bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma: Patterns of Recurrence and Efficacy of Salvage Treatments
Authors: Oh Jiwon , Sahgal Arjun , Sanghera Paul , Tsao May N. , Davey Phil , Lam Kelvin , Symons Sean , Aviv Richard , Perry James R. 
Published: December 2014

Abstract:Background:It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.Methods:We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.Results:58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).Conclusion:The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.
Amyloid β-related Angiitis of the Central Nervous System: Report of 3 Cases
Authors: Rigby Heather , Easton Alexander , Bhan Virender 
Published: December 2014

Objective:Amyloid-β (Aβ) related angiitis (ABRA) is a recently described clinicopathological entity characterized by cerebrovascular Aβ deposition and arteritis. Cerebral Aβ deposition is commonly present in cerebal amyloid angiopathy (CAA) and Alzheimer's disease (AD) but is rarely associated with inflammatory infiltration of vessel walls. Our objective is to help clarify the clinical spectrum, radiographic findings, response to treatment, and outcomes of ABRA. The neuropathological relationship between ABRA, cerebral amyloid angiopathy, and Alzheimer's disease is discussed.Methods:We present three cases of ABRA managed at a tertiary care centre.Results:All three patients presented with seizures and cognitive dysfunction; one had multifocal neurologic findings. Brain biopsies revealed inflammatory arteritis with Aβ deposits in the vessel walls. All were treated with steroids and cyclophosphamide. Two had favorable outcomes and one stabilized but with severe residual neurologic disability.Conclusions:ABRA is an unusual but likely under-recognized and potentially treatable disorder. As in other reported cases, our findings suggest that many patients respond favorably to immunosuppressive therapy. We believe that all biopsy specimens consistent with primary angiitis of the central nervous system (CNS) should be further examined for vascular Aβ deposition.
Gamma Knife for Cerebral Arteriovenous Malformations at a Single Centre
Authors: Zeiler F. A. , McDonald P. J. , Kaufmann A. , Fewer D. , Butler J. , Schroeder G. , West M. 
Published: December 2014

Background:We report the results of a consecutive series of patients treated with Gamma Knife (GK) Surgery for cerebral arteriovenous malformations (AVMs).Methods:We retrospectively reviewed 69 patients treated with GK for cerebral AVMs between November 2003 and April 2009, recording clinical data, treatment parameters, and AVM obliteration rates in order to assess our effectiveness with GK in treating these lesions.Results:Ten patients were lost to follow-up. Presentations included: seizure (24), hemorrhage (18), persistent headache (12), progressing neurological signs (10), and incidental (9). In 24 patients (34.8%) treatment planning consisted of digital subtraction angiography (DSA), magnetic resonance imaging (MRI), and computed tomogram (CT) angiography (CTA). Currently we rely predominantly on CTA and/or MRI scanning only. Fourty-one patients have been followed for a minimum of 3 years; average age 40.9yr., 58.5% males. Average dose at the 50% isodose line was 20.3 Gy (range 16 to 26.4 Gy). Obliteration was observed in 87.8% by MRI, CT, or DSA. Not all obliteration was confirmed by DSA. Complications occurred in 12 of 59 (20.3%) patients, and in 11 of 41 (26.8%) with 3 year follow-up. Major (temporary) complications for the 59 included symptomatic cerebral edema (7), seizure (2), and hemorrhage (1). Major permanent complications occurred in one patient suffering a cranial nerve V deafferentation, and in two patients suffering a hemorrhage.Conclusion:GKS for cerebral AVM's offers an effective and safe method of treatment, with low permanent complication rate.
Depolarization Induces NR2A Tyrosine Phosphorylation and Neuronal Apoptosis
Authors: Liu Yong , Yan Jing-Zhi , Gu Ying-Hui , Wang Wei , Zong Yan-Yan , Hou Xiao-Yu , Zhang Guang-Yi 
Published: December 2014

