bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Absorption and Disposition of alpha‐Linolenic, Rumenic and Vaccenic Acids After Administration as a Naturally Enriched Goat Dairy Fat to Rats
Authors: Rodríguez‐Alcalá Luís Miguel , Ares Irma , Fontecha Javier , Juarez Manuela , Castellano Victor , Martínez‐Larrañaga María Rosa , Anadón Arturo , Martínez María Aránzazu
Published: June 2015

Although there is extensive information describing the positive biological effects of conjugated linoleic acid and its main isomer rumenic acid (RA; C18:2 cis 9, trans 11), and alpha‐linolenic acid (ALA) and vaccenic acid (TVA), data about their bioavailability are not available. In this work, we investigated the oral absorption and disposition of these fatty acids in Wistar rats. A naturally enriched goat dairy fat (EDF) was obtained by supplementing ruminant diets with oils or oilseeds rich in polyunsaturated fatty acids (PUFA). The EDF was administered orally (single dose of 3000 mg EDF/kg body weight equivalent to 153 mg TVA/kg body weight, 46 mg RA/kg body weight and 31 mg ALA/kg body weight), and serial blood and liver samples were collected and TVA, RA and ALA concentrations determined by GC/MS. The fatty acids TVA, RA and ALA were rapidly absorbed (t1/2a, 0.36, 0.66 and 0.76 h, respectively, for plasma) and slowly eliminated (t1/2β, 17.04, 18.40 and 16.52 h, respectively, for plasma). The maximum concentration (Cmax) was detected in liver > plasma > erythrocyte. Our study shows that when orally administered EDF, its components TVA, RA and ALA were rapidly absorbed and distributed throughout the body by the blood circulation to exert systemic effects.
A Screening Method to Evaluate Soybean Oil‐Based Biodiesel Oxidative Quality During Its Shelf Life
Authors: Pereira Gustavo G. , Alberici Rosana M. , Ferreira Lucas L. , Santos Jandyson M. , Nascimento Heliara L. , Eberlin Marcos N. , Barrera‐Arellano Daniel
Published: June 2015

Biodiesel quality is negatively affected by oxidation, which occurs primarily during the storage and distribution steps. Therefore, the use of suitable analytical methods to assess the oxidation of this biofuel is a fundamental requirement. A direct ambient ionization mass spectrometric technique (EASI‐MS) was tested as a screening method to evaluate the oxidative quality of biodiesel during its shelf life. Using EASI‐MS, the relative abundance of the hydroperoxide ion of m/z 349 was monitored during the induction period (IP) in soybean and a blend of soybean/beef‐tallow (70/30) biodiesel samples. The peroxide value obtained by AOCS Cd 8b‐90 was used as a standard method to evaluate the EASI‐MS data by comparison. The results showed that the peroxide value and EASI‐MS data were highly correlated during the IP for both samples (r > 0.98). Relative abundances of the ion of m/z 349 below 72 % was also found to characterize biodiesel in an initial oxidation stage, whereas abundances exceeding 72 % indicated biodiesel samples nearing the end of their stability. EASI‐MS was therefore found to provide a simple and effective analytical protocol to evaluate the oxidative quality of biodiesel during the IP.
Application of Infrared Spectroscopy for Characterization of Dietary Omega‐3 Oil Supplements
Authors: Plans Marçal , Wenstrup Michael J. , Rodriguez‐Saona Luis E.
Published: June 2015

Fish oil dietary supplements have been linked with health benefits, due to high omega‐3 concentration. The sources of these effects, polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, are almost exclusively found in seafood products. Our objectives were to characterize the composition of commercial omega‐3 dietary supplements dietary supplements and to generate partial least square regression (PLSR) models using infrared spectroscopy and chemometrics. Fatty acid (FA) composition of oils was determined by FA methyl ester gas chromatography. The supplements encompassed a wide range of FA profiles and delivery methods. Infrared spectral data were collected by portable mid‐infrared Fourier transform infrared (MID FT‐IR) equipment. Principal components analysis (PCA) separated samples based on the type of ester present in the fish oil dietary supplements, showing a strong influence of the 1038 cm−1 band, which is typically associated with C=C and C–O stretching vibrations. In addition, PLSR was used to correlate the spectra data with GC‐FAME results. PCA using the spectroscopy data allowed for tight clustering of fish oil into distinct classes, depending on the source and processing. PLSR using MID FT‐IR spectra and FA composition generated multivariate models with high correlation coefficient (R ≥ 0.93), and SEP between 0.53 and 2.13 g of FA per 100 g of oil. Our results indicate that IR spectroscopy combined with chemometrics provides for robust screening of FA composition of fish oil supplements, and discriminate types of FAs esterification.
Existence and uniqueness of a density probability solution for the stationary Doi–Edwards equation
Authors: Ciuperca Ionel Sorin , Heibig Arnaud
Published: June 2015

We prove the existence, uniqueness and non-negativity of solutions for a nonlinear stationary Doi–Edwards equation. The existence is proved by a perturbation argument. We get the uniqueness and the non-negativity by showing the convergence in time of the solution of the evolutionary Doi–Edwards equation towards any stationary solution.
Lagrangian flows for vector fields with anisotropic regularity
Authors: Crippa Gianluca , Bohun Anna , Bouchut François
Published: June 2015

