bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression
Authors: Zhou Bin , Qi Fei , Wu Fangyi , Nie Hongbo , Song Yifan , Shao Lu , Han Jingxuan , Wu Zhen , Saiyin Hexige , Wei Gang , Wang Penghua , Ni Ting , Qian Feng
Published: July 2019

Endogenous retroviruses are transposable genetic elements comprising 8% to 10% of the human and mouse genomes. Although most ERVs have been inactivated due to deleterious mutations, some are still transcribed. However, the biological functions of transcribed ERVs are largely unknown. Here, we identified a full-length ERV-derived lncRNA, designated lnc-EPAV, as a positive regulator of host innate immune responses. We found that silencing lnc-EPAV impaired virus-induced cytokine production, resulting in increased viral replication in cells. The lnc-EPAV-deficient mice exhibited enhanced susceptibility to viral challenge. We also found that lnc-EPAV regulated expression of RELA, an NF-κB subunit that plays a critical role in antiviral responses. ERV-derived lncRNA coordinated with a transcription repressor, SFPQ, to control
Rela
transcription. Our report provides new insights into the previously unrecognized immune gene regulatory mechanism of ERV-derived lncRNAs.
Microbial Similarity between Students in a Common Dormitory Environment Reveals the Forensic Potential of Individual Microbial Signatures
Authors: Richardson Miles , Gottel Neil , Gilbert Jack A. , Lax Simon
Published: July 2019

Humans leave behind a microbial trail, regardless of intention. This may allow for the identification of individuals based on the “microbial signatures” they shed in built environments. In a shared living environment, these trails intersect, and through interaction with common surfaces may become homogenized, potentially confounding our ability to link individuals to their associated microbiota. We sought to understand the factors that influence the mixing of individual signatures and how best to process sequencing data to best tease apart these signatures.
Pseudomonas aeruginosa Increases the Sensitivity of Biofilm-Grown Staphylococcus aureus to Membrane-Targeting Antiseptics and Antibiotics
Authors: Orazi Giulia , Ruoff Kathryn L. , O’Toole George A.
Published: July 2019

The thick mucus in the airways of cystic fibrosis (CF) patients predisposes them to frequent, polymicrobial respiratory infections.
Pseudomonas aeruginosa
and
Staphylococcus aureus
are frequently coisolated from the airways of individuals with CF, as well as from diabetic foot ulcers and other wounds. Both organisms form biofilms, which are notoriously difficult to eradicate and promote chronic infection. In this study, we have shown that
P. aeruginosa
-secreted factors can increase the efficacy of compounds that alone have little or no bactericidal activity against
S. aureus
biofilms. In particular, we discovered that
P. aeruginosa
exoproducts can potentiate the antistaphylococcal activity of phenol-based antiseptics and other membrane-active drugs. Our findings illustrate that polymicrobial interactions can dramatically increase antibacterial efficacy
in vitro
and suggest that altering membrane physiology promotes the ability of certain drugs to kill bacterial biofilms—knowledge that may provide a path for the discovery of new biofilm-targeting antimicrobial strategies.
Experimental Microbiomes: Models Not to Scale
Authors: Chevrette Marc G. , Bratburd Jennifer R. , Currie Cameron R. , Stubbendieck Reed M.
Published: July 2019

Low-cost, high-throughput nucleic acid sequencing ushered the field of microbial ecology into a new era in which the microbial composition of nearly every conceivable environment on the planet is under examination. However, static “screenshots” derived from sequence-only approaches belie the underlying complexity of the microbe-microbe and microbe-host interactions occurring within these systems.
Women’s occupational performance and quality of life during breast cancer treatment
Authors: Nascimento Pamela Ferreira , Mello Maria Julia Gonçalves , Correia Nancy de Barros , Lucena Nahãmi Cruz , Albuquerque Raquel Costa , de Matos Raisa Mayara Alves , Bergmann Anke
Published: July 2019

Objectives

To analyse the association between occupational performance and women’s health-related quality of life (HRQoL) during breast cancer treatment.

Methods

An analytical cross-sectional study was conducted using the Canadian Occupational Performance Measure, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and its specific breast cancer-specific module (BR-23). The association between occupational performance scores and the HRQoL domains was evaluated using multiple linear regression analysis.

Results

The sample included 97 women. Overall, occupational performance was poor and the women’s dissatisfaction with their performance resulted in a decrease in HRQoL. Following adjustment, satisfaction was associated with HRQoL in the global health status, functional, role, emotional and social functioning domains of the functional scale. In BR-23, a statistically significant association was found between satisfaction and HRQoL in the functional scale and in the body image domain.

Conclusions

Women’s occupational performance was impaired during breast cancer treatment, with limitations and/or restrictions in activities related to self-care, productivity and leisure that were ultimately associated with poorer HRQoL. During cancer treatment, rehabilitation strategies should focus on restoring occupational performance to levels as close as possible to that present prior to the beginning of the disease process, enabling the woman to preserve her occupational life, consequently resulting in an improvement in HRQoL.
010 Neuroimaging and CSF findings in autoimmune encephalitis with neuronal cell surface antibodies
Authors: Broadley James , Wesselingh Robb , Beech Paul , Seneviratne Udaya , Buzzard Katherine , Butzkueven Helmut , O’Brien Terence , Monif Mastura
Published: July 2019

Introduction

Neuroimaging and CSF analysis compose essential steps in evaluating patients with autoimmune encephalitis (AE). No study has compared the magnitude and prognostic implications of these findings between different subtypes. Herein we examine cases of AE with neuronal cell surface antibodies, and contrast the results of early investigations.

