bluuebunny/crossref_metadata_2025 huggingface dataset:
024 Resistance exercises with blood flow restriction in patients with sporadic inclusion body myositis
Authors: Liang Christina , Burk Melanie , Wall Abby , Davis Ryan , Augustine Libby , Bright Sarah , Brown Whitney , Harris Anneliese , Holmes Sarah , Jeyalingam Sayanthinie , Large Sarah , Mai Sylvia , Raper Eleanor , Judtih Wong Hang Wah , Wong Pok Man , Sue Carolyn M , Lucas Barbara
Published: July 2019

Introduction

Sporadic inclusion body myositis (sIBM) is the most common muscle disease affecting older adults with no disease-modifying treatment. Resistance exercises increase muscle hypertrophy, but weakness prevents exercising with higher resistance. In healthy subjects, augmentation of light-load training with blood flow restriction improved muscle strength1; and similar exercises were safe in the elderly.2 We therefore investigate whether resistance exercises with blood flow restriction is safe and helpful in sIBM patients. We explored methods for exercising weak leg muscles, and options for better outcome measures.

Methods

A matched-control pilot study, with 12-week treatment and 4-week follow-up periods, where participants concentrated on lower limbs resistance exercises with 50% blood flow restriction 3 times/week, at 20%-30% of their repetition maximum. Patients are reviewed 4-weekly for muscle strength, blood biomarkers, 2-minute walk test (2MWT), timed up-and-go (TUG) test, minimal chair height standing ability test (MCHSAT), thigh girths, and quality of life scales.

Results

4 patients with varying abilities were on the exercise arm, and 3 acted as controls. Muscle groups with MRC score ≥2 were able to be exercised. We found strength testing by hand-held dynamometer was unreliable, whereas the 2MWT, TUG test and MCHSAT showed less variability. All patients could perform their exercises at significantly increased repetitions or weights by week 4, without concerning adverse events, with trend towards continued improvement over the 4-month period.

Conclusion

Resistance exercises with blood flow restriction appear safe, and may be helpful in sIBM patients, even in weakened muscles, enabling improvement in muscle strength and endurance.

References

Hughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports 2017.

Vechin FC, Libardi CA, Conceicao MS, et al. Comparisons between low-intensity resistance training with blood flow restriction and high-intensity resistance training on quadriceps muscle mass and strength in elderly. J Strength Cond Res 2015.
036 The impact of a clinical support tool on stroke key performance indicators
Authors: Alanati Khaled , Evans James
Published: July 2019

Introduction

Adherence to key performance indicators (KPIs) in stroke care is associated with better outcomes.1–6 The complexity in management of acute strokes, however, has created barriers towards delivering best care with plateauing of KPIs as measured by The National Stroke Foundation Clinical Audit.

We examined the impact on stroke KPIs in our local health district of a web-based decision support stroke platform which provides clinicians with up-to-date information about the patient’s management flagging potential areas for improvement, allowing treatment to be optimised in real time.

Methods

Six months following the introduction of the platform we performed a retrospective analysis of Electronic medical records of patients admitted to Gosford hospital with acute stroke between June 2018 and September 2018 assessing access to the stroke unit as well as being discharged on appropriate secondary prophylactics, including antihypertensives and correct antithrombotic therapy. Patients whose direction of care was palliative and patients with documented contraindication to secondary prophylactics were excluded.

Results

Over four months, 136 patients presented with acute ischaemic stroke and 11 patients had a haemorrhagic stroke. 49 ischaemic stroke patients had atrial fibrillation. Stroke unit access was higher following its introduction in 2018 compared to 2017 (97% vs 76%, respectively). Similar findings were noted for patients with atrial fibrillation who received oral anticoagulants on discharge (90% vs 50%) and patients discharged on antihypertensives (95% vs 80%).

Conclusion

Use of a clinical support platform in managing acute stroke is an intervention that improves stroke care.

References

Urimubenshi G, Langhorne P, Cadilhac DA, Kagwiza JN, Wu O. Association between patient outcomes and key performance indicators of stroke care quality: A systematic review and meta-analysis. European Stroke Journal 2017;2(4):287–307. https://doi.org/10.1177/2396987317735426

Sandercock P, Gubitz G, Foley P. Antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev 2003;2: CD000029. Google Scholar

Kwan J, Sandercock P. In-hospital care pathways for stroke. Cochrane Database Syst Rev2004;4: CD002924. Google Scholar

Saxena R, Koudstaal PJ. Anticoagulants for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. Cochrane Database Syst Rev 2004;4: CD000187. Google Scholar

Goyal M, Menon BK, van Zwam WH. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trial. Lancet 2016;387:1723–1731. Google Scholar | Crossref | Medline | ISI

Middleton S, McElduff P, Ward J. Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet 2011;378:1699–1706. Google Scholar | Crossref | Medline | ISI
039 Estimating the health and economic burden of investigating tumefactive demyelination compared to conventional multiple sclerosis
Authors: Silsby Matthew , Lopez Pedro S , Spies Judy , Reddel Stephen , Frith Jane , Barton Joshua , Beadnall Heidi , Barnett Michael , Hardy Todd
Published: July 2019

Introduction

Tumefactive demyelinating lesions, defined as demyelinating lesions > 2cm in diameter, occur most commonly in association with multiple sclerosis (MS), and can pose a diagnostic challenge. The aim of this study was to estimate the cost and morbidity associated with the diagnostic investigation of patients with tumefactive demyelination (TD) compared to patients with conventional relapsing-remitting MS.

