bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of mHealth interventions during the perinatal period on maternal psychosocial outcomes: a systematic review protocol
Authors: Dol Justine , Richardson Brianna , Tomblin Murphy Gail , Aston Megan , McMillan Douglas , Campbell-Yeo Marsha
Published: July 2019

Objective:

This review aims to evaluate the effectiveness of mother-targeted mobile health (mHealth) education interventions during the perinatal period on maternal psychosocial outcomes in high-income countries.

Introduction:

Mobile health (i.e. mHealth) is defined as the use of mobile devices to transmit health content and services. The use of mHealth to provide education and support to mothers is a growing field of health innovation. Mothers seek health information online during the postpartum period to learn about health concerns and get advice and support. Despite the potential benefits of mHealth, the potential impact on maternal psychosocial outcomes requires further evaluation.

Inclusion criteria:

The review will consider studies that include mHealth interventions targeting mothers in high-income countries. The mHealth education interventions must occur during the antenatal or postnatal period. This review will consider studies that compare the intervention to any comparators. Studies published in English from 2000 will be included.

Methods:

The search strategy will aim to locate both published and unpublished studies. Following the search, all identified citations will be collated and duplicates removed. Titles and abstracts will be screened and full text of selected citations will then be assessed in detail against inclusion criteria. The results of the search will be reported in full in the final systematic review. Eligible studies will be critically appraised by two independent reviewers. Data extracted will include specific details about the interventions, populations, study methods and outcomes. Studies will be pooled in statistical meta-analysis or presented in narrative form including tables and figures.
Data Assimilation and Optimal Calibration in Nonlinear Models of Flame Dynamics
Authors: Yu Hans , Jaravel Thomas , Ihme Matthias , Juniper Matthew P. , Magri Luca
Published: July 2019

We propose an on-the-fly statistical learning method to take a qualitative reduced-order model of the dynamics of a premixed flame and make it quantitatively accurate. This physics-informed data-driven method is based on the statistically optimal combination of (i) a reduced-order model of the dynamics of a premixed flame with a level-set method, (ii) high-quality data, which can be provided by experiments and/or high-fidelity simulations, and (iii) assimilation of the data into the reduced-order model to improve the prediction of the dynamics of the premixed flame. The reduced-order model learns the state and the parameters of the premixed flame on the fly with the ensemble Kalman filter, which is a Bayesian filter used, for example, in weather forecasting. The proposed method and algorithm are applied to two test cases with relevance to reacting flows and instabilities. First, the capabilities of the framework are demonstrated in a twin experiment, where the assimilated data are produced from the same model as that used in prediction. Second, the assimilated data are extracted from a high-fidelity reacting-flow direct numerical simulation (DNS), which provides the reference solution. The results are analyzed by using Bayesian statistics, which robustly provide the level of confidence in the calculations from the reduced-order model. The versatile method we propose enables the optimal calibration of computationally inexpensive reduced-order models in real-time when experimental data become available, for example, from gas-turbine sensors.
Spatial release from informational masking declines with age: Evidence from a detection task in a virtual separation paradigm
Authors: Zobel Benjamin H. , Wagner Anita , Sanders Lisa D. , Başkent Deniz
Published: July 2019

Declines in spatial release from informational masking may contribute to the speech-processing difficulties that older adults often experience within complex listening environments. The present study sought to answer two fundamental questions: (1) Does spatial release from informational masking decline with age and, if so, (2) does age predict this decline independently of age-typical hearing loss? Younger (18–34 years) and older (60–80 years) adults with age-typical hearing completed a yes/no target-detection task with low-pass filtered noise-vocoded speech designed to reduce non-spatial segregation cues and control for hearing loss. Participants detected a target voice among two-talker masking babble while a virtual spatial separation paradigm [Freyman, Helfer, McCall, and Clifton, J. Acoust. Soc. Am. 106(6), 3578–3588 (1999)] was used to isolate informational masking release. The younger and older adults both exhibited spatial release from informational masking, but masking release was reduced among the older adults. Furthermore, age predicted this decline controlling for hearing loss, while there was no indication that hearing loss played a role. These findings provide evidence that declines specific to aging limit spatial release from informational masking under challenging listening conditions.
Deep metric learning for bioacoustic classification: Overcoming training data scarcity using dynamic triplet loss
Authors: Thakur Anshul , Thapar Daksh , Rajan Padmanabhan , Nigam Aditya
Published: July 2019

Bioacoustic classification often suffers from the lack of labeled data. This hinders the effective utilization of state-of-the-art deep learning models in bioacoustics. To overcome this problem, the authors propose a deep metric learning-based framework that provides effective classification, even when only a small number of per-class training examples are available. The proposed framework utilizes a multiscale convolutional neural network and the proposed dynamic variant of the triplet loss to learn a transformation space where intra-class separation is minimized and inter-class separation is maximized by a dynamically increasing margin. The process of learning this transformation is known as deep metric learning. The triplet loss analyzes three examples (referred to as a triplet) at a time to perform deep metric learning. The number of possible triplets increases cubically with the dataset size, making triplet loss more suitable than the cross-entropy loss in data-scarce conditions. Experiments on three different publicly available datasets show that the proposed framework performs better than existing bioacoustic classification methods. Experimental results also demonstrate the superiority of dynamic triplet loss over cross-entropy loss in data-scarce conditions. Furthermore, unlike existing bioacoustic classification methods, the proposed framework has been extended to provide open-set classification.
Associations of School Day Sedentary Behavior and Physical Activity With Gross Motor Skills: Use of Compositional Data Analysis
Authors: Burns Ryan D. , Kim Youngwon , Byun Wonwoo , Brusseau Timothy A.
Published: July 2019