Methods

We performed medical records search from 2008–2018 in 5 Victorian hospitals. Cases of AE were established in accordance with diagnostic criteria by Graus et al.1 Clinical and laboratory data was collected. All neuroimaging was evaluated independently by a neuroradiologist.

Results

We identified 52 patients with AE with neuronal cell surface antibodies (21 NMDAR, 27 VGKC, 3 AMPAR, 1 GABAb).

We found that among patients with anti-LGI1 antibodies the presence of abnormal CSF correlated with increased rates of mortality (50% vs 0%). This effect was largely mediated by CSF lymphocytosis, which was present in 2 patients who both died within 12 months of diagnosis.

We found that the development of hippocampal atrophy was more common amongst patients with abnormal MRI findings, but in particular those with changes affecting the medial temporal lobe. This effect was evident both in the cases with anti-VGKC antibodies (60% vs 18%, 75% vs 17%) and the cohort as a whole (56% vs 15%, 83% vs 13%).

Conclusions

This is the first study of its kind in Australia, and identifies some unique correlation between early investigation findings, and the clinical and radiological outcome. A larger cohort is required to determine if these findings are statistically significant.

Reference

Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.
120 Prospective study determining the predictive value of inattention in the evaluation of suspected acute stroke; a territory wide study
Authors: Baird-Gunning Jonathan JD , Zhai Shaun , Jones Brett , Nandal Neha , Das Chandi , Patel Ronak , Gawarikar Yash , Lueck Christian
Published: July 2019

Introduction

25%-30% of patients admitted with acute stroke are stroke mimics. Clinical assessment plays a major role in diagnosis in the hyperacute clinical setting. Identifying physical signs that correctly identify stroke is therefore important. A retrospective study1 suggested that the presence of sensory inattention (or neglect) was seen exclusively in stroke patients, suggesting that inattention might be a reliable discriminator between stroke and mimics. This study aimed to test that hypothesis.

Methods

Prospective assessment of suspected stroke patients for the presence of neglect (NIHSS definition). Neglect could be visual and/or somatosensory. The presence of neglect was then correlated with eventual diagnosis at 48 hours. Sensitivity, specificity and predictive values were calculated. A post-hoc analysis evaluated the correlation of neglect with large vessel occlusion in patients who underwent angiography.

Results

115 patients were recruited, 70 ultimately with stroke and 45 with other diagnoses. Neglect was present in 27 patients (of whom 23 had stroke) and absent in 88. This yielded: sensitivity 32.9%, specificity 91.1%, positive predictive value 85.2%, and negative predictive value 41.9%. Two patients with neglect had a diagnosis of functional illness, one a seizure, and one a brain tumour. Neglect was present in 7 out of 8 patients with large vessel occlusion (sensitivity 87.5%) and was absent in all patients who did not have large vessel occlusion on angiogram.

Conclusion

When present, neglect is a strong predictor of organic pathology and large vessel occlusion. However, it is not 100% specific and can be seen in functional presentations.

Reference

Gargalas S, Weeks R, Khan-Bourne N, Shotbolt P, Simblett S, Ashraf L, Doyle C, Bancroft V, David AS: Incidence and outcome of functional stroke mimics admitted to a hyperacute stroke unit. J Neurol Neurosurg Psychiatry 2017, 88:2–6.
012 Mechanical thrombectomy in pediatric stroke: systematic review, individual patient-data meta-analysis, and case series
Authors: Bhatia Kartik , Kortman Hans , Blair Chris , Parker Geoffrey , Brunacci David , Ang Tim , Worthington John , Muthusami Prakash , Krings Timo
Published: July 2019

Introduction

In adults, there is strong evidence demonstrating the superiority of mechanical thrombectomy (MT) plus intravenous thrombolysis over thrombolysis alone for the treatment of acute ischemic stroke due to large vessel occlusion (LVO). The role of MT in the paediatric stroke population is less clear. Here we present an updated systematic review addressing the use of MT in paediatric patients, including three cases from our centre in Sydney, Australia. We have also completed an individual participant data (IPD) meta-analysis of clinical and angiographic outcomes based on these results.

Method

Our systematic review and IPD meta-analysis was performed according to PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Individual Participant Data) guidelines. Primary outcomes measures were change in NIHSS (National Institute of Health Stroke Scale) score following MT, and mRS (modified Rankin Scale) score at final reported follow-up. The secondary outcome measure was final angiographic result using the mTICI (modified Treatment in Cerebral Ischemia) scale.

Results

MT resulted in good long-term neurological outcomes (mRS 0–2) in 60/67 cases (89.6%;follow-up timing µ=4.1 months: 95%CI 2.9–5.3), good short-term neurological outcomes (reduction in NIHSS by 8 or more points or post-MT NIHSS of 0–1) in 37/52 cases (71.2%), and successful recanalization (mTICI 2b/3) in 57/67 cases (85.1%).

Conclusions

In paediatric patients, MT is an effective treatment for ischaemic stroke due to LVO. In the absence of a dedicated prospective registry and with randomized control trails unfeasible, this report represents the best available evidence for the use of MT in the paediatric setting.
013 The impact of aggressive blood pressure management in the post-thrombolysis setting
Authors: Harper Bethan , McNaughton Harry , Ranta Anna
Published: July 2019

Introduction

High blood pressure (BP) post-thrombolysis has been associated with an increased rate of bleeding and poorer outcome. We noted frequent BPs of >180 mmHg with a target of keeping BP <180. We tested whether a more aggressive target of SBP <160 mmHg would result in fewer BP protocol violations.

