bluuebunny/crossref_metadata_2025_split huggingface dataset:
103 Exploring the influence of quantitative magnetic resonance imaging on decision-making in multiple sclerosis clinical practice
Authors: Beadnall Heidi N , Ly Linda , Wang Chenyu , Billiet Thibo , Ribbens Annemie , Hecke Wim Van , Zivadinov Robert , Barnett Michael H 
Published: May 2018

IntroductionQuantitative magnetic resonance imaging (MRI) analysis is currently used in multiple sclerosis (MS) clinical trials. Quantitative MRI (QMRI) data derived using formal analysis techniques is not used in routine MS clinical practice and its effect on clinical decision-making is unknown. The study objective is to explore the influence that QMRI data has on clinical decision-making in real-world MS patients.MethodsClinical MS brain MRI scans (separated by one-year minimum, acquired on the same scanner from the same patient) were evaluated. All patients were on the same disease-modifying therapy (DMT) six months prior to and during the study. QMRI analyses were performed on scan pairs by; imaging analysts using specialised software [semi-automated], and MSmetrix [fully-automated]. Data was presented in two separate reports; local QMRI (semi-automated) and centralised QMRI (MSmetrix). Questionnaires were completed by the same neurologist for each subject using clinical data and standard MRI and QMRI reports.Results31 relapsing-MS patients (77.4% female), with baseline age 42.14 [10.70] years, disease duration 7.68 [4.89] years and EDSS score 1.40 (1.36), were evaluated. Injectable, oral and infusion DMTs were administered in 29.0%, 61.3% and 9.7% of patients respectively. According to questionnaire responses, 83.9% were predicted to have stable disease over the next year based on clinical reports alone and 67.7% with the addition of QMRI report data. DMT change would be considered in 16.1% based on clinical reports and 32.3% with QMRI report inclusion. Earlier clinical ±MRI follow up was considered in 51.6% (MRI only 41.9%;both 9.7%) when QMRI reports were reviewed.ConclusionThis preliminary retrospective study indicates that QMRI report data has the potential to influence clinical decision-making in relapsing-MS patients on DMT regarding disease stability assessment, therapy change contemplation, and consideration of earlier follow-up. This work supports a role for formal QMRI analysis and reporting as a clinical-decision support system in MS.
105 Snake eyes in the thoracic spine
Authors: Corbett Joel , Walsh Stephen , Bhuta Sandeep , Sabet Arman 
Published: May 2018

IntroductionBilateral anterior horn cell hyperintensity on spinal imaging (‘snake eyes’ sign) is seen in pathologies including cervical spondylosis, spinal cord infarction and Hirayama’s disease. Below is the first report of lower limb monomelic amyotrophy (MMA) with thoracic spine snake eyes sign. We present a case report of lower limb MMA with bilateral anterior horn hyperintensity, and literature review of cases with this clinico-radiologic presentation.CaseA 47 year old man presented with an 11 year history of asymmetric, progressive, proximal right lower limb weakness and wasting following traumatic back injury. Eight years into the disease course left leg changes developed. There was no upper limb, bulbar nor respiratory involvement. Examination revealed widespread lower limb wasting, normal tone, marked proximal weakness, brisk reflexes and non-sustained clonus bilaterally. Upper limb and cranial nerve examinations were normal. MRI demonstrated T11–12 bilateral anterior horn cell hyper-intensity. Electromyography demonstrated denervation/re-innervation changes in the right vastus lateralis and to a lesser extent tibialis anterior. Muscle biopsy showed chronic denervation atrophy. Anti-ganglioside GM1 IgM was elevated. Further autoimmune testing, infectious screen, cerebrospinal fluid and neuromuscular disease gene analysis were negative. Steroid and intravenous immunoglobulin therapy were ineffective.Case series describing lower motor neuron diseases (LMND) including MMA have not previously reported snake eyes sign in association with lower limb disease.1 Two recent publications describing thirty-two cases of LMND with cervical spine snake eyes sign report that all cases were associated with a relatively benign course and many were misdiagnosed as motor neuron disease (MND).2 3 The authors propose this as a previously unidentified mimic of motor neuron disease.ConclusionThis is the first reported case of thoracic snake eyes sign with corresponding lower limb MMA. Lower motor neuron diseases with bilateral anterior horn cell hyper-intensity may represent a unique clinical form of MND with relatively slower progression.References. Nalini A, Gourie-Devi, Thennarasu K, et al. Monomelic Amyotrophy: Clinical profile and natural history of 279 cases seen over 35 years (1976–2010). Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration2014;15:457–465.. Saski S. Sporadic lower motor neuron disease with a snake eyes appearance on the cervical anterior horns by MRI. Clinical Neurology and Neurosurgery2015;136:122–131.. Lebouteux M, Franques J, Guillevin R, et al. Revisiting the Spectrum of Lower Motor Neuron Diseases with Snake Eyes Appearance on Magnetic Resonance Imaging. European Journal of Neurology2014;21:1233–1241.
110 Atrophy of the mediodorsal thalamus is associated with visual hallucinations in lewy body diseases
Authors: Matar Elie , Brooks Daniel , Harding Antony , Halliday Glenda 
Published: May 2018