Background: To examine the relationships among school day sedentary times (SED), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) with gross motor skills in children using Compositional Data Analysis. Methods: Participants were 409 children (mean age = 8.4 [1.8] y) recruited across 5 low-income schools. Gross motor skills were assessed using the test for gross motor development—third edition (TGMD-3), and physical activity was assessed using accelerometers. Isometric log-ratio coordinates were calculated by quantifying the relative proportion of percentage of the school day spent in SED, LPA, and MVPA. The associations of the isometric log-ratio coordinates with the TGMD-3 scores were estimated using general linear mixed-effects models adjusted for age, body mass index, estimated aerobic capacity, and school affiliation. Results: A higher proportion of the school day spent in %MVPA relative to %SED and %LPA was significantly associated with higher TGMD-3 total scores (γMVPA = 14.44, P = .01). This relationship was also observed for the ball skills subtest scores (γMVPA = 16.12, P = .003). Conclusions: Replacing %SED and %LPA with %MVPA during school hours may be an effective strategy for improving gross motor skills, specifically ball skills, in low-income elementary school-aged children.
Exploring Stakeholders’ Perceptions of the Acceptability, Usability, and Dissemination of the Australian 24-Hour Movement Guidelines for the Early Years
Authors: Stanley Rebecca , Jones Rachel , Swann Christian , Christian Hayley , Sherring Julie , Shilton Trevor , Okely Anthony
Published: July 2019

Background: Australian 24-Hour Movement Guidelines for the Early Years were recently developed. To maximize the uptake of the guidelines, perceptions of key stakeholders were sought.Methods: Thirty-five stakeholders (11% Aboriginal or Torres Strait Islander descent) participated in focus groups or key informant interviews. Stakeholders included parents of children aged 0–5 years, early childhood educators, and health and policy professionals, recruited using convenience and snowballing techniques. Focus groups and interviews were audio-recorded and transcribed verbatim. Data were analyzed inductively using thematic analysis.Results: There was general acceptance of the Movement Guidelines. The stakeholders suggested that the Guidelines were highly aspirational and needed to be carefully messaged, so parents did not feel guilty if their child was not meeting them. Stakeholders identified that the messaging needed to be culturally appropriate and visually appealing. Dissemination strategies differed depending on the stakeholder.Conclusion: Seeking stakeholder perceptions is an important process in the development of national Movement Guidelines. This study successfully examined stakeholders’ perceptions regarding the acceptability, usability, and dissemination of the Australian 24-Hour Movement Guidelines. Effective and innovative strategies for maximizing compliance and uptake of the Guidelines should be prioritized.
A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1)
In Vivo
To Promote Latent Infection of Germinal Center B Cells
Authors: Wang Yiping , Feldman Emily R. , Bullard Whitney L. , Tibbetts Scott A.
Published: July 2019

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies.
In vivo
, these viruses infect B cells and manipulate B cell biology to establish lifelong infection. To accomplish this, gammaherpesviruses employ an array of gene products, including miRNAs, short noncoding RNAs that bind to and repress protein synthesis from specific target mRNAs. The
in vivo
relevance of repression of targets of gammaherpesvirus miRNAs remains highly elusive. Here, we identified a murine gammaherpesvirus miRNA as critical for
in vivo
infection and validated the host mRNA
EWSR1
(Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using a novel technology, we demonstrated that repression of
EWSR1
was essential for
in vivo
infection of the critical B cell reservoir. These findings provide the first
in vivo
demonstration of the significance of repression of a specific host mRNA by a gammaherpesvirus miRNA.
Chromosome Dynamics in Bacteria: Triggering Replication at the Opposite Location and Segregation in the Opposite Direction
Authors: Meléndez Ady B. , Menikpurage Inoka P. , Mera Paola E.
Published: July 2019

Bacteria can accomplish surprising levels of organization in the absence of membrane organelles by constructing subcellular asymmetric protein gradients. These gradients are composed of regulators that can either trigger or inhibit cell cycle events from distinct cell poles. In
Caulobacter crescentus
, the onset of chromosome replication and segregation from the stalked pole are regulated by asymmetric protein gradients. We show that the activators of chromosome replication and segregation are not restricted to the stalked pole and that their organization and directionality can be flipped in orientation. Our results also indicate that the subcellular location of key chromosomal loci play important roles in the establishment of the asymmetric organization of cell cycle regulators.
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the Plasmodium falciparum STEVOR Protein Family
Authors: Wichers J. Stephan , Scholz Judith A. M. , Strauss Jan , Witt Susanne , Lill Andrés , Ehnold Laura-Isabell , Neupert Niklas , Liffner Benjamin , Lühken Renke , Petter Michaela , Lorenzen Stephan , Wilson Danny W. , Löw Christian , Lavazec Catherine , Bruchhaus Iris , Tannich Egbert , Gilberger Tim W. , Bachmann Anna
Published: July 2019

