bluuebunny/crossref_metadata_2025_split huggingface dataset:
117 Employment-activity status and multidisciplinary care engagement in patients with newly diagnosed dementia: a 16-month audit study within an inner sydney community neurology clinic
Authors: Rigney Louise , Selby Alexis , Chen Lily , Patel Tejas , Hwang Yun T , Mobbs Anthony ED , Mobbs Rowena EA 
Published: July 2019

IntroductionDementia is one of the leading causes of mortality and morbidity in Australia. Attitudes towards dementia in the workplace, tailored adjustments for disability, and patient-centred ‘exit with dignity’ strategies are of objective and subjective importance to patient wellbeing. This study aimed to assess employment characteristics in those with newly diagnosed dementia, and engagement with multidisciplinary supports.MethodsAn audit of patients with diagnosis of dementia (n=136,age51–96 yrs,M:F1.1:1) and mild cognitive impairment (MCI)(n=28,age56–83M:F0.6:1) over a 16 month period in 2017–18 was performed using online server data collection and retrospective analysis of general and employment demographic characteristics, presenting clinical information, and care across clinical psychology, psychotherapy, occupational therapy, speech pathology, and dietetics.ResultsYounger onset dementia was present in 14(10%). Of the 122 dementia cases aged above 65 years, 24(20%) were employed-active, 98(80%) were retired, and none were unemployed. Approximately 5% had a background in healthcare. Allied health support was provided in 106 cases (78%) with ≥3 supports in 28(21%) and was more common in those who were retired(76%) versus employed-active (21%). Clinical psychology or psychotherapy support was provided in 50(37%) cases of dementia. ConclusionsThe onset of dementia often co-exists with active employment. Community perception of employment status in dementia would be of future research interest. Provision of multidisciplinary allied health supports in dementia may facilitate coping, adjustment and cooperative strategies for exit with dignity but further studies are required in this cohort.
121 Diabetic ulnar neuropathy with non-localizing electrophysiology: a nerve ultrasound study
Authors: Pelosi Luciana , Blumhardt Lance , Yong Vivien 
Published: July 2019

IntroductionThe classification and management of diabetic ulnar mono-neuropathy with non-localizing electrophysiology (NL-UN) is challenging, as this could be due to a focal axonal lesion at the elbow that may require surgery or, be part of the mono-neuritis multiplex spectrum of diabetic neuropathy. The distinction cannot be made by clinical examination and electrophysiology.We investigated the value of nerve ultrasound in this situation.MethodsWe analysed ulnar nerve ultrasound in 9 consecutive diabetic patients (5 males, mean age 65.4 years) with 12 NL-UN affected nerves. The ulnar neuropathy was clinically and electrophysiologically severe in 9 nerves and moderate in 3.ResultsUltrasound showed diffuse ulnar nerve abnormality in 9 nerves (75%) and focal nerve abnormalities at the elbow in 3 (25%)ConclusionsThe majority of NL-UNs in this small sample of patients with diabetes were not due to focal lesions at the elbow. This is in contrast with the nerve ultrasound findings in non-diabetic patients with NL-UN, which almost invariably show a focal lesion at the elbow (Pelosi et al, 2018), and confirms that the pathophysiology of ulnar mono-neuropathy is different and more complex in diabetes.Ultrasound appears to be a useful tool to classify NL-UN in the patient with diabetes and larger studies are indicated.ReferencesPelosi, et al. Ulnar neuropathy with abnormal non-localizing electrophysiology: Clinical, electrophysiological and ultrasound findings. Clin Neurophysiol 2018, 129:2155–2161.
122 ‘My migraine voice: burden of migraine and it’s management in an australian cohort’
Authors: Jenkins Bronwyn , Hutton Elspeth , Stark Richard , Quintana Rebeca , Carboni Veruska , Yaghobian Dania , Wieliczko Guillaume , Vo Pamela 
Published: July 2019