Methods

Retrospective review of patients seen between 2013–2018 in clinics at the Brain and Mind Centre, Sydney; a centre with tertiary referral expertise in MS. Records were searched for the terms ‘tumefactive’ and ‘pseudotumour’. All patients diagnosed with TD were included and paired with a patient of similar age diagnosed in the same year with MS according to 2010 McDonald criteria.

Results

There were 31 patients with TD and 31 patients with conventional relapsing remitting MS. The estimated cost of investigating TD was more than 7.5 times higher per patient than in MS ($18,300 AUD vs $2,418 AUD, p<0.001). Brain biopsy was performed in 6/31 TD patients and 0/31 MS patients and was the cause of more adverse outcomes in the TD versus MS group. More patients in the TD group were admitted to hospital (22/31 vs 10/31) and ICU admissions only occurred in the TD group (10/22 vs 0/10).

Conclusion

The cost and adverse outcomes associated with investigating TD are higher than in conventional MS. Improvements in the diagnosis of TD have the potential to improve health and economic outcomes.
004 Vestibular event monitoring in the emergency department
Authors: Nham Benjamin , Reid Nicole , Argaet Emma , Young Allison , Bein Kendall , Halmagyi Gabor M , Welgampola Miriam S
Published: July 2019

Introduction

Acute vertigo is often accompanied by ictal-nystagmus which may assist with diagnosis. We examine the merits of a structured assessment combined with vestibular event-monitoring in the Emergency Department (ED).

Methods

We undertook a structured clinical assessment and video-nystagmography in 220 non-consecutive patients presenting to a public-hospital ED with acute vertigo, during a 10-month period. The records of 115 consecutive vertiginous patients who underwent standard-assessment were compared.

Results

For the structured assessment group: 54% presented with acute vestibular syndrome (AVS), 24% with episodic spontaneous vertigo (EVS), and 20% with recurrent positional-vertigo (RPV).

For AVS (n=119), most common diagnoses were vestibular neuritis (34%), stroke (34%) and vestibular migraine (13%). Nystagmus slow-phase velocity (SPV) for VN, stroke and VM were 11±5.5o/s, 5.6±2.5o/s, 5.4±5.9o/s; Mean ipsilesional video-head impulse gains were 0.51±0.29, 0.89±0.20 and 0.96±0.13. For EVS(n=53), diagnoses included vestibular migraine (63%), Meniere’s Disease (11%) and others (26%). Nystagmus SPV was 5.4±3.6o/s, 7.6±6.3o/s, 4.1±1.5o/s. In RPV (n=43), common diagnoses were posterior-canal BPPV (66%), horizontal-canal BPPV (23%), migraine (7%). Positional nystagmus SPV profile showed Peak SPV of 42.5o/s, 77.6o/s, 20.64o/s and Time-constants of 6.52s, 22.51s, 34.56s for Posterior-canal BPPV, Horizontal-canal BPPV and Atypical Positional-Vertigo. A final diagnosis was reached in 96% of patients.

In the ED control group, only 77% were separated into spontaneous or positional-vertigo. A diagnosis was provided in 57% and was concordant with the history and examination in 34%.

Conclusion

Vestibular event-monitoring and structured clinical assessment secured a diagnosis in 96% of cases compared with 34% for the control group, reinforcing its merit.
045 Primary cutibacterium acnes central nervous system infection causing focal seizures: an unusual presentation of a rare disease
Authors: Waller Sophie E , Browning Sarah , Pepper Elizabeth
Published: July 2019

Introduction

Cutibacterium acnes is a Gram positive, anaerobic bacterium of low pathogenic potential that forms part of the normal cutaneous flora. Although most often identified as a contaminant in culture of microbiological specimens, it is commonly implicated in both postoperative wound and implantable device infection. Neurosurgical device infections secondary to C. acnes are well recognised and are likely secondary to bacterial contamination from the skin during surgery. Indolent infection characterised by delayed presentation of weeks to months following intervention is common. C. acnes infection involving the central nervous system (CNS) in the absence of previous neurosurgical intervention is rare, but has been described following dental or mastoid infections and following facial trauma. A further case series has reported de novo C. acnes CNS infection occurring in the absence of these recognised risk factors, but with clinical features of meningitis being common to all.

Methods and results

We describe a unique case of primary C. acnes extra-dural collection in a previously well patient with no neurosurgical history presenting with sub-acute focal seizures and progressive focal leptomeningeal thickening on MRI.

Conclusion

C. acnes CNS infection can occur in the immunocompetent and in the absence of neurosurgical intervention.
053 GLUT-1 deficiency presenting as dopa-responsive dystonia: an atypical phenotype of a rare disease
Authors: Waller Sophie E , Blackie Jeffrey , Goel Himanshu
Published: July 2019

Introduction

The SLC2A1 gene encodes the glucose transporter GLUT1, responsible for normal glucose transport across the blood-brain barrier. Mutations in this gene have classically been associated with an epileptic encephalopathy referred to as GLUT-1 Deficiency Syndrome, which typically presents with early-onset refractory epilepsy, developmental delay and complex movement disorders.1 2 More recently, SLC2A1 variants have been identified in patients with paroxysmal exercise-induced dyskinesia (PED), with or without a history of epilepsy.3 4 Response to medication is typically poor; however, both seizures and dyskinesia may improve following implementation of a ketogenic diet.5 A single case of levodopa responsiveness has previously been described in a subject with SLC2A1 mutation and PED.5

