bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical Auditory Evoked Potentials in Response to Frequency Changes with Varied Magnitude, Rate, and Direction
Authors: Vonck Bernard M.D. , Lammers Marc J.W. , van der Waals Marjolijn , van Zanten Gijsbert A. , Versnel Huib
Published: June 2019

Recent literature on cortical auditory evoked potentials has focused on correlations with hearing performance with the aim to develop an objective clinical tool. However, cortical responses depend on the type of stimulus and choice of stimulus parameters. This study investigates cortical auditory evoked potentials to sound changes, so-called acoustic change complexes (ACC), and the effects of varying three stimulus parameters. In twelve normal-hearing subjects, ACC waveforms were evoked by presenting frequency changes with varying magnitude, rate, and direction. The N1 amplitude and latency were strongly affected by magnitude, which is known from the literature. Importantly, both of these N1 variables were also significantly affected by both rate and direction of the frequency change. Larger and earlier N1 peaks were evoked by increasing the magnitude and rate of the frequency change and with downward rather than upward direction of the frequency change. The P2 amplitude increased with magnitude and depended, to a lesser extent, on rate of the frequency change while direction had no effect on this peak. The N1–P2 interval was not affected by any of the stimulus parameters. In conclusion, the ACC is most strongly affected by magnitude and also substantially by rate and direction of the change. These stimulus dependencies should be considered in choosing stimuli for ACCs as objective clinical measure of hearing performance.
Genome mining for lasso peptides: past, present, and future
Authors: Cheung-Lee Wai Ling , Link A James
Published: June 2019

Over the course of roughly a decade, the lasso peptide field has been transformed. Whereas new compounds were discovered infrequently via activity-driven approaches, now, the vast majority of lasso peptide discovery is driven by genome-mining approaches. This paper starts with a historical overview of the first genome-mining approaches for lasso peptide discovery, and then covers new tools that have emerged. Several examples of novel lasso peptides that have been discovered via genome mining are presented as are examples of new enzymes found associated with lasso peptide gene clusters. Finally, this paper concludes with future directions and unsolved challenges in lasso peptide genome mining.
Creativity and productivity in product design for additive manufacturing: Mechanisms and platform outcomes of remixing
Authors: Friesike Sascha , Flath Christoph M. , Wirth Marco , Thiesse Frédéric
Published: June 2019

The present study explores the phenomenon of remixing in product design for additive manufacturing (AM). In contrast to other manufacturing techniques, AM offers unprecedented flexibility in adapting existing product designs to changing requirements. However, in order to benefit from this potential, structured design procedures and tools are indispensable. As a possible solution, online platforms for collaborative 3D model creation are increasingly implementing features for remixing, a concept describing the creation of new models on the foundation of existing design elements. Against this backdrop, the objective of this research is to provide evidence for the value of remixing as an organizational intervention for improving product design processes. To this end, we present a mixed methods approach using data from Thingiverse, the world's largest AM‐related online community. In a first step, we investigate qualitative data from 81 individual remix‐based designs to identify the underlying mechanisms of remixing. We identify six such mechanisms that can further be grouped by the intended outcome of the respective process (creativity‐oriented: inspiration, play, learning;productivity‐oriented: speed, improvement, empowerment). In a second step, we turn to a quantitative analysis of platform data, which indicates that remixing may lead to better design process outcomes in terms of quantity and diversity of designs. Furthermore, we find that designs created by remixing designers are significantly more often printed by community members suggesting that remixing helps ensure manufacturing compatibility akin to continuous process improvement. Our research has several implications for individual designers and organizations engaging with product design for AM.
C.05 Direct visualization of the human zona incerta region using ultra-high field imaging: implications for stereotactic neurosurgery
Authors: Lau JC , Peters TM , Xiao Y , Gilmore G , MacDougall KW , Currie C , Khan AR , Parrent AG
Published: June 2019

