bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Brain-Machine Interfaces for Motor Control: A Guide for Neuroscience Clinicians
Authors: Martin Allan R. , Sankar Tejas , Lipsman Nir , Lozano Andres M.
Published: December 2014

With the growing interdependence between medicine and technology, the prospect of connecting machines to the human brain is rapidly being realized. The field of neuroprosthetics is transitioning from the proof of concept stage to the development of advanced clinical treatments. In one area of brain-machine interfaces (BMIs) related to the motor system, also termed ‘motor neuroprosthetics’, research successes with implanted microelectrodes in animals have demonstrated immense potential for restoring motor deficits. Early human trials have also begun, with some success but also highlighting several technical challenges. Here we review the concepts and anatomy underlying motor BMI designs, review their early use in clinical applications, and offer a framework to evaluate these technologies in order to predict their eventual clinical utility. Ultimately, we hope to help neuroscience clinicians understand and participate in this burgeoning field.
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

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

Background:

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

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.
Stem Cells in Brain Tumour Development and Therapy- Two-Sides of the Same Coin
Authors: Lee Cathy , Dunn Sandra E. , Yip Stephen
Published: December 2014

Primary brain tumours are difficult to manage clinically due to their abilities to invade adjacent tissue and infiltrate distant neuropil. These contribute to challenges in surgical management and also limit the effectiveness of radiotherapy. Despite initial responses to chemotherapy, most tumours become chemo-resistant, leading to relapse. Recent identification and isolation of brain cancer stem cells (BCSCs) have broadened our understanding of the molecular pathogenesis and potential Achilles' heel of brain tumours. BCSCs are thought to drive and propagate the tumour and therefore present an important target for further investigations. This review explores the history of the discovery of BCSCs and the evolving concept of “cancer stem cells” in neuro-oncology. We attempt to present a balanced view on the subject and also to update the readers on the molecular biology of BCSCs. Lastly, we outline the potential strategies to target BCSCs which will translate into specific and effective therapies for brain tumours.
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.
Pathologic Evaluation of the Supraoptic and Paraventricular Nuclei in Dementia
Authors: Diodati David , Cyn-Ang Lee , Kertesz Andrew , Finger Elizabeth
Published: December 2014

Background:

The neuropeptide oxytocin, produced in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, is now understood to function as a neurotransmitter critical for various aspects of social cognition and pro-social behaviour. While patients with Frontotemporal dementia (FTD) display prominent and progressive deficits in such social behaviours, the integrity of these nuclei in FTD is not known.

Methods:

We conducted a quantitative neuropathologic examination of the SON and PVN from patients with FTLD with TDP-43 proteinopathy, Alzheimer's disease, Lewy body disease and controls to determine whether significant pathologic changes or neuronal loss may contribute to the striking behavioural symptoms of FTD.

Results:

Contrary to predictions, we found both nuclei to be free of significant pathologic change (TDP-43) in FTLD. In contrast, tau related pathology was found in the PVN in Alzheimer's disease, and alpha-synuclein pathology in the SON in patients with Lewy body dementia.

Conclusions:

These results indicate that the SON and PVN are resistant to FTLD TDP-43 pathology. They also support prior suggestions that the SON is resistant to Alzheimer's disease (AD) related pathology, and extend this to demonstrate SON susceptibility to alpha-synuclein pathology in patients with Lewy body dementia.
Clinical Overlap between Jakob-Creutzfeldt Disease and Lewy Body Disease
Authors: Tartaglia Maria Carmela , Johnson David Y. , Thai Julie Ngoc , Cattaruzza Tatiana , Wong Katherine , Garcia Paul , DeArmond Stephen J. , Miller Bruce L. , Geschwind Michael D.
Published: December 2014

Objective:

Sporadic Jakob-Creutzfeldt disease (sCJD) and dementia with Lewy bodies (DLB) have overlapping clinical symptoms that can lead to their misdiagnosis. We delineated the clinical overlap between sCJD and DLB, and assessed the value of magnetic resonance imaging (MRI) to differentiate between them.

Methods:

Medical records, MRI, electroencephalogram (EEG) and cerebrospinal fluid (CSF) were reviewed from 56 sCJD and 30 DLB subjects.

