Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function.

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with poor patient prognosis. Although the standard treatment of GBM is surgery followed by chemotherapy and radiotherapy, often a small portion of surviving tumor cells acquire therapeutic resistance and become more aggressive. Recently, altered kinase expression and activity have been shown to determine metabolic flux in tumor cells and metabolic reprogramming has emerged as a tumor progression regulatory mechanism. Here we investigated novel kinase-mediated metabolic alterations that lead to acquired GBM radioresistance and malignancy. We utilized transcriptomic analyses within a radioresistant GBM orthotopic xenograft mouse model that overexpresses the dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3). We find that within GBM cells, radiation exposure induces DYRK3 expression and DYRK3 regulates mammalian target of rapamycin complex 1 (mTORC1) activity through phosphorylation of proline-rich AKT1 substrate 1 (PRAS40). We also find that DYRK3 knockdown inhibits dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, leading to increased oxidative phosphorylation (OXPHOS) and reduced glycolysis. Importantly, enforced DYRK3 downregulation following irradiation significantly impaired GBM cell migration and invasion. Collectively, we suggest DYRK3 suppression may be a novel strategy for preventing GBM malignancy through regulating mitochondrial metabolism.

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas.

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.

Thrombectomy in acute vertebrobasilar occlusion: a single-centre experience.

PURPOSE: Acute vertebrobasilar occlusion (VBO) has a grave clinical course; however, thrombectomy in VBO patients has rarely been reported. We retrospectively evaluated the clinical and radiological outcomes of thrombectomy in VBO patients. METHODS: From March 2010 to December 2017, 38 patients with 40 acute VBOs underwent thrombectomy at our hospital. Thrombectomy was performed using catheter aspiration (n = 11, 26.8%) or a stent retriever (n = 29, 70.7%). RESULTS: Good clinical outcomes (3-month modified Rankin scale (mRS) of 2 or lower) were achieved in 9 cases (22.5%), and successful recanalization (thrombolysis in cerebral infarction (TICI) grade of 2b or 3) was achieved in 35 cases (87.5%). Good clinical outcomes were significantly related to aetiologies other than atherosclerosis (p = 0.020) and lower National Institutes of Health Stroke Scale (NIHSS) scores on admission (p = 0.025). The clinical and radiological outcomes did not differ significantly between catheter aspiration and stent retriever thrombectomy (p = 1.000 and p = 0.603, respectively); however, stent retriever thrombectomy had a shorter procedure time than catheter aspiration (59.7 ± 31.2 vs. 84.5 ± 35.1 min, p = 0.037). CONCLUSION: In our series, good clinical outcomes were associated with a lower NIHSS score on admission and stroke aetiologies other than atherosclerosis. The two thrombectomy modalities showed similar clinical and radiological outcomes. However, stent retrievers seemed to allow more rapid recanalization than catheter aspiration in VBO.

Predictive value of neurophysiologic monitoring during neurovascular intervention for postoperative new neurologic deficits.

PURPOSE: Forms of intraoperative neurophysiologic monitoring (IONM), including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs), have been widely used in the field of neurosurgery. This study aimed to evaluate the diagnostic efficacy of IONM in identifying intraoperative events and predicting postoperative neurologic deficits in neurovascular intervention. METHODS: From January 2013 to December 2016, we retrospectively reviewed patients who underwent neurovascular intervention under general anesthesia with the use of IONM. Associations between significant changes in MEPs or SSEPs which were defined as a decrease more than 50% in amplitude and/or an increase more than 10% in latency and any identifiable intraoperative events and/or postoperative neurologic deficits were determined. The sensitivity and specificity values for both MEPs and SSEPs were calculated. RESULTS: In total, 578 patients (175 men and 403 women) were included. Their mean age was 59.5 years. SSEP changes occurred in 1% (n = 6), and MEP changes occurred in 1.2% (n = 7). Four patients suffered postoperative neurologic deficits, and identifiable intraoperative events were observed in seven patients. Both SSEP and MEP changes were significantly associated with identifiable intraoperative events and/or postoperative neurologic deficits (p < 0.001, Fisher's exact test). The calculated sensitivity and specificity of MEP monitoring were 50 and 99.5%, respectively. The sensitivity and specificity of SSEP monitoring were both 100%. CONCLUSION: Intraoperative SSEP monitoring might be a reliable and sensitive method to surveil neurologic complications during neurovascular intervention. Intraoperative MEP monitoring appears to be feasible. However, it is unclear whether MEP monitoring has any additive benefit over SSEP monitoring.