Background: The zona incerta (ZI) is a small structure in the deep brain first identified by Auguste Forel for which robust in vivo visualization has remained elusive. The increased inherent signal from ultra-high field (7-Tesla or greater; 7T) magnetic resonance imaging (MRI) presents an opportunity to see structures not previously visible. In this study, we investigated the possibility of using quantitative T1 mapping at 7T to visualize the ZI region. Methods: We recruited healthy participants (N=32) and patients being considered for deep brain stimulation therapy as part of a prospective imaging study at 7T. Computational methods were used to process and fuse images to produce a high-resolution group average from which ZI anatomy could be delineated. Results: We pooled 7T data using image fusion methods and found that the contrast from quantitative T1 mapping was strikingly similar to classic histological staining, permitting facile identification of the ZI and nearby structures in reference to conventional stereotactic atlases. Conclusions: Using computational neuroimaging techniques, we demonstrate for the first time that the ZI is visible in vivo. Furthermore, we determined that this nuclear region can be decoupled from surrounding fibre pathways. This work paves the way for more accurate patient-specific optimization of deep brain targets for neuromodulation.
P.017 Worldwide neurologist survey on management of autoimmune encephalitis
Authors: Ganesh A , Wesley SF
Published: June 2019

Background: Diagnosis of autoimmune encephalitis (AE) is complicated by issues with sensitivity/specificity of antibody testing, non-specific MRI/EEG/CSF findings, and competing differential diagnoses. We explored practice differences in AE diagnosis and management. Methods: We utilized a worldwide electronic survey with practice-related demographic questions, and clinical questions about 2 cases: (1) a 20-year-old woman with a neuropsychiatric presentation strongly suspicious of AE, (2) a 40-year-old man with new temporal lobe seizures and cognitive impairment. Responses among different groups were compared using multi-variable logistic regression. Results: We received 1,333 responses from 94 countries; 12.0% identified as neuro-immunologists. Case 1: Those treating >5 AE cases/year were more likely to send antibodies in both serum and CSF (aOR vs 0/year: 3.29,95%CI 1.31-8.28,p=0.011), pursue empiric immunotherapy (aOR:2.42,1.33-4.40,p=0.004), and continue immunotherapy despite no response and negative antibodies at 2-weeks (aOR:1.65,1.02-2.69,p=0.043). Case 2: Neuro-immunologists were more likely to send antibodies in both serum and CSF (aOR:1.80,1.12-2.90,p=0.015). Those seeing >5 AE cases/year (aOR:1.86,1.22-2.86,p=0.004) were more likely to start immunotherapy without waiting for antibody results. Conclusions: Our findings highlight the heterogenous management of AE. Neuroimmunologists and those treating more AE cases generally take a more proactive approach to testing and immunotherapy than peers. Results emphasize the need for higher-quality treatment/outcome data and evidence-based guidelines.
P.022 Myasthenia gravis following dabrafenib and trametinib for metastatic melanoma
Authors: Zaloum A , Falet JR , Elkrief A , Chalk C
Published: June 2019

Background: Inhibitors of BRAF and MEK, enzymes in the mitogen-activated protein kinase (MAPK) pathway, are now widely used in the treatment of metastatic melanoma. We report a case of acetylcholine receptor (AChR) antibody-positive myasthenia gravis developing after exposure to dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor. Methods: A 68-year-old man presented with dysarthria, dysphagia, cough, dyspnea, and fever. Examination revealed fatigable ptosis and proximal muscle weakness. He had started dabrafenib and trametinib for metastatic melanoma two weeks prior. He was diagnosed with myasthenia gravis and superimposed aspiration pneumonia. AChR antibodies were positive. Dabrafenib and trametinib were stopped. He improved rapidly with pyridostigmine alone, and remained free of myasthenic symptoms for the next two months. Another course of dabrafenib and trametinib was given, and seven weeks later, his myasthenic symptoms recurred. Pyridostigmine produced only partial improvement, and treatment with intravenous immunoglobulin and prednisone was initiated. Results: We are unaware of prior reports of an association between BRAF/MEK inhibitors and seropositive myasthenia gravis. The development of myasthenic symptoms twice after BRAF/MEK inhibitor exposure suggests that the association is more than coincidental. Conclusions: Myasthenia gravis may be a complication of treatment of melanoma with dabrafenib and trametinib. The mechanism by which this occurs is unknown.
P.024 Long-term use of patisiran in patients with hereditary transthyretin amyloidosis (hATTR): 12 month efficacy & safety data from a global open label extension (OLE) study
Authors: Gonzalez-Duarte A , Coelho T , Adams D , Yang C , Polydefkis M , Kristen A , Tournev I , Schmidt H , Berk J , Lin K , Gandhi PJ , Sweetser M , White M , Gollob J , Suhr OB ,   APOLLO Study Investigators
Published: June 2019

