bluuebunny/crossref_metadata_2025_split huggingface dataset:
066 Avxs-101 gene-replacement therapy (GRT) for spinal muscular atrophy type 1 (SMA1): pivotal phase 3 study (STR1VE) update
Authors: Day John W , Chiriboga Claudia A , Crawford Thomas O , Darras Basil T , Finkel Richard S , Connolly Anne M , Iannaccone Susan T , Kuntz Nancy L , Pena Loren DM , Schultz Meredith , Shieh Perry B , Smith Edward C , Farrar Michelle , Feltner Douglas E , Ogrinc Francis G , Macek Thomas A , Kernbauer Elaine , Muehring Lynlee M , L’Italien James , Sproule Douglas M , Kaspar Brian K , Mendell Jerry R 
Published: July 2019

IntroductionSMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion.MethodsSTR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) and Bayley Scales of Infant and Toddler Development scores.ResultsEnrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months. Updates will be provided at the congress.ConclusionsPreliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
073 Acute spinal infarction: treatment and outcomes with and without hyperbaric oxygen therapy at fiona stanley hospital
Authors: Ashton Catherine , Banham Neil , Needham Merrilee 
Published: July 2019

IntroductionSpinal cord infarction is a potentially devastating disorder commonly presenting with anterior spinal artery syndrome developing over minutes to hours, accounting for an estimated 1% of stroke presentations. Aetiologies range from aortic surgical complications, systemic hypotension and other rare causes including fibrocartilaginous embolism and vascular malformations. Diagnosis is clinical combined with restriction on diffusion-weighted MRI. There are no specific treatment guidelines. The evidence for hyperbaric oxygen therapy (HBOT) in acute spinal infarction is mixed. This case series describes ten cases of acute spinal infarction at Fiona Stanley Hospital (FSH), half of which received HBOT.MethodsData for all MRI-proven spinal cord infarctions at FSH between 2014 and 2018 were reviewed.ResultsTen patients, median age 55years (31–74), 60% male. Aetiologies: three fibrocartilaginous emboli, five likely atheroembolic disease, one antiphospholipid syndrome, one cryptogenic. Sixty percent presented with flaccid paraplegia ranging from levels C4 to T11. Five patients received HBOT within a median time of 31 hours from symptom onset, with average 15 treatments. Three patients received triple therapy of HBOT, pentoxyfiline and high-volume lumbar-puncture drainages and had median MRC muscle power of 5- on discharge, compared with 2+ power in those who did not. Nine required inpatient rehabilitation, of average eight weeks’ duration, with median disability at discharge of 3 on the Modified Rankin Scale.ConclusionSpinal infarctions can be severely disabling. Fibrocartilaginous embolism may be more common than previously thought. More research is needed on the role of acute triple therapy with pentoxyfiline, spinal drains and HBOT given the marked difference in this case series.
079 Glial fibrillary acidic protein (GFAP) astrocytopathy associated with cerebral micro-infarction and poor therapeutic response
Authors: MacDonald Allycia , Triplett James , Vijayan Srimathy , Bynevelt Michael , Lakshmanan Rahul , Chemmanam Thomas 
Published: July 2019

IntroductionGlial fibrillary acidic protein (GFAP) astrocytopathy is a lesser recognised immune-mediated meningo-encephalomyelitis, which is steroid responsive in the majority of cases. Neuroimaging is unique with a distinctive symmetric white matter perivascular linear and punctate enhancement pattern. We present a case with classical phenotype but delayed clinical response, and highlight the importance of early recognition and treatment.CaseA 59-year-old Caucasian female presented with a two month history of headache, gait disturbance, insomnia, agitation, disorientation and reduced oral intake. Examination revealed a high frequency upper limb tremor, hypertonicity and pathologically brisk reflexes with impaired cognitive function. MRI brain and spinal cord demonstrated high T2 signal and striking perivascular and punctate enhancement in supratentorial white matter, cervical and upper thoracic cord. CSF examination revealed lymphocytic pleocytosis and elevated protein. Brain biopsy demonstrated reduced GFAP expression, perivascular T-lymphocytic infiltrate, and recent white matter microinfarction. CSF and serum GFAP antibodies were positive.Motor deterioration accompanied progression to a stuporous state. High dose corticosteroids were commenced, followed by intravenous immunoglobulin and mycophenolate. While there was marked improvement of perivascular contrast enhancement on imaging, the patient continued to demonstrate prominent tremor, gait disturbance and behavioural issues 9 months following symptom onset.ConclusionsThe persistence of disability in this case is likely the result of axonal loss from the initial insult, reflected by the biopsy evidence of microinfarction. Awareness of the unique pattern on MRI and the clinical phenotype will aid in early recognition and prompt treatment of this condition, thus preventing the potential long term morbidity.
007 The outcome of a cohort of pregnancies in australian women with epilepsy
Authors: Vajda Frank JE , Graham Janet E , Hitchcock Alison A , Lander Cecilie M , O’Brien Terry J , Eadie Mervyn J 
Published: July 2019