Methods and results

We describe a 47-year-old female with mild intellectual disability since childhood but no history of epilepsy, who developed episodic dystonia affecting the lower limbs in her early 20’s. A clinical diagnosis of dopa-responsive dystonia was made following a marked, sustained response to levodopa. There was no significant family history. In her 40’s she developed breakthrough dystonia with exertion and choreiform movements affecting the fingers and face. A subsequent dystonia panel identified a heterozygous variant c.[1199G>T];[=] (p.Arg400Leu) in the SLC2A1 gene. Cerebrospinal fluid glucose concentration was low (2.0 mmol/L). She declined a trial of a ketogenic diet.

SLC2A1 variants are associated with PED; however, response to levodopa has not been widely reported.

Conclusion

It is becoming increasingly evident that the phenotypic presentations of GLUT1 deficiency are diverse, and SLC2A1 testing should be considered in a broader range of patients.

References

Wang, D, Kranz-Eble P, De Vivo DK. Mutational analysis of GLUT1 (SLC2A1) in Glut-1 Deficiency Syndrome. Human Mutation 2001;16:224–231.

Klepper J, Leiendecker B. GLUT1 deficiency syndrome – 2007 update. Developmental Medicine & Child Neurology 2007;49:707–716.

Schneider SA, Paisan-Ruiz C, Garcia-Gorostiaga I, Quinn NP, Weber YG, et al. GLUT1 gene mutations cause sporadic paroxysmal exercise-induced dyskinesias. Mov Disord 2009;24(11):1684–1696.

Suls A, Dedeken P, Goffin K, Van Esch H, Dupont P. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, endoding the glucose transporter GLUT1. Brain 2008;131:1831–1844.

Baschieri F, Batla A, Erro R, Ganos C, Cordivari C, Bhatia KP. Paroxysmal exercise-induced dystonia due to GLUT-1 mutation can be responsive to levodopa: a case report. J Neurol 2014;261:615–616.
059 Takotsubo cardiomyopathy and myasthenic crises: a case series
Authors: Katz Matthew , Walsh Stephen , Tsang Benjamin , McCombe Pamela , Sabet Arman
Published: July 2019

Introduction

Takotsubo cardiomyopathy (TCM) is an acute, reversible cardiomyopathy that can mimic acute coronary syndrome.1 It is characterised by left ventricular dysfunction, electrocardiogram (ECG) changes and transient apical ballooning in the absence of significant coronary artery disease.1 It is usually triggered by acute stress with catecholamine surge but the exact pathogenesis is not known.1 Takotsubo cardiomyopathy has been described in patients with myasthenic crisis. We present the first and largest case series of four patients with TCM in the setting of myasthenic crisis and discuss possible causes.

Methods

Two patients from each tertiary neurologic centre were identified by their treating neurologist for inclusion in the series. We performed a review of their case notes with respect to history, examination, investigations and management. A brief literature review was also completed.

Results

The mean age was 78 with a 1:1 female to male ratio. Three of the patients were newly diagnosed with myasthenia gravis (MG) at the time of their TCM. All patients were AChRab positive. One patient had a previous thymectomy but the others had no evidence of thymoma.

On review of the literature most cases of TCM in myasthenic crisis occurred in older females. Abnormalities of the ECG were universal. Most cases did not have a thymoma or history of thymectomy.

Conclusion

Takotsubo cardiomyopathy may be easily overlooked in those presenting with myasthenic crises as they share overlapping clinical features. Rigorous attention to the cardiac status of these patients, especially the ECG, may help to avoid missing this important diagnosis.

Reference

Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 2008;118:2754–2762.
070 Burden of migraine is australia: a systematic literature review
Authors: Benhaddi Hicham , McCabe Sophie , Lau Diana T
Published: July 2019

Introduction

Migraine is a disabling neurological disease characterised by recurrent attacks of moderate to severe headaches. This systematic literature review (SLR) aimed to investigate the clinical, humanistic, and economic burden of chronic migraine (CM), episodic migraine (EM), and of current preventive migraine treatments in Australia.

Methods

The methodology of this SLR was aligned with the National Institute for Health and Care Excellence (NICE) guidelines. An electronic database search was conducted in Embase, MEDLINE and the Cochrane Library, with a time frame of 2008 to 2018.

Results

In total, 1,122 records were identified and 168 of these were included for data extraction. The prevalence of migraine in Australia is estimated at 18.9%. Of those, 44% of people with EM and 86% of people with CM reported moderate-to-severe disability. Over one-third (36%) of people with EM and nearly two-thirds (64%) of people with CM reported visiting a healthcare provider in the previous three months. No data relating to the economic burden of migraine were returned by the searches. In people with EM and CM, anti-calcitonin gene-related peptide (anti-CGRP) preventive treatments for migraine safely, effectively and significantly reduced the mean number of monthly migraine and/or headache days from baseline compared with placebo.