We prove quantitative estimates for flows of vector fields subject to anisotropic regularity conditions: some derivatives of some components are (singular integrals of) measures, while the remaining derivatives are (singular integrals of) integrable functions. This is motivated by the regularity of the vector field in the Vlasov–Poisson equation with measure density. The proof exploits an anisotropic variant of the argument in [14,20] and suitable estimates for the difference quotients in such anisotropic context. In contrast to regularization methods, this approach gives quantitative estimates in terms of the given regularity bounds. From such estimates it is possible to recover the well posedness for the ordinary differential equation and for Lagrangian solutions to the continuity and transport equations.
Recent Canadian neurosurgery graduate employment outcomes
Authors: Tso MK , Findlay JM , Lownie SP , Wallace MC , Toyota BD , Fleetwood IG
Published: June 2015

Background: The American Board of Neurological Surgeons (ABNS) made persons beginning neurosurgical training in Canada after 1997 ineligible for ABNS board exams and certification in the United States (US). We set out to track employment outcomes for graduates who are “ABNS ineligible.” Methods: Graduates from Canadian neurosurgical programs who began training from 1998 to 2008 (ABNS ineligible) were followed regarding their employment status (n=143). Data was obtained from public-domain websites and direct connections though Canadian Neurosurgical Society (CNSS) members. Association between pursuit of research during residency (MSc, PhD, or ≥ 2 years of non-degree research) and full employment was determined by Fisher’s exact test. Results: 60% and 26% of graduates currently have full-time staff positions in Canada and the US, respectively. “Underemployment,” defined as failure to secure a full-time position in neurosurgery despite a desire to do so (including locums, additional fellowship positions, unemployment and career changes) is currently seen in 12% of graduates, with 20% having been underemployed at some point within 5 years of graduation. Pursuit of research during residency was significantly associated with obtaining full employment (94% vs. 73%, p=0.011). Conclusions: Underemployment is a significant issue in recent neurosurgical graduates from Canadian training programs. Research training during residency appears strongly associated with obtaining full employment.
Regional variation in lumbar spine surgery in Saskatchewan: a population-based analysis
Authors: Fourney DR , Dalkilic T , Barrett P , Buwembo J , Ekong C , Groot G
Published: June 2015

Background: Unexplained significant variation may suggest a quality care problem in a health care system. The objective of this study was to determine the extent of variance in spine surgery Saskatchewan and determine possible causes. Methods: Provincial billing records for new spine surgery consultations from May 2011 through October 2012 were correlated with subsequent lumbar surgery. Two tertiary centers (TC1 and TC2) were compared with reference to the Health Region of origin of the patient. Wait times for surgery and utilization of spine pathway clinics was analyzed. Results: TC1 had significantly higher rates of spine fusion and lumbar spine surgery. The percentage of new referrals that went to surgery was 14.0% in TC1 and 11.8% in TC2 (p<0.0001, Z-Test). Population-based calculation of the rate of new referrals was 1581/482387 = 0.33% for TC1 vs. 970/601739 = 0.16% for TC2 (p<0.0001, Z-Test). Utilization of the spine pathway clinic was lower and wait times for surgery were longer in TC1. Conclusions: Causes of regional variation are unknown and likely multifactorial. In Saskatchewan, the most striking variance was that the rate of primary care referrals for lower back conditions in regions served by TC1 was double that for TC2. This could potentially be reduced through more regionally consistent utilization of the spine pathway.
Successful treatment of paroxysmal tonic upgaze with low dose Gravol ®
Authors: Sawicka K , Huntsman R
Published: June 2015

Background: We present a case of paroxysmal tonic upgaze (PTU) of infancy treated with a daily low dose of Gravol ® to improve symptoms. Method: Case report Results: A one year-old boy presented with episodes of sustained conjugate upgaze that persisted for 30 to 45 minutes, varied in severity, and occurred with increasing frequency over the past two months. The episodes were worse when fatigued and were relieved by sleep. Pregnancy, delivery, and development were normal. Neurological examination between episodes was normal, as were EEG, brain MRI, and blood analysis. CSF neurotransmitter analysis showed serotonin and dopamine metabolites at lower levels of normal. The patient was diagnosed with paroxysmal tonic upgaze of infancy and was treated with 12.5 mg of Gravol ® daily with complete cessation of episodes. Conclusions: Paroxysmal tonic upgaze (PTU) of infancy is a disorder seen in infants where the eyes are forcibly deviated upwards for minutes to hours at a time. PTU often resolves spontaneously over several months, however episodes are extremely debilitating. Currently, treatments with levodopa have been tried with some success. Via its anticholinergic effects, Gravol may be a novel therapeutic option for PTU, negating the need to use serotonergic medications.
EEG in asymptomatic relatives of idiopathic epilepsy; a prospective study
Authors: Duaa BM , Boelman C , Brunga L , Minassian BA , Andrade D
Published: June 2015

Introduction: The mainstay of diagnosis in Idiopathic Epilepsies (IE) is the electroencephalogram (EEG). The characteristic EEG of each syndrome is an electrographic endophenotype of the larger clinical phenotype of each and more directly associated with potential gene defects than the full phenotype. Endophenotypes represents primary abnormalities elicited by the gene defect, which, in some patients, blossom into full seizures. Revealing the percentage of abnormal EEGs in asymptomatic relative of patients with IE may help to describe the mode of inheritance that would help the ongoing genetics studies to discover the pathologic gene defect. Method: This is a prospective cohort study to identify the percentage of abnormal EEG in asymptomatic first-degree relatives of patients with IE Results: 20 out of 141 EEGs (14%) of first-degree relatives were abnormal. The abnormalities included generalized polyspikes and waves , generalized 3-Hz spike and waves or centro-temporal spikes in 50% of the abnormal EEGs. 50% of the abnormalities were nonspecific. Conclusion: These results may indicate that the EEG endophenotypes in IEs do not follow a Mendelian pattern of inheritance. Nevertheless, the EEG endophenotype is relatively common and thus genetically simpler than the full epilepsy, which will aid in gene identification
Progressive contralateral hippocampal atrophy following Temporal Lobe Epilepsy Surgery (TLS)
Authors: Elliott CA , Yasuda C , Concha L , Liu M , Wheatley M , Beaulieu C , Sankar T
Published: June 2015