Malaria claims about half a million lives each year.
Plasmodium falciparum
, the causative agent of the most severe form of the disease, uses proteins that are translocated to the surface of infected erythrocytes for immune evasion. To circumvent the detection of these gene products by the immune system, the parasite evolved a complex strategy that includes gene duplications and elaborate sequence polymorphism. STEVORs are one family of these variant surface antigens and are encoded by about 40 genes. Using deep RNA sequencing of blood-stage parasites, including free merozoites, we first established
stevor
expression of the cultured isolate and compared it with published transcriptomes. We reveal a biphasic expression of most
stevor
genes and confirm this for individual STEVORs at the protein level. The membrane topology of a rhoptry-associated variant was experimentally elucidated and linked to host cell invasion, underlining the importance of this multifunctional protein family for parasite proliferation.
Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in Pseudomonas putida KT2440
Authors: Zhang Manman , Kang Zhaoqi , Guo Xiaoting , Guo Shiting , Xiao Dan , Liu Yidong , Ma Cuiqing , Xu Ping , Gao Chao
Published: July 2019

Glutarate is an attractive dicarboxylate with various applications. Clarification of the regulatory mechanism of glutarate catabolism could help to block the glutarate catabolic pathways, thereby improving glutarate production through biotechnological routes. Glutarate is a toxic metabolite in humans, and its accumulation leads to a hereditary metabolic disorder, glutaric aciduria type I. The elucidation of the functions of CsiR and GcdR as regulators that respond to glutarate could help in the design of glutarate biosensors for the rapid detection of glutarate in patients with glutaric aciduria type I. In addition, CsiR was identified as a regulator that also regulates
l
-2-HG metabolism. The identification of CsiR as a regulator that responds to
l-
2-HG could help in the discovery and investigation of other regulatory proteins involved in
l-
2-HG catabolism.
Hepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122
Authors: Lowey Brianna , Hertz Laura , Chiu Stephan , Valdez Kristin , Li Qisheng , Liang T. Jake
Published: July 2019

Chronic hepatitis C virus (HCV) infection is a major global public health problem. Infection often leads to severe liver injury that may progress to cirrhosis, hepatocellular carcinoma, and death. HCV coopts cellular machineries for propagation and triggers pathological processes in the liver. We previously identified a pivotal role of IKK-α in regulating cellular lipid metabolism and HCV assembly. In this study, we characterized NIK as acting upstream of IKK-α and characterized how HCV exploits this innate pathway to its advantage. Through extensive mechanistic studies, we demonstrated that NIK is a direct target of miR-122, which is regulated at the transcription level by HNF4A, a hepatocyte-specific transcription factor. We show in HCV infection that NIK expression is increased while both HNF4A and miR-122 levels are decreased. NIK represents an important host dependency that links HCV assembly, hepatic lipogenesis, and miRNA biology.
001 Altered interval timing as a novel marker of cognitive fluctuations in lewy body dementia
Authors: Matar Elie , Martens Kaylena Ehgoetz , Phillips Joseph , Halliday Glenda , Lewis Simon
Published: July 2019

Introduction

Cognitive fluctuations are a core clinical feature of Dementia with Lewy Bodies(DLB), characterized by marked spontaneous variations in cognitive abilities and alertness. There is a paucity of objective measurements of fluctuations in the clinical setting. Altered time awareness represents a potential clinical marker of fluctuations and/or their severity. In this study we aimed to investigate qualities of interval timing in patients with DLB.

Methods

25 patients with probable DLB and 14 older controls underwent testing using a simple time perception paradigm testing probing different aspects of interval timing including time estimation(retrospective estimation of interval length),time production(prospective determination of an interval) and time pacing(explicit timing of an interval).Intervals of 10 to 90s were randomized between trials.Self/carer-reporting of fluctuations were measured using the clinician assessment of fluctuation(CAF) and one-day fluctuation(OFS) scales.

Results

We found significant differences in interval timing between controls and DLB for time estimation and time production. Overall, DLB patients estimated less time which was significant at 90 seconds(proportion of interval=0.92 vs 0.69; p=0.03). DLB produced less time(proportion of 90s interval 0.58 vs 1.0; p<0.001). Errors in time estimation at 90 seconds correlated with fluctuation presence according to the CAF(r­=0.47;p=0.009) whilst errors in time pacing at 90s correlated strongest with fluctuation severity according to the OFS(r=0.65,p<0.001). ROC analysis identified time production(90s) as a good test to distinguish DLB from controls (AUC=0.8;95%CI:0.75–0.98).

Conclusion

We demonstrate objective evidence for altered temporal processing in DLB and suggest abnormal interval timing as a novel and clinically useful bedside marker of cognitive fluctuations.
113 A case of suspected autoimmune encephalitis secondary to nivolumab
Authors: Ho Jaimie , Hwang Yun , Tio Martin , Long Georgina , Zhang Eva
Published: July 2019

Objective

To describe a case of suspected immune encephalitis following nivolumab for metastatic melanoma.

Methods

Retrospective review of clinical records and diagnostic tests.