Background:Cytosol Ca2+overload plays a vital role in ischemic neuronal damage, which is largely contributed by the Ca2+influx through L-type voltage-gated calcium channels (L-VGCCs) and N-methyl-D-aspartate (NMDA) type glutamate receptors. In this article, L-VGCCs were activated by depolarization to investigate the cross-talk between NMDA receptors and L-VGCCs.Methods:Depolarization was induced by 20 minutes incubation of 75 mM KCl in cultured rat cortical neuron. Apoptosis-like neuronal death was detected by DAPI staining. Tyrosine phosphorylation of NMDA receptor subunit 2A (NR2A), interactions of Src and NR2A were detected by immunoblot and immunoprecipitation.Results:Depolarization induced cortical neuron apoptosis-like cell death after 24 hours of restoration. The apoptosis was partially inhibited by 5 mM EGTA, 100 μM Cd2+, 10 μM nimodipine, 100 μM genistein, 20 μM MK-801, 2 μM PP2 and combined treatment of nimodipine and MK-801. NR2A tyrosine phosphorylation increased after depolarization, and the increase was inhibited by the drugs listed above. Moreover, non-receptor tyrosine kinase Src bound with NR2A after depolarization and restoration. The binding was also inhibited by the drugs listed above.Conclusions:The results indicated that depolarization-induced neuronal death might be due to extracellular Ca2+influx through L-VGCCs and subsequently Src activationmediated NR2A tyrosine phosphorylation.
Assessment of Outcome Predictors after First Attack of Optic Neuritis
Authors: Mamarabadi Mansoureh , Razjouyan Hadie , Mohammadi Fatemeh , Moghaddasi Mehdi 
Published: December 2014

Background:Optic Neuritis (ON) is one of the most common clinically isolated syndromes which develops into clinically diagnosed Multiple Sclerosis (CDMS) over time.Objective:To assess the conversion rate of Iranian patients presenting with idiopathic ON to CDMS as well as monitoring potential demographic and clinical risk factors.Methods:Atotal of 219 patients' medical records of idiopathic ON from March 2001 to May 2009 were reviewed. Demographic findings, ophthalmologic characteristics on admission and discharge, diagnostic approaches, type and dosage of therapy were retrospectively reviewed. A structured telephone interview was then conducted to identify patients who had subsequently been diagnosed with MS. Survival analysis was used to evaluate the cumulative probability of MS conversion and contributory risk factors.Results:From the 219 ON patients, 109 [age 11-51, female: 81%] were followed up. Among the male gender the mean age of patients developing MS was significantly lower (P=0.01). In cox regression model, female sex (p=0.07), bilateral ON (p=0.003), MRI abnormalities (p <0.001) and high dose (5g) corticosteroid therapy (p<0.001) were identified as risk factors for the development of MS. The two and five year cumulative probability of developing MS were 27% and 45%, respectively.Conclusions:Idiopathic ON in Iranian patients carries higher risk of progression to MS compared to other Asian countries. MRI lesions are the strongest independent risk factor of developing CDMS. Bilateral ON, female gender and high dose corticosteroid therapy are also important factors in predicting CDMS development.
Essential Role of Excessive Tryptophan and its Neurometabolites in Fatigue
Authors: Yamamoto Takanobu , Azechi Hirotsugu , Board Mary 
Published: December 2014