IntroductionAlthough limbic system dysfunction has been thought to underlie visual hallucinations in patients with Lewy body disorders, neuropathology within thalamic structures subserving limbic functions have not been examined. In this study, we assessed the degree of neuronal degeneration in thalamic regions involved in perceptual integration in patients with Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB).MethodsPost-mortem samples were acquired from twenty-four individuals with Lewy body disease (5 PD, 9 PDD, 10 DLB) and 10 age-matched controls. The anterior principal (AP) and mediodorsal (MD) thalamic nuclei were delineated and analysed using stereological and quantitative neuropathological techniques.ResultsVolume loss within the MD nucleus was observed in patients with DLB (31%) and PDD (18%) but not PD compared to controls (ANOVA, p<0.05). The atrophy was significantly greater in those patients with hallucinations than those without (p<0.05). Somal atrophy was seen in all patient groups and did not correlate with volume loss or visual hallucinations. Interestingly, there was no neuronal loss in this region compared to controls in the Lewy body disease groups. Analysis of the AP nucleus revealed similar patterns of volume loss but with somal atrophy only in patients with PDD and DLB. Both these measures did not correlate significantly with visual hallucinations, but was significantly different in patients with dementia compared to PD only and controls (p<0.05).ConclusionThese results suggest that afferent denervation of the mediodorsal thalamus may contribute to visual hallucinations. This appears to support models that implicate upstream components of the limbic circuitry in the generation of this phenomenon.
111 Epileptic seizures in multiple sclerosis
Authors: Walsh Stephen , Corbett Joel , Meng Tan K , Broadley Simon 
Published: May 2018

IntroductionEpileptic seizures have been described in association with multiple sclerosis (MS) in both anecdotal case reports and case series. The recent identification of specific antibodies to myelin oligodendrocyte glycoprotein (MOG) protein in a small number of patients with demyelinating disease which may resemble neuromyelitis optica or acute disseminated encephalopathy, which may involve seizures, raises the possibility that anti-MOG antibody related demyelination may account for the association of epilepsy with MS.MethodsWe have undertaken a retrospective review of cases of MS diagnosed at the Gold Coast MS clinic over a 10 year period. All cases were systematically asked if they had ever had an epileptic seizure either via a patient completed questionnaire or at a clinic visit. Demographic and clinical information were also recorded. These data have been analysed using descriptive statistics and appropriate tests for significant differences between those with epilepsy and those without.Results428 cases with complete data were identified. Those with a history of epilepsy were slightly younger (median (range); 44.5 (27–64) years vs 4715–88 years), but this difference was not statistically significantly different. The gender ratio was the same for both groups (9/12 (75%) for those with epilepsy and 326/416 (78%)). There was no significant difference in age of onset, disease course, relapse frequency or level of disability. Although numbers are small, seizure appear to occur most frequently earlier in the disease course and are rarely an ongoing issue.ConclusionThese data support earlier work indicating that epilepsy occurs in people with MS who are younger. This fits with the notion that seizures arise in the context of the inflammatory stage of multiple sclerosis rather than the degenerative phase. Further work needs to be undertaken to assess any association with anti-MOG antibodies and epileptic seizures in demyelinating disease.
020 Postural sway as a measure of disease severity in parkinson’s disease
Authors: Lueck Christian J , Ilschner Susanne , Smith Alex , Vlieger Robin , Das Chandi P , Looi Jeff CL , Apthorp Deborah 
Published: May 2018