Results

A 78-year-old man with cerebral and lung melanoma metastases was treated with nivolumab, the newly developed monoclonal antibody which inhibits PD-1 deactivation of T-cells. He showed good radiological response.

Three months after ceasing nivolumab, he presented to ED with acute confusion, aphasia, left-sided weakness and neglect as a stroke call. MRI demonstrated no evidence of stroke or acute encephalitis. EEG showed diffuse slowing. Lumbar puncture was not performed as he was therapeutically anticoagulated and had begun to improve on empirical antibiotics and acyclovir. One week later, he suddenly deteriorated with fevers and reduced level of consciousness. Acyclovir was restarted. Repeat EEG revealed periodic epileptic discharges over the right hemisphere and MRI demonstrated hyperintense signal and diffusion restriction of the right mesial temporal lobe suggestive of encephalitis. Subsequent lumbar puncture was negative for HSV, VZV, enterovirus, and autoimmune encephalitis antibodies.

The patient’s oncology team had been in support of a course of methylprednisone on suspicion of autoimmune encephalitis, but by the time the lumbar puncture results returned he was again improving. A diagnosis of suspected nivolumab-induced encephalitis was made based on exclusion of other possible diagnoses.

Conclusions

The rising use of immune checkpoint inhibitors heralds an array of new and unexpected neurological complications including autoimmune encephalitis. A nationwide registry of possible cases may be helpful in improving our currently limited understanding of these emerging complications.
125 Characterising sleep and fatigue in patients with primary mitochondrial disease
Authors: Wools Christine , Sue Carolyn , Cistulli Peter , Davis Ryan
Published: July 2019

Introduction

Fatigue is common in patients with primary mitochondrial disease (PMD). There has been little prospective research into sleep pathology in these patients and assessment of scontributory factors to fatigue.

Methods

Patients with PMD were prospectively assessed with overnight polysomnography in addition to measures of fatigue, muscle fatiguability, disease severity, sleep propensity and depression.

Results

16 patients participated, 15 completing inpatient polysomnography. Obstructive sleep apnoea (OSA) was common (53%), affecting 5/9 females (56%) and 3/6 males (50%), although most cases were mild in severity. There was a trend to higher incidence of OSA in older patients but not other traditional risk factors, nor presence of myopathy. The Epworth Sleepiness Scale (ESS) was the best predictor of OSA, although not reaching significance.

Fatigue was common, with 81% of patients having significant fatigue on the Fatigue Severity score and 69% on the Fatigue Impact Scale. The two scores correlated well (r =0.85, p 0.01).

The mean 5 times sit to stand time of 16 seconds was significantly higher than community normals (p 0.04), demonstrating muscle fatiguability, not isolated to patients with myopathy.

Conclusion

OSA is common in patients with PMD, although mostly mild in severity. ESS likely remains a relevant tool in screening patients when considering overnight polysomnography to investigate fatigue in these patients. OSA does not explain the high prevalence of fatigue, with other factors including depressive symptoms, important considerations.
126 Incidence of dementia in elderly patients with epilepsy
Authors: Upadhyay Viral , Ng Aloysius , Wijayath Manori
Published: July 2019

Introduction

The incidence of epilepsy is higher in patients with underlying dementia.1 The goal of the present study is to look at the incidence of dementia in patients presented to our epilepsy clinic and analyse electroencephalogram (EEG), imaging findings and response to antiepileptic drug (AED) in these individuals.

Methods

A retrospective study was performed on patients presented to Nepean Hospital epilepsy clinic from 2015 to 2017. Multiple clinical parameters were obtained from electronic medical records.

Results

A total of 258 patients presented to the clinic, of which 38 patients were above the age of 65 years. 11 patients were excluded due to insufficient information or patients without any history of seizures. Out of the remaining 27 patients studied, nine patients (33%) had dementia including five patients (19%) with Alzheimer’s dementia. Sixteen patients (59%) experienced complex partial seizures. Brain MRI was performed in twenty one patients (78%). Sixteen patients (59%) had MRI-identified structural lesions including prior stroke or intracerebral haemorrhage. EEGs were performed in twenty patients (74%). Eight patients (40%) had abnormal EEG with one patient (5%) having epileptiform discharges, three patients (15%) having focal slowing and four patients (20%) having generalised slowing. Overall, nineteen patients (70%) were on AEDs with good control and four patients (15%) required more than one AED to achieve seizure control.

Conclusion

The study showed that there is higher incidence of dementia in patients with epilepsy compared with general population.2 Most patients experience complex partial seizures and can be adequately controlled on single AED.

References

Rao S, Dove G, Cascino G, Petersen R. Recurrent seizures in patients with dementia: Frequency, seizure types, and treatment outcome. Epilepsy & Behavior 2009, 14(1), pp.118–120.

ABS (Australian Bureau of Statistics) 2016, Life Tables, States, Territories and Australia, 2013–2015, cat. no. 3302.0.55.001, ABS, Canberra
129 Pilot study: the validity of the queens square screening test for visual deficits in a cohort of patients with dementia
Authors: Kim Leah , Cordato Dennis , McDougall Alan , Fraser Clare
Published: July 2019

Introduction

There is limited research on the visual deficits found in dementia. The Queens Square Screening Test for Visual Deficits (QS test) is designed to screen for changes in visual processing. Our study aimed to validate this test and examine the types of visual processing deficits found in dementia.