Methods

Patients were prospectively captured comparing patients thrombolysed during the 12 months before and 12 months following the introduction of a new more aggressive BP protocol, allowing for a 6 month transition period. Results were adjusted for baseline function and stroke severity using regression analysis.

Results

Pre-protocol change 68 and post- 100 patients were thrombolysed. Baseline characteristics were similar between groups. There was a trend for a lower rate of SBPs >180 mmHg (adjusted OR 0.49; 95% CI 0.31–1.1; p=0.097) and a significantly higher rate of SBPs <120 mmHg (adjusted OR 3.06; 95% CI 1.52–6.17; p=0.002) in the aggressive BP protocol group; although events of extreme SBPs (>200 and <100 mmHg) were similar between groups. Favourable outcomes (mRS = 0–2) at 3 months were similar between groups (adjusted OR 1.27; 95% CI 0.58–2.8; p=0.56) as was the rate of symptomatic haemorrhages (adjusted OR 1.26; 95% CI 0.28–5.7; p=0.76). Model fit was improved by adding study group to the model.

Conclusions

More aggressive post-thrombolysis BP management lowered the overall BP, but did not result in improved patient outcomes. Potential explanations include a small sample size, reduced cerebral perfusion off-setting reduced bleeding risk, or high BP being merely an epiphenomenon of worse outcome rather than causative.
025 The utility of nerve blood flow in the assessment of peripheral neuropathy
Authors: Borire Adeniyi , Issar Tushar , Kwai Natalie , Visser Leo , Poynten Ann , Simon Neil , Kiernan Matthew , Krishnan Arun
Published: July 2019

Introduction

Animal and human studies of diabetes have shown significant alterations in nerve blood flow (NBF), which may also play a role in the development of neuropathy. However, the non-invasive assessment of NBF in human subjects has remained elusive until the recent technological advancements in ultrasound (US) technology. We undertook sonographic assessment of NBF in 75 patients with type 2 diabetes and correlated the findings with neuropathy severity scores and electrophysiological parameters.

Methods

Blinded median and tibial nerve ultrasound scans were performed at non-entrapment sites using a high-resolution linear probe. NBF was quantified using power Doppler techniques to obtain the vessel score (VSc) and maximum perfusion intensity (MPI). Routine nerve conduction studies were performed, and neuropathy severity was assessed using the total neuropathy score (TNS). Aged- and gender-matched controls were enrolled.

Results

Diabetic nerves had higher rates of NBF detection (28%) compared to the control group (p<0.0001). Significant correlations were found between NBF parameters and nerve size (p<0.001), reported sensory symptoms (p<0.05) and neuropathy severity scores (p<0.001). The cohort with diabetes had significantly larger median (8.5 ± 0.3 mm2 vs. 7.2 ± 0.1 mm2, p<0.05) and tibial (18.0 ± 0.9 mm2 vs. 12. 8 ±0.5 mm2, p<0.05) nerves compared to controls.

Conclusions

Peripheral nerve hypervascularity is detectable by US in moderate to severe diabetic neuropathy with prominent sensory dysfunction. Consistent with previous studies, the sonographic detection of NBF is a pathological finding.
003 Subthalamic nucleus deep brain stimulation evoked resonant neural activity predicts clinical response to DBS
Authors: Xu San San , Sinclair Nicholas C , Bulluss Kristian J , Perera Thushara , Lee Wee-Lih , McDermott Hugh J , Thevathasan Wesley
Published: July 2019

Introduction

DBS can improve motor deficit in Parkinson’s disease (PD) patients. Existing devices have limitations due to electrode positioning errors, fallible manual programming and delivery of continuous ‘open-loop’ stimulation despite fluctuating patient state. This results in partial efficacy, adverse effects and increased cost. One solution is to use an electrical feedback signal or ‘biomarker’ recorded from DBS electrodes. The most widely studied signal has been spontaneous local field potentials (LFPs), particularly beta band (13–30 Hz) and high frequency oscillations (HFO) (200–400 Hz). Here, we report a novel biomarker in the form of a large amplitude, evoked potential, with a characteristic oscillatory decay, termed evoked resonant neural activity (ERNA).1

Methods

LFPs and ERNA were recorded in 14 patients with PD (28 hemispheres) undergoing STN DBS surgery. The four contacts in each electrode array were ranked according to ERNA amplitude, beta power, HFO power and proximity to the anatomically ideal stimulation location. At least 3 months after surgery, motor scores (UPDRS III, reaction time) were evaluated off-DBS and during stimulation delivered through each electrode contact in a randomised order.

Results

ERNA amplitude, beta power and contact proximity to the anatomically ideal stimulation location predicted magnitude of therapeutic response to DBS. However, after exclusion of covariance, ERNA amplitude remained the only significant predictor of DBS response.

Conclusion

ERNA is a readily recordable, large amplitude signal that accurately correlates with motor response to DBS. It holds significant potential as a biomarker for guiding electrode implantation, ideal contact selection, automated parameter fitting and delivery of closed-loop DBS.