IntroductionThe severity of Parkinson’s disease (PD) is difficult to assess accurately owing to the lack of a robust biological marker of disease progression, with consequent implications for prognosis and treatment. The current standard measure is the Unified Parkinson’s Disease Rating Scale (UPDRS) but this is hampered by considerable variability between observers and within subjects. Postural sway correlates well with complex brain functioning in other conditions. This study aimed to investigate the correlation of postural sway with the UPDRS and other non-motor measures of disease severity in patients with PD.Methods28 patients with PD (mean age 68 years, range 54–91; 18 male) underwent tests of cognition and quality of life [Montreal Cognitive Assessment (MoCA), Neuropsychiatry Unit Cognitive Assessment (NUCOG) and Parkinson’s Diseases Questionnaire (PDQ-39–1)], assessment of postural sway using a force plate, and assessment of clinical status using the motor component of the UPDRS.ResultsSway path length showed strong correlations with PDQ-39–1, MoCA and the verbal fluency component of the NUCOG (r=0.63,–0.75 and −0.57, respectively; p=0.002,<0.001 and 0.002, respectively) and, to a lesser degree, with the UPDRS III (r=0.45, p=0.018).ConclusionPostural sway shows potential as a sensitive measure of disease severity and brain function in PD, either alone or in combination with other measures. It appears to correlate better with measures of cognition, both general and executive (verbal fluency), and the PDQ measure of disease severity than with the motor component of the UPDRS.
022 Piloting home infusions of natalizumab: a randomised crossover trial
Authors: Schultz Tim , Thomas Anne , Georgiou Paul , Juaton Mahasen , Simon Lorraine , Cusack Lynette , Naidoo Kerisha , Webb Kevin , Karnon Jon , Ravindran Janakan 
Published: May 2018

IntroductionFor people with multiple sclerosis, monthly infusions at specialist clinics are time consuming, potentially costly and restrictive. Conversely, increased demand for hospital services is driving innovation, including delivery of care in the home. We developed a rigorous model of care for home infusions of natalizumab, which was evaluated in a randomised crossover trial. This pilot study (i) tested feasibility and safety of home infusions, and (ii) compared acceptability and clinical effectiveness with usual clinic-based care in a hospital outpatients clinic.MethodsWe recruited 37 stable adult patients (at least 6 prior natalizumab infusions and assessed as safe by their neurologist) who were randomised to an AB or BA trial arm. After 3 infusions, patients crossed over to the alternate treatment for another 3 infusions. The following outcomes were assessed treatment adherence, patient safety outcomes, quality of life (Multiple Sclerosis Quality of Life Inventory, MSQLI), and patient satisfaction (Treatment Satisfaction Questionnaire for Medication, TSQM).ResultsTwo patients moved out of Adelaide and withdrew. No adverse events resulting from the infusion in either the home or clinic setting were reported. There was no difference between home and clinic in the adherence rate (86/104, 82.7% at home) and (84/103, 81.6% at clinic) (X2=0.0, p=1.0) and number of infections during home care8 compared to clinic10 (X2=0.04, p=0.84). There was no difference in any of the nine sub-scales of the MSQLI (p>0.05). Of the four sub-scales of the TSQM (‘Effectiveness’, ‘Side effects’, ‘Convenience’, ‘Global satisfaction’), patients most recently receiving home care were significantly more satisfied with the Convenience of their treatment (p=0.0008).ConclusionData from the pilot study suggest that delivery of infusions of natalizumab at home is feasible, safe and as effective as the hospital setting. Patients reported that home infusions were more convenient than the clinic.
025 The neural correlates of doorway freezing in parkinson’s disease
Authors: Matar Elie , Shine James M , Gilat Moran , Ehgoetz-Martens Kaylena , Ward Phillip B , Frank Michael J , Moustafa Ahmed , Naismith Sharon L , Lewis Simon JG 
Published: May 2018