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
P.025 APOLLO, a phase 3 study of patisiran for the treatment of hereditary transthyretin amyloidosis (hATTR): 18-month safety and efficacy in subgroup with cardiac involvement
Authors: Vest J , Solomon S , Adams D , Gonzalez-Duarte A , O’Riordan W , Yang C , Coelho T , Berk J , Lin K , Dyck P , Gandhi PJ , Sweetser M , Suhr OB , Kristen A ,   The APOLLO Investigators Group
Published: June 2019

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
P.029 Facial onset sensorimotor neuronopathy syndrome (FOSMN) associated with Non-Hodgkin Lymphoma (NHL)
Authors: Vargas DA , Botez S , Massie R
Published: June 2019

Background: FOSMN is a recently describe neurological syndrome, characterizes by slow onset of facial sensory abnormalities and motor deficits. The initial description showed a very uniform clinical presentation. Since the initial description there are clinical cases describe in literature with subtle phenotype variations. Methods: We describe a clinical case associated with NHL. We will report clinical data, laboratory and neurophysiological findings. Results: Patient initiated with left perioral and mental sensory symptoms on her left side. It spread up to include left V2 area and spread to the right side. After 2 years she developed sensory symptoms on her right hand. Progressed to weakness and atrophy on the right upper limb. Also developed dysarthria, dysphonia, dysphagia, as well as photophobia, anisocoria and double vision. Had thorough work-up and everything unrevealing. Except for Spep that showed increased free kappa. Bone marrow biopsy showed evidence of a clonal cell expansion consistent with indolent lymphoma Conclusions: This case provides evidence of FOSMN associated with NHL. To our knowledge this is a first case describe with NHL. There had been reports with motor neuro diseases phenotype with lymphoma that may represent a paraneoplastic disorder. Our patient expands the clinical presentation. This finding should not lessen the diagnosis of FOSMN.
P.031 Intravenous immunoglobulins (IVIG) therapy in chronic inflammatory demyelinating polyneuropathy (CIDP): time to maximal recovery
Authors: Opala A , Baker S
Published: June 2019

Background: The response of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) to Intravenous Immunoglobulins (IVIG) treatment is well established . However, determination if patients not responding to 2 IVIG treatments or those whose condition stabilizes (ICE Trial) may benefit from additional doses remains unclear. We aim to identify time period required to reach maximal strength gains from IVIG treatment. Methods: Retrospective chart review of 14 patients with CIDP was performed. Change in Grip strength (GS), Knee extension (KE), Elbow Flexion (EF) and Dorsflexion(DF) was analyzed with a dynamometer during IVIG therapy. Averages for : percent change from baseline(Max%Δ),cumulative grams(g) of IVIG and time in weeks(w) required for maximal strength recovery was determined per function (+/−SEM).Anciliary therapy for all patients was recorded. Results: Strongest improvement was observed for DF(124+/−30%,p<0.001), followed by KE(113+/−19%,p<0.01),GS(100+/−21%,p<0.001) and EF(98+/−14%p<0.05).GS improved the fastest(19.1+/−3w) followed by DF(29.5+/−7w),KE(29.6+/−4w) and EF(31+/−6w). Cumulative IVIG dose to reach Max%Δ was highest for EF(869+/−201g) and lowest for GS(573+/−78g). Conclusions: Our study has demonstrated effectiveness of multiple treatments with IVIG to reach significant improvement in strength. Different muscle groups manifested different time-dependency ,reflecting variable amounts of IVIG required. Improvement was identified to be present on a ongoing basis ,with therapy lasting between 19.1-31 weeks,requiring between 869-573g of IVIG.
P.039 Generating choosing wisely Canada recommendations for neurology
Authors: Beyak C , Costello F , Couillard P
Published: June 2019

