Advances in Brain Metastasis Models

To obtain achievements in addressing the clinical challenges of brain metastasis, we need a clear understanding of its biological mechanisms. Brain metastasis research is challenged by many practical scientific barriers. Depending on the purpose of the study, experimental brain metastasis models in vivo can be used. It is now possible to re-create the architecture and physiology of human organs. Human organoids provide unique opportunities for the study of human disease and complement animal models. The translation of experimental findings to clinical application has several barriers in the development of treatment for brain metastasis. A variety of models have provided significant contributions to the knowledge of brain metastasis pathology and remain pivotal tools for examining novel therapeutic strategies.

Assessment of Bacterial Communities Within the Biofilm of Bladder Calculi in the Neurogenic Bladder Rat Model Following Spinal Cord Injury / 대한배뇨장애요실금학회지

Purpose@#To develop a rat model of bladder calculi in the neurogenic bladder following spinal cord injury (SCI) and assess bacterial communities within the biofilm of bladder calculi using denaturing gradient gel electrophoresis (DGGE). @*Methods@#The silk tied to a small segment of the Teflon IV catheter was implanted through the urethra into the bladder of rats with SCI induced by T9 laminectomy. After 6 months, the rats were sacrificed and their bladder calculi were collected by opening the bladders through the low-midline incision. Genomic DNA was extracted from the biofilm of bladder calculi followed by DGGE to obtain bacterial DNA. The DNA sequences were compared and analyzed using BLAST (Basic Local Alignment Search Tool) to identify bacteria. @*Results@#After placing silk nidus in the bladder for 6 months, all 6 rats developed bladder calculi. According to DGGE analysis, Pseudomonas aeruginosa was the most dominant strain, while Clostridium sp. and Lactobacillus sp. were relatively dominant strains within the biofilm of bladder calculi in the rats with SCI. @*Conclusions@#DGGE analysis showed various microorganisms in the biofilm of calculi arising from a neurogenic bladder rat model. This research design can be the basis for clinical studies and may be applied to calculi in patients with neurogenic bladder following SCI.

Modified Orbitozygomatic Approach for Resecting a Parasellar Tumor in a Single Institution

Background@#Modified orbitozygomatic craniotomy is characterized by simplicity and wide exposure. The purpose of the present study was to describe a modified orbitozygomatic approach without resecting the zygomatic arch for large parasellar tumor surgeries. @*Methods@#Between April 2016 and December 2019, seven patients with parasellar tumor underwent surgiest with a modified orbitozygomatic approach. Surgical procedures, clinical outcomes, and complications were analyzed. @*Results@#This study included 3 meningiomas, 2 pituitary adenomas, 1 chondrosarcoma, and 1 schwannoma. Modified orbitozygomatic craniotomy provides a wider surgical freedom in the opticocarotid and prechiasmatic cistern than frontotemporal craniotomy without orbitotomy, Total, subtotal, and partial resections were achieved for 3, 2, and 2 patients, respectively. Reasons for partial resections were tight adhesion to the carotid artery and encasing of the carotid artery. Permanent morbidities developed in one patient with 3rd nerve palsy and one patient with hemiparesis. @*Conclusion@#Modified orbitozygomatic approach can provide the shortest access to the interpeduncular cistern with a minimum brain retraction. Surgeons who experience surgical challenge during the conventional approach for parasellar tumor resection are recommended to learn the modified orbitozygomatic approach.

Epidemiological Study of Malignant Gliomas in Korea Using Nationwide Dataset from 2007 to 2017

Background@#The purpose of the study was to investigate the incidence, prevalence, and survival of malignant gliomas (MGs) using population-based Korean National Health Insurance Database (NHID) data. @*Methods@#Using the Korean NHID, we identified patients with MG as C71 codes in KCD 5–7 according to ICD-10 from January 1, 2007 to December 31, 2017. Epidemiological characteristics of MG, including annual incidence, prevalence, mortality rates, and survival rates, were collected and analyzed according to socioeconomic state (SES) and treatments received. @*Results@#We identified 45,066 newly diagnosed-MG patients from 2007 to 2017, for an age-adjusted incidence of 7.47 per 100,000 people. The mean age at diagnosis was 54 years. The male to female ratio was 1.11. Mortality and survival probability were analyzed among total subjects and in subgroups. The mortality rates were lower in female than that of male patients (hazard ratio, 0.69; 95% confidence interval, 0.67–0.71), and in younger age population and in higher income group. Patients operated had a slightly higher survival rate. The 1-, 3-, 5-, and 10-year survival rates were estimated at 63.4%, 46.2%, 39.4%, and 34.8%, respectively. This is the first population-based study to determine the incidence and prevalence of MG according to epidemiological characteristics in Korea using NHID. @*Conclusion@#Our study found that female sex and high SES were factors that significantly lowered the mortality rate in MG, and younger groups and operated patients showed significantly higher survival rates.