IntroductionFreezing of gait (FOG) in Parkinson’s disease (PD) is a disabling symptom of advanced PD and is frequently triggered upon passing through narrow spaces such as doorways.1 Despite being common, the mechanisms underlying this phenomenon are poorly understood. We have previously shown that increased footstep latency in a virtual reality (VR) environment is a surrogate measure of FOG.2 In this study we aimed to model doorway freezing utilising the VR paradigm in conjunction with functional magnetic resonance imaging (fMRI) to determine the neural correlates of this phenomenon.MethodsIn our study, nineteen patients who routinely experience FOG performed a previously validated VR gait paradigm3 where they used foot-pedals to navigate a series of doorways. Patients underwent testing randomised between both their ‘ON’ and ‘OFF’ medication states. Task performance in conjunction with blood oxygenation level dependent signal changes were compared within each patient.ResultsWe were able to reproduce the finding that patients in the OFF state demonstrated significantly longer ‘footstep’ latencies as they passed through a doorway in the VR environment compared to the ON state. As seen clinically with FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. fMRI analysis revealed that doorway-provoked footstep delay was associated with selective hypoactivation in the pre-supplementary motor area (pSMA) bilaterally. Task-based functional connectivity analyses showed that this delay was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN.ConclusionThese findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the ‘hyperdirect’ pathway in the generation of this phenomenon.References. Giladi N, Treves TA, Simon ES, Shabtai H, Orlov Y, Kandinov B, Paleacu D, Korczyn AD. Freezing of gait in patients with advanced Parkinson’s disease. J Neural Transm (Vienna)2001;108:53–61.. Matar E, Shine JM, Naismith SL, Lewis SJ.Virtual realitywalking and dopamine: opening new doorways to understanding freezing of gait in Parkinson’s disease. J Neurol Sci 2014;344:182–5.. Shine JM, Matar E, Bolitho SJ, Dilda V, Morris TR, Naismith SL, Moore ST, Lewis SJ. Modelling freezing of gait in Parkinson’s disease with a virtual reality paradigm. Gait Posture2013;38:104–8.
026 Characteristics of advanced parkinson’s disease patients seen in movement disorder clinics – australian results from the cross-sectional observe study
Authors: Evans Andrew , Fung Victor SC , O’Sullivan John , Stell Rick , White Richard , Williams David , Onuk Koray 
Published: May 2018

IntroductionTo evaluate the proportion of Parkinson’s disease (PD) patients identified as having advanced Parkinson’s disease (APD) according to physician’s judgement: Australian results.MethodsThis cross-sectional, non-interventional observational study was performed in movement disorder clinics from 18 countries. Results from the Australian cohort are presented here. Participants included consecutive adults with PD attending a routine clinical visit, or inpatients at participating clinical sites, and who could speak English. The primary outcome was the proportion of patients diagnosed with APD via physician judgement. Secondary objectives included to evaluate clinical characteristics of APD versus non-APD; to assess the percentage of APD considered for device-aided therapies (DAT); to explore referral practices for APD; and to compare the percentage of APD identified in routine clinical practice by physician’s judgment to APD identified based on APD criteria derived using the Delphi method.Results100 patients were recruited in Australia: 61.0% (95%CI 51.4%–70.6%) diagnosed with APD by physician judgement. Patients were 66.6±8.5 years, 65% were male, were living at home (97%), and diagnosed for median 10.7 years (0–30.5 years). Motor fluctuations were present in 68%. For those with APD, referral was predominantly to enable access to DAT (49%), while for non-APD, referral was largely for diagnostic purposes (41%). Referral to a movement disorder clinic occurred 4.8 years (median) following diagnosis for APD, or 3.6 years for non-APD. While 62% were eligible for DAT, only two-thirds of these received them. The most commonly used DAT was deep brain stimulation (64.3%). There was fair agreement between physician’s judgement and the APD criteria by Delphi method (Cohen’s kappa) 0.325 (95%CI 0.150–0.500).ConclusionThe definition of APD requires refinement in order to facilitate greater agreement among movement disorder specialists. A third of PD patients eligible for DAT remain untreated. Current Australian practice is weighted towards deep brain stimulation.
028 Treating progressive multiple sclerosis
Authors: Hughes Jordana , Jokubaitis Vilija , Slee Mark , Lechner-Scott Jeannette , Walt Anneke Van der , Butzkueven Helmut , Kalincik Tomas 
Published: May 2018

