bluuebunny/crossref_metadata_2025 huggingface dataset:
P.037 Keeping track of time: emphasizing symptom onset-to-hospital time in stroke care
Authors: Freedman DE , Behih N , Elmeligi A , Sahlas D
Published: June 2019

Background: The Canadian Stroke Best Practice Recommendations target a median door-to-needle time of 30 minutes. However, brain tissue becomes damaged with any delay from symptom onset. Efficiencies may be gained prior to hospital arrival, by evaluating the timeliness of patient access to hospital from symptom onset, as well as by improving healthcare provider communication, prior to arrival of the patient. Methods: We engaged with hospital administration, paramedic services, allied health colleagues, physicians, and engineers, to develop Kairos, a secure online platform that healthcare providers can utilize to track progress en route to hospital, as well as to share pertinent stroke patient information, prior to arrival. Results: Kairos is built on React Native, allowing users to access it on android or iOS devices. Paramedics select patient identification, symptom onset time, and associated symptoms. The receiving hospital can add doctors to the patient’s thread, and the stroke team can prepare for patient arrival. Conclusions: We plan to measure the median symptom onset-to-hospital time in patients with strokes, and monitor the change in door-to-needle time following implementation at an Ontario Regional Stroke Centre.
P.043 Cannabis treatment in children with epilepsy: practices and attitudes of neurologists in Canada
Authors: DeGasperis SM , Webster R , Pohl D
Published: June 2019

Background: Cannabis has been shown to be an effective therapy for epilepsy in children with Dravet and Lennox-Gastaut syndrome. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about pediatric neurologists’ attitudes towards it. Methods: A 26-item online survey was distributed to 148 pediatric neurologists across Canada. Results: 56/148 neurologists responded and reported that over 600 children with epilepsy are currently taking cannabinoids. 34% of neurologists authorized cannabis to children, 38% referred children for authorization, and 29% did not authorize or refer their patients. Of those neurologists who referred, 76% referred to a community-based non-neurologist. The majority of physicians authorized cannabis to patients with Dravet syndrome (68%) and Lennox-Gastaut syndrome (64%). Cannabis was never authorized as a first-line treatment. 54% of neurologists stated that their patients were taking CBD alone, despite this option not being available in Canada. All physicians reported having at least one hesitation regarding cannabis, the most common ones being poor evidence (66%), poor quality control (52%), and cost (50%). Conclusions: The majority of Canadian pediatric neurologists use cannabis as a treatment for epilepsy in children. However, there appear to be knowledge gaps and hesitations.
P.050 Epilepsy phenotypes in patients with Sotos syndrome
Authors: Fortin O , Vincelette C , Khan AQ , Berrahmoune S , Scheffer IE , Lu J , Davis K , Myers KA
Published: June 2019

Background: Sotos syndrome is a genetic condition caused by NSD1 alterations, characterized by overgrowth, macrocephaly, dysmorphic features, and learning disability. Approximately half of children with Sotos syndrome develop seizures. We investigated the spectrum of seizure phenotypes in these patients. Methods: Patients were recruited from clinics and referral from support groups. Those withclinical or genetic diagnosis of Sotos syndrome and seizures were included. Phenotyping data was collected via structured clinical interview and medical chart review. Results: 25 patients with typical Sotos syndrome features were included. Of 14 tested patients, 64% (n=9) had NSD1 alterations. Most had developmental impairment (80%, n=20) and neuropsychiatric comorbidities (68%, n=17). Seizure onset was variable (2 months to 12 years). Febrile and absence seizures were the most frequent types (64%, n=16). Afebrile generalized tonicclonic (40%, n=10) and atonic (24%, n=6) seizures followed. Most patients (60%, n=15) had multiple seizure types. The majority (72%, n=18) was controlled on a single antiepileptic, or none; 4% (n=1) remained refractory to antiepileptics. Conclusions: The seizure phenotype in Sotos syndrome most commonly involves febrile convulsions or absence seizures. Afebrile tonic-clonic or atonic seizures may also occur. Seizures are typically well-controlled with antiepileptics. The rate of developmental impairment and neuropsychiatric comorbidities is high.
P.062 Burden of illness of spinal muscular atrophy (SMA): an update
Authors: Droege M , Dabbous O , Arjunji R , Gauthier-Loiselle M , Cloutier M , Sproule DM
Published: June 2019

