Radiological predictive factors for regrowth of residual benign meningiomas.

The pre- and postoperative radiological predictive factors for the regrowth of residual benign meningiomas were investigated in 80 of 327 patients who underwent first surgery for intracranial meningioma, who met the following conditions: residual tumor observed on postoperative imaging, follow up for more than 5 years or until regrowth of the residual tumor, histological diagnosis of World Health Organization grade I, and no additional therapy performed within 1 month after surgery. These 80 patients were divided into those with no regrowth during the follow-up period (Group A, n = 54) and those with regrowth (Group B, n = 26), and the clinical characteristics and pre- and postoperative imaging findings were compared. Univariate analysis of factors influencing regrowth showed 6 factors were significant: tumor size ≥4 cm (p = 0.043), tumor volume ≥30 cm(3) (p = 0.026), presence of edema (p = 0.036), unclear brain-tumor interface (p < 0.001), presence of a pial-cortical blood supply (p = 0.031), and residual tumor volume ≥3.0 cm(3) (p < 0.001). Multivariate analysis showed only residual tumor volume ≥3.0 cm(3) was significant (p = 0.001). Generally, the significant imaging findings on univariate analysis suggest malignant meningioma. Similar findings may be observed even in grade I cases, and residual tumors may regrow in such cases. The possibility is particularly high if the residual tumor volume exceeds 3.0 cm(3), so early radiotherapy should be performed to prevent regrowth.

Post-operative dexmedetomidine-based sedation after uneventful intracranial surgery for unruptured cerebral aneurysm: comparison with propofol-based sedation.

BACKGROUND: Clinical applications of dexmedetomidine (DEX) for neurosurgical procedures have not been adequately investigated. This study aimed to test the use of DEX infusion, alone or as an adjunct to propofol infusion, as compared to propofol infusion in patients with an unruptured cerebral aneurysm after uneventful intracranial procedures. METHODS: In this retrospective observational study from a single institute, of 184 patients who underwent uneventful intracranial procedures for an unruptured cerebral aneurysm between January 2003 and March 2007, we reviewed 50 managed with DEX-based sedation (DEX alone or as an adjunct to propofol infusion) between April 2005 and March 2007, and 50 managed with propofol-based sedation (propofol alone) between January 2003 and April 2005. With DEX-based sedation, both intubated and extubated patients received DEX infusion at an initial dose of 0.4 µg/kg/h, followed by a maintenance dose of 0.2-0.7 µg/kg/h. Propofol was used in both groups at a dose range of 0.5-5.0 mg/kg/h. Hemodynamic variables, including heart rate (HR) and blood pressure (BP), and adverse events were recorded and compared between the groups. RESULTS: HR during sedation and systolic BP at 2 h after beginning sedation were significantly lower in the DEX group. No serious adverse events were observed. In the DEX group, 66% were sedated in combination with propofol, of whom 94% were intubated. CONCLUSIONS: DEX could be used safely for both intubated and extubated patients following uneventful intracranial procedures for an unruptured cerebral aneurysm, though it significantly reduced HR. Our findings also indicate that it is preferable to add low-dose propofol to DEX for management of intubated patients.

DNA ligase IV is a potential molecular target in ACNU sensitivity.

Nimustine (ACNU) is a chloroethylating agent which was the most active chemotherapy agent used for patients with high-grade gliomas until the introduction of temozolomide, which became the standard of care for patients with newly diagnosed glioblastomas in Japan. Since temozolomide was established as the standard first-line therapy for glioblastoma multiforme (GBM), ACNU has been employed as a salvage chemotherapy agent for recurrent GBM in combination with other drugs. The acting molecular mechanism in ACNU has yet to be elucidated. ACNU is a cross-linking agent which induces DNA double-strand breaks (DSBs). The work described here was intended to clarify details in repair pathways which are active in the repair of DNA DSBs induced by ACNU. DSBs are repaired through the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. Cultured mouse embryonic fibroblasts were used which have deficiencies in DNA DSB repair genes which are involved in HR repair (X-ray repair cross-complementing group 2 [XRCC2] and radiation sensitive mutant 54 [Rad54]), and in NHEJ repair (DNA ligase IV [Lig4]). Cellular sensitivity to ACNU treatment was evaluated with colony forming assays. The most effective molecular target which correlated with ACNU cell sensitivity was Lig4. In addition, it was found that Lig4 small-interference RNA (siRNA) efficiently enhanced cell lethality which was induced by ACNU in human glioblastoma A172 cells. These findings suggest that the down-regulation of Lig4 might provide a useful tool which can be used to increase cell sensitivity in response to ACNU chemotherapy.