Reference

Sinclair NC, McDermott HJ, Bulluss KJ, Fallon JB, Perera T, Xu SS, et al. Subthalamic nucleus deep brain stimulation evokes resonant neural activity. Annals of neurology 2018;83(5).
034 Prospective study of 24-hour levodopa-carbidopa intestinal gel therapy for unresponsive freezing of gait
Authors: Nagaratnam Sai , Chang Florence Ching-Fen , Tsui David S , Mahant Neil , Wolfe Nigel , Kim Samuel D , Ha Ainhi D , Griffith Jane M , Fung Victor SC
Published: July 2019

Introduction

We report a prospective, open-label study of 24-hour levodopa-carbidopa intestinal gel (LCIG) as treatment for levodopa ‘unresponsive’ freezing of gait (FOG) associated with Parkinson’s disease.

Method

14 patients with disabling FOG, documented as being levodopa ‘unresponsive’ following dose cycle assessment, were commenced on continuous 24-hour infusion LCIG therapy with the night-time rate at 50–80% of the daytime infusion rate. Patients underwent baseline and 6 months gait assessments, documentation of their falls frequency and completed FOG questionnaires. The statistical analysis was performed with SPSS 25 software (IBM), using Wilcoxon Signed Rank test and p < 0.05 was set as statistically significant.

Result

The fall frequency score reduced from 3 to 1 at 6 months (p=0.011), The FOG questionnaire was 19.3±1.5 at baseline and reduced to 16.0±1.7, at 6 months, respectively (p=0.039). The mean 360 degree turn time was not significantly changed (p=0.77). The daytime LCIG infusion rate was not significantly different before and after 24-hour LCIG therapy (p=0.315). 7 subjects developed visual hallucinations, one required temporary withdrawal from 24-hour LCIG, but as FOG worsened on 16-hour LCIG, he elected to recommence 24-hour LCIG infusion with improvement in FOG with a reduction in falls. 1 subject had postural hypotension which was ameliorated after adjustment of LCIG infusion rate.

Conclusion

We provide further evidence that 24-hour LCIG therapy can reduce levodopa ‘unresponsive’ FOG and associated falls.
037 Frontotemporal dementia or frontal variant alzheimer’s disease? A case series
Authors: Powell Alice , Foxe David , Halliday Glenda M , Piguet Olivier , Hodges John R , Burrell James R
Published: July 2019

Introduction

Accurate prediction of the underlying neuropathology in behavioural variant frontotemporal dementia (bvFTD) is essential for future targeted therapy trials and prognostication. Alzheimer’s disease (AD) pathology has been reported in a significant proportion of patients with clinical bvFTD. We sought to determine whether detailed clinical and neuroradiological assessment was sufficient to distinguish bvFTD with AD pathology from bvFTD with frontotemporal lobar degeneration (FTLD).

Methods

Two patients with clinically diagnosed probable bvFTD but AD pathology at autopsy, were identified. The clinical, neuropsychological and imaging features of these patients were compared with those of ten patients with clinically probable bvFTD and proven FTLD pathology (tau, TDP-43, FUS).

Results

Both patients with AD pathology presented with behavioural symptoms typical of bvFTD as well as memory impairment. Executive function, memory and visuospatial skills were impaired in both pathologic groups. Language skills were relatively spared in those with AD pathology. Neuropsychiatric symptoms were frequent in both groups but significant depression and anxiety were seen only in those with FTLD pathology. Dementia severity and caregiver burden were similar. The degree or topographical distribution of atrophy on MRI did not differ.

Conclusions

Alzheimer’s pathology may cause bvFTD symptoms which are otherwise indistinguishable to those caused by FTLD pathology. While there may be subtle differences in patterns of cognitive deficits, standard neuropsychological testing is insufficient to discern the underlying pathology. Similarly, structural imaging cannot be used to reliably identify AD pathology. Better access to amyloid biomarkers may be needed to more accurately define bvFTD caused by AD pathology.
038 Tremor: a clinical and neurophysiological study
Authors: Fois Alessandro , Mahant Neil , Vucic Steve , Fung Victor SC
Published: July 2019

Introduction

Tremor is a common clinical problem seen in a number of diseases. Robust classification and diagnosis of tremor remains controversial due to overlap in clinical features and lack of established biomarkers. This hampers effective research including therapeutic trials. We present our research protocol for a cross-sectional study which aims to find more robust methods of tremor classification and diagnosis.

Methods

Adults with upper limb tremor of varying aetiologies, diagnosed using current clinical criteria (including essential tremor, Parkinsonian tremor, and dystonic tremor), and age-matched controls are eligible for recruitment. Participants undergo a clinical and neurophysiological assessment, including accelerometry, surface electromyography, long-latency stretch reflexes, temporal discrimination, and tonic vibration reflexes. Data will be analysed using a cluster analysis to identify robust tremor syndromes and biomarkers associated with them. We aim to recruit 100 participants prior to analysis.

Results

At time of writing, 13 participants with upper limb tremor have been studied (6 with essential tremor, 5 with dystonic tremor, and 2 with indeterminate tremor; mean age 66 years, range 18–85). Participants tolerated the clinical and neurophysiological studies well with 100% completion rate after recruitment. With current rates of recruitment we anticipate completion of recruitment and commencement of data analysis in October 2019.