Background: Temporal Lobe Epilepsy is associated with bilateral gray (GM) and white matter (WM) loss. After surgical treatment progressive bilateral temporal and extra-temporal WM change occur, however, less is known regarding post-operative GM change. We set out to measure contralateral hippocampal volume (CHV) following TLS. Methods: 1.5T-3D-1mm-isotropic-MPRAGE scans in 26 TLE patients and 3 controls in two groups: longitudinal (n=10)(imaged POD1,2,3,6,60,120 and >360d) and single post-operative scan (n=16). Manual volumetry protocols. Results: We find significant CHV atrophy at delayed scan relative to baseline (mean atrophy 26.8%). In the longitudinal group there is significant and progressive atrophy from baseline to POD4-8 (72.6+/-6.5%), POD60-360 (69.7+/-12.3%) and >360 (58.5+/-10.6%). No significant atrophy in either the control group HV or contralateral CV over time. No significant difference in mean HV at the most delayed exam for surgery type (p=0.13) or side (p=0.24). Conclusions: We find a statistically significant CHV atrophy following surgery which is progressive over time. Our longitudinal within-subject design describes the time course and extent more fully than previous work. Caudate analysis indicates that early CHV atrophy is not due to global atrophy following brain surgery but rather may be due to deafferentation and deefferentation. Finally, we find no significant difference in atrophy when analyzed by surgical approach or surgical side.
Neurology (General Neurology)
Authors: Alkhotani A , Alrishi N , Alhalabi M
Published: June 2015

Background: Leptomeningeal Carcinomatosis (LMC) is defined as a diffuse or multifocal malignant infiltration of the Pia matter and arachnoid membrane. It is clinically diagnosed in 5-10% of all cancer patients. The most commonly reported cancers associated with LMC are breast, lung and hematological malignancies. Patients with LMC commonly present with multifocal neurological symptoms. Symptoms are related to increase intracranial pressure, hemispheric dysfunction, cranial neuropathies and spinal roots dysfunction. We report a case of LMC secondary to Gastroesophageal junction cancer present initially with Cauda equine syndrome. Methods: A 51 year old male patient with adenocarcinoma of Gastroesophageal junction who underwent surgical resection, chemotherapy and radiation therapy. Nine month after diagnosis he presented with left leg pain, mild weakness and saddle area numbness. Initial radiological examination were unremarkable. Subsequently he had worsening of his leg weakness, fecal incontinence and urine retention. Two days later he developed rapidly progressive cranial neuropathies including facial diplegia, sensorineural hearing loss, dysarthria and dysphagia. Results: MRI with and without contrast showed diffuse enhancement of leptomeninges surrounding the brain, spinal cord and Cauda equine extending to the nerve roots. Cerebrospinal fluid cytology was positive for malignant cells. Conclusion: In cancer patient with Cauda equina syndrome and absence of structural lesion on imaging, LMC should be considered.
Dancing eyes: a case of opsoclonus, tremor and truncal ataxia secondary to West Nile encephalitis
Authors: Wasyliw S , Hunter G , Moien F
Published: June 2015

Background: Opsoclonus can result from paraneoplastic, parainfectious, autoimmune, ischemic or toxic etiologies. Neuroinvasive complications develop in less than one percent of individuals infected with West Nile Virus. Methods: Case report. Results: A 63-year-old female presented with subacute disorientation, dizziness, oscillopsia, and unsteady gait, associated with fever. Examination demonstrated opsoclonus, bilateral upper extremity postural and action tremor and truncal ataxia. MRI of the brain was normal. CT of the body showed no evidence of neoplasia. Vasculitic and paraneoplastic panels were negative. An extensive infectious work-up was only positive for West Nile IgM antibodies. She was treated with clonazepam and received a five-day-course of IVIG. Her symptoms improved after treatment and she continued to demonstrate gradual recovery during the months following her discharge. Conclusions: There are only a few published case reports of WNV-associated opsoclonus, and our patient appears to be the oldest reported with this constellation of neurological symptoms. Even though treatment for WNV is mostly supportive, this case demonstrates the importance of a thorough work-up in patients of similar presentations to determine the etiology and to guide early immunomodulation in selected cases. Video available.
Natalizumab-associated progressive multifocal leukoencephalopathy occurring at low positive anti-JC virus antibody level
Authors: Parks NE , Bhan V
Published: June 2015