Angiographic and clinical outcomes of non-patent anastomosis after bypass surgery in adult moyamoya disease.

BACKGROUND: The clinical and radiologic outcomes of symptomatic adult moyamoya disease (MMD) patients who have an occluded anastomosis immediately after bypass surgery are poorly studied. The clinical and angiographic outcomes of non-patent anastomosis in symptomatic adult MMD patients were retrospectively reviewed. METHODS: From August 2011 to November 2016, 31 revascularization surgeries, consisting of direct and indirect bypass, were performed on 29 adult MMD patients. Primary outcomes were evaluated based on the frequency of transient ischaemic attack (TIA) incidence and the recurrence of cerebral infarction and were assessed as improvement or worsening. RESULTS: Among 31 cases, computed tomography angiography (CTA) on the first day after surgery showed patent anastomosis in 20 hemispheres and non-patent anastomosis in 11 hemispheres. Follow-up conventional angiographies showed spontaneous recanalization of non-patent anastomosis in all occlusion cases. The incidence of TIA decreased in both the non-patent and the patent groups. Two newly developed cerebral infarctions were observed, which occurred in the patent group. Patients in the non-patent group also showed clinical improvement after surgery (p = 0.04), and no significant relationship was found between immediate postoperative patency and the primary outcome (p = 0.53). CONCLUSIONS: In our series, regardless of patency immediately after bypass surgery, delayed recanalization and clinical improvement can be expected after bypass surgery for adult MMD.

Bilateral pallidal stimulation for "sticking-out tongue" feature in patients with primary focal tongue protrusion dystonia.

INTRODUCTION: Tongue protrusion dystonia can cause difficulty with speech, mastication, breathing, and swallowing. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a widespread therapeutic alternative for treating medically refractory dystonia. To our knowledge, detailed reports regarding DBS for tongue protrusion dystonia are rare. In this report, we describe two patients with "sticking out" tongue protrusion who had undergone bilateral GPi DBS. METHODS: Operations were performed with surface electromyographic (EMG) monitoring, microelectrode recording, and macrostimulation to identify the point at which tongue kinetic cells respond most effectively. The most effective location for active contacts was identified according to burst EMG response in the posteroventral GPi. RESULTS: Two years after DBS, total Burke, Fahn, and Marsden Dystonia Rating Scale scores of two patients were improved from 12.5 to 1 (92.0%) and from 13 to 1 (92.3%), respectively. One 58-year-old woman who lost 7 kg weight from not eating well improved enough to eat solid food and became free from choking. Another 54-year-old woman who had dysarthria and mumbled could speak more fluently and would not have complained difficulty in reading any more. CONCLUSION: Stimulation on posteroventral GPi for patients with idiopathic "sticking-out" tongue movement changes EMG pattern in orofacial muscles. This fact supports a reason for modulation of unknown circuit connecting tongue-specific area in motor cortex, and basal ganglia.

Mitochondrial glutamate transporter SLC25A22 uni-directionally export glutamate for metabolic rewiring in radioresistant glioblastoma.