Background: Many guidelines in neurology encompass the principles of Choosing Wisely Canada (CWC): resource stewardship, patient safety, and high value care. There are currently 49 medical societies with CWC recommendations excluding the Canadian Neurologic Society (CNS). Methods: A descriptive process for list generation is outlined. A review of the American Choosing Wisely recommendations was undertaken to generate an adapted list of ten recommendations. CNS board members vetted this list and an online survey was sent to each CNS member. Results: A short list of recommendations endorsed by the CNS membership at large will be presented according to the survey results. CWC promotion of the list will take place to reach specialists, primary care providers, and trainees to ensure high value neurological care delivery is the standard across Canada. Conclusions: The process to delineate CWC recommendations for neurology is outlined. Participating in the CWC movement is an important leadership initiative for the CNS. It demonstrates the commitment of Canadian neurologists to the principles of high value patient care in neurology.
P.041 Magnesium and calcium reduce severity of spatial memory impairments in kainate mouse model of mesial temporal lobe epilepsy
Authors: Toffa DH , Kpadonou C , Massi D Gams , Ouedraogo M , Sow AD , Ndiaye M , Samb A
Published: June 2019

Background: Calcium (Ca) and magnesium (Mg) are crucial in metabolism, excitability and neuroglial plasticity. Our aim was to evaluate whether Mg (20 mg/kg) or Ca (100 mg/kg) could improve the memory prognosis in the kainic model of mesial temporal epilepsy. Methods: Seizures were induced by systemic injection of kainate (8mg/kg) and mice were then treated by ions every 48 hours. A placebo (physiological solution) replaced kainate or ions in specific groups. Six cohorts were studied for seven weeks: control group (G0: no kainate and no ion, only placebo); untreated reference group (GR: kainate and then placebo); G1 groups were treated from the third day (G1m, G1c: kainate and then Mg/Ca); G2 groups were treated from the third week (G2m, G2c: kainate and then Mg/Ca). Radial maze and a classic maze were used for cognition evaluation. Results: The memory (short/long term) was differently affected by kainate or improved by Mg/Ca. The treated groups performed better than GR mice, but Mg was more effective. In addition, Mg demonstrated an increasing therapeutic effect over time while Ca showed an acute and apparently decreasing action in the G1c group. Conclusions: Mg should be considered for a clinical evaluation of its effect on epileptic disorders.
P.044 Quality of life in children with epilepsy treated with the low glycemic index diet – a pilot study
Authors: Boles S , Webster R , Parnel S , Murray J , Ieradi S , Sell E , Pohl D
Published: June 2019

Background: The classic ketogenic diet is the main non-pharmacological treatment for refractory epilepsy; however, adherence is often challenging. The low glycemic index diet (LGID) is less strict, almost equally effective, and associated with improved adherence. Little is known about the quality of life of children treated with LGID. The objective of this study was to explore changes in the quality of life of children with epilepsy transitioning to the LGID. Methods: Patients on LGID and their parents filled out Pediatric Quality of Life Epilepsy Module questionnaires; one while being on the LGID, and one retrospectively for the time prior to starting the LGID. Results: Data was collected from five children ages 3-13 and their parents. Complete seizure control was seen in two children, >50% seizure reduction in one, and no change in two children. Parental reported quality of life while on the LGID increased with two participants but decreased in all child self reports. Conclusions: Although the LGID led to improved seizure control in three out of five patients, the child-reported quality of life decreased in all children. Larger prospective studies are warranted to reliably assess the impact of the LGID on the quality of life in children with epilepsy.
P.049 Quality of life in children with absence epilepsy
Authors: Sidhu M , Streiner D , Ronen G
Published: June 2019

Background: Childhood absence epilepsy is a common generalized epilepsy in pediatric patients. Although this was considered a “benign” syndrome, new data suggests there are associated neurocognitive effects. This is the first study comparing quality of life and social functioning in those with absence epilepsy to those with other types of epilepsy. Methods: This observational study recruited patients from six Canadian academic centers. 106 patients had absence seizures, and 219 had other seizures. Established measures of depression, anxiety, social skills, social support, participation, quality of life, and epilepsy severity were assessed. MANCOVA was used to evaluate differences in social function, quality of life, and epilepsy severity measures, while accounting for age and gender. Results: This yielded a statistically significant result (Wilk’s lambda <0.05), with partial eta squared of 0.163. Follow up of between subjects tests revealed lower health related quality of life interpersonal/ social subscale and close friend social support scores in those with absence epilepsy, while other measures were not significant. Conclusions: Children with absence epilepsy have similar social function, quality of life and epilepsy severity measures compared to those with other types of epilepsy. This indicates that any dysfunction in these domains is similar to those with other types of epilepsy.
P.054 Electroconvulsive therapy and epilepsy: a case report
Authors: Kassiri J , Ogilvie R , Elliott C , Sinclair DB
Published: June 2019