Background: Risk of progressive multifocal leukoencephalopathy (PML), a serious adverse event of natalizumab therapy, is higher with positive anti-JC virus antibody status, greater cumulative exposure to natalizumab and prior immunosuppressant use. Plavina et al. (2014) showed that plasma or serum anti-JC virus antibody index value may allow further PML risk stratification. Among anti-JC virus antibody positive multiple sclerosis patients with no prior immunosuppressant treatment receiving natalizumab, anti-JC virus antibody index >6 months prior to PML diagnosis was significantly higher among those who developed PML with 96% consistently having an anti-JC virus antibody index >0.9. Methods: We describe a case of natalizumab-associated PML with low positive anti-JC virus index value prior to diagnosis. Results: A 53 year old man with 20 year history of relapsing remitting multiple sclerosis was diagnosed with PML following 46 infusions of natalizumab. Glatiramer acetate was his only prior immunomodulatory therapy. Routine MRI surveillance resulted in diagnosis of PML following detection of a confluent right anterior frontal T2 hyperintense lesion extending across the corpus callosum. Six months prior, routine MRI surveillance demonstrated a small right frontal T2 hyperintensity with no diffusion restriction while serum anti-JC virus antibody index was 0.69. Conclusions: Natalizumab-associated PML may develop despite low positive anti-JC virus index value.
Prolonged-release fampridine as adjunct therapy to active enabled motor training in multiple sclerosis patients: a pilot, double-blind, placebo-controlled study
Authors: Jacques FH , Schembri A , Nativ A , Paquette C , Kalinowski P
Published: June 2015

Objectives: To investigate if MS subjects treated with PRF 10mg BID will show a greater benefit from active enabled motor training compared with placebo. Methods: Single center, phase 4, pilot, placebo-controlled, double-blind 18 weeks study. Fifteen patients were randomized to receive PRF 10 mg BID and fifteen to received placebo BID. All patients participated in active enabled motor training of 3 sessions of 1 hour/week for 6 weeks. Patients were evaluated at -4, 0, 6 and 14 weeks using the timed 8 meters walk (8 MW), the 6 minute walk (6 MW) and the timed sit to stand (STS). Results: The PRF treated group achieved a higher mean percent improvement from baseline in all tasks at both 6 and 14 week time points. The difference reached statistical significance (mean difference of 14.29, p=0.046) for the 8MW at the 14 week time point. A higher incidence of responders (>20% improvement from baseline) was seen in the PRF treated group at 6 weeks on the 8MW (odds ratio [OR] of 2.31) and the 6MW (OR of 1.63), and at 14 weeks on the 8MW and the STS (OR of 2.0). Conclusions: PRF in MS patients appears to enhance the benefit of active enabled motor training and to better sustain it over the following 8 weeks.
Neurology (Neuromuscular)
Authors: Wang Y , Zhu Y , Zhang W , Liu M , Li G , Zhang H
Published: June 2015

Background: IL-27 acts as a ‘master regulator’ in modulating inflammation and was responsible for a number of autoimmune diseases. However, the role of IL-27 was not addressed in Guillain-Barré syndrome (GBS). Methods: Sixty-five subjects including 19 with GBS, 7 with encephalitis or meningitis, 23 with multiple sclerosis or neuromyelitis optica as well as 11 with other non-inflammatory neurological disorders were enrolled. ELISA was used to detect the concentrations of IL-27 in paired samples of cerebrospinal fluid and plasma. Results: The mean concentration of IL-27 in GBS patients was significantly lower than in other neurological disorders both in CSF and in plasma (all p<0.05). GBS patients with cranial involvement, decreased reflexes, hypaesthesia, autonomic nerve dysfunction, MRC score <30 are inclined to have a lower CSF IL-27 level than patients without these symptoms (182 pg/ml, 181 pg/ml, 185 pg/ml, 185 pg/ml, 194 pg/ml vs 211 pg/ml, 205 pg/ml, 202 pg/ml, 198 pg/ml, 199 pg/ml, respectively). Similar results were noted in plasma except for cranial involvement. Conclusions: Production of IL-27 was disparate between GBS and other neurological diseases and a significantly lower level of IL-27 was observed in GBS patients, indicative of an anti-inflammatory role of IL-27 in GBS.
Auto-antibodies against gangliosides in patients with Charcot-Marie-Tooth disease
Authors: Catapano M , Ewart T , Baker S
Published: June 2015

Background: In Charcot-Marie Tooth (CMT), vital components of either the myelin sheath or axon are abnormal, slowing nerve conduction and causing functional disability. Recently, there has been speculation the CMT may have an autoimmune component resulting from abnormal protein expression. Methods: Custom autoimmune neuropathy-focused microarray panels were printed in-house using antigens from Sigma, Abnova, Fitzgerald and Matreya according to Cambridge Life Science instructions. Antigens including Myelin Protein Zero, Peripheral Myelin Protein 22, and 20 other well-known gangliosides were tested for IgM and IgG antibodies. Students T-Test and Bonferroni correction factor were used to determine statistical significance between groups and in post-hoc subgroup analysis. Results: Plasma was tested from 17 patients with CMT and 25 young healthy individuals. CMT population consisted of 9 CMT-1a, 1 CMT-1b, 4 CMT-2a, 2 CMT-2f and 2 undetermined CMT type 2 patients. No ganglioside reached statistical significance under a Bonferroni Correction factor (p>0.01) nor were any gangliosides notably raised compared to normal. Sub-group analysis did not reveal theorized peak auto-antibodies levels depending upon their CMT sub-type compared to normal. Conclusions: Although previously shown to have increased auto-antibodies to myelin or axonal proteins, CMT individuals did not demonstrate increased autoantibody levels for the proteins tested at our centre.
Novel VCP mutation associated with CMT2 phenotype
Authors: Steven BK
Published: June 2015