Purpose:Serotonin, a neurotransmitter synthesized from tryptophan, has been proposed to play a key role in central fatigue. In this study, we examined whether tryptophan itself and/or its two metabolites, kynurenic acid (KYNA) and quinolinic acid (QUIN), are involved in central fatigue.Materials and Methods:Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase analbuminemic rats (NAR). Central fatigue was assessed by treadmill running and a Morris water maze test. Microdialysis was used to collect samples for measurement of extracellular concentration of tryptophan, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) and to infuse test agents. To examine the kinetics of release, synaptosomes in the striatum were prepared in vitro to measure intra- and extrasynaptosomal concentration of tryptophan, serotonin and 5-HIAA.Results:The concentration of tryptophan secreted into the extracellular space of the striatum was higher during fatigue only, and quickly returned to basal levels with recovery from fatigue. Running time to exhaustion was reduced by activation of tryptophan receptors. Time to exhaustion was shorter in NAR, which maintain a higher extracellular level of striatum tryptophan than SDR. Impaired memory performance in a water maze task after tryptophan treatment was attributable to high levels of KYNA and QUIN in the hippocampus acting synergistically on N-methyl-D-aspartic acid receptors. When branched-chain amino acids were administered, tryptophan transport to the extracellular space of the striatum was drastically inhibited.Conclusion:Our findings demonstrate that the increase in fatigue which occurs because of excessively elevated brain tryptophan can be further amplified by the use of synthetic KYNA and QUIN.
Cytokine Gene Polymorphisms and Parkinson's Disease: A Meta-Analysis
Authors: Ketan Chu , Xiao Zhou , Ben-yan Luo 
Published: December 2014

Background:Cytokines, which are involved in immunological responses, play important role in the development and progression of Parkinson's disease (PD). The functional polymorphisms identified in cytokine genes are thought to influence PD risk. However, the findings of studies investigating the association between cytokine gene polymorphisms and PD risk are still controversial. Therefore, we conducted a meta-analysis, in order to investigate the potential associations between cytokine gene polymorphisms and PD.Methods:Studies of PD and cytokine polymorphisms were identified by searches of PubMed and PDGene. Pooled analyses were performed to assess the association between cytokine gene polymorphisms and PD.Results:Our results indicated a positive association of TNFα -1031 CC genotype in overall analysis(CC vs. TT: OR=3.146; 95%CI: 1.631-6.070, p=0.008; CC vs. CT+TT: OR=3.187; 95%CI: 1.657-6.128, p=0.008), and an Asian subgroup, C variant(OR=1.328; 95%CI: 1.053-1.675, p=0.034) also conveyed an increased PD risk as well as CC genotype (CC vs. TT: OR=3.207; 95%CI: 1.614-6.373, p=0.004; CC vs. CT+TT: OR=3.238; 95%CI: 1.636-6.410, p=0.004). A decreased risk for PD was associated with IL-6-174C allele (OR=0.761; 95%CI: 0.641-0.903, p=0.008) and IL-1RA VNTR 2 allele(OR=0.641; 95%CI: 0.456-0.826 p=0.004). For the polymorphisms of IL-1β C[-511]T, IL-1α C[-889]T, TNFα G[-308]A, and IL-10 G[-1082]A no significant association was found between the gene polymorphisms and PD risk.Conclusions:Our meta-analysis suggested that gene polymorphisms of TNFα -1031, IL-6-174 and IL-1RA VNTR may be associated with PD risk. However, more large well-designed studies will be necessary to validate our findings.
Serum CRP Concentrations and Severity of Ischemic Stroke Subtypes
Authors: Luo Yun , Wang Zhongyuan , Li Jingwei , Xu Yun 
Published: December 2014

Objective:The aim of this retrospective study was to investigate if elevated C reactive protein (CRP) was related to the stroke severity, and to analyze its different distribution in stroke subtypes.Methods:316 patients with acute ischemic stroke (AIS) were enrolled and had CRP determinations; they were dichotomized as<7 or ≥7mg/L according to the previous report. 128 patients with transient ischemic attack who also had CRP measurements were selected as controls. A possible level-risk relationship between elevated CRP and NIHSS, which considered relatively severe illness as a value≥8, was studied within the AIS group.Results:CRP was elevated in 21% of the AIS compared to 4% in the control group (p = 0.000). Within the AIS group, patients with CRP levels ≥7mg/L had a significantly increased risk of severe stroke (OR 3.33, 95% CI 1.84-6.00, p =0.00). In subtype stroke, the highest rate of elevated CRP and NIHSS were in those with cardioembolic stroke (CE) using TOAST classification, total anterior circulation infarction (TACI) of OCSP classification and large volume infarction (LVI) of Adams classification; the odds ratio(OR) between elevated CRP and NIHSS was 6.14 (95% CI 1.43-26.44) in CE, 1.714 (95% CI 1.30-2.26) in TACI, 2.32 (95% CI 1.08-4.99) in LVI, and the p value were all below 0.05.Conclusion:Elevated CRP level can reflect the severity of AIS, which was association with stroke subtype.
Sex Differences in Adult Cerebral Venous Sinus Thrombosis: A 10-Year Experience
Authors: Hinnell Claire , Nadeau Janel , Lam Vanessa , Hill Michael D. , Coutts Shelagh B. 
Published: December 2014