IntroductionMigraine is the greatest cause of disability under the age of 50. It impairs ability to function, work and maintain relationships. This survey aimed to assess the impact of migraine and its management.MethodsA questionnaire was sent to patients >18 years old who had taken at least one preventive treatment for migraine in the past. We report here the Australian results.Results68% were women, mean age 41 years. 53% were in paid employment whilst 13% received a disability allowance due to migraine. All patients (n=320) in the Australian survey had ≥ 4 migraine days each month. 90% had taken at least one preventive (274), with 80% (194) needing to change the preventive treatments previously. Common comorbidities were depression (41%), anxiety (40%), chronic pain (29%), sleep disorder (25%) and overweight (24%).Diagnosis rate on initial GP visit was 57%, with 26% receiving a diagnosis in <1 month and 55% by 6 months.There was greater retention of use (60%) and satisfaction (60%) with acute therapies, compared with use (43%) and satisfaction (53%) with preventives. Dissatisfaction with preventives included lack of efficacy (54%) and too many side effects (36%). Most (>60%) patients reported fear of the next attack, feeling hopeless and difficulty thinking clearly during attacks. Employers were often (69%) aware of the migraines, but only 24% offered any support. Migraine had negative impacts on relationships.ConclusionThe Migraine Voice Survey highlights the true burden of migraine in Australia and limitations of current management options.
011 Melbourne mobile stroke unit halves workflow for acute stroke reperfusion therapy
Authors: Zhao Henry , Coote Skye , Langenberg Francesca , Easton Damien , Stephenson Michael , Smith Karen , Bernard Stephen , Desmond Patricia , Mitchell Peter , Yan Bernard , Campbell Bruce CV , Parsons Mark , Donnan Geoffrey A , Davis Stephen M 
Published: July 2019

BackgroundThe Melbourne Mobile Stroke Unit (MSU) utilises a specialised ambulance with on-board CT scanner and multidisciplinary team to provide on-scene imaging, treatment and triage for central Melbourne, Australia. We describe the operational impact of the MSU on commencement of acute reperfusion therapy.MethodsData from the first 12 months of operation were collected for all patients receiving reperfusion therapy from November 2017. Workflow times were compared to contemporary published Australian data and historical controls from Royal Melbourne Hospital.ResultsIn the first calendar 12 months of operation, the Melbourne MSU operated 30.5 service weeks and provided prehospital thrombolysis (tPA) to n=52 patients (44% of eligible infarcts) and directed n=33 patients for endovascular thrombectomy, of which 48% required bypass from the closest non-thrombectomy hospital. The overall median onset-to-tPA for MSU patients was 97.5 mins compared to the Australian metropolitan median of 150 mins. Thrombolysis in the first ‘golden hour’ increased to 13.5% from 3.3% in-hospital. Median onset-to-groin for MSU patients receiving EVT was 162 mins compared to 234 mins from historical controls.DiscussionPrehospital treatment and triage using the Mobile Stroke Unit in metropolitan Melbourne resulted in substantial improvements in commencement of reperfusion therapy. Workflow times are approximately halved for thrombolysis and endovascular thrombectomy respectively. Prehospital thrombolysis also allowed a >400% increase in the proportion of treatment in the first ‘golden hour’.
124 Correlating structure and function to better identify surrogate end points for clinical trial design: a longitudinal clinical and imaging study of primary progressive aphasia
Authors: Mahoney Colin 
Published: July 2019

IntroductionMeasuring longitudinal change in white matter tracts offers a highly sensitive way of monitoring the course of a range of neurodegenerative conditions. However, it remains unclear how structural changes correlate with symptom progression. Clinically meaningful outcomes remain a key requirement in therapeutic trial design so imaging biomarkers need to accurately predict these outcomes. Identifying surrogate clinical end points is of particular importance in neurodegenerative conditions where clinical change evolves slowly. To address this the current study aims to identify potential surrogate end points by assessing correlations between clinical and neuroimaging measures.Methods30 patients meeting consensus criteria for a diagnosis of primary progressive aphasia underwent longitudinal imaging and neuropsychological assessments at baseline and one year. A mixed effects model was designed to test for significant interactions over time between changes in neuropsychological performance and Fractional Anisotropy (FA) in key white matter tracts.ResultsDeclining single word comprehension correlated with reducing FA within bilateral inferior longitudinal fasciculus (ILF), bilateral superior longitudinal fasciculus (SLF) and the genu of the corpus callosum; declining naming ability correlated with reducing FA in the left ILF, right uncinate fasciculus and right SLF; declining word repetition correlated with reducing FA within the left ILF.ConclusionsDeclining neuropsychological scores correlated with longitudinal decline in FA in a number of white matter tracts across an anatomically distributed language network. Correlations between function and structure provide evidence that monitoring structural white matter changes in the tracks identified may have value as a surrogate end point for future clinical trials.
132 Brushstrokes after stroke – art and neuroplasticity
Authors: Narasimhan Manisha , Ramon Lucy 
Published: July 2019