Background: Charcot-Marie-Tooth (CMT) neuropathy is an increasingly polygenic disorder which limits clinical diagnoses due to phenotypic overlap resulting from the common final pathway of length-dependent axonal degeneration. The proband exhibited features of an axonal neuropathy manifesting upper and lower extremity distal amyotrophy, mild sensory loss, absent upper motor neuron findings, and mild hyperCKemia. Methods: Whole-exome sequencing (WES) was performed after failure to identify the familial variant with sequencing of multiple discrete CMT2 genes. Results: A novel VCP mutation (c.511A>C;p.Ser171Arg) was identified. This mutation segregated with an affected brother and father. All manifested a CMT2 phenotype with motor predominance. Further investigation of the proband revealed 1) a muscle biopsy with no inclusions or myopathic changes, 2) a skeletal survey negative for lucencies and hyerostoses, and 3) normal cognitive function. Conclusions: Mutations in valosin-containing protein (VCP) are associated with distinct neurologic phenotypes including 1) inclusion body myopathy, Paget disease, and frontotemporal dementia, 2) hereditary spastic paraplegia, and 3) amyotrophic lateral sclerosis. Recently, CMT2 has been described as a VCP-associated phenotype. This is the second report of a peripheral neuropathic phenotype resulting from a mutation in the VCP gene. The clinical presentation in this family suggests a unique clinical-biochemical phenotype consisting of motor-predominant CMT2 with mild hyperCKemia.
Violence-related brain injuries sustained in youth ice hockey
Authors: Shirazi M , Cusimano MD , McFaull S
Published: June 2015

Background: Violence is a frequent occurrence in ice hockey and has been associated with an increased risk of injury. Methods: Case-control study. The study population consisted of youth aged 0-19 years who presented to a participating emergency department (ED) with an injury resulting from participation in ice hockey. In order to examine the outcomes following brain injuries in ice hockey, the outcome was admission to the hospital (cases) or discharge from the ED (controls). In order to examine the relationship between brain injury and violence, the outcome was brain injury (cases) or a non-brain injury (controls). Logistic regression was used to determine the associations controlling for potential confounders. Results: In total, 56,835 youth suffered an injury related to ice hockey. 11.0% (n=6,293) were brain injuries. Youth who engaged in violence were at significantly higher odds of sustaining a brain injury as opposed to an injury to another body part (OR: 1.67; 95% CI: 1.55-1.80). Youth who sustained violence-related injuries were at significantly higher odds of being admitted to the hospital compared to youth who sustained non-violence related injuries (OR: 2.34; 95% CI: 1.49-5.68). Conclusions: Youth who engage in violence are at higher odds of sustaining a brain injury and of being admitted to the hospital.
Brain injuries sustained by Canadian youth participating in Rugby Union
Authors: Shirazi M , Cusimano MD , Di Michele J , McFaull S
Published: June 2015

Background: Rugby is a high-intensity, full-body contact sport in which there is an increased risk of injury associated with participation. The objectives of this study were to identify the mechanisms and characteristics of rugby-related injury sustained amongst Canadian youth. Methods: Data were obtained from the Canadian Hospitals Injury Reporting and Prevention Program database. The study population consisted of individuals aged 10-19 who sustained an injury while participating in rugby between the years 1990 and 2014. Proportions of body parts injured, mechanisms of brain injury, and nature of injury were calculated with 95% confidence intervals. Results: There were a total of 6200 rugby-related injuries sustained among individuals aged 10-19 between the years 1990 and 2014. 16.0% (N=993) of all injuries were brain injuries, 48.9% (n=486) of which were concussions. 70.7% (n=4838) of all injuries were sustained by males. The predominant mechanism of brain injury was tackling which accounted for 48.3% of all brain injuries n=480. Conclusion: Participation in rugby is rapidly increasing, and brain injury as a result of participation is a common occurrence. Possible changes to reduce injury include stricter penalties for high tackles to the head and neck area, and rules against blindside tackles.
Use of drains versus no drains after burr-hole evacuation of chronic subdural hematoma
Authors: Moores M , Fenerty L , Thibault-Halman G , Kureshi N , Walling S , Clarke DB
Published: June 2015

Background: Chronic subdural hematomas (cSDH) are a common neurosurgical problem with significant morbidity and mortality. Current treatment methods are variable. Post-operative subdural drain used in conjunction with burr-hole craniostomy may reduce recurrence. This study compared recurrence rates for cSDH between two surgical practices with and without use of post-operative subdural drain at the QEII Health Sciences Center. Methods: A retrospective chart review was conducted to compare recurrence rates between surgical patients treated with or without a post-operative drain between 1997- 2012. The primary endpoint was recurrence, defined as occurrence of symptoms due to hematoma confirmed by CT within six months of the original operation. Categorical frequencies were compared with chi square or Fisher’s exact test. Logistic regression was performed to identify risk factors for recurrence. Results: There were 85 patients (mean age 73 years; SD 13.0) who had burr-hole craniostomy. Age, cSDH volume, site, GCS, anticoagulation, drain, conservative treatment with steroids and perioperative steroids were not found to be independent predictors of recurrence. Recurrence occurred in 2 of 34 (5.9%) patients with drain, and in 7 of 51 (13.7%) without (p=0.305). There were insufficient data to compare mortality and complications. Conclusions: Use of post-operative subdural drain did not significantly alter the cSDH recurrence rate.
Acute stress decreases bimanual psychomotor performance during resection of simulated brain tumors
Authors: Bajunaid K , Winkler-Schwartz A , Fares J , Baggiani M , Christie S , Alotaibi F , Al Zharni G , Sabbagh A , Azarnoush H , Werthner P , Delmaestro RF
Published: June 2015