Methods

We assessed the QS test in participants with dementia, mild cognitive impairment (MCI), and healthy controls. Participants were recruited from the Neurology and Geriatrics departments of a tertiary hospital over 3-months. Cognitive impairment was measured using the Rowland Universal Dementia Assessment Scale (RUDAS).

Results

Twenty-six patients were examined. There were no statistically significant differences in age, gender, English fluency, and education between the three groups. Participants with dementia (n=8, mean RUDAS 17.5/30) scored 51.4/71 on the QS test, compared to 60.7/71 in MCI (n=7, mean RUDAS 25.0/30) and 64.6/71 in controls (n=11, mean RUDAS 27.4/30). The mean scores for each subset of the QS test for dementia, MCI and normal cognition, respectively, were: early visual processing – 19.6/25, 22.4/25, 23.7/25; object perception – 5.6/11, 7.9/11, 8.7/11; space perception – 11.4/14, 11.1/14, 12.4/14; face perception – 4.4/8, 6.4/8, 7.0/8; reading – 10.4/13, 12.9/13, 12.8/13.

Conclusion

In this pilot study, the QS test was markedly abnormal in dementia but did not differentiate between MCI and normal cognition. Our findings suggest that deficits in early visual processing, reading, and the perception of objects and faces are common in dementia. Understanding the types of visual difficulties may improve the care of patients with dementia.
130 Continuous EEG monitoring in australia: s first year audit of practice 2018–2019 of a combined hospital epilepsy program in melbourne
Authors: Laing Joshua , Grant Georgia , Harb Cecilia , White Elise , O’Brien Terence , Kwan Patrick
Published: July 2019

Introduction

Continuous EEG (cEEG) monitoring is essential for the optimal diagnosis and management of non-convulsive seizures. We audited the use of cEEG across two major metropolitan hospitals in Melbourne, Australia as part of a new combined epilepsy program. There are no reported case series of cEEG in Australia.

Methods

Data was collected retrospectively from consecutive patients who underwent cEEG monitoring as part of their acute inpatient care between Jan 2018 to Dec 2018 at the Alfred and Royal Melbourne Hospitals. All inpatient EEG studies over 1 hr were included. Elective cases from the epilepsy monitoring unit were excluded. Demographic and clinical information regarding their admission was collected. Descriptive statistics, and comparative analysis was performed.

Results

There were 94 patients identified that underwent cEEG. 50% were male and 50% female, with an average age of 51.3 yrs. 45% were performed in the ICU, and 55% on the acute medical ward. The average duration of recording per patient was 86.2 hrs or 3.6 days. Of 89 of 94 available cEEG reports, seizures were seen in 55%, the majority being non-convulsive. Interictal discharges were seen in 60%. 19% (13/67 of available records) were dead at the time of the audit.

Conclusion

Non-convulsive seizures and non-convulsive status epilepticus is common and widely underrecognized without cEEG. We present 94 cases as part of our newly expanding cEEG program across two major Australian hospitals over a one year period, 55% with seizures which were predominantly non-convulsive. A prospective database will be designed for further quality improvement and future research.
022 Patient-initiated event monitoring for acute vertigo
Authors: Young Allison S , Lechner Corinna , Bradshaw Andrew P , MacDougall Hamish G , Black Deborah A , Halmagyi Michael G , Welgampola Miriam S
Published: July 2019

Introduction

The diagnosis of vestibular disorders may be facilitated by analysing patient-initiated capture of ictal nystagmus.

Methods

Adults with a history of recurrent vertigo were taught to self-record spontaneous and positional-nystagmus at home while symptomatic, using video-goggles. Patients with final diagnoses of disorders presenting with recurrent vertigo were analysed: 121 patients with Ménière’s Disease (MD), Vestibular Migraine (VM), Benign Positional Vertigo (BPV), Episodic Ataxia Type II (EAII), Vestibular Paroxysmia (VP) or Superior Semicircular Canal Dehiscence (SSCD) were included.

Results

Of 43 MD patients, 40 showed high-velocity spontaneous horizontal-nystagmus (median slow-phase velocity (SPV) 39.7 degrees/second (°/s); Twenty-one showed horizontal-nystagmus reversing direction within 12-hours (24 on separate days). In 44 of 67 patients with VM, low velocity spontaneous horizontal (n=28, 4.9°/s), up-beating (n=6, 15.5°/s) or down-beating-nystagmus (n=10, 5.1°/s) was observed; Sixteen showed positional-nystagmus only, and seven had no nystagmus. Spontaneous horizontal-nystagmus with SPV >12.05°/s had a sensitivity and specificity of 95.3% and 82.1% for MD. Nystagmus direction-change within 12-hours was highly specific (95.7%) for MD. Spontaneous vertical-nystagmus was highly specific (93.0%) for VM. In the seven BPV patients, spontaneous-nystagmus was absent or <3°/s, and characteristic paroxysmal positional nystagmus was observed in all cases. Patients with central and MD-related positional vertigo demonstrated persistent nystagmus. Two patients with EAII showed spontaneous vertical nystagmus, one patient with VP showed short bursts of horizontal-torsional nystagmus lasting 5–10s, and one patient with SSCD demonstrated paroxysmal torsional down-beating nystagmus when supine.