Results:

46% of sCJD subjects met probable DLB criteria and 40% of DLB subjects met probable CJD criteria. A greater proportion of sCJD subjects had cerebellar signs (66% vs. 10%, p<0.001), myoclonus (64% vs. 30%, p=0.002), and visual symptoms (other than hallucinations) (61% vs. 7%, p<0.001), whereas more DLB subjects had hallucinations (70% vs. 39%, p=0.007) and fluctuations (57% vs. 23%, p=0.002). Cortical and/or basal ganglia MRI diffusion weighted imaging hyperintensities consistent with sCJD were seen in 96% of sCJD subjects but in none with DLB. Logistic regression in sCJD revealed that those meeting probable DLB criteria were more likely to have occipital lobe involvement on MRI (OR 1.4, p=0.058, model p=0.022). Parietal lobe involvement on MRI was a predictor of “Other Focal Cortical signs” (OR 1.9, p=0.021). EEG and CSF assessments lacked sensitivity for sCJD as 48% of sCJD patients had a negative EEG; 67% of the 36 sCJD patents with a CSF evaluation had a negative or inconclusive 14-3-3 result. Too few DLB patients had EEG or CSF to assess their utility.

Conclusion:

Sporadic CJD and DLB have significant symptom overlap. MRI helps differentiate these diseases and is related to the signs/symptoms observed in sCJD.
Brain Region Specific Monoamine and Oxidative Changes During Restraint Stress
Authors: Ahmad Ausaf , Rasheed Naila , Ashraf Ghulam Md , Kumar Rajnish , Banu Naheed , Khan Farah , Al-Sheeha Muneera , Palit Gautam
Published: December 2014

Background and Purpose:

Stress-induced central effects are regulated by brain neurotransmitters, glucocorticoids and oxidative processes. Therefore, we aimed to evaluate the simultaneous alterations in the monoamine and antioxidant systems in selected brain regions (frontal cortex, striatum and hippocampus) at 1 hour (h) and 24h following the exposure of restraint stress (RS), to understand their initial response and possible crosstalk.

Methods and Results:

RS (150 min immobilization) significantly increased the dopamine levels in the frontal cortex and decreased them in the striatum and hippocampus, with selective increase of dopamine metabolites both in the 1h and 24h RS groups compared to control values. The serotonin and its metabolite levels were significantly increased in both time intervals, while noradrenaline levels were decreased in the frontal cortex and striatum only. The activities of superoxide dismutase, glutathione peroxidase and the levels of lipid peroxidation were significantly increased with significant decrease of glutathione levels in the frontal cortex and striatum both in the 1h and 24h RS groups. There was no significant change in the catalase activity in any group. In the hippocampus, the glutathione levels were significantly decreased only in the 1h RS group.

Conclusions:

Our study implies that the frontal cortex and striatum are more sensitive to oxidative burden which could be related to the parallel monoamine perturbations. This provides a rational look into the simultaneous compensatory central mechanisms operating during acute stress responses which are particular to precise brain regions and may have long lasting effects on various neuropathological alterations.
Carotid Artery Angioplasty and Stenting for Patients Less than 70 Years-of-Age
Authors: Alkins Ryan , Matouk Charles C. , Cruz Juan P. , Marotta Thomas , Montanera Walter , Spears Julian
Published: December 2014

Background:

Recent studies have suggested that carotid artery angioplasty and stenting (CAS) is a safe alternative to carotid endarterectomy (CEA) in average risk patients <70 years of age. We examined a consecutive series of patients who underwent CAS in order to determine the influence of patient age on outcome.

Methods:

A retrospective, longitudinal cohort study of consecutive patients who underwent CAS at St. Michael's Hospital, Canada between January 2001 and November 2010 was performed. The outcome measures were 30-day stroke and 30-day composite death, stroke and acute myocardial infarction (MI). Patients were stratified based on age <70 and ≥70 years.

Results:

One hundred and fifty-nine patients underwent 165 CAS procedures. The 30-day risk of stroke was 3.8% while the composite outcome of death/stroke/MI was 8.2%. When stratified by age <70 and ≥70 years, the 30-day stroke rate was 0% versus 7.4% (p=0.03), and the composite outcome of death/stroke/MI was 2.6% versus 13.6% (p=0.02), respectively.