IntroductionWe showed that the available immunotherapies do not modify disability outcomes when used in secondary progressive multiple sclerosis. However, these therapies are effective in advanced active multiple sclerosis. Primary progressive multiple sclerosis may present with or without superimposed relapses. Significance of these relapses for disability accumulation and treatment remains contested. We aimed to examine the effect of the available immunotherapies in primary progressive multiple sclerosis.Methods1427 eligible patients with primary progressive multiple sclerosis from MSBase were studied. Confirmed disability progression of disability was compared between treated and untreated propensity score-matched cohorts. Multivariable regression models were used to compare disability accrual between primary progressive multiple sclerosis with and without superimposed relapses. Finally, the effect of therapy on disability accrual in cohorts with and without superimposed relapses was analysed.Results173 treated and 373 untreated patients were matched. No differences in the risk of disability progression (p=0.79) and improvement (p=0.98) were observed over the median 3 year follow-up.The likelihood of disability progression was relatively lower in patients with superimposed relapses (hazard ratio=0.83, p<0.01). We observed an association between the proportion of time on immunotherapy and the hazard of disability progression in active (hazard ratio=0.96, p=0.01) but not in the inactive primary progressive disease (p=0.21).ConclusionSuperimposed relapses in primary progressive multiple sclerosis represent a favourable prognostic marker, associated with slower disability accrual. This is most likely attributed to the effectiveness of immunotherapy in active primary progressive disease. Relapse activity, therefore, is a treatable modifier of disability accrual in primary progressive disease.
003 A markov/multi-state model of progression and dynamics of seizure freedom in in large cohort of patients with epilepsy
Authors: Simpson Hugh D , Chen Zhibin , Kwan Patrick , Brodie Martin 
Published: May 2018

IntroductionEpilepsy is a common and often highly morbid disease, associated with a not insignificant mortality. Some aspects of epilepsy have been well studied, for example the genetic basis and phenomenology of certain epilepsy syndromes, while other aspects such as long-term outcomes in large cohorts of epilepsy patients are less well studied. Mathematical modelling can assist in the analysis and interpretation of patterns and trends in long-term cohort data, that might not otherwise be obvious intuitively or using standard statistical methods.MethodsMarkov chain and state based modelling have been successfully used in analysing the progression of stages of disease in other specialties, such as chronic kidney disease and diabetic retinopathy. We applied this methodology to disease progression in epilepsy, by applying it to long-term cohort data. We used data from a longitudinal observational cohort study of 1795 patients with newly diagnosed epilepsy, for up to 30 years. The patients were managed in typical, real world clinical practice.ResultsWe created a framework for conceptualising the natural history of epilepsy as a step-wise progression of disease through various stages, determined by seizure freedom and antiepileptic drug schedule. We adapted mathematical frameworks based on Markov chain and multi-state models to this model. We generated transition probabilities representing the dynamics of moving between stages of disease. This allowed us to analyse the dynamics of progression, and hence prognosis, in one of the largest and longest followed epilepsy cohorts in the world.ConclusionEpilepsy can be conceptualised as multi-stage, stepwise disease process. Markov and multistate models can be used to model the natural history of epilepsy, and inform us of the likely outcomes of epilepsy at the various stages in its progression. This quantification of outcomes can help us better inform patients of their prognosis at various stages in their illness.