BackgroundThe Australian Pregnancy Register (APR) established in 1998, collects data concerning the hazard of foetal malformations from intrauterine exposure to antiepileptic drugs.Methods4 telephone interviews, ethical approval, informed consent, observational study, statistical analyses.ResultsBy December 2017, the APR recorded 1879 pregnancies, followed prospectively. There had been 1766 live births (94.0%), 5 stillbirths (0.3%), 54 spontaneous abortions (2.9%), and 30 induced abortions (1.6%), while 24 pregnancies had an unknown outcome due to loss of contact with the women involved (1.3%). Foetal malformations had occurred in 71 of the live-born infants. Of the induced abortions, 15 had been for intrauterine foetal death, 10 for major foetal malformation (spina bifida, anencephaly and left heart underdevelopment), 2 for detected chromosome defects and 3 for maternal reasons (major illness in 2).By the end of the post-pregnancy year a further 99 pregnancies had become unavailable for follow-up (resulting in an 84.9% live-born infant final retention rate). An additional 33 pregnancies that had resulted in late recognised foetal malformations had been identified, nearly all in the first 6 months after birth. Intrauterine valproate exposure was involved in 447 of the 1731 antiepileptic drug treated pregnancies, a malformation-carrying pregnancy rate of 11.86%, as compared with a rate of 2.70% in the 148 drug-unexposed pregnancies (O.R. = 4.84; 95% C.I. 1.72, 13.62), used as comparators.ConclusionThis report confirms previous interpretations of the APR data, also providing insights into the pregnancies of women with epilepsy that did not result in live- born offspring.
087 Endovascular clot retrieval (ECR) in the elderly. For better or worse in the real world?
Authors: Jankelowitz Stacey K , Tastula Kylie , Mitchell Nicola , Tang Patrick , Ang Tim , Brunacci David , Parker Geoffrey , Winters Stephen , Wong Johnny , Allen Rodney , Worthington John 
Published: July 2019

IntroductionAcross multicentre trials ECR is safe and effective in octogenarians. Despite RCT evidence elderly patients may be denied ECR due to perceived poor risk-benefit. We examine impact of age on ECR outcomes and outcomes in transcatheter aortic valve implantation (TAVI) cases (where stroke risk is high), in a real world setting.MethodsWe analysed 311 consecutive ECR cases between 2016 and 2019 in 10 year age bands for ECR outcomes including 90 day mRS and mortality. Impact of premorbid function (mRS), NIHSS, recorded co-morbidities, and aetiology was assessed. TAVI case outcomes were examined.ResultsThirty one percent of ECR outcome cases were over 79 years of age; 90 day mortality was 34%; 25% had a 90 day mRS 0–2. Early NIHSS improvement was 5. Ninety-day mortality and mRS 0–2 for 10–19 (n=3), 20–29 (n=2), 30–39 (n=4), 40–49 (n=23), 50–59 (n=27), 60–69 (n=69), 70–79 (n=84),80–89 (n=62) and 90–99 (n=11) years were 0 and 100%, 0 and 100%, 33 and 67%, 4 and 78%, 15 and 52%, 13 and 49%, 17 and 33%, 24 and 2% and 55 and 18%, respectively. There was 9% lost to follow-up.Six TAVI cases had a NIHSS of 8–20 and pre-morbid mRS<3, four with mRS 0. Mean 24 hour NIHSS improvement was 8.ConclusionWithout age exclusions older patients had worse unadjusted outcomes. However, patients over 79 years had clinically important early improvement in NIHSS score and ninety day outcomes were comparable to favourable RCT data and TAVI patients also had early improvement.
008 Associations between comorbidities and adverse events of antiepileptic drugs and quality of life: a survey of epilepsy patients in australia
Authors: Welton Jeremy M , Walker Christine , Riney Kate , Ng Alvin , Todd Lisa M , D’Souza Wendyl 
Published: July 2019

