ganglia hematoma. Hematoma aspiration with a frameless navigation system using external fiducials has been published in the literature. But the literature is lacking in the use of a fiducial-free method for frameless aspiration of hematoma. We report an effective and safe method for the aspiration of intracerebral hematoma with a frameless and fiducial-free navigation system. Methods: Six patients with hypertensive basal ganglia hematoma underwent stereotactic aspiration of hematoma with a frameless and fiducial-free navigation system during January 2007 to April 2007. Patient registration to 3D data was done with surface matching. An articulated holder was used to maintain the trajectory. A catheter was inserted into the hematoma through the trajectory. Urokinase was injected into the hematoma. CT scan was performed after a few days of hematoma drainage. The pre- and postoperative hematoma volume and neurological function were compared. Results: The patients’ GCS improved from an average of 11.25 to an average of 14.83 after several days of hematoma drainage. Brain CT carried out after several days of drainage showed a 68–100% (average 79.3%) reduction of hematoma. No surgery-induced complication was noted. Conclusion: The use of a frameless and fiducial-free navigation system appears to be a time-efficient, safe, and effective method for the aspiration of hypertensive intracerebral hematoma.

We compared the preliminary outcomes of cervical fusion performed using radiolucent cages containing either cancellous bone or hydroxyapatite graft. From July 2004 to June 2006, 45 consecutive patients presented with a total of 109 levels of degenerative disc disease between the C2 and C7 levels. Each patient underwent anterior cervical discectomy and fusion (ACDF) for each affected cervical disc. The retrospective analysis of the cage fillers was divided into group 1 (23 patients with 56 affected cervical levels) who received cages packed with cancellous bone marrow, and group 2 (22 patients with 53 affected cervical levels) who received cages packed with hydroxyapatite graft. Bone marrow was harvested from the anterior iliac crest. The Prolo scale was used to assess both the economic and functional status postoperatively. The Yates' correction to test independence in a contingency was used to compare the fusion rate of both groups post-operatively at day 1 and at 1, 3 and 6 month follow-up. At a mean follow-up of 12 months, the fusion rates observed in groups 1 and 2, respectively, were 21.4% and 13.2% after 1 month, 76.8% and 64.2% after 3 months, and 98.2% and 96.2% after 6 months. Functional and economic status were better in group 2, with a statistical significance (p

Background Gunshot accidents are not uncommon in Taiwan, but involvement limited to the ocular region and sphenoid sinus is rare. Minimal invasive treatment by endonasal transsphenoidal endoscopy-assisted procedure should be considered if there are no additional injuries in the craniocerebral region. Case Description A 39-year–old man had severe pain in the left eye with resulting blindness after being accidentally hit in the left eye by a gunshot pellet while walking in a wooded area. He was referred from another hospital with the impression of left eyeball rupture. There was no severe neurologic deficit except for blindness of the left eye when he arrived at the emergency department of our hospital. Brain and orbits CT scans showed a round metallic foreign body at the right sphenoid sinus without predominant damages of brain parenchyma. Endonasal transsphenoidal endoscopy-assisted procedure was used to remove the shotgun pellet, and the patient had good clinical outcomes. Conclusion Herein we present this rare case to show the possibility of a shotgun pellet injury remaining in the sphenoid sinus. The role of radiological studies such as CT scans and intraoperative C-arm fluoroscope plain films in diagnosis and management of this case is affirmed. The strategy of minimally invasive treatment by endonasal transsphenoidal endoscopy-assisted procedure for those limited injuries is a good choice for treatment.

Background Intracranial lipomas are thought to be congenital in origin and are very rare, representing 0.1% to 1.7% of all intracranial tumors. Most ICLs are located at midline. Lipomas at sylvian fissure are extremely rare. They are slow growing, and biological course is favorable even without surgical treatment. A Medline search of the literature from 1965 to 2007 revealed only 13 cases of sylvian fissure lipomas reported. Of 9 patients with sylvian fissure lipoma diagnosed during life, 6 patients were operated on with no mortality and got improvement of symptoms. Surgical intervention should be considered if there are problems such as compressive effect or resistance to anticonvulsive medical treatment. Case Description We report a 57-year–old woman with a sylvian fissure lipoma presenting with persistent intractable headache. Imaging study showed a lobular nonenhanced lesion associated with abnormal vessels in the right sylvian fissure. The patient underwent minimally invasive pterion keyhole approach, and the lipoma was successfully and totally removed. Headache and subsided postoperatively. Conclusions There are only few cases of sylvian fissure lipomas in which surgical excision has been attempted. Because of improvement of microsurgical techniques, direct surgical approach with total removal of lipomas, via a minimally invasive pterion keyhole approach, is feasible. Therefore, it should be kept in mind that the primary goal of the surgery is adequate decompression; and total removal may be achieved if the lesion permits.