Conclusions

Our protocol aims to identify robust tremor phenotypes and biomarkers for them. This will allow patients with tremor to be classified into more biologically homogeneous diagnostic categories, aiding future research into the mechanism of tremor and more rational clinical trial design.
042 Respiratory function and cognitive profile in motor neuron disease
Authors: Huynh William , Sharplin Lara E , Caga Jashelle , Highton-Williamson Elizabeth , Kiernan Matthew C
Published: July 2019

Introduction

Motor neuron disease (MND) is increasingly recognised as a multisystems disorder with 30–50% of patients having mild to moderate cognitive impairment. Mechanisms of cognitive dysfunction in MND are multifactorial but chronic hypoxia secondary to respiratory dysfunction may contribute to cognitive decline in patients.

Objectives

The current study aimed to identify the relationship between respiratory function in MND patients and the presence and degree of cognitive impairment.

Methods

MND patients were prospectively recruited from a multidisciplinary MND clinic. Patients meeting the criteria for frontotemporal dementia were excluded. Baseline clinical assessments including respiratory function as assessed by spirometry were recorded with FVC ≤ 75% considered to have reduced respiratory function. Cognitive testing was performed utilising the Addenbrooke’s Cognitive Examination (ACE).

Results

From a cohort of 100 MND patients 48% were categorised as having impaired respiratory function whilst 52% had normal function. Compared to the group with normal respiratory function (ACE: 86.83±1.5), patients with respiratory dysfunction had significantly reduced cognitive function (ACE: 90.68±0.89, P=0.025). Subscores demonstrated significant differences between the groups with respect to domains in memory, attention with a trend observed in fluency. There was a significant correlation between FVC and ACE scores as well as between FVC and memory and fluency subscores (P<0.01).

Conclusion

MND patients with respiratory compromise were more likely to develop reduced cognitive function. In addition to improving physical function, it remains plausible that non-invasive ventilation may alter the progression of cognitive impairment in MND patients, thereby potentially improving their overall quality of life and carer burden.
051 Overlapping syndrome of giant cell arteritis and ANCA-associated vasculitis complicated by severe axonal neuropathy: a case report
Authors: Perju-Dumbrava Laura , Islam Fariha , Makonahalli Rohitha , McLean Catriona , Griffiths Hedley , Malhotra Abhishek
Published: July 2019

Case

A 61-year- old woman presented with what was thought to be a refractory, temporal artery biopsy-proven giant cell arteritis (GCA). After 4 months of therapy she was unable to get the prednisolone dose below 40 mg/day, so weekly subcutaneous Tocilizumab was introduced but with minimal response after 8 weeks. She was then admitted to hospital with a severe rapidly progressive length dependent sensorimotor peripheral neuropathy. Nerve conduction studies showed predominantly an axonal neuropathy with multiple pseudo-conduction blocks.

Sural nerve and gastrocnemius biopsies revealed a necrotising vasculitis with numerous giant cells and active axonal degeneration. She proved to be ANCA-PR3 positive, without other systemic manifestations. ANCA-associated vasculitic neuropathy was diagnosed and she was treated with two 1g Rituximab infusions, 2 weeks apart.

On follow-up after a month, she had regained some strength but still required a wheelchair for mobility. Further Rituximab infusion after 6 months is planned; prednisolone had been successfully weaned to 10 mg/day.

Conclusion

Peripheral nerve involvement, which is relatively common in ANCA-associated vasculitis, has also been reported in 14% of GCA cases. But ANCA-PR3 positivity is rare in biopsy-proven GGA, with only a handful of well-documented cases.

Heightened suspicion of an alternative diagnosis in the face of an unusual clinical course (lack of steroid response and appearance of small vessel vasculitic symptoms for what is accepted to be a large vessel vasculitis) is critical and our experience highlights the important fact that a diagnosis of one of these disorders does not preclude the subsequent diagnosis of the other.
054 Impact of online adult headache guideline on headache referral to neurology clinic
Authors: Huang Leon , Bourke David , Ranta Anna
Published: July 2019

Introduction

Headache is a common problem in primary care and is one of the main reasons for general practitioners to consult neurology service. Decision for referral may be influenced by uncertainty of diagnosis and referrer’s clinical confidence in identifying risks of secondary causes. We examined the effect of an online guideline for adult headache on referrals to neurology service, and analyse the quality of the referrals and outcome of their clinical assessment.

Methods

We examined the referrals in selected months within 2 years before and 2 years after online publication of a headache guideline developed by our neurology department. Referrals for headaches being the primary complaint were analysed. The primary outcome was the proportion of neurology referrals for headache as the primary complaint pre- versus post guideline.

Results

Nine hundred neurology referrals before and 801 neurology referrals after the publication of online headache guideline were included. There was a significant reduction in proportion of neurology referrals for headaches (OR = 0.73 (0.55 – 0.96), p = 0.026). The proportion of headache referrals requiring face-to-face assessment in clinic was also reduced from 69% before and 53% after publication of the headache guideline (p=0.014). There are similar proportions of patient referred without adequate trial of preventative medication prior (33.8% vs. 27.7%), and over used analgesics (21.9% vs. 25.0%).

Conclusions

The headache guideline demonstrated effectiveness in reducing demand for assessment of headaches in neurology clinic. Headache management prior to referral is an ongoing area of concern.
005 Electroclinical characteristics of autoimmune encephalitis as outcome biomarkers
Authors: Wesselingh Robb , Broadley James , Kyndt Chris , Buzzard Katherine , O’Brien Terence , Monif Mastura
Published: July 2019

Introduction

Seizures are a common characteristic of Autoimmune encephalitis (AIE). The use of the electroclinical characteristics to assist in the diagnosis of AIE has been explored1 however use of specific electroencephalogram (EEG) changes has not been examined with regards to outcome prediction.