Conclusions:

Patients <70 years of age undergoing CAS have a low rate of major complications, comparing favourably with historical CEA adverse event rates, and supporting the recent carotid stenosis literature that in the younger population CAS has a similar complication rate compared to CEA.
Conus Medullaris Syndrome as a Complication of Radioisotope Cisternography
Authors: Park Bek-San , Park Jinse , Koh Seong-Ho , Choi Hojin , Yu Hyun-Jeung , Lee Koo-Eun , Lee Young Joo , Lee Kyu-Yong
Published: December 2014

Objective:

Conus medullaris syndrome (CMS) is a clinical neurologic syndrome caused by a conus medullaris lesion. CMS is a heterogeneous entity with various etiologies such as trauma or a space-occupying lesion. Multiple cases of CMS following spinal anesthesia have been reported, but CMS after radioisotope (RI) cisternography has not yet been reported.

Methods:

We present four patients who developed CMS after RI cisternography.

Results:

All experienced neurological deficits such as paraparesis, sensory loss, and urinary incontinence three to four days after RI cisternography. Two showed abnormalities on lumbar magnetic resonance imaging, and three had complete symptom resolution within ten weeks.

Conclusions:

The pathomechanism of the CMS is unclear, but we hypothesize that RI neurotoxicity might be responsible. It is possible that the use of low-dose 99mTc-DTPA or an alternative diagnostic tool such as magnetic resonance cisternography could help to prevent this complication.
MS Patients Report Excellent Compliance with Oral Prednisone for Acute Relapses
Authors: Morrow Sarah A. , McEwan Lynn , Alikhani Katayoun , Hyson Christopher , Kremenchutzky Marcelo
Published: December 2014

Background:

Multiple Sclerosis is characterized by relapses separated by periods of relative quiescence. High dose intravenous corticosteroid pulses for three to five days is the current standard for the treatment of acute relapses, but recent evidence supports the use of equivalent doses of oral therapy as an alternative. The highest single dose preparation of oral prednisone is a 50mg tablet, requiring patients to take 25 tablets a day. Questions regarding compliance with this oral regimen have been raised.

Objectives:

To determine whether MS patients are complaint with 1250mg of oral prednisone daily for acute relapses.

Methods:

Between November 2008 and December 2009, all patients diagnosed with an acute relapse in the London (Ontario) MS clinic were prospectively identified. If treatment with oral prednisone was initiated, subjects were given a survey to be mailed anonymously to the clinic.

Results:

Sixtyeight MS relapses were diagnosed and treated with corticosteroids in 66 patients of which 60 (58 subjects) were treated with 1250mg prednisone. Fifty-three (91.4%) surveys were returned. The reported compliance rate was high at 94.3% (50/53) with only one patient reporting being unable to take all the required pills due to intolerance. Most subjects (43, 86.0%) encountered at least one side effect, most commonly insomnia, mood changes and increased appetite. Two thirds of subjects (69.8%) indicated a preference for oral medication for future relapses.

Conclusion:

High dose (1250mg) oral prednisone is an acceptable therapy to MS patients for the treatment of acute relapses with a high rate of compliance.
Spontaneous Intracranial Hypotension: Recommendations for Management
Authors: Amoozegar Farnaz , Guglielmin Darryl , Hu William , Chan Denise , Becker Werner J.
Published: December 2014

A literature search found no clinical trials or guidelines addressing the management of spontaneous intracranial hypotension (SIH). Based on the available literature and expert opinion, we have developed recommendations for the diagnosis and management of SIH. For typical cases, we recommend brain magnetic resonance (MR) imaging with gadolinium to confirm the diagnosis, and conservative measures for up to two weeks. If the patient remains symptomatic, up to three non-directed lumbar epidural blood patches (EBPs) should be considered. If these are unsuccessful, non-invasive MR myelography, radionuclide cisternography, MR myelography with intrathecal gadolinium, or computed tomography with myelography should be used to localize the leak. If the leak is localized, directed EPBs should be considered, followed by fibrin sealant or neurosurgery if necessary. Clinically atypical cases with normal brain MR imaging should be investigated to localize the leak. Directed EBPs can be used if the leak is localized; non-directed EBPs should be used only if there are indirect signs of SIH.
Prevalence of Nonlesional Focal Epilepsy in an Adult Epilepsy Clinic
Authors: Nguyen Dang Khoa , Mbacfou Manuela Temgoua , Nguyen Dong Bach , Lassonde Maryse
Published: December 2014