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor. Radiotherapy, one of the standard treatments for GBM patients, could induce GBM radioresistance via rewiring cellular metabolism. However, the precise mechanism attributing to GBM radioresistance or targeting strategies to overcome GBM radioresistance are lacking. Here, we demonstrate that SLC25A22, a mitochondrial bi-directional glutamate transporter, is upregulated and showed uni-directionality from mitochondria to cytosol in radioresistant GBM cells, resulting in accumulating cytosolic glutamate. However, mitochondrial glutaminolysis-mediated TCA cycle metabolites and OCR are maintained constantly. The accumulated cytosolic glutamate enhances the glutathione (GSH) production and proline synthesis in radioresistant GBM cells. Increased GSH protects cells against ionizing radiation (IR)-induced reactive oxygen species (ROS) whereas increased proline, a rate-limiting substrate for collagen biosynthesis, induces extracellular matrix (ECM) remodeling, leading to GBM invasive phenotypes. Finally, we discover that genetic inhibition of SLC25A22 using miR-184 mimic decreases GBM radioresistance and aggressiveness both in vitro and in vivo. Collectively, our study suggests that SLC25A22 upregulation confers GBM radioresistance by rewiring glutamate metabolism, and SLC25A22 could be a significant therapeutic target to overcome GBM radioresistance.

Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies.

Glioblastoma (GBM) is the most malignant primary brain tumor. The current standard approach in GBM is surgery, followed by treatment with radiation and temozolomide (TMZ); however, GBM is highly resistant to current therapies, and the standard of care has not been revised over the last two decades, indicating an unmet need for new therapies. GBM stem cells (GSCs) are a major cause of chemoresistance due to their ability to confer heterogeneity and tumorigenic capacity. To improve patient outcomes and survival, it is necessary to understand the properties and mechanisms underlying GSC chemoresistance. In this review, we describe the current knowledge on various resistance mechanisms of GBM to therapeutic agents, with a special focus on TMZ, and summarize the recent findings on the intrinsic and extrinsic mechanisms of chemoresistance in GSCs. We also discuss novel therapeutic strategies, including molecular targeting, autophagy inhibition, oncolytic viral therapy, drug repositioning, and targeting of GSC niches, to eliminate GSCs, from basic research findings to ongoing clinical trials. Although the development of effective therapies for GBM is still challenging, this review provides a better understanding of GSCs and offers future directions for successful GBM therapy.

NRBF2-mediated autophagy contributes to metabolite replenishment and radioresistance in glioblastoma.

Overcoming therapeutic resistance in glioblastoma (GBM) is an essential strategy for improving cancer therapy. However, cancer cells possess various evasion mechanisms, such as metabolic reprogramming, which promote cell survival and limit therapy. The diverse metabolic fuel sources that are produced by autophagy provide tumors with metabolic plasticity and are known to induce drug or radioresistance in GBM. This study determined that autophagy, a common representative cell homeostasis mechanism, was upregulated upon treatment of GBM cells with ionizing radiation (IR). Nuclear receptor binding factor 2 (NRBF2)-a positive regulator of the autophagy initiation step-was found to be upregulated in a GBM orthotopic xenograft mouse model. Furthermore, ATP production and the oxygen consumption rate (OCR) increased upon activation of NRBF2-mediated autophagy. It was also discovered that changes in metabolic state were induced by alterations in metabolite levels caused by autophagy, thereby causing radioresistance. In addition, we found that lidoflazine-a vasodilator agent discovered through drug repositioning-significantly suppressed IR-induced migration, invasion, and proliferation by inhibiting NRBF2, resulting in a reduction in autophagic flux in both in vitro models and in vivo orthotopic xenograft mouse models. In summary, we propose that the upregulation of NRBF2 levels reprograms the metabolic state of GBM cells by activating autophagy, thus establishing NRBF2 as a potential therapeutic target for regulating radioresistance of GBM during radiotherapy.

Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia.

BACKGROUND: Deep brain stimulation (DBS) is generally a safe and effective method to treat intractable movement disorders. However, complications of surgery have been reported, such as hemorrhage, infection and hardware failure. OBJECTIVES AND METHODS: We describe an unusual complication associated with DBS of the globus pallidus internus (GPi). The patient was a 34-year-old man with a 5-year history of progressive cervical dystonia that was unresponsive to medical treatment. He underwent bilateral DBS of the posteroventral GPi. After test stimulation, the patient developed left facial weakness, as well as dysarthria and hemiparesis of the left side. Magnetic resonance imaging showed a small infarct in the right posterior internal capsule. There was no misplacement of the microelectrode. RESULTS AND CONCLUSION: The authors present this unique case of cerebral infarction as a complication of DBS. The mechanism of ischemia is unclear. However, in this case, we had performed microstimulation with high amplitude in order to determine the adverse effects. This magnitude of electrical stimulation may have led to small-vessel vasospasm, which may have induced ischemia. Although ischemia after DBS surgery is seldom reported, cerebral ischemia may be a surgical complication after DBS implantation.