Conclusions

Migraine is associated with a substantial burden, and people living with migraine feel the impact in their day-to-day lives. Anti-CGRPs are a promising class of preventive treatments for all people with migraine. Longer-term studies are needed to determine if the positive effects of anti-CGRPs are sustained over greater time periods.
080 The incidence, diagnosis and outcomes of idiopathic intracranial hypertension in the southern tasmanian catchment
Authors: Krishnadas Natasha , Taylor Bruce
Published: July 2019

Introduction

This study aimed to identify the incidence of idiopathic intracranial hypertension (IIH) in Southern Tasmania, Australia. Secondary aims were to elucidate demographics, current approaches to investigation, treatment and outcomes. To our knowledge, similar regional studies have not been performed.

Methods

The study was approved by the University of Tasmania Human Ethics Committee. Patients presented between June 2016-June 2018 to Royal Hobart Hospital, the single tertiary Neurology service in Tasmania. Cases were identified by screening lumbar punctures (LP) performed by Neurology services (inpatient, outpatient, Radiologically-assisted) and by surveying all regional Neurologists. Medical records were used to corroborate LP results and determine whether patients met Modified Dandy Criteria (MDC) (used to define IIH in current literature). Regional population statistics were obtained from the Australian Bureau of Statistics (ABS). Duplicate records were excluded. Exclusion criteria included age <18 at data collection, LP opening pressure <20cm of water or secondary causes for IIH.

Results

45 cases identified; 30 within the Greater Hobart region, population of 229,088 (June 2016-June 2017). Cumulative incidence was 6.55/100,000 (incidence rate 0.06/1000) with classification based on Neurologist diagnosis and 5.46/100,000 (0.05/1000) with classification according to MDC. 100% of the cohort were female. Mean age was 26.7 (range 17–45) and mean weight was 105.3kg (range 78–170). Headache was the most commonly reported symptom. 8.9% (4/45) of the total cohort were medically refractory (requiring VP/LP shunting). Ophthalmology services initiated 51% (23/45) of the referrals.

Conclusions

Our incidence rates are higher than rates in previous studies for population subsets of young women.
082 The gastrointestinal microbiome in parkinson’s disease: impacts of motor and non-motor features, medications, lifestyle and diet
Authors: Lubomski Michal , Tan Ai Huey , Lim Shen-Yang , Holmes Andrew , Davis Ryan L , Sue Carolyn M
Published: July 2019

Introduction

The human gastrointestinal microbiome (GM) has been proposed to be integral in the pathogenesis of Parkinson’s disease (PD). Evidence supports a bidirectional interaction between the brain and the gut that is mediated by the GM. Dysbiosis of the GM is believed to negatively influence vital physiological functions in many diseases.

Methods

We reviewed the literature on changes in human physiological function associated with gut microbial community states in PD. In particular, we evaluated the literature for effects of GM dysbiosis on motor and non-motor features, dietary and lifestyle factors and medication use in PD.

Results

Altered GM profiles in PD have been suggested to disrupt vital signalling pathways within the microbiota-gut-brain axis, integral to regulating physiological digestive function and metabolic homeostasis. Unfavourable variations in the GM have been shown to perturb mood (anxiety/depression), cognition, perception (hallucinations/delusions), gastrointestinal motility, including constipation in PD. Further, varied clinical motor phenotypes, including postural instability and gait disturbance have been attributed to alterations in the GM, in addition to the use of catechol-O-methyltransferase inhibitors, anticholinergics and levodopa. Variations in dietary and lifestyle factors have also been inferred to cause alterations in GM profiles, including caffeine consumption, macronutrient intake, smoking and the effects of ageing and exercise.

Conclusions

It is apparent from the mounting evidence that alterations in the GM are intimately involved in PD pathogenesis. However, the GM can also be modulated by dietary, lifestyle and treatment factors that may influence motor and non-motor features as well as disease progression.
088 Cladribine tablets were associated with rapid onset of improvements in MRI outcomes in the ORACLE-MS trial
Authors: Gillett Alan , Scarberry Susan , Damian Doris , Hyvert Yann , Dangond Fernando , Lebson Lori , Leist Thomas
Published: July 2019

Introduction

In ORACLE-MS (616 subjects with a first demyelinating event at high risk of converting to multiple sclerosis), cladribine tablets (CT) 10 mg (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years) significantly delayed the time-to-conversion to clinically definite multiple sclerosis (CDMS), and reduced new/persisting T1 gadolinium-enhancing (T1 Gd+), new/enlarged or active T2 and combined unique active (CUA) lesion number. Here, the timing of CT effect is evaluated.

Methods

MRI scans were performed at screening and every 12 weeks, for non-converting CDMS subjects. MRI-based endpoints were analyzed using analysis of covariance (ANCOVA) and negative binomial models. The temporal effects of the first yearly treatment course of CT and placebo on T1 Gd+, active T2, and CUA lesions were evaluated.

Results

96 weeks: the reduction in mean T1 Gd+, active T2, or CUA lesion number per patient per scan was nominally significantly greater for CT versus placebo (p<0.0001). Early change in Gd+ lesion volume (at Week 13) from baseline was CT, -155.73 mm3; placebo, -14.76 mm3. Comparatively larger reductions in mean active T2 and CUA lesion numbers with CT at Week 13 versus placebo were observed (active T2: CT, -1.25; placebo, -1.43; CUA: CT, -1.56; placebo, -2.41). The mean number of T1 Gd+ lesions at 13 weeks following CT was 0.37 versus 1.0 with placebo.