[Symptomatic radiation necrosis 10 years after gamma knife surgery for arteriovenous malformations: a case report].

We present a case of symptomatic radiation necrosis after gamma knife surgery for arteriovenous malformations (AVMs). Initially, at the age of 30 years the patient was treated with gamma knife surgery. Angiography performed 2 years after radiation therapy revealed that the AVMs were completely obliterated. Five years later, the patient had a generalized convulsion and a computed tomography (CT) scan showed a cystic formation in the irradiated area. The patient was treated with a cyst-peritoneal (CP) shunt. Thereafter, the patient seemed to be cured, but 5 years after CP shunt treatment, the patient had right hemiparesis, agraphia, and right hemianopsia. Magnetic resonance imaging (MRI) revealed radiation necrosis in the left parietooccipital region and midline shift of the brain. The patient was operated on and the hyalinized nidus and CP shunt tube were removed. The patient fully recovered from the symptoms and resumed work.

Orbital schwannoma extending to the lateral wall of the cavernous sinus through the superior orbital fissure--case report.

A 58-year-old man presented with a rare orbitocavernous sinus schwannoma that originated from the orbital opthalmic nerve, and manifested as slowly progressive hypesthesia of the right side of the forehead, proptosis, and ocular pain with rapidly worsening visual acuity. Magnetic resonance imaging revealed a huge orbital tumor extending to the lateral wall of the cavernous sinus through the superior orbital fissure. Microsurgical total resection of the tumor was achieved using an epidural orbitofrontal approach with orbito-fronto-zygomatic craniotomy. The histological diagnosis was schwannoma with Antoni type A formation. The postoperative course was uneventful except for the hypesthesia on the right side of the forehead and transient oculomotor paralysis. Surgery was effective to relieve the symptoms and improve the activities of daily living.

DNA ligase IV as a new molecular target for temozolomide.

Temozolomide (TMZ) is a methylating agent used in chemotherapy against glioblastoma. This work was designed to clarify details in repair pathways acting to remove DNA double-strand breaks (DSBs) induced by TMZ. Cultured mouse embryonic fibroblasts were used which were deficient in DSB repair genes such as homologous recombination repair-related genes X-ray repair cross-complementing group 2 (XRCC2)and radiation sensitive mutant54 (Rad54), non-homologous end joining repair-related gene DNAligase IV (Lig4). Cell sensitivity to drug treatments was assessed using colony forming assays. The most effective molecular target which was correlated with TMZ cell sensitivity was Lig4. In addition, it was found that small interference RNAs (siRNA) for Lig4 efficiently enhanced cell lethality induced by TMZ in human glioblastoma A172 cells. These findings suggest that down regulation of Lig4 might provide a useful tool for cell sensitization during TMZ chemotherapy.

Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 x 10(-9) M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.

OBJECTIVE: The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations. MATERIALS AND METHODS: ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with cyclosporine A. RESULTS: Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH(+) cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3. CONCLUSION: Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period.

Cotransplantation of Mouse Embryonic Stem Cells and Bone Marrow Stromal Cells following Spinal Cord Injury Suppresses Tumor Development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 × 10-9 M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

Carpal tunnel syndrome: electrophysiological grading and surgical results by minimum incision open carpal tunnel release.