Methods

Patients with AIE were recruited retrospectively across 4 hospitals in Victoria. Clinical Data was collected during admission and at final follow-up. EEGs of patients were reviewed using an objective proforma. Associations between EEG biomarkers and clinical outcomes were demonstrated using logistic regression modelling.

Results

We recruited 88 patients with AIE and available EEGs. Presence of rhythmic delta, superimposed fast activity and an abnormal background were significantly more common in N-methyl-D-aspartame receptor (NMDAR) antibody associated AIE patients (p<0.05). ICU admission was associated with rhythmic delta epileptiform activity (OR 3.25, p=0.046), sharp elements in the EEG abnormality (OR 3.55, p=0.05), and an abnormal background rhythm (OR 3.56, p=0.03). Development of drug resistant epilepsy was associated with prolonged duration of abnormality on EEG (OR 11.99, p=0.013), and sharp elements in the EEG abnormality (OR 7.29, p=0.02).

Conclusion

We have identified EEG biomarkers that differentiate NMDAR AIE from other subtypes, and likely represents an objective description of extreme delta brush which has previously been described in NMDAR AIE.2 We have also demonstrated biomarkers associated with important outcomes that can be used to help guide treatment and prognosis.

References

Limotai C, Denlertchaikul C, Saraya AW, Jirasakuldej S. Predictive values and specificity of electroencephalographic findings in autoimmune encephalitis diagnosis. Epilepsy Behav 2018;84:29–36.

Veciana M, Becerra JL, Fossas P, Muriana D, Sansa G, Santamarina E, et al. EEG extreme delta brush: An ictal pattern in patients with anti-NMDA receptor encephalitis. Epilepsy Behav 2015;49:280–5.
057 A rare presentation of a rare disease: adult onset krabbe’s disease presenting with progressive hypertrophic polyradiculoneuropathy
Authors: MacDonald Allycia , Lamont Phillipa , Leong Wai
Published: July 2019

Introduction

Globoid Cell Leukodystrophy (Krabbe’s disease) is a rare autosomal recessive condition caused by defects in the lysosomal enzyme galactosylceramidase. The disease typically occurs in infants and is rapidly progressive. Fewer than 5% of cases develop symptoms in adulthood, the majority of which present with spastic paraparesis.

Case

A 40-year-old Italian man presented with a 20 year history of gradually progressive asymmetrical hand paraesthesias and weakness. EMG demonstrated demyelinating features and absent sensory responses. CSF examination revealed elevated protein with no cells and negative oligoclonal bands. Treatment with intravenous immunoglobulin (IVIg) was commenced and continued for 2 years for presumed CIDP without clinical response. Upper limb wasting and weakness progressed over the following 10 years with associated loss of reflexes, prompting consideration of an underlying genetic neuropathy. DNA testing for common CMT mutations was negative. MRI cervical spine and brachial plexus demonstrated diffuse bilateral non-enhancing enlargement of cervical nerve roots. IVIg was recommenced over the next 10 years with continued clinical deterioration to the point of bilateral flail arms with relatively preserved lower limb motor function, in addition to bulbar and respiratory dysfunction by age 64. MRI brain demonstrated thickening of a number of cranial nerves without contrast enhancement, and extensive T2-hyperintensity of periventricular white matter. Next generation sequencing revealed two novel mutations in the galactosylceramidase (GALC) gene, and beta-galactocerebrosidase activity was reduced, confirming the diagnosis of Krabbe’s disease.

Conclusion

This case highlights an unusual presentation of Krabbe’s disease with progressive hypertrophic polyradiculoneuropathy, associated with a novel genetic mutation.
006 Can seizure-related heart rate differentiate epileptic seizures from psychogenic non-epileptic seizures?
Authors: Yong Hue Mun Au , Minato Erica , Paul Eldho , Seneviratne Udaya
Published: July 2019

Introduction

This study aims to (i)evaluate the diagnostic sensitivity, specificity and predictive values of seizure-related heart rate (HR) in differentiating epileptic seizures(ES) from psychogenic non-epileptic seizures(PNES), (ii)define the most useful point of HR measurement: pre-ictal, ictal-onset, maximal-ictal or post-ictal, and (iii)define the HR cut-off points to differentiate ES from PNES.

Methods

All video EEG(VEEG) at Monash Health from May 2009 to November 2015 were retrospectively reviewed. Baseline(during wakefulness), one-minute pre-ictal, ictal-onset, maximal-ictal and one-minute post-ictal HR were measured for each ES and PNES event. Events less than ten seconds or with uninterpretable ECG due to artefacts were excluded. ROC curve analysis was performed to study the diagnostic accuracy reflected by area under the curve(AUC). The AUC was interpreted as follows; ≤0.5, differentiation of PNES from ES no better than chance; 0.80–0.89, good differentiation; and 0.9–1, excellent differentiation.

Results

VEEG of 341 ES and 265 PNES from 130 patients were analysed. The AUC for pre-ictal, ictal-onset, maximal-ictal and post-ictal HR were found to have poor differentiation between ES and PNES. Comparing PNES and bilateral tonic-clonic ES, AUC for absolute maximal-ictal HR was 0.84(CI 0.73–0.95) and for absolute post-ictal HR was 0.90(CI 0.81–1.00). Using Youden’s index, to diagnose tonic-clonic ES, the optimal cut-off point for absolute maximal-ictal HR was 114bpm (sensitivity 84%;specificity 82%;PPV 26.7%,NPV 98.5%) and for absolute post-ictal HR was 90bpm(sensitivity 91%;specificity 82%;PPV 30.3%;NPV 99.1%).