IntroductionThis study explored the impact of specific types of comorbidities and adverse events (AEs) from antiepileptic drugs (AEDs) on quality of life (QoL) among adult patients with epilepsy (PwE) in Australia.MethodsCross-sectional surveys were completed by PwE, or caregiver proxies, recruited via the online pharmacy application MedAdvisor and Australian PwE Facebook groups from May–August 2018 Data were collected on demographics, epilepsy severity and management, AEs, comorbidities, and QoL (using QOLIE-10-P total score).1 Multiple linear regression models were constructed to explore associations between AEs or comorbidities and QOLIE-10-P, with possible confounders determined using stepwise selection.Results978 responses were included (mean age 44.5 years, 64% female, 52% employed). 97% reported recent AED use, 47% on AED monotherapy, 35% exposed to ≤2 lifetime AEDs, and 55% seizure-free for >1 year. After stepwise selection, control variables included in both models were: time since diagnosis, employment status, seizure frequency, number of currently prescribed AEDs, and number of general practitioner visits per year. In the model for comorbidities, ‘psychiatric disorders’ was associated with the largest QOLIE-10-P decrease (-23.30, p<0.001). In the model for AEs, which additionally controlled for depression and anxiety disorder, ‘memory problems’ was associated with the largest decrease in QOLIE-10-P (-14.27, p<0.001).ConclusionsIn this survey of Australian PwE, of which many had relatively well-controlled epilepsy, psychiatric and memory problems were common and associated with the greatest detrimental impact on QoL. Further research is needed to understand causality, relationships between possibly interrelated or overlapping symptoms, and management strategies. UCB Pharma-sponsored.ReferenceCramer JA, Perrine K, Devinsky O, Meador K. A brief questionnaire to screen for quality of life in epilepsy: The QOLIE-10. Epilepsia 1996;37:577–582.
093 How to diagnose lewy body dementia? Prevalence and underlying relationship between clinical and neuropsychological features of DLB
Authors: Matar Elie , Ehgoetz Martens Kaylena A , Halliday Glenda M , Lewis Simon JG 
Published: July 2019

IntroductionDespite its importance for management, prognostication and selection of patients for clinical trials, the diagnosis of Dementia with Lewy Bodies (DLB) remains challenging. Complicating this is a recent change in the diagnostic criteria which has arguably shifted the expected phenotype of DLB patients. In this study we aimed to characterize and examine the relationship between cognitive and clinical diagnostic variables in DLB patients to uncover latent symptom clusters that may streamline future diagnostic approaches in the clinic.MethodsThe clinical and neuropsychological profile of 27 prospectively recruited participants diagnosed with probable DLB and 25 age-matched controls was characterized according to the most recent consensus criteria.Symptoms were scored using a novel combination of established clinical and research instruments.ResultsWe demonstrate comparable sensitivity of formal neuropsychological testing and bedside screening tools (MOCA/MMSE) for identifying domain-specific differences between controls and patients(p<0.001). Optimal sensitivity thresholds for diagnosis of Parkinsonism (88.9%) were explored yielding a prevalence range of 50%-90% within our cohort.Factor analysis using all core and supportive features of the diagnostic criteria identified 6 independent factors accounting for 81% of the total variance. Unique relationships identified included between hallucinations and fluctuations and excessive daytime somnolence; between REM sleep behavior disorder and orthostatic hypotension; and Parkinsonism and urinary disturbance. ‘Prodromal’ symptoms including autonomic and early neuropsychiatric features are represented in the remaining factors.ConclusionParsimonious delineation of clinical variables using identified symptom clusters can aid DLB diagnosis.Clusters are also used to highlight latent pathological relationships. Appropriate instruments and thresholds for detecting dementia and core and suggestive features are presented.
095 Predicting parkinson’s and dementia with lewy bodies (pre-D) research study – a sydney-based longitudinal biobanking program
Authors: Matar Elie , Ehgoetz Martens Kaylena A , Soberats Maria Comas , Halliday Glenda M , Lewis Simon JG 
Published: July 2019