Conclusions

Patient-initiated vestibular event-monitoring is feasible and could facilitate rapid and accurate diagnosis of episodic vestibular disorders.
026 Variation in the anatomy of the normal human optic chiasm: an MRI study
Authors: Lueck Christian J , Bosler Nicholas , Neely Andrew , Ashton David
Published: July 2019

Introduction

Compression of the optic chiasm gives rise to bitemporal hemianopia. The reason for this is unclear, but one hypothesis suggests it relates to the fact that nasal retinal fibres cross each other while temporal fibres do not. This ‘crossing’ hypothesis has been investigated using finite element modelling but this requires accurate anatomical data. The precise shape of the chiasm is not clear: nasal fibres may not decussate centrally (as if the chiasm were ‘X’-shaped) but, instead, decussate paracentrally and run parallel to each other in the central arm of an ‘H’. This study aimed to determine the population variance in chiasmal shape.

Methods

68 MRI scans of healthy individuals without visual abnormality were randomly selected. A 2D image was created and images were analysed using AutoCAD software to determine the offset between lines drawn down the centres of the optic nerves and contralateral optic tracts. A positive offset would suggest an ‘H’ shape while an ‘X’-shaped chiasm would have a offset of 0.

Results

The mean width of the chiasm was 12.0 mm, and the mean offset was 4.7 mm generating a mean offset:width ratio of 0.38. No chiasm had an offset of zero. Fibre crossings occurred approximately 2.35 mm lateral to the midline, and nasal (crossing) fibres travelled an average of 4.7 mm in the mediolateral plane before entering the contralateral optic tract.

Conclusions

The human optic chiasm is H-shaped, not X-shaped. This information will inform future models of chiasmal compression.
035 Valproate-induced parkinsonism ‘an early warning’: case reports and review of literature
Authors: Dal Shoaib , Whyte Scott
Published: July 2019

Introduction

We describe two cases of valproate-induced parkinsonism, where the parkinsonian features develop after commencing valproate (VPA), in a time frame and manner well described by previous publications.1 In contrast to the published literature, that has short duration of follow-up, we have had a prolonged follow-up of these two cases, who initially improved on ceasing valproate, but then after a period progressed again, with the development of levodopa-responsive asymmetrical Parkinson’s disease.2

Cases

67 years old man, on VPA 500 mg twice a day for seizures since 2008, developed new rest, re-emergent left hand tremor and hypomimia in 2012. Within months, the parkinsonism progressed to decremental bradykinesia, cog-wheel rigidity and hypophonia. The symptoms initially improved with changing VPA to levetiracetam; however, the disease reappeared after 6 months and although levodopa-responsive, it has been progressive since then.

88 years old man, on VPA 700 mg twice a day for seizures since 2010, developed upper limb decremental bradykinesia, cog-wheel rigidity, camptocormia and rest, re-emergent tremor in hands in 2011. The parkinsonism improved significantly with cessation of VPA; however, the disease re-emerged after 2 years and has been progressive since then.

Conclusion

VPA may be responsible for unmasking underlying subclinical parkinsonism and these patients represent an earlier onset of Parkinson’s disease related to VPA exposure, rather than a purely drug related parkinsonian dysfunction. These cases also highlight the importance of long-term follow up in VPA-induced parkinsonism. These observations are an important consideration for clinicians treating patients with parkinsonian features secondary to VPA exposure.

References

Brugger F, Bhatia KP, Besag FM. Valproate-associated parkinsonism: a critical review of the literature. CNS Drugs 2016;30(6):527–540.

Mahmoud F, Tampi RR. Valproic acid-induced parkinsonism in the elderly: a comprehensive review of the literature. Am J Geriatr Pharmacother 2011;9(6):405–412.
040 Acute cerebellar ataxia following epstein-barr virus infection
Authors: Barnes Stephanie L , Brew Bruce J
Published: July 2019

Introduction

Infectious aetiologies such as acute Epstein-Barr virus (EBV) infection are in the differential diagnosis for acute cerebellar ataxia (ACA). This syndrome remains exceptionally rare and not well characterised in adults.e.g. 1 2

Methods

A retrospective case review of a patient diagnosed with ACA following EBV infection with implications for pathogenesis and treatment.

Results

A 29-year-old Caucasian male presented with a three day history of ACA. Seven days prior he was diagnosed with infectious mononucleosis; bloodwork was consistent with acute EBV infection. These symptoms improved rapidly with oral prednisolone. He took no regular medications, drank alcohol moderately and had no significant family history.

On examination, he was afebrile, ataxic and mildly dysarthric. Sensory examination was normal, particularly proprioception. Romberg’s test was negative. Remaining neurological and general examination was normal.

Bloodwork showed mild liver dysfunction and positive ANA (titre 1/320, homogenous and speckled patterns). Immune screen was otherwise negative. Antineuronal antibody panel was negative in serum and CSF. CSF glucose was 3.1 mmol/L, protein 751 mg/L, albumin 523 mg/L, neopterin 24 nmol/L and B2 microglobulin 1.1 mg/L. The sample was acellular with negative EBV PCR (<500 copies/mL). Other infective serology and PCRs were also negative. MRI brain with gadolinium showed no abnormality.

