Repurposing Penfluridol in Combination with Temozolomide for the Treatment of Glioblastoma.

Despite the presence of aggressive treatment strategies, glioblastoma remains intractable, warranting a novel therapeutic modality. An oral antipsychotic agent, penflurido (PFD), used for schizophrenia treatment, has shown an antitumor effect on various types of cancer cells. As glioma sphere-forming cells (GSCs) are known to mediate drug resistance in glioblastoma, and considering that antipsychotics can easily penetrate the blood-brain barrier, we investigated the antitumor effect of PFD on patient-derived GSCs. Using five GSCs, we found that PFD exerts an antiproliferative effect in a time- and dose-dependent manner. At IC50, spheroid size and second-generation spheroid formation were significantly suppressed. Stemness factors, SOX2 and OCT4, were decreased. PFD treatment reduced cancer cell migration and invasion by reducing the Integrin α6 and uPAR levels and suppression of the expression of epithelial-to-mesenchymal transition (EMT) factors, vimentin and Zeb1. GLI1 was found to be involved in PFD-induced EMT inhibition. Furthermore, combinatorial treatment of PFD with temozolomide (TMZ) significantly suppressed tumor growth and prolonged survival in vivo. Immunostaining revealed decreased expression of GLI1, SOX2, and vimentin in the PFD treatment group but not in the TMZ-only treatment group. Therefore, PFD can be effectively repurposed for the treatment of glioblastoma by combining it with TMZ.

Extraocular Pressure Measurements to Avoid Orbital Compartment Syndrome in Aneurysm Surgery.

BACKGROUND: Orbital compartment syndrome (OCS) is a rare but devastating complication following pterional craniotomy. Although the causes of OCS are unclear, external compression of the orbit by a myocutaneous flap is commonly mentioned as a major factor. We evaluated the ocular influence of external compression using an extraocular pressure monitor. METHODS: We measured extraocular pressure in 86 patients who underwent surgery for cerebral aneurysm via a pterional approach. Clinical information and radiologic parameters, including the area of the medial rectus muscle (MRM) and the craniotomy height from the bottom of the anterior skull base, were collected. As a control group, 117 patients who underwent surgery without pressure monitoring were also evaluated. RESULTS: Extraocular pressure reached a maximum during craniotomy (mean, 22.0 mm Hg; range, 18.4-51.0 mm Hg) and decreased after myocutaneous flap adjustment (mean, 7.9 mm Hg; range, 5.4-17.5 mm Hg). Pressure before myocutaneous flap manipulation differed between patients with anterior communicating artery (Acomm) aneurysms and other patients (mean, 16.5 mm Hg vs. 9.4 mm Hg; P = 0.003). Among Acomm aneurysm cases, the monitored group showed a significantly lower MRM swelling ratio (postoperative MRM area/preoperative MRM area) compared with the control group (1.03 ± 0.10 vs. 1.17 ± 0.15; P = 0.036). CONCLUSIONS: Myocutaneous flaps can produce unnoticed overpressure on the orbit, resulting in OCS-related blindness during aneurysm clipping surgery, especially in cases involving mandatory lower craniotomy. The continuous extraocular compressive pressure monitoring technique is a simple and effective approach to prevent such a serious complication.

Factors Associated with Clinical Outcomes in Patients with Primary Intraventricular Hemorrhage.