IntroductionDespite current developments in acute stroke therapies, 65% of stroke patients have varying degrees of disability. Whilst focus on acute stroke reperfusion strategies is vital, stroke survivors still need support and appropriate opportunities for rehabilitation.Methods and resultsThis is an inspiring story of an 86-year old patient with locked in syndrome who rediscovered her artistic talent after a disabling stroke. She presented with right hemiparesis, bilateral ptosis, ophthalmoplegia and aphasia. Her MRI showed multiple infarcts affecting the midbrain, thalamic, cerebellar and occipital regions. There was stenosis of the right vertebral artery- the left was hypoplastic, and new atrial fibrillation was detected.There was no response to early rehabilitation strategies and her husband decided to care for her at home. He used creative strategies to encourage motor skills and participation in daily activities, and despite never regaining speech or independent mobility, she was able to interact meaningfully with him and her environment. They enjoyed a full and active life until her demise last year.The patient was an accomplished artist and, with the help of her husband, reengaged in painting. This resulted in an original collection of paintings that formed an exhibition in Wollongong Art Gallery.ConclusionThis is a life affirming story of love, enablement and ingenuity after disabling strokes, and a reminder that neuroplasticity can occur at any age. Art can provide a way to harness neuroplasticity to improve neurological deficits and quality of life, even despite significant disability. ‘A man paints with his brains and not with his hands. ‘(Michaelangelo).
134 Cladribine: a multicentre long-term efficacy biomarker australian study (CLOBAS)
Authors: Lechner-Scott Jeannette , Maltby Vicky , Lyndon Amanda , Monif Mastura , Kilpatrick Trevor , Butzkueven Helmut , Taylor Bruce , McCombe Pamela , Hodgkinson Suzanne , Fabis-Pedrini Marzena , Kermode Allan , Barnett Michael , Kalincik Tomas 
Published: July 2019

IntroductionCladribine tablets (marketed as Mavenclad®) is a new oral therapy, which has recently been listed on the pharmaceuticals benefit scheme (PBS) in Australia for treatment of relapsing MS. The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS up to 4 years in 75% of patients (based on annualised relapse rate). However, re-initiation of therapy after year 4 has not been studied.MethodsThis will be a multicentre, 6-year, phase IV, low interventional trial. Subjects considered for treatment with cladribine will receive an initial treatment course in year 1 and a continuing treatment course in year 2. After year 3, patients will have the option for re-dosing, if clinically indicated or to switch to another disease modifying therapy. Throughout the duration of the study we will assess blood based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation and RNA analysis as well as MRI findings (brain volume/lesion load) and cognitive performance.ResultsThis study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. The study is due to commence on March 14th.ConclusionsThis will be the first long-term efficacy trial of cladribine which offers re-initiation of therapy after the initial two courses. We expect this study will be an indication if any of the assessed biomarkers can be used to predict treatment efficacy or the need for re-initiation of Cladribine in MS patients.
014 AVXS-101 gene-replacement therapy (GRT) in presymptomatic spinal muscular atrophy (SMA): study update
Authors: Farrar Michelle , Swoboda Kathryn J , Schultz Meredith , McMillan Hugh , Parsons Julie , Alexander Ian E , Kernbauer Elaine , Farrow Marcia , Ogrinc Francis G , Feltner Douglas E , McGill Bryan E , Spector Sidney A , L’Italien James , Sproule Douglas M , Strauss Kevin A 
Published: July 2019

IntroductionSMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron 1 gene (SMN1). Copies of a similar gene (SMN2) modify disease severity. In a phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA patients with two SMN2 copies (2xSMN2) dosed ≤6 months. Because motor neuron loss can be insidious and disease progression is rapid, early intervention is critical. This study evaluates AVXS-101 in presymptomatic SMA newborns.MethodsSPR1NT is a multicenter, open-label, phase 3 study (NCT03505099) enrolling ≥27 SMA patients with 2–3xSMN2. Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1×1014 vg/kg). Safety and efficacy are assessed through study end (18 [2xSMN2] or 24 months [3xSMN2]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2xSMN2]) or assisted standing (24 months [3xSMN2]).ResultsFrom April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2xSMN2) at ages 8–37 days. Mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score was 41.7 (n=6), which increased by 6.8, 11.0, 18.0, and 22.5 points at day 14 (n=4), month 1 (n=3), 2 (n=3), and 3 (n=2). As of January 31, 2019, 15 asymptomatic infants have been enrolled in SPR1NT and dosed with AVXS-101. Updated data available at the time of the congress will be presented.ConclusionsPreliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.
017 Widespread extra-motor abnormality is a prominent MRI signature of ALS: a cross-cohort study
Authors: Tu Sicong , Turner Martin R , Kiernan Matthew C 
Published: July 2019

IntroductionAmyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease characterised by motor dysfunction, but now recognised as a complex multi-system disorder. Neuroimaging studies’ indicate an expanding, though inconsistent, list of extra-motor neural involvement. The objective of the current study was to examine pattern of grey matter change across two clinically well matched patient cohorts to identify core neural changes underlying ALS.MethodsIndependent ALS and age-matched healthy control cohorts were compared from Oxford (ALS: 45; Control: 34) and Sydney (ALS: 45; Control: 27). Whole-brain voxel-based morphometry and subcortical volumetric analyses were carried out.ResultsSubcortical volumetric reduction was consistently observed in the thalamus, caudate and hippocampus (all p < 0.05). Pattern of cortical grey matter atrophy showed variability across ALS cohorts, but consistently implicated crus I-II of the cerebellum and orbitofrontal cortices (p < 0.01, family-wise error corrected).ConclusionsThe core grey matter MRI signature of ALS comprises extensive extra-motor cortical and subcortical abnormality. Significant variability exists, which highlights the heterogeneous nature of ALS as defined by current diagnostic guidelines.
018 Role of transcallosal inhibition in disease spread in ALS
Authors: Bos Mehdi Van den , Howells James , Higashihara Mana , Geevasinga Nimeshan , Kiernan Matthew , Vucic Steve 
Published: July 2019

IntroductionThere is substantial evidence for the cortical origin of amyotrophic lateral sclerosis (ALS). Impaired function of the corpus callosum has been demonstrated in ALS patients and may play a role in disease spread, potentially mediating the spread of cortical hyperexcitability between hemispheres. We assessed transcallosal inhibition, utilising the threshold tracking transcranial magnetic stimulation (TMS) technique to assess transcallosal inhibition and related the changes to disease involvement.MethodsThreshold tracking TMS was undertaken in 15 ALS patients and results were compared to 16 healthy controls. Interhemispheric inhibition was assessed using a figure of eight coil over each hemisphere across interstimulus intervals ranging from 8 to 40ms.ResultsTranscallosal inhibition was reduced in ALS patients (0.9 ± 1.0%) when compared to controls (6.6 ± 1.0%, P=0.03). Importantly differences in transcallosal inhibition between hemispheres were evident in ALS patients. Specifically, transcallosal inhibition projecting from the motor cortex contralateral to disease onset (0.9 ± 1.0%) was significantly lower when compared to projection form the ipsilateral motor cortex (3.2 ± 1.0%, P=0.036). Abnormalities of transcallosal inhibition correlated with upper motor neurone dysfunction and greater functional disability in ALS.ConclusionAbnormalities of transcallosal inhibition were demonstrated in ALS patients and were associated with clinical features. Consequently, dysfunction of transcallosal fibres may contribute to development of cortical hyperexcitability, a pathogenic mechanism in ALS. Strategies aimed at modulating dysfunction may prove therapeutically useful in ALS.
027 Will refractory patients respond to erenumab in the real world?
Authors: Jenkins Bronwyn , Cheng Shuli , Hutton Elspeth 
Published: July 2019