Background: In this retrospective claims analysis, real-world healthcare resource use (HRU) and costs among SMA type 1 (SMA1) patients were assessed. Methods: SMA1 patients were identified from Symphony Health’s Integrated Dataverse® (09/01/2016–08/31/2018). The study period spanned from the index date (date of first SMA1 diagnosis after nusinersen approval [12/23/2016]) until death/end of available data. HRU and costs per-patient-per-year (PPPY; 2018USD) were described during the study period for all patients and after treatment initiation for nusinersen-treated patients. Results: A total of 349 SMA1 patients (median age=1 year; 55.6% female) with median follow-up of 7.9 months were included. The proportion of patients receiving mechanical ventilation, nutritional support, and physical therapy/rehabilitation was 46.4%, 46.1%, and 22.6%. Patients had, on average, 59.4 days with medical visits/year (14.1 inpatient, 13.4 respiratory failure-related). The 45 nusinersen-treated patients had, on average, 56.6 days with medical visits/year (4.6 inpatient, 11.4 respiratory failure-related). Excluding nusinersen-related costs, mean healthcare costs PPPY were $137,627 (median: $43,167) for all patients and $92,618 ($29,425) for nusinersen-treated patients. Mean nusinersen-related costs were $191,909 ($144,487) per month for the first 3 months post-initiation and $36,882 ($16,132) per month thereafter. Conclusions: HRU and costs associated with SMA1 are substantial, even among patients treated with nusinersen.
P.063 SUNFISH Part 1 results and Part 2 trial design in patients with type 2/3 spinal muscular atrophy (SMA) receiving risdiplam (RG7916)
Authors: Campbell C , Mercuri E , Baranello G , Kirschner J , Servais L , Goemans N , Pera M , Buchbjerg J , Yeung W , Kletzl H , Gerber M , Czech C , Cleary Y , Gorni K , Khwaja O
Published: June 2019

Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
P.064 FIREFISH Part 1: 1-year results on motor function in infants with Type 1 spinal muscular atrophy (SMA) receiving risdiplam (RG7916)
Authors: Seabrook TJ , Baranello G , Servais L , Day JW , Deconinck N , Mercuri E , Klein A , Darras B , Masson R , Kletzl H , Cleary Y , El-Khairi M , Czech C , Gerber M , Nguyen C , Gelblin K , Gorni K , Khwaja O , Cabalteja C
Published: June 2019

Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
P.068 Abnormal fatty acid metabolism is a feature of spinal muscular atrophy
Authors: Deguise M , Beauvais A , Baranello G , Pileggi C , Mastella C , Tierney A , Chehade L , Leone A , De Amicis R , Battezzati A , De Repentigny Y , Warman Chardon J , McMillan HJ , Llavero-Hurtado M , Huang Y , Courtney NL , Mole AJ , Lamont D , Atrih A , Kubinski S , Claus P , Murray LM , Wishart TM , Bowerman M , Gillingwater TH , Harper M , Bertoli S , Parson SH , Kothary R
Published: June 2019

Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
P.072 Fetal alcohol spectrum disorder - is this a ciliopathy?
Authors: Urquhart JL , Goez HR
Published: June 2019

Background: Fetal alcohol spectrum disorder (FASD) is used to describe the spectrum of birth defects due to prenatal alcohol exposure; these include craniofacial abnormalities and intellectual disabilities. The prevalence of FASD is estimated at 1 in 100. Diagnostic criteria include distinct facial features, neurodevelopmental deficits and confirmation of alcohol use during pregnancy. Unfortunately, often criteria are missed or absent. No biochemical marker is available for screening and diagnosis of FASD that is easy, accurate and cost-effective. Methods: Five children are being recruited from both the FASD clinic at the Glenrose Rehabilitation Hospital and the Healthy Infants and Children’s Clinical Research Program (HICUPP) registry. The levels of exhaled nasal NO will be measured and compared between the two groups. Metabolomics analysis on urine samples targeting metabolites of the NO pathway, along with other urinary metabolites is being performed. Bioinformatic statistical tools will be applied to determine whether measured metabolite profiles can provide distinct signatures between healthy children and children with FASD. Results: This project is ongoing. Conclusions: We hope to correlate NO levels with FASD, illustrating the relationship between NO, ciliopathies and development of FASD. As well, we hope to determine whether urinary metabolites may yield diagnostic markers of FASD.
P.079 4H leukodystrophy: a case series of siblings with an unusually mild phenotype
Authors: DeGasperis SM , Bernard G , Pohl D
Published: June 2019

Background: 4H leukodystrophy is a genetic disorder typically characterized by hypomyelination, hypodontia and hypogonatotropic hypogonadism. Previously reported patients had considerable cognitive and motor deficits. We present a pair of siblings with a less severe phenotype. Methods: Patient data was obtained from medical records from the Children’s Hospital of Eastern Ontario. Results: The first patient was diagnosed with 4H leukodystrophy at the age of 21 years after genetic testing revealed a POLR3B mutation with a homozygous V523E variant. She has hypomyelination on MRI and a history of optic neuritis, as well as intermittent sensory and motor symptoms in the context of a diagnosis of multiple sclerosis. She has no clinical manifestations of 4H leukodystrophy. The patient is now 26 years old and has only mild neurological deficits. Her younger brother was diagnosed with 4H leukodystrophy at the age of 18 years and found to have the same genetic mutation as his sister. He has a history of seizures and mild learning disabilities. He is now 23 years old with no typical symptoms of 4H leukodystrophy. Conclusions: 4H leukodystrophy is usually associated with a severe, disabling phenotype and a poor prognosis. Our patients illustrate that a much milder phenotype exists.
P.080 Effects of REM sleep in anti-NMDA receptor encephalitis with extreme delta brush pattern
Authors: Jain DK , Ng M
Published: June 2019