BACKGROUND Primary intraventricular hemorrhage (PIVH) is an uncommon type of intracerebral hemorrhage. Owing to its rarity, the clinical and radiological factors affecting outcomes in patients with PIVH have not been widely studied. MATERIAL AND METHODS We retrospectively reviewed 112 patients (mean age 53 years) treated for PIVH at our institution from January 2004 to December 2014. Clinical and radiological parameters were analyzed 3 months after initial presentation to identify factors associated with clinical outcomes, as assessed by the Glasgow Outcome Scale (favorable ≥4, unfavorable <4). RESULTS Of the 99 patients who underwent angiography, causative vascular abnormalities were found in 46%, and included Moyamoya disease, arteriovenous malformation, and cerebral aneurysm. At 3 months after initial presentation, 64% and 36% of patients were in the favorable and unfavorable outcome groups, respectively. The mortality rate was 19%. However, most survivors had no or mild deficits. Age, initial Glasgow Coma Scale (GCS) score, simplified acute physiology score (SAPS II), modified Graeb score, and various radiological parameters reflecting ventricular dilatation were significantly different between the groups. Specifically, a GCS score of less than 13 (p=0.015), a SAPS II score of less than 33 (p=0.039), and a dilated fourth ventricle (p=0.043) were demonstrated to be independent predictors of an unfavorable clinical outcome. CONCLUSIONS In this study we reveal independent predictors of poor outcome in primary intraventricular hemorrhage patients, and show that nearly half of the patients in our study had predisposing vascular abnormalities. Routine angiography is recommended in the evaluation of PIVH to identify potentially treatable etiologies, which may enhance long-term prognosis.

Phase III randomized trial of autologous cytokine-induced killer cell immunotherapy for newly diagnosed glioblastoma in Korea.

PURPOSE: Adoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer (CIK) cells before their reinfusion into the host. We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas. EXPERIMENTAL DESIGN: In this multi-center, open-label, phase 3 study, we randomly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy group) or standard TMZ chemoradiotherapy alone (control group). The efficacy endpoints were analyzed in the intention-to-treat set and in the per protocol set. RESULTS: Between December 2008 and October 2012, a total of 180 patients were randomly assigned to the CIK immunotherapy (n = 91) or control group (n = 89). In the intention-to-treat analysis set, median PFS was 8.1 months (95% confidence interval (CI), 5.8 to 8.5 months) in the CIK immunotherapy group, as compared to 5.4 months (95% CI, 3.3 to 7.9 months) in the control group (one-sided log-rank, p = 0.0401). Overall survival did not differ significantly between two groups. Grade 3 or higher adverse events, health-related quality of life and performance status between two groups did not show a significant difference. CONCLUSIONS: The addition of CIK cells immunotherapy to standard chemoradiotherapy with TMZ improved PFS. However, the CIK immunotherapy group did not show evidence of a beneficial effect on overall survival.

World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia.

When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment.

Role of vincristine in the inhibition of angiogenesis in glioblastoma.

OBJECTIVE: Vincristine, a microtubule-destabilizing drug, was found to exhibit anti-angiogenic effects and anti-tumoral activity. However, the precise mechanism by which vincristine inhibits angiogenesis in glioblastomas is not well understood. Our aim was to investigate whether vincristine affects vascular endothelial growth factor (VEGF) expression in glioblastoma cells and determine whether it is mediated by the downregulation of hypoxia-inducible factor-1α (HIF-1α). METHODS: We investigated the expression of HIF-1α in glioblastoma tissues resected from patients and in human glioblastoma cell lines using immunohistochemistry, Western blot analysis, and immunocytochemistry. In addition to an MTT assay assessing the effect of vincristine on cell proliferation and viability, the effects of vincristine on VEGF mRNA expression and HIF-1α protein were examined using real-time RT-PCR and Western blot analysis under 1% O2 (hypoxia). RESULTS: HIF-1α was expressed in the majority of glioblastoma tissues and was detected mainly in the nucleus. Strong immunoreactivity for HIF- 1 α was found often in the hypercellular zones. Under hypoxic conditions, HIF-1α protein levels in the glioblastoma cell lines increased, primarily localizing into the nucleus similar to glioblastoma tissues. Exposure of glioblastoma cells to vincristine resulted in enrichment of the G2-M fraction of the cell cycle, which suggests that vincristine-mediated growth inhibition of glioblastoma is correlated with mitotic inhibition. Using doses lower than those found to reduce the viability and proliferation of cells by 50% (IC50), vincristine decreased both the expression of VEGF mRNA and the level of HIF-1α protein in hypoxic glioblastoma cells. In addition, following exposure to vincristine, the expression of VEGF mRNA was correlated with HIF-1α protein levels. CONCLUSIONS: Our results suggest that the mechanism by which vincristine elicits an anti-angiogenic effect in glioblastomas under hypoxic conditions might be mediated, in part, by HIF-1α inhibition.

Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial.

CONTEXT: Spinal cord injury (SCI) can cause irreversible damage to neural tissues. However, there is currently no effective treatment for SCI. The therapeutic potential of adipose-derived mesenchymal stem cells (ADMSCs) has been emerged. OBJECTIVE: We evaluated the effects and safety of the intrathecal transplantation of autologous ADMSCs in patients with SCI. Participants/Interventions: Fourteen patients with SCI were enrolled (12 for ASIA A, 1 for B, and 1 for D; duration of impairments 3-28 months). Six patients were injured at cervical, 1 at cervico-thoracic, 6 at thoracic, and 1 at lumbar level. Autologous ADMSCs were isolated from lipoaspirates of patients' subcutaneous fat tissue and 9 × 107 ADMSCs per patient were administered intrathecally through lumbar tapping. MRI, hematological parameters, electrophysiology studies, and ASIA motor/sensory scores were assessed before and after transplantation. RESULTS: ASIA motor scores were improved in 5 patients at 8 months follow-up (1-2 grades at some myotomes). Voluntary anal contraction improvement was seen in 2 patients. ASIA sensory score recovery was seen in 10, although degeneration was seen in 1. In somatosensory evoked potential test, one patient showed median nerve improvement. There was no interval change of MRI between baseline and 8 months post-transplantation. Four adverse events were observed in three patients: urinary tract infection, headache, nausea, and vomiting. CONCLUSIONS: Over the 8 months of follow-up, intrathecal transplantation of autologous ADMSCs for SCI was free of serious adverse events, and several patients showed mild improvements in neurological function. Patient selection, dosage, and delivery method of ADMSCs should be investigated further.

Reactive oxygen species production has a critical role in hypoxia-induced Stat3 activation and angiogenesis in human glioblastoma.

Glioblastoma is the most aggressive primary brain tumor with hypoxia-associated morphologic features including pseudopalisading necrosis and endothelial hyperplasia. It has been known that hypoxia can activate signal transducer and activator of transcription 3 (Stat3) and subsequently induce angiogenesis. However, the molecular mechanism underlying hypoxia-induced Stat3 activation has not been defined. In this study, we explored the possible implication of reactive oxygen species (ROS) in hypoxia-driven Stat3 activation in human glioblastoma. We found that hypoxic stress increased ROS production as well as Stat3 activation and that ROS inhibitors (diphenyleneiodonium, rotenone and myxothiazol) and an antioxidant (N-acetyl-L-cysteine) blocked Stat3 activation under hypoxic conditions. To determine a major route of ROS production, we tested whether nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is involved in hypoxia-induced ROS production. Nox4 expression was found to be increased at both mRNA and protein levels in hypoxic glioblastoma cells. In addition, siRNA-mediated knockdown of Nox4 expression abolished hypoxia induced Stat3 activation and vascular endothelial growth factor expression, which is associated with tumor cells' ability to trigger tube formation of endothelial cells in vitro. Our findings indicate that elevated ROS production plays a crucial role for Stat3 activation and angiogenesis in hypoxic glioblastoma cells.

Quantitative analysis of tumor volume reduction after three-dimensional conformal radiation therapy for intracranial meningiomas.

To provide radiobiological information on the inherent response of intracranial meningiomas after three-dimensional conformal radiation therapy. Quantitative tumor volume measurements were generated from 120 magnetic resonance images of a total of 24 patients. Gross tumor volumes were delineated on a series of contrast-enhanced T1-weighted magnetic resonance images by using commercial software. The percentage of tumor volume reduction at each follow-up was determined and compared to the baseline tumor volume. The median follow-up time was 103.5 months (range 30-137 months). The mean pre-radiation therapy tumor volume was 30.0 cm(3) (range 1.3-167.4 cm(3)). Tumor volume reduction was observed in 96 % of the study population. The mean absolute and relative tumor volume reduction were 14.0 cm(3) (range -0.6-84.5 cm(3)) and 40.8 % (range -6.8-82.9 %), respectively. The mean relative tumor volume reduction was 15.9, 28.9, 40.5, 50.3, and 52.6 % at 2, 4, 6, 8, and 10 years after irradiation. The quantitative volumetric analysis of the pattern of tumor volume reduction in response to irradiation gives an insight into the radiobiological nature of intracranial meningiomas after conventionally fractionated radiation therapy.