Epidemiological Study of Malignant Gliomas in Korea Using Nationwide Dataset from 2007 to 2017

Background@#The purpose of the study was to investigate the incidence, prevalence, and survival of malignant gliomas (MGs) using population-based Korean National Health Insurance Database (NHID) data. @*Methods@#Using the Korean NHID, we identified patients with MG as C71 codes in KCD 5–7 according to ICD-10 from January 1, 2007 to December 31, 2017. Epidemiological characteristics of MG, including annual incidence, prevalence, mortality rates, and survival rates, were collected and analyzed according to socioeconomic state (SES) and treatments received. @*Results@#We identified 45,066 newly diagnosed-MG patients from 2007 to 2017, for an age-adjusted incidence of 7.47 per 100,000 people. The mean age at diagnosis was 54 years. The male to female ratio was 1.11. Mortality and survival probability were analyzed among total subjects and in subgroups. The mortality rates were lower in female than that of male patients (hazard ratio, 0.69; 95% confidence interval, 0.67–0.71), and in younger age population and in higher income group. Patients operated had a slightly higher survival rate. The 1-, 3-, 5-, and 10-year survival rates were estimated at 63.4%, 46.2%, 39.4%, and 34.8%, respectively. This is the first population-based study to determine the incidence and prevalence of MG according to epidemiological characteristics in Korea using NHID. @*Conclusion@#Our study found that female sex and high SES were factors that significantly lowered the mortality rate in MG, and younger groups and operated patients showed significantly higher survival rates.

Effect of Pioglitazone on Perihematomal Edema in Intracerebral Hemorrhage Mouse Model by Regulating NLRP3 Expression and Energy Metabolism

Objective@#: Cerebral edema is the predominant mechanism of secondary inflammation after intracerebral hemorrhage (ICH). Pioglitazone, peroxisome proliferator-activated receptor gamma agonist has been shown to play a role in regulation of central nervous system inflammation. Here, we examined the pharmacological effects of pioglitazone in an ICH mouse model and investigated its regulation on NLRP3 inflammasome and glucose metabolism. @*Methods@#: The ICH model was established in C57 BL/6 mice by the stereotactical inoculation of blood (30 µL) into the right frontal lobe. The treatment group was administered i.p. pioglitazone (20 mg/kg) for 1, 3, and 6 days. The control group was administered i.p. phosphate-buffered saline for 1, 3, and 6 days. We investigated brain water contents, NLRP3 expression, and changes in the metabolites in the ICH model using liquid chromatography-tandem mass spectrometry. @*Results@#: On day 3, brain edema in the mice treated with pioglitazone was decreased more than that in the control group. Expression levels of NLRP3 in the ICH model treated with pioglitazone were decreased more than those of the control mice on days 3 and 7. The pioglitazone group showed higher levels of glycolytic metabolites than those in the ICH mice. Lactate production was increased in the ICH mice treated with pioglitazone. @*Conclusion@#: Our results demonstrated less brain swelling following ICH in mice treated with pioglitazone. Pioglitazone decreased NLRP3-related brain edema and increased anaerobic glycolysis, resulting in the production of lactate in the ICH mice model. NLRP3 might be a therapeutic target for ICH recovery.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01

BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

OBJECTIVE: Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum.METHODS: Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed.RESULTS: Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category.CONCLUSION: Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

OBJECTIVE: Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. METHODS: Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. RESULTS: Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. CONCLUSION: Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade III Cerebral Gliomas in Adults: Version 2019.01

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.

High-Dose Metformin Plus Temozolomide Shows Increased Anti-tumor Effects in Glioblastoma In Vitro and In vivo Compared with Monotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in Vitro and in vivo. MATERIALS AND METHODS: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5×105 U87 cells and treatedwith metformin, TMZ, and the combination for 4weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway. RESULTS: The combination of TMZ and metformin showed higher cytotoxicity than single agents in U87, U251, and A172 cell lines. A combination of high-dose metformin and TMZ showed the highest apoptotic activity. The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression. The median survival of each group was 43.6, 55.2, 53.2, 65.2, and 71.3 days for control, metformin treatment (2 mg/25 g/day or 10 mg/25 g/day), TMZ treatment (15 mg/kg/day), combination treatment with low-dose metformin and TMZ, and combination treatment with high-dose metformin and TMZ, respectively. Expression of fatty acid synthase (FASN) was significantly decreased in tumor specimens treated with metformin and TMZ. CONCLUSION: The combination of metformin and TMZ was superior to monotherapy using metformin or TMZ in terms of cell viability in Vitro and survival in vivo. The combination of high-dose metformin and TMZ inhibited FASN expression in an orthotopic model. Inhibition of FASN might be a potential therapeutic target of GBM.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation

BACKGROUND: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. METHODS: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m²) on day 1 and procarbazine (60 mg/m²) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2–6). RESULTS: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5–73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7–12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. CONCLUSION: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Risk factors of bilateral chronic subdural hematoma compared to unilateral chronic subdural hematoma

Chronic subdural hematoma (CSDH) is a common and relatively benign disease. The aim of this study was to investigate the differences between unilateral and bilateral chronic subdural hematoma in terms of predisposing factors. A retrospective analysis was made of all patients who underwent operation for CSDH at our institution between January 2010 and December 2015. Patients were divided into two groups (unilateral versus bilateral CSDH) and univariate and multivariate analysis was performed to assess demographic data, symptoms, cause of SDH, medical history, laboratory data, and initial radiologic findings. A total of 246 patients were enrolled. There were 63 (25.6%) patients with bilateral CSDH. There were no significant differences concerning sex and initial symptoms between the two groups. Only malignancy history was a significant risk factor for bilateral CSDH in both univariate and multivariate analysis (p = 0.002 and 0.001, respectively). In multivariate analysis, diabetes mellitus (OR 2.03, 95% CI: 1.05 - 3.92, p = 0.0350), malignancy (OR 5.09, 95% CI: 1.93 - 13.40, p= 0.0010), membrane septation (OR 0.50, 95% CI: 0.25 - 0.96, p = 0.0392), and brain atrophy (mild: OR 2.34, 95% CI: 1.16 - 4.71, p = 0.0164, moderate: OR 3.85, 95% CI: 1.32-11.18, p = 0.0131) were significantly associated with bilateral CSDH. The present study suggests that diabetes mellitus, malignancy, membrane septation and mild to moderate brain atrophy is independent predisposing factors of bilateral CSDH.

Similarity Analysis of Korean Medical Literature and Its Association with Efforts to Improve Research and Publication Ethics

In the present study, the frequency of research misconduct in Korean medical papers was analyzed using the similarity check software iThenticate®. All Korean papers written in English that were published in 2009 and 2014 in KoreaMed Synapse were identified. In total, 23,848 papers were extracted. 4,050 original articles of them were randomly selected for similarity analysis. The average Similarity Index of the 4,050 papers decreased over time, particularly in 2013: in 2009 and 2014, it was 10.15% and 5.62%, respectively. And 357 (8.8%) had a Similarity Index of ≥ 20%. Authors considered a Similarity Index of ≥ 20% as suspected research misconduct. It was found that iThenticate® cannot functionally process citations without double quotation marks. Papers with a Similarity Index of ≥ 20% were thus individually checked for detecting such text-matching errors to accurately identify papers with suspected research misconduct. After correcting text-matching errors, 142 (3.5% of the 4,050 papers) were suspected of research misconduct. The annual frequency of these papers decreased over time, particularly in 2013: in 2009 and 2014, it was 5.2% and 1.7%, respectively. The decrease was associated with the introduction of CrossCheck by KoreaMed and the frequent use of similarity check software. The majority (81%) had Similarity Indices between 20% and 40%. The fact suggested that low Similarity index does not necessarily mean low possibility of research misconduct. It should be noted that, although iThenticate® provides a fundamental basis for detecting research misconduct, the final judgment should be made by experts.

Predictive Factors for Recurrence after Burr-Hole Craniostomy of Chronic Subdural Hematoma

OBJECTIVE: Chronic subdural hematoma is a common and relatively benign disease. However, recurrence is common after surgical treatment, and the recurrence rate varies from 5% to 33%. The aim of this study was to investigate the predictive factors for recurrence of chronic subdural hematoma. METHODS: We analyzed data from 248 patients with chronic subdural hematoma who were treated by burr-hole craniostomy with a closed drainage system for hematoma evacuation in this five-year retrospective study. RESULTS: Thirty-one (12.6%) patients underwent re-operation for recurrence of chronic subdural hematoma. Univariate analysis revealed that anticoagulation (p=0.0279), headache (p=0.0323), and preoperative midline shifting (p=0.0321) showed significant differences with respect to recurrent chronic subdural hematoma. We performed a multivariate logistic regression analysis and found that diabetes mellitus (odds ratio [OR], 2.618; 95% confidence interval [CI], 1.0899–6.2898; p=0.0314), anticoagulation (OR, 6.739; 95% CI, 1.1287–40.2369; p=0.0364), headache (OR, 2.951; 95% CI, 1.1464–7.5964; p=0.0249), and preoperative midline shifting (OR, 1.0838; 95% CI, 1.0040–1.1699; p=0.0391) were independent predictive factors for recurrence of chronic subdural hematoma. CONCLUSION: We showed that diabetes mellitus, anticoagulation, headache, and preoperative midline shifting were independent predictors of recurrence of chronic subdural hematoma.