The patient received supportive care and was neurologically normal within three months.

Conclusions

ACA related to EBV is rare in adults. This report is important because it documents an adult case, other ACA causes have been rigorously excluded, resolution without antiviral therapy is detailed, and investigations support an immune-mediated pathogenesis.

References

McCarthy CL, McColgan P, Martin P. Acute cerebellar ataxia due to Epstein-Barr virus. Pract Neurol 2012;12:238–240.

Lascelles RG, Longson M, Johnson PJ, Chiang A. Infectious mononucleosis presenting as acute cerebellar syndrome. Lancet 1973;2:707.
044 Dramatic delayed recovery following severe anti-NMDAR encephalitis
Authors: MacDonald Allycia , Jordan Nerissa , Leong Wai
Published: July 2019

Introduction

Long term outcomes in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are reported to be favourable in 80% of cases, but there is little information regarding recovery following prolonged severe neurological disability.

Case 1

A 16-year-old female presented with headache, fever and acute encephalopathy. Anti-NMDAR antibodies were positive, with an ovarian teratoma. Treatment included oophorectomy, plasmapheresis, corticosteroids, cyclophosphamide, intravenous and intrathecal rituximab, and alemtuzumab. After 15 months hospitalisation, she remained in a vegetative state, with tracheostomy and percutaneous gastrostomy tubes, on multiple anticonvulsants. She received no further immunotherapy. MRI brain 2 years after illness onset demonstrated severe generalised cerebral atrophy. Three years after onset, she began to improve. At 5+ years she was seizure-free without anticonvulsants, fully independent and ambulatory, without overt cognitive deficits or personality change. MRI brain at 5 1/2 years demonstrated recovery of cerebral volume to within normal limits, but residual hippocampal atrophy.

Case 2

A 21-year-old female presented with headache, fever and personality change. NMDAR-antibodies were positive. A malignant ovarian teratoma was treated with salpingoophorectomy and chemotherapy (bleomycin/etoposide/cyclophosphamide). She received plasmapheresis, immunoglobulins, corticosteroids, intravenous and intrathecal rituximab, and bortezomib. She was finally discharged after 21 months hospitalisation with tracheostomy and gastrostomy tubes, severe behavioural disturbance, minimal functional limb movement, and fully dependent care needs. Clinical recovery began 2 1/2 years after disease onset, and at 4 years she is fully independent with residual cognitive deficits, engaging in volunteer work.

Conclusions

These cases highlight the potential for dramatic delayed clinical improvement despite prolonged severe neurological disability in anti-NMDAR encephalitis.
055 An unusual presentation of SOD1-ALS: a case report
Authors: MacDonald Allycia , Dyke Jason , Khangure Simon , Kelly Andrew
Published: July 2019

Introduction

Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are inherited, of which 20% are due to mutations in the superoxide dismutase-1 gene (SOD1). MRI abnormalities are not uncommon in ALS, and there have been previous case reports of peripheral nerve enhancement in patients with SOD1 mutations, typically attributed to rapid neuronal degeneration.

Case

A 31-year-old previously well Malaysian woman presented with a 3 month history of progressive lower limb weakness, initially involving the right lower limb but progressing to involve the left, requiring the use of a walking aid. Initial examination demonstrated asymmetric upper and lower motor neuron signs in bilateral upper and lower limbs. EMG findings were of a severe pure motor axonal process. CSF examination revealed elevated protein without significant elevation of white cells. MRI brain and spine demonstrated smooth cauda-equina ventral nerve root thickening and enhancement. Treatment with intravenous immunoglobulin and high dose corticosteroid was commenced for a presumed inflammatory process, with no clinical improvement. A cauda-equina nerve root biopsy was performed, demonstrating features consistent with an immune-mediated demyelinating neuropathy. The patient continued to deteriorate, developing flaccid upper limb weakness and facial involvement. Plasma exchange, azathioprine, cyclophosphamide, and rituximab were sequentially administered over the following two months without altering the rate of disease progression. Genetic testing returned a positive SOD1 heterozygous gene mutation, confirming the diagnosis of ALS.

Conclusions

We present a case of SOD1-ALS with atypical features on imaging and histopathology suggesting an underlying demyelinating process, expanding the known clinical spectrum of this mutation.
056 Efficacy and safety of the Bruton’s tyrosine kinase inhibitor evobrutinib (M2951) in patients with relapsing multiple sclerosis over 48 weeks: a randomized, placebo-controlled, phase 2 study
Authors: Montalban Xavier , Arnold Douglas L , Weber Martin S , Staikov Ivan , Piasecka-Stryczynska Karolina , Gillett Alan , Martin Emily C , Syed Sana , Dangond Fernando , Wolinsky Jerry S
Published: July 2019

Introduction

Evobrutinib (M2951) is a highly specific oral inhibitor of Bruton’s tyrosine kinase, a key regulator of B cell and macrophage functions implicated in MS.