Romo1 is associated with ROS production and cellular growth in human gliomas.

Romo1 is a mitochondrial protein whose elevated expression is commonly observed in various types of human cancers. However, the expression status of Romo1 and its implication in the pathogenesis of human glioblastoma (GBM) remain largely undefined. To understand the role of Romo1 in the progression of GBM, we explored its expression in a series of GBM tissues and cell lines and determined its effect on ROS production, cell proliferation, and tumor growth. Romo1 was frequently overexpressed at the mRNA level in both primary tumors and cell lines and its elevation was more commonly observed in high grade tumors versus low grade tumors. Romo1 expression was associated with ROS production and its knockdown led to a marked reduction of in vitro cellular growth and anchorage-independent growth of GBM. Consistently, Romo1 depletion induced a G2/M arrest of the cell cycle that was accompanied with accumulation of phospho-cdc2. Furthermore, a mouse xenograft assay revealed that Romo1 depletion significantly decreased tumor formation and growth. Therefore, our data demonstrate that Romo1 upregulation is a common event in human GBMs and contributes to the malignant tumor progression, suggesting that Romo1 could be a new therapeutic target for human GBM.

Expression of astrocyte elevated gene-1 (AEG-1) in human meningiomas and its roles in cell proliferation and survival.

Astrocyte elevated gene-1 (AEG-1) has recently been proposed to be involved in tumor development, invasion, and metastasis in several human cancers. However, the functional importance of AEG-1 expression in human meningioma has not been determined. We investigate the level of AEG-1 expression by quantitative reverse transcription PCR, immunohistochemistry analysis, and western blotting in various human meningioma tissues and cells. To determine the suppressive effect of AEG-1 on meningioma progression, we inhibited AEG-1 expression using small interfering RNA and examined cell proliferation, apoptosis, colony formation and tumorigenicity in a mouse xenograft model. AEG-1 expression was frequently elevated at both mRNA and protein levels in meningioma tumor tissues and in meningioma-derived cells as well. This elevation was more commonly observed in high-grade tumors than in benign ones. The knockdown of AEG-1 led to a decrease in overall cell proliferation, as well as anchorage-independent growth of malignant meningioma. In addition, apoptotic cell death occurred in AEG-1 depleted meningioma cells through p-Akt and Bcl-2 suppression. Furthermore, a mouse xenograft meningioma model showed that inhibition of AEG-1 expression significantly decreased tumor growth. Altogether, these data show that the elevation of AEG-1 contributes to the malignant progression of meningiomas, suggesting that AEG-1 could be a novel therapeutic target against human meningiomas.

Risk factors associated with poor outcomes in patients with brain abscesses.

OBJECTIVE: The purpose of this study was to describe the clinical characteristics, treatment outcomes, and prognostic factors in patients with brain abscesses treated in a single institute during a recent 10-year period. METHODS: Fifty-one patients with brain abscesses who underwent navigation-assisted abscess aspiration with antibiotic treatment were included in this study. Variable parameters were collected from the patients' medical records and radiological data. A comparison was made between patients with favorable [Glasgow Outcome Scale (GOS) ≥4] and unfavorable (GOS <4) outcomes at discharge. Additionally, we investigated the factors influencing the duration of antibiotic administration. RESULTS: The study included 41 male and 10 female patients with a mean age of 53 years. At admission, 42 patients (82%) showed either clear or mildly disturbed consciousness (GCS ≥13) and 24 patients (47%) had predisposing factors. The offending microorganisms were identified in 25 patients (49%), and Streptococcus species were the most commonly isolated bacteria (27%). The mean duration of antibiotic administration was 42 days. At discharge, 41 patients had a favorable outcome and 10 had an unfavorable outcome including 8 deaths. The decreased level of consciousness (GCS <13) on admission was likely associated with an unfavorable outcome (p=0.052), and initial hyperglycemia (≥140 mg/dL) was an independent risk factor for prolonged antibiotic therapy (p=0.032). CONCLUSION: We found that the level of consciousness at admission was associated with treatment outcomes in patients with brain abscesses. Furthermore, initial hyperglycemia was closely related to the long-term use of antibiotic agents.