The safety and effectiveness of the minimum incision technique were assessed in 138 hands of 108 consecutive patients with carpal tunnel syndrome treated from April 1, 1997 to March 31, 2006. Clinical and electrophysiological examinations were conducted before and after surgical decompression. All hands were divided into early, mild, moderate, and severe groups based on preoperative electrophysiological severity. We examined the surgical outcomes of the affected hands in each group. Nocturnal or daytime dysesthesia, which had been present in 132 (96%) of the 138 hands preoperatively, was completely relieved in 124 (94%) of the 132 hands. Complete relief was achieved in 7 (100%) of the 7 hands in the early group, 68 (99%) of the 69 hands in the mild group, and 45 (94%) of the 48 hands in the moderate group. Complete relief was achieved only in 4 (50%) of the 8 hands in the severe group, and 3 (38%) of the 8 hands did not show any improvement. No painful or hypertrophic scar formation was observed in this series. Only 2 patients complained of postoperative scar discomfort after more than 12 months, which completely disappeared by 14 months after surgery. Minimum incision open carpal tunnel release is a safe and reliable procedure with a high rate of functional improvement and patient satisfaction. Postoperative results were satisfactory regardless of the degree of preoperative electrophysiological severity if preoperative sensory nerve action potentials were detected.

[Surgical treatment of intrarcranial dural arteriovenous fistulas].

Surgical treatment is indicated in patients who present clinical symptoms for intracranial dural arteriovenous fistula and retrograde cortical venous filling on cerebral angiography. Further, surgery is indicated in those patients that cannot be cured by endovascular procedures. For dural arteriovenous fistulas in the anterior fossa, tentorium, craniovertebral junction or convex, surgery was considered as the first option. Morphologically, non-sinus dural arteriovenous fistulas and dural arteriovenous fistulas with isolated sinus should be treated with surgery. The surgical procedure for intracranial dural arteriovenous fistulas basically consisted of the coagulation and disconnection of the retrograde-flow cortical veins at the point of entry into the dural sinus, and the coagulation of the affected dura and dural sinus. The remaining affected dural sinus could be removed if the patient could tolerate the surgery. Preoperative transarterial embolization of the feeding artery is effective in reducing the amount of blood loss intraoperatively. During surgery, microvascular Doppler sonography is useful for confirming the retrograde-flow cortical veins, and stereotactic localization system and duplicated ultrasound sonography are also useful in detecting the shunting point of the dural arteriovenous fistula and the range of the affected dura and dural sinus. The surgical procedure for intracranial dural arteriovenous fistulas is a radical and invasive treatment. However, surgery is a reliable treatment because it can cure the intracranial dural arteriovenous fistula and correct the intracranial hemodynamics immediately after surgery due to the extirpation of the dural arteriovenous shunt and retrograde-flow cortical veins.

The effects of the neuromuscular blockade levels on amplitudes of posttetanic motor-evoked potentials and movement in response to transcranial stimulation in patients receiving propofol and fentanyl anesthesia.

BACKGROUND: Patient movement in response to transcranial stimulation during monitoring of myogenic motor-evoked potentials (MEPs) may interfere with surgery. We recently reported a new technique to augment the amplitudes of myogenic MEPs, called "post-tetanic MEPs (p-MEPs)," in which tetanic stimulation of a peripheral nerve was applied prior to transcranial stimulation. We conducted the present study to determine an appropriate level of neuromuscular blockade during the monitoring of p-MEPs with a focus on patient movement. METHODS: In 15 patients under propofol/fentanyl anesthesia, conventional MEPs (c-MEPs) and p-MEPs in response to transcranial electrical stimulation were recorded from the abductor hallucis muscle. For p-MEP recording, tetanic stimulation to the posterior tibial nerve at an intensity of 50 mA for 5 s was started 6 s prior to transcranial stimulation. The level of neuromuscular blockade was assessed by recording the amplitude of compound muscle action potentials (T1) from the abductor hallucis brevis muscle in response to supramaximal electrical stimulation of the median nerve at the wrist. After the baseline recordings of c-MEP and p-MEP at a T1 of 50% of control, 0.1 mg/kg of vecuronium was injected and the amplitudes of c-MEPs and p-MEPs were recorded. Patient movement was also assessed with the movement score ranging from 1 to 4 (1 = no movement, 4 = severe movement). RESULTS: T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score changed in parallel after the administration of vecuronium. The amplitudes of p-MEPs before and 15-45 min after the administration of vecuronium were significantly higher than those of c-MEPs. When T1 and %T1 were less than and equal to 1 mV and 10%, respectively, the movement score was 1 or 2 in all patients, indicating that microscopic surgery was possible without the interruption of surgical procedures. When T1 was around 1 mV (0.8-1.2 mV), the success rates of recording of c-MEPs and p-MEPs were 73% (11 of 15) and 100% (15 of 15), respectively. CONCLUSIONS: Under propofol/fentanyl anesthesia, p-MEP could be recorded at a T1 of 1 mV, in which patient movement in response to transcranial stimulation did not interfere with surgery. This technique may be used in patients without preoperative motor deficits, in which patient movement during surgical procedures is not preferable.