Purpose:

To evaluate the prevalence of nonlesional focal epilepsy in an adult epilepsy clinic and its refractoriness to antiepileptic drug therapy.

Background:

Focal epilepsy is frequently, but not always, associated with structural epileptogenic lesions identifiable on magnetic resonance imaging (MRI).

Methods:

We analyzed the data from all patients evaluated at an adult epilepsy clinic from January 2002 to December 2011. Clinical and paraclinical findings were used to diagnose focal epilepsy. Magnetic resonance imaging were reviewed and classified as normal, with an epileptogenic lesion, or with a lesion of unclear epileptogenicity. Epileptogenic lesions were further categorized as tumours, vascular malformations, gliosis (including hippocampal atrophy/sclerosis), and malformations of cortical development. Our study group included patients with no lesions on MRI. Pharmacoresistance of patients with nonlesional focal epilepsy was assessed using the ILAE and Perucca's criterias.

Results:

Out of 1521 patients evaluated (mean age 44 years; range 14-93 years), 843 had focal epilepsy. Magnetic resonance imaging data, available for 806 (96%) subjects, showed epileptogenic lesions in 65%, no obvious epileptogenic lesions in 31% and lesions of unclear epileptogenicity in 4%. Magnetic resonance imaging-identified lesions included gliosis due to an acquired insult (52% including 17% of hippocampal atrophy or sclerosis), tumours (29%), vascular malformations (16%) and malformations of cortical development (10%). Fifty-two percent of nonlesional focal epileptic patients were drug-refractory.

Conclusion:

In a tertiary epilepsy clinic, close to a third of patients with focal epilepsy were found to be nonlesional, half of which were drug-resistant.
Clinical Predictors of EMG-confirmed Cervical and Lumbosacral Radiculopathy
Authors: Hassan Ali , Hameed Bilal , Islam Muhammad , Khealani Bhojo , Khan Mustafa , Shafqat Saad
Published: December 2014

Background:

Electromyography (EMG) for suspected cervical or lumbosacral root compression is often negative, producing expense and physical discomfort that could have been avoided. To improve patient selection for testing, we sought to identify clinical features that would accurately predict presence of radiculopathy on EMG.

Methods:

Adult patients consecutively evaluated for suspected cervical or lumbosacral root compression at an academic clinical neurophysiology laboratory were prospectively enrolled. Presence of clinical features suggesting root disease (neck or back pain, dermatomal pain or numbness, myotomal weakness, segmental reflex loss, and straight leg-raising) was recorded prior to testing. EMG examination to confirm root compression was conducted per standard protocols. Analysis was based on computation of sensitivity, specificity, predictive values, and accuracy.

Results:

A total of 200 patients (55% male; mean age 46.4 years; 38% suspected of cervical and 62% of lumbosacral disease) were included. EMG evidence of root disease was detected in 31% of cervical and 62% of lumbosacral referrals. Dermatomal pain was the most sensitive, and segmental reflex loss and myotomal weakness the most specific individual predictors of root disease. Combined presence of dermatomal pain or numbness with segmental reflex loss and myotomal weakness approached specificities of 78% (lumbosacral disease) and 99% (cervical disease). In all cases, myotomal weakness was the most accurate predictor of root disease.