Background: Electroconvulsive therapy (ECT) involves the induction of a generalized seizure with an electrical current and has been used worldwide when treating medically refractory psychiatric illness. Here we describe a patient with no prior history or risk factors for epilepsy who developed temporal lobe epilepsy after chronic treatment of ECT. Methods: A 16-year-old right-handed boy with severe refractory depression received ECT treatment every 10 days for 8 months. Six months into his ECT treatment, the patient developed seizures and was admitted to a pediatric epilepsy monitoring unit. Results: Initial clinical events included lightheadedness, diaphoresis, and nausea with associated kaleidoscopic vision changes. Seizures progressed to confusion, fear and paranoia by the time the patient was admitted for monitoring. Long-term video EEG captured many focal seizures with impaired awareness, all originating from both temporal lobes. MRI was normal. ECT was terminated and the patient started on carbamazepine. He has been seizure free for the past 2 years on medication Conclusions: While rare, we present a case of a patient with no prior risk factors for epilepsy who developed temporal lobe epilepsy after chronic ECT treatment. Although ECT is an indispensable treatment for many medically refractory psychiatric illnesses, we suggest caution in young patient undergoing ECT.
P.058 Tuberous sclerosis complex associated intracranial abnormalities identified in utero via antenatal ultrasound
Authors: Hanes IE , Abdeen N , Muir K , Sell E
Published: June 2019

Background: Tuberous sclerosis complex (TSC) is characterized by growth of benign tumors in the skin, brain, kidneys, lung and heart. Prognosis is mostly determined by the extent of brain involvement as tumors in the brain lead to seizures and cognitive problems. Epilepsy is highly associated with the cognitive abnormalities in TSC and recent evidence suggests anti-epileptic treatment before onset of seizures reduces epilepsy severity and risk of mental retardation. Screening and potential identification of TSC in utero via ultrasound would allow for prophylactic seizure management in these children. The sensitivity of antenatal ultrasound in the identification of brain abnormalities associated with TSC has not yet been published. In this case, we review the antenatal ultrasounds of a child with TSC for evidence of brain abnormalities in utero. Methods: Retrospective review Results: Retrospective review of antenatal ultrasounds showed some evidence of intracranial abnormalities. Ultrasound at 34 weeks and 4 days gestation revealed an echogenic density in the right ventricle that correlates with SEGA on post-natal MRI brain at 12 days of life. Post-natal brain ultrasound at 37 weeks revealed multiple cranial abnormalities not seen in utero. Conclusions: There are limitations to antenatal neurosonography in the detection of intracranial abnormalities associated with TSC.
P.059 Brachial plexus enhancement in acute flaccid myelitis: A novel radiographic finding
Authors: Hammond SC , Almomen M , Mineyko A , Pauranik A
Published: June 2019

Background: Acute flaccid myelitis (AFM) is a condition which causes acute paralysis in pediatric patients. Although awareness of AFM is increasing, the pathophysiology and full spectrum of clinical, biochemical, and radiographic features remain to be fully elucidated. Methods: We report a 5 year-old, previously healthy, male patient who presented with acute right upper extremity weakness following a two day history of fever, cough, and fatigue. The patient underwent extensive inflammatory and infectious workup in addition to MRI imaging of the brain, spinal cord, and bilateral brachial plexuses. Results: Infectious and inflammatory workup did not identify a causative agent. The patient was seen to have bilateral asymmetric (R>L) thickening and enhancement of the anterior horn cells of his cervical (C3-C7) spine, consistent with the spinal grey matter lesions previously described in patients with AFM. Enhancement of the corresponding anterior nerve rootlets and bilateral brachial plexuses was also seen. Conclusions: Patients with acute flaccid myelitis may demonstrate grey matter enhancement extending beyond the spinal cord to the peripheral nerves and plexuses, a radiographic finding which has not previously been published.
P.060 Time to treatment effect in Spinal Muscular Atrophy Type 1 (SMA1): an indirect comparison of treatments
Authors: Finkel RS , Dabbous O , Arjunji R , Droege M , Feltner DE , Novack A , Menier M , Sproule DM
Published: June 2019