Reported herein is an unusual case of atypical teratoid/ rhabdoid tumor (AT/RT) of the lumbar spine with an intradural extramedullary location in a 7-year-old boy. Histologically, this tumor contained rhabdoid cells, pale cells, and sickle-shaped embracing cells without primitive neuroectodermal tumor (PNET), mesenchymal or epithelial components. Immunohistochemical staining showed that these tumor cells react positively for epithelial membrane antigen (EMA), vimentin, cytokeratin (AE1/AE3), CD99 and neurofilament protein, but negatively for INI1 antibody. Chromosome 22q deletion was demonstrated on fluorescence in situ hybridization.

Background Previous reports of the efficacy of percutaneous pulsed radiofrequency have been confounded by fewer case numbers, poor patient selection, and limited data on cervical or lumbar radicular pain. We used percutaneous pulsed radiofrequency for cervical and lumbar radicular pain, and the study has more than 100 cases for the analysis of the efficacy of percutaneous pulsed radiofrequency. Methods We collected 154 cases of patients with lumbar or cervical radicular pain due to a herniated intervertebral disk or previous failed surgery. They underwent pulsed radiofrequency therapy in 2 to 4 spinal levels unilaterally. Follow-up period was from 1 week to 1 year postoperatively. Results Twenty-six (53.06%) of 49 patients and 59 (50.86%) of 116 patients after cervical and lumbar pulsed radiofrequency stimulation, respectively, had an initial improvement of 50% or more in the first week of follow-up. Twenty-seven (55.10%) of 49 patients and 52 (44.83%) of 116 patients after cervical and lumbar pulsed radiofrequency stimulation, respectively, had pain relief of 50% or more at the follow-up period of 3 months. In the analysis of patients with pain relief of 50% or more for at least 1 month, the most effective period was during postoperation 1 month later. No complication was found among these patients. Conclusions The results of this retrospective analysis showed that the application of pulsed radiofrequency is a safe and useful intervention for cervical and lumbar radicular pain. The satisfactory pain relief obtained by most of our patients justifies the start of this study for at least 6 months. Although pulsed radiofrequency appears to provide intermediate-term relief of pain, further studies with long-term follow-up are necessary.

Study design A case of unusual dumbbell-shaped cystic teratoma is presented. Objectives To investigate and describe an unusual case of retroperitoneal cystic teratoma with spinal invasion in an adult. The image findings, minimally invasive surgical procedures, and clinical outcome were discussed, and the literature was reviewed. Summary of background data Primary benign cystic teratomas of the retroperitoneum are rare. Extension of these lesions into the spinal canal is more rare. In this report, by presenting a case of cystic teratoma with such extension, the origin of the tumor, and the value of computerized tomography and magnetic resonance imaging (MRI) in the preoperative diagnosis and surgical approach for the extended lesion are discussed. Methods The patient was a 24-year-old female who had had low back pain with bilateral sciatica for 2 months. Preoperative computerized tomography and MRI of the thoracic and lumbar spines showed a dumbbell-shaped tumor, with the solid part residing in the right retroperitoneum near the neuroforamen of the L2-L3 spines and the cystic part extending into the spinal canal. By performing right L2-L4 hemilaminectomies with a mini retroperitoneal approach, the tumor was removed en bloc in one stage. Results Diagnosis of cystic teratoma was confirmed by pathologic examination. The patient recovered well without any neurologic deficits, and recurrence of tumor has not been found for 9 years postoperatively. Conclusions Total surgical removal of tumor is an ideal treatment for retroperitoneal and intraspinal dumbbell-shaped cystic teratoma. MRI displays the precise location, morphology, and adjacent structures of the tumor, which provide for better preoperative planning and more complete removal of tumor with less neurologic damage.

Ganglion cysts of the spine are uncommon. They occur mostly in the dorsolateral trunk and arise with the greatest frequency in the lumbar spine. However, they are rarely symptomatic. We report a rare case of a patient with a ganglion cyst of the lower cervical spine presenting with acute Brown-Sequard syndrome. The patient had no history of trauma. Magnetic resonance imaging of the cervical spine showed a cystic lesion connecting to the synovial joint C6-7 and compressing the posterior aspect of the spinal cord. The patient underwent emergent C6-7 laminectomy with total removal of the cyst. Neurological function recovered completely 4 months after operation. Ganglion cysts should be considered in the differential diagnosis of an extradural mass of the cervical spine. Magnetic resonance imaging provides a rapid and correct diagnosis, and laminectomy with removal of the cyst results in good neurological recovery.