Perfusion-Weighted MRI Parameters for Prediction of Early Progressive Infarction in Middle Cerebral Artery Occlusion

OBJECTIVE: Early progressive infarction (EPI) is frequently observed and related to poor functional outcome in patients with middle cerebral artery (MCA) infarction caused by MCA occlusion. We evaluated the perfusion parameters of magnetic resonance imaging (MRI) as a predictor of EPI. METHODS: We retrospectively analyzed patients with acute MCA territory infarction caused by MCA occlusion. EPI was defined as a National Institutes of Health Stroke Scale increment ≥2 points during 24 hours despite receiving standard treatment. Regional parameter ratios, such as cerebral blood flow and volume (rCBV) ratio (ipsilateral value/contralateral value) on perfusion MRI were analyzed to investigate the association with EPI. RESULTS: Sixty-four patients were enrolled in total. EPI was present in 18 (28%) subjects and all EPI occurred within 3 days after hospitalization. Diabetes mellitus, rCBV ratio and regional time to peak (rTTP) ratio showed statically significant differences in both groups. Multi-variate analysis indicated that history of diabetes mellitus [odds ratio (OR), 6.13; 95% confidence interval (CI), 1.55-24.24] and a low rCBV ratio (rCBV, <0.85; OR, 6.57; 95% CI, 1.4-30.27) was significantly correlated with EPI. CONCLUSION: The incidence of EPI is considerable in patients with acute MCA territory infarction caused by MCA occlusion. We suggest that rCBV ratio is a useful neuro-imaging parameter to predict EPI.

Evaluation and Treatment of the Acute Cerebral Infarction with Convexal Subarachnoid Hemorrhage

Non-traumatic convexal subarachnoid hemorrhage (CSAH) is a comparatively infrequent with various vascular and nonvascular causes, it rarely occurs concomitant to acute ischemic stroke. We report a case of a 59-year-old woman, visited emergency room with right side subjective weakness spontaneously. Magnetic resonance diffusion-weighted images revealed an acute infarction of anterior cerebral arterial territory. Computed tomographic angiography showed a left frontal CSAH without any vascular lesions. And other laboratory studies were non-specific. We treated with dual antiplatelet drugs (cilostazole [Otsuka Pharmaceutical Co., Ltd. tokyo, Japan] and Aspirin [Bayer Pharma AG., Leverkusen, Germany]). She has done well for a follow-up period. (5 months) This case demonstrates the CSAH with acute infarction is rare but need to work up to identify the etiology and antiplatelet dugs are taken into account for treatments.

Clinical and Radiological Comparison between Ipsilateral and Contralateral Side Canal Decompression Using an Unilateral Laminotomy Approach

OBJECTIVE: To compare the clinical and radiological outcome of both sides using the unilateral approach. METHODS: Unilateral laminotomy was performed to achieve bilateral decompression. Thirty-nine patients who underwent this procedure were analyzed prospectively using the Oswestry Disability Index (ODI), the visual analog scale (VAS) pain score to evaluate symptoms in both legs, and the radiological morphometric index to calculate the anteriorposterior diameter and midcanal width. The incidence of complications from this approach was then evaluated. RESULTS: The mean follow-up time was 12.2 months. The mean ODI was 48.4 preoperatively and 14.2 postoperatively. The mean dural sac widening of the ipsilateral side (187.0%) was significantly larger (p<0.01) than that of the the contralateral side (145.6%). The VAS improvement ratio ([preoperative VAS score-postoperative VAS score]/[preoperative VAS score]×100) for the pain in each leg was 75.4%(ipsilateral side) and 73.7%(contralateral side). While the VAS improvement ratio for pain in each side was significantly reduced, the difference in the VAS ratio between sides was statistically insignificant (p=0.64). There were 2 cases (5.1%) of dural tearing during the procedure, 1 case (2.6%) of transient paresthesia of nerve roots, and 2 cases (5.1%) of transient paresthesia of the contralateral nerve root. The transient paresthesias of nerve roots never lasted more than 2 weeks. CONCLUSION: This technique allows for significant decompression of the contralateral canal and excellent clinical outcomes without troublesome complications. Although ipsilateral the dural sac widening was significantly larger than contralateral side, the difference in the clinical outcome between sides was statistically insignificant.

Continuous Low-Dose Temozolomide Chemotherapy and Microvessel Density in Recurrent Glioblastoma

OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. METHODS: Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at 50 mg/m2/day until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). RESULTS: The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was 22.7+/-24.1/mm2 (mean+/-standard deviation), and this was lower than that of the initial tumor (61.4+/-32.7/mm2) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. CONCLUSION: The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.