IntroductionIdiopathic REM sleep behaviour(iRBD) disorder represents the most specific prodromal marker of an impending synucleinopathy with over 90% developing either Parkinson’s disease(PD), Dementia with Lewy Bodies(DLB) or Multiple System Atrophy(MSA) after 15 years. This finding has stimulated efforts to actively register and track progression of such patients. Here we present experience of a biobanking program established with the aim of identifying prodromal synucleinopathies to facilitate recruitment to neuroprotective trials as they become available.MethodsPatients with iRBD were prospectively and sequentially recruited. Cross-sectional comparator groups consisting of healthy controls, idiopathic PD (within 5 years of diagnosis) and DLB were also recruited. Patients underwent a standardized assessment protocol including clinical phenotyping, neuropsychometric testing, multimodal MRI, polysomnography, quantitative electroencephalography, chronobiology (melatonin and clock gene expression profiling) and gait testing. Subjects were invited for annual and biennial review.Results102 patients have been recruited into the study since July 2016 including 35 patients with iRBD, 26 DLB, 19 early PD and 16 controls. 15 patients have returned for follow-up with 3 converting to a synucleinopathy(2 DLB, 1 PD). 75% of participants were able to complete all elements of assessment protocol. Preliminary evaluation of iRBD participants reveals early changes in clock gene expression(BMAL1) and subtle changes in patterns of gait compared to older controls.ConclusionsOur preliminary findings demonstrate utility and feasibility of a prodromal biobanking program within the Australian context aimed at identifying prodromal synucleinopathies. Similar models can be applied to other centers to improve access and create an extended national collaborative network.
097 Associations between cognitive and memory problems, employment and quality of life: a survey of epilepsy patients in australia
Authors: Welton Jeremy M , Walker Christine , Riney Kate , Ng Alvin , Todd Lisa M , D’Souza Wendyl 
Published: July 2019

IntroductionThis analysis explored relationships between memory/cognitive issues, quality of life (QoL), and employment among patients with epilepsy (PwE) in Australia.MethodsCross-sectional surveys were completed by PwE, or caregiver proxies, recruited via the online pharmacy application MedAdvisor and Australian PwE Facebook groups from May–August 2018. Data were collected on adverse events from antiepileptic drugs (AEDs), comorbidities, epilepsy severity and management, QoL (using QOLIE-10-P total score)1 and demographics. Descriptive statistics were stratified by employment status: employed; not looking for work (NLW); looking for work (LW); or unable to work (UW), and differences in means or distributions were analysed using chi-squared, Mann-Whitney U or Kruskal-Wallis H tests. Regression models were constructed to explore associations between memory/cognition-related variables and QOLIE-10-P within each employment group.Results950 eligible responses reporting current AED use were included (71% via MedAdvisor, 29% via Facebook; 55% seizure-free for >1 year). Mean QOLIE-10-P score was significantly different across employment groups (p<0.001): 49.61 in employed PwE (n=493), 48.87 in NLW (n=227), 32.75 in LW (n=52), and 25.97 in UW (n=178). After controlling for possible confounders, presence of memory problems from AEDs was associated with a -7.50 decrease in QOLIE-10-P only among employed PwE (p=0.002). The extent that PwE felt bothered by memory difficulties, however, was significantly associated with QOLIE-10-P in all employment groups; generally, as level of concern about memory difficulties increased, estimated QOLIE-10-P decreased.ConclusionsSelf-reported memory problems are prevalent among PwE in Australia and may impact QoL differentially depending on employment status. UCB Pharma-sponsored.ReferencesCramer JA, Perrine K, Devinsky O, Meador K. A brief questionnaire to screen for quality of life in epilepsy: The QOLIE-10. Epilepsia 1996;37:577–582.
098 A case of delayed post-hypoxic leukoencephalopathy complicating drug overdose
Authors: Fong Min , Rigby Nicholas , Pun Paul , Mitchell Roger , Schweitzer Daniel , Swayne Andrew 
Published: July 2019