Conclusion:

The diverse symptoms and signs of cervical and lumbosacral root compression predict a positive electrodiagnosis of radiculopathy with varying degrees of accuracy, and may be used to guide patient selection for EMG testing.
Early-Onset Familial Alzheimer's Disease (EOFAD)
Authors: Wu Liyong , Rosa-Neto Pedro , Hsiung Ging-Yuek R. , Sadovnick A. Dessa , Masellis Mario , Black Sandra E. , Jia Jianping , Gauthier Serge
Published: December 2014

Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.
Outcomes of Surgically Treated Giant Pituitary Tumours
Authors: Cusimano Michael D. , Kan Peter , Nassiri Farshad , Anderson Jennifer , Goguen Jeannette , Vanek Irene , Smyth Harley S. , Fenton Ronald , Muller Paul J. , Kovacs Kalman
Published: December 2014

Objective:

To evaluate the outcomes of patients with giant pituitary tumours (GPTs) who underwent a purely binasal endoscopic transsphenoidal surgery (BETS) and compare their outcomes with those achieved through craniotomy and microscopic transsphenoidal surgery (MTS).

Methods:

Seventy-two consecutive patients with GPTs (greater than 10 cm3 in volume) who were treated surgically with BETS, craniotomy, or MTS from October 1994 to July 2009 were reviewed for clinical outcomes, degree of tumor resection, recurrence rates, and surgical complications.

Results:

The BETS group had significantly better mean reduction of tumor volume (91%) than the craniotomy (63%, p = 0.001), and the MTS (63%, p = 0.010) groups. Gross total resection rates were also higher for BETS patients than for craniotomy patients (p = 0.010). Improvements in vision and headaches were noted in 96% and 100% of patients in the BETS group, respectively; these rates were similar to those in the craniotomy and MTS groups. Of the four patients with hormone-secreting tumours in the BETS group, three remained in remission. The median length-of-stay (four days) for the BETS group was shorter (p = 0.010), and surgical complications were less frequent (p = 0.037) and less severe compared to the craniotomy group. There were no differences in the recurrence rates: 79% percent of patients in the BETS group, 69% in the craniotomy group, and 79% in the MTS group were recurrence free at last follow-up (p = 0.829).

Conclusions:

Treatment of GPT with BETS offers excellent oncologic and clinical outcomes and can frequently obviate the need for craniotomy in these patients.
Routine CT Angiography in Acute Stroke Does Not Delay Thrombolytic Therapy
Authors: Bal Simerpreet , Menon Bijoy K. , Demchuk Andrew M. , Hill Michael D. ,   for the Calgary CTA Study Group
Published: December 2014

Introduction:

Lack of additional utility over non-contract computed tomography (NCCT) in decision making and delay in door to needle time are arguments used against routine computed tomographic angiography (CTA) use in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center.

Methods:

We reviewed 850 stroke thrombolysis patients in a university hospital in Canada from April 1996 to December 2009. Time to treatment was divided into the following interval times: onset-to-door, door-to-needle and onset-to-needle. Patients were categorized into: Group 1 (April 1996-Dec 2002) (Non-contrast CT Scan based thrombolysis) n=297, Group 2 (Jan 2004-Dec 2009) (CTA based thrombolysis) n=504. The period from Jan to Dec 2003 (n=49) was considered a washout period as we had started the CTA protocol that year. Interval times were compared between the two groups.

Results:

Interval times in Group 1 and Group 2 were: median onset-to-door times in Group 1 [55 minutes (IQR 48),] and Group 2 [61 minutes (IQR 57)] (p=0.019); median door-to-needle times in Group 1 [67 minutes(IQR 43)] and Group 2 [62.5 minutes (IQR 52)] (p=0.519); median onset-to-needle times in Group 1 (139 minutes (IQR 73)] and Group 2 (141.5 min (IQR 109.5) (p=0.468). In multivariable linear regression analysis, age and onset-to-door time influenced the door-to-needle time. For every decade of age, door-to-needle times were 5.4 minutes faster.

Conclusions:

CTA based thrombolytic approach for acute ischemic stroke does not significantly delay thrombolysis in routine clinical practice.
Variability of Phenotype in Two Sisters with Pyridoxine Dependent Epilepsy
Authors: Alfadhel Majid , Sirrs Sandra , Waters Paula J. , Szeitz András , Struys Eduard , Coulter-Mackie Marion , Stockler-Ipsiroglu Sylvia
Published: December 2014

Background:

Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. Recently an autosomal recessive deficiency in Antiquitin (ALDH7A1), a gene involved in the catabolism of lysine has been identified as the underlying cause.