Expression of angiogenic growth factor in the rat DAVF model.

OBJECTIVE: The precise mechanisms responsible for the development and growth of dural arteriovenous fistula (DAVF) remain unclear, but it has been hypothesized that vascular endothelial growth factor (VEGF) might be involved in the pathogenesis. The aim of this study was to examine the expression of VEGF in the rat DAVF model. METHODS: Forty-five Sprague-Dawley rats were used in two experiments. In Experiment 1 (n = 20, including sham-operated controls), VEGF expression was analysed by Western blots in three different rat DAVF models: model I: common carotid artery-external jugular vein (CCA-EJV) anastomosis (n = 5); model II: sagittal sinus thrombosis and bipolar coagulation of the vein draining the transverse sinus (n = 5); model III: CCA-EJV anastomosis and bipolar coagulation of the vein draining the transverse sinus and sagittal sinus thrombosis to induce venous hypertension (n = 5). Based on the results of Experiment 1, Western blots were performed at weekly intervals 1, 2 and 3 weeks in Experiment 2 following induction of venous hypertension in model III (n = 5 at each time point and n = 5 sham controls); in addition, VEGF expression was immunohistochemically examined in the dura and the brain near the occluded sinus in five model III animals after 1 week. RESULTS: In Experiment 1, Western blot analysis showed barely detectable bands with molecular weights of 45 kD, corresponding to VEGF, in the sham group, but the highest level of VEGF was induced in model III, followed by models I and II (model III>model I>model II). In Experiment 2, the expression of VEGF peaked 1 week after induction of venous hypertension in model III, decreasing in a linear fashion over 2 and 3 weeks (week 1>weeks 2 and 3). The expression of immunoreactive VEGF was restricted in the connective tissue and the endothelial layer of the dura matter, cerebral cortical tissue and neurons of the basal ganglia. CONCLUSION: Our results strongly suggest a possible contribution of an angiogenic factor to the growth of DAVF. Venous ischemia by venous hypertension might be a mechanism for inducing up-regulation of angiogenic factor expression.

Long-term follow-up outcome after surgical treatment for lesional temporal lobe epilepsy.

OBJECTIVES: Lateral or neocortical temporal lobe epilepsy (TLE) is regarded as a distinct clinical entity from medial TLE. Surgery for neocortical TLE can be considered as a viable treatment option; however, there is very limited information available on aspects such as long-term seizure outcome. Thus, we retrospectively reviewed our ten surgical cases of lateral TLE with a minimum 2 year follow-up outcome. METHODS: The series comprised four male and six female patients, ranging in age from 3 to 46 years (mean: 28.8 years). Seven cases were found to be drug-resistant. Invasive pre-surgical evaluation for intractable epilepsy was performed in six patients. RESULTS: The pathologic lesions were removed completely in nine cases. Lesionectomy alone was performed in four cases and total epileptogenic focus resection was confirmed in four cases. The epileptogenic regions within eloquent areas were preserved in two cases. The medial temporal structure was intact and preserved in all cases. Neuropathologic diagnoses were cavernoma in three cases, astrocytoma (grade 2) in two cases, arteriovenous malformation in two cases, gliosis in two cases and ganglioglioma in one case. The mean duration of follow-up was 6.5 years (range: 2.2-9.3 years). Outcomes categorized according to Engel classes were class I (E1) in six cases and class II (E2) in four cases. Patients who had post-operative seizures may also achieve long-term seizure decrease or freedom in three cases: case 5 (E4-E2), case 6 (E4-E2) and case 7 (E3-E1). Thus, worthwhile improvement was achieved in 100% of the cases in this series, with 60% of patients being seizure-free during the followed-up period. CONCLUSIONS: The controlled long-term follow-up results suggested that surgery for lesional TLE can be considered as a viable treatment option to control seizure with a low morbidity rate and good outcomes.