Background: Seizures are rare in REM sleep. To our knowledge, the effects of different sleep stages in anti-NMDA encephalitis have not been studied. Methods: Case report. Results: 32 year-old healthy female presented with acute fluctuating level of consciousness with episodic impulsivity, disorientation, and emotional outbursts following 3 days of headache. Her temperature was 37.8°C and she was started on ceftriaxone, vancomycin, and acyclovir. CSF only showed a total nuclear cell count of 182 and pleocytosis. MRI revealed increased T2 hyperintense right lateral temporal and parietal cortical thickening. EEG revealed right frontotemporal seizures with left sided rhythmic jerking, and an extreme delta brush pattern. Interestingly, seizures and extreme delta brush disappeared in REM sleep. After HSV PCR was negative, she was immunosuppressed with corticosteroids, IVIG, rituximab, and cyclophosphamide, given the extreme delta brush pattern. Repeat CSF analysis eventually yielded highly positive anti-NMDA antibodies. Ten weeks later, she became seizure free. Conclusions: For the first time, we report REM sleep in a case of anti-NMDA encephalitis during which there was absence of extreme delta brush and ictal EEG patterns. This observation may provide insight into the ongoing debate over whether extreme delta brush is an ictal EEG pattern.
P.083 Radiology reporting of low-grade glioma growth underestimates tumor expansion
Authors: Gui C , Lau JC , Kosteniuk SE , Lee DH , Megyesi JF
Published: June 2019

Background: Surveillance by serial magnetic resonance imaging (MRI) is important in the management of diffuse low-grade gliomas (LGGs). Radiological interpretations of LGG scans, however, are typically qualitative and difficult to use clinically. Methods: We retrospectively compared radiological interpretations of LGG growth/stability to volume change measured by manual segmentation. Tumour diameter was measured to evaluate methods for assessing glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumour diameter/ellipsoid method. Results: Tumours evaluated as stable by radiologists grew a median 5.1 mL (11.1%) relative to the comparison scan. Those evaluated as having grown increased by 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate segmented volumes, and overestimation error increased with tumour size. Agreement with segmented volume improved from a mean difference of 17.6 to 4.5 to 3.9 mm for diameter and from 104.0 to 25.3 to 15.9 mL for volume with measurements in one, two, and three dimensions. Conclusions: Given evidence that LGG volume and growth are prognostic factors, lesions should be accurately measured. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. Volumetric analysis remains the gold standard for growth assessment, but diametric measurements in three dimensions may be an acceptable alternative.
P.087 The influence of disease lateralization in Parkinson’s Disease on tractography in DBS patients
Authors: Leck E , Schmidt M , Rigby H , Weise L
Published: June 2019

Background: Asymmetric motor symptoms are typical in Parkinson’s disease (PD), with potential implications on disease course. Imaging modalities have demonstrated asymmetry, including thinning of motor-related cortex in the contralateral hemisphere of symptomatic side. The objective is to assess correlation between lateralized symptoms and Diffusion Tensor Imaging (DTI) characteristics of pyramidal tract. Methods: 34 PD patients and 30 controls were evaluated. Disease dominance was assessed using UDPRS III. DTI was performed with 60-directional 3Tesla MRI protocol. A 1cm3 subcortical region of interest was positioned underneath motor cortex. Primary outcome was the difference in fibers between disease-dominant and non disease-dominant cortex. Results: There was a significantly higher number of fibers in the hemisphere corresponding to disease dominance (p=0.0031). The same was true for seed number (p=0.0032) and fractional anisotropy (p=0.0427). Based on 23 patients operated on, the threshold for stimulation-induced side effects on the left side was inversely correlated with number of fibers in left ROI (Spearman -0.497, p=0.0158). Conclusions: Based on current literature we expected a reduction of fibers in the contralateral hemisphere to symptom dominant side. Surprisingly, DTI analysis showed an inverse correlation. The underlying pathophysiology remains unclear with the possibility of a compensatory mechanism or compacting of fibers underneath a shrinking motor cortex.
P.089 Ultra-high frequency deep brain stimulation at 10,000 Hz improves motor function
Authors: Harmsen IE , Lee DJ , Dallapiazza RF , De Vloo P , Chen R , Fasano A , Kalia SK , Hodaie M , Lozano AM
Published: June 2019