Background: SMA1 is a rapidly progressing disease resulting in death/permanent ventilation by 2 years. This study compared clinical trial data evaluating the relationship between treatment timing, time to treatment effect, and clinical outcomes in SMA1 patients Methods: A post-hoc indirect treatment comparison was conducted to measure time-to-effect differences in AVXS-101 (CL-101, NCT02122952, cohort 2) vs nusinersen (ENDEAR, NCT02193074) or risdiplam (FIREFISH, NCT02913482) using CHOP-INTEND scores. Results: Compared with nusinersen, AVXS-101 more rapidly increased mean CHOP-INTEND score from baseline (9.8- and 14.9-point increase at 1- and 2-months post-AVXS-101 vs ≤5-point increase at 2-months post-nusinersen). Greater survival benefits and lower rates of permanent ventilatory support were also observed in AVXS-101- vs nusinersen-treated patients. Compared with risdiplam treatment, AVXS-101 improved median CHOP-INTEND scores (14.0-point increase at 2-months post-AVXS-101 vs 5.5-point increase at ~2-months post-risdiplam). Treatment differences were maintained through 8-months with additional improvements at all time-points. Conclusions: Although patients in these 3 cohorts are not entirely matched (e.g. age, disease severity), useful comparisons can still be made. Based on CHOP-INTEND scores, the treatment effect of AVXS-101 appears to be more rapid vs nusinersen or risdiplam. These findings suggest that timely restoration of SMN protein may be essential for maximizing outcomes in SMA1 patients.
P.066 AVXS-101 gene-replacement therapy (GRT) in spinal muscular atrophy type 1 (SMA1): long-term follow-up from the phase 1 clinical trial
Authors: Mendell JR , Lehman KJ , McColly M , Lowes LP , Alfano LN , Miller NF , Iammarino MA , Church K , Schultz M , Ogrinc FG , L’Italien J , Kernbauer E , Shah S , Sproule DM , Feltner DE
Published: June 2019

Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.
P.081 Critical illness neuropathy and clinical correlates in severely burned patients
Authors: Kaviani R , Chapman KM , Papp A
Published: June 2019

Background: Reported incidence of critical illness neuropathy (CIN) in burn patients is between 7-41%. Methods: Retrospective review including patients admitted to quaternary ICU for burn injuries between 2010-16. Variables include demographics, burn and neurologic characteristics, EMG reports, and measurements of illness severity. Patients with and without neuropathies were compared. Results: Of 147 patients admitted to ICU, thirteen had EMG studies and eight met CIN criteria. Five had electrophysiological CIN evidence, three had clinical diagnosis. Six EMGs focused on upper limb injuries only, insufficient to diagnose CIN. One patient was diagnosed with critical illness myopathy and nine had superimposed focal mononeuropathies or plexopathy. CIN patients had a mean of larger burns (TBSA 63% vs 21%), more operations (8 vs 2) and escharotomies performed (63% vs 12%), longer ICU admissions (23 vs 9 days), longer ventilation (28 vs 8 days), higher revised Baux score (101 vs 76) and initial APACHE II scores (21 vs 15) than those without. Conclusions: CIN was identified in 5.4% of burn patients admitted to ICU, lower than previously reported in literature, and associated with higher illness severity. CIN may be under recognized if not screened for. Unit examinations should include screening neurological measures and indicated EMGs to evaluate for CIN.
P.091 Surgical outcomes for patients undergoing repeat endoscopic endonasal trans-sphenoidal surgery for recurrent pituitary adenomas
Authors: Toyota E , Wang J , Pirouzmand N , Ijad N , Ali M , Nassiri F , Zadeh G
Published: June 2019

Background: Endoscopic endonasal trans-sphenoidal surgery (EETS) is a commonly used approach for the surgical treatment of primary pituitary adenomas. The role of this approach in patients with recurrent disease remains unclear. Here we review a high-volume institutional experience with repeat EETS for recurrent pituitary adenomas and compare outcomes against primary surgeries. Methods: A retrospective chart review of patients who underwent EETS at Toronto Western Hospital from 2008-2016 for pituitary adenomas was completed. Baseline patient characteristics and surgical outcomes were recorded for each surgery. Primary and repeat operations were compared for analysis using Fisher’s exact test and t-test where appropriate. Results: 347 primary and 48 repeat surgery patients were identified. The median follow-up was 3.6 years (range 0-10.6 years). Rates of GTR, optic decompression, endocrinopathy cure, and visual improvement in repeat EETS were 44%, 21%, 22%, and 21%, respectively. While these rates are lower when compared to primary surgeries (75% p<0.001, 58% p<0.001, 75% p=0.01, 37% and p=0.04), they demonstrate that desirable outcomes are still achievable after EETS for recurrent disease. Conclusions: These results from a quaternary-care centre suggest that repeat EETS is a viable option that is safe and effective at improving the visual and endocrine status in select patients with recurrent pituitary disease.
P.101 Conservative management of meningiomas with a moderate to high peritumoral brain edema index: a single-institution report
Authors: Yan H , Karmur B , Jeong D , Bernstein M
Published: June 2019