A combination procedure with double C-shaped skin incision and dual-floor burr hole method to prevent skin erosion on the scalp and reduce postoperative skin complications in deep brain stimulation.

BACKGROUND: The purpose of this study was to introduce a combination procedure with double C-shaped skin incision and an adjusted dual-floor burr hole to prevent skin complications on the scalp with deep brain stimulation (DBS) surgery. METHODS: Between March 2000 and March 2010, 504 DBS electrodes were implanted in 268 patients. We included both bilateral and unilateral DBS surgery cases for Parkinson's disease, tremor, pain, obsessive-compulsive disorder and intractable seizure accompanied with cranial and IPG insertion procedure, but excluded motor cortex stimulation, and spinal cord stimulation. We used a straight skin incision in 118 patients, double C-shaped skin incision only in 113 patients since March 2006, and combined a double C-shaped skin incision and dual-floor burr hole in 37 patients since August 2009. We compared scalp wound complications and the height subscale of the Vancouver Scar Scale between previous straight or C-shaped skin incision and the combination procedure. RESULTS: We had eight scalp erosions associated with infection (3.0%) and six disconnection (2.2%) cases among 268 patients. Before the use of the double C-skin incision or adjusted dual-floor burr hole technique, we had 5 (4.2%) scalp erosion cases among 118 patients. With the introduction of the C-shaped incision, only 3 patients (2.7%) developed scalp erosion. However, no patient among 37 patients developed scalp erosion after using both double C-shaped skin incision and dual-floor burr hole technique. Scalp bump measured by the height subscale of the Vancouver Scar Scale was more cosmetic in the combination procedure. CONCLUSION: The combination procedure prevents skin complications associated with DBS surgery, with tensile strength, less impaired vascular supply and better cosmetic outcome. This promising approach prevents unwanted skin complications associated with DBS surgery and improves patient satisfaction.

Bilateral subthalamic deep brain stimulation using single track microelectrode recording.

BACKGROUND: Microelectrode recording (MER) is widely used during deep brain stimulation (DBS) procedures because MER can identify structural borders and eloquent structures, localize somatotopic arrangements, and provide an outline of the three-dimensional shapes of target nuclei. However, MER may cause intracranial hemorrhage. We preformed single track MER during DBS procedures, analyzed the accuracy of electrode positioning with MRI, and compared the amount of air and the potential risk of intracranial hemorrhage. METHOD: A total of 46 electrodes were placed in 23 patients who suffered from advanced Parkinson's disease and who underwent bilateral subthalamic nucleus DBS using single track MER. Each patient's Unified Parkinson's Disease Rating Scale (UPDRS) score and levo-dopa equivalent dosage (LED) were estimated pre- and postoperatively. The accuracy of electrode positioning and fontal air thickness was measured by a pre- or postoperative magnetic resonance imaging (MRI) merging technique. FINDINGS: The mean electrode positioning error was 0.92 mm (0.3-2.94 mm). The mean frontal air thickness on postoperative MRI was 3.85 mm (0-10.3 mm), which did not affect the electrode accuracy statistically (p = 0.730). A total of nine electrodes required repositioning after single-track MER because they affected microstimulation or because an abnormally short STN length was observed during MER. In this series, one patient suffered from an intracranial hemorrhage after surgery that appeared to be due to venous infarction rather than related to MER. CONCLUSIONS: Although MER can facilitate accurate positioning of electrodes, multi-track MER may increase the risk of intracranial hemorrhage. The accuracy of electrode positioning appears to be acceptable under single track MER during STN DBS with careful electrophysiological and neurological monitoring. The risk of intracranial hemorrhage appears to be minimal, especially in elderly patients with atrophic brains.

Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma.

BACKGROUND: Glioblastoma Multiforme (GBM) is a malignant primary brain tumor in which the standard treatment, ionizing radiation (IR), achieves a median survival of about 15 months. GBM harbors glioblastoma stem-like cells (GSCs), which play a crucial role in therapeutic resistance and recurrence. METHODS: Patient-derived GSCs, GBM cell lines, intracranial GBM xenografts, and GBM sections were used to measure mRNA and protein expression and determine the related molecular mechanisms by qRT-PCR, immunoblot, immunoprecipitation, immunofluorescence, OCR, ECAR, live-cell imaging, and immunohistochemistry. Orthotopic GBM xenograft models were applied to investigate tumor inhibitory effects of glimepiride combined with radiotherapy. RESULTS: We report that GSCs that survive standard treatment radiation upregulate Speedy/RINGO cell cycle regulator family member A (Spy1) and downregulate CAP-Gly domain containing linker protein 3 (CLIP3, also known as CLIPR-59). We discovered that Spy1 activation and CLIP3 inhibition coordinately shift GBM cell glucose metabolism to favor glycolysis via two cellular processes: transcriptional regulation of CLIP3 and facilitating Glucose transporter 3 (GLUT3) trafficking to cellular membranes in GBM cells. Importantly, in combination with IR, glimepiride, an FDA-approved medication used to treat type 2 diabetes mellitus, disrupts GSCs maintenance and suppresses glycolytic activity by restoring CLIP3 function. In addition, combining radiotherapy and glimepiride significantly reduced GBM growth and improved survival in a GBM orthotopic xenograft mouse model. CONCLUSIONS: Our data suggest that radioresistant GBM cells exhibit enhanced stemness and glycolytic activity mediated by the Spy1-CLIP3 axis. Thus, glimepiride could be an attractive strategy for overcoming radioresistance and recurrence by rescuing CLIP3 expression.

Microneurovascular decompression in patients with hemifacial spasm caused by vascular compression of facial nerve at cisternal portion.

BACKGROUND: Hemifacial spasm is commonly caused by arterial compression of the facial nerve. Although vascular compression usually occurs at the facial nerve exit zone, in some cases, the facial nerve is compressed more distally. We analyzed the clinical outcome of microneurovascular decompression in patients with hemifacial spasm caused by either distal or proximal compression. METHOD: From September 1978 to March 2009, 2,137 patients underwent microneurovascular decompression for hemifacial spasm due to vascular compression of the facial nerve, including 2,022 patients (94.6%) with proximal compression, 101 patients (4.7%) with both proximal and distal (mixed) compression, and 14 patients (0.7%) with only distal compression. FINDINGS: Complete remission of facial spasm occurred in 10 of 14 patients (71.4%) with compression of the cisternal portion, compared with 1,773 of 2,022 patients (87.7%) with proximal compression (P = 0.08) and 87 of 101 patients (86.1%) with mixed compression (P = 0.23). Permanent facial weakness occurred in one patient (7.1%) with compression of the cisternal portion, 18 patients (0.9%) with proximal compression, and one patient (1.0%) with mixed compression. Permanent hearing loss occurred in no patients with compression of the cisternal portion, 29 patients (1.4%) with proximal compression, and three patients (3.0%) with mixed compression. CONCLUSIONS: Outcomes after microneurovascular decompression for hemifacial spasm with compression of the cisternal portion were not statistically different than with proximal compression of the facial nerve. When the clinical diagnosis of hemifacial spasm is confirmed and vascular compression is seen only in the cisternal portion of the facial nerve, microneurovascular decompression for these patients provides outcomes similar to those with proximal compression of the facial nerve.

Cervical Spinal Fracture Caused by Untreated Tourette Syndrome: A Case Report.