Background: Objective methods to assess the influence of significant stress on neurosurgical bimanual psychomotor performance have not been developed. We utilized NeuroTouch, a virtual reality simulator, to answer two questions: 1) What is the impact of significant stress on bimanual psychomotor performance during the resection of a simulated tumor? 2) Does stress influence performance immediately following the stressful episode? Methods: Uncontrollable ‘intraoperative’ bleeding during one of the tumor resections resulting in simulated patient cardiac arrest served as the acute stressor. Six neurosurgeons, 6 senior and 6 junior neurosurgical residents and 6 senior medical students were studied. The evaluated advanced tier 2 metrics were efficiency index, ultrasonic aspirator path length index, suction coordination index and ultrasonic aspirator bimanual forces ratio. Results: The stress scenario significantly decreased the efficiency index of all groups and significantly decreased performance for many groups for suction coordination index and ultrasonic aspirator path length index. Performance in all advanced tier 2 metrics returned to pre-stress levels in post stress resection scenarios. Conclusions: Our results are consistent with the concept that acute stress initiated by severe intraoperative bleeding significantly decreases bimanual psychomotor performance during the acute episode but had no significant influence on immediate post stress operative performance.
Importance of ventricle-to-brain ratio (VBR) and volume of CSF drainage in the treatment of very low pressure hydrocephalus
Authors: Houlden D , Li M , Portman S
Published: June 2015

Introduction: Low pressure hydrocephalus is a known complication of prolonged hydrocephalus sometimes treatable with continued low-pressure drainage at subatmospheric pressures. Clarke et. al. and Filipidis et. al. have reported poor outcomes when treating very low pressure hydrocephalus (VLPH). We present 4 cases of very low pressure hydrocephalus (VLPH) following transnasal endoscopic resection of suprasellar lesions and hypothesize that poor prognostic cases can be identified thereby avoiding prolonged futile treatments. Methods: We performed a retrospective chart review of 4 cases of VLPH and tried to identify metrics contributing to successful treatment. We examined the Pearson correlations between Glasgow Coma Scale and ventricle-to-brain ratio (VBR); volume of CSF drained; net fluids; and serum sodium, urea, and creatinine. Results: Our investigation reveals that Glasgow Coma Score is positively correlated with increased CSF drainage and negatively correlated with increased ventricle-to-brain ratio. The most important determinant of good outcome is brain compliance as measured by the brain’s ability to maintain a good GCS score in the face of wide ranges in ventricle-to-brain ratio (VBR). Conclusion: We propose that futile prolonged subatmospheric drainage be avoided by declining treatment in patients who have ventriculitis and patients who have a narrow range of ventricle-to-brain ratio (VBR) concurrent with a good neurological examination.
Natural history of the anterior visual pathway after surgical decompression in patients with pituitary tumors
Authors: Won Hyung RA , Chan W , Starreveld Y , Costello F
Published: June 2015

Introduction: Visual dysfunction is one of the primary indications for surgical management of pituitary tumors with the goal of terminating the progressive decline in vision. Unfortunately, it is difficult to predict how successful surgical decompression will be in these patients. The purpose of this study was to assess the structural changes seen in the anterior visual pathway after pituitary tumor resection. Methods: 13 patients (7F) underwent endoscopic tumor resection for pituitary macroadenoma. Each patient underwent a full ophthalmologic assessment including optical coherence tomography (OCT) preoperatively and postoperatively at 3-6months and 9-12months. Post-surgical changes in the retinal nerve fiber layer thickness (RNFLT) for each eye (N=26) were compared in cases with normal preoperative RNFLT (greater than 80 μm) versus those with abnormally thinned RNFLT (less than 80 μm). Results: For 9 cases with thinned RNFLT preoperatively (mean=70.1 μm±8.5), there was a significant decline in RNFLT at 3-6 months follow-up (mean change= −3.8 μm;p=0.002), which did not recover even at 9-12months after surgery (mean=67.6 μm±12.7). Contrastingly, eyes with normal RNFLT preoperatively (mean=89.7 μm±9.4) did not show significant postoperative thinning (mean change= −1.9 μm). Conclusion: Even after a complete surgical decompression, there are ongoing structural changes in the anterior visual pathway in patients with compressive neuropathy. There may be a point of no return where surgical decompression may not prevent further structural degeneration.
Familial pineal tumours in two siblings
Authors: Maroun FB , Avery R , Walsh E
Published: June 2015

Background: The occurrence of familial brain tumours, particularly gliomas, hemangioblastomas in Von Hippel Lindau and other endocrine neoplasia, is well documented in the literature. On the other hand, familial pineal tumours are extremely rare and only a handful of cases have been reported. Methods and Results: Two female siblings presented at ages 12 and 15 with histories of progressive headaches. Neurological examination in each was completely normal. Magnetic Resonance Imaging confirmed the presence of cystic and solid lobulated pineal lesions with mild enhancement, consistent with pineocytoma, in both girls. Follow-up for 15 years in the first sibling and 4 years in the second showed no evolution in radiological or clinical manifestations. No active treatments have been carried out. Conclusion: The occurrence of familial pineal lesions raises the possibility of a close relationship between heredity and oncogenicity, and should be further explored.
Latency period for radiological appearance of new intracranial metastases
Authors: Larjani S , Klironomos G , Mansouri A , Kilian A , Gentili F , Zadeh G
Published: June 2015