Summary Interleukin-6 (IL-6) is frequently produced in gliomas and has been implicated as a mediator of growth control in several human neoplasms. In this study, IL-6 expression was examined in 11 surgically resected glioblastomas and a cell line U87MG by immunohistochemical staining and quantitative real-time RT-PCR. The relationships between IL-6 expression level and clinical presentation, survival, imaging findings, age and preoperative Karnofsky performance status were analyzed. The median survival times were 16 months in patients with negative IL-6 expression and 7 months in those with positive IL-6 expression ( P = 0.075). Three of these patients with a relatively longer survival time (>1 year) did not express IL-6 in the tumor. Relatively more severe peri-focal edema on imaging was also noted in the glioblastomas with IL-6 expression. IL-6 was also found in the cytoplasm of endothelial cells of newly formed vessels and infiltrating inflammatory cells. These preliminary results implicate IL-6 expression as a possible prognostic indicator in glioblastoma. This cytokine may also play a role in tissue edema, angiogenesis and inflammation of this tumor, but whether IL-6 expression promotes malignancy is uncertain.

Being the most common childhood tumor to involve the hypothalamus and pituitary gland, craniopharyngioma, a histologically benign tumor, is usually related to growth retardation and hypogonadism. The presentation of precocious puberty is very rare for a hypothalamic craniopharyngioma. Here, we report such a case. The female patient had presented with symptoms of menarche and breast development since she was 6 years old. Hormonal therapy with a gonadotropin-releasing hormone analogue was instituted to cease precocious puberty but was unsuccessful. Magnetic resonance imaging of the sella showed a 1-cm tumor in the hypothalamic area. Through a pterional approach, the tumor was removed en bloc with endoscope-assisted microsurgery. After the operation, our patient’s symptoms improved, so the hormone therapy was discontinued. This extremely unique association of craniopharyngioma and precocious puberty, the causes and mechanisms involved along with the advantages of endoscope-assisted microsurgery are discussed.

Study design This report analyzed the likely locations of lesions that cause a combination of Horner's and Brown-Sequard syndromes. One must know the anatomic structure of spinal cord and the sympathetic nerve chain. Objectives A hypertensive patient had Brown-Sequard and Horner's syndromes after neck trauma. The magnetic resonance imaging and surgical findings showed the correlation between the clinical symptoms and the likely lesion. Methods The patient underwent right hemilaminectomy from C2 to C6 with total removal of hematoma. Conclusion The spinal epidural hematoma rarely is a surgical emergency. The patient presented with Brown-Sequard and Horner's syndromes. Magnetic resonance imaging made a rapid and correct diagnosis. The patient received an emergent right hemilaminectomy from C2 to C6 with removal of hematoma and subsequently made a complete recovery.

Background: Open discectomy remains the standard method for treatment of lumbar disc herniation, but can traumatize spinal structure and leaves symptomatic epidural scarring in more than 10% of cases. The usual transforaminal approach may be associated with difficulty reaching the epidural space due to anatomical peculiarities at the L5–S1 level. The endoscopic interlaminar approach can provide a direct pathway for decompression of disc herniation at the L5–S1 level. This study aimed to evaluate the clinical results of endoscopic interlaminar lumbar discectomy at the L5–S1 level and compare the technique feasibility, safety, and efficacy under local and general anesthesia (LA and GA, respectively). Methods: One hundred twenty-three patients with L5–S1 disc herniation underwent endoscopic interlaminar lumbar discectomy from October 2006 to June 2009 by two spine surgeons using different anesthesia preferences in two medical centers. Visual analog scale (VAS) scores for back pain and leg pain and Oswestry Disability Index (ODI) sores were recorded preoperatively, and at 3, 6, and 12 months postoperatively. Results were compared to evaluate the technique feasibility, safety, and efficacy under LA and GA. Results: VAS scores for back pain and leg pain and ODI revealed statistically significant improvement when they were compared with preoperative values. Mean hospital stay was statistically shorter in the LA group. Complications included one case of dural tear with rootlet injury and three cases of recurrence within 1 month who subsequently required open surgery or endoscopic interlaminar lumbar discectomy. There were no medical or infectious complications in either group. Conclusion: Disc herniation at the L5–S1 level can be adequately treated endoscopically with an interlaminar approach. GA and LA are both effective for this procedure. However, LA is better than GA in our opinion.

Background: Low back pain (LBP) has become a main cause of absenteeism and disability in industrialized societies. Chronic LBP is an important health issue in modern countries. Discogenic LBP is one of the causes of chronic low back pain. The management of chronic discogenic LBP has been limited to either conservative treatment or operative treatment. Intradiscal electrothermal therapy (IDET) is now being performed as an alternative treatment. Methods: Ninety-three consecutive patients undergoing IDET at 134 disc levels from October 2004 to January 2007 were prospectively evaluated. All patients had discogenic disease with chronic LBP, as determined by clinical features, physical examination and image studies, and had failed to improve with conservative treatment for at least 6 months. Follow-up period was from 1 week to 3 or more years postoperatively. Results: There were 50 male and 43 female patients, with a mean age of 46.07 years (range, 21-65 years). The results were classified as symptom free (100% improvement), better (≥50% improvement), slightly better (