Conclusions

MRI data from ORACLE-MS subjects suggest the first yearly treatment course of CT has a rapid onset of action, with beneficial treatment effects on active lesion number and volume evident by Week 13.
089 Breaking the cycle of chronic daily headache with a low-dose subcutaneous lignocaine and ketamine infusion
Authors: Rofe Christopher JF , Garrick Raymond , Burke David , Brew Bruce J , Tomlinson Susan E
Published: July 2019

Introduction

Management of chronic migraine includes correcting analgesic rebound headache and implementing suitable medication for prevention and acute episodes. However, in many cases this management paradigm oversimplifies the complexity of chronic migraine, particularly the entrenched central pathways that perpetuate chronic migraine. Intravenous lignocaine can curtail chronic migraine and analgesic rebound headache (1). Further, ketamine provides short-term analgesia and enables reduction in central sensitisation of pain pathways, particularly in the setting of codeine/opiod overuse (2). This paper describes use of subcutaneous lignocaine and ketamine infusion in chronic migraine.

Methods

A prospective observational cohort study was undertaken in patients with chronic migraine. Patients received a prolonged subcutaneous lignocaine and ketamine infusion (mean duration 11 days) and underwent evaluation at four-time points over six months. The effects on the excitability of motor axons in the median nerve were documented using standard procedures.

Results

Fourteen patients were recruited. The infusion was well tolerated; no major side effects were seen. There were no significant long-term changes in the excitability of motor axons. At six months, 13/14 patients had sustained benefit. Three of 4 patients remained free of analgesic rebound headache. One patient remained headache-free. Conversion to episodic migraine occurred in 6/14. Improvement in chronic migraine was reported by 6/14. Three of six were able to return to work, with 1 returning to studies. Benefit was greater in those with depression and history of opiod/codeine use.

Conclusion

Subcutaneous lignocaine and ketamine can help break entrenchment in chronic migraine as part of a structured management plan.
090 The effect of cladribine tablets on delaying the time to conversion to clinically definite multiple sclerosis (MS) or McDonald MS is consistent across subgroups in the ORACLE-MS study
Authors: Bowen James , Gillett Alan , Damian Doris , Hyvert Yann , Dangond Fernando , Grosso Megan , Leist Thomas
Published: July 2019

Introduction

In the Phase 3 ORACLE-MS trial in 616 subjects with a first demyelinating event at high risk of converting to multiple sclerosis (MS), treatment with cladribine tablets 10 mg (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years [CT3.5 and CT5.25, respectively]) significantly delayed time to conversion to clinically definite multiple sclerosis (CDMS) according to Poser criteria (67% or 62% risk reduction [RR], respectively) and time to conversion to 2005 McDonald MS (50% or 57% RR, respectively), versus placebo. The objective was to analyze the effect of cladribine tablets vs placebo on converstion to CDMS and McDonald MS across ORACLE-MS patient subgroups based on baseline characteristics.

Methods

In this post-hoc analysis, time-to-conversion to CDMS or McDonald MS over the double-blind period was analyzed for patients treated with CT5.25 (N=204), CT3.5 (N=206) or placebo (N=206) across different subgroups. Subgroups were defined by baseline characteristics which have been investigated as potential predictors of CDMS conversion (age [<30 or ≥30 years], gender, first classification demyelinating event [monofocal or multifocal], presence of T1 Gd+ lesions and number of T2 lesions [<9 or ≥9]).

Results

Treatment with CT3.5 or CT5.25 was consistently efficacious across the subgroups examined on conversion to CDMS versus placebo for most comparisons (RR range: CT3.5, 39%–72%; CT5.25, 36%–79%). Similarly, treatment effect of both doses on conversion to 2005 McDonald MS was consistent across subgroups (CT3.5,40%–59%;CT5.25,42%–79%).

Conclusions

The effect of cladribine tablets on delaying the time-to-conversion to CDMS, or to McDonald MS, is consistent across subgroups.
091 Cerebellar oedema in fulminant adult leigh syndrome
Authors: Edwards Leon S , Halmagyi Gabor M , Barnett Michael H , Blair Christopher A , Kiernan Matthew C
Published: July 2019

Introduction

We report a case of adult Leigh syndrome resulting in rapidly fatal cerebellar oedema.

Case

A 19-year-old female presented with a five-week history of hyperventilation, generalised weakness, dysarthria and bilateral ptosis. Brain Magnetic resonance imaging (MRI) findings and the presence of a mitochondrial mutation (NC_012920.1(MT-ATP6):m.9176T>C) in blood and urine with approximately 97% heteroplasmy, confirmed a diagnosis of Leigh syndrome.

Two-days after a normal lumbar puncture, opening pressure 8cm water, her conscious level rapidly declined. CT revealed marked cerebellar oedema with brainstem compression. Despite immediate decompression, she did not recover consciousness and died six-weeks after symptom onset.

Conclusion

Adult Leigh syndrome is a progressive untreatable inherited mitochondrial disorder typically of infants and children. Adult cases are rare and described mostly in single case reports. There is marked phenotypic and genotypic variability. Over 83% of Leigh’s syndrome is identified by the age of 2 years, however, there have been cases reported in patients up to 74 years old. There are over 60 mutations described in Leigh syndrome, which are identified in only half of reported cases. Classic MRI changes include bilateral symmetric T2 hyper-intensities in the basal ganglia and brainstem. To our knowledge, this is the first reported case resulting in fulminant cerebellar oedema. A challenge of diagnosis remains the marked heterogeneity in presenting symptoms including cognitive decline, behavioural change and ophthalmoparesis. Typically, this syndrome has been confirmed by histopathology at autopsy. Advances in genetics and imaging have allowed earlier accurate diagnosis, potentially paving the way for improved therapeutics.
104 Silent multilevel vertebral fractures in a severe case of glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus (PERM)
Authors: Min Myintzu , Liu Han , Silberstein Paul
Published: July 2019

Introduction

Autoimmune encephalitides are a heterogenous and potentially devastating group of disorders. Antibodies to glycine receptor (GlyR) are rare and increasingly reported in patients with progressive encephalomyelitis with rigidity and myoclonus (PERM). PERM patients develop early brainstem and autonomic dysfunction, and if untreated, can be fatal. We aim to discuss the complications and treatments in this PERM case and review the literature on management of PERM.