Prognostic factors of clinical outcome after neuronavigation-assisted hematoma drainage in patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: The prognostic factors that contribute to outcome after navigation-assisted drainage in patients with spontaneous intracerebral hemorrhage (ICH) have not been defined. We compared the characteristics and clinical outcomes of patients with spontaneous ICHs who underwent neuronavigation-assisted hematoma drainage. METHODS: Forty-seven patients were enrolled from January 2004 to August 2013. The patients were divided into two groups according to Glasgow Outcome Scale (GOS) scores: the good- (GOS 4-5) and poor-outcome (GOS 1-3) groups. A variety of factors, characteristics, and clinical outcomes were analyzed. RESULTS: Among the 47 patients, 16 and 31 showed good and poor outcomes, respectively. The mortality rate was 4.3%. Patients' ages, horizontal and vertical diameters and volume of the hematoma on the initial brain computed tomography scan, and the initial Glasgow Coma Scale (GCS) scores were significantly different between the two groups (P<0.05). Ages less than 60 years, smaller horizontal and vertical diameters of the hematoma, less initial hematoma volume, higher initial GCS scores, and the absence of intraventricular hemorrhages were significantly associated with good outcome (P<0.05). Among these factors, initial hematoma volume was a borderline prognostic factor (odds ratio [OR], 0.951; 95% confidence interval [CI], 0.904-1.001; P=0.054), whereas initial GCS score was a significant prognostic factor (OR, 2.737; 95% CI, 1.371-5.465; P=0.004), in the multivariate analysis. CONCLUSION: Initial GCS score and hematoma volume were important prognostic factors of clinical outcome in patients with spontaneous ICHs who underwent navigation-assisted drainage. Such factors should be carefully considered before patients are treated with navigation-assisted hematoma drainage.

Risk factors of delayed surgical evacuation for initially nonoperative acute subdural hematomas following mild head injury.

BACKGROUND: Although the majority of patients with minimal acute subdural hematomas (aSDHs) can be managed conservatively, some require delayed aSDH evacuation due to hematoma enlargement. This study was designed to determine the risk factors associated with delayed hematoma enlargement leading to surgery in patients with aSDHs who did not initially require surgical intervention. METHODS: From 2002 to 2012, 98 patients were treated for nonoperative aSDHs following mild head injury (Glasgow Coma Scale scores of 13-15). The outcome variables were radiographic evidence of SDH enlargement on serially obtained computed tomography (CT) images and later surgical evacuation. Univariate and multivariate analyses were applied to both the demographic and initial radiographic features to identify risk factors for SDH progression and surgery. RESULTS: Overall, 64 patients (65 %) revealed minimal SDH or spontaneous hematoma resolution (conservative group) with conservative management at their last follow-up CT scan. The remaining 34 patients (35 %) received delayed hematoma evacuation (delayed surgery group) a median of 17 days after the head trauma. There were no significant differences between the two groups for baseline characteristics, including age, injury type, degree of brain atrophy, prior history of antithrombotic drugs, and coagulopathy. The presence of cerebral contusions and subarachnoid hemorrhages was more common in the conservative group (p = 0.003 and p = 0.003, respectively). On multivariate analysis, hematoma volume (p = 0.01, odds ratio [OR] = 1.094, 95 % confidence interval [CI] = 1.021-1.173) and degree of midline shift (p = 0.01, OR = 1.433, 95 % CI = 1.088-1.888) on the initial CT scan were independently associated with delayed hematoma evacuation. CONCLUSIONS: A critical proportion of patients with minimal aSDHs occurring after mild head injury can progress over several weeks and require hematoma evacuation. Especially patients with a large initial SDH volume and accompanying midline shift require careful monitoring of hematoma progression.

Glioma mimicking a hypertensive intracerebral hemorrhage.