Background: Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultra-high frequency (UHF) spinal cord stimulation at 10kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. Methods: We studied the effects of conventional (130Hz) and UHF stimulation in five patients with Parkinson’s disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. Results: Motor performance improved in all six patients with UHF DBS. 10kHz stimulation at amplitudes ≥3.0mA appeared to be as effective as 130Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, p=0.110, N=90 trials). Interestingly, 10kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130Hz stimulation. Conclusions: Our results indicate that DBS at 10kHz produces clinical benefits while possibly reducing stimulation-induced adverse effects in patients with movement disorders.
P.094 Incorporating Navigated Transcranial Magnetic Stimulation (nTMS) into the neurosurgical practice: oncological, vascular and research potentials
Authors: Khan OH
Published: June 2019

Background: Surgical managment of eloquent lesions in the brain require a multidisciplinary approach. Radiographic imaging, such as magnetic resosnance, can provide details of “normal” anatomy however are limited when lesions can distort/displace due to mass effect or neuroplasticity. Functional MRI (fMRI) has limitations due to patient dependent actions can often be limited due oncological or vascular lesions but known to still be near or involving “eloquent” cortex. Navigated transcranial magnetic stimulation (nTMS) provides the physician with the ability to accurately (~2mm error) stimulate cortex of the brain, in a clinical setting, and to understand function of areas of motor and language and incorporate this information into the surgical theatre. Methods: We will present a personal expierience of complex oncological and vascular cases to illustrate how nTMS can assist in the determination of surgical approaches and educating patients of potential morbidities. Will also review potential research opportunities that nTMS provides. Details of Phase 2 clinical trial of nTMS for improving neuro-cognitive outcomes will be discussed. Results: Case ilustrations will be provided. Preliminary results of Phase 2 clinical study will be discussed. Conclusions: Navigated TMS provides another tool in the armamentarium of neurosurgeons to better manage and approach complex and eloquent lesions in the brain.
P.104 The diagnostic value of the nerve root sedimentation sign for symptomatic lumbar stenosis
Authors: Huschi Z , Neuburger L , Ahmed U , Cheng Y , Fourney DR
Published: June 2019

Background: Previous studies have shown varied results with respect to the diagnostic utility of a positive nerve root sedimentation sign (SedSign) on MRI for symptomatic lumbar stenosis. The objective of this study was to analyze the clinical characteristics of SedSign utilizing a validated classification for low back and leg pain (Saskatchewan Spine Pathway classification; SSPc). Methods: This was a retrospective review of prospectively-collected data in 367 consecutive adult patients presenting to a spine surgeon with back and/or leg pain between January 1, 2012 and May 31, 2018. Inter- and intra-rater reliability for SedSign was 73% and 91%, respectively (3 examiners). Results: SedSign was positive in 111 (30.2%) and negative in 256 (69.8%) of patients. On the univariate analysis, a positive SedSign was correlated with age, male sex, several components of ODI, EQ5D mobility, cross-sectional area (CSA) of stenosis, and SSPc pattern 4 (intermitted leg dominant pain). On multivariate analysis, SedSign was associated with age, male sex, CSA stenosis and ODI sub-score for walking distance. The sensitivity and specificity of SedSign for neurogenic claudication was 50.3 and 82.9, respectively (positive predictive value 65.8%, negative predictive value 71.9%). Conclusions: The SedSign has high specificity for neurogenic claudication, but the sensitivity is poor.
P.106 A pilot-project for neurosurgery competency-based design implementation
Authors: Cadieux M , Jacobs B , Riva-Cambrin J , Phitayakorn R
Published: June 2019

Background: In preparation for July 2019 rollout of competency-based design (CBD) in Canadian neurosurgery residency training, the University of Calgary launched a pilot-program of five representative EPAs using the One45 program. Our study objectives were to examine the uptake of CBD with residents and faculty and to quantify CBD implementation barriers. Methods: Phase one of the One45-based CBD pilot-program launched on November 1st, 2018 and ended on January 8th, 2019, after which a questionnaire was sent to each participating resident. The questionnaire examined number of EPAs initiated, measures of favourability, importance, ease of use, and barriers encountered. Results: Results obtained from the survey show 93.8% response rate (15/16 residents). 66.7% of residents feel that CBD is moderately important or higher to their education. Over the 10 study weeks, there were only 8 completed EPAs (expected was 50), five of which were completed by a single resident. Major expressed barriers of implementation of CBD were time involved (50.0%) and technical unfamiliarity with the platform itself (50.0%). Conclusions: This study demonstrates the critical importance of piloting a CBD program prior to official implementation as immediate buy-in was significantly slower than anticipated. Technical and time barriers exist which need to be rectified in advance of July 2019.
P.107 Traumatic spinal cord injuries among aboriginal and non-aboriginal populations of Saskatchewan: a prospective outcomes study
Authors: Ahmed S , Humphreys S , Liu L , Fourney D
Published: June 2019