Cervical myelopathy can occur in Tourette syndrome patients with severe motor tics showing repetitive and violent neck movements. However, motor tics causing spinal fractures have been rarely reported. A 15-year-old girl presented at our clinic, complaining of recent development of motor weakness of all 4 extremities. She had untreated motor tics involving the neck. Computed tomography and magnetic resonance imaging findings suggested cervical spinal fractures and myelopathy. After diagnosing of Tourette syndrome, medical and psychologic therapies were started. Her motor tics were well controlled, and no complications in the patient's daily life were observed later. Cervical radiography taken at a 9-month follow-up showed bony healings of the fractured cervical spines. Uncontrolled severe motor tics may cause spinal fractures. Conservative treatments would suffice for proper control of these tics and stabilize the spine, and considered as initial treatment in patients with Tourette syndrome.

Anterior Spinal Artery Syndrome Occurring after One Level Segmental Artery Ligation during Spinal Surgery.

In treating the ventral pathology of spine, ligating the segmental vessels is sometimes necessary. This may cause spinal cord ischemia, and concerns of neurologic injury have been presented. However, spinal cord ischemic injury after sacrificing segmental vessels during spine surgery is very rare. Reports of this have been scarce in the literature and most of these complications occur after multi-level segmental vessel ligation. Here we report a case of a patient with postoperative anterior spinal artery syndrome, which occurred after ligating one level segmental vessels during spinal surgery for a T8 vertebral pathologic fracture. Despite its rarity, the risk of spinal cord ischemic injury after segmental vessel ligation is certainly present. Surgeons must keep in mind such risk, and surgery should be planned under a careful risk-benefit consideration.

Disappearance of a Distal Shunt Catheter: A Case Report of an Unusual Cause of Shunt Malfunction.

Shunt malfunction is a common complication in patients who undergo ventriculoperitoneal shunt (VPS) placement for the treatment of hydrocephalus. A plethora of reports regarding shunt malfunctions due to distal catheter migration have been demonstrated in the literature. However, to our knowledge, there have been no reports thus far of shunt malfunctions caused by the complete disappearance of a distal catheter. A 70-year-old man was admitted to our hospital for progressive gait disturbance beginning approximately 5 months ago. He received a VPS for posthemorrhagic hydrocephalus and was doing well over the course of 18 months of follow-up. Since no increase in the size of the ventricle was observed on brain computed tomography taken at the outpatient clinic, we tried to readjust the pressure setting of his programmable shunt valve to relieve his symptoms. Without any progression, we discovered later by chance that the distal shunt catheter was missing. Shunt revision surgery was performed. At the 2-year follow-up, a slight improvement in gait was observed. Although it is very rare, the distal catheter can disappear without any noticeable symptoms. If shunt malfunction is suspected, it is important to check whether the entire shunt system is structurally intact.

The Effect of Epidermal Growth Factor Receptor Mutation on Intracranial Progression-Free Survival of Non-Small Cell Lung Cancer Patients with Brain Metastasis Underwent Gamma Knife Radiosurgery.

BACKGROUND: The aim of this study was to survey prognostic factors, particularly those focusing on epidermal growth factor receptor (EGFR) mutations, of patients with non-small cell lung cancer (NSCLC) after Gamma Knife Radiosurgery (GKRS) for metastatic brain tumors. METHODS: We retrospectively reviewed the medical records of 98 patients with NSCLC who underwent GKRS for brain metastases from August 2010 to July 2017. The primary endpoint was progression-free survival (PFS) of the intracranial disease. We analyzed variables such as age, sex, Karnofsky Performance Status, recursive partitioning analysis (RPA) class, smoking status, primary cancer pathology, EGFR mutations, and time to brain metastases as prognostic factors. RESULTS: The median overall survival (OS) of the patients was 16 months [95% confidence interval (CI), 13-21 months]. Median systemic PFS and intracranial PFS were 9 months (95% CI, 8-11 months) and 11 months (95% CI, 7-14 months), respectively. Kaplan-Meier survival analysis revealed that the patients with EGFR mutations had longer intracranial PFS than those without EGFR mutation (median intracranial PFS: 19 vs. 10 months with p=0.01) while they had no benefits in OS and systemic PFS. Furthermore, the patients harboring adenocarcinoma had longer OS (p<0.01) and intracranial PFS (p<0.01) and the patients with lower RPA class had longer OS (p=0.02) and intracranial PFS (p=0.03). CONCLUSION: EGFR mutations, primary cancer pathology, and RPA class may be proposed as prognostic factors for intracranial PFS in NSCLC patients after GKRS for brain metastasis in this study.