IntroductionErenumab has been studied in Randomised Controlled Trials (RCT), with stricter exclusion criteria than real world populations.Methods65 patients from two Australian headache centres on Erenumab had primary outcomes of ≥ 50% response in monthly migraine days (MMD) and monthly headache days (MHD), compared to their demographics, frequency, duration of Chronic Migraine (CM), failed prophylactic medications, severity scores and medication overuse headache (MOH).Results35% (23/65) had daily headaches, with ≥ 50% MHD and MMD reduction in this subgroup of 17% (4/23) and 65% (13/20), respectively. Duration of CM was >10 years in 48% (29/61), with ≥ 50% MHD and MMD reduction in 28% (8/29) and 48% (13/27), respectively. 100% (64/64) had failed > 3 prophylactic medications with ≥50% MHD and MMD reduction in 30% (19/64) and 47% (27/58), respectively, with reducing rates of ≥ 50%MMD reduction if >5 (29%; 17/58) and >10 (22%;2/9). 95% had high severity scores (HIT-6 score >60), with a ≥ 50% MMD reduction in 43% (23/54). MOH occurred in 41% (24/58) for triptan and 29% (17/58) for codeine medications, with a ≥ 50% MMD reduction in 71% (17/24) and 41% (7/17), respectively (all groups p>0.05).ConclusionThis real world cohort treated with Erenumab included patients that would be excluded from RCT analysis- including more chronic, frequent, severe and refractory migraine. Despite this, there were still ≥50% responders in more severe subgroups, particularly daily headache, high severity scores and triptan MOH. Measuring MMD may be more sensitive for assessing improvement than MHD.
028 Delayed CT imaging leading to delays in acute stroke management in regional australia
Authors: Nindra Udit , Wonson Toni M , Fuller Karen 
Published: July 2019

IntroductionUrgent CT imaging is crucial for acute stroke management to allow for timely thrombolysis and early referral to a peripheral endovascular thrombectomy (ECR) service. Delays in CT imaging are suspected to correlate with lengthening door-to-needle time (DNT) and arrival-to-referral time (ART) in regional Australia.Methods and resultsWe retrospectively analysed 656 acute stroke admissions between 2016 and 2018 to determine mean DNT and ART in addition to influencing factors such as age, gender, onset to arrival time & baseline National Institute of Health Stroke Scale (NIHSS) score. Over 3 years, 70 patients underwent thrombolysis and 56 ECR. The mean DNT was 108 minutes with mean arrival to CT time of 30 minutes. Multiple linear regression displayed a positive correlation between arrival to CT time and DNT (p<0.01). For every 10-minute delay in CT imaging, there was a 6-minute delay in DNT (95% CI 2 – 11 minutes). The mean ART was 150 minutes. A positive correlation was again seen between ART and arrival to CT Time (p=0.02). For every 10-minute delay in CT imaging, there was a 9-minute delay in ART (95% CI 1 – 16 minutes).ConclusionsIt is known that early initiation of both thrombolysis and ECR are associated with positive patient outcomes. There is a need to reduce time taken to complete CT imaging in regional Australia, as it is clearly shown to be associated with lengthened time for treatment initiation and timely referral. Reduction in this arrival to CT time will likely improve patient outcomes.
046 A critical review of biomarkers for hereditary spastic paraplegia
Authors: Siow Sue-Faye , Wali Gautam , Sue Carolyn , Kumar Kishore R 
Published: July 2019

IntroductionHereditary spastic paraplegia (HSP) is a rare neurodegenerative condition characterised by lower limb weakness and spasticity. Currently, treatment is symptomatic and there is no disease modifying therapy. Though candidate therapeutic agents have been identified, sensitive biomarkers to measure treatment efficacy in clinical drug trials are lacking. There are many challenges in the search for appropriate biomarkers including the rarity of HSP, clinical and genetic heterogeneity of HSP and slow disease progression.MethodsWe performed a search on PubMed and Medline using the search terms (‘hereditary spastic paraplegia’ OR ‘spastic paraparesis’) AND ‘biomarker*’. We searched the reference lists of relevant articles to identify further studies. We collected data on number of participants, HSP genotype, methodology, and outcomes.Results72 papers were identified: 2 on Rating scales, 9 on gait analysis, 33 on neurophysiological measures, 23 on neuroimaging markers and 5 on biochemical markers. The studies reviewed demonstrated variation in methodologies and outcomes, including mixed genotype (41/72 papers) and genotype-specific (31/72 papers) patient cohorts, varied neurophysiological techniques and different outcome measures. 68/72 studies reviewed had small patient numbers (<50 patients). All potential biomarkers reviewed were able to differentiate HSP patients from controls. Only diffusion tensor imaging (DTI) parameters showed significant correlation with disease severity.ConclusionAlthough useful as diagnostic biomarkers, further studies are required to evaluate these potential biomarkers longitudinally and to assess their reliability as surrogates for underlying neurodegenerative changes and clinical disease severity. DTI showed the most promise as a biomarker for disease severity in HSP.