Methods

In this double-blind, phase 2 study (NCT02975349), adult patients (≤65 years) with relapsing MS (RMS) were randomized to evobrutinib 25 mgQD, 75 mgQD, 75 mgBID, placebo, or open-label dimethyl fumarate (240 mgBID; reference arm) for 48 weeks; placebo-treated patients switched to evobrutinib 25 mgQD after 24 weeks. The primary endpoint was the total number of T1 gadolinium-enhancing (T1Gd+) lesions at Weeks 12, 16, 20, and 24. Secondary endpoints included annualized relapse rate (ARR), MRI measures at Weeks 24 and 48, and safety.

Results

Among 261 patients, the sum of T1Gd+ lesions over Weeks 12–24 was reduced with evobrutinib 75 mgQD (p=0.002) and 75 mgBID (p=0.03); a dose response was observed (p=0.001). There was no evidence of change in effect on T1Gd+ lesions (mean±SD; Wilcoxon signed-rank test) between Weeks 24 and 48 with evobrutinib 75 mgQD (0.28±0.91 to 0.85±2.87; p=0.57) or 75 mgBID (0.24±0.88 to 0.49±1.22; p=0.23). ARR (unadjusted [95%CI]) was 0.25 (0.12–0.44) for evobrutinib 75 mgQD and 0.11 (0.04–0.25) for 75 mgBID over 48 weeks, and 0.37 (0.17–0.70) for placebo over 24 weeks. Evobrutinib appeared well-tolerated. Shifts to Grade 3–4 ALT and AST elevations from normal (grade 0) occurred in 8 (5.4%) and 6 (3.9%) evobrutinib-treated patients respectively, driven by events with onset within the first 24 weeks.

Conclusions

Evobrutinib is the first BTK inhibitor to demonstrate disease activity reduction in RMS. The observed benefit-risk profile supports further clinical development.
060 Impaired color discrimination is associated with hallucinations in dementia with lewy bodies
Authors: Matar Elie , Phillips Joseph R , Ehgoetz Martens Kaylena A , Halliday Glenda M , Lewis Simon JG
Published: July 2019

Introduction

Emerging evidence indicates that color discrimination impairments can predict the development of dementia across a range of prodromal Lewy body conditions. However, color vision deficits are not seen uniformly in patients with Dementia with Lewy Bodies (DLB), suggesting a more nuanced association. Visual hallucinations(VH) represent a discriminating feature of DLB, and recent evidence implicates visual pathway dysfunction as a significant contributor to this phenomenon. We therefore hypothesized that color impairment will more closely associate with VH in DLB rather than general cognition.

Methods

In this study, we examined the relationship between color vision impairment and VH, along with other clinical and neuropsychological features in 24 patients with DLB alongside 25 age-matched controls. Color discrimination was assessed using the Farnsworth-Munsell-100 Hue (FM-100) test.

Results

Color discrimination impairment was seen in 16/24 DLB participants (67%) with a higher error score relative to controls(p=0.001). We demonstrate for the first time a strong association between color discrimination errors and both the presence and severity of VH in DLB based on clinician-derived(p=0.008) and questionnaire-derived(p=0.03) measures. Correlation with clinical and neuropsychological variables revealed that color discrimination is significantly related to visuospatial impairment(p=0.02) but not to global measures of cognition, motor severity, age or disease duration. Factor analysis confirmed a unique relationship between color discrimination, visual hallucinations and visuospatial function.

Conclusion

Our results suggest that color impairments may be a specific biomarker of visual hallucinations and associated visuoperceptual deficits in evolving Lewy body disorders rather than dementia per se and thus providing insight into a shared pathophysiological substrate.
061 Training in headache in australia, new zealand and asia
Authors: Zhang Lin , Jenkins Bronwyn , Stark Richard , Hutton Elspeth
Published: July 2019

Introduction

Migraine is the leading cause of age-adjusted neurological disability in Australia, but little is known about headache training in our region. We aimed to assess the quantity of teaching in headache subjects during undergraduate and postgraduate years.

Method

This is a cross-sectional survey study where questionnaires were sent to 137 delegates from Australia, New Zealand and Asia, prior to the Headache Master School in Sydney in August 2018. The Main outcome measured are recalled number of hours of teaching in undergraduate year and postgraduate years in: 1) Migraine; 2) Trigeminal autonomic cephalalgias (TACs); 3) Asthma; 4) Myasthenia gravis (MG).

Results

The questionnaire response rate was 73% (100 of 137), of which 29 delegates were within 10 years of completing their undergraduate degree and 98 were neurologists. In undergraduate training, there was much greater quantity of teaching in asthma than migraine (Z=5.007, p<0.000) despite both being high-prevalent (asthma 11%, migraine 15–20%) conditions. Similarly, for diseases of medium-to-low prevalence, there was less training in TACs (1/1000), compared to MG (1.2/10,000) (Z=6.196, p<0.000). These major differences in training were also seen in postgraduate years even though overall headache teaching was greater in postgraduate than undergraduate training (p<0.000).

Conclusions

Despite the high prevalence and morbidity of headache disorders, they receive less attention in training than conditions with similar prevalence. We propose that headache training opportunities should be improved in our region, particularly in the undergraduate course and preceptorships or fellowships in postgraduate years.