Background: Meningiomas are the most commonly occurring benign intracranial tumors. When presenting with peritumoral brain edema (PTBE), surgical treatment can lead to patient morbidity. This retrospective case series aims to describe the conservative medical management of moderate to large meningiomas with large PTBE. Methods: Patients with suspected meningiomas greater than 2.0cm and edema index greater than 2.0 were identified by screening 3345 MRI scans between 2012-2017. Imaging analysis included MR imaging features of suspected meningiomas and clinical data was gathered from the electronic patient record (patient age, sex, patient symptoms, follow-up duration, and follow-up symptoms). Results: We report on 31 patients who received conservative medical management. Presenting complaints included headache, seizure, weakness; many presented asymptomatically. The average follow-up time was 3.96 years. At the final follow-up appointment, 19 (61%) patients were asymptomatic. Among symptomatic patients, seizures were the most common complaint. There was no mortality reported in our cohort and the average tumor progression was 7.04cm3/year. Conclusions: In this retrospective report of meningioma patients with high edema index, we found that most patients remained asymptomatic or had stable symptoms after at least 1-yr follow up after medical treatment. This study provides insight around the surgical decision-making for meningiomas with large spread of edema.
P.110 Systematic review of civilian pediatric intracranial gunshot wounds
Authors: Duda T , Sharma A , Ellenbogen Y , Shakil H , Sharma S
Published: June 2019

Background: Pediatric craniocerebral gunshot wounds occur in the context of both accidental and intentional trauma. Unique physiologic factors merited research into prognostic factors and treatment priorities in the pediatric population. Methods: A systematic search of MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Registered Trials and Systematic Reviews, ISRCTN, and ClinicalTrials.gov was conducted. Selection criteria included all studies published in any language since 2000 which described intracranial isolated gunshot wounds in a civilian individual or population of pediatric age. Post-mortem and epidemiological studies were excluded. Screening was conducted through Covidence. Results: Initial database search revealed 349 unique studies for abstract and title screening. Fifty studies were selected for full text screening. Nine studies were included in the final review. Study quality was assessed with the Newcastle-Ottawa Scale. Case series noted bullet migration, pituitary deficiency, neurovascular and neuropsychological concerns. Three single-center retrospective studies of 71, 30, and 48 pediatric patients suggested multiple negative prognostic signs on initial presentation. Early aggressive surgical treatment was recommended by some authors. Conclusions: This systematic review analyzed the best current understanding of evidence for prognostic factors and treatment considerations of intracranial gunshot wounds in the pediatric neurotrauma context. Areas for future research with larger multi-center studies were highlighted.
P.126 Enhancing patient understanding of spinal conditions through advanced imaging platforms
Authors: Walsh MT , Khan OH
Published: June 2019

Background: In spite of the shift towards “personalized medicine,” ambulatory medicine lags behind the cutting edge technology employed in non-medical fields to convey information in unique ways to enhance customer interactions. Furthermore, the complex nature of neurosurgical concepts can be difficult to convey within the confines of a short outpatient visit. These factors, coupled with potentially long wait times, can limit a patient’s engagement in the treatment process. We propose that application of advanced video platforms will empower patients to feel that neurosurgical concepts are accessible and understandable and enable the face-to-face time with the physician to begin at a more sophisticated level, ultimately improving patient engagment. Methods: 3D modeling, animation, and video game design were used in conjuction with tablet computers and VR headsets to create a video-driven “choose-your-own-adventure style patient experience” with initial use during waiting times prior to face-to-face interaction with the neurosurgery providers. Results: 3D modeling, animation, and virtual reality were successfully implemented in the Northwestern Medicine neurosurgery clinic with positive impact on patient engagement, including preliminary improvements in multiple patient satisfaction/”Likelihood to Recommend” scores. Conclusions: Advanced imaging platforms, including 3D modeling, animation, and virtual reality show great promise in improving patient engagement, patient retention, and “Likelihood to Recommend” scores.
P.128 Percutaneous cortical screws: a novel approach to posterior spinal stabilization
Authors: Jack AS , Ramey WL , Tymchak ZA , Hart RA , Roh JS
Published: June 2019