Background:Sex differences in the risk factors, presentation and outcome of cerebral venous sinus thrombosis (CVST) are poorly defined, despite a discrepant prevalence between males and females. The proportion of patients on hormonal therapy who develop CVST varies widely. We describe the clinical features, risk factors and outcome by sex and by hormone-related risk factors among a large cohort of patients.Methods:We reviewed records of 108 consecutive patients with CVST at a tertiary hospital in Calgary between 1999 and 2009. Descriptive statistics were used for between group comparisons (men, women with hormone-related risk factors and women without hormone-related risk factors).Results:Females made up 62% of patients, half of whom were on systemic hormonal therapy. Men and women without hormonal risk factors were older at onset. Oral contraceptive use was the major risk factor in women (45%) while concurrent mastoiditis was the most common predisposing factor in men (27%). Complications were frequent and overall mortality was 6%. Persisting deficits at discharge were more common in men (54% vs. 35% and 32%, p = 0.036). There was a trend for women with hormone-related risk factors to have less residual focal neurologic deficit than the other groups (5% vs. 15% and 17%, p=0.051).Conclusions:There are differences between sexes in the presentation, risk factors and outcome of patients with CVST.
Tissue Window in Stroke Thrombolysis Study (TWIST): A Safety Study
Authors: Hill Michael D. , Kenney Carol , Dzialowski Imanuel , Boulanger Jean-Martin , Demchuk Andrew M. , Barber Philip A. , Watson Timothy W.J. , Weir Nicolas U. , Buchan Alastair M. ,   Calgary Stroke Program
Published: December 2014

Abstract:Background:Stroke thrombolysis is limited by the “last-seen well” principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were “last-seen well” at the time they went to bed implying an interval that is most often greater than three hours.Methods:A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death.Results:Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10).Conclusions:Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.
Nonmotor Symptoms in Drug-Induced Parkinsonism and Drug-Naïve Parkinson Disease
Authors: Kim Ji Sun , Youn Jinyoung , Shin Hyeeun , Cho Jin Whan 
Published: December 2014

AbstractBackground:The clinical manifestations of drug-induced parkinsonism (DIP) and Parkinson disease (PD) are nearly indistinguishable, making it difficult to differentiate DIP from PD, especially in the early stages. We compared non-motor symptoms between patients with DIP and those with drug-naïve PD in the early stages using the Non Motor Symptoms Scale (NMSS).Methods:We prospectively enrolled 28 patients with DIP, 35 patients with drug-naïve PD, and 32 controls with no history of neurological diseases or related medical problems. We investigated demographic characteristics, medical and drug history, parkinsonian motor symptoms, and non-motor symptoms. We used the NMSS to evaluate non-motor symptoms in all patients.Results:The total NMSS scores were higher in patients with PD than those with DIP, as were the scores for certain domains, including the cardiovascular, sleep/fatigue, urinary, sexual, and miscellaneous domains. When controlling for age and gender, the correlation analysis revealed that scores for urinary symptoms (urgency, frequency and nocturia), sleep disturbances (daytime sleep, restless legs), concentration, taste or smell were significantly associated with PD.Conclusions:Our data suggest that non-motor symptoms, particularly urinary symptoms, excessive daytime sleepiness, restless leg syndrome, attention deficit and hyposmia may be helpful to differentiate between DIP and PD in the early stages.
Depth Electrodes in Pediatric Epilepsy Surgery
Authors: Kassiri Janani , Pugh Jeff , Carline Sharon , Jurasek Laura , Snyder Thomas , Wheatley Matt , Sinclair D. Barry 
Published: December 2014