IntroductionDelayed post-hypoxic leukoencephalopathy (DPHL) is a syndrome characterised by neurological deterioration following a period of recovery after an initial hypoxic event with striking white-matter change on magnetic resonance imaging. We present a case characterised by insidious onset and a fluctuating course of cognitive and neuropsychiatric symptoms.MethodsSingle case report.ResultsA 61 year old lady, with a background history of previously well managed bipolar affective disorder, was found unresponsive following an intentional overdose of temazepam and tramadol. She was hypotensive, hypoxic and required ventilatory and inotropic support. Following extubation, the patient had residual left-sided weakness and MRI confirmed a right frontal watershed infarction. A three week period of clinical improvement was followed by marked deterioration firstly with fluctuating mood and other neuropsychiatric symptoms which progressed to severe impairment of cognition and alertness. There was generalised slowing on the EEG and the CSF was unremarkable. Repeat neuroimaging undertaken on day 41 of the admission, revealed new symmetric and confluent cerebral white matter changes with high signal on the Diffusion Weighted Images (DWI) and Fluid Attenuated Inversion Recovery (FLAIR) images. The patient was managed with supportive care and sustained a clinically significant recovery (MOCA 26/30), despite ongoing cognitive impairments including working memory and deficits in social cognition including mood instability and disinhibition. Repeat neuroimaging 3 months after initial presentation revealed partial resolution of the white matter changes.ConclusionA diagnosis of DPHL should be considered in patients with variable mood and cognition following initial improvement after a hypoxic event.
106 Haemorrhagic spinal cord infarct – a rare complication of sympathomimetic amine toxicity
Authors: Wall Ellen L , Leow Jerome A , Ho Jonathan , Hwang Yun T 
Published: July 2019

IntroductionSympathomimetic amines are recreational substances, available illegally as amphetamine derivatives (eg, ‘ecstasy’ and ‘speed’). Ingestion can lead to significant medical complications such as hyperthermia, tachyarrhythmia, seizures and strokes, attributed to catecholamine surge and sympathetic overstimulation.MethodWe report an unusual case of sympathomimetic amine ingestion manifesting as hypertension followed by acute onset flaccid paralysis of lower limbs bilaterally and T11 level anaesthesia in a 64 year old woman secondary to haemorrhagic cord infarct.ResultsAn MRI spine showed features compatible with spinal cord infarction from thoracic level 6/7 to conus associated with cord haemorrhage. There was no evidence of vascular malformations on imaging and the screen for inflammatory myelitides was negative. A urine drug screen tested positive for sympathomimetic amines and the patient acknowledged ingesting a pill of ‘unknown identity’.ConclusionThis case highlights a previously unreported complication of recreational sympathomimetics associated with significant patient morbidity. Unfortunately, this woman failed to make significant improvements during admission with ongoing severe motor and sensory deficits of her lower limbs.
Enhancement of O-atom density through collisions with Ne by laser-produced plasma in Ne–O2 gas mixtures and possible energy transfer mechanism
Authors: Khan Muhammad Ibrahim , Khan Muhammad Aslam , Zaman Muhammad Iqbal , ur Rehman Najeeb , Masood Asad , Ullah Naqib 
Published: July 2019

Laser-produced plasma in Ne and O2 gases and Ne–O2 gas mixture with different O2 fractions have been investigated. The plasma were produced by focusing a laser beam of 5 ns pulse duration from a Nd:YAG laser ([Formula: see text] = 1064 nm) through a lens of 5 cm focal length into the chamber filled with different gas species at different pressures. Possible enhancement in O-atom densities through collisions with metastable Ne atoms by the laser-created plasma in Ne–O2 gas mixtures and possible energy transfer mechanism was studied. Study of energy transfer through collisions was carried out by comparisons of the line intensities of the emitted spectra from laser-created plasma in gas mixtures and pure gases with the technique of optical emission spectroscopy (OES). Strong evidence of energy transfer from Ne to O was recorded. From the result, it was suggested that the high-lying metastable levels of Ne were responsible for enhancement of O-atoms density in gas mixture and Ne also play important role in energy transfer mechanism through collision. Also, behaviors of the line intensities under different laser energies were studied. Behaviors of line intensities and line widths were the main parameters measured. Stark broadening of lines in Ne with different laser energies was recorded. The electron temperature T[Formula: see text] and number density N[Formula: see text] were found to be 1.01 eV and 9.44 × 10[Formula: see text] cm[Formula: see text] in Ne at different laser energy/pulse with total pressure of 1000 mbar.