Here, we report a rare case of an anaplastic astrocytoma masquerading as a hypertensive basal ganglia hemorrhage. A 69-year-old woman who had been under medical management for hypertension during the past 3 years suddenly developed right hemiparesis with dysarthria. Brain computed tomography (CT) scans with contrast and CT angiograms revealed an intracerebral hemorrhage (ICH) in the left basal ganglia, without an underlying lesion. She was treated conservatively, but underwent a ventriculoperitoneal shunt operation 3 months after the initial attack due to deteriorated mental status and chronic hydrocephalus. Three months later, her mental status deteriorated further. Magnetic resonance imaging (MRI) with gadolinium demonstrated an irregular enhanced mass in which the previous hemorrhage occurred. The final histological diagnosis which made by stereotactic biopsy was an anaplastic astrocytoma. In the present case, the diagnosis of a high grade glioma was delayed due to tumor bleeding mimicking hypertensive ICH. Thus, a careful review of neuroradiological images including MRI with a suspicion of tumor bleeding is needed even in the patients with past medical history of hypertension.

Isolated lateral sinus thrombosis presenting as cerebellar infarction in a patient with iron deficiency anemia.

As a rare cerebrovascular disease, cerebral venous thrombosis (CVT) is caused by various conditions including trauma, infection, oral contraceptive, cancer and hematologic disorders. However, iron deficiency anemia is not a common cause for CVT in adult. Posterior fossa infarction following CVT is not well demonstrated because posterior fossa has abundant collateral vessels. Here, we report a case of a 55-year-old man who was admitted with complaints of headache, nausea, and mild dizziness. The patient was diagnosed with isolated lateral sinus thrombosis presenting as cerebellar infarction. Laboratory findings revealed normocytic normochromic anemia due to iron deficiency, and the patient's symptoms were improved after iron supplementation.

Prediction of outcomes in young adults with aneurysmal subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is rare in young adults and little is known about aneurysms in this subgroup. The effect of clinical and prognostic factors on the outcome based on the Glasgow Outcome Scale (GOS) scores and the predictors of unfavorable outcomes were analyzed in young adults with aneurysmal SAH. A retrospective review of the clinical parameters, including age, sex, hypertension, smoking status, hyperlipidemia, location of the cerebral aneurysm, size of the aneurysm, multiplicity, perioperative complication such as hydrocephalus, vasospasm, and hematoma, and Hunt and Hess and Fisher grading on presentation, was conducted in 108 young adults (mean age 34.8 years) managed at our institute. The outcome was classified based on GOS grading into unfavorable (GOS scores 1-3) or favorable (GOS scores 4 or 5). The overall mortality rate was 3.7% (4/108 patients). Univariate regression analysis for the outcomes at discharge found that age at the time of presentation, male sex, size of aneurysm, multiple aneurysms, hyperlipidemia, and poor Hunt and Hess and Fischer grades were associated with unfavorable outcome. Multivariate regression analysis found independent effects of sex, multiple aneurysms, size of aneurysm, and Hunt and Hess grade on the outcome at discharge. Size of aneurysm, presence of multiple aneurysms, Hunt and Hess grade, and hypertension were the predictors of outcome at mean 2-year follow up based on multivariate exact regression analysis. The multimodal approach with aggressive medical management, early intervention, and surgical treatment might contribute to favorable long-term outcomes in patients with poor expected outcomes.

Coil embolization of a ruptured basilar tip aneurysm associated with bilateral cervical internal carotid artery occlusion: a case report and literature review.

We report here on a rare case of a ruptured basilar tip aneurysm that was successfully treated with coil embolization in the bilateral cervical internal carotid artery (ICA) occlusions with abnormal vascular networks from the posterior circulation. A 43-year old man with a familial history of moyamoya disease presented with subarachnoid hemorrhage. Digital subtraction angiography demonstrated complete occlusion of the bilateral ICAs at the proximal portion and a ruptured aneurysm at the basilar artery bifurcation. Each meningeal artery supplied the anterior cranial base, but most of both hemispheres were supplied with blood from the basilar artery and the posterior cerebral arteries through a large number of collateral vessels to the ICA bifurcation as well as the anterior cerebral and middle cerebral arteries. The perfusion computed tomography (CT) scans with acetazolamide (ACZ) injection revealed no reduction of cerebral blood flow and normal cerebrovascular reactivity to ACZ. An abdominal CT aortogram showed no other extracranial vessel abnormalities. A ruptured basilar tip aneurysm was successfully treated with coil embolization without complications. Endovascular embolization may be a good treatment option with excellent safety for a ruptured basilar tip aneurysm that accompanies proximal ICA occlusion with vulnerable collateral flow.