[Three cases of de novo aneurysms].

We report 3 cases of de novo aneurysms that developed long after neck clipping of the initial aneurysms (range, 7 to 20 years, mean 12 years). Case 1 was a 58-year-old female who had undergone clipping of a ruptured aneurysm 17 years previously. Ten years later, she suffered another subarachnoid hemorrhage due to rupture of a new aneurysm, for which neck clipping was performed. Another seven years later, she had a third subarachnoid hemorrhage, and angiography revealed a new aneurysm, for which neck clipping was performed. Case 2 and 3 were both 68-year-old females who had suffered subarachnoid hemorrhage with two aneurysms and had undergone neck clipping for them respectively, 20 years and 12 years previously. Each patient was admitted to our hospital with complaints of headache, diplopia, vertigo, etc., and newly formed aneurysms were detected by magnetic resonance angiography. Conventional angiography revealed three and one new aneurysms, respectively. Since case 1 was a special case of multiple aneurysms in which lesions appeared in series rather than in parallel, all three patients harbored multiple aneurysms. It is recommended that patients with multiple aneurysms, especially those after a long period postoperatively, undergo periodic examination on an outpatient basis to detect formation of de novo aneurysms by magnetic resonance angiography or 3D-CT angiography.

Molecular pathogenesis of pediatric astrocytic tumors.

Astrocytomas are the most common pediatric brain tumors, accounting for 7%-8% of all childhood cancers. Relatively few studies have been performed on their molecular properties; therefore, classification of pediatric astrocytic tumors into genetic subtypes similar to that of adult tumors remains to be defined. Here, we report an extensive characterization of 44 pediatric astrocytomas--16 diffuse astrocytomas (WHO grade II), 10 anaplastic astrocytomas (WHO grade III), and 18 glioblastomas (WHO grade IV)--in terms of genetic alterations frequently observed in adult astrocytomas. Some form of p53 mutation was found in three diffuse astrocytomas, in three anaplastic astrocytomas, and in six glioblastomas examined; PTEN mutations were detected only in two glioblastomas. EGFR amplification was detected in only one anaplastic astrocytoma and two glioblastomas, but no amplification was observed for the PDGFR-alpha gene. Loss of heterozygosity (LOH) on 1p/19q and 10p/10q was less common in pediatric astrocytic tumors than in those seen in adults, but the frequency of LOH on 22q was comparable, occurring in 44% of diffuse astrocytomas, 40% of anaplastic astrocytomas, and 61% of glioblastomas. Interestingly, a higher frequency of p53 mutations and LOH on 19q and 22q in tumors from children six or more years of age at diagnosis was found, compared with those from younger children. Our results suggest some differences in children compared to adults in the genetic pathways leading to the formation of de novo astrocytic tumors. In addition, this study suggests potentially distinct developmental pathways in younger versus older children.

Displacement of the facial nerve course by vestibular schwannoma: preoperative visualization using diffusion tensor tractography.

PURPOSE: To preoperatively visualize the course of the facial nerve, which is displaced by vestibular schwannoma, using diffusion tensor (DT) tractography, and to evaluate the agreement with surgical findings. MATERIALS AND METHODS: The subjects were eight patients with vestibular schwannoma who had undergone removal surgery. DT MR images were obtained and tracts that were considered to represent the facial nerve were constructed. We assessed the success rate for tract construction and evaluated the agreement between tractography findings and surgery. RESULTS: We obtained a tract that connected the internal auditory meatus and brainstem, and was considered to represent the facial nerve in seven of eight cases. The course of the constructed tract agreed with surgical findings in five of these seven cases. One exception was a case in which the tumor was too large to enable intraoperative observation of the facial nerve; however, the facial nerve appeared to be displaced anteriorly at intracapsular resection, in agreement with tractography. In the other case, the schwannoma was mostly cystic. CONCLUSION: Tractographs constructed using MR tensor images enabled us to identify tracts considered to represent facial nerves. We consider DT tractography to be a useful tool for preoperatively predicting facial nerve displacement in vestibular schwannoma.