Background: Pedicle screw (PS) fixation is considered the gold-standard for spine stabilization. However, minimally invasive surgery (MIS) and cortical screw (CS) fixation have become commonplace. The biomechanical and safety profiles of CS compared to PS have yet to be determined. To our knowledge, this is the first study to describe a novel percutaneous CS approach and compare its safety and accuracy to PS fixation. Methods: Standard percutaneous PS fixation was performed using fluoroscopy from L1-L5 on one-side with percutaneous CS being placed on the other-side (10-instrumented PS and CS levels each). Anatomical confirmation and comparison of pedicle breach incidence was performed afterward via open dissection. Results: Dissection revealed no breaches of either construct. As such, no statistical comparison was possible. At one-level however, a CS was seen breaching the posterior-third lateral vertebral body under the superior end-plate. A couple of exposed screw threads were visualized well away from any entering and/or exiting foraminal or extra-spinal neurovascular structures. Conclusions: MIS and CS-based constructs are relatively new fixation techniques. We describe a novel percutaneous CS technique incorporating advantages of both MIS and CS-constructs. Although no difference was found in pedicle breach incidence, further study comparing these techniques and rigorous patient selection for application are necessary.
GP.04 Prevalence and determinants of seizure action plans in a pediatric epilepsy population
Authors: Chiu M , Peinhof S , Borhani M , DeGuzman C , Siu C , Kuzeljevic B , Schrader D , Huh L , Connolly MB
Published: June 2019

Background: Status epilepticus (SE) is the most common pediatric neurological emergency. Timely treatment is crucial, yet administration of rescue medications is often delayed and under-dosed. We aim to improve SE management by ensuring that every child at risk of SE in our province has an individualized seizure action plan (SAP) outlining the steps that should be taken during SE. Methods: A survey was distributed to parents of epilepsy patients aged 1 month to 19 years. Primary outcome was percentage of patients with SAPs. Secondary outcome was parental interest in a SAP mobile application. Following chart review, univariate and multivariate analysis was performed to identify variables that predict whether patients have SAPs. Results: Of 192 participants, 61.5% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of having a SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82.2% of patients with SAPs. 83.3% of parents were interested in a SAP mobile application. Conclusions: This is one of the first studies to examine SAP prevalence in a pediatric epilepsy population. There is a need to increase the percentage of epilepsy patients with SAPs. Most parents would find a SAP mobile application valuable in their child’s management.
GP.06 Differential microglia and macrophage profiles in human IDH-mutant and -wildtype glioblastoma reveal therapeutic vulnerabilities
Authors: Poon CC , Gordon P , Liu K , Yang R , Sarkar S , Yong VW , Kelly J
Published: June 2019

Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
B.03 Clinical utility of critical care EEG monitoring in a Canadian paediatric centre
Authors: Din F , Ganesan S Lalgudi , Ochi A , Otsubo H , Go C , Whitney R , Chau V , Cortez M , Sharma R , Hahn CD
Published: June 2019

Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.
B.06 Whole exome sequencing in genetic ataxias associated with cerebellar atrophy: the Canadian experience
Authors: Gauquelin L , Hartley T , Tarnopolsky M , Dyment DA , Brais B , Geraghty MT , Tétreault M , Ahmed S , Rojas S ,   Care4Rare Canada Consortium, Majewski J , Bernier F , Innes A , Rouleau G , Suchowersky O , Boycott KM , Yoon G
Published: June 2019

Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.
C.01 Neck and arm pain after surgery for cervical myelopathy: outcomes and predictors of improvement
Authors: Dakson A , Christie S , Jacobs B , Johnson M , Bailey C , Charest-Morin R , Paquet J , Nataraj A , Cadotte D , Wilson J , Manson N , Hall H , Thomas K , Rampersaud R , McIntosh G , Fisher C , Dea N
Published: June 2019

Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.