Case report:

In 21 and 23 year-old sisters, who had presented with neonatal / early infantile onset seizures, PDE was confirmed by elevated urinary alpha aminoadipic- 6- semialdehyde (α-AASA) excretion and compound heterozygosity for two knownALDH7A1missense mutations. Although epilepsy was well controlled upon treatment with pyridoxine, thiamine, phenytoin and carbamazepine since early infancy, both had developmental delay with prominent speech delay as children. As adults, despite the same genetic background and early treatment with pyridoxine, their degree of intellectual disability (ID) differed widely. While the older sister's cognitive functions were in the moderate ID range and she was not able to live unattended, the younger sister had only mild ID and was able to live independently.

Conclusion:

Although seizures are a defining feature of PDE, other disease manifestations can vary widely even within the same family. Adult neurologists should be aware that the diagnosis of PDE can be delayed and PDE should be considered in the differential diagnosis of adults with seizure disorders dating from childhood.
Levator Palpebrae Biopsy and Diagnosis of Progressive External Ophthalmoplegia
Authors: Pfeffer Gerald , Waters Paula J. , Maguire John , Vallance Hilary D. , Wong V. A. , Mezei Michelle M.
Published: December 2014

Background:

Progressive external ophthalmoplegia (PEO) is a mitochondrial myopathy of ocular muscles. Diagnostic investigation usually involves limb skeletal muscle biopsy and molecular genetic studies, although diagnostic yield tends to be low. The purpose of this study was to evaluate the diagnostic yield obtained by analysis of levator palpebrae (LP) muscle tissue.

Methods:

This is a clinicopathologic study of 8 patients with a diagnosis of PEO, who had LP muscle biopsies as part of oculoplastic procedures. Six of these patients also had limb muscle biopsies. Histopathology, electron microscopy and genetic studies were performed.

Results:

Diagnostic histopathologic findings were present in 4/6 quadriceps biopsies, and 7/8 LP biopsies. Genetic testing on DNA extracted from LP muscle revealed abnormalities in 4 patients.

Conclusion:

In patients whose LP muscle demonstrate both genetic defects and histopathological abnormalities, the diagnosis of PEO can be confirmed without limb muscle biopsy. Patients having LP resection during oculoplastics procedures for treatment of ptosis may therefore be able to avoid a separate procedure for limb muscle biopsy. Further study is required to determine the specificity of these findings.
The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas
Authors: Wu Wenhao , Tian Yongji , Wan Hong , Song Yongmei , Li Junhua , Zhang Liwei
Published: December 2014

Background:

The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.

Methods:

This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.

Results:

Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.

Conclusions:

Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.
Priority Setting in Neurosurgery as Exemplified by an Everyday Challenge
Authors: Ibrahim George M. , Tymianski Michael , Bernstein Mark
Published: December 2014

Background:

The allocation of limited healthcare resources poses a constant challenge for clinicians. One everyday example is the prioritization of elective neurosurgical operating room (OR) time in circumstances where cancellations may be encountered. The bioethical framework, Accountability for Reasonableness (A4R) may inform such decisions by establishing conditions that should be met for ethically-justifiable priority setting.

Objective:

Here, we describe our experience in implementing A4R to guide decisions regarding elective OR prioritization.

Methods:

The four primary expectations of the A4R process are: (1) relevance, namely achieved by support for the process and criteria for decisions amongst all stakeholders; (2) publicity, satisfied by the effective communication of the results of the deliberation; (3) challengeability through a fair appeals process; and (4) Oversight of the process to ensure that opportunities for its improvement are available.

Results:

A4R may be applied to inform OR time prioritization, with benefits to patients, surgeons and the institution itself. We discuss various case-, patient-, and surgeon-related factors that may be incorporated into the decision-making process. Furthermore, we explore challenges encountered in the implementation of this process, including the need for timely neurosurgical decision-making and the presence of hospital-based power imbalances.

Conclusion:

The authors recommend the implementation of a fair, deliberative process to inform priority setting in neurosurgery, as demonstrated by the application of the A4R framework to allocate limited OR time.