Introduction: This study sought to determine the overall and disease-specific latency period for radiological appearance of new intracranial metastases for patients with metastatic involvement of the brain. Methods: A retrospective chart review of patients with intracranial metastases between 2008–2010 was conducted. For each patient, the following were recorded: cancer type, gender, age at diagnosis of primary cancer and first intracranial metastases, treatments (chemotherapy, whole-brain-radiotherapy (WBRT), radiosurgery), and latency period for radiological appearance of new intracranial metastases. Results: 137 patients with multiple metastatic tumors were included in our study. Majority (>90%) of patients received chemotherapy and WBRT. The latency periods for appearance of new metastases for different cancer types were (in months): breast 12.7, lung 11.3, colorectal 9.0, melanoma 6.6, renal cell 8.1, other 8.1. The overall average latency period was 10.1 months. There was no relation between latency period for new metastases and the following: age at diagnosis of metastases(p=0.174), age at treatment(p=0.199), and cancer type(p=0.124). The latency period for new metastatic lesions differed significantly between males (8.1 months) and females (11.7 months) (p=0.009). Conclusions: The average latency period for new metastases is approximately 10 months. Our data suggests that males develop new metastatic tumors at a faster rate.
Neurosurgery (Neuro Vascular)
Authors: Lee CK , Alarfaj A , Ai J , Alharbi B , Vasdev P , Macdonald RL
Published: June 2015

Background: Blood breakdown products such as bilirubin and bilirubin oxidation products damage cortex and white matter after intracerebral hemorrhage(ICH). Here, we tested whether albumin can antagonize axonal damage caused by bilirubin. Methods: The effect of albumin on white matter injury was investigated using brain slices in vitro. After CD-1 mice brain slices were cut using a vibratome, they were incubated in one of five solutions: artificial cerebral spinal fluid (ACSF), bilirubin ACSF, bilirubin and albumin ACSF, bilirubin ACSF that had albumin added 1 hour(h) later, and bilirubin and denatured albumin ACSF. All solutions were continuously aerated with 95% O2 and 5% CO2. Subsequently, electrophysiological recordings of axonal response to electrical stimulation were performed 8h after incubation of brain slices. Results: Bilirubin treatment profoundly damaged both myelinated and unmeylinated axons in brain slices, but had a greater effect on myelinated axons. Unmyelinated axons were found to be more susceptible to damage from denatured albumin. Albumin treatment at 0 h and 1 h significantly diminished bilirubin toxicity for both myelinated and unmyelinated axons, with 1 h delayed albumin treatment conferring greater neuroprotection. Conclusions: These results implicate the role of albumin in preventing bilirubin-induced axonal damage following ICH and its potential therapeutic value for hemorrhagic stroke.
Peripheral hypersensitivity to subthreshold stimuli persists after resolution of acute experimental disc-herniation neuropathy
Authors: Shamji MF , Tu Y , Salter MW
Published: June 2015

Objective: While acute disc-herniation radiculopathy frequently resolves without clinical sequelae, some patients experience long-term sensory or motor dysfunction. This study examined chronic sensitivity of the rodent hindpaw after resolution of an acute inflammatory neuropathy. Methods: C57BL/6 mice underwent mid-thigh sciatic nerve exposure, with sham animals exposed and experimental animals injured by placement of littermate tail nucleus pulposus (NP). Animals were evaluated for mechanical allodynia (Von Frey), thermal sensitivity (heat withdrawal and acetone latency), and gait stability (RotaRod), until the acute nociceptive phenotype resolved. Thereafter, animals were injected with intraplantar subthreshold capsaicin or vehicle followed by the same testing. At sacrifice, sciatic nerves were assessed for macrophage infiltration by immunohistochemistry, and dorsal root ganglion (DRG) explants were assessed for capsaicin sensitivity using cobalt staining. Results: NP-treated animals were allodynic after subthreshold capsaicin delivery compared with sham-operated controls and NP-treated animals delivered vehicle only. Early intraneural macrophage infiltration at one week dissipated by this three week timepoint. DRGs derived from NP-treated animals exhibited greater cobalt staining upon capsaicin exposure compared with shams. Conclusion: Non-compressive disc herniation creates long-term sensitization in the sciatic nerve distribution. This persists despite resolution of acute intraneural macrophage migration, and the demonstrated role of TRPV1 provides insight into the transformation of acute inflammatory pain into chronic neuropathic pain.
The long-term outcome of children with refractory epilepsy after a vagal nerve stimulator implantation: CHU Sainte-Justine experience
Authors: Kaseka ML , Carmant LS , Desplats E , Crevier L , Major P , Diadori P , Lortie A , Mercier C , Carmant L
Published: June 2015

Background: Debate persists in Canada about the cost and benefit of vagal nerve stimulation in patients with refractory epilepsy. The aim of our study was to evaluate the impact of a vagal nerve stimulator on the seizure frequency and the admission rate of children with refractory epilepsies over five years of follow-up. Methods: 52 patients were implanted between 2000-2013. Of these, 37 were followed at CHU Sainte-Justine and 21 kept seizure diaries. Seizure frequency was compared to the baseline at 6 months, 12 months, 24 months and 60 months of follow up using a multivariate ANOVA analysis. The hospitalization rate was calculated as the mean difference between the number of hospitalizations prior to and after the implantation. Results: Seizure frequency decreased by 58% at 6 months, by 61% at 12 months, by 53% at 24 months and by 63% at 60 months of follow up respectively compared to the baseline (p<0.001). The hospitalization rate decreased by 50.87% after surgery (p<0.001). Conclusion: In our population, vagal nerve stimulation has a sustained impact on seizure frequency and hospitalization rates. This supports previous data from our group and others on cost-effectiveness of the technique in children with refractory epilepsy.
KCNQ2 mutations: genotype-phenotype association beyond epilepsy
Authors: Buerki SE , Horwath GA , Van Allen MI , Datta A , Boelman C , Abu Sharar Z , Sayson B , Connolly MB , van Karnebeek CD , Demos MK
Published: June 2015