Background: People of aboriginal ancestry are more likely to suffer traumatic spinal cord injury (TSCI) compared to other Canadians; however, outcome studies are limited. This study aims to compare aboriginal and non-aboriginal populations with acute TSCI with respect to: pre-injury baseline, injury severity, treatment, outcomes, and length-of-stay characteristics. Methods: This was a retrospective analysis of 159 patients with TSCI prospectively enrolled in the prospective Rick Hansen Spinal Cord Injury Registry (RHSCIR), Saskatoon site between February 13, 2010 and December 17, 2016. Results: Sixty-two patients consented to the full dataset, which includes ethnic background: 21 ‘aboriginal’ (33.9%); 41 ‘non-aboriginal’ (66.1%). Aboriginal patients were younger, had fewer medical comorbidities and had similar severity of neurological injury and similar outcomes compared to non-aboriginal patients. However, the time to discharge to the community was significantly longer (median 104.0 days versus 38.5 days, p=0.021). While 35% of non-aboriginal patients were discharged home from the acute care site, no aboriginal patients were transferred home directly. Conclusions: This study suggests a need for better allocation of resources for transition to the community for First Nations patients with TSCI in Saskatchewan. We plan a further study to assess outcomes from TSCI for First Nations patients across Canada.
P.114 Headache outcomes after treatment of unruptured intracranial aneurysms: systematic review and meta-analysis
Authors: Dandurand C , Parhar H , Naji F , Prakash S , Gooderham PA
Published: June 2019

Background: Headaches are a major cause of disability and healthcare cost worldwide. When investigating headaches etiology, incidental unruptured intracranial aneurysms are often considered unrelated. We conducted a systematic review and meta-analysis to assess headaches outcomes (severity) after treatment of unruptured intracranial aneurysm. Methods: MEDLINE and EMBASE were systematically reviewed. Results: The data from eligible studies (n=7) was extracted and analyzed. 309 nonduplicated patients provided patient-level data for analysis. All studies used the 10-point numeric rating scale (NRS). 88% of patients were treated with endovascular technique. Overall, the observed effect estimate under a random effects model was found to be a standard mean difference in pre- and post-intervention headache severity of -0.448 (95% CI: -0.566 to -0.329). No significant heterogeneity was noted. No significant publication bias was demonstrated. Conclusions: This is the first and largest systematic review assessing postoperative headache outcomes after treatment of unruptured intracranial aneurysm. A significant reduction in headache intensity after treatment is observed in the current published literature. This study highlights an interesting clinical phenomenon that still warrants scientific effort before it can influence clinical practice. We encourage future study to stratify headache outcomes by aneurysm size, location and treatment modality.
A.01 Relieving the burden of myasthenia gravis: eculizumab reduces exacerbation, hospitalization and rescue therapy rates
Authors: Siddiqi Z , Howard JF , Jacob S , Guptill JT , Meisel A , Wiendl H , Murai H , Utsugisawa K , Nowak RJ , Fujita KP , O’Brien F , Patra K , Muppidi S
Published: June 2019

Background: Patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (MG) unresponsive to conventional treatment experience greater disease burden than responsive patients. This is partly due to exacerbations, which may result in significant healthcare resource utilization. Eculizumab is well tolerated and gives clinically meaningful benefits in these patients. We evaluated the effect of long-term eculizumab treatment on exacerbations, hospitalizations and rescue therapy in the REGAIN study and its open-label extension. Methods: Exacerbations were defined as clinical worsening/deterioration, MG crises or rescue therapy usage; pre-study exacerbations/hospitalizations were defined from patient records. Event rates adjusted for patient-years were calculated for all patients in the pre-study year, patients receiving placebo during REGAIN, and patients receiving eculizumab during REGAIN and its open-label extension (median exposure, 27.5 months [range, 22 days–42.8 months]); rates were compared using a Poisson regression model. Results: Eculizumab treatment reduced exacerbations by 65% (p=0.0057), hospitalizations by 71% (p=0.0316) and rescue therapy use by 66% (p=0.0072) versus placebo. Eculizumab treatment reduced exacerbations by 74% and hospitalizations by 83% (both p<0.0001) versus the pre-study year. Conclusions: Long-term eculizumab treatment reduces disease burden and healthcare resource utilization, demonstrating continuing improvements in clinical endpoints that lead to additional meaningful outcomes for patients with AChR+ generalized MG. (NCT01997229, NCT02301624).
A.04 The classification of autosomal recessive cerebellar ataxias: a consensus statement from the society for research on the cerebellum and ataxias task force
Authors: Beaudin M , Matilla-Dueñas A , Soong B , Pedroso J , Barsottini OG , Mitoma H , Tsuji S , Schmahmann JD , Manto M , Rouleau GA , Klein CJ , Dupre N
Published: June 2019