Methods

We report a case of PERM currently undergoing treatment in our hospital.

Results

Mr GT is a 46-year-old male who presented with a prodromal phase of altered sensation and acute cerebellar signs. He rapidly deteriorated with bulbar dysfunction and developed generalised muscle rigidity and hyperreflexia. Infective work-up, cerebrospinal fluid analysis, magnetic resonance imaging of brain and spine were initially normal. He was started on first line immunosuppressants for a clinical diagnosis of autoimmune encephalitis. Despite sedation in intensive care, generalised myoclonus and truncal extensor spasms were severe and presented on-going management difficulties. A computed tomography scan of his abdomen to exclude malignancy revealed incidental findings of vertebral fractures at multiple thoracic and lumbar levels. He was subsequently administered rituximab and demonstrated some signs of recovery. GlyR antibody positive results from Oxford University Hospital consequently confirmed his diagnosis.

Conclusion

This is the fourth reported GlyR antibody-positive PERM case in Australia and the first description to our knowledge with intractable rigidity and myoclonus leading to vertebral fractures. Awareness and screening for this complication may assist in management of patients with PERM.
105 A presentation resembling transient global amnesia with underlying tako-tsubo cardiomyopathy and multifocal ischaemic stroke (with restricted diffusion in the left mesiotemporal lobe)
Authors: Lefever Kristen , Tyson Chloe , Shelley Lisa , Schweitzer Daniel , Swayne Andrew
Published: July 2019

Introduction

We present a case of a 65 year-old female with a presentation resembling transient global amnesia (TGA) with investigations revealing a Tako-tsubo cardiomoyopathy and multifocal punctate areas of restricted diffusion consistent with ischaemic stroke.

Methods

Single case report.

Results

A 65 year-old female presented altered behaviour with anterograde amnesia consistent with an episode of TGA. There was no clearly identifiable stressor to provoke this episode. The TGA-like symptoms persistent for 12 hours before the patient made a full recovery.

During the presentation the patient complained of chest pain with elevated troponin. Cardiac investigation was notable for mild left ventricular dilation with mid- and apical hypokinesis on transthoracic echocardiogram and a normal coronary angiogram consistent with Tako-tsubo cardiomyopathy. Magnetic resonance imaging of the brain revealed multifocal infarcts including punctate foci of restricted diffusion within the left mesiotemporal lobe.

Conclusion

This case is notable as it is rare to have a combined presentation with TGA-type symptoms with Tako-tsubo cardiomyopathy and multifocal ischaemia stroke.1 This is the first clinical case presentation involving the aforementioned triad and mesiotemporal lobe restricted diffusion. We hypothesise that the Tako-tsubo cardiomyopathy acted as the triggering event and the mesiotemporal lobe involvement caused the TGA-like symptoms thereby accounting for the clinical presentation and investigation findings. As mesiotemporal/hippocampal restricted diffusion may be seen with transient global amnesia,2 this case is of special interest mechanistically although we cannot exclude the alternative hypothesis that the episode of TGA resulted in the Tako-tsubo cardiomyopathy which subsequently caused the cardioembolic shower.

References

Stollberger C, DeCillia N, Finsterer J. ‘Tako-tsubo cardiomyopathy with transient global amnesia and cerebellar embolic stroke triggered by existential fear.’Neurol Neurochir Pol 2018; 52(3):394–396.

Enzinger C, Thimary F, Kapeller P, Ropele S, Schmidt R, Ebner F, Fazekas F. ‘Transient global amnesia: diffusion-weighted imaging lesions and cerebrovascular disease.’Stroke 2008;39(8):2219–2225.
108 Endovascular clot retrieval beyond 24 hours for top of the carotid occlusion
Authors: Kopanidis Paul , Zhai Shaun , Lalloo Shivendra , Patel Ronak , Gawarikar Yash
Published: July 2019

Introduction

Sub-clinoid proximal occlusion is defined by internal carotid artery (ICA) occlusion with intact Circle of Willis flow. We hypothesise that such cases of large vessel occlusion provide collateral blood flow to preserve the ischaemic penumbra and may benefit from endovascular clot retrieval (ECR) beyond 24 hours.

Method

We retrospectively searched the stroke database from 2018 at Calvary Hospital, Canberra, Australia for ECR cases performed beyond 24 hours from symptom onset.

Results

Two patients were identified from the registry data.

64-year-old man awoke with left hemiparesis and was last seen well 9.5 hours prior. ECR for ICA occlusion was not initially performed due to rapidly improving National Institute of Health Stroke Scale (NIHSS) of three to zero. ECR was later performed at 38.5 hours for clinical deterioration. Stroke aetiology was atrial fibrillation. At 90-day NIHSS and modified Rankin Scale (mRS) were three.