Background: KCNQ2 abnormalities were described in infants with benign familial neonatal seizures (BFNS) and epileptic encephalopathy (EE). Associated features possibly include abnormal neuroimaging findings such as hypomyelination and/or T2 high signal of basal ganglia. Methods: This report describes 4 infants carrying different heterozygous KCNQ2 variants and 2 infants with 20q13.33 deletions encompassing KCNQ2 gene. Results: The different KCNQ2 mutations led to EE in 3 patients and included a novel de novo missense variant, p.Arg201Cys/c.601C>T, in an infant with severe EE and global developmental delay, hyperkinetic movement disorder, autonomic dysfunction with chronic hypoventilation, apnea, low GABA levels in CSF, and hypomyelination. She died at age 3 years of respiratory failure. One patient with BFNS and normal MRI has a previously reported c.508delG frame shift mutation in KCNQ2. Of the two de novo 22q13.33 deletions (1.2Mb versus 254.1 Kb) the larger caused a more severe phenotype, including focal epilepsy from infancy until 4 years, moderate developmental delay and diffuse brain volume loss. Conclusions: Along with varied epilepsy phenotypes and neuroimaging findings KCNQ abnormalities were associated with severe autonomic dysfunction and reduced CSF GABA levels. This might have further treatment implications, besides that the altered potassium channel function itself presents a therapeutic target.
CNSS Chair’s Select Abstract Presentations
Authors: Purzner T , Purzner J , Cho Y , Elias J , Scott M
Published: June 2015

Background: The hedgehog pathway (Hh) is an important developmental signaling pathway that is commonly dysregulated in brain tumors, most notably in medulloblastomas. To identify novel therapeutic targets within the Hh pathway, we performed the first quantitative proteome-wide evaluation of phosphorylation events resulting from in vitro SHH administration and occurring throughout Hh-driven cerebellar development in vivo. Methods: Multiplexed quantitative mass spectrometry was done using Tandem Mass Tags 10-plex reagents, TiO2 phosphopeptide enrichment and HPLC-MS/MS/MS. Results: Motif analysis of 2-fold changing phosphorylation events suggested casein kinase 2 (CK2) was responsible for mediating 45% of all changes in phosphorylation. Epistasis studies revealed that CK2 activity is necessary for hedgehog signaling and affects terminal signaling components, thereby circumventing challenges of emergence of resistance and a priori resistance that are commonly encountered with existing small molecule inhibitors in medulloblastoma. In vivo, mice harboring MB allografts resistant to current therapies showed near-complete cessation of tumor growth in response to a CK2 inhibitor. Conclusion: Our use of developmental phosphoproteomics revealed casein kinase 2 as a key regulator of hedgehog signaling and therapeutic target in medulloblastoma. Our success establishes a foundation for us, and others, to apply a similar approach in different tumor initiating pathways.
[18F]-sodium fluoride PET/CT is an imaging-derived biomarker of hydroxyapatite expression in carotid plaque: sub-study of the Canadian Atherosclerosis Imaging Network (CAIN-2)
Authors: Cocker MS , Spence J , Hammond R , Wells GA , Mc Ardle B , deKemp RA , Lum C , Adeeko A , Khan A , Alturkustani M , Hammond L , Hill A , Nagpal S , Stotts G , Renaud JM , Kelly C , Brennan J , Garrard L , DaSilva J , Yaffe M , Tardif J , Beanlands R
Published: June 2015

Background: It has been hypothesized that [18F]-sodium fluoride (NaF) uptake imaged with positron emission tomography (PET) binds to hydroxyapatite molecules expressed in regions with active calcification. Therefore, we aimed to validate NaF as a marker of hydroxyapatite expression in high-risk carotid plaque. Methods: Eleven patients (69 ± 5 years, 3 female) scheduled for carotid endarterectomy were prospectively recruited for NaF PET/CT. One patient received a second contralateral endarterectomy; two patients were excluded (intolerance to contrast media and PET/CT misalignment). The bifurcation of the common carotid was used as the reference point; NaF uptake (tissue to blood ratio - TBR) was measured at every PET slice extending 2 cm above and below the bifurcation. Excised plaque was immunostained with Goldner’s Trichrome and whole-slide digitized images were used to quantify hydroxyapatite expression. Pathology was co-registered with PET. Results: NaF uptake was related to the extent of hydroxyapatite expression (r=0.45, p<0.001). Upon classifying bilateral plaque for symptomatology, symptomatic plaque was associated with cerebrovascular events (3.75±1.1 TBR, n=9) and had greater NaF uptake than clinically silent asymptomatic plaque (2.79±0.6 TBR, n=11) (p=0.04). Conclusion: NaF uptake is related to hydroxyapatite expression and is increased in plaque associated with cerebrovascular events. NaF may serve as a novel biomarker of active calcification and plaque vulnerability.