Background: There is currently no accepted classification of recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus and develop a clinical and pathophysiological classification for recessive ataxias. Methods: The work of this task force was based on a scoping systematic review of the literature that identified recessive disorders characterized primarily by a cerebellar motor syndrome and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. Results: We identified 59 disorders that are classified as primary recessive ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. The primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders in which ataxia is a secondary feature. Conclusions: This classification is based on a scoping systematic review of the literature and results from a sconsensus among a panel of international experts. It promotes a unified understanding of recessive cerebellar disorders for clinicians and researchers.
C.04 Comparison of clinical outcomes between posterior instrumented fusion with and without interbody fusion for isthmic spondylolisthesis
Authors: Chan V , Nataraj A
Published: June 2019

Background: The purpose of this study is to compare 1-year postoperative clinical outcomes between posterior instrumented fusion with (P/TLIF) and without (PLF) interbody fusion in patients with isthmic spondylolisthesis. Methods: This is a multi-centre retrospective study using the Canadian Spine Outcomes and Research Network. Adult patients who received surgical management for isthmic spondylolisthesis were included in this study. The primary outcome was change in Oswestry Disability Index at 1-year. Secondary outcomes were change in EQ-5D, SF-12 PCS, back pain, leg pain, estimated blood loss, length of surgery, length of stay, rate of transfusions and adverse events. Descriptive statistics, Student t-test, Chi-Squared test, and stepwise multivariable regression were used for analysis. Results: A total of 300 patients (252 P/TLIF, 48 PLF) were included in this study. The mean age was 50 years. The P/TLIF group had poorer baseline leg pain scores (t=2.02, p=0.01). There were no significant differences in primary and secondary outcomes between the two groups. Addition of interbody fusion was not a significant variable in the stepwise multivariable regression analysis. Conclusions: There were no significant differences in clinical outcomes at 1 year. Addition of interbody fusion was not associated with higher complication rates or length of stay.
‘Craven subserviency had vanished. Bitter hostility had arrived’: agrarian violence and the Tenant League on the Ulster borderlands, 1849–52
Authors: Luain Kerron Ó
Published: June 2019

On the Ulster borderlands, the years 1849 to 1852 represented a crucial period in the development of a correlation between agrarian violence and constitutional political agitation. The emergence of the Tenant League in the region from 1848, along with a parallel clandestine violence from 1849, foreshadowed the better-known Land War of the latter part of the nineteenth century. This article analyses the hitherto unacknowledged interplay between agrarian violence and constitutional politics in south Armagh and surrounding districts. In so doing, it emphasises the years in the immediate wake of the Great Famine as being critical in the long-term development of more politicised forms of collective action. Such methods, in turn, would ultimately be deployed to the detriment of the landed ascendancy in subsequent decades.
Irish republican women in Australia: Kathleen Barry and Linda Kearns's tour in 1924–5
Authors: Hall Dianne
Published: June 2019

The 1924–5 fundraising tour in Australia by republican activists, Kathleen Barry and Linda Kearns, although successful, has received little attention from historians, more focused on the controversial tour of Fr Michael O'Flanagan and J. J. O'Kelly the previous year. While O'Flanagan and O'Kelly's tour ended with their deportation, Barry and Kearns successfully navigated the different agendas of Irish-Australian political and social groups to organise speaking engagements and raise considerable funds for the Irish Republican Prisoners’ Dependants' Fund. The women were experienced republican activists, however on their Australian tour they placed themselves firmly in traditional female patriotic roles, as nurturers and supporters of men fighting for Irish freedom. This article analyses their strategic use of gendered expectations to allay suspicions about their political agenda to successfully raise money and negotiate with political and ecclesiastical leaders.
Locating women within the Irish Department of External Affairs: a case study of Irish women at the League of Nations and United Nations, 1923–76
Authors: O'Brien Ann Marie
Published: June 2019

By using the League of Nations and United Nations as case studies, this article identifies the women working at the diplomatic level in the Irish Department of External Affairs (D.E.A.) in the period 1923–76. Drawing on gender analysis, the article assesses where men and women were positioned in Irish diplomacy and asks if the role of women in the D.E.A. was shaped by a gendered viewpoint. It argues that there were more opportunities for women within the United Nations than the League of Nations and it questions if these increased diplomatic opportunities were reflective of women's changing status within the D.E.A. in the period under investigation. Overall, the article offers a new perspective on the conduct of Irish foreign policy between 1923 and 1976.
Quelques cadres du français moderne
Authors: Vachon-Spilka Irène
Published: June 2019

Dans l’espoir d’apporter un peu d’ordre aux “règles” des grammaires traditionnelles et de fournir aux étudiants étrangers une explication facilement assimilable des cadres les plus fréquents de la prose française, nous avons commencé a appliquer la méthode des substitutions à quelques problèmes de morphologie avec des résultats qui nous ont paru satisfaisants dans leur application pédagogique.