75-year-old man awoke with left hemiparesis and was last seen well 10 hours prior. Baseline NIHSS was four. Off-label thrombolysis was administered based on salvageable penumbra on CTP, however ECR for ICA occlusion was not performed as neurointervention was unavailable. After 24 hours his NIHSS score improved to one but hemispheric hypoperfusion persisted on CTP. At 36 hours he underwent ECR with carotid stenting. Stroke aetiology was large-vessel atherosclerosis. At 90 days his NIHSS and mRS were zero.

Conclusion

Acute sub-clinoid proximal carotid occlusion requires tissue viability assessment with imaging to guide decision of ECR beyond 24 hours and may be of benefit.
Harvest–release decisions in recreational fisheries
Authors: Kaemingk Mark A. , Hurley Keith L. , Chizinski Christopher J. , Pope Kevin L.
Published: July 2019

Most fishery regulations aim to control angler harvest. Yet, we lack a basic understanding of what actually determines the angler’s decision to harvest or release fish caught. We used XGBoost, a machine learning algorithm, to develop a predictive angler harvest–release model by taking advantage of an extensive recreational fishery data set (24 water bodies, 9 years, and 193 523 fish). We were able to successfully predict the harvest–release outcome for 99% of fish caught in the training data set and 96% of fish caught in the test data set. Unsuccessful predictions were mostly attributed to predicting harvest of fish that were released. Fish length was the most essential feature examined for predicting angler harvest. Other important predictive harvest–release features included the number of individuals of the same species caught, geographic location of an angler’s residence, distance traveled, and time spent fishing. The XGBoost algorithm was able to effectively predict the harvest–release decision and revealed hidden and intricate relationships that are often unaccounted for with classical analysis techniques. Exposing and accounting for these angler–fish intricacies is critical for fisheries conservation and management.
Renormalization of the bilocal sine-Gordon model
Authors: Steib I. , Nagy S.
Published: July 2019

The functional renormalization group treatment is presented for the two-dimensional sine-Gordon model including a bilocal term in the potential, which contributes to the flow at the tree level. It is shown that the flow of the bilocal term can substitute the evolution of the wave function renormalization constant, since it can recover the Kosterlitz–Thouless type phase transition. The flows can also reveal the connection between the sine-Gordon and the noninteracting Thirring models at a special value of the wave number parameter.
Influence of nuclear surface diffuseness on systems involving spherical and deformed targets
Authors: Rajni  , Sharma Manoj K.
Published: July 2019

The effect of diffuseness of nucleus–nucleus interaction potential is tested on the nuclear potential depth, barrier characteristics and fusion excitation functions by considering spherical+spherical and [Formula: see text] colliding partners. It is manifested from the calculations that fusion barrier height and fusion pocket depth get significantly modified with change in diffuseness parameter [Formula: see text] and deeper fusion pocket appears with an increase in the magnitude of diffuseness. We further observed that, depending on the value of [Formula: see text], the fusion pocket depth decreases more sharply for the reactions involving oblate target [Formula: see text] as compared to prolate [Formula: see text] systems, though the overall shift in the pocket (left or right) is almost equal i.e., [Formula: see text]0.5[Formula: see text]fm for both cases. Furthermore, the effect of diffuseness on fusion cross-section is such that, on taking both spherical and/or deformed target-projectile combinations, lower strength of nuclear surface diffuseness (0.60[Formula: see text]fm) seems more suitable upto charge product [Formula: see text] [Formula: see text]200. However, for [Formula: see text], higher value of diffuseness parameter (0.99[Formula: see text]fm) is desirable for systems with spherical as well as deformed target-projectile combinations. Finally, we have explored the effect of angle dependence on the nuclear surface diffuseness within [Formula: see text]C+[Formula: see text]Tb reaction. The study reveals the significant contribution of angular diffuseness in fusion cross-section of reactions involving lanthanide target.
A Multi-Pass GAN for Fluid Flow Super-Resolution
Authors: Werhahn Maximilian , Xie You , Chu Mengyu , Thuerey Nils
Published: July 2019

We propose a novel method to up-sample volumetric functions with generative neural networks using several orthogonal passes. Our method decomposes generative problems on Cartesian field functions into multiple smaller sub-problems that can be learned more efficiently. Specifically, we utilize two separate generative adversarial networks: the first one up-scales slices which are parallel to the XY-plane, whereas the second one refines the whole volume along the Z---axis working on slices in the YZ-plane. In this way, we obtain full coverage for the 3D target function and can leverage spatio-temporal supervision with a set of discriminators. Additionally, we demonstrate that our method can be combined with curriculum learning and progressive growing approaches. We arrive at a first method that can up-sample volumes by a factor of eight along each dimension, i.e., increasing the number of degrees of freedom by 512. Large volumetric up-scaling factors such as this one have previously not been attainable as the required number of weights in the neural networks renders adversarial training runs prohibitively difficult. We demonstrate the generality of our trained networks with a series of comparisons to previous work, a variety of complex 3D results, and an analysis of the resulting performance.
Building Accurate Physics-based Face Models from Data
Authors: Kadleček Petr , Kavan Ladislav
Published: July 2019