Conclusions

These findings suggest that seizure-related HR increase is useful in differentiating bilateral tonic-clonic ES from PNES. Based on the AUC, the best diagnostic measureme.
072 Signal recognition particle antibody associated necrotizing myositis with ‘burnt-out’ paravertebral muscle atrophy
Authors: Harinesan Nimalan , Reddel Stephen W
Published: July 2019

Introduction

Necrotizing autoimmune myositis (NAM) is an increasingly recognised myositis.1 While diagnosis is primarily from muscle pathology, antibodies to signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl–coenzyme A reductase (HMGCR) are also associated.

Case

A 67 year old woman presented with proximal weakness and elevated creatine kinase (CK) levels following a complicated AMI, CABG and commencement of atorvastatin. Muscle biopsy confirmed necrotizing myositis and SRP (not HMGCoAR) antibodies were positive. Recovery and rehabilitation was slow and her CK did not normalise for 12 months. She was treated with immunotherapy including intravenous immunoglobulin, oral and intravenous corticosteroids, azathioprine, and mycophenolate.

Residual hip, abdominal and truncal weakness remained, affecting her gait and posture. CK levels during this period remained normal. MRI demonstrated extensive paravertebral muscle loss with fatty replacement without oedema. Small myopathic units without active features were present on EMG.

Conclusion

This case illustrates several important aspects of NAM, which remains a rare disorder. Recovery can be incomplete in up to 40%, especially if control is delayed.2 In our opinion, normalisation of CK is an important target and may be necessary for full recovery, and rising CK may predict relapse.3 We suggest MRI and EMG of weak muscles may assist in distinguishing persisting myositis from ‘burnt-out’ disease, clarifying whether immunotherapy should be increased or not. However relapse on weaning immunosuppression remains frequent. While SRP antibodies in patients who had also taken statins has been previously reported, the quick sequential onset in this case suggests possible causality.

References

Mammen AL. Autoimmune Myopathies. Contin Lifelong Learn Neurol. 2016;22(6):1852–1870.

Watanabe Y, Uruha A, Suzuki S, et al. Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry 2016;87(10):1038–1044.

Ramanathan S, Langguth D, Hardy TA, et al. Clinical course and treatment of anti-HMGCR antibody–associated necrotizing autoimmune myopathy. Neurol Neuroimmunol Neuroinflammation 2015;2:e96.
081 Lymphoma: a great imitator in neurology and its many faces
Authors: Yeh Wei Z , Muthusamy Subramanian , McKelvie Penny , Collins Steven , French Ann , Filshie Robin , Reardon Katrina
Published: July 2019

Introduction

The label ‘great imitator’ refers to conditions which can cause varied manifestations and mimic diseases. Lymphoma is worthy of this title. We present three cases.

Cases

1: 66-year-old-man with progressive vertical diplopia and unsteady gait over four weeks. MRI brain and spine demonstrated a supratentorial para-falcine soft tissue lesion, mid-thoracic cord enhancement and right axillary mass. Serum ACE was elevated. Serum HIV serology was positive. Right axillary mass core biopsy diagnosed Burkitt lymphoma.

2: 50-year-old man with a 4-week history of constitutional symptoms on a background of ITP and splenomegaly. During admission he developed urinary retention, bilateral lower limb weakness and numbness and confusion. Infectious and vasculitic screens were unremarkable. CT chest, abdomen and pelvis demonstrated splenomegaly. CSF and bone marrow analyses were non-diagnostic. A random skin biopsy diagnosed intravascular lymphoma.

3: 65-year-old man with two weeks of headache and diplopia on a background of previously treated Burkitt lymphoma. CSF analysis showed 45×106/L white cells and glucose < 0.6 mmol/L. Cytologic analysis was negative for malignancy. Bacterial culture and Cryptococcal antigen were negative. FDG-PET dramatically showed disseminated spinal and cranial leptomeningeal disease. MRI brain showed thin dural thickening correlating to area of increased uptake on PET. He was diagnosed with Burkitt lymphoma relapse and treated with chemotherapy and autologous stem cell transplant.

Conclusion

The varied manifestations in our cases demonstrate the ability for lymphoma to mimic infective, inflammatory, granulomatous (including sarcoidosis) and neoplastic aetiologies. When the diagnosis is uncertain, the possibility of this great imitator should be considered.
086 Clinical, investigational and treatment factors do not determine prognosis of patients with inflammatory neuropathies
Authors: Kapoor Mahima , Carr Aisling , Lunn Michael P , Reilly Mary M
Published: July 2019

Introduction

Identifying patients who need long-term immunoglobulin (IVIg) treatment in patient with inflammatory neuropathies is essential as recent treatment trials show a remission rate of up to 40%.

Aims

Compare retrospective data on clinical, investigational and treatment factors in patients who have ceased IVIg with patients who have failed a cessation trial.

Methods

15 patients who successfully suspended IVIg infusions were compared with 15 in whom decreasing or stopping IVIg was unsuccessful.