An investigation of thalamic nuclei volumes and the intrinsic thalamic structural network based on motor subtype in drug naïve patients with Parkinson's disease.

INTRODUCTION: This study aimed to investigate the alterations in thalamic nuclei volumes and the intrinsic thalamic structural network in patients with de novo Parkinson's disease (PD) based on their predominant symptoms. METHODS: We enrolled 65 patients with de novo PD (44 patients with tremor-dominant [TD] subtype and 21 patients with postural instability and gait disturbance [PIGD] subtype) and 20 healthy controls. All subjects underwent three-dimensional T1-weighted magnetic resonance imaging. The thalamic nuclei were segmented using the FreeSurfer program. RESULTS: We obtained volumetric differences in the thalamic nuclei of each subtype of PD in comparison of healthy control. Volumes of the right and left suprageniculate nuclei were significantly increased, whereas that of the left parafascicular nucleus was decreased in patients with the TD subtype. Volumes of the right and left suprageniculate nuclei and right ventromedial nucleus were significantly increased, whereas those of the right and left parafascicular nuclei volumes were decreased in patients with the PIGD subtype. The measures of the intrinsic thalamic global network were not different between patients with TD PD and healthy controls. However, in patients with the PIGD subtype, the global and local efficiencies were significantly increased compared to healthy controls. Moreover, although there were no differences in thalamic volume and intrinsic thalamic global network between patients with the TD and PIGD variants, we identified significant differences in the intrinsic thalamic local network between the two groups. CONCLUSIONS: Alterations in thalamic nuclei volumes and the intrinsic thalamic network in patients with PD differed based on their predominant symptoms. These findings might be related to the underlying pathogenesis and suggest that PD is a heterogeneous syndrome.

Recurrence of Small Cerebral Aneurysms (< 4 mm) Treated Endovascularly Using Target® Nano™ Coils.

OBJECTIVE: In our series, endovascular coiling with Target® Nano™ coils (Stryker Neurovascular, Fremont, CA, USA) with diameters of 1 or 1.5 mm exhibited favorable technical feasibility in the treatment of small cerebral aneurysms (< 4 mm). However, little is known about the recurrence of small cerebral aneurysms treated using Target® Nano™ coils. We investigated recurrence following the treatment of small cerebral aneurysms using Target® Nano™ coils. MATERIALS AND METHODS: Between January 2012 and November 2013, 143 patients with 148 small cerebral aneurysms (< 4 mm) were included our study. A total of 135 cerebral aneurysms (91.2%) were unruptured; 45 cerebral aneurysms (30.4%) were treated by endovascular coiling using Target® Nano™ coils. Follow-up radiological images were obtained for 132 cerebral aneurysms (89.2%) over a range of 3 to 58 months (mean, 34.3 months; standard deviation, 14.2). RESULTS: In the group treated with Target® Nano™ coils, radiological outcomes revealed complete occlusion in 33 (73.3%), residual necks in eight (17.8%), and residual sacs in four (8.9%) cases. Follow-up radiological outcomes revealed complete occlusion in 35 (77.8%) and residual necks in four (8.9%) cases that exhibited stable coil masses. In the group that was not treated with Target® Nano™ coils, radiological outcomes revealed complete occlusion in 69 (67%), residual necks in 18 (17.5%), and residual sacs in 16 (15.5%) cases. Follow-up radiological outcomes revealed complete occlusion in 87 (84.5%) and residual necks (5.8%) in six cases that exhibited stable coil masses. No significant differences were observed in the radiological outcomes or follow-up radiological outcomes between the two groups. No recurrences or retreatments occurred in our series. CONCLUSION: Endovascular treatment using Target® Nano™ coils may be a robust treatment option for small cerebral aneurysms (< 4 mm).