The human face is an anatomical system exhibiting heterogenous and anisotropic mechanical behavior. This leads to complex deformations even in a neutral facial expression due to external forces such as gravity. We start by building a volumetric model from magnetic resonance images of a neutral facial expression. To obtain data on facial deformations we capture and register 3D scans of the face with different gravity directions and with various facial expressions. Our main contribution consists in solving an inverse physics problem where we learn mechanical properties of the face from our training data (3D scans). Specifically, we learn heterogenous stiffness and prestrain (which introduces anisotropy). The generalization capability of our resulting physics-based model is tested on 3D scans. We demonstrate that our model generates predictions of facial deformations more accurately than recent related physics-based techniques.
A Second-Order Advection-Reflection Solver
Authors: Narain Rahul , Zehnder Jonas , Thomaszewski Bernhard
Published: July 2019

Zehnder et al. [2018] recently introduced an advection-reflection method for fluid simulation that dramatically reduces artificial dissipation. We establish a connection between their method and the implicit midpoint time integration scheme, and present a simple modification to obtain an advection-reflection scheme with second-order accuracy in time. We compare with existing alternatives, including a second-order semi-Lagrangian method based on BDF2, and demonstrate the improved energy-preservation properties.
Simulation and Visualization of Ductile Fracture with the Material Point Method
Authors: Wang Stephanie , Ding Mengyuan , Gast Theodore F. , Zhu Leyi , Gagniere Steven , Jiang Chenfanfu , Teran Joseph M.
Published: July 2019

We present novel techniques for simulating and visualizing ductile fracture with the Material Point Method (MPM). We utilize traditional particle-based MPM [Stomakhin et al. 2013; Sulsky et al. 1994] as well as the Lagrangian energy formulation of [Jiang et al. 2015] that utilizes a tetrahedron mesh, rather than particle-based estimation of the deformation gradient and potential energy. We model failure and fracture via elastoplasticity with damage. Material is elastic until its deformation exceeds a Rankine or von Mises yield condition, at which point we use a softening model that shrinks the yield surface until a damage threshold is reached. Once damaged, the material Lamé coefficients are modified to represent failed material. We design visualization techniques for rendering the boundary of the material and its intersections with evolving crack surfaces. Our approach uses a simple and efficient element splitting strategy for tetrahedron meshes to represent crack surfaces that utilizes an extrapolation technique based on the MPM simulation. For traditional particle-based MPM we use an initial Delaunay tetrahedralization to connect randomly initialized MPM particles. Our visualization technique is a post-process and can be run after the MPM simulation for efficiency. We demonstrate our method with a number of challenging simulations of ductile failure with considerable and persistent self-contact.
Lambda calculus with algebraic simplification for reduction parallelization by equational reasoning
Authors: Morihata Akimasa
Published: July 2019

Parallel reduction is a major component of parallel programming and widely used for summarization and aggregation. It is not well understood, however, what sorts of nontrivial summarizations can be implemented as parallel reductions. This paper develops a calculus named λ
as
, a simply typed lambda calculus with algebraic simplification. This calculus provides a foundation for studying parallelization of complex reductions by equational reasoning. Its key feature is δ abstraction. A δ abstraction is observationally equivalent to the standard λ abstraction, but its body is simplified before the arrival of its arguments by using algebraic properties such as associativity and commutativity. In addition, the type system of λ
as
guarantees that simplifications due to δ abstractions do not lead to serious overheads. The usefulness of λ
as
is demonstrated on examples of developing complex parallel reductions, including those containing more than one reduction operator, loops with jumps, prefix-sum patterns, and even tree manipulations.
Synthesizing differentially private programs
Authors: Smith Calvin , Albarghouthi Aws
Published: July 2019

Inspired by the proliferation of data-analysis tasks, recent research in program synthesis has had a strong focus on enabling users to specify data-analysis programs through intuitive specifications, like examples and natural language. However, with the ever-increasing threat to privacy through data analysis, we believe it is imperative to reimagine program synthesis technology in the presence of formal privacy constraints.

In this paper, we study the problem of automatically synthesizing randomized, differentially private programs, where the user can provide the synthesizer with a constraint on the privacy of the desired algorithm. We base our technique on a linear dependent type system that can track the resources consumed by a program, and hence its privacy cost. We develop a novel type-directed synthesis algorithm that constructs randomized differentially private programs. We apply our technique to the problems of synthesizing database-like queries as well as recursive differential privacy mechanisms from the literature.
Demystifying differentiable programming: shift/reset the penultimate backpropagator
Authors: Wang Fei , Zheng Daniel , Decker James , Wu Xilun , Essertel Grégory M. , Rompf Tiark
Published: July 2019

Deep learning has seen tremendous success over the past decade in computer vision, machine translation, and gameplay. This success rests crucially on gradient-descent optimization and the ability to “learn” parameters of a neural network by backpropagating observed errors. However, neural network architectures are growing increasingly sophisticated and diverse, which motivates an emerging quest for even more general forms of differentiable programming, where arbitrary parameterized computations can be trained by gradient descent. In this paper, we take a fresh look at automatic differentiation (AD) techniques, and especially aim to demystify the reverse-mode form of AD that generalizes backpropagation in neural networks. We uncover a tight connection between reverse-mode AD and delimited continuations, which permits implementing reverse-mode AD purely via operator overloading and without managing any auxiliary data structures. We further show how this formulation of AD can be fruitfully combined with multi-stage programming (staging), leading to an efficient implementation that combines the performance benefits of deep learning frameworks based on explicit reified computation graphs (e.g., TensorFlow) with the expressiveness of pure library approaches (e.g., PyTorch).