Long-term outcome of unruptured giant cerebral aneurysms.

The long-term outcome of 39 patients with unruptured giant aneurysm (>2.5 cm) treated during the last 12 years was retrospectively reviewed. The 7 male and 32 female patients, aged 32 to 81 years, presented with symptoms related to compression of the surrounding structures by the aneurysm in 28 cases, cerebral infarction in one, and asymptomatic in 10. The locations were the internal carotid artery (ICA) in 27 cases, middle cerebral artery in three, anterior cerebral artery in one, and basilar artery in eight. Therapeutic modalities were direct clipping in 11 patients, ICA occlusion combined with extracranial-intracranial bypass in 15, and conservative treatment in 13. The follow-up period ranged from 16 to 128 months (mean 54.0 months). The mortality was 9% (1/11), 0% (0/15), and 31% (4/13), and morbidity was 18% (2/11), 20% (3/15), and 8% (1/13), respectively. Surgery reduced the mortality (from 31% to 4%) but increased the morbidity (from 8% to 19%) as compared with conservatively treated patients (p < 0.05). Giant intracranial aneurysm has a poor prognosis if left untreated, but these lesions are difficult to treat with the present management options.

Effect of carotid artery stenting on ocular circulation and chronic ocular ischemic syndrome.

BACKGROUND: The authors evaluated the effect of carotid artery stenting (CAS) on ocular circulation and chronic ocular ischemic syndrome. METHODS: We examined 38 patients with carotid artery stenosis (>80%) at its origin treated with CAS. Ocular circulation and symptoms were examined before, within 24 h, and 1 week, 1 month, and 3 months after CAS based on ophthalmic artery color Doppler flow imaging and ophthalmological examinations. RESULTS: Ocular circulation: Before CAS, 13 patients showed reversed ophthalmic artery flow, and 25 antegrade flow. Average peak systolic flow velocity was -0.038 m/s. Within 24 h after CAS, all patients showed antegrade ophthalmic artery flow; reversed flow before CAS was thus resolved. Average peak systolic flow velocity rose significantly to 0.36 m/s (p < 0.05). One week, 1 month and 3 months after CAS, there were no significant changes compared to the findings at 1 week after CAS. Ocular symptoms: Before CAS, 8 patients showed chronic ocular ischemic syndrome. During the follow-up period (mean: 2.8 years), the visual acuity improved in 7 cases. Average retinal artery pressure and arm-to-retina circulation time improved significantly to the normal level (p < 0.05). The other 30 patients complained of recurrent and worsened visual symptoms during the follow-up period. CONCLUSION: CAS was effective in improving ocular circulation, and also improved the chronic ocular ischemic syndrome caused by the severe carotid artery stenosis.

Defective expression of HRK is associated with promoter methylation in primary central nervous system lymphomas.

OBJECTIVES: Recently, it has been reported that expression of the HRK gene was significantly reduced by hypermethylation in astrocytic tumors. Our aim is to verify the alterations in the HRK gene in primary central nervous system lymphomas (PCNSLs). METHODS: We analyzed the hypermethylation status and expression of the gene and 12q13.1 loss of heterozygosity in 31 PCNSLs. RESULTS: A total of 13 PCNSLs (31%) demonstrated hypermethylation in either the promoter or exon 1; loss of HRK expression was immunohistochemically observed in 9 tumors and was significantly associated with promoter methylation. In addition, higher apoptotic counts were associated with HRK positivity. PCNSLs with HRK methylation also showed methylation of multiple genes, such as p14ARF, p16INK4a, RB1, p27Kip1 and O6-MGMT. Patients with tumors demonstrating concurrent methylation of more than half of their genes demonstrated significantly poorer survival and earlier recurrence. Hypermethylation of the HRK promoter alone was not associated with overall outcome, but relapse-free survival was significantly shorter. CONCLUSIONS: Our findings suggest that transcriptional repression of HRK is caused by promoter hypermethylation in PCNSL, and that the loss of HRK associated with the methylation profile of other genes is a potential step in the modulation of cellular death by apoptosis during PCNSL tumorigenesis.