Au cours de l’exposé qui va suivre, nous nous appliquerons à découvrir la situation précise du mot de dans la structure essentielle du français moderne, c’est-à-dire sans tenir compte des effets stylistiques ni des tournures archaïques égarées dans la langue contemporaine.
Labrador, St. John’s and Newfoundland: Some Pronunciations
Authors: Kirwin William
Published: June 2019

The well-known names of Labrador, St. John’s and Newfoundland have variant pronunciations among the older speakers of the oldest communities on the Avalon Peninsula in southeast Newfoundland. The following description is based on field interviews; made during the summer of 1960. It is important to note that possible trends and changes in pronunciation in the younger and middle generations have not been examined; the informants ranged in age from two in the 40s and 50s up to 94 years. Almost all were associated with the fishery since childhood.
Developments in Investment Policy During the Last Decade
Authors: Day J. G.
Published: June 2019

Investment conditions have changed widely and rapidly in the post-war era; and since the publication of Mr Lewis G. Whyte's textbook, Principles of Finance and Investment, there has been a spate of papers on investment theory, each of them either covering a small part of the subject or setting forth a particular view.

The aims of this paper are:

I. To suggest a balanced and consistent approach to investment principles as they affect funds of actuarial interest.

II. To discuss the application of these principles to particular types of funds.

III. To discuss the characteristics of the securities that are available in present-day conditions to implement investment policy.

These aims may sound comprehensive, but within the limitations of a paper it is only possible to touch on them briefly.
Operational Research, Its Methods and Application: A Review and Prospect
Authors: Gould A. H.
Published: June 2019

A feature of modern wars has been the impetus which is given to the development of scientific and technical progress, a phenomenon which is very easily explained by the general urgency of development under the pressure of war requirements, the removal of normal limits on expenditure and the realization of the part that science can play in the development of the engines of war. This was shown to a marked extent in the second world war and amongst the examples can be quoted the vast development of electronic equipment, the emergence of the jet engine as an alternative to the internal combustion engine for motive power and the realization of the use of nuclear power, in the first instance in the form of explosive energy. However, over and above these examples of scientific and technical progress there was one development in the second world war of particular interest, the use of the scientific method of ‘operational research’ (hereafter denoted by O.R.).
Observations on luminescence inNoctiluca
Authors: Nicol J. A. C.
Published: June 2019

Noctiluca miliarisSuriray is a well-known luminescent organism, and its light emission has been studied repeatedly. Hitherto, however, no attempt has been made to record the luminescent flashes of this species, either under normal conditions, or after experimental treatment. With the sensitive photo-electric recording methods now available it has become possible to subject the luminescent flashes ofNoctilucato experimental analysis, and with this end in view the present study ofNoctilucawas undertaken.
On some Pogonophora from the north-east Atlantic, including two new species
Authors: Southward Eve C. , Southward A. J.
Published: June 2019

In the course of dredging for the rich epifauna of the continental slope near 48° 30′N., 10° W. (Southward & Southward, 1958b) in May 1957, several hauls were made by chance on a muddy bottom at 500–700 fin. depth. At the time, these hauls were examined only cursorily after sieving, and the con-tents immediately preserved. One of the hauls contained several damaged siliceous sponges, and a recent careful examination disclosed a number of pogonophore tubes entangled among the threads and spicules of the sponges.
On the occurrence and behaviour of two little-known barnacles, Hexelasma hirsutum and Verruca recta, from the continental slope
Authors: A. J.  , Southward Eve C. , Cooper L. H. N.
Published: June 2019

The fauna of the continental shelf and slope between Ireland and Spain has been described by Le Danois (1948), but very little faunistic work has been carried out in the area recently. Since R.V. ‘Sarsia’ was brought into service at Plymouth there have been several opportunities of investigating that part of the slope lying to the south-west of the British Isles. It has been found that, in addition to beds of coral, quite extensive exposures of rocks, stones and gravel occur between 200 and 1000 fathoms. There is a rich epifauna in this area and barnacles are one of the dominant groups.
Observations on luminescence in pelagic animals
Authors: Nicol J. A. C.
Published: June 2019