Results

30 patients (12 with CIDP and 3 with MMN in both groups) were diagnosed 39.5 months from onset of symptoms in the successful group vs. 40.7 months in the unsuccessful group (p=0.953). There was a significant difference in the summed upper limb sensory amplitudes on electrophysiology prior to starting IVIg between the patients with CIDP (17.4 mV vs. 9.8mV p=0.007). There was no difference in the average doses between the groups. A successful cessation trial was attempted at a mean of 60.5 months post starting treatment, compared with 60 months in the unsuccessful patients.

Conclusion

There is a need for objective biomarker to measure disease activity because other than one neurophysiology marker, other factors did not help predict a successful cessation trial of IVIg.
099 Do clinical nurse specialist led stroke follow-up clinics reduce post-stroke hospital readmissions and recurrent vascular events?
Authors: Kao Alex , Lanford Jeremy , Wong Lai-Kin , Ranta Anna
Published: July 2019

Introduction

Post-discharge stroke follow-up clinics have been associated with improved outpatient care and reduced readmission. Pre-2014 there was no consistent follow-up care offered at Wellington Hospital. Our aim was to determine whether the establishment of a clinical nurse specialist (CNS) follow-up clinic reduced the readmission 12-monthrate.

Methods

This is a sequential comparison of patient admitted with stroke one year prior and one year after the clinic was established in 2013. The primary outcome was hospital 12-month hospital readmission rate; main secondary outcome was recurrent vascular event. Patients were identified from the hospital discharge records and underwent detailed electronic chart review. Results were adjusted for differences in baseline characteristics.

Results

We identified 874 patients; 439 pre- and 435 post-nurse clinic implementation. There was no significant difference between the one-year readmission rate after the establishment of the stroke follow up clinic (adjusted OR=1.06; 95% CI, 0.85–1.64; p=0.804) and no difference in recurrent composite vascular events at one-year (adjusted OR=1.20; 95% CI, 0.68–2.11; p=0.528). The median (IQR) time to follow-up to clinic after discharge was 85 (63–98.5) days. There was a trend towards a reduction in vascular events when limiting the analysis to patients who actually attended clinic, but this trend disappeared when adjusting for baseline inter-group differences.

Conclusions

There was no reduction in the one-year hospital readmission or vascular event recurrence rate for patients with stroke following the establishment of a nurse specialist led stroke follow up clinic. Earlier timed follow-up and the psychosocial value offered by these clinics requires further evaluation.
109 Severe dysautonomia in NMDAR encephalitis
Authors: Donaldson Alana , Venkat Abhay , Zhai Shaun , Patel Ronak , Gawarikar Yash
Published: July 2019

Introduction

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the more common forms of autoimmune encephalitis, predominantly affecting children and women of the child-bearing age. It is characterised by memory deficit, behavioural disturbance and seizures. Dysautonomia is recognised as a feature but rarely the first symptom of the condition.1 Here we present a case of severe dysautonomia preceding the diagnosis of NMDAR encephalitis.

Methods

We conducted a retrospective review of the admissions to the neurology ward at the Calvary Hospital, Canberra in 2018 to identify patients diagnosed with NMDAR encephalitis.

Results

One patient was identified from the registry data. A 37-year-old woman presented with a week-long history of symptomatic orthostatic hypotension. Her supine systolic blood pressure was 110mmHg with a 46mmHg postural drop. Over the first week of hospitalisation, she became increasingly disoriented and erratic in behaviour with fluctuating levels of consciousness requiring intensive unit care. Her CSF demonstrated lymphocytic pleocytosis and NMDAR antibodies were detected in both CSF and serum. She was treated with IVIG, IV steroids and subsequently Rituximab. A pelvic teratoma was found and removed. Her symptomatology including dysautonomia improved substantially by the end of her six-week hospital admission. Her modified Rankin Scale was zero at three months.

Conclusion

Autonomic dysfunction is not a common feature of autoimmune encephalitides. Our case highlighted the possibility that dysautonomia can be the initiating symptom of this disease entity. Physician awareness is important in the early recognition and treatment of this condition.

Reference

Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157–165.
110 The benefits of a clinical triage tool in acute stroke
Authors: Alanati Khaled , Byrnes Sean , Evans James , Campbell David , Wall Ellen
Published: July 2019

Introduction

The advances in management of ischemic stroke and the extended treatment window have greatly increased the demand for acute stroke assessment. There is a need for fast and accurate triage both to identify candidates for acute stroke assessment and to minimize cost and time expended on unnecessary assessments and investigations.

We examined the potential benefit of a web-based triage tool designed to be used in the emergency department to identify patients suitable for hyperacute treatment based on the current standard of care.

Methods

We performed a retrospective analysis of Electronic medical records of 235 patients, reviewed by the neurology team at Gosford Hospital for the consideration of hyperacute treatment over six months in 2017. Each patient’s time of onset of symptoms, premorbid function and presenting deficit, as well as the type of treatment received, were collected. By entering those data to our new triage system, we estimated the number of clinical reviews and advanced imaging that could have been avoided.

Results

Out of the 235 patients that were reviewed, 71 patients either received thrombolysis and/or were sent for endovascular treatment, and 164 patients were not suitable for hyperacute treatment. Using the triage tool, we identified that 26% (n=61) of the rapid clinical assessment and 32% (n=42) of CT perfusion scans performed could have been avoided.

Conclusion

Use of a web-based triage tool is not only effective to identify patients suitable for hyperacute management but also to avoid over-investigation and prioritize rapid neurological clinical assessments.