Comparison of cerebrospinal fluid biomarkers between idiopathic normal pressure hydrocephalus and subarachnoid hemorrhage-induced chronic hydrocephalus: a pilot study.

BACKGROUND: We examined the cerebrospinal fluid (CSF) markers of subarachnoid hemorrhage (SAH)-induced and idiopathic normal pressure hydrocephalus (INPH) to investigate the pathophysiology and mechanism of communicating hydrocephalus compared to obstructive hydrocephalus. MATERIAL/METHODS: We obtained CSF samples from 8 INPH, 10 SAH-induced hydrocephalus, and 6 unmatched patients with non-hemorrhagic obstructive hydrocephalus during their ventriculoperitoneal shunt operations. Transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and total tau in the CSF were analyzed via enzyme-linked immunosorbent assay. RESULTS: The mean VEGF levels in the CSF of patients with SAH-induced hydrocephalus, INPH, and obstructive hydrocephalus were 239 ± 131, 239 ± 75, and 163 ± 122 pg/mL, respectively. The total tau concentrations in the CSF of the groups were 1139 ± 1900, 325 ± 325, and 1550 ± 2886 pg/mL, respectively. TNF-α values were 114 ± 34, 134 ± 38, and 55 ± 16 pg/mL, respectively. TGF-ß1 values were 953 ± 430, 869 ± 447, and 136 ± 63 pg/mL, respectively. A significant difference in TNF-α and TGF-ß1 levels was observed only between SAH-induced and chronic obstructive hydrocephalus, and between INPH and chronic obstructive hydrocephalus (p<0.01). CONCLUSIONS: No significant differences in the 4 CSF biomarker levels were observed between INPH and SAH-induced hydrocephalus, whereas CSF TNF-α and TGF-ß1 levels were increased compared to those in patients with chronic obstructive hydrocephalus. Post-SAH hydrocephalus and INPH are probably more destructive to neural tissues, and then stimulate the inflammatory reaction and healing process, compared with obstructive hydrocephalus.

Angiographic features and clinical outcomes of intra-arterial nimodipine injection in patients with subarachnoid hemorrhage-induced vasospasm.

OBJECTIVE: The aim of this study was to determine the role of intra-arterial (IA) nimodipine injections for cerebral vasospasm secondary to ruptured subarachnoid hemorrhage (SAH) and to investigate the factors that influence vasodilation and clinical outcomes. METHODS: We enrolled 29 patients who underwent aneurysm clipping for ruptured cerebral aneurysms between 2009 and 2011, and who received IA nimodipine after subsequently presenting with symptomatic vasospasm. The degree of vasodilation shown in angiography was measured, and the correlation between the degree of vasodilation and both the interval from SAH to cerebral vasospasm and the interval from clipping to cerebral vasospasm was determined. The change in blood flow rate after IA injection was assessed by transcranial Doppler ultrasound. Multiple clinical parameters were completed before and after IA nimodipine injection to evaluate any improvements in clinical symptoms. RESULTS: For eight patients, Glasgow Coma Scale (GCS) scores increased by two or more points. The regression analysis demonstrated a positive correlation between the change in GCS scores after IA nimodipine injection and the change in blood vessel diameter (p=0.025). A positive correlation was also observed between the interval from SAH to vasospasm and the change in diameter (p=0.040); and the interval from clipping to vasospasm and the change in diameter (p=0.022). CONCLUSION: IA nimodipine injection for SAH-induced vasospasm led to significant vasodilation in angiography and improvement in clinical symptoms without significant complications. Our findings suggest that IA nimodipine injection should be utilized when intractable vasospasm develops despite rigorous conservative management.