Luminescence is very common among marine animals, and many species possess highly developed photophores or light-emitting organs. It is probable, therefore, that luminescence plays an important part in the economy of their lives. A few determinations of the spectral composition and intensity of light emitted by marine animals are available (Coblentz & Hughes, 1926; Eymers & van Schouwenburg, 1937; Clarke & Backus, 1956; Kampa & Boden, 1957; Nicol, 1957b, c, 1958a, b). More data of this kind are desirable in order to estimate the visual efficiency of luminescence, distances at which luminescence can be perceived, the contribution it makes to general back-ground illumination, etc. With such information it should be possible to discuss more profitably such biological problems as the role of luminescence in intraspecific signalling, sex recognition, swarming, and attraction or repulsion between species. As a contribution to this field I have measured the intensities of light emitted by some pelagic species of animals.
Observations on the littoral algae of the Isle of Wight
Authors: Kain Joanna M.
Published: June 2019

As a result of the geological formation of the Isle of Wight there is a great variety in the type of shore. Although much of the coastline is unsuitable for the establishment of algal communities there are some parts where a few species can exist, and others where full zonation is achieved. It therefore seemed worth making some study of the algal distribution. Towards this end a general survey was made of the south coast of the island in April 1955, with more detailed studies of the places of interest by means of transects in April and July 1955.
John Heigham of S. Omer (c. 1568–c. 1632)
Authors: Allison A. F.
Published: June 2019

To anyone who has studied English Catholic books of the early seventeenth century, the imprints, “Doway, for John Heigham” and “S. Omers, for John Heigham” have a familiar—not to say monotonous—ring. There are over sixty books in existence today, printed between 1609 and 1631, which bear one or other of these imprints. Yet very little is generally known about the man himself. The biographies of him which appear in works of reference tell us next to nothing about him and what they do tell us is for the most part incorrect. In this note I shall try to unravel some of the muddles which have arisen and set out briefly the main outline of his career in so far as it can be established from the evidence.
II.—On the Structure of Calymmatotheca kidstoni Calder (emended) and Genomosperma latens gen. et sp. nov. from the Calciferous Sandstone Series of Berwickshire
Authors: Long Albert G.
Published: June 2019

Synopsis

The Lower Carboniferous fossil Calymmatotheca kidstoni Calder is shown to be a simple seed and is redescribed under the new name Genomosperma kidstoni. A second species G. latens is also described. Genomosperma gen. nov. is of interest in possessing a free nucellus with a lagenostome and short salpinx. The nucellus is surrounded by an integument of about eight lobes which are free from one another and from the nucellus from near the base of the seed. The vascular details of t h e seeds have been studied and in each species pollen has been observed in the pollen chamber.

Genomosperma is compared with various Pteridosperm seeds.
V.—The Geochemistry of the Older Granodiorite, Co. Donegal, Ireland
Authors: Mercy Edward L. P.
Published: June 2019

Synopsis

Chemical analysis of samples of the Older Granodiorite, Co. Donegal, Ireland, shows that it has a geographical variation in which Si, K and O increase, Na is about constant and all other major elements decrease in amount from east to west. There is a high degree of positive linear correlation between Mg and Fe2 + Fe3 which implies derivation of these elements from some previously existing ferromagnesiam mineral in which the appropriate ratio was maintained. There is a low degree of negative linear correlation between Na and K which implies that these elements are mobile and independent of each other.

The chemical relationships of the granodiorite to its pelitic country rocks are shown and discussed. The relations are such that the preferred hypothesis for the origin of the granodiorite is one of influx of Na, K and Ca ions in an alumino-silicate medium. Country rocks are diluted by this influx and it is unnecessary to assume any great migration of Mg and Fe. With time the nature of the influx changes—Ca decreases in amount whereas Na, K and Si all increase but K and Si to a very much greater extent than Na.
VII.—The Structural History of the Moine Thrust Zone at Lochcarron, Wester Ross
Authors: Johnson M. R. W.
Published: June 2019

Synopsis

Torridonian and Lewisian rocks lying in inverted order between the Kishorn thrust and the Moine thrust, and Moine rocks, lying above the Moine thrust, exhibit a remarkable parallelism of structure.

New evidence shows that three sets of minor structures have been developed in the formations during the Caledonian movements. At least two of these sets pre-date the Moine thrust movements. The mylonites, which are not restricted to the vicinity of the Moine thrust outcrop, belong to an earlier movement phase than these structures and are not directly related to the clean-cut thrust movements. They appear to represent narrow zones of shearing and sliding, mainly within the Lewisian gneisses that developed early in the Caledonian orogeny.

There is reason to suppose that the inversion of the rocks to the west of the Moine thrust occurred before the formation of the minor structures recognized in the paper.

The minor structures are described and their order of formation established. The plastic, para-crystalline style of the earlier deformation is contrasted with the post-crystalline brittle style of the later deformations.