Abstract:Background:The surgical removal of the epileptogenic zone in medically intractable seizures depends on accurate localization to minimize the neurological sequelae and prevent future seizures. To date, few studies have demonstrated the use of depth electrodes in a pediatric epilepsy population. Here, we report our study of pediatric epilepsy patients at our epilepsy center who were successfully operated for medically intractable seizures following the use of intracranial depth electrodes. In addition, we detail three individuals with distinct clinical scenarios in which depth electrodes were helpful and describe our technical approach to implantation and surgery.Methods:We retrospectively reviewed 18 pediatric epilepsy patients requiring depth electrode studies who presented at the University of Alberta Comprehensive Epilepsy Program between 1999 and 2010 with medically intractable epilepsy. Patients underwent cortical resection following depth electrode placement according to the Comprehensive Epilepsy Program surgical protocols after failure of surface electroencephalogram and magnetic resonance imaging to localize ictal onset zone.Result:The ictal onset zone was successfully identified in all 18 patients. Treatment of all surgical patients resulted in successful seizure freedom (Engel class I) without neurological complications.Conclusion:Intracranial depth electrode use is safe and able to provide sufficient information for the identification of the epileptogenic zone in pediatric epilepsy patients previously not considered for epilepsy surgery.
Eye Exercises for Treatment of Idiopathic Cranial Nerve VII Paresis: Pilot Study
Authors: Rodriguez Sylvia L. , Hopman Wilma M. , ten Hove Martin W. 
Published: December 2014

Background:To determine if fine-motor eye exercises can be used for treatment of unilateral, idiopathic cranial nerve VII paresis to improve rate of recovery.Methods:In this prospective, randomized controlled trial, eligible patients were randomized to perform fine-motor eye exercises (n=18) or to do no exercise (n=9) for a period of four weeks. Orbicularis oculi muscle strength was measured in paretic and unaffected eyes at baseline, two weeks and four weeks using an Orbicularis Oculi Pressure Sensor.Results:The average initial strength of the paretic orbicularis oculi muscle was 34±10 mm Hg compared to the unaffected muscle which was 103±17 mm Hg at baseline (n=27). By four weeks, patients who performed eye exercises improved more than those who did not (74.4 versus 47.4 mm Hg, p=0.029). While there was some loss to follow-up, 63.8% of patients performing exercises (7/11) achieved functional recovery at four weeks compared to 12.5% (1/8) of those who did not (p=0.059). Steroids and antivirals were found to have independent positive effects on improving functional outcome.Conclusions:Eye exercises have a potential role in the treatment of idiopathic cranial nerve VII paresis and warrant consideration in the management of these patients.
Health Status, Stress and Life Satisfaction in a Community Population with MS
Authors: Patten Scott B. , Williams Jeanne V. A. , Lavorato Dina H. , Berzins Sandy , Metz Luanne M. , Bulloch Andrew G. M. 
Published: December 2014

Background:Community-based studies can describe health status and related variables in people with Multiple Sclerosis (MS) while avoiding biases introduced by help-seeking in specific clinical settings.Objective:To describe general health status, stress perceptions and life satisfaction in people with MS, in comparison to those with other types of disabilities.Materials & Methods:The Participation and Activity Limitation Survey (PALS) was a post-censual survey conducted by Statistics Canada in association with the 2006 Canadian Census. PALS collected data from a random sample of n = 22,513 respondents identified as having health-related impairments. Frequencies and quartiles as well as mean values, along with associated 95% confidence intervals, were calculated in the analysis.Results:PALS identified 245 individuals with MS. Health status, both perceived and when weighted for societal preference, was markedly lower than that of other disabled groups. No differences in self-perceived stress were seen. People with MS reported lower levels of satisfaction with their health but slightly higher levels of satisfaction with their family and friends.Conclusions:People with MS report lower levels of general health status and more impairment than those with other disabling conditions. Higher levels of satisfaction with friends and family may